Sample records for liver function alanine

  1. Crystal structure of the S187F variant of human liver alanine: Aminotransferase associated with primary hyperoxaluria type I and its functional implications

    PubMed Central

    Oppici, Elisa; Fodor, Krisztian; Paiardini, Alessandro; Williams, Chris; Voltattorni, Carla Borri; Wilmanns, Matthias; Cellini, Barbara

    2013-01-01

    The substitution of Ser187, a residue located far from the active site of human liver peroxisomal alanine:glyoxylate aminotransferase (AGT), by Phe gives rise to a variant associated with primary hyperoxaluria type I. Unexpectedly, previous studies revealed that the recombinant form of S187F exhibits a remarkable loss of catalytic activity, an increased pyridoxal 5?-phosphate (PLP) binding affinity and a different coenzyme binding mode compared with normal AGT. To shed light on the structural elements responsible for these defects, we solved the crystal structure of the variant to a resolution of 2.9 Å. Although the overall conformation of the variant is similar to that of normal AGT, we noticed: (i) a displacement of the PLP-binding Lys209 and Val185, located on the re and si side of PLP, respectively, and (ii) slight conformational changes of other active site residues, in particular Trp108, the base stacking residue with the pyridine cofactor moiety. This active site perturbation results in a mispositioning of the AGT-pyridoxamine 5?-phosphate (PMP) complex and of the external aldimine, as predicted by molecular modeling studies. Taken together, both predicted and observed movements caused by the S187F mutation are consistent with the following functional properties of the variant: (i) a 300- to 500-fold decrease in both the rate constant of L-alanine half-transamination and the kcat of the overall transamination, (ii) a different PMP binding mode and affinity, and (iii) a different microenvironment of the external aldimine. Proposals for the treatment of patients bearing S187F mutation are discussed on the basis of these results. Proteins 2013; 81:1457–1465. © 2013 Wiley Periodicals, Inc. PMID:23589421

  2. Liver Histopathology and Liver and Serum Alanine Aminotransferase and Alkaline Phosphatase Activities in Epileptic Dogs Receiving Phenobarbital

    Microsoft Academic Search

    C. L. Gaskill; L. M. Miller; J. S. Mattoon; W. E. Hoffmann; S. A. Burton; H. C. J. Gelens; S. L. Ihle; J. B. Miller; D. H. Shaw; A. E. Cribb

    2005-01-01

    Phenobarbital (PB) therapy is frequently associated with elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (AP) activities in dogs without clinical signs of liver disease. The goal of this study was to determine if increased serum ALT and AP activities in clinically healthy PB-treated epileptic dogs are due to hepatic enzyme induction or to subclinical liver injury. Liver biopsies were

  3. The subcellular distribution of alanine-glyoxylate aminotransferase and serine-pyruvate aminotransferase in dog liver.

    PubMed Central

    Okuno, E; Minatogawa, Y; Nakanishi, J; Nakamura, M; Kamoda, N; Makino, M; Kido, R

    1979-01-01

    The subcellular distributions of alanine-glyoxylate aminotransferase and serine-pyruvate aminotransferase in the particulate fraction of dog liver were examined by centrifugation in a sucrose density gradient. Most of both enzyme activities in the particulate fraction were localized in the mitochondria, but not in the peroxisomes. PMID:518570

  4. Rapid mapping of protein functional epitopes by combinatorial alanine scanning

    E-print Network

    Weiss, Gregory A.

    Rapid mapping of protein functional epitopes by combinatorial alanine scanning Gregory A. Weiss be useful for analyzing functional epitopes in proteins. Because protein­protein interactions are involved accurately define structural binding epitopes (i.e., residues in direct contact with a ligand), they do

  5. Hepatic glucose production from L-alanine is absent in perfused liver of diabetic rats.

    PubMed

    Ferraz, M; Brunaldi, K; Oliveira, C E; Bazotte, R B

    1997-02-01

    The effects of L-alanine on hepatic glucose production in diabetic rats and the corresponding controls was investigated. Diabetes was obtained with an injection iv of streptozotocin (STZ) or alloxan. Livers from diabetic and control rats after 24 hours of fasting were perfused in situ and glucose production from L-alanine and several gluconeogenic substrates were measured. Hepatic gluconeogenesis from L-alanine was absent in rats with diabetes induced by STZ or alloxan. STZ-diabetic rats also shown this metabolic change when the period of diabetes was prolonged. It was concluded that this effect may be partly at least, the consequence of an increased NADH/NAD+ ratio in the diabetic rat liver, which indicates that the cytosolic redox potential is favorable to pyruvate conversion to L-lactate but not to glucose. However, considering that glucose production from pyruvate, L-lactate, glycerol and sorbitol was not affected by the diabetic condition, the rate of conversion of L-alanine to pyruvate can contribute to the lack of gluconeogenesis when this amino acid was employed as a substrate. PMID:9090751

  6. Purification and properties of hydroxypyruvate: L-alanine transaminase from rabbit liver

    Microsoft Academic Search

    R. D. Feld; H. J. Sallach

    1973-01-01

    A procedure is described for the extensive purification of hydroxypyruvate:L-alanine transaminase from rabbit liver. On the basis of gel filtration studies, the molecular weight of the enzyme is estimated to be about 41,000 daltons. A similar value was obtained when the enzyme was subjected to gel electrophoresis in the presence of sodium dodecyl sulfate indicating that the enzyme consists of

  7. Noncovalent and covalent functionalization of a (5, 0) single-walled carbon nanotube with alanine and alanine radicals

    Microsoft Academic Search

    Muthusivarajan Rajarajeswari; Kombiah Iyakutti; Yoshiyuki Kawazoe

    We have systematically investigated the noncovalent and covalent adsorption of alanine and alanine radicals, respectively,\\u000a onto a (5, 0) single-walled carbon nanotube using first-principles calculation. It was found that XH···? (X?=?N, O, C) interactions\\u000a play a crucial role in the non-ovalent adsorption and that the functional group close to the carbon nanotube exhibits a significant\\u000a influence on the binding strength.

  8. Liver function tests

    MedlinePLUS

    ... laboratory results. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 22nd ... liver function. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 22nd ...

  9. Valine-alanine manganese superoxide dismutase polymorphism is not associated with alcohol-induced oxidative stress or liver fibrosis

    Microsoft Academic Search

    Stephen F. Stewart; Julian B. Leathart; Yuanneng Chen; Ann K. Daly; Roberta Rolla; Daria Vay; Elisa Mottaran; Matteo Vidali; Emanuele Albano; Chris P. Day

    2002-01-01

    The role of genetic factors in the pathogenesis of alcohol-induced liver disease (ALD) is receiving increasing attention. Recently, it has been reported that homozygosity for a valine to alanine substitution in the mitochondrial targeting sequence of manganese superoxide dismutase (Mn-SOD) represents a risk factor for severe ALD. Because this mutation is postulated to modify enzyme transport into mitochondria, we have

  10. A stable and selective electrochemical biosensor for the liver enzyme alanine aminotransferase (ALT).

    PubMed

    Jamal, Mamun; Worsfold, Oliver; McCormac, Timothy; Dempsey, Eithne

    2009-05-15

    An electrochemical method to determine alanine aminotransferase (ALT) activity over its normal and elevated physiological range was developed based upon detection of L-glutamate at a glutamate oxidase-modified platinum electrode. Measurements were carried out in the presence of ALT co-substrates L-alanine and alpha-ketoglutarate and current response from either the oxidation of hydrogen peroxide or the re-oxidation of the mediator ferrocene carboxylic acid was employed. The enzyme electrode was tested over a 6-month period and found to retain 79% of its original activity towards ALT detection with >200 measurements performed over this time. Signals associated with interfering electroactive species (ascorbic acid and uric acid) were eliminated using background subtraction at a denatured glutamate oxidase enzyme electrode. The sensitivity of the device was found to be 0.845 nA U(-1) L ALT with t(90)=180 s, linear range 10-1000 U L(-1) and LOD of 3.29 U L(-1) using amperometry at E(app)=0.4 V vs. Ag/AgCl at 308 K (35 degrees C). PMID:19356918

  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. Effect of glucagon and some other alpha and beta adrenergic agonists and antagonists on alanine amino transferase of perfused rat liver

    Microsoft Academic Search

    Nasim Ara Begum; Asoke G. Datta

    1991-01-01

    Glucagon increased alanine amino transferase (AAT) activity in perfused rat liver by about 90% over control. Propranolol, the beta receptor antagonist, abolished the effect of glucagon on this enzyme. Well known beta receptor agonists like isoproterenol, norepinephrine and epinephrine also increased the enzyme activity under identical condition and the enhancement was similarly abolished by propranolol. These experiments suggest that the

  13. Histologic Abnormalities in Children with Nonalcoholic Fatty Liver Disease and Normal or Mildly Elevated Alanine Aminotransferase Levels

    PubMed Central

    Molleston, Jean P; Schwimmer, Jeffrey B; Yates, Katherine P; Murray, Karen F; Cummings, Oscar W; Lavine, Joel E.; Brunt, Elizabeth M; Scheimann, Ann O; Unalp-Arida, Aynur

    2013-01-01

    Objectives To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26–50 U/L boys, 23–44 U/L girls), or elevated (> 50 boys, > 44 girls) serum alanine aminotransferase (ALT) levels. Study design The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) enrolls children 5–18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy within 180 days of ALT, and compared them with 392 children with elevated ALT. Results Of 91 children, 17 (19%) had normal and 74 (81%) had mildly elevated ALT levels. Overall, 45% of biopsies had ? 33% steatosis, lobular inflammation grade was ? 2 in 22%, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had “suspicious/borderline” steatohepatitis, and 8% had definite NASH, 34% had NAFLD activity score (NAS) ? 4. Overall, 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in mildly elevated vs normal, with no difference in ballooning, inflammation, or NAS ? 4. Fibrosis stage 3/4 was seen in none of the children with normal ALT, and in 9% of the mildly elevated and 15% of the elevated. Conclusions Liver biopsies of children with NAFLD with normal or mildly elevated ALT levels show significant histologic abnormalities, including advanced fibrosis in children with mildly elevated ALT. ALT thus may underestimate liver injury in NAFLD. Appropriate ALT cut-off levels can help identify children at risk for more severe disease. PMID:24360992

  14. High peak alanine aminotransferase determines extra risk for nonanastomotic biliary strictures after liver transplantation with donation after circulatory death.

    PubMed

    den Dulk, A Claire; Sebib Korkmaz, Kerem; de Rooij, Bert-Jan F; Sutton, Michael E; Braat, Andries E; Inderson, Akin; Dubbeld, Jeroen; Verspaget, Hein W; Porte, Robert J; van Hoek, Bart

    2015-04-01

    Orthotopic liver transplantation (OLT) with donation after circulatory death (DCD) often leads to a higher first week peak alanine aminotransferase (ALT) and a higher rate of biliary nonanastomotic strictures (NAS) as compared to donation after brain death (DBD). This retrospective study was to evaluate whether an association exists between peak ALT and the development of NAS in OLT with livers from DBD (n = 399) or DCD (n = 97) from two transplantation centers. Optimal cutoff value of peak ALT for risk of development of NAS post-DCD-OLT was 1300 IU/l. The 4-year cumulative incidence of NAS after DCD-OLT was 49.5% in patients with a high ALT peak post-OLT, compared with 11.3% in patients with a low ALT peak. (P < 0.001). No relation between peak ALT and NAS was observed after DBD-OLT. Multivariate analysis revealed peak ALT ?1300 IU/l [adjusted hazard ratio (aHR) = 3.71, confidence interval (CI) (1.26-10.91)] and donor age [aHR = 1.04, CI 1.00-1.07] to be independently associated with development of NAS post-DCD-OLT. A peak ALT of <1300 IU/l carries a risk for NAS similar to DBD-OLT. Thus, in DCD-OLT, but not in DBD-OLT, peak ALT discriminates patients at high or low risk for NAS. PMID:25601020

  15. Crystallization and characterization of human liver kynurenine–glyoxylate aminotransferase. Identity with alanine–glyoxylate aminotransferase and serine–pyruvate aminotransferase

    PubMed Central

    Okuno, Etsuo; Minatogawa, Yohsuke; Nakamura, Masayuki; Kamoda, Naoki; Nakanishi, Junko; Makino, Minoru; Kido, Ryo

    1980-01-01

    Kynurenine–glyoxylate aminotransferase, alanine–glyoxylate aminotransferase and serine–pyruvate aminotransferase were co-purified and crystallized as yellow cubes from human liver particulate fraction. The crystalline enzyme was homogeneous by the criteria of electrophoresis, isoelectric focusing, gel filtration, sucrose-density-gradient centrifugation and analytical ultracentrifugation. The molecular weight of the enzyme was calculated as approx. 90000, 89000 and 99000 by the use of gel filtration, analytical ultracentrifugation and sucrose-density-gradient centrifugation respectively, with two identical subunits. The enzyme has a s20,w value of 5.23S, an isoelectric point of 8.3 and a pH optimum between 9.0 and 9.5. The enzyme solution showed absorption maxima at 280 and 420nm. The enzyme catalysed transamination between several l-amino acids and pyruvate or glyoxylate. The order of effectiveness of amino acids was alanine>serine>glutamine>glutamate>methionine>kynurenine = phenylalanine = asparagine>valine>histidine>lysine>leucine>isoleucine>arginine>tyrosine = threonine>aspartate, with glyoxylate as amino acceptor. The enzyme was active with glyoxylate, oxaloacetate, hydroxypyruvate, pyruvate, 4-methylthio-2-oxobutyrate and 2-oxobutyrate, but showed little activity with phenylpyruvate, 2-oxoglutarate and 2-oxoadipate, with kynurenine as amino donor. Kynurenine–glyoxylate aminotransferase activity was competitively inhibited by the addition of l-alanine or l-serine. From these results we conclude that kynurenine–glyoxylate aminotransferase, alanine–glyoxylate aminotransferase and serine–pyruvate aminotransferase activities of human liver are catalysed by a single protein. Kinetic parameters for the kynurenine–glyoxylate aminotransferase, alanine–glyoxylate aminotransferase, serine–pyruvate aminotransferase and alanine–hydroxypyruvate aminotransferase reactions of the enzyme are presented. ImagesFig. 7. PMID:6783036

  16. Alanine scan of core positions in ubiquitin reveals links between dynamics, stability, and function

    PubMed Central

    Lee, Shirley Y.; Pullen, Lester; Virgil, Daniel J.; Castañeda, Carlos A.; Abeykoon, Dulith; Bolon, Daniel N. A.; Fushman, David

    2014-01-01

    Mutations at solvent inaccessible core positions in proteins can impact function through many biophysical mechanisms including alterations to thermodynamic stability and protein dynamics. As these properties of proteins are difficult to investigate, the impacts of core mutations on protein function are poorly understood for most systems. Here, we determined the effects of alanine mutations at all 15 core positions in ubiquitin on function in yeast. The majority (13 of 15) of alanine substitutions supported yeast growth as the sole ubiquitin. The two null mutants (I30A and L43A) were both less stable to temperature-induced unfolding in vitro than wild-type, but were well folded at physiological temperatures. Heteronuclear NMR studies indicated that the L43A mutation reduces temperature stability while retaining a ground-state structure similar to wild-type. This structure enables L43A to bind to common ubiquitin receptors in vitro. Many of the core alanine ubiquitin mutants, including one of the null variants (I30A), exhibited an increased accumulation of high molecular weight species, suggesting that these mutants caused a defect in the processing of ubiquitin-substrate conjugates. In contrast, L43A exhibited a unique accumulation pattern with reduced levels of high molecular weight species and undetectable levels of free ubiquitin. When conjugation to other proteins was blocked, L43A ubiquitin accumulated as free ubiquitin in yeast. Based on these findings we speculate that ubiquitin's stability to unfolding may be required for efficient recycling during proteasome-mediated substrate degradation. PMID:24361330

  17. Molecular Structure of Alanine

    NSDL National Science Digital Library

    2002-08-20

    Alanine is a non-essential amino acid whose main function seems to be the metabolism of tryptophan and pyridoxine. Alanine is located in prostate fluid, and may play an important role in prostate health. Good sources of alanine are meat, poultry, eggs, dairy products, and fish. High levels of alanine along with low levels of tyrosine and phenylalanine have been associated with the Epstein-Barr virus and chronic fatigue syndrome. Low levels have been found in patients with hypoglycemia, diabetes, and alcohol induced hepatitis.

  18. The design, synthesis, and characterization of novel alanine-rich polypeptides with varied functional group density

    NASA Astrophysics Data System (ADS)

    Farmer, Robin S.

    Protein engineering methods have proven valuable for the synthesis of protein-based polymers with controlled conformational properties and functional group placement for use in a variety of biological and materials applications. These strategies were employed to produce alanine-rich polypeptides with the general sequence [(AAAQ)y(AAAE)(AAAQ)y]x, which utilizes the high helical propensity of alanine and chemical functionality of glutamic acid. Modifications to the general sequence allow for variations in both the spacing between and the number of glutamic acid residues along the protein backbone. Three families of alanine-rich polypeptides with similar amino acid compositions were designed with glutamic acid residues displayed at nominal distances of 17A, 35A, and 65A. From these three families, four of these polypeptides were focused on for this work, 17-H-3, 17-H-6, 35-H-6 and 65-H-2. Understanding the conformational and thermal behavior of the polypeptides can give insight into how these molecules will behave after functionalization. The conformational behavior of the four polypeptides from the three alanine-rich families have been investigated via circular dichroic spectroscopy under multiple solution conditions; pH 2.3, 10 mM phosphate, pH 2.3, 10 mM phosphate, 150 mM NaCl, and pH 7.4 PBS. All the polypeptides adopt an alpha-helical conformation under all solution conditions and exhibit an alpha-helical to non-alpha-helical transition with increasing temperature. In pH 2.3, 10 mM phosphate buffer, the conformation differs between sequences at high temperature and high polypeptide concentration. Although the compositions of the three families are similar, changes in the amino acid sequences result in variations in hydrophobicity. The most hydrophobic sequence, 65-H-2 , undergoes the helix-to-coil transition but at high polypeptide concentrations and temperatures above 45°C, the polypeptide irreversibly adopts a beta-sheet structure. The less hydrophobic polypeptide, 35-H-6 also shows a tendency to adopt a beta-sheet structure at high concentrations and elevated temperatures; however, the transition is kinetically slower than the transition observed for 65-H-2. In pH 2.3, 10 mM phosphate, 150 mM NaCl, the transition to a beta-sheet structure in 35-H-6 and 65-H-2 is suppressed, indicating the salt stabilizes the alpha-helical structure. These polypeptides were designed to be used in biological applications, and the aggregation behavior of the polypeptides was monitored via analytical ultracentrifugation and electrophoresis under physiologically relevant salt conditions (pH 2.3, 10 mM phosphate, 150 mM NaCl or pH 7.4 PBS). Because of the hydrophobic nature of the sequence, 65-H-2 displays high levels of association in pH 2.3, 10 mM phosphate, 150 mM NaCl buffer, and low levels of association are also seen in pH 7.4 PBS buffer. The less hydrophobic sequences, 17-H-3, 17-H-6, and 35-H-6, do not aggregate in pH 7.4 PBS. The ability to manipulate the conformational behavior and association of the polypeptides via changes in salt, polypeptide concentration, and temperature allows these polypeptides to be tailored for specific applications in materials science or biology.

  19. Impact of distal aortic and visceral perfusion on liver function during thoracoabdominal and descending thoracic aortic repair

    Microsoft Academic Search

    Hazim J. Safi; Charles C. Miller III; David H. Yawn; Dimitrious C. Iliopoulos; Mahesh Subramaniam; Stuart Harlin; George V. Letsou

    1998-01-01

    Purpose: We examined the impact of distal aortic and visceral perfusion on liver function during thoracoabdominal and descending thoracic aortic repair. Methods: Between January 1991 and July 1996, 367 patients underwent thoracoabdominal and descending thoracic aortic repair. Baseline and postoperative total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, fibrinogen, prothrombin time (PT), and partial thromboplastin time (PTT) were

  20. The subcellular distribution of rat liver l-alanine–glyoxylate aminotransferase in relation to a pathway for glucose formation involving glyoxylate

    PubMed Central

    Rowsell, E. V.; Snell, K.; Carnie, J. A.; Rowsell, Kathleen V.

    1972-01-01

    1. The distribution of l-alanine–glyoxylate aminotransferase activity between subcellular fractions prepared from rat liver homogenates was investigated. The greater part of the homogenate activity (about 80%) was recovered in the `total-particles' fraction sedimented by high-speed centrifugation and the remainder in the cytosol fraction. 2. Subfractionation of the particles by differential sedimentation and on sucrose density gradients revealed a specific association between the aminotransferase and the mitochondrial enzymes glutamate dehydrogenase and rhodanese. 3. The aminotransferase activities in the cytosol and the mitochondria are due to isoenzymes. The solubilized mitochondrial enzyme has a pH optimum of 8.6, an apparent Km of 0.24mm with respect to glyoxylate and is inhibited by glyoxylate at concentrations above 5mm. The cytosol aminotransferase shows no distinct pH optimum (over the range 7.0–9.0) and has an apparent Km of 1.11mm with respect to glyoxylate; there is no evidence of inhibition by glyoxylate. 4. The mitochondrial location of the bulk of the rat liver l-alanine–glyoxylate aminotransferase activity is discussed in relation to a pathway for gluconeogenesis involving glyoxylate. PMID:5073739

  1. [Liver function and pathogenetic therapy for echinococcosis].

    PubMed

    Streliaeva, A V; Mamysheva, N O; Abdiev, F T; Sagieva, A T; Iusupova, F Sh; Sadykov, V M; Mukhitdininov, Sh M; Vakhidova, A M

    2013-01-01

    This paper contains the results of examining and treating 64 patients with hepatic echinococcosis, treated at the Surgery Unit of the Samarkand Medical Institute Clinic. Forty-five healthy donors of a blood transfusion station formed a control group. There were a total of 109 examined persons. The liver functional status depended on segmental liver involvement by an echinococcal cyst. The cysts were most frequently located in the 7th-8th segments of the liver (32.31%). The number and sizes of cysts also affected the functional status of the cyst-affected liver. The sizes of hepatic cysts varied from 4 to 2 cm. Hepatoprotective agents should be used in different forms of hydatid disease of the liver to correct its function that is changed in multiple and complicated echinococcosis and giant hepatic cysts. They normalize liver function and enzyme activity in the hepatocytes, reduce energy expenditure in the liver, promote hepatocyte regeneration, and convert neutral fats and cholesterol into easily metabolizing forms. PMID:24003518

  2. Electrical impedimetric biosensors for liver function detection

    Microsoft Academic Search

    Ya-Hsuan Chuang; Yun-Tzu Chang; Kuo-Liang Liu; Hwan-You Chang; Tri-Rung Yew

    2011-01-01

    In this study, electrical impedimetric biosensors composed of Au-electrodes were fabricated for the quantitative detection of human serum albumin (HSA), an essential biomarker of liver function. The Au-electrodes were fabricated via a single-step photolithography process, and can be easily integrated in biochips for assessing liver function in the future. The glass sensing surface between two adjacent Au-electrodes was modified with

  3. Association of Reduced Renal Function with Hepatitis B Virus Infection and Elevated Alanine Aminotransferase

    PubMed Central

    Cai, Jianfang; Fan, Xiaohong; Mou, Lijun; Gao, Bixia; Liu, Xuejiao; Li, Jinhong; Liu, Lili; Wang, Haiyun; Guo, Zengyu; Liu, Xiaoqing; Li, Hang; Li, Xuemei

    2012-01-01

    Summary Background and objectives Clinically, hepatitis B virus (HBV) infection is observed to be associated with nephropathy. However, previous population-based studies failed to show an association between HBV infection and CKD. Therefore, this cross-sectional study was designed to further explore this association. Design, setting, participants, & measurements A representative sample of 6854 Chinese adults aged 30–75 years was tested for levels of serum hepatitis B surface antigen, alanine aminotransferase (ALT), creatinine, urinary albumin/creatinine ratio, and potential CKD risk factors. Results Neither HBV infection nor elevated ALT (ALT+; ? sex-specific 90th percentile of ALT levels of noninfected persons) was significantly associated with reduced estimated GFR (eGFR < 60 ml/min per 1.73 m2). Compared with noninfected persons, HBV-infected persons with ALT+, but not those with ALT? (P=0.26), were more likely to have reduced eGFR (odds ratio, 4.07; 95% confidence interval, 1.18–14.0; P=0.03). Further analysis with a general linear model revealed a significant difference in eGFR (mean ± SEM) between HBV-infected and noninfected persons (87.8±0.8 versus 90.2±0.4 ml/min per 1.73 m2; P=0.002). This difference was mainly derived from that between HBV-infected persons with ALT+ and noninfected persons, with an average difference in eGFR of ?4.5 (95% confidence interval, ?0.9 to ?8.1; P=0.01). HBV infection and ALT+, alone or in combination, were not significantly associated with albuminuria or CKD. Conclusions HBV infection with elevated ALT, rather than HBV infection alone, was associated with reduced renal function. PMID:22859746

  4. Regulation of Rat Liver Glutamine Synthetase: Activation by alpha -ketoglutarate and Inhibition by Glycine, Alanine, and Carbamyl Phosphate

    Microsoft Academic Search

    Suresh S. Tate; Alton Meister

    1971-01-01

    Rat liver glutamine synthetase (s20,w15.0 S; MW about 352,000) resembles ovine brain glutamine synthetase in that it (a) has 8 subunits, (b) acts on both L- and D-glutamate and certain glutamate analogs (e.g., beta -glutamate, cis-cycloglutamate, and alpha -methyl-L-glutamate), and (c) is irreversibly inhibited by L-methionine-S-sulfoximine. The liver enzyme (but not the brain enzyme) is (a) markedly activated by alpha

  5. Detoxification Functions of the Liver

    Microsoft Academic Search

    Udayan Apte; Partha Krishnamurthy

    \\u000a The body is exposed to a variety of chemicals everyday in the form of pharmaceutical agents, household chemicals, dietary\\u000a supplements, and environmental contaminants, many of which are extremely toxic. The primary defense mechanisms against xenobiotics\\u000a in the body are the drug metabolizing enzymes (DMEs) involved in metabolism and excretion of xenobiotics [1]. Liver is the\\u000a primary organ involved in the

  6. 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.

  7. Effects of extract derived from Eriobotrya japonica on liver function improvement in rats.

    PubMed

    Nishioka, Yutaka; Yoshioka, Saburo; Kusunose, Masahiko; Cui, Tailin; Hamada, Atuhide; Ono, Masahide; Miyamura, Mituhiko; Kyotani, Shojiro

    2002-08-01

    Eriobotrya japonica is considered a medicinal plant, and its leaves (Eriobotrya folia) have been used to treat skin diseases, as well as to relieve inflammation, pain, coughing, and sputa. In our evaluation of the pharmacological efficacy of the seed extracts, constituents of the seeds were found to contain the unsaturated fatty acids linolenic and linoleic acids and the sterol beta-sitosterol in the 70% EtOH and the MeOH extracts. The seed extracts were orally administered to rats with dimethylnitrosamine-induced hepatopathy, and blood L-asparate aminotransferase (AST) and L-alanine aminotransferase (ALT) levels, liver retinoid level, and hydroxyproline level were measured. Liver fibrosis rates calculated after Azan-Mallory staining and evaluation of the liver function-improving effects of extracts were showed that AST, ALT, and hydroxyproline levels and liver fibrosis rates were significantly lower, and retinoid levels were significantly higher in hepatopathic rats treated with 70% EtOH and MeOH extracts of the seed than in water-treated control rats. This suggests that the positive effect on liver function of the extracts varies depending on the extracting solvent used. 70% EtOH and MeOH extract of the seeds inhibited the development of liver fibrosis in hepatopathic rats, thus exhibiting potent improvement. The unsaturated linolenic and linoleic acids and the sterol beta-sitosterol contained in these extracts may also contribute to the improvement of liver function. PMID:12186409

  8. Platelet function in chronic liver disease

    Microsoft Academic Search

    M. H. Rubin; M. J. Weston; P. G. Langley; Yvette White; Roger Williams

    1979-01-01

    Abnormalities of platelet aggregation in response to adenosine diphosphate in 56 patients with chronic liver disease correlated with impairment of hepatocellular function but not with the etiology of the liver disease. Platelet-poor plasma from some patients appeared to contain an inhibitor since, in cross-over studies, it reduced the degree of aggregation of control subjects. However, platelet-poor plasma from some other

  9. Attenuation of liver normothermic ischemia-reperfusion injury by preservation of mitochondrial functions with S-15176, a potent trimetazidine derivative 1 1 Abbreviations: ASAT, aspartate aminotransferase; ALAT, alanine aminotransferase; PTP, permeability transition pore; RCR, respiratory control ratio; ROS, reactive oxygen species; and ??, mitochondrial membrane potential

    Microsoft Academic Search

    Aziz Elimadi; Rosa Sapena; Abdellatif Settaf; Herve Le Louet; Jean-Paul Tillement; Didier Morin

    2001-01-01

    We investigated the antiischemic properties of a new compound, S-15176, in an experimental model of rat liver subjected to 120-min normothermic ischemia followed by 30-min reperfusion. Rats were divided into groups, pretreated with different doses of S-15176 (1.25, 2.5, 5 and 10 mg\\/kg\\/day by intramuscular injection) or solvent alone, and subjected to the ischemia-reperfusion process. Another group served as the

  10. Inflammasome activation and function in liver disease.

    PubMed

    Szabo, Gyongyi; Petrasek, Jan

    2015-07-01

    Inflammation contributes to the pathogenesis of most acute and chronic liver diseases. Inflammasomes are multiprotein complexes that can sense danger signals from damaged cells and pathogens and assemble to mediate caspase-1 activation, which proteolytically activates the cytokines IL-1? and IL-18. In contrast to other inflammatory responses, inflammasome activation uniquely requires two signals to induce inflammation, therefore setting an increased threshold. IL-1?, generated upon caspase-1 activation, provides positive feed-forward stimulation for inflammatory cytokines, thereby amplifying inflammation. Inflammasome activation has been studied in different human and experimental liver diseases and has been identified as a major contributor to hepatocyte damage, immune cell activation and amplification of liver inflammation. In this Review, we discuss the different types of inflammasomes, their activation and biological functions in the context of liver injury and disease progression. Specifically, we focus on the triggers of inflammasome activation in alcoholic steatohepatitis and NASH, chronic HCV infection, ischaemia-reperfusion injury and paracetamol-induced liver injury. The application and translation of these discoveries into therapies promises novel approaches in the treatment of inflammation in liver disease. PMID:26055245

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

    PubMed

    Liu, Leah Y; Fox, Caroline S; North, Trista E; Goessling, Wolfram

    2013-09-01

    Genome-wide association studies (GWAS) have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf) and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10) decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50) decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes. PMID:23813869

  12. A mutant androgen receptor from patients with Reifenstein syndrome: identification of the function of a conserved alanine residue in the D box of steroid receptors.

    PubMed Central

    Kaspar, F; Klocker, H; Denninger, A; Cato, A C

    1993-01-01

    Reifenstein syndrome is an eponymic term that describes partial androgen-insensitive disorders. Androgen receptor isolated from five patients with this syndrome contains a specific mutation in the DNA binding domain of the receptor. This mutation converts an alanine to a threonine at position 596 next to the zinc catenation site at the second finger. The threonine 596 mutant receptor mediated normal androgen response at promoters with closely positioned multiple regulatory elements for the androgen receptor and other transcription factors. Promoters with single isolated androgen response elements were not transactivated by the mutant receptor. In in vitro receptor-DNA binding studies, interaction with DNA by the mutant receptor was achieved only in the presence of an anti-androgen receptor antibody. Exchanging alanine 596 in the wild-type androgen receptor with serine or valine produced mutants with properties indistinguishable from those of the naturally occurring threonine 596 mutant receptor. These results indicate that an alanine residue at position 596 contributes important structural and functional activities to the androgen receptor. In the androgen receptor from the patients with Reifenstein syndrome, in which this alanine is converted to a threonine, wild-type receptor properties can be restored by exchanging an additional threonine at position 602 to an alanine. An alanine residue at position 596 or 602 in the DNA binding domain of the androgen receptor is therefore important for the full function of this receptor. In all steroid receptors that bind the core sequence AGAACANNNTGTTCT, an alanine residue is also present at a position equivalent to alanine 596 in the androgen receptor. Images PMID:8246999

  13. Correlation of ammonia clearance with classical liver function tests in normal and liver-damaged sheep 

    E-print Network

    Hansson, Lucille Ann

    1984-01-01

    function, Hypoalbuminemia is associated with severe chronic liver disease. Hypergammaglobulinemia, seen in acute hepatitis and portasystemic vascular shunting, is due to the liver's failure to remove antigens from portal circulation but is more commonly... found in chronic hepatitis. (1, 2, 3, 7) Liver biopsy is the single most important procedure for the accurate evaluation of hepatic disease. However, liver biopsy is the most dangerous and traumatic diagnostic technique for liver disease. (1 2 ~ 3...

  14. Proposal of Noninvasive Liver Function Measurement Method via Saliva

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Masaki; Kawabata, Yuji; Hatakeyama, Toyomasa; Kashii, Yoshiro

    The authors studied the correlation between serum alanine aminotransferase (ALT) activity and salivary ALT activity using ten healthy young adults and ten liver disease patients. Firstly, in order to establish the experimental conditions, we investigated the influence of occult blood and salivary secretion rate on the salivary ALT activity using healthy subjects. Then, simultaneous analysis of the serum and salivary ALT activities were conducted to investigate the correlation using the twenty subjects. As the results, although salivary ALT activity was as low as one third of serum ALT activity, the presence of salivary ALT activity was confirmed in healthy young adults whose saliva was not contaminated with serum. The salivary ALT activity of liver disease patients showed higher values than that of healthy young adults. In other word, if a threshold of salivary ALT activity was established, healthy young adults could be distinguished from liver disease patients.

  15. Preoperative liver function assessments to estimate the prognosis and safety of liver resections.

    PubMed

    Mizuguchi, Toru; Kawamoto, Masaki; Meguro, Makoto; Hui, Thomas T; Hirata, Koichi

    2014-01-01

    Liver function assessment is important to ensure safe surgical procedures in patients with hepatocellular disease. Because the liver influences a wide variety of functions, including protein synthesis and metabolic, immune and storage functions, no single parameter is sufficient to adequately address all of these functions. We reviewed the relevant literature concerning the scoring systems, functional tests, plasma parameters and imaging modalities currently used to evaluate the liver function in an attempt to determine which parameters provide the most comprehensive and useful results. While the Child-Pugh scoring system is the gold standard for liver disease assessment, the liver damage grading system recommended by the Liver Cancer Study Group of Japan is also useful. Various models for end-stage liver disease scoring are used for organ allocation. While the indocyanine green clearance test is widely accepted throughout the world, other assessments have not been used routinely for clinical evaluations. The levels of plasma proteins, including albumin, prealbumin, retinol binding protein, apolipoprotein, coagulation factors and antithrombin III, represent the liver productivity. Liver fibrotic markers also correlate with liver function. Imaging modalities such as (99m)Tc-galactosyl serum albumin scintigraphy, (99m)Tc-mebrofenin hepatobiliary scintigraphy and transient elastography are also available, but future studies are needed to validate their clinical efficacy. PMID:23474700

  16. Comparison of remnant to total functional liver volume ratio and remnant to standard liver volume ratio as a predictor of postoperative liver function after liver resection

    PubMed Central

    Kim, Hee Joon; Kim, Choong Young; Hur, Young Hoe; Koh, Yang Seok; Kim, Jung Chul; Kim, Hyun Jong

    2013-01-01

    Backgrounds/Aims The future liver remnant (FLR) is usually calculated as a ratio of the remnant liver volume (RLV) to the total functional liver volume (RLV/TFLV). In liver transplantation, it is generally accepted that the ratio of the graft volume to standard liver volume (SLV) needs to be at least 30% to 40% to fit the hepatic metabolic demands of the recipient. The aim of this study was to compare RLV/TFLV versus RLV/SLV as a predictor of postoperative liver function and liver failure. Methods CT volumetric measurements of RLV were obtained retrospectively in 74 patients who underwent right hemihepatectomy for a malignant tumor from January 2010 to May 2013. RLV and TFLV were obtained using CT volumetry, and SLV was calculated using Yu's formula: SLV (ml)=21.585×body weight (kg)0.732×height (cm)0.225. The RLV/SLV ratio was compared with the RLV/TFLV as a predictor of postoperative hepatic function. Results Postheptectomy liver failure (PHLF), morbidity, and serum total bilirubin level at postoperative day 5 (POD 5) were increased significantly in the group with the RLV/SLV ?30% compared with the group with the RLV/SLV >30% (p=0.002, p=0.004, and p<0.001, respectively). But RLV/TFLV was not correlated with PHLF and morbidity (p=1.000 and 0.798, respectively). RLV/SLV showed a stronger correlation with serum total bilirubin level than RLV/TFLV (RLV/SLV vs. RLV/TFLV, R=0.706 vs. 0.499, R2=0.499 vs. 0.239). Conclusions RLV/SLV was more specific than RLV/TFLV in predicting the postoperative course after right hemihepatectomy. To determine the safe limit of hepatic resection, a larger-scaled prospective study is needed.

  17. Abnormal liver function test results are related to metabolic syndrome and BMI in Taiwanese adults without chronic hepatitis B or C

    Microsoft Academic Search

    M-H Hsieh; C-K Ho; N-J Hou; M-Y Hsieh; W-Y Lin; J-F Yang; C-C Chiu; J-F Huang; N-C Chang; C-L Wang; C-Y Dai; W-L Chuang; M-L Yu

    2009-01-01

    Background:Metabolic syndrome (MS) is considered a cause of abnormal deposition of fat into hepatocytes, which might be associated with hepatic steatosis or abnormal liver function.Objective:The aim of this study was to explore the factors associated with MS and the relationship between MS and abnormal aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ?-glutamyl transferase (GGT) levels in Taiwanese subjects without chronic

  18. Assessment of canine liver function by metabolism of lidocaine to monoethylglycinexylidide: a preclinical study 

    E-print Network

    Fradkin, Jonathan Matthew

    2000-01-01

    in diagnosing and monitoring dogs with chronic progressive liver disease. The lidocaine-MEGX test is used in humans for evaluation of liver function during organ transplant selection, prognostication of chronic liver disease, prioritization of liver transplant...

  19. Effect of Amino Acid Substitutions in the GerAA Protein on the Function of the Alanine-Responsive Germinant Receptor of Bacillus subtilis Spores?

    PubMed Central

    Mongkolthanaruk, Wiyada; Cooper, Gareth R.; Mawer, Julia S. P.; Allan, Raymond N.; Moir, Anne

    2011-01-01

    Spores of Bacillus subtilis require the GerAA, GerAB, and GerAC receptor proteins for l-alanine-induced germination. Mutations in gerAA, both random and site directed, result in phenotypes that identify amino acid residues important for receptor function in broad terms. They highlight the functional importance of two regions in the central, integral membrane domain of GerAA. A P324S substitution in the first residue of a conserved PFPP motif results in a 10-fold increase in a spore's sensitivity to alanine; a P326S change results in the release of phase-dark spores, in which the receptor may be in an “activated” or “quasigerminated” state. Substitutions in residues 398 to 400, in a short loop between the last two likely membrane-spanning helices of this central domain, all affect the germination response, with the G398S substitution causing a temperature-sensitive defect. In others, there are wider effects on the receptor: if alanine is substituted for conserved residue N146, H304, or E330, a severe defect in l-alanine germination results. This correlates with the absence of GerAC, suggesting that the assembly or stability of the entire receptor complex has been compromised by the defect in GerAA. In contrast, severely germination-defective mutants such as E129K, L373F, S400F, and M409N mutants retain GerAC at normal levels, suggesting more local and specific effects on the function of GerAA itself. Further interpretation will depend on progress in structural analysis of the receptor proteins. PMID:21378197

  20. Functional imaging of radiation liver injury in a liver metastasis patient: imaging and pathologic correlation

    PubMed Central

    Chapman, Tobias R.; Kumarapeli, Asangi R.; Nyflot, Matthew J.; Bowen, Stephen R.; Yeung, Raymond S.; Vesselle, Hubert J.; Yeh, Matthew M.

    2015-01-01

    Background Radiation therapy (RT) is increasingly being utilized as a treatment modality for the treatment of primary and metastatic liver malignancies. Accurate assessment of liver function and prediction of radiation induced liver disease (RILD) remains a challenge with conventional laboratory tests and imaging. Imaging-pathology correlation of hepatic injury after RT has been described with computer tomography (CT) imaging that depicts perfusion changes. However, these imaging changes may not directly characterize the functional capacity of the liver. Case presentation This case report describes a patient that received preoperative chemoradiation and surgical resection for a liver metastasis from endometrial cancer. Sulfur colloid (SC) single photon emission computed tomography (SPECT/CT) was obtained post-chemoradiation and prior to surgery. Imaging-pathology correlation between radiation changes depicted on functional imaging using SC SPECT/CT and corresponding histopathology is described. Discussion Quantitative SC SPECT/CT may allow non-invasive assessment of global and spatial liver function before treatment and enable personalized treatment approaches for liver-directed therapies.

  1. Blockade of Neutrophil Elastase Attenuates Severe Liver Injury in Hepatitis B Transgenic Mice

    Microsoft Academic Search

    Shinji Takai; Kiminori Kimura; Masahito Nagaki; Shinichi Satake; Kazuhiro Kakimi; Hisataka Moriwaki

    2005-01-01

    Serine proteinases produced by polymorphonuclear neutrophils play important roles in neutrophil-mediated tissue injury at inflammatory sites. Although neutrophil recruitment to the liver has been shown to be involved in the exacerbation of liver inflammation, the function of neutrophil elastase (NE) in liver injury remains unclear. Here, we found that administration of an NE inhibitor (NEI) reduced serum alanine aminotransferase (sALT)

  2. Peripheral Blood Stem Cell Transplantation Improves Liver Functional Reserve

    PubMed Central

    Cai, Ting; Deng, Qinzhi; Zhang, Shun; Hu, Airong; Gong, Qinghai; Zhang, Xingfen

    2015-01-01

    Background Currently available treatment options for decompensated hepatitis B-induced liver cirrhosis are limited and largely ineffective. Recently, stem cell transplantation has emerged as a promising treatment for cirrhosis. The aim of this study was to determine whether autologous peripheral blood stem cell transplantation can improve liver functional reserve in patients with hepatitis B-induced cirrhosis. Material/Methods In this study, 51 patients with hepatitis B-induced liver cirrhosis were assigned to the treatment group (n=23) or the control group (n=28). The treatment group underwent autologous peripheral blood stem cell transplantation in addition to comprehensive medical treatment, and the control group received comprehensive medical treatment alone. Liver functional reserve was monitored for 48 weeks after autologous peripheral blood stem cell transplantation. Results After transplantation, most patients showed improvements in symptoms such as fatigue, anorexia, and abdominal distension. The retention rate of indocyanine green at 15 minutes, a common indicator of liver functional reserve, declined from 41.99±4.68 at baseline to 37.79±3.75 by 48 weeks after transplantation, showing significant improvement. Conclusions Autologous peripheral blood stem cell transplantation can improve several markers of liver health and liver functional reserve and is a promising prospect for clinical application. PMID:25970080

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

    PubMed Central

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

    2014-01-01

    By performing regular blood transfusion and iron chelation therapy, most patients with beta thalassemia major (BTM) now survive beyond the third decade of life. Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are both important causes of liver pathology. Iron chelation with desferrioxamine (DFO) reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox ( DFX ), an oral single dose therapy, has improved the compliance to chelation. Aims To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX treatment in relation to ferritin level. Methods Only BTM patients with hepatitis negative screening (checked every year) and on treatment with DFO for at least five years and with DFX for four years were enrolled. Liver function tests including serum bilirubin, alanine transferase (ALT), aspartate transferase (AST), albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every six months in 40 patients with BTM. Results DFX treatment (20 mg/kg/day) significantly decreased serum ferritin level in patients with BTM; this was associated with a significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum ferritin concentrations ( r = 0.45 and 0.33 respectively, p < 0.05). IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels. The negative correlation between serum ferritin concentrations and ALT suggests that the impairment of hepatic function negatively affect IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis. Conclusions Some impairment of liver function can occur in hepatitis negative thalassemic patients with iron overload. The use of DFX was associated with mild but significant reduction of ALT, AST and ALP and increase in IGF-I levels. The negative correlation between IGF-I and ALT concentrations suggest that preventing hepatic dysfunction may improve the growth potential in these patients. PMID:24803998

  4. 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

  5. Icaritin ameliorates carbon tetrachloride-induced acute liver injury mainly because of the antioxidative function through estrogen-like effects.

    PubMed

    Liu, Peng; Jin, Xiang; Lv, Hao; Li, Jing; Xu, Wen; Qian, Hai-hua; Yin, Zhengfeng

    2014-12-01

    To investigate the effects of icaritin, an active ingredient extracted from Epimedium Sagittatum (Sieb. et Zucc.), on CCl4-induced liver injury and its possible mechanisms. Hepatocytes isolated from Sprague-Dawley male rats were treated with 3 mmol/L CCl4 for 24 h to induce acute liver cell injury, then icaritin (0.1, 1, 10, 100 ?mol/L, respectively) was administrated to the cells, and estrogen receptor antagonist ICI182,780 (1 ?mol/L) was co-treated with 10 ?mol/L icaritin. Biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD)) and cell apoptosis were detected to evaluate the injury degree. Protein expressions of Bax, Bcl-2, liver fatty acid-binding protein (L-FABP), and peroxisome proliferator-activated receptor-? (PPAR-?) as well as reactive oxygen species (ROS) generation were determined by western blot. Icaritin alleviated CCl4-induced liver cell injury in a concentration-dependent manner and 10 ?mol/L was the optimal concentration. Icaritin (10 ?mol/L) significantly reduced activities of ALT, AST in cell culture medium and MDA level of the impaired liver cells, but increased the intercellular SOD activity. The apoptotic rate of the impaired liver cells was also decreased by icaritin (10 ?mol/L) treatment. Icaritin might exert antioxidative and anti-apoptotic functions via estrogen-like effect, as the ratio of Bcl-2/Bax was significantly increased, while protein expressions of L-FABP and PPAR-? were markedly increased, and this function was blocked by the estrogen receptor antagonist ICI182,780 efficiently. Icaritin may be a promising drug candidate for acute liver injury benefiting from the antioxidative and anti-apoptotic functions via estrogen-like effect. PMID:25148823

  6. Sarcopenia, obesity and sarcopenic obesity: effects on liver function and volume in patients scheduled for major liver resection

    PubMed Central

    Lodewick, Toine M; Roeth, Anjali AJ; Olde Damink, Steven WM; Alizai, Patrick H; van Dam, Ronald M; Gassler, Nikolaus; Schneider, Mark; Dello, Simon AWG; Schmeding, Maximilian; Dejong, Cornelis HC; Neumann, Ulf P

    2015-01-01

    Background Sarcopenia, obesity and sarcopenic obesity have been linked to impaired outcome after liver surgery. Preoperative liver function of sarcopenic, obese and sarcopenic-obese patients might be reduced, possibly leading to more post-operative morbidity. The aim of this study was to explore whether liver function and volume were influenced by body composition in patients undergoing liver resection. Methods In 2011 and 2012, all consecutive patients undergoing the methacetin breath liver function test were included. Liver volumetry and muscle mass analysis were performed using preoperative CT scans and Osirix® software. Muscle mass and body-fat% were calculated. Predefined cut-off values for sarcopenia and the top two body-fat% quintiles were used to identify sarcopenia and obesity, respectively. Histologic assessment of the resected liver gave insight in background liver disease. Results A total number of 80 patients were included. Liver function and volume were comparable in sarcopenic(-obese) and non-sarcopenic(-obese) patients. Obese patients showed significantly reduced liver function [295 (95–508) vs. 358 (96–684) µg/kg/h, P?=?0.018] and a trend towards larger liver size [1694 (1116–2685) vs. 1533 (869–2852) mL, P?=?0.079] compared with non-obese patients. Weight (r?=??0.40), body surface area (r?=??0.32), estimated body-fat% (r?=??0.43) and body mass index (r?=??0.47) showed a weak but significant negative (all P?liver function. Moreover, body-fat% was identified as an independent factor negatively affecting the liver function. Conclusion Sarcopenia and sarcopenic obesity did not seem to influence liver size and function negatively. However, obese patients had larger, although less functional, livers, indicating dissociation of liver function and volume in these patients.

  7. Single, double and quadruple alanine substitutions at oligomeric interfaces identify hydrophobicity as the key determinant of human neutrophil alpha defensin HNP1 function.

    PubMed

    Zhao, Le; Tolbert, W David; Ericksen, Bryan; Zhan, Changyou; Wu, Xueji; Yuan, Weirong; Li, Xu; Pazgier, Marzena; Lu, Wuyuan

    2013-01-01

    HNP1 is a human alpha defensin that forms dimers and multimers governed by hydrophobic residues, including Tyr¹?, Ile²?, Leu²?, and Phe²?. Previously, alanine scanning mutagenesis identified each of these residues and other hydrophobic residues as important for function. Here we report further structural and functional studies of residues shown to interact with one another across oligomeric interfaces: I20A-HNP1 and L25A-HNP1, plus the double alanine mutants I20A/L25A-HNP1 and Y16A/F28A-HNP1, and the quadruple alanine mutant Y16A/I20A/L25A/F28A-HNP1. We tested binding to HIV-1 gp120 and HNP1 by surface plasmon resonance, binding to HIV-1 gp41 and HNP1 by fluorescence polarization, inhibition of anthrax lethal factor, and antibacterial activity using the virtual colony count assay. Similar to the previously described single mutant W26A-HNP1, the quadruple mutant displayed the least activity in all functional assays, followed by the double mutant Y16A/F28A-HNP1. The effects of the L25A and I20A single mutations were milder than the double mutant I20A/L25A-HNP1. Crystallographic studies confirmed the correct folding and disulfide pairing, and depicted an array of dimeric and tetrameric structures. These results indicate that side chain hydrophobicity is the critical factor that determines activity at these positions. PMID:24236072

  8. Single, Double and Quadruple Alanine Substitutions at Oligomeric Interfaces Identify Hydrophobicity as the Key Determinant of Human Neutrophil Alpha Defensin HNP1 Function

    PubMed Central

    Zhan, Changyou; Wu, Xueji; Yuan, Weirong; Li, Xu; Pazgier, Marzena; Lu, Wuyuan

    2013-01-01

    HNP1 is a human alpha defensin that forms dimers and multimers governed by hydrophobic residues, including Tyr16, Ile20, Leu25, and Phe28. Previously, alanine scanning mutagenesis identified each of these residues and other hydrophobic residues as important for function. Here we report further structural and functional studies of residues shown to interact with one another across oligomeric interfaces: I20A-HNP1 and L25A-HNP1, plus the double alanine mutants I20A/L25A-HNP1 and Y16A/F28A-HNP1, and the quadruple alanine mutant Y16A/I20A/L25A/F28A-HNP1. We tested binding to HIV-1 gp120 and HNP1 by surface plasmon resonance, binding to HIV-1 gp41 and HNP1 by fluorescence polarization, inhibition of anthrax lethal factor, and antibacterial activity using the virtual colony count assay. Similar to the previously described single mutant W26A-HNP1, the quadruple mutant displayed the least activity in all functional assays, followed by the double mutant Y16A/F28A-HNP1. The effects of the L25A and I20A single mutations were milder than the double mutant I20A/L25A-HNP1. Crystallographic studies confirmed the correct folding and disulfide pairing, and depicted an array of dimeric and tetrameric structures. These results indicate that side chain hydrophobicity is the critical factor that determines activity at these positions. PMID:24236072

  9. Safety and yield of diagnostic ERCP in liver transplant patients with abnormal liver function tests.

    PubMed

    Ramesh, Jayapal; Reddy, Nipun; Kim, Hwasoon; Mönkemüller, Klaus; Varadarajulu, Shyam; McGuire, Brendan; DuBay, Derek; Eckhoff, Devin; Wilcox, C Mel

    2014-01-01

    Background. Abnormal liver enzymes postorthotopic liver transplant (OLT) may indicate significant biliary pathology or organ rejection. There is very little known in the literature regarding the current role of diagnostic ERCP in this scenario. Aim. To review the utility of diagnostic ERCP in patients presenting with abnormal liver function tests in the setting of OLT. Methods. A retrospective review of diagnostic ERCPs in patients with OLT from 2002 to 2013 from a prospectively maintained, IRB approved database. Results. Of the 474 ERCPs performed in OLT patients, 210 (44.3%; 95% CI 39.8-48.8) were performed for abnormal liver function tests during the study period. Majority of patients were Caucasian (83.8%), male (62.4%) with median age of 55 years (IQR 48-62 years). Biliary cannulation was successful in 99.6% of cases and findings included stricture in 45 (21.4 %); biliary stones/sludge in 23 (11%); biliary dilation alone in 31 (14.8%); and normal in 91 (43.3%). Three (1.4%) patients developed mild, self-limiting pancreatitis; one patient (0.5%) developed cholangitis and two (1%) had postsphincterotomy bleeding. Multivariate analyses showed significant association between dilated ducts on imaging with a therapeutic outcome. Conclusion. Diagnostic ERCP in OLT patients presenting with liver function test abnormalities is safe and frequently therapeutic. PMID:25110455

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

    PubMed Central

    Reddy, Nipun; Kim, Hwasoon; Mönkemüller, Klaus; Varadarajulu, Shyam; McGuire, Brendan; Wilcox, C. Mel

    2014-01-01

    Background. Abnormal liver enzymes postorthotopic liver transplant (OLT) may indicate significant biliary pathology or organ rejection. There is very little known in the literature regarding the current role of diagnostic ERCP in this scenario. Aim. To review the utility of diagnostic ERCP in patients presenting with abnormal liver function tests in the setting of OLT. Methods. A retrospective review of diagnostic ERCPs in patients with OLT from 2002 to 2013 from a prospectively maintained, IRB approved database. Results. Of the 474 ERCPs performed in OLT patients, 210 (44.3%; 95% CI 39.8–48.8) were performed for abnormal liver function tests during the study period. Majority of patients were Caucasian (83.8%), male (62.4%) with median age of 55 years (IQR 48–62 years). Biliary cannulation was successful in 99.6% of cases and findings included stricture in 45 (21.4 %); biliary stones/sludge in 23 (11%); biliary dilation alone in 31 (14.8%); and normal in 91 (43.3%). Three (1.4%) patients developed mild, self-limiting pancreatitis; one patient (0.5%) developed cholangitis and two (1%) had postsphincterotomy bleeding. Multivariate analyses showed significant association between dilated ducts on imaging with a therapeutic outcome. Conclusion. Diagnostic ERCP in OLT patients presenting with liver function test abnormalities is safe and frequently therapeutic. PMID:25110455

  11. Liver Function Parameters in Hip Fracture Patients: Relations to Age, Adipokines, Comorbidities and Outcomes

    PubMed Central

    Fisher, Leon; Srikusalanukul, Wichat; Fisher, Alexander; Smith, Paul

    2015-01-01

    Aim: To asses liver markers in older patients with hip fracture (HF) in relation to age, comorbidities, metabolic characteristics and short-term outcomes. Methods: In 294 patients with HF (mean age 82.0±7.9 years, 72.1% women) serum alanine aminotransferase (ALT), gammaglutamyltransferase (GGT), alkaline phosphatase (ALP), albumin, bilirubin, 25(OH)vitaminD, PTH, calcium, phosphate, magnesium, adiponectin, leptin, resistin, thyroid function and cardiac troponin I were measured. Results: Elevated ALT, GGT, ALP or bilirubin levels on admission were observed in 1.7% - 9.9% of patients. With age GGT, ALT and leptin decrease, while PTH and adiponectin concentrations increase. Higher GGT (>30U/L, median level) was associated with coronary artery disease (CAD), diabetes mellitus (DM), and alcohol overuse; lower ALT (?20U/L, median level) with dementia; total bilirubin >20?mol/L with CAD and alcohol overuse; and albumin >33g/L with CAD. Multivariate adjusted regression analyses revealed ALT, ALP, adiponectin, alcohol overuse and DM as independent and significant determinants of GGT (as continuous or categorical variable); GGT for each other liver marker; and PTH for adiponectin. The risk of prolonged hospital stay (>20 days) was about two times higher in patients with GGT>30U/L or adiponectin >17.14 ng/L (median level) and 4.7 times higher if both conditions coexisted. The risk of in-hospital death was 3 times higher if albumin was <33g/L. Conclusions: In older HF patients liver markers even within the normal range are associated with age-related disorders and outcomes. Adiponectin (but not 25(OH)vitaminD, PTH, leptin or resistin) is an independent contributor to higher GGT. Serum GGT and albumin predict prolonged hospital stay and in-hospital death, respectively. A unifying hypothesis of the findings presented. PMID:25589886

  12. Alanine increases blood pressure during hypotension

    NASA Technical Reports Server (NTRS)

    Conlay, L. A.; Maher, T. J.; Wurtman, R. J.

    1990-01-01

    The effect of L-alanine administration on blood pressure (BP) during haemorrhagic shock was investigated using anesthetized rats whose left carotid arteries were cannulated for BP measurement, blood removal, and drug administration. It was found that L-alanine, in doses of 10, 25, 50, 100, and 200 mg/kg, increased the systolic BP of hypotensive rats by 38 to 80 percent (while 100 mg/kg pyruvate increased BP by only 9.4 mmhg, not significantly different from saline). The results suggest that L-alanine might influence cardiovascular function.

  13. Abnormal liver function in different patients with Schistosoma japonicum.

    PubMed

    Ning, An; Wu, Xiaoying; Li, Hongyu; Liang, Jinyi; Gao, Zulu; Shen, Jia; Liu, Zhen; Xu, Jun; Hu, Fei; Wu, Feng; Ji, Pengyu; Wu, Zhongdao; Sun, Xi

    2015-01-01

    Schistosomiasis japonica, caused by Schistosoma japonicum, is still a serious public health problem in China. It is important for schistosomiasis control to prevent from infection and advanced patients. Recent years, however, the form of the prevalence of schistosomiasis japonica in China was changed these days. Paying attention to the quality of life of these patients already infected with S. japonicum becomes a new objective to schistosomiasis control program. Although most of the chronic infections with S. japonicum will finally appear as liver fibrosis symptoms, it is still unknown liver function abnormalities in patients with severe forms of schistosomiasis, and there is also no evidence whether S. japonicum infection will directly cause damage to liver cells. Thus, this study investigated 494 patients diagnosed with S. japonicum (87.7%) and 69 healthy subjects from a endemic areas belonging to Jiangxi Province of China and aimed to evaluate the liver function abnormalities in patients with severe forms of schistosomiasis and possible associations with coinfection with HBV. The results showed that the hepatic metabolism situation significantly changed in patients infected with S. japonicum; meanwhile, the abnormal rates of ALT and AST in patients with schistosomiasis were significantly higher than that in the control group, which confirmed that patients infected with S. japonicum not only had damaged liver function but also the hepatic cells were directly influenced. And the coinfection of CHB and schistosomiasis japonica can be a risk factor for more serious outcomes in patients from endemic areas. These results give us the advice that in the further treatment of patients infected with S. japonicum, especially these coinfections, we should better give the routine liver-protection treatment in advance. PMID:25287714

  14. Biochemical parameters of liver function in artisans occupationally exposed to “vat dyes”

    PubMed Central

    Soyinka, Oluwatosin O.; Adeniyi, Francis A.; Ajose, Olabamiji A.

    2007-01-01

    Background: Vat dyes are the class of dyes used in textile dyeing in Abeokuta, South Western Nigeria. While some dyes (including vat dyes intermediates) have been associated with adverse effects on manufacturer's health, there is paucity of data on effects of occupational exposure to vat dyes among end users, such as those involved in textile dyeing and finishing. Aims and Objectives: To investigate the possible effect of occupational exposure to vat dyes on the functions of the liver. Materials and Methods: Using convenience sampling technique, a cohort of dye workers (n=117) with a minimum of one year and a maximum of 60 years duration of exposure (mean =17.03 ± 1.19 years) were recruited in this study. Sixty traders, matched for age and sex and who had no previous exposure to vat dyes were selected as controls. A structured questionnaire was used to obtain information on demographic, occupational and environmental characteristics of the subjects. Plasma activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and plasma concentrations of total protein, albumin and total bilirubin were measured using standard spectrophotometric methods. Statistical analyses: SPSS version 11.0 was used for statistical analyses. Tests of significance were carried out using Student's t test, and correlation co-efficient. Results and Conclusion: The activity of ALP and the concentrations of total protein and albumin were significantly lower (P <0.05) in the exposed group. ALT and AST activities were significantly higher (P <0.05) in the exposed group. Occupational exposure to vat dyes may result in sub-clinical adverse effects on the liver, involving inhibition of its synthetic function. PMID:21938220

  15. In Vitro antioxidative activity of pumpkin seed (Cucurbita pepo) protein isolate and its In Vivo effect on alanine transaminase and aspartate transaminase in acetaminophen-induced liver injury in low protein fed rats.

    PubMed

    Nkosi, C Z; Opoku, A R; Terblanche, S E

    2006-09-01

    The antioxidative effects of pumpkin seed protein isolate (Cucurbita pepo) were investigated in vitro. The isolate exhibited about 80% radical scavenging activity, chelating activity of approximately 64% on Fe2+ ions and an inhibition of approximately 10% of xanthine oxidase. Subsequently the effects of the isolate on the plasma activity levels of alanine transaminase and aspartate transaminase against acetaminophen induced acute liver injury in low-protein fed male Sprague-Dawley rats were ascertained. The rats were maintained on a low-protein diet for 5 days and divided into three subgroups. Two subgroups were injected with acetaminophen and the other with an equivalent amount of polyethylene glycol 400. Two hours after intoxication one of the two subgroups was administered with the protein isolate. Rats from the different subgroups were killed at 24, 48 and 72 h after treatment. After 5 days on the low-protein diet the activity levels of the enzymes were significantly higher than their counterparts on a normal balanced diet. The administration of protein isolate after acetaminophen intoxication resulted in significantly reduced activity levels. It is concluded that the protein isolate has promising antioxidative properties. Furthermore, the isolate administration was effective in alleviating the detrimental effects associated with protein malnutrition and acetaminophen intoxication. PMID:16807884

  16. Adrenal Function in Chronic Liver Failure

    Microsoft Academic Search

    Javier Fernández; Juan Acevedo

    \\u000a Adequate adrenal function is fundamental to survive critical illness. Cortisol is vital in the host adaptation to stress.\\u000a It is essential to maintain the normal vascular tone, endothelial integrity, vascular permeability, and the distribution of\\u000a total body water within the vascular compartment (1–5). Consequently, the failure of an appropriate adrenal response in the\\u000a setting of critical illness, an abnormality known

  17. Amino Acid Residues in the GerAB Protein Important in the Function and Assembly of the Alanine Spore Germination Receptor of Bacillus subtilis 168?

    PubMed Central

    Cooper, Gareth R.; Moir, Anne

    2011-01-01

    The paradigm gerA operon is required for endospore germination in response to l-alanine as the sole germinant, and the three protein products, GerAA, GerAB, and GerAC are predicted to form a receptor complex in the spore inner membrane. GerAB shows homology to the amino acid-polyamine-organocation (APC) family of single-component transporters and is predicted to be an integral membrane protein with 10 membrane-spanning helices. Site-directed mutations were introduced into the gerAB gene at its natural location on the chromosome. Alterations to some charged or potential helix-breaking residues within membrane spans affected receptor function dramatically. In some cases, this is likely to reflect the complete loss of the GerA receptor complex, as judged by the absence of the germinant receptor protein GerAC, which suggests that the altered GerAB protein itself may be unstable or that the altered structure destabilizes the complex. Mutants that have a null phenotype for l-alanine germination but retain GerAC protein at near-normal levels are more likely to define amino acid residues of functional, rather than structural, importance. Single-amino-acid substitutions in each of the GerAB and GerAA proteins can prevent incorporation of GerAC protein into the spore; this provides strong evidence that the proteins within a specific receptor interact and that these interactions are required for receptor assembly. The lipoprotein nature of the GerAC receptor subunit is also important; an amino acid change in the prelipoprotein signal sequence in the gerAC1 mutant results in the absence of GerAC protein from the spore. PMID:21378181

  18. Allosteric inhibition of Staphylococcus aureus D-alanine:D-alanine ligase revealed by crystallographic studies.

    PubMed

    Liu, Shenping; Chang, Jeanne S; Herberg, John T; Horng, Miao-Miao; Tomich, Paul K; Lin, Alice H; Marotti, Keith R

    2006-10-10

    D-alanine:D-alanine ligase (DDl) is an essential enzyme in bacterial cell wall biosynthesis and an important target for developing new antibiotics. It catalyzes the formation of D-alanine:D-alanine dipeptide, sequentially by using one D-alanine and one ATP as substrates for the first-half reaction, and a second D-alanine substrate to complete the reaction. Some gain of function DDl mutants can use an alternate second substrate, causing resistance to vancomycin, one of the last lines of defense against life-threatening Gram-positive infections. Here, we report the crystal structure of Staphylococcus aureus DDl (StaDDl) and its cocrystal structures with 3-chloro-2,2-dimethyl-N-[4(trifluoromethyl)phenyl]propanamide (inhibitor 1) (Ki=4 microM against StaDDl) and with ADP, one of the reaction products, at resolutions of 2.0, 2.2, and 2.6 A, respectively. The overall structure of StaDDl can be divided into three distinct domains. The inhibitor binds to a hydrophobic pocket at the interface of the first and the third domain. This inhibitor-binding pocket is adjacent to the first D-alanine substrate site but does not overlap with any substrate sites. An allosteric inhibition mechanism of StaDDl by this compound was proposed. The mechanism provides the basis for developing new antibiotics targeting D-alanine:D-alanine ligase. Because this compound only interacts with residues from the first D-alanine site, inhibitors with this binding mode potentially could overcome vancomycin resistance. PMID:17015835

  19. 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

  20. 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

  1. Association of Abnormal Liver Function Parameters with HIV Serostatus and CD4 Count in Antiretroviral-Naive Rwandan Women.

    PubMed

    Dusingize, Jean Claude; Hoover, Donald R; Shi, Qiuhu; Mutimura, Eugene; Rudakemwa, Emmanuel; Ndacyayisenga, Victorien; Gakindi, Léonard; Mulvihill, Michael; Sinayobye, Jean D'Amour; Musabeyezu, Emmanuel; Anastos, Kathryn

    2015-07-01

    We determined the associations of HIV infection/CD4 count with markers of hepatocellular damage [elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and liver synthetic function (decreased albumin) in HIV-infected (HIV(+)) antiretroviral therapy (ART)-naive and uninfected (HIV(-)) Rwandan women. In 2005, 710 HIV(+) ART-naive and 226 HIV(-) women enrolled in the Rwanda Women's Interassociation Study and Assessment. Liver enzymes were measured with abnormality defined as either AST or ALT ?1.25 times the upper limit of normal. Low serum albumin level was defined as <3.5?g/dl. Multivariable logistic regression analysis identified independent predictors of elevated AST/ALT and low serum albumin. HIV(-) women had the lowest prevalence (6.6%) of abnormal AST/ALT, with the highest prevalence (16.4%) in HIV(+) women with CD4 <200 cells/?l (p=0.01). The odds of having serum albumin <3.5?g/dl was 5.7-fold higher in HIV(+) than HIV(-) women (OR=5.68, 95% CI: 3.32-9.71). The risk of low albumin decreased from low to high CD4 count, with OR=2.62, 95% CI: 1.66, 4.14 and OR=1.57, 95% CI: 1.01, 2.43 in HIV(+) women with a CD4 count <200 and 200-350 cells/?l, respectively vs. HIV(+) with CD4 >350 (p<0.001 and p<0.05 for all comparisons). Our findings suggest that HIV-associated liver damage may occur in ART-naive patients. Although liver abnormality prevalences in this cohort of HIV-infected Rwandan women are less than reported in developed countries, caution is needed for risk assessment measures to monitor and screen HIV-infected patients pre- and post-ART initiation in African clinical settings to curtail potential risks associated with HIV infection. PMID:25924728

  2. Electrochemical synthesis of polyaniline nano-network on alpha-alanine functionalized glassy carbon electrode and its application for the direct electrochemistry of horse heart cytochrome c.

    PubMed

    Zhang, Lei; Zhang, Jing; Zhang, Chunhua

    2009-03-15

    Polyaniline (PAN) nano-particles, nano-fibrils, and nano-network have been synthesized via electrochemical polymerization of aniline using a three-step electrochemical deposition procedure on alpha-alanine (ALA)-monolayer functionalized glassy carbon electrode (GCE). The structure and properties of PAN nano-structures have been characterized using field emission scanning electron microscope (SEM), Fourier transform infrared spectra (FT-IR), and electrochemical techniques. The 3-dimensional (3D) PAN nano-network/ALA composite film coated GCE (PAN-ALA/GCE) leads to the direct electrochemistry of horse heart cytochrome c (Cyt c) immobilized on this electrode surface. The immobilized Cyt c maintains its activity, showing a surface-controlled electrode process with the electron transfer rate constant (k(s)) of 21.9s(-1) and the charge-transfer coefficient (alpha) of 0.37, and could be used for the electrocatalytic reduction of hydrogen peroxide (H(2)O(2)). The steady-state current response increases linearly with H(2)O(2) concentration from 2.5 x 10(-5) to 3.0 x 10(-4) moll(-1). The detection limit (3delta) is 8.2 x 10(-6) moll(-1). PMID:19084388

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

    PubMed Central

    Eun, Chai Ryoung; Ahn, Jae Hee; Seo, Ji A

    2014-01-01

    Pheochromocytoma is a rare neuroendocrine tumor arising from the medulla of the adrenal glands, which causes an overproduction of catecholamines. The common symptoms are headache, palpitations, and sweating; however, various other clinical manifestations might also be present. Accurate diagnosis of pheochromocytoma is important because surgical treatment is usually successful, and associated clinical problems are reversible if treated early. A 49-year-old man with a history of uncontrolled hypertension and diabetes mellitus presented with chest pain, fever, and sweating. His liver function tests and white blood cell counts were markedly increased and his echocardiography results suggested stress-induced cardiomyopathy. His abdominal computed tomography showed a 5×5-cm-sized tumor in the left adrenal gland, and laboratory tests confirmed catecholamine overproduction. After surgical resection of the left adrenal gland, his liver function tests and white blood cell counts normalized, and echocardiography showed normal cardiac function. Moreover, his previous antihypertensive regimen was deescalated, and his previously uncontrolled blood glucose levels normalized without medication. PMID:24741459

  4. Transient liver function abnormality following treatment with rabbit antithymocyte globulin for nonmyeloablative hematopoetic stem cell transplant: Two case reports.

    PubMed

    Chang, Abraham; Lee-Lam, Fu-Ying; Wang, Joanna; Cheng, Ya-Hwei

    2015-02-01

    Rabbit antithymocyte globulin (rATG) is increasingly used in nonmyeloablative hematopoetic stem cell transplant (HSCT). Elevated liver function tests (LFTs) have been reported for antithymocyte globulin in the treatment of aplastic anemia, but not when used in a conditioning regimen for HSCT. We describe two cases of patients receiving a conditioning regimen for HSCT containing rATG who developed a transient, severe transaminase elevation. In the first case, a 66-year-old woman with a history of acute myeloid leukemia received the first dose of rATG and the patient's transaminases were found to be extremely elevated within a few hours. The aspartate transaminase (AST) peaked at 1286?U/L and alanine transaminase (ALT) peaked at 991?U/L and both resolved within a week. In the second case, a 72-year-old woman with a history of non-Hodgkin lymphoma received the first dose of rATG and the AST and ALT were found to be 1212?U/L and 689?U/L, respectively, 1?h after finishing the infusion. Like the previous case, the transaminase elevation resolved within a week. LFT abnormalities induced by rATG during conditioning therapy for HSCT may be transient and have a rapid onset after the first dose, but quickly subside without any complications or sequelae. It is important to follow the LFTs closely, as well as monitor for any signs and symptoms of acute liver failure. PMID:24395543

  5. Impact of Serum Chemerin Levels on Liver Functional Reserves and Platelet Counts in Patients with Hepatocellular Carcinoma

    PubMed Central

    Imai, Kenji; Takai, Koji; Hanai, Tatsunori; Shiraki, Makoto; Suzuki, Yusuke; Hayashi, Hideki; Naiki, Takafumi; Nishigaki, Youichi; Tomita, Eiichi; Shimizu, Masahito; Moriwaki, Hisataka

    2014-01-01

    Obesity-related metabolic abnormalities, including adipokine imbalance and chronic inflammation, are involved in liver carcinogenesis. Chemerin, a novel adipokine, plays a critical role in adipogenesis, energy metabolism, and inflammation. We evaluated the impact of serum chemerin levels on liver functional reserves in hepatocellular carcinoma (HCC) patients and on the recurrence and prognosis of HCC. This study included 44 patients with any stage of HCC who underwent curative treatment at Gifu Municipal Hospital (Gifu, Japan) between 2006 and 2007. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Serum albumin levels (Pearson’s correlation coefficient; r = 0.3110, p = 0.0399), platelet counts (r = 0.4159, p = 0.0050), and prothrombin times (r = 0.3775, p = 0.0115) were significantly correlated with serum chemerin levels in patients with HCC, and they were inversely correlated with Child-Pugh scores (r = ?0.3732, p = 0.0126), serum alanine aminotransferase levels (r = ?0.3864, p = 0.0105), and total bilirubin levels (r = ?0.4023, p = 0.0068). Among these variables, a multiple comparison test identified that platelet counts and total bilirubin levels were associated with serum chemerin levels (p < 0.0083). No significant correlation was found between serum chemerin levels and recurrence-free survival (p = 0.3691) or overall survival (p = 0.7916). In HCC patients, serum chemerin concentrations were correlated with liver functional reserves and platelet counts, but not with recurrence or prognosis. PMID:24968270

  6. Advances in solid alanine radiolysis understanding

    NASA Astrophysics Data System (ADS)

    Raffi, J.; Talbi, S.; Dolo, J.-M.; Garcia, T.; Kister, J.

    2008-03-01

    To better understand the composite character of irradiated alanine ESR spectra, a comparative study of few simple amino acids is performed in order to identify the different radio-induced radicals and their proportions. A dedicated spin-trapping method coupled with High Performance Liquid Chromatography (HPLC) is developed and carried out on irradiated alanine, glycine and valine; labeled or not. This study leads us to obtain different isolated trapped radical spectra where hyperfine coupling constants could be evaluated. For alanine, only two species are identified with relative proportions around 97 and 3% in contradiction with recent published articles. The main species has a particularity on its hyperfine coupling constants when labeled carbons are used. Very high hyperfine coupling constants are observed with the carboxylic acid function carbon for the three studied amino acid.

  7. Evolution of alanine:glyoxylate aminotransferase 1 peroxisomal and mitochondrial targeting. A survey of its subcellular distribution in the livers of various representatives of the classes Mammalia, Aves and Amphibia.

    PubMed

    Danpure, C J; Fryer, P; Jennings, P R; Allsop, J; Griffiths, S; Cunningham, A

    1994-08-01

    As part of a wider study on the molecular evolution of alanine:glyoxylate aminotransferase 1 (AGT1) intracellular compartmentalization, we have determined the subcellular distribution of immunoreactive AGT1, using postembedding protein A-gold immunoelectron microscopy, in the livers of various members of the classes Mammalia, Aves, and Amphibia. As far as organellar distribution is concerned, three categories could be distinguished. In members of the first category (type I), all, or nearly all, of the immunoreactive AGT1 was concentrated within the peroxisomes. In the second category (type II), AGT1 was found more evenly distributed in both peroxisomes and mitochondria. In the third category (type III), AGT1 was localized mainly within the mitochondria with much lower, but widely variable, amounts in the peroxisomes. Type I animals include the human, two great apes (gorilla, orangutan), two Old World monkeys (anubis baboon, Japanese macaque), a New World monkey (white-faced Saki monkey), a lago, morph (European rabbit), a bat (Seba's short-tailed fruit bat), two caviomorph rodents (guinea pig, orange-rumped agouti), and two Australian marsupials (koala, Bennett's wallaby). Type II animals include two New World monkeys (common marmoset, cotton-top tamarin), three prosimians (brown lemur, fat-tailed dwarf lemur, pygmy slow loris), five rodents (a hybrid crested porcupine, Colombian ground squirrel, laboratory rat, laboratory mouse, golden hamster), an American marsupial (grey short-tailed opossum), and a bird (raven). Type III animals include the large tree shrew, three insectivores (common Eurasian mole, European hedgehog, house shrew), four carnivores (domestic cat, ocelot, domestic dog, polecat ferret), and an amphibian (common frog). In addition to these categories, some animals (e.g. guinea pig, common frog) possessed significant amounts of cytosolic AGT1. Whereas the subcellular distribution of AGT1 in some orders (e.g. Insectivora and Carnivora) did not appear to vary markedly between the different members, in other orders (e.g. Primates, Rodentia and Marsupialia) it fluctuated widely between the different species. Phylogenetic analysis indicates that the subcellular distribution of AGT1 has changed radically on numerous occasions during the evolution of mammals. The new observations presented in this paper are compatible with our previous demonstration of a relationship between AGT1 subcellular distribution and either present or putative ancestral dietary habit, and our previous suggestion that the molecular evolution of the AGT gene has been markedly influenced by dietary selection pressure. PMID:7813517

  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. PMID:25920182

  9. MicroRNAs: the fine modulators of liver development and function.

    PubMed

    Chen, Yemiao; Verfaillie, Catherine M

    2014-08-01

    MicroRNAs are a class of small non-coding RNAs involved in the transcriptional and post-transcriptional regulation of gene expression. The function of miRNAs in liver disease including hepatocellular carcinoma (HCC), hepatitis, and alcoholic liver disease, have been widely studied and extensively reviewed. Increasing evidence demonstrates that miRNAs also play a critical role in normal liver development and in the fine-tuning of fundamental biological liver processes. In this review, we highlight the most recent findings on the role of miRNAs in liver specification and differentiation, liver cell development, as well as in the many metabolic functions of the liver, including glucose, lipid, iron and drug metabolism. These findings demonstrate an important role of miRNAs in normal liver development and function. Further researches will be needed to fully understand how miRNAs regulate liver generation and metabolic function, which should then lead to greater insights in liver biology and perhaps open up the possibility to correct errors that cause liver diseases or metabolic disorders. PMID:24517588

  10. STE20/SPS1-Related Proline/Alanine-Rich Kinase Is Involved in Plasticity of GABA Signaling Function in a Mouse Model of Acquired Epilepsy

    PubMed Central

    Zhou, Jueqian; Chen, Shuda; Chen, Yishu; Chen, Ziyi; Wang, Qian; Fang, Ziyan; Zhou, Liemin

    2013-01-01

    The intracellular concentration of chloride ([Cl-]i) determines the strength and polarity of GABA neurotransmission. STE20/SPS1-related proline/alanine-rich kinase (SPAK) is known as an indirect regulator of [Cl-]i for its activation of Na-K-2 Cl-co-transporters (NKCC) and inhibition of K-Cl-co-transporters (KCC) in many organs. NKCC1 or KCC2 expression changes have been demonstrated previously in the hippocampal neurons of mice with pilocarpine-induced status epilepticus (PISE). However, it remains unclear whether SPAK modulates [Cl-]i via NKCC1 or KCC2 in the brain. Also, there are no data clearly characterizing SPAK expression in cortical or hippocampal neurons or confirming an association between SPAK and epilepsy. In the present study, we examined SPAK expression and co-expression with NKCC1 and KCC2 in the hippocampal neurons of mice with PISE, and we investigated alterations in SPAK expression in the hippocampus of such mice. Significant increases in SPAK mRNA and protein levels were detected during various stages of PISE in the PISE mice in comparison to levels in age-matched sham (control) and blank treatment (control) mice. SPAK and NKCC1 expression increased in vitro, while KCC2 was down-regulated in hippocampal neurons following hypoxic conditioning. However, SPAK overexpression did not influence the expression levels of NKCC1 or KCC2. Using co-immunoprecipitation, we determined that the intensity of interaction between SPAK and NKCC1 and between SPAK and KCC2 increased markedly after oxygen-deprivation, whereas SPAK overexpression strengthened the relationships. The [Cl-]i of hippocampal neurons changed in a corresponding manner under the different conditions. Our data suggests that SPAK is involved in the plasticity of GABA signaling function in acquired epilepsy via adjustment of [Cl-]i in hippocampal neurons. PMID:24058604

  11. Measurement of urinary thiamine propyl disulfide metabolites as an index of liver function.

    PubMed

    Oda, R; Okumura, M; Yamano, S; Yoshimura, H

    1984-11-01

    Thiamine propyl disulfide (TPD) was orally administered in patients with liver disease to measure the main metabolite, 2-hydroxypropyl methyl sulfone (2HPMS), in urine, for the test of liver function. The amount of urinary excretion of 2HPMS decreased in proportion to the degree of severity of liver disease, with intimate correlation with various tests reflecting hepatic reserve function (p less than 0.01). Phenobarbital (PB), one of the inducers of hepatic microsomal drug metabolizing enzymes scarcely influenced the results of this test. In patients with ordinary liver disease without remarkable disturbance of intestinal absorption and renal excretory function, this method appears to be clinically applicable. PMID:6500755

  12. Conventional liver CD4 T cells are functionally distinct and suppressed by environmental factors.

    PubMed

    Katz, Steven C; Pillarisetty, Venu G; Bleier, Joshua I; Kingham, T Peter; Chaudhry, Umer I; Shah, Alaap B; DeMatteo, Ronald P

    2005-08-01

    The contribution of intrahepatic conventional T cells to the unique immunologic properties of the liver has not been clearly defined. We isolated bulk and CD4 T cells from mouse liver and compared their functions with each other and with their splenic counterparts. Unlike bulk spleen T cells, bulk liver T cells reacted minimally to allogeneic or antigen-loaded syngeneic dendritic cells. However, after exclusion of natural killer T cells (NKTs) and gammadelta T cells by FACS, liver and spleen CD4 T cells actually proliferated to a similar extent upon allogeneic or antigen-specific stimulation. Liver CD4 T cells were more sensitive to interleukin 2 (IL-2) than were spleen CD4 T cells, but had a similar proliferative potential based on their response to CD3 ligation. In addition, activated liver CD4 T cells produced higher levels of IL-4, IL-5, IL-10, and interferon gamma (IFN-gamma) than did splenic CD4 T cells. Therefore, liver CD4 T cells are intrinsically different from spleen CD4 T cells. In vitro, liver or spleen NKTs and gammadelta T cells suppressed liver and spleen CD4 T-cell proliferation in a dose-dependent fashion. In conclusion, unconventional T cells constrain liver CD4 T-cell function. Our findings have implications for pathological conditions of the liver that involve the response of conventional CD4 T lymphocytes. PMID:16025518

  13. The role of CUGBP1 in age-dependent changes of liver functions

    PubMed Central

    Jones, Karlie; Timchenko, Lubov; Timchenko, Nikolai A.

    2013-01-01

    Aging liver is characterized by alterations of liver biology and by a reduction of many functions which are important for the maintenance of body homeostasis. The main dysfunctions include appearance of enlarged hepatocytes, impaired liver regeneration after partial hepatectomy (PH), development of hepatic steatosis, reduction of secretion of proteins and alterations in the hepatic sinusoid. RNA binding proteins are involved in the regulation of gene expression in all tissues including regulation of biological processes in the liver. This review is focused on the role of a conserved, multi-functional RNA-binding protein, CUGBP1, in the development of aging phenotype in the liver. CUGBP1 has been identified as a protein which binds to RNA CUG repeats expanded in Myotonic Dystrophy type 1 (DM1). CUGBP1 is highly expressed in the liver and regulates translation of proteins which are critical for maintenance of liver functions. In livers of young mice, CUGBP1 forms complexes with eukaryotic translation initiation factor eIF2 and supports translation of C/EBP? and HDAC1 proteins, which are involved in liver growth, differentiation and liver cancer. Aging changes several signaling pathways which lead to the elevation of the CUGBP1-eIF2? complex and to an increase of translation of C/EBP? and HDAC1. These proteins form multi-protein complexes with additional transcription factors and with chromatin remodeling proteins causing epigenetic alterations of gene expression in livers of old mice. It appears that CUGBP1-mediated translational elevation of HDAC1 is one of the key events in the epigenetic changes in livers of old mice, leading to the development of age- associated dysfunctions of the liver. This review will also discuss a possible role of CUGBP1 in liver dysfunction in patients affected with DM1. PMID:22446383

  14. Alanine repeats influence protein localization in splicing speckles and paraspeckles

    PubMed Central

    Chang, Shuo-Hsiu; Chang, Wei-Lun; Lu, Chia-Chen; Tarn, Woan-Yuh

    2014-01-01

    Mammalian splicing regulatory protein RNA-binding motif protein 4 (RBM4) has an alanine repeat-containing C-terminal domain (CAD) that confers both nuclear- and splicing speckle-targeting activities. Alanine-repeat expansion has pathological potential. Here we show that the alanine-repeat tracts influence the subnuclear targeting properties of the RBM4 CAD in cultured human cells. Notably, truncation of the alanine tracts redistributed a portion of RBM4 to paraspeckles. The alanine-deficient CAD was sufficient for paraspeckle targeting. On the other hand, alanine-repeat expansion reduced the mobility of RBM4 and impaired its splicing activity. We further took advantage of the putative coactivator activator (CoAA)-RBM4 conjoined splicing factor, CoAZ, to investigate the function of the CAD in subnuclear targeting. Transiently expressed CoAZ formed discrete nuclear foci that emerged and subsequently separated—fully or partially—from paraspeckles. Alanine-repeat expansion appeared to prevent CoAZ separation from paraspeckles, resulting in their complete colocalization. CoAZ foci were dynamic but, unlike paraspeckles, were resistant to RNase treatment. Our results indicate that the alanine-rich CAD, in conjunction with its conjoined RNA-binding domain(s), differentially influences the subnuclear localization and biogenesis of RBM4 and CoAZ. PMID:25414336

  15. Role of the functional state of the liver RES in the pathogenesis of toxic liver injury.

    PubMed

    Simek, J; Kutina, S N; Mayansky, D N; Vosvrdová, H; Cervinková, Z; Holecek, M

    1987-01-01

    In rats to which E. coli endotoxin (250 micrograms/kg i.p.) was administered 24 h before they were given tetrachlormethane (CCl4) (1.5 ml/kg intragastrically), stimulation of liver DNA synthesis was observed during the first 48 h after administration of the hepatatoxin. In experimental rats to which prodigiosan (a Serratia marcescens polysaccharide, 250 micrograms/kg i.p.) was administered 24 h before CCl4 (1.5 ml/kg i.p.), liver damage 24 h after CCl4 poisoning was expressed less--judging from the size of liver necrosis and the size of glycogen-free zones in the liver lobules than in the controls. To elucidate the role of activated macrophages in the induction of liver resistance to CCl4, liver injury caused by this hepatotoxin was compared after the pre-administration of protein extract from the Kupffer cells or hepatocytes of prodigiosan-stimulated rats. In rats given the larger dose of Kupffer cell extract (6 mg/ml i.p.), the necrotic foci formed after the administration of CCl4 were significantly smaller. The results confirm the conception that liver macrophages participate in the development of resistance to CCl4. PMID:2962209

  16. Functional Human Liver Preservation and Recovery by Means of Subnormothermic Machine Perfusion

    PubMed Central

    Weeder, Pepijn D.; Sridharan, Gautham V.; Uygun, Basak E.; Karimian, Negin G.; Porte, Robert J.; Markmann, James F.; Yeh, Heidi; Uygun, Korkut

    2015-01-01

    There is currently a severe shortage of liver grafts available for transplantation. Novel organ preservation techniques are needed to expand the pool of donor livers. Machine perfusion of donor liver grafts is an alternative to traditional cold storage of livers and holds much promise as a modality to expand the donor organ pool. We have recently described the potential benefit of subnormothermic machine perfusion of human livers. Machine perfused livers showed improving function and restoration of tissue ATP levels. Additionally, machine perfusion of liver grafts at subnormothermic temperatures allows for objective assessment of the functionality and suitability of a liver for transplantation. In these ways a great many livers that were previously discarded due to their suboptimal quality can be rescued via the restorative effects of machine perfusion and utilized for transplantation. Here we describe this technique of subnormothermic machine perfusion in detail. Human liver grafts allocated for research are perfused via the hepatic artery and portal vein with an acellular oxygenated perfusate at 21 °C. PMID:25938299

  17. Assessment of canine liver function by metabolism of lidocaine to monoethylglycinexylidide: a preclinical study

    E-print Network

    Fradkin, Jonathan Matthew

    2000-01-01

    function of the liver can be routinely evaluated by measuring resting levels of serum bilirubin, albumin, ammonia, serum urea nitrogen (SUN', and bile acid concentrations. Conjugated, water-soluble, bilirubin is synthesized in the liver from unconjugated..., Hank, Rowdy, Patch and Goldie TABLE OF CONTENTS ABSTRACT DEDICATION ACKNOWVLEDGEMENTS TABLE Ol' CONTENTS LIST OF TABLES LIST OF FICrURFS CHAP TLR I INTRODUCTION: CI. IRONIC PROGRESSIVE LIVER DISEASE IN DOGS II DIAGNOSIS OF CANINE CHRONIC...

  18. Liver structure and function in cholelithiasis: Effect of chenodeoxycholic acid 1

    Microsoft Academic Search

    G. D. Bell; H. Y. I. Mok; M. Thwe; G. M. Murphy; K. Henry; R. H. Dowling

    1974-01-01

    Although, in suitable patients, oral chenodeoxycholic acid (CDCA) dissolves gallstones, the results of recent animal studies suggest that it might be hepatotoxic. Liver function was therefore studied in patients with gallstones before and during treatment with CDCA and liver biopsies were carried out both in patients with cholelithiasis given bile acid therapy and in those who had been given no

  19. Renal function in tyrosinaemia type I after liver transplantation: a long-term follow-up.

    PubMed

    Pierik, L J W M; van Spronsen, F J; Bijleveld, C M A; van Dael, C M L

    2005-01-01

    Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent porphyria. When treated with liver transplantation, tyrosinaemia type I was considered to be cured. Some years after the first liver transplantations in these patients, some reports focused on the renal function after transplantation. These reports showed that urinary succinylacetone excretion remained but that tubular function normalized. In this report we discuss the long-term renal follow-up (mean follow-up time 11 years, range 7-14 years) after liver transplantation in 9 patients with tyrosinaemia type I treated by liver transplantation in our centre. An evaluation was made of renal function and succinylacetone excretion in urine. In all patients we found a persistent excretion of succinylacetone in the urine. With respect to the glomerular function, we can conclude that there is no clear change in GFR. At the same time, tubulopathy persisted in some patients. We consider that excretion of metabolites such as succinylacetone will be an important contributing factor to tubular dysfunction after liver transplantation in patients with tyrosinaemia type I. Therefore, notwithstanding the major effect of liver transplantation on tyrosine metabolism, renal tubular dysfunction remains at risk and needs careful monitoring. Progressive tubular dysfunction can cause glomerular damage. The use of low-dose NTBC might be considered after liver transplantation in case of tubulopathy to prevent progression of tubular and glomerular dysfunction. PMID:16435179

  20. 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.

  1. [Abnormal liver function during therapy with amiodarone in patients with persistent atrial fibrillation].

    PubMed

    Sviridenko, A V; Buniatian, N D; Korsun, L V; Uteshev, D B; Voronkina, M V

    2011-01-01

    The aim of this work was to analyze the prevalence of level function disorder in patients with atrial fibrillation taking constantly amiodarone. Two groups of patients were studied: in group 1 (n = 78) patients with persistent atrial fibrillation taking constantly amiodarone for rhythm control were included, group 2 (n = 67) consisted of patients with permanent atrial fibrillation taking propafenon, ethacizine and digoxin for rate control. In studied groups liver transaminase activity and data of liver echography after 90 +/- 8 days of treatment were estimated. In 51.58% patients of group 1 asymptomatic increase of liver transaminase activity was found. If liver transaminase activity had been raised before taking amiodarone, frequency and degree of liver transaminase increase extended. Consequently, patients taking constantly amiodarone, require dynamic control of GGTP, AIAT, AsAT once a quarter. If liver transaminase activity increases because of amiodarone taking the method of treatment is possible to be changed and rate control therapy may be chosen. PMID:22629774

  2. N-Acetyl-L-alanine N'-methylamide: a density functional analysis of the vibrational absorption and vibrational circular dichroism spectra

    NASA Astrophysics Data System (ADS)

    Jalkanen, K. J.; Suhai, S.

    1996-07-01

    Ab initio 6-31G ? Becke 3LYP DFT optimized geometries, vibrational frequencies, vibrational absorption (VA) intensities and vibrational circular dichroism (VCD) intensities have been calculated for the eight low energy conformers of N-acetyl-L-alanine N'-methylamide (L-AANMA) in the gas phase and one conformer stabilized by the addition of four water molecules. The VA and VCD spectra are calculated with the 6-31G ? Becke 3LYP force fields (Hessians) and atomic polar tensors (APT); 6-31G ?? RHF atomic axial tensors (AAT) for the eight gas phase structures and 6-31G ?/6-31G RHF AAT for the L-AANMA-water complex. The VA and VCD spectra are also calculated using the 6-31G ? Becke 3LYP Hessians; 6-31G ?? RHF APT and AAT for the eight gas phase structures and 6-31G ?/6-31G RHF APT and AAT for the L-AANMA-water complex. The rotational strengths of the amide A, I, II, III, IV, V and VI modes found in proteins as a function of ? and ? (for various secondary structures) are for the first time reported for an inherently optically active molecule (non-glycine model) using the 6-31G ?? and 6-31G ?/6-31G RHF DOG AAT and 6-31G ? Becke 3LYP Hessians and APT. This is also the first reported VCD calculation of a molecule with the solvent present. The molecule is not completely solvated, but the important hydrogen-bonded interactions are present and the feasibility of the calculation of the Hessian, APT and AAT with solvent molecules present is demonstrated. The VA and VCD spectra are compared to the experimental VA and VCD spectra in the literature and the conformational analysis (CA) and vibrational assignment of L-AANMA are reinvestigated. The rotational strengths of the amide modes for the various conformers are also compared to peptide and protein VCD spectra of molecules with known secondary structures. The agreement between the calculated rotational strengths of the various amide modes for which experimental measurements have been made is very good, in particular, for the right handed ?-helical conformation of a poly(L-amino acid) we correctly predict the negative couplet for the amide A band, the positive couplet for the amide I band and the negative monosignate signal for the amide II band as measured by the groups of Nafie and Keiderling. The large change in the amide I region in aqueous solution from this region in carbon tetrachloride or the Ar matrix is also reproduced, documenting that the qualitative features of the vibrational absorption and VCD spectra can reproduced by explicitly adding water molecules to the Hessian and tensor calculations.

  3. Evaluation of liver function using gadoxetate disodium (Gd-EOB-DTPA) enhanced MR imaging

    NASA Astrophysics Data System (ADS)

    Yamada, Akira; Hara, Takeshi; Li, Feng; Doi, Kunio

    2010-03-01

    Indocyanine green (ICG) is widely used for its clearance test in the evaluation of liver function. Gadoxetate disodium (Gd-EOB-DTPA) is a targeted MR contrast agent partially taken up by hepatocytes. The objective of this study was to evaluate the feasibility of an estimation of the liver function corresponding to plasma disappearance rate of indocyanine green (ICG-PDR) by use of the signal intensity of the liver alone in Gd-EOB-DTPA enhanced MR imaging (EOB-MRI). We evaluated fourteen patients who had EOB-MRI and ICG clearance test within 1 month. 2D-GRE T1 weighted images were obtained at pre contrast, 3 min (equilibrium phase) and 20 min (hepatobiliary phase) after the intravenous administration of Gd-EOB-DTPA, and the mean signal intensity of the liver was measured. The correlation between ICG-PDR and many parameters derived from the signal intensity of the liver in EOB-MRI was evaluated. The correlation coefficient between ICG-PDR and many parameters derived from the signal intensity of the liver in EOBMRI was low and not significant. The estimation of the liver function corresponding to ICG-PDR by use of the signal intensity of the liver alone in EOB-MRI would not be reliable.

  4. Characteristics of hepatic alanine-glyoxylate aminotransferase in different mammalian species.

    PubMed Central

    Noguchi, T; Okuno, E; Takada, Y; Minatogawa, Y; Okai, K; Kido, R

    1978-01-01

    Mitochondrial extracts of dog, cat, rat and mouse liver contain two forms of alanine-glyoxylate aminotransferase (EC 2.6.1.44): one, designated isoenzyme 1, has mol.wt. approx. 80 000 and predominates in dog and cat liver; the other, designated isoenzyme 2, has mol.wt. approx. 175 000 and predominates in rat and mouse liver. In rat and mouse liver, isoenzyme 1 activity was increased by the injection in vivo of glucagon, but not isoenzyme 2 activity. Isoenzyme 1 was purified and characterized from liver mitochondrial extracts of the four species. Both rat and mouse enzyme preparations catalysed transamination between a number of L-amino acids and glyoxylate, and with L-alanine as amino donor the effective amino acceptors were glyoxylate, phenylpyruvate and hydroxypyruvate. In contrast, both dog and cat enzyme preparations were specific for L-alanine and L-serine with glyoxylate, and used glyoxylate and hydroxypyruvate as effective amino acceptors with L-alanine. Evidence that isoenzyme 1 is identical with serine-pyruvate aminotransferase (EC 2.6.1.51) was obtained. Isoenzyme 2 was partially purified from mitochondrial extracts of rat and mouse liver. Both enzyme preparations were specific for L-alanine and glyoxylate. On the basis of physical properties and substrate specificity, it was concluded that isoenzyme 2 is a separate enzyme. Some other properties of isoenzymes 1 and 2 are described. PMID:629740

  5. Transcriptome temporal and functional analysis of liver regeneration termination.

    PubMed

    Rychtrmoc, D; Hubálková, L; Víšková, A; Libra, A; Bun?ek, M; ?ervinková, Z

    2012-01-01

    Decades of liver regeneration studies still left the termination phase least elucidated. However regeneration ending mechanisms are clinicaly relevant. We aimed to analyse the timing and transcriptional control of the latest phase of liver regeneration, both controversial. Male Wistar rats were subjected to 2/3 partial hepatectomy with recovery lasting from 1 to 14 days. Time-series microarray data were assessed by innovative combination of hierarchical clustering and principal component analysis and validated by real-time RT-PCR. Hierarchical clustering and principal component analysis in agreement distinguished three temporal phases of liver regeneration. We found 359 genes specifically altered during late phase regeneration. Gene enrichment analysis and manual review of microarray data suggested five pathways worth further study: PPAR signalling pathway; lipid metabolism; complement, coagulation and fibrinolytic cascades; ECM remodelling and xenobiotic biotransformation. Microarray findings pertinent for termination phase were substantiated by real-time RT-PCR. In conclusion, transcriptional profiling mapped late phase of liver regeneration beyond 5(th) day of recovery and revealed 5 pathways specifically acting at this time. Inclusion of longer post-surgery intervals brought improved coverage of regeneration time dynamics and is advisable for further works. Investigation into the workings of suggested pathways might prove helpful in preventing and managing liver tumours. PMID:23130906

  6. Pretransplant levels of endotoxin can predict the risk of bacterial infections and graft liver function after liver transplantation.

    PubMed

    Sanada, Yukihiro; Urahashi, Taizen; Ihara, Yoshiyuki; Okada, Noriki; Yamada, Naoya; Hirata, Yuta; Mizuta, Koichi

    2015-06-01

    Background?Although endotoxin (Et) has been used as a biological index of bacterial infections, Et can also be used to evaluate liver functions because Et present in the portal vein blood is processed by the hepatic reticuloendothelial system. In the field of posttransplant management, it is important for liver transplant recipients to monitor the presence of posttransplant bacterial infections and graft liver functions because these results are directly correlated with a graft prognosis. Therefore, the measurement of Et during liver transplantation (LT) may be the detection of posttransplant infections and graft liver functions. This retrospective study investigated whether Et measured by the Et activity assay (EAA) in the peripheral venous blood during living donor LT (LDLT) can predict the incidence of posttransplant bacterial infections and graft liver functions. Materials and Methods?The study subjects consisted of 21 patients who underwent LDLT between April 2010 and February 2011. Et activity (EA) was measured using the EAA in peripheral venous blood samples collected 1 or 2 days before LDLT, and on postoperative days (PODs) 1, 5, 7, and 14. We included LDLT recipients with intra-abdominal infections, respiratory infections, and bacteremia in the group with posttransplant bacterial infections. Results?The incidence rates of posttransplant bacterial infections or hyperbilirubinemia after LDLT were 57.1%. The LDLT recipients with posttransplant bacterial infections or hyperbilirubinemia had significantly higher levels of EA in comparison with patients without complications before LDLT (0.22?±?0.10 vs. 0.07?±?0.05, p?

  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. Identification and functional characterization of lipid binding proteins in liver and adipose tissues of Gallus domesticus 

    E-print Network

    Sams, Gretchen Hubler

    1990-01-01

    IDENTIFICATION AND FUNCTIONAL CHARACTERIZATION OF LIPID BINDING PROTEINS IN LIVER AND ADIPOSE TISSUES OF GALLUS DOMESTICUS A Thesis by GRETCHEN HUBLER SAMS Submitted to the Office of Graduate Studies of Texas A&M University in partial... fulfillment of the requirements for the degree of MASTER OF SCIENCE August 1990 Major subject: Nutrition IDENTIFICATION AND FUNCTIONAL CHARACTERIZATION OF LIPID BINDING PROTEINS IN LIVER AND ADIPOSE TISSUES OF GALLUS DOMESTICUS A Thesis by GRETCHEN...

  9. Serum Alanine Transaminase Total Bilirubin Concentrations Predict CYP3A Activity as Measured by Midazolam and 1?-Hydroxylation

    PubMed Central

    He, Rui; Li, Yuhong; Ruan, Jinguang

    2015-01-01

    Background Microsomal enzyme P450 (CYP450) plays an important role in metabolism of most xenobiotics. The activity of CYP3A decreases in patients with liver dysfunction. However, whether serum concentrations of liver enzymes reflect the activity of CYP3A is unclear. We aimed to search for a new clue to predict the activity of CYP3A and guide clinical medication. Material/Methods Forty-five patients undergoing surgery under general anesthesia were enrolled in the study, including 15 cases with normal liver function (Group N), 15 cases with moderate fatty liver according to both the results of ultrasonic diagnosis of moderate fatty liver and the laboratory results of elevated alanine transaminase less than 3 times the normal (Group M), and 15 cases with end-stage liver disease (Group S). Each patient received a single dose of 5 mg midazolam intravenously. CYP3A activity was measured by plasma 1?hydroxymidsazolam/midazolam (1?-OH-MDZ/MDZ) ratio at 2 h after administration of midazolam. Results They was no significant difference in CYP3A activity between the patients with normal liver function and moderate fatty liver (P=0.332). The activity of CYP3A in Group S was lower than in Group N and Group M (P=0.000). Multiple linear regression analysis showed a statistically significant linear relationship between the activity of CYP3A and alanine transaminase (ALT, R2=0.682, P=0.000), and total bilirubin (TB, R2=0.519, P=0.002). There were no other factors, including albumin (ALB, P=0.881) and alkaline phosphatase (ALP, P=0.497), correlated with the activity of CYP3A. Conclusions We conclude that the activity of CYP3A in patients with end-stage liver disease decreased. The decrease in the activity of CYP3A was determined by the increase in the serum concentration of ALT and TB and not by patient’s age or body weight. ALT and TB therefore might have predictive value for the activity of CYP3A. An abnormal liver function test likely gives the clinician a hint about dosage adjustment. PMID:25648948

  10. 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

  11. Methamphetamine causes acute hyperthermia-dependent liver damage.

    PubMed

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-10-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

  12. Methamphetamine causes acute hyperthermia-dependent liver damage

    PubMed Central

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-01-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

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

    PubMed Central

    Aziz-Seible, Razia S; Casey, Carol A

    2011-01-01

    Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in fact stimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. Studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this reactive glycoprotein plays in the progression of injury but also for the insight further studies could provide towards the development of novel therapies for alcoholic liver disease. PMID:21633653

  14. Melatonin reduces oxidative stress and restores mitochondrial function in the liver of rats exposed to chemotherapeutics.

    PubMed

    Madhu, P; Reddy, K Pratap; Reddy, P Sreenivasula

    2015-06-01

    This study was undertaken to investigate whether administration of melatonin protects PVB-Induced oxidative and metabolic toxicity in the liver of Wistar rats. Adult male Wistar rats were intraperitoneally injected with either melatonin or PVB (cisplatin, vinblastine, and bleomycin) alone or combination for a period of 9 weeks. A significant increase in lipid peroxidation levels and decrease in catalase and superoxide dismutase activity levels were observed in the liver mitochondria of rats treated with PVB indicating increased oxidative stress. PVB treatment significantly decreased the succinate dehydrogenase activity with a significant increase in lactate dehydrogenase, glucose-6-phosphate dehydrogenase, aspartate aminotransaminase, alanine aminotransaminase, and glutamate dehydrogenase activities indicating deranged hepatic metabolism. Melatonin administration, on the other hand was found to significantly improve PVB-Induced biochemical changes, bringing them closer to the controls. The results from the study provide evidence that treatment with PVB affects hepatic metabolism in rats by inducing oxidative stress followed by decreasing mitochondrial oxidation and also point towards the clinical potential of melatonin as an adjuvant therapy to conventional chemotherapeutic regimens. J. Exp. Zool. 323A: 301-308, 2015. © 2015 Wiley Periodicals, Inc. PMID:25755110

  15. 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 could aid in individualizing therapy, particularly for patients at risk for liver injury after RT. PMID:22520476

  16. Altered functional and immunophenotypical properties of neutrophilic granulocytes in postpartum cows associated with fatty liver.

    PubMed

    Zerbe, H; Schneider, N; Leibold, W; Wensing, T; Kruip, T A; Schuberth, H J

    2000-09-15

    The intention of the study was to analyze the relationship between liver triacyl glycerol content (liver TAG content) and immunophenotypical and functional properties of polymorphonuclear neutrophilic granulocytes (PMN) of dairy cows in the peripartum period. We investigated characteristics of bovine PMN from the blood and uterus of clinically healthy cows in the periparturient period. The numbers of circulating leukocytes and segmented granulocytes continuously increased until parturition and declined afterwards to starting values. This was independent of the liver TAG content and mainly affected neutrophils. The liver TAG content exceeded 40 mg/g liver, the reference value, in 12 of 19 cows in the first two weeks postpartum. Increased liver TAG content, > 40 mg/g, went in parallel with a reduced expression of function-associated surface molecules on blood neutrophils (e.g. CD11b/CD18 = CR3 and CD11c/CD18 = CR4). Moreover, in cows with high liver TAG levels the antibody-independent and -dependent cellular cytotoxicity (AICC, ADCC) of blood PMN was markedly reduced. PMN also were less capable of ROS generation after stimulation with Phorbol Myristate Acetate (PMA). In comparison with contemporarily harvested blood PMN, neutrophils recovered from the uterine lumen showed a decreased expression of 4/6 examined surface structures. Only the expression densities of CR3 molecules and those detected by mAb IL-A110 were enhanced on uterine PMN. The cytotoxic capacity and the ROS generation were significantly lower for uterine PMN than for blood PMN. The results suggest that increased liver TAG content in the first and second week after calving is associated with decreased functional capacities of PMN derived from blood and uterus. This may help to explain why cows who are too fat at calving (who therefore have an increased liver TAG content) have a higher incidence of infectious diseases such as endometritis PMID:11101037

  17. Isolation of rat liver spectrin and identification of functional domains.

    PubMed

    Falchetto, R; Leutenegger, S; Bachs, O; Serratosa, J; Bloemhard, Y; Gazzotti, P

    1990-05-31

    Immunohistochemical studies carried out with liver sections show that spectrin is uniformly distributed along the whole plasma membrane of hepatocytes. The bilecanalicular spectrin is released during the purification of liver subplasma membrane fractions, whereas most of the basolateral spectrin remains tightly bound to the membrane. Spectrin associated with the basolateral membranes has been purified and its subunits isolated. The alpha-subunit retains the ability to bind both calmodulin and actin. Fragments have been obtained either by chemical or by proteolytical digestion of the 240 kDa alpha-subunit. Treatment with CNBr yields fragments of about 30 kDa which bind actin and calmodulin. Digestion with Staphylococcus aureus V-8 proteinase yields a calmodulin-binding fragment of 27 kDa and an actin-binding fragment of 31 kDa. PMID:2354203

  18. [Data analysis of real world clinical changes in indexes of liver and kidney function to use of parenterally administered kudiezi at different doses and time periods].

    PubMed

    Liao, Xing; Zhang, Hui; Xie, Yan-Ming; Yang, Wei; Yang, Wei

    2013-09-01

    This is a retrospective study based on a 18 hospital information system data warehouse. Records of 1 982 patients who used Kudiezi intravenous infusion (KDZ) were extracted from the data warehouse. All the patients were divided into two groups, one group of 1 707 patients used KDZ, < or = 14 days under the instruction, the other group of 275 patients used KDZ, > 14 days, off label use. Generalized boosted models (GBM) with propensity score were applied to compare the two groups on four indexes of liver and kidney functions, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and blood urea nitrogen (BUN). Seventy one confounders were identified and balanced by GBM. And another two logistic analysis methods were used to confirm the results from GBM. The results indicated that there were no significant difference on the four indexes except the AST (P < 0. 05) by all the three analyzing models. It is hard to conclude that ultra long, off label using Kudiezi intravenous infusion could influence the four indexed of liver and kidney from this data analysis. More conclusive evidence should be collected by further prospective study. PMID:24471333

  19. Differential roles of alanine in GABAergic and glutamatergic neurons.

    PubMed

    Schousboe, A; Sonnewald, Ursula; Waagepetersen, Helle S

    2003-01-01

    Studies in different preparations of neurons and astrocytes of alanine transport and activities of its metabolizing enzyme alanine aminotransferase have led to the proposal that this amino acid is preferentially synthesized in astrocytes and transferred from the astrocytic to the neuronal compartment. From a functional point of view this may well be the case in a GABAergic synapse since theoretically alanine can be utilized as a metabolic fuel in GABAergic neurons where the GABA shunt is operating. Thus, a metabolic scheme is proposed, according to which alanine catabolism is coupled to the TCA cycle where the GABA shunt replaces the alpha-ketoglutarate dehydrogenase/succinyl CoA synthetase reactions. In a glutamatergic synapse in which the large demand for synthesis of neurotransmitter glutamate leads to a large production of ammonia, it is possible that alanine could play a completely different role. Hence, experimental evidence is reviewed suggesting that alanine may serve as a carrier of ammonia nitrogen from the neuronal compartment to the astrocytic compartment using a flux of lactate in the opposite direction to account for transfer of the C-3 carbon skeleton. PMID:12742074

  20. Correlation Between Fibroscan, Liver Biopsy, and Clinical Liver Function in Patients With Hepatitis C Virus Infection After Renal Transplantation

    Microsoft Academic Search

    R. Muñoz; E. Ramírez; I. Fernandez; A. Martin; M. Romero; E. Romero; B. Dominguez-Gil; A. Hernandez; E. Morales; A. Andres; G. Castellano; J. M. Morales

    2009-01-01

    Hepatitis C virus (HCV) infection is the most important liver disease (LD) after renal transplantation. Liver biopsy is the gold standard for the diagnosis and follow-up of LD. The aim of this retrospective study was to evaluate the correlation between values of Fibroscan (EchoSens, Paris, France), a new noninvasive method to assess liver fibrosis, liver biopsy, and clinical data among

  1. Nuclear imaging for functional evaluation and theragnosis in liver malignancy and transplantation

    PubMed Central

    Eo, Jae Seon; Paeng, Jin Chul; Lee, Dong Soo

    2014-01-01

    Currently, nuclear imaging such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) is increasingly used in the management of liver malignancy. 18F-fluorodeoxyglucose (FDG)-PET is the most widely used nuclear imaging in liver malignancy as in other cancers, and has been reported to be effective in diagnosis, response monitoring, recurrence evaluation, and prognosis prediction. Other PET imaging such as 11C-acetate PET is also used complementarily to FDG-PET in diagnosis of liver malignancy. Additionally, image-based evaluation of regional hepatic function can be performed using nuclear imaging. Those imaging modalities are also effective for candidate selection, treatment planning, and perioperative evaluation in liver surgery and transplantation. Recently, nuclear imaging has been actively adopted in the transarterial radioembolization therapy of liver malignancy, according to the concept of theragnosis. With the development of new hybrid imaging technologies such as PET/magnetic resonance imaging and SPECT/CT, nuclear imaging is expected to be more useful in the management of liver malignancy, particularly regarding liver surgery and transplantation. In this review, the efficacy and roles of nuclear imaging methods in diagnosis, transplantation and theragnosis are discussed. PMID:24833867

  2. [Effects of ß-alanine supplementation on athletic performance].

    PubMed

    Domínguez, Raúl; Hernández Lougedo, Juan; Maté-Muñoz, José Luis; Garnacho-Castaño, Manuel Vicente

    2015-01-01

    Carnosine, dipeptide formed by amino acids ß-alanine and L-histidine, has important physiological functions among which its antioxidant and related memory and learning. However, in connection with the exercise, the most important functions would be associated with muscle contractility, improving calcium sensitivity in muscle fibers, and the regulatory function of pH. Thus, it is proposed that carnosine is the major intracellular buffer, but could contribute to 7-10% in buffer or buffer capacity. Since carnosine synthesis seems to be limited by the availability of ß-alanine supplementation with this compound has been gaining increasing popularity among the athlete population. Therefore, the objective of this study literature review was to examine all those research works have shown the effect of ß-alanine supplementation on athletic performance. Moreover, it also has attempted to establish a specific dosage that maximizing the potential benefits, minimize paresthesia, the main side effect presented in response to supplementation. PMID:25561107

  3. Functions of Liver Natural Killer Cells Are Dependent on the Severity of Liver Inflammation and Fibrosis in Chronic Hepatitis C

    PubMed Central

    Macek Jílková, Zuzana; Van Campenhout, Nicolas; Dufeu-Duchesne, Tania; Leroy, Vincent; Zarski, Jean-Pierre; Sturm, Nathalie; Marche, Patrice N.; Jouvin-Marche, Evelyne

    2014-01-01

    During chronic hepatitis C virus (HCV) infection, the role of intra-hepatic (IH) natural killer (NK) cells is still controversial. To clarify their functions, we investigated anti-viral and cytotoxic activity of NK cells in human fresh liver biopsies. We compared the functions of IH-NK cells in HCV-infected and NASH patients in physiological conditions as well as after stimulation using flow cytometric and immunohistochemical analyses. Interestingly, few IH-NK cells produced anti-viral cytokine IFN-? in HCV-infected patients similarly as in non-infected individuals. Spontaneous degranulation activity was extremely low in peripheral NK cells compared to IH-NK cells, and was significantly higher in IH-NK cells from HCV-infected patients compared to non-infected individuals. Immunohistochemical analysis revealed that perforin granules were polarized at the apical pole of IH-NK cells. The presence of CD107a and perforin in IH-NK cells demonstrated that NK cells exerted a cytolytic activity at the site of infection. Importantly, IH-NK cell functions from HCV-infected patients were inducible by specific exogenous stimulations. Upon ex vivo K562 target cell stimulations, the number of degranulating NK cells was significantly increased in the pool of IH-NK cells compared to circulating NK cells. Interestingly, after stimulation, the frequency of IFN-?-producing IH-NK cells in HCV-infected patients was significantly higher at early stage of inflammation whereas the spontaneous IH-NK cell degranulation activity was significantly impaired in patients with highest inflammation and fibrosis Metavir scores. Our study highlights that some IH-NK cells in HCV-infected patients are able to produce INF-? and degranulate and that those two activities depend on liver environment including the severity of liver injury. Thus, we conclude that critical roles of IH-NK cells have to be taken into account in the course of the liver pathogenesis associated to chronic HCV infection. PMID:24759660

  4. 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

  5. Dynamic adaptation of liver mitochondria to chronic alcohol feeding in mice: biogenesis, remodeling, and functional alterations.

    PubMed

    Han, Derick; Ybanez, Maria D; Johnson, Heather S; McDonald, Jeniece N; Mesropyan, Lusine; Sancheti, Harsh; Martin, Gary; Martin, Alanna; Lim, Atalie M; Dara, Lily; Cadenas, Enrique; Tsukamoto, Hidekazu; Kaplowitz, Neil

    2012-12-01

    Liver mitochondria undergo dynamic alterations following chronic alcohol feeding to mice. Intragastric alcohol feeding to mice resulted in 1) increased state III respiration (109% compared with control) in isolated liver mitochondria, probably due to increased levels of complexes I, IV, and V being incorporated into the respiratory chain; 2) increased mitochondrial NAD(+) and NADH levels (?2-fold), with no change in the redox status; 3) alteration in mitochondrial morphology, with increased numbers of elongated mitochondria; and 4) enhanced mitochondrial biogenesis in the liver, which corresponded with an up-regulation of PGC-1? (peroxisome proliferator-activated receptor ? coactivator-1?). Oral alcohol feeding to mice, which is associated with less liver injury and steatosis, slightly enhanced respiration in isolated liver mitochondria (30.8% compared with control), lower than the striking increase caused by intragastric alcohol feeding. Mitochondrial respiration increased with both oral and intragastric alcohol feeding despite extensive N-acetylation of mitochondrial proteins. The alcohol-induced mitochondrial alterations are probably an adaptive response to enhance alcohol metabolism in the liver. Isolated liver mitochondria from alcohol-treated mice had a greater rate of acetaldehyde metabolism and respiration when treated with acetaldehyde than control. Aldehyde dehydrogenase-2 levels were unaltered in response to alcohol, suggesting that the greater acetaldehyde metabolism by isolated mitochondria from alcohol-treated mice was due to increased mitochondrial respiration that regenerated NAD(+), the rate-limiting substrate in alcohol/acetaldehyde metabolism. Overall, our work suggests that mitochondrial plasticity in the liver may be an important adaptive response to the metabolic stress caused by alcohol intake and could potentially play a role in many other vital functions performed by the liver. PMID:23086958

  6. [Liver cell function test based on selective laboratory studies].

    PubMed

    Sliwi?ska-Przyjemska, H; Pilawska, H

    1981-01-01

    Laboratory tests have been carried out in 517 workers of a Chemical Fibres Plant. This was aimed at the detection of the changes resulting from cumulative exposure to caprolactam, dowtherm and physical factors. There have been performed hematological investigations, uninalyses and biochemical tests: total protein level, activity of enzymes: ASPAT, ALAT, PA, ChE, thymol test. The results have been analysed as the mean values for particular divisions and workstands; then they have been compared with standards. In order to evaluate the degree of occupational exposure of particular groups of workers, an index of the liver cell damage has been calculated. It was expressed in % of the results exceeding the standards in relation to all results in a given group of workers. The highest values of the index were those in the group employed at the polymerization division. The authoresses promote the advisability of special care for this group of workers. PMID:7289867

  7. Inhibition of Key Digestive Enzymes Related to Diabetes and Hyperlipidemia and Protection of Liver-Kidney Functions by Trigonelline in Diabetic Rats

    PubMed Central

    Hamden, Khaled; Mnafgui, Kais; Amri, Zahra; Aloulou, Ahmed; Elfeki, Abdelfattah

    2013-01-01

    Diabetes is a serious health problem and a source of risk for numerous severe complications such as obesity and hypertension. Treatment of diabetes and its related diseases can be achieved by inhibiting key digestive enzymes related to starch and lipid digestion. The findings revealed that the administration of trigonelline to surviving diabetic rats helped to protect the pancreas ?-cells from death and damage. Additionally, the supplement of trigonelline to surviving diabetic rats significantly decreased intestinal ?-amylase and maltase by 36 and 52%, respectively, which led to a significant decrease in the blood glucose rate by 46%. Moreover, the administration of trigonelline to surviving diabetic rats potentially inhibited key enzymes of lipid metabolism and absorption such as lipase activity in the small intestine by 56%, which led to a notable decrease in serum triglyceride (TG) and total cholesterol (TC) rates and an increase in the HDL cholesterol level. This treatment also improved glucose, maltase, starch, and lipid oral tolerance. Trigonelline was also observed to protect the liver-kidney functions efficiently, which was evidenced by the significant decrease in the serum aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), and lactate dehydrogenase (LDH) activities and creatinine, albumin, and urea rates. The histological analysis of the pancreas, liver, and kidney tissues further established the positive effect of trigonelline. Overall, the findings presented in this study demonstrate that the administration of trigonelline to diabetic rats can make it a potentially strong candidate for industrial application as a pharmacological agent for the treatment of hyperglycemia, hyperlipidemia, and liver-kidney dysfunctions. PMID:23641341

  8. Cholestatic Liver Injury After Biliary Reconstruction Impairs Transplanted Islet Viability and Function.

    PubMed

    Hata, T; Sakata, N; Yoshimatsu, G; Tsuchiya, H; Fukase, M; Ishida, M; Aoki, T; Katayose, Y; Egawa, S; Unno, M

    2015-08-01

    Islet autotransplantation following total pancreatectomy differs from allograft transplantation with respect to the requirement of biliary reconstruction. Although it is known that careful consideration should be given to postoperative cholestatic liver injury after biliary reconstruction, its direct effects on transplanted islets have not been completely elucidated. In this study, we developed a murine model of postoperative cholestatic liver injury after biliary reconstruction with islet autotransplantation that involved syngeneic intraportal islet transplantation into chemically induced diabetic mice and common bile duct ligation. We assessed the viability and function of the transplanted islets. The impaired viability of transplanted islets and increased blood glucose levels indicated restoration of the diabetic state after common bile duct ligation in this murine model. Furthermore, impaired islet viability and function occurred earlier in the transplanted islets than in the surrounding liver tissues, which was consistent with the faster and higher expression of oxidative stress markers in the transplanted islets. Transplanted islets may be more vulnerable to oxidative stress caused by cholestatic liver injury than the surrounding liver tissue. Therefore, patients should be intensively managed after total pancreatectomy with islet autotransplantation to preserve viability and function of the transplanted islets. PMID:25908212

  9. The effect of highly active antiretroviral therapy on liver function in human immunodeficiency virus-infected pediatric patients with or without hepatitis virus co-infection

    PubMed Central

    Wu, Lijuan; Jin, Changzhong; Bai, Shi; Davies, Henry; Rao, Heping; Liang, Yong; Wu, Nanping

    2015-01-01

    Background: Co-infection of hepatitis virus is common in human immunodeficiency virus (HIV) infected adults in China. But little is known about hepatitis virus co-infection in pediatric HIV-infected subjects. The study aimed to investigate the impact of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection and highly active antiretroviral therapy (HAART) on liver function of pediatric HIV-infected subjects. Materials and Methods: A cohort study including 101 pediatric HIV-infected subjects with HBV/HCV co-infection and 44 pediatric comparators with HIV mono-infection was carried out in Henan Province of China from September 2011 to September 2012. All patients received HAART for 1-year. HBV and HCV infection was determined by antibody tests. HIV RNA load, CD4+ T-cell counts and liver function were determined before and after HAART. The Student's t-test or a one-way ANOVA was used for normally distributed values and A Mann-Whitney U-test was performed for values without normal distribution using SPSS statistical package 18.0 (SPSS Inc.). Results: After HAART for 1-year, the median levels of viral load were decreased to lower limit of detection in 90.34% pediatric HIV-infected subjects with/without HBV/HCV co-infection (P < 0.001), and CD4+ T-cell counts increased significantly (P < 0.001). Compared with the pre-HAART, mean level of alanine aminotransferase (ALT) in each group had a significant increase after HAART (P < 0.01). The mean levels of ALT and aspartate aminotransferase (AST) in nevirapine (NVP) based HAART group increased significantly after HAART (P < 0.01). Mean change values of ALT and AST were significantly higher in the NVP based regimen group than in the efavirenz (EFV) based regimen group (P < 0.01). For HIV/HBV/HCV co-infected patients, mean change values of ALT and AST in NVP-based HAART group was significantly higher than that in EFV-based HAART group (P < 0.01). Conclusion: Highly active antiretroviral therapy can damage liver function in pediatric HIV-infected subjects, especially in those with HBV/HCV co-infection. NVP was more harmful to liver function of pediatric HIV-infected subjects than EFV. PMID:25983763

  10. The multiple functional roles of mesenchymal stem cells in participating in treating liver diseases

    PubMed Central

    Liu, Wei-hui; Song, Fu-qiang; Ren, Li-na; Guo, Wen-qiong; Wang, Tao; Feng, Ya-xing; Tang, Li-jun; Li, Kun

    2015-01-01

    Mesenchymal stem cells (MSCs) are a group of stem cells derived from the mesodermal mesenchyme. MSCs can be obtained from a variety of tissues, including bone marrow, umbilical cord tissue, umbilical cord blood, peripheral blood and adipose tissue. Under certain conditions, MSCs can differentiate into many cell types both in vitro and in vivo, including hepatocytes. To date, four main strategies have been developed to induce the transdifferentiation of MSCs into hepatocytes: addition of chemical compounds and cytokines, genetic modification, adjustment of the micro-environment and alteration of the physical parameters used for culturing MSCs. Although the phenomenon of transdifferentiation of MSCs into hepatocytes has been described, the detailed mechanism is far from clear. Generally, the mechanism is a cascade reaction whereby stimulating factors activate cellular signalling pathways, which in turn promote the production of transcription factors, leading to hepatic gene expression. Because MSCs can give rise to hepatocytes, they are promising to be used as a new treatment for liver dysfunction or as a bridge to liver transplantation. Numerous studies have confirmed the therapeutic effects of MSCs on hepatic fibrosis, cirrhosis and other liver diseases, which may be related to the differentiation of MSCs into functional hepatocytes. In addition to transdifferentiation into hepatocytes, when MSCs are used to treat liver disease, they may also inhibit hepatocellular apoptosis and secrete various bioactive molecules to promote liver regeneration. In this review, the capacity and molecular mechanism of MSC transdifferentiation, and the therapeutic effects of MSCs on liver diseases are thoroughly discussed. PMID:25534251

  11. 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-?B). 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

  12. Hepatoprotection by Elephantopus scaber Linn. in CCl4-induced liver injury.

    PubMed

    Rajesh, M G; Latha, M S

    2001-10-01

    The efficacy of the medicinal plant Elephantopus scaber Linn. (Asteraceae), to prevent carbon teterachloride (CCI4)-induced chronic liver dysfunction in the rats was examined by determining different biochemical markers in serum and tissues. In serum, liver function marker enzymes like aspartate aminotrasferase (AST), alanine aminotrasferase (ALT), alkaline phosphatase (ALP) and also protein were evaluated. The concentrations of total lipid, cholesterol and phospholipids were studied in serum and the different tissues. The concentration of serum triglycerides was also studied. The biochemical changes induced by CCI4 in different tissues particularly in the liver tissue improved following treatment with E. scaber Linn. The results suggest the hepatoprotective effect of this medicinal plant. PMID:11883157

  13. Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease.

    PubMed

    Kathirvel, Elango; Morgan, Kengathevy; French, Samuel W; Morgan, Timothy R

    2013-11-01

    Mitochondrial abnormalities are suggested to be associated with the development of nonalcoholic fatty liver. Liver mitochondrial content and function have been shown to improve in oral feeding of acetyl-L-carnitine (ALC) to rodents. Carnitine is involved in the transport of acyl-coenzyme A across the mitochondrial membrane to be used in mitochondrial ?-oxidation. We hypothesized that oral administration ALC with the antioxidant lipoic acid (ALC + LA) would benefit nonalcoholic fatty liver. To test our hypothesis, we fed Balb/C mice a standard diet (SF) or SF with ALC + LA or high-fat diet (HF) or HF with ALC + LA for 6 months. Acetyl-L-carnitine and LA were dissolved at 0.2:0.1% (wt/vol) in drinking water, and mice were allowed free access to food and water. Along with physical parameters, insulin resistance (blood glucose, insulin, glucose tolerance), liver function (alanine transaminase [ALT], aspartate transaminase [AST]), liver histology (hematoxylin and eosin), oxidative stress (malondialdehyde), and mitochondrial abnormalities (carbamoyl phosphate synthase 1 and electron microscopy) were done. Compared with SF, HF had higher body, liver, liver-to-body weight ratio, white adipose tissue, ALT, AST, liver fat, oxidative stress, and insulin resistance. Coadministration of ALC + LA to HF animals significantly improved the mitochondrial marker carbamoyl phosphate synthase 1 and the size of the mitochondria in liver. Alanine transaminase and AST levels were decreased. In a nonalcoholic fatty liver mice model, ALC + LA combination improved liver mitochondrial content, size, serum ALT, and AST without significant changes in oxidative stress, insulin resistance, and liver fat accumulation. PMID:24176233

  14. Structure-based modification of D-alanine-D-alanine ligase from Thermotoga maritima ATCC 43589 for depsipeptide synthesis.

    PubMed

    Nakagawa, Tomoki; Satake, Ryoko; Sato, Masaru; Kino, Kuniki

    2011-01-01

    Depsipeptides are peptide-like polymers consisting of amino acids and hydroxy acids, and are expected to be new functional materials for drug-delivery systems and polymer science. In our previous study, D-alanyl-D-lactate, a type of depsipeptide, was enzymatically synthesized using D-alanine-D-alanine ligase from Thermotoga maritima ATCC 43589 (TmDdl) by Y207F substitution. Thereafter, in this study, further mutagenesis was introduced, based on structural comparison between TmDdl and a well-characterized D-alanine-D-alanine ligase from Escherichia coli. The S137A/Y207F mutant showed higher D-alanyl-D-lactate and lower D-alanyl-D-alanine synthesizing activity than the Y207F mutant. This suggests that substitution at the S137 residue contributes to product selectivity. Saturated mutagenesis on S137 revealed that the S137G/Y207F mutant showed the highest D-alanyl-D-lactate synthesizing activity. Moreover, the mutant showed broad substrate specificity toward D-amino acid and recognized D-lactate and D,L-isoserine as substrates. On the basis of these characteristics, various depsipeptides can be produced using S137G/Y207F-replaced TmDdl. PMID:21512246

  15. The Complex Myeloid Network of the Liver with Diverse Functional Capacity at Steady State and in Inflammation

    PubMed Central

    Eckert, Christoph; Klein, Niklas; Kornek, Miroslaw; Lukacs-Kornek, Veronika

    2015-01-01

    In recent years, it has been an explosion of information regarding the role of various myeloid cells in liver pathology. Macrophages and dendritic cell (DC) play crucial roles in multiple chronic liver diseases such as fibrosis and non-alcoholic fatty liver disease (NAFLD). The complexity of myeloid cell populations and the missing exclusive marker combination make the interpretation of the data often extremely difficult. The current review aims to summarize the multiple roles of macrophages and DCs in chronic liver diseases, especially pointing out how these cells influence liver immune and parenchymal cells thereby altering liver function and pathology. Moreover, the review outlines the currently known marker combinations for the identification of these cell populations for the study of their role in liver immunology. PMID:25941527

  16. Liver Regeneration

    PubMed Central

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

    2014-01-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review will provide an overview of the models of study currently utilized in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus will be placed on clinical applications of current knowledge in liver regeneration including small for size liver transplant. Furthermore, cutting edge topics in liver regeneration including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a three dimensional scaffold for liver repopulation will be proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration. PMID:24495569

  17. Examination of the liver in personnel working with liquid rocket propellant

    PubMed Central

    Petersen, Palle; Bredahl, Erik; Lauritsen, Ove; Laursen, Thomas

    1970-01-01

    Petersen, P., Bredahl, E., Lauritsen, O., and Laursen, T. (1970).Brit. J. industr. Med.,27, 141-146. Examination of the liver in personnel working with liquid rocket propellants. Personnel working with liquid rocket propellants were subjected to routine health examinations, including liver function tests, as the propellant, unsymmetrical dimethylhydrazine (UDMH) is potentially toxic to the liver. In 46 persons the concentrations of serum alanine aminotransferase (SGPT) were raised. Liver biopsy was performed in 26 of these men; 6 specimens were pathological (fatty degeneration), 5 were uncertain, and 15 were normal. All 6 pathological biopsies were from patients with a raised SGPT at the time of biopsy. Of the 15 persons with a normal liver biopsy, 14 had a normal SGPT, while one (who was an alcoholic) had a raised SGPT. The connection between SGPT and histology of the liver, as well as the possible causal relation between the pathological findings and exposure to UDMH, is discussed. Images PMID:5428632

  18. Association of Heme Oxygenase 1 with the Restoration of Liver Function after Damage in Murine Malaria by Plasmodium yoelii

    PubMed Central

    Dey, Sumanta; Mazumder, Somnath; Siddiqui, Asim Azhar; Iqbal, M. Shameel; Banerjee, Chinmoy; Sarkar, Souvik; De, Rudranil; Goyal, Manish; Bindu, Samik

    2014-01-01

    The liver efficiently restores function after damage induced during malarial infection once the parasites are cleared from the blood. However, the molecular events leading to the restoration of liver function after malaria are still obscure. To study this, we developed a suitable model wherein mice infected with Plasmodium yoelii (45% parasitemia) were treated with the antimalarial ?/?-arteether to clear parasites from the blood and, subsequently, restoration of liver function was monitored. Liver function tests clearly indicated that complete recovery of liver function occurred after 25 days of parasite clearance. Analyses of proinflammatory gene expression and neutrophil infiltration further indicated that hepatic inflammation, which was induced immediately after parasite clearance from the blood, was gradually reduced. Moreover, the inflammation in the liver after parasite clearance was found to be correlated positively with oxidative stress and hepatocyte apoptosis. We investigated the role of heme oxygenase 1 (HO-1) in the restoration of liver function after malaria because HO-1 normally renders protection against inflammation, oxidative stress, and apoptosis under various pathological conditions. The expression and activity of HO-1 were found to be increased significantly after parasite clearance. We even found that chemical silencing of HO-1 by use of zinc protoporphyrin enhanced inflammation, oxidative stress, hepatocyte apoptosis, and liver injury. In contrast, stimulation of HO-1 by cobalt protoporphyrin alleviated liver inflammation and reduced oxidative stress, hepatocyte apoptosis, and associated tissue injury. Therefore, we propose that selective induction of HO-1 in the liver would be beneficial for the restoration of liver function after parasite clearance. PMID:24818663

  19. Liver-enriched transcription factors uncoupled from expression of hepatic functions in hepatoma cell lines.

    PubMed Central

    Chaya, D; Fougère-Deschatrette, C; Weiss, M C

    1997-01-01

    Among the liver-enriched transcription factors identified to date, only expression of hepatocyte nuclear factor 4 (HNF4) and hepatocyte nuclear factor 1 (HNF1) is in strict correlation with hepatic differentiation in cultured rat hepatoma cells. Indeed, differentiated hepatoma cells that stably express an extensive set of adult hepatic functions express liver-enriched transcription factors, while dedifferentiated cells that have lost expression of all these hepatic functions no longer express HNF4 and HNF1. We describe a new heritable phenotype, designated as uncoupled, in which there is a spontaneous dissociation between the expression of these transcription factors and that of the hepatic functions. Cells presenting this phenotype, isolated from differentiated hepatoma cells, cease to accumulate all transcripts coding for hepatic functions but nevertheless maintain expression of HNF4 and HNF1. Transitory transfection experiments indicate that these two factors present in these cells have transcriptional activity similar to that of differentiated hepatoma cells. Characterization of the appropriate intertypic cell hybrids demonstrates that this new phenotype is recessive to the dedifferentiated state and fails to be complemented by differentiated cells. These results indicate the existence of mechanisms that inhibit transcription of genes coding for hepatocyte functions in spite of the presence of functional HNF4 and HNF1. Cells of the uncoupled phenotype present certain properties of oval cells described for pathological states of the liver. PMID:9343392

  20. Effects of polysaccharide ginsan from Panax ginseng on liver function

    Microsoft Academic Search

    Jie-Young Song; Medea Akhalaia; Alexander Platonov; Hyung-Doo Kim; In-Sung Jung; Young-Soo Han; Yeon-Sook Yun

    2004-01-01

    Ginsan, a polysaccharide isolated fromPanax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-?, IL-1? IL-2, IL-6, IL-12,\\u000a IFN-? and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1st-5th days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme

  1. Alanine Racemase Mutants of Burkholderia pseudomallei and Burkholderia mallei and Use of Alanine Racemase as a Non-Antibiotic-Based Selectable Marker

    PubMed Central

    Zajdowicz, Sheryl L. W.; Jones-Carson, Jessica; Vazquez-Torres, Andres; Jobling, Michael G.; Gill, Ronald E.; Holmes, Randall K.

    2011-01-01

    Burkholderia pseudomallei and Burkholderia mallei are category B select agents and must be studied under BSL3 containment in the United States. They are typically resistant to multiple antibiotics, and the antibiotics used to treat B. pseudomallei or B. mallei infections may not be used as selective agents with the corresponding Burkholderia species. Here, we investigated alanine racemase deficient mutants of B. pseudomallei and B. mallei for development of non-antibiotic-based genetic selection methods and for attenuation of virulence. The genome of B. pseudomallei K96243 has two annotated alanine racemase genes (bpsl2179 and bpss0711), and B. mallei ATCC 23344 has one (bma1575). Each of these genes encodes a functional enzyme that can complement the alanine racemase deficiency of Escherichia coli strain ALA1. Herein, we show that B. pseudomallei with in-frame deletions in both bpsl2179 and bpss0711, or B. mallei with an in-frame deletion in bma1575, requires exogenous d-alanine for growth. Introduction of bpsl2179 on a multicopy plasmid into alanine racemase deficient variants of either Burkholderia species eliminated the requirement for d-alanine. During log phase growth without d-alanine, the viable counts of alanine racemase deficient mutants of B. pseudomallei and B. mallei decreased within 2 hours by about 1000-fold and 10-fold, respectively, and no viable bacteria were present at 24 hours. We constructed several genetic tools with bpsl2179 as a selectable genetic marker, and we used them without any antibiotic selection to construct an in-frame ?flgK mutant in the alanine racemase deficient variant of B. pseudomallei K96243. In murine peritoneal macrophages, wild type B. mallei ATCC 23344 was killed much more rapidly than wild type B. pseudomallei K96243. In addition, the alanine racemase deficient mutant of B. pseudomallei K96243 exhibited attenuation versus its isogenic parental strain with respect to growth and survival in murine peritoneal macrophages. PMID:21720554

  2. cDNA cloning, expression, purification, distribution, and characterization of biologically active canine alanine aminotransferase-1

    Microsoft Academic Search

    Francis Rajamohan; Linda Nelms; Diane L. Joslin; Bin Lu; William J. Reagan; Michael Lawton

    2006-01-01

    Alanine aminotransferase (ALT) is a pyridoxal enzyme found mainly in the liver and kidney, but also in small amounts in the heart, muscle, fat, and brain. Serum aminotransferase activities have been used broadly as surrogate markers for tissue injury and disease in human and veterinary clinical settings and in safety assessment of chemicals and pharmaceuticals. Because of its relative abundance

  3. 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 patients.

  4. Effect on liver function of acetonaemia and the fat cow syndrome in cattle.

    PubMed

    West, H J

    1990-03-01

    The effect of fatty infiltration on liver function was studied in 29 dairy cows aged 6 +/- 0.4 (SEM) years with primary acetonaemia, secondary acetonaemia or the fat cow syndrome. The average interval from calving at diagnosis was 16.4 +/- 2.0 days and the animals had been anorexic for a mean of 5.6 +/- 0.8 days. Fatty infiltration of the liver occurred well before calving and was associated with severe clinical illness and intercurrent infections. The percentage of fatty infiltration in the liver (mean 53.1 +/- 2.8 per cent) was significantly correlated with both the degree of clinical illness (P less than 0.001) and the period of anorexia (P less than 0.05). Alterations in uptake, conjugation and excretion at the hepatocyte level were determined by measuring bromsulphthalein clearance, and plasma total bilirubin and total bile acid concentrations. Values for all three were positively correlated with the extent of fatty infiltration. Plasma albumin, urea and glucose concentrations were reliable indicators of the liver's synthetic function and together with plasma aspartate aminotransferase, iditol and glutamate dehydrogenase were correlated with the degree of hepatic lipidosis. PMID:2333429

  5. Probing alanine transaminase catalysis with hyperpolarized 13CD3-pyruvate

    PubMed Central

    Barb, A.W.; Hekmatyar, S.K.; Glushka, J.N.; Prestegard, J.H.

    2013-01-01

    Hyperpolarized metabolites offer a tremendous sensitivity advantage (>104 fold) when measuring flux and enzyme activity in living tissues by magnetic resonance methods. These sensitivity gains can also be applied to mechanistic studies that impose time and metabolite concentration limitations. Here we explore the use of hyperpolarization by dissolution dynamic nuclear polarization (DNP) in mechanistic studies of alanine transaminase (ALT), a well-established biomarker of liver disease and cancer that converts pyruvate to alanine using glutamate as a nitrogen donor. A specific deuterated, 13C-enriched analog of pyruvic acid, 13C3D3-pyruvic acid, is demonstrated to have advantages in terms of detection by both direct 13C observation and indirect observation through methyl protons introduced by ALT-catalyzed H–D exchange. Exchange on injecting hyperpolarized 13C3D3-pyruvate into ALT dissolved in buffered 1H2O, combined with an experimental approach to measure proton incorporation, provided information on mechanistic details of transaminase action on a 1.5 s timescale. ALT introduced, on average, 0.8 new protons into the methyl group of the alanine produced, indicating the presence of an off-pathway enamine intermediate. The opportunities for exploiting mechanism-dependent molecular signatures as well as indirect detection of hyperpolarized 13C3-pyruvate and products in imaging applications are discussed. PMID:23357427

  6. Chronic carriers of hepatitis B virus in Bangladesh: a comparative analysis of HBV-DNA, HBeAg/anti-HBe, and liver function tests.

    PubMed

    Hasan, K N; Rumi, M A K; Hasanat, M A; Azam, M G; Ahmed, S; Salam, M A; Islam, L N; Hassan, M S

    2002-03-01

    Serological markers of hepatitis B virus (HBV), liver function tests and quantitative estimation of HBV-DNA are important in the assessment of the state of infection and prognosis following treatment for hepatitis B. This study aimed to determine whether low-cost assays, eg hepatitis B e antigen (HBeAg) and liver function tests, could be used for the assessment of infectivity as an alternative to HBV-DNA estimation. We tested 125 hepatitis B carriers for HBeAg, antibody to HBeAg (anti-HBe), and serum HBV-DNA; we also carried out a range of standard liver function tests. Seventy-three subjects were positive and 52 were negative for HBeAg. Of the HBeAg positive cases, 3 were also positive for anti-HBe; of the HBeAg negative cases, 5 were also negative for anti-HBe. Of these 8 cases, 7 had no detectable HBV-DNA. Most of the HBeAg positive but anti-HBe negative subjects were positive for HBV-DNA (74.3%; 52/ 70) whereas most of the HBeAg negative and anti-HBe positive subjects (93.6%; 44/47) were also negative for HBV-DNA. Of 56 HBV-DNA positive individuals, alanine transaminase (ALT) was found to be raised in 69.6% (p=0.066) and aspartate transaminase (AST) was raised in 66.1% (p=0.011), while 67.9% had normal alkaline phosphatase (ALP) (p=0.054). HBeAg (p=0.018) and raised ALT (p=0.008) were found to be independent predictors for HBV-DNA positivity among HBV carriers. This study suggests that HBeAg positive and anti-HBe negative hepatitis B carriers with raised ALT and AST are likely to be positive for HBV-DNA; the combination of routine serology and biochemical tests may be considered as an alternative to HBV-DNA in evaluating the state of chronic HBV infection. However, HBV-DNA should be specifically assessed if discordance is observed between seromarkers and transaminases. PMID:12118438

  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. [Department of Diagnostic Radiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120Heidelberg (Germany); Sauer, P. [Department of Gastroenterology, University of Heidelberg, Heidelberg (Germany); Richter, G.M. [Department of Diagnostic Radiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120Heidelberg (Germany)

    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. Investigation on liver function among population in high background of rare earth area in South China

    Microsoft Academic Search

    Weifang Zhu; Suqin Xu; Pinpin Shao; Hui Zhang; Donseng Wu; Wenjia Yang; Jia Feng; Lei Feng

    2005-01-01

    The health effects of long-term ingestion of rare earth elements (REEs) on the villagers living in high-REE-background areas\\u000a in South Jangxi Province, China were studied. Major health complaints from the REE area population included indigestion, diarrhea,\\u000a abdominal distension, anorexia, weakness, and fatigue, especially after high-fat or high-protein intake. Liver function tests\\u000a were conducted for adult villagers. Among them, 45 live

  9. Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers

    PubMed Central

    Aurich1, Ines; Mueller1, Lutz P; Aurich, Hendryk; Luetzkendorf, Jana; Tisljar, Kai; Dollinger, Matthias M; Schormann, Wiebke; Walldorf, Jens; Hengstler, Jan G; Fleig, Wolfgang E; Christ, Bruno

    2007-01-01

    Aims At present, clinical success of hepatocyte transplantation as an alternative to whole liver transplantation is hampered by the limited availability of suitable donor organs for the isolation of transplantable hepatocytes. Hence, novel cell sources are required to deliver hepatocytes of adequate quality for clinical use. Mesenchymal stem cells (MSCs) from human bone marrow may have the potential to differentiate into hepatocytes in vitro and in vivo. Methods Isolated MSCs were selected by density gradient centrifugation and plastic adherence, differentiated in the presence of human hepatocyte growth medium and transplanted in immunodeficient Pfp/Rag2 mice. Results Here, we demonstrate that human MSCs gain in vitro the characteristic morphology and function of hepatocytes in response to specified growth factors. Specifically, preconditioned MSCs store glycogen, synthesise urea and feature the active hepatocyte?specific gene promoter of phosphoenolpyruvate carboxykinase (PCK1). After transplantation into livers of immunodeficient mice, preconditioned MSCs engraft predominantly in the periportal portion of the liver lobule. In situ, the cells continue to store glycogen and express PCK1, connexin32, albumin and the human hepatocyte?specific antigen HepPar1, indicating that the transplanted cells retain prominent qualities of hepatocytes after their regional integration. Conclusion MSCs derived from human bone marrow may serve as a novel source for the propagation of hepatocyte?like cells suitable for cell therapy in liver diseases. PMID:16928726

  10. Frostbite of the liver: an unrecognized cause of primary non-function?

    PubMed

    Potanos, Kristina; Kim, Heung Bae

    2014-02-01

    Appropriate hypothermic packaging techniques are an essential part of organ procurement. We present a case in which deviation from standard packaging practice may have caused sub-zero storage temperatures during transport, resulting in a clinical picture resembling PNF. An 18-month-old male with alpha-1-antitrypsin deficiency underwent liver transplant from a size-matched pediatric donor. Upon arrival at the recipient hospital, ice crystals were noted in the UW solution. The transplant proceeded uneventfully with short ischemia times. Surprisingly, transaminases, INR, and total bilirubin were markedly elevated in the postoperative period but returned to near normal by discharge. Follow-up of over five yr has demonstrated normal liver function. Upon review, it was discovered that organ packaging during recovery included storage in the first bag with only 400 mL of UW solution, and pure ice in the second bag instead of slush. This suggests that the postoperative delayed graft function was related to sub-zero storage of the graft during transport. This is the first report of sub-zero cold injury, or frostbite, following inappropriate packaging of an otherwise healthy donor liver. The clinical picture closely resembled PNF, perhaps implicating this mechanism in other unexpected cases of graft non-function. PMID:24384052

  11. Spectrophotometric readout for an alanine dosimeter for food irradiation applications

    NASA Astrophysics Data System (ADS)

    Ebraheem, S.; Beshir, W. B.; Eid, S.; Sobhy, R.; Kovács, A.

    2003-06-01

    The alanine-electron spin resonance (EPR) readout system is well known as a reference and transfer dosimetry system for the evaluation of high doses in radiation processing. The high cost of an EPR/alanine dosimetry system is a serious handicap for large-scale routine application in irradiation facilities. In this study, the use of a complex produced by dissolving irradiated L-alanine in 1,4-phenyl diammonium dichloride solution was investigated for dosimetry purposes. This complex—having a purple colour—has an increasing absorbance with increasing dose in the range of 1-20 kGy. The applicability of spectrophotometric evaluation was studied by measuring the absorbance intensity of this complex at 360 and 505 nm, respectively. Fluorimetric evaluation was also investigated by measuring the emission of the complex at 435 nm as a function of dose. The present method is easy for routine application. The effect of the dye concentration as well as the suitable amount of irradiated alanine has been studied. With respect to routine application, the stability of the product complex after its formation was also investigated.

  12. 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

  13. Functional Proteomics Study Reveals SUMOylation of TFII-I is Involved in Liver Cancer Cell Proliferation.

    PubMed

    Tu, Jun; Chen, Yalan; Cai, Lili; Xu, Changming; Zhang, Yang; Chen, Yanmei; Zhang, Chen; Zhao, Jian; Cheng, Jinke; Xie, Hongwei; Zhong, Fan; He, Fuchu

    2015-06-01

    SUMOylation has emerged as a new regulatory mechanism for proteins involved in multiple physiological and pathological processes. However, the detailed function of SUMOylation in liver cancer is still elusive. This study reveals that the SUMOylation-activating enzyme UBA2 is highly expressed in liver cancer cells and clinical samples. Silencing of UBA2 expression could to some extent suppress cell proliferation. To elucidate the function of UBA2, we used a large scale proteomics strategy to identify SUMOylation targets in HepG2 cells. We characterized 827 potential SUMO1-modified proteins that were not present in the control samples. These proteins were enriched in gene expression processes. Twelve candidates were validated as SUMO1-modified proteins by immunoprecipitation-Western blotting. We further characterized SUMOylated protein TFII-I that was identified in this study and determined that TFII-I was modified by SUMO1 at K221 and K240. PIAS4 was an E3 ligase for TFII-I SUMOylation, and SENP2 was responsible for deSUMOylating TFII-I in HepG2 cells. SUMOylation reduced TFII-I binding to its repressor HDAC3 and thus promoted its transcriptional activity. We further show that SUMOylation is critical for TFII-I to promote cell proliferation and colony formation. Our findings contribute to understanding the role of SUMOylation in liver cancer development. PMID:25869096

  14. 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. PMID:24894115

  15. A case of Hodgkin’s lymphoma with severely impaired liver function treated successfully with gemcitabine followed by ABVD

    PubMed Central

    Chakraborty, Rajshekhar; Mukkamalla, Shiva Kumar Reddy; Gutzmore, Garfield; Chan, Hon Cheung

    2015-01-01

    Hodgkin’s lymphoma (HL) originates from clonal B cells and is the most common malignancy in the second decade of life. Liver involvement is uncommon at presentation in patients with HL and there is a paucity of data for treatment of patients with severely impaired liver function. We present an unusual case of HL with severe hepatic impairment, splenomegaly and multiple chromosomal abnormalities that was treated initially with gemcitabine and steroids. Once liver function tests improved, six cycles of Adriamycin, bleomycin, vinblastine, and dacarbazine were administered. The patient remains in remission at 3.5 years of follow-up. PMID:25848330

  16. Effects of alanine aminotransferase inhibition on the intermediary metabolism in Sparus aurata through dietary amino-oxyacetate supplementation.

    PubMed

    González, Juan D; Caballero, Albert; Viegas, Ivan; Metón, Isidoro; Jones, John G; Barra, Joana; Fernández, Felipe; Baanante, Isabel V

    2012-06-01

    In liver, through the reaction catalysed by alanine aminotransferase (ALT), alanine becomes an effective precursor for gluconeogenesis. In the present study amino-oxyacetate (AOA) was used to evaluate its effect on liver ALT activity of the carnivorous fish Sparus aurata. Moreover, the derived metabolic effects on metabolites and other key enzymes of glycolysis, gluconeogenesis and the pentose phosphate pathway were also studied. A dose-effect-dependent inhibition of AOA on hepatic cytosolic and mitochondrial ALT activity was observed in vitro. In vivo, AOA behaved as an inhibitor of hepatic cytosolic ALT activity. A long-term exposure to AOA increased pyruvate kinase activity in the liver irrespective of the composition of the diet supplied to fish. 1H NMR studies showed that inclusion of AOA to the diet decreased the hepatic levels of alanine, glutamate and glycogen. Moreover, 2H NMR analysis indicated a higher renewal rate for alanine in the liver of fish fed with a high-carbohydrate/low-protein diet, while AOA decreased alanine 2H-enrichment irrespective of the diet. The present study indicates that AOA-dependent inhibition of the cytosolic ALT activity could help to increase the use of dietary carbohydrate nutrients. PMID:22018819

  17. Liver response to indomethacin-induced intestinal injury.

    PubMed

    Cervinková, Zuzana; Radvaková, Dagmar; Kohout, Pavel

    2002-01-01

    The aim of our study was to evaluate the impact of impaired barrier function of the small intestine induced by indomethacin on biochemical markers of liver damage (serum levels of alanine aminotransferase, aspartate aminotransferase, bilirubin), and liver functional parameters (serum concentration of albumin, liver DNA synthesis). Indomethacin (Sigma) was administered in 2 injections in a dose of 7.5 mg/kg subcutaneously spaced 24 hours apart, rats were sacrificed 24, 48 or 72 hours after the second dose of indomethacin. Control rats received indomethacin vehicle (5% NaHCO3, pH 7.4, 1.0 ml/kg) in the same manner. Small intestine injury was approved by increased permeability (measured as a lactulose-mannitol index). Significant increase of small intestine DNA synthesis (estimated by incorporation of 3H thymidine) in indomethacin-treated rats 48 (p < 0.01) and 72 (p < 0.05) hours after the second dose of indomethacin documents induction of reparative process. All biochemical markers of liver injury were significantly decreased in indomethacin treated rats in all recorded intervals (p < 0.05). By contraries, serum concentration of albumin, which predicates about liver function, was in indomethacin-treated rats significantly decreased in all intervals (p < 0.01). To explain these contrarious results of indomethacin-induced impaired barrier function of the small intestine on the liver deserves further studies. PMID:12143106

  18. Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation

    PubMed Central

    Arshad, Freeha; Adelmeijer, Jelle; Blokzijl, Hans; van den Berg, Aad; Porte, Robert; Lisman, Ton

    2014-01-01

    Background: The long-term risk of thrombotic and vascular complications is elevated in liver transplant recipients compared to the general population. Patients with cirrhosis are in a hypercoagulable status during and directly after orthotopic liver transplantation, but it is unclear whether this hypercoagulability persists over time. Aim: We aimed to investigate the hemostatic status of liver transplant recipients one year after transplantation. Methods: We prospectively collected blood samples of 15 patients with a functioning graft one year after orthotopic liver transplantation and compared the hemostatic status of these patients with that of 30 healthy individuals. Results: Patients one year after liver transplantation had significantly elevated plasma levels of von Willebrand factor (VWF). Thrombin generation, as assessed by the endogenous thrombin potential, was decreased in patients, which was associated with increased plasma levels of the natural anticoagulants antithrombin and tissue factor pathway inhibitor.  Plasma fibrinolytic potential was significantly decreased in patients and correlated inversely with levels of plasminogen activator inhibitor-1. Conclusion: One year after liver transplantation, liver graft recipients have a dysregulated hemostatic system characterised by elevation of plasma levels of endothelial-derived proteins. Increased levels of von Willebrand factor and decreased fibrinolytic potential may (in part) be responsible for the increased risk for vascular disease seen in liver transplant recipients. PMID:25285204

  19. Alanine germination receptors of Bacillus subtilis.

    PubMed

    McCann, K P; Robinson, C; Sammons, R L; Smith, D A; Corfe, B M

    1996-11-01

    The alanine-stimulated spore germination responses of Bacillus subtilis 168 have been dissected by combining physiological and genetical approaches. From the analyses the authors infer that there are three classes of alanine response. Two of the responses are mediated via the GerA proteins, with and without germinal adjuncts, the third is mediated via the GerB proteins and obligately requires adjuncts. PMID:8987707

  20. Comparison of the liver function and hepatic specific genes expression in cultured mesenchymal stem cells and hepatocytes

    PubMed Central

    Nikoozad, Zahra; Ghorbanian, Mohammad Taghi; Rezaei, Arezou

    2014-01-01

    Objective(s): Stem cell therapy is believed to be as a promising treatment strategy for tissue repair and regeneration. The plasticity specification of the adult stem cells, such as MSCs, has enabled that these cells to be used in the treatment of a broad spectrum of diseases like liver disorders. In this study, the production of urea and Albumin (Alb), glycogen storage, and expression of some liver genes including ?-fetoprotein (AFP), Alb, cytokeratin18 (CK18) and cytokeratin19 (CK19) was compared between mesenchymal stem cells (MSCs) and isolated rat hepatocytes. Materials and Methods: The MSCs were isolated from rat femurs and tibias and cultured in ?-MEM, DMEM and RPMI mediums supplemented with serum. Hepatocytes were isolated from Rat livers and cultured in DMEM with serum. The expression of AFP, Alb, CK18, and CK19 genes was evaluated using the reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, the synthesis of albumin and urea of the cells was measured. Results: In vitro conditions, MSCs and hepatocytes exhibited the characteristic functions of the liver such as capacity to synthesize Alb, urea, the storage of glycogen. In this study, the expression of some liver genes such as AFP, Alb, CK18 and CK19 at mRNA levels was also shown. Conclusion: The results showed that MSCs exhibited some liver functions, and may be considered as an alternative source for adult stem cell transplantation in liver repair due to the excellent proliferation and differentiation capacities. PMID:24592304

  1. Suppression of intralysosomal proteolysis aggravates structural damage and functional impairment of liver lysosomes in rats with toxic hepatitis

    SciTech Connect

    Korolenko, T.A.; Gavrilova, N.I.; Kurysheva, N.G.; Malygin, A.E.; Pupyshev, A.B.

    1986-01-01

    This paper estimates the effect of lowering protein catabolism in the lysosomes on structural and functional properties of the latter during liver damage. For comparison, polyvinylpyrrolidone (PVP), which is inert relative to intralysosomal proteolysis, and which also accumulates largely in lysosomes of the kupffer cells of the liver, was used. The uptake of labeled bovine serum albuman (C 14-BSA) by the liver is shown and the rate of intralysosomal proteolysis is given 24 hours after administration of suramin an CCl/sub 4/ to rats. It is suggested that it is risky to use drugs which inhibit intralysosomal proteolysis in the treatment of patients with acute hepatitis.

  2. CEPP regimen (cyclophosphamide, etoposide, procarbazine and prednisone) as initial treatment for Hodgkin lymphoma patients presenting with severe abnormal liver function

    PubMed Central

    2014-01-01

    ABVD regimen (doxorubicin, bleomycin, vinblastine and dacarbazine) remains the most commonly used front-line therapy for Hodgkin lymphoma. However, atypical and extranodal presentations present challenges to initial therapy, especially in the presence of renal and liver failure. We hereby present two cases of young male patients with atypical presentation of Hodgkin lymphoma with severe abnormal liver function. Patients showed excellent response to cyclophosphamide, etoposide, procarbazine and prednisone (CEPP regimen). PMID:24991411

  3. Functions of anaphylatoxin C5a in rat liver: direct and indirect actions on nonparenchymal and parenchymal cells

    Microsoft Academic Search

    Henrike L Schieferdecker; Gerald Schlaf; Kurt Jungermann; Otto Götze

    2001-01-01

    Growing evidence obtained in recent years indicates that anaphylatoxin C5a receptors (C5aR) are not restricted to myeloid cells but are also expressed on nonmyeloid cells in different tissues such as brain, lung, skin and liver. In contrast to its well-defined systemic functions, the actions of anaphylatoxins in these organs are poorly characterized. The liver can be a primary target organ

  4. Primary hepatocytes outperform Hep G2 cells as the source of biotransformation functions in a bioartificial liver.

    PubMed Central

    Nyberg, S L; Remmel, R P; Mann, H J; Peshwa, M V; Hu, W S; Cerra, F B

    1994-01-01

    OBJECTIVE: Metabolic activity of transformed human liver (Hep G2) cells and primary rat hepatocytes were compared during in vitro application of a gel entrapment bioartificial liver. BACKGROUND: Clinical trials of bioartificial liver devices containing either transformed liver cells or primary hepatocytes have been initiated. A study comparing transformed liver cells and primary hepatocytes in a bioartificial liver under similar conditions has not been reported previously. METHODS: Gel entrapment bioartificial liver devices were inoculated with 100 million cells, Hep G2 cell line (n = 4), or rat hepatocytes (n = 16), and studied for up to 60 days of in vitro cultivation. RESULTS: Hep G2 cells grew to confluence within the gel entrapment configuration with a doubling time of 20 +/- 3 hours. Rat hepatocytes significantly outperformed Hep G2 cells at confluence in all categories of biotransformation, including ureagenesis (3.5 +/- 0.7 vs. 0.3 +/- 0.1 mumol/hr, p < 0.05), glucuronidation (630 +/- 75 vs. 21 +/- 2 nmol/hr, p < 0.005), sulfation (59 +/- 13 vs. 5 +/- 2 nmol/hr, p < 0.05), and oxidation (233 +/- 38 vs. < 1 nmol/hr, p < 0.005). At the conclusion of one experiment, Hep G2 cells were found in the extracapillary compartment of the bioartificial liver, analogous to the patient's compartment during clinical application. CONCLUSIONS: Primary rat hepatocytes were superior to the Hep G2 cell line as the source of hepatic function in a bioartificial liver and avoided the potential risk of tumor transmigration from the bioartificial liver into the patient's circulation. Images Figure 1. Figure 3. PMID:8024360

  5. Preparation of L-Alanine Crystals Containing Gold Nanoparticles

    Microsoft Academic Search

    Masako Koyama; Masaharu Shiraishi; Koji Sasaki; Kijiro Kon-no

    2008-01-01

    Amino acids provide useful foods, medicines, health foods, and nutritional supplements. We studied the morphology control of alanine, an amino acid. We also studied the effects of amino acid addition on the dispersion stability of gold nanoparticles. We then studied hybridization between alanine crystals and arginine-capped gold nanoparticles. Alanine crystal growth in a supersaturated alanine solution was found to increase

  6. Impaired functional capacity in potential liver transplant candidates predicts short-term mortality before transplantation.

    PubMed

    Ow, Maggie M G; Erasmus, Paul; Minto, Gary; Struthers, Richard; Joseph, Moby; Smith, Aileen; Warshow, Usama M; Cramp, Matthew E; Cross, Tim J S

    2014-09-01

    Liver transplantation (LT) is a lifesaving treatment. Because of the shortage of donor organs, some patients will not survive long enough to receive a transplant. The identification of LT candidates at increased risk of short-term mortality without transplantation may affect listing decisions. Functional capacity, determined with cardiopulmonary exercise testing (CPET), is a measure of cardiorespiratory reserve and predicts perioperative outcomes. This study examined the association between functional capacity and short-term survival before LT and the potential for CPET to predict 90-day mortality without transplantation. A total of 176 patients who were assessed for nonacute LT underwent CPET. Ninety days after the assessment, 10 of the 164 patients who had not undergone transplantation were deceased (mortality rate?=?6.1%). According to a comparison of survivors and nonsurvivors, the Model for End-Stage Liver Disease score, UK Model for End-Stage Liver Disease (UKELD) score, age, anaerobic threshold, and peak oxygen uptake (VO(2)) were significant univariate predictors of 90-day mortality without transplantation, but only the UKELD score and peak VO(2) retained significance in a multivariate analysis. The mean peak VO(2) was significantly lower for nonsurvivors versus survivors (15.2?±?3.3 versus 21.2?±?5.3 mL/minute/kg, P??17.6 mL/minute/kg died (P?=?0.03). In conclusion, patients assessed for LT with an impaired functional capacity have poorer short-term survival; this is particularly true for individuals with worse liver disease severity. PMID:24805969

  7. Relations between liver cadmium, cumulative exposure, and renal function in cadmium alloy workers.

    PubMed Central

    Mason, H J; Davison, A G; Wright, A L; Guthrie, C J; Fayers, P M; Venables, K M; Smith, N J; Chettle, D R; Franklin, D M; Scott, M C

    1988-01-01

    Detailed biochemical investigations of renal function were made on 75 male workers exposed to cadmium and an equal number of referents matched for age, sex, and employment status. The exposed group consisted of current and retired workers who had been employed in the manufacture of copper-cadmium alloy at a single factory in the United Kingdom for periods of up to 39 years and for whom cumulative cadmium exposure indices could be calculated. In vivo measurements of liver and kidney cadmium burden were made on exposed and referent workers using a transportable neutron activation analysis facility. Significant increases in the urinary excretion of albumin, retinol binding protein, beta 2 microglobulin, N-acetylglucosaminidase (NAG), alkaline phosphatase, gamma-glutamyl transferase and significant decreases in the renal reabsorption of calcium, urate, and phosphate were found in the exposed group compared with the referent group. Measures of glomerular filtration rate (GFR) (creatinine clearance, serum creatinine, and beta 2 microglobulin) indicated a reduction in GFR in the exposed population. Many of these tubular and glomerular function indicators were significantly correlated with both cumulative exposure index and liver cadmium burden. Using cumulative exposure index and liver cadmium as estimates of dose, a two phase linear regression model was applied to identify an inflection point signifying a threshold level above which changes in renal function occur. Many biochemical variables fitted this model; urinary total protein, retinol binding protein, albumin, and beta 2 microglobulin gave similar inflection points at cumulative exposure levels of about 1100 y.micrograms/m3 whereas changes in the tubular reabsorption of urate and phosphate occurred at higher cumulative exposure indices. Measures of GFR, although fitting the threshold model did not give well defined inflection points. Fewer variables fitted the two phase model using liver cadmium; those that did gave threshold levels in the range 20.3-55.1 ppm. When cadmium workers with cumulative exposure indices of less than 1100 y.micrograms/m3 were compared with their respective referents only serum beta 2 microglobulin and urinary NAG were significantly increased in the exposed group and these differences were not related to the degree of cadmium exposure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3219304

  8. Deletion of Smad2 in Mouse Liver Reveals Novel Functions in Hepatocyte Growth and Differentiation

    PubMed Central

    Ju, Wenjun; Ogawa, Atsushi; Heyer, Joerg; Nierhof, Dirk; Yu, Liping; Kucherlapati, Raju; Shafritz, David A.; Böttinger, Erwin P.

    2006-01-01

    Smad family proteins Smad2 and Smad3 are activated by transforming growth factor ? (TGF-?)/activin/nodal receptors and mediate transcriptional regulation. Although differential functional roles of Smad2 and Smad3 are apparent in mammalian development, the relative functional roles of Smad2 and Smad3 in postnatal systems remain unclear. We used Cre/loxP-mediated gene targeting for hepatocyte-specific deletion of Smad2 (S2HeKO) in adult mice and generated hepatocyte-selective Smad2/Smad3 double knockouts by intercrossing AlbCre/Smad2f/f (S2HeKO) and Smad3-deficient Smad3ex8/ex8 (S3KO) mice. All strains were viable and had normal adult liver. However, necrogenic CCL4-induced hepatocyte proliferation was significantly increased in S2HeKO compared to Ctrl and S3KO livers, and transplanted S2HeKO hepatocytes repopulated recipient liver at dramatically increased rates compared to Ctrl hepatocytes in vivo. Using primary hepatocytes, we found that TGF-?-induced G1 arrest, apoptosis, and epithelial-to-mesenchymal transition in Ctrl and S2HeKO but not in S3KO hepatocytes. Interestingly, S2HeKO cells spontaneously acquired mesenchymal features characteristic of epithelial-to-mesenchymal transition (EMT). Collectively, these results demonstrate that Smad2 suppresses hepatocyte growth and dedifferentiation independent of TGF-? signaling. Smad2 is not required for TGF-?-stimulated apoptosis, EMT, and growth inhibition in hepatocytes. PMID:16382155

  9. Extracorporeal liver support.

    PubMed

    Leckie, Pamela; Davenport, Andrew; Jalan, Rajiv

    2012-01-01

    Mortality of patients with liver failure remains unacceptably high. As the liver has an enormous potential to regenerate, extracorporeal liver support devices may allow patients with liver failure to be bridged to recovery. Alternatively, liver assist may allow patients with advanced liver disease to be managed until a suitable organ for transplant is available. Current approaches to liver support include the use of biological devices that contain hepatocytes and those that function as detoxification devices, and artificial liver support systems. This review describes the current state of the art and existing data on the use of these devices to treat patients with liver failure. PMID:23095415

  10. Concomitant hepatic radiation and intraarterial fluorinated pyrimidine therapy: Correlation of liver scan, liver function tests, and plasma CEA with tumor response

    SciTech Connect

    Lokich, J. (New England Deaconess Hospital, Boston, MA); Kinsella, T.; Perri, J.; Malcolm, A.; Clouse, M.

    1981-12-15

    Sixteen patients with metastatic disease to the liver (12 colorectal and four unknown primary tumors) were treated in a pilot study of hepatic irradiation (2500-3000 rads in 10-12 fractions) delivered concomitantly with continuous short-term intraarterial infusion of 5-fluorouracil (1 g/d) or FUDR (0.5 mg/kg/d) via a percutaneously placed hepatic artery catheter. Abnormal liver function tests, including SGOT, LDH, and alkaline phosphatase, decreased in all patients by day 7-10 of treatment, and other metabolic factors, including serum cholesterol, calcium, albumin, phosphorous, and uric acid, also decreased, often to subnormal levels by termination of treatment (day 15-20). These chemical alterations did not correlate with tumor response in that the identical pattern was observed in responders (ten patients) as well as nonresponders (six patients). Objective determinants of response were assessed by serial monitoring of plasma carcinoembryonic antigen (CEA) and liver scan. In 14 patients with elevated CEA levels, tumor response (nine patients), nonresponse (four patients), and relapse (five patients) was predicted and confirmed by sequential monitoring of CEA. In one patient, a paradoxical decrease in plasma CEA was associated with progressive disease. The liver scan identified all responding patients but was difficult to quantitate and was delayed for months following subjective clinical response and changes in plasma CEA levels.

  11. Concomitant hepatic radiation and intraarterial fluorinated pyrimidine therapy: correlation of liver scan, liver function tests, and plasma CEA with tumor response

    SciTech Connect

    Lokich, J.; Kinsella, T.; Perri, J.; Malcolm, A.; Clouse, M.

    1981-12-15

    Sixteen patients with metastatic disease to the liver (12 colorectal and four unknown primary tumors) were treated in a pilot study of hepatic irradiation (2500-3000 rads in 10-12 fractions) delivered concomitantly with continuous short-term intraarterial infusion of 5-fluorouracil (1 g/d) or FUDR (0.5 mg/kg/d) via a percutaneously placed hepatic artery catheter. Abnormal liver function tests, including SGOT, LDH, and alkaline phosphatase, decreased in all patients by day 7-10 of treatment, and other metabolic factors, including serum cholesterol, calcium, albumin, phosphorous, and uric acid, also decreased, often to subnormal levels by termination of treatment (day 15-20). These chemical alterations did not correlate with tumor response in that the identical pattern was observed in responders (ten patients) as well as nonresponders (six patients). Objective determinants of response were assessed by serial monitoring of the plasma carcinoembryonic antigen (CEA) and liver scan. In 14 patients with elevated CEA levels, tumor response (nine patients), nonresponse (four patients), and relapse (five patients) was predicted and confirmed by sequential monitoring of CEA. In one patient, a paradoxical decrease in plasma CEA was associated with progressive disease. The liver scan identified all responding patients but was difficult to quantitate and was delayed for months following subjective clinical response and changes in plasma CEA levels.

  12. Beneficial effects of ventromedial hypothalamus (VMH) lesioning on function and morphology of the liver after hepatectomy in rats.

    PubMed

    Lee, Eun Young; Inoue, Shuji; Senoo, Akira; Shimizu, Hiroyuki; Suzuki, Yoko; Ishizuka, Noriko; Imazeki, Nobuo; Sasaki, Kahoru; Kako, Masako; Osaka, Toshimasa; Miki, Takashi

    2011-11-01

    Liver has a high regenerative capacity and restores its mass and function shortly after partial hepatectomy through increased proliferation and metabolic modification of hepatocytes. The proliferation of hepatocytes can be triggered by its mass reduction after hepatectomy or by the neural factors including lesioning of the ventromedial hypothalamus (VMH). In the present study, we examined the effect of VMH lesioning on liver regeneration in hepatectomized rats by evaluating liver function and morphology. We found that functional deficits caused by partial hepatectomy [prolonged prothrombin time (PT), increased indocyanine green (ICG) retention, and decrease in PAS (periodic Acid-Schiff staining)-positive hepatocytes] were restored by VMH lesioning at 1 week after the surgery, whereas these alterations disappeared at 4 weeks. Morphologically, lipid microdroplets, which are considered to be important for maintaining contiguous liver function via supplying fuel for cell proliferation, were found to accumulate in hepatocytes of the hepatectomized rats at early period (1 day) after partial hepatectomy. Interestingly, such lipid microdroplets were also detected in the VMH lesioned rats and the more abundantly in the VMH lesioned, hepatectomized rats up to 1 week after the surgery. In conclusion, our results suggest that VMH lesioning in rats promotes recovery of liver anatomically and functionally after partial hepatectomy by promoting cell proliferation process. PMID:21962532

  13. Alanine Aminotransferase-Old Biomarker and New Concept: A Review

    PubMed Central

    Liu, Zhengtao; Que, Shuping; Xu, Jing; Peng, Tao

    2014-01-01

    Measurement of serum alanine aminotransferase (ALT) is a common, readily available, and inexpensive laboratory assay in clinical practice. ALT activity is not only measured to detect liver disease, but also to monitor overall health. ALT activity is influenced by various factors, including viral hepatitis, alcohol consumption, and medication. Recently, the impact of metabolic abnormalities on ALT variation has raised concern due to the worldwide obesity epidemic. The normal ranges for ALT have been updated and validated considering the metabolic covariates in the various ethnic districts. The interaction between metabolic and demographic factors on ALT variation has also been discussed in previous studies. In addition, an extremely low ALT value might reflect the process of aging, and frailty in older adults has been raised as another clinically significant feature of this enzyme, to be followed with additional epidemiologic investigation. Timely updated, comprehensive, and systematic introduction of ALT activity is necessary to aid clinicians make better use of this enzyme. PMID:25013373

  14. Gut-liver axis improves with meloxicam treatment after cirrhotic liver resection

    PubMed Central

    Hamza, Astrit R; Krasniqi, Avdyl S; Srinivasan, Pramod Kadaba; Afify, Mamdouh; Bleilevens, Christian; Klinge, Uwe; Tolba, René H

    2014-01-01

    AIM: To investigate the effect of meloxicam on the gut-liver axis after cirrhotic liver resection. METHODS: Forty-four male Wistar rats were assigned to three groups: (1) control group (CG); (2) bile duct ligation with meloxicam treatment (BDL + M); and (3) bile duct ligation without meloxicam treatment (BDL). Secondary biliary liver cirrhosis was induced via ligature of the bile duct in the BDL + M and BDL groups. After 2 wk, the animals underwent a 50% hepatectomy. In the BDL + M group 15 min prior to the hepatectomy, one single dose of meloxicam was administered. Parameters measured included: microcirculation of the liver and small bowel; portal venous flow (PVF); gastrointestinal (GI) transit; alanine aminotransferase (ALT); malondialdehyde; interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-?1) and hypoxia-inducible factor 1 alpha (HIF-1?) levels; mRNA expression of cyclooxigenase-2 (COX-2), IL-6 and TGF-?1; liver and small bowel histology; immunohistochemical evaluation of hepatocyte and enterocyte proliferation with Ki-67 and COX-2 liver expression. RESULTS: Proliferative activity of hepatocytes after liver resection, liver flow and PVF were significantly higher in CG vs BDL + M and CG vs BDL group (P < 0.05), whereas one single dose of meloxicam ameliorated liver flow and proliferative activity of hepatocytes in BDL + M vs BDL group. COX-2 liver expression at 24 h observation time (OT), IL-6 concentration and mRNA IL-6 expression in the liver especially at 3 h OT, were significantly higher in BDL group when compared with the BDL + M and CG groups (P < 0.01, P < 0.001, P < 0.01, respectively). Liver and small bowel histology, according to a semi quantitative scoring system, showed better integrity in BDL + M and CG as compared to BDL group. ALT release and HIF-1? levels at 1 h OT were significantly higher in BDL + M compared to CG and BDL group (P < 0.001 and P < 0.01, respectively). Moreover, ALT release levels at 3 and 24 h OT were significantly higher in BDL group compared to CG, P < 0.01. GI transit, enterocyte proliferative activity and number of goblet cells were in favor of meloxicam treatment vs BDL group (P < 0.05, P < 0.001, P < 0.01, respectively). Additionally, villus length were higher in BDL + M as compared to BDL group. CONCLUSION: One single dose of meloxicam administered after cirrhotic liver resection was able to cause better function and integrity of the remaining liver and small bowel. PMID:25356044

  15. Quantitative Proteomic and Functional Analysis of Liver Mitochondria from High Fat Diet (HFD) Diabetic Mice*

    PubMed Central

    Guo, Yurong; Darshi, Manjula; Ma, Yuliang; Perkins, Guy A.; Shen, Zhouxin; Haushalter, Kristofer J.; Saito, Rintaro; Chen, Ai; Lee, Yun Sok; Patel, Hemal H.; Briggs, Steven P.; Ellisman, Mark H.; Olefsky, Jerrold M.; Taylor, Susan S.

    2013-01-01

    Insulin resistance plays a major role in the development of type 2 diabetes and obesity and affects a number of biological processes such as mitochondrial biogenesis. Though mitochondrial dysfunction has been linked to the development of insulin resistance and pathogenesis of type 2 diabetes, the precise mechanism linking the two is not well understood. We used high fat diet (HFD)-induced obesity dependent diabetes mouse models to gain insight into the potential pathways altered with metabolic disease, and carried out quantitative proteomic analysis of liver mitochondria. As previously reported, proteins involved in fatty acid oxidation, branched chain amino acid degradation, tricarboxylic acid cycle, and oxidative phosphorylation were uniformly up-regulated in the liver of HFD fed mice compared with that of normal diet. Further, our studies revealed that retinol metabolism is distinctly down-regulated and the mitochondrial structural proteins—components of mitochondrial inter-membrane space bridging (MIB) complex (Mitofilin, Sam50, and ChChd3), and Tim proteins—essential for protein import, are significantly up-regulated in HFD fed mice. Structural and functional studies on HFD and normal diet liver mitochondria revealed remodeling of HFD mitochondria to a more condensed form with increased respiratory capacity and higher ATP levels compared with normal diet mitochondria. Thus, it is likely that the structural remodeling is essential to accommodate the increased protein content in presence of HFD: the mechanism could be through the MIB complex promoting contact site and crista junction formation and in turn facilitating the lipid and protein uptake. PMID:24030101

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

    NASA Astrophysics Data System (ADS)

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

    2005-05-01

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

  17. Development of a non-transformed human liver cell line with differentiated-hepatocyte and urea-synthetic functions: applicable for bioartificial liver.

    PubMed

    Yoon, J H; Lee, H V; Lee, J S; Park, J B; Kim, C Y

    1999-11-01

    There is a need to develop human hepatocyte cell lines which retain both replicating capacity and highly differentiated functions to facilitate the development of an efficient bioartificial liver. The present study was undertaken to differentiate, using sodium butyrate, the actively replicating immortalized human liver cell line. The effects of butyrate on cell growth and cell cycle were analyzed, and the albumin synthesis, cytochrome P450 and ammonia-detoxifying activity of the butyrate-treated cells were measured. Butyrate treatment resulted in G2/M arrest of the cell cycle and polygonal changes in the cell morphology. Neither the control nor the butyrate-treated cells showed transformed characteristics. Butyrate treatment increased the amount of albumin secretion, cytochrome P450 activity, and the urea production rate of the cells. The present study provides non-transformed human hepatocytes, which can replicate unlimitedly and then restore differentiated hepatocyte-specific functions by butyrate, and therefore, have applications for the development of an efficient bioartificial liver. PMID:10612305

  18. Association of elevated serum alanine aminotransferase with metabolic factors in obese children: sex-related analysis

    Microsoft Academic Search

    Procolo Di Bonito; Eduardo Sanguigno; Teresa Di Fraia; Claudia Forziato; Gabriella Boccia; Francesco Saitta; Maria Rosaria Iardino; Brunella Capaldo

    2009-01-01

    Alanine aminotransferase (ALT) elevations are considered a surrogate marker of nonalcoholic liver disease and predict later development of diabetes and metabolic syndrome in adults. The aim of the present study is to evaluate the prevalence of high ALT levels in obese children using updated and sex-related cutoff ALT value (ALT >30 IU\\/L for boys and >19 IU\\/L for girls). We

  19. Succinate and alanine as anaerobic end-products in the diving turtle ( Chrysemys picta bellii)

    Microsoft Academic Search

    L. T Buck

    2000-01-01

    The western painted turtle is an extremely anoxia-tolerant vertebrate capable of tolerating blood lactate levels of 150–200 mM. Since lactate increases to such high levels, other fermentation end-products such as succinate and alanine, which have not been previously measured in this species, might also be expected to increase. Therefore, I measured turtle heart, liver, and blood concentrations of lactate, succinate,

  20. Shaping macrophages function and innate immunity by bile acids: mechanisms and implication in cholestatic liver diseases.

    PubMed

    Calmus, Yvon; Poupon, Raoul

    2014-10-01

    The liver is selectively enriched in innate immune cells, macrophages (Kupffer cells), natural killer, and natural killer T cells. These cells release an array of mediators with cytotoxic, pro- and anti-inflammatory, angiogenic, fibrogenic, and mitogenic activity that function to fight infections, limit tissue injury, and promote wound healing. The diverse activity of macrophages is mediated by distinct subpopulations that develop in response to signals within their microenvironment. Understanding the mechanisms and role of the microenvironment contributing to modulation of macrophage populations is crucial for comprehension of the pathophysiology of liver injury in diverse conditions. Several studies initiated in the 1990s have shown that bile acids modulate innate and adaptive immunity. In the last decade, bile acids turned into hormones and signalling molecules involved in many metabolic and inflammatory processes. Biological properties of bile acids are thought to be mediated mainly through activation of the nuclear receptor FXR, the membrane receptor TGR5, as well as PK, ERK, MAP kinases signalling pathways. FXR and TGR5 agonists are currently under development for clinical purpose. This review analyses the mechanisms involved in the immunomodulatory effects of bile acids on the macrophage and discuss their implications in the pathophysiology of cholestasis, primary biliary cirrhosis and primary sclerosing cholangitis. PMID:25176586

  1. Analysis of Common and Specific Mechanisms of Liver Function Affected by Nitrotoluene Compounds

    PubMed Central

    Deng, Youping; Meyer, Sharon A.; Guan, Xin; Escalon, Barbara Lynn; Ai, Junmei; Wilbanks, Mitchell S.; Welti, Ruth; Garcia-Reyero, Natàlia; Perkins, Edward J.

    2011-01-01

    Background Nitrotoluenes are widely used chemical manufacturing and munitions applications. This group of chemicals has been shown to cause a range of effects from anemia and hypercholesterolemia to testicular atrophy. We have examined the molecular and functional effects of five different, but structurally related, nitrotoluenes on using an integrative systems biology approach to gain insight into common and disparate mechanisms underlying effects caused by these chemicals. Methodology/Principal Findings Sprague-Dawley female rats were exposed via gavage to one of five concentrations of one of five nitrotoluenes [2,4,6-trinitrotoluene (TNT), 2-amino-4,6-dinitrotoluene (2ADNT) 4-amino-2,6-dinitrotoulene (4ADNT), 2,4-dinitrotoluene (2,4DNT) and 2,6-dinitrotoluene (2,6DNT)] with necropsy and tissue collection at 24 or 48 h. Gene expression profile results correlated well with clinical data and liver histopathology that lead to the concept that hematotoxicity was followed by hepatotoxicity. Overall, 2,4DNT, 2,6DNT and TNT had stronger effects than 2ADNT and 4ADNT. Common functional terms, gene expression patterns, pathways and networks were regulated across all nitrotoluenes. These pathways included NRF2-mediated oxidative stress response, aryl hydrocarbon receptor signaling, LPS/IL-1 mediated inhibition of RXR function, xenobiotic metabolism signaling and metabolism of xenobiotics by cytochrome P450. One biological process common to all compounds, lipid metabolism, was found to be impacted both at the transcriptional and lipid production level. Conclusions/Significance A systems biology strategy was used to identify biochemical pathways affected by five nitroaromatic compounds and to integrate data that tie biochemical alterations to pathological changes. An integrative graphical network model was constructed by combining genomic, gene pathway, lipidomic, and physiological endpoint results to better understand mechanisms of liver toxicity and physiological endpoints affected by these compounds. PMID:21346803

  2. [Activity of the marker liver enzymes under the conditions of toxic hepatitis and alimentary deprivation of protein].

    PubMed

    Voloshchuk, O N; Kopyl'chuk, G P; Buchkovskaia, I M

    2014-01-01

    The activity of the sorbitoldehydrogenase (SDH), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the blood serum of rats with acetaminophen-induced hepatitis under the conditions of alimentary deprivation of protein was studied. The animals were divided into 3 groups: 1--rats with acute acetaminophen-induced hepatitis, maintained on the full ration; 2--rats with acute acetaminophen-induced hepatitis, maintained under the conditions of alimentary deprivation of protein; 3--control. The activity of the sorbitol dehydrogenase in blood serum was determined by the kinetic method, activity of the alanine aminotransferase and alkaline phosphatase - photometrically. It is shown, that in animals with the model hepatitis the activity of sorbitol dehydrogenase in blood serum increases 20-fold, wherein statistical significance between animals with hepatitis maintained under the conditions of full ration and those of low-protein diet is not established. In the group of animals with acetaminophen-induced hepatitis the preservation on the control level of the alkaline phosphatase activity on the base of the increase of alanine aminotransferase by 2.2 times and ratio ALT/ALP>5 testifies about hepatocellular liver injury. In the group of animals with drug-induced hepatitis and alimentary deprivation of protein, the increase of the alkaline phosphatase and alanine aminotransferase activity is observed, herewith the ratio ALT/ALP ranges from 2 to 5 and testifies about mixed liver injury. The conclusion was made, that alimentary deprivation of protein is the critical factor for the development of the disturbances of functional and structural liver integrity, and the therapeutic approaches to the correction of the drug-induced liver injury should be different depending on the value of protein ration in the anamnesis, taking into account the different types of liver injury. PMID:25911920

  3. Oroxylin A Accelerates Liver Regeneration in CCI4-Induced Acute Liver Injury Mice

    PubMed Central

    Chen, Yinqin; Zhang, Qingyu; Liu, Bin; Liu, Jie; Chen, Hege; Li, Mingyi

    2013-01-01

    Introduction Based on the previous research that oroxylin A can suppress inflammation, we investigated the hepatoprotective role of oroxylin A against CCl4-induced liver damage in mice and then studied the possible alteration of the activities of cytokine signaling participating in liver regeneration. Wild type (WT) mice were orally administrated with oroxylin A (60 mg/kg) for 4 days after CCl4 injection, the anti-inflammatory effects of oroxylin A were assessed directly by hepatic histology and indirectly by measuring serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Albumin. Proliferating cell nuclear antigen (PCNA) staining was performed to evaluate the role of oroxylin A in promoting hepatocyte proliferation. Serum IL-1?, TNF-?, IL-6 and IL-1Ra levels were measured by enzyme-linked immunosorbent assay (ELISA) and liver HGF, EGF, TNF-?, IL-6, IL-1Ra and IL-1? gene expression was determined by quantitative real-time PCR. The data indicated that the IL-6 and TNF-? mRNA of oroxylin A administered group significantly increased higher than the control within 12 hours after CCl4 treatment. Meanwhile, oroxylin A significantly enhanced the expression of IL-1Ra at the early phase, which indicated that oroxylin A could facilitate the initiating events in liver regeneration by increasing IL-1Ra which acts as an Acute-Phase Protein (APP). In addition, a lethal CCl4-induced acute liver failure model offers a survival benefit in oroxylin A treated WT mice. However, oroxylin A could not significantly improve the percent survival of IL-1RI?/? mice with a lethal CCl4-induced acute liver failure. Conclusions Our study confirmed that oroxylin A could strongly promote liver structural remodeling and functional recovery through IL-1Ra/IL-1RI signaling pathway. All these results support the possibility of oroxylin A being a therapeutic candidate for acute liver injury. PMID:23951204

  4. A paper-based multiplexed transaminase test for low-cost, point-of-care liver function testing

    PubMed Central

    Pollock, Nira R.; Rolland, Jason P.; Kumar, Shailendra; Beattie, Patrick D.; Jain, Sidhartha; Noubary, Farzad; Wong, Vicki L.; Pohlmann, Rebecca A.; Ryan, Una S.; Whitesides, George M.

    2013-01-01

    In developed nations, monitoring for drug-induced liver injury via serial measurements of serum transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) in at-risk individuals is the standard of care. Despite the need, monitoring for drug-related hepatotoxicity in resource-limited settings is often limited by expense and logistics, even for patients at highest risk. This manuscript describes the development and clinical testing of a paper-based, multiplexed microfluidic assay designed for rapid, semi-quantitative measurement of AST and ALT in a fingerstick specimen. Using 223 clinical specimens obtained by venipuncture and 10 fingerstick specimens from healthy volunteers, we have shown that our assay can, in 15 minutes, provide visual measurements of AST and ALT in whole blood or serum which allow the user to place those values into one of three readout “bins” (<3x upper limit of normal (ULN), 3-5x ULN, and >5x ULN, corresponding to tuberculosis/HIV treatment guidelines) with >90% accuracy. These data suggest that the ultimate point-of-care fingerstick device will have high impact on patient care in low-resource settings. PMID:22993296

  5. Implications of metal exposure and liver function in Parkinsonian patients resident in the vicinities of ferroalloy plants.

    PubMed

    Squitti, Rosanna; Gorgone, G; Panetta, V; Lucchini, R; Bucossi, S; Albini, E; Alessio, L; Alberici, A; Melgari, J M; Benussi, L; Binetti, G; Rossini, P M; Draicchio, F

    2009-10-01

    Valcamonica is an Italian valley where ferro-manganese industries have been active for a century and where an increased prevalence of parkinsonism was observed. A group of 93 patients (65 from Valcamonica, 28 from the reference area of Brescia city) and 76 controls (52 from Valcamonica, 24 from Brescia) were screened for serum Cu, Zn, Fe, Mn in blood (MnB) and urine (MnU), transferrin, peroxides, alanine (ALT) and aspartate (AST) transaminases and direct bilirubin. Test results were compared among groups according to the residential area and related to the disease severity. Valcamonica patients had a serum-increase of Cu, as well as of AST/ALT ratio, and a serum-decrease of Zn and Fe compared with other subgroups of cases and controls. Cases and controls from Valcamonica had higher MnB and MnU levels compared to cases and controls from Brescia. After controlling for the duration of illness, the Unified Parkinson's Disease Rating Scale III domain correlated with serum Cu and AST/ALT ratio. Our results suggest the possibility that, in this area, a lifetime exposure to neurotoxicants and to Mn in particular, when accompanied to a subclinical liver dysfunction, may pose an increased risk for neurodegenerative disorders via metal metabolism (Cu, Zn, Fe) abnormalities. PMID:19680597

  6. Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish

    PubMed Central

    Rai, Kunal; Chidester, Stephanie; Zavala, Chad V.; Manos, Elizabeth J.; James, Smitha R.; Karpf, Adam R.; Jones, David A.; Cairns, Bradley R.

    2007-01-01

    The roles of DNA methyltransferase-2 (DNMT2) enzymes are controversial; whether DNMT2 functions primarily as a nuclear DNA methyltransferase or as a cytoplasmic tRNA methyltransferase, and whether DNMT2 activity impacts development, as dnmt2 mutant mice or Drosophila lack phenotypes. Here we show that morpholino knockdown of Dnmt2 protein in zebrafish embryos confers differentiation defects in particular organs, including the retina, liver, and brain. Importantly, proper organ differentiation required Dnmt2 activity in the cytoplasm, not in the nucleus. Furthermore, zebrafish Dnmt2 methylates an RNA species of ?80 bases, consistent with tRNA methylation. Thus, Dnmt2 promotes zebrafish development, likely through cytoplasmic RNA methylation. PMID:17289917

  7. Effects of crystalloids and colloids on liver and intestine microcirculation and function in cecal ligation and puncture induced septic rodents

    PubMed Central

    2012-01-01

    Background Septic acute liver and intestinal failure is associated with a high mortality. We therefore investigated the influence of volume resuscitation with different crystalloid or colloid solutions on liver and intestine injury and microcirculation in septic rodents. Methods Sepsis was induced by cecal ligation and puncture (CLP) in 77 male rats. Animals were treated with different crystalloids (NaCl 0.9% (NaCl), Ringer’s acetate (RA)) or colloids (Gelafundin 4% (Gel), 6% HES 130/0.4 (HES)). After 24 h animals were re-anesthetized and intestinal (n?=?6/group) and liver microcirculation (n?=?6/group) were obtained using intravital microscopy, as well as macrohemodynamic parameters were measured. Blood assays and organs were harvested to determine organ function and injury. Results HES improved liver microcirculation, cardiac index and DO2-I, but significantly increased IL-1?, IL-6 and TNF-? levels and resulted in a mortality rate of 33%. Gel infused animals revealed significant reduction of liver and intestine microcirculation with severe side effects on coagulation (significantly increased PTT and INR, decreased haemoglobin and platelet count). Furthermore Gel showed severe hypoglycemia, acidosis and significantly increased ALT and IL-6 with a lethality of 29%. RA exhibited no derangements in liver microcirculation when compared to sham and HES. RA showed no intestinal microcirculation disturbance compared to sham, but significantly improved the number of intestinal capillaries with flow compared to HES. All RA treated animals survided and showed no severe side effects on coagulation, liver, macrohemodynamic or metabolic state. Conclusions Gelatine 4% revealed devastated hepatic and intestinal microcirculation and severe side effects in CLP induced septic rats, whereas the balanced crystalloid solution showed stabilization of macro- and microhemodynamics with improved survival. HES improved liver microcirculation, but exhibited significantly increased pro-inflammatory cytokine levels. Crystalloid infusion revealed best results in mortality and microcirculation, when compared with colloid infusion. PMID:23245375

  8. Prospective Randomized Trial Comparing Hepatic Venous Outflow and Renal Function after Conventional versus Piggyback Liver Transplantation

    PubMed Central

    Brescia, Marília D’Elboux Guimarães; Massarollo, Paulo Celso Bosco; Imakuma, Ernesto Sasaki; Mies, Sérgio

    2015-01-01

    Background This randomized prospective clinical trial compared the hepatic venous outflow drainage and renal function after conventional with venovenous bypass (n = 15) or piggyback (n = 17) liver transplantation. Methods Free hepatic vein pressure (FHVP) and central venous pressure (CVP) measurements were performed after graft reperfusion. Postoperative serum creatinine (Cr) was measured daily on the first week and on the 14th, 21st and 28th postoperative days (PO). The prevalence of acute renal failure (ARF) up to the 28th PO was analyzed by RIFLE-AKIN criteria. A Generalized Estimating Equation (GEE) approach was used for comparison of longitudinal measurements of renal function. Results FHVP-CVP gradient > 3 mm Hg was observed in 26.7% (4/15) of the patients in the conventional group and in 17.6% (3/17) in the piggyback group (p = 0.68). Median FHVP-CVP gradient was 2 mm Hg (0–8 mmHg) vs. 3 mm Hg (0–7 mm Hg) in conventional and piggyback groups, respectively (p = 0.73). There is no statistically significant difference between the conventional (1/15) and the piggyback (2/17) groups regarding massive ascites development (p = 1.00). GEE estimated marginal mean for Cr was significantly higher in conventional than in piggyback group (2.14 ± 0.26 vs. 1.47 ± 0.15 mg/dL; p = 0.02). The conventional method presented a higher prevalence of severe ARF during the first 28 PO days (OR = 3.207; 95% CI, 1.010 to 10.179; p = 0.048). Conclusion Patients submitted to liver transplantation using conventional or piggyback methods present similar results regarding venous outflow drainage of the graft. Conventional with venovenous bypass technique significantly increases the harm of postoperative renal dysfunction. Trial Registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01707810 PMID:26115520

  9. Effect of a New Oral Contraceptive with Drospirenone on Vital Signs, Complete Blood Count, Glucose, Electrolytes, Renal, and Liver Function

    Microsoft Academic Search

    Surasak Taneepanichskul

    vital signs, complete blood count, glucose, electrolytes, and renal and liver function. Material and Method: An open-label non-comparative clinical trial was conducted. One hundred women who were planning to use oral contraception for at least six months were recruited. The subjects received a blister pack which contained 21 tablets of 3 mg drospirenone \\/30 µg ethinyl estradiol for the first

  10. CORRELATION OF MIXED-FUNCTION OXIDASE ACTIVITY WITH ULTRASTRUCTURAL CHANGES IN THE LIVER OF A MARINE FISH

    EPA Science Inventory

    Specimens of mullet (Mugil cephalus), a marine fish, were given single doses of 3-methylcholanthrene intraperitoneally and the activity of the microsomal mixed-function oxygenase system in the liver was measured by the metabolism of benzo(a)-pyrene. The enzyme system was found to...

  11. Investigation on liver function among population in high background of rare earth area in South China.

    PubMed

    Zhu, Weifang; Xu, Suqin; Shao, Pinpin; Zhang, Hui; Wu, Donseng; Yang, Wenjia; Feng, Jia; Feng, Lei

    2005-04-01

    The health effects of long-term ingestion of rare earth elements (REEs) on the villagers living in high-REE-background areas in South Jangxi Province, China were studied. Major health complaints from the REE area population included indigestion, diarrhea, abdominal distension, anorexia, weakness, and fatigue, especially after high-fat or high-protein intake. Liver function tests were conducted for adult villagers. Among them, 45 live in a heavy rare earth (HREE) area, 62 in a light rare earth (LREE) area, and 49 in the control area. Test results showed that serum total protein and globulin from both HREE and LREE areas, as well as albumin from the LREE area, were significantly lower (p < 0.01 - 0.01) compared to the results from the control area, whereas albumin from the HREE area showed no significant variance (p > 0.05). The chi-square test showed that Serum-glutamic pyruvic transaminase (SGPT) in both areas were not significant (p > 0.05), whereas the IgM in the HREE area was significantly elevated. It is our conclusion that long-term ingestion of REE affected activities of some digestive enzymes, causing malabsorption and indigestion, and might further lead to a low-protein effect for the villagers in the LREE area. However, the damage to the liver was rather mild. The elevation of IgM was probably the result of stimulation induced by the formation of a large amount of granules as a result of direct binding of REEs to globulin or albumin (combination of REEs with globulin or albumin). PMID:15851827

  12. Alterations in Ventricular Structure and Function in Obese Adolescents with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Singh, Gautam K.; Vitola, Bernadette E.; Holland, Mark R.; Sekarski, Timothy; Patterson, Bruce W.; Magkos, Faidon; Klein, Samuel

    2012-01-01

    Objective To determine the association among nonalcoholic fatty liver disease (NAFLD), metabolic function, and cardiac function in obese adolescents. Study design Intrahepatic triglyceride (IHTG) content (magnetic resonance spectroscopy), insulin sensitivity and ?-cell function (5-hour oral glucose tolerance test with mathematical modeling), and left ventricular (LV) function (speckle tracking echocardiography) were determined in three groups of age, sex, and Tanner matched adolescents: 1) lean (n=14, BMI=20±2 kg/m2); 2) obese with normal (2.5%) IHTG content (n=15, BMI=35±3 kg/m2); and 3) obese with increased (8.7%) IHTG content (n=15, BMI=37±6 kg/m2). Results The disposition index (?-cell function) and insulin sensitivity index (ISI) were ~45% and ~70% lower, respectively, and whole body insulin resistance (HOMA-IR) was ~60% greater, in obese than in lean subjects, and ~30% and ~50% lower and ~150% greater, respectively, in obese subjects with NAFLD than those without NAFLD (P <0.05 for all). LV global longitudinal systolic strain and early diastolic strain rates were significantly decreased in obese than in lean subjects, and in obese subjects with NAFLD than those without NAFLD (P <0.05 for all), and were independently associated with HOMA-IR (? = 0.634). IHTG content was the only significant independent determinant of ISI (? = ?0.770), disposition index (? = ?0.651), and HOMA-IR (? = 0.738). Conclusions These findings demonstrate that the presence of NAFLD in otherwise asymptomatic obese adolescents is an early marker of cardiac dysfunction. PMID:23260104

  13. Renal function in tyrosinaemia type I after liver transplantation: A long-term follow-up

    Microsoft Academic Search

    L. J. W. M. Pierik; F. J. van Spronsen; C. M. A. Bijleveld; C. M. L. van Dael

    2005-01-01

    Summary  Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the\\u000a enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent\\u000a porphyria. When treated with liver transplantation, tyrosinaemia type I was considered to be cured. Some years after the first\\u000a liver transplantations in these patients, some reports

  14. Cultured mycelium Cordyceps sinensis protects liver sinusoidal endothelial cells in acute liver injured mice.

    PubMed

    Peng, Yuan; Chen, Qian; Yang, Tao; Tao, Yanyan; Lu, Xiong; Liu, Chenghai

    2014-03-01

    Cultured mycelium Cordyceps sinensis (CMCS) was widely used for a variety of diseases including liver injury, the current study aims to investigate the protective effects of CMCS on liver sinusoidal endothelial cells (LSECs) in acute injury liver and related action mechanisms. The mice were injected intraperitoneally with lipopolysaccharide (LPS) and D-galactosamine (D-GalN). 39 male BABL/c mice were randomly divided into four groups: normal control, model control, CMCS treatment and 1,10-phenanthroline treatment groups. The Serum liver function parameters including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were assayed with the commercial kit. The inflammation and scaffold structure in liver were stained with hematoxylin and eosin and silver staining respectively. The LSECs and sub-endothelial basement membrane were observed with the scanning and transmission electronic microscope. The protein expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in liver were analyzed with Western blotting. Expression of von Willebrand factor (vWF) was investigated with immunofluorescence staining. The lipid peroxidation indicators including antisuperoxideanion (ASAFR), hydroxyl free radical (·OH), superoxide dismutase (SOD), malondialdehyde and glutathione S-transferase (GST) were determined with kits, and matrix metalloproteinase-2 and 9 (MMP-2/9) activities in liver were analyzed with gelatin zymography and in situ fluorescent zymography respectively. The model mice had much higher serum levels of ALT and AST than the normal mice. Compared to that in the normal control, more severe liver inflammation and hepatocyte apoptosis, worse hepatic lipid peroxidation demonstrated by the increased ASAFR, ·OH and MDA, but decreased SOD and GST, increased MMP-2/9 activities and VCAM-1, ICAM-1 and vWF expressions, which revealed obvious LSEC injury and scaffold structure broken, were shown in the model control. Compared with the model group, CMCS and 1,10-phenanthroline significantly improved serum ALT/AST, attenuated hepatic inflammation and improved peroxidative injury in liver, decreased MMP-2/9 activities in liver tissue, improved integration of scaffold structure, and decreased protein expression of VCAM-1 and ICAM-1. CMCS could protect LSECs from injury and maintain the microvasculature integration in acute injured liver of mice induced by LPS/D-GalN. Its action mechanism was associated with the down-regulation of MMP-2/9 activities and inhibition of peroxidation in injured liver. PMID:24442316

  15. Effects of PBBs on cattle. III. Target organ modification as shown by renal function and liver biochemistry.

    PubMed

    Schanbacher, F L; Willett, L B; Moorhead, P D; Mercer, H D

    1978-04-01

    Efforts were made to more clearly delineate target organs and mechanisms of toxicity for PBBs in cattle. Methods were developed to obtain sequential liver biopsies on bovine heifers which yield 0.5 to 1.0 g of tissue. PBB was fed at a dose of 250 mg/head/day to Holstein heifers for 202 days. This dose produced no clinical signs of toxicity in any of the heifers, yet this produced tissue PBB concentration of greater than 100 times the FDA tolerance in body fat of 0.3 ppm. Liver biopsies (0.5-1.0 g each) were taken at days 0, 90, and 180. The liver tissue was homogenized and microsomes were prepared. Dithionite difference spectra were determined on the carbon monoxide treated microsome suspension and the cytochrome P-450 content determined. Also, the 100,000g supernatant was saved for ornithine decarboxylase analysis as a measure of hepatocyte proliferative activity. Results of the cytochrome P-450 analysis showed a significant (p < 0.05) two-fold elevation (per gram of wet liver) by day 90 and remained significantly (p < 0.05) elevated on day 180. The cytochrome P-450 values of control animals not receiving PBBs showed no such increase with time. The biopsy procedure appeared not to adversely affect the liver cytochrome P-450 concentration in the control heifers. These results show that PBBs at a dose of 250 mg/day induced the drug metabolism system of the liver, of which the cytochrome P-450 is a part, indicating that the liver is a potential target organ for PBBs. However, this has not been shown to cause clear signs of hepatotoxicity in the cow as determined from histopathology or serum enzyme analyses. The observed elevation of gross liver weights of the PBB-treated animals might be an expected consequence of the cytochrome P-450 induction. In contrast to rodents, the kidney has been identified by histopathology as a target organ for PBB toxicity in cattle. However, renal function studies with (131)I-sodium-iodohippurate and (125)I-sodium iodothalamate in PBB treated cows indicated that PBB toxicity to the kidney did not affect glomerular filtration rate or effective renal plasma flow even though nephrotoxic effects were produced. From these studies, both liver (as expected) and kidney (unexpected) were affected by PBBs. For liver this did not result in hepatotoxicity while for kidney nephrotoxicity was produced but could not be mechanistically explained. PMID:209963

  16. A Role for Serotonin (5-HT) in Hepatic Stellate Cell Function and Liver Fibrosis

    PubMed Central

    Ruddell, Richard G.; Oakley, Fiona; Hussain, Ziafat; Yeung, Irene; Bryan-Lluka, Lesley J.; Ramm, Grant A.; Mann, Derek A.

    2006-01-01

    Hepatic stellate cells (HSCs) are key cellular components of hepatic wound healing and fibrosis. There is emerging evidence that the fibrogenic function of HSCs may be influenced by neurochemical and neurotrophic factors. This study addresses the potential for the serotonin (5-HT) system to influence HSC biology. Rat and human HSCs express the 5-HT1B, 5-HT1F 5-HT2A 5-HT2B, and 5-HT7 receptors, with expression of 5-HT1B 5-HT2A and 5-HT2B being induced on HSC activation. Induction of 5-HT2A and 5-HT2B was 106 ± 39- and 52 ± 8.5-fold that of quiescent cells, respectively. 5-HT2B was strongly associated with fibrotic tissue in diseased rat liver. Treatment of HSCs with 5-HT2 antagonists suppressed proliferation and elevated their rate of apoptosis; by contrast 5-HT was protective against nerve growth factor-induced apoptosis. 5-HT synergized with platelet-derived growth factor to stimulate increased HSC proliferation. HSCs were shown to express a functional serotonin transporter and to participate in both active uptake and release of 5-HT. We conclude that HSCs express key regulatory components of the 5-HT system enabling them to store and release 5-HT and to respond to the neurotransmitter in a profibrogenic manner. Antagonists that selectively target the 5-HT class of receptors may be exploited as antifibrotic drugs. PMID:16936262

  17. Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

    SciTech Connect

    Moreira, Paula I. [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Physiology, Faculty of Medicine, University of Coimbra, 3005-504 Coimbra (Portugal); Custodio, Jose B.A. [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Biochemistry, Faculty of Pharmacy, University of Coimbra, 3005-504 Coimbra (Portugal); Nunes, Elsa [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Physiology, Faculty of Medicine, University of Coimbra, 3005-504 Coimbra (Portugal); Moreno, Antonio [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Department of Zoology, Faculty of Sciences and Technology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Marine Research, University of Coimbra, 3005-504 Coimbra (Portugal); Seica, Raquel [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Physiology, Faculty of Medicine, University of Coimbra, 3005-504 Coimbra (Portugal); Oliveira, Catarina R. [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal); Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3005-504 Coimbra (Portugal); Santos, Maria S. [Center for Neuroscience and Cell Biology, University of Coimbra, 3005-504 Coimbra (Portugal) and Department of Zoology, Faculty of Sciences and Technology, University of Coimbra, 3005-504 Coimbra (Portugal)]. E-mail: mssantos@ci.uc.pt

    2007-05-15

    Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17{beta}-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca{sup 2+} delaying the opening of the permeability transition pore. The presence of 25 {mu}M E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H{sub 2}O{sub 2} in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered.

  18. Application of a proteomic approach to identify proteins associated with primary graft non-function after liver transplantation.

    PubMed

    Kornasiewicz, Oskar; Bojarczuk, Kamil; Bugajski, Marek; Golab, Jakub; Krawczyk, Marek

    2012-10-01

    Primary graft non-function (PNF) is a rare, life-threatening complication of liver transplantation. Increasing use of extended criteria donor pools and high-risk recipients seem to influence the incidence of PNF. Primary failure is associated with high patient morbidity and inferior graft survival. The only available treatment for PNF is emergency hepatic retransplantation, which is also correlated with significant morbidity and mortality. Therefore, researchers are working to identify risk factors of diagnostic value to prevent PNF. The current study attempted to explore liver proteomic patterns in patients with PNF. Using two-dimensional gel electrophoresis and liquid chromatography-mass spectrometry (LC-MS), we compared liver protein homogenates from 3 patients with PNF to those obtained from 6 healthy liver samples to identify potential new biomarkers of PNF. Our comparisons revealed 21 proteins with differential expression (13 upregulated and 8 downregulated). Most of these proteins are involved in energy metabolism, lipid metabolism, peptide cleavage, cell differentiation, and apoptosis. Although none of these proteins appeared more than once in separate analyses, this preliminary study shows that two-dimensional gel electrophoresis and LC-MS may allow identification of characteristic proteins to be used as biomarkers of a life-threatening complication of liver transplantation. Larger-scale analyses could improve patient care by finding suitable prognostic and therapeutic options. These data represent the first global proteomic approach to study PNF. PMID:22825711

  19. Liver bioengineering

    PubMed Central

    Caralt, Mireia; Velasco, Enrique; Lanas, Angel; Baptista, Pedro M

    2014-01-01

    Liver bioengineering has been a field of intense research and popular excitement in the past decades. It experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization1–3. Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue. Even notable novel strategies that rely on iPSC-derived liver progenitor cells potential to self-organize in association with endothelial cells in hepatic organoids are lacking critical components of the native tissue (e.g., bile ducts, functional vascular network, hepatic microarchitecture, etc)4. Hence, it is vital to understand the strengths and short comes of our current strategies in this quest to re-create liver organogenesis in vitro. To shed some light into these issues, this review describes the different actors that play crucial roles in liver organogenesis and highlights the steps still missing to successfully generate whole livers and hepatic organoids in vitro for multiple applications. PMID:25102189

  20. Engineering nitrogen use efficiency with alanine aminotransferase

    Microsoft Academic Search

    Allen G. Good; Susan J. Johnson; Mary De Pauw; Rebecka T. Carroll; Nic Savidov; John Vidmar; Zhongjin Lu; Gregory Taylor; Virginia Stroeher

    2007-01-01

    Nitrogen (N) is the most important factor limiting crop productivity worldwide. The ability of plants to acquire N from applied fertilizers is one of the critical steps limiting the efficient use of nitrogen. To improve N use efficiency, genetically modified plants that overexpress alanine aminotransferase (AlaAT) were engineered by introducing a barley AlaAT cDNA driven by a canola root specific

  1. Induced pluripotent stem cell–derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice

    PubMed Central

    Espejel, Silvia; Roll, Garrett R.; McLaughlin, K. John; Lee, Andrew Y.; Zhang, Jenny Y.; Laird, Diana J.; Okita, Keisuke; Yamanaka, Shinya; Willenbring, Holger

    2010-01-01

    The ability to generate induced pluripotent stem (iPS) cells from a patient’s somatic cells has provided a foundation for organ regeneration without the need for immune suppression. However, it has not been established that the differentiated progeny of iPS cells can effectively reverse failure of a vital organ. Here, we examined whether iPS cell–derived hepatocytes have both the functional and proliferative capabilities needed for liver regeneration in mice with fumarylacetoacetate hydrolase deficiency. To avoid biases resulting from random genomic integration, we used iPS cells generated without viruses. To exclude compensation by hepatocytes not derived from iPS cells, we generated chimeric mice in which all hepatocytes were iPS cell derived. In vivo analyses showed that iPS cells were intrinsically able to differentiate into fully mature hepatocytes that provided full liver function. The iPS cell–derived hepatocytes also replicated the unique proliferative capabilities of normal hepatocytes and were able to regenerate the liver after transplantation and two-thirds partial hepatectomy. Thus, our results establish the feasibility of using iPS cells generated in a clinically acceptable fashion for rapid and stable liver regeneration. PMID:20739754

  2. Cognitive and academic outcomes after pediatric liver transplantation: Functional Outcomes Group (FOG) results.

    PubMed

    Sorensen, L G; Neighbors, K; Martz, K; Zelko, F; Bucuvalas, J C; Alonso, E M

    2011-02-01

    This multicenter study examined prevalence of cognitive and academic delays in children following liver transplant (LT). One hundred and forty-four patients ages 5-7 and 2 years post-LT were recruited through the SPLIT consortium and administered the Wechsler Preschool and Primary Scale of Intelligence, 3rd Edition (WPPSI-III), the Bracken Basic Concept Scale, Revised (BBCS-R), and the Wide Range Achievement Test, 4th edition (WRAT-4). Parents and teachers completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants performed significantly below test norms on intelligence quotient (IQ) and achievement measures (Mean WPPSI-III Full Scale IQ = 94.7 ± 13.5; WRAT-4 Reading = 92.7 ± 17.2; WRAT-4 Math = 93.1 ± 15.4; p < 0001). Twenty-six percent of patients (14% expected) had 'mild to moderate' IQ delays (Full Scale IQ = 71-85) and 4% (2% expected) had 'serious' delays (Full Scale IQ ? 70; p < 0.0001). Reading and/or math scores were weaker than IQ in 25%, suggesting learning disability, compared to 7% expected by CDC statistics (p < 0.0001). Executive deficits were noted on the BRIEF, especially by teacher report (Global Executive Composite = 58; p < 0.001). Results suggest a higher prevalence of cognitive and academic delays and learning problems in pediatric LT recipients compared to the normal population. PMID:21272236

  3. Biguanides inhibit complex I, II and IV of rat liver mitochondria and modify their functional properties.

    PubMed

    Drahota, Z; Palenickova, E; Endlicher, R; Milerova, M; Brejchova, J; Vosahlikova, M; Svoboda, P; Kazdova, L; Kalous, M; Cervinkova, Z; Cahova, M

    2014-01-01

    In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeability transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to previously published data, we found that phenformin, after a 5 min pre-incubation, dose-dependently inhibits not only mitochondrial complex I but also complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potential. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca(2+) ions. Our data might be in agreement with the hypothesis of Schäfer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity. PMID:24182344

  4. Sustained linear growth and preserved renal function in 10-year survivors of pediatric liver transplantation.

    PubMed

    Lee, Sanghoon; Kim, Jong-Man; Choi, Gyu-Seong; Kwon, Choon Hyuck D; Choe, Yon-Ho; Joh, Jae-Won; Lee, Suk-Koo

    2015-07-01

    The aim of this study was to characterize the clinical outcomes of children and adolescents who achieved survival of more than 10 years following liver transplantation (LT) in a single center in Korea. From June 1996 to October 2003, 57 pediatric LTs were performed. The medical records of 44 patients who had survived more than 10 years were reviewed retrospectively. Median age of patients at LT was 0.8 years. Forty-one patients received living donor LT, and three patients received deceased donor LT. Biliary atresia was the most common indication (65.9%). Thirty-five patients were on tacrolimus monotherapy at 10 years post-LT with a mean trough level of 2.73 ng/ml, and five patients were maintaining stable graft function without any immunosuppression. There were no patients receiving antihypertensive medication and one case of diabetes mellitus. Renal dysfunction was seen in two patients (4.5%), while none required renal replacement therapy. Mean height z-score prior to LT was -1.35 and at 10 years post-transplant was 0.05. Good linear growth was sustained in this cohort throughout the 10 years, approaching the 50th percentile. Also, there were remarkably low incidences of renal dysfunction and patients requiring medications for glycemic or hypertensive control, all hallmarks of continued use of immunosuppressive agents. PMID:25711921

  5. Cognitive and Academic Outcomes after Pediatric Liver Transplantation: Functional Outcomes Group (FOG) Results

    PubMed Central

    Sorensen, L.G.; Neighbors, K.; Martz, K.; Zelko, F.; Bucuvalas, J.C.; Alonso, E.M.

    2010-01-01

    This multi-center study examined prevalence of cognitive and academic delays in children following liver transplant (LT). 144 patients ages 5–7 and 2 years post-LT were recruited through the SPLIT consortium and administered the Wechsler Preschool and Primary Scale of Intelligence, 3rd Edition (WPPSI-III), the Bracken Basic Concept Scale, Revised (BBCS-R), and the Wide Range Achievement Test, 4th edition (WRAT-4). Parents and teachers completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants performed significantly below test norms on intelligence quotient (IQ) and achievement measures (Mean WPPSI-III Full Scale IQ = 94.7± 13.5; WRAT-4 Reading = 92.7± 17.2; WRAT-4 Math = 93.1± 15.4; p<0001). 26% of patients (14% expected) had “mild to moderate” IQ delays (Full Scale IQ=71–85) and 4% (2% expected) had “serious” delays (Full Scale IQ ?70; p<0.0001). Reading and/or math scores were weaker than IQ in 25%, suggesting learning disability, compared to 7% expected by CDC(1) statistics (p<0.0001). Executive deficits were noted on the BRIEF, especially by teacher report (Global Executive Composite = 58; p<0.001). Results suggest a higher prevalence of cognitive and academic delays and learning problems in pediatric LT recipients compared to the normal population. PMID:21272236

  6. The phenotypic fate and functional role for bone marrow-derived stem cells in liver fibrosis

    PubMed Central

    Kisseleva, Tatiana; Brenner, David A.

    2012-01-01

    Summary Liver fibrosis is an outcome of chronic liver injury of any etiology. It is manifested by extensive deposition of extracellular matrix (ECM) proteins that produce a fibrous scar in the injured liver. Bone marrow (BM) cells may play an important role in pathogenesis and resolution of liver fibrosis. BM cells contribute to the inflammatory response by TGF-?1 secretion and activation of liver resident myofibroblasts. Moreover, BM itself can serve as a source of collagen expressing cells, e.g. BM-derived fibrocytes and mesenchymal progenitors, which in turn, have a potential to in situ differentiate into fibrogenic myofibroblasts and facilitate fibrosis. Finally, BM cells play an active part in resolution of liver fibrosis after cessation of fibrogenic stimuli. While natural killer (NK) cells are implicated in apoptosis of activated hepatic stellate cells/myofibroblasts, cells of myelo-monocitic lineage secrete matrix metalloproteinases to actively degrade the fibrous scar. The focus of this review is on the current understanding of the role of different subsets of BM cells in the onset, development and resolution of liver fibrosis. PMID:22173163

  7. [Effect of combined administration of Angelica polysaccharide and cytarabine on liver of human leukemia NOD/SCID mouse model].

    PubMed

    Zhu, Jia-Hong; Xu, Chun-Yan; Mu, Xin-Yi; Liu, Jun; Zhang, Meng-Si; Jia, Dao-Yong; Zhang, Yan-Yan; Huang, Guo-Ning; Wang, Ya-Ping

    2014-01-01

    Leukemia is a type of malignant tumors of hematopoietic system with the abnormal increased immature leukemia cells showing metastasis and invasion ability. Liver is one of the main targets of the leukemia cells spread to, where they may continue to proliferate and differentiate and cause liver function damage, even liver failure. Our previous studies showed that Angelica polysscharides (APS), the main effective components in Angelica sinensis of Chinese traditional medicine, was able to inhibit the proliferation and induced differentiation of the leukemia cells, however, its effect on the liver during the treatment remains elucidated. In the present study, the human leukemia NOD/SCID mouse model were established by implantation human leukemia K562 cells line, then the leukemia mouse were treated with APS, Ara-c or APS + Ara-c respectively by peritoneal injection for 14 days, to explore the effect and mechanism of the chemicals on the mouse liver. Compared to the human leukemia NOD/SCID mouse model group with the treatments of APS, Ara-c and APS + Ara-c, We found that severe liver damage and pathological changes of the liver were able to alleviate: First, the number of white blood cells in the peripheral blood was significantly lower and with less transplanted K562 leukemia cells; Second, liver function damage was alleviated as liver function tests showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBiL) were significantly reduced, while the albumin (Alb) was notably increased; Third, liver antioxidant ability was improved as the activities of the antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were significantly increased, and the contents of GSH and malonaldehyde (MDA) were decreased significantly in the liver; Fourth, the inflammation of the liver was relieved as the level of IL-1beta and IL-6, the inflammatory cytokines, were decreased significantly in the liver. Fifth, liver index was increased as the pathological observation showed that leukemia cells with diffused infiltration into the liver lobules were significantly reduced and with a remarkable increase of apoptotic positive cell rate by TUNEL test. Furthermore, the APS + Ara-c combined administration showed an even more significant positive effect. In conclusion, the APS, Ara-c therapy reduced the accumulation of leukemia cells within the liver, reduced the liver function damage and levels of inflammatory factors, improved antioxidant capacity of the liver tissue and thus alleviate the pathological changes of the liver. Moreover, the APS + Ara-c combination therapy may have an additive effect. PMID:24754180

  8. Effect of peripartum dietary energy supplementation of dairy cows on metabolites, liver function and reproductive variables.

    PubMed

    Castañeda-Gutiérrez, E; Pelton, S H; Gilbert, R O; Butler, W R

    2009-06-01

    Multiparous Holstein cows (n=58) were used to study the effects of peripartum dietary supplementation on metabolic status, liver function and reproduction variables. Diets for cows were as follows: (a) no supplementation (CTL), (b) prilled fatty acids as 1.9% of DM (PrFA), (c) calcium salts of long chain n-6 fatty acids as 2.24% of DM (CaLFA) or (d) daily topdressing with 769 g of 65% propylene glycol (PGLY). Supplements were fed during the last 21 days before expected calving except for PGLY that continued until 21 days after parturition. Ovarian activity was monitored by transrectal ultrasonography and days to first ovulation were recorded. Liver biopsies were obtained on day 8 and 21 postpartum and analyzed for triglyceride content and mRNA expression of pyruvate carboxylase, cytosolic phosphoenolpyruvate carboxykinase, carnitine palmytoyltransferase 1A, and peroxisome proliferator-activated receptor-alpha. At 71 days following parturition, stage of ovarian cycles was synchronized and at day15 of the cycle oxytocin was injected i.v., blood samples were obtained at frequent intervals, and analyzed for 13,14 dihydro, 15-keto PGF(2alpha) (PGFM). Milk production and milk components were not different among treatment groups. Cows in PGLY gained body condition score (BCS) prepartum and net energy balance prepartum tended to be greater, but was not different postpartum from other groups. PGLY supplementation increased plasma insulin concentration prepartum, but not during the postpartum period. No significant differences were observed in plasma concentrations of glucose, NEFA, and insulin-like growth factor or hepatic triglyceride content, but all supplements tended to decrease beta hydroxybutyrate postpartum compared to CTL cows. Abundance of mRNA of gluconeogenic and lipid oxidation genes was not different among treatment groups. Days to first ovulation and uterine PGF(2alpha) production in response to an oxytocin treatment were not significantly different among treatment groups. Peripartum supplementation did not result in the substantial improvement of metabolic profile in early lactation nor significantly affect days to first ovulation and PGFM response to an oxytocin treatment. PMID:18534791

  9. Functions of anaphylatoxin C5a in rat liver: direct and indirect actions on nonparenchymal and parenchymal cells.

    PubMed

    Schieferdecker, H L; Schlaf, G; Jungermann, K; Götze, O

    2001-03-01

    Growing evidence obtained in recent years indicates that anaphylatoxin C5a receptors (C5aR) are not restricted to myeloid cells but are also expressed on nonmyeloid cells in different tissues such as brain, lung, skin and liver. In contrast to its well-defined systemic functions, the actions of anaphylatoxins in these organs are poorly characterized. The liver can be a primary target organ for the C5a anaphylatoxin since the liver is directly connected to the gut, via the mesenteric veins and portal vein which is a main source of complement activating lipopolysaccharides (LPS). In the normal rat liver, the C5aR is only expressed by nonparenchymal cells, i.e. strongly by Kupffer cells (KC) and hepatic stellate cells (HSC) and weakly by sinusoidal endothelial cells (SEC), but not expressed by the parenchymal hepatocytes (HC). Accordingly, direct effects of C5a were only found in the C5aR-expressing KC and HSC: C5a induced the release of prostanoids from KC and HSC and enhanced the LPS-dependent release of interleukin-6 from KC. These soluble mediators indirectly influenced effector functions of the C5aR-free HC. C5a enhanced the glycogen phosphorylase activity and thus the glucose output from HC indirectly via prostanoids released from KC and HSC. Glucose can serve as an energy substrate as well as an electron donor for the synthesis of reactive oxygen intermediates by KC. Moreover, C5a also enhanced transcription of the gene for the type-2 acute phase protein alpha 2-macroglobulin in HC indirectly by increasing LPS-dependent IL-6 release from KC. Under pathological conditions, C5aR was found to be upregulated in various organs including the liver. Simulation of inflammatory conditions by treatment of rats with IL-6, a main inflammatory mediator in the liver, caused a de novo expression of functional C5aR in HC. In livers of IL-6-treated rats, C5a initiated glucose output from HC and perhaps other HC-specific defense reactions directly without the intervention of soluble mediators from nonparenchymal cells. PMID:11367531

  10. Liver enzyme activity and histological changes in the liver of silver foxes ( Vulpes vulpes fulva ) experimentally infected with opisthorchiid liver flukes. A contribution to the pathogenesis of opisthorchiidosis

    Microsoft Academic Search

    Rolf Schuster; Kerstin Dell; Karsten Nöckler; Jens Vöster; Dorothea Schwartz-Porsche; Wolfram Haider

    2003-01-01

    Blood samples from silver foxes experimentally infected with Opisthorchis felineus and Metorchis bilis, respectively, were examined for the activity of liver enzymes. The average activities of aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), alkaline phosphatase and alanine aminotransferase in uninfected control animals were 20, 1.8, 57 and 44 units\\/l, respectively. The liver enzymes in infected foxes reacted differently, depending on dose,

  11. Liver disease in menopause.

    PubMed

    Brady, Carla W

    2015-07-01

    There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure. PMID:26167064

  12. Liver disease in menopause

    PubMed Central

    Brady, Carla W

    2015-01-01

    There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure.

  13. Conversion to everolimus monotherapy in maintenance liver transplantation: feasibility, safety, and impact on renal function.

    PubMed

    De Simone, Paolo; Carrai, Paola; Precisi, Arianna; Petruccelli, Stefania; Baldoni, Lidiana; Balzano, Emanuele; Ducci, Juri; Caneschi, Francesco; Coletti, Laura; Campani, Daniela; Filipponi, Franco

    2009-03-01

    We present the 12-month results of a prospective trial of conversion from calcineurin inhibitors (CNI) to everolimus (EVL) in maintenance liver transplant (LT) recipients. Forty (M:F = 28:12; 54.9 +/- 11 years) patients were enrolled at a mean interval of 45.5 +/- 31.2 months from transplantation. Conversion was with EVL at a dosage of 0.75 mg b.i.d., withdrawal of antimetabolites, and a 50%-per-week reduction of CNI to a complete stop within 4 weeks. The treatment success was conversion to EVL monotherapy at 12 months while failure was presence of CNI, death, and graft loss. Indication to conversion was deteriorating renal function in 36 (90%). At 12 months, patient- and graft survival were 100% and the success rate was 75% (30/40). Ten patients (25%) were failures: four (10%) for acute rejection; three hepatitis C virus-RNA positive patients (7.5%) for hypertransaminasemia; one (2.5%) for acute cholangitis; and two (5%) due to persistent pruritus and oral ulcers. In patients on EVL monotherapy, at 12 months the mean change of calculated creatinine clearance (cCrCl) was 4.03 +/- 12.6 mL/min and the only variable correlated with the probability of improvement was baseline cCrCl (P < 0.0001). Conversion from CNI to EVL is feasible in 75% of the cases and associated with improvement in renal function for patients with higher baseline cCrCl. PMID:19054383

  14. Telbivudine is associated with improvement of renal function in patients transplanted for HBV liver disease.

    PubMed

    Cholongitas, E; Vasiliadis, T; Goulis, I; Fouzas, I; Antoniadis, N; Papanikolaou, V; Akriviadis, E

    2015-07-01

    Recent studies showed that telbivudine in patients with hepatitis B virus (HBV) infection improved their glomerular filtration rate (GFR), but data regarding its impact on renal function in liver transplant (LT) recipients are very limited. We evaluated 17 consecutive recipients who received at baseline nucleos(t)ide analogue(s) (NAs) other than telbivudine for 12 months, and then they were switched to telbivudine prophylaxis for another 12 months. In each patient, laboratory data including evaluation of GFR (using MDRD and CKD-EPI) were prospectively recorded. The changes in GFR (?GFR) between baseline and after 12 months (1st period) and between telbivudine initiation and 24 months (2nd period) were evaluated. All patients remained serum HBsAg and HBV-DNA negative. GFR-MDRD at baseline, 12 months and 24 months were 72 ± 18, 67.8 ± 16 and 70.3 ± 12mL/min, respectively, (P = 0.025 for comparison between 12 months and 24 months). ?GFR at the 1st period was significantly lower, compared with ?GFR at the 2nd period [mean ?GFR-MDRD: -4.2 (range: -24-9) vs 2.5 (range: -7-22) mL/min, P = 0.013; mean ?GFR-CKD-EPI: -4.2 (range: -19-10) vs 4.0 (range: -7-23) mL/min, P = 0.004], although the serum levels of calcineurin inhibitors were similar between the two periods. A second group of recipients (n = 17) who remained under the same nontelbivudine NA(s) for 24 months had a decline in the mean eGFR during the total follow-up period. In conclusion, we showed that telbivudine administration in LT recipients for HBV cirrhosis was effective and it was associated with significant improvement in renal function, but this remains to be confirmed in larger well-designed studies. PMID:25385239

  15. Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

    PubMed

    Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

    2015-08-01

    To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P < 0.05 uncorrected). This study found that, at 1 month after LT, spontaneous brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function. PMID:25703240

  16. Telomerase activity and hepatic functions of rat embryonic liver progenitor cell in nanoscaffold-coated model bioreactor.

    PubMed

    Giri, Shibashish; Nieber, Karen; Acikgöz, Ali; Pavlica, Sanja; Keller, Mario; Bader, Augustinus

    2010-03-01

    Presently, there is growing interest on telomerase activity in all cells (somatic cells, stem cells, cancerous cells and others) since this activity is associated with cellular changes such as proliferation, differentiation, immortalization, cell injury and ageing. Telomerase activity is absent in most of the somatic cells but present in over 90% of cancerous cells and other immortalized cell lines. In our present study, we cultured a rat embryonal liver progenitor cell line RLC-18 in a self-assembly nanostructured scaffold-coated bioreactor (NCB), collagen-coated plates (CCP) and uncoated plates (UP), and evaluated changes of telomerase activity by non radioactive techniques (Telo TAGGG Telomerase PCR ELISA, cell proliferation based on mitochondria number by MTT assay and hepatic functions such as albumin secretion, urea metabolism, Cytochrome P450 activity like ethoxyresorufin-O-deethylase (EROD) activity. We found less telomerase activity and less cell proliferation, but more hepatic functions on the NCB than on the CCP and UP. Our data support the concept that cell-scaffold interaction may play a significant in controlling the telomerase activity as well as enhanced hepatic functions. Although our present study does not focus on the exact mechanism of telomerase regulation, our result may provide basic clues on cell differentiation whereby telomerase activity inhibits differentiation of cells as in the rat embryonic liver cell line, may be regulated by cell-scaffold interaction and where there is less proliferation, cells perform enhanced hepatic functions, thereby implying that bioartificial liver support may be possible. PMID:19816756

  17. Anti-fibrogenic function of angiotensin II type 2 receptor in CCl 4-induced liver fibrosis

    Microsoft Academic Search

    Yoshitaka Nabeshima; Susumu Tazuma; Keishi Kanno; Hideyuki Hyogo; Masaru Iwai; Masatsugu Horiuchi; Kazuaki Chayama

    2006-01-01

    The renin-angiotensin system (RAS) contributes to fibrogenesis in a variety of organs. We recently showed that a lack of angiotensin (Ang) II type 1 (AT1) receptor activity reduces liver fibrosis. In this study, we investigated whether the Ang II type 2 (AT2) receptor is implicated in the development of liver fibrosis. A comparison was made between AT2-receptor knockout (AT2KO) and

  18. The effect of immunonutrition (glutamine, alanine) on fracture healing

    PubMed Central

    Küçükalp, Abdullah; Durak, Kemal; Bayyurt, Sarp; Sönmez, Gürsel; Bilgen, Muhammed S.

    2014-01-01

    Background There have been various studies related to fracture healing. Glutamine is an amino acid with an important role in many cell and organ functions. This study aimed to make a clinical, radiological, and histopathological evaluation of the effects of glutamine on fracture healing. Methods Twenty rabbits were randomly allocated into two groups of control and immunonutrition. A fracture of the fibula was made to the right hind leg. All rabbits received standard food and water. From post-operative first day for 30 days, the study group received an additional 2 ml/kg/day 20% L-alanine L-glutamine solution via a gastric catheter, and the control group received 2 ml/kg/day isotonic via gastric catheter. At the end of 30 days, the rabbits were sacrificed and the fractures were examined clinically, radiologically, and histopathologically in respect to the degree of union. Results Radiological evaluation of the control group determined a mean score of 2.5 according to the orthopaedists and 2.65 according to the radiologists. In the clinical evaluation, the mean score was 1.875 for the control group and 2.0 for the study group. Histopathological evaluation determined a mean score of 8.5 for the control group and 9.0 for the study group. Conclusion One month after orally administered glutamine–alanine, positive effects were observed on fracture healing radiologically, clinically, and histopathologically, although no statistically significant difference was determined.

  19. Purification and characterization of alanine aminotransferase from Panicum miliaceum leaves.

    PubMed

    Son, D; Jo, J; Sugiyama, T

    1991-09-01

    Three alanine aminotransferases, two minor (AlaAT-1, AlaAT-3) and one major (AlaAT-2), were detected by native gel electrophoresis of leaf extracts from Panicum miliaceum L. AlaAT-2 was purified to homogeneity and a specific polyclonal antibody was raised against it which did not react with the other two forms of the enzyme. The enzyme, with an apparent molecular size of 102 kDa, appeared to be a dimer of a single 50-kDa polypeptide. The enzyme has a relatively broad pH optima with similar curves for the forward and reverse directions, ranging between 6.5 and 7.5. The Km values of this enzyme were 6.67, 0.15, 5.00, and 0.33 mM for alanine, 2-oxoglutarate, glutamate, and pyruvate, respectively. The activity of AlaAT-2 was found to increase markedly during leaf greening in parallel with the increase of immunochemically titrated protein, and it is suggested to function in the C4 photosynthetic cycle. PMID:1898070

  20. A prospective evaluation of changes in neuropsychological and liver function tests following transjugular intrahepatic portosystemic stent-shunt

    Microsoft Academic Search

    Rajiv Jalan; Rebecca Gooday; Ronan E. O'Carroll; Doris N. Redhead; Robert A. Elton; Peter C. Hayes

    1995-01-01

    Background\\/Aims: This study was designed to assess changes in: (a) neuropsychological tests, measures of memory, quality of life and scores for anxiety and depression; (b) liver function tests; and (c) the relationship between these following transjugular intrahepatic portosystemic stent-shunt.Methods: Twenty-nine patients undergoing transjugular intrahepatic portosystemic stent-shunt for recurrent variceal haemorrhage, 12 matched patients with cirrhosis and variceal haemorrhage manage with

  1. Zeaxanthin Dipalmitate Therapeutically Improves Hepatic Functions in an Alcoholic Fatty Liver Disease Model through Modulating MAPK Pathway

    PubMed Central

    Xing, Feiyue; Han, Tao; Jiao, Rui; Liong, Emily C.; Fung, Man-Lung; So, Kwok-Fai; Tipoe, George L.

    2014-01-01

    In the current study, the therapeutic effects of zeaxanthin dipalmitate (ZD) on a rat alcoholic fatty liver disease (AFLD) model were evaluated. After-treatment with ZD from the 5th week to the 10th week in a 10-week ethanol intragastric administration in rats significantly alleviated the typical AFLD symptoms, including reduction in rat body weight, accumulation of hepatic fat droplets, occurrence of oxidative stress, inflammation, chemoattractive responses and hepatic apoptosis in the liver. The reduction of liver function abnormalities by ZD was partly through lower expression level of cytochrome P450 2E1 (CYP2E1), diminished activity of nuclear factor kappa B (NF-?B) through the restoration of its inhibitor kappa B alpha (I?B?), and the modulation of MAPK pathways including p38 MAPK, JNK and ERK. ZD treatment alone did not pose obvious adverse effect on the healthy rat. In the cellular AFLD model, we also confirmed the inhibition of p38 MAPK and ERK abolished the beneficial effects of ZD. These results provide a scientific rationale for the use of zeaxanthin and its derivatives as new complementary agents for the prevention and treatment of alcoholic liver diseases. PMID:24740309

  2. The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver.

    PubMed

    Patel, Kashyap; Foretz, Marc; Marion, Allison; Campbell, David G; Gourlay, Robert; Boudaba, Nadia; Tournier, Emilie; Titchenell, Paul; Peggie, Mark; Deak, Maria; Wan, Min; Kaestner, Klaus H; Göransson, Olga; Viollet, Benoit; Gray, Nathanael S; Birnbaum, Morris J; Sutherland, Calum; Sakamoto, Kei

    2014-01-01

    LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver. PMID:25088745

  3. The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver

    PubMed Central

    Patel, Kashyap; Foretz, Marc; Marion, Allison; Campbell, David G.; Gourlay, Robert; Boudaba, Nadia; Tournier, Emilie; Titchenell, Paul; Peggie, Mark; Deak, Maria; Wan, Min; Kaestner, Klaus H.; Göransson, Olga; Viollet, Benoit; Gray, Nathanael S.; Birnbaum, Morris J.; Sutherland, Calum; Sakamoto, Kei

    2014-01-01

    LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1–SIK pathway functions as a key gluconeogenic gatekeeper in the liver. PMID:25088745

  4. Novel intravenous 13C-methionine breath test as a measure of liver function in children with short bowel syndrome

    PubMed Central

    Duro, Debora; Duggan, Christopher; Valim, Clarissa; Bechard, Lori; Fitzgibbons, Shimae; Jaksic, Tom; Yu, Yong-Ming

    2011-01-01

    Monitoring hepatic function in children with short bowel syndrome (SBS) and parenteral nutrition-associated liver disease (PNALD) is currently limited to conventional blood testing or liver biopsy. Metabolism of the stable isotope L[1-13C]methionine occurs exclusively in liver mitochondria and can be noninvasively quantified in expired breath samples. We hypothesized that the 13C-methionine breath test (13C-MBT) could be a safe, noninvasive, and valid measure of hepatic mitochondrial function in children with SBS and PNALD. Methods Baseline breath samples were collected in 8 children with SBS before intravenous administration of 2 mg/kg of L[1-13C]methionine. Six paired breath samples were obtained at 20-minute intervals. The 13CO2 enrichment was analyzed using isotope ratio mass spectrometry. Results All 8 patients (5 males; mean age, 8.9 months) tolerated the 13C-MBT without adverse events. Two patients underwent serial testing. One patient, tested before and after resolution of cholestasis, demonstrated increased cumulative percentage dose (4.7% to 6.6%) and area under the curve (AUC) (270–303). A second patient with progressive PNALD demonstrated decreased cumulative percentage dose (from 7.8% to 5.9%) and AUC (from 335 to 288). Conclusion The 13C-MBT is a feasible, safe, and potentially clinically relevant measure of hepatic mitochondrial function in children with SBS and PNALD. PMID:19159749

  5. Factors predicting abnormal liver function tests induced by graves' disease alone: a retrospective cohort study.

    PubMed

    Zhang, Ruiguo; Tian, Xun; Qin, Lan; Wei, Xiaoer; Wang, Junqi; Shen, Jie

    2015-05-01

    Abnormal liver function tests (LFTs) are often observed in patients with Graves' disease (GD). To date, there are limited data demonstrating the factors or biochemical indexes contributing to LFT abnormalities in this patient population. The aim of this study was to explore factors predicting abnormal LFTs induced by GD alone. This was a retrospective study of 289 consecutive cases of newly diagnosed and untreated patients with GD. All patients were divided into abnormal LFTs (group A) and normal LFTs (group B). In total, 205 (70.9%) cases were found to have at least 1 LFT abnormality. Among them, the frequencies of ALT, AST, ALP, ?-GTP, TBIL and DBIL abnormalities were 52.7%, 32.2%, 45.9%, 38.5%, 23.4%, 2.9%, respectively, and the number of patients with 1 to 6 hepatic variable abnormalities were 89, 64, 30, 16, 6 and 0, respectively. Logistic regression analysis was used to determine predictive factors contributing to abnormal LFTs. A receiver operating characteristic (ROC) curve was also plotted to verify the accuracy of predictors. In the univariate analysis, patients in group A had significantly higher FT3 concentration (37.5 vs 33.4?pmol/L, P?=?0.009), FT4 concentration (85.7 vs 77.4?pmol/L, P?=?0.002) and TRAb level (22.2 vs 17.4?IU/L, P?

  6. Adherence to risk evaluation and mitigation strategies (REMS) requirements for monthly testing of liver function

    PubMed Central

    Blanchette, Christopher M; Nunes, Anthony P; Lin, Nancy D; Mortimer, Kathleen M; Noone, Joshua; Tangirala, Krishna; Johnston, Stephen; Gutierrez, Benjamin

    2015-01-01

    Background: Risk evaluation and mitigation strategies (REMS), as mandated by the US Food and Drug Administration (FDA) for medications with the potential for harm, are increasingly incorporating rigid protocols for patient evaluation, but little is known about compliance with these programs. Despite the inherent limitations, data on administrative claims may provide an opportunity to investigate adherence to these programs. Methods: We assessed adherence to liver function test (LFT) requirements included in the REMS program for bosentan through use of administrative claims. Patients observed in the Optum Research Database who were initiators of bosentan from November 20, 2001 to March 31, 2013 were included. Adherence to LFTs was calculated using pharmacy claims for bosentan dispensation and medical claims for laboratory services, and was assessed at the time of drug initiation and within specified time intervals throughout follow-up. Results: Of 742 patients, 523 (70.5%) had ?1 qualifying LFT. Among patients with ?12 dispensations, claims for LFTs at individual dispensations were 53.2–64.0%. Median proportion of dispensations with ?1 LFT was 0.8 among patients with ?6 (interquartile range, 0.7–1.0) or ?12 (0.7–0.9) dispensations. Adherence was 90–100% for 33.3% of all initiators, whereas 29.3% of initiators were non-adherent (defined as <50% of on-therapy LFTs). Conclusions: Analyses of administrative claims suggest that the REMS program for bosentan may not have adequately guaranteed adherence to the program’s monthly monitoring of LFTs. Such investigations of existing REMS programs may provide insight on how to accomplish more successful evaluation of REMS. PMID:25709706

  7. A controlled trial on the effect of feeding dietary chestnut extract and glycerol monolaurate on liver function in newborn calves.

    PubMed

    Wieland, M; Weber, B K; Hafner-Marx, A; Sauter-Louis, C; Bauer, J; Knubben-Schweizer, G; Metzner, M

    2015-02-01

    Beginning in the fall of 2010, an increasing and alarming number of cases of calves suffering from liver dystrophy were reported in the south of Germany. An epidemiological investigation was carried out by the authors between November 2010 and July 2011, leading to the implication of a commercial dietary supplement as the potential cause for this outbreak. The components of this product were first tested in a cell culture model and two of them (dietary chestnut extract and glycerol monolaurate) showed a cytotoxic effect. The objective of this study was therefore to evaluate the effect of supplemental feeding of both components alone or in combination on liver function in newborn calves on a commercial dairy farm. Ten calves were enrolled in each of the three treatment groups and the control group (group O) following a blocked design. Treatment consisted of supplementation with chestnut extract at 0.02% of birth body mass (BM) (group C), supplementation with glycerol monolaurate at 0.006% of BM (group G) or a combined treatment (group CG) for five consecutive days. The effect of treatments on liver function was evaluated clinically and by measurement of glutamate dehydrogenase (GLDH) and aspartate aminotransferase (AST) activities as well as the determination of the concentrations of glucose, L-lactate and total bilirubin in serum. There was a significant increase in GLDH and AST activities and a significant decrease in glucose concentration in treatment groups C and CG compared with the control group (p ? 0.035), whereas no difference was shown for group G. Survival was significantly decreased in groups C (p = 0.029) and CG (p = 0.001) compared with both group G and the control group. These results suggest that dietary chestnut extract in an amount of 0.02% of BM alone or in combination has a toxic effect on liver function in newborn calves. PMID:24605953

  8. Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

    PubMed Central

    Watson, Christa Y; Molina, Ramon M; Louzada, Andressa; Murdaugh, Kimberly M; Donaghey, Thomas C; Brain, Joseph D

    2015-01-01

    Background Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration. Materials and methods First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated 65ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa. Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively. Results We found that the liver was the major site of initial uptake of 65ZnO ENPs. There was a time-dependent decrease in tissue levels of 65Zn in all organs examined, refecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P. aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes) delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of hepatocyte damage and marginated neutrophils were observed in the liver. Conclusion Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys. Our data show that diminished Kupffer cell organelle motion correlated with ZnO ENP-induced liver injury. PMID:26170657

  9. Postoperative Insulin-Like Growth Factor 1 Levels Reflect the Graft’s Function and Predict Survival after Liver Transplantation

    PubMed Central

    Mocchegiani, Federico; Coletta, Martina; Brugia, Marina; Montalti, Roberto; Fava, Giammarco; Taccaliti, Augusto; Risaliti, Andrea; Vivarelli, Marco

    2015-01-01

    Background The reduction of insulin-like growth factor 1 (IGF-1) plasma levels is associated with the degree of liver dysfunction and mortality in cirrhotic patients. However, little research is available on the recovery of the IGF-1 level and its prognostic role after liver transplantation (LT). Methods From April 2010 to May 2011, 31 patients were prospectively enrolled (25/6 M/F; mean age±SEM: 55.2±1.4 years), and IGF-1 serum levels were assessed preoperatively and at 15, 30, 90, 180 and 365 days after transplantation. The influence of the donor and recipient characteristics (age, use of extended criteria donor grafts, D-MELD and incidence of early allograft dysfunction) on hormonal concentration was analyzed. The prognostic role of IGF-1 level on patient survival and its correlation with routine liver function tests were also investigated. Results All patients showed low preoperative IGF-1 levels (mean±SEM: 29.5±2.1), and on postoperative day 15, a significant increase in the IGF-1 plasma level was observed (102.7±11.7 ng/ml; p<0.0001). During the first year after LT, the IGF-1 concentration remained significantly lower in recipients transplanted with older donors (>65 years) or extended criteria donor grafts. An inverse correlation between IGF-1 and bilirubin serum levels at day 15 (r = -0.3924, p = 0.0320) and 30 (r = -0.3894, p = 0.0368) was found. After multivariate analysis, early (within 15 days) IGF-1 normalization [Exp(b) = 3.913; p = 0.0484] was the only prognostic factor associated with an increased 3-year survival rate. Conclusion IGF-1 postoperative levels are correlated with the graft’s quality and reflect liver function. Early IGF-1 recovery is associated with a higher 3-year survival rate after LT. PMID:26186540

  10. Effect of ?-alanine supplementation on high-intensity exercise performance.

    PubMed

    Harris, Roger C; Stellingwerff, Trent

    2013-01-01

    Carnosine is a dipeptide of ?-alanine and L-histidine found in high concentrations in skeletal muscle. Combined with ?-alanine, the pKa of the histidine imidazole ring is raised to ?6.8, placing it within the muscle intracellular pH high-intensity exercise transit range. Combination with ?-alanine renders the dipeptide inert to intracellular enzymic hydrolysis and blocks the histidinyl residue from participation in proteogenesis, thus making it an ideal, stable intracellular buffer. For vegetarians, synthesis is limited by ?-alanine availability; for meat-eaters, hepatic synthesis is supplemented with ?-alanine from the hydrolysis of dietary carnosine. Direct oral ?-alanine supplementation will compensate for low meat and fish intake, significantly raising the muscle carnosine concentration. This is best achieved with a sustained-release formulation of ?-alanine to avoid paresthesia symptoms and decreasing urinary spillover. In humans, increased levels of carnosine through ?-alanine supplementation have been shown to increase exercise capacity and performance of several types, particularly where the high-intensity exercise range is 1-4 min. ?-Alanine supplementation is used by athletes competing in high-intensity track and field cycling, rowing, swimming events and other competitions. PMID:23899755

  11. Clinical, biochemical, and histological studies of osteomalacia, osteoporosis, and parathyroid function in chronic liver disease

    Microsoft Academic Search

    R G Long; E Meinhard; R K Skinner; Z Varghese; M R Wills; S Sherlock

    1978-01-01

    Twenty of 32 patients with either chronic cholestatic or hepatocellular liver disease had bone pain or recent fractures. On bone biopsy five patients had normal bone, 15 had osteomalacia, five had osteoporosis, and seven had a combination of osteomalacia and osteoporosis. In the presence of osteoporosis, osteomalacia was minimal or absent. There was no biochemical, radiological, or histological evidence of

  12. Insights into the requirement of phosphatidylcholine synthesis for liver function in mice

    Microsoft Academic Search

    Anna A. Noga; Dennis E. Vance

    2003-01-01

    Phosphatidylcholine (PC) is made in the liver by the CDP-choline pathway and via phosphatidylethanol- amine N -methyltransferase (PEMT), which catalyzes the con- version of phosphatidylethanolamine to PC. Unexpect- edly, hepatic apolipoprotein B-100 secretion is inhibited in male, but not female, Pemt ? \\/ ? mice (Noga, A. A., Y. Zhao, and D. E. Vance. 2002. J. Biol. Chem. 277: 42358-42365;

  13. Hypoxic induction of vascular endothelial growth factor regulates erythropoiesis but not hematopoietic stem cell function in the fetal liver.

    PubMed

    Rehn, Matilda; Kertész, Zsuzsanna; Cammenga, Jörg

    2014-11-01

    Hypoxia is an important factor in the hematopoietic stem cell (HSC) niche in the bone marrow, but whether it also plays a role in the regulation of fetal liver (FL) HSCs is unclear. Vascular endothelial growth factor A (VEGFA) is essential for adult HSC survival, and hypoxic induction of VEGFA in adult HSCs is required for proper function. Loss of hypoxia-regulated VEGFA expression increases the number of phenotypically defined hematopoietic stem and progenitor cells in the FL, but whether stem cell function is affected in FL HSCs has not, to our knowledge, been assessed. We show that fetal erythropoiesis is severely impaired when hypoxic induction of VEGFA is lacking. FL HSCs deficient for hypoxia-induced VEGFA expression have normal HSC function, arguing against a hypoxic FL HSC niche. However, after adaptation of FL HSCs to the bone marrow microenvironment, FL HSCs lose their function, as measured by serial transplantation. PMID:25220588

  14. Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant.

    PubMed

    Takebe, Takanori; Zhang, Ran-Ran; Koike, Hiroyuki; Kimura, Masaki; Yoshizawa, Emi; Enomura, Masahiro; Koike, Naoto; Sekine, Keisuke; Taniguchi, Hideki

    2014-02-01

    Generation of functional and vascularized organs from human induced pluripotent stem cells (iPSCs) will facilitate our understanding of human developmental biology and disease modeling, hopefully offering a drug-screening platform and providing novel therapies against end-stage organ failure. Here we describe a protocol for the in vitro generation of a 3D liver bud from human iPSC cultures and the monitoring of further hepatic maturation after transplantation at various ectopic sites. iPSC-derived specified hepatic cells are dissociated and suspended with endothelial cells and mesenchymal stem cells. These mixed cells are then plated onto a presolidified matrix, and they form a 3D spherical tissue mass termed a liver bud (iPSC-LB) in 1-2 d. To facilitate additional maturation, 4-d-old iPSC-LBs are transplanted in the immunodeficient mouse. Live imaging has identified functional blood perfusion into the preformed human vascular networks. Functional analyses show the appearance of multiple hepatic functions in a chronological manner in vivo. PMID:24457331

  15. Growth and characterization of pure and semiorganic nonlinear optical Lithium Sulphate admixtured l-alanine crystal

    NASA Astrophysics Data System (ADS)

    Vela, T.; Selvarajan, P.; Freeda, T. H.; Balasubramanian, K.

    2013-04-01

    Lithium sulphate admixtured l-alanine (LSLA) salt was synthesized and the solubility of the commercially available l-alanine and the synthesized LSLA sample was determined in de-ionized water at various temperatures. In accordance with the solubility data, the saturated aqueous solutions of l-alanine and lithium admixtured l-alanine were prepared separately and the single crystals of the samples were grown by the solution method with a slow evaporation technique. Studying single x-ray diffraction shows that pure and LSLA crystal belong to the orthorhombic system with a non-centrosymmetric space group P212121. Using the powder x-ray diffraction study, the crystallinity of the grown crystals is confirmed and the diffraction peaks are indexed. The various functional groups present in the pure and LSLA crystal are elucidated from Fourier transform infrared spectroscopy study. UV-visible transmittance is recorded to study the optical transmittance range for the grown crystals. The powder second harmonic generation test confirms the nonlinear optical property of the grown crystals. From the microhardness test, the hardness of the grown crystals is estimated. The dielectric behaviour, such as the dielectric constant and the loss of the sample, are measured as a function of temperature and frequency. The ac conductivity of the grown crystals is also studied and the activation energy is calculated.

  16. Adaptation of hepatic mitochondrial function in humans with non-alcoholic Fatty liver is lost in steatohepatitis.

    PubMed

    Koliaki, Chrysi; Szendroedi, Julia; Kaul, Kirti; Jelenik, Tomas; Nowotny, Peter; Jankowiak, Frank; Herder, Christian; Carstensen, Maren; Krausch, Markus; Knoefel, Wolfram Trudo; Schlensak, Matthias; Roden, Michael

    2015-05-01

    The association of hepatic mitochondrial function with insulin resistance and non-alcoholic fatty liver (NAFL) or steatohepatitis (NASH) remains unclear. This study applied high-resolution respirometry to directly quantify mitochondrial respiration in liver biopsies of obese insulin-resistant humans without (n = 18) or with (n = 16) histologically proven NAFL or with NASH (n = 7) compared to lean individuals (n = 12). Despite similar mitochondrial content, obese humans with or without NAFL had 4.3- to 5.0-fold higher maximal respiration rates in isolated mitochondria than lean persons. NASH patients featured higher mitochondrial mass, but 31%-40% lower maximal respiration, which associated with greater hepatic insulin resistance, mitochondrial uncoupling, and leaking activity. In NASH, augmented hepatic oxidative stress (H2O2, lipid peroxides) and oxidative DNA damage (8-OH-deoxyguanosine) was paralleled by reduced anti-oxidant defense capacity and increased inflammatory response. These data suggest adaptation of the liver ("hepatic mitochondrial flexibility") at early stages of obesity-related insulin resistance, which is subsequently lost in NASH. PMID:25955209

  17. Differentiation of liver progenitor cell line to functional organotypic cultures in 3D nanofibrillar cellulose and hyaluronan-gelatin hydrogels.

    PubMed

    Malinen, Melina M; Kanninen, Liisa K; Corlu, Anne; Isoniemi, Helena M; Lou, Yan-Ru; Yliperttula, Marjo L; Urtti, Arto O

    2014-06-01

    Physiologically relevant hepatic cell culture models must be based on three-dimensional (3D) culture of human cells. However, liver cells are generally cultured in two-dimensional (2D) format that deviates from the normal in vivo morphology. We generated 3D culture environment for HepaRG liver progenitor cells using wood-derived nanofibrillar cellulose (NFC) and hyaluronan-gelatin (HG) hydrogels. Culture of undifferentiated HepaRG cells in NFC and HG hydrogels induced formation of 3D multicellular spheroids with apicobasal polarity and functional bile canaliculi-like structures, structural hallmarks of the liver tissue. Furthermore, hepatobiliary drug transporters, MRP2 and MDR1, were localized on the canalicular membranes of the spheroids and vectorial transport of fluorescent probes towards the biliary compartment was demonstrated. Cell culture in 3D hydrogel supported the mRNA expression of hepatocyte markers (albumin and CYP3A4), and metabolic activity of CYP3A4 in the HepaRG cell cultures. On the contrary, the 3D hydrogel cultures with pre-differentiated HepaRG cells showed decreasing expression of albumin and CYP3A4 transcripts as well as CYP3A4 activity. It is concluded that NFC and HG hydrogels expedite the hepatic differentiation of HepaRG liver progenitor cells better than the standard 2D culture environment. This was shown as improved cell morphology, expression and localization of hepatic markers, metabolic activity and vectorial transport. The NFC and HG hydrogels are promising materials for hepatic cell culture and tissue engineering. PMID:24698520

  18. Amelioration of Murine Schistosoma mansoni Induced Liver Fibrosis by Mesenchymal Stem Cells

    PubMed Central

    Abdel Aziz, MT; Atta, HM; Roshdy, NK; Rashed, LA; Sabry, D; Hassouna, AA; Aboul Fotouh, GI; Hasan, NM; Younis, RH; Chowdhury, JR

    2012-01-01

    Schistosomiasis is a common chronic helminthic infection of the liver that causes hepatic fibrosis and portal hypertension,contributing to the death of over half a million people a year. Infusion of autologous bone marrow cells into patients with hepatic cirrhosis has been reported to ameliorate symptoms of portal hypertension and improve liver function, either by conversion of the infused mesenchymal stem cells (MSCs) to hepatocytes or by modulating of the hepatic fibrosis. Here,we have investigated the antifibrotic effect of mesenchymal stem cells (MSCs) using S. mansoni-induced liver fibrosis in mice, which causes an intense, stable fibrosis. MSCs derived from bone marrow of male mice were then infused intravenously into female mice that had received intraperitoneal injection of S.mansoni cercariae. Mice were divided into 4 groups: Untreated control; MSCs infusion only; Schistosomiasis only; and Schistosomiasis plus MSCs infusion. Serum alanine aminotransferase (ALT) and liver histopathology were evaluated. Expression of the collagen gene (type I),transforming growth factor (TGF-?), matrix metalloproteinase (MMP2), tissue inhibitor of metalloproteinase (TIMP-1),stromal cell–derived factor–1(SDF-1) and its receptor (CXCR4) were analyzed. MSC infusion resulted in significant decrease in liver collagen and TGF-? gene expression in the Schistosomiasis mice. The ratio of MMP-2 to TIMP-1 expression increased. SDF-1 and CXCR4 mRNA expression also increased. There was overall improvement of liver histology and a statistically significant reduction of serum ALT level. MSCs infusion ameliorated S. mansoni-induced liver fibrosis, probably by modulating the relative expression of MMP and TIMP. The findings support the hypothesis that MSCs participate in liver regeneration and functional improvement by reducing liver fibrosis. PMID:24693190

  19. Liver function test abnormalities in Nigerian patients with human immunodeficiency virus and hepatitis B virus co-infection.

    PubMed

    Iroezindu, M O; Agbaji, O O; Daniyam, C A; Isiguzo, G C; Isichei, C; Akanbi, M O

    2013-06-01

    Data on baseline hepatic function of HIV and hepatitis B virus (HBV) co-infected patients are limited in sub-Saharan Africa. We assessed liver function test (LFT) abnormalities in Nigerian patients with HIV/HBV co-infection to highlight the impact of HIV on HBV-related liver disease in sub-Saharan Africa. A cross-sectional study involving 100 HIV/HBV co-infected patients and 100 age- and sex-matched HBV mono-infected controls. Blood testing for HIV antibodies, CD4+ cell count, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), LFTs, platelet count, fasting blood glucose and lipid profile were carried out. Non-invasive hepatic fibrosis scores (aspartate aminotransferase-platelet ratio index [APRI] and FIB-4) were also calculated. Co-infected patients had deranged liver enzymes more than the controls (77% versus 64%, P = 0.04). The predominant patterns of enzyme derangement in co-infected patients were either predominantly ?ALP (30% versus 4%, P < 0.0001) or mixed (30% versus 15%, P = 0.01) but predominantly ?AST/ALT in the controls (25% versus 9%, P = 0.003). Co-infected patients had higher fibrosis scores for both APRI (P = 0.002) and FIB-4 (P = 0.0001). On further analysis, LFT abnormalities and fibrosis scores were only significantly higher in co-infected patients in the immune clearance and HBeAg-negative chronic hepatitis phases. LFT abnormalities are common in Nigerians with HBV infection and co-infection with HIV negatively impacts on hepatic function. PMID:23970749

  20. Blood alanine aminotransferase levels >1,000 IU/l - causes and outcomes.

    PubMed

    Galvin, Zita; McDonough, Anna; Ryan, John; Stewart, Stephen

    2015-06-01

    Standard medical education dictates that the vast majority of cases of an alanine aminotransferase (ALT) level >1,000 IU/l will be due to acute ischaemia, acute drug-induced liver injury (DILI) (usually paracetamol) or acute viral hepatitis. There are very few references in the literature to other potential causes of an ALT >1,000 IU/l nor to the prognosis ascribed to each aetiology. In this study, we have confirmed that the main causes of a dramatic ALT rise are ischaemic liver injury, DILI and viral hepatitis. Common bile duct stones and hepatitis E are two causes for which there needs to be a high index of suspicion as the necessary tests may not be in the clinician's first-line investigation panel. Failing to find a cause and determining that the cause was ischaemic both have poor prognostic implications. PMID:26031973

  1. Gene expression and enzyme function of two cytochrome P450 3A isoenzymes in rat and cattle precision cut liver slices.

    PubMed

    Maté, María Laura; Ballent, Mariana; Larsen, Karen; Lifschitz, Adrian; Lanusse, Carlos; Virkel, Guillermo

    2015-07-01

    1.?Precision-cut liver slices are one of the in vitro models used in studies concerning xenobiotic metabolism. Sparse information on this field is actually available for cattle and other veterinary species. 2.?The aim of the current work was to study the effect of dexamethasone (DEX) on the gene expression and function of CYP3A23 (in rat), CYP3A28 (in cattle) and the transcriptional factors involved in their regulation. 3.?DEX (at 100?µM) up-regulated CYP3A23 mRNA (3.2-fold, p?=?0.028) in rat liver slices after 12?h culture, whereas the gene expression profiles of transcriptional factors involved in CYP3A regulation were unaffected. A CYP3A-dependent enzyme activity (triacetyl-oleandomycin N-demethylase) increased 3.4-fold (p?liver slices cultured in the presence of DEX. 4.?The protocol used for rat liver slices was used as reference to study the expression of a CYP3A isoenzyme in cattle liver slices. Oppositely, DEX did neither affect the gene expression profile of CYP3A28 nor the CYP3A activity tested in cattle liver slices. 5.?The data reported here are a further contribution to demonstrate the usefulness of liver slices as an in vitro tool for studies on the expression and function of xenobiotic metabolizing enzymes in cattle and in other ruminant species. PMID:25630049

  2. Occupational lead exposure and amino acid profiles and liver function tests in industrial workers

    Microsoft Academic Search

    F. R. M. Al-Neamy; A. M. Almehdi; R. Alwash; M. A. H. Pasha; A. Ibrahim; A. Bener

    2001-01-01

    The aim of the present study is to determine the effect of blood lead on the plasma levels of amino acids and serum liver enzymes in industrial workers in United Arab Emirates (UAE). This comparison study consisted of 100 industrial workers (exposed) and 100 non-industrial workers (non-exposed), matched for age, sex and nationality selected from Al-Ain, Abu-Dhabi Emirates. Industrial workers

  3. Overexpression of Functional Hydrolase Domain of Rat Liver 10-Formyltetrahydrofolate Dehydrogenase in Escherichia coli

    Microsoft Academic Search

    Sergey A. Krupenko; Conrad Wagner

    1998-01-01

    Rat liver 10-formyltetrahydrofolate dehydrogenase (FDH) is a tetrameric enzyme composed of four identical 902-amino-acid-residue (99 kDa) monomers. We expressed the enzyme and its 310-amino-acid-residue amino-terminal domain, which is 10-formyltetrahydrofolate hydrolase, inEscherichia coliBL21 (DE3) cells using the pRSET expression vector. We removed the entire translated region of the vector including the polyhistidyl tag and the recombinant proteins were expressed, not as

  4. Compartmental analysis of asialoglycoprotein receptor scintigraphy for quantitative measurement of liver function: A multicentre study

    Microsoft Academic Search

    Sang Kil Ha-Kawa; Yoshimasa Tanaka; Shin Hasebe; Yoshio Kuniyasu; Kiyoshi Koizumi; Yasushi Ishii; Kazutaka Yamamoto; Toru Kashiwagi; Akihiko Ito; Masatoshi Kudo; Katsuji Ikekubo; Takaharu Tsuda

    1997-01-01

    A multicentre study on multicompartmental analysis of hepatic scintigraphy using technetium-99m labelled galactosyl serum\\u000a albumin (GSA), which binds to the asialoglycoprotein receptor, was carried out at seven institutions in Japan. Seventy-four\\u000a patients with liver disease received 3 mg (185 MBq) of99mTc-GSA by intravenous injection. Sequential scanning was performed 30 min after injection to obtain anterior images of the\\u000a heart and

  5. Functional differences between transplantable human hematopoietic stem cells from fetal liver, cord blood, and adult marrow

    Microsoft Academic Search

    Tessa L Holyoake; Franck E Nicolini; Connie J Eaves

    1999-01-01

    The purpose of this study was to develop a simple assay for quantitating transplantable human lymphomyeloid stem cells (competitive repopulating units [CRU]) to enable comparison among the numbers and types of progeny generated in NOD\\/SCID mice by such cells from different ontologic sources. Sublethally irradiated NOD\\/SCID mice were transplanted with varying numbers of CD34+ cell-enriched suspensions of human fetal liver,

  6. Submitochondrial localization and function of enzymes of glutamine metabolism in avian liver

    PubMed Central

    1977-01-01

    Glutamine synthetase (EC 6.3.1.2) was localized within the matrix compartment of avian liver mitochondria. The submitochondrial localization of this enzyme was determined by the digitonin-Lubrol method of Schnaitman and Greenawalt (35). The matrix fraction contained over 74% of the glutamine synthetase activity and the major proportion of the matirx marker enzymes, malate dehydrogenase (71%), NADP- dependent isocitrate dehydrogenase (83%), and glutamate dehydrogenase (57%). The highest specific activities of these enzymes were also found in the matrix compartment. Oxidation of glutamine by avian liver mitochondria was substantially less than that of glutamate. Bromofuroate, an inhibitor of glutamate dehydrogenase, blocked oxidation of glutamate and of glutamine whereas aminoxyacetate, a transaminase inhibitor, had little or no effect with either substrate. These results indicate that glutamine metabolism is probably initiated by the conversion of glutamine to glutamate rather than to an alpha- keto acid. The localization of a glutaminase activity within avian liver mitochondria plus the absence of an active mitochondrial glutamine transaminase is consistent with the differential effects of the transaminase and glutamate dehydrogenase inhibitors. The high glutamine synthetase activity (40:1) suggests that mitochondrial catabolism of glutamine is minimal, freeing most of the glutamine synthesized for purine (uric acid) biosynthesis. PMID:16018

  7. Cardiovascular function following acute volume overload for hydrodynamic gene delivery to the liver.

    PubMed

    Sawyer, G J; Dong, X; Whitehorne, M; Grehan, A; Seddon, M; Shah, A M; Zhang, X; Fabre, J W

    2007-08-01

    Hydrodynamic gene delivery to the liver is a valuable experimental tool and an attractive option for nonviral gene therapy of liver disease. However, little attention has been paid to the major obstacle to clinical application: acute volume overload of the cardiovascular system. We delivered volumes of DNA solution (pGL3 plasmid) corresponding to 1, 2, 4, 6 and 8% of the body weight at 100 ml/min to the inferior vena cava (IVC) of DA strain rats. Central venous pressure (CVP), arterial pressure, pulse and electrocardiogram (ECG) were continuously recorded for subsequent analysis. Each volume produced a characteristic response, but all (including the 1% volume) caused severe falls in blood pressure and pulse within 1-2 s of the infusion, with ectopic beats and widening of the QRS complex in the ECG. The response to volumes of 4% and higher suggested that the liver acted as a volume sink, mitigating the immediate effects of volume overload. The 6 and 8% volumes caused profound and protracted falls in blood pressure and pulse, with a multitude of severe electrical abnormalities in the heart, including electromechanical dissociation. Vagal blockade with atropine, and the use of Ringer's solution to prevent electrolyte disturbances, did not ameliorate this picture. PMID:17568768

  8. Emerging Therapies for Liver Fibrosis

    Microsoft Academic Search

    Andrew J. Fowell; John P. Iredale

    2006-01-01

    Liver fibrosis occurs as a result of a wide range of injurious processes and in its end-stage results in cirrhosis. This gross disruption of liver architecture is associated with impaired hepatic function, portal hypertension and significant resultant morbidity and mortality. Indeed, liver fibrosis and cirrhosis represent a major worldwide healthcare burden. Recent progress in liver transplantation, the management of portal

  9. Determination of the upper cut-off values of serum alanine aminotransferase and aspartate aminotransferase in Chinese

    PubMed Central

    Zhang, Peng; Wang, Chun-Yan; Li, Yu-Xiang; Pan, Yu; Niu, Jun-Qi; He, Shu-Mei

    2015-01-01

    AIM: To determine the upper cut-off values of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a Northern Chinese population. METHODS: A total of 3769 subjects in Jilin Province Northeast China were stratified to determine the potential factors affecting serum ALT and AST levels. The upper cut-off values of serum ALT and AST in these subjects were determined using receiver operating characteristic analysis and their sensitivity and specificity were evaluated. RESULTS: Stratification analysis revealed that serum ALT and AST levels were associated with gender, alcohol consumption, serum cholesterol and triglyceride levels, and body mass index. The upper cut-off values of serum ALT and AST were 22.15 U/L and 25.35 U/L for healthy men and 22.40 U/L and 24.25 U/L for healthy women, respectively. The new cut-off values had a higher sensitivity, but a slightly lower specificity than the current standards. CONCLUSION: Our results indicate that the new upper cut-off values of serum ALT and AST are markedly lower than current standards and may be valuable for the evaluation of liver function. PMID:25741150

  10. The structure of alanine racemase from Acinetobacter baumannii

    PubMed Central

    Davis, Emily; Scaletti-Hutchinson, Emma; Opel-Reading, Helen; Nakatani, Yoshio; Krause, Kurt L.

    2014-01-01

    Acinetobacter baumannii is an opportunistic Gram-negative bacterium which is a common cause of hospital-acquired infections. Numerous antibiotic-resistant strains exist, emphasizing the need for the development of new antimicrobials. Alanine racemase (Alr) is a pyridoxal 5?-phosphate dependent enzyme that is responsible for racemization between enantiomers of alanine. As d-alanine is an essential component of the bacterial cell wall, its inhibition is lethal to prokaryotes, making it an excellent antibiotic drug target. The crystal structure of A. baumannii alanine racemase (AlrAba) from the highly antibiotic-resistant NCTC13302 strain has been solved to 1.9?Å resolution. Comparison of AlrAba with alanine racemases from closely related bacteria demonstrates a conserved overall fold. The substrate entryway and active site of the enzymes were shown to be highly conserved. The structure of AlrAba will provide the template required for future structure-based drug-design studies. PMID:25195891

  11. Effects of Iron Overload and Lindane Intoxication in Relation to Oxidative Stress, Kupffer Cell Function, and Liver Injury in the Rat

    Microsoft Academic Search

    Barbara Junge; Yasna Carrion; Cleofina Bosco; Monica Galleano; Susana Puntarulo; Gladys Tapia; Luis A. Videla

    2001-01-01

    Parameters related to liver oxidative stress, Kupffer cell function, and hepatocellular injury were assessed in control rats and in animals subjected to lindane (40 mg\\/kg; 24 h) and\\/or iron (200 mg\\/kg; 4 h) administration. Independently of lindane treatment, iron overload enhanced the levels of iron in serum and liver. Biliary efflux of glutathione disulfide increased by 140, 160, or 335%

  12. Effects of total parenteral nutrition enriched with branched chain amino acid infusion on liver function and serum amino acid pattern in dogs undergoing hepatectomy

    Microsoft Academic Search

    Maurizio De Caterina; Domenico Piccolboni; Raffaele Alfieri; Giuliano Spagnuolo; Claudio Petrè; Giuseppe Aliperti; Freddy Del Gaudio; Franco Rendano

    1985-01-01

    Summary  In order to study effects of different total parenteral nutritional regimens on the recovery of liver function and on plasma\\u000a amino acid pattern after major hepatectomy, twelve healthy mongrel dogs were submitted to 70% liver resection and randomly\\u000a divided into three different groups:group I (control group) received only 10% glucose;group II received 10% glucose plus 8.85% Freamine®;group III received 10%

  13. Alanine production in an H+-ATPase- and lactate dehydrogenase-defective mutant of Escherichia coli expressing alanine dehydrogenase.

    PubMed

    Wada, Masaru; Narita, Kotomi; Yokota, Atsushi

    2007-09-01

    Previously, we reported that pyruvate production was markedly improved in TBLA-1, an H(+)-ATPase-defective Escherichia coli mutant derived from W1485lip2, a pyruvate-producing E. coli K-12 strain. TBLA-1 produced more than 30 g/l pyruvate from 50 g/l glucose by jar fermentation, while W1485lip2 produced only 25 g/l pyruvate (Yokota et al. in Biosci Biotechnol Biochem 58:2164-2167, 1994b). In this study, we tested the ability of TBLA-1 to produce alanine by fermentation. The alanine dehydrogenase (ADH) gene from Bacillus stearothermophilus was introduced into TBLA-1, and direct fermentation of alanine from glucose was carried out. However, a considerable amount of lactate was also produced. To reduce lactate accumulation, we knocked out the lactate dehydrogenase gene (ldhA) in TBLA-1. This alanine dehydrogenase-expressing and lactate dehydrogenase-defective mutant of TBLA-1 produced 20 g/l alanine from 50 g/l glucose after 24 h of fermentation. The molar conversion ratio of glucose to alanine was 41%, which is the highest level of alanine production reported to date. This is the first report to show that an H(+)-ATPase-defective mutant of E. coli can be used for amino acid production. Our results further indicate that H(+)-ATPase-defective mutants may be used for fermentative production of various compounds, including alanine. PMID:17583806

  14. Serial changes in expression of functionally clustered genes in progression of liver fibrosis in hepatitis C patients

    PubMed Central

    Takahara, Yoshiyuki; Takahashi, Mitsuo; Zhang, Qing-Wei; Wagatsuma, Hirotaka; Mori, Maiko; Tamori, Akihiro; Shiomi, Susumu; Nishiguchi, Shuhei

    2008-01-01

    AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients. METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) in clinical biopsy specimens from HCV-positive patients (n = 61). Analysis of changes in expression patterns and interactions of marker genes in functional categories was used to assess the biological mechanism of fibrosis. RESULTS: The profile data showed several biological changes associated with progression of hepatic fibrosis. Clustered genes in functional categories showed sequential changes in expression. Several sets of clustered genes, including those related to the extracellular matrix (ECM), inflammation, lipid metabolism, steroid metabolism, and some transcription factors important for hepatic biology showed expression changes in the immediate early phase (F1/F2) of fibrosis. Genes associated with aromatic amino acid (AA) metabolism, sulfur-containing AA metabolism and insulin/Wnt signaling showed expression changes in the middle phase (F2/F3), and some genes related to glucose metabolism showed altered expression in the late phase of fibrosis (F3/F4). Therefore, molecular networks showing serial changes in gene expression are present in liver fibrosis progression in hepatitis C patients. CONCLUSION: Analysis of gene expression profiles from a perspective of functional categories or molecular networks provides an understanding of disease and suggests new diagnostic methods. Selected marker genes have potential utility for biological identification of advanced fibrosis. PMID:18395900

  15. Cloning and functional characterization of the bile acid-sensitive methotrexate carrier from rat liver cells.

    PubMed

    Honscha, W; Dötsch, K U; Thomsen, N; Petzinger, E

    2000-06-01

    We have cloned two complementary DNAs (cDNAs), RL-Mtx-1 and RL-Mtx-2, corresponding to the bile acid- sensitive methotrexate carrier from rat liver by direct full-length rapid amplification of cDNA ends polymerase chain reaction (RACE-PCR) using degenerated primers that were deduced from published sequences of tumor cell methotrexate transporters. When expressed in Xenopus laevis oocytes and cosM6 cells, both clones mediate methotrexate and bumetanide transport. RL-Mtx-1 consists of 2,445 bp with an open reading frame of 1,536 bp. The corresponding protein with 512 amino acids has a molecular weight of 58 kd. RL-Mtx-2 (2,654 bp) differs by an additional insert of 203 bp. This insert is located in frame at position 1,196 of the RL-Mtx-1 and contains the typical splice junction sites at the 5' and 3' end, indicating that the RL-Mtx-2 messenger RNA (mRNA) is generated by alternative splicing. The insert contains a stop codon that shortens the RL-Mtx-2 protein to 330 amino acids (38 kd). Both cDNAs contain the binding site sequence for the dioxin/nuclear translocator responsive element (Ah/Arnt-receptor) in conjunction with a barbiturate recognition sequence (Barbie box). Preliminary results show that the Barbie box acts as a negative regulatory element. The two liver cDNA clones show homologies to the published sequences of folate and the reduced folate carriers, but no homology is found to the transport systems for organic anions like the Ntcp1, oatp1, OAT-K1, and OAT1. Expression of the mRNA for the methotrexate carrier is found in liver, kidney, heart, brain, spleen, lung, and skeletal muscle, but not in the testis as revealed by Northern blot analysis. The highest abundance of the mRNA is found in the kidney. PMID:10827155

  16. Recent progress on liver kinase B1 (LKB1): expression, regulation, downstream signaling and cancer suppressive function.

    PubMed

    Gan, Ren-You; Li, Hua-Bin

    2014-01-01

    Liver kinase B1 (LKB1), known as a serine/threonine kinase, has been identified as a critical cancer suppressor in many cancer cells. It is a master upstream kinase of 13 AMP-activated protein kinase (AMPK)-related protein kinases, and possesses versatile biological functions. LKB1 gene is mutated in many cancers, and its protein can form different protein complexes with different cellular localizations in various cell types. The expression of LKB1 can be regulated through epigenetic modification, transcriptional regulation and post-translational modification. LKB1 dowcnstream pathways mainly include AMPK, microtubule affinity regulating kinase (MARK), salt-inducible kinase (SIK), sucrose non-fermenting protein-related kinase (SNRK) and brain selective kinase (BRSK) signalings, etc. This review, therefore, mainly discusses recent studies about the expression, regulation, downstream signaling and cancer suppressive function of LKB1, which can be helpful for better understanding of this molecular and its significance in cancers. PMID:25244018

  17. Recent Progress on Liver Kinase B1 (LKB1): Expression, Regulation, Downstream Signaling and Cancer Suppressive Function

    PubMed Central

    Gan, Ren-You; Li, Hua-Bin

    2014-01-01

    Liver kinase B1 (LKB1), known as a serine/threonine kinase, has been identified as a critical cancer suppressor in many cancer cells. It is a master upstream kinase of 13 AMP-activated protein kinase (AMPK)-related protein kinases, and possesses versatile biological functions. LKB1 gene is mutated in many cancers, and its protein can form different protein complexes with different cellular localizations in various cell types. The expression of LKB1 can be regulated through epigenetic modification, transcriptional regulation and post-translational modification. LKB1 dowcnstream pathways mainly include AMPK, microtubule affinity regulating kinase (MARK), salt-inducible kinase (SIK), sucrose non-fermenting protein-related kinase (SNRK) and brain selective kinase (BRSK) signalings, etc. This review, therefore, mainly discusses recent studies about the expression, regulation, downstream signaling and cancer suppressive function of LKB1, which can be helpful for better understanding of this molecular and its significance in cancers. PMID:25244018

  18. The polyproline II conformation in short alanine peptides is noncooperative

    PubMed Central

    Chen, Kang; Liu, Zhigang; Kallenbach, Neville R.

    2004-01-01

    The finding that short alanine peptides possess a high fraction of polyproline II (PII) structure (? = -75°, ? = +145°) at low temperature has broad implications for unfolded states of proteins. An important question concerns whether or not this structure is locally determined or cooperative. We have monitored the conformation of alanine in a series of model peptides AcGG(A)nGGNH2 (n = 1–3) over a temperature range from -10°C to +80°C. Use of 15N-labeled alanine substitutions makes it possible to measure 3J?N coupling constants accurately over the full temperature range. Based on a 1D next-neighbor model, the cooperative parameter ? of PII nucleation is evaluated from the coupling constant data. The finding that ? is close to unity (1 ± 0.2) indicates a noncooperative role for alanine in PII structure formation, consistent with statistical surveys of the Protein Data Bank that suggest that most PII structure occurs in isolated residues. Lack of cooperativity in these models implies that hydration effects that influence PII conformation in water are highly localized. Using a nuclear Overhauser effect ratio strategy to define the alanine ? angle, we estimate that, at 40°C, the time-averaged alanine conformation (? = -80°, ? = +170°) deviates from canonical PII structure, indicating that PII melts at high temperature. Thus, the high-temperature state of short alanine peptides seems to be an unfolded ensemble with higher distribution in the extended ? structure basin, but not a coil. PMID:15489268

  19. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease

    PubMed Central

    Kozlitina, Julia; Smagris, Eriks; Stender, Stefan; Nordestgaard, Børge G.; Zhou, Heather H.; Tybjærg-Hansen, Anne; Vogt, Thomas F.; Hobbs, Helen H.; Cohen, Jonathan C.

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease. To elucidate the molecular basis of NAFLD we performed an exome-wide association study of liver fat content. Three variants were associated with increased liver fat at the exome-wide significance level: two in PNPLA3, an established locus for NAFLD, and one (Glu167Lys) in TM6SF2, a gene of unknown function. The Glu167LysTM6SF2 variant was also associated with higher circulating levels of alanine transaminase, a marker of liver injury, and lower levels of LDL-cholesterol, triglycerides and alkaline phosphatase in 3 independent populations (n>80,000). Recombinant Glu167LysTM6SF2 produced 50% less protein than wild-type TM6SF2 when expressed in cultured hepatocytes. Adeno-associated virus-mediated shRNA knockdown of Tm6sf2 in mice increased liver triglyceride content 3-fold and decreased VLDL secretion by 50%. Taken together, these data indicate that TM6SF2 activity is required for normal VLDL secretion, and that impaired TM6SF2 function causally contributes to NAFLD. PMID:24531328

  20. Contradictory functions of NF-kappaB in liver physiology and cancer.

    PubMed

    Vainer, Gilad W; Pikarsky, Eli; Ben-Neriah, Yinon

    2008-08-28

    Rudolf Virchow (1821-1902), one of the founding fathers of modern pathology, hypothesized that cancer and inflammatory processes are linked, due to the presence of leukocytes in the tumor tissue. Today, chronic inflammation is believed to be one of the major causes for cancer development, accounting for nearly 20% of cancer cases worldwide. Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality throughout the world, and its incidence is increasing in the United States. HCC is widely accepted to be the outcome of continuous injury and chronic inflammation, and thus provides a good model to gain insight into inflammatory related cancer processes. Nuclear Factor- kappa B (NF-kappaB) was first identified as an enhancer protein of the kappa light-chain gene in B lymphocytes. Later it was realized that there are five NF-kappaB transcription factors with important roles in inflammation, innate immunity, cancer and apoptosis aborting. Consequently, NF-kappaB was shown to link inflammation and cancer, but recent reports have revealed it to play a much more complex role, where in some disease processes it promotes cancer and in others it impedes carcinogenesis. In this review, we will focus on the seemingly contradictory role of NF-kappaB in liver homeostasis, as well as in liver cancer. PMID:18479806

  1. Metallothionein can function as a chaperone for zinc uptake transport into prostate and liver mitochondria

    PubMed Central

    Costello, Leslie C.; Guan, Zhixin; Franklin, Renty B.; Feng, Pei

    2015-01-01

    In mammalian cells the cytosolic concentration of free Zn2+ ions is extremely low (nM–fM range) and unlikely to provide an adequate pool for the uptake and accumulation of zinc in mitochondria. We previously identified a mitochondrial uptake transport process that effectively transports zinc directly from low molecular weight zinc ligands independent of and in the absence of available free Zn2+ ions. Since metallothionein (MT) is an important ligand form of cellular zinc, we determined if Zn7-MT was an effective chaperone and donor for delivery and uptake of zinc by prostate and liver mitochondria. The results reveal that both intact mitochondria and mitoplasts effectively accumulated zinc from Zn7-MT. The study confirms and extends our previous report that the putative zinc transporter is associated with the inner mitochondrial membrane and involves a direct exchange of zinc from the ligand to the transporter. The ventral prostate cells contain no detectable MT; so that ligands (such as citrate, aspartate) other than MT are zinc donors for mitochondrial zinc accumulation. However, in liver and perhaps other cells, Zn7-MT is probably important in the cytosolic trafficking of zinc to the mitochondria for the uptake of zinc into the mitochondrial matrix by the putative zinc uptake transporter. PMID:15041247

  2. SOD Mimetic Improves the Function, Growth and Survival of Small Size Liver Grafts after Transplantation in Rats

    PubMed Central

    Cui, Yi-Yao; Qian, Jian-Ming; Yao, Ai-Hua; Ma, Zhen-Yu; Qian, Xiao-Feng; Zha, Xiao-Min; Zhao, Yi; Ding, Qiang; Zhao, Jia; Wang, Shui; Wu, Jian

    2012-01-01

    BACKGROUND Small-for-size syndrome (SFSS) may occur when graft volume is less than 45% of the standard liver volume, and it manifests as retarded growth and failure of the grafts and an increased mortality. However, its pathogenesis is poorly understood, and few effective interventions have been attempted. AIMS The present study aims to delineate the critical role of oxidant stress in SFSS and protective effects of a superoxide dismutase (SOD) mimetic, MnTBAP, on graft function, growth and survival in the recipient rats. METHODS Small size graft liver transplantation (SSGLT) was performed to determine the survival, graft injury and growth. MnTBAP was administered in SSGLT recipients (SSGLT+MnTBAP). RESULTS Serum ALT levels were sustained higher in SSGLT recipients, which were correlated with an increased apoptotic cell count and hepatocellular necrosis in liver sections. Malondialdehyde content, gene expression of TNF-? and IL-1? and DNA binding activity of NF-?B in the grafts were increased significantly in SSGLT recipients compared to sham-operated controls. Both phosphorylated p38 MAPK and nuclear c-jun were increased in SSGLT. All these changes were strikingly reversed by the administration of MnTBAP, with an increase in serum SOD activity. Moreover, in situ bromo-deoxyuridine incorporation demonstrated that graft regeneration in SSGLT+MnTBAP group was much profound than in the SSGLT group. Finally, the survival of recipients with MnTBAP treatments was significantly improved. CONCLUSIONS Enhanced oxidant stress with activation of the p38-c-Jun-NF-?B signaling pathway contributes to SFS-associated graft failure, retarded graft growth and poor survival. MnTBAP effectively reversed the pathologic changes in SFS-associated graft failure. PMID:22955229

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

    PubMed Central

    Rui, Mengjie; Guo, Wei; Ding, Qian; Wei, Xiaohui; Xu, Jianrong; Xu, Yuhong

    2012-01-01

    Background Natural high-density lipoproteins (HDL) possess important physiological functions to the transport of cholesterol from the peripheral tissues to the liver for metabolic degradation and excretion in the bile. Methods and results In this work, we took advantage of this pathway and prepared two different gadolinium (Gd)-DTPA-labeled cholesterol-containing recombinant HDL nanoparticles (Gd-chol-HDL) and Gd-(chol)2-HDL as liver-specific magnetic resonance imaging (MRI) contrast agents. The reconstituted HDL nanoparticles had structural similarity to native HDL, and could be taken up by HepG2 cells via interaction with HDL receptors in vitro. In vivo MRI studies in rats after intravenous injections of 10 ?mol gadolinium per kg of recombinant HDL nanoparticles indicated that both nanoparticles could provide signal enhancement in the liver and related organs. However, different T1-weighted image details suggested that they participated in different cholesterol metabolism and excretion pathways in the liver. Conclusion Such information could be highly useful to differentiate functional changes as well as anatomic differences in the liver. These cholesterol-derived contrast agents and their recombinant HDL preparations may warrant further development as a new class of contrast agents for MRI of the liver and related organs. PMID:22888232

  4. Associations between liver enzymes, psychopathological and clinical features in eating disorders.

    PubMed

    Lelli, Lorenzo; Castellini, Giovanni; Gabbani, Tommaso; Godini, Lucia; Rotella, Francesco; Ricca, Valdo

    2014-11-01

    Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are frequently reported in patients with anorexia nervosa (AN) and in subjects who are overweight or with hyperlipidemia, which can be found to be associated with binge eating disorder (BED) and bulimia nervosa (BN). Liver functioning and psychopathological features have been evaluated in 43 patients with AN, 33 with BN, and 32 with BED. Body mass index was found to be inversely associated with AST and ALT in AN, and directly associated with AST and ALT in BED. A positive association between ALT and AST and body shape concern in AN was observed. Liver enzymes could be considered as an index of severity in AN and BED patients. PMID:25139759

  5. Protective effect of Tribulus terrestris linn on liver and kidney in cadmium intoxicated rats.

    PubMed

    Lakshmi, G Dhana; Kumar, P Ravi; Bharavi, K; Annapurna, P; Rajendar, B; Patel, Pankaj T; Kumar, C S V Satish; Rao, G S

    2012-02-01

    Administration of cadmium (Cd) significantly increased the peroxidation markers such as malondialdehyde and protein carbonyls along with significant decrease in antioxidant markers such as super oxide dismutase and reduced glutathione in liver and kidney tissues. Cadmium also caused a significant alteration in hepatic and renal functional markers in serum viz. total protein, albumin, alanine transaminase, blood urea nitrogen and creatinine. Prominent pathological changes observed in liver were severe vascular and sinusoidal congestion with diffuse degenerative changes and mononuclear infiltration into peripheral areas, while the kidney showed vascular and glomerular congestion, cloudy swelling of tubular epithelium. Coadministration of ethonolic extract of T. terrestris or vitamin E along with Cd significantly reversed the Cd induced changes along with significant reduction in Cd load. PMID:22670477

  6. Longitudinal Blood Pressure Control, Long-Term Mortality, and Predictive Utility of Serum Liver Enzymes and Bilirubin in Hypertensive Patients.

    PubMed

    McCallum, Linsay; Panniyammakal, Jeemon; Hastie, Claire E; Hewitt, Jonathan; Patel, Rajan; Jones, Gregory C; Muir, Scott; Walters, Matthew; Sattar, Naveed; Dominiczak, Anna F; Padmanabhan, Sandosh

    2015-07-01

    There is accruing evidence from general population studies that serum bilirubin and liver enzymes affect blood pressure (BP) and cardiovascular risk, but it is unclear whether these have an impact on hypertensive patients in terms of long-term survival or BP control. We analyzed 12?000 treated hypertensive individuals attending a tertiary care clinic followed up for 35 years for association between baseline liver function tests and cause-specific mortality after adjustment for conventional cardiovascular covariates. Generalized estimating equations were used to study the association of liver tests and follow-up BP. The total time at risk was 173?806 person years with median survival 32.3 years. Follow-up systolic BP over 5 years changed by -0.4 (alanine transaminase and bilirubin), +2.1(alkaline phosphatase), +0.9(?-glutamyl transpeptidase) mm?Hg for each standard deviation increase. Serum total bilirubin and alanine transaminase showed a significant negative association with all-cause and cardiovascular mortality, whereas alkaline phosphatase and ?-glutamyl transpeptidase showed a positive association and aspartate transaminase showed a U-shapedassociation. Serum bilirubin showed an incremental improvement of continuous net reclassification improvement by 8% to 26% for 25 year and 35 year cardiovascular mortality, whereas all liver markers together improved continuous net reclassification improvement by 19% to 47% compared with reference model. In hypertensive patients, serum liver enzymes and bilirubin within 4 standard deviations of the mean show independent effects on mortality and BP control. Our findings would support further studies to elucidate the mechanisms by which liver enzymes and bilirubin may exert an effect on BP and cardiovascular risk, but there is little support for using them in risk stratification. PMID:25941342

  7. Longitudinal Blood Pressure Control, Long-Term Mortality, and Predictive Utility of Serum Liver Enzymes and Bilirubin in Hypertensive Patients

    PubMed Central

    McCallum, Linsay; Panniyammakal, Jeemon; Hastie, Claire E.; Hewitt, Jonathan; Patel, Rajan; Jones, Gregory C.; Muir, Scott; Walters, Matthew; Sattar, Naveed; Dominiczak, Anna F.

    2015-01-01

    There is accruing evidence from general population studies that serum bilirubin and liver enzymes affect blood pressure (BP) and cardiovascular risk, but it is unclear whether these have an impact on hypertensive patients in terms of long-term survival or BP control. We analyzed 12?000 treated hypertensive individuals attending a tertiary care clinic followed up for 35 years for association between baseline liver function tests and cause-specific mortality after adjustment for conventional cardiovascular covariates. Generalized estimating equations were used to study the association of liver tests and follow-up BP. The total time at risk was 173?806 person years with median survival 32.3 years. Follow-up systolic BP over 5 years changed by ?0.4 (alanine transaminase and bilirubin), +2.1(alkaline phosphatase), +0.9(?-glutamyl transpeptidase) mm?Hg for each standard deviation increase. Serum total bilirubin and alanine transaminase showed a significant negative association with all-cause and cardiovascular mortality, whereas alkaline phosphatase and ?-glutamyl transpeptidase showed a positive association and aspartate transaminase showed a U-shapedassociation. Serum bilirubin showed an incremental improvement of continuous net reclassification improvement by 8% to 26% for 25 year and 35 year cardiovascular mortality, whereas all liver markers together improved continuous net reclassification improvement by 19% to 47% compared with reference model. In hypertensive patients, serum liver enzymes and bilirubin within 4 standard deviations of the mean show independent effects on mortality and BP control. Our findings would support further studies to elucidate the mechanisms by which liver enzymes and bilirubin may exert an effect on BP and cardiovascular risk, but there is little support for using them in risk stratification. PMID:25941342

  8. Structural and function changes in organelles of liver cells in rats exposed to magnetic fields

    SciTech Connect

    Gorczynska, E. (Pomeranian Medical Academy, Szczecin (Poland)); Wegrzynowicz, R. (Academy of Agriculture, Szczecin (Poland))

    1991-08-01

    Exposure of rats to magnetic fields of 10{sup {minus}3} and 10{sup {minus}2} T for 1 hr daily generated structural changes in hepatocytes mitochondria, endoplasmic reticulum, and ribosomes. Simultaneously there was an increase in the activities of the mitochondrial respiratory enzymes: NADH dehydrogenase, succinic dehydrogenase, and cytochrome oxidase. The extent of the changes in liver cell properties following exposure depend on the duration of exposure to and the strength of the applied magnetic fields. Ultrastructural studies did not reveal any changes in external membranes of hepatocytes or in the membranes of cell nuclei. An increase in the amount of glycogen in hepatocytes of rats exposed to both 10{sup {minus}3} and 10{sup {minus}2} T was noted. The high level of cortisol in serum of exposed rats suggests that magnetic field may be a stress generating factor.

  9. The VA and VCD spectra of various isotopomers of l-alanine in aqueous solution

    Microsoft Academic Search

    S. Abdali; K. J. Jalkanen; H. Bohr; S. Suhai; R. M. Nieminen

    2002-01-01

    Density functional theory (DFT) at the Becke 3LYP level has been used to calculate the vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of various deuterated species of l-alanine. The effect of replacing the methine hydrogen, CH1, the methyl group, CH3, and both the methine and methyl group hydrogens, CH1 and CH3, with the deuteriated species Cd1, Cd3 and

  10. Markers of bone health, renal function, liver function, anthropometry and perception of mood: a comparison between Flat and National Hunt Jockeys.

    PubMed

    Wilson, G; Fraser, W D; Sharma, A; Eubank, M; Drust, B; Morton, J P; Close, G L

    2013-05-01

    Given the requirement of professional jockeys to make-weight daily, we tested the hypothesis that Flat and National Hunt (Jump) jockeys would display compromised health markers (bone health, vitamin D, liver and kidney function and mood) compared with established clinical norms, with Flat jockeys affected the greater. Daily energy intake was lower in Flat compared with Jump jockeys (6.11±1.25 vs. 7.47±0.83 MJ.day - 1, P=0.01) whereas there was no difference in urine osmolality (811±198 vs. 678±317 mOsmol x kg(-1) respectively, P=0.13). Serum total 25(OH)D was insufficient in Flat and Jump jockeys (37.6±28 vs. 35.1±14 nmol x L(-1) respectively although there was no difference between groups (P=0.79). Markers of bone metabolism (Plasma ?-carboxy-terminal cross-linked teleopeptide (CTX) and Intact Parathyroid Hormone (PTH) and liver and kidney function were within clinical normative ranges although CTX and PTH were higher than average. Abnormal mood profiles were observed in both groups although significantly poorer in the Flat jockeys (P=0.01). We conclude that the current practices of jockeys to make-weight may have detrimental effects upon their health with Flat jockeys affected more so than Jump jockeys. Future studies should investigate the effects of improved dietary practices on the mental and physical health of Flat and Jump jockeys. PMID:23184478

  11. Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis

    PubMed Central

    Hoofnagle, J. H.; Van Natta, M. L.; Kleiner, D. E.; Clark, J. M.; Kowdley, K. V.; Loomba, R.; Neuschwander-Tetri, B. A.; Sanyal, A. J.; Tonascia, J.

    2013-01-01

    SUMMARY Background Non-alcoholic steatohepatitis (NASH) is a common cause of serum alanine aminotransferase (ALT) elevations and chronic liver disease, but it is unclear how well ALT elevations reflect the liver injury. Aim To assess how well changes in ALT elevations reflect improvements in liver histology in response to vitamin E therapy. Methods The vitamin E and placebo arms of the Pioglitazone vs. Vitamin E vs. Placebo in Non-alcoholic Steatohepatitis (PIVENS) trial were reassessed for associations among changes in ALT levels, body weight and liver histology. An ALT response was defined as a decrease to ?40 U/L and by ?30% of baseline. Liver biopsies taken before and after treatment were scored for non-alcoholic fatty liver disease activity (NAS) and fibrosis. Results ALT responses were more frequent among vitamin E (48%) than placebo (16%) recipients (P < 0.001). Among vitamin E recipients, ALT responses were associated with decreases in NAS (P < 0.001), but not fibrosis scores (P = 0.34), whereas among placebo recipients, ALT responses were associated with significant decreases in both (P < 0.05). Weight loss (?2 kg) was also associated with ALT response (P < 0.001), improvements in NAS (P < 0.001) and fibrosis (P < 0.02), but vitamin E had an added effect both with and without weight loss. Weight gain (?2 kg) was associated with lack of ALT response and worsening NAS and fibrosis scores in patients not on vitamin E. Conclusions Decrease of ALT levels to normal in patients with NASH is usually associated with improved histological activity. Management should stress the value of weight loss and strongly discourage weight gain. Vitamin E can improve both ALT levels and histology with and without weight loss. Clinical Trial Number: NCT00063622. PMID:23718573

  12. Recent progress in JAERI alanine?ESR dosimetry system

    NASA Astrophysics Data System (ADS)

    Kojima, T.; Tachibana, H.; Haruyama, Y.; Tanaka, R.; Okamoto, J.

    1993-10-01

    Alanine/ESR (electron spin resonance) dosimetry system has been developed on the basis of precise, mass-productive alanine dosimeters of various shapes, and easy-handling ESR reading system. Polymers as binders enable us to mass-produce homogeneous and dimensionally uniform alanine dosimeters of different shapes and thickness relative to penetration range of radiations, for instance, rods for gamma and X-rays, and thin films for electrons and heavy charged particles. They also allow us to simplify parameters of ESR operation exclusively for specific dosimeters and to achieve good reproducibility of measurement. An easy-handling ESR spectrometric reading system was developed on the basis of custom-made ESR spectrometer with a permanent magnet, and automated with auxiliary interfaces and a personal computer. Alanine/ESR dosimetry in JAERI works for domestic and international transfer dosimetry, for simple and reliable routine dosimetry in radiation processing, and for dosimetry of short-penetration range radiations.

  13. Mechanism of inhibition of alanine absorption by Na ricinoleate.

    PubMed

    Hajjar, J J; Murphy, D M; Scheig, R L

    1979-05-01

    The mechanism of inhibition of alanine absorption by Na ricinoleate has been examined in the rabbit intestine. This fatty acid in a concentration of 2--5 mM inhibits alanine absorption in vivo and in vitro. The inhibition is more evident in the jejunum than in the ileum. Strips of ileal mucosa treated with Na ricinoleate gain Na. Sodium ricinoleate inhibits alanine influx across rabbit ileum, even in the presence of a sodium gradient across these cells. The results suggest that the main action of Na ricinoleate is on the alanine-transport system at the brush-border membrane. The fatty acid may also inhibit amino acid absorption by increasing intestinal cell Na concentration, which results in a decreased Na gradient across the brush-border membrane. PMID:443374

  14. [Evaluation of liver function in carbon tetrachloride-damaged rabbits by dynamic SPECT: comparison of 99mTc-GSA and 99mTc-Sn colloid].

    PubMed

    Kiuchi, T; Kawasaki, Y; Hino, I; Kojima, K; Ohkawa, M; Tamai, T; Tanabe, M

    1994-09-25

    Technetium-99m-DTPA-galactosyl human serum albumin (99mTc-GSA) is a new ligand that binds specifically to asialoglycoprotein receptors in hepatocytes. We performed liver dynamic SPECT using 99mTc-GSA and 99mTc-Sn colloid in nine normal control rabbits and 17 chronically CCI4-damaged rabbits (total 29 examinations), and also performed liver function tests (ICGR15, Alb, etc). Using the obtained dynamic SPECT data, we analyzed the liver kinetics of 99mTc-Sn colloid using a one-compartment model (hepatic blood flow [K]) and 99mTc-GSA using a two-compartment model (hepatic blood flow and receptor binding [K1], catabolism [K2]). As the CCl4-treated period increased, K1 decreased most significantly. K1 showed the most significant statistical correlation with the results of liver function tests, ICGR15 (p < 0.0001), Alb, PT, HP, Bil and GPT. Further, only K1 showed a correlation with the hepatic fibrosis of the HAI score. From the present results, liver dynamic SPECT using 99mTc-GSA may be said to provide a novel method for the evaluation of hepatic functional reserve. PMID:7971180

  15. Roles of Sulfur Metabolism and Rhodanese in Detoxification and Anti-Oxidative Stress Functions in the Liver: Responses to Radiation Exposure.

    PubMed

    Nakajima, Tetsuo

    2015-01-01

    Organisms must confront various environmental stresses. The liver is central to protecting against such stresses in mammals, and it has many detoxification and anti-oxidative stress functions. Radiation is a source of oxidative stress and is known to affect the liver and induce anti-oxidative responses. The detoxification enzyme rhodanese, which is also called thiosulfate sulfurtransferase (TST), has been demonstrated to be induced in the liver in response to radiation. Cyanide detoxification is a function of the liver, and rhodanese is a key enzyme involved in sulfur metabolism in that detoxification. Though the anti-oxidative stress system in which sulfur molecules such as thiol compounds are involved has attracted attention as a defense against radiation, detoxification enzymes may have other roles in this defense. Understanding how these functions are affected by alterations of sulfur metabolism (including thiol compounds) after irradiation would help uncover their roles in defense against cancer and other deleterious health effects, as well as environmental stress responses. This article reviews the roles of sulfur-related metabolism in oxidative stress regulation and detoxification for recovery from liver damage after radiation exposure, with particular attention to recent findings of sulfur-related enzymes such as rhodanese, which is unique in sulfur metabolism. PMID:26071878

  16. Roles of Sulfur Metabolism and Rhodanese in Detoxification and Anti-Oxidative Stress Functions in the Liver: Responses to Radiation Exposure

    PubMed Central

    Nakajima, Tetsuo

    2015-01-01

    Organisms must confront various environmental stresses. The liver is central to protecting against such stresses in mammals, and it has many detoxification and anti-oxidative stress functions. Radiation is a source of oxidative stress and is known to affect the liver and induce anti-oxidative responses. The detoxification enzyme rhodanese, which is also called thiosulfate sulfurtransferase (TST), has been demonstrated to be induced in the liver in response to radiation. Cyanide detoxification is a function of the liver, and rhodanese is a key enzyme involved in sulfur metabolism in that detoxification. Though the anti-oxidative stress system in which sulfur molecules such as thiol compounds are involved has attracted attention as a defense against radiation, detoxification enzymes may have other roles in this defense. Understanding how these functions are affected by alterations of sulfur metabolism (including thiol compounds) after irradiation would help uncover their roles in defense against cancer and other deleterious health effects, as well as environmental stress responses. This article reviews the roles of sulfur-related metabolism in oxidative stress regulation and detoxification for recovery from liver damage after radiation exposure, with particular attention to recent findings of sulfur-related enzymes such as rhodanese, which is unique in sulfur metabolism. PMID:26071878

  17. Supplementing antioxidants to pigs fed diets high in oxidants: I. Effects on growth performance, liver function, and oxidative status.

    PubMed

    Lu, T; Harper, A F; Zhao, J; Estienne, M J; Dalloul, R A

    2014-12-01

    The objective of the study was to determine the effects of a dietary antioxidant blend (ethoxyquin and propyl gallate) and vitamin E on growth performance, liver function, and oxidative status in pigs fed diets high in oxidants. Crossbred barrows (n=100, 10.91±0.65 kg BW, 36±2 d of age, Landrace×Duroc) were allotted to 5 treatments on the basis of BW (5 replicate pens per treatment, 4 pigs per pen). Treatments included 1) HO, high-oxidant diet containing 5% oxidized soybean oil and 10% PUFA source (providing 2.05% docosahexaenoic acid in the diet), 2) VE, the HO diet with 11 IU/kg of added vitamin E, 3) AOX, the HO diet with antioxidant blend (135 mg/kg), 4) VE+AOX, the HO diet with both vitamin E and antioxidant blend, and 5) SC, a standard corn-soy control diet. The trial lasted for 118 d; on d 83, the HO diet pigs were switched to the SC diet because the animals were displaying very poor health. Compared with SC pigs, HO pigs had decreased ADG (0.92 vs. 0.51 kg for d 26 to 55, 1.29 vs. 0.34 kg for d 56 to 82; P<0.05) and ADFI (1.84 vs. 0.96 kg for d 26 to 55, 3.41 vs. 1.14 kg for d 56 to 82; P<0.05). However, switching the HO pigs to the SC diet resulted in HO pigs having a greater ADG than VE-fed pigs from d 83 to 118 (0.90 vs. 0.60 kg; P<0.05). The antioxidant blend restored pig performance to a level similar that of pigs fed the SC diet (P>0.05) with greater G:F for the entire period (0.44 vs. 0.38; P<0.05). A greater liver to BW ratio was found in HO compared with other treatments on d 55 and in VE on d 118. Total bilirubin concentration in plasma of HO pigs on d 55 was greater than that in VE+AOX pigs (P<0.05), whereas on d 118, bilirubin concentration in VE was higher than those in VE+AOX and SC (P<0.05). A similar trend was observed in aspartate transaminase. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) and carbonyl were elevated (P<0.05) in the HO pigs compared with the SC pigs on d 55 but not on d 118. Liver TBARS and carbonyl concentrations showed a similar trend, except that HO pigs had the greatest carbonyl concentration on d 118. Pigs fed AOX diets had plasma and liver TBARS and carbonyl concentrations similar to those fed SC diets. In the oxidative stress model used in this study, dietary addition of antioxidant blend or antioxidant blend+vitaimin E was effective in improving growth, liver function, and plasma markers of oxidative stress, but VE alone was not. PMID:25367515

  18. Effect of hepatic dysfunction due to liver metastases on the pharmacokinetics of capecitabine and its metabolites.

    PubMed

    Twelves, C; Glynne-Jones, R; Cassidy, J; Schüller, J; Goggin, T; Roos, B; Banken, L; Utoh, M; Weidekamm, E; Reigner, B

    1999-07-01

    Capecitabine (Xeloda) is a rationally designed oral, tumor-selective fluoropyrimidine carbamate aimed at preferential conversion to 5-fluorouracil (5-FU) within the tumor. Because capecitabine is extensively metabolized by the liver, it is important to establish whether liver dysfunction altered the pharmacokinetics of capecitabine and its metabolites. This was investigated in 14 cancer patients with normal liver function and in 13 with mild to moderate disturbance of liver biochemistry due to liver metastases. They received a single oral dose of capecitabine (1255 mg capecitabine/m2) with serial blood and urine samples collected up to 72 h after administration. Concentrations of capecitabine and its metabolites were determined in plasma by high-performance liquid chromatography or liquid chromatography coupled to mass spectrometry and in urine by 19F-nuclear magnetic resonance spectroscopy. Although plasma concentrations of capecitabine, 5'-deoxy-5-fluorouridine, 5-FU, dihydro-5-FU, and alpha-fluoro-beta-alanine were, in general, higher in patients with liver dysfunction, the opposite was found for 5'-deoxy-5-fluorocytidine. These effects were not clinically significant. Total urinary recovery of capecitabine and its metabolites was 71% of the administered dose in patients with normal hepatic function and 77% in patients with hepatic impairment. The absolute bioavailability of 5'-deoxy-5-fluorouridine was estimated as 42% in patients with normal hepatic function and 62% in patients with impaired hepatic function. In summary, mild to moderate hepatic dysfunction had no clinically significant influence on the pharmacokinetic parameters of capecitabine and its metabolites. Although caution should be exercised when capecitabine is administered to patients with mildly to moderately impaired hepatic function, there is no need for, a priori, adjustment of the dose. PMID:10430071

  19. Liver Wellness

    MedlinePLUS

    ... virus (HAV). HAV can cause the liver to swell and not work well. Prevention: Hepatitis A vaccination ... virus (HBV). HBV can cause the liver to swell and can lead to cirrhosis and liver cancer. ...

  20. Low G preconditioning reduces liver injury induced by high +Gz exposure in rats

    PubMed Central

    Shi, Bin; Feng, Zhi-Qiang; Li, Wen-Bing; Zhang, Hong-Yi

    2015-01-01

    AIM: To investigate the effect of repeated lower +Gz exposure on liver injury induced by high +Gz exposure in rats. METHODS: Sixty male Wister rats were randomly divided into a blank control group, a low G preconditioning group (LG) (exposed to +4 Gz/5 min per day for 3 d before +10 Gz/5 min exposure), and a +10 Gz/5 min group (10G) (n = 20 in each group). Blood specimens and liver tissue were harvested at 0 h and 6 h after +10 Gz/5 min exposure. Liver function was analyzed by measuring serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, and liver injury was further assessed by histopathological observation. Malondialdehyde (MDA), superoxide dismutase (SOD) and Na+-K+-ATPase were determined in hepatic tissue. RESULTS: The group LG had lower ALT, AST, and MDA values at 0 h after exposure than those in group 10G. SOD values and Na+-K+-ATPase activity in the LG group were higher than in group 10G 0 h post-exposure. Hepatocyte injury was significantly less in group LG than in group 10G on histopathological evaluation. CONCLUSION: It is suggested that repeated low +Gz exposure shows a protective effect on liver injury induced by high +Gz exposure in rats.

  1. Measuring Markers of Liver Function Using a Micro-Patterned Paper Device Designed for Blood from a Fingerstick

    PubMed Central

    Vella, Sarah J.; Beattie, Patrick; Cademartiri, Rebecca; Laromaine, Anna; Martinez, Andres W.; Phillips, Scott T.; Mirica, Katherine A.

    2012-01-01

    This paper describes a paper-based microfluidic device that measures two enzymatic markers of liver function (alkaline phosphatase ALP, and aspartate aminotransferase AST) and total serum protein. A device consists of four components: i) a top plastic sheet, ii) a filter membrane, iii) a patterned paper chip containing the reagents necessary for analysis, and iv) a bottom plastic sheet. The device performs both the sample preparation (separating blood plasma from erythrocytes) and the assays; it also enables both qualitative and quantitative analysis of data. The data obtained from the paper-microfluidic devices show standard deviations in calibration runs and “spiked” standards that are acceptable for routine clinical use. This device illustrates a type of test useable for a range of assays in resource-poor settings. PMID:22390675

  2. Dimethylformamide-induced liver damage among synthetic leather workers

    SciTech Connect

    Wang, J.D.; Lai, M.Y.; Chen, J.S.; Lin, J.M.; Chiang, J.R.; Shiau, S.J.; Chang, W.S. (Center for the Research of Environmental and Occupational Disease, Graduate Institute of Public Health and Department of Internal Medicine, National Taiwan University, College of Medicine (China))

    1991-05-01

    Prevalence of liver injury associated with dimethylformamide (DMF) exposure was determined. Medical examinations, liver function tests, and creatine phosphokinase (CPK) determinations were performed on 183 of 204 (76%) employees of a synthetic leather factory. Air concentrations of solvents were measured with personal samplers and gas chromatography. The concentration of DMF in air to which each worker was exposed was categorized. High exposure concentrations of DMF (i.e., 25-60 ppm) were significantly associated with elevated alanine aminotransferase (ALT) levels (ALT greater than or equal to 35 IU/l), a result that did not change even after stratification by hepatitis B carrier status. Modeling by logistic regression demonstrated that exposure to high concentrations of DMF was associated with an elevated ALT (p = .01), whereas hepatitis B surface antigen (HBsAg) was slightly but independently associated with an elevated ALT (p = .07). In those workers who had normal ALT values, there occurred still significantly higher mean ALT and aspartate aminotransferase (AST) activities, especially among those who were not HBsAg carriers. A significant association existed between elevated CPK levels and exposure to DMF. However, an analysis of the CPK isoenzyme among 143 workers did not reveal any specific damage to muscles. This outbreak of liver injury among synthetic leather workers is ascribed to DMF. It is recommended that the occupational standard for DMF and its toxicity among HBsAg carriers be evaluated further.

  3. Monopeptide versus Monopeptoid: Insights on Structure and Hydration of Aqueous Alanine and Sarcosine via X-ray Absorption Spectroscopy

    SciTech Connect

    Uejio, Janel S.; Schwartz, Craig P.; Duffin, Andrew M.; England, Alice; Prendergast, David; Saykally, Richard J.

    2009-11-19

    Despite the obvious significance, the aqueous interactions of peptides remain incompletely understood. Their synthetic analogues called peptoids (poly-N-substituted glycines), have recently emerged as a promising biomimetic material, particularly due to their robust secondary structure and resistance to denaturation. We describe comparative near-edge x-ray absorption fine structure (NEXAFS) spectroscopy studies of aqueous sarcosine, the simplest peptoid, and alanine, its peptide isomer, interpreted by density functional theory calculations. The sarcosine nitrogen K-edge spectrum is blue-shifted with respect to that of alanine, in agreement with our calculations; we conclude that this shift results primarily from the methyl group substitution on the nitrogen of sarcosine. Our calculations indicate that the nitrogen K-edge spectrum of alanine differs significantly between dehydrated and hydrated scenarios, while that of the sarcosine zwitterion is less affected by hydration. In contrast, the computed sarcosine spectrum is greatly impacted by conformational variations, while the alanine spectrum is not. This relates to a predicted solvent dependence for alanine, as compared to sarcosine. Additionally, we show the theoretical nitrogen K-edge spectra to be sensitive to the degree of hydration, indicating that experimental X-ray spectroscopy may be able to distinguish between bulk and partial hydration, such as found in confined environments near proteins and in reverse micelles.

  4. Serum Ferritin is Associated with Non-alcoholic Fatty Liver Disease and Decreased B-cell Function in Non-diabetic Men and Women

    PubMed Central

    Utzschneider, Kristina M; Largajolli, Anna; Bertoldo, Alessandra; Marcovina, Santica; Nelson, James E; Yeh, Matthew M; Kowdley, Kris V; Kahn, Steven E

    2014-01-01

    Aims We sought to determine whether NAFLD is associated with poorer ?-cell function and if any ?-cell dysfunction is associated with abnormal markers of iron or inflammation. Methods This was a cross-sectional study of 15 non-diabetic adults with NAFLD and 15 non-diabetic age and BMI-matched controls. Insulin sensitivity was measured by isotope-labeled hyperinsulinemic-euglycemic clamps and ?-cell function by both oral (OGTT) and intravenous glucose tolerance tests. Liver and abdominal fat composition was evaluated by CT scan. Fasting serum levels of ferritin, transferrin-iron saturation, IL-6, TNF? and hsCRP were measured. Results Compared to controls, subjects with NAFLD had lower hepatic and systemic insulin sensitivity and ?-cell function was decreased as measured by the oral disposition index. Fasting serum ferritin and transferrin-iron saturation were higher in NAFLD and were positively associated with liver fat. Serum ferritin was negatively associated with ?-cell function measured by both oral and intravenous tests, but was not associated with insulin sensitivity. IL-6, TNF? and hsCRP did not differ between groups and did not correlate with serum ferritin, liver fat or measures of ?-cell function. Conclusions These findings support a potential pathophysiological link between iron metabolism, liver fat and diabetes risk. PMID:24360972

  5. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat.

    PubMed

    Yousef, Mokhtar I; Omar, Sahar A M; El-Guendi, Marwa I; Abdelmegid, Laila A

    2010-11-01

    The present study was carried out to evaluate the potential protective role of quercetin and curcumin against paracetamol-induced oxidative injury, liver damage and impairment of kidney function, as well as haematotoxicity in rats. Also, N-acetylcysteine was used to evaluate the potency of quercetin and curcumin. Paracetamol caused an elevation in thiobarbituric acid-reactive substances (TBARS) paralleled with significant decline in glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase activities (in plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in lung, liver and kidney). The apparent oxidative injury was associated with evident hepatic necrosis confirmed in histological examination, elevated plasma transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol reduced plasma total protein, albumin and globulin, while increased bilirubin, urea and creatinine, and induced haematotoxicity. The presence of quercetin or curcumin with paracetamol successfully mitigated the rise in TBARS and restored the activities of antioxidant enzymes compared to the group treated with both paracetamol and N-acetylcysteine. They also protected liver histology, normalized liver and kidney functions, which was more pronounced with curcumin. Therefore, it can be concluded that concomitant administration of quercetin or curcumin with paracetamol may be useful in reversing the toxicity of the drug compared to N-acetylcysteine. PMID:20804811

  6. Crystal growth, structure and characterizations of a new semiorganic nonlinear optical material-{beta}-Alanine zinc chloride

    SciTech Connect

    Anbuchezhiyan, M. [Department of Physics, Valliammai Engineering College, S.R.M. Nagar, Kattankulathur, Chennai 603203 (India)] [Department of Physics, Valliammai Engineering College, S.R.M. Nagar, Kattankulathur, Chennai 603203 (India); Ponnusamy, S., E-mail: suruponnus@gmail.com [Centre for Material Science and Nano Devices, Department of Physics, SRM University, Kattankulathur, Kanchipuram, Chennai 603203 (India); Muthamizhchelvan, C. [Centre for Material Science and Nano Devices, Department of Physics, SRM University, Kattankulathur, Kanchipuram, Chennai 603203 (India)] [Centre for Material Science and Nano Devices, Department of Physics, SRM University, Kattankulathur, Kanchipuram, Chennai 603203 (India); Sivakumar, K. [Department of Physics, Anna University, Chennai 600 025 (India)] [Department of Physics, Anna University, Chennai 600 025 (India)

    2010-08-15

    The title compound, {beta}-alanine zinc chloride-a new semiorganic nonlinear optical crystal was grown by slow evaporation technique. Single crystals of {beta}-alanine zinc chloride have been subjected to X-ray diffraction analysis to determine the crystal structure. The powder X-ray diffractogram of the crystal has also been recorded. The amount of carbon, nitrogen and hydrogen in the crystals was also estimated. Fourier Transform Infrared and Raman spectral measurements have been carried out on the grown crystals in order to identify the functional groups. The presence of hydrogen and carbon in the {beta}-alanine zinc chloride was confirmed by using proton and carbon nuclear magnetic resonance spectral analyses. The percentage of zinc in the crystal was determined by atomic absorption spectroscopy. Optical behavior such as ultraviolet-vis-near infrared transmittance spectrum and second harmonic generation has been investigated. The mechanical strength and thermal behavior of the grown crystal have been analyzed.

  7. Proteomic analysis of liver mitochondria from rats with nonalcoholic steatohepatitis

    PubMed Central

    Li, Lin; Lu, De-Zhao; Li, You-Ming; Zhang, Xue-Qun; Zhou, Xin-Xin; Jin, Xi

    2014-01-01

    AIM: To explore mitochondrial dysfunction in nonalcoholic steatohepatitis (NASH) by analyzing the proteome of liver mitochondria from a NASH model. METHODS: The NASH rat model was established by feeding rats a fat-rich diet for 24 wk and was confirmed using hematoxylin and eosin staining of liver tissue and by changes in the levels of serum alanine transaminase, aspartate aminotransferase, triglyceride, total cholesterol and other markers. Liver mitochondria from each group were isolated using differential centrifugation. The mitochondrial samples were lyzed, purified and further analyzed using two-dimensional electrophoresis combined with matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. Bioinformatic analyses of assigned gene ontology and biological pathway was used to study functional enrichments in the abundant proteomic data. RESULTS: Eight up-regulated and sixteen down-regulated proteins were identified that showed greater than 1.5-fold differences between the controls and the NASH group. These dysregulated proteins were predicted to be involved in different metabolic processes including fatty acid ?-oxidation processes, lipid metabolic processes, cell-cycle arrest, cell polarity maintenance, and adenosine triphosphate/sex hormone metabolic processes. Novel proteins that may be involved in NASH pathogenesis including the trifunctional enzyme Hadha, thyroxine, prohibitin, aldehyde dehydrogenase ALDH1L2, UDP-glucuronosyltransferase 2B31, and carbamoyl-phosphate synthase were identified using bioinformatics tools. The decreased expression of Hadha in NASH liver was verified by Western blotting, which was used as a complementary technique to confirm the proteomic results. CONCLUSION: This novel report on the liver mitochondrial proteome of a NASH model may provide a reservoir of information on the pathogenesis and treatment of NASH. PMID:24782632

  8. A cell-specific activator in the Xenopus A2 vitellogenin gene: promoter elements functioning with rat liver nuclear extracts.

    PubMed Central

    Döbbeling, U; Ross, K; Klein-Hitpass, L; Morley, C; Wagner, U; Ryffel, G U

    1988-01-01

    Transfection experiments using Xenopus vitellogenin A2 gene constructs allowed us to identify an activator which increases the activity of the thymidine kinase promoter. The activator is located between -121 and -87 of the A2 vitellogenin gene and is separated by a stretch of curved DNA from the estrogen-responsive DNA element at -331. The activator functions in a cell-specific manner, as it is active in human breast cancer cells (MCF-7) as well as hepatoma cells but not in fibroblasts or HeLa cells. The activator is composed of at least three elements: elements 1 and 2 which form a partial palindrome, function independently, but act synergistically when combined. Element 3 is not active on its own, but supports elements 1 and 2. A TATA box region derived from the Xenopus albumin gene is sufficient for the function of the activator. In vitro transcription experiments using rat liver nuclear extracts demonstrate that the activator interacts with transcription factors. These factors are distinct from those recognizing HP1, a regulatory element common to several genes specifically expressed in hepatocytes. Images PMID:2847920

  9. Long Term Results (>5 Years) in Patients With Peritoneovenous Shunting for Intractable Ascites: Liver Function and Cancer Mortality

    PubMed Central

    Meakins, Jonathan L.; Wu, Andrew; Smadja, Claude; Bonnet, Patrick; Gouffier, Etienne; Campillo, Bernard

    1989-01-01

    This report is based on twenty-eight (26%) of 107 patients included in a protocol for prospective evaluation of elective peritoneo-venous shunting for intractable ascites in cirrhosis. These patients had no other procedures and survived more than 5 years after the operation. All patients were free of ascites except one in whom it was mild. One patient refused follow-up. Shunt patency was assessed in 23 patients. In 14 patients (60.9%), the shunt was obstructed and the superior vena cava was occluded in 5 of them. In 9 patients (39.1%), the shunt was still functioning. No clinical or biological parameters differentiated these two groups of patients. Of the 24 patients who were alcoholics, 2 abstained completely and 20 significantly reduced their drinking habits. In 25 patients, the Pugh's score improved and was A at the time of the study. Seven patients (25.9%) developed a malignant tumor of the oro-pharynx or digestive tract, all other patients were alive and in good health. This study suggests that patients with intractable ascites treated by a peritoneo-venous shunt may survive for a long period. In patients abstaining from heavy drinking, it may function as a therapeutic bridge permitting spontaneous improvement of liver function. The risk of supervening neoplasms suggests that a continuous follow-up of these patients is warranted. PMID:2487384

  10. Radiation tolerance of cirrhotic livers in relation to the preserved functional capacity: Analysis of patients with hepatocellular carcinoma treated by focused proton beam radiotherapy

    Microsoft Academic Search

    Kiyoshi Ohara; Toshiyuki Okumura; Hiroshi Tsuji; Toshiya Chiba; Myo Min; Hideo Tatsuzaki; Hirohiko Tsujii; Yasuyuki Akine; Yuji Itai

    1997-01-01

    Purpose: To determine the preserved functional capacity of the liver as a probable determinant of radiation tolerance in patients with cirrhosis and hepatocellular carcinoma, who underwent proton beam radiotherapy.Materials and Methods: We reviewed computed tomographic (CT) scans of 26 patients with cirrhosis and hepatocellular carcinoma during a period of 12–27 months after proton beam radiotherapy. Tumors were treated with focused

  11. Establishment of the tree shrew as an alcohol-induced Fatty liver model for the study of alcoholic liver diseases.

    PubMed

    Xing, Huijie; Jia, Kun; He, Jun; Shi, Changzheng; Fang, Meixia; Song, Linliang; Zhang, Pu; Zhao, Yue; Fu, Jiangnan; Li, Shoujun

    2015-01-01

    Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals' suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. Therefore, the established fatty liver model of tree shrews induced by alcohol should be a promising tool for the study of ALDs. PMID:26030870

  12. Establishment of the Tree Shrew as an Alcohol-Induced Fatty Liver Model for the Study of Alcoholic Liver Diseases

    PubMed Central

    Xing, Huijie; Jia, Kun; He, Jun; Shi, Changzheng; Fang, Meixia; Song, Linliang; Zhang, Pu; Zhao, Yue; Fu, Jiangnan; Li, Shoujun

    2015-01-01

    Currently, the pathogenesis of alcoholic liver diseases (ALDs) is not clear. As a result, there is no effective treatment for ALDs. One limitation is the lack of a suitable animal model for use in studying ALDs. The tree shrew is a lower primate animal, characterized by a high-alcohol diet. This work aimed to establish a fatty liver model using tree shrews and to assess the animals’ suitability for the study of ALDs. Tree shrews were treated with alcohol solutions (10% and 20%) for two weeks. Hemophysiology, blood alcohol concentrations (BACs), oxidative stress factors, alcohol metabolic enzymes and hepatic pathology were checked and assayed with an automatic biochemical analyzer, enzyme-linked immunosorbent assay (ELISA), western blot, hematoxylin-eosin (HE) staining and oil red O staining, and magnetic resonance imaging (MRI). Compared with the normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly enhanced in alcohol-treated tree shrews. However, the activity of reduced glutathione hormone (GSH) and superoxide dismutase (SOD) declined. Notable changes in alcohol dehydrogenase(ADH1), aldehyde dehydrogenase(ALDH2), CYP2E1, UDP-glucuronosyl transferase 1A1 (UGT1A1) and nuclear factor erythroid-related factor 2 (Nrf2) were observed. HE and oil red O staining showed that hepatocyte swelling, hydropic degeneration, and adipohepatic syndrome occurred in the tree shrews. Alcohol can induce fatty liver-like pathological changes and result in alterations in liver function, oxidative stress factors, alcohol metabolism enzymes and Nrf2. Therefore, the established fatty liver model of tree shrews induced by alcohol should be a promising tool for the study of ALDs. PMID:26030870

  13. Immunopathogenesis of hepatic fibrosis in chronic liver injury induced by repeatedly administered concanavalin A

    Microsoft Academic Search

    Kiminori Kimura; Kazuki Ando; Hiroo Ohnishi; Tetsuya Ishikawa; Shinichi Kakumu; Masao Takemura; Yasutoshi Muto; Hisataka Moriwaki

    1999-01-01

    Liver fibrosis is commonly observed in chronic liver disease. However, the immunological mechanisms underlying hepatic fibrosis due to chronic inflammation are not well defined, mainly because suitable experimental models have not been established. We have found that weekly i.v. administration of concanavalin A (Con A) in BALB\\/c mice brought about a striking alanine aminotransferase increase, resulting in piecemeal necrosis with

  14. Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not ?-cell function in humans123

    PubMed Central

    Marcovina, Santica; Nelson, James E; Yeh, Matthew M; Kowdley, Kris V; Callahan, Holly S; Song, Xiaoling; Di, Chongzhi; Utzschneider, Kristina M

    2014-01-01

    Background: Plasma phospholipid concentrations of trans-palmitoleic acid (trans-16:1n?7), a biomarker of dairy fat intake, are inversely associated with incident type 2 diabetes in 2 US cohorts. Objective: The objective was to investigate whether the intake of trans-16:1n?7 in particular, or dairy fat in general, is associated with glucose tolerance and key factors determining glucose tolerance. Design: A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index (BMI)- and age-matched controls. The concentrations of trans-16:1n?7 and 2 other biomarkers of dairy fat intake, 15:0 and 17:0, were measured in plasma phospholipids and free fatty acids (FFAs). Liver fat was estimated by computed tomography–derived liver-spleen ratio. Intravenous-glucose-tolerance tests and oral-glucose-tolerance test (OGTT) and hyperinsulinemic-euglycemic clamps were performed to assess ?-cell function and hepatic and systemic insulin sensitivity. Results: In multivariate analyses adjusted for age, sex, and BMI, phospholipid 17:0, phospholipid trans-16:1n?7, FFA 15:0, and FFA 17:0 were inversely associated with fasting plasma glucose, the area under the curve for glucose during an OGTT, and liver fat. Phospholipid trans-16:1n?7 was also positively associated with hepatic and systemic insulin sensitivity. None of the biomarkers were associated with ?-cell function. The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat, but strengthened by adjusting for ?-cell function. Conclusion: Although we cannot rule out reverse causation, these data support the hypothesis that dairy fat improves glucose tolerance, possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat. This trial was registered at clinicaltrials.gov as NCT01289639. PMID:24740208

  15. Testing the validity of a receptor kinetic model via TcNGA functional imaging of liver transplant recipients. Final report

    SciTech Connect

    Stadalnik, R.C.

    1993-03-25

    The author had accomplished the expertise for I-125-HSA plasma volume, galactose clearance for determination of hepatic plasma flow as well as finalizing the kinetic model. They have just completed modifying the microscale Scatchard assay for greater precision of receptor measurement using only 5--10 mg of liver tissue. In addition, he determined during the past year that the most practical method and clinically reasonable measurement of liver volume was to measure the transplanted liver in vivo using Tc-NGA images in the anterior, posterior, and right lateral projections, using the method of Rollo and DeLand. Direct measurement of liver weight obtained during transplant operation was not reliable due to variability of fluid retention in the donor liver secondary to ischemia, preservation fluid, etc., which thereby did not reflect an accurate liver weight which is needed in the kinetic analysis comparison, i.e., V{sub h} (hepatic plasma volume).

  16. Effects of chronic exposure to lead, cadmium, and manganese mixtures on oxidative stress in rat liver and heart.

    PubMed

    Markiewicz-Górka, Iwona; Januszewska, Lidia; Michalak, Aleksandra; Prokopowicz, Adam; Januszewska, Ewa; Pawlas, Natalia; Pawlas, Krystyna

    2015-03-01

    The aim of this study was to assess the effects of chronic combined exposure to low, environmental doses of Cd, Pb, and Mn on oxidative stress in the liver and heart of rats and on their liver function parameters. Male Wistar rats were divided randomly into eight groups. For nine months controls were receiving drinking water alone, whereas the exposed groups were receiving drinking water with Pb (0.2 mg L(-1)), Cd (1 mg L(-1)), and Mn (2 mg L(-1)) alone or in combinations. Malondialdehyde (MDA) significantly increased in both heart and liver of the animals after combined exposure to metals. Heart MDA correlated with blood Cd, Pb, and Mn and liver MDA with blood Cd. Aspartate aminotransferase (AST) activity and bilirubin concentration also increased significantly in the animal group exposed to all three metals and correlated positively with blood Cd, Pb, and Mn. Our study has confirmed the synergistic effect of the Cd, Mn, and Pb combination on the increase in heart MDA. A similar synergy was observed for Pb+Mn in the increase of serum alanine aminotransferase (ALT) activity as an indicator of liver function. PMID:25781514

  17. Low-dose splenic radiation inhibits liver tumor development of rats through functional changes in CD4+CD25+Treg cells.

    PubMed

    Wang, Baofeng; Li, Baohua; Dai, Zhijun; Ren, Song; Bai, Minghua; Wang, Zhongwei; Li, Zongfang; Lin, Shuai; Wang, Zhidong; Huang, Na; Yang, Pengtao; Liu, Mengjie; Min, Weili; Ma, Hongbing

    2014-10-01

    The increased number of CD4(+)CD25(+)Treg cells in tumor local and peripheral splenic tissues is related to the low immune function as well as to tumor recurrence and metastasis. Our pre-clinical studies showed that low-dose radiation (LDR) of the spleen in liver cancer patients significantly improves immune functions. However, the molecular mechanisms of such radiation remained ill defined. This study explores the role of CD4(+)CD25(+)Treg cells in radiation-induced immunomodulatory effects. Using the diethylnitrosamine (DEN)-induced rat liver tumor model and in vitro cell experiments, the percentage of CD4(+)CD25(+)Treg/CD4(+) cells in the blood and the expressions of Foxp3(+), IL-10, TGF-?, and cytotoxic T lymphocyte-associated antigen-4(CTLA-4) in spleen and liver tumors significantly decreased after LDR of the spleen in rats with liver cancer. The tumors became smaller than those in the non-radiated group, with both showing a parallel relation. Flow cytometry and MTT results revealed that LDR failed to inhibit CD4(+)CD25(+)Treg cell proliferation. Conversely, apoptosis was reduced and proliferation was stimulated. This process also changed CTLA-4 molecule expression on the surfaces of CD4(+)CD25(+)Treg cells and reduced their inhibitory function against CD4(+)CD25(-)T cell proliferation, and the suppression function of CD4(+)CD25(+)Treg cells was further weakened with the introduction of the CTLA-4 inhibitor. Findings demonstrate that the reduction of CTLA-4 expression on the CD4(+)CD25(+)Treg cell surface and the further inhibition of cell function may be considered as important regulators of LDR-induced immunomodulatory effects. This study provides experimental evidence to elucidate the immune enhancement induced by this process and presents a novel method for liver cancer immunotherapy. PMID:25168696

  18. Blood brain barrier permeability in acute liver necrosis of mice

    Microsoft Academic Search

    Sa Lu; Hong-Li Song; Jing-Yan Wang; Pei Liu

    2004-01-01

    AIM: To study the permeability of the blood brain barrier (BBB) in a mouse model of acute liver necrosis. METHODS: Male Balb\\/c mice were divided into 4 groups. In one group, mice were intraperitoneal of lipopolysaccharide (LPS, 10 ?g\\/kg) with D-galactosamine (GalN, 800 mg\\/kg) to induce acute liver necrosis. Other groups were controls. Serum levels of alanine transaminase (ALT) were

  19. Unusually Stable Helix Formation in Short Alanine-Based Peptides

    NASA Astrophysics Data System (ADS)

    Marqusee, Susan; Robbins, Virginia H.; Baldwin, Robert L.

    1989-07-01

    Short, 16-residue, alanine-based peptides show stable ? -helix formation in H2O. This result is surprising when contrasted with the classical view that regards the ? -helix as a marginally stable structure in H2O and considers short helices unstable. The alanine-based peptides are solubilized by insertion of three or more residues of a single charge type, lysine (+) or glutamic acid (-). The results cannot be explained by helix stabilization resulting from concentration-dependent association or by the interaction of charged residues with the helix dipole. Our results are not predicted by the parameters for alanine and lysine that have been determined by the ``host-guest'' method: these parameters predict that a 16-residue peptide should not show measurable ? -helix formation. Analysis of the role of the hydrophobic interaction in ? -helix formation [Richards, F. M. & Richmond, T. (1978) in Molecular Interactions and Activity in Proteins, Ciba Foundation Symposium 60, ed. Wolstenholme, G. E. (Excepta Medica Amsterdam), pp. 23-25] does not show an unusually strong hydrophobic interaction in a helical block of alanine residues. The likely explanation for our results is, therefore, that individual alanine residues have a high helical potential. It is not yet known whether any other amino acids show this property, and the origin of this property is also unknown.

  20. Kinetics and mechanism of the beta-alanine + OH gas phase reaction: a quantum mechanical approach.

    PubMed

    Cruz-Torres, Armando; Galano, Annia; Alvarez-Idaboy, J Raúl

    2006-01-14

    The OH hydrogen abstraction reaction from beta-alanine has been studied using the BHandHLYP hybrid HF-density functional and 6-311G(d,p) basis sets. The energies have been improved by single point calculations at the CCSD(T)/6-311G(d,p) level of theory. The structures of the different stationary points are discussed. Reaction profiles are modeled including the formation of pre-reactive and product complexes. Negative net activation energy is obtained for the overall reaction. A complex mechanism is proposed, and the rate coefficients are calculated using transition state theory over the temperature range of 250-400 K. The rate coefficients are proposed for the first time and it was found that in the gas phase the hydrogen abstraction occurs mainly from the CH(2) group next to the amino end. The following expressions, in cm(3) mol(-1) s(-1), are obtained for the overall rate constants, at 250-400 and 290-310 K, respectively: k(250-400)= 2.36 x 10(-12) exp(340/T), and k(290-310)= 1.296 x 10(-12) exp(743/T). The three parameter expression that best describes the studied reaction is k(250-400)= 1.01 x 10(-21)T(3.09) exp(1374/T). The beta-alanine + OH reaction was found to be 1.5 times faster than the alpha-alanine + OH reaction. PMID:16482271

  1. Overexpression of the alanine carrier protein gene from thermophilic bacterium PS3 in Escherichia coli.

    PubMed

    Kanamori, M; Kamata, H; Yagisawa, H; Hirata, H

    1999-03-01

    The alanine transporter (alanine carrier protein, ACP) gene of thermophilic bacterium PS3 was previously cloned and expressed in a functionally active form in Escherichia coli cells. To achieve controlled overproduction of the ACP protein, we designed a plasmid encoding a fusion protein comprising ACP joined to the carboxyl terminus of the maltose binding protein (MBP-ACP). Upon transduction of the plasmid into E. coli RM1 cells defective in alanine/glycine transport, the transport activity was expressed even before induction with 1-thio-beta-D-galacto-pyranoside (IPTG), and increased slightly on induction with IPTG at low concentrations. However, overexpression of the MBP-ACP gene, induced by higher concentrations of IPTG, resulted in death of the host cells. Hence we screened other host cells and found that the MBP-ACP fusion protein was produced in a large quantity in E. coli TB1 cells 3 h after IPTG induction. The MBP-ACP fusion protein was accumulated in cytoplasmic membranes in an amount reaching more than 20% of the total membrane protein. The affinity-purified MBP-ACP exhibited very low transport activity when reconstituted into proteoliposomes. PMID:10050032

  2. Use of IGL-1 preservation solution in liver transplantation.

    PubMed

    Wiederkehr, J C; Igreja, M R; Nogara, M S; Goncalves, N; Montemezzo, G P; Wiederkehr, H A; Wassen, M P; Nobrega, H A; Zenatti, K B; Mori, L Y; Tudisco, M S

    2014-01-01

    University of Wisconsin (UW) solution has been known as the standard solution for liver graft preservation. Alternative preservation solutions have been used in liver transplantation, such as histidine-tryptophan-ketoglutarate (HTK) and Celsior solution. Institut Georges Lopez-1 (IGL-1) is a new preservation solution with lower potassium and lower viscosity than UW solution that has recently been used in liver transplant. Data from 178 patients who received transplants from August 2008 to June 2013 at Hospital Santa Isabel, Blumenau, Brazil, were analyzed. All patients received grafts from brain death donors. In November 2011 we started to use IGL-1 as an alternate preservation solution. Therefore, 53 patients using IGL-1 preserved grafts were compared to 125 using HTK solution. The donor age in the HTK group ranged from 11-77 years, with a mean of 43.4 ± 4.8. In the IGL-1 group donor age ranged from 9-62 years, with a mean of 35.8 ± 4.5. Cold ischemia time in the HTK group ranged from 85-1145 minutes, mean 443.5 ± 183.5 minutes. In the IGL-1 group, cold ischemia time ranged from 85-670 minutes, mean 329.3 ± 134.8 minutes. The overall operative mortality rate was 14% (25 patients); in the HTK group, 14.4% (18 patients); and in the IGL-1 group, 13.4% (7 patients). One graft in the HTK group presented with primary non-function (PNF), 0.7%; there were none in the IGL-1 group. In our study, IGL-1 has been shown to be safe to use as a preservation solution for liver transplantation. Early post-transplant graft function was comparable to that observed with HTK solution, although a tendency for lower alanine aminotransferase levels was noticed. IGL-1 has been shown to be safe, cost efficient, and an effective preservation solution. PMID:25131043

  3. Analysis of Common and Specific Mechanisms of Liver Function Affected by Nitrotoluene Compounds

    Microsoft Academic Search

    Youping Deng; Sharon A. Meyer; Xin Guan; Barbara Lynn Escalon; Junmei Ai; Mitchell S. Wilbanks; Ruth Welti; Natàlia Garcia-Reyero; Edward J. Perkins; Vladimir N. Uversky

    2011-01-01

    BackgroundNitrotoluenes are widely used chemical manufacturing and munitions applications. This group of chemicals has been shown to cause a range of effects from anemia and hypercholesterolemia to testicular atrophy. We have examined the molecular and functional effects of five different, but structurally related, nitrotoluenes on using an integrative systems biology approach to gain insight into common and disparate mechanisms underlying

  4. Studies on aromatic hydrocarbon quinone metabolism and DT-Diaphorase function in liver of fish species

    Microsoft Academic Search

    Philippe Lemaire; Joachim Sturve; Lars Förlin; David R. Livingstone

    1996-01-01

    Studies were carried out to examine the role of aromatic hydrocarbon (AH)-quinone metabolism and DT-diaphorase (quinone oxidoreductase; EC 1.6.99.2; DTD) function in pollution-caused oxidative damage in fish. Redox cycling of quinones to produce reactive oxygen species (ROS) was studied by oxygen consumption and oxidation of the hydroxyl radical scavenger 2-keto-4-methiolbutyric acid. NADH-dependent redox cycling by hepatic microsomes of flounder (Platichthys

  5. Anti-tumour necrosis factor agent and liver injury: Literature review, recommendations for management

    PubMed Central

    Rossi, Roberta Elisa; Parisi, Ioanna; Despott, Edward John; Burroughs, Andrew Kenneth; O'Beirne, James; Conte, Dario; Hamilton, Mark Ian; Murray, Charles Daniel

    2014-01-01

    Abnormalities in liver function tests, including transient and self-limiting hypertransaminasemia, cholestatic disease and hepatitis, can develop during treatment with anti-tumour-necrosis-factor (TNF) therapy. The optimal management of liver injury related to anti-TNF therapy is still a matter of debate. Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than 5 times the upper limit of normal, or the occurrence of jaundice, there are no standard guidelines for the management of anti-TNF-related liver injury. Bibliographical searches were performed in PubMed, using the following key words: inflammatory bowel disease (IBD); TNF inhibitors; hypertransaminasemia; drug-related liver injury; infliximab. According to published data, elevation of transaminases in patients with IBD treated with anti-TNF is a common finding, but resolution appears to be the usual outcome. Anti-TNF agents seem to be safe with a low risk of causing severe drug-related liver injury. According to our centre experience, we found that hypertransaminasemia was a common, mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate analyses. An algorithm for the management of liver impairment occurring during anti-TNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of transaminases. However, hepatic injury is generally self-limiting and drug withdrawal seems to be an exception. PMID:25516646

  6. Formation of ?-sheets in glutamine and alanine tripeptides.

    PubMed

    Bauer, Marianne T; Gilmore, Kelly A; Petty, Sarah A

    2011-03-18

    The misfolding and aggregation of proteins is associated with many different diseases including the trinucleotide repeat disorders and Prion diseases. We have studied three residue peptides comprising alanine and glutamine in order to understand the short range interactions affecting the formation of ?-rich aggregates. Using infrared spectroscopy, we have found that trialanine and triglutamine form significant amounts of ?-sheet, but that tripeptides containing alanine and glutamine are only able to form ?-sheet if the glutamine side-chains extend outward on both faces of the sheet. From our data, we conclude that different stabilizing interactions are responsible for ?-sheet formation in trialanine and triglutamine. PMID:21329666

  7. Hypoxia and fatty liver

    PubMed Central

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-01-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease. PMID:25386057

  8. Gamma aminobutyric acid B and 5-hydroxy tryptamine 2A receptors functional regulation during enhanced liver cell proliferation by GABA and 5-HT chitosan nanoparticles treatment.

    PubMed

    Shilpa, Joy; Pretty, Mary Abraham; Anitha, Malat; Paulose, Cheramadathikudyil Skaria

    2013-09-01

    Liver is one of the major organs in vertebrates and hepatocytes are damaged by many factors. The liver cell maintenance and multiplication after injury and treatment gained immense interest. The present study investigated the role of Gamma aminobutyric acid (GABA) and serotonin or 5-hydroxytryptamine (5-HT) coupled with chitosan nanoparticles in the functional regulation of Gamma aminobutyric acid B and 5-hydroxy tryptamine 2A receptors mediated cell signaling mechanisms, extend of DNA methylation and superoxide dismutase activity during enhanced liver cell proliferation. Liver injury was achieved by partial hepatectomy of male Wistar rats and the GABA and 5-HT chitosan nanoparticles treatments were given intraperitoneally. The experimental groups were sham operated control (C), partially hepatectomised rats with no treatment (PHNT), partially hepatectomised rats with GABA chitosan nanoparticle (GCNP), 5-HT chitosan nanoparticle (SCNP) and a combination of GABA and 5-HT chitosan nanoparticle (GSCNP) treatments. In GABA and 5-HT chitosan nanoparticle treated group there was a significant decrease (P<0.001) in the receptor expression of Gamma aminobutyric acid B and a significant increase (P<0.001) in the receptor expression of 5-hydroxy tryptamine 2A when compared to PHNT. The cyclic adenosine monophosphate content and its regulatory protein, presence of methylated DNA and superoxide dismutase activity were decreased in GCNP, SCNP and GSCNP when compared to PHNT. The Gamma aminobutyric acid B and 5-hydroxy tryptamine 2A receptors coupled signaling elements played an important role in GABA and 5-HT chitosan nanoparticles induced liver cell proliferation which has therapeutic significance in liver disease management. PMID:23748019

  9. Effect of cholera enterotoxin on carbohydrate metabolism in the liver and small intestinal mucosa of rabbits

    SciTech Connect

    Vengrov, P.R.; Cherkasova, T.D.; Yurkiv, V.A.; Pokrovskii, V.I.

    1987-09-01

    The effect of cholera enterotoxin injected in vivo on glucose formation from alanine, and also on glucose-6-phosphatase activity in the liver and mucosa of the small intestine was studied. L-(2,3-/sup 3/H)-alanine was added to the incubation medium. Chromatograms were developed with 5% AgNO/sub 3/ with the addition of an aqueous solution of ammonia. The quantity of radioactive glucose was determined in a scintillation counter.

  10. The Effect of Helicobacter Pylori Eradication on Liver Fat Content in Subjects With Non-Alcoholic Fatty Liver Disease: A Randomized Open-Label Clinical Trial

    PubMed Central

    Jamali, Raika; Mofid, Alireza; Vahedi, Homayoon; Farzaneh, Rojin; Dowlatshahi, Shahab

    2013-01-01

    Background The role of Helicobacter pylori (HP) in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) is unclear. Objectives The aim of this study was to evaluate the effect of HP eradication on liver fat content (LFC), liver function tests (LFT), lipid profile, and homeostasis model assessment-IR (HOMA-IR) index in NAFLD. Patients and Methods Dyspeptic patients with increased serum aminotransferase levels were enrolled in the study. The exclusion criteria were factors affecting serum aminotransferase or HP treatment strategy. Participants with persistent elevated serum aminotransferase level and ultrasound criteria for identification of fatty liver were presumed to have NAFLD. “NAFLD liver fat score” was used to classify NAFLD. Those with “NAFLD liver fat score” greater than -0.64 and positive results for urea breath test (UBT), were included. Lifestyle modification was provided to all participants. HP eradication was performed in intervention arm. LFC, fasting serum glucose (FSG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), cholesterol (CHOL), high and low-density lipoprotein (HDL, LDL), and HOMA-IR were checked at baseline and after that, at intervals of eight weeks and twenty four weeks. Results One hundred (49 males) patients with the mean age of 43.46 (± 11.52) were studied. Repeated measure ANOVA showed a significant reduction in LFC, anthropometric measurements, and laboratory parameters (except for HDL) in the both groups during the study; however, no significant difference was observed between the groups. Conclusions It seems that HP eradication per se might not affect LFC, LFT, lipid profile, and insulin resistance in dyspeptic NAFLD patients. PMID:24358044

  11. Intrahepatic transplantation of adipose?derived stem cells attenuates the progression of non?alcoholic fatty liver disease in rats.

    PubMed

    Pan, Fan; Liao, Naishun; Zheng, Youshi; Wang, Yingchao; Gao, Yunzhen; Wang, Sen; Jiang, Yi; Liu, Xiaolong

    2015-09-01

    Non?alcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury affecting the general health of various populations. In the present study, adipose tissue?derived stem cells (ADSCs), which were isolated from the adipose tissues of Sprague?Dawley rats, were transplanted into the liver of high?fat?diet?induced NAFLD rats via the portal vein to attenuate the disease progression of NAFLD. The results demonstrated that ADSC transplantation reduced the serum levels of alanine aminotransferase, total bilirubin, total cholesterol, triglycerides and fatty acids, and reduced the content of malondialdehyde in the liver homogenates. By contrast, ADSC transplantation caused a significant increase in superoxide dismutase activity. These data suggested that the ADSC transplantation improved the liver function, and reduced lipid metabolism and oxidative stress. In addition, the hepatic pathological changes were decelerated, lipid accumulation was reduced, and serum levels of the pro?inflammatory factors, tumor necrosis factor?? and interleukin?6, were downregulated by the ADSC transplantation. Taken together, transplantation with ADSCs attenuates the disease progression of high?fat?diet induced NAFLD, therefore, may offer a potential therapeutic approach for the treatment of NAFLD. PMID:26018346

  12. Treatment of pig serum-induced rat liver fibrosis with Boschniakia rossica, oxymatrine and interferon-? ? ? ? ?

    Microsoft Academic Search

    Chun-Song Wu; Xi-Xu Piao; Dong-Ming Piao; Yong-Ri Jin; Cheng-Hao Li

    AIM: To investigate the effect of Boschniakia rossica (BR), oxymatrine (OM) and interferon-alpha (IFN-? ) 1b on the therapy of rat liver fibrosis and its mechanism. METHODS: By establishing a rat model of pig serum-induced liver fibrosis, liver\\/weight index and serum alanine transaminase (ALT) were observed to investigate the therapeutic effect of BR,OM and IFN-? . Radioimmunoassay was utilized to

  13. 13C-methionine breath tests for mitochondrial liver function assessment.

    PubMed

    Candelli, M; Miele, L; Armuzzi, A; Nista, E C; Pignataro, G; Fini, L; Cazzato, I A; Zocco, M A; Bartolozzi, F; Gasbarrini, G; Grieco, A; Gasbarrini, A

    2008-01-01

    13C-methionine breath test has been proposed as a non-invasive tool for the assessment of human hepatic mithocondrial function. Two methionine breath labeled with 13C in differents point of his molecular structure have been used for breath test analisys. Aim of this study was to compare two differently 13C-labeled methionines in the evaluation of mitochondrial oxidation in basal conditions and after an acute oxidative stress. 15 healthy male subjects (mean age 30.5 +/- 3.1) received [methyl-13C]-methionine dissolved in water. Breath samples were taken at baseline and and 10, 20, 30, 45, 60, 75, 90, 105 and 120 minutes after the ingestion of the labeled substrate. Forthy-eight hours later, subjects underwent the same test 30 minutes after ethanol ingestion (0,3 g/kg of body weight). Seven-day later, subjects underwent breath test using (L-methionine-1-13COOH) as substrate, in basal condition and after ethanol ingestion. At basal condition, the cumulative percentage of 13CO2 recovered in breath during the test period (%cum-dose) was higher using L-methionine-1-13COOH than [methyl-13C]-methionine (10.25 +/- 1.0 vs 4.07 +/- 0.8; p < 0.01). After ethanol ingestion, % cum dose was significantly decreased at 60 and 120 minutes with both methionines (120 min: 10.25 +/- 1.0 vs 5.03% +/- 1.8; < 0.01 and 4.07 +/- 0.8 vs 2.16% +/- 0.9; p < 0.01, respectively). However, %cum-dose during L-methionine-1-13C-breath test was significantly lower than that observed during methyl-13C-methionine breath test (120 minutes: 5.03% +/- 1.8 vs 2.16% +/- 0.9; p < 0.01). In conclusion, breath test based on L-methionine-1-13COOH seems to show a greater reliability when compared to [methyl-13C]-methionine to assess mitochondrial function because a larger amount of labeled carbon that reaches the Krebs' cicle. PMID:18727456

  14. Stimulation of Cl(-) secretion by L-alanine oligopeptides in the mammalian large intestine.

    PubMed

    Ikehara, O; Shinbo, I; Kuwahara, A; Suzuki, Y

    2000-06-01

    A variety of oligopeptides are probably released within the intestinal tissue under inflammatory conditions or during peptide absorption. To examine whether some of these peptides can affect intestinal transport functions, we determined the effects of L-alanine oligopeptide on short-circuit current (I(sc)) and transmucosal conductance (G(t)) in submucosa-mucosa preparations from the mouse cecum and guinea pig distal colon in vitro in Ussing chambers. L-Alanyl-L-alanine (Ala-Ala, 10 mM) added to the serosal side increased I(sc) and G(t), giving a peak followed by a sustained phase (the peak increase in I(sc) was 45 +/-6 microA/cm(2) and the increase in G(t) was 0.55+/-0.11 mS/cm(2)). The tripeptide, L-alanyl-L-alanyl-L-alanine (Ala-Ala-Ala, 10 mM), added to the serosal side also induced increases in I(sc) and G(t) by a similar degree. On the other hand, luminal Ala-Ala, and serosal L-alanine and L-alanine (10 mM) caused significantly smaller increases in I(sc) and G(t) ( approximately 15 microA/cm(2) and approximately 0. 15 mS/cm(2), respectively). The Ala-Ala induced increase in I(sc) was partially inhibited by serosal bumetanide (0.1 mM) and mucosal 5-nitro-2-(3-phenylpropylamino)benzoic acid (0.1 mM), and largely suppressed by removing Cl(-) from the bathing solution. The increase in I(sc) was largely suppressed by serosal low Ca(2+) and tetrodotoxin, but was not affected by indomethacin. In the guinea pig distal colon, serosal Ala-Ala (10 mM) evoked a transient increase in I(sc) by 23+/-7 microA/cm(2) and an increase in G(t) by 1.2+/-0.3 mS/cm(2). These results suggest that Ala-Ala, and probably also Ala-Ala-Ala, added to the serosal side stimulated electrogenic Cl(-) secretion mainly through the activation of submucosal secretomotor neurons in the mammalian large intestine. PMID:11016982

  15. Synthesis of ?-C-galactosyl d- and l-alanines†‡

    PubMed Central

    Thota, V. Narasimharao; Gervay-Hague, Jacquelyn

    2015-01-01

    Synthesis of ?-C-d-galactosyl d- and l-alanines is carried out via a highly stereoselective Grignard reaction of glycosyl iodides, Sharpless dihydroxylation and SN2 displacement of the corresponding mesylate or tosylate. Alternatively, attempted triflation of the intermediate alcohols triggers a stereoselective debenzylative cyclization leading to interesting bicyclic trans-fused compounds. PMID:22961309

  16. Fatty Liver

    Microsoft Academic Search

    Jaideep Behari

    \\u000a The liver plays a central role in maintaining energy balance in the body. After a meal, dietary lipids are transported to\\u000a the liver in the form of chylomicrons by the lymphatic system. The liver then releases the dietary lipids by the action of\\u000a lipoprotein lipase and incorporates them into very-low-density lipoproteins (VLDL), which are then secreted from the liver\\u000a and

  17. A novel synthetic oleanolic acid derivative (CPU-II 2 ) attenuates liver fibrosis in mice through regulating the function of hepatic stellate cells

    Microsoft Academic Search

    Li-Mei Wu; Xing-Xin Wu; Yang Sun; Xiang-Wen Kong; Yi-Hua Zhang; Qiang Xu

    2008-01-01

    Regulation on the function of the hepatic stellate cells (HSCs) is one of the proposed therapeutic approaches to liver fibrosis.\\u000a In the present study, we examined the in vitro and in vivo effects of CPU-II2, a novel synthetic oleanolic acid (OLA) derivative with nitrate, on hepatic fibrosis. This compound alleviated CCl4-induced hepatic fibrosis in mice with a decrease in hepatic

  18. Association of high viral load and abnormal liver function with high aflatoxin B1–albumin adduct levels in HIV-positive Ghanaians: preliminary observations

    Microsoft Academic Search

    P. E. Jolly; F. M. Shuaib; Y. Jiang; P. Preko; J. Baidoo; J. K. Stiles; J.-S. Wang; T. D. Phillips; J. H. Williams

    2011-01-01

    We examined the association between certain clinical factors and aflatoxin B1–albumin adduct (AF-ALB) levels in HIV-positive people. Plasma samples collected from 314 (155 HIV-positive and 159 HIV-negative) people were tested for AF-ALB levels, viral load, CD4+ T-cell count, liver function profile, malaria parasitaemia, and hepatitis B and C virus infections. HIV-positive participants were divided into high and low groups based

  19. Threshold Doses for Focal Liver Reaction After Stereotactic Ablative Body Radiation Therapy for Small Hepatocellular Carcinoma Depend on Liver Function: Evaluation on Magnetic Resonance Imaging With Gd-EOB-DTPA

    SciTech Connect

    Sanuki, Naoko; Takeda, Atsuya; Oku, Yohei [Radiation Oncology Center, Ofuna Chuo Hospital, Kanagawa (Japan); Department of Radiation Oncology, Tokai University, Kanagawa (Japan); Eriguchi, Takahisa; Nishimura, Shuichi; Aoki, Yosuke [Radiation Oncology Center, Ofuna Chuo Hospital, Kanagawa (Japan); Mizuno, Tomikazu [Department of Radiology, Ofuna Chuo Hospital, Kanagawa (Japan); Iwabuchi, Shogo [Department of Hepatology and Gastroenterology, Ofuna Chuo Hospital, Kanagawa (Japan); Kunieda, Etsuo, E-mail: kunieda-mi@umin.ac.jp [Department of Radiation Oncology, Tokai University, Kanagawa (Japan)

    2014-02-01

    Purpose: Focal liver reaction (FLR) appears on radiographic images after stereotactic ablative body radiation therapy (SABR) in patients with hepatocellular carcinoma (HCC) and chronic liver disease. We investigated the threshold dose (TD) of FLR and possible factors affecting the TD on gadoxetate acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). Methods and Materials: In 50 patients who were treated with SABR for small HCC and followed up by MRI for >6 months, FLR, seen as a hypointense area, was evaluated on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. The follow-up MRI with the largest extent of FLR was fused to the planning computed tomography (CT) image, and patients with good image fusion concordance were eligible. After delineating the border of the FLR manually, a dose–volume histogram was used to identify the TD for the FLR. Clinical and volumetric factors were analyzed for correlation with the TD. Results: A total of 45 patients were eligible for analysis with a median image fusion concordance of 84.9% (range, 71.6-95.4%). The median duration between SABR and subsequent hepatobiliary phase MRI with the largest extent of FLR was 3 months (range, 1-6 months). The median TD for FLR was 28.0 Gy (range, 22.3-36.4 Gy). On univariate analysis, pre-treatment Child-Pugh (CP) score and platelet count were significantly correlated with the TD. On multiple linear regression analysis, CP score was the only parameter that predicted TD. Median TDs were 30.5 Gy (range, 26.2.3-36.4 Gy) and 25.2 Gy (range, 22.3-27.5 Gy) for patients with CP-A and CP-B disease, respectively. Conclusion: The TD was significantly correlated with baseline liver function. We propose 30 Gy for CP-A disease and 25 Gy for CP-B disease in 5 fractions as TDs for FLR after SABR for patients with HCC and chronic liver disease. Use of these TDs will help to predict potential loss of liver tissue after SABR.

  20. Inhibition study of alanine aminotransferase enzyme using sequential online capillary electrophoresis analysis.

    PubMed

    Liu, Lina; Chen, Yuanfang; Yang, Li

    2014-12-15

    We report the study of several inhibitors on alanine aminotransferase (ALT) enzyme using sequential online capillary electrophoresis (CE) assay. Using metal ions (Na(+) and Mg(2+)) as example inhibitors, we show that evolution of the ALT inhibition reaction can be achieved by automatically and simultaneously monitoring the substrate consumption and product formation as a function of reaction time. The inhibition mechanism and kinetic constants of ALT inhibition with succinic acid and two traditional Chinese medicines were derived from the sequential online CE assay. Our study could provide valuable information about the inhibition reactions of ALT enzyme. PMID:25217806

  1. Early maternal undernutrition programs increased feed intake, altered glucose metabolism and insulin secretion, and liver function in aged female offspring

    PubMed Central

    George, Lindsey A.; Zhang, Liren; Tuersunjiang, Nuermaimaiti; Ma, Yan; Long, Nathan M.; Uthlaut, Adam B.; Smith, Derek T.; Nathanielsz, Peter W.

    2012-01-01

    Insulin resistance and obesity are components of the metabolic syndrome that includes development of cardiovascular disease and diabetes with advancing age. The thrifty phenotype hypothesis suggests that offspring of poorly nourished mothers are predisposed to the various components of the metabolic syndrome due to adaptations made during fetal development. We assessed the effects of maternal nutrient restriction in early gestation on feeding behavior, insulin and glucose dynamics, body composition, and liver function in aged female offspring of ewes fed either a nutrient-restricted [NR 50% National Research Council (NRC) recommendations] or control (C: 100% NRC) diet from 28 to 78 days of gestation, after which both groups were fed at 100% of NRC from day 79 to lambing and through lactation. Female lambs born to NR and C dams were reared as a single group from weaning, and thereafter, they were fed 100% NRC recommendations until assigned to this study at 6 yr of age. These female offspring were evaluated by a frequently sampled intravenous glucose tolerance test, followed by dual-energy X-ray absorptiometry for body composition analysis prior to and after ad libitum feeding of a highly palatable pelleted diet for 11 wk with automated monitoring of feed intake (GrowSafe Systems). Aged female offspring born to NR ewes demonstrated greater and more rapid feed intake, greater body weight gain, and efficiency of gain, lower insulin sensitivity, higher insulin secretion, and greater hepatic lipid and glycogen content than offspring from C ewes. These data confirm an increased metabolic “thriftiness” of offspring born to NR mothers, which continues into advanced age, possibly predisposing these offspring to metabolic disease. PMID:22277936

  2. Liver transplantation?

    PubMed Central

    Rossi, M.; Mennini, G.; Lai, Q.; Ginanni Corradini, S.; Drudi, F.M.; Pugliese, F.; Berloco, P.B.

    2007-01-01

    Orthotopic liver transplantation (OLT) involves the substitution of a diseased native liver with a normal liver (or part of one) taken from a deceased or living donor. Considered an experimental procedure through the 1980s, OLT is now regarded as the treatment of choice for a number of otherwise irreversible forms of acute and chronic liver disease. The first human liver transplantation was performed in the United States in 1963 by Prof. T.E. Starzl of the University of Colorado. The first OLT to be performed in Italy was done in 1982 by Prof. R. Cortesini. The procedure was successfully performed at the Policlinico Umberto I of the University of Rome (La Sapienza). The paper reports the indications for liver transplantation, donor selection and organ allocation in our experience, surgical technique, immunosuppression, complications and results of liver transplantation in our center. PMID:23396075

  3. Cholesterol biosynthesis from lanosterol: molecular cloning, chromosomal localization, functional expression and liver-specific gene regulation of rat sterol delta8-isomerase, a cholesterogenic enzyme with multiple functions.

    PubMed Central

    Bae, S; Seong, J; Paik, Y

    2001-01-01

    Sterol Delta(8)-isomerase (SI) (EC 5.3.3.5), also known as emopamil binding protein or sigma receptor, catalyses the conversion of the 8-ene isomer into the 7-ene isomer in the cholesterol biosynthetic pathway in mammals. Recently, mutations of SI have been found to be associated with Conradi-Hünermann syndrome in humans. To investigate the in vitro and in vivo modes of molecular regulation of SI and its role in cholesterol biosynthesis in mammals, we isolated a full-length cDNA encoding rat SI. The deduced amino-acid sequence of rat SI predicts a 230-residue protein (26737 Da) with 87% and 80% amino-acid identity to mouse and human counterparts. The rat SI gene was mapped to chromosome 12q1.2 using fluorescence in situ hybridization (FISH). The biological function of the cloned rat SI cDNA was verified by overexpressing recombinant Myc-SI in Saccharomyces cerevisiae. It showed a characteristic pattern of inhibition on exposure to trans-2-[4-(1,2-diphenylbuten-1-yl)phenoxy]-N,N-dimethylethylamine (tamoxifen; IC(50)=11.2 microM) and 3beta-[2-(diethylamino)ethoxy]androst-5-en-17-one (U18666A; IC(50)=4.2 microM), two well known potent inhibitors of SI. Northern-blot analysis of 3-week-old rats compared with 2-year-old rats showed that SI mRNA expression in both age groups was restricted to liver, where a 70% reduction in mRNA levels was observed in 2-year-old rats. The FISH studies revealed ubiquitous expression of SI mRNA in rat hepatocytes. The in vitro studies showed that the SI mRNA was highly suppressed by 25-hydroxycholesterol in H4IIE cells. Treatment of H4IIE cells grown in medium supplemented with fetal bovine serum with tamoxifen for 24 h resulted in a dose-dependent induction of SI mRNA, with a concomitant suppression of sterol regulatory element binding protein-1 mRNA. Interestingly, this effect was not seen in emopamil-treated cells. The in vivo experiments also indicate that both mRNA expression and enzymic activity of SI in liver were induced approx. 3-fold in rats fed 5% (w/w) cholestyramine plus 0.1% (w/w) lovastatin in normal chow for 2 weeks. With this newly cloned rat SI cDNA, it becomes possible to gain molecular understanding of previously unknown and tamoxifen-mediated gene regulation of SI that is involved in cholesterol metabolism, ischaemia and genetic diseases. PMID:11171067

  4. Effect of tolbutamide on sup 14 C-sodium bicarbonate and sup 14 C-alanine metabolism in isolated rat hepatocytes

    SciTech Connect

    Kunjathoor, V.V.; Ye, Y.; Pillai, U.A.; Ferguson, P.W.; Medon, P.J. (Northeast Louisiana Univ., Monroe (United States))

    1990-02-26

    Tolbutamide (TOLB) is a sulfonylurea commonly used in the treatment of noninsulin-dependent diabetes mellitus. Studies have shown that TOLB affects gluconeogenesis and glycolysis from various substrates in the liver. Specifically, TOLB inhibits gluconeogenesis from lactate in a dose-dependent manner. In order to further clarify tolbutamide's mechanism of action, its effect on the incorporation of {sup 14}C from NaH{sup 14}CO{sub 3} and {sup 14}C-alanine into glucose, lactate or pyruvate in the presence of lactate was measured. Rat hepatocytes were incubated with lactate (2.0 mM) with or without TOLB (1.0 mM) in the presence of NaH{sup 14}CO{sub 3} or {sup 14}C-alanine. TOLB inhibited the incorporation of C{sup 14} from NaHCO{sub 3} and alanine into glucose by 55 and 56%, respectively. TOLB did not alter the incorporation of C{sup 14} from NaHCO{sub 3} into lactate or pyruvate. TOLB did not affect the incorporation of {sup 14}C from alanine into lactate but produced a pooling of {sup 14}C as pyruvate. The authors data support studies demonstrating the TOLB produces its actions, in part, by increasing the concentration of fructose-2,6-bisphosphate and inhibiting pyruvate carboxylase.

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

    PubMed Central

    Jassem, Wayel; Vilca-Melendez, Hector; Prachalias, Andreas; Srinivasan, Parthi

    2015-01-01

    Donation after cardiac death (DCD) livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF) or early graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ? 1000 IU/L and EGD (n=9) peak AST ? 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p<0.05). On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049). From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression patterns have a low diagnostic potential clinically in discriminating DCD liver quality and outcome. PMID:25978529

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

    PubMed

    Khorsandi, Shirin Elizabeth; Quaglia, Alberto; Salehi, Siamak; Jassem, Wayel; Vilca-Melendez, Hector; Prachalias, Andreas; Srinivasan, Parthi; Heaton, Nigel

    2015-01-01

    Donation after cardiac death (DCD) livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF) or early graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ? 1000 IU/L and EGD (n=9) peak AST ? 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p<0.05). On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049). From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression patterns have a low diagnostic potential clinically in discriminating DCD liver quality and outcome. PMID:25978529

  7. Peripheral vein infusion of autologous mesenchymal stem cells in Egyptian HCV-positive patients with end-stage liver disease

    PubMed Central

    2014-01-01

    Introduction We have assessed the utility of autologous mesenchymal stem cell (MSC) peripheral vein infusion as a possible therapeutic modality for patients with end-stage liver diseases. Methods Forty patients with post-hepatitis C virus (HCV) end-stage liver disease were randomized into two groups: Group 1 (GI): 20 patients who received granulocyte colony-stimulating factor (G-CSF) for 5 days followed by autologous MSCs peripheral-vein infusion and group 2 (GII): 20 patients who received regular liver-supportive treatment only (control group). Results In MSC-infused patients (GI), 54% showed near normalization of liver enzymes and improvement in liver synthetic function. Significant changes were reported in albumin (P?=?0.000), bilirubin (P?=?0.002), increased international normalized ratio (INR) (P?=?0.017), prothrombin concentration (P?=?0.029) and alanine transaminase (ALT) levels (P?=?0.029), with stabilization of clinical and biochemical status in 13% of cases. None of the patients in GII showed any significant improvement. Hepatic fibrosis was assessed in GI by detection of procollagen IIIC peptide level (PIIICP) and procollagen III N peptide level (PIIINP). The pretreatment values of s-PIIICP and s-PIIINP were 9.4?±?4.2 and 440?±?189, respectively, with a decrease to 8.1?±?2.6 and 388?±?102, respectively, 3 months after MSC therapy. However, the difference was statistically nonsignificant (P?=?0.7). A significant correlation coefficient was reported after 3 months between the s-PIIINP and prothrombin concentration (P?=?-0.5) and between s-PIIICP and ascites (P?=?0.550). Conclusions First, autologous MSC infusion into a peripheral vein is as effective as the previously reported intrahepatic infusion. Second, MSCs have a supportive role in the treatment of end-stage liver disease, with satisfactory tolerability and beneficial effects on liver synthetic functions and hepatic fibrosis. Third, IV infusion of MSCs after G-CSF mobilization improves s-albumin within the first 2 weeks and prothrombin concentration and alanine Taransaminase after 1 month. According to the data from this current study and those previously reported by our group, we recommend further studies on patients’ infusion with pure CD133 and CD34 followed by IV infusion of in vitro-differentiated MSCs within 1 week and another infusion after 3 months. Trial registration ClinicalTrials.gov NCT01729221. Registered 17 November 2012. PMID:24886681

  8. Inhibition of the Mitochondrial Respiratory Chain by Alanine in Rat Cerebral Cortex

    Microsoft Academic Search

    Virginia C. Rech; Luciane R. Feksa; Carlos S. Dutra-Filho; Angela T. S. Wyse; Moacir Wajner; Clovis M. D. Wannmacher

    2002-01-01

    Alanine is a nutritionally nonessential amino acid synthesized by transamination of pyruvate originated from glucose. Alanine is the principal gluconeogenic amino acid because it can originate pyruvate and glucose through the inverse pathway. Considering that it has been suggested that alanine could be used as a dietary supplement in combination with growth hormone in the treatment of undernourished children affected

  9. Transferability of ASTM\\/NIST alanine–polyethylene recipe at ISS

    Microsoft Academic Search

    C. De Angelis; P. Fattibene; S. Onori; E. Petetti; A. Bartolotta; A. Sansone Santamaria

    2000-01-01

    Alanine–polyethylene solid state dosimeters were prepared at Istituto Superiore di Sanità (ISS) following the recipe proposed by National Institute of Standards and Technology (NIST) with the goal of testing its transferability. Dosimeters were prepared using 95% alanine and 5% polyethylene, by weight. They are rugged and of increased sensitivity, repeatability and reproducibility as respect to the ISS alanine-paraffin pellets. Reproducibility

  10. MicroRNA-31 functions as a tumor suppressor by regulating cell cycle and epithelial-mesenchymal transition regulatory proteins in liver cancer

    PubMed Central

    Bae, Hyun Jin; Eun, Jung Woo; Shen, Qingyu; Park, Se Jin; Shin, Woo Chan; Yang, Hee Doo; Park, Mijung; Park, Won Sang; Kang, Yong-Koo; Nam, Suk Woo

    2015-01-01

    MicroRNA-31 (miR-31) is among the most frequently altered microRNAs in human cancers and altered expression of miR-31 has been detected in a large variety of tumor types, but the functional role of miR-31 still hold both tumor suppressive and oncogenic roles in different tumor types. MiR-31 expression was down-regulated in a large cohort of hepatocellular carcinoma (HCC) patients, and low expression of miR-31 was significantly associated with poor prognosis of HCC patients. Ectopic expression of miR-31 mimics suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins. Additional study evidenced miR-31 directly to suppress HDAC2 and CDK2 expression by inhibiting mRNA translation in HCC cells. We also found that ectopic expression of miR-31 mimics reduced metastatic potential of HCC cells by selectively regulating epithelial-mesenchymal transition (EMT) regulatory proteins such as N-cadherin, E-cadherin, vimentin and fibronectin. HCC tissues derived from chemical-induced rat liver cancer models validated that miR-31 expression is significantly down-regulated, and that those cell cycle- and EMT-regulatory proteins are deregulated in rat liver cancer. Overall, we suggest that miR-31 functions as a tumor suppressor by selectively regulating cell cycle and EMT regulatory proteins in human hepatocarcinogenesis providing a novel target for the molecular treatment of liver malignancies. PMID:25797269

  11. Effects of dose fractionation on the response of alanine dosimetry

    NASA Astrophysics Data System (ADS)

    Lundahl, Brad; Logar, John; Desrosiers, Marc; Puhl, James

    2014-12-01

    Alanine dosimetry is well established as a transfer standard and is becoming more prevalently used in routine dosimetry systems for radiation processing. Many routine measurement applications in radiation processing involve absorbed dose measurements resulting from fractioned exposures to ionizing radiation. Fractioning of absorbed dose is identified as an influence quantity (ISO/ASTM, 2013). This paper reports on study results of absorbed dose fractioning characteristics of alanine for gamma and high energy electron beam radiation sources. The results of this study indicate a radiation response difference due to absorbed dose fractioning in response can be observed after four fractionations for high-energy electron beams and no difference up to seven fractions for gamma rays using an ANOVA evaluation method.

  12. Physiological hypercortisolemia increases proteolysis, glutamine, and alanine production

    SciTech Connect

    Darmaun, D.; Matthews, D.E.; Bier, D.M. (Washington Univ. School of Medicine, St. Louis, MO (USA) Cornell Univ. Medical College, New York, NY (USA))

    1988-09-01

    Physiological elevations of plasma cortisol levels, as are encountered in stress and severe trauma, were produced in six normal subjects by infusing them with hydrocortisone for 64 h. Amino acid kinetics were measured in the postabsorptive state using three 4-h infusions of L-(1-{sup 13}C)leucine, L-phenyl({sup 2}H{sub 5})phenylalanine, L-(2-{sup 15}N)glutamine, and L-(1-{sup 13}C)alanine tracers (1) before, (2) at 12 h, and (3) at 60 h of cortisol infusion. Before and throughout the study, the subjects ate a normal diet of adequate protein and energy intake. The cortisol infusion raised plasma cortisol levels significantly from 10 {plus minus} 1 to 32 {plus minus} 4 {mu}g/dl, leucine flux from 83 {plus minus} 3 to 97 {plus minus} 3 {mu}mol{center dot}kg{sup {minus}1}{center dot}h{sup {minus}1}, and phenylalanine flux from 34 {plus minus} 1 to 39 {plus minus} 1 (SE) {mu}mol{center dot}kg{sup {minus}1}{center dot}h{sup {minus}1} after 12 h of cortisol infusion. These increases were maintained until the cortisol infusion was terminated. These nearly identical 15% increases in two different essential amino acid appearance rates are reflective of increased whole body protein breakdown. Glutamine flux rose by 12 h of cortisol infusion and remained elevated at the same level at 64 h. The increase in flux was primarily due to a 55% increase in glutamine de novo synthesis. Alanine flux increased with acute hypercortisolemia and increased further at 60 h of cortisol infusion, a result primarily of increased alanine de novo synthesis. Insulin, alanine, and lactate plasma levels responded similarly with significant rises between the acute and chronic periods of cortisol infusion. Thus hypercortisolemia increases both protein breakdown and the turnover of important nonessential amino acids for periods of up to 64 h.

  13. ?-alanine supplementation improves isometric endurance of the knee extensor muscles

    PubMed Central

    2012-01-01

    Background We examined the effect of four weeks of ?-alanine supplementation on isometric endurance of the knee extensors at 45% maximal voluntary isometric contraction (MVIC). Methods Thirteen males (age 23?±?6 y; height 1.80?±?0.05?m; body mass 81.0?±?10.5?kg), matched for pre-supplementation isometric endurance, were allocated to either a placebo (n?=?6) or ?-alanine (n?=?7; 6.4?g·d-1 over 4?weeks) supplementation group. Participants completed an isometric knee extension test (IKET) to fatigue, at an intensity of 45% MVIC, before and after supplementation. In addition, two habituation tests were completed in the week prior to the pre-supplementation test and a further practice test was completed in the week prior to the post-supplementation test. MVIC force, IKET hold-time, and impulse generated were recorded. Results IKET hold-time increased by 9.7?±?9.4?s (13.2%) and impulse by 3.7?±?1.3 kN·s-1 (13.9%) following ?-alanine supplementation. These changes were significantly greater than those in the placebo group (IKET: t(11)?=?2.9, p ?0.05; impulse: t(11)?=?3.1, p???0.05). There were no significant changes in MVIC force in either group. Conclusion Four weeks of ?-alanine supplementation at 6.4?g·d-1 improved endurance capacity of the knee extensors at 45% MVIC, which most likely results from improved pH regulation within the muscle cell as a result of elevated muscle carnosine levels. PMID:22697405

  14. Crystal Structures of Aedes Aegypt Alanine Glyoxylate Aminotransferase

    SciTech Connect

    Han,Q.; Robinson, H.; Gao, Y.; Vogelaar, N.; Wilson, S.; Rizzi, M.; Li, J.

    2006-01-01

    Mosquitoes are unique in having evolved two alanine glyoxylate aminotransferases (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily responsible for catalyzing the transamination of 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). Interestingly, XA is used by malaria parasites as a chemical trigger for their development within the mosquito. This 3-HK to XA conversion is considered the major mechanism mosquitoes use to detoxify the chemically reactive and potentially toxic 3-HK. The other AGT is a typical dipteran insect AGT and is specific for converting glyoxylic acid to glycine. Here we report the 1.75{angstrom} high-resolution three-dimensional crystal structure of AGT from the mosquito Aedes aegypti (AeAGT) and structures of its complexes with reactants glyoxylic acid and alanine at 1.75 and 2.1{angstrom} resolution, respectively. This is the first time that the three-dimensional crystal structures of an AGT with its amino acceptor, glyoxylic acid, and amino donor, alanine, have been determined. The protein is dimeric and adopts the type I-fold of pyridoxal 5-phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently bound to the active site in the crystal structure, and its binding site is similar to those of other AGTs. The comparison of the AeAGT-glyoxylic acid structure with other AGT structures revealed that these glyoxylic acid binding residues are conserved in most AGTs. Comparison of the AeAGT-alanine structure with that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe motif in the latter may be responsible for the substrate specificity of HKT enzymes for 3-HK.

  15. Portal vein arterialization promotes liver regeneration after extended partial hepatectomy in a rat model

    PubMed Central

    Li, Jian; Cai, Chaonong; Guo, Hui; Guan, Xiaodong; Yang, Lukun; Li, Yuechan; Zhu, Yanhua; Li, Peiping; Liu, Xialei; Zhang, Baimeng

    2015-01-01

    Abstract In the current study, we sought to establish a novel rat model of portal vein arterialization (PVA) and evaluate its impact on liver regeneration after extended partial hepatectomy (PH). A total of 105 Sprague-Dawley rats were randomly assigned to three groups: 68% hepatectomy (the PH group), portal arterialization after 68% hepatectomy (the PVA group), and right nephrectomy only (the control group). Liver regeneration rate (LRR), 5-bromo-2-deoxyuridine (BrdU) labeling index, and liver functions were assessed on postoperative day 2, 7, 14 and 28. The 28-day survival rates were compared among the three groups. The 28-day survival rates were similar in all groups (P ?=? 0.331), and the anastomotic patency was 100%. The LRR in the PVA group was significantly higher than that of the PH group within postoperative 14 days (P < 0.05). The PVA and PH group had increased serum alanine aminotransferase levels (232 ± 61?U/L and 212 ± 53?U/L, respectively) compared with the control group (101 ± 13?U/L) on postoperative day 2, whereas from postoperative day 7 to day 28 there were no differences among the three groups. Serum albumin values were higher after the PVA procedure within postoperative day 14, which gradually became comparable on postoperative day 28 among the three groups. The peaks of BrdU labeling index appeared on postoperative day 2 in all rats, and the PVA procedure was associated with increased BrdU labeling index from postoperative day 7 to 28. The 28-day survival of the PVA rats was comparable. Our findings demonstrate that the PVA procedure utilizing portal vein trunk-renal artery microvascular reconstruction promotes remnant liver regeneration and confers beneficial effects on maintaining and even optimizing liver function after extended partial hepatectomy in rats. PMID:25745478

  16. Diagnosis of alcoholic liver disease

    PubMed Central

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-01-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  17. Expression and function of fibroblast growth factor (FGF) 9 in hepatic stellate cells and its role in toxic liver injury

    SciTech Connect

    Antoine, Marianne [Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg (Germany); Wirz, Werner [Institute of Clinical Chemistry and Pathobiochemistry, RWTH Aachen D-52073 (Germany); Tag, Carmen G. [Institute of Clinical Chemistry and Pathobiochemistry, RWTH Aachen D-52073 (Germany); Gressner, Axel M. [Institute of Clinical Chemistry and Pathobiochemistry, RWTH Aachen D-52073 (Germany); Marvituna, Meltem [Institute of Clinical Chemistry and Pathobiochemistry, RWTH Aachen D-52073 (Germany); Wycislo, Mathias [Institute of Clinical Chemistry and Pathobiochemistry, RWTH Aachen D-52073 (Germany); Hellerbrand, Claus [Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg (Germany); Kiefer, Paul [Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg (Germany)]. E-mail: paul.kiefer@klinik.uni-regensburg.de

    2007-09-21

    Hepatic injury and regeneration of the liver are associated with activation of hepatic stellate cells (HSC). Fibroblast growth factors (FGFs) and their receptors are important regulators of repair in various tissues. HSC express FGFR3IIIc as well as FGFGR4 and different spliced FGFR1IIIc and FGFR2IIIc isoforms which differ in the presence or absence of the acid box and of the first Ig-like domain. Expression of FGF9, known to be capable to activate the HSC FGFR2/3-isoforms, was increased in HSC in liver slice cultures after exposition to carbon tetrachloride, as an acute liver injury model. FGF9 significantly stimulated 3-H thymidine incorporation of hepatocytes, but failed to induce DNA synthesis in HSC despite the fact that FGF9 induced a sustained activation of extracellular signal-related kinases (ERK) 1/2. FGF9 induced an increased phosphorylation of Tyr436 of the fibroblast growth factor receptor substrate (FRS) 2, while phosphorylation of Tyr196 which is required for efficient Grb2 recruitment remained unchanged. Our findings suggest that HSC FGF9 provide a paracrine mitogenic signal to hepatocytes during acute liver injury, while the autocrine FGF9 signaling appears to be not sufficient to induce cell proliferation.

  18. Liver mitochondrial respiratory function and coenzyme Q content in rats on a hypercholesterolemic diet treated with atorvastatin.

    PubMed

    Uli?ná, O; Van?ová, O; Waczulíková, I; Božek, P; Šikurová, L; Bada, V; Kucharská, J

    2012-01-01

    Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are effective drugs in the treatment of hypercholesterolemia, however, their undesirable actions are not fully known. We investigated the effects of atorvastatin on the oxidative phosphorylation and membrane fluidity in liver mitochondria, and also on the coenzyme Q (CoQ) content in the mitochondria, liver tissue, and plasma of rats on a standard (C) and hypercholesterolemic (HCh) diet. Atorvastatin was administered at either low (10 mg kg(-1)) or high dose (80 mg kg(-1)) for four weeks. The high dose of the drug decreased the concentrations of total cholesterol and triacylglycerols in the plasma and liver of rats on a HCh diet. Administration of atorvastatin was associated with decreased oxygen uptake (state 3), and oxidative phosphorylation rate in the mitochondria of both C and HCh rats. Further, the drug influenced mitochondrial membrane fluidity and dose-dependently reduced concentrations of oxidized and reduced forms of CoQ in the mitochondria. Our findings point to an association between in vivo administration of atorvastatin and impaired bioenergetics in the liver mitochondria of rats, regardless of diet, in conjunction with simultaneous depletion of oxidized and reduced CoQ forms from the mitochondria. This fact may play a significant role in the development of statin-induced hepatopathy. PMID:22292717

  19. Liver trauma grading and biochemistry tests.

    PubMed

    Arslan, Gozde; Gemici, Aysegul Akdogan; Yirgin, Inci Kizildag; Gulsen, Esma; Inci, Ercan

    2013-10-01

    Among solid organ blunt traumas, the liver and spleen are mostly subject to injury. In addition, the liver is also commonly injured in penetrating traumas because of its size, location, and the ease of injury to the "Glisson Capsule". Several enzymes are known to be elevated following trauma. In our study, we evaluated the correlation between the levels of serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and gamma-glutamyl transpeptidase in 57 patients with blunt trauma to the liver and compared these values to the American Association for the Surgery of Trauma trauma grading system. Additionally, we compared the enzyme level elevations in these patients to the enzyme levels of 29 healthy subjects. As expected, we found significant elevations in enzyme levels of trauma patients compared to the control group. The calculated point estimates were not significantly different between grades 1 and 2 trauma. However, grade 3 trauma group showed a significant increase in enzyme levels. PMID:23793528

  20. Dysregulation of protein degradation pathways may mediate the liver injury and phospholipidosis associated with a cationic amphiphilic antibiotic drug.

    PubMed

    Mosedale, Merrie; Wu, Hong; Kurtz, C Lisa; Schmidt, Stephen P; Adkins, Karissa; Harrill, Alison H

    2014-10-01

    A large number of antibiotics are known to cause drug-induced liver injury in the clinic; however, interpreting clinical risk is not straightforward owing to a lack of predictivity of the toxicity by standard preclinical species and a poor understanding of the mechanisms of toxicity. An example is PF-04287881, a novel ketolide antibiotic that caused elevations in liver function tests in Phase I clinical studies. In this study, a mouse diversity panel (MDP), comprised of 34 genetically diverse, inbred mouse strains, was utilized to model the toxicity observed with PF-04287881 treatment and investigate potential mechanisms that may mediate the liver response. Significant elevations in serum alanine aminotransferase (ALT) levels in PF-04287881-treated animals relative to vehicle-treated controls were observed in the majority (88%) of strains tested following a seven day exposure. The average fold elevation in ALT varied by genetic background and correlated with microscopic findings of hepatocellular hypertrophy, hepatocellular single cell necrosis, and Kupffer cell vacuolation (confirmed as phospholipidosis) in the liver. Global liver mRNA expression was evaluated in a subset of four strains to identify transcript and pathway differences that distinguish susceptible mice from resistant mice in the context of PF-04287881 treatment. The protein ubiquitination pathway was highly enriched among genes associated with PF-04287881-induced hepatocellular necrosis. Expression changes associated with PF-04287881-induced phospholipidosis included genes involved in drug transport, phospholipid metabolism, and lysosomal function. The findings suggest that perturbations in genes involved in protein degradation leading to accumulation of oxidized proteins may mediate the liver injury induced by this drug. PMID:24967691

  1. Combined liver-kidney transplantation in primary hyperoxaluria type 1.

    PubMed

    Cochat, P; Gaulier, J M; Koch Nogueira, P C; Feber, J; Jamieson, N V; Rolland, M O; Divry, P; Bozon, D; Dubourg, L

    1999-12-01

    Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder characterised by an increased urinary excretion of calcium oxalate, leading to recurrent urolithiasis, nephrocalcinosis and accumulation of insoluble oxalate throughout the body (oxalosis) when the glomerular filtration rate falls to below 40-20 mL/min per 1.73 m(2). The disease is due to a functional defect of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), the gene of which is located on chromosome 2q37.3. The diagnosis is based on increased urinary oxalate and glycollate, increased plasma oxalate and AGT measurement in a liver biopsy. AGT mistargeting may be investigated by immuno-electron microscopy and DNA analysis. End-stage renal failure is reached by the age of 15 years in 50% of PH1 patients and the overall death rate approximates 30%. The conservative treatment includes high fluid intake, pyridoxine and crystallisation inhibitors. Since the kidney is the main target of the disease, isolated kidney transplantation (Tx) has been proposed in association with vigorous peri-operative haemodialysis in an attempt to clear plasma oxalate at the time of Tx. However, because of a 100% recurrence rate, the average 3-year graft survival is 15%-25% in Europe, with a 5-10-year patient survival rate ranging from 10% to 50%. Since the liver is the only organ responsible for the detoxification of glyoxylate by AGT, deficient host liver removal is the first rationale for enzyme replacement therapy. Subsequent orthotopic liver Tx aims to supply the missing enzyme in its normal cellular and subcellular location and thus can be regarded as a form of gene therapy. Because of the usual spectrum of the disease, isolated liver Tx is limited to selected patients prior to having reached an advanced stage of chronic renal failure. Combined liver-kidney Tx has therefore become a conventional treatment for most PH1 patients: according to the European experience, patient survival approximates 80% at 5 years and 70% at 10 years. In addition, the renal function of survivors remains stable over time, between 40 and 60 mL/min per 1.73 m(2) after 5 to 10 years. In addition, liver Tx may allow the reversal of systemic storage disease (i.e. bone, heart, vessels, nerves) and provide valuable quality of life. Whatever the transplant strategy, the outcome is improved when patients are transplanted early in order to limit systemic oxalosis. According to the European experience, it appears that combined liver-kidney Tx is performed in PH1 patients with encouraging results, renal Tx alone has little role in the treatment of this disease, and liver Tx reverses the underlying metabolic defect and its clinical consequences. PMID:10603104

  2. Effect of alloxan-diabetes on gluconeogenesis and ureogenesis in isolated rabbit liver cells.

    PubMed Central

    Zaleski, J; Bry?a, J

    1978-01-01

    1. Neither alloxan-diabetes nor starvation affected the rate of glucose production in hepatocytes incubated with lactate, pyruvate, propionate or fructose as substrates. In contrast, glucose synthesis with either alanine or glutamine was increased nearly 3- and 12-fold respectively, in comparison with that in fed rabbits. 2. The addition of amino-oxyacetate resulted in about a 50% decrease in glucose formation from lactate in hepatocytes isolated from fed, alloxan-diabetic and starved rats, suggesting that both mitochondrial and cytosolic forms of rabbit phosphoenolpyruvate carboxykinase function actively during gluconeogenesis. 3. Alloxan-diabetes resulted in about 2-3-fold stimulation of urea production from either amino acid studied or NH4Cl as NH3 donor, whereas starvation caused a significant increase in the rate of ureogenesis only in the presence of alanine as the source of NH3. 4. As concluded from changes in the [3-hydroxybutyrate]/[acetoacetate] ratio, in hepatocytes from diabetic animals the mitochondrial redox state was shifted toward oxidation in comparison with that observed in liver cells isolated from fed rabbits. PMID:743258

  3. Radiation-Associated Liver Injury

    SciTech Connect

    Pan, Charlie C., E-mail: cpan@umich.ed [Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI (United States); Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado, Aurora, CO (United States); Dawson, Laura A. [Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Li, X. Allen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Das, Shiva K. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Miften, Moyed [Department of Radiation Oncology, University of Colorado, Aurora, CO (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI (United States)

    2010-03-01

    The liver is a critically important organ that has numerous functions including the production of bile, metabolism of ingested nutrients, elimination of many waste products, glycogen storage, and plasma protein synthesis. The liver is often incidentally irradiated during radiation therapy (RT) for tumors in the upper- abdomen, right lower lung, distal esophagus, or during whole abdomen or whole body RT. This article describes the endpoints, time-course, and dose-volume effect of radiation on the liver.

  4. Liver Biopsy

    MedlinePLUS

    ... for a liver biopsy by talking with a health care provider having blood tests arranging for a ride home fasting before the ... for a liver biopsy by talking with a health care provider having blood tests arranging for a ride home fasting before the ...

  5. Bone marrow-derived mesenchymal stem cells inhibits hepatocyte apoptosis after acute liver injury

    PubMed Central

    Cai, Yijing; Zou, Zhuolin; Liu, Liyuan; Chen, Si; Chen, Yi; Lin, Zhuo; Shi, Keqing; Xu, Lanman; Chen, Yongping

    2015-01-01

    Objective: To investigate the protective effect of bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on acute liver injury (ALI) rats. Material and Methods: BMSCs were extracted from rat bone marrow, cultured and expansion in vitro, and identified by flow cytometer. Rat model with acute liver injury was established by employing D-galactosamine and Lipopolysaccharide. Male rats were randomly divided into ALI model group and BMSCs transplantation group. Rats were sacrificed 24 h, 72 h and 120 h after BMSCs injection to determine alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum. Proliferating cell nuclear antigen (PCNA) immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction (RT-PCR) of ?-fetoprotein (AFP) and glypican-3 (GPC3) were performed to analysis proliferation. Terminal deoxynucleontidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) assays were used to analyze apoptosis and mitochondria-dependent-pathway related factors Bax and Bcl-2 were examined by Western blot. Results: Compared with the ALI model group, the BMSCs transplantation group presented the lower levels of ALT, AST, decreased Bax proteins expression, and increased Bcl-2 expression. The mRNA levels of AFP and GPC3 and expression of PCNA were significantly higher in BMSCs transplantation group. Conclusions: BMSCs transplantation could significantly restore liver function. These effects were supposed to be mediated by suppressing hepatocyte apoptosis as well as promoting proliferation. Reduction of apoptosis seemed to correlate with mitochondria-dependent-pathway. PMID:25755697

  6. Tandem analysis of transcriptome and proteome changes after a single dose of corticosteroid: a systems approach to liver function in pharmacogenomics.

    PubMed

    Kamisoglu, Kubra; Sukumaran, Siddharth; Nouri-Nigjeh, Eslam; Tu, Chengjian; Li, Jun; Shen, Xiaomeng; Duan, Xiaotao; Qu, Jun; Almon, Richard R; DuBois, Debra C; Jusko, William J; Androulakis, Ioannis P

    2015-02-01

    Corticosteroids (CS) such as methylprednisolone (MPL) affect almost all liver functions through multiple mechanisms of action, and long-term use results in dysregulation causing diverse side effects. The complexity of involved molecular mechanisms necessitates a systems approach. Integration of information from the transcriptomic and proteomic responses has potential to provide deeper insights into CS actions. The present report describes the tandem analysis of rich time-series transcriptomic and proteomic data in rat liver after a single dose of MPL. Hierarchical clustering of the common genes represented in both mRNA and protein datasets displayed two dominant patterns. One of these patterns exhibited complementary mRNA and protein expression profiles indicating that MPL affected the regulation of these genes at the transcriptional level. Some of the classic pharmacodynamic markers for CS actions, including tyrosine aminotransferase (TAT), were among this group, together with genes encoding urea cycle enzymes and ribosomal proteins. The other pattern was rather unexpected. For this group of genes, MPL had distinctly observable effects at the protein expression level, although a change in the reverse direction occurred at the transcriptional level. These genes were functionally associated with metabolic processes that might be essential to elucidate side effects of MPL on liver, most importantly including modulation of oxidative stress, fatty acid oxidation, and bile acid biosynthesis. Furthermore, profiling of gene and protein expression data was also done independently of one another by a two-way sequential approach. Prominent temporal shifts in expression and relevant cellular functions were described together with the assessment of changes in the complementary side. PMID:25611119

  7. Hepatocellular integrity in swine after prolonged desflurane (I-653) and isoflurane anesthesia: evaluation of plasma alanine aminotransferase activity.

    PubMed

    Holmes, M A; Weiskopf, R B; Eger, E I; Johnson, B H; Rampil, I J

    1990-09-01

    Desflurane, formerly known as I-653 (CF2H-O-CFH-CF3), is a new inhalation anesthetic derived by fluorine substitution for the alpha-ethyl chlorine of isoflurane (CF2H-O-CClH-CF3). The lower solubility and increased stability of desflurane provided by the C-F bond lessen biotransformation to potentially hepatotoxic metabolites. Repeated administration of desflurane to rats, with or without induced hepatic enzymes, does not result in evidence of hepatic injury. In the recent study we extended the tests for liver cell injury to another species, the pig. Our test included prolonged exposure to desflurane or isoflurane, both in the absence and presence of commonly used adjuvants. We measured plasma alanine aminotransferase activity in eight young female swine anesthetized in random order with desflurane (0.8-1.6 MAC) and isoflurane (0.7-1.4 MAC), for a total dose of about 5.5 MAC-hours of each anesthetic, 3-8 days apart. Plasma alanine aminotransferase activities remained in the normal range, and were not significantly greater over baseline values in samples drawn immediately after, 4 h after, or 3-8 days after (mean +/- SD, 6.1 +/- 2.1) the administration of either anesthetic was discontinued after the first study with either desflurane or isoflurane. Five additional pigs were given a mean total dose of 9.7 MAC-hours of desflurane or isoflurane in conjunction with succinylcholine, N2O, fentanyl, naloxone, atracurium, thiopental, edrophonium, and atropine. No changes in plasma alanine aminotransferase activity were detected in blood samples drawn at termination of the anesthesia, 24 h later, and 4-7 days later (mean +/- SD, 5.8 +/- 1.3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2393108

  8. Elevation of HO-1 Expression Mitigates Intestinal Ischemia-Reperfusion Injury and Restores Tight Junction Function in a Rat Liver Transplantation Model

    PubMed Central

    Chi, Xinjin; Yao, Weifeng; Xia, Hua; Jin, Yi; Li, Xi; Cai, Jun; Hei, Ziqing

    2015-01-01

    Aims. This study was aimed at investigating whether elevation of heme oxygenase-1 (HO-1) expression could lead to restoring intestinal tight junction (TJ) function in a rat liver transplantation model. Methods. Intestinal mucosa injury was induced by orthotopic autologous liver transplantation (OALT) on male Sprague-Dawley rats. Hemin (a potent HO-1 activator) and zinc-protoporphyrin (ZnPP, a HO-1 competitive inhibitor), were separately administered in selected groups before OALT. The serum and intestinal mucosa samples were collected at 8 hours after the operation for analysis. Results. Hemin pretreatment significantly reduced the inflammation and oxidative stress in the mucosal tissue after OALT by elevating HO-1 protein expression, while ZnPP pretreatment aggravated the OALT mucosa injury. Meanwhile, the restriction on the expression of tight junction proteins zonula occludens-1 and occludin was removed after hemin pretreatment. These molecular events led to significant improvement on intestinal barrier function, which was proved to be through increasing nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and reducing nuclear translocation of nuclear factor kappa-B (NF-?B) in intestinal injured mucosa. Summary. Our study demonstrated that elevation of HO-1 expression reduced the OALT-induced intestinal mucosa injury and TJ dysfunction. The HO-1 protective function was likely mediated through its effects of anti-inflammation and antioxidative stress.

  9. A comparative integrated transcript analysis and functional characterization of differential mechanisms for induction of liver hypertrophy in the rat

    SciTech Connect

    Boitier, Eric, E-mail: eric.boitier@sanofi-aventis.com [sanofi aventis R and D, Disposition, Safety and Animal Research, Vitry sur Seine (France); Amberg, Alexander [sanofi aventis R and D, Disposition, Safety and Animal Research, Frankfurt (Germany); Barbie, Valerie [Merck Serono S.A., Stratified Medicine, Geneva (Switzerland); Blichenberg, Arne [Nycomed GmbH, Institute for Pharmacology and Preclinical Drug Safety, Barsbuettel (Germany); Brandenburg, Arnd; Gmuender, Hans [Genedata AG, Basel (Switzerland); Gruhler, Albrecht [Novo Nordisk A/S, Protein Science, Malov (Denmark); McCarthy, Diane [Bio-Rad Laboratories, Hercules, CA (United States); Meyer, Kirstin; Riefke, Bjoern; Raschke, Marian [Bayer Schering Pharma AG, Investigational Toxicology, Berlin (Germany); Schoonen, Willem [MSD, Toxicology and Drug Disposition, Oss (Netherlands); Sieber, Maximilian [Universitaet Wuerzburg, Institut fuer Toxikologie, Wuerzburg (Germany); Suter, Laura [Hoffmann-La Roche Ltd., Investigative Toxicology, Basel (Switzerland); Thomas, Craig E. [Eli Lilly and Company, Investigative Toxicology, Indianapolis, IN (United States); Sajot, Nicolas [Servier, Drug Safety Assessment, Orleans-Gidy (France)

    2011-04-15

    The main goal of the present work was to better understand the molecular mechanisms underlying liver hypertrophy (LH), a recurrent finding observed following acute or repeated drug administration to animals, using transcriptomic technologies together with the results from conventional toxicology methods. Administration of 5 terminated proprietary drug candidates from participating companies involved in the EU Innomed PredTox Project or the reference hepatotoxicant troglitazone to rats for up to a 14-day duration induced LH as the main liver phenotypic toxicity outcome. The integrated analysis of transcriptomic liver expression data across studies turned out to be the most informative approach for the generation of mechanistic models of LH. In response to a xenobiotic stimulus, a marked increase in the expression of xenobiotic metabolizing enzymes (XME) was observed in a subset of 4 studies. Accumulation of these newly-synthesized proteins within the smooth endoplasmic reticulum (SER) would suggest proliferation of this organelle, which most likely is the main molecular process underlying the LH observed in XME studies. In another subset of 2 studies (including troglitazone), a marked up-regulation of genes involved in peroxisomal fatty acid {beta}-oxidation was noted, associated with induction of genes involved in peroxisome proliferation. Therefore, an increase in peroxisome abundance would be the main mechanism underlying LH noted in this second study subset. Together, the use of transcript profiling provides a means to generate putative mechanistic models underlying the pathogenesis of liver hypertrophy, to distinguish between subtle variations in subcellular organelle proliferation and creates opportunities for improved mechanism-based risk assessment.

  10. Ov-APR-1, an aspartic protease from the carcinogenic liver fluke, Opisthorchis viverrini: Functional expression, immunolocalization and subsite specificity

    Microsoft Academic Search

    Sutas Suttiprapa; Jason Mulvenna; Ngo Thi Huong; Mark S. Pearson; Paul J. Brindley; Thewarach Laha; Sopit Wongkham; Sasithorn Kaewkes; Banchob Sripa; Alex Loukas

    2009-01-01

    The human liver fluke Opisthorchis viverrini is endemic in Thailand, Laos and Cambodia where long standing infection is associated with cancer of the bile ducts, cholangiocarcinoma. Here we describe a cathepsin D-like aspartic protease from the gut and other tissues in O. viverrini. Phylogenetic analysis indicated that Ov-APR-1 is cathepsin D-like, conforming with Clan AA, Family A1 of the MEROPS

  11. Comparative genomics and experimental promoter analysis reveal functional liver-specific elements in mammalian hepatic lipase genes

    Microsoft Academic Search

    Diederik van Deursen; Gert-Jan Botma; Hans Jansen; Adrie JM Verhoeven

    2007-01-01

    BACKGROUND: Mammalian hepatic lipase (HL) genes are transcribed almost exclusively in hepatocytes. The basis for this liver-restricted expression is not completely understood. We hypothesized that the responsible cis-acting elements are conserved among mammalian HL genes. To identify these elements, we made a genomic comparison of 30 kb of 5'-flanking region of the rat, mouse, rhesus monkey, and human HL genes.

  12. Structural and functional characterization of microcystin detoxification-related liver genes in a phytoplanktivorous fish, Nile tilapia ( Oreochromis niloticus)

    Microsoft Academic Search

    Lin Wang; Xu-Fang Liang; Wan-Qin Liao; La-Mei Lei; Bo-Ping Han

    2006-01-01

    Liver genes related to phase I and phase II detoxification, as well as inhibition of reactive oxygen species (ROS) production, were cloned, and their response to microcystin-LR (MC-LR) and lipopolysaccharide (LPS) exposure via intraperitoneal injection, was determined in a phytoplanktivorous fish, Nile tilapia (Oreochromis niloticus). The cloned full-length cDNA of tilapia soluble glutathione S-transferase (sGST) was classified as alpha-class GST

  13. An application of coupled reference interaction site model/molecular dynamics to the conformational analysis of the alanine dipeptide.

    PubMed

    Freedman, Holly; Truong, Thanh N

    2004-12-22

    We present an application of our recently proposed coupled reference interaction site model (RISM) molecular dynamics (MD) solvation free energy methodology [Freedman and Truong, Chem. Phys. Lett. 381, 362 (2003); J. Chem. Phys. 121, 2187 (2004)] to study the conformational stability of alanine dipeptide in aqueous solution. In this methodology, radial distribution functions obtained from a single MD simulation are substituted into a RISM expression for solvation free energy. Consequently, iterative solution of the RISM equation is not needed. The relative solvation free energies of seven different conformations of the alanine dipeptide in aqueous solution are calculated. Results from the coupled RISM/MD methodology are in good agreement with those from earlier simulations using the accurate free energy perturbation approach, showing that the alphaR conformation is most stabilized by solution. This study establishes a framework for applying this coupled RISM/MD method to larger biological systems. PMID:15606265

  14. Inelastic neutron scattering, Raman, vibrational analysis with anharmonic corrections, and scaled quantum mechanical force field for polycrystalline L-alanine

    NASA Astrophysics Data System (ADS)

    Williams, Robert W.; Schlücker, Sebastian; Hudson, Bruce S.

    2008-01-01

    A scaled quantum mechanical harmonic force field (SQMFF) corrected for anharmonicity is obtained for the 23 K L-alanine crystal structure using van der Waals corrected periodic boundary condition density functional theory (DFT) calculations with the PBE functional. Scale factors are obtained with comparisons to inelastic neutron scattering (INS), Raman, and FT-IR spectra of polycrystalline L-alanine at 15-23 K. Calculated frequencies for all 153 normal modes differ from observed frequencies with a standard deviation of 6 wavenumbers. Non-bonded external k = 0 lattice modes are included, but assignments to these modes are presently ambiguous. The extension of SQMFF methodology to lattice modes is new, as are the procedures used here for providing corrections for anharmonicity and van der Waals interactions in DFT calculations on crystals. First principles Born-Oppenheimer molecular dynamics (BOMD) calculations are performed on the L-alanine crystal structure at a series of classical temperatures ranging from 23 K to 600 K. Corrections for zero-point energy (ZPE) are estimated by finding the classical temperature that reproduces the mean square displacements (MSDs) measured from the diffraction data at 23 K. External k = 0 lattice motions are weakly coupled to bonded internal modes.

  15. Uptake and release of beta-alanine in cerebellar granule cells in primary culture: regulation of release by glutamatergic and GABAergic receptors.

    PubMed

    Saransaari, P; Oja, S S

    1993-03-01

    The uptake and release of beta-[3H]alanine were studied in cultured glutamatergic cerebellar granule cells of the rat. The uptake of beta-alanine was saturable and sodium-dependent, comprising one high-affinity transport component. It was inhibited by hypotaurine, taurine, GABA and homotaurine but not by glycine or glutamate. The release was enhanced by homoexchange, veratridine and high K+ concentrations (50 mM). The K(+)-stimulated release was at least partially Ca(2+)-dependent. The release was shown to be subject to regulation by GABAA receptors and glutamate receptors of the kainate type. The results signify that beta-alanine may have a functional role in cerebellar granule cells. PMID:8098513

  16. Tumour necrosis factor-? promotes liver ischaemia-reperfusion injury through the PGC-1?/Mfn2 pathway.

    PubMed

    Li, Jun; Ke, Wenbo; Zhou, Qi; Wu, Yongzhong; Luo, Hong; Zhou, Hong; Yang, Bin; Guo, Yu; Zheng, Qichang; Zhang, Yong

    2014-09-01

    Tumour necrosis factor (TNF)-? has been considered to induce ischaemia-reperfusion injury (IRI) of liver which is characterized by energy dysmetabolism. Peroxisome proliferator-activated receptor-? co-activator (PGC)-1? and mitofusion2 (Mfn2) are reported to be involved in the regulation of mitochondrial function. However, whether PGC-1? and Mfn2 form a pathway that mediates liver IRI, and if so, what the underlying involvement is in that pathway remain unclear. In this study, L02 cells administered recombinant human TNF-? had increased TNF-? levels and resulted in down-regulation of PGC-1? and Mfn2 in a rat liver IRI model. This was associated with hepatic mitochondrial swelling, decreased adenosine triphosphate (ATP) production, and increased levels of reactive oxygen species (ROS) and alanine aminotransferase (ALT) activity as well as cell apoptosis. Inhibition of TNF-? by neutralizing antibody reversed PGC-1? and Mfn2 expression, and decreased hepatic injury and cell apoptosis both in cell culture and in animals. Treatment by rosiglitazone sustained PGC-1? and Mfn2 expression both in IR livers, and L02 cells treated with TNF-? as indicated by increased hepatic mitochondrial integrity and ATP production, reduced ROS and ALT activity as well as decreased cell apoptosis. Overexpression of Mfn2 by lentiviral-Mfn2 transfection decreased hepatic injury in IR livers and L02 cells treated with TNF-?. However, there was no up-regulation of PGC-1?. These findings suggest that PGC-1? and Mfn2 constitute a regulatory pathway, and play a critical role in TNF-?-induced hepatic IRI. Inhibition of the TNF-? or PGC-1?/Mfn2 pathways may represent novel therapeutic interventions for hepatic IRI. PMID:24898700

  17. Tumour necrosis factor-? promotes liver ischaemia-reperfusion injury through the PGC-1?/Mfn2 pathway

    PubMed Central

    Li, Jun; Ke, Wenbo; Zhou, Qi; Wu, Yongzhong; Luo, Hong; Zhou, Hong; Yang, Bin; Guo, Yu; Zheng, Qichang; Zhang, Yong

    2014-01-01

    Tumour necrosis factor (TNF)-? has been considered to induce ischaemia-reperfusion injury (IRI) of liver which is characterized by energy dysmetabolism. Peroxisome proliferator–activated receptor-? co-activator (PGC)-1? and mitofusion2 (Mfn2) are reported to be involved in the regulation of mitochondrial function. However, whether PGC-1? and Mfn2 form a pathway that mediates liver IRI, and if so, what the underlying involvement is in that pathway remain unclear. In this study, L02 cells administered recombinant human TNF-? had increased TNF-? levels and resulted in down-regulation of PGC-1? and Mfn2 in a rat liver IRI model. This was associated with hepatic mitochondrial swelling, decreased adenosine triphosphate (ATP) production, and increased levels of reactive oxygen species (ROS) and alanine aminotransferase (ALT) activity as well as cell apoptosis. Inhibition of TNF-? by neutralizing antibody reversed PGC-1? and Mfn2 expression, and decreased hepatic injury and cell apoptosis both in cell culture and in animals. Treatment by rosiglitazone sustained PGC-1? and Mfn2 expression both in IR livers, and L02 cells treated with TNF-? as indicated by increased hepatic mitochondrial integrity and ATP production, reduced ROS and ALT activity as well as decreased cell apoptosis. Overexpression of Mfn2 by lentiviral-Mfn2 transfection decreased hepatic injury in IR livers and L02 cells treated with TNF-?. However, there was no up-regulation of PGC-1?. These findings suggest that PGC-1? and Mfn2 constitute a regulatory pathway, and play a critical role in TNF-?-induced hepatic IRI. Inhibition of the TNF-? or PGC-1?/Mfn2 pathways may represent novel therapeutic interventions for hepatic IRI. PMID:24898700

  18. Mapping the Energy of Superantigen Staphylococcus Enterotoxin C3 Recognition of an a \\/ b T Cell Receptor Using Alanine Scanning Mutagenesis

    Microsoft Academic Search

    Hywyn R. O. Churchill; Peter S. Andersen; Evan A. Parke; Roy A. Mariuzza; David M. Kranz

    Binding of the T cell receptor (TCR) to a bacterial superantigen (SAG) results in stimulation of a large population of T cells and subsequent inflammatory reactions. To define the functional contribution of TCR residues to SAG recognition, binding by 24 single-site alanine substitu- tions in the TCR V b domain to Staphylococcus aureus enterotoxin (SE) C3 was measured, pro- ducing

  19. Causes of Persistently Elevated Alanine Aminotransferase Levels in Patients who Presented to Two Referral Hospitals in Mashhad, Iran during 2011.

    PubMed

    Khorashad, Ahmad; Vossoughinia, Hassan; Saadatnia, Hassan; Esmaelzadeh, Abbas; Ahadi, Mitra; Farzanehfar, Mohammad Reza; Hosseini, Seyed Mossareza; Afzalaghaii, Monavvar; Amirmajdi, Elham; Barari, Linda; Saadatnia, Farzad

    2014-01-01

    BACKGROUND Worldwide, chronic liver disease is a major cause of morbidity and mortality. Causes of elevated serum alanine aminotransferase (ALT) levels vary depending on the population under study. The aim of this study is to evaluate the frequency and causes of persistently elevated ALT levels in patients of the Gastroenterology (GI) Clinics in Ghaem and Emam Reza Hospitals in Mashhad, Iran. METHODS A total of 100 consecutive patients with persistently elevated ALT levels that referred to the GI Clinics at Ghaem and Emam Reza Hospitals in 2011 were studied. Elevated levels were defined as ALT ?40 U/L at least twice within six months. A comprehensive history that included previous surgeries, transfusion, alcohol consumption and medications was obtained. Patients underwent physical examinations, laboratory analyses and ultrasonography studies. When necessary, liver biopsies were performed. RESULTS Patients' mean age was 44.4 ± 11.83 years. Females comprised 62% of cases. Patients presented with the following conditions: non-alcoholic fatty liver disease (NAFLD, 55%), hepatitis B (17%), autoimmune hepatitis (13%), hepatitis C (4%), autoimmune hepatitis and hepatitis C (2%), overlapping autoimmune disease (2%), Wilson disease (1%), celiac disease (1%), alcoholiche patitis (1%), primary biliary cirrhosis (PBC, 1%), primary sclerosing cholangitis (PSC, 1%), and cryptogenic (2%). CONCLUSION NAFLD was the most common cause of persistently elevated serum ALT levels in this study. PMID:24829700

  20. Causes of Persistently Elevated Alanine Aminotransferase Levels in Patients who Presented to Two Referral Hospitals in Mashhad, Iran during 2011

    PubMed Central

    Khorashad, Ahmad; Vossoughinia, Hassan; Saadatnia, Hassan; Esmaelzadeh, Abbas; Ahadi, Mitra; Farzanehfar, Mohammad Reza; Hosseini, Seyed Mossareza; Afzalaghaii, Monavvar; Amirmajdi, Elham; Barari, Linda; Saadatnia, Farzad

    2014-01-01

    BACKGROUND Worldwide, chronic liver disease is a major cause of morbidity and mortality. Causes of elevated serum alanine aminotransferase (ALT) levels vary depending on the population under study. The aim of this study is to evaluate the frequency and causes of persistently elevated ALT levels in patients of the Gastroenterology (GI) Clinics in Ghaem and Emam Reza Hospitals in Mashhad, Iran. METHODS A total of 100 consecutive patients with persistently elevated ALT levels that referred to the GI Clinics at Ghaem and Emam Reza Hospitals in 2011 were studied. Elevated levels were defined as ALT ?40 U/L at least twice within six months. A comprehensive history that included previous surgeries, transfusion, alcohol consumption and medications was obtained. Patients underwent physical examinations, laboratory analyses and ultrasonography studies. When necessary, liver biopsies were performed. RESULTS Patients’ mean age was 44.4 ± 11.83 years. Females comprised 62% of cases. Patients presented with the following conditions: non-alcoholic fatty liver disease (NAFLD, 55%), hepatitis B (17%), autoimmune hepatitis (13%), hepatitis C (4%), autoimmune hepatitis and hepatitis C (2%), overlapping autoimmune disease (2%), Wilson disease (1%), celiac disease (1%), alcoholiche patitis (1%), primary biliary cirrhosis (PBC, 1%), primary sclerosing cholangitis (PSC, 1%), and cryptogenic (2%). CONCLUSION NAFLD was the most common cause of persistently elevated serum ALT levels in this study. PMID:24829700

  1. PPAR{alpha} regulates the hepatotoxic biomarker alanine aminotransferase (ALT1) gene expression in human hepatocytes

    SciTech Connect

    Thulin, Petra [Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, S-171 76 Stockholm (Sweden); Rafter, Ingalill; Stockling, Kenneth [AstraZeneca, Safety Assessment, Molecular Toxicology, S-151 85 Soedertaelje (Sweden); Tomkiewicz, Celine [Universite Paris Descartes, UMR-S-747 INSERM, Paris F-75006 (France); Norjavaara, Ensio [AstraZeneca, Clinical Pharmacology, 431 83 Moelndal (Sweden); Aggerbeck, Martine [Universite Paris Descartes, UMR-S-747 INSERM, Paris F-75006 (France); Hellmold, Heike [AstraZeneca, Safety Assessment, Molecular Toxicology, S-151 85 Soedertaelje (Sweden); Ehrenborg, Ewa [Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, S-171 76 Stockholm (Sweden); Andersson, Ulf; Cotgreave, Ian [AstraZeneca, Safety Assessment, Molecular Toxicology, S-151 85 Soedertaelje (Sweden); Glinghammar, Bjoern [AstraZeneca, Safety Assessment, Molecular Toxicology, S-151 85 Soedertaelje (Sweden)], E-mail: Bjorn.Glinghammar@astrazeneca.com

    2008-08-15

    In this work, we investigated a potential mechanism behind the observation of increased aminotransferase levels in a phase I clinical trial using a lipid-lowering drug, the peroxisome proliferator-activated receptor (PPAR) {alpha} agonist, AZD4619. In healthy volunteers treated with AZD4619, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were elevated without an increase in other markers for liver injury. These increases in serum aminotransferases have previously been reported in some patients receiving another PPAR{alpha} agonist, fenofibrate. In subsequent in vitro studies, we observed increased expression of ALT1 protein and mRNA in human hepatocytes after treatment with fenofibric acid. The PPAR effect on ALT1 expression was shown to act through a direct transcriptional mechanism involving at least one PPAR response element (PPRE) in the proximal ALT1 promoter, while no effect of fenofibrate and AZD4619 was observed on the ALT2 promoter. Binding of PPARs to the PPRE located at - 574 bp from the transcriptional start site was confirmed on both synthetic oligonucleotides and DNA in hepatocytes. These data show that intracellular ALT expression is regulated by PPAR agonists and that this mechanism might contribute to increased ALT activity in serum.

  2. Serum Chemerin Concentrations Associate with Beta-Cell Function, but Not with Insulin Resistance in Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)

    PubMed Central

    Tsiavou, Anastasia; Teichert, Tom; Chounta, Athina; Nowotny, Peter; Pacini, Giovanni; Dimitriadis, George; Roden, Michael

    2015-01-01

    The novel adipokine chemerin has been related to insulin-resistant states such as obesity and non alcoholic fatty liver disease (NAFLD). However, its association with insulin resistance and beta cell function remains controversial. The main objective was to examine whether serum chemerin levels associate with insulin sensitivity and beta cell function independently of body mass index (BMI), by studying consecutive outpatients of the hepatology clinics of a European university hospital. Individuals (n=196) with NAFLD were stratified into persons with normal glucose tolerance (NGT; n=110), impaired glucose tolerance (IGT; n=51) and type 2 diabetes (T2D; n=35) and the association between serum chemerin and measures of insulin sensitivity and beta cell function as assessed during fasting and during oral glucose tolerance test (OGTT) was measured. Our results showed that serum chemerin positively associated with BMI (P=0.0007) and C peptide during OGTT (P<0.004), but not with circulating glucose, insulin, lipids or liver enzymes (all P>0.18). No BMI independent relationships of chemerin with fasting and OGTT derived measures of insulin sensitivity were found (P>0.5). Chemerin associated positively with fasting beta cell function as well as the OGTT derived insulinogenic index IGI_cp and the adaptation index after adjustment for age, sex and BMI (P=0.002-0.007), and inversely with the insulin/C peptide ratio (P=0.007). Serum chemerin neither related to the insulinogenic index IGI_ins nor the disposition index. In conclusion, circulating chemerin is likely linked to enhanced beta cell function but not to insulin sensitivity in patients with NAFLD. PMID:25933030

  3. Serum Chemerin Concentrations Associate with Beta-Cell Function, but Not with Insulin Resistance in Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD).

    PubMed

    Hatziagelaki, Erifili; Herder, Christian; Tsiavou, Anastasia; Teichert, Tom; Chounta, Athina; Nowotny, Peter; Pacini, Giovanni; Dimitriadis, George; Roden, Michael

    2015-01-01

    The novel adipokine chemerin has been related to insulin-resistant states such as obesity and non alcoholic fatty liver disease (NAFLD). However, its association with insulin resistance and beta cell function remains controversial. The main objective was to examine whether serum chemerin levels associate with insulin sensitivity and beta cell function independently of body mass index (BMI), by studying consecutive outpatients of the hepatology clinics of a European university hospital. Individuals (n=196) with NAFLD were stratified into persons with normal glucose tolerance (NGT; n=110), impaired glucose tolerance (IGT; n=51) and type 2 diabetes (T2D; n=35) and the association between serum chemerin and measures of insulin sensitivity and beta cell function as assessed during fasting and during oral glucose tolerance test (OGTT) was measured. Our results showed that serum chemerin positively associated with BMI (P=0.0007) and C peptide during OGTT (P<0.004), but not with circulating glucose, insulin, lipids or liver enzymes (all P>0.18). No BMI independent relationships of chemerin with fasting and OGTT derived measures of insulin sensitivity were found (P>0.5). Chemerin associated positively with fasting beta cell function as well as the OGTT derived insulinogenic index IGI_cp and the adaptation index after adjustment for age, sex and BMI (P=0.002-0.007), and inversely with the insulin/C peptide ratio (P=0.007). Serum chemerin neither related to the insulinogenic index IGI_ins nor the disposition index. In conclusion, circulating chemerin is likely linked to enhanced beta cell function but not to insulin sensitivity in patients with NAFLD. PMID:25933030

  4. Effects of Ergot Alkaloids on Liver Function of Piglets as Evaluated by the 13C-Methacetin and 13C-?-Ketoisocaproic Acid Breath Test

    PubMed Central

    Dänicke, Sven; Diers, Sonja

    2013-01-01

    Ergot alkaloids (the sum of individual ergot alkaloids are termed as total alkaloids, TA) are produced by the fungus Claviceps purpurea, which infests cereal grains commonly used as feedstuffs. Ergot alkaloids potentially modulate microsomal and mitochondrial hepatic enzymes. Thus, the aim of the present experiment was to assess their effects on microsomal and mitochondrial liver function using the 13C-Methacetin (MC) and 13C-?-ketoisocaproic acid (KICA) breath test, respectively. Two ergot batches were mixed into piglet diets, resulting in 11 and 22 mg (Ergot 5-low and Ergot 5-high), 9 and 14 mg TA/kg (Ergot 15-low and Ergot 15-high) and compared to an ergot-free control group. Feed intake and live weight gain decreased significantly with the TA content (p < 0.001). Feeding the Ergot 5-high diet tended to decrease the 60-min-cumulative 13CO2 percentage of the dose recovery (cPDR60) by 26% and 28% in the MC and KICA breath test, respectively, compared to the control group (p = 0.065). Therefore, both microsomal and mitochondrial liver function was slightly affected by ergot alkaloids. PMID:23322130

  5. D-Galactosamine Intoxication in Experimental Animals: Is it Only an Experimental Model of Acute Liver Failure?

    PubMed Central

    Saracyn, Marek; Zdanowski, Robert; Brytan, Marek; Kade, Grzegorz; Nowak, Zbigniew; Patera, Janusz; Dyrla, Przemys?aw; Gil, Jerzy; Wa?kowicz, Zofia

    2015-01-01

    Background Short-term administration of Galactosamine to experimental animals causes liver damage and acute liver failure (ALF), as well as acute renal failure in some cases. The aim of our study was to describe kidney disorders that developed in the course of galactosamine-induced liver failure. Material/Methods Sprague-Dawley rats were randomly divided into 2 groups: a study group administered galactosamine intraperitoneally and a control group administered saline. Results All the animals in the study group developed liver damage and failure within 48 h, with significant increase of alanine (p<0.001), aspartate aminotransferases (p<0.0001), bilirubin (p<0.004), and ammonia (p<0.005) and decrease of albumin (p<0.001) concentrations. Acute renal failure was observed in all test animals, with a significant increase in creatinine (p<0.001) and urea (p<0.001) concentrations and a decrease in creatinine clearance (p<0.0012). Moreover, osmotic clearance (p<0.001), daily natriuresis (p<0.003), and fractional sodium excretion (p<0.016) decreased significantly in this group of animals. The ratio of urine osmolality to serum osmolality did not change. Histopathology of the liver revealed massive necrosis of hepatocytes, whereas renal histopathology showed no changes. Conclusions Acute renal failure that developed in the course of galactosamine-induced ALF was of a functional nature, with the kidneys retaining the ability to concentrate urine and retain sodium, and there were no renal changes in the histopathological examination. It seems that the experimental model of ALF induced by galactosamine can be viewed as a model of hepatorenal syndrome that occurs in the course of acute damage and liver failure. PMID:26009004

  6. Hydrogen gas inhalation protects against liver ischemia/reperfusion injury by activating the NF-?B signaling pathway

    PubMed Central

    ZHANG, CHAO-BIN; TANG, YI-CHEN; XU, XUE-JUN; GUO, SHI-XIANG; WANG, HUAI-ZHI

    2015-01-01

    Hydrogen has been demonstrated to function as a novel antioxidant and exert therapeutic antioxidant activity in a number of diseases. The present study was designed to investigate the effect of hydrogen inhalation on liver ischemia/reperfusion (I/R) injury in rats. The portal triad to the left lobe and the left middle lobe of the liver were completely occluded for 90 min. This was followed by reperfusion for 180 min. The rats subsequently underwent syngeneic orthotopic liver transplantation. Inhalation of various concentrations (1, 2 and 3%) of hydrogen gas and its administration for different durations (1, 3 and 6 h) immediately prior to the I/R injury allowed the optimal dose and duration of administration to be determined. Liver injury was evaluated through biochemical and histopathological examinations. The expression levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-? and interleukin (IL)-6, were measured by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction (qPCR). Liver nuclear factor ?B (NF-?B) was detected by qPCR and western blot analysis. Inhalation of hydrogen gas at 2% concentration for 1 h significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, the expression of cytokines, including IL-6, TNF-?, early growth response protein 1 (Egr-1) and IL-1?, and morphological damage. In addition, the mRNA and protein expression levels of NF-?B, heme oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2) and zinc finger protein A20 (A20) in rats where only the donors received hydrogen were significantly increased compared with those in rats where both the donor and recipient, or only the recipient received hydrogen. The results indicate that hydrogen inhalation at 2% concentration for 1 h prior to liver transplantation protected the rats from ischemia/reperfusion injury by activation of the NF-?B signaling pathway.

  7. Liver tumors.

    PubMed

    Stringer, M D

    2000-11-01

    Liver tumors in children are rare, potentially complex, and encompass a broad spectrum of disease processes. Any age group may be affected, including the fetus. Most present with abdominal distension and/or a mass. Accurate preoperative diagnosis is usually possible using a combination of ultrasound scanning and cross-sectional imaging techniques (CT and/or MR), supplemented by liver biopsy and measurement of tumor markers. The most common benign tumors are hemangiomas, but mesenchymal hamartoma, focal nodular hyperplasia, and adenoma also are found. In Western countries, hepatoblastoma is the most common primary malignant liver tumor; disease-free survival is now possible in more than 80% of affected patients because of advances in combination chemotherapy, improved techniques of surgical resection, and the selective use of liver transplantation. In contrast, there has been less progress in the management of hepatocellular cancer, which still poses many therapeutic challenges. PMID:11112837

  8. Metabolism of 18S rRNA in rat liver cells in different functional states of protein-synthesizing apparatus

    SciTech Connect

    Chirkov, G.P.; Druzhinina, M.K.; Todorov, I.N.

    1986-04-10

    The ratio of the absolute radioactivities of 28S and 18S RNAs in the fractions of membrane-bound and free polysomes and the fraction of free rat liver ribosomes was studied under conditions of inhibition of translation by cycloheximide, insulin, and cAMP. It was found that insulin and cAMP, in contrast to cycloheximide, do not induce selective degradation of 18S rRNA. The results are discussed from the standpoint of the possible role of the phosphorylation of protein S6 in the degradation of the 40S ribosomal subunit.

  9. Hepatoprotective Activity of Licorice in Rat Liver Injury Models

    Microsoft Academic Search

    A. A. Al-Qarawi; H. A. Abdel-Rahman; S. A. El-Mougy

    2001-01-01

    The hepatoprolective activity of a water extract of Glycyrrhiza glabra L. was studied against CCI4 induced, acute hepatotoxicity in rats. Liver damage was assessed by estimating serum enzyme activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, albumin, globulin, and A\\/G ratio. Pre- and post-treatment with licorice extract showed a dose-dependent reduction of CCI4-induced elevated serum levels of enzyme

  10. Liver Enzymes and Ultrastructure in Rabbit Haemorrhagic Disease (RHD)

    Microsoft Academic Search

    P. G. Ferreira; A. Costa-e-Silva; E. Monteiro; M. J. R. Oliveira; A. P. Águas

    2006-01-01

    Rabbit haemorrhagic disease (RHD) is caused by a calicivirus infection that kills most adult rabbits 24–72 h after viral inoculation.\\u000a Two liver enzymes (AST, aspartate aminotransferase, and ALT, alanine aminotransferase) were monitored in blood samples of\\u000a calicivirus-infected rabbits during the short course of RHD. Values of AST were used to differentiate three stages of hepatocellular\\u000a degeneration in RHD: mild (up

  11. Liver tumors

    Microsoft Academic Search

    Mark D. Stringer

    2000-01-01

    Liver tumors in children are rare, potentially complex, and encompass a broad spectrum of disease processes. Any age group may be affected, including the fetus. Most present with abdominal distension and\\/or a mass. Accurate preoperative diagnosis is usually possible using a combination of ultrasound scanning and cross-sectional imaging techniques (CT and\\/or MR), supplemented by liver biopsy and measurement of tumor

  12. Protective Effect of Ternatin, a Flavonoid Isolated from Egletes viscosa less.,in Experimental Liver Injury

    Microsoft Academic Search

    V. S. N. Rao; E. G. Figueiredo; C. L. Melo; G. S. B. Viana; D. B. Menezes; M. S. F. Matos; E. R. Silveira

    1994-01-01

    The effect of ternatin, a tetramethoxyflavone from Egletes viscosa Less., on liver injury induced by carbon tetrachloride (CCI4) was investigated in rats. Twenty-four hours following CCI4 insult (2.5 ml\\/kg s.c), changes in the serum enzymes, alanine aminotransferase, aspartate aminotransferase and ?-glutamyltransferase, as well as liver cell histology were used as indices of hepatic dysfunction. The results show that ternatin (30

  13. Should liver transplantation be performed before advanced renal insufficiency in primary hyperoxaluria type 1?

    Microsoft Academic Search

    Pierre Cochatl; Karl Schiirer

    1993-01-01

    Primary hyperoxaluria type 1 (PH1) is a rare recessive autosomal inborn error of glyoxylate metabolism leading to oxalate retention, the first target of which is the kidney. The disease is caused by a defect of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase. Patients with pyridoxine-resistant forms of PH1 usually require organ replacement therapy, i.e. liver transplantation to supply the deficient

  14. Biosynthesis of phenylalanine, tyrosine, 3-(3-carbocyphenyl) alanine and 3-(3-carbocy-4-hydroxyphenyl) alanine in higher plants. Examples of the transformation possibilities for chorismic acid.

    PubMed

    Larsen, P O; Onderka, D K; Floss, H G

    1975-02-13

    14C-labelled shikimic acid and double labelled shikimic acid tritiated stereospicifically at C-6 are incorporated into 3-(3-carboxyphenyl) alanine, 3-(3-carboxy-4-hydroxyphenyl) alanine, phenylalanine, and tyrosine in Reseda lutea L., Reseda odorata L., Iris x Hollandica cv. Prof. Blauw, and Iris x hollandica cv. Wedgwood. The experiments with 14C-labelled shikimic acid confirm that the aromatic carboxyl groups and rings in 3-(3-carboxyphenyl) alanine and 3-(3-carbocy-4-hydroxyphenyl) alanine derive from the carbocyl group and ring in shikimic acid whereas the experiments with double labelled shikimic acid demonstrate that the pro-6S-hydrogen atom is retained and the pro-6R-hydrogen atom lost in the biosynthesis of 3-(3-carboxyphenyl) alanine, phenylalanine, and tyrosine in the plants used. 3H was located in the ortho-position in the aromatic rings of phenylalanine and tyrosine but in a position para to the alanine side chain of 3- (3-carboxyphenly) alanine. No 3H was found in 3- (3-carboxy-4-hydroxyphenyl) alanine. This supports a derivation of the last two compounds from chorismic acid via isochorismic acid, isoprephenic acid, and 3'-carboxyphenylpyruvic acid and 3'-carbocy-4'-hydroxyphenylphruvic acid. The 3H/14C ratio in 3-(3-carboxyphenyl) alanine was found higher than in the precursor used. This isotope effect must operate by competition between the pathways from isoprephenic acid to 3'-carbocyphenylpyruvic acid and to 3'-carbocy-4'- hydroxyphenylpyruvic acic. The proposed biosynthetic pathways for the two carboxy-substituted amino acids are in agreement with their distribution patterns in the plant kingdom and suggest that they may derive from minor changes of enzymes involved in the general pathways of aromatic biosynthesis. PMID:1120151

  15. Alanine Esters of Enterococcal Lipoteichoic Acid Play a Role in Biofilm Formation and Resistance to Antimicrobial Peptides

    PubMed Central

    Fabretti, Francesca; Theilacker, Christian; Baldassarri, Lucilla; Kaczynski, Zbigniew; Kropec, Andrea; Holst, Otto; Huebner, Johannes

    2006-01-01

    Enterococcus faecalis is among the predominant causes of nosocomial infections. Surface molecules like d-alanine lipoteichoic acid (LTA) perform several functions in gram-positive bacteria, such as maintenance of cationic homeostasis and modulation of autolytic activities. The aim of the present study was to evaluate the effect of d-alanine esters of teichoic acids on biofilm production and adhesion, autolysis, antimicrobial peptide sensitivity, and opsonic killing. A deletion mutant of the dltA gene was created in a clinical E. faecalis isolate. The absence of d-alanine in the LTA of the dltA deletion mutant was confirmed by nuclear magnetic resonance spectroscopy. The wild-type strain and the deletion mutant did not show any significant differences in growth curve, morphology, or autolysis. However, the mutant produced significantly less biofilm when grown in the presence of 1% glucose (51.1% compared to that of the wild type); adhesion to eukaryotic cells was diminished. The mutant absorbed 71.1% of the opsonic antibodies, while absorption with the wild type resulted in a 93.2% reduction in killing. Sensitivity to several cationic antimicrobial peptides (polymyxin B, colistin, and nisin) was considerably increased in the mutant strain, confirming similar results from other studies of gram-positive bacteria. Our data suggest that the absence of d-alanine in LTA plays a role in environmental interactions, probably by modulating the net negative charge of the bacterial cell surface, and therefore it may be involved in the pathogenesis of this organism. PMID:16790791

  16. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values

    Microsoft Academic Search

    Pouneh Mofrad; Melissa J. Contos; Mahmadul Haque; Carol Sargeant; Robert A. Fisher; Velimir A. Luketic; Richard K. Sterling; Mitchell L. Shiffman; Richard T. Stravitz; Arun J. Sanyal

    2003-01-01

    A retrospective study was performed to (1) characterize the clinical and histologic features of those with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) values, (2) compare the spectrum of NAFLD associated with normal versus elevated ALT levels, and (3) determine whether there were differences in the clinical or histologic spectrum of NAFLD between those with a low

  17. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    SciTech Connect

    Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus) [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)] [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States)] [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus)] [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ? After 30-day chronic CCl{sub 4} intoxication mitochondria displayed considerable changes. ? The functional parameters of mitochondria were similar to the control values. ? Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ? The above complex enhanced regenerative processes in the liver.

  18. Bone mesenchymal stem cell transplantation via four routes for the treatment of acute liver failure in rats

    PubMed Central

    SUN, LIHUA; FAN, XIAOTANG; ZHANG, LIJUAN; SHI, GUIXIU; AILI, MAIMAITI; LU, XIAOBO; JIANG, TAO; ZHANG, YUEXIN

    2014-01-01

    In the present study, we assessed the efficiency of four BMSC transplantation methods as a therapy for liver failure. A rat model (80 Sprague-Dawley rats) of D-galactosamine (D-gal)/lipopolysaccharide (LPS)-induced acute liver failure (ALF) was established and the rats were divided into 5 groups: a hepatic artery injection group, a portal vein injection group, a vena caudalis injection group, an intraperitoneal injection group and a control group (16 per group). Following transplantation, the liver tissue and blood samples were collected on days 1, 3 and 7, we detected the EdU (5-ethynyl-2?-deoxyuridine)-labeled cells homing to the liver tissue and assessed the proliferating cell nuclear antigen (PCNA) and cysteine-containing aspartate-specific protease (caspase)-3 expression in the liver tissue and detected the levels of stromal cell-derived factor 1 (SDF-1) and hepatocyte growth factor (HGF) in the liver tissues. Compared with the control group, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and damage to the liver tissue in the hepatic artery group, the portal vein group and the vena caudalis group improved in vivo. The expression of PCNA and HGF in the liver was higher and caspase-3 expression was lower in the hepatic artery injection group, the portal vein injection group and the vena caudalis injection group than that in the intraperitoneal injection and control groups. The EdU-labeled BMSCs were only observed homing to the liver tissue in these three groups. However, no significant differences were observed between these three groups. Liver function in the rats with ALF was improved following BMSC transplantation via 3 endovascular implantation methods (through the hepatic artery, portal vein and vena caudalis). These 3 methods were effective in transplanting BMSCs for the treatment of ALF. However, the selection of blood vessel in the implantation pathway does not affect the transplantation outcome. Transplantation via intraperitoneal injection showed no therapeutic effect in our animal experiments. PMID:25110277

  19. Sodium-alanine cotransport in renal proximal tubule cells investigated by whole-cell current recording

    PubMed Central

    1991-01-01

    Sodium-alanine cotransport was investigated in single isolated proximal tubule cells from rabbit kidney with the whole-cell current recording technique. Addition of L-alanine at the extracellular side induced an inward-directed sodium current and a cell depolarization. The sodium- alanine cotransport current was stereospecific and sodium dependent. Competition experiments suggested a common cotransport system for L- alanine and L-phenylalanine. Sodium-alanine cotransport current followed simple Michaelis-Menten kinetics, with an apparent Km of 6.6 mM alanine and 11.6 mM sodium and a maximal cotransport current of 0.98 pA/pF at -60 mV clamp potential. Hill plots of cotransport current suggested a potential-independent coupling ratio of one sodium and one alanine. The apparent Km for sodium and the maximal cotransport current were potential dependent, whereas the apparent Km for L-alanine was not affected by transmembrane potential. The increase in Km for alanine with decreasing inward-directed sodium gradients suggested a simultaneous transport mechanism. These results are consistent with a cotransport model with potential-dependent binding or unbinding of sodium (high-field access channel) and a potential-dependent translocation step. PMID:1650810

  20. Use of alanine-silicone pellets for electron paramagnetic resonance gamma dosimetry

    SciTech Connect

    Flores, J.; Galindo, S. (Instituto Nacional de Investigaciones Nucleares (Mexico))

    1991-03-01

    Silicone is proposed as an alternative binding substance in the production of D-L alanine pellets used in electron paramagnetic resonance (EPR) dosimetry of gamma rays. The dosimeters are manufactured at room temperature, making the production simple. Examination by EPR silicone-alanine pellets irradiated with 60Co gamma rays in the dose range 10 to 10(6) Gy shows that the proposed silicone binder does not affect typical alanine dose-response curves. Thermal stability of the pellets below 40 degrees C is good, but their pre-dose EPR signal amplitude is slightly higher than for nonirradiated alanine.

  1. Presinusoidal and proximal intrasinusoidal confluence of hepatic artery and portal vein in rat liver: functional evidence by orthograde and retrograde bivascular perfusion.

    PubMed

    Watanabe, Y; Püschel, G P; Gardemann, A; Jungermann, K

    1994-05-01

    The site of confluence of the artery and the portal vein in the liver still appears to be controversial. Anatomical studies suggested a presinusoidal or an intrasinusoidal confluence in the first, second or even final third of the sinusoids. The objective of this investigation was to study the problem with functional biochemical techniques. Rat livers were perfused through the hepatic artery and simultaneously either in the orthograde direction from the portal vein to the hepatic vein or in the retrograde direction from the hepatic vein to the portal vein. Arterial flow was linearly dependent on arterial pressure between 70 cm H2O and 120 cm H2O at a constant portal or hepatovenous pressure of 18 cm H2O. An arterial pressure of 100 cm H2O was required for the maintenance of a homogeneous orthograde perfusion of the whole parenchyma and of a physiologic ratio of arterial to portal flow of about 1:3. Glucagon was infused either through the artery or the portal vein and hepatic vein, respectively, to a submaximally effective "calculated" sinusoidal concentration after mixing of 0.1 nmol/L. During orthograde perfusions, arterial and portal glucagon caused the same increases in glucose output. Yet during retrograde perfusions, hepatovenous glucagon elicited metabolic alterations equal to those in orthograde perfusions, whereas arterial glucagon effected changes strongly reduced to between 10% and 50%. Arterially infused trypan blue was distributed homogeneously in the parenchyma during orthograde perfusions, whereas it reached clearly smaller areas of parenchyma during retrograde perfusions. Finally, arterially applied acridine orange was taken up by all periportal hepatocytes in the proximal half of the acinus during orthograde perfusions but only by a much smaller portion of periportal cells in the proximal third of the acinus during retrograde perfusions. These findings suggest that in rat liver, the hepatic artery and the portal vein mix before and within the first third of the sinusoids, rather than in the middle or even last third. PMID:8175142

  2. Solvation Effect on the Conformations of Alanine Dipeptide: Integral Equation Approach

    PubMed Central

    2010-01-01

    We present an implicit solvent model based on the extended reference interaction site model (XRISM) integral equation theory, which is a molecular theory of solvation. The solvation free energy is composed of additive potentials of mean force (PMF) of various functional groups. The XRISM theory is applied to determine the PMF of each group in water and NaBr electrolyte solutions. The method has been coupled to Brownian dynamics (BD) and is illustrated here on alanine dipeptide. The results of the method are compared with those obtained by explicit water simulations and other popular implicit solvent models for detailed discussion. The comparison of our model with other methods indicates that the intramolecular correlation and the solvation structure influence the stability of the PII and ?R conformers. The results of NaBr electrolyte solutions show that the concentration of electrolyte also has a substantial effect on the favored conformations. PMID:20694049

  3. Neuropilins and liver

    PubMed Central

    Elpek, Gülsüm Özlem

    2015-01-01

    Neuropilins (NRPs) are highly conserved transmembrane glycoproteins that possess pleiotropic functions. Neuropilin-1 (NRP1) and its homologue neuropilin-2 interact as coreceptors with both class 3 semaphorins and vascular endothelial growth factor and are involved in neuronal guidance and angiogenesis, respectively. The contribution of NRPs to tumor angiogenesis has been highlighted in previous studies, leading to the development of NRP antagonists as novel anti-angiogenesis therapies. However, more recent studies have demonstrated that NRPs have a much broader spectrum of activity in the integration of different pathways in physiological and pathological conditions. A few studies investigated the role of NRPs in both malignant and non-neoplastic liver diseases. In normal liver, NRP1 is expressed in hepatic stellate cells and liver sinusoidal endothelial cells. NRP1 expression in hepatocytes has been associated with malignant transformation and may play an important role in tumor behavior. A contribution of NRPs in sinusoidal remodeling during liver regeneration has been also noted. Studies in chronic liver diseases have indicated that, besides its influence on angiogenesis, NRP1 might contribute to the progression of liver fibrosis owing to its effects on other growth factors, including transforming growth factor ?1. As a result, NRP1 has been identified as a promising therapeutic target for future antifibrotic therapies based on the simultaneous blockade of multiple growth factor signaling pathways. In this review, the structure of NRPs and their interactions with various ligands and associated cell surface receptors are described briefly. The current understanding of the roles of the NRPs in liver diseases including tumors, regeneration and fibrogenesis, are also summarized. PMID:26109793

  4. STRUCTURAL AND FUNCTIONAL INTERACTION OF FATTY ACIDS WITH HUMAN LIVER FATTY ACID BINDING PROTEIN (L-FABP) T94A VARIANT

    PubMed Central

    Huang, Huan; McIntosh, Avery L.; Martin, Gregory G.; Landrock, Kerstin K.; Landrock, Danilo; Gupta, Shipra; Atshaves, Barbara P.; Kier, Ann B.; Schroeder, Friedhelm

    2014-01-01

    The human liver fatty acid binding protein (L-FABP) T94A variant, the most common in the FABP family, has been associated with elevated liver triglyceride (TG) levels. How this amino acid substitution elicits these effects is not known. This issue was addressed with human recombinant wild-type (WT, T94T) and T94A variant L-FABP proteins as well as cultured primary human hepatocytes expressing the respective proteins (genotyped as TT, TC, and CC). T94A substitution did not or only slightly alter L-FABP binding affinities for saturated, monounsaturated, or polyunsaturated long chain fatty acids (LCFA), nor did it change the affinity for intermediates in TG synthesis. Nevertheless, T94A substitution markedly altered the secondary structural response of L-FABP induced by binding LCFA or intermediates of TG synthesis. Finally, T94A substitution markedly diminished polyunsaturated fatty acid, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), induction of peroxisome proliferator-activated receptor alpha (PPAR?) - regulated proteins such as L-FABP, fatty acid transport protein 5 (FATP5), and PPAR? itself in cultured primary human hepatocytes. Thus, while T94A substitution did not alter the affinity of human L-FABP for LCFAs, it significantly altered human L-FABP structure and stability as well as conformational and functional response to these ligands. PMID:24628888

  5. Serum-free, long-term cultures of human hepatocytes: maintenance of cell morphology, transcription factors, and liver-specific functions.

    PubMed

    Runge, D; Runge, D M; Jäger, D; Lubecki, K A; Beer Stolz, D; Karathanasis, S; Kietzmann, T; Strom, S C; Jungermann, K; Fleig, W E; Michalopoulos, G K

    2000-03-01

    Since human hepatocytes are available only in limited number, the development of a serum-free culture system for long-term cultivation of differentiated and functional hepatocytes is of great importance. Here we describe the culture of human hepatocytes in a chemically defined serum-free medium for up to 5 weeks. Cell morphology was assayed by light and electron microscopy and revealed a well-preserved cellular morphology. Marker proteins for epithelial and bile duct cells, cytokeratin (CK) 18 and 19, and liver-specific proteins, like phosphoenolpyruvate carboxykinase-2 (PCK2) and serum proteins, were expressed. Liver-enriched transcription factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and hepatocyte nuclear factor-4 (HNF-4), cytokine and mitogen activated factors (nuclear factor kappa B) NFkappaB, and activator protein-1 (AP-1) were maintained and active for several weeks in our cultures. In summary, our serum-free culture system allows the culture of differentiated human hepatocytes for several weeks. It may serve as a model system for metabolic, pharmacologic-toxicologic studies, and studies on human pathogens under defined chemical conditions. PMID:10694475

  6. Bone marrow-derived mesenchymal stem cells attenuate acute liver injury and regulate the expression of fibrinogen-like-protein 1 and signal transducer and activator of transcription 3.

    PubMed

    Zou, Zhuolin; Cai, Yijing; Chen, Yi; Chen, Si; Liu, Liyuan; Shen, Zhonghai; Zhang, Sainan; Xu, Lanman; Chen, Yongping

    2015-08-01

    In recent years, bone marrow-derived mesenchymal stem cells (BMSCs) have been demonstrated to exert extensive therapeutic effects on acute liver injury; however, the underlying mechanisms of these effects have remained to be elucidated. The present study focused on the potential anti?apoptotic and pro?regenerative effects of BMSCs in D?galactosamine (D?Gal) and lipopolysaccharide (LPS)?induced acute liver injury in rats. An experimental rat acute liver injury model was established by intraperitoneal injection of D?Gal (400 mg/kg) and LPS (80 µg/kg). BMSCs and an identical volume of saline were administered via the caudal vein 2 h after the D?Gal and LPS challenge. Subsequently, the serum samples were collected to detect the levels of alanine aminotransferase and aspartate aminotransferase. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase?mediated nick?end labeling assay and immunohistochemical staining were performed to determine apoptosis, regeneration and histological changes of liver sections. Western blotting and reverse transcription?quantitative polymerase chain reaction were performed to detect the protein and mRNA expression levels of fibrinogen?like?protein 1 (FGL1), phosphorylated signal transducer and activator of transcription 3 (p?STAT3), STAT3 and B?cell lymphoma 2 (Bcl?2) and Bcl?2 associated X protein (Bax) in liver tissue samples. The results indicated that intravenous transplantation of BMSCs significantly decreased the levels of alanine aminotransferase and aspartate aminotransferase, and reduced hepatocellular necrosis and inflammatory cell infiltration. Additionally, a terminal deoxynucleotidyl transferase?mediated nick?end labeling assay and immunohistochemical staining revealed that BMSC treatment reduced hepatocyte apoptosis and enhanced liver regeneration. Furthermore, Bcl?2 expression was increased, whilst the protein expression of Bax was reduced. The expression of FGL1 and p?STAT3 were elevated concurrently with the improvement of liver function. These results demonstrated that BMSCs may provide a promising potential agent for the prevention of acute liver injury via inhibition of hepatocyte apoptosis and acceleration of liver regeneration. The mechanism may be, a least in part, a consequence of the upregulation of FGL1 expression and the induction of STAT3 phosphorylation. PMID:25901902

  7. Thermochemical study of complexation and solvation in ?-alanine-Cu(NO 3 ) 2 -water-ethanol system: 1. Enthalpy characteristics of complexing copper(II) Ion with ?-alanine

    Microsoft Academic Search

    V. N. Vandyshev; S. F. Ledenkov

    2011-01-01

    The heats of the reaction between copper(II) nitrate and sodium alaninate and the heats of dilution of Cu(NO3)2 solution in aqueous ethanol have been measured at 298 K using calorimetry. The standard molar enthalpies of the reaction\\u000a of copper(II) complexing with alaninate ion in solvents of various compositions have been calculated. The complexing process\\u000a in ethanol is more exothermic than

  8. Removal of l -alanine from the production of l -2-aminobutyric acid by introduction of alanine racemase and d -amino acid oxidase

    Microsoft Academic Search

    Li Zhu; Rongsheng Tao; Yi Wang; Yu Jiang; Xin Lin; Yunliu Yang; Huabao Zheng; Weihong Jiang; Sheng Yang

    2011-01-01

    l-2-Aminobutyric acid can be synthesized in a transamination reaction from l-threonine and l-aspartic acid as substrates by the action of threonine deaminase and aromatic aminotransferase, but the by-product l-alanine was produced simultaneously. A small amount of l-alanine increased the complexity of the l-2-aminobutyric acid recovery process because of their extreme similarity in physical and chemical properties. Acetolactate\\u000a synthase has been

  9. A Secreted Form of the Asialoglycoprotein Receptor, sH2a, as a Novel Potential Noninvasive Marker for Liver Fibrosis

    PubMed Central

    Lurie, Yoav; Ron, Efrat; Santo, Moshe; Reif, Shimon; Elashvili, Irma; Bar, Lana; Lederkremer, Gerardo Z.

    2011-01-01

    Background and Aim The human asialoglycoprotein receptor is a membrane heterooligomer expressed exclusively in hepatocytes. A soluble secreted form, sH2a, arises, not by shedding at the cell surface, but by intracellular cleavage of its membrane-bound precursor, which is encoded by an alternatively spliced form of the receptor H2 subunit. Here we determined and report that sH2a, present at constant levels in serum from healthy individuals is altered upon liver fibrosis, reflecting the status of hepatocyte function. Methods We measured sH2a levels in serum using a monoclonal antibody and an ELISA assay that we developed, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of 44 hepatitis C patients, which had METAVIR-scored biopsies, with 28 healthy individuals. Results sH2a levels varied minimally for the healthy individuals (150±21 ng/ml), whereas the levels deviated from this normal range increasingly in correlation with fibrosis stage. A simple algorithm combining sH2a levels with those of alanine aminotransferase allowed prediction of fibrosis stage, with a very high area under the ROC curve of 0.86. Conclusions sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function. PMID:22096539

  10. Heat stability and activity levels of aspartate aminotransferase and alanine aminotransferase in British Littorinidae

    Microsoft Academic Search

    S. L Hull; J Grahame; P. J Mill

    1999-01-01

    Aspartate aminotransferase and alanine aminotransferase activity levels were determined in crude homogenates of Littorina arcana, Littorina littorea, Littorina compressa, Littorina neglecta, Littorina obtusata, Littorina fabalis, Melarhaphe neritoides and three forms of Littorina saxatilis; high shore thin-shelled H, midshore thick-shelled M and barnacle dwelling B. In all the groups investigated, aspartate aminotransferase activity was higher than alanine aminotransferase, and high shore

  11. Absorbed-dose/dose-rate dependence studies for the alanine-EPR dosimetry system

    E-print Network

    Absorbed-dose/dose-rate dependence studies for the alanine-EPR dosimetry system M.F. Desrosiers à but significant observation that, after examination, led to the characterization of a previously unknown absorbed-dose-dependent, dose-rate effect for the alanine system. The newly discovered rate effect is of potential concern

  12. Effects of glycine and alanine on short-term storage and cryopreservation of striped bass

    E-print Network

    Hamza, Iqbal

    , ethylene glycol, and propylene glycol. Jenkins-Keeran and Woods [18] reported as high as 23% postEffects of glycine and alanine on short-term storage and cryopreservation of striped bass (Morone experiments were designed to examine the effects of the amino acids glycine and alanine on short-term storage

  13. An alteration of the gut-liver axis drives pulmonary inflammation after intoxication and burn injury in mice.

    PubMed

    Chen, Michael M; Zahs, Anita; Brown, Mary M; Ramirez, Luis; Turner, Jerrold R; Choudhry, Mashkoor A; Kovacs, Elizabeth J

    2014-10-01

    Approximately half of all adult burn patients are intoxicated at the time of their injury and have worse clinical outcomes than those without prior alcohol exposure. This study tested the hypothesis that intoxication alters the gut-liver axis, leading to increased pulmonary inflammation mediated by burn-induced IL-6 in the liver. C57BL/6 mice were given 1.2 g/kg ethanol 30 min prior to a 15% total body surface area burn. To restore gut barrier function, the specific myosin light chain kinase inhibitor membrane-permeant inhibitor of kinase (PIK), which we have demonstrated to reduce bacterial translocation from the gut, was administered 30 min after injury. Limiting bacterial translocation with PIK attenuated hepatic damage as measured by a 47% reduction in serum alanine aminotransferase (P < 0.05), as well as a 33% reduction in hepatic IL-6 mRNA expression (P < 0.05), compared with intoxicated and burn-injured mice without PIK. This mitigation of hepatic damage was associated with a 49% decline in pulmonary neutrophil infiltration (P < 0.05) and decreased alveolar wall thickening compared with matched controls. These results were reproduced by prophylactic reduction of the bacterial load in the intestines with oral antibiotics before intoxication and burn injury. Overall, these data suggest that the gut-liver axis is deranged when intoxication precedes burn injury and that limiting bacterial translocation in this setting attenuates hepatic damage and pulmonary inflammation. PMID:25104501

  14. Liver disease - resources

    MedlinePLUS

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation - www.liverfoundation.org Children's Liver Association for Support Services - www.classkids.org Hepatitis ...

  15. Dietary supplementation with glutamate precursor ?-ketoglutarate attenuates lipopolysaccharide-induced liver injury in young pigs.

    PubMed

    Wang, Lei; Hou, Yongqing; Yi, Dan; Li, Yongtang; Ding, Binying; Zhu, Huiling; Liu, Jian; Xiao, Hang; Wu, Guoyao

    2015-07-01

    There is growing interest in glutamate as a functional amino acid in nutrition and health. This study was conducted to determine whether glutamate precursor ?-ketoglutarate (AKG) could alleviate lipopolysaccharide (LPS)-induced liver injury in young pigs. Twenty-four piglets were randomly assigned to the control, LPS, or LPS + AKG group. Piglets in the control and LPS groups were fed a basal diet, whereas piglets in the NAC group were fed the basal diet supplemented with 1 % AKG. On days 10, 12, 14, and 16 of the trial, piglets in the LPS and LPS + AKG groups received intraperitoneal administration of LPS (80 ?g/kg BW), whereas piglets in the control group received the same volume of saline. On day 16 of the trial, blood samples were collected 3 h after LPS or saline injection. Twenty-four hours post-administration of LPS or saline (on day 17 of the trial), piglets were killed to obtain liver for analysis. Dietary AKG supplementation alleviated LPS-induced histomorphological abnormalities and mitigated LPS-induced increases in aspartate aminotransferase (AST) activity and AST/ALT ratio (P < 0.05). Compared with the LPS group, dietary supplementation with AKG decreased plasma glutamate concentration, while increasing hepatic concentrations of glutamate, glutamine, leucine, asparagine, lysine, alanine, serine, threonine, valine, and phenylalanine (P < 0.05). LPS challenge dramatically increased concentrations of malondialdehyde and decreased glutathione peroxidase activity in the liver. Additionally, LPS challenge enhanced concentrations of AMP and total protein, as well as RNA/DNA and total protein/DNA ratios, while decreasing hepatic ADP concentrations. These adverse effects of LPS challenge were ameliorated by AKG supplementation. Collectively, dietary AKG supplementation provides a new means to ameliorate LPS-induced liver injury by increasing anti-oxidative capacity and improving energy metabolism in young pigs. PMID:25795418

  16. Calcium Signaling in the Liver

    PubMed Central

    Amaya, Maria Jimena; Nathanson, Michael H.

    2014-01-01

    Intracellular free Ca2+ ([Ca2+]i) is a highly versatile second messenger that regulates a wide range of functions in every type of cell and tissue. To achieve this versatility, the Ca2+ signaling system operates in a variety of ways to regulate cellular processes that function over a wide dynamic range. This is particularly well exemplified for Ca2+ signals in the liver, which modulate diverse and specialized functions such as bile secretion, glucose metabolism, cell proliferation, and apoptosis. These Ca2+ signals are organized to control distinct cellular processes through tight spatial and temporal coordination of [Ca2+]i signals, both within and between cells. This article will review the machinery responsible for the formation of Ca2+ signals in the liver, the types of subcellular, cellular, and intercellular signals that occur, the physiological role of Ca2+ signaling in the liver, and the role of Ca2+ signaling in liver disease. PMID:23720295

  17. Cholera Toxin-Sensitive GTP-Binding Protein-Coupled Activation of Augmenter of Liver Regeneration (ALR) Receptor and Its Function in Rat Kupffer Cells

    PubMed Central

    Gandhi, Chandrashekhar R.; Murase, Noriko; Starzl, Thomas E.

    2010-01-01

    Mitogenic effect of augmenter of liver regeneration (ALR), a protein produced and released by hepatocytes, on hepatocytes in vivo but not in vitro suggests that the effect is mediated by nonparenchymal cells. Since mediators produced by Kupffer cells are implicated in hepatic regeneration, we investigated receptor for ALR and its functions in rat Kupffer cells. Kupffer cells were isolated from rat liver by enzymatic digestion and centrifugal elutriation. Radioligand ([125I] ALR) receptor binding, ALR-induced GTP/G-protein association, and nitric oxide (NO), tumor necrosis factor (TNF)-?, and interleukin-6 (IL-6) synthesis were determined. High-affinity receptor for ALR, belonging to the G-protein family, with Kd of 1.25 ± 0.18 nM and Bmax of 0.26 ± 0.02 fmol/?g DNA was identified. ALR stimulated NO, TNF-?, and IL-6 synthesis via cholera toxin-sensitive G-protein, as well as p38-MAPK activity and nuclear translocation of NF?B. While inhibitor of NF?B (MG132) inhibited ALR-induced NO synthesis, MG132 and p38-MAPK inhibitor (SB203580) abrogated ALR-induced TNF-? and IL-6 synthesis. ALR also prevented the release of mediator(s) from Kupffer cells that cause inhibition of DNA synthesis in hepatocytes. Administration of ALR to 40% partially hepatectomized rats increased expression of TNF-?, IL-6, and inducible nitric oxide synthase (iNOS) and caused augmentation of hepatic regeneration. These results demonstrate specific G-protein coupled binding of ALR and its function in Kupffer cells and suggest that mediators produced by ALR-stimulated Kupffer cells may elicit physiologically important effects on hepatocytes. PMID:19859909

  18. Effect of Estrogen on Mitochondrial Function and Intracellular Stress Markers in Rat Liver and Kidney following Trauma-Hemorrhagic Shock and Prolonged Hypotension

    PubMed Central

    Kozlov, Andrey V; Duvigneau, J Catharina; Hyatt, Tanya C; Raju, Raghavan; Behling, Tricia; Hartl, Romana T; Staniek, Katrin; Miller, Ingrid; Gregor, Wolfgang; Redl, Heinz; Chaudry, Irshad H

    2010-01-01

    Trauma-hemorrhage (T-H) is known to impair tissue perfusion, leading to tissue hypoxia, and thus affecting mitochondria, the organelles with the highest oxygen demand. In a model of T-H and prolonged hypotension without fluid resuscitation, administration of a small volume of 17?-estradiol (E2), but not vehicle, prolonged the survival of rats for 3 h, even in the absence of fluid resuscitation. The main finding of this study is that T-H followed by prolonged hypotension significantly affects mitochondrial function, endoplasmic reticulum (ER) stress markers and free iron levels, and that E2 ameliorated all these changes. All of these changes were observed in the liver but not in the kidney. The sensitivity of mitochondrial respiration to exogenous cytochrome c can reflect increased permeability of the outer mitochondrial membrane for cytochrome c. Increased levels of free iron are indicative of oxidative stress, but neither oxidative nor nitrosylative stress markers changed. The spliced isoform of XBP1 mRNA (an early marker of ER stress) and the expression of C/EBP homologous protein (CHOP) (a protein regulating ER stress-induced apoptosis) were elevated in T-H animals but remained unchanged if T-H rats received E2. Both the prevention of elevated sensitivity of mitochondrial respiration to cytochrome c and a decrease in ER stress by E2 maintain functional integrity of the liver and may help the organ during prolonged hypotension and following resuscitation. A decrease in free iron levels by E2 is more relevant for resuscitation, often accompanied by oxidative stress reaction. Thus, E2 appears to be a novel hormonal adjunct that prolongs permissive hypotension during lengthy transportation of the injured patient between the injury site and the hospital in both civilian and military injuries. PMID:20379612

  19. The effects of Syzygium aromaticum-derived oleanolic acid on kidney function of male Sprague-Dawley rats and on kidney and liver cell lines.

    PubMed

    Madlala, Hlengiwe P; Masola, Bubuya; Singh, Moganavelli; Musabayane, Cephas T

    2012-01-01

    Studies indicate that Syzygium spp-derived oleanolic acid (OA) enhances renal function of streptozotocin (STZ)-induced diabetic rats as evidenced by its reversal of the previously reported inability of the kidney to excrete Na(+) in these animals. We postulated that OA influences Na(+) excretion in the proximal tubule, the site where two-thirds of filtered NaCl is reabsorbed through a process mediated by transport proteins. Therefore, the study investigated the effects of OA on proximal tubular Na(+) handling in male Sprague-Dawley rats using renal lithium clearance (C(Li)). Renal C(Li) has been used widely in animal and clinical studies to assess proximal tubular function. Sub-chronic doses of OA were administered to rats twice every third day for 5 weeks. Rats treated with deionized water served as control animals. Cytotoxicity of OA on kidney and liver cell lines was assessed by the MTT and comet assays. OA increased Na(+) excretion of conscious male Sprague-Dawley rats from week 3 to week 5. By the end of the 5-week experimental period, OA treatment significantly reduced (p < 0.05) plasma creatinine concentration of STZ-induced diabetic rats with a concomitant elevation in glomerular filtration rate (GFR). Acute OA infusion was also associated with increases in fractional excretion of sodium (FE(Na)) and lithium (FE(Li)) in anesthetized rats in the absence of significant changes in GFR. The MTT assay studies demonstrated that OA increased the metabolic activity of kidney and liver cell lines. Taken together with previous observations, this study implicates the proximal tubule in OA-evoked increases in urinary Na(+) output. PMID:22512664

  20. Liver Damage due to Methotrexate in Patients with Psoriasis

    PubMed Central

    Dahi, M. G. C.; Gregory, M. M.; Scheuer, P. J.

    1971-01-01

    Liver function and histological changes in liver biopsies were studied in 37 patients who had been treated for psoriasis with methotrexate. Cirrhosis was found in seven (19%) and hepatic fibrosis of varying severity in 10 (27%). Minor abnormalities in another 17 (46%) consisted of fatty change, round cell infiltration, and extensive vacuolation of liver cell nuclei. In only three (8%) was hepatic histology entirely normal. The severity of liver damage was related to the duration of methotrexate treatment. Minor abnormalities of liver function tests and liver histology were also found in eight control psoriatic patients. Standard liver function tests were of little value in predicting the degree of liver damage. It appears that methotrexate, in the doses normally used to control psoriasis, may cause cirrhosis if treatment is prolonged and that liver biopsy is necessary for evaluation of liver damage in these patients. ImagesFIG. 2FIG. 3FIG. 4FIG. 5 PMID:5548839

  1. Artificial and Bioartificial Liver Support

    PubMed Central

    2007-01-01

    The fact that liver failure constitutes a life-threatening condition and can, in most cases, only be overcome by orthotopic liver transplantation, lead to the development of various artificial and bioartificial liver support devices. While artificial systems are based on the principles of adsorption and filtration, the more complex concept of bioartificial devices includes the provision of liver cells. Instead of solely focussing on detoxification, these concepts also support the failing organ concerning synthetic and regulative functions. The systems were evaluated in a variety of clinical studies, demonstrating their safety and investigating the impact on the patient's clinical condition. This review gives an overview over the most common artificial and bioartificial liver support devices and summarizes the results of the clinical studies. PMID:19279696

  2. Recovery of menstruation and pregnancy after liver transplantation

    Microsoft Academic Search

    T F Cundy; J G OGrady; R Williams

    1990-01-01

    The effect of successful liver transplantation on menstrual function was assessed by questionnaire in 44 women transplanted for various types of end stage liver disease, acute liver failure or malignant disease. Significant amenorrhoea (greater than one year) was present in 48% of women with chronic liver disease before transplantation, and was reversed within 10 months of surgery in all but

  3. Regenerative and fibrotic pathways in canine liver disease

    Microsoft Academic Search

    Bart Spee

    2006-01-01

    Liver diseases occur quite frequently in dogs; the overall incidence in dogs has been estimated around 1-2% of the clinical cases. Most liver diseases are, like in humans, chronic and occur through chronic inflammation due to different causes. In all cases the on-going liver cell damage leads to a reduction of the functional liver cell mass and progressive deposition of

  4. [Reversibility of the morphological and functional dedifferentiation occurring in cultures of avian embryonic liver cells (author's transl)].

    PubMed

    Houssaint, E

    1976-04-01

    Primary cell cultures are established from 8-day quail embryo livers. During the first three days the culture is made up of areas of epithelial-like cells and scattered fibroblasts. The cytoplasm of the epithelial cells shows a high glycogen content as detected by the PAS reaction controlled with salivary amylase digestion. During the following days an important increase in the number of fibroblastic cells is observed. After 6-7 days of cultivation, the epithelial cells have disappeared and the culture is entirely fibroblastic. PAS technique does not show any trace of glycogen in these cultures which have been prolonged up to 45 days. Six-to 45-day primary cultures entirely made up of fibroblasts were associated with hepatic or pulmonary mesenchyme in organotypic culture for 3-4 days. In some cases the explant was first cultivated in vitro for 2 days and then grafted into a 5-day-old chick embryo on the chorioallantoic membrane for 6 days. In the secondary cultures hepatocytes showing an epithelial arrangement and a high glycogen content were observed. It appears from this observation that some of the primary culture fibroblasts are in fact dedifferentiated parenchymal cells. Such a dedifferentiation is a reversible phenomenon since the cells retain the ability to express their initial determination if they are placed in convenient environmental conditions. The role of the specific tissular arrangement in the stability of the differentiated state is discussed. PMID:939937

  5. Fatty liver in dairy cows.

    PubMed

    Herdt, T H

    1988-07-01

    An increase in liver fat concentration during the peripartum period is extremely common in dairy cows and, to some degree, is probably normal. When severe, it is associated with clinical problems including increased morbidity and mortality and reduced breeding efficiency. Fatty liver develops when serum NEFA concentrations rise and hepatic uptake of NEFA exceeds the liver's ability to synthesize and secrete lipoproteins. In most cases, hepatic lipid accumulation appears to commence prepartum, in association with rising serum NEFA concentrations and declining serum lipoprotein concentrations. Commonly used clinicopathologic tests of liver function do not yield clearly abnormal results except in animals with extremely high concentrations of liver fat. Clinically useful estimates of hepatic lipid concentration can be obtained in the field by determining the buoyancy of needle biopsy samples in liquids of various specific gravities. Clinically ill animals with liver fat concentrations of greater than 35 per cent by weight have a poor prognosis, and those that do survive will have a protracted convalescence. Treatment of dairy cows with clinical fatty liver should be aimed at reducing further adipose lipid mobilization and promoting hepatic lipoprotein synthesis; however, protocols for therapy have not as yet been evaluated critically. Prevention of fatty liver is more rewarding than treatment. Dry cows should be maintained in a moderately fat condition and fed high-quality, palatable feeds in amounts necessary to met or slightly exceed their energy requirements. Free-choice feeding of high-energy feeds should be avoided in late lactation and during the nonlactating period. PMID:3061611

  6. Tb(3+)-triggered luminescence in a supramolecular gel and its use as a fluorescent chemoprobe for proteins containing alanine.

    PubMed

    Jung, Sung Ho; Kim, Ka Young; Woo, Dong Kyun; Lee, Shim Sung; Jung, Jong Hwa

    2014-11-01

    A tetracarboxylic acid-appended thiacalix[4]arene-based ligand with Tb(3+) formed a supramolecular gel which showed novel fluorogenic sensor capability for probing alanine and proteins containing alanine. PMID:25224027

  7. The Association of Low Serum Alanine Aminotransferase Activity With Mortality in the US Population

    PubMed Central

    Ruhl, Constance E.; Everhart, James E.

    2013-01-01

    Elevated alanine aminotransferase (ALT) activity, an important marker of liver injury, has been associated inconsistently with higher mortality. We evaluated whether persons with nonelevated ALT levels are the most appropriate comparison group by examining the relationships of low ALT with mortality and body composition in the US National Health and Nutrition Examination Survey (NHANES). In NHANES 1988–1994, the mortality risk of persons in ALT deciles 1, 2, 3, and 10 was compared with that of persons in deciles 4–9 (mortality was relatively flat across these deciles) over an 18-year period (through 2006) among 14,950 viral-hepatitis-negative adults. In NHANES 1999–2006, low ALT was evaluated in association with dual-energy x-ray absorptiometry body composition measures among 15,028 adults. Multivariate-adjusted mortality was higher for decile 1 (hazard ratio (HR) = 1.42, 95% confidence interval (CI): 1.24, 1.63), decile 2 (HR = 1.27, 95% CI: 1.06, 1.53), and decile 3 (HR = 1.25, 95% CI: 1.04, 1.50) and nonsignificantly higher for decile 10 (HR = 1.21, 95% CI: 0.91, 1.61) than for deciles 4–9. Adjusted appendicular lean mass was decreased among the lowest ALT deciles. In the US population, low ALT was associated with higher mortality risk, possibly attributable to decreased appendicular lean mass. For mortality studies of elevated ALT levels, the most appropriate comparison group is persons in the middle range of ALT rather than all persons with nonelevated ALT. PMID:24071009

  8. The association of low serum alanine aminotransferase activity with mortality in the US population.

    PubMed

    Ruhl, Constance E; Everhart, James E

    2013-12-15

    Elevated alanine aminotransferase (ALT) activity, an important marker of liver injury, has been associated inconsistently with higher mortality. We evaluated whether persons with nonelevated ALT levels are the most appropriate comparison group by examining the relationships of low ALT with mortality and body composition in the US National Health and Nutrition Examination Survey (NHANES). In NHANES 1988-1994, the mortality risk of persons in ALT deciles 1, 2, 3, and 10 was compared with that of persons in deciles 4-9 (mortality was relatively flat across these deciles) over an 18-year period (through 2006) among 14,950 viral-hepatitis-negative adults. In NHANES 1999-2006, low ALT was evaluated in association with dual-energy x-ray absorptiometry body composition measures among 15,028 adults. Multivariate-adjusted mortality was higher for decile 1 (hazard ratio (HR) = 1.42, 95% confidence interval (CI): 1.24, 1.63), decile 2 (HR = 1.27, 95% CI: 1.06, 1.53), and decile 3 (HR = 1.25, 95% CI: 1.04, 1.50) and nonsignificantly higher for decile 10 (HR = 1.21, 95% CI: 0.91, 1.61) than for deciles 4-9. Adjusted appendicular lean mass was decreased among the lowest ALT deciles. In the US population, low ALT was associated with higher mortality risk, possibly attributable to decreased appendicular lean mass. For mortality studies of elevated ALT levels, the most appropriate comparison group is persons in the middle range of ALT rather than all persons with nonelevated ALT. PMID:24071009

  9. Engineering of sugar metabolism of Corynebacterium glutamicum for production of amino acid l -alanine under oxygen deprivation

    Microsoft Academic Search

    Toru Jojima; Miho Fujii; Eiji Mori; Masayuki Inui; Hideaki Yukawa

    2010-01-01

    Corynebacterium glutamicum was genetically engineered to produce l-alanine from sugar under oxygen deprivation. The genes associated with production of organic acids in C. glutamicum were inactivated and the alanine dehydrogenase gene (alaD) from Lysinibacillus sphaericus was overexpressed to direct carbon flux from organic acids to alanine. Although the alaD-expressing strain produced alanine from glucose under oxygen deprivation, its productivity was

  10. Sinusoidal swinging dynamics of the telomere repair and cell growth activation functions of telomerase in rat liver cancer cells.

    PubMed

    Wolfrom, Claire; Martin, Olivier C; Laurent, Michel; Deschatrette, Jean

    2007-01-01

    Telomerase is a multimolecular complex of reverse transcriptase, RNA template, and regulatory proteins. It has two known functions: catalysis of the addition of [TTAGGG] repeats to telomeric DNA and the activation of various genes controlling cell proliferation. The possible coordination of these two functions is a key issue in understanding the growth of cancer cells. We report long-term changes to this complex system, as shown by specific data analysis methods. We show that the dynamics of the two functions of telomerase are tightly linked, with a change in predominant function every 13-14 weeks. The conservative behavior of this dynamic system probably accounts for the persistent proliferation of cancer cells. PMID:17182040

  11. Hypothermic preservation of rat liver microorgans (LMOs) in bes-gluconate solution. Protective effects of polyethyleneglycol (PEG) on total water content and functional viability.

    PubMed

    Mandolino, Cecilia; Pizarro, Ma Dolores; Quintana, Alejandra B; Rodríguez, Joaquín V; Mamprin, María Eugenia

    2011-01-01

    We have reported of an alternative solution to preserve hepatocytes that have three key components: gluconate, sucrose and an aminosulfonic acid (BGS solution). In order to extend the use of this solution to organs as the liver, we evaluate the effect of the addition of PEG of 8, 20 and 35 kDa to BG Solution on the total water content and functional viability of rat liver microorgans (LMOs). LMOs were preserved (48 h 0 ºC) in the following solutions: ViaSpan(®); BGS; BG plus 4% PEG 8000 (BG8); BG plus 4% PEG 20.000 (BG20) and BG plus 4% PEG 35.000 (BG35). LDH Release and Total Water Content showed a marked increase in LMOs preserved in BGS. This indicates that, in the absence of PEG, the tissue showed important cell membrane integrity deterioration and was incapable of regulating cell volume. After the preservation period, all groups were reoxygenated (120 min, 37 ºC, KHR) and Total Water Content, Glycogen Content and Oxygen Consumption were determined. After 120 min LMOs preserved in BG35 showed values of Oxygen Consumption similar to controls. On the other hand, LMOs preserved in BG8, BG20 and ViaSpan(®) showed oxygen consumption rates and glycogen content significantly smaller than controls. In conclusion, BG35 was the most effective preservation solution to protect LMOs against cold preservation injury due to ischemia and reoxygenation. It is a good alternative to ViaSpan(®) because of its higher buffer capacity, its best indexes of respiration activity and for being considerably less expensive. PMID:21502682

  12. Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats.

    PubMed

    Menon, B Rajalakshmy; Rathi, M A; Thirumoorthi, L; Gopalakrishnan, V K

    2010-10-01

    The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observed in extract treated liver injured experimental rats. Histopathological examination of the liver tissues supported the hepatoprotection. It is concluded that the ethanolic extract of Bacopa monieri plant possess good hepatoprotective activity. PMID:21966114

  13. Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats

    PubMed Central

    Menon, B. Rajalakshmy; Rathi, M. A.; Thirumoorthi, L.

    2010-01-01

    The study was designed to evaluate the hepatoprotective activity of ethanolic extract of Bacopa monnieri in acute experimental liver injury induced by Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was administered orally once every day for 10 days. The increased serum marker enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase were restored towards normalization significantly by the extract. Significant increase in SOD, CAT and GPx was observed in extract treated liver injured experimental rats. Histopathological examination of the liver tissues supported the hepatoprotection. It is concluded that the ethanolic extract of Bacopa monieri plant possess good hepatoprotective activity. PMID:21966114

  14. Relationship between obesity, metabolic syndrome, and nonalcoholic fatty liver disease in the elderly agricultural and fishing population of Taiwan

    PubMed Central

    Shen, Hsi-Che; Zhao, Zi-Hao; Hu, Yi-Chun; Chen, Yu-Fen; Tung, Tao-Hsin

    2014-01-01

    Background The purpose of this study was to explore the relationship between obesity, the metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) in the elderly agricultural and fishing population of Taipei, Taiwan. Methods The study participants comprised 6,511 (3,971 male and 2,540 female) healthy elderly subjects voluntarily attending a teaching hospital for a physical check-up in 2010. Blood samples and real-time ultrasound-proven fatty liver sonography results were collected. Results The prevalence of NAFLD in this elderly population was 27.2%, including mild NAFLD (16.0%), moderate NAFLD (10.3%), and severe NAFLD (0.9%). The prevalence of moderate or severe NAFLD for metabolic syndrome proved to be substantially greater (P<0.0001, ?2 test) for one or two metabolic factors. Using multinomial logistic regression analysis, age, sex, metabolic syndrome, and higher body mass index had a statistically significant association with mild NAFLD. Age, sex, metabolic syndrome, higher body mass index, and higher alanine aminotransferase were significantly related to moderate NAFLD. In addition, higher body mass index, higher uric acid, and higher alanine aminotransferase levels were significantly related to severe NAFLD. The sensitivity and specificity of body mass index and waist circumference as markers of NAFLD were estimated to be 81% and 84%, respectively, and 77% and 69%, respectively. Conclusion The prevalence of mild or moderate NAFLD was related to obesity and metabolic syndrome. Higher body mass index was also related to severe NAFLD but not to metabolic syndrome. Targeting this population for control of obesity and improved metabolic function is important. PMID:24741297

  15. Acute phalloidin toxicity in living hepatocytes. Evidence for a possible disturbance in membrane flow and for multiple functions for actin in the liver cell.

    PubMed Central

    Watanabe, S.; Phillips, M. J.

    1986-01-01

    Actin filament based cell functions were examined in freshly isolated hepatocytes using phalloidin as an inhibitor. In particular, cell motility events, namely, surface bleb formation and canalicular contractile movements, were assessed and compared with morphologic changes in the cells. Phalloidin (in 0.1, 1.0, and 10.0 micrograms/ml dosages) was added to the culture medium 4 hours after isolation of the hepatocytes. Cell motility was recorded with time-lapse cinephotomicrography, and the morphologic changes were evaluated by phase-contrast optics and by transmission electron microscopy of serial sections. Membrane-bound pericanalicular cytoplasmic vacuoles appeared first, followed by cytoplasmic protrusions at the cell surface. Vacuolar membrane continuities with the canalicular membrane were noted, and later, with other regions of the cell surface, such that large tortuous irregular membrane-bound canals are seen on serial sectioning to link extracellular and canalicular spaces. These findings suggest a possible disturbance in membrane flow. Canalicular motility was greatly reduced and was dose-dependent. The time-based difference in the changes at the canalicular and sinusoidal surfaces may be indicative of different functions and/or sensitivities of the actin filaments within the liver cell. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 p107-a Figure 8 PMID:3942195

  16. Identification of fetal liver tyrosine kinase 3 (flt3) ligand domain required for receptor binding and function using naturally occurring ligand isoforms.

    PubMed

    Mwangi, W; Brown, W C; Palmer, G H

    2000-12-15

    We used a comparative approach to identify the fetal liver tyrosine kinase 3 (flt3) ligand structure required for binding and function. Two conserved bovine flt3 ligand isoforms, which differ in a defined region within the extracellular domain, were identified and shown to be uniformly transcribed in individuals with diverse MHC haplotypes. Notably, at the amino acid level, the extracellular domain of the bovine flt3 ligand isoform 1 is 81 and 72% identical with the extracellular domains of the human and murine flt3 ligands, respectively, whereas isoform-2 has a deletion within this domain. Bovine flt3 ligand isoform 1, but not 2, bound the human flt3 receptor and stimulated murine pro B cells transfected with the murine flt3 receptor. This retention of binding and function allowed definition of key residues by identifying sequences conserved among species. We have shown that a highly conserved, 18 aa sequence within the flt3 ligand extracellular domain is required for flt3 receptor binding and function. However, a peptide representing this sequence is insufficient for receptor binding as demonstrated by its failure to inhibit the bovine flt3 ligand isoform 1 binding to the human flt3 receptor. The requirement for flanking structure was confirmed by testing bovine flt3 ligand isoform 1 constructs truncated at specific residues outside the 18 aa sequence. Overall, the flt3 ligand structure required for function is markedly similar to that of the related hemopoietic growth factors, CSF-1 and steel factor. This definition of the required flt3 ligand structure will facilitate development of agonists to enhance dendritic cell recruitment for vaccines and immunotherapy. PMID:11120823

  17. The "kidney-liver" multiorgan ex vivo perfused model improves the circuit's biochemical milieu during perfusion compared to the "liver-kidney" counterpart.

    PubMed

    Chung, Wen Yuan; Gravante, Gianpiero; Eltweri, Amar; Sorge, Roberto; Ong, Seok Ling; Pollard, Cristina; Metcalfe, Mathew; Dennison, Ashley

    2015-06-01

    The multiorgan ex vivo perfused liver-kidney model allows studying the hepatic pathophysiology and purifying waste products. We tested if the addition of the kidney first followed by the liver (KL circuit) produces better results compared to the classic liver-first approach (LK). Intact livers and kidneys were obtained post mortem from ten female domestic white pigs, five experiments were conducted with the KL circuit and five with the LK. Bile, urine production, arterial blood gases, glucose, renal and liver tests were collected hourly during the perfusions. The KL circuit had values more close to physiological ranges, more stable over time and showed less variability compared to the LK circuit for urine production, glucose, PH, anion gap, lactate, urea, sodium, potassium and Alanine Transaminase (ANOVA test for repeated measures p < 0.05). The KL circuit produced a more physiological and reliable biochemical milieu. PMID:25557139

  18. Structural and functional comparison of agents interfering with dihydroorotate, succinate and NADH oxidation of rat liver mitochondria

    Microsoft Academic Search

    Johannes Jöckel; Bernd Wendt; Monika Löffler

    1998-01-01

    Mitochondrially bound dihydroorotate dehydrogenase (EC 1.3.99.11) catalyses the fourth sequential step in the de novo synthesis of uridine monophosphate; this enzyme uses ubiquinone as the proximal and cytochrome oxidase as is the ultimate electron transfer system. Here, seven compounds with proven antiproliferative activity and in vitro antipyrimidine effects were investigated with isolated functional mitochondria of rat tissues in order to

  19. Deletion of SIRT1 from Hepatocytes in Mice Disrupts Lipin-1 Signaling and Aggravates Alcoholic Fatty liver

    PubMed Central

    Yin, Huquan; Hu, Ming; Liang, Xiaomei; Ajmo, Joanne M.; Li, Xiaoling; Bataller, Ramon; Odena, Gemma; Stevens, Stanley M.; You, Min

    2013-01-01

    Background&Aims: Sirtuin (SIRT1) is a NAD+-dependent protein deacetylase that regulates hepatic lipid metabolism by modifying histones and transcription factors. Ethanol exposure disrupts SIRT1 activity and contributes to alcoholic liver disease (ALD) in rodents, but the exact pathogenic mechanism is not clear. We compared mice with liver-specific deletion of Sirt1 (Sirt1LKO) mice with their LOX littermates (controls). Methods: We induced alcoholic liver injury in male Sirt1LKO and control mice, placing them on Lieber-DeCarli ethanol-containing diets for 10 days and then administering a single dose of ethanol (5 g/kg body weight) via gavage. Liver and serum samples were collected. We also measured mRNA levels of SIRT1, SFRS10, and lipin-1? and lipin-1? in liver samples from patients with alcoholic hepatitis (AH) and individuals without AH (controls). Results: On the ethanol-containing diet, livers of Sirt1LKO mice accumulated larger amounts of hepatic lipid and expressed higher levels of inflammatory cytokines than control mice; serum of Sirt1LKO mice had increased levels of alanine aminotransferase and aspartate aminotransferase. Hepatic deletion of SIRT1 exacerbated ethanol-mediated defects in lipid metabolism, mainly by altering the function of lipin-1, a transcriptional regulator of lipid metabolism. In cultured mouse AML-12 hepatocytes, transgenic expression of SIRT1 prevented fat accumulation in response to ethanol exposure, largely by reversing the aberrations in lipin-1 signaling induced by ethanol. Liver samples from patients with AH had reduced levels of SIRT1 and a higher ratio of Lpin1?:? mRNAs than controls. Conclusions: In mice, hepatic deletion of Sirt1 promotes steatosis, inflammation, and fibrosis in response to ethanol challenge. Ethanol-mediated impairment of hepatic SIRT1 signaling via lipin-1 contributes to development of alcoholic steatosis and inflammation. Reagents designed to increase SIRT1 regulation of lipin-1 might be developed to treat patients with alcoholic fatty liver disease. PMID:24262277

  20. Platelet factor 4 limits Th17 differentiation and ischaemia-reperfusion injury after liver transplantation in mice.

    PubMed

    Guo, H; Wang, Y; Zhao, Z; Shao, X

    2015-02-01

    Liver ischaemia/reperfusion injury (IRI) is a serious pathologic process encountered in a number of clinical syndromes including liver transplantation, liver resection, trauma and haemorrhagic shock. Platelet factor 4 (PF4) was the first discovered CXC chemokine and is found in platelet granules at very high concentration. In this study, we provide strong evidence that PF4 is involved directly in liver innate immune response against IRI by regulating Th17 differentiation. PF4 deficiency aggravates liver IRI, as shown by higher serum alanine aminotransferase (ALT) levels and Suzuki scores. PF4 deficiency promotes Th17 response with higher levels of IL-23, IL-6 and IL-17, which aggravates liver IRI. Furthermore, PF4 deficiency limits suppressor of cytokine signalling 3 (SOCS3) expressions, and PF4 fails to suppress expression of IL-17 in cells transfected with SOCS3 SiRNA. In conclusion, PF4 limits liver IRI through IL-17 inhibition via upregulation of SOCS3. PMID:25440775

  1. Functional characterization of estrogen receptor subtypes, ER{alpha} and ER{beta}, mediating vitellogenin production in the liver of rainbow trout

    SciTech Connect

    Leanos-Castaneda, Olga [Department of Integrative Biology, University of Guelph, Ontario, N1G 2W1 (Canada)], E-mail: olgalidia09@yahoo.com; Kraak, Glen van der [Department of Integrative Biology, University of Guelph, Ontario, N1G 2W1 (Canada)

    2007-10-15

    The estrogen-dependent process of vitellogenesis is a key function on oviparous fish reproduction and it has been widely used as an indicator of xenoestrogen exposure. The two estrogen receptor (ER) subtypes, ER{alpha} and ER{beta}, are often co-expressed in the liver of fish. The relative contribution of each ER subtype to modulate vitellogenin production by hepatocytes was studied using selected compounds known to preferentially interact with specific ER subtypes: propyl-pyrazole-triol (PPT) an ER{alpha} selective agonist, methyl-piperidino-pyrazole (MPP) an ER{alpha} selective antagonist, and diarylpropionitrile (DPN) an ER{beta} selective agonist. First, the relative binding affinity of the test compounds to estradiol for rainbow trout hepatic nuclear ER was determined using a competitive ligand binding assay. All the test ligands achieved complete displacement of specific [{sup 3}H]-estradiol binding from the nuclear ER extract. This indicates that the test ligands have the potential to modify the ER function in the rainbow trout liver. Secondly, the ability of the test compounds to induce or inhibit vitellogenin production by primary cultures of rainbow trout hepatocytes was studied. Estradiol and DPN were the only compounds that induced a dose-dependent increase on vitellogenin synthesis. The lack of vitellogenin induction by PPT indicates that ER{alpha} could not have a role on this reproductive process whereas the ability of DPN to induce vitellogenin production supports the participation of ER{beta}. In addition, this hypothesis is reinforced by the results obtained from MPP plus estradiol. On one hand, the absence of suppressive activity of MPP in the estradiol-induced vitellogenin production does not support the participation of ER{alpha}. On the other hand, once blocked ER{alpha} with MPP, the only manifestation of agonist activity of estradiol would be achieved via ER{beta}. In conclusion, the present results indicate that vitellogenin production is mainly mediated through ER{beta}, implying, furthermore that compounds which only exhibit ER{alpha} selectivity are not detected by vitellogenin bioassay.

  2. Structural and functional changes after the administration of tetrachlormethane in the liver of rats fed on diets with different protein contents.

    PubMed

    Cervinková, Z; Bgatova, N P; Shorina, T G; Holecek, M; Subrtová, D; Vosvrdová, H; Shkurupy, V A; Simek, J

    1987-01-01

    Morphological and biochemical changes characterizing the degree of liver damage and the development of liver repair were studied in rats fed 21 days on a low protein diet (LPD), a standard diet (SLD) and a high protein diet (HPD) and then given a single i.p. injection of tetrachlormethane (CCl4) in a dose of 0.75 ml/kg body weight. The HPD was found to increase sensitivity to CCl4, but it also promoted the liver repair process, as seen from the increment in liver DNA synthesis and the total DNA content of the liver, increased ploidy of the hepatocytes and growth of the size of their nuclei and of the hepatocytes themselves. An increase in the total surface area of the membranes of the granular endoplasmic reticulum and the inner and outer membrane of the mitochondria, but a decrease in the surface area of the membranes of the smooth endoplasmic reticulum, were also observed after the administration of CCl4. The LPD raised liver resistance to CCl4, but the development of liver repair activity differed from the process after the SLD and HPD, since polyploidy of the hepatocytes (especially the growth of octaploid cells) predominated and there was also an increase in the number of binuclear hepatocytes. Cell hypertrophy was expressed less in rats fed on the LPD than in animals given the HPD. As far as liver repair was concerned, the HPD showed no explicit advantages over the SLD. PMID:2958893

  3. Fasciola hepatica cathepsin L-like proteases: biology, function, and potential in the development of first generation liver fluke vaccines

    Microsoft Academic Search

    John P Dalton; Sandra O Neill; Colin Stack; Peter Collins; Alan Walshe; Mary Sekiya; Sean Doyle; Grace Mulcahy; Deborah Hoyle; Eric Khaznadji; Nathalie Moiré; Gerard Brennan; Angela Mousley; Natalia Kreshchenko; Aaron G Maule; Sheila M Donnelly

    2003-01-01

    Fasciola hepatica secretes cathepsin L proteases that facilitate the penetration of the parasite through the tissues of its host, and also participate in functions such as feeding and immune evasion. The major proteases, cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) are members of a lineage that gave rise to the human cathepsin Ls, Ks and Ss, but while they exhibit

  4. Microwave tissue coagulation technique in anatomical liver resection

    PubMed Central

    TAN, KAI; DU, XILIN; YIN, JIKAI; DONG, RUI; ZANG, LI; YANG, TAO; CHEN, YAFENG

    2014-01-01

    Anatomical liver resection is currently the preferred treatment for liver cancer. With the recent introduction of medical microwave coagulation for liver metastases, anatomical hepatectomy may be performed more efficiently. The present study retrospectively reviewed the results of microwave tissue coagulation performed during anatomical liver resection for patients with liver disease at the TangDu Hospital (Xi’an, China) between January, 2009 and June, 2012. A total of 128 patients met the inclusion criteria and were divided into two groups for comparison; those treated with the microwave coagulation technique (n=66) and the conventional group (n=62), who were treated with standard partial hepatectomy. There was no reported perioperative mortality. The univariate analysis revealed that the duration of liver dissection, intraoperative blood loss, intraoperative erythrocyte transfusion volume and alanine aminotransferase levels on the 5th postoperative day were significantly different between the microwave and conventional groups (P<0.05). Therefore, microwave tissue coagulation in anatomical liver resection was shown to be efficacious and safe and, provided proficient skills are developed in this technique, microwave tissue coagulation may be an effective alternative to anatomical hepatectomy. PMID:24649092

  5. Liver disease in cystic fibrosis

    PubMed Central

    Klincewicz, Beata; Cichy, Wojciech

    2014-01-01

    Cystic fibrosis-associated liver disease (CFLD) affects ca. 30% of patients. The CFLD is now considered the third cause of death, after lung disease and transplantation complications, in CF patients. Diagnostics, clinical assessment and treatment of CFLD have become a real challenge since a striking increase of life expectancy in CF patients has recently been observed. There is no elaborated “gold standard” in the diagnostic process of CFLD; clinical evaluation, laboratory tests, ultrasonography and liver biopsy are used. Clinical forms of CFLD are elevation of serum liver enzymes, hepatic steatosis, focal biliary cirrhosis, multilobular biliary cirrhosis, neonatal cholestasis, cholelithiasis, cholecystitis and micro-gallbladder. In children, CFLD symptoms mostly occur in puberty. Clinical symptoms appear late, when damage of the hepatobiliary system is already advanced. The CFLD is more common in patients with severe mutations of CFTR gene, in whom a complete loss of CFTR protein function is observed. CFLD, together with exocrine pancreatic insufficiency and meconium ileus, is considered a component of the severe CF phenotype. Treatment of CFLD should be complex and conducted by a multispecialist team (gastroenterologist, hepatologist, dietician, radiologist, surgeon). The main aim of the treatment is to prevent liver damage and complications associated with portal hypertension and liver cirrhosis. Ursodeoxycholic acid is used in the treatment of CFLD. There is no treatment of proven long-term efficacy in CFLD. Liver transplantation is a treatment of choice in end-stage liver disease. PMID:25097709

  6. Liver disease in cystic fibrosis.

    PubMed

    Kobelska-Dubiel, Natalia; Klincewicz, Beata; Cichy, Wojciech

    2014-01-01

    Cystic fibrosis-associated liver disease (CFLD) affects ca. 30% of patients. The CFLD is now considered the third cause of death, after lung disease and transplantation complications, in CF patients. Diagnostics, clinical assessment and treatment of CFLD have become a real challenge since a striking increase of life expectancy in CF patients has recently been observed. There is no elaborated "gold standard" in the diagnostic process of CFLD; clinical evaluation, laboratory tests, ultrasonography and liver biopsy are used. Clinical forms of CFLD are elevation of serum liver enzymes, hepatic steatosis, focal biliary cirrhosis, multilobular biliary cirrhosis, neonatal cholestasis, cholelithiasis, cholecystitis and micro-gallbladder. In children, CFLD symptoms mostly occur in puberty. Clinical symptoms appear late, when damage of the hepatobiliary system is already advanced. The CFLD is more common in patients with severe mutations of CFTR gene, in whom a complete loss of CFTR protein function is observed. CFLD, together with exocrine pancreatic insufficiency and meconium ileus, is considered a component of the severe CF phenotype. Treatment of CFLD should be complex and conducted by a multispecialist team (gastroenterologist, hepatologist, dietician, radiologist, surgeon). The main aim of the treatment is to prevent liver damage and complications associated with portal hypertension and liver cirrhosis. Ursodeoxycholic acid is used in the treatment of CFLD. There is no treatment of proven long-term efficacy in CFLD. Liver transplantation is a treatment of choice in end-stage liver disease. PMID:25097709

  7. A Mechanistic Pharmacokinetic Model for Liver Transporter Substrates Under Liver Cirrhosis Conditions

    PubMed Central

    Li, R; Barton, HA; Maurer, TS

    2015-01-01

    Liver cirrhosis is a disease characterized by the loss of functional liver mass. Physiologically based pharmacokinetic (PBPK) modeling was applied to interpret and predict how the interplay among physiological changes in cirrhosis affects pharmacokinetics. However, previous PBPK models under cirrhotic conditions were developed for permeable cytochrome P450 substrates and do not directly apply to substrates of liver transporters. This study characterizes a PBPK model for liver transporter substrates in relation to the severity of liver cirrhosis. A published PBPK model structure for liver transporter substrates under healthy conditions and the physiological changes for cirrhosis are combined to simulate pharmacokinetics of liver transporter substrates in patients with mild and moderate cirrhosis. The simulated pharmacokinetics under liver cirrhosis reasonably approximate observations. This analysis includes meta-analysis to obtain system-dependent parameters in cirrhosis patients and a top-down approach to improve understanding of the effect of cirrhosis on transporter-mediated drug disposition under cirrhotic conditions.

  8. In silico study of VP35 inhibitors: from computational alanine scanning to essential dynamics.

    PubMed

    Dapiaggi, F; Pieraccini, S; Sironi, M

    2015-07-14

    In recent years the Ebola virus has spread through several countries in Africa, highlighting the need to develop new treatments for this disease and boosting a new research effort on this subject. The Ebola virus Viral Protein 35 (VP35) carries out multiple functions necessary for virus replication and infection, in particular interfering with (IFN)-?/? signaling. Recently, VP35 has been crystallized in complex with small organic molecules able to inhibit its interaction with viral nucleoproteins, thus reducing Ebola infections of cultured cells. In this work, starting from these structures, we carry out a computational study aimed at investigating the energetic and dynamical aspects of the interaction between VP35 and its ligands at the atomic level. Molecular dynamics simulations, computational alanine scanning, root mean square fluctuations bootstrap analysis and essential dynamics analysis were performed. Our results expand the experimental ones obtained in previous works, adding information about the interactions landscape with the identification of a set of new hot-spots residues exerting a critical function in the protein-ligand interaction. Moreover we characterized the dynamics of the complexes, showing that the presence of ligands modifies the overall protein dynamics as well as the behavior of particular protein segments. PMID:26118819

  9. Relation between liver pathology and prognosis in patients with portal hypertension

    Microsoft Academic Search

    P. Aiden McCormick; Andrew K. Burroughs

    1994-01-01

    The most common causes of variceal bleeding are cirrhosis, schistosomiasis, and extrahepatic portal venous obstruction. The prognosis for an individual patient depends on the severity of the bleeding episode and the underlying liver function. Liver function is determined to a large extent by the underlying liver pathology. Patients with noncirrhotic portal hypertension or cirrhosis with good liver function have good

  10. 21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1030 Alanine amino transferase (ALT/SGPT) test...

  11. 21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1030 Alanine amino transferase (ALT/SGPT) test system....

  12. 21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1030 Alanine amino transferase (ALT/SGPT) test system....

  13. Ultraviolet detector response of glycine and alanine homopeptides: Some specic features in capillary electrophoresis

    E-print Network

    Miksik, Ivan

    buffer pH 2.5 containing or devoid of 0.35% hydroxypropyl-methylcellulose (HPMC), the detector's response a constant value (glycine and alanine peptides) run in the absence of HPMC at elevated (508C) temperature

  14. Solvation Free Energies of Alanine Peptides: The Effect of Flexibility

    SciTech Connect

    Kokubo, Hironori; Harris, Robert C.; Asthagiri, Dilip; Pettitt, Bernard M.

    2013-12-03

    The electrostatic (?Gel), cavity-formation (?Gvdw), and total (?G) solvation free energies for 10 alanine peptides ranging in length (n) from 1 to 10 monomers were calculated. The free energies were computed both with xed, extended conformations of the peptides and again for some of the peptides without constraints. The solvation free energies, ?Gel, ?Gvdw, and ?G, were found to be linear in n, with the slopes of the best-fit lines being gamma_el, gamma_vdw, and gamma, respectively. Both gamma_el and gamma were negative for fixed and flexible peptides, and gamma_vdw was negative for fixed peptides. That gamma_vdw was negative was surprising, as experimental data on alkanes, theoretical models, and MD computations on small molecules and model systems generally suggest that gamma_vdw should be positive. A negative gamma_vdw seemingly contradicts the notion that ?Gvdw drives the initial collapse of the protein when it folds by favoring conformations with small surface areas, but when we computed ?Gvdw for the flexible peptides, thereby allowing the peptides to assume natural ensembles of more compact conformations, gamma-vdw was positive. Because most proteins do not assume extended conformations, a ?Gvdw that increases with increasing surface area may be typical for globular proteins. An alternative hypothesis is that the collapse is driven by intramolecular interactions. We show that the intramolecular van der Waal's interaction energy is more favorable for the flexible than for the extended peptides, seemingly favoring this hypothesis, but the large fluctuations in this energy may make attributing the collapse of the peptide to this intramolecular energy difficult.

  15. Interaction of occupational manganese exposure and alcohol drinking aggravates the increase of liver enzyme concentrations from a cross-sectional study in China

    PubMed Central

    2013-01-01

    Background Over exposure to manganese (Mn) can damage the human central nervous system and potentially cause liver toxicity. Alcohol drinking is also one of the well-known harmful factors to hepatic organism. The interaction between Mn exposure and alcohol consumption to liver function was investigated in this study. Methods A total of 1112 on-the-spot workers were included in the cross-sectional survey from a large scale of manganese exposed workers healthy cohort (MEWHC) in a ferro-manganese refinery company. A questionnaire was used to collect the demographic information, occupational history, and alcohol drinking habits. Occupational health examination was carried out for each worker. The five key serum indices, including total bilirubin (TBILI), direct bilirubin (DBILI), indirect bilirubin (IBILI), alanine transaminase (ALT), and aspartate transaminase (AST), were determined to evaluate the liver function of each subject. Results Workers exposed to high levels of Mn had significantly elevated serum concentrations of liver enzymes (DBILI: 3.84±1.20 ?mol/L, ALT: 27.04±19.12 IU/L, and AST: 29.96±16.68 IU/L), when compared to those in the low-exposure group (DBIL: 3.54±0.85 ?mol/L, ALT: 20.38±10.97 IU/L, and AST: 26.39±8.07 IU/L), all P<0.01. These serum indices had a significantly increasing trend with the elevation of Mn exposure level (Ptrend <0.01). In addition, the workers with alcohol drinking also showed higher concentrations of liver enzymes than those non-drinkers, especially, and there was significant interaction between Mn exposure and alcohol consumption in terms of these three indices (P<0.001). Conclusions Occupational exposure to Mn can lead to a dose-dependent increase of liver enzyme concentrations, and interact with alcohol drinking to potentially aggravate the liver damage. It will be important for Mn exposed workers to control drinking and also assess liver function in the occupational health examination. PMID:23587294

  16. Ethanol-induced hepatic steatosis is modulated by glycogen level in the liver.

    PubMed

    Gu, Jin; Zhang, Yongxian; Xu, Daqian; Zhao, Zilong; Zhang, Yuxue; Pan, Yi; Cao, Peijuan; Wang, Zhenzhen; Chen, Yan

    2015-07-01

    Alcoholic liver disease (ALD) is a major health problem worldwide and hepatic steatosis is an early response to alcohol consumption. Fat and glycogen are two major forms of energy storage in the liver; however, whether glycogen metabolism in the liver impacts alcohol-induced steatosis has been elusive. In this study, we used a mouse model with overexpression of PPP1R3G in the liver to dissect the potential role of glycogen on alcohol-induced fatty liver formation. PPP1R3G is a regulatory subunit of protein phosphatase 1 and stimulates glycogenesis in the liver. Chronic and binge ethanol (EtOH) feeding reduced glycogen level in the mouse liver and such inhibitory effect of EtOH was reversed by PPP1R3G overexpression. In addition, PPP1R3G overexpression abrogated EtOH-induced elevation of serum levels of alanine aminotransferase and aspartate aminotransferase, increase in liver triglyceride concentration, and lipid deposition in the liver. EtOH-stimulated sterol regulatory element-binding protein (SREBP)-1c, a master regulator of lipogenesis, was also reduced by PPP1R3G overexpression in vivo. In AML-12 mouse hepatocytes, PPP1R3G overexpression could relieve EtOH-induced lipid accumulation and SREBP-1c stimulation. In conclusion, our data indicate that glycogen metabolism is closely linked to EtOH-induced liver injury and fatty liver formation. PMID:26022806

  17. Liver bioengineering: Current status and future perspectives

    PubMed Central

    Booth, Christopher; Soker, Tom; Baptista, Pedro; Ross, Christina L; Soker, Shay; Farooq, Umar; Stratta, Robert J; Orlando, Giuseppe

    2012-01-01

    The present review aims to illustrate the strategies that are being implemented to regenerate or bioengineer livers for clinical purposes. There are two general pathways to liver bioengineering and regeneration. The first consists of creating a supporting scaffold, either synthetically or by decellularization of human or animal organs, and seeding cells on the scaffold, where they will mature either in bioreactors or in vivo. This strategy seems to offer the quickest route to clinical translation, as demonstrated by the development of liver organoids from rodent livers which were repopulated with organ specific cells of animal and/or human origin. Liver bioengineering has potential for transplantation and for toxicity testing during preclinical drug development. The second possibility is to induce liver regeneration of dead or resected tissue by manipulating cell pathways. In fact, it is well known that the liver has peculiar regenerative potential which allows hepatocyte hyperplasia after amputation of liver volume. Infusion of autologous bone marrow cells, which aids in liver regeneration, into patients was shown to be safe and to improve their clinical condition, but the specific cells responsible for liver regeneration have not yet been determined and the underlying mechanisms remain largely unknown. A complete understanding of the cell pathways and dynamics and of the functioning of liver stem cell niche is necessary for the clinical translation of regenerative medicine strategies. As well, it will be crucial to elucidate the mechanisms through which cells interact with the extracellular matrix, and how this latter supports and drives cell fate. PMID:23322990

  18. Hydrogen sulfide and the liver.

    PubMed

    Mani, Sarathi; Cao, Wei; Wu, Lingyun; Wang, Rui

    2014-09-15

    Hydrogen sulfide (H2S) is a gasotransmitter that regulates numerous physiological and pathophysiological processes in our body. Enzymatic production of H2S is catalyzed by cystathionine ?-lyase (CSE), cystathionine ?-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST). All these three enzymes present in the liver and via H2S production regulate liver functions. The liver is the hub for metabolism of glucose and lipids, and maintains the level of circulatory lipids through lipoprotein metabolism. Hepatic H2S metabolism affects glucose metabolism, insulin sensitivity, lipoprotein synthesis, mitochondrial biogenetics and biogenesis. Malfunction of hepatic H2S metabolism may be involved in many liver diseases, such as hepatic fibrosis and hepatic cirrhosis. PMID:24582857

  19. Liver transplantation in children.

    PubMed

    Muiesan, Paolo; Vergani, Diego; Mieli-Vergani, Giorgina

    2007-02-01

    Liver transplantation (LT) is now a standard treatment for children with end-stage liver disease with excellent 1- and 5-year survival. This has been achieved through improvement of surgical techniques and anti-rejection treatment and management. The donor pool for children has been extended by the use of cut-down, split, living-related and, recently, non-heart-beating donor and isolated hepatocyte transplantation. Though the majority of transplanted children enjoy an excellent quality of life, there remain a high number of possible complications, including short-term primary non-function, vascular and biliary problems, bowel perforation, severe rejection, infection, hypertension and long-term renal impairment, chronic rejection, de novo autoimmunity, lymphoproliferative disease and cancer, most of which are related to anti-rejection drug toxicity. Hence, the focus of research for paediatric LT should be induction of tolerance, avoiding long-term immunosuppression and its toxicity. PMID:17161491

  20. Role of Ras signaling in erythroid differentiation of mouse fetal liver cells: functional analysis by a flow cytometry-based novel culture system.

    PubMed

    Zhang, Jing; Socolovsky, Merav; Gross, Alec W; Lodish, Harvey F

    2003-12-01

    Ras signaling plays an important role in erythropoiesis. Its function has been extensively studied in erythroid and nonerythroid cell lines as well as in primary erythroblasts, but inconclusive results using conventional erythroid colony-forming unit (CFU-E) assays have been obtained concerning the role of Ras signaling in erythroid differentiation. Here we describe a novel culture system that supports terminal fetal liver erythroblast proliferation and differentiation and that closely recapitulates erythroid development in vivo. Erythroid differentiation is monitored step by step and quantitatively by a flow cytometry analysis; this analysis distinguishes CD71 and TER119 double-stained erythroblasts into different stages of differentiation. To study the role of Ras signaling in erythroid differentiation, different H-ras proteins were expressed in CFU-E progenitors and early erythroblasts with the use of a bicistronic retroviral system, and their effects on CFU-E colony formation and erythroid differentiation were analyzed. Only oncogenic H-ras, not dominant-negative H-ras, reduced CFU-E colony formation. Analysis of infected erythroblasts in our newly developed system showed that oncogenic H-ras blocks terminal erythroid differentiation, but not through promoting apoptosis of terminally differentiated erythroid cells. Rather, oncogenic H-ras promotes abnormal proliferation of CFU-E progenitors and early erythroblasts and supports their erythropoietin (Epo)-independent growth. PMID:12907435

  1. Effects of alanine substitutions in alpha-helices of sperm whale myoglobin on protein stability.

    PubMed Central

    Pinker, R. J.; Lin, L.; Rose, G. D.; Kallenbach, N. R.

    1993-01-01

    The peptide backbones in folded native proteins contain distinctive secondary structures, alpha-helices, beta-sheets, and turns, with significant frequency. One question that arises in folding is how the stability of this secondary structure relates to that of the protein as a whole. To address this question, we substituted the alpha-helix-stabilizing alanine side chain at 16 selected sites in the sequence of sperm whale myoglobin, 12 at helical sites on the surface of the protein, and 4 at obviously internal sites. Substitution of alanine for bulky side chains at internal sites destabilizes the protein, as expected if packing interactions are disrupted. Alanine substitutions do not uniformly stabilize the protein, either in capping positions near the ends of helices or at mid-helical sites near the surface of myoglobin. When corrected for the extent of exposure of each side chain replaced by alanine at a mid-helix position, alanine replacement still has no clear effect in stabilizing the native structure. Thus linkage between the stabilization of secondary structure and tertiary structure in myoglobin cannot be demonstrated, probably because of the relatively small free energy differences between side chains in stabilizing isolated helix. By contrast, about 80% of the variance in free energy observed can be accounted for by the loss in buried surface area of the native residue substituted by alanine. The differential free energy of helix stabilization does not account for any additional variation. PMID:8358293

  2. Fed-batch two-phase production of alanine by a metabolically engineered Escherichia coli.

    PubMed

    Smith, Geoffrey M; Lee, Sarah A; Reilly, Kevin C; Eiteman, Mark A; Altman, Elliot

    2006-10-01

    DL-Alanine was produced from glucose in an Escherichia coli pfl pps poxB ldhA aceEF pTrc99A-alaD strain which lacked pyruvate-formate lyase, phosphoenolpyruvate (PEP) synthase, pyruvate oxidase, lactate dehydogenase, components of the pyruvate dehydogenase complex and over-produced alanine dehydrogenase (ALD). A two-phase process was developed with cell growth under aerobic conditions followed by alanine production under anaerobic conditions. Using the batch mode, cells grew to 5.3 g/l in 9 h with the accumulation of 6-10 g acetate/l, and under subsequent anaerobic conditions achieved 34 g alanine/l in 13 h with a yield of 0.86 g/g glucose. Using the fed-batch mode at micro = 0.15 h(-1), only about 1 g acetate/l formed in the 25 h required for the cells to reach 5.6 g/l, and 88 g alanine/l accumulated during the subsequent 23 h. This fed-batch process attained an alanine volumetric productivity of 4 g/lh during the production phase, and a yield that was essentially 1 g/g. PMID:16902848

  3. EPR dosimetry of radiotherapy photon beams in inhomogeneous media using alanine films

    NASA Astrophysics Data System (ADS)

    Helge Østerås, Bjørn; Olaug Hole, Eli; Rune Olsen, Dag; Malinen, Eirik

    2006-12-01

    In the current work, EPR (electron paramagnetic resonance) dosimetry using alanine films (134 µm thick) was utilized for dose measurements in inhomogeneous phantoms irradiated with radiotherapy photon beams. The main phantom material was PMMA, while either Styrofoam or aluminium was introduced as an inhomogeneity. The phantoms were irradiated to a maximum dose of about 30 Gy with 6 or 15 MV photons. The performance of the alanine film dosimeters was investigated and compared to results from ion chamber dosimetry, Monte Carlo simulations and radiotherapy treatment planning calculations. It was found that the alanine film dosimeters had a linear dose response above approximately 5 Gy, while a background signal obscured the response at lower dose levels. For doses between 5 and 60 Gy, the standard deviation of single alanine film dose estimates was about 2%. The alanine film dose estimates yielded results comparable to those from the Monte Carlo simulations and the ion chamber measurements, with absolute differences between estimates in the order of 1 15%. The treatment planning calculations exhibited limited applicability. The current work shows that alanine film dosimetry is a method suitable for estimating radiotherapeutical doses and for dose measurements in inhomogeneous media.

  4. Comparison Between IGL-1 and HTK Preservation Solutions in Deceased Donor Liver Transplantation.

    PubMed

    Meine, M H; Leipnitz, I; Zanotelli, M L; Schlindwein, E S; Kiss, G; Martini, J; de Medeiros Fleck, A; Mucenic, M; de Mello Brandão, A; Marroni, C A; Craco Cantisani, G P

    2015-05-01

    The effectiveness of liver preservation solutions remains in evidence. Cold ischemia time, steatosis, expanded criterion donors, operational cost, and survival represent important roles in its success. In a prospective cohort study between August 2009 and April 2014, 178 patients were allocated into an Institut Georges Lopez - 1 (IGL-1) solution group (63.5%) or histidine-tryptophan-ketoglutarate (HTK) group (36.5%). There were no differences among recipient's characteristics including age, skin color, gender, Model for End-stage Liver Disease score, acute rejection, cholestasis, and reperfusion syndrome incidences. Also, donors, age average, skin color, donor risk index, time in intensive care unit, hemodynamic variables, infections, and steatosis incidences were similar. The average cold ischemia time was 494 minutes in the IGL-1 group and 489 minutes in the HTK group (P = .77). Alanine aminotransferase and aspartate aminotransferase serum levels on the first postoperative day were 707 and 1185 mg/dL, respectively, with IGL-1 and 1298 and 2291 mg/dL, respectively, with HTK (P = .016) and similar at day 15 (P > .88). The incidence of delayed graft function was 4.5% with IGL-1 and 4.6% with HTK (P = .90). The incidence primary nonfunction was 2.7% with IGL-1 and 3.1% with HTK (P = .71). The incidence of perioperative death was 11.5% with IGL-1 and 13.8% with HTK (P = .94). The survival in 30 months was 86% in IGL-1 group and 82% in HTK group (P = .66). Both preservation solutions are efficient to liver transplantations with deceased donors. Major prospective trials are necessary to evaluate each preservation solution's particularities. The preservation solution availability in each transplantation center must guide its use at the present moment. PMID:26036479

  5. Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury

    PubMed Central

    Jang, Sun-Hee; Cho, Sung-woo; Yoon, Hyun-Min; Jang, Kyung-Jeon; Song, Chun-Ho; Kim, Cheol-Hong

    2014-01-01

    Objectives: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP) against hepatotoxicity induced by acute ethanol (EtOH) intoxication in rats. Methods: Sprague-Dawley (SD) rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP) and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW). The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14) and Taechung (LR3). A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. Results: GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT) enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST) enzyme. It also significantly ameliorated the superoxide dismutase (SOD) and the catalase (CAT) activities. Conclusion: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol-metabolizing enzymes and by attenuating oxidative stress. PMID:25780705

  6. Liver Cell Death

    Microsoft Academic Search

    Harmeet Malhi; Gregory J. Gores

    \\u000a Hepatocyte cell death is an indispensible and cardinal element that precipitates and perpetuates liver injury [1]. Accordingly,\\u000a liver injury can result in acute or chronic liver disease. This distinction between acute and chronic liver disease is arbitrary;\\u000a a reflection of the etiology and time course of liver injury. Hepatocytes are the predominant parenchymal cell type in the\\u000a liver. Commonly encountered

  7. Cell Sources, Liver Support Systems and Liver Tissue Engineering: Alternatives to Liver Transplantation

    PubMed Central

    Lee, Soo Young; Kim, Han Joon; Choi, Dongho

    2015-01-01

    The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells. PMID:26019753

  8. Cell sources, liver support systems and liver tissue engineering: alternatives to liver transplantation.

    PubMed

    Lee, Soo Young; Kim, Han Joon; Choi, Dongho

    2015-05-01

    The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells. PMID:26019753

  9. Toxic Effects of Silver Nanoparticles on Liver and Some Hematological Parameters in Male and Female Mice (Mus musculus).

    PubMed

    Heydrnejad, M Saeed; Samani, Roya Jafarzadeh; Aghaeivanda, Simin

    2015-06-01

    This research was carried out to evaluate toxic effects of nanosilver (Ag-NPs) on liver function and some blood parameters of male and female mice Mus musculus. A group of 54 BALB/c mice was randomly divided into three groups (each with two replications): Ag-NP (2) and control (1), each with nine mice. The experiment lasted for 14 days. In the treatment groups, two different doses of 20 and 50 ppm of Ag-NP solution were administered orally, while in the untreated (control) group, no Ag-NP solution but distilled water was used. At the end of the experiment, the serum was obtained by centrifugation of the whole blood at 3000 rpm for 15 min. The biochemical levels including alanine aminotransferase (ALT), aspartate amino transferase (AST), and blood cells were assayed by an automatic biochemical analyzer. Also, liver biopsy was performed and samples were stained using hematoxylin and eosin (H&E) staining. The values of red blood cells (RBC), hemoglobin (Hb), and hematocrit (Hct) did not vary significantly in the control and Ag-NP-treated animals. There were significant changes in the treatment and control groups in the levels of liver enzymes so that at both doses, there were significantly elevated levels of ALT and AST in mice treated with Ag-NPs compared with the control (p?liver with no significant changes between male and female mice. PMID:25637567

  10. Association of Liver Enzymes and Computed Tomography Markers of Liver Steatosis with Familial Longevity

    PubMed Central

    Sala, Michiel; Kroft, Lucia J. M.; Röell, Boudewijn; van der Grond, Jeroen; Slagboom, P. Eline; Mooijaart, Simon P.; de Roos, Albert; van Heemst, Diana

    2014-01-01

    Objective Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT). Research Design and Methods: We measured nonfasting alanine transaminase (ALT), aspartate aminotransferase (AST), and ?-glutamyl transferase (GGT) in 1625 subjects (736 men, mean age 59.1 years) from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n?=?230) were evaluated and CT was performed (n?=?268) for assessment of liver-spleen (L/S) ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD). Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. Results Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p?=?0.03), while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p?=?0.25 and 8% versus 8%, p?=?0.91, respectively). Conclusions Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver steatosis is similar between offspring of long-lived siblings and control subjects. PMID:24632889

  11. Normal liver stiffness: A study in living donors with normal liver histology

    PubMed Central

    Alsebaey, Ayman; Allam, Naglaa; Alswat, Khalid; Waked, Imam

    2015-01-01

    AIM: To define the normal range of liver stiffness (LS) values using transient elastography in living-related liver transplantation candidate donors with normal liver histology. METHODS: LS was measured using Fibroscan in 50 (16 women, 34 men) healthy potential donors (mean age 28.4 ± 5.9 years) who were being evaluated for liver donation for their relatives at the National Liver Institute, Menoufeya University, Egypt. All potential donors had normal liver tests and were negative for hepatitis B or C virus infection. Abdominal ultrasounds showed normal findings. None of the subjects had diabetes, hypertension, renal impairment, heart disease, or body mass index > 30 kg/m2. All subjects had normal liver histology upon liver biopsy. They all donated the right lobe of their liver with successful outcomes. RESULTS: The mean LS was 4.3 ± 1.2 kPa (range: 1.8-7.1 kPa). The 5th and 95th percentiles of normal LS were 2.6 kPa and 6.8 kPa, respectively, with a median of 4 kPa; the interquartile range was 0.6 ± 0.4. LS measurements were not significantly different between men and women (4.4 ± 1.1 kPa vs 3.9 ± 1.3 kPa) and did not correlate with age. However, stiffness values were significantly lower in subjects with a body mass index < 26 kg/m2 compared to those with an index ? 26 kg/m2 (4.0 ± 1.1 kPa vs 4.6 ± 1.2 kPa; P <0.05). There were no differences in hospital stay or postoperative bilirubin, albumin,alanine and aspartate transaminases, or creatinine levels (at discharge) between donors with livers stiffness ? 4 kPa and those with stiffness > 4 kPa. CONCLUSION: Healthy donors with normal liver histology have a median LS of 4 kPa. Stiffness values are elevated relative to increase in body mass index. PMID:26052404

  12. Acute Liver Failure in an Antimitochondrial Antibody-Positive 63-Year-Old Man

    PubMed Central

    Wakamatsu, Toru; Kanda, Tatsuo; Tawada, Akinobu; Miyamura, Tatsuo; Takahashi, Masanori; Chiba, Tetsuhiro; Arai, Makoto; Maruyama, Hitoshi; Fujiwara, Keiichi; Imazeki, Fumio; Yokosuka, Osamu

    2012-01-01

    Antimitochondrial antibody (AMA) is one of the representative features of primary biliary cirrhosis (PBC). PBC is a female-dominant disease usually presenting intrahepatic bile duct destruction, cholestasis and fibrosis with or without chronic nonsuppurative destructive cholangitis. We presented the case of a 63-year-old man with acute liver failure who had AMA, pronounced alanine aminotransferase elevation and high bilirubinemia. We administered corticosteroids and rescued this patient without liver transplantation. It is well known that some patients within the spectrum of autoimmune liver disease present with characteristics of both PBC and autoimmune hepatitis. Although corticosteroids may be associated with a significant worsening of adverse events in patients with PBC, if acute liver failure in AMA-positive cases is progressive, the administration of corticosteroids has to be considered, as well as the preparation of urgent liver transplantation. PMID:22933985

  13. HIF-1{alpha} is necessary to support gluconeogenesis during liver regeneration

    SciTech Connect

    Tajima, Toshihide [Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)] [Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Goda, Nobuhito, E-mail: goda@waseda.jp [Department of Life Science and Medical Bio-Science, School of Advanced Science and Engineering, Waseda University, TWIns 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan)] [Department of Life Science and Medical Bio-Science, School of Advanced Science and Engineering, Waseda University, TWIns 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan); Fujiki, Natsuko; Hishiki, Takako; Nishiyama, Yasumasa [Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)] [Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Senoo-Matsuda, Nanami [Department of Life Science and Medical Bio-Science, School of Advanced Science and Engineering, Waseda University, TWIns 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan)] [Department of Life Science and Medical Bio-Science, School of Advanced Science and Engineering, Waseda University, TWIns 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan); Shimazu, Motohide [Department of Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998 (Japan)] [Department of Surgery, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo 193-0998 (Japan); Soga, Tomoyoshi [The Institute for Advanced Biosciences, Keio University, Tsuruoka City, Yamagata 997-0052 (Japan)] [The Institute for Advanced Biosciences, Keio University, Tsuruoka City, Yamagata 997-0052 (Japan); Yoshimura, Yasunori [Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)] [Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan); Johnson, Randall S. [Molecular Biology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093 (United States)] [Molecular Biology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093 (United States); Suematsu, Makoto [Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)] [Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 (Japan)

    2009-10-02

    Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1{alpha} (HIF-1{alpha}) for hepatic glucose homeostasis during the reparative process, we inactivated the gene in hepatocytes in vivo. Following partial hepatectomy (PH), recovery of residual liver weight was initially retarded in the mutant mice by down-regulation of hepatocyte proliferation, but occurred comparably between the mutant and control mice at 72 h after PH. At this time point, the mutant mice showed lowered blood glucose levels with enhanced accumulation of glycogen in the liver. The mutant mice exhibited impairment of hepatic gluconeogenesis as assessed by alanine tolerance test. This appeared to result from reduced expression of PGK-1 and PEPCK since 3-PG, PEP and malate were accumulated to greater extents in the regenerated liver. In conclusion, these findings provide evidence for roles of HIF-1{alpha} in the regulation of gluconeogenesis under liver regeneration.

  14. Evaluation of fatty liver by using in-phase and opposed-phase MR images and in-vivo proton MR spectroscopy

    NASA Astrophysics Data System (ADS)

    Lee, Jae-Seung; Im, In-Chul; Goo, Eun-Hoe; Park, Hyong-Hu; Kwak, Byung-Joon

    2012-12-01

    The purpose of this study was to evaluate the necessity of in-phase and opposed-phase MR images and their correlations with weight, the aspartate aminotransferase/alanine aminotransferase (AST/ALT) value, and age. Magnetic resonance spectroscopy (MRS) was used as a reference in this study. We selected 68 people as subjects, among which 14 were volunteers with normal AST/ALT values ( <40/35 U/L) on a liver function study and 54 were non-alcoholic fatty liver patients for whom ultrasonic images had been obtained within 3 months of the study. In this study, the liver was more enhanced than the spleen or kidney. When the Eq. (3) formula was applied to normal volunteers, the difference between the in-phase and the opposed-phase images was -3.54 ± 12.56. The MRS study result showed a high sensitivity of 96.6% and a specificity of 100% ( p = 0.000) when the cutoff value was 20%. Furthermore, this result showed a high sensitivity of 94% and a specificity of 80% with a similar cutoff when the Eq. (2) formula was applied to non-alcoholic fatty liver patients ( p = 0.000). The MRS study revealed a strong correlation between normal volunteers and non-alcoholic fatty liver patients (r = 0.59, p = 0.04). The correlations between AST/ALT and Eq. (3) (r = 0.45, p = 0.004), age and Eq. (3) (r = 0.73, p = 0.03), and weight and Eq. (3) (r = 0.77, p = 0.000) values were all statistically significant. In the case of non-alcoholic liver disease, MRS was found to be significantly correlated with Eq. (1) (r = 0.39, p = 0.002), Eq. (2) (r = 0.68, p = 0.04), Eq. (3) (r = 0.67, p = 0.04), and AST/ALT (r = 0.77, p = 0.000). In conclusion, in-phase and opposed-phase images can help to distinguish a normal liver from a fatty liver in order to identify non-alcoholic fatty liver patients. The intensity difference between the in-phase and opposed-phase MR signals showed valuable correlations with respect to weight, AST/ALT value, and age, with all values being above the mild lipid value (r = 0.3).

  15. ABS–Scan: In silico alanine scanning mutagenesis for binding site residues in protein–ligand complex

    PubMed Central

    Anand, Praveen; Nagarajan, Deepesh; Mukherjee, Sumanta; Chandra, Nagasuma

    2014-01-01

    Most physiological processes in living systems are fundamentally regulated by protein–ligand interactions. Understanding the process of ligand recognition by proteins is a vital activity in molecular biology and biochemistry. It is well known that the residues present at the binding site of the protein form pockets that provide a conducive environment for recognition of specific ligands. In many cases, the boundaries of these sites are not well defined. Here, we provide a web-server to systematically evaluate important residues in the binding site of the protein that contribute towards the ligand recognition through in silico alanine-scanning mutagenesis experiments. Each of the residues present at the binding site is computationally mutated to alanine. The ligand interaction energy is computed for each mutant and the corresponding ??G values are calculated by comparing it to the wild type protein, thus evaluating individual residue contributions towards ligand interaction. The server will thus provide a ranked list of residues to the user in order to obtain loss-of-function mutations. This web-tool can be freely accessed through the following address: http://proline.biochem.iisc.ernet.in/abscan/. PMID:25685322

  16. Effect of hepatic function on the EC50 of midazolam and the BIS50 at the time of loss of consciousness*

    PubMed Central

    Li, Yu-hong; He, Rui; Ruan, Jin-guang

    2014-01-01

    Objective: To explore the effect of hepatic function on loss of consciousness (LOC) and bispectral index (BIS) during sedation with midazolam (MDZ). Methods: Forty-five patients were assigned to three groups according to their liver function. Thirty of these patients with diagnoses of cholelithiasis were scheduled laparoscopic cholecystectomy, including 15 patients with normal liver function (normal group), and 15 patients with moderately abnormal liver function based on the results of ultrasonic diagnosis of a moderately fatty liver and elevated alanine transaminase levels of less than three times normal (moderate group). The other 15 patients with end-stage liver disease (severe group) underwent liver transplantation. Each patient was administered MDZ by way of target-controlled infusion to increase the concentration gradually. At the time of LOC, the BIS was recorded and a blood sample was withdrawn for measurement of the concentration of MDZ. The concentration of MDZ (EC50) and the BIS value (BIS50) at which 50% of patients lose consciousness were calculated using logistic regression. Results: At the time of LOC, the EC50 of MDZ and the BIS50 were similar in the normal and moderate groups (P>0.05). LOC occurred at a lower EC50 of MDZ and at a higher BIS50 in the severe group, compared with the normal and moderate groups (P<0.01). Conclusions: Patients with end-stage liver disease were more sensitive to MDZ and this affected the prediction of their time of LOC following MDZ administration. There were no changes in response in patients with moderately abnormal hepatic function. PMID:25091993

  17. Novel function of glutathione transferase in rat liver mitochondrial membrane: Role for cytochrome c release from mitochondria

    SciTech Connect

    Lee, Kang Kwang; Shimoji, Manami; Hossain, Quazi Sohel [Laboratory of Molecular Genetics and Pharmacology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 (Japan); Sunakawa, Hajime [Department of Oral and Maxillofacial Functional Rehabilitation, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 (Japan); Aniya, Yoko [Laboratory of Molecular Genetics and Pharmacology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215 (Japan)], E-mail: yaniya@med.u-ryukyu.ac.jp

    2008-10-01

    Microsomal glutathione transferase (MGST1) is activated by oxidative stress. Although MGST1 is found in mitochondrial membranes (mtMGST1), there is no information about the oxidative activation of mtMGST1. In the present study, we aimed to determine whether mtMGST1 also undergoes activation and about its function. When rats were treated with galactosamine/lipopolysaccharide (GalN/LPS), mtMGST1 activity was significantly increased, and the increased activity was reduced by the disulfide reducing agent dithiothreitol. In mitochondria from GalN/LPS-treated rats, disulfide-linked mtMGST1 dimer and mixed protein glutathione disulfides (glutathionylation) were detected. In addition, cytochrome c release from mitochondria isolated from GalN/LPS-treated rats was observed, and the release was inhibited by anti-MGST1 antibodies. Incubation of mitochondria from control rats with diamide and diamide plus GSH in vitro resulted in dimer- and mixed disulfide bond-mediated activation of mtMGST1, respectively. The activation of mtMGST1 by diamide plus GSH caused cytochrome c release from the mitochondria, and the release was prevented by treatment with anti-MGST1 antibodies. In addition, diamide plus GSH treatment caused mitochondrial swelling accompanied by cytochrome c release, which was inhibited by cyclosporin A (CsA) and bongkrekic acid (BKA), inhibitors of the mitochondrial permeability transition (MPT) pore. Furthermore, mtMGST1 activity was also inhibited by CsA and BKA. These results indicate that mtMGST1 is activated through mixed disulfide bond formation that contributes to cytochrome c release from mitochondria through the MPT pore.

  18. Identification of the roles of individual amino acid residues of the helix E of the major antenna of photosystem II (LHCII) by alanine scanning mutagenesis.

    PubMed

    Liu, Cheng; Rao, Yan; Zhang, Lei; Yang, Chunhong

    2014-10-01

    The functions of the helix E (W97-F105), an amphiphilic lumenal 310 helix of the major antenna of photosystem II (LHCII), are still unidentified. To elucidate the roles of individual amino acid residue of the helix E, alanine scanning mutagenesis has been performed to mutate every residue of this domain to alanine. The influence of every alanine substitution on the structure and function of LHCII has been investigated biochemically and spectroscopically. The results show that all mutations have little impact on the pigment binding and configuration. However, many mutants presented decreased thermo- or photo-stability compared with the wild type, highlighting the significance of this helix to the stability of LHCII. The most critical residue for stability is W97. The mutant W97A yielded very fragile trimeric pigment protein complexes. The structural analysis revealed that the hydrogen bonding and aromatic interactions between W97, F195, F194 and a water molecule contributed greatly to the stability of LHCII. Moreover, Q103A and F105A have been identified to be able to reinforce the tendency of aggregation in vitro. The structural analysis suggested that the enhancement in aggregation formation for Q103A and F105A might be attributed to the changing hydrophobicity of the region. PMID:24753330

  19. Mapping protein-protein interactions with phage-displayed combinatorial peptide libraries and alanine scanning.

    PubMed

    Kokoszka, Malgorzata E; Kay, Brian K

    2015-01-01

    One avenue for inferring the function of a protein is to learn what proteins it may bind to in the cell. Among the various methodologies, one way for doing so is to affinity select peptide ligands from a phage-displayed combinatorial peptide library and then to examine if the proteins that carry such peptide sequences interact with the target protein in the cell. With the protocols described in this chapter, a laboratory with skills in microbiology, molecular biology, and protein biochemistry can readily identify peptides in the library that bind selectively, and with micromolar affinity, to a given target protein on the time scale of 2 months. To illustrate this approach, we use a library of bacteriophage M13 particles, which display 12-mer combinatorial peptides, to affinity select different peptide ligands for two different targets, the SH3 domain of the human Lyn protein tyrosine kinase and a segment of the yeast serine/threonine protein kinase Cbk1. The binding properties of the selected peptide ligands are then dissected by sequence alignment, Kunkel mutagenesis, and alanine scanning. Finally, the peptide ligands can be used to predict cellular interacting proteins and serve as the starting point for drug discovery. PMID:25616333

  20. The cyanobacterial amino acid ?-N-methylamino-l-alanine perturbs the intermediary metabolism in neonatal rats.

    PubMed

    Engskog, Mikael K R; Karlsson, Oskar; Haglöf, Jakob; Elmsjö, Albert; Brittebo, Eva; Arvidsson, Torbjörn; Pettersson, Curt

    2013-10-01

    The neurotoxic amino acid ?-N-methylamino-l-alanine (BMAA) is produced by most cyanobacteria. BMAA is considered as a potential health threat because of its putative role in neurodegenerative diseases. We have previously observed cognitive disturbances and morphological brain changes in adult rodents exposed to BMAA during the development. The aim of this study was to characterize changes of major intermediary metabolites in serum following neonatal exposure to BMAA using a non-targeted metabolomic approach. NMR spectroscopy was used to obtain serum metabolic profiles from neonatal rats exposed to BMAA (40, 150, 460mg/kg) or vehicle on postnatal days 9-10. Multivariate data analysis of binned NMR data indicated metabolic pattern differences between the different treatment groups. In particular five metabolites, d-glucose, lactate, 3-hydroxybutyrate, creatine and acetate, were changed in serum of BMAA-treated neonatal rats. These metabolites are associated with changes in energy metabolism and amino acid metabolism. Further statistical analysis disclosed that all the identified serum metabolites in the lowest dose group were significantly (p<0.05) decreased. The neonatal rat model used in this study is so far the only animal model that displays significant biochemical and behavioral effects after a low short-term dose of BMAA. The demonstrated perturbation of intermediary metabolism may contribute to BMAA-induced developmental changes that result in long-term effects on adult brain function. PMID:23886855

  1. Anisotropy-Guided Enantiomeric Enhancement in AlanineUsing Far-UV Circularly Polarized Light

    NASA Astrophysics Data System (ADS)

    Meinert, Cornelia; Cassam-Chenaï, Patrick; Jones, Nykola C.; Nahon, Laurent; Hoffmann, Søren V.; Meierhenrich, Uwe J.

    2015-06-01

    All life on Earth is characterized by its asymmetry - both the genetic material and proteins are composed of homochiral monomers. Understanding how this molecular asymmetry initially arose is a key question related to the origins of life. Cometary ice simulations, l-enantiomeric enriched amino acids in meteorites and the detection of circularly polarized electromagnetic radiation in star-forming regions point to a possible interstellar/protostellar generation of stereochemical asymmetry. Based upon our recently recorded anisotropy spectra g( ?) of amino acids in the vacuum-UV range, we subjected amorphous films of racemic 13C-alanine to far-UV circularly polarized synchrotron radiation to probe the asymmetric photon-molecule interaction under interstellar conditions. Optical purities of up to 4 % were reached, which correlate with our theoretical predictions. Importantly, we show that chiral symmetry breaking using circularly polarized light is dependent on both the helicity and the wavelength of incident light. In order to predict such stereocontrol, time-dependent density functional theory was used to calculate anisotropy spectra. The calculated anisotropy spectra show good agreement with the experimental ones. The European Space Agency's Rosetta mission, which successfully landed Philae on comet 67P/Churyumov-Gerasimenko on 12 November 2014, will investigate the configuration of chiral compounds and thereby obtain data that are to be interpreted in the context of the results presented here.

  2. Anisotropy-Guided Enantiomeric Enhancement in AlanineUsing Far-UV Circularly Polarized Light.

    PubMed

    Meinert, Cornelia; Cassam-Chenaï, Patrick; Jones, Nykola C; Nahon, Laurent; Hoffmann, Søren V; Meierhenrich, Uwe J

    2015-06-01

    All life on Earth is characterized by its asymmetry - both the genetic material and proteins are composed of homochiral monomers. Understanding how this molecular asymmetry initially arose is a key question related to the origins of life. Cometary ice simulations, L-enantiomeric enriched amino acids in meteorites and the detection of circularly polarized electromagnetic radiation in star-forming regions point to a possible interstellar/protostellar generation of stereochemical asymmetry. Based upon our recently recorded anisotropy spectra g(?) of amino acids in the vacuum-UV range, we subjected amorphous films of racemic (13)C-alanine to far-UV circularly polarized synchrotron radiation to probe the asymmetric photon-molecule interaction under interstellar conditions. Optical purities of up to 4 % were reached, which correlate with our theoretical predictions. Importantly, we show that chiral symmetry breaking using circularly polarized light is dependent on both the helicity and the wavelength of incident light. In order to predict such stereocontrol, time-dependent density functional theory was used to calculate anisotropy spectra. The calculated anisotropy spectra show good agreement with the experimental ones. The European Space Agency's Rosetta mission, which successfully landed Philae on comet 67P/Churyumov-Gerasimenko on 12 November 2014, will investigate the configuration of chiral compounds and thereby obtain data that are to be interpreted in the context of the results presented here. PMID:25773582

  3. D-Alanine in the Islets of Langerhans of Rat Pancreas

    PubMed Central

    Ota, Nobutoshi; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2014-01-01

    Relatively high levels of D-alanine (D-Ala), an endogenous D-amino acid, have been found in the endocrine systems of several animals, especially in the anterior pituitary; however, its functional importance remains largely unknown. We observed D-Ala in islets of Langerhans isolated from rat pancreas in significantly higher levels than in the anterior/intermediate pituitary; specifically, 180 ± 60 fmol D-Ala per islet (300 ± 100 nmol/g islet), and 10 ± 2.5 nmol/g of wet tissue in pituitary. Additionally, 12 ± 5% of the free Ala in the islets was in the D-isomer, almost an order of magnitude higher than the percentage of D-Ala found in the pituitary. Surprisingly, glucose stimulation of the islets resulted in D-Ala release of 0.6 ± 0.5 fmol per islet. As D-Ala is stored in islets and released in response to changes in extracellular glucose, D-Ala may have a hormonal role. PMID:24721429

  4. Two alanine aminotranferases link mitochondrial glycolate oxidation to the major photorespiratory pathway in Arabidopsis and rice

    PubMed Central

    Niessen, Markus; Krause, Katrin; Horst, Ina; Staebler, Norma; Klaus, Stephanie; Gaertner, Stefanie; Kebeish, Rashad; Araujo, Wagner L.; Fernie, Alisdair R.; Peterhansel, Christoph

    2012-01-01

    The major photorespiratory pathway in higher plants is distributed over chloroplasts, mitochondria, and peroxisomes. In this pathway, glycolate oxidation takes place in peroxisomes. It was previously suggested that a mitochondrial glycolate dehydrogenase (GlcDH) that was conserved from green algae lacking leaf-type peroxisomes contributes to photorespiration in Arabidopsis thaliana. Here, the identification of two Arabidopsis mitochondrial alanine:glyoxylate aminotransferases (ALAATs) that link glycolate oxidation to glycine formation are described. By this reaction, the mitochondrial side pathway produces glycine from glyoxylate that can be used in the glycine decarboxylase (GCD) reaction of the major pathway. RNA interference (RNAi) suppression of mitochondrial ALAAT did not result in major changes in metabolite pools under standard conditions or enhanced photorespiratroy flux, respectively. However, RNAi lines showed reduced photorespiratory CO2 release and a lower CO2 compensation point. Mitochondria isolated from RNAi lines are incapable of converting glycolate to CO2, whereas simultaneous overexpression of GlcDH and ALAATs in transiently transformed tobacco leaves enhances glycolate conversion. Furthermore, analyses of rice mitochondria suggest that the side pathway for glycolate oxidation and glycine formation is conserved in monocotyledoneous plants. It is concluded that the photorespiratory pathway from green algae has been functionally conserved in higher plants. PMID:22268146

  5. Association between serum concentrations of hexachlorobenzene and polychlorobiphenyls with thyroid hormone and liver enzymes in a sample of the general population

    PubMed Central

    Sala, M; Sunyer, J; Herrero, C; To-Figueras, J; Grimalt, J

    2001-01-01

    OBJECTIVES—Hexachlorobenzene (HCB) is a highly lipophilic organochlorine compound of widespread environmental occurrence, that accumulates in the biological system. It affects the porphyrine metabolism, thyroid hormones, and the liver function in animals. Although HCB is one of the most common organochlorine compound in humans, little investigation on its health effects has been done. Polychlorobiphenyls (PCBs) are also widespread toxic environmental contaminants. The aim of the present study was to investigate the association of serum HCB and PCB concentrations with thyroid hormone status and liver enzymes in human.?METHODS—Thyroid stimulating hormone (TSH), total and free thyroxine (T4), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ?-glutamyltransferase (GGT) were measured as biological markers of thyroid and liver function in a rural population sample older than 14 years (n=192, except for TSH with n=608) highly exposed to HCB. Serum concentrations of HCB were measured by gas chromatography coupled to electron capture detection.?RESULTS—After adjustment for confounding variables, there was a significant negative association between serum HCB concentrations and total T4 (a decrease of 0.32 µg/dl per each unit, ln ng/ml, of increase of HCB) and a positive association with GGT (a relative increase of 10 % per each ln unit of increase of HCB), although most subjects (92%) were within the normal range for both T4 and GGT. These associations were not modified after adjustment for total lipid content or for other organochlorine compounds. The association of T4 and GGT with PCB was smaller although significant. No association was found with the other biochemical markers.?CONCLUSIONS—These results suggest that the internal dose of HCB of this population may reflect a subtle metabolic effect on thyroid function and an enzymatic induction activity. Further studies are needed to evaluate the health impact of these effects in more susceptible populations, such as infants.???Keywords: hexachlorobenzene; environmental exposure; thyroid; liver enzymes PMID:11171930

  6. Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: current status and challenges.

    PubMed

    Senior, John R

    2014-11-01

    Prompted by approval in 1997 of troglitazone and bromfenac, two drugs that promptly began to show serious and sometimes fatal liver toxicity, we began at the Food and Drug Administration (FDA) a series of annual conferences in 1999 to consider issues of drug-induced liver injury (DILI). First inviting reviewers of new drug applications we opened the audiences in 2001 to pharmaceutical industry and academic consultants to industry and FDA, and slides shown at the meetings were posted on the internet to be available at the website of the American Association for the Study of Liver Diseases (AASLD)-go to ( http://www.aasld.org/dili/Pages/default.aspx ). Observations by Dr. Hyman J. Zimmerman that "drug-induced hepatocellular jaundice is a serious lesion" with possible mortality formed a basis for developing a computer program to plot peak serum values for alanine aminotransferase (ALT) and total bilirubin (TBL) in an x-y log-log graph for all subjects enrolled in clinical trials. This program had the capability to show the time course of all liver tests for individuals who had both hepatocellular injury and reduced whole liver function, plus clinical narratives to diagnose the severity and most likely cause of the abnormalities. We called the program eDISH (for evaluation of Drug-Induced Serious Hepatotoxicity), and began in 2004 to use it to assess DILI in clinical trial subjects. From 2008, comments made by the presenters at the conferences about their slides and ensuing discussions have been added to the website. All this has raised awareness of the problem, and since 1997, the FDA has not had to withdraw a single drug because of post-marketing hepatotoxicity. Many issues still remain to be resolved; among the most controversial is the best method to estimate likelihood that a given liver injury was actually caused by the drug in question. On November 9, 2012, a workshop was convened to discuss the best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. PMID:25352324

  7. Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease

    Microsoft Academic Search

    Xi Chen; Shihui Xing; Yanqing Feng; Songlin Chen; Zhong Pei; Chuhuai Wang; Xiuling Liang

    2011-01-01

    Background  Recent studies have demonstrated that normal bone marrow (BM) cells transplantation can correct liver injury in a mouse model\\u000a of Wilson disease (WD). However, it still remains unknown when BM cells transplantation should be administered. The aim of\\u000a this study was to investigate the potential impact of normal BM cells transplantation at different stages of WD to correct\\u000a liver injury

  8. The effect of warm liver ischaemia & reperfusion injury on circulating plasma lipid levels & lipolytic enzyme activity in rat & the impact of ischaemic preconditioning

    PubMed Central

    Lanitis, Sophocles; Lolis, Evangelos; Dafnios, Nikolaos; Sgourakis, George; Voros, Dionysios C.; Vassiliou, Ioannis

    2012-01-01

    Background & objectives: Ischaemia/reperfusion (I/R) associated with major liver surgery compromises liver function. Ischaemic preconditioning (IPC) may be effective in minimizing hepatic I/R injury. This study aimed to investigate the impact of liver ischaemic manipulations on lipid metabolism in rat during the process of liver recovery after liver surgery. Methods: Sixty three male Wistar rats were assigned to three groups: the sham group, the I/R group which underwent warm ischaemia and reperfusion (I/R), and the IPC group. The animals were subdivided in 3 groups [1st, 3rdand 7th postoperative day (PO)]. Hepatic lipase (HL) and total lipase (TL) activity and the levels of aspartate and alanine transaminases (AST, ALT), triglycerides, HDL and cholesterol were measured in plasma. Results: There was no significant difference in the activity of HL and TL between the groups. Significant higher levels of HDL (P<0.0001) were observed in the IPC group when compared to the other groups on the 3rd PO day. Triglycerides (P<0.0001) and HDL (P=0.003) in the IPC group were higher than the sham group on the 7th PO day while HDL was also higher in the I/R group. Significantly higher cholesterol levels were found in the I/R and IPC groups on the 7th PO day, which were not observed in the sham group. There was a similar curve for triglycerides in the sham and IPC groups while there were significantly higher levels of triglycerides on day 7 for the I/R group. The levels of HDL in the IPC group were higher on the 3rd and 7th PO day, compared to day 1. Interpretation & conclusion: Warm ischaemia and I/R injury do not seem to affect lipolytic enzyme activity after the 1st PO day despite the effects on plasma lipids. IPC seems to prevent accumulation of triglycerides and cholesterol in plasma. PMID:22960895

  9. The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension.

    PubMed

    Seo, Yeon Seok; Shah, Vijay H

    2012-12-01

    Because of the anatomical position and its unique vascular system, the liver is susceptible to the exposure to the microbial products from the gut. Although large amount of microbes colonize in the gut, translocation of the microbes or microbial products into the liver and systemic circulation is prevented by gut epithelial barrier function and cleansing and detoxifying functions of the liver in healthy subjects. However, when the intestinal barrier function is disrupted, large amount of bacterial products can enter into the liver and systemic circulation and induce inflammation through their receptors. Nowadays, there have been various reports suggesting the role of gut flora and bacterial translocation in the pathogenesis of chronic liver disease and portal hypertension. This review summarizes the current knowledge about bacterial translocation and its contribution to the pathogenesis of chronic liver diseases and portal hypertension. PMID:23323248

  10. Voriconazole and the liver

    PubMed Central

    Mih?il?, Romeo-Gabriel

    2015-01-01

    Voriconazole is an azole useful for the prophylaxis and the treatment of aspergillosis and other fungal infections in immunosuppressed subjects, as those found in aplasia after aggressive polychemotherapy treatments, after hematopoietic stem cell, liver or lung transplantation. Its administration in therapeutic doses lead to extremely varied serum levels from patient to patient and even to the same patient. The explanations are varied: nonlinear pharmacokinetics, certain patient-related factors, including genetic polymorphisms in the cytochrome P450 2C19 gene, the kidney and liver function, simultaneous administration with other drugs metabolised by the same cytochrome. It is recommended to maintain the serum concentrations of voriconazole between 1.5 and 4 ?g/mL. At lower values its efficacy decreases and at higher values the risk of neurological toxicity increases. Even at these concentrations it is not excluded the possible appearance of a variety of toxic effects, including on the liver, manifested by cholestasis, hepatocytolisis, or their combination. It is recommended to monitor the clinical and laboratory evolution of all patients treated with voriconazole, and of the serum levels of the drug of those who belong to risk groups, even if there is still no consensus on this issue, given the lack of correlation between the serum level and the occurrence of adverse effects in many patients.

  11. Impact of Obstructive Sleep Apnea on Liver Fat Accumulation According to Sex and Visceral Obesity

    PubMed Central

    Toyama, Yoshiro; Tanizawa, Kiminobu; Kubo, Takeshi; Chihara, Yuichi; Harada, Yuka; Murase, Kimihiko; Azuma, Masanori; Hamada, Satoshi; Hitomi, Takefumi; Handa, Tomohiro; Oga, Toru; Chiba, Tsutomu; Mishima, Michiaki; Chin, Kazuo

    2015-01-01

    Rationale Associations between obstructive sleep apnea (OSA) and liver fat accumulation have been frequently investigated because both morbidities are common. Visceral fat was reported to be closely related to OSA and liver fat accumulation. Recently, sex differences in the association between OSA and mortality have gained much attention. Objectives To investigate the associations among OSA, liver fat accumulation as determined by computed tomography, and visceral fat area and their sex differences. Methods Studied were 188 males and 62 females who consecutively underwent polysomnography and computed tomography. Results Although the apnea-hypopnea index was positively correlated with liver fat accumulation in the total males, none of the OSA-related factors was independently associated with liver fat accumulation in either the total male or female participants in the multivariate analyses. When performing subanalyses using a specific definition for Japanese of obesity or visceral obesity (body mass index (BMI) ?25 kg/m2 or visceral fat area ?100 cm2), in only males without visceral obesity, percent sleep time with oxygen saturation <90%, in addition to BMI, insulin resistance, and serum triglyceride values, was independently correlated with liver fat accumulation (R2 = 15.1%, P<0.001). In males, percent sleep time of oxygen saturation <90% was also a determining factor for alanine aminotransferase values regardless of visceral fat area. In contrast, OSA was not associated with liver fat accumulation or alanine aminotransferase values in females whether or not visceral obesity was absent. Conclusions Sex differences in the visceral fat-dependent impact of OSA on liver fat accumulation existed. Although the mechanisms are not known and ethnic differences may exist in addition to the specific criteria of visceral obesity in Japan, the treatment of male patients with OSA might be favorable from the viewpoint of preventing liver fat accumulation and liver dysfunction even in patients without obvious visceral fat accumulation. PMID:26076443

  12. [The catalase inhibitor aminotriazole alleviates acute alcoholic liver injury].

    PubMed

    Ai, Qing; Ge, Pu; Dai, Jie; Liang, Tian-Cai; Yang, Qing; Lin, Ling; Zhang, Li

    2015-02-25

    In this study, the effects of catalase (CAT) inhibitor aminotriazole (ATZ) on alcohol-induced acute liver injury were investigated to explore the potential roles of CAT in alcoholic liver injury. Acute liver injury was induced by intraperitoneal injection of alcohol in Sprague Dawley (SD) rats, and various doses of ATZ (100-400 mg/kg) or vehicle were administered intraperitoneally at 30 min before alcohol exposure. After 24 h of alcohol exposure, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in plasma were determined. The degree of hepatic histopathological abnormality was observed by HE staining. The activity of hepatic CAT, hydrogen peroxide (H?O?) level and malondialdehyde (MDA) content in liver tissue were measured by corresponding kits. The levels of tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) in plasma were determined by ELISA method. The results showed that treatment with ATZ dose-dependently suppressed the elevation of ALT, AST and LDH levels induced by alcohol exposure, and that ATZ alleviated alcohol-induced histopathological alterations. Furthermore, ATZ inhibited the activity of CAT, reduced hepatic levels of H?O?and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-? and IL-6 in rats with alcohol exposure. These results indicated that ATZ attenuated alcohol-induced acute liver injury in rats, suggesting that CAT might play important pathological roles in the pathogenesis of alcoholic liver injury. PMID:25672632

  13. Ultrasonography and amoebic liver abscesses.

    PubMed Central

    Abul-Khair, M H; Kenawi, M M; Korashy, E E; Arafa, N M

    1981-01-01

    Twenty-four patients were admitted to Kasr-El-Aini Hospital with suspected diagnoses of amoebic liver abscesses. The patients underwent clinical examinations, stool specimen analyses for cysts and trophozoites of Entamoeba histolytica, radiologic examinations, and routine liver function tests. In one patient, a liver scintiscan was obtained. Ultrasonographic examination was performed on all patients using the gray scale imaging technique. In 20 patients, the diagnoses of amoebic liver abscesses were demonstrated by ultrasonographic examination. In 19 patients, amoebic liver abscesses were verified by aspiration biopsies (95%), and one patient had a false-positive result. This false-positive result was due to a degenerated hepatoma, demonstrated by aspiration biopsy. Of the 19 patients, 12 patients (63.12%) had right lobe abscesses and seven (36.89%) had left lobe abscesses. The site, size and nature of the pus contained in the abscess could be determined by ultrasonographic examination and, therefore, helped in the management and technique of the aspiration biopsy. In addition, follow-up data could be more detailed using ultrasonographic examinations. Ultrasonographic examination is a noninvasive, safe, accurate, and rapid method of diagnosis, and is highly recommended as a routing procedure in all cases of suspected amoebic liver abscesses in the pre- and posttreatment stages of the disease. It is also recommended as an indicator of complete cure at follow-up examination. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. PMID:7469556

  14. Neurologic complications after liver transplantation

    PubMed Central

    Živkovi?, Saša A

    2013-01-01

    Neurologic complications are relatively common after solid organ transplantation and affect 15%-30% of liver transplant recipients. Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections. Most common complications include seizures and encephalopathy, and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients. Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor, headaches and encephalopathy. Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement. Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system (CNS) infections, but viral and fungal CNS infections still affect 1% of liver transplant recipients, and the morbidity and mortality in the affected patients remain fairly high. Critical illness myopathy may also affect up to 7% of liver transplant recipients. Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation. Accurate diagnosis and timely intervention are essential to improve outcomes, while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting. PMID:24023979

  15. ?-alanine improves punch force and frequency in amateur boxers during a simulated contest.

    PubMed

    Donovan, Tim; Ballam, Tim; Morton, James P; Close, Graeme L

    2012-10-01

    The aim of this study was to test the hypothesis that ß-alanine supplementation improves punch power and frequency in amateur boxers during a simulated contest. Sixteen amateur boxers (each approximately 6 yr experience) were assigned to ß-alanine (n = 8; 1.5 g 4 times/d for 4 wk) or placebo supplementation (n = 8) after initially being assessed for baseline punch performance. Before and after the supplementation period, all boxers completed a simulated contest consisting of 3 × 3-min rounds (interspersed with 60-s rests) on a punching bag (with a force transducer attached). Each round involved performing 2 min 50 s standardized punching (standardized jab, cross combination) based on notation analysis, whereas the last 10 s involved maximal-output punching (standardized jab, cross combination), during which time punch force and frequency were recorded. Postcontest blood lactate was significantly increased in the ß-alanine group (presupplementation 9.5 ± 0.9 mmol/L, postsupplementation 12.6 ± 0.5 mmol/L, p < .05), whereas the placebo group showed no change (presupplementation 8 ± 2.8 mmol/L, postsupplementation 7.0 ± 2.7 mmol/L; p > .05). During the 10-s maximal-output punching, changes in mean punch force (ß-alanine 20 ± 1.01 kg, placebo 1 ± 1 kg) and punch frequency (ß-alanine 5 ± 4, placebo -2 ± 3) were greater (p < .05) in the ß-alanine-supplemented group. The authors conclude that ß-alanine supplementation improves punching performance in amateur boxers and suggest that this supplementation protocol may also prove ergogenic for other combat-related sports. PMID:22805175

  16. ß-alanine improves punch force and frequency in amateur boxers during a simulated contest.

    PubMed

    Donovan, Tim; Ballam, Tim; Morton, James P; Close, Graeme L

    2012-10-01

    The aim of this study was to test the hypothesis that ß-alanine supplementation improves punch power and frequency in amateur boxers during a simulated contest. Sixteen amateur boxers (each approximately 6 yr experience) were assigned to ß-alanine (n = 8; 1.5 g 4 times/d for 4 wk) or placebo supplementation (n = 8) after initially being assessed for baseline punch performance. Before and after the supplementation period, all boxers completed a simulated contest consisting of 3 × 3-min rounds (interspersed with 60-s rests) on a punching bag (with a force transducer attached). Each round involved performing 2 min 50 s standardized punching (standardized jab, cross combination) based on notation analysis, whereas the last 10 s involved maximal-output punching (standardized jab, cross combination), during which time punch force and frequency were recorded. Postcontest blood lactate was significantly increased in the ß-alanine group (presupplementation 9.5 ± 0.9 mmol/L, postsupplementation 12.6 ± 0.5 mmol/L, p < .05), whereas the placebo group showed no change (presupplementation 8 ± 2.8 mmol/L, postsupplementation 7.0 ± 2.7 mmol/L; p > .05). During the 10-s maximal-output punching, changes in mean punch force (ß-alanine 20 ± 1.01 kg, placebo 1 ± 1 kg) and punch frequency (ß-alanine 5 ± 4, placebo -2 ± 3) were greater (p < .05) in the ß-alanine-supplemented group. The authors conclude that ß-alanine supplementation improves punching performance in amateur boxers and suggest that this supplementation protocol may also prove ergogenic for other combat-related sports. PMID:23011650

  17. Comparative evaluation of fatty infiltration of the liver in dairy cattle by using blood and serum analysis, ultrasonography, and digital analysis.

    PubMed

    Acorda, J A; Yamada, H; Ghamsari, S M

    1995-03-01

    Blood samples were collected from 158 Holstein-Friesian cows and analysed for aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and ornithine carabamoyltransferase activities and glucose, total bilirubin, triglyceride, cholesterol-ester and non-esterified fatty acids concentrations. Ultrasonography of the liver was performed, and hepatic ultrasonograms were evaluated subjectively or analysed digitally, and liver samples were examined histopathologically. The diagnostic rates for the different tests were compared. Of the 158 animals, 117 had a normal liver and 41 had fatty infiltration of the liver. For diagnosis of fatty infiltration, digital analysis had the highest sensitivity, specificity, accuracy, and positive and negative predictive values, followed by ultrasonography. PMID:7610550

  18. COACH syndrome associated with multifocal liver tumors

    Microsoft Academic Search

    Gabriele I. Kirchner; Siegfried Wagner; Peer Flemming; Joerg S. Bleck; Michael Gebel; Ingolf Schedel; Andreas Schüler; Michael Galanski; Michael P. Manns

    2002-01-01

    Here, we describe a 20-yr-old woman with COACH syndome (hypoplasia of Cerebellar vermis, Oligophrenia, congenital Ataxia, Coloboma, and Hepatic fibrosis) developing multiple liver lesions. Epigastric and right upper abdominal pain and lack of appetite led to clinical evaluation. Liver function tests showed an increase in transaminases and cholestatic parameters; ?-fetoprotein was in the normal range. Ultrasound and magnetic resonance imaging

  19. Liver abnormalities in connective tissue diseases.

    PubMed

    De Santis, Maria; Crotti, Chiara; Selmi, Carlo

    2013-08-01

    The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios. PMID:24090941

  20. A study of the prevalence of thalassemia and its correlation with liver function test in different age and sex group in the Chittagong district of Bangladesh

    PubMed Central

    Palit, Sarmi; Bhuiyan, Robiul H.; Aklima, Jannatul; Emran, Talha B.; Dash, Raju

    2012-01-01

    Thalassemia is the name of a group of genetic, inherited disorders of the blood. More specifically, it is a disorder of the hemoglobin molecule inside the red blood cells. According to World health Organization (WHO), there are about 3% beta-thalassemia carrier and about 4% Hb E/beta-thalassemia carrier in Bangladesh. Our objective is to identify the prevalence of beta-thalassemia in our adolescent populations and to review risk factors that would most easily identify a subset of adolescent patients at greatest risk for the development of beta-thalassemia. We also made a study of clinical profile of 53 thalassemic patients, observing the relationship between the patients with their verity ages and sex. The cases are taken on the basis of their age (2-30 years), beta-thalassemia major, clinical jaundice with history of chronic blood transfusion. The cases excluded those who had jaundice due to viral hepatitis or hepatitis due to heavy metal poisoning (Arsenic) and those with spleenectomy. Liver function test has been evaluated in 53 patients. That were recorded with some relevant demographical data such as age, sex, blood group where median age was of 16 years and mean (±SD) age 15.4151 ± 7.90918. Among them were 21 (39.6%) female and 32 (60.4%) male. With an average 15.1% (8 in no.) beta-thalassemia, 7.5% (4 in no.) beta-thalassemia major and 77.4% (41 in no.) E-beta-thalassemia cases have been found in the study. Mean (±SD) TSB in total 53 subjects with age group 2-10 years and 21-30 years is significant. The study revealed that in thalassemic patients when the age is more, the disease progresses with their complication. Hepatic complication is mainly due to being hepatocellular in nature than that of obstructive one. PMID:24826050

  1. The prognostic role of WHO classification, urinary 5-hydroxyindoleacetic acid and liver function tests in metastatic neuroendocrine carcinomas of the gastroenteropancreatic tract

    PubMed Central

    Formica, V; Wotherspoon, A; Cunningham, D; Norman, A R; Sirohi, B; Oates, J; Chong, G

    2007-01-01

    The World Health Organisation (WHO) classification (2000) is widely used to classify neuroendocrine carcinomas (NECs), yet its prognostic value needs to be confirmed. In this study, patients with metastatic NECs (n=119) were classified according to WHO guidelines into well differentiated and poorly differentiated (WDNECs and PDNECs). Histological differentiation based on WHO criteria had the highest impact on overall survival (OS) (PDNECs?:?WDNECs hazard ratio (HR)=4.02, P=0.02); however, PDNECs represented only a small percentage of patients (8%). In a WDNEC-restricted analysis, abnormal liver function tests (LFTs) and elevated urinary 5-hydroxyindoleacetic acid (u5HIAA) were independent prognostic factors for survival (HR=2.65, P=0.006 and HR=2.51, P=0.003, respectively) and were used to create a WDNEC-specific prognostic model (low risk=both normal, intermediate risk=one of them abnormal, high risk=both abnormal). Low-risk WDNECs had the most favourable prognosis (median OS, mOS 8.1 years), which was significantly better compared to both intermediate-risk and high-risk WDNECs (mOS 3.2 and 1.4 years, with P=0.01 and P<0.001, respectively). High-risk WDNECs displayed the shortest OS (1.3 years), which was similar to that of PDNECs (P=0.572). This analysis supports the prognostic value of WHO classification for metastatic NECs arising from the gastroenteropancreatic tract; however, risk stratification using readily available u5HIAA and LFTs may be necessary for the heterogeneous group of WDNECs. PMID:17406366

  2. Diminazene aceturate liposomes: morphometric and biochemical liver, kidney, and spleen of rats infected with Trypanosoma evansi.

    PubMed

    Oliveira, Camila Belmonte; Rigo, Lucas Almeida; França, Raqueli T; Gressler, Lucas T; Dalla Rosa, Luciana; Ourique, Aline F; Oliveira, Dionatan T; Doyle, Rovaina L; Moreira, Karen Luise dos Santos; Veiga, Marcelo L; Lopes, Sonia T A; Beck, Ruy Carlos R; Da Silva, Aleksandro S; Monteiro, Silvia G

    2014-12-01

    The aim of this study was to evaluate the effect of treatment with liposomal (L-DMZ) and conventional (C-DMZ) diminazene aceturate formulations on hepatic and renal functions of rats, experimentally infected with Trypanosoma evansi. For this purpose, 72 Wistar rats (Rattus norvegicus) were divided into six groups (A, B, C, D, E, and F). Each group was subdivided into two other subgroups in order to assess the biochemical and histological results on days 7 and 40 post-treatment (PT). Treatments were carried out based on two different therapeutic protocols: L-DMZ and C-DMZ at 3.5mg/kg(-1), single dose (groups C and D), and five successive doses within intervals of 24h (groups E and F). Groups A and B corresponded to uninfected and infected (without treatment) animals, respectively. Sample collections were held on days 7 and 40 PT for the assessment of hepatic [alkaline phosphatase (AP), alanine transferase (ALT), albumin, gamma glutamil transferase (GGT) and renal functions (creatinine and urea). Additionally, the histology of fragments of liver, kidney, and spleen was performed. Animals in group B showed a significant increase in AP, GGT, ALT, and urea when compared with group A. On day 7 post-inoculation (PI), the biochemical analysis showed a reduction (P<0.05) of AP and GGT, while the levels of urea were increased in groups C, D, E, F. On day 40 PT, ALT was increased in these same groups when compared with group A. In histopathology, changes in liver samples were observed on day 7 PT in groups D and F, especially regarding the area and density of the hepatocytes. Renal analysis exhibited changes in glomerular space, glomerular, and corpuscular areas in group E. Therefore, these results allowed us to conclude that the treatment with L-DMZ and C-DMZ led to variable biochemical changes, which defined the functions of the liver and kidneys of treated animals, since the main histopathology alterations were observed in animals treated with liposomes, at their higher dosages. Thus, treatments with L-DMZ and C-DMZ in five consecutive doses were effective although being followed by liver toxicity. PMID:25270332

  3. Increased Density of the Liver and Amiodarone-Associated Phospholipidosis

    PubMed Central

    Kojima, Sunao; Kojima, Shinobu; Ueno, Hirofumi; Takeya, Motohiro; Ogawa, Hisao

    2009-01-01

    This is a case report in which a 60-year-old man who suffered from ventricular tachycardia with dilated cardiomyopathy was prescribed amiodarone. After taking amiodarone, liver enzymes were increased and computed tomographic (CT) scanning of the abdomen showed a significant increase in the density of the liver without contrast medium. He was suspecte