Sample records for column improves liver
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Pérez-Fernández, Virginia; Castro-Puyana, María; González, María José; Marina, María Luisa; García, María Ángeles; Gómara, Belén
2012-07-01
The potential of three capillary columns based on β-cyclodextrin (i.e., Chirasil-Dex, BGB-172, and BGB-176SE) has been studied for the simultaneous enantiomeric separation of polychlorinated biphenyls (PCBs) and methylsulfonyl metabolites of PCBs (MeSO(2)-PCBs) employing a heart-cut multidimensional gas chromatographic system (heart-cut MDGC). Among the columns studied, the BGB-176SE capillary column provided the best results, allowing the simultaneous enantioselective resolution of six MeSO(2)-PCBs and six chiral PCBs; the Chirasil-Dex column did not resolve any of the studied MeSO(2)-PCBs; and a poor resolution was obtained for three MeSO(2)-PCBs when the BGB-172 column was employed. The developed method was successfully applied to two fish oil and one cow liver samples commercially available, which showed different enantioselective pattern. PCBs 91 and 176 presented a clear enrichment of the second eluted atropisomer in codfish oil, whereas in fish oil sample, slight enrichment of the first eluted atropisomer of CB45 and the second eluted atropisomer of CB136 were observed. © 2012 Wiley Periodicals, Inc.
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Tomescu, Dana R; Olimpia Dima, Simona; Ungureanu, Daniela; Popescu, Mihai; Tulbure, Dan; Popescu, Irinel
2016-05-16
Emergency transplantation of a donor liver that is not matched for the major blood antigens can produce marked immune-mediated cytokine release that can cause donor graft loss. Control of the inflammatory response may be a key element in treatment. We present the case of a 46-year-old man with primary graft nonfunction after liver transplantation who underwent emergency retransplantation with an ABO-incompatible graft. A severe inflammatory response syndrome (SIRS) was noted in the perioperioperative period of retransplantation. The patient was successfully treated for this condition with a new hemoadsorption column (CytoSorb®), in combination with continuous venovenous hemofiltration (CVVH) throughout the intraoperative and early postoperative period. During and after each treatment a significant and rapid decrease of pro- and anti-inflammatory cytokines was observed, especially for interleukin-6 (IL-6), IL-10 and monocyte chemotactic protein 1 (MCP-1). Reduction of cytokines was associated with normalization of cardiac output and systemic vascular resistance, and improved liver function. We believe this is the first case in which hemoadsorptionin combination with CVVH has been used to manage SIRS in a patient with primary graft nonfunction undergoing emergency retransplantation.
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Toxicity and Kinetics of (3H)Microcystin-LR in Isolated Perfused Rat Livers
1990-03-20
with a Waters 490 multiwavelength detector, as described by Robinson et al. (1989). A C-18 column (Adsorbosphere HS, 4.6 x 250 mm, 5 Am, Alltech ...1988). The isolated perfused liver has several advantages over other model systems for the study of hepatotoxins. Unlike the in-vitro cell systems
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Adewoye, E O; Ige, A O
2013-06-30
Diabetes mellitus is a metabolic disorder resulting from necrosis of β-cell and insulin resistance at the cellular level. Musa sapientum has been shown to possess anti-diabetic properties, however, the mechanism of its action is unknown. The effect of Methanolic extract of Musa sapientum leaves (MEMSL) and its fractions were assessed for in vitro inhibitory activity of α-amylase enzyme, in vivo hypoglycemic properties and liver glycogen content in alloxan-induced diabetic rats. Dried plant powder of Musa sapientum was successively extracted using n-hexane, ethyl acetate, dichloromethane and methanol respectively. The filtrate obtained was evaporated using rotary evaporator and the extract was stored at 4°C until use. The methanolic extract obtained was further fractionated using column chromatography. In vitro alpha amylase inhibitory activity of the methanolic extract at different doses (2.5mg/ml, 5mg/ml, 10mg/ml, 25mg/ml and 50mg/ml) and column fractions (100ug/ml) were assessed and compared with that of acarbose (5mg/ml), a standard oral α-amylase inhibitor. Hypoglycemic activity and liver glycogen content was studied using alloxan -induced diabetic male rats treated with MEMSL (250mg/kg and 500mg/kg), column fractions F2 and F5 (100μg/kg) for 14 days respectively. Results obtained showed a dose -dependent increase in α-amylase inhibitory activity of the methanolic extract at 5, 10, 25 and 50mg/ml exhibiting 29%, 61%, and 72% and 80% inhibitory activities respectively. Column fractions 2 and 5 showed the highest α-amylase inhibitory activity of 79% and 74% respectively. The MEMSL at 250mg/kg and 500mg/kg exhibited 66% and 59% hypoglycemic activities respectively compared with diabetic controls. Fractions 2 and 5 showed 48% and 75% reduction in blood glucose level respectively. Liver glycogen in diabetic animals treated with MEMSL (250mg/kg and 500mg/kg), F2 and F5 were significantly increased (5.5±0.5, 5.9±0.7, 3.6±0.5, 8.0±0.4 mg/100gwt. liver) compared with Diabetic controls (1.2±0.3 mg/100gwt. liver) respectively suggesting an increase in glucose storage or reduction in glycogen breakdown. It seems possible that the anti-diabetic properties in the leaf extract of Musa sapientum and its fractions maybe due to the inhibition of α-amylase, increased storage of glucose as glycogen in the liver and/or reduced breakdown of liver glycogen stores.
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2014-01-01
Background Tylosin and Josamycin are macrolide antibiotics. They are used in the treatment of pneumonia, arthritis and mastitis in cattle, and mycoplasma infections in poultry. The incorrect use of antibiotics has lead to the presence of antibiotic residues in foods. The residues cause toxic effects on consumers. Results A simple and sensitive method was optimized and validated for the analysis of tylosin and josamycin residues in food samples. Analytical separation was performed in less than 10 min using a RP C18 monolithic column with time-programmed UV detection at 287 nm and 232 nm and a micellar solution of 0.17 M sodium dodecyl sulphate, 14% methanol and 0.3% triethylamine in 0.02 M phosphoric acid buffered at pH 4 as the mobile phase. The method was fully validated in accordance with ICH guidelines. The micellar method was successfully applied to quantitatively determine tylosin and josamycin residues in spiked chicken muscles, chicken liver, bovine muscles, liver, milk and eggs. It was also extended to the determination of tylosin and josamycin residues in chicken-based baby food and baby formulae. The compounds were separated by a monolithic column which, on account of its particular structure, could bear higher flow rates than usually found for this kind of analysis. High extraction efficiency for tylosin and josamycin was obtained without matrix interference in the extraction process and in the subsequent chromatographic determination. No organic solvent was used during the pretreatment step. Hence, it is considered an interesting technique for “green” chemistry. Conclusion The proposed method was validated and successfully applied for the determination of tylosin and josamycin residues in spiked chicken muscles, chicken liver, bovine muscles, liver, milk and eggs. It was also extended to the determination of tylosin and josamycin residues in chicken-based baby food and baby formulae. PMID:24976860
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Acharya, Miteshkumar; Lau-Cam, Cesar A.
2012-01-01
A simple reversed-phase HPLC method for measuring hepatic levels of acetaminophen- (APAP-) protein adduct following an overdose of APAP was developed. An aliquot of liver homogenate in phosphate-buffered saline pH 7.4 (PBS) was placed on a Nanosep centrifugal device, which was centrifuged to obtain a protein residue. This residue was incubated with a solution of p-aminobenzoic acid (PABA), the internal standard, and bacterial protease in PBS, transferred to a Nanosep centrifugal device, and centrifuged. A 100 μL portion of the filtrate was analyzed on a YMC-Pack ODS-AMQ C18 column, using 100 mM potassium dihydrogen phosphate-methanol-acetic acid (100 : 0.6 : 0.1) as the mobile phase, a flow rate of 1 mL/min, and photometric detection at 254 nm. PABA and APAP-cystein-S-yl (APAP-Cys) eluted at ~14.7 min and 22.7 min, respectively. Method linearity, based on on-column concentrations of APAP-Cys, was observed over the range 0.078–40 μg. Recoveries of APAP-Cys from spiked blank liver homogenates ranged from ~83% to 91%. Limits of detection and of quantification of APAP-Cys, based on column concentrations, were 0.06 μg and 0.14 μg, respectively. RSD values for interday and intraday analyses of a blank liver homogenate spiked with APAP-Cyst at three levels were, in all cases, ≤1.0% and <1.5%, respectively. The proposed method was found appropriate for comparing the antidotal properties of N-acetylcysteine and taurine in a rat model of APAP poisoning. PMID:22619591
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Holroyde, M J; Chesher, J M; Trayer, I P; Walker, D G
1976-01-01
The synthesis of N-(6-aminohexanoyl)-2-amino-2-deoxy-D-glucose is described and it was shown to be a competitive inhibitor (Ki, 0.75 mM) with respect to glucose of rat hepatic glucokinase (EC 2.7.1.2). After attachment to CNBr-activated Sepharose 4B, this derivative was able to remove glucokinase quantitatively from crude liver extracts and release it when the columns were developed with glucose, glucosamine, N-acetyl-glucosamine or KC1. Repeated exposure of the columns to liver extracts led to rapid loss in their effectiveness as affinity matrices because proteins other than glucokinase are bound to the columns. The nature of such protein binding and methods for the rejuvenation of "used" columns are discussed along with the effect of the mode of preparation of the Sepharose-ligand conjugate and the concentration of bound ligand on the purification of glucokinase. Glucose 6-phosphate dehydrogenase is cited as an example of both non-specific protein binding to the affinity column and of the importance of the control of ligand concentration in removing such non-specifically bound proteins. Some guidelines emerged that should be generally applicable to other systems, particularly those which involve affinity chromatography of enzymes that are present in tissue extracts in very low amounts and possess only a relatively low association constant for the immobilized ligand. PMID:1275893
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Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.
Heemann, Uwe; Treichel, Ulrich; Loock, Jan; Philipp, Thomas; Gerken, Guido; Malago, Massimo; Klammt, Sebastian; Loehr, Matthias; Liebe, Stephan; Mitzner, Steffen; Schmidt, Reinhardt; Stange, Jan
2002-10-01
Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Reich, S.; Schurig, V.; Jimenez, B.
1999-06-01
Blubber and liver samples from six striped dolphins (Stenella coeruleoalba) found dead in the Mediterranean Sea in 1989--1990 were tested for 37 coplanar and chiral polychlorinated biphenyls (PCBs), including the enantiomeric ratios of 9 chiral PCBs. The method includes a fractionation step using HPLC (PYE column) for separating the PCBs according to the number of chlorine atoms in the ortho positions. HRGC/ECD and HRGC/LRMS with an a chiral column (DB-5) were used to determine the PCB congeners. The enantiomeric ratios of nine chiral PCBs were determined by HRGC/LRMS (SIM) with a chiral column (Chirasil-Dex) and by MDGC as the confirmatorymore » technique. The total PCB concentration (sum of 37 congeners) ranged from 7.2 to 89.6 {micro}g/g (wet weight) and from 0.52 to 29.2 {micro}g/g (wet weight) for blubber and liver samples, respectively. PCB profiles were dominated by congeners 138, 153, 170, and 180. The toxic equivalent values (TEQ) ranged from 0.17 to 3.93 ng/g (wet weight) and from 0.02 to 0.73 ng/g (wet weight) for blubber and liver samples, respectively. PCBs 95, 132, 135, 149, and 176 revealed an enantiomeric excess of the second eluted enantiomer in almost all of the samples, whereas PCBs 136 and 174 were racemic or almost racemic. PCBs 88 and 91 were under the detection limits of the methodology used.« less
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The 30 kDa protein co-purified with chick liver glutathione S-transferases is a carbonyl reductase.
Tsai, S P; Wang, L Y; Yeh, H I; Tam, M F
1996-02-08
An unidentified 30 kDa protein was co-purified with chick liver glutathione S-transferases from S-hexylglutathione affinity column. The protein was isolated to apparent homogeneity with chromatofocusing. The molecular mass of the protein was determined to be 30 277 +/- 3 dalton by mass spectrometry. The protein was digested with Achromobacter proteinase I. Amino-acid sequence analyses of the resulting peptides show a high degree of identity with those of human carbonyl reductase. The protein is active with menadione as substrate. Thus, it is identified as chick liver carbonyl reductase.
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Purification and characterization of rat liver nuclear thyroid hormone receptors.
Ichikawa, K; DeGroot, L J
1987-01-01
Nuclear thyroid hormone receptor was purified to 904 pmol of L-3,5,3'-triiodothyronine (T3) binding capacity per mg of protein with 2.5-5.2% recovery by sequentially using hydroxylapatite column chromatography, ammonium sulfate precipitation, Sephadex G-150 gel filtration, DNA-cellulose column chromatography, DEAE-Sephadex column chromatography, and heparin-Sepharose column chromatography. Assuming that one T3 molecule binds to the 49,000-Da unit of the receptor, we reproducibly obtained 6.4-14.7 micrograms of receptor protein with 4.2-4.9% purity from 4-5 kg of rat liver. Elution of receptor from the heparin-Sepharose column was performed using 10 mM pyridoxal 5'-phosphate, which was observed to diminish binding of receptor to heparin-Sepharose or DNA-cellulose. This effect was specific for pyridoxal 5'-phosphate, since related compounds were not effective. Purified receptor bound T3 with high affinity (6.0 X 10(9) liter/mol), and the order of affinity of iodothyronine analogues to purified receptor was identical to that observed with crude receptor preparations [3,5,3'-triiodothyroacetic acid greater than L-T3 greater than D-3,5,3'-triiodothyronine (D-T3) greater than L-thyroxine greater than D-thyroxine]. Purified receptor had a sedimentation coefficient of 3.4 S, Stokes radius of 34 A, and calculated molecular mass of 49,000. Among several bands identified by silver staining after electrophoresis in NaDodSO4/polyacrylamide gels, one 49,000-Da protein showed photoaffinity labeling with [125I]thyroxine that was displaceable with excess unlabeled T3. The tryptic fragment and endogenous proteinase-digested fragment of the affinity-labeled receptor showed saturable binding in 27,000-Da and 36,000-Da peptides, respectively. These molecular masses are in agreement with estimates from gel filtration and gradient sedimentation, indicating that affinity labeling occurred at the hormone binding domain of nuclear thyroid hormone receptor. This procedure reproducibly provides classical native rat liver T3 nuclear receptor in useful quantity and purity and of the highest specific activity so far reported. Images PMID:3472213
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Ocque, Andrew J; Hagler, Colleen E; Difrancesco, Robin; Woolwine-Cunningham, Yvonne; Bednasz, Cindy J; Morse, Gene D; Talal, Andrew H
2016-07-01
Determination of paritaprevir and ritonavir in rat liver tissue samples. We successfully validated a UPLC-MS/MS method to measure paritaprevir and ritonavir in rat liver using deuterated internal standards (d8-paritapervir and d6-ritonavir). The method is linear from 20 to 20,000 and 5 to 10,000 pg on column for paritaprevir and ritonavir, respectively, and is normalized per milligram tissue. Interday and intraday variability ranged from 0.591 to 5.33% and accuracy ranged from -6.68 to 10.1% for quality control samples. The method was then applied to the measurement of paritaprevir and ritonavir in rat liver tissue samples from a pilot study. The validated method is suitable for measurement of paritaprevir and ritonavir within rat liver tissue samples for PK studies.
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Akachi, Toshiyuki; Shiina, Yasuyuki; Kawaguchi, Takumi; Kawagishi, Hirokazu; Morita, Tatsuya; Sugiyama, Kimio
2010-01-01
To evaluate the protective effects of fruit juices against D-galactosamine (GalN)-induced liver injury, lyophilized fruit juices (total 12 kinds) were fed to rats for 7 d, and then we evoked liver injury by injecting GalN. The juice of camu-camu (Myrciaria dubia) significantly suppressed GalN-induced liver injury when the magnitude of liver injury was assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, although some other juices (acerola, dragon fruit, shekwasha, and star fruit) also tended to have suppressive effects. An active compound was isolated from camu-camu juice by solvent fractionation and silica gel column chromatography. The structure was determined to be 1-methylmalate. On the other hand, malate, 1,4-dimethylmalate, citrate, and tartrate had no significant effect on GalN-induced liver injury. It is suggested that 1-methylmalate might be a rather specific compound among organic acids and their derivatives in fruit juices in suppressing GalN-induced liver injury.
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High pressure liquid chromatography of zearalenone and zearalenols in rat urine and liver.
James, L J; McGirr, L G; Smith, T K
1982-01-01
A high pressure liquid chromatographic technique with internal standardization has been developed for determining zearalenone and metabolites in rat urine and liver. Following extraction with methylene chloride and solvent partition, samples are cleaned up by applying the extract to a Sephadex LH-20 column and eluting with a mixture of benzene-methanol (85 + 15). Compounds were resolved on 2 Part-isil-10 columns (25 cm x 4.6 mm id) in series with a mobile phase of isooctane-chloroform-methanol (35 + 25 + 3), and detected at 280 nm. The internal standard was 6'alpha-acetoxyzearalane. Limits of detection were about 2.0 ng for zearalenone and 5.0 ng for zearalenols (6'-hydroxyzearalane). Zearalenone and zearalenols were excreted mainly in free form with relatively little glucuronide conjugation. Metabolism of zearalenone to free zearalenol was minor compared with formation of bound forms.
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Unique properties of arginase purified from camel liver cytosol.
Maharem, Tahany M; Zahran, Walid E; Hassan, Rasha E; Abdel Fattah, Mohamed M
2018-03-01
Arginase (ARG) is an enzyme involved in urea cycle, where it catalyzes the hydrolysis of L-arginine into L-ornithine and urea. Since there is no information about the isolation and purification of ARG from camel liver, this investigation was designed to purify and characterize ARG from camel liver and compare its molecular and kinetic properties with that reported from other species. Camel liver arginase (CL-ARG) was purified to homogeneity using heat denaturation followed by ammonium sulphate precipitation with a combination of DEAE-cellulose, SP-Sepharose and Sephadex G 100-120 chromatography columns. The specific activity of CL-ARG was increased to 18,485 units/mg proteins with 23.5-fold purification over crude homogenate. It was observed that CL-ARG showed a similarity with other species such as behaviour on DEAE-cellulose column, kinetics of inhibition, necessity for metal ions as cofactor, and alkaline optimum pH. On the contrary, CL-ARG differed in its molecular weight (180kDa), oligomeric protein structure, slightly neutral-alkaline pI value (7.7), K m value (7.1mM), optimum pH (9, 10.7), and higher optimum temperature (70°C). In conclusion, this study investigated the properties of CL-ARG via a simple and reproducible purification procedure and provided valuable information for its production from available source in Egypt for medical and industrial purposes. Copyright © 2017 Elsevier B.V. All rights reserved.
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[Quantitative evaluation of Gd-EOB-DTPA uptake in phantom study for liver MRI].
Hayashi, Norio; Miyati, Tosiaki; Koda, Wataru; Suzuki, Masayuki; Sanada, Shigeru; Ohno, Naoki; Hamaguchi, Takashi; Matsuura, Yukihiro; Kawahara, Kazuhiro; Yamamoto, Tomoyuki; Matsui, Osamu
2010-05-20
Gd-EOB-DTPA is a new liver specific MRI contrast media. In the hepatobiliary phase, contrast media is trapped in normal liver tissue, a normal liver shows high intensity, tumor/liver contrast becomes high, and diagnostic ability improves. In order to indicate the degree of uptake of the contrast media, the enhancement ratio (ER) is calculated. The ER is obtained by calculating (signal intensity (SI) after injection-SI before injection) / SI before injection. However, because there is no linearity between contrast media concentration and SI, ER is not correctly estimated by this method. We discuss a method of measuring ER based on SI and T(1) values using the phantom. We used a column phantom, with an internal diameter of 3 cm, that was filled with Gd-EOB-DTPA diluted solution. Moreover, measurement of the T(1) value by the IR method was also performed. The ER measuring method of this technique consists of the following three components: 1) Measurement of ER based on differences in 1/T(1) values using the variable flip angle (FA) method, 2) Measurement of differences in SI, and 3) Measurement of differences in 1/T(1) values using the IR method. ER values calculated by these three methods were compared. In measurement made using the variable FA method and the IR method, linearity was found between contrast media concentration and ER. On the other hand, linearity was not found between contrast media concentration and SI. For calculation of ER using Gd-EOB-DTPA, a more correct ER is obtained by measuring the T(1) value using the variable FA method.
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Purification and characterization of the protein kinase eEF-2 isolated from rat liver cells.
Gajko, A; Gałasiński, W; Gindzieński, A
1994-01-01
The elongation factor 2 (eEF-2) protein kinase was isolated from rat liver cells, purified and partly characterized. It was found that the enzyme exists in an inactive form in the homogenate of rat liver. The active fraction of kinase eEF-2 was obtained after removal of the inhibitory substance by hydroxyapatite column chromatography. The purified enzyme is an electrophoretically homogeneous protein with relative molecular mass of approximately 90,000 and isoelectric point, pI = 5.9. The enzyme specifically phosphorylates the elongation factor eEF-2 in the presence of calmodulin and Ca2+.
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MCNP study for epithermal neutron irradiation of an isolated liver at the Finnish BNCT facility.
Kotiluoto, P; Auterinen, I
2004-11-01
A successful boron neutron capture treatment (BNCT) of a patient with multiple liver metastases has been first given in Italy, by placing the removed organ into the thermal neutron column of the Triga research reactor of the University of Pavia. In Finland, FiR 1 Triga reactor with an epithermal neutron beam well suited for BNCT has been extensively used to irradiate patients with brain tumors such as glioblastoma and recently also head and neck tumors. In this work we have studied by MCNP Monte Carlo simulations, whether it would be beneficial to treat an isolated liver with epithermal neutrons instead of thermal ones. The results show, that the epithermal field penetrates deeper into the liver and creates a build-up distribution of the boron dose. Our results strongly encourage further studying of irradiation arrangement of an isolated liver with epithermal neutron fields.
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Tomatsu, Shunji; Montaño, Adriana M.; Oikawa, Hirotaka; Dung, Vu Chi; Hashimoto, Amiko; Oguma, Toshihiro; Takahashi, Tatsuo; Shimada, Tsutomu; Orii, Tadao; Sly, William S.
2014-01-01
We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology (1). To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250 units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in liver and spleen, with detectable activity in bone and brain. Second, newborn ERT was conducted after tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th week were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in liver, spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than adult mice treated with ERT; however, hyaline and fibrous cartilage cells in femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mouse. PMID:24953405
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jeong, J M; Knapp Jr, Russ F
2008-01-01
This work describes the installation, use, and quality control (QC) of the alumina-based tungsten-188 ({sup 188}W)/rhenium-188 ({sup 188}Re) generators provided by the Oak Ridge National Laboratory (ORNL). In addition, methods used for concentration of the {sup 188}Re-perrhenate bolus and preparation of {sup 188}Re-labeled HDD (4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol) for trans-arterial administration for therapy of nonresectable liver cancer also are described. The {sup 188}W/{sup 188}Re generator has a long useful shelf-life of several months and is a convenient on-site {sup 188}Re production system. {sup 188}Re has excellent therapeutic and imaging properties (T{sub 1/2} 16.9 hours; E{sub {beta}max} 2.12 MeV; 155-keV gamma ray, 15%) andmore » is cost effectively obtained on demand by saline elution of the generator. The clinical efficacy of a variety of {sup 188}Re-labeled agents has been demonstrated for several therapeutic applications. Because of the favorable physical properties of {sup 188}Re, several {sup 188}Re-labeled agents are being developed and evaluated for the treatment of nonresectable/refractory liver cancer. {sup 188}Re-labeled HDD has been the most widely studied of these agents for this application and has been introduced into clinical trials at a number of institutions. The trans-arterial administration of {sup 188}Re-labeled agents for treatment of inoperable liver cancer requires use of high-level (1-2 Ci) {sup 188}W/{sup 188}Re generators. The handling of such high levels of {sup 188}Re imposes radiological precautions normally not encountered in a radiopharmacy and adequate care and ALARA (i.e., 'As Low As Reasonably Achievable') principles must be followed. The ORNL generator provides consistently high {sup 188}Re yields (>75%) and low {sup 188}W parent breakthrough (<10{sup -3}%) over an extended shelf-life of several months. However, the high elution volumes (20-40 mL for 1-2 Ci generators) can require concentration of the {sup 188}Re bolus by postelution passage through silver cation chloride trapping columns used in the cost-effective tandem cation/anion column system. The silver column removes the high levels of chloride anion as insoluble AgCl, thus allowing subsequent specific trapping of the perrhenate anion on the small (QMA SeaPak) anion column. This method permits subsequent elution of {sup 188}Re-perrhenate with a small volume of saline, providing a very high activity-concentration solution. Because the {sup 188}Re-specific volume-activity concentration continually decreases with time, the tandem system is especially effective method for extending the useful generator shelf-life. Low elution flow rates (<1 mL/min) minimize any high back pressure which may be encountered during generator/tandem column elution when using tightly packed, small-particle-size commercial columns. In-house preparation of silver cation columns is recommended since the chloride trapping capacity is essentially unlimited, it is inexpensive and not limited in availability to any one supplier, and back pressure can be eliminated by the use of larger particles. Methods for the preparation of {sup 188}Re-HDD have been optimized and this agent can be obtained in high yield (80%).« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Knapp Jr, Russ F; Jeong, J M
2008-01-01
This work describes the installation, use, and quality control (QC) of the alumina-based tungsten-188 ({sup 188}W)/rhenium-188 ({sup 188}Re) generators provided by the Oak Ridge National Laboratory (ORNL). In addition, methods used for concentration of the {sup 188}Re-perrhenate bolus and preparation of {sup 188}Re-labeled HDD (4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol) for trans-arterial administration for therapy of nonresectable liver cancer also are described. The {sup 188}W/{sup 188}Re generator has a long useful shelf-life of several months and is a convenient on-site {sup 188}Re production system. {sup 188}Re has excellent therapeutic and imaging properties (T{sub 1/2} 16.9 hours; E{beta}{sub max} 2.12 MeV; 155-keV gamma ray, 15%) andmore » is cost effectively obtained on demand by saline elution of the generator. The clinical efficacy of a variety of {sup 188}Re-labeled agents has been demonstrated for several therapeutic applications. Because of the favorable physical properties of {sup 188}Re, several {sup 188}Re-labeled agents are being developed and evaluated for the treatment of nonresectable/refractory liver cancer. {sup 188}Re-labeled HDD has been the most widely studied of these agents for this application and has been introduced into clinical trials at a number of institutions. The trans-arterial administration of {sup 188}Re-labeled agents for treatment of inoperable liver cancer requires use of high-level (1-2 Ci) {sup 188}W/{sup 188}Re generators. The handling of such high levels of {sup 188}Re imposes radiological precautions normally not encountered in a radiopharmacy and adequate care and ALARA (ie, 'As Low As Reasonably Achievable') principles must be followed. The ORNL generator provides consistently high {sup 188}Re yields (>75%) and low {sup 188}W parent breakthrough (<10{sup -3}%) over an extended shelf-life of several months. However, the high elution volumes (20-40 mL for 1-2 Ci generators) can require concentration of the {sup 188}Re bolus by postelution passage through silver cation chloride trapping columns used in the cost-effective tandem cation/anion column system. The silver column removes the high levels of chloride anion as insoluble AgCl, thus allowing subsequent specific trapping of the perrhenate anion on the small (QMA SeaPak) anion column. This method permits subsequent elution of {sup 188}Re-perrhenate with a small volume of saline, providing a very high activity-concentration solution. Because the {sup 188}Re-specific volume-activity concentration continually decreases with time, the tandem system is especially effective method for extending the useful generator shelf-life. Low elution flow rates (<1 mL/min) minimize any high back pressure which may be encountered during generator/tandem column elution when using tightly packed, small-particle-size commercial columns. In-house preparation of silver cation columns is recommended since the chloride trapping capacity is essentially unlimited, it is inexpensive and not limited in availability to any one supplier, and back pressure can be eliminated by the use of larger particles. Methods for the preparation of {sup 188}Re-HDD have been optimized and this agent can be obtained in high yield (80%).« less
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Granja, Rodrigo H M M; Niño, Alfredo M Montes; Zucchetti, Roberto A M; Niño, Rosario E Montes; Salerno, Alessandro G
2008-01-01
Ethopabate is frequently used in the prophylaxis and treatment of coccidiosis in poultry. Residues of this drug in food present a potential risk to consumers. A simple, rapid, and sensitive column high-performance liquid chromatographic (HPLC) method with UV detection for determination of ethopabate in poultry liver is presented. The drug is extracted with acetonitrile. After evaporation, the residue is dissolved with an acetone-hexane mixture and cleaned up by solid-phase extraction using Florisil columns. The analyte is then eluted with methanol. LC analysis is carried out on a C18 5 microm Gemini column, 15 cm x 4.6 mm. Ethopabate is quantified by means of UV detection at 270 nm. Parameters such as decision limit, detection capability, precision, recovery, ruggedness, and measurement uncertainty were calculated according to method validation guidelines provided in 2002/657/EC and ISO/IEC 17025:2005. Decision limit and detection capability were determined to be 2 and 3 microg/kg, respectively. Average recoveries from poultry samples fortified with 10, 15, and 20 microg/kg levels of ethopabate were 100-105%. A complete statistical analysis was performed on the results obtained, including an estimation of the method uncertainty. The method is to be implemented into Brazil's residue monitoring and control program for ethopabate.
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Oikari, Sanna; Venäläinen, Tuula; Tammi, Markku
2014-01-03
In this paper we describe a method optimized for the purification of uridine diphosphate (UDP)-sugars from liver, adipose tissue, brain, and heart, with highly reproducible up to 85% recoveries. Rapid tissue homogenization in cold ethanol, lipid removal by butanol extraction, and purification with a graphitized carbon column resulted in isolation of picomolar quantities of the UDP-sugars from 10 to 30mg of tissue. The UDP-sugars were baseline separated from each other, and from all major nucleotides using a CarboPac PA1 anion exchange column eluted with a gradient of acetate and borate buffers. The extraction and purification protocol produced samples with few unidentified peaks. UDP-N-acetylglucosamine was a dominant UDP-sugar in all the rat tissues studied. However, brain and adipose tissue showed high UDP-glucose levels, equal to that of UDP-N-acetylglucosamine. The UDP-N-acetylglucosamine showed 2.3-2.7 times higher levels than UDP-N-acetylgalactosamine in all tissues, and about the same ratio was found between UDP-glucose and UDP-galactose in adipose tissue and brain (2.6 and 2.8, respectively). Interestingly, the UDP-glucose/UDP-galactose ratio was markedly lower in liver (1.1) and heart (1.7). The UDP-N-acetylglucosamine/UDP-glucuronic acid ratio was also constant, between 9.7 and 7.7, except in liver with the ratio as low as 1.8. The distinct UDP-glucose/galactose ratio, and the abundance of UDP-glucuronic acid may reflect the specific role of liver in glycogen synthesis, and metabolism of hormones and xenobiotics, respectively, using these UDP-sugars as substrates. Copyright © 2013 Elsevier B.V. All rights reserved.
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Saarinen, M T; Kettunen, H; Pulliainen, K; Peuranen, S; Tiihonen, K; Remus, J
2001-02-01
Betaine was measured from liver tissue by a high-performance liquid chromatographic (HPLC) method developed for this study. The method involves homogenization of liver in acetate buffer at pH 6 and precipitation of protein with trichloroacetic acid, which was removed by diethyl ether extraction. Betaine was separated using a cation exchange column in Ca(2+) form and detected with a refractive index detector. This method also allows the determination of S-adenosylmethionine (S-AM) from the same liver extract but with different HPLC conditions. Broiler chicks were fed with experimental diets supplemented with four different doses of betaine or choline ranging from 0 to 5 mol equiv. After a 3 week feeding period, the livers were analyzed for betaine and S-AM. Dietary betaine was twice as efficient in increasing the hepatic betaine concentration as dietary choline. The hepatic S-AM concentrations were similar in all dietary treatments.
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Qureshi, A A; Elson, C E; Lebeck, L A
1982-11-19
The isolation and identification of three major alpha-keto end products (glyoxylate, pyruvate, alpha-ketoglutarate) of the isocitrate lyase reaction in 18-day chick embryo liver have been described. This was accomplished by the separation of these alpha-keto acids as their 2,4-dinitrophenylhydrazones (DNPHs) by high-performance liquid chromatography (HPLC). The DNPHs of alpha-keto acids were eluted with an isocratic solvent system of methanol-water-acetic acid (60:38.5:1.5) containing 5 mM tetrabutylammonium phosphate from a reversed-phase ultrasphere C18 (IP) and from a radial compression C18 column. The separation can be completed on the radial compression column within 15-20 min as compared to 30-40 min with a conventional reversed-phase column. Retention times and peak areas were integrated for both the assay samples and reference compounds. A relative measure of alpha-keto acid in the peak was calculated by comparison with the standard. The identification of each peak was done on the basis of retention time matching, co-chromatography with authentic compounds, and stopped flow UV-VIS scanning between 240 and 440 nm. Glyoxylate represented 5% of the total product of the isocitrate lyase reaction. Day 18 parallels the peak period of embryonic hepatic glycogenesis which occurs at a time when the original egg glucose reserve has been depleted.
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Enantioselective Tissue Distribution of Ketorolac and its Enantiomers in Rats.
Dubey, S K; Anand, A; Saha, R N
2015-08-01
The difference in tissue distribution of Ketorolac and its enantiomers were investigated in wistar rats. Separate high performance liquid chromatographic method was developed and validated for determination of Ketorolac and its enantiomers. Oyster BDS (150 × 4.6 mm id., 5 μm particle size) column was used for determination of concentration of Ketorolac. Ketorolac enantiomers were determined using Chiral-AGP column (100 × 4.0 mm I.D., particle size 5 μ, Chrom tech Ltd, Sweden). Detection was done at wavelength of 322 nm using an ultraviolet detector in the analytical system. Ketorolac enantiomers exhibit difference in their disposition in Wistar rats. In kidney, there was a significant difference in pharmacokinetic parameters. The Cmax was nearly 4 times and AUC 0-∞ was found to be more than double for S (-) Ketorolac than that of R (+) Ketorolac. MRT, Ke and t1/2 differ significantly in kidney. In liver, Cmax was found to be approximately 69% higher for S (-) Ketorolac compared to R (+) Ketorolac. AUC 0-∞ did not differ significantly for the enantiomers in liver. In liver, S (-) Ketorolac eliminated very fast in comparison to R (+) Ketorolac having t1/2 (one third) in comparison to R (+) Ketorolac. In lungs, there was no difference observed for Cmax and other parameters but AUC 0-∞ was found to be marginally higher for S (-) ketorolac. © Georg Thieme Verlag KG Stuttgart · New York.
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Wang, Hongwei; Yao, Yating; Li, Ya; Ma, Shujuan; Peng, Xiaojun; Ou, Junjie; Ye, Mingliang
2017-08-01
An open tubular (OT) column (25 μm i.d.) was prepared by in situ ring-opening polymerization of octaglycidyldimethylsilyl polyhedral oligomeric silsesquioxanes (POSS-epoxy) with 4-aminophenyl disulfide (APDS) in a binary porogenic system of ethanol/H 2 O. It was found that porogenic composition played an important role in the formation of OT stationary phases. The ratio of ethanol/H 2 O at 6/1 (v/v) would lead to the fabrication of hybrid monoliths, while the ratio of ethanol/H 2 O at 13/1 (v/v) would result in the synthesis of OT phases. In addition, the effects of precursor content and reaction duration on the thickness of OT stationary phases were investigated. Either lower precursor content or shorter reaction duration would produce thinner layer of OT column. The repeatability of OT columns was evaluated through relative standard deviation (RSD%) with benzene as the analyte. The run-to-run, column-to-column and batch-to-batch repeatabilities were 1.7%, 4.8% and 5.6%, respectively, exhibiting satisfactory repeatability of the OT column. Then tryptic digest of mouse liver proteins was used to evaluate the performance of the resulting OT columns (25 μm i.d. × 2.5 m in length) by cLC-MS/MS analysis, demonstrating their potential in proteome analysis. Copyright © 2017 Elsevier B.V. All rights reserved.
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NASA Astrophysics Data System (ADS)
Madun, A.; Meghzili, S. A.; Tajudin, SAA; Yusof, M. F.; Zainalabidin, M. H.; Al-Gheethi, A. A.; Dan, M. F. Md; Ismail, M. A. M.
2018-04-01
The most important application of various geotechnical construction techniques is for ground improvement. Many soil improvement project had been developed due to the ongoing increase in urban and industrial growth and the need for greater access to lands. Stone columns are one of the best effective and feasible techniques for soft clay soil improvement. Stone columns increase the bearing capacity and reduce the settlement of soil. Finite element analyses were performed using the program PLAXIS 2D. An elastic-perfectly plastic constitutive relation, based on the Mohr–Coulomb criterion, governs the soft clay and stone column behaviour. This paper presents on how the response surface methodology (RSM) software is used to optimize the effect of the diameters and lengths of column on the load bearing capacity and settlement of soft clay. Load tests through the numerical modelling using Plaxis 2D were carried out on the loading plate at 66 mm. Stone column load bearing capacity increases with the increasing diameter of the column and settlement decreases with the increasing length of the column. Results revealed that the bigger column diameter, the higher load bearing capacity of soil while the longer column length, the lower settlement of soil. However, the optimum design of stone column was varied with each factor (diameter and length) separately for improvement.
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Why work was done?
To be able to identify, on a proteomic level, cytochromes P450 (CYP) and UDP-glucuronosyltransferases (UGT) in mouse liver microsomes for the conazole exposure study IRP # NHEERL-ECD-SCN-CZ-2002-01-R1_Addendum 1. The new enrichment method was necessary beca...
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Production of thrombopoietin (TPO) by rat hepatocytes and hepatoma cell lines.
Shimada, Y; Kato, T; Ogami, K; Horie, K; Kokubo, A; Kudo, Y; Maeda, E; Sohma, Y; Akahori, H; Kawamura, K
1995-12-01
Recently, we purified rat thrombopoietin (TPO) from plasma of irradiated rats (XRP) by measuring its activity that stimulated the production of megakaryocytes from megakaryocyte progenitor cells (CFU-MK) in vitro. We then cloned the cDNAs for rat and human TPO. In this study, we found the production of TPO by hepatocytes isolated with the collagenase perfusion method from both normal and thrombocytopenic rats, by a two-step fractionation of hepatocyte culture medium (CM). Subsequently, CM of rat hepatoma cell lines was screened for the presence of TPO; three cell lines, H4-II-E, McA-RH8994, and HTC, were found to produce TPO. According to the purification procedure for TPO from XRP, TPO was partially purified from 2 L CM of each of three cell lines with a six-step procedure. In the final reverse-phase column, TPO from each cell line was eluted with the same retention time as that from XRP, and the TPO fraction exhibited megakaryocyte colony-stimulating activity (Meg-CSA). TPO-active fraction eluted from the final reverse-phase column was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), extracted from the gel, and assayed. TPO activity from each cell line was found in the respective molecular weight region, indicating the heterogeneity of the TPO molecule. Using reverse transcriptase-polymerase chain reaction (RT-PCR), we detected the expression of TPO mRNA in hepatocytes, three hepatoma cell lines, normal rat liver, and X-irradiated rat liver. Northern blot analysis showed that TPO mRNA was expressed mainly in liver among the various organs tested. These data demonstrate that TPO is produced by rat hepatocytes and hepatoma cell lines and suggest that liver may be the primary organ that produces TPO.
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Arroyo-Abad, Uriel; Lischka, Susanne; Piechotta, Christian; Mattusch, Jürgen; Reemtsma, Thorsten
2013-12-01
The present study was focused on the determination and identification of arsenic species in methanolic extracts of cod liver. Arsenic species were fractionated and the fractions analysed by RP-HPLC-ICP-MS coupled with ESI-Q-TOF-MS. The total concentration of arsenic in the fresh cod liver was analysed by ICP-MS to be 1.53±0.02 mg As kg(-1)w.w. and the extraction recovery was ca. 100% and the column recovery >93%. Besides polar inorganic and methylated arsenic species (>70%) more hydrophobic arsenic-containing fatty acids and hydrocarbons occurred. Based on the mass spectrometric data proposals for molecular structures were elaborated for 20 of the organic As species included 10 arsenic-containing fatty acids (AsFA) and an arsenic-containing hydrocarbon (AsHC) mentioned for the first time in fresh cod liver. Arsenobetaine was found as main water-soluble arsenic compound in cod liver followed by higher molecular mass arsenic-containing fatty acids and hydrocarbons. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Age dependency of base modification in rabbit liver DNA
NASA Technical Reports Server (NTRS)
Yamamoto, O.; Fuji, I.; Yoshida, T.; Cox, A. B.; Lett, J. T.
1988-01-01
Age-related modifications of DNA bases have been observed in the liver of the New Zealand white (NZW) rabbit (Oryctolagus cuniculus), a lagomorph with a median life span in captivity of 5-7 yr. The ages of the animals studied ranged from 6 wk to 9 yr. After the DNA had been extracted from the liver cell nuclei and hydrolyzed with acid, the bases were analyzed by column chromatography with Cellulofine gels (GC-15-m). Two peaks in the chromatogram, which eluted before the four DNA bases, contained modified bases. Those materials, which were obtained in relatively large amounts from old animals, were highly fluorescent, and were shown to be crosslinked base products by mass spectrometry. The yield of crosslinked products versus rabbit age (greater than 0.5 yr) can be fitted by an exponential function (correlation coefficient: 0.76 +/- 0.09).
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Device to improve detection in electro-chromatography
Garguilo, Michael G.; Paul, Phillip H.; Rakestraw, David J.
2000-01-01
Apparatus and method for improving the resolution of non-pressure driven capillary chromatographic systems, and particularly for capillary electrochromatography (CEC) systems. By reducing the cross-sectional area of a packed capillary column by means of a second open capillary contiguous with the outlet end of a packed capillary column, where the packed capillary column has a cross sectional area of between about 2 and 5 times that of the open capillary column, the phenomenon of band broadening in the transition region between the open capillary and the packed capillary column, where the individual components of the mixture are analyzed, can be eliminated, thereby providing for a significant improvement in resolution and more accurate detection and analysis.
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Device to improve detection in electro-chromatography
Garguilo, Michael G.; Paul, Phillip H.; Rakestraw, David J.
2002-01-01
Apparatus and method for improving the resolution of non-pressure driven capillary chromatographic systems, and particularly for capillary electrochromatography (CEC) systems. By reducing the cross-sectional area of a packed capillary column by means of a second open capillary contiguous with the outlet end of a packed capillary column, where the packed capillary column has a cross sectional area of between about 2 and 5 times that of the open capillary column, the phenomenon of band broadening in the transition region between the open capillary and the packed capillary column, where the individual components of the mixture are analyzed, can be eliminated, thereby providing for a significant improvement in resolution and more accurate detection and analysis.
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2009-01-01
Background It has been demonstrated in many studies that quality of life can be improved after liver transplantation in patients with liver disease. Nevertherless quality of life improvement in specific groups of transplantated patients such as those with Familial Amyloid Polineuropathy hasn't yet been explored. The present study aimed to compare the change in quality of life following liver transplantation between patients with Familial Amyloid Polineuropathy (FAP) and patients with liver disease. Results Patient's mental quality of life showed an improvement in all liver disease patients, and a worsening in FAP patients, resulting in a significant difference between the two groups. Regarding physical quality of life, although a similar improvement was seen in both groups, FAP patients had significantly less improvement than the sub-group of decompensated liver disease (Child-Pugh B and C). Conclusion It is concluded that liver transplantation has a less beneficial impact in FAP patient's physical quality of life, probably because they are not so much disabled by their disease at the moment of liver transplantation. The lesser improvement in mental quality of life of FAP patients may be due to their particular psychological profile and greater expectations towards transplantation. PMID:19604387
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Knold, Lone; Reitov, Marianne; Mortensen, Anna Birthe; Hansen-Møller, Jens
2002-01-01
A rapid and quantitative method for the extraction, derivatization, and liquid chromatography with fluorescence detection of ivermectin (IVM) and doramectin (DOM) residues in porcine liver was developed and validated. IVM and DOM were extracted from the liver samples with acetonitrile, the supernatant was evaporated to dryness at 37 degrees C under nitrogen, and the residue was reconstituted in 1-methylimidazole solution. After 2 min at room temperature, IVM and DOM were converted to a fluorescent derivative and then separated on a Hypersil ODS column. The derivatives of IVM and DOM were detected and quantitated with high specificity by fluorescence (excitation: 365 nm, emission: 475 nm). Abamectin was used as an internal standard. The mean extraction efficiencies from fortified samples (15 ng/g) were 75% for IVM and 70% for DOM. The limit of detection was 0.8 ng/g for both IVM and DOM.
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Subcellular distribution of trace elements in the liver of sea turtles.
Anan, Yasumi; Kunito, Takashi; Sakai, Haruya; Tanabe, Shinsuke
2002-01-01
Subcellular distribution of Cu, Zn, Se, Rb, Mo, Ag, Cd and Pb was determined in the liver of green turtles (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) from Yaeyama Islands, Japan. Also, hepatic cytosol from sea turtles was applied on a Sephadex G-75 column and elution profiles of trace elements were examined. Copper, Zn, Se, Rb, Ag and Cd were largely present in cytosol in the liver of both species, indicating that cytosol was the significant site for the accumulation of these elements in sea turtles. In contrast, Mo and Pb were accumulated specifically in nuclear and mitochondrial fraction and microsomal fraction, respectively. Gel filtration analysis showed that Cu, Zn, Ag and Cd were bound to metallothionein (MT) in the cytosol of sea turtles. To our knowledge, this is the first report on the association of trace elements with MT in sea turtles.
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Ferslew, K E; Hagardorn, A N; McCormick, W F
1989-01-01
A case is presented of a death caused by self-injection of sufentanil and midazolam. Biological fluids and tissues were analyzed for midazolam by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS) and for sufentanil by GC/MS. Midazolam was extracted from basified fluids or tissues homogenated with n-butyl chloride and analyzed by HPLC by using a phosphate buffer: acetonitrile (60:40) mobile phase on a mu-Bondapak C18 column at 240 nm. Sufentanil was extracted from basified fluids and tissue homogenates with hexane:ethanol (19:1). GC/MS methodology for both compounds consisted of chromatographic separation on a 15-m by 0.25-mm inside diameter (ID) DB-5 (1.0-micron-thick film) bonded phase fused silica capillary column with helium carrier (29 cm/s) splitless injection at 260 degrees C; column 200 degrees C (0.8 min) 10 degrees C/min to 270 degrees C; and electron ionization and multiple ion detection for midazolam (m/z 310), methaqualone (IS, m/z 235), sufentanil (m/z 289), and fentanyl (IS, m/z 245). Sufentanil concentrations were: blood 1.1 ng/mL, urine 1.3 ng/mL, vitreous humor 1.2 ng/mL, liver 1.75 ng/g, and kidney 5.5 ng/g. Midazolam concentrations were: blood 50 ng/mL, urine 300 ng/mL, liver 930 ng/g, and kidney 290 ng/g. Cause of death was attributed to an acute sufentanil/midazolam intoxication and manner of death a suicide.
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Hsieh, C Y; Huang, J D
1992-03-13
A two-dimensional high-performance liquid chromatographic method was developed to assay the enantiomers of a major phenytoin metabolite, p-hydroxyphenylphenylhydantoin (p-HPPH). Racemic p-HPPH was first separated from phenytoin and other interfering peaks by a reversed-phase column and monitored by an ultraviolet detector. At the retention time of p-HPPH, the racemic p-HPPH peak was automatically transferred to a chiral ligand-exchange column to separate R-p-HPPH and S-p-HPPH by a time-programmed column-switching valve. The ratio of enantiomers was measured by a second ultraviolet detector. The method can be used to assay R- and S-p-HPPH enantiomers with reasonable sensitivity and reproducibility. By using this method, the stereoselectivity of enzyme induction and inhibition of phenytoin metabolism was investigated. Male rats were treated with phenobarbital, 3-methylcholanthrene, acetone, Aroclor 1254, pregnenolone-16 alpha-carbonitrile, dexamethasone and isosafrole. Microsomes were prepared from the rat liver and phenytoin hydroxylation was measured. Pretreatment with phenobarbital, pregnenolone-16 alpha-carbonitrile or acetone induced phenytoin metabolism non-stereoselectively. Pretreatment with dexamethasone decreased R-p-HPPH formation without affecting the formation of S-p-HPPH. Liver microsomes from female rats showed a higher S-p-HPPH formation, whereas R-p-HPPH formation remained the same. Various inhibitors were added to inhibit phenytoin metabolism by control microsomes. Sulphaphenazole, ketoconazole, 4,4-di(p-methoxyphenyl)hydantoin, cimetidine and diazepam inhibited the formation of R- and S-p-HPPH. Quinidine, tolbutamide and mephenytoin showed no significant inhibitory activity. None of these inhibitors showed stereoselectivity.
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REDISTRIBUTOR FOR LIQUID-LIQUID EXTRACTION COLUMNS
Bradley, J.G.
1957-10-29
An improved baffle plate construction to intimately mix immiscible liquid solvents for solvent extraction processes in a liquid-liquid pulse column is described. To prevent the light and heavy liquids from forming separate continuous homogeneous vertical channels through sections of the column, a baffle having radially placed rectangular louvers with deflection plates opening upon alternate sides of the baffle is placed in the column, normal to the axis. This improvement substantially completely reduces strippiig losses due to poor mixing.
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Sae-Leaw, Thanasak; Benjakul, Soottawat
2018-02-01
Lipase from liver of seabass (Lates calcarifer), with a molecular weight of 60kDa, was purified to homogeneity using ammonium sulfate precipitation and a series of chromatographies, including diethylaminoethyl sepharose (DEAE) and Sephadex G-75 size exclusion columns. The optimal pH and temperature were 8.0 and 50°C, respectively. Purified lipase had Michaelis-Menten constant (K m ) and catalytic constant (k cat ) of 0.30mM and 2.16s -1 , respectively, when p-nitrophenyl palmitate (p-NPP) was used as the substrate. When seabass skin was treated with crude lipase from seabass liver at various levels (0.15 and 0.30units/g dry skin) for 1-3h at 30°C, the skin treated with lipase at 0.30 units/g dry skin for 3h had the highest lipid removal (84.57%) with lower lipid distribution in skin. Efficacy in defatting was higher than when isopropanol was used. Thus, lipase from liver of seabass could be used to remove fat in fish skin. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Improved Thermal Modulator for Gas Chromatography
NASA Technical Reports Server (NTRS)
Hasselbrink, Ernest Frederick, Jr.; Hunt, Patrick J.; Sacks, Richard D.
2008-01-01
An improved thermal modulator has been invented for use in a variant of gas chromatography (GC). The variant in question denoted as two-dimensional gas chromatography (2DGC) or GC-GC involves the use of three series-connected chromatographic columns, in the form of capillary tubes coated interiorly with suitable stationary phases (compounds for which different analytes exhibit different degrees of affinity). The two end columns are relatively long and are used as standard GC columns. The thermal modulator includes the middle column, which is relatively short and is not used as a standard GC column: instead, its temperature is modulated to affect timed adsorption and desorption of analyte gases between the two end columns in accordance with a 2DGC protocol.
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Krynitsky, A.J.; Stafford, C.J.; Wiemeyer, Stanley N.
1988-01-01
Dicofol in avian eggs was completely oxidized to dichlorobenzophenone (DCBP) when a hexane Soxhlet extraction procedure was used. This degradation did not occur with other avian tissues (muscle and liver). For this reason, a combined extraction-cleanup column chromatographic procedure, without added heat, was developed for the determination of dicofol in avian eggs. Homogenized subsamples of eggs were mixed with sodium sulfate, and the mixture was added as the top layer on a column prepacked with Florisil. The dicofol and other compounds of interest were then eluted with ethyl ether-hexane. The extracts, relatively free from lipids, were quantitated on a gas chromatograph equipped with a 63Ni electron-capture detector and a methyl silicone capillary column. Recoveries from chicken eggs, fortified with dicofol and other DDT-related compounds, averaged 96%. Analysis of eggs of eastern screech-owls, fed a meat diet containing 10 ppm technical Kelthane, showed that both dicofol and DCBP were present. Results were confirmed by gas chromatography/mass spectrometry. This method is rapid and reliable, involves a minimum of sample handling, and is well suited for high volume determination of dicofol in eggs and other avian tissues.
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Kopacz-Jodczyk, T; Paszkiewicz-Gadek, A; Lopaczyński, W; Gałasiński, W
1984-04-06
A rapid and simple procedure for isolation of 40S and 60S ribosomal subunits by ion-exchange column chromatography is described. The dissociated ribosomes can be separated and non-ribosomal proteins and low-molecular-weight substances removed. An assessment by physicochemical and functional criteria showed that the ribosomal subunits obtained are active and sufficiently homogeneous.
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Xie, Rui; Tu, Maobing; Wu, Yonnie; Adhikari, Sushil
2011-04-01
5-Hydroxymethylfurfural (HMF) and furfural could be separated by the Aminex HPX-87H column chromatography, however, the separation and quantification of acetic acid and levulinic acid in biomass hydrolysate have been difficult with this method. In present study, the HPLC separation of acetic acid and levulinic acid on Aminex HPX-87H column has been investigated by varying column temperature, flow rate, and sulfuric acid content in the mobile phase. The column temperature was found critical in resolving acetic acid and levulinic acid. The resolution for two acids increased dramatically from 0.42 to 1.86 when the column temperature was lowered from 60 to 30 °C. So did the capacity factors for levulinic acid that was increased from 1.20 to 1.44 as the column temperature dropped. The optimum column temperature for the separation was found at 45 °C. Variation in flow rate and sulfuric acid concentration improved not as much as the column temperature did. Published by Elsevier Ltd.
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Measurement of glucuronidation by isolated rat liver cells using [14C]fructose.
Dawson, J; Knowles, R G; Pogson, C I
1992-03-03
We have developed a simple and sensitive method for the study of the relative rates of glucuronidation of compounds, in isolated liver cells, based on the incorporation of 14C from fructose into glucuronide conjugates. Liver cells from fasted rats are used to minimize any reduction of the specific activity by glycogenolysis. Although rates of glucuronidation are lower in isolated liver cells from fasted rats than in those from fed rats, because of a reduction in the concentration of UDP-glucuronic acid, it is possible to compare the rates of glucuronidation of different compounds. Radiolabelled glucuronides are separated from [14C]fructose and [14C]glucose, produced by the liver cells, by normal-phase HPLC on a polar amino-cyano column. The specific activity of the glucuronide was found to be approximately 50% of that of the [14C]fructose. Absolute amounts of glucuronide can be determined by measuring the specific activity of the [14C]glucose, also produced by liver cells from fructose, which reflects that of the glucose-6-phosphate and hence the UDP-glucuronic acid used for glucuronidation, although for the measurement of relative rates this would not be necessary. We have used this method to examine the kinetics of the glucuronidation of N-acetyl-p-aminophenol (acetaminophen), 4-nitrophenol and 1-naphthol in isolated rat liver cells. The method should be applicable to the study of the rates of glucuronidation of a range of aglycones and, unlike other methods, does not require glucuronide standards or radiolabelled aglycone.
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Determination of Selected Amino Acids in Serum of Patients with Liver Disease.
Kanďár, Roman; Drábková, Petra; Toiflová, Tereza; Čegan, Alexander
2016-01-01
The determination of amino acids can be a reliable approach for extended diagnosis of liver diseases. This is because liver disease can be a cause of impaired amino acid metabolism. Therefore, a method for the determination of serum amino acids, applicable for clinical purposes, is necessary. The aim of this study was to find differences in the levels of selected amino acids between patients with liver disease and a control group. Samples of peripheral venous blood were obtained from a group of patients with liver disease (n = 131, 59 women at an average age of 60 years and 72 men at an average age of 52 years) and a control group (n = 105, 47 women at an average age of 62 years and 58 men at an average age of 58 years). Before the separation, the amino acids were derivatized with naphthalene-2,3-dicarboxaldehyde. For the separation, reverse phase column was used. The effluent was monitored with a fluorescence detector. There were significant differences in the concentrations of some amino acids between the patients and the control group, but also between women and men. Correlations between some amino acids and markers of liver blood tests and lipid metabolism were observed. A simple, relatively rapid and selective HPLC method with fluorescence detection for the determination of selected amino acids in serum has been developed.
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Gas-liquid chromatographic determination of kepone in field-collected avian tissues and eggs
Stafford, C.J.; Reichel, W.L.; Swineford, D.M.; Prouty, R.M.; Gay, M.L.
1978-01-01
A procedure is described for determining Kepone (decachlorooctahydro-1,3,4-metheno-2H-cyclobuta [cd] pentalene-2-one) residues in avian egg, liver, and tissue. Samples were extracted with benzene-isopropanol, and the extract was cleaned up with fuming H2SO4-concentrated H2SO4. Kepone was separated from organochlorine pesticides and polychlorinated biphenyls on a Florisil column and analyzed by electron capture gas-liquid chromatography (GLC). The average recovery from spiked tissues was 86%. The analyses performed on 14 bald eagle carcasses and livers, 3 bald eagle eggs, and 14 osprey eggs show measurable levels which indicate that Kepone accumulates in the tissues of fish-eating birds. Residues were confirmed by GLC-mass spectrometry.
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USDA-ARS?s Scientific Manuscript database
An LC-MS/MS method was developed and validated to determine 7alpha-OH cholesterol in liver microsome. This method was convenient and fast with high specificity and sensitivity. Briefly, a gradient elution was performed on a Synergi polar-C18 column (50 x 4.6mm i.d., 3microm). The mobile phase (cons...
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Ecotoxicological assessment of bluegill sunfish inhabiting a selenium-enriched fly ash stream
DOE Office of Scientific and Technical Information (OSTI.GOV)
Reash, R.J.; Lohner, T.W.; Wood, K.V.
1999-07-01
Little Scary Creek (LSC), a 2nd-order tributary of the Kanawha River in West Virginia, receives treated fly ash produced during coal combustion. Selenium and other trace metals were determined in water column and sediment samples, caddisflies, and bluegill sunfish liver and gonads during 1995--96 to estimate pathways of selenium exposure and assess the likelihood of toxic effects. Selenium levels in LSC water and sediment samples, and in caddisflies were elevated compared to reference sites. Mean dry weight selenium concentrations in bluegill liver, ovary, and tested tissue equaled or exceeded published toxic thresholds. Other trace metals were significantly higher in LSCmore » bluegill. Leukopenia, elevated serum salts, and lowered liver weight were found in LSC bluegill. Fewer older bluegill were found in LSC. Sunfish in LSC are experiencing various kinds of sublethal stress, presumably due to metals exposure. However, major toxic effects that would be predicted to occur based on tissue selenium levels (complete reproductive failure or mortality) have not been observed in this population.« less
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Yin, Xianzhe; Kiriake, Aya; Ohta, Akira; Kitani, Yoichiro; Ishizaki, Shoichiro; Nagashima, Yuji
2017-09-15
Marine pufferfish of the Tetraodontidae family contain high levels of tetrodotoxin (TTX) in the liver and ovary. TTX is suggested to transfer from the liver to the ovary in female pufferfish during maturation. TTX in pufferfish eggs may act as a repellent against predators and as a sexual pheromone to attract male pufferfish. The toxification mechanism of the pufferfish ovary is poorly understood. Here we evaluated the chemical form of TTX and its related substances in the ovary of the panther pufferfish Takifugu pardalis by LC-ESI/MS. TTX and its analogs 4-epi-TTX, 4, 9-anhydroTTX, deoxyTTX, dideoxyTTX, and trideoxyTTX were detected in a low molecular weight fraction by Sephacryl S-400 column chromatography. The finding of an unknown TTX-related substance in a high molecular weight fraction from the Sephacryl S-400 column suggested the occurrence of toxin-binding protein in the ovary. The toxin-binding protein in the ovary was purified by ion-exchange HPLC, gel filtration HPLC, and SDS-PAGE. Amino acid sequencing and cDNA cloning revealed that the toxin-binding protein, TPOBP-10 (Takifugu pardalis ovary toxin-binding protein with a molecular mass of 10 kDa) was homologous with the predicted vitellogenin-1-like protein [Takifugu rubripes] subdomain, a von Willebrand factor type D domain. TPOBP-10 mRNA was highly expressed in the ovary and liver and less in other organs of female individuals based on RT-PCR. These findings reveal a novel function of the vitellogenin subdomain as binding with TTX-related substances, and its involvement in the toxification of the pufferfish ovary. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Tata, P N; Fu, C H; Browder, N J; Chow, P C; Bramer, S L
1998-11-01
A high-performance liquid chromatography-ultraviolet (HPLC-UV) method for the quantitation of cilostazol and four of its principal metabolites (i.e. OPC-13015, OPC-13213, OPC-13217 and OPC-13326) in human liver microsomal solutions was developed and validated. Cilostazol, its metabolites, and the internal standard (OPC-3930), were analyzed by protein precipitation followed by reverse-phase HPLC separation on a TSK-Gel ODS-80TM (150 x 4.6 mm, 5 microm) column and a Cosmil C-18 column (150 x 4.6 mm, 5 microm) in tandem and UV detection at 254 nm. An 80 min gradient elution of mobile phase acetonitrile in acetate buffer (pH = 6.50) was used to obtain quality chromatography and peak resolution. All the analytes were separated from each other, with the resolution being 2.43-17.59. The components of liver microsomal incubation mixture and five metabolic inhibitor probes (quinidine sulfate, diethyl dithiocarbamate (DEDTC), omeprazole, ketoconazole and furafylline) did not interfere with this analytical method. The LOQ was 1000 ng ml(-1) for cilostazol and 100 ng ml(-1) for each of the metabolites. This method has been validated for linear ranges of 100-4000 ng ml(-1) for OPC-13213, OPC-13217 and OPC-13326; 100-2000 ng ml(-1) for OPC-13015; and 1000-20000 ng ml(-1) for cilostazol. The percent relative recovery of this method was established to be 81.2-101.0% for analytes, with the precision (% coefficient of variation (CV)) being 2.8-7.7%. The autosampler stability of the analytes was evaluated and it was found that all analytes were stable at room temperature for a period of at least 17 h. This assay has been shown to be precise, accurate and reproducible.
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Davies, Benjamin J; Herbert, Megan K; Coller, Janet K; Somogyi, Andrew A; Milne, Robert W; Sallustio, Benedetta C
2006-11-07
The use of perhexiline (PHX) is limited by hepatic and neurological toxicity associated with elevated concentrations in plasma that are the result of polymorphism of the cytochrome P450 2D6 isoform (CYP2D6). PHX is cleared by hepatic oxidation that produces three 4-monohydroxy metabolites: cis-OH-PHX, trans1-OH-PHX and trans2-OH-PHX. The current study describes an HPLC-fluorescent method utilising pre-column derivatization with dansyl chloride. Following derivatization, the metabolites were resolved on a C18 column with a gradient elution using a mobile phase composed of methanol and water. The method described is suitable for the quantification of the metabolites in human plasma and urine following clinical doses and for kinetic studies using human liver microsomes. The method demonstrates sufficient sensitivity, accuracy and precision between 5.0 and 0.01, 50.0 and 0.2 and 1.0 and 0.005 mg/l in human plasma, urine and liver microsomes, respectively, with intra-assay coefficients of variation and bias <15%, except at the lowest limit of quantification (<20%). The inter-assay coefficients of variation and bias were <15%. The application of this method to plasma and urine samples of five CYP2D6 extensive metaboliser (EM) patients at steady state with respect to PHX dosing determined that the mean (+/-S.D.) renal clearances of trans1-OH-PHX and cis-OH-PHX were 1.58+/-0.35 and 0.16+/-0.06l/h, respectively. The mean (+/-S.D.) dose recovered in urine as free and glucuronidated 4-monohydroxy PHX metabolites was 20.6+/-11.6%.
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Huang, He-Qing; Xiao, Zhi-Qun; Chen, Xu; Lin, Qing-Mei; Cai, Zong-Wei; Chen, Ping
2004-11-01
The ferritin consists of a protein shell constructed of 24 subunits and an iron core. The liver ferritin of Sphyrna zygaena (SZLF) purified by column chromatography is a protein composed of eight ferritins containing varying iron numbers ranging from 400+/-20 Fe3+/SZLF to 1890+/-20 Fe3+/SZLF within the protein shell. Nature SZLF (SZLFN) consisting of holoSZLF and SZLF with unsaturated iron (SZLFUI) to have been purified with polyacrylamide gel electrophoresis (PAGE) exhibited five ferritin bands with different pI values ranging from 4.0 to 7.0 in the gel slab of isoelectric focusing (IEF). HoloSZLF purified by PAGE (SZLFE) not only had 1890+/-20 Fe3+/SZLFE but also showed an identical size of iron core observed by transmission electron microscopy (TEM). Molecular weight of approximately 21 kDa for SZLFE subunit was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Four peaks of molecular ions at mass/charge (m/z) ratios of 10611.07, 21066.52, 41993.16, and 63555.64 that come from the SZLFE were determined by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS), which were identified as molecular ions of the ferritin subunit (M+) and its polymers, namely, [M]2+, [M]+, [2M]+, and [3M]+, respectively. Both SZLFE and a crude extract from shark liver of S. zygaena showed similar kinetic characteristics of complete iron release with biphasic behavior. In addition, a combined technique of visible spectrometry and column chromatography was used for studying ratio of phosphate to Fe3+ within the SZLFE core. Interestingly, this ratio maintained invariable even after the iron release, which differed from that of other mammal ferritins.
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Quality Improvement of Liver Ultrasound Images Using Fuzzy Techniques.
Bayani, Azadeh; Langarizadeh, Mostafa; Radmard, Amir Reza; Nejad, Ahmadreza Farzaneh
2016-12-01
Liver ultrasound images are so common and are applied so often to diagnose diffuse liver diseases like fatty liver. However, the low quality of such images makes it difficult to analyze them and diagnose diseases. The purpose of this study, therefore, is to improve the contrast and quality of liver ultrasound images. In this study, a number of image contrast enhancement algorithms which are based on fuzzy logic were applied to liver ultrasound images - in which the view of kidney is observable - using Matlab2013b to improve the image contrast and quality which has a fuzzy definition; just like image contrast improvement algorithms using a fuzzy intensification operator, contrast improvement algorithms applying fuzzy image histogram hyperbolization, and contrast improvement algorithms by fuzzy IF-THEN rules. With the measurement of Mean Squared Error and Peak Signal to Noise Ratio obtained from different images, fuzzy methods provided better results, and their implementation - compared with histogram equalization method - led both to the improvement of contrast and visual quality of images and to the improvement of liver segmentation algorithms results in images. Comparison of the four algorithms revealed the power of fuzzy logic in improving image contrast compared with traditional image processing algorithms. Moreover, contrast improvement algorithm based on a fuzzy intensification operator was selected as the strongest algorithm considering the measured indicators. This method can also be used in future studies on other ultrasound images for quality improvement and other image processing and analysis applications.
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Quality Improvement of Liver Ultrasound Images Using Fuzzy Techniques
Bayani, Azadeh; Langarizadeh, Mostafa; Radmard, Amir Reza; Nejad, Ahmadreza Farzaneh
2016-01-01
Background: Liver ultrasound images are so common and are applied so often to diagnose diffuse liver diseases like fatty liver. However, the low quality of such images makes it difficult to analyze them and diagnose diseases. The purpose of this study, therefore, is to improve the contrast and quality of liver ultrasound images. Methods: In this study, a number of image contrast enhancement algorithms which are based on fuzzy logic were applied to liver ultrasound images - in which the view of kidney is observable - using Matlab2013b to improve the image contrast and quality which has a fuzzy definition; just like image contrast improvement algorithms using a fuzzy intensification operator, contrast improvement algorithms applying fuzzy image histogram hyperbolization, and contrast improvement algorithms by fuzzy IF-THEN rules. Results: With the measurement of Mean Squared Error and Peak Signal to Noise Ratio obtained from different images, fuzzy methods provided better results, and their implementation - compared with histogram equalization method - led both to the improvement of contrast and visual quality of images and to the improvement of liver segmentation algorithms results in images. Conclusion: Comparison of the four algorithms revealed the power of fuzzy logic in improving image contrast compared with traditional image processing algorithms. Moreover, contrast improvement algorithm based on a fuzzy intensification operator was selected as the strongest algorithm considering the measured indicators. This method can also be used in future studies on other ultrasound images for quality improvement and other image processing and analysis applications. PMID:28077898
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Temperature programmable microfabricated gas chromatography column
Manginell, Ronald P.; Frye-Mason, Gregory C.
2003-12-23
A temperature programmable microfabricated gas chromatography column enables more efficient chemical separation of chemical analytes in a gas mixture by the integration of a resistive heating element and temperature sensing on the microfabricated column. Additionally, means are provided to thermally isolate the heated column from their surroundings. The small heat capacity and thermal isolation of the microfabricated column improves the thermal time response and power consumption, both important factors for portable microanalytical systems.
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Loguercio, Carmela; Andreone, Pietro; Brisc, Ciprian; Brisc, Michaela Cristina; Bugianesi, Elisabetta; Chiaramonte, Maria; Cursaro, Carmela; Danila, Mirela; de Sio, Ilario; Floreani, Annarosa; Freni, Maria Antonietta; Grieco, Antonio; Groppo, Marzia; Lazzari, Roberta; Lobello, Salvatore; Lorefice, Elisabetta; Margotti, Marzia; Miele, Luca; Milani, Stefano; Okolicsanyi, Lajos; Palasciano, Giuseppe; Portincasa, Piero; Saltarelli, Patrizia; Smedile, Antonina; Somalvico, Francesco; Spadaro, Aldo; Sporea, Ioan; Sorrentino, Paolo; Vecchione, Raffaela; Tuccillo, Concetta; Del Vecchio Blanco, Camillo; Federico, Alessandro
2012-05-01
The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.
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Faizan, Mohammad; Esatbeyoglu, Tuba; Bayram, Banu; Rimbach, Gerald
2014-04-01
Malondialdehyde (MDA) is a biomarker of lipid peroxidation and is present in foods and biological samples such as plasma. A high-performance liquid chromatography (HPLC) method was applied to determine MDA in fish liver samples after derivatization with 2,4-dinitrophenylhydrazine (DNPH) using a ODS2 column (10 cm × 4.6 mm, 3 μm) and a photodiode array detector. The mobile phase consisted of 0.2% acetic acid (v/v) in distilled water and acetonitrile (42:58, v/v). The present method was validated in terms of linearity, lower limit of quantification, lower limit of detection, precision, accuracy, recovery, and stability of MDA according to U.S. Food and Drug Administration (FDA) guidelines. The limit of quantification of MDA was 0.39 μmol/L, which is comparable to other methods. The recovery of the spiked MDA liver samples was in the range of 92.4% to 104.2%. This newly modified HPLC method is specific, sensitive, and accurate and allows the analysis of MDA within 4 min in fish liver but also in other tissues and plasma. © 2014 Institute of Food Technologists®
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Dahrenmöller, Carola; Reding, Raymond
2017-09-15
Transplant surgeons are currently faced with the challenge to accept marginal liver transplants due to steatosis or old age. Improving organ quality by implementing a selective organ protective donor management could be the first step towards a graft of enhanced quality. However, the molecular mechanisms of such treatments are still poorly understood. Glucocorticoid medication in donor medicine has been carried out and discussed for a long time. In a recent study published in Clinical Science , Jiménez-Castro et al. [Clin. Sci. (2017) 131, 733-746] demonstrate how liver histology and transplant liver function can be improved by administration of glucocorticoids to brain-dead donor rats with steatotic livers. This work illustrates the need for further trials in order to selectively improve the quality of steatotic livers with a potential for liver transplantation. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
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The Effects of Physical Exercise on Fatty Liver Disease
van der Windt, Dirk J.; Sud, Vikas; Zhang, Hongji; Tsung, Allan; Huang, Hai
2018-01-01
The increasing prevalence of obesity has made nonalcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the fastest increasing etiology of end-stage liver disease and hepatocellular carcinoma. Physical inactivity is related to the severity of fatty liver disease irrespective of body weight, supporting the hypothesis that increasing physical activity through exercise can improve fatty liver disease. This review summarizes the evidence for the effects of physical exercise on NAFLD and NASH. Several clinical trials have shown that both aerobic and resistance exercise reduce the hepatic fat content. From clinical and basic scientific studies, it is evident that exercise affects fatty liver disease through various pathways. Improved peripheral insulin resistance reduces the excess delivery of free fatty acids and glucose for free fatty acid synthesis to the liver. In the liver, exercise increases fatty acid oxidation, decreases fatty acid synthesis, and prevents mitochondrial and hepatocellular damage through a reduction of the release of damage-associated molecular patterns. In conclusion, physical exercise is a proven therapeutic strategy to improve fatty liver disease. PMID:29212576
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Aota, Arata; Date, Yasumoto; Terakado, Shingo; Ohmura, Naoya
2013-01-01
Polychlorinated biphenyls (PCBs) are persistent organic pollutants that are present in the insulating oil inside a large number of transformers. To aid in eliminating PCB-contaminated transformers, PCBs in oil need to be measured using a rapid and cost-effective analytical method. We previously reported a pretreatment method for the immunoassay of PCBs in oil using a large-scale multilayer column and a microchip with multiple microrecesses, which permitted concentrated solvent extraction. In this paper, we report on a more rapid and facile pretreatment method, without an evaporation process, by improving the column and the microchip. In a miniaturized column, the decomposition and separation of oil were completed in 2 min. PCBs can be eluted from the capillary column at concentrations seven-times higher than those from the previous column. The total volume of the microrecesses was increased by improving the microrecess structure, the enabling extraction of four-times the amount of PCBs achieved with the previous system. By interfacing the capillary column with the improved microchip, PCBs in the eluate from the column were extracted into dimethyl sulfoxide in microrecesses with high enrichment and without the need for evaporation. Pretreatment was completed within 20 min. The pretreated oil was analyzed using a flow-based kinetic exclusion immunoassay. The limit of detection of PCBs in oil was 0.15 mg kg(-1), which satisfies the criterion set in Japan of 0.5 mg kg(-1).
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Tao, Dingyin; Zhang, Lihua; Shan, Yichu; Liang, Zhen; Zhang, Yukui
2011-01-01
High-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS-MS) is regarded as one of the most powerful techniques for separation and identification of proteins. Recently, much effort has been made to improve the separation capacity, detection sensitivity, and analysis throughput of micro- and nano-HPLC, by increasing column length, reducing column internal diameter, and using integrated techniques. Development of HPLC columns has also been rapid, as a result of the use of submicrometer packing materials and monolithic columns. All these innovations result in clearly improved performance of micro- and nano-HPLC for proteome research.
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Distillation sequence for the purification and recovery of hydrocarbons
Reyneke, Rian; Foral, Michael; Papadopoulos, Christos G.; Logsdon, Jeffrey S.; Eng, Wayne W. Y.; Lee, Guang-Chung; Sinclair, Ian
2007-12-25
This invention is an improved distillation sequence for the separation and purification of ethylene from a cracked gas. A hydrocarbon feed enters a C2 distributor column. The top of the C2 distributor column is thermally coupled to an ethylene distributor column, and the bottoms liquid of a C2 distributor column feeds a deethanizer column. The C2 distributor column utilizes a conventional reboiler. The top of the ethylene distributor is thermally coupled with a demethanizer column, and the bottoms liquid of the ethylene distributor feeds a C2 splitter column. The ethylene distributor column utilizes a conventional reboiler. The deethanizer and C2 splitter columns are also thermally coupled and operated at a substantially lower pressure than the C2 distributor column, the ethylene distributor column, and the demethanizer column. Alternatively, a hydrocarbon feed enters a deethanizer column. The top of the deethanizer is thermally coupled to an ethylene distributor column, and the ethylene distributor column utilizes a conventional reboiler. The top of the ethylene distributor column is thermally coupled with a demethanizer column, and the bottoms liquid of the ethylene distributor column feeds a C2 splitter column. The C2 splitter column operates at a pressure substantially lower than the ethylene distributor column, the demethanizer column, and the deethanizer column.
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Sustainable materials used as stone column filler: A short review
NASA Astrophysics Data System (ADS)
Zukri, Azhani; Nazir, Ramli
2018-04-01
Stone columns (also known as granular piles) are one of the methods for soft soil stabilization and typically used to increase bearing capacity and stability of slope.; Apart from decreasing the compressibility of loose and fine graded soils, it also accelerates the consolidation effect by improving the drainage path for pore water pressure dissipation and reduces the liquefaction potential of soils during earthquake event. Stone columns are probably the most “natural” ground treatment method or foundation system in existence to date. The benefit of stone columns is owing to the partial replacement of compressible soil by more competent materials such as stone aggregate, sand and other granular materials. These substitutes also act as reinforcement material, hence increasing overall strength and stiffness of the soft soil. Nowadays, a number of research has been conducted on the behaviour and performance of stone columns with various materials utilized as column filler replacing the normal aggregate. This paper will review extensively on previously conducted research on some of the materials used as stone column backfill materials, its suitability and the effectiveness as a substitute for regular aggregates in soft soil improvement works.
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Effectiveness of sacrificial anodes in high-resistivity shotcrete repairs.
DOT National Transportation Integrated Search
2005-01-01
This study investigated the use of discrete sacrificial anodes to improve the durability and extend the life of a shotcrete patch repair in a column. Three columns were used in the investigation. In two columns, anodes were placed around the perimete...
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Cawley, William E.; Warnick, Robert F.
1982-01-01
1. In a nuclear reactor incorporating a plurality of columns of tubular fuel elements disposed in horizontal tubes in a mass of graphite wherein water flows through the tubes to cool the fuel elements, the improvement comprising at least one control column disposed in a horizontal tube including fewer fuel elements than in a normal column of fuel elements and tubular control elements disposed at both ends of said control column, and means for varying the horizontal displacement of the control column comprising a winch at the upstream end of the control column and a cable extending through the fuel and control elements and attached to the element at the downstream end of the column.
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Ezquer, Fernando; Bahamonde, Javiera; Huang, Ya-Lin; Ezquer, Marcelo
2017-01-28
The liver has the remarkable capacity to regenerate in order to compensate for lost or damaged hepatic tissue. However, pre-existing pathological abnormalities, such as hepatic steatosis (HS), inhibits the endogenous regenerative process, becoming an obstacle for liver surgery and living donor transplantation. Recent evidence indicates that multipotent mesenchymal stromal cells (MSCs) administration can improve hepatic function and increase the potential for liver regeneration in patients with liver damage. Since HS is the most common form of chronic hepatic illness, in this study we evaluated the role of MSCs in liver regeneration in an animal model of severe HS with impaired liver regeneration. C57BL/6 mice were fed with a regular diet (normal mice) or with a high-fat diet (obese mice) to induce HS. After 30 weeks of diet exposure, 70% hepatectomy (Hpx) was performed and normal and obese mice were divided into two groups that received 5 × 10 5 MSCs or vehicle via the tail vein immediately after Hpx. We confirmed a significant inhibition of hepatic regeneration when liver steatosis was present, while the hepatic regenerative response was promoted by infusion of MSCs. Specifically, MSC administration improved the hepatocyte proliferative response, PCNA-labeling index, DNA synthesis, liver function, and also reduced the number of apoptotic hepatocytes. These effects may be associated to the paracrine secretion of trophic factors by MSCs and the hepatic upregulation of key cytokines and growth factors relevant for cell proliferation, which ultimately improves the survival rate of the mice. MSCs represent a promising therapeutic strategy to improve liver regeneration in patients with HS as well as for increasing the number of donor organs available for transplantation.
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KernelADASYN: Kernel Based Adaptive Synthetic Data Generation for Imbalanced Learning
2015-08-17
eases [35], Indian liver patient dataset (ILPD) [36], Parkinsons dataset [37], Vertebral Column dataset [38], breast cancer dataset [39], breast tissue...Both the data set of Breast Cancer and Breast Tissue aim to predict the patient is normal or abnormal according to the measurements. The data set SPECT...9, pp. 1263–1284, 2009. [3] M. Elter, R. Schulz-Wendtland, and T. Wittenberg, “The prediction of breast cancer biopsy outcomes using two cad
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Yazawa, S; Kochibe, N; Nishimura, T; Shima, C; Takai, I; Adachi, M; Asao, T; Hada, T; Enoki, Y; Juneja, L R
1998-09-01
A new method for determination of alpha1,6fucosyltransferase activity has been described. Recently, the disialyl-biantennary undecasaccharide was prepared in high yield from egg yolk [(1996), Carbohydr Lett 2: 137-42]. By treatment of this oligosaccharide with neuraminidase and beta-galactosidase, we readily obtained an asialo-agalacto-biantennary heptasaccharide (GlcNAcbeta 1,2Manalpha1,6[GlcNAcbeta1,2Manalpha1,3]Manbeta1 ,4GlcNAcbeta1,4GlcNAc). Using this asialo-agalacto-oligosaccharide as an acceptor, fucosyltransferases from human plasma and extracts of various human hepatoma cell lines were assayed in the presence of GDP-[3H]fucose. The reaction mixture was applied to a column of GlcNAc-binding, Psathyrella velutina lectin coupled gel. All the fucosylated acceptor were bound to the column which was eluted with 50 mM GlcNAc. Structural analyses revealed that only the innermost GlcNAc residue of the acceptor was fucosylated through an alpha1,6-linkage, and the oligosaccharide prepared could be used as a specific acceptor for alpha1,6fucosyltransferase. The present method was used to screen plasma alpha1,6fucosyltransferase in several patient groups, and significantly elevated activities were found in samples from patients with liver diseases, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.
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Alvares, K; Carrillo, A; Yuan, P M; Kawano, H; Morimoto, R I; Reddy, J K
1990-01-01
Clofibrate and many of its structural analogues induce proliferation of peroxisomes in the hepatic parenchymal cells of rodents and certain nonrodent species including primates. This induction is tissue specific, occurring mainly in the liver parenchymal cells and to a lesser extent in the kidney cortical epithelium. The induction of peroxisomes is associated with a predictable pleiotropic response, characterized by hepatomegaly, and increased activities and mRNA levels of certain peroxisomal enzymes. Using affinity chromatography, we had previously isolated a protein that binds to clofibric acid. We now show that this protein is homologous with the heat shock protein HSP70 family by analysis of amino acid sequences of isolated peptides from trypsin-treated clofibric acid binding protein and by cross-reactivity with a monoclonal antibody raised against the conserved region of the 70-kDa heat shock proteins. The clofibric acid-Sepharose column could bind HSP70 proteins isolated from various species, which could then be eluted with either clofibric acid or ATP. Conversely, when a rat liver cytosol containing multiple members of the HSP70 family was passed through an ATP-agarose column, and eluted with clofibric acid, only P72 (HSC70) was eluted. These results suggest that clofibric acid, a peroxisome proliferator, preferentially interacts with P72 at or near the ATP binding site. Images PMID:2371272
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Wu, Changzhe; Cao, Yue; Huo, Xiaolin; Li, Ming
2015-01-01
Bioartificial liver support system (BALSS) based on culturing hepatocytes is an important research field for the treatment of acute liver failure. It is necessary to monitor the state of liver cell functions during the treatment of BALSS in order to guide clinical treatment. To design a micro-channel chip to achieve flash mixing for timely detection of liver cell status in bioreactors and improving liver cells growth environment to ensure the efficacy of the bio-artificial liver support system. Alanine aminotransferase (ALT) and Urea are chosen as detection indicators to reflect the degree of liver cell injury and the detoxification function. A diamond tandem structure micro-channel is designed and optimized to achieve the efficient mixing of serum and ALT or Urea reagent. The simulation and experimental results show that the diamond tandem structure micro-channel can significantly improve the mixing efficiency and meet the online detecting requirements. The easily controllable diamond tandem structure micro-channel combines the advantages of active and passive mixer and can effectively mix the serum and ALT or Urea reagent. It lays the foundation for online monitoring of liver cells and will help to improve the viability of liver cell in the bioreactor.
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Carrig, Sean; Bijjiga, Enoch; Wopat, Mitchell J; Martino, Ashley T
2016-11-01
Adeno-associated virus (AAV) gene transfer is a promising treatment for genetic abnormalities. Optimal AAV vectors are showing success in clinical trials. Gene transfer to skeletal muscle and liver is being explored as a potential therapy for some conditions, that is, α 1 -antitrypsin (AAT) disorder and hemophilia B. Exploring approaches that enhance transduction of liver and skeletal muscle, using these vectors, is beneficial for gene therapy. Regulating hormones as an approach to improve AAV transduction is largely unexplored. In this study we tested whether insulin therapy improves liver and skeletal muscle gene transfer. In vitro studies demonstrated that the temporary coadministration (2, 8, and 24 hr) of insulin significantly improves AAV2-CMV-LacZ transduction of cultured liver cells and differentiated myofibers, but not of lung cells. In addition, there was a dose response related to this improved transduction. Interestingly, when insulin was not coadministered with the virus but given 24 hr afterward, there was no increase in the transgene product. Insulin receptor gene (INSR) expression levels were increased 5- to 13-fold in cultured liver cells and differentiated myofibers when compared with lung cells. Similar INSR gene expression profiles occurred in mouse tissues. Insulin therapy was performed in mice, using a subcutaneously implanted insulin pellet or a high-carbohydrate diet. Insulin treatment began just before intramuscular delivery of AAV1-CMV-schFIX or liver-directed delivery of AAV8-CMV-schFIX and continued for 28 days. Both insulin augmentation therapies improved skeletal muscle- and liver-directed gene transduction in mice as seen by a 3.0- to 4.5-fold increase in human factor IX (hFIX) levels. The improvement was observed even after the insulin therapy ended. Monitoring insulin showed that insulin levels increased during the brief period of rAAV delivery and during the entire insulin augmentation period (28 days). This study demonstrates that AAV transduction of liver or skeletal muscle can be improved by insulin therapy.
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Tian, Xiaoting; Xu, Zhou; Chen, Mingcang; Hu, Pei; Liu, Fang; Sun, Zhaolin; Liu, Huan; Guo, Xiaozheng; Li, Zhixiong; Huang, Chenggang
2018-05-01
Only focusing on the circulating levels is insufficient for the comprehensive understanding of the physiological disposition of herbal medicine in vivo. Therefore, we conducted the comprehensive investigation on the in vivo dynamic process of orally administrated Gouteng-Baitouweng (GB), a classical herb pair with anti-Parkinson potentials. Serving as the technical base, a sensitive and selective liquid chromatography-tandem mass spectrometry method was established and validated in the plasma, liver and brain, for simultaneous determination of five alkaloids (rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine and geissoschizine methyl ether) and three saponins (anemoside B4, anemoside A3 and 23-hydroxybetulinic acid). Following liquid-liquid extraction, favorable chromatographic behaviors of eight analytes were obtained on Waters Xbrigde C18 column within 13 min. This method elicited good linearity for the analytes at the concentration range of 0.3-1000 or 1.8-6000 ng/mL with favorable precision, accuracy and stability. Following oral administration of GB (25 g/kg) in rats, this method was applied to the quantitative analysis in the portal vein plasma, liver, systemic plasma, and brain. Consequently, anemoside B4 was of the highest exposure, followed by 23-hydroxybetulinic acid, anemoside A3, rhynchophylline and isocorynoxeine in vivo. Notably, three saponins were all observed with certain exposure in the brain, along with rhynchophylline at low levels. Besides, five alkaloids and 23-hydroxybetulinic acid underwent serious liver first-pass effect. Hence, the pharmacokinetics, liver first-pass effect, liver and brain distribution of ingredients in GB were clarified, which laid a solid foundation for interpreting its efficacy and safety. Copyright © 2018. Published by Elsevier B.V.
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Hsu, Evelyn K; Mazariegos, George V
2017-01-01
Current literature and policy in pediatric liver allocation and organ procurement are reviewed here in narrative fashion, highlighting historical context, ethical framework, technical/procurement considerations, and support for a logical way forward to an equitable pediatric liver allocation system that will improve pediatric wait-list and posttransplant outcomes without adversely affecting adults. Where available, varying examples of successful international pediatric liver allocation and split-liver policy will be compared to current US policy to highlight potential strategies that can be considered globally. Liver Transplantation 23:86-95 2017 AASLD. © 2016 by the American Association for the Study of Liver Diseases.
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Recent Progress in Monolithic Silica Columns for High-Speed and High-Selectivity Separations.
Ikegami, Tohru; Tanaka, Nobuo
2016-06-12
Monolithic silica columns have greater (through-pore size)/(skeleton size) ratios than particulate columns and fixed support structures in a column for chemical modification, resulting in high-efficiency columns and stationary phases. This review looks at how the size range of monolithic silica columns has been expanded, how high-efficiency monolithic silica columns have been realized, and how various methods of silica surface functionalization, leading to selective stationary phases, have been developed on monolithic silica supports, and provides information on the current status of these columns. Also discussed are the practical aspects of monolithic silica columns, including how their versatility can be improved by the preparation of small-sized structural features (sub-micron) and columns (1 mm ID or smaller) and by optimizing reaction conditions for in situ chemical modification with various restrictions, with an emphasis on recent research results for both topics.
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NASA Astrophysics Data System (ADS)
Zhou, Yanguo; Sun, Zhengbo; Chen, Jie; Chen, Yunmin; Chen, Renpeng
2017-04-01
The evaluation and design of stone column improvement ground for liquefaction mitigation is a challenging issue for the state of practice. In this paper, a shear wave velocity-based approach is proposed based on the well-defined correlations of liquefaction resistance (CRR)-shear wave velocity ( V s)-void ratio ( e) of sandy soils, and the values of parameters in this approach are recommended for preliminary design purpose when site specific values are not available. The detailed procedures of pre- and post-improvement liquefaction evaluations and stone column design are given. According to this approach, the required level of ground improvement will be met once the target V s of soil is raised high enough (i.e., no less than the critical velocity) to resist the given earthquake loading according to the CRR- V s relationship, and then this requirement is transferred to the control of target void ratio (i.e., the critical e) according to the V s- e relationship. As this approach relies on the densification of the surrounding soil instead of the whole improved ground and is conservative by nature, specific considerations of the densification mechanism and effect are given, and the effects of drainage and reinforcement of stone columns are also discussed. A case study of a thermal power plant in Indonesia is introduced, where the effectiveness of stone column improved ground was evaluated by the proposed V s-based method and compared with the SPT-based evaluation. This improved ground performed well and experienced no liquefaction during subsequent strong earthquakes.
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Deugnier, Yves; Turlin, Bruno; Ropert, Martine; Cappellini, M Domenica; Porter, John B; Giannone, Vanessa; Zhang, Yiyun; Griffel, Louis; Brissot, Pierre
2011-10-01
Most data on the effects of iron chelation therapy for patients with liver fibrosis come from small studies. We studied the effects of the oral iron chelator deferasirox on liver fibrosis and necroinflammation in a large population of patients with iron overload β-thalassemia. We studied data from 219 patients with β-thalassemia, collected from histologic analyses of biopsy samples taken at baseline and after at least 3 years of treatment with deferasirox. Treatment response was assessed from liver iron concentrations at baseline and the end of the study. Liver fibrosis, necroinflammation, and markers of iron overload and liver enzymes were recorded. Patients were also assessed, by serologic analysis at baseline, for hepatitis C virus infection. By the end of the study, stability of Ishak fibrosis staging scores (change of -1, 0, or +1) or improvements (change of ≤-2) were observed in 82.6% of patients; Ishak necroinflammatory scores improved by a mean value of -1.3 (P<.001). Improvements in fibrosis stage and necroinflammation were independent of hepatitis C virus exposure or reduction in liver iron concentration defined by the response criteria. Absolute changes in concentrations of liver iron by the end of the study did not correlate with improved Ishak fibrosis or necroinflammatory scores. Deferasirox treatment for 3 or more years reversed or stabilized liver fibrosis in 83% of patients with iron-overloaded β-thalassemia. This therapeutic effect was independent of reduced concentration of liver iron (defined by the response criteria) or previous exposure to hepatitis C virus. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
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Mattar, Samer G.; Velcu, Laura M.; Rabinovitz, Mordechai; Demetris, A J.; Krasinskas, A M.; Barinas-Mitchell, Emma; Eid, George M.; Ramanathan, Ramesh; Taylor, Debra S.; Schauer, Philip R.
2005-01-01
Objective: To evaluate the effects of surgical weight loss on fatty liver disease in severely obese patients. Summary Background Data: Nonalcoholic fatty liver disease (NAFLD), a spectrum that extends to liver fibrosis and cirrhosis, is rising at an alarming rate. This increase is occurring in conjunction with the rise of severe obesity and is probably mediated in part by metabolic syndrome (MS). Surgical weight loss operations, probably by reversing MS, have been shown to result in improvement in liver histology. Methods: Patients who underwent laparoscopic surgical weight loss operations from March 1999 through August 2004, and who agreed to have an intraoperative liver biopsy followed by at least one postoperative liver biopsy, were included. Results: There were 70 patients who were eligible. All patients underwent laparoscopic operations, the majority being laparoscopic Roux-en-Y gastric bypass. The mean excess body weight loss at time of second biopsy was 59% ± 22% and the time interval between biopsies was 15 ± 9 months. There was a reduction in prevalence of metabolic syndrome, from 70% to 14% (P < 0.001), and a marked improvement in liver steatosis (from 88% to 8%), inflammation (from 23% to 2%), and fibrosis (from 31% to 13%; all P < 0.001). Inflammation and fibrosis resolved in 37% and 20% of patients, respectively, corresponding to improvement of 82% (P < 0.001) in grade and 39% (P < 0.001) in stage of liver disease. Conclusion: Surgical weight loss results in significant improvement of liver morphology in severely obese patients. These beneficial changes may be associated with a significant reduction in the prevalence of the metabolic syndrome. PMID:16192822
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Vainshtein, Jeffrey M.; Kabarriti, Rafi; Mehta, Keyur J.
2014-07-15
Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local diseasemore » control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment of HCC.« less
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Wang, L; Eriksson, S
2010-06-01
Deficiency in thymidine kinase 2 (TK2) activity due to genetic alterations caused tissue specific mitochondrial DNA (mtDNA) depletion syndrome with symptoms resembling these of AIDS patients treated with nucleoside analogues. Mechanisms behind this mitochondrial effects is still not well understood. With rat as a model we isolated mitochondrial and cytosolic fractions from major organs and studied enzymes involved in thymidine (dT) and deoxycytidine (dC) phosphorylation by using ionic exchange column chromatography. A cytosolic form of TK2 was identified in all tested tissues in addition to mitochondrial TK2. TK1 was detected in liver and spleen cytosolic extracts while dCK was found in liver, spleen and lung cytosolic extracts. Thus, the nature of dT and dC salvage enzymes in each tissue type was determined. In most tissues TK2 is the only salvage enzyme present except liver and spleen. These results may help to explain the mechanisms of mitochondrial toxicity of antiviral nucleoside analogues and mtDNA depletion caused by TK2 deficiency.
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Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen
2013-01-01
Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”. PMID:24098410
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Ren, Zhigang; Cui, Guangying; Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen
2013-01-01
Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the "gut-liver axis".
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Awan, Sana Javaid; Baig, Maria Tayyab; Yaqub, Faiza; Tayyeb, Asima; Ali, Gibran
2017-01-01
Hepatic oval cells are likely to be activated during advanced stage of liver fibrosis to reconstruct damaged hepatic tissue. However, their scarcity, difficulties in isolation, and in vitro expansion hampered their transplantation in fibrotic liver. This study was aimed to investigate the repair potential of in vitro differentiated hepatic oval-like cells in CCl 4 -induced liver fibrosis. BMSCs and oval cells were isolated and characterized from C57BL/6 GFP + mice. BMSCs were differentiated into oval cells by preconditioning with HGF, EGF, SCF, and LIF and analyzed for the oval cells-specific genes. Efficiency of oval cells to reduce hepatocyte injury was studied by determining cell viability, release of LDH, and biochemical tests in a co-culture system. Further, in vivo repair potential of differentiated oval cells was determined in CCl 4 -induced fibrotic model by gene expression analysis, biochemical tests, mason trichrome, and Sirius red staining. Differentiated oval cells expressed hepatic oval cells-specific markers AFP, ALB, CK8, CK18, CK19. These differentiated cells when co-cultured with injured hepatocytes showed significant hepato-protection as measured by reduction in apoptosis, LDH release, and improvement in liver functions. Transplantation of differentiated oval cells like cells in fibrotic livers exhibited enhanced homing, reduced liver fibrosis, and improved liver functions by augmenting hepatic microenvironment by improved liver functions. This preconditioning strategy to differentiate BMSCs into oval cell leads to improved survival and homing of transplanted cells. In addition, reduction in fibrosis and functional improvement in mice with CCl 4 -induced liver fibrosis was achieved. © 2016 International Federation for Cell Biology.
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Kim, Z-Hun; Park, Hanwool; Lee, Ho-Sang; Lee, Choul-Gyun
2016-07-28
A split-column photobioreactor (SC-PBR), consisting of two bubble columns with different sizes, was developed to enhance the photon utilization efficiency in an astaxanthin production process from Haematococcus lacustris. Among the two columns, only the smaller column of SC-PBR was illuminated. Astaxanthin productivities and photon efficiencies of the SC-PBRs were compared with a standard bubble-column PBR (BC-PBR). Astaxanthin productivity of SC-PBR was improved by 28%, and the photon utilization efficiencies were 28-366% higher than the original BC-PBR. The results clearly show that the effective light regime of SC-PBR could enhance the production of astaxanthin.
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Transport Advances in Disposable Bioreactors for Liver Tissue Engineering
NASA Astrophysics Data System (ADS)
Catapano, Gerardo; Patzer, John F.; Gerlach, Jörg Christian
Acute liver failure (ALF) is a devastating diagnosis with an overall survival of approximately 60%. Liver transplantation is the therapy of choice for ALF patients but is limited by the scarce availability of donor organs. The prognosis of ALF patients may improve if essential liver functions are restored during liver failure by means of auxiliary methods because liver tissue has the capability to regenerate and heal. Bioartificial liver (BAL) approaches use liver tissue or cells to provide ALF patients with liver-specific metabolism and synthesis products necessary to relieve some of the symptoms and to promote liver tissue regeneration. The most promising BAL treatments are based on the culture of tissue engineered (TE) liver constructs, with mature liver cells or cells that may differentiate into hepatocytes to perform liver-specific functions, in disposable continuous-flow bioreactors. In fact, adult hepatocytes perform all essential liver functions. Clinical evaluations of the proposed BALs show that they are safe but have not clearly proven the efficacy of treatment as compared to standard supportive treatments. Ambiguous clinical results, the time loss of cellular activity during treatment, and the presence of a necrotic core in the cell compartment of many bioreactors suggest that improvement of transport of nutrients, and metabolic wastes and products to or from the cells in the bioreactor is critical for the development of therapeutically effective BALs. In this chapter, advanced strategies that have been proposed over to improve mass transport in the bioreactors at the core of a BAL for the treatment of ALF patients are reviewed.
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Quality measurement and improvement in liver transplantation.
Mathur, Amit K; Talwalkar, Jayant
2018-06-01
There is growing interest in the quality of health care delivery in liver transplantation. Multiple stakeholders, including patients, transplant providers and their hospitals, payers, and regulatory bodies have an interest in measuring and monitoring quality in the liver transplant process, and understanding differences in quality across centres. This article aims to provide an overview of quality measurement and regulatory issues in liver transplantation performed within the United States. We review how broader definitions of health care quality should be applied to liver transplant care models. We outline the status quo including the current regulatory agencies, public reporting mechanisms, and requirements around quality assurance and performance improvement (QAPI) activities. Additionally, we further discuss unintended consequences and opportunities for growth in quality measurement. Quality measurement and the integration of quality improvement strategies into liver transplant programmes hold significant promise, but multiple challenges to successful implementation must be addressed to optimise value. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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Isolation and structural determination of squalene synthase inhibitor from Prunus mume fruit.
Choi, Sung-Won; Hur, Nam-Yoon; Ahn, Soon-Cheol; Kim, Dong-Seob; Lee, Jae-Kwon; Kim, Dae-Ok; Park, Seung-Kook; Kim, Byung-Yong; Baik, Moo-Yeol
2007-12-01
Squalene synthase plays an important role in the cholesterol biosynthetic pathway. Inhibiting this enzyme in hypercholesterolemia can lower not only plasma cholesterol but also plasma triglyceride levels. A squalene synthase inhibitor was screened from Prunus mume fruit, and then purified via sequential processes of ethanol extraction, HP-20 column chromatography, ethyl acetate extraction, silica gel column chromatography, and crystallization. The squalene synthase inhibitor was identified as chlorogenic acid with a molecular mass of 354 Da and a molecular formula of C16H18O9 based on UV spectrophotometry, 1H and 13C NMRs, and mass spectrometry. Chlorogenic acid inhibited the squalene synthase of pig liver with an IC50 level of 100 nM. Since chlorogenic acid was an effective inhibitor against the squalene synthase of an animal source, it may be a potential therapeutic agent for hypercholesterolemia.
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Simplified technique for auxiliary orthotopic liver transplantation using a whole graft
ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro
2015-01-01
Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253
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Liu, Wei; Qi, Shenglan; Xu, Ying; Xiao, Zhun; Fu, Yadong; Chen, Jiamei; Yang, Tao; Liu, Ping
2017-12-08
A method for the determination of hydroxyproline (Hyp) in liver tissue of mice by hydrophilic interaction chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (HILIC-HRMS) was developed. The liver tissue samples of normal mice and liver fibrosis mice induced by carbon tetrachloride were hydrolyzed by concentrated hydrochloric acid. After filtrated and diluted by solution, the diluent was separated on an Hypersil GOLD HILIC column (100 mm×2.1 mm, 3 μm). Water-acetonitrile (28:72, v/v)were used as the mobile phases with isocratic elution. Finally, the target analytes were detected in positive model by HRMS equipped with an electrospray ionization source. The linear range of hydroxyproline was from 0.78 to 100.00 μg/L with the correlation coefficient ( R 2 ) of 0.9983. The limit of quantification was 0.78 μg/L. By detecting the spiked samples, the recoveries were in the range of 97.4%-100.9% with the relative standard deviations (RSDs) between 1.4% and 2.0%. In addition, comparison of the measurement results by this method and the chloramine T method was proceeded. It was found that the linear correlation between the two methods was very good, and the Pearson correlation coefficient was 0.927. And this method had simpler operation procedure and higher accuracy than chloramine T method. This method can be used for the quick determination of hydroxyproline in liver tissue samples.
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Wong, Weng-Yew; Poudyal, Hemant; Ward, Leigh C.; Brown, Lindsay
2012-01-01
Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome. PMID:23201770
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Boursier, J; Brochard, C; Bertrais, S; Michalak, S; Gallois, Y; Fouchard-Hubert, I; Oberti, F; Rousselet, M-C; Calès, P
2014-07-01
Recent longitudinal studies have emphasised the prognostic value of noninvasive tests of liver fibrosis and cross-sectional studies have shown their combination significantly improves diagnostic accuracy. To compare the prognostic accuracy of six blood fibrosis tests and liver biopsy, and evaluate if test combination improves the liver-prognosis assessment in chronic hepatitis C (CHC). A total of 373 patients with compensated CHC, liver biopsy (Metavir F) and blood tests targeting fibrosis (APRI, FIB4, Fibrotest, Hepascore, FibroMeter) or cirrhosis (CirrhoMeter) were included. Significant liver-related events (SLRE) and liver-related deaths were recorded during follow-up (started the day of biopsy). During the median follow-up of 9.5 years (3508 person-years), 47 patients had a SLRE and 23 patients died from liver-related causes. For the prediction of first SLRE, most blood tests allowed higher prognostication than Metavir F [Harrell C-index: 0.811 (95% CI: 0.751-0.868)] with a significant increase for FIB4: 0.879 [0.832-0.919] (P = 0.002), FibroMeter: 0.870 [0.812-0.922] (P = 0.005) and APRI: 0.861 [0.813-0.902] (P = 0.039). Multivariate analysis identified FibroMeter, CirrhoMeter and sustained viral response as independent predictors of first SLRE. CirrhoMeter was the only independent predictor of liver-related death. The combination of FibroMeter and CirrhoMeter classifications into a new FM/CM classification improved the liver-prognosis assessment compared to Metavir F staging or single tests by identifying five subgroups of patients with significantly different prognoses. Some blood fibrosis tests are more accurate than liver biopsy for determining liver prognosis in CHC. A new combination of two complementary blood tests, one targeted for fibrosis and the other for cirrhosis, optimises assessment of liver-prognosis. © 2014 John Wiley & Sons Ltd.
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Mitigation of Liquefaction in Sandy Soils Using Stone Columns
NASA Astrophysics Data System (ADS)
Selcuk, Levent; Kayabalı, Kamil
2010-05-01
Soil liquefaction is one of the leading causes of earthquake-induced damage to structures. Soil improvement methods provide effective solutions to reduce the risk of soil liquefaction. Thus, soil ground treatments are applied using various techniques. However, except for a few ground treatment methods, they generally require a high cost and a lot of time. Especially in order to prevent the risk of soil liquefaction, stone columns conctructed by vibro-systems (vibro-compaction, vibro-replacement) are one of the traditional geotechnical methods. The construction of stone columns not only enhances the ability of clean sand to drain excess pore water during an earthquake, but also increases the relative density of the soil. Thus, this application prevents the development of the excess pore water pressure in sand during earthquakes and keeps the pore pressure ratio below a certain value. This paper presents the stone column methods used against soil liquefaction in detail. At this stage, (a) the performances of the stone columns were investigated in different spacing and diameters of columns during past earthquakes, (b) recent studies about design and field applications of stone columns were presented, and (c) a new design method considering the relative density of soil and the capacity of drenage of columns were explained in sandy soil. Furthermore, with this new method, earthquake performances of the stone columns constructed at different areas were investigated before the 1989 Loma Prieta and the 1994 Northbridge earthquakes, as case histories of field applications, and design charts were compiled for suitable spacing and diameters of stone columns with consideration to the different sandy soil parameters and earhquake conditions. Key Words: Soil improvement, stone column, excess pore water pressure
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Castro, Jorge
2017-07-11
This paper reviews the main modeling techniques for stone columns, both ordinary stone columns and geosynthetic-encased stone columns. The paper tries to encompass the more recent advances and recommendations in the topic. Regarding the geometrical model, the main options are the "unit cell", longitudinal gravel trenches in plane strain conditions, cylindrical rings of gravel in axial symmetry conditions, equivalent homogeneous soil with improved properties and three-dimensional models, either a full three-dimensional model or just a three-dimensional row or slice of columns. Some guidelines for obtaining these simplified geometrical models are provided and the particular case of groups of columns under footings is also analyzed. For the latter case, there is a column critical length that is around twice the footing width for non-encased columns in a homogeneous soft soil. In the literature, the column critical length is sometimes given as a function of the column length, which leads to some disparities in its value. Here it is shown that the column critical length mainly depends on the footing dimensions. Some other features related with column modeling are also briefly presented, such as the influence of column installation. Finally, some guidance and recommendations are provided on parameter selection for the study of stone columns.
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2017-01-01
This paper reviews the main modeling techniques for stone columns, both ordinary stone columns and geosynthetic-encased stone columns. The paper tries to encompass the more recent advances and recommendations in the topic. Regarding the geometrical model, the main options are the “unit cell”, longitudinal gravel trenches in plane strain conditions, cylindrical rings of gravel in axial symmetry conditions, equivalent homogeneous soil with improved properties and three-dimensional models, either a full three-dimensional model or just a three-dimensional row or slice of columns. Some guidelines for obtaining these simplified geometrical models are provided and the particular case of groups of columns under footings is also analyzed. For the latter case, there is a column critical length that is around twice the footing width for non-encased columns in a homogeneous soft soil. In the literature, the column critical length is sometimes given as a function of the column length, which leads to some disparities in its value. Here it is shown that the column critical length mainly depends on the footing dimensions. Some other features related with column modeling are also briefly presented, such as the influence of column installation. Finally, some guidance and recommendations are provided on parameter selection for the study of stone columns. PMID:28773146
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Methylation of nuclear proteins by dimethylnitrosamine and by methionine in the rat in vivo
Turberville, C.; Craddock, V. M.
1971-01-01
1. The incorporation of methyl groups into histones from dimethylnitrosamine and from methionine was studied by injection of the labelled compounds, isolation of rat liver and kidney histones, and analysis of hydrolysates by column chromatography. 2. Labelled methionine gave rise to labelled ∈-N-methyl-lysine, di-∈-N-methyl-lysine and an amino acid presumed to be ω-N-methyl-arginine. 3. Administration of labelled dimethylnitrosamine gave rise to labelled S-methylcysteine, 1-methylhistidine, 3-methylhistidine and ∈-N-methyl-lysine derived from the alkylating metabolite of dimethylnitrosamine. In addition, labelled formaldehyde released by metabolism of dimethylnitrosamine leads to the formation of labelled S-adenosylmethionine, and hence to labelling of ∈-N-methyl-lysine, di-∈-N-methyl-lysine and ω-N-methylarginine by enzymic methylation. 4. The formation of ∈-N-methyl-lysine by alkylation of liver histones was confirmed by using doubly labelled dimethylnitrosamine to discriminate between direct chemical alkylation and enzymic methylation via S-adenosylmethionine. These experiments also suggested the possibility that methionine residues in the histones were alkylated to give methylmethionine sulphonium residues. 5. The extent of alkylation of liver histones was maximal at about 5h after dosing and declined between 5 and 24h. The methylated amino acids resulting from direct chemical alkylation were preferentially lost: this is ascribed to necrosis of the more highly alkylated cells. 6. Liver histones were about four times as alkylated as kidney histones; the extent of alkylation of liver histones was similar to that of liver total nuclear proteins. 7. Methyl methanesulphonate (120mg/kg) alkylated liver histones to a greater extent than did dimethylnitrosamine. Diethylnitrosamine also alkylated liver histones. 8. The results are discussed with regard to the possible effects of alkylation on histone function, and the possible role of histone alkylation in carcinogenesis by the three compounds. PMID:5131729
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jun, Seung-Hyun; Chang, Mun Seock; Kim, Byoung Chan
2010-09-15
The construction of a trypsin reactor in a chromatography column for rapid and efficient protein digestion in proteomics is described. Electrospun and alcohol-dispersed polymer nanofibers were used for the fabrication of highly stable trypsin coating, which was prepared by a two-step process of covalent attachment and enzyme crosslinking. In a comparative study with the trypsin coatings on asspun and non-dispersed nanofibers, it has been observed that a simple step of alcohol dispersion improved not only the enzyme loading but also the performance of protein digestion. In-column digestion of enolase was successfully performed in less than twenty minutes. By applying themore » alcohol dispersion of polymer nanofibers, the bypass of samples was reduced by filling up the column with well-dispersed nanofibers, and subsequently, interactions between the protein and the enzymes were improved yielding more complete and reproducible digestions. Regardless of alcohol-dispersion or not, trypsin coating showed better digestion performance and improved performance stability under recycled uses than covalently-attached trypsin. The combination of highly stable trypsin coating and alcoholdispersion of polymer nanofibers has opened up a new potential to develop a trypsin column for on-line and automated protein digestion.« less
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Jegatheeswaran, Santhalingam; Siriwardena, Ajith K
2011-01-01
Background Hepatic ischaemia–reperfusion (I/R) injury occurs in both liver resectional surgery and in transplantation. The biochemistry of I/R injury involves short-lived oxygen free radicals. N-acetylcysteine (NAC) is a thiol-containing synthetic compound used in the treatment of acetaminophen toxicity. The present study is a detailed overview of the experimental and clinical evidence for the use of NAC as a pharmaco-protection agent in patients undergoing major liver surgery or transplantation. Methods A computerized search of the Medline, Embase and SCI databases for the period from 1st January 1988 to 31st December 2008 produced 40 reports. For clinical studies, the quality of reports was assessed according to the criteria reported by the Cochrane communication review group. Results Nineteen studies evaluated NAC in experimental liver I/R injury. NAC was administered before induction of ischaemia in 13. The most widely used concentration was 150 mg/kg by intravenous bolus. Fifteen studies report an improvement in outcome, predominantly a reduction in transaminase. Seven studies used an isolated perfused liver model with all showing improvement (predominantly an improvement in bile production after N-acetylcysteine). Two out of four transplantation models showed an improvement in hepatic function. Clinical studies in transplantation show a modest improvement in transaminase levels with no beneficial effect on either patient or graft survival. Conclusion N-acetylcysteine, given before induction of a liver I/R injury in an experimental model can ameliorate liver injury. Clinical outcome data are limited and there is currently little evidence to justify use either in liver transplantation or in liver resectional surgery. PMID:21241423
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Development of and fabrication of high resolution gas chromatographic capillary columns
NASA Technical Reports Server (NTRS)
Zlatkis, A.
1982-01-01
Gas chromatographic columns which are used in the trace gas analyzer (TGA) for the space shuttle are coated with a polyoxyethylene lauryl ether. This stationary phase is of medium polarity and has a temperature limit of 160 C. A polymer for this application which has an improved thermal stability is investigated. The use of fused silica capillary columns with specially bonded phases as well as an introduction system (on column) was also studied.
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Aguilar-Olivos, Nancy E; Almeda-Valdes, Paloma; Aguilar-Salinas, Carlos A; Uribe, Misael; Méndez-Sánchez, Nahum
2016-08-01
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD is strongly associated with obesity and metabolic syndrome (MetS). Current treatment of NAFLD is based on weight reduction. Bariatric surgery is the most effective treatment for morbid obesity and its associated metabolic comorbidities. There is evidence indicating that bariatric surgery improves histological and biochemical parameters of NAFLD, but currently is not considered a treatment option for NAFLD. The aim of this work is to review the evidence for the effects of bariatric surgery on NAFLD and the MetS. We found that insulin resistance, alterations in glucose metabolism, hypertension, plasma lipids, transaminases, liver steatosis, steatohepatitis and fibrosis improve after bariatric surgery. Weight loss and improvement of NAFLD are greater after RYGB than after other interventions. These findings were obtained from retrospective or cohort studies. There are no studies designed to evaluate liver-specific mortality, liver transplantation, or quality of life. Patients with indications for bariatric surgery will benefit from the improvements in the MetS and NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.
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Using old liver grafts for liver transplantation: where are the limits?
Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique
2014-08-21
The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts.
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Using old liver grafts for liver transplantation: Where are the limits?
Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique
2014-01-01
The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts. PMID:25152573
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Recent Progress of Nano-drug Delivery System for Liver Cancer Treatment.
Zhou, Feilong; Teng, Fangfang; Deng, Peizong; Meng, Ning; Song, Zhimei; Feng, Runliang
2018-02-07
Liver cancer is one of serious diseases which threaten human life and health. Studies on the treatment of liver cancer have attracted widespread attention. Application of nano-drug delivery system (NDDS) can not only improve selective drug delivery to liver tissue and improve the bioavailability of drug, but also can reduce the side effects of drugs when it is specially modified in the respects of structure modification or specific target molecules decoration. This review will address the latest development of liver-targeted drug delivery system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Huang, D Y; Ichikawa, Y
1997-03-07
Rabbit liver cytosol exhibits very high retinol dehydrogenase activity. At least two retinol dehydrogenases were demonstrated to exist in rabbit liver cytosol, and the major one, a cytosolic NADP(H)-dependent retinol dehydrogenase (systematic name: retinol oxidoreductase) was purified about 1795-fold to electrophoretic and column chromatographic homogeneity by a procedure involving column chromatography on AF-Red Toyopearl twice and then hydroxyapatite. Its molecular mass was estimated to be 34 kDa by SDS-PAGE, and 144 kDa by HPLC gel filtration, suggesting that it is a homo-tetramer. The enzyme uses free retinol and retinal, and their complexes with CRBP as substrates in vitro. The optimum pH values for retinol oxidation of free retinol and CRBP-retinol were 8.8-9.2 and 8.0-9.0, respectively, and those for retinal reduction of free retinal and retinal-CRBP were the same, 7.0-7.6. Km for free retinol and Vmax for retinal formation were 2.8 microM and 2893 nmol/min per mg protein at 37 degrees C (pH 9.0) and the corresponding values with retinol-CRBP as a substrate were 2.5 microM and 2428 nmol/min per mg protein at 37 degrees C (pH 8.6); Km for free retinal and Vmax for retinol formation were 6.5 microM and 4108 nmol/min per mg protein, and the corresponding values with retinal-CRBP as a substrate were 5.1 microM and 3067 nmol/min per mg protein at 37 degrees C, pH 7.4. NAD(H) was not effective as a cofactor. 4-Methylpyrazole was a weak inhibitor (IC50 = 28 mM) of the enzyme, and ethanol was neither a substrate nor an inhibitor of the enzyme. This enzyme exhibits relatively broad aldehyde reductase activity and some ketone reductase activity, the activity for aromatic substitutive aldehydes being especially high and effective. Whereas, except in the case of retinol, oxidative activity toward the corresponding alcohols was not detected. This novel cytosolic enzyme may play an important role in vivo in maintaining the homeostasis of retinal, the substrate of retinoic acid synthesis, at least in rabbit liver, since a high concentration of retinol in liver and the lower Km of the enzyme for retinol force the oxidative reaction, while higher activity of retinal reductase at physiological pH forces the reductive reaction.
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Han, J R; Yuan, S W; Ren, Q F
1990-06-01
Fresh fetal liver obtained from 3- to 6-month fetus was prepared. Fetal liver cell suspension (FLC) or fetal liver cell-free suspension (FLCF) were then transfused into two groups of patient of aplastic anemia. 15 of 21 patients of aplastic anemia treated with FLC showed reconstitution of haemopoietic function or improvement of peripheral blood pictures, while 27 of 30 patients treated with FLCF showed reconstitution or improvement. It is verified that there is a stimulating factor for CFU-CM, BFU-E, and CFU-E and also a immunologic stimulant for improving the nonspecific immunologic function of the organism as shown by clinical analysis and experimental study. It is obvious that the therapeutic effect of FLCF is much better than that of the FLC.
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Liu, Qinlong; Rehman, Hasibur; Krishnasamy, Yasodha; Schnellmann, Rick G; Lemasters, John J; Zhong, Zhi
2015-07-01
Inclusion of liver grafts from cardiac death donors (CDD) would increase the availability of donor livers but is hampered by a higher risk of primary non-function. Here, we seek to determine mechanisms that contribute to primary non-function of liver grafts from CDD with the goal to develop strategies for improved function and outcome, focusing on c-Jun-N-terminal kinase (JNK) activation and mitochondrial depolarization, two known mediators of graft failure. Livers explanted from wild-type, inducible nitric oxide synthase knockout (iNOS(-/-)), JNK1(-/-) or JNK2(-/-) mice after 45-min aorta clamping were implanted into wild-type recipients. Mitochondrial depolarization was detected by intravital confocal microscopy in living recipients. After transplantation of wild-type CDD livers, graft iNOS expression and 3-nitrotyrosine adducts increased, but hepatic endothelial NOS expression was unchanged. Graft injury and dysfunction were substantially higher in CDD grafts than in non-CDD grafts. iNOS deficiency and inhibition attenuated injury and improved function and survival of CDD grafts. JNK1/2 and apoptosis signal-regulating kinase-1 activation increased markedly in wild-type CDD grafts, which was blunted by iNOS deficiency. JNK inhibition and JNK2 deficiency, but not JNK1 deficiency, decreased injury and improved function and survival of CDD grafts. Mitochondrial depolarization and binding of phospho-JNK2 to Sab, a mitochondrial protein linked to the mitochondrial permeability transition, were higher in CDD than in non-CDD grafts. iNOS deficiency, JNK inhibition and JNK2 deficiency all decreased mitochondrial depolarization and blunted ATP depletion in CDD grafts. JNK inhibition and deficiency did not decrease 3-nitrotyrosine adducts in CDD grafts. The iNOS-JNK2-Sab pathway promotes CDD graft failure via increased mitochondrial depolarization, and is an attractive target to improve liver function and survival in CDD liver transplantation recipients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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Ferriero, Rosa; Nusco, Edoardo; De Cegli, Rossella; Carissimo, Annamaria; Manco, Giuseppe; Brunetti-Pierri, Nicola
2018-03-24
Acute liver failure is a rapidly progressive deterioration of hepatic function resulting in high mortality and morbidity. Metabolic enzymes can translocate to the nucleus to regulate histone acetylation and gene expression. Levels and activities of pyruvate dehydrogenase complex (PDHC) and lactate dehydrogenase (LDH) were evaluated in nuclear fractions of livers of mice exposed to various hepatotoxins including CD95-antibody, α-amanitin, and acetaminophen. Whole-genome gene expression profiling by RNA-seq was performed in livers of mice with acute liver failure and analyzed by gene ontology enrichment analysis. Cell viability was evaluated in cell lines knocked-down for PDHA1 or LDH-A and in cells incubated with the LDH inhibitor galloflavin after treatment with CD95-antibody. We evaluated whether the histone acetyltransferase inhibitor garcinol or galloflavin could reduce liver damage in mice with acute liver failure. Levels and activities of PDHC and LDH were increased in nuclear fractions of livers of mice with acute liver failure. The increase of nuclear PDHC and LDH was associated with increased concentrations of acetyl-CoA and lactate in nuclear fractions, and histone H3 hyper-acetylation. Gene expression in livers of mice with acute liver failure suggested that increased histone H3 acetylation induces the expression of genes related to damage response. Reduced histone acetylation by the histone acetyltransferase inhibitor garcinol decreased liver damage and improved survival in mice with acute liver failure. Knock-down of PDHC or LDH improved viability in cells exposed to a pro-apoptotic stimulus. Treatment with the LDH inhibitor galloflavin that was also found to inhibit PDHC, reduced hepatic necrosis, apoptosis, and expression of pro-inflammatory cytokines in mice with acute liver failure. Mice treated with galloflavin also showed a dose-response increase in survival. PDHC and LDH translocate to the nucleus, leading to increased nuclear concentrations of acetyl-CoA and lactate. This results in histone H3 hyper-acetylation and expression of damage response genes. Inhibition of PDHC and LDH reduces liver damage and improves survival in mice with acute liver failure. Thus, PDHC and LDH are targets for therapy of acute liver failure. Acute liver failure is a rapidly progressive deterioration of liver function resulting in high mortality. In experimental mouse models of acute liver failure, we found that two metabolic enzymes, namely pyruvate dehydrogenase complex and lactic dehydrogenase, translocate to the nucleus resulting in detrimental gene expression. Treatment with an inhibitor of these two enzymes was found to reduce liver damage and to improve survival. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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Platelets in liver disease, cancer and regeneration.
Kurokawa, Tomohiro; Ohkohchi, Nobuhiro
2017-05-14
Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.
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"Resuscitation" of marginal liver allografts for transplantation with machine perfusion technology.
Graham, Jay A; Guarrera, James V
2014-08-01
As the rate of medically suitable donors remains relatively static worldwide, clinicians have looked to novel methods to meet the ever-growing demand of the liver transplant waiting lists worldwide. Accordingly, the transplant community has explored many strategies to offset this deficit. Advances in technology that target the ex vivo "preservation" period may help increase the donor pool by augmenting the utilization and improving the outcomes of marginal livers. Novel ex vivo techniques such as hypothermic, normothermic, and subnormothermic machine perfusion may be useful to "resuscitate" marginal organs by reducing ischemia/reperfusion injury. Moreover, other preservation techniques such as oxygen persufflation are explored as they may also have a role in improving function of "marginal" liver allografts. Currently, marginal livers are frequently discarded or can relegate the patient to early allograft dysfunction and primary non-function. Bench to bedside advances are rapidly emerging and hold promise for expanding liver transplantation access and improving outcomes. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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Brown, R.L.; Levi, P.E.; Hodgson, E.; Melancon, M.J.
1996-01-01
Livers from mallards (Anas platyrhynchos) were treated with either -naphthoflavone (50 mg/kg) or phenobarbital (70 mg/kg). Purification of induced hepatic cytochrome P450 was accomplished using both DEAE and hydroxyapatite columns, as well as sodium dodecyl sulfate polyacrylamide gel electrophoresis separation. Polyclonal antibodies to these proteins were then produced in young male New Zealand White rabbits. ?-naphthoflavone (?NF)- and phenobarbital(PB)-treated red-winged blackbird, screech owl, European starling and lesser scaup liver microsomes were analyzed in western blots for species cross-reactivity. Although all four of these avian species exhibited cross-reactivity with antibodies to ?NF-induced mallard P450, all but the lesser scaup revealed a protein of higher molecular weight than that of the ?NF-induced mallard. In addition, only the lesser scaup exhibited cross-reactivity with the anti-PB-induced mallard P450 antibodies.
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Talus, Eric S; Witt, Klaus E; Stoll, Dwight R
2015-01-23
Users of online comprehensive two-dimensional liquid chromatography (LCxLC) frequently acknowledge that the mechanical instability of HPLC columns installed in these systems, particularly in the second dimension, is a significant impediment to its use. Such instability is not surprising given the strenuous operating environment to which these columns are subjected, including the large number (thousands per day) of fast and large pressure pulses resulting from interface valve switches (on the timescale of tens of milliseconds) associated with very fast second dimension separations. There appear to be no published reports of systematic studies of the relationship between second dimension column lifetime and any of these variables. In this study we focused on the relationship between the lifetimes of commercially available columns and the pressure pulses observed at the inlet of the second dimension column that occur during the switching of the valve that interfaces the two dimensions of a LCxLC system. We find that the magnitude of the pressure drop at the inlet of the second dimension column during the valve switch, which may vary between 10 and 95% of the column inlet pressure, is dependent on valve switching speed and design, and has a dramatic impact on column lifetime. In the worst case, columns fail within the first few hours of use in an LCxLC system. In the best case, using a valve that exhibits much smaller pressure pulses, the same columns exhibit much improved lifetimes and have been used continuously under LCxLC conditions for several days with no degradation in performance. This result represents a first step in understanding the factors that affect second dimension column lifetime, and will significantly improve the usability of the LCxLC technique in general. Copyright © 2014 Elsevier B.V. All rights reserved.
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Wang, Qing; Wang, Guomin; Xi, Cunxian; Li, Xianliang; Chen, Dongdong; Tang, Bobin; Zhang, Lei; Zhao, Hua
2014-06-01
A combination immunoaffinity column (IAC-CZ) clean-up and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method was successfully developed for zearalenol, beta-zearalenol and zearalenone) and chloramphenicol (CAP) in foodstuffs of animal origin. The samples (fish, liver, milk and honey) were enzymatically digested by beta-glucuronidase/sulfatase for about 16 h and then extracted with ether. The extracts were evaporated to dryness and then the residues were dissolved by 1.0 mL of 50% acetonitrile solution. After filtered and diluted with PBS buffer, the reconstituted solution were cleaned-up with a IAC-CZ and then analyzed by LC-MS/MS in multiple reaction monitoring (MRM) mode. The chromatographic separation was performed on a Shimadzu Shim-pack VP-ODS column with gradient elution by acetonitrile and 2 mmol/L ammonium acetate solution. The detection was carried out by electrospray negative ionization mass spectrometry in MRM mode. The proposed method was validated by the limit of detection (0.04-0.10 microg/kg), linearity (R2 > or = 0.999 0), average recoveries (70.9%-95.6%) and precisions (2.0% - 11.8%). The developed method is reliable, sensitive and has good applicability. The combination immunoaffinity column was proved to be an effective pretreatment technique to decrease the matrix effect, and it met the requirements of residue analysis of co-occurring zeranols and chloramphenicol.
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Major Challenges Limiting Liver Transplantation in the United States
Wertheim, Jason A.; Petrowsky, Henrik; Saab, Sammy; Kupiec-Weglinski, Jerzy W.; Busuttil, Ronald W.
2011-01-01
Liver transplantation is the gold standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. From 1988 to 2009, liver transplantation in the United States grew 3.7-fold from 1713 to 6320 transplants annually. The expansion of liver transplantation is chiefly driven by scientific breakthroughs that have extended patient and graft survival well beyond those expected 50 years ago. The success of liver transplantation is now its primary obstacle, as the pool of donor livers fails to keep pace with the growing number of patients added to the national liver transplant waiting list. This review focuses on three major challenges facing liver transplantation in the United States and discusses new areas of investigation that address each issue: 1) the need for an expanded number of useable donor organs, 2) the need for improved therapies to treat recurrent hepatitis C after transplantation and 3) the need for improved detection, risk stratification based upon tumor biology and molecular inhibitors to combat hepatocellular carcinoma. PMID:21672146
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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
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Portal Vein Embolization: State-of-the-Art Technique and Options to Improve Liver Hypertrophy.
Huang, Steven Y; Aloia, Thomas A
2017-12-01
Portal vein embolization (PVE) is associated with a high technical and clinical success rate for induction of future liver remnant hypertrophy prior to surgical resection. The degree of hypertrophy is variable and depends on multiple factors, including technical aspects of the procedure and underlying chronic liver disease. For patients with insufficient liver volume following PVE, adjunctive techniques, such as intra-portal administration of stem cells, dietary supplementation, transarterial embolization, and hepatic vein embolization, are available. Our purpose is to review the state-of-the-art technique associated with high-quality PVE and to discuss options to improve hypertrophy of the future liver remnant.
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USDA-ARS?s Scientific Manuscript database
An improved column-based process for production of biodiesel was developed using a column containing a strongly basic anion-exchange resin in sequence with a column containing a resin to which a lipase biocatalyst is bound. Currently most biodiesel is produced by transesterification of triglyceride...
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NASA Astrophysics Data System (ADS)
Jinghai, Zhou; Tianbei, Kang; Fengchi, Wang; Xindong, Wang
2017-11-01
Eight less stirrups in the core area frame joints are simulated by ABAQUS finite element numerical software. The composite reinforcement method is strengthened with carbon fiber and increasing column section, the axial compression ratio of reinforced specimens is 0.3, 0.45 and 0.6 respectively. The results of the load-displacement curve, ductility and stiffness are analyzed, and it is found that the different axial compression ratio has great influence on the bearing capacity of increasing column section strengthening method, and has little influence on carbon fiber reinforcement method. The different strengthening schemes improve the ultimate bearing capacity and ductility of frame joints in a certain extent, composite reinforcement joints strengthening method to improve the most significant, followed by increasing column section, reinforcement method of carbon fiber reinforced joints to increase the minimum.
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Fu, Ling; Wang, Pan; Sun, Yiqun; Wang, Yangyang; Zhao, Jing; Ye, Yuting; Zhang, Yanbin; Bi, Yuefeng
2015-01-01
Background: Chrysanthemi indici Flos, a traditional herbal medicine is used to clearing heat–toxicity, removing the liver fire, and improving eyesight. In our preliminary work, an active extract of CTC in C. An indici Flos with anti-hepatitis B virus and liver protective activity was found by HepG2.2.1.5 test and experiment of protein synthesis in mice's injured liver. In this work, we aimed to study the active faction CTC further by qualitative and quantitative analysis method. Materials and Methods: High performance liquid chromatography time of flight electrospray ionization mass spectrometry (HPLC TOF ESI-MS) analysis method of the CTC was established. Cumambrin A and angeloylcumambrin B in CTC were analyzed by high performance liquid chromatography-ultraviolet-evaporative light scattering detector (HPLC-UV-ELSD) analysis methods. A binary gradient elution program was conducted for chromatographic separation with acetonitrile (A) and ultrapure water (B) as follows: 0–10 min, 42–46% A; 10–20 min, 46–55% A; 20–25 min, 55–60% A; and 25–35 min, 60–75% A. The column temperature and UV wavelength were set at 30°C and 205 nm. Result: Ten constituents including (3R, 5R, 6S, 7S, 10R)-7-(2-hydroxy-2-propyl)-10-methyl-4-methyleneperhy, dronaphthal-ene-3, 5, 6-triol acetone solvate; (+)-edusmance-4, (14)-ene-11, 13-diol; linarin; luteolin; apigenin; tricin; 5, 3’,4’- trimethyl-6,7-dimethoxy flavones; cumambrin A; acacetin; and angeloylcumambrin B in CTC were identified by HPLC TOF ESI-MS. The contents of sesquiterpenes in CTC were decreased by storing years. Conclusions: The results showed that both UV and ELSD methods were feasible, accurate, and the determination results were in good consistency. The contents of two sesquiterpenes decreased with storing years. Two sesquiterpenes could be used as quality control for C. indici flos CTC. PMID:26600718
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Gerth, Hans U; Pohlen, Michele; Thölking, Gerold; Pavenstädt, Hermann; Brand, Marcus; Wilms, Christian; Hüsing-Kabar, Anna; Görlich, Dennis; Kabar, Iyad; Schmidt, Hartmut H J
2017-01-01
The primary therapeutic goals in the treatment of liver injury are to support liver regeneration or bridge the gap to liver transplantation (LT). Molecular adsorbent recirculating system (MARS) therapy has shown beneficial effects for specific symptoms of liver failure; however, general survival advantages have not yet been demonstrated. We studied the effects of MARS therapy compared to standard medical treatment (SMT) in two patient cohorts: in patients with an acute liver injury and in those with graft dysfunction (GD). We report on our experience over a 6.5-year period with 73 patients treated with SMT or with SMT and MARS (MARS group). In total, 53 patients suffered from acute liver injury in their native liver without a preexisting liver disease (SMT: n = 31, MARS: n = 22), and 20 patients showed a severe GD after LT (SMT: n = 10, MARS: n = 10). The entire cohort was predominantly characterized by hemodynamically and respiratorily stable patients with a low hepatic encephalopathy (HE) grade and a model of end-stage liver disease (MELD) score of 20.57 (MARS) or 22.51 (SMT, p = 0.555). Within the MARS group, the median number of extracorporeal therapy sessions was four (range = 3-5 sessions). Independent of the underlying etiology, MARS improved the patients' bilirubin values in the short term compared to SMT alone. In patients with acute liver injury, this response was sustained even after the end of MARS therapy. By contrast, the majority of patients with GD and an initial response to MARS therapy experienced worsened hyperbilirubinemia. No differences in 28-day mortality were observed with respect to acute liver injury (MARS 5.3% (95% CI: 0-15.3); SMT 3.3% (95% CI: 0-9.8), p = 0.754) or GD (MARS 20.0% (95% CI: 0-44.7), SMT 11.1% (95% CI: 0-31.7), p = 0.478). Although it did not improve 28-day mortality, MARS therapy improved the short-term response in patients with acute liver injury as well as in those with GD. In cases of acute hepatic injury, the use of MARS therapy resulted in the sustained stabilization of liver function and improved liver regeneration. A short-term response to MARS may predict the future course of the disease.
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Thölking, Gerold; Pavenstädt, Hermann; Brand, Marcus; Wilms, Christian; Hüsing-Kabar, Anna; Görlich, Dennis; Kabar, Iyad; Schmidt, Hartmut H. J.
2017-01-01
Background The primary therapeutic goals in the treatment of liver injury are to support liver regeneration or bridge the gap to liver transplantation (LT). Molecular adsorbent recirculating system (MARS) therapy has shown beneficial effects for specific symptoms of liver failure; however, general survival advantages have not yet been demonstrated. Aim We studied the effects of MARS therapy compared to standard medical treatment (SMT) in two patient cohorts: in patients with an acute liver injury and in those with graft dysfunction (GD). Methods We report on our experience over a 6.5-year period with 73 patients treated with SMT or with SMT and MARS (MARS group). In total, 53 patients suffered from acute liver injury in their native liver without a preexisting liver disease (SMT: n = 31, MARS: n = 22), and 20 patients showed a severe GD after LT (SMT: n = 10, MARS: n = 10). Results The entire cohort was predominantly characterized by hemodynamically and respiratorily stable patients with a low hepatic encephalopathy (HE) grade and a model of end-stage liver disease (MELD) score of 20.57 (MARS) or 22.51 (SMT, p = 0.555). Within the MARS group, the median number of extracorporeal therapy sessions was four (range = 3–5 sessions). Independent of the underlying etiology, MARS improved the patients’ bilirubin values in the short term compared to SMT alone. In patients with acute liver injury, this response was sustained even after the end of MARS therapy. By contrast, the majority of patients with GD and an initial response to MARS therapy experienced worsened hyperbilirubinemia. No differences in 28-day mortality were observed with respect to acute liver injury (MARS 5.3% (95% CI: 0–15.3); SMT 3.3% (95% CI: 0–9.8), p = 0.754) or GD (MARS 20.0% (95% CI: 0–44.7), SMT 11.1% (95% CI: 0–31.7), p = 0.478). Conclusions Although it did not improve 28-day mortality, MARS therapy improved the short-term response in patients with acute liver injury as well as in those with GD. In cases of acute hepatic injury, the use of MARS therapy resulted in the sustained stabilization of liver function and improved liver regeneration. A short-term response to MARS may predict the future course of the disease. PMID:28403210
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Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals
Song, Fang; Xie, Mei-Lin; Zhu, Lu-Jia; Zhang, Ke-Ping; Xue, Jie; Gu, Zhen-Lun
2006-01-01
AIM: To evaluate the effects of osthole on fatty liver, and investigate the possible mechanism. METHODS: A quail model with hyperlipidemic fatty liver and rat model with alcoholic fatty liver were set up by feeding high fat diet and alcohol, respectively. These experimental animals were then treated with osthole 5-20 mg/kg for 6 wk, respectively. Whereafter, the lipid in serum and hepatic tissue, and coefficient of hepatic weight were measured. RESULTS: After treatment with osthole the levels of serum total cholesterol (TC), triglyceride (TG), lower density lipoprotein-cholesterol (LDL-C), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased. The activity of superoxide dismutase (SOD) in liver was improved. In alcohol-induced fatty liver rats, the level of malondialdehyde (MDA) in liver was decreased. In high fat-induced fatty liver quails, glutathione peroxidase (GSH-PX) in liver was significantly improved. The histological evaluation of liver specimens demonstrated that the osthole dramatically decreased lipid accumulation. CONCLUSION: These results suggested that osthole had therapeutic effects on both alcohol and high fat-induced fatty liver. The mechanism might be associated with its antioxidation. PMID:16865778
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Ito, Yoichiro; Clary, Robert
2016-01-01
High-speed countercurrent chromatography with a spiral tube assembly can retain a satisfactory amount of stationary phase of polymer phase systems used for protein separation. In order to improve the partition efficiency a simple tool to modify the tubing shapes was fabricated, and the following four different tubing modifications were made: intermittently pressed at 10 mm width, flat, flat-wave, and flat-twist. Partition efficiencies of the separation column made from these modified tubing were examined in protein separation with an aqueous-aqueous polymer phase system at flow rates of 1–2 ml/min under 800 rpm. The results indicated that the column with all modified tubing improved the partition efficiency at a flow rate of 1 ml/min, but at a higher flow rate of 2 ml/min the columns made of flattened tubing showed lowered partition efficiency apparently due to the loss of the retained stationary phase. Among all the modified columns, the column with intermittently pressed tubing gave the best peak resolution. It may be concluded that the intermittently pressed and flat-twist improve the partition efficiency in a semi-preparative separation while other modified tubing of flat and flat-wave configurations may be used for analytical separations with a low flow rate. PMID:27790621
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Ito, Yoichiro; Clary, Robert
2016-12-01
High-speed countercurrent chromatography with a spiral tube assembly can retain a satisfactory amount of stationary phase of polymer phase systems used for protein separation. In order to improve the partition efficiency a simple tool to modify the tubing shapes was fabricated, and the following four different tubing modifications were made: intermittently pressed at 10 mm width, flat, flat-wave, and flat-twist. Partition efficiencies of the separation column made from these modified tubing were examined in protein separation with an aqueous-aqueous polymer phase system at flow rates of 1-2 ml/min under 800 rpm. The results indicated that the column with all modified tubing improved the partition efficiency at a flow rate of 1 ml/min, but at a higher flow rate of 2 ml/min the columns made of flattened tubing showed lowered partition efficiency apparently due to the loss of the retained stationary phase. Among all the modified columns, the column with intermittently pressed tubing gave the best peak resolution. It may be concluded that the intermittently pressed and flat-twist improve the partition efficiency in a semi-preparative separation while other modified tubing of flat and flat-wave configurations may be used for analytical separations with a low flow rate.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Wenxuan; Lu, Chunfeng; Yao, Lu
Alcoholic liver disease (ALD) is a common etiology of liver diseases, characterized by hepatic steatosis. We previously identified farnesoid X receptor (FXR) as a potential therapeutic target for ALD. Dihydroartemisinin (DHA) has been recently identified to possess potent pharmacological activities on liver diseases. This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies. Results demonstrated that DHA rescued FXR expression and activity in alcoholic rat livers. DHA also reduced serodiagnostic markers of liver injury, including aspartatemore » aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. DHA improved alcohol-induced liver histological lesions, expression of inflammation genes, and inflammatory cell infiltration. In addition, DHA not only attenuated hyperlipidemia but also reduced hepatic steatosis through regulating lipogenesis and lipolysis genes. In vitro experiments further consolidated the concept that DHA ameliorated ethanol-caused hepatocyte injury and steatosis. Noteworthily, DHA effects were reinforced by FXR agonist obeticholic acid or FXR expression plasmids but abrogated by FXR antagonist Z-guggulsterone or FXR siRNA. In summary, DHA significantly improved alcoholic liver injury by inhibiting hepatic steatosis, which was dependent on its activation of FXR in hepatocytes. - Highlights: • DHA rescues FXR expression in alcoholic livers. • DHA improves alcoholic liver inflammation and steatosis in a FXR-dependent way. • DHA alleviates ethanol-induced hepatocyte steatosis by activation of FXR.« less
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Assimilation of ZDR Columns for Improving the Spin-Up and Forecasts of Convective Storms
NASA Astrophysics Data System (ADS)
Carlin, J.; Gao, J.; Snyder, J.; Ryzhkov, A.
2017-12-01
A primary motivation for assimilating radar reflectivity data is the reduction of spin-up time for modeled convection. To accomplish this, cloud analysis techniques seek to induce and sustain convective updrafts in storm-scale models by inserting temperature and moisture increments and hydrometeor mixing ratios into the model analysis from simple relations with reflectivity. Polarimetric radar data provide additional insight into the microphysical and dynamic structure of convection. In particular, the radar meteorology community has known for decades that convective updrafts cause, and are typically co-located with, differential reflectivity (ZDR) columns - vertical protrusions of enhanced ZDR above the environmental 0˚C level. Despite these benefits, limited work has been done thus far to assimilate dual-polarization radar data into numerical weather prediction models. In this study, we explore the utility of assimilating ZDR columns to improve storm-scale model analyses and forecasts of convection. We modify the existing Advanced Regional Prediction System's (ARPS) cloud analysis routine to adjust model temperature and moisture state variables using detected ZDR columns as proxies for convective updrafts, and compare the resultant cycled analyses and forecasts with those from the original reflectivity-based cloud analysis formulation. Results indicate qualitative and quantitative improvements from assimilating ZDR columns, including more coherent analyzed updrafts, forecast updraft helicity swaths that better match radar-derived rotation tracks, more realistic forecast reflectivity fields, and larger equitable threat scores. These findings support the use of dual-polarization radar signatures to improve storm-scale model analyses and forecasts.
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Selden, Clare; Spearman, Catherine Wendy; Kahn, Delawir; Miller, Malcolm; Figaji, Anthony; Erro, Eloy; Bundy, James; Massie, Isobel; Chalmers, Sherri-Ann; Arendse, Hiram; Gautier, Aude; Sharratt, Peter; Fuller, Barry; Hodgson, Humphrey
2013-01-01
Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4–6×1010cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell group, human proteins accumulated in pigs' plasma. Delivery of biomass using a short-term cold-chain enabled transport and use without loss of function over 3days. Thus, a fluidised-bed bioreactor containing alginate-encapsulated HepG2cell-spheroids improved important parameters of acute liver failure in pigs. The system can readily be up-scaled and transported to point-of-use justifying development at clinical scale. PMID:24367515
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Cystic echinococcosis of the pelvic bone with recurrences: a case report.
Jain, Sunila; Chopra, Prem
2011-09-01
Hydatid cysts commonly affect the liver and the lung. However, they rarely involve bones with vertebral column. We hereby report a case of a female patient with cystic echinococcosis of the hip bone and ilium. She presented with a long history of frequent recurrences highlighting the dismal prognosis at this rare site. Resection of the hydatid cyst from the sacroiliac region was done with allograft and autograft (rib graft) with lumbosacroiliac fixation. Follow-up of the patient at 6 months showed no detectable abnormality on radiology and the patient was doing well.
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Sexual dysfunction in chronic liver disease: is liver transplantation an effective cure?
Burra, Patrizia; Germani, Giacomo; Masier, Annalisa; De Martin, Eleonora; Gambato, Martina; Salonia, Andrea; Bo, Patrizio; Vitale, Alessandro; Cillo, Umberto; Russo, Francesco Paolo; Senzolo, Marco
2010-06-27
The goal of liver transplantation is not only to ensure patient long-term survival but also to offer the opportunity to achieve psychologic and physical integrity. Quality of life after liver transplantation may be affected by unsatisfactory sexual function. Before liver transplantation, sexual dysfunction and sex hormone disturbances are reported in men and women mainly due to abnormality of physiology of the hypothalamic-pituitary-gonadal axis and, in some cases, origin of liver disease. Successful liver transplantation should theoretically restore hormonal balance and improve sexual function both in men and women, thus improving the reproductive performance. However, after transplantation, up to 25% of patients report persistent sexual dysfunction, and approximately one third of patients describe the appearance of de novo sexual dysfunction. Despite the described high prevalence of this condition, epidemiologic data are relatively scant. Further studies on pathophysiology and risk factors in the field of sexual function after liver transplantation along with new strategies to support and inform patients on the waiting list and after surgery are needed.
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Okumura, Shinya; Uemura, Tadahiro; Zhao, Xiangdong; Masano, Yuki; Tsuruyama, Tatsuaki; Fujimoto, Yasuhiro; Iida, Taku; Yagi, Shintaro; Bezinover, Dmitri; Spiess, Bruce; Kaido, Toshimi; Uemoto, Shinji
2017-09-01
The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.
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Wu, Naijun; Bradley, Ashley C; Welch, Christopher J; Zhang, Li
2012-08-01
Effects of extra-column volume on apparent separation parameters were studied in ultra-high pressure liquid chromatography with columns and inlet connection tubings of various internal diameters (id) using 50-mm long columns packed with 1.8-μm particles under isocratic conditions. The results showed that apparent retention factors were on average 5, 11, 18, and 41% lower than those corrected with extra-column volumes for 4.6-, 3.0-, 2.1-, and 1.0-mm id columns, respectively, when the extra-column volume (11.3 μL) was kept constant. Also, apparent pressures were 31, 16, 12, and 10% higher than those corrected with pressures from extra-column volumes for 4.6-, 3.0-, 2.1-, and 1.0-mm id columns at the respective optimum flow rate for a typical ultra-high pressure liquid chromatography system. The loss in apparent efficiency increased dramatically from 4.6- to 3.0- to 2.1- to 1.0-mm id columns, less significantly as retention factors increased. The column efficiency was significantly improved as the inlet tubing id was decreased for a given column. The results suggest that maximum ratio of extra-column volume to column void volume should be approximately 1:10 for column porosity more than 0.6 and a retention factor more than 5, where 80% or higher of theoretically predicted efficiency could be achieved. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Changes in Life-Style After Liver Transplantation
Zitelli, Basil J.; Miller, Joanne W.; Gartner, J. Carlton; Malatack, J. Jeffrey; Urbach, Andrew H.; Belle, Steven H.; Williams, Laurel; Kirkpatrick, Beverly; Starzl, Thomas E.
2010-01-01
Sixty-five pediatric patients who received liver transplants between May 1981 and May 1984 were observed for as many as 5 years and examined for changes in lifestyle. Children were less frequently hospitalized, spent less time hospitalized, required fewer medications, and generally had excellent liver and renal function after hepatic transplantation as compared with their pre-transplantation status. Most children were in age-appropriate and standard school classes or were only 1 year behind. Cognitive abilities remained unchanged. Children improved in gross motor function and patients’ behavior significantly improved according to parents’ perceptions. Enuresis was more prevalent, however, than in the population of children who had not received liver transplants. Parental divorce rates were no greater than those reported for other families with chronically ill children. Overall, objective changes in life-style as well as parents’ perceptions of behavior of children appear to be improved after liver transplantation. PMID:3041361
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Zeng, Meng-Su; Ye, Hui-Yi; Guo, Liang; Peng, Wei-Jun; Lu, Jian-Ping; Teng, Gao-Jun; Huan, Yi; Li, Ping; Xu, Jian-Rong; Liang, Chang-Hong; Breuer, Josy
2013-12-01
Contrast agents help to improve visibility in magnetic resonance (MR) imaging. However, owing to the large interstitial spaces of the liver, there is a reduction in the natural contrast gradient between lesions and healthy tissue. This study was undertaken to evaluate the efficacy and safety of the liver-specific MR imaging contrast agent gadoxetate disodium (Gd-EOB-DTPA) in Chinese patients. This was a single-arm, open-label, multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging. MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA (0.025 mmol/kg body weight). Images were evaluated by clinical study investigators and three independent, blinded radiologists. The primary efficacy endpoint was sensitivity in lesion detection. Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46% compared with pre-contrast imaging for the average of the three blinded readers (94.78% vs 85.32% for Gd-EOB-DTPA vs pre-contrast, respectively). Improvements in detection were more pronounced in lesions less than 1 cm. Gd-EOB-DTPA improved diagnostic accuracy in lesion classification. This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions, particularly in those smaller than 1 cm. Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification, and furthermore, Gd-EOB-DTPA is safe in Chinese patients with liver lesions.
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Hayashi, Hiromitsu; Beppu, Toru; Masuda, Toshiro; Okabe, Hirohisa; Imai, Katsunori; Hashimoto, Daisuke; Ikuta, Yoshiaki; Chikamoto, Akira; Watanabe, Masayuki; Baba, Hideo
2014-01-01
Partial splenic embolization (PSE) for cirrhotic patients has been reported not only to achieve an improvement in thrombocytopenia and portal hypertension, but also to induce PSE-associated fringe benefit such as individual liver functional improvement. The purpose of this study was to clarify the predictive marker of liver functional improvement due from PSE in cirrhotic patients. From April 1999 to January 2009, 83 cirrhotic patients with hypersplenism-induced thrombocytopenia (platelet count <10 × 10(4)/μl) underwent PSE. Of them, 71 patients with follow-up for more than one year after PSE were retrospectively investigated. In liver tissues after PSE, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were remarkably increased, speculating that PSE induced liver regenerative response. Indeed, serum albumin and cholinesterase levels increased to 104 ± 14% and 130 ± 65% each of the pretreatment level at one year after PSE. In a multiple linear regression analysis, preoperative splenic volume was extracted as the predictive factor for the improvement in cholinesterase level after PSE. Cirrhotic patients with preoperative splenic volume >600 ml obtained significantly higher serum albumin and cholinesterase levels at one year after PSE compared to those with less than 600 ml (P-values were 0.029 in both). A large preoperative splenic volume was the useful predictive marker for an effective PSE-induced liver functional improvement. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
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Sub-to super-ambient temperature programmable microfabricated gas chromatography column
Robinson, Alex L.; Anderson, Lawrence F.
2004-03-16
A sub- to super-ambient temperature programmable microfabricated gas chromatography column enables more efficient chemical separation of chemical analytes in a gas mixture by combining a thermoelectric cooler and temperature sensing on the microfabricated column. Sub-ambient temperature programming enables the efficient separation of volatile organic compounds and super-ambient temperature programming enables the elution of less volatile analytes within a reasonable time. The small heat capacity and thermal isolation of the microfabricated column improves the thermal time response and power consumption, both important factors for portable microanalytical systems.
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Normothermic ex-situ liver preservation: the new gold standard.
Laing, Richard W; Mergental, Hynek; Mirza, Darius F
2017-06-01
Normothermic machine perfusion of the liver (NMP-L) is a novel technology recently introduced into the practice of liver transplantation. This review recapitulates benefits of normothermic perfusion over conventional static cold storage and summarizes recent publications in this area. The first clinical trials have demonstrated both safety and feasibility of NMP-L. They have shown that machine perfusion can entirely replace cold storage or be commenced following a period of cold ischaemia. The technology currently allows transplant teams to extend the period of organ preservation for up to 24 h. Results from the first randomized control trial comparing NMP-L with static cold storage will be available soon. One major advantage of NMP-L technology over other parallel technologies is the potential to assess liver function during NMP-L. Several case series have suggested parameters usable for liver viability testing during NMP-L including bile production and clearance of lactic acidosis. NMP-L allows viability testing of high-risk livers. It has shown the potential to increase utilization of donor organs and improve transplant procedure logistics. NMP-L is likely to become an important technology that will improve organ preservation as well as have the potential to improve utilization of extended criteria donor livers.
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Ogata, Satoshi; Kianmanesh, Reza; Varma, Deepak; Belghiti, Jacques
2005-01-01
Complete resection of colorectal liver metastases (LM) has been the only curative treatment. However, when LM are multiple and bilobar, only a few patients are candidates for curative surgery. We report on a 53-year-old woman with synchronous multiple and bilobar LM from sigmoidal cancer who became resectable after a multimodal strategy including preoperative systemic chemotherapy and two-step surgery. The spectacular decrease in tumor size after systemic chemotherapy led us to perform two-step surgery, including right portal-vein ligation and left liver metastasectomies, with a coupled saline-radiofrequency device, in order to improve the surgical margin. An extended right hepatectomy was performed later to remove the remaining right liver lesions. The patient was discharged after 28 days without major complication and was recurrence-free 14 months later. We conclude that improving the surgical margin with a coupled saline-radiofrequency device is feasible and effective, avoiding small remnant liver even after multiple tumorectomies. The multimodal strategy, including preoperative chemotherapy, two-step surgery, and tumorectomies, using a coupled saline-radiofrequency device, could increase the number of patients with diffuse bilobar liver metastases who can benefit from liver resection.
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Anatomic Peculiarities of Pig and Human Liver.
Nykonenko, Andriy; Vávra, Petr; Zonča, Pavel
2017-02-01
Many investigations on surgical methods and medical treatment are currently done on pigs. This is possible because the pig is sufficiently close genetically to humans. In recent years, progress in liver surgery has opened new possibilities in surgical treatment of liver diseases. Because the methods are relatively novel, various improvements are still needed, and it is thus helpful to conduct experimental surgeries on pig livers. We reviewed the literature to compare the anatomic and functional features of pig and human livers, information that will be of great importance for improving surgical techniques. During the literature review, we used various sources, such as PubMed, Scopus, and veterinary journals. Our results were summarized in diagrams to facilitate understanding of the vascular structure and biliary systems. We conclude that, although the shapes of the human and pig livers are quite different, the pig liver is divided into the same number of segments as the human liver, which also shows a common structure of the vascular system. Thus, with the anatomic and structural features of the pig liver taken into account, this animal model can be used in experimental hepatic surgery.
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Hammerstingl, R M; Schwarz, W; Hochmuth, K; Staib-Sebler, E; Lorenz, M; Vogl, T J
2001-01-01
The development in oncologic liver surgery as well as modified interventional therapy strategies of the liver have resulted in improved diagnostic imaging. The evolution of contrast agents for MR imaging of the liver has proceeded along several different paths with the common goal of improving liver-lesion contrast. In MRI contrast agents act indirectly by their effects on relaxation times. Contrast agents used for hepatic MR imaging can be categorized in those that target the extracellular space, the hepatobiliary system, and the reticuloendothelial system. The first two result in a positive enhancement, the last one in a negative enhancement. Positive enhancers allow a better characterization of liver metastases using dynamic sequence protocols. Detection rate of liver metastases is increased using hepatobiliary contrast-enhanced MRI compared to unenhanced MRI. Negative enhancers, iron oxide particles, significantly increase tumor-to-liver contrast and allow detection of more lesions than other diagnostic methods. Iron-oxide enhanced MRI enables differential diagnosis of liver metastases comparing morphologic features using T2 and T1-weighted sequences.
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Moro orange juice prevents fatty liver in mice.
Salamone, Federico; Li Volti, Giovanni; Titta, Lucilla; Puzzo, Lidia; Barbagallo, Ignazio; La Delia, Francesco; Zelber-Sagi, Shira; Malaguarnera, Michele; Pelicci, Pier Giuseppe; Giorgio, Marco; Galvano, Fabio
2012-08-07
To establish if the juice of Moro, an anthocyanin-rich orange, may improve liver damage in mice with diet-induced obesity. Eight-week-old mice were fed a high-fat diet (HFD) and were administrated water or Moro juice for 12 wk. Liver morphology, gene expression of lipid transcription factors, and metabolic enzymes were assessed. Mice fed HFD displayed increased body weight, insulin resistance and dyslipidemia. Moro juice administration limited body weight gain, enhanced insulin sensitivity, and decreased serum triglycerides and total cholesterol. Mice fed HFD showed liver steatosis associated with ballooning. Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase, a key enzyme of lipid oxidation. Consistently, Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase, and restored liver glycerol-3-phosphate acyltransferase 1 activity. Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.
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Pediatric liver transplantation
Spada, Marco; Riva, Silvia; Maggiore, Giuseppe; Cintorino, Davide; Gridelli, Bruno
2009-01-01
In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation. PMID:19222089
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A new method for the preparation of polymeric porous layer open tubular columns for GC application
NASA Technical Reports Server (NTRS)
Shen, T. C.; Wang, M. L.
1995-01-01
A new method to prepare polymeric PLOT columns by using in situ polymerization technology is described. The method involves a straightforward in situ polymerization of the monomer. The polymer produced is directly coated on the metal tubing. This eliminates many of the steps needed in conventional polymeric PLOT column preparation. Our method is easy to operate and produces very reproducible columns, as shown previously (T. C. Shen. J. Chromatogr. Sci. 30, 239, 1992). The effects of solvents, tubing pretreatments, initiators and reaction temperatures in the preparation of PLOT columns are studied. Several columns have been developed to separate (1) highly polar compounds, such as water and ammonia or water and HCN, and (2) hydrocarbons and inert gases. A recent improvement has allowed us to produce bonded polymeric PLOT columns. These were studied, and the results are included also.
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Haczeyni, Fahrettin; Barn, Vanessa; Mridha, Auvro R; Yeh, Matthew M; Estevez, Emma; Febbraio, Mark A; Nolan, Christopher J; Bell-Anderson, Kim S; Teoh, Narci C; Farrell, Geoffrey C
2015-09-01
Adipose inflammation and dysfunction underlie metabolic obesity. Exercise improves glycemic control and metabolic indices, but effects on adipose function and inflammation are less clear. Accordingly, it was hypothesized that exercise improves adipose morphometry to reduce adipose inflammation in hyperphagic obese mice. Alms1 mutant foz/foz mice housed in pairs were fed an atherogenic or chow diet; half the cages were fitted with a computer-monitored wheel for voluntary exercise. Insulin-induced AKT-phosphorylation, adipocyte size distribution, and inflammatory recruitment were studied in visceral versus subcutaneous depots, and severity of fatty liver disease was determined. Exercise prevented obesity and diabetes development in chow-fed foz/foz mice and delayed their onset in atherogenic-fed counterparts. Insulin-stimulated phospho-AKT levels in muscle were improved with exercise, but not in adipose or liver. Exercise suppressed adipose inflammatory recruitment, particularly in visceral adipose, associated with an increased number of small adipocyte subpopulations, and enhanced expression of beige adipocyte factor PRDM16 in subcutaneous fat. In atherogenic-fed foz/foz mice liver, exercise suppressed development of nonalcoholic steatohepatitis and related liver fibrosis. Exercise confers metabo-protective effects in atherogenic-fed hyperphagic mice by preventing early onset of obesity and diabetes in association with enhanced muscle insulin sensitivity, improved adipose morphometry, and suppressed adipose and liver inflammation. © 2015 The Obesity Society.
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Lü, Haixia; Li, Qingyin; Yu, Xiaowei; Yi, Jiaojiao; Xie, Zenghong
2013-07-01
A novel open-tubular CEC column coated with chitosan-graft-(β-CD) (CDCS) was prepared using sol-gel technique. In the sol-gel approach, owing to the 3D network of sol-gel and the strong chemical bond between the stationary phase and the surface of capillary columns, good chromatographic characteristics and unique selectivity in separating isomers were shown. The column efficiencies of 55,000∼163,000 plates/m for the isomeric xanthopterin and phenoxy acid herbicides using the sol-gel-derived CDCS columns were achieved. Good stabilities were demonstrated that the RSD values for the retention time of thiourea and isoxanthopterin were 1.3 and 1.4% (run to run, n = 5), 1.6 and 2.0% (day to day, n = 3), 2.9 and 3.1% (column to column, n = 3), respectively. The sol-gel-coated CDCS columns have shown improved separations of isomeric xanthopterin in comparison with CDCS-bonded capillary column. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Müllhaupt, Beat; Dimitroulis, Dimitrios; Gerlach, J Tilman; Clavien, Pierre-Alain
2008-01-01
Liver transplantation has become the mainstay for the treatment of end-stage liver disease, hepatocellular cancer and some metabolic disorders. Its main drawback, though, is the disparity between the number of donors and the patients needing a liver graft. In this review we will discuss the recent changes regarding organ allocation, extended donor criteria, living donor liver transplantation and potential room for improvement. The gap between the number of donors and patients needing a liver graft forced the transplant community to introduce an objective model such as the modified model for end-stage liver disease (MELD) in order to obtain a transparent and fair organ allocation system. The use of extended criteria donor livers such as organs from older donors or steatotic grafts is one possibility to reduce the gap between patients on the waiting list and available donors. Finally, living donor liver transplantation has become a standard procedure in specialized centers as another possibility to reduce the donor shortage. Recent data clearly indicate that center experience is of major importance in achieving good results. Great progress has been made in recent years. However, further research is needed to improve results in the future.
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Perricone, Giovanni; Duvoux, Christophe; Berenguer, Marina; Cortesi, Paolo A; Vinaixa, Carmen; Facchetti, Rita; Mazzarelli, Chiara; Rockenschaub, Susanne-Rasoul; Martini, Silvia; Morelli, Cristina; Monico, Sara; Volpes, Riccardo; Pageaux, Georges-Philippe; Fagiuoli, Stefano; Belli, Luca S
2018-05-11
Treating patients with decompensated cirrhosis with direct-acting antiviral (DAA) therapy while on the waiting list for liver transplantation results in substantial improvement of liver function allowing 1 in 4 patients to be removed from the waiting list or delisted, as reported in a previous study promoted by the European Liver and Intestine Transplant Association (ELITA). The aim of this study was to report on clinical outcomes of delisted patients, including mortality risk, hepatocellular carcinoma development and clinical decompensation requiring relisting. One hundred and forty-two HCV-positive patients on the liver transplant waiting list for decompensated cirrhosis, negative for hepatocellular carcinoma, between February 2014 and June 2015 were treated with DAA therapy and were prospectively followed up. Forty-four patients (30.9%) were delisted following clinical improvement. This percentage was higher than in the original study because of a number of patients being delisted long after starting DAAs. The median Child-Pugh and MELD score of delisted patients was 5.5 and 9 respectively. Four patients were relisted, because of HCC diagnosis in 1 case and 3 patients developed ascites. One further patient died (2.4%) because of rapidly progressing hepatocellular carcinoma twenty-two months after delisting. Of the 70 patients who received a liver graft, 9 died (13%). Antiviral therapy allows for a long-term improvement of liver function and the delisting of one-third of treated patients with risk of liver-related complications after delisting being very low. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Jung, Stephanie; Effelsberg, Uwe; Tallarek, Ulrich
2011-12-01
Dynamic changes in mobile phase composition during high-performance liquid chromatography (HPLC) gradient elution coupled to mass spectrometry (MS) sensitively affect electrospray modes. We investigate the impact of the eluent composition on spray stability and MS response by infusion and injection experiments with a small tetrapeptide in water-acetonitrile mixtures. The employed HPLC/electrospray (ESI)-MS configuration uses a microchip equipped with an enrichment column, a separation column, and a makeup flow (MUF) channel. One nano pump is connected to the separation column, while a second one delivers solvent of exactly inverted composition to the MUF channel. Both solvent streams are united behind the separation column, before the ESI tip, such that the resulting electrosprayed solution always has identical composition during a gradient elution. Analyte peak parameters without and with MUF compensation are determined and discussed with respect to the electrospray mode and eluent composition. The postcolumn MUF significantly improves spray and signal stability over the entire solvent gradient, without compromising the performance of the HPLC separation column. It can also be conveniently implemented on microchip platforms.
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METHOD OF AND APPARATUS FOR WITHDRAWING LIGHT ISOTOPIC PRODUCT FROM A LIQUID THERMAL DIFFUSION PLANT
Dole, M.
1959-09-22
An improved process and apparatus are described for removing enriched product from the columns of a thermal diffusion plant for separation of isotopes. In the removal cycle, light product at the top cf the diffusion columns is circulated through the column tops and a shipping cylinder connected thereto unttl the concertation of enriched product in the cylinder reaches the desired point. During the removal, circulation through the bottoms is blocked bv freezing. in the diffusion cycle, the bottom portion is unfrozen, fresh feed is distributed to the bottoms of the columns, ard heavy product is withdrawn from the bottoms, while the tops of the columns are blocked by freezing.
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Salas, Alfonso Leija; Montezuma, Tania Díaz; Fariña, German Garrido; Reyes-Esparza, Jorge; Rodríguez-Fragoso, Lourdes
2008-01-01
To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats. Hepatic fibrosis was brought about by chronic administration of carbon tetrachloride to rats. To evaluate the effect of genistein on liver fibrosis and function, total collagen content and proteolytic activity in the liver were quantified. Urokinase-type plasminogen activator (uPA) expression during experimental fibrosis was localized by immunohistochemistry. Histopathological changes were evaluated using light and electron microscopy. Animals with fibrosis and treated with genistein showed an important reduction (73%) in hepatic collagen content as well as an improvement in liver function (p < 0.001). Genistein increased the capacity of the liver to degrade type I collagen and Matrigel (3.1- and 3.7-fold, respectively; p < 0.001) in animals with liver fibrosis. Genistein increased the number of uPA-immunoreactive cells. The increase in the uPA expression correlated with an increase in proteolytic activity. Histological analysis revealed a reduction in the number of fiber septa in pericentral and perisinusoidal areas. Transmission electron micrographs of livers from animals with fibrosis and treated with genistein showed a reduction in the number of hepatic stellate cells activated and a smaller number of collagen fibers. Genistein is able to improve the liver after injury and fibrosis induced by chronic administration of carbon tetrachloride. This finding suggests that genistein has antifibrogenic potential and could therefore be useful for treating chronic liver disease. (c) 2008 S. Karger AG, Basel.
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Qian, Weibin; Cai, Xinrui; Zhang, Xinying; Wang, Yingying; Qian, Qiuhai; Hasegawa, Junichi
2016-01-01
Background Daisaikoto (DSKT), a classical traditional Chinese herbal formula, has been used for treating digestive diseases for 1800 years in China. Therefore, in this study, we are going to investigate the effect of DSKT on diabetic fatty liver rats induced by a high-fat diet and streptozotocin (STZ), and the effects of DSKT on silent mating type information regulation 2 homolog 1 (SIRT1) and nuclear factor kappa B (NF-kappaB). Methods Diabetic fatty liver rat model was selected to establish a high-fat diet and STZ. Sixty Wistar rats were divided into six groups (n = 10): control group, high-fat diet + STZ group, simvastatin treatment group, DSKT low dose, medial dose and high dose treatment groups. After 8 weeks of drug intervention, body and liver weights, blood chemistry, blood glucose and insulin were examined. The expressions of sirtuin 1 and NF-kappaB in the liver were observed by RT-PCR and immunohistochemistry, respectively. Results A high-fat diet increased body, liver weights, and serum cholesterol concentrations. Intraperitoneal injection of STZ increased blood glucose and decreased body weights. DSKT improved them. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) indices were increased in the high-fat diet groups. DSKT improved them too. In histological examinations of the liver, we observed a significant improvement after treatment. Immunostaining expression of NF-kappaB in the liver was improved by DSKT and simvastatin. The mRNA expressions of SIRT1 in the liver were increased by DSKT and simvastatin. Conclusion We have demonstrated that DSKT is capable of reversing dyslipidemia and insulin resistance induced by a high-fat diet and STZ. High dose DSKT reveals a stronger effect than simvastatin on the expressions of SIRT1 and NF-kappaB. Furthermore, DSKT has shown a strong dose-depended protective effect on diabetic fatty liver. PMID:27493486
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NASA Astrophysics Data System (ADS)
Akin, Muge K.
2016-04-01
The term of ground improvement states to the modification of the engineering properties of soils. Jet-grouting is one of the grouting methods among various ground improvement techniques. During jet-grouting, different textures of columns can be obtained depending on the characteristics of surrounding subsoil as well as the adopted jet-grouting system for each site is variable. In addition to textural properties, strength and index parameters of jet-grout columns are highly affected by the adjacent soil. In this study, the physical and mechanical properties of jet-grout columns constructed at two different sites in silty and sandy soil conditions were determined by laboratory tests. A number of statistical relationships between physical and mechanical properties of soilcrete were established in this study in order to investigate the dependency of numerous variables. The relationship between qu and γd is more reliable for sandy soilcrete than that of silty columns considering the determination coefficients. Positive linear relationships between Vp and γd with significantly high determination coefficients were obtained for the jet-grout columns in silt and sand. The regression analyses indicate that the P-wave velocity is a very dominant parameter for the estimation of physical and mechanical properties of jet-grout columns and should be involved during the quality control of soilcrete material despite the intensive use of uniaxial compressive strength test. Besides, it is concluded that the dry unit weight of jet-grout column is a good indicator of the efficiency of employed operational parameters during jet-grouting.
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Scorletti, Eleonora; Bhatia, Lokpal; McCormick, Keith G; Clough, Geraldine F; Nash, Kathryn; Hodson, Leanne; Moyses, Helen E; Calder, Philip C; Byrne, Christopher D
2014-10-01
There is no licensed treatment for non-alcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes and cardiovascular disease. We tested whether 15-18 months treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) (Omacor/Lovaza) (4 g/day) decreased liver fat and improved two histologically-validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomised in a double blind placebo-controlled trial [DHA+EPA(n=51), placebo(n=52)]. We quantified liver fat percentage (%) by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA) (placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of: a) DHA+EPA treatment (ITT analyses) and b) erythrocyte DHA and EPA enrichment (secondary analysis). Median (IQR) baseline and end of study liver fat% were 21.7 (19.3) and 19.7 (18.0) (placebo), and 23.0 (36.2) and 16.3 (22.0), (DHA+EPA). In the fully adjusted regression model there was a trend towards improvement in liver fat% with DHA+EPA treatment (β=-3.64 (95%CI -8.0,0.8); p=0.1) but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat% (for each 1% enrichment, β=-1.70 (95%CI -2.9,-0.5); p=0.007). No improvement in the fibrosis scores occurred. Conclusion. Erythrocyte DHA enrichment with DHA+EPA treatment is linearly associated with decreased liver fat%. Substantial decreases in liver fat% can be achieved with high percentage erythrocyte DHA enrichment in NAFLD. (Hepatology 2014;).
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Kaldenbach, Michaela; Cubero, Francisco Javier; Erschfeld, Stephanie; Liedtke, Christian; Trautwein, Christian; Streetz, Konrad
2014-01-01
Hepatocyte transplantation (HT) is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF)-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT) and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa). Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and opens a new door for the applicability of this technique to combat liver disease in the human clinic.
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Kaldenbach, Michaela; Cubero, Francisco Javier; Erschfeld, Stephanie; Liedtke, Christian; Trautwein, Christian; Streetz, Konrad
2014-01-01
Background Hepatocyte transplantation (HT) is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF)-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. Methods Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT) and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa). Results Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. Conclusion This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and opens a new door for the applicability of this technique to combat liver disease in the human clinic. PMID:24979756
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Miyake, Teruki; Matsuura, Bunzo; Furukawa, Shinya; Todo, Yasuhiko; Yamamoto, Shin; Yoshida, Osamu; Imai, Yusuke; Watanabe, Takao; Yamamoto, Yasunori; Hirooka, Masashi; Tokumoto, Yoshio; Kumagi, Teru; Abe, Masanori; Seike, Hirotaka; Miyauchi, Shozo; Hiasa, Yoichi
2016-01-01
3,5,3'-triiodo-L-thyronine regulates the glucose metabolism, lipid metabolism, and hepatic steatosis. Several groups have shown the relationships between hypothyroidism and nonalcoholic fatty liver and hypothyroidism and nonalcoholic steatohepatitis (NASH). However, the effect of hyperthyroidism on NASH has not yet been investigated. We herein report effects of thyroid hormone on the pathological condition of NASH in a patient with NASH complicated by Graves' disease. In our case, the liver enzyme level improved with the increasing thyroid hormone level; however, the liver enzyme level was aggravated with the improving thyroid hormone level. Therefore, hyperthyroidism may improve the pathological condition of NASH.
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Biomechanics of liver injury by steering wheel loading.
Lau, I V; Horsch, J D; Viano, D C; Andrzejak, D V
1987-03-01
Abdominal injury induced by steering wheel contact at a velocity of 32 km/hr was investigated using anesthetized swine as the surrogate on a Hyge sled. The lower rim of the wheel was positioned 5 cm below the xyphoid. By varying wheel stiffness, wheel orientation, and column angle, resultant abdominal injury ranged from fatal or critical to minor or none. Wheel stiffness was found to be the primary determinant of abdominal injury severity. The mechanism of abdominal injury was identified to be the rim impacting the abdomen and exceeding a combined velocity and compression sensitive tolerance limit. Abdominal injury occurred within the initial 15 ms of wheel contact before whole body movement of the surrogate of column compression, which were initiated by hub contact with the thorax. The severity of abdominal injury correlated with the peak viscous response which can be represented by the product of the instantaneous velocity of abdominal deformation and abdominal compression. It did not correlate with spinal acceleration.
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Cyclic performance of concrete-filled steel batten built-up columns
NASA Astrophysics Data System (ADS)
Razzaghi, M. S.; Khalkhaliha, M.; Aziminejad, A.
2016-03-01
Steel built-up batten columns are common types of columns in Iran and some other parts of the world. They are economic and have acceptable performance due to gravity loads. Although several researches have been conducted on the behavior of the batten columns under axial loads, there are few available articles about their seismic performance. Experience of the past earthquakes, particularly the 2003 Bam earthquake in Iran, revealed that these structural members are seismically vulnerable. Thus, investigation on seismic performance of steel batten columns due to seismic loads and providing a method for retrofitting them are important task in seismic-prone areas. This study aims to investigate the behavior of concrete-filled batten columns due to combined axial and lateral loads. To this end, nonlinear static analyses were performed using ANSYS software. Herein, the behaviors of the steel batten columns with and without concrete core were compared. The results of this study showed that concrete-filled steel batten columns, particularly those filled with high-strength concrete, may cause significant increases in energy absorption and capacity of the columns. Furthermore, concrete core may improve post-buckling behavior of steel batten columns.
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Design and construction of stone columns, vol. I.
DOT National Transportation Integrated Search
1983-12-01
k Abstract tone columns have been used since the 1950s as a technique for improving both cohesive soils and silty sands. Potential applicationsj include (1) stabilizing foundation soils to support embankments and approach fills, 12) ,supporting re...
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Meza-Ríos, Alejandra; García-Benavides, Leonel; García-Bañuelos, Jesus; Salazar-Montes, Adriana; Armendáriz-Borunda, Juan; Sandoval-Rodríguez, Ana
2016-01-01
hADSCs transplantation in cirrhosis models improves liver function and reduces fibrosis. In addition, Ad-huPA gene therapy diminished fibrosis and increased hepatocyte regeneration. In this study, we evaluate the combination of these therapies in an advanced liver fibrosis experimental model. hADSCs were expanded and characterized before transplantation. Ad-huPA was simultaneously administrated via the ileac vein. Animals were immunosuppressed by CsA 24 h before treatment and until sacrifice at 10 days post-treatment. huPA liver expression and hADSCs biodistribution were evaluated, as well as the percentage of fibrotic tissue, hepatic mRNA levels of Col-αI, TGF-β1, CTGF, α-SMA, PAI-I, MMP2 and serum levels of ALT, AST and albumin. hADSCs homed mainly in liver, whereas huPA expression was similar in Ad-huPA and hADSCs/Ad-huPA groups. hADSCs, Ad-huPA and hADSCs/Ad-huPA treatment improves albumin levels, reduces liver fibrosis and diminishes Collagen α1, CTGF and α-SMA mRNA liver levels. ALT and AST serum levels showed a significant decrease exclusively in the hADSCs group. These results showed that combinatorial effect of cell and gene-therapy does not improve the antifibrogenic effects of individual treatments, whereas hADSCs transplantation seems to reduce liver fibrosis in a greater proportion.
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Rotating Apparatus for Isoelectric Focusing
NASA Technical Reports Server (NTRS)
Bier, M.
1986-01-01
Remixing of separated fractions prevented. Improved isoelectric focusing apparatus helps to prevent electro-osmosis and convection, both of which cause remixing of separated fractions. Fractionating column segmented and rotated about horizontal axis: Only combined effects of both features fully effective in making good separations. Improved apparatus slowly rotated continuously or rocked (at rotational amplitude of at least 180 degrees) about its horizontal axis so average gravitational vector experienced by fluid is zero and convection is therefore suppressed. Electro-osmosis suppressed and convection further suppressed by separating column into disklike compartments along its length with filters. Experiments have shown dimensions of apparatus not critical. Typical compartment and column volumes are 2 and 40 ml, respectively. Rotation speeds lie between 3 and 30 rpm.
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Engstrand, Jennie; Kartalis, Nikolaos; Strömberg, Cecilia; Broberg, Mats; Stillström, Anna; Lekberg, Tobias; Jonas, Eduard; Freedman, Jacob; Nilsson, Henrik
2017-09-01
Assessing patients with colorectal cancer liver metastases (CRCLM) by a liver multidisciplinary team (MDT) results in higher resection rates and improved survival. The aim of this study was to evaluate the potentially improved resection rate in a defined cohort if all patients with CRCLM were evaluated by a liver MDT. A retrospective analysis of patients diagnosed with colorectal cancer during 2008 in the greater Stockholm region was conducted. All patients with liver metastases (LM), detected during 5-year follow-up, were re-evaluated at a fictive liver MDT in which previous imaging studies, tumor characteristics, medical history, and patients' own treatment preferences were presented. Treatment decisions for each patient were compared to the original management. Odds ratios (ORs) and 95% confidence intervals were estimated for factors associated with referral to the liver MDT. Of 272 patients diagnosed with LM, 102 patients were discussed at an original liver MDT and 69 patients were eventually resected. At the fictive liver MDT, a further 22 patients were considered as resectable/potentially resectable, none previously assessed by a hepatobiliary surgeon. Factors influencing referral to liver MDT were age (OR 3.12, 1.72-5.65), American Society of Anaesthesiologists (ASA) score (OR 0.34, 0.18-0.63; ASA 2 vs. ASA 3), and number of LM (OR 0.10, 0.04-0.22; 1-5 LM vs. >10 LM), while gender ( p = .194) and treatment at a teaching hospital ( p = .838) were not. A meaningful number of patients with liver metastases are not managed according to best available evidence and the potential for higher resection rates is substantial. Patients with liver metastatic colorectal cancer who are assessed at a hepatobiliary multidisciplinary meeting achieve higher resection rates and improved survival. Unfortunately, patients who may benefit from resection are not always properly referred. In this study, the potential improved resection rate was assessed by re-evaluating all patients with liver metastases from a population-based cohort, including patients with extrahepatic metastases and accounting for comorbidity and patients' own preferences towards treatment. An additional 12.9% of the patients were found to be potentially resectable. The results highlight the importance of all patients being evaluated in the setting of a hepatobiliary multidisciplinary meeting. © AlphaMed Press 2017.
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Pojjanapornpun, Siriluck; Nolvachai, Yada; Aryusuk, Kornkanok; Kulsing, Chadin; Krisnangkura, Kanit; Marriott, Philip J
2018-02-17
New generation inert ionic liquid (iIL) GC columns IL60i, IL76i and IL111i, comprising phosphonium or imidazolium cationic species, were investigated for separation of fatty acid methyl esters (FAME). In general, the iIL phases provide comparable retention times to their corresponding conventional columns, with only minor selectivity differences. The average tailing factors and peak widths were noticeably improved (reduced) for IL60i and IL76i, while they were slightly improved for IL111i. Inert IL phase columns were coupled with conventional IL columns in comprehensive two-dimensional GC (GC × GC) with a solid-state modulator which offers variable modulation temperature (T M ), programmable T M during analysis and trapping stationary phase material during the trap/release (modulation) process, independent of oven T and column sets. Although IL phases are classified as polar, relative polarity of the two phases comprising individual GC × GC column sets permits combination of less-polar IL/polar IL and polar IL/less-polar IL column sets; it was observed that a polar/less-polar column set provided better separation of FAME. A higher first dimension ( 1 D) phase polarity combined with a lower 2 D phase polarity, for instance 1 D IL111i with 2 D IL59 gave the best result; the greater difference in 1 D/ 2 D phase polarity results in increasing occupancy of peak area in the 2D space. The IL111i/IL59 column set was selected for analysis of fatty acids in fat and oil products (butter, margarine, fish oil and canola oil). Compared with the conventional IL111, IL111i showed reduced column bleed which makes this more suited to GC × GC analysis of FAME. The proposed method offers a fast profiling approach with good repeatability of analysis of FAME.
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Using Satellite Remote Sensing and Modelling for Insights into N02 Air Pollution and NO2 Emissions
NASA Technical Reports Server (NTRS)
Lamsal, L. N.; Martin, R. V.; Krotkov, N. A.; Bucsela, E. J.; Celarier, E. A.; vanDonkelaar, A.; Parrish, D.
2012-01-01
Nitrogen oxides (NO(x)) are key actors in air quality and climate change. Satellite remote sensing of tropospheric NO2 has developed rapidly with enhanced spatial and temporal resolution since initial observations in 1995. We have developed an improved algorithm and retrieved tropospheric NO2 columns from Ozone Monitoring Instrument. Column observations of tropospheric NO2 from the nadir-viewing satellite sensors contain large contributions from the boundary layer due to strong enhancement of NO2 in the boundary layer. We infer ground-level NO2 concentrations from the OMI satellite instrument which demonstrate significant agreement with in-situ surface measurements. We examine how NO2 columns measured by satellite, ground-level NO2 derived from satellite, and NO(x) emissions obtained from bottom-up inventories relate to world's urban population. We perform inverse modeling analysis of NO2 measurements from OMI to estimate "top-down" surface NO(x) emissions, which are used to evaluate and improve "bottom-up" emission inventories. We use NO2 column observations from OMI and the relationship between NO2 columns and NO(x) emissions from a GEOS-Chem model simulation to estimate the annual change in bottom-up NO(x) emissions. The emission updates offer an improved estimate of NO(x) that are critical to our understanding of air quality, acid deposition, and climate change.
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Neal, G E; Colley, P J
1978-01-01
The metabolism of aflatoxin B1 in vitro was examined in rat liver microsomal preparations. 2. H.p.l.c. (high-performance liquid-chromatographic) systems were used. A silica column was used to separate non-polar metabolites. A system utilizing a reversed-phase column which separates both poar and non-polar metabolites was also developed. 3. The principal metabolites of aflatoxin B1 found were aflatoxin M1, aflatoxin Q1 and a compound which co-chromatographed with a degradation product of aflatoxin B1 2,3-dihydrodiol. 4. The time course of metabolism of aflatoxin B1 by microsomal preparations isolated from control and phenobarbitone-pretreated rats was examined. The rate and extent of metabolism was greater with microsomal preparations from the latter. The formation of aflatoxin Q1 was enhanced 4--5-fold by phenobarbitone pretreatment, whereas the production of aflatoxin M1 was only increased 1--2-fold. The formation of the degradation product of aflatoxin B1 2,3-dihydrodiol was increased 4--5-fold by the pretreatment with phenobarbitone. 5. The microsomal metabolism of aflatoxins M1, P1 and Q1 was examined. Aflatoxin M1 apparently underwent very limited microsomal metabolism to more polar compounds. Aflatoxin P1 was not metabolized. The situation with aflatoxin Q1 was complicated in that it was metabolized in the absence of NADPH to an unidentified metabolite. Aflatoxin B1 appeared as a metabolite of aflatoxin Q1 only when NADPH was present, and the formation of more polar metabolites was also then observed. PMID:728090
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Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis.
Díaz, Francia C; Sáez-González, Esteban; Benlloch, Salvador; Álvarez-Sotomayor, Diego; Conde, Isabel; Polo, Begoña; García, María; Rodríguez, María; Prieto, Martín
Background and aims. Steroid-related hepatotoxicity has become one of the most relevant causes of drug induced liver cholestasis. Some patients do not improve after standard medical treatment (SMT) and may therefore require other approaches, like extracorporeal liver support. We report four cases of patients with pruritus, abnormal liver function tests and biopsy-proven anabolic steroid-induced cholestasis who were unresponsive to SMT. They underwent treatment with albumin dialysis (Molecular Adsorbent Recirculating System -MARS®-). A minimum of two MARS sessions were performed. After MARS® procedure, patients' symptoms improved, as well as liver function tests, thus avoiding liver transplantation. Albumin dialysis appears as a valuable therapeutic option for the management of anabolic steroid-induced cholestasis in patients that are unresponsive to SMT.
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Ischemia-reperfusion injury in rat fatty liver: role of nutritional status.
Caraceni, P; Nardo, B; Domenicali, M; Turi, P; Vici, M; Simoncini, M; De Maria, N; Trevisani, F; Van Thiel, D H; Derenzini, M; Cavallari, A; Bernardi, M
1999-04-01
Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P <.01). Accordingly, fasting and fatty degeneration had a synergistic effect in exacerbating liver injury. Mitochondrial damage was a predominant feature of ultrastructural hepatocyte injury in fasted fatty livers. Glucose supplementation partially prevented the fasting-induced depletion of glycogen and improved the 7-day rat survival to 45%. These data indicate that rat fatty livers exposed to normothermic ischemia-reperfusion injury are much more sensitive to fasting than histologically normal livers. Because glucose supplementation improves both the hepatic glycogen stores and the rat survival, a nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.
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[Effect of fenicaberan on liver function in patients with chronic noncalculous cholecystitis].
Skroban, N V
1989-06-01
The author studied the effect of fenicaberan on the functional state of the liver in 34 patients with chronic noncalculous cholecystitis. It was found that fenicaberan favours improvement of the functional state of the liver but complete normalization of all liver values indicates necessity continuation of treatment in outpatient conditions.
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Sexual dysfunction after liver transplantation.
Burra, Patrizia
2009-11-01
1. The goal of liver transplantation is not only to ensure the survival of patients but also to offer patients the opportunity to achieve a good balance between the functional efficacy of the graft and their psychological and physical integrity. The quality of life after transplantation may be affected by unsatisfactory sexual activity and reproductive performance. 2. Sexual dysfunction and sex hormone disturbances are widely reported in men and women with chronic liver disease before liver transplantation. 3. Successful liver transplantation should lead to improvements in sexual function and sex hormone disturbances in both men and women, therefore improving reproductive performance, but immunosuppressive drugs may interfere with hormone metabolism. 4. Pregnancy is often successful after liver transplantation, despite the potentially toxic effects of immunosuppressive drug therapy, but fetal and maternal outcomes should be regularly assessed. 5. More detailed and comprehensive data are needed in the field of sexual function after transplantation, and new strategies are needed to support and inform patients on the waiting list and after liver transplantation. (c) 2009 AASLD.
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Baig, Maria Tayyab; Ali, Gibran; Awan, Sana Javaid; Shehzad, Umara; Mehmood, Azra; Mohsin, Sadia; Khan, Shaheen N; Riazuddin, Sheikh
2017-10-01
Cellular therapies hold promise to alleviate liver diseases. This study explored the potential of allogenic serum isolated from rat with acute CCl 4 injury to differentiate adipose derived stem cells (ADSCs) towards hepatic lineage. Acute liver injury was induced by CCl 4 which caused significant increase in serum levels of VEGF, SDF1α and EGF. ADSCs were preconditioned with 3% serum isolated from normal and acute liver injury models. ADSCs showed enhanced expression of hepatic markers (AFP, albumin, CK8 and CK19). These differentiated ADSCs were transplanted intra-hepatically in CCl 4 -induced liver fibrosis model. After one month of transplantation, fibrosis and liver functions (alkaline phosphatase, ALAT and bilirubin) showed marked improvement in acute injury group. Elevated expression of hepatic (AFP, albumin, CK 18 and HNF4a) and pro survival markers (PCNA and VEGF) and improvement in liver architecture as deduced from results of alpha smooth muscle actin, Sirius red and Masson's trichome staining was observed.
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Bell-Anderson, K S; Aouad, L; Williams, H; Sanz, F R; Phuyal, J; Larter, C Z; Farrell, G C; Caterson, I D
2011-12-01
Fat Aussie mice (foz/foz) are morbidly obese, glucose intolerant and have liver steatosis that develops into steatohepatitis on a high-fat diet. The cannabinoid 1 receptor (CB1) antagonist SR141716 has been shown to improve obesity-associated metabolic complications in humans and rodent models. The aim of this study was to assess the effect of SR141716 in foz/foz mice. Male wildtype (WT) and foz/foz mice were fed a chow or high-fat diet (45% saturated fat). Vehicle or SR141716 (10 mg kg(-1) per day) was administered in jelly once daily for 4 weeks from 4 months of age. Foz/foz mice were obese but had less epididymal adipose tissue mass than fat-fed WT mice despite being significantly heavier. Liver weight was increased by twofold in foz/foz compared with WT mice and showed significant steatogenesis associated with impaired liver function. Foz/foz and fat-fed WT mice were glucose intolerant as determined by oral glucose tolerance test. In chow-fed foz/foz mice, SR141716 reduced body weight, liver weight, reversed hepatosteatosis and glucose intolerance. Subcutaneous white adipose tissue gene expression of the macrophage-specific marker Cd68 reflected the improvements in the metabolic status by SR141716 in these mice. The results are consistent with the hypothesis that foz/foz mice have defective lipid metabolism, are unable to adequately store fat in adipose tissue but instead sequester fat ectopically in other metabolic tissues (liver) leading to insulin resistance and hepatic steatosis associated with inflammation. Our findings suggest that SR141716 can improve liver lipid metabolism in foz/foz mice in line with improved insulin sensitivity and adipose tissue inflammation.
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[Surgical techniques in liver transplantation].
Chan, Carlos; Plata-Muñoz, Juan José; Franssen, Bernardo
2005-01-01
Liver transplantation (LT) is probably the biggest surgical aggression that a patient can endure. It was considered only as a last option in the era of experimental LT, yet it evolved into the definitive treatment for some types of acute and chronic end stage liver disease. In terms of technique LT is the most complex of all types of transplantations. The surgical procedure in itself is well established and has changed little through time. Liver transplantation owes its improvement to better and more systematic anesthetic procedures and to perioperative care more than being due to improvement of the surgical technique. The first surgical procedure was described by Thomas Starzl in 1969. His initial work has been strengthened with the development of venous bypass, the refinement in vascular and biliary reconstruction technique and the development of the split liver. Up to date technical aspects of orthotopic liver transplantation are described in the present article.
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N-Acetylcysteine Use in Non-Acetaminophen-Induced Acute Liver Failure.
McPheeters, Chelsey M; VanArsdale, Vanessa M; Weant, Kyle A
2016-01-01
This article will review the available evidence related to the management of non-acetaminophen induced acute liver failure with N-acetylcysteine. Randomized controlled trials and a meta-analysis were included in this review. The efficacy of N-acetylcysteine in the treatment of acute liver failure from causes other than acetaminophen toxicity was evaluated. The efficacy of N-acetylcysteine in non-acetaminophen-induced acute liver failure is limited to specific patient populations. Patients classified as Coma Grade I or II are more likely to benefit from the use of this agent. The use of N-acetylcysteine is associated with improved transplant-free survival, not overall survival, in adults. N-Acetylcysteine does not improve the overall survival of patients with non-acetaminophen-induced acute liver failure but may be beneficial in those patients with Coma Grades I-II. Liver transplantation remains the only definitive therapy in advanced disease.
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Babor, F; Hadzik, B; Stannigel, H; Mayatepek, E; Hoehn, T
2013-01-01
Neonatal hemochromatosis (NH) is a rare and severe liver disease of mainly intra-uterine onset, characterized by neonatal liver failure, hepatic and extrahepatic iron accumulation. This leads to an altered iron metabolism with resulting siderosis. The disease represents the most common cause of liver failure in neonates and is also the most common indication for neonatal liver transplantation. We present a case of a newborn diagnosed with NH and life threatening liver failure. Initial treatment consisted of chelation therapy and antioxidants, but lack of laboratory and clinical improvement led to an exchange transfusion followed by the singular substitution of intravenous immunoglobulin (IVIG). Both, exchange transfusion and IVIG were tolerated well and led to an improvement of the general condition of the patient and recovery of liver synthetic function. The subsequent favorable course of the disease is described in this case report.
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A Different Perspective for Management of Diabetes Mellitus: Controlling Viral Liver Diseases.
Zhao, Yingying; Xing, Huichun
2017-01-01
Knowing how to prevent and treat diabetes mellitus (DM) earlier is essential to improving outcomes. Through participating in synthesis and catabolism of glycogen, the liver helps to regulate glucose homeostasis. Viral related liver diseases are associated with glycometabolism disorders, which means effective management of viral liver diseases may be a therapeutic strategy for DM. The present article reviews the correlation between DM and liver diseases to give an update of the management of DM rooted by viral liver diseases.
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Lee, Chang Hun; Kim, In Hee; Moon, Jin Chang; Seo, Seung Young; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul
2017-01-14
To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis ( P = 0.046) but also in those with decompensated cirrhosis ( P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume ( P = 0.002 and 0.005, respectively). Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program.
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Spontaneous and induced tolerance for liver transplant recipients.
Feng, Sandy
2016-02-01
Transformative medical and surgical advances have remarkably improved short-term survival after liver transplantation. There is, however, pervasive concern that the cumulative toxicities of modern immunosuppression regimens severely compromise both quality and quantity of life for liver transplant recipients. The inherently tolerogenic nature of the liver offers the tantalizing opportunity to change the current paradigm of nonspecific and lifelong immunosuppression. Safe minimization or discontinuation of immunosuppression without damage to the liver allograft is an attractive strategy to improve long-term survival after liver transplantation. Recent prospective, multicenter clinical trials have demonstrated that immunosuppression can be safely withdrawn from selected liver transplant recipients with preservation of allograft histology. These successes have spurred multiple avenues of investigation to identify peripheral blood and/or tissue biomarkers and delineate mechanisms of tolerance. Concomitant advances in the ability to expand regulatory T cells in the laboratory have spawned clinical trials to facilitate immunosuppression minimization and/or discontinuation. This review will delineate the unique liver immunobiology that has driven the recent clinical trials to unmask spontaneous tolerance or induce tolerance for liver transplant recipients. The emerging results of these trials over the next 5 years hold promise to reduce the burden of lifelong immunosuppression and thereby optimize the long-term health of liver transplant recipients.
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Herrero, Astrid; Prigent, Julie; Lombard, Catherine; Rosseels, Valérie; Daujat-Chavanieu, Martine; Breckpot, Karine; Najimi, Mustapha; Deblandre, Gisèle; Sokal, Etienne M.
2017-01-01
There is growing evidence that cell therapy constitutes a promising strategy for liver regenerative medicine. In the setting of hepatic cancer treatments, cell therapy could prove a useful therapeutic approach for managing the acute liver failure that occurs following extended hepatectomy. In this study, we examined the influence of delivering adult-derived human liver stem/progenitor cells (ADHLSCs) at two different early time points in an immunodeficient mouse model (Rag2−/-IL2Rg-/-) that had undergone a 70% hepatectomy procedure. The hepatic mesenchymal cells were intrasplenically infused either immediately after surgery (n = 26) or following a critical 3-day period (n = 26). We evaluated the cells' capacity to engraft at day 1 and day 7 following transplantation by means of human Alu qPCR quantification, along with histological assessment of human albumin and α-smooth muscle actin. In addition, cell proliferation (anti-mouse and human Ki-67 staining) and murine liver weight were measured in order to evaluate liver regeneration. At day 1 posttransplantation, the ratio of human to mouse cells was similar in both groups, whereas 1 week posttransplantation this ratio was significantly improved (p < 0.016) in mice receiving ADHLSC injection at day 3 posthepatectomy (1.7%), compared to those injected at the time of surgery (1%). On the basis of liver weight, mouse liver regeneration was more extensive 1 week posttransplantation in mice transplanted with ADHLSCs (+65.3%) compared to that of mice from the sham vehicle group (+42.7%). In conclusion, infusing ADHLSCs 3 days after extensive hepatectomy improves the cell engraftment and murine hepatic tissue regeneration, thereby confirming that ADHLSCs could be a promising cell source for liver cell therapy and hepatic tissue repair. PMID:27657746
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Alam, Md. Ashraful; Kauter, Kathleen; Brown, Lindsay
2013-01-01
Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats. PMID:23446977
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Selbig, William R.
2014-01-01
A new sample collection system was developed to improve the representation of sediment in stormwater by integrating the entire water column. The depth-integrated sampler arm (DISA) was able to mitigate sediment stratification bias in storm water, thereby improving the characterization of particle size distribution from urban source areas. Collector streets had the lowest median particle diameter of 8 μm, followed by parking lots, arterial streets, feeder streets, and residential and mixed land use (32, 43, 50, 80 and 95 μm, respectively). Results from this study suggest there is no single distribution of particles that can be applied uniformly to runoff in urban environments; however, integrating more of the entire water column during the sample collection can address some of the shortcomings of a fixed-point sampler by reducing variability and bias caused by the stratification of solids in a water column.
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Habib, Shahid; Khan, Khalid; Hsu, Chiu-Hsieh; Meister, Edward; Rana, Abbas; Boyer, Thomas
2017-01-01
Background We evaluated the concept of whether liver failure patients with a superimposed kidney injury receiving a simultaneous liver and kidney transplant (SLKT) have similar outcomes compared to patients with liver failure without a kidney injury receiving a liver transplantation (LT) alone. Methods Using data from the United Network of Organ Sharing (UNOS) database, patients were divided into five groups based on pre-transplant model for end-stage liver disease (MELD) scores and categorized as not having (serum creatinine (sCr) ≤ 1.5 mg/dL) or having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT, 14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis. Results Survival in those (liver failure with renal dysfunction) receiving SLKT was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL (liver failure only). The highest mortality rate observed was 21% in the 36+ MELD group with renal dysfunction with or without SLKT. In high MELD recipients (MELD > 30) with renal dysfunction, presence of renal dysfunction affects the outcome and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of renal dysfunction at the time of transplantation does affect post-transplant survival, but survival is improved with SLKT. Conclusions SLKT improved 1-year survival only in low MELD (16 - 20) recipients but not in other groups. Performance of SLKT should be limited to patients where a benefit in survival and post-transplant outcomes can be demonstrated. PMID:28496531
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Tron, Camille; Rayar, Michel; Petitcollin, Antoine; Beaurepaire, Jean-Marie; Cusumano, Caterina; Verdier, Marie-Clémence; Houssel-Debry, Pauline; Camus, Christophe; Boudjema, Karim; Bellissant, Eric; Lemaitre, Florian
2016-12-02
Tacrolimus whole-blood concentrations imperfectly reflect concentrations at the effect site. Tacrolimus concentrations in the transplanted organ could be more relevant to predict rejection events. Because liver biopsy cannot be repeatedly performed after liver transplantation, we suggested measuring tacrolimus in the bile to have a cost-effective and clinically implementable surrogate marker of intra-hepatic tacrolimus concentration. We developed and fully validated a liquid chromatography-tandem mass spectrometry method for the determination of tacrolimus in human bile. Sample purification was achieved using protein precipitation and liquid-liquid extraction with ethyl-acetate. Gradient elution was performed using a C18 analytical column with a 5min run-time. The method was linear from 0.5ng/mL to 20ng/mL. In this concentration range, within-day and between-day precisions as well as overall bias were within ±15%. Matrix effect was fully corrected by the internal standard (ascomycin). The assay was optimized to achieve good selectivity in this complex biological matrix. Tacrolimus was found to be stable in bile stored 6 months at -80°C, after 3 freeze and thaw cycles, 20h at room temperature and 24h in extracts kept at 15°C in the auto-sampler. The method was applied to quantify tacrolimus in bile from liver transplant recipients. It allowed getting preliminary data about tacrolimus excretion profile in bile and showed the lack of correlation between tacrolimus whole blood concentration and tacrolimus liver exposition. This alternative and innovative analytical approach of tacrolimus bio-analysis appears suitable for further studies evaluating relevance of biliary tacrolimus concentration as a new pharmacological marker of immunosuppressive activity. Copyright © 2016 Elsevier B.V. All rights reserved.
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NASA Astrophysics Data System (ADS)
Wang, Ji Zhong; Cheng, Lu; Wang, Xin Pei
2018-06-01
A new column of FRP composite tube confined steel-reinforced concrete (FTCSRC) column was proposed. This paper elaborates on laboratorial and analytical studies on the behavior of FCTSRC columns subjected to axial compressive load. Eight circular FTCSRC stub columns and one circular steel tube confined concrete (STCC) stub column were tested to investigate the failure mode and axial compression performance of circular FTCRSC columns. Parametric analysis was implemented to inquire the influence of confinement material (CFRP-steel tube or CFRP-GFRP tube), internal steel and CFRP layers on the ultimate load capacity. CFRP-steel composite tube was composed of steel tube and CFRP layer which was wrapped outside the steel tube, while CFRP-GFRP composite tube was composite of GFRP tube and CFRP layer. The test results indicate that the confinement effect of CFRP-steel tube is greatly superior to CFRP-GFRP tube. The ductility performance of steel tube confined high-strength concrete column can be improved obviously by encasing steel in the core concrete. Furthermore, with the increase in the layers of FRP wraps, the axial load capacity increases greatly.
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Tsai, Fuu-Jen; Chen, Shih-Yin; Liu, Yu-Ching; Liao, Hsin-Yi; Chen, Chao-Jung
2017-01-01
In nanoflow liquid chromatography-matrix-assisted laser desorption/ionization tandem time-of-flight (nanoLC-MALDI-TOF/TOF) approaches, it is critical to directly apply small amounts of the sample elutes on the sample target using a nanoLC system due to its low flow rate of 200 ~ 300 nl/min. It is recommended to apply a sheath liquid containing a matrix with a several μL/min flow rate at the end of the nanoLC column to ensure a larger co-eluted droplet for more reproducible sample spotting and avoid the laborious task of post-manual matrix spotting. In this study, to achieve a better nanoLC-MALDI performance on sample spotting, we first compared α-Cyano-4-hydroxycinnamic acid (CHCA) solvent composition for efficiently concentrating nanoLC elutes on an anchor chip. The solvent composition of isopropanol (IPA): acetonitrile (ACN):acetone:0.1% Trifluoroacetic acid (TFA) (2:7:7:2) provided strong and homogeneous signals with higher peptide ion yields than the other solvent compositions. Then, nanoLC-MALDI-TOF/TOF was applied to study the impact of aflatoxin B1 on the liver proteome from diabetes mellitus type 1 mice. Aflatoxin B1 (AFB1), produced by Aspergillus flavus and Aspergillus parasiticus is a carcinogen and a known causative agent of liver cancer. To evaluate the effects of long-term exposure to AFB1 on type 1 diabetes mellitus (TIDM), the livers of T1DM control mice and mice treated with AFB1 were analyzed using isotope-coded protein labeling (ICPL)-based quantitative proteomics. Our results showed that gluconeogenesis, lipid, and oxidative phosphorylation mechanisms, normally elevated in T1DM, were disordered following AFB1 treatment. In addition, major urinary protein 1 (MUP1), an indicator of increased insulin sensitivity, was significantly decreased in the T1DM/AFB1 group and may have resulted in higher blood glucose levels compared to the T1DM group. These results indicate that T1DM patients should avoid the AFB1 intake, as they could lead to increased blood glucose levels and disorders of energy-producing mechanisms.
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Gumuscu, Burcu; Erdogan, Zeynep; Guler, Mustafa O.; Tekinay, Turgay
2014-01-01
In this work, a new detection method for complete separation of 2,4,6-trinitrotoluene (TNT); 2,4-dinitrotoluene (2,4-DNT); 2,6-dinitrotoluene (2,6-DNT); 2-aminodinitrotoluene (2-ADNT) and 4-aminodinitrotoluene (4-ADNT) molecules in high-performance liquid-chromatography (HPLC) with UV sensor has been developed using diol column. This approach improves on cost, time, and sensitivity over the existing methods, providing a simple and effective alternative. Total analysis time was less than 13 minutes including column re-equilibration between runs, in which water and acetonitrile were used as gradient elution solvents. Under optimized conditions, the minimum resolution between 2,4-DNT and 2,6-DNT peaks was 2.06. The recovery rates for spiked environmental samples were between 95–98%. The detection limits for diol column ranged from 0.78 to 1.17 µg/L for TNT and its byproducts. While the solvent consumption was 26.4 mL/min for two-phase EPA and 30 mL/min for EPA 8330 methods, it was only 8.8 mL/min for diol column. The resolution was improved up to 49% respect to two-phase EPA and EPA 8330 methods. When compared to C-18 and phenyl-3 columns, solvent usage was reduced up to 64% using diol column and resolution was enhanced approximately two-fold. The sensitivity of diol column was afforded by the hydroxyl groups on polyol layer, joining the formation of charge-transfer complexes with nitroaromatic compounds according to acceptor-donor interactions. Having compliance with current requirements, the proposed method demonstrates sensitive and robust separation. PMID:24905826
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Gumuscu, Burcu; Erdogan, Zeynep; Guler, Mustafa O; Tekinay, Turgay
2014-01-01
In this work, a new detection method for complete separation of 2,4,6-trinitrotoluene (TNT); 2,4-dinitrotoluene (2,4-DNT); 2,6-dinitrotoluene (2,6-DNT); 2-aminodinitrotoluene (2-ADNT) and 4-aminodinitrotoluene (4-ADNT) molecules in high-performance liquid-chromatography (HPLC) with UV sensor has been developed using diol column. This approach improves on cost, time, and sensitivity over the existing methods, providing a simple and effective alternative. Total analysis time was less than 13 minutes including column re-equilibration between runs, in which water and acetonitrile were used as gradient elution solvents. Under optimized conditions, the minimum resolution between 2,4-DNT and 2,6-DNT peaks was 2.06. The recovery rates for spiked environmental samples were between 95-98%. The detection limits for diol column ranged from 0.78 to 1.17 µg/L for TNT and its byproducts. While the solvent consumption was 26.4 mL/min for two-phase EPA and 30 mL/min for EPA 8330 methods, it was only 8.8 mL/min for diol column. The resolution was improved up to 49% respect to two-phase EPA and EPA 8330 methods. When compared to C-18 and phenyl-3 columns, solvent usage was reduced up to 64% using diol column and resolution was enhanced approximately two-fold. The sensitivity of diol column was afforded by the hydroxyl groups on polyol layer, joining the formation of charge-transfer complexes with nitroaromatic compounds according to acceptor-donor interactions. Having compliance with current requirements, the proposed method demonstrates sensitive and robust separation.
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Casas-Grajales, Sael; Muriel, Pablo
2015-01-01
Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. PMID:26261734
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Treatment Option Overview (Adult Primary Liver Cancer)
... adult primary liver cancer may include the following: Total hepatectomy and liver transplant . Partial hepatectomy . Ablation Transarterial chemoembolization and targeted therapy with sorafenib , as palliative therapy to relieve symptoms and improve quality of life . A clinical trial of a new ...
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Treatment Options for Adult Primary Liver Cancer
... adult primary liver cancer may include the following: Total hepatectomy and liver transplant . Partial hepatectomy . Ablation Transarterial chemoembolization and targeted therapy with sorafenib , as palliative therapy to relieve symptoms and improve quality of life . A clinical trial of a new ...
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Stages of Adult Primary Liver Cancer
... adult primary liver cancer may include the following: Total hepatectomy and liver transplant . Partial hepatectomy . Ablation Transarterial chemoembolization and targeted therapy with sorafenib , as palliative therapy to relieve symptoms and improve quality of life . A clinical trial of a new ...
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E-beam column monitoring for improved CD SEM stability and tool matching
NASA Astrophysics Data System (ADS)
Hayes, Timothy S.; Henninger, Randall S.
2000-06-01
Tool matching is an important metric for in-line semiconductor metrology systems. The ability to obtain the same measurement results on two or more systems allows a semiconductor fabrication facility (fab) to deploy product in an efficient manner improving overall equipment efficiency (OEE). Many parameters on the critical dimension scanning electron microscopes (CDSEMs) can affect the long-term precision component to the tool-matching metric. One such class of parameters is related to the electron beam column stability. The alignment and condition of the gun and apertures, as well as astigmatism correction, have all been found to affect the overall measurements of the CDSEM. These effects are now becoming dominant factors in sub-3nm tool-matching criteria. This paper discusses the methodologies of column parameter monitoring and actions and controls for improving overall stability. Results have shown that column instabilities caused by contamination, gun fluctuations, component failures, detector efficiency, and external issues can be identified through parameter monitoring. The Applied Materials (AMAT) 7830 Series CDSEMs evaluated at IBM's Burlington, Vermont manufacturing facility have demonstrated 5 nm tool matching across 11 systems, which has resulted in non-dedicated product deployment and has significantly reduced cost of ownership.
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Song, Ji-Yeon; Oh, Donghoon; Lee, Chang-Ha
2015-07-17
The effects of a malfunctional column on the performance of a simulated moving bed (SMB) process were studied experimentally and theoretically. The experimental results of conventional four-zone SMB (2-2-2-2 configuration) and FeedCol operation (2-2-2-2 configuration with one feed column) with one malfunctional column were compared with simulation results of the corresponding SMB processes with a normal column configuration. The malfunctional column in SMB processes significantly deteriorated raffinate purity. However, the extract purity was equivalent or slightly improved compared with the corresponding normal SMB operation because the complete separation zone of the malfunctional column moved to a lower flow rate range in zones II and III. With the malfunctional column configuration, FeedCol operation gave better experimental performance (up to 7%) than conventional SMB operation because controlling product purity with FeedCol operation was more flexible through the use of two additional operating variables, injection time and injection length. Thus, compared with conventional SMB separation, extract with equivalent or slightly better purity could be produced from FeedCol operation even with a malfunctional column, while minimizing the decrease in raffinate purity (less than 2%). Copyright © 2015 Elsevier B.V. All rights reserved.
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Mu, Jingzhou; Chen, Qiuyu; Zhu, Liang; Wu, Yunhong; Liu, Suping; Zhao, Yufei; Ma, Tonghui
2018-04-27
Liver transplantation is currently a standard therapy for patients with end-stage liver diseases and hepatocellular carcinoma. Given that liver transplantation has undergone a thriving development in these decades, the survival rates after liver transplantation have markedly improved as a result of the critical advancement in surgical techniques, immunosuppressive therapies, and postoperative care. However, infection remains a fatal complication after liver transplantation surgery. In particular, enterogenic infection represents a major complication in liver transplant recipients. This article gives an overview of infection cases after liver transplantation and focuses on the discussion of enterogenic infection in terms of its pathophysiology, risk factor, outcome, and treatment.
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Langdon, Jonathan H; Elegbe, Etana; Gonzalez, Raul S; Osapoetra, Laurentius; Ford, Tristan; McAleavey, Stephen A
2017-11-01
The clinical use of elastography for monitoring fibrosis progression is challenged by the subtle changes in liver stiffness associated with early-stage fibrosis and the comparatively large variance in stiffness estimates provided by elastography. Single-tracking-location (STL) shear wave elasticity imaging (SWEI) is an ultrasound elastography technique previously found to provide improved estimate precision compared with multiple-tracking-location (MTL) SWEI. Because of the improved precision, it is reasonable to expect that STL-SWEI would provide improved ability to differentiate liver fibrosis stage compared with MTL-SWEI. However, this expectation has not been previously challenged rigorously. In this work, the performance of STL- and MTL-SWEI in the setting of a rat model of liver fibrosis is characterized, and the advantages of STL-SWEI in staging fibrosis are explored. The purpose of this study was to determine what advantages, if any, arise from using STL-SWEI instead of MTL-SWEI in the characterization of fibrotic liver. Thus, the ability of STL-SWEI to differentiate livers at various METAVIR fibrosis scores, for ex vivo postmortem measurements, is explored. In addition, we examined the effect of the common confounding factor of fluid versus solid boundary conditions in SWEI experiments. Sprague-Dawley rats were treated with carbon tetrachloride over several weeks to produce liver disease of varying severity. STL and MTL stiffness measurements were performed ex vivo and compared with the METAVIR scores from histological analysis and the duration of treatment. A strong association was observed between liver stiffness and weeks of treatment with the liver toxin carbon tetrachloride. Direct comparison of STL- and MTL-SWEI measurements revealed no significant difference in ability to differentiate fibrosis stages based on SWEI mean values. However, image interquartile range was greatly improved in the case of STL-SWEI, compared with MTL-SWEI, at small beam spacing. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
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Drug-Induced Liver Injury Associated with Complementary and Alternative Medicines
Takahashi, Koji; Kanda, Tatsuo; Yasui, Shin; Haga, Yuki; Kumagai, Junichiro; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Nakamura, Masato; Arai, Makoto; Yokosuka, Osamu
2016-01-01
A 24-year-old man was admitted due to acute hepatitis with unknown etiology. After his condition and laboratory data gradually improved with conservative therapy, he was discharged 1 month later. Two months after his discharge, however, liver dysfunction reappeared. After his mother accidentally revealed that he took complementary and alternative medicine, discontinuation of the therapy caused his condition to improve. Finally, he was diagnosed with a recurrent drug-induced liver injury associated with Japanese complementary and alternative medicine. It is important to take the medical history in detail and consider complementary and alternative medicine as a cause of liver disease. PMID:28100990
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Chang, Hong-Chou; Peng, Chiung-Huei; Yeh, Da-Ming; Kao, Erl-Shyh; Wang, Chau-Jong
2014-04-01
Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our previous report suggested that Hibiscus sabdariffa extracts (HSE) had a metabolic-regulating and liver-protecting potential. In this study, we performed a clinical trial to further confirm the effect of HSE. Subjects with a BMI ≧ 27 and aged 18-65, were randomly divided into control (n = 17) and HSE-treated (n = 19) groups, respectively, for 12 weeks. Our data showed that consumption of HSE reduced body weight, BMI, body fat and the waist-to-hip ratio. Serum free fatty acid (FFA) was lowered by HSE. Anatomic changes revealed that HSE improved the illness of liver steatosis. Ingestion of HSE was well tolerated and there was no adverse effect during the trial. No alteration was found for serum α-amylase and lipase. The clinical effect should mainly be attributed to the polyphenols of HSE, since composition analysis showed that branched chain-amino acids, which is associated with obesity, is not obviously high. In conclusion, consumption of HSE reduced obesity, abdominal fat, serum FFA and improved liver steatosis. HSE could act as an adjuvant for preventing obesity and non-alcoholic fatty liver.
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Melgar-Lesmes, Pedro; Balcells, Mercedes; Edelman, Elazer R.
2017-01-01
Objective Liver transplantation is limited by ischemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recover after hepatectomy and engraftment. Design Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomized recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analyzed 7 days post-op. Results Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts, and allogeneic engraftment. Conclusions Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischemic injury after major hepatectomy and engraftment. This study highlights endothelial-hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation. PMID:26851165
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NASA Astrophysics Data System (ADS)
Mandai, Shingo; Jain, Vishwas; Charbon, Edoardo
2014-02-01
This paper presents a digital silicon photomultiplier (SiPM) partitioned in columns, whereas each column is connected to a column-parallel time-to-digital converter (TDC), in order to improve the timing resolution of single-photon detection. By reducing the number of pixels per TDC using a sharing scheme with three TDCs per column, the pixel-to-pixel skew is reduced. We report the basic characterization of the SiPM, comprising 416 single-photon avalanche diodes (SPADs); the characterization includes photon detection probability, dark count rate, afterpulsing, and crosstalk. We achieved 264-ps full-width at half maximum timing resolution of single-photon detection using a 48-fold column-parallel TDC with a temporal resolution of 51.8 ps (least significant bit), fully integrated in standard complementary metal-oxide semiconductor technology.
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Steel-reinforced concrete-filled steel tubular columns under axial and lateral cyclic loading
NASA Astrophysics Data System (ADS)
Farajpourbonab, Ebrahim; Kute, Sunil Y.; Inamdar, Vilas M.
2018-03-01
SRCFT columns are formed by inserting a steel section into a concrete-filled steel tube. These types of columns are named steel-reinforced concrete-filled steel tubular (SRCFT) columns. The current study aims at investigating the various types of reinforcing steel section to improve the strength and hysteresis behavior of SRCFT columns under axial and lateral cyclic loading. To attain this objective, a numerical study has been conducted on a series of composite columns. First, FEM procedure has been verified by the use of available experimental studies. Next, eight composite columns having different types of cross sections were analyzed. For comparison purpose, the base model was a CFT column used as a benchmark specimen. Nevertheless, the other specimens were SRCFT types. The results indicate that reinforcement of a CFT column through this method leads to enhancement in load-carrying capacity, enhancement in lateral drift ratio, ductility, preventing of local buckling in steel shell, and enhancement in energy absorption capacity. Under cyclic displacement history, it was observed that the use of cross-shaped reinforcing steel section causes a higher level of energy dissipation and the moment of inertia of the reinforcing steel sections was found to be the most significant parameter affecting the hysteresis behavior of SRCFT columns.
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Ning, Jia; Sun, Yongliang; Xie, Sheng; Zhang, Bida; Huang, Feng; Koken, Peter; Smink, Jouke; Yuan, Chun; Chen, Huijun
2018-05-01
To propose a simultaneous acquisition sequence for improved hepatic pharmacokinetics quantification accuracy (SAHA) method for liver dynamic contrast-enhanced MRI. The proposed SAHA simultaneously acquired high temporal-resolution 2D images for vascular input function extraction using Cartesian sampling and 3D large-coverage high spatial-resolution liver dynamic contrast-enhanced images using golden angle stack-of-stars acquisition in an interleaved way. Simulations were conducted to investigate the accuracy of SAHA in pharmacokinetic analysis. A healthy volunteer and three patients with cirrhosis or hepatocellular carcinoma were included in the study to investigate the feasibility of SAHA in vivo. Simulation studies showed that SAHA can provide closer results to the true values and lower root mean square error of estimated pharmacokinetic parameters in all of the tested scenarios. The in vivo scans of subjects provided fair image quality of both 2D images for arterial input function and portal venous input function and 3D whole liver images. The in vivo fitting results showed that the perfusion parameters of healthy liver were significantly different from those of cirrhotic liver and HCC. The proposed SAHA can provide improved accuracy in pharmacokinetic modeling and is feasible in human liver dynamic contrast-enhanced MRI, suggesting that SAHA is a potential tool for liver dynamic contrast-enhanced MRI. Magn Reson Med 79:2629-2641, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.
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Meza-Ríos, Alejandra; García-Benavides, Leonel; García-Bañuelos, Jesus; Salazar-Montes, Adriana; Armendáriz-Borunda, Juan; Sandoval-Rodríguez, Ana
2016-01-01
Background and Aims hADSCs transplantation in cirrhosis models improves liver function and reduces fibrosis. In addition, Ad-huPA gene therapy diminished fibrosis and increased hepatocyte regeneration. In this study, we evaluate the combination of these therapies in an advanced liver fibrosis experimental model. Methods hADSCs were expanded and characterized before transplantation. Ad-huPA was simultaneously administrated via the ileac vein. Animals were immunosuppressed by CsA 24 h before treatment and until sacrifice at 10 days post-treatment. huPA liver expression and hADSCs biodistribution were evaluated, as well as the percentage of fibrotic tissue, hepatic mRNA levels of Col-αI, TGF-β1, CTGF, α-SMA, PAI-I, MMP2 and serum levels of ALT, AST and albumin. Results hADSCs homed mainly in liver, whereas huPA expression was similar in Ad-huPA and hADSCs/Ad-huPA groups. hADSCs, Ad-huPA and hADSCs/Ad-huPA treatment improves albumin levels, reduces liver fibrosis and diminishes Collagen α1, CTGF and α-SMA mRNA liver levels. ALT and AST serum levels showed a significant decrease exclusively in the hADSCs group. Conclusions These results showed that combinatorial effect of cell and gene-therapy does not improve the antifibrogenic effects of individual treatments, whereas hADSCs transplantation seems to reduce liver fibrosis in a greater proportion. PMID:27992438
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Chan, Justin; Gogela, Neliswa; Zheng, Hui; Lammert, Sara; Ajayi, Tokunbo; Fricker, Zachary; Kim, Arthur Y; Robbins, Gregory K; Chung, Raymond T
2018-02-01
Liver fibrosis stage determines risk of morbidity and mortality from chronic hepatitis C virus (HCV) infection. Prior data have shown long-term reversal of liver fibrosis, measured by vibration-controlled transient elastography (VCTE), in patients successfully treated with interferon-based therapies. Our study sought to determine the effect of treatment with modern HCV direct-acting antiviral (DAA) therapy on noninvasive liver fibrosis measurements. A total of 70 patients had VCTE-based liver stiffness measurement (LSM) taken before treatment, directly after treatment completion, and at least 12 months after completion of DAA therapy. Our primary outcome was a >30% improvement in VCTE score at the end of follow-up, relative to baseline. The sustained virologic response rate in our cohort was 95.7%. In our cohort, 34 (48.6%) met the primary outcome. Those who had baseline elevated alanine aminotransferase (OR 3.27; 95% CI 1.13-9.47) and genotype 1 (OR 14.63; 95% CI 1.70-125.83) had higher odds of meeting that outcome, and this remained significant after adjusting for age, baseline body mass index, gender, baseline elevated alkaline phosphatase levels, treatment experience, liver transplant status, smoking, and baseline liver stiffness. Treatment of chronic HCV with modern DAA therapy was associated with a significant improvement in LSM by VCTE measurement, suggesting possible early improvement in liver fibrosis along with resolution of inflammation over the first year after treatment completion.
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LABELING WITH 14C AMINO ACIDS OF ALBUMIN-LIKE PROTEIN BY RAT LIVER RIBONUCLEOPROTEIN PARTICLES
von der Decken, Alexandra
1963-01-01
Ribonucleoprotein particles were prepared by treatment of rat liver microsomes with detergents and high concentrations of KCl. They were active in incorporating 14C amino acids into protein when incubated with cell sap together with ATP, GTP, and a system to regenerate the triphosphates. The albumin of the incubation mixture, soluble at 105,000 g, and that of the fraction released by ultrasonication of the particles were studied by immunoelectrophoresis in agar gel. When the ribonucleoprotein particles were incubated with cell sap the immunological precipitation lines formed with antiserum to rat serum albumin were highly radioactive as tested by autoradiography. After zone electrophoresis on cellulose acetate, two immunologically reactive albumins were obtained which differed in their electrophoretic mobility from rat serum albumin. Labeled albumin, when purified on DEAE-cellulose columns, retained its radioactivity as tested by autoradiography following immunoelectrophoresis. On cellulose acetate this purified albumin showed an electrophoretic mobility higher than that of rat serum albumin. PMID:14026307
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Nakamura, Michiko; Miura, Sayaka; Takagaki, Akiko; Nanjo, Fumio
2017-05-01
Crude tea polysaccharide (crude TPS) was prepared from instant green tea by ethanol precipitation followed by ultrafiltration membrane treatment and its effects on blood lipid, liver lipid, and fecal lipid levels were examined with Sprague-Dawley rats fed a high-fat diet. Although crude TPS showed no effects on the serum lipid levels, it suppressed the liver lipid accumulation and increased the fecal excretion of dietary fat. Then, the structural features of crude TPS were investigated. After separation of crude TPS by DEAE-cellulose and gel-filtration column chromatography, two kinds of neutral tea polysaccharides (NTPS-LP and NTPS-HH) and an acidic polysaccharide (ATPS-MH) were obtained. According to monosaccharide composition, methylation, and NMR analyses, NTPS-LP, NPTS-HH, and ATPS-MH were presumed to be starch, arabinogalactan with β-1,3-linked galactosyl backbone blanched at position 6 and with 1,5-linked arabinofuranosyl residues, and α-1,4-linked galacturonic acid backbone with arabinogalactan region, respectively.
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Boumrah, Yacine; Humbert, Luc; Phanithavong, Melodie; Khimeche, Kamel; Dahmani, Abdallah; Allorge, Delphine
2016-02-01
One of the main challenges posed by the emergence of new psychoactive substances is their identification in human biological samples. Trying to detect the parent drug could lead to false-negative results when the delay between consumption and sampling has been too long. The identification of their metabolites could then improve their detection window in biological matrices. Oxidative metabolism by cytochromes P450 and glucuronidation are two major detoxification pathways in humans. In order to characterize possible CYP- and UGT-dependent metabolites of the 2-(4-bromo-2,5-dimethoxy-phenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25B-NBOMe), a synthetic psychoactive drug, analyses of human liver microsome (HLM) incubates were performed using an ultra-high performance liquid chromatography system coupled with a quadrupole-time of flight mass spectrometry detector (UHPLC-Q-TOF/MS). On-line analyses were performed using a Waters OASIS HLB column (30 x 2.1 mm, 20 µm) for the automatic sample loading and a Waters ACQUITY HSS C18 column (150 x 2 mm, 1.8 µm) for the chromatographic separation. Twenty-one metabolites, consisting of 12 CYP-derived and 9 UGT-derived metabolites, were identified. O-Desmethyl metabolites were the most abundant compounds after the phase I process, which appears to be in accordance with data from previously published NBOMe-intoxication case reports. Although other important metabolic transformations, such as sulfation, acetylation, methylation or glutathione conjugation, were not studied and artefactual metabolites might have been produced during the HLM incubation process, the record of all the metabolite MS spectra in our library should enable us to characterize relevant metabolites of 25B-NBOMe and allow us to detect 25B-MBOMe users. Copyright © 2015 John Wiley & Sons, Ltd.
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Yang, Yi; Aisa, Haji Akber; Ito, Yoichiro
2009-01-01
The toroidal column using a zigzag pattern has been improved in both retention of the stationary phase and peak resolution. To further improve the retention of stationary phase and peak resolution, a series of novel geometric designs of tubing (plain, mid-clamping, flattened and flat-twisted tubing) was evaluated their performance in CCC. The results showed that the tubing which was flattened vertically against centrifugal force (vert-flattened tubing) produced the best peak resolution among them. Using vert-flattened tubing a series of experiments was performed to study the effects of column capacity and sample size. The results indicated that a 0.25 ml capacity column is ideal for analysis of small amount samples. PMID:20454530
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Antiorthostatic test as a model to study antigravity mechanisms of the cardiovascular system.
Yarullin, K K; Vasilyeva, T D; Alekseev, D A
1976-01-01
The paper presents rheographic investigations of regional haemodynamics (brain, lungs, liver and limbs) during antiorthostatic exposures of varying intensity (-15, -30, -45 degrees, times of exposure 20, 40 and 60 min). Our findings show that the pattern and time of the function of compensatory mechanisms preventing excessive vascular compliance [correction of complicance] under the influence of the hydrostatic blood column depend on the value and length of antiorthostasis, because prolonged venous congestion results not only in congestive circulatory hypoxia but also in arterial hypoxia due to compensatory limitation of arterial inflow.
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Furukawa, Shigetada; Tsurumi, Yasuhisa; Murakami, Kana; Nakanishi, Tomoko; Ohsumi, Keisuke; Hashimoto, Michizane; Nishikawa, Motoaki; Takase, Shigehiro; Nakayama, Osamu; Hino, Motohiro
2005-08-01
FR258900 is a novel glycogen synthesis activator produced by Fungus No. 138354. This compound was isolated from the culture broth by solvent extraction and reverse-phase column chromatography. FR258900 stimulated glycogen synthesis and glycogen synthase activity in primary rat hepatocytes. FR258900 exhibited a potent inhibitory effect on the activity of liver glycogen phosphorylase, suggesting that this compound may activate hepatic glycogen synthesis via glycogen phosphorylase inhibition. Thus, this glycogen phosphorylase inhibitor may be useful in the treatment of postprandial hyperglycemia in type 2 diabetes.
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Rodriguez, Natalie S; Yanuaria, Lisa; Parducho, Kevin Murphy R; Garcia, Irving M; Varghese, Bino A; Grubbs, Brendan H; Miki, Toshio
2017-07-01
Mucopolysaccharidosis type 1 (MPS1) is an inherited lysosomal storage disorder caused by a deficiency in the glycosaminoglycan (GAG)-degrading enzyme α-l-iduronidase (IDUA). In affected patients, the systemic accumulation of GAGs results in skeletal dysplasia, neurological degeneration, multiple organ dysfunction, and early death. Current therapies, including enzyme replacement and bone marrow transplant, improve life expectancy but the benefits to skeletal and neurological phenotypes are limited. In this study, we tested the therapeutic efficacy of liver-directed transplantation of a placental stem cell, which possesses multilineage differentiation potential, low immunogenicity, and high lysosomal enzyme activity. Unfractionated human amniotic epithelial cells (hAECs) were transplanted directly into the liver of immunodeficient Idua knockout mouse neonates. The hAECs engraftment was immunohistochemically confirmed with anti-human mitochondria staining. Enzyme activity assays indicated that hAECs transplantation restored IDUA function in the liver and significantly decreased urinary GAG excretion. Histochemical and micro-computed tomography analyses revealed reduced GAG deposition in the phalanges joints and composition/morphology improvement of cranial and facial bones. Neurological assessment in the hAEC treated mice showed significant improvement of sensorimotor coordination in the hAEC treated mice compared to untreated mice. Results confirm that partial liver cell replacement with placental stem cells can provide long-term (>20 weeks) and systemic restoration of enzyme function, and lead to significant phenotypic improvement in the MPS1 mouse model. This preclinical data indicate that liver-directed placental stem cell transplantation may improve skeletal and neurological phenotypes of MPS1 patients. Stem Cells Translational Medicine 2017;6:1583-1594. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
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Wilson, Ryan B; Siegler, W Christopher; Hoggard, Jamin C; Fitz, Brian D; Nadeau, Jeremy S; Synovec, Robert E
2011-05-27
By taking into consideration band broadening theory and using those results to select experimental conditions, and also by reducing the injection pulse width, peak capacity production (i.e., peak capacity per separation time) is substantially improved for one dimensional (1D-GC) and comprehensive two dimensional (GC×GC) gas chromatography. A theoretical framework for determining the optimal linear gas velocity (the linear gas velocity producing the minimum H), from experimental parameters provides an in-depth understanding of the potential for GC separations in the absence of extra-column band broadening. The extra-column band broadening is referred to herein as off-column band broadening since it is additional band broadening not due to the on-column separation processes. The theory provides the basis to experimentally evaluate and improve temperature programmed 1D-GC separations, but in order to do so with a commercial 1D-GC instrument platform, off-column band broadening from injection and detection needed to be significantly reduced. Specifically for injection, a resistively heated transfer line is coupled to a high-speed diaphragm valve to provide a suitable injection pulse width (referred to herein as modified injection). Additionally, flame ionization detection (FID) was modified to provide a data collection rate of 5kHz. The use of long, relatively narrow open tubular capillary columns and a 40°C/min programming rate were explored for 1D-GC, specifically a 40m, 180μm i.d. capillary column operated at or above the optimal average linear gas velocity. Injection using standard auto-injection with a 1:400 split resulted in an average peak width of ∼1.5s, hence a peak capacity production of 40peaks/min. In contrast, use of modified injection produced ∼500ms peak widths for 1D-GC, i.e., a peak capacity production of 120peaks/min (a 3-fold improvement over standard auto-injection). Implementation of modified injection resulted in retention time, peak width, peak height, and peak area average RSD%'s of 0.006, 0.8, 3.4, and 4.0%, respectively. Modified injection onto the first column of a GC×GC coupled with another high-speed valve injection onto the second column produced an instrument with high peak capacity production (500-800peaks/min), ∼5-fold to 8-fold higher than typically reported for GC×GC. Copyright © 2011 Elsevier B.V. All rights reserved.
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Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review.
Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R; Partovi, Nilufar; Yoshida, Eric M
2016-09-28
Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present.
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Nieuwenhuijs, Vincent B; De Bruijn, Menno T; Padbury, Robert T A; Barritt, Gregory J
2006-06-01
Liver resection and liver transplantation have been successful in the treatment of liver tumors and end-stage liver disease. This success has led to an expansion in the pool of patients potentially treatable by liver surgery and, in the case of transplantation, to a shortage of liver donors. At present, there are significant numbers of potential candidates for liver resection and liver donation who have fatty livers, are aged, or have livers damaged by chemotherapy. All of these are at high risk for ischemic reperfusion (IR) injury. The aims of this review are to assess current knowledge of the clinical effectiveness of ischemic preconditioning and intermittent ischemia in reducing IR damage in liver surgery; to evaluate the use of bile flow as a sensitive indicator of IR liver damage; and to analyze the molecular mechanisms, especially intracellular Ca2+, involved in IR injury and ischemic preconditioning. It is concluded that bile flow is a sensitive indicator of IR injury. Together with reactive oxygen species (ROS) and other extracellular and intracellular signaling molecules, intracellular Ca2+ in hepatocytes plays a key role in the normal regulation of bile flow and in IR-induced injury and cell death. Ischemic preconditioning is an effective strategy to reduce IR injury but there is considerable scope for improvement, especially in patients with fatty and aged livers. The development of effective new strategies to reduce IR injury will depend on improved understanding of the molecular mechanisms involved, especially by gaining a better perspective of the relative importance of the various intrahepatocyte signaling pathways involved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Gans, J.H.; Korson, R.
1984-02-01
Long-term, continuous (twice per week) administration of CCl/sub 4/ to male mice resulted in a high incidence of liver nodules which appear to be resistant to the necrotizing effects of CCl/sub 4/ but showed no features of malignant neoplasia. Liver nuclear DNA synthesis was compared in mice given CCl/sub 4/ and in mice subjected to partial hepatectomy (PH). Mice were given by gavage corn oil or CCl/sub 4/ in corn oil for periods of 2 to 25 weeks and several mice were subjected to PH after 12 and 25 weeks of corn oil treatment. Mice were given (/sup 3/H)TdR duringmore » liver regeneration and newly synthesized liver nuclear DNA was isolated and separated by BND-cellulose chromatography. Greater than 85% of the labeled DNA from PH mice eluted from BND-cellulose columns as double-stranded (ds) DNA with single-stranded (ss) regions or ends and less than 15% as ds DNA. When mice were treated with CCl/sub 4/ for 8 weeks or longer a significantly greater portion of liver nuclear DNA eluted as ds DNA. Administration of HU and 5-FU with (/sup 3/H)TdR decreased (/sup 3/H)TdR incorporation into DNA to low levels incompatible with unscheduled DNA synthesis. Single doses of CCl/sub 4/ given to mice treated with corn oil for 2 to 12 weeks provided newly synthesized DNA which was primarily (>80%) ds DNA with ss regions or ends, but after 25 weeks of corn oil administration, a single dose of CCl/sub 4/ resulted in newly synthesized DNA with a greater proportion of ds DNA. The high labeling of ds DNA in mice treated with CCl/sub 4/ may have resulted from an alternate pathway of DNA synthesis catalyzed by the enzymes or enzyme complexes associated with semiconservative DNA synthesis or from proliferation of nonparenchymal cells with a rapid turn-over rate.« less
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Annabi, Ali; El Mouadeb, Rahma; Herrel, Anthony
2018-01-01
The present study assessed the impact of metal pollution on two widely consumed types of wild fish Sardinella aurita and Mugil cephalus captured from the Gulf of Gabes (Tunisia) which is currently experiencing acute environmental problems. A study of the Cd, Cu, Zn, and Pb levels present in the studied site and vital in fish tissues (gills, liver, gonad, and muscle) was undertaken. As expected, muscle, liver, and gonad tissues contained the highest concentrations of all metals except for Zn. The metal levels showed a significant variation of accumulation between species with overall effects of the tested tissues. In addition, the results address the significant effects of the species/tissue interaction. Liver sections showed structural alterations consisting mainly of a significant desquamation of the tissue, a fibroblast proliferation, and a lipid droplet accumulation in both species. Additionally, the presence of skeletal abnormalities affecting the vertebral column was observed in the M. cephalus specimens. As a whole, our data provide the first evidence of distinctive metal accumulation patterns in vital fish tissues as well as the interspecific difference that can be correlated with the biological habits of the two selected models, S. aurita and M. cephalus, known respectively as pelagic and benthopelagic species.
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Gao, Weihua; Kishida, Tomoyuki; Kimura, Keisuke; Kageyama, Michiharu; Sumi, Masaki; Yoshikawa, Yukako; Shibata, Nobuhito; Takada, Kanji
2002-06-01
A sensitive and simultaneous liquid chromatographic-mass spectrometric (LC/MS) method for the determination of current four HIV protease inhibitors (PIs), indinavir (IDV), saquinavir (SQV), nelfinavir (NFV) and amprenavir (APV) in rat plasma and liver dialysate by a microdialysis method was described. An isocratic LC/MS method in combination with atmospheric pressure chemical ionization was developed for the determination of these four PIs in biological samples in the same run. The analytes including an internal standard were extracted from 100 microL of plasma or 150 microL of liver dialysate samples by salting-out with 100 microL of ice-cold 2 M K(3)PO(4) followed by ether extraction. The separation of analytes was carried out on a reversed-phase semi-micro column using 50% of acetonitrile containing 1% acetic acid as mobile phase at a flow rate of 0.2mL/min(-1). The separation was completed within 5 min. Precision, recovery and limits of detection indicated that the method was suitable for the quantitative determination of these PIs in rat plasma or liver dialysate. This simple, sensitive and highly specific LC/MS method is suitable for pharmacokinetic studies and therapeutic drug monitoring in AIDS patients who receive double protease therapy. Copyright 2002 John Wiley & Sons, Ltd.
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Sasaki, Nozomi; Moriwaki, Kenta; Uozumi, Naofumi; Noda, Katsuhisa; Taniguchi, Naoyuki; Kameyama, Akihiko; Narimatsu, Hisashi; Takeishi, Shunsaku; Yamada, Masao; Koyama, Nobuto; Miyoshi, Eiji
2009-12-01
Oligosaccharides serve as markers of the cell surface and have been used as certain kinds of tumor markers. In the present study, we established a simple method for isolating hepatic progenitor cells using a lectin, which recognizes a characteristic oligosaccharide structure. Rat liver epithelial (RLE) cells, which have been established as a hepatic stem-like cell, were used to identify characteristic oligosaccharide structures on hepatic stem cells. As a result from lectin micro array, several types of lectin including E4-PHA were identified to bind RLE cells specifically. Furthermore, lectin blot and lectin flow cytometry analyses showed that binding to E(4)-PHA lectin was significantly increased in RLE cells, compared to hepatocytes, and hepatoma cells. The induction of differentiation into a hepatocyte lineage of RLE cells by treatment with Oncostatin M and dexamethasone resulted in a decrease in E(4)-PHA binding. Using an E(4)-PHA column, we succeeded in isolating hepatic stem cells from LEC (Long-Evans with cinnamon coat color) rat livers with fluminant hepatitis. The characteristics of the established cells were similar to RLE cells and had a potential of proliferating in rat liver. These results suggest that oligosaccharides can serve as a novel marker for the isolation of the hepatic progenitor cells.
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Salisbury, Craig D C; Sweet, Jason C; Munro, Roger
2004-01-01
A liquid chromatographic method for the determination of sulfachloropyridazine, sulfadiazine, sulfadimethoxine, sulfadoxine, sulfaethoxypyridazine, sulfamethazine, sulfaquinoxaline, and sulfathiazole residues in the muscle, liver, and kidney of food animals using sulfapyridine as internal standard is reported. Tissues are extracted using a modified version of AOAC Official Method 983.31 (Sulfonamide Residues in Animal Tissues). The sample extract is reconstituted in pH 3.0 buffer-acetonitrile (60 + 40) and filtered into an autosampler vial. Using a programmable autosampler of a liquid chromatograph, a portion of the sample is derivatized precolumn with fluorescamine. The sulfonamide derivatives are separated by liquid chromatography using a C18 column with a mobile phase of 0.02M phosphoric acid-acetonitrile (60.5 + 39.5) and detected by fluorescence (excitation, 405 nm; emission, 495 nm). The method was applied to swine and cattle muscle, liver, and kidney; sheep and horse muscle and kidney; and chicken muscle and liver. The mean values for samples fortified with sulfonamides at levels between 0.05 and 0.2 microg/g agreed within 96-99% of spiked levels, with coefficients of variation ranging from 4-10%. The limit of detection (LOD) for all sulfonamides was 0.01 microg/g, with the exception of sulfaquinoxaline, for which the LOD was 0.015 microg/g.
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Bertrais, Sandrine; Boursier, Jérôme; Ducancelle, Alexandra; Oberti, Frédéric; Fouchard-Hubert, Isabelle; Moal, Valérie; Calès, Paul
2017-06-01
There is currently no recommended time interval between noninvasive fibrosis measurements for monitoring chronic liver diseases. We determined how long a single liver fibrosis evaluation may accurately predict mortality, and assessed whether combining tests improves prognostic performance. We included 1559 patients with chronic liver disease and available baseline liver stiffness measurement (LSM) by Fibroscan, aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Hepascore, and FibroMeter V2G . Median follow-up was 2.8 years during which 262 (16.8%) patients died, with 115 liver-related deaths. All fibrosis tests were able to predict mortality, although APRI (and FIB-4 for liver-related mortality) showed lower overall discriminative ability than the other tests (differences in Harrell's C-index: P < 0.050). According to time-dependent AUROCs, the time period with optimal predictive performance was 2-3 years in patients with no/mild fibrosis, 1 year in patients with significant fibrosis, and <6 months in cirrhotic patients even in those with a model of end-stage liver disease (MELD) score <15. Patients were then randomly split in training/testing sets. In the training set, blood tests and LSM were independent predictors of all-cause mortality. The best-fit multivariate model included age, sex, LSM, and FibroMeter V2G with C-index = 0.834 (95% confidence interval, 0.803-0.862). The prognostic model for liver-related mortality included the same covariates with C-index = 0.868 (0.831-0.902). In the testing set, the multivariate models had higher prognostic accuracy than FibroMeter V2G or LSM alone for all-cause mortality and FibroMeter V2G alone for liver-related mortality. The prognostic durability of a single baseline fibrosis evaluation depends on the liver fibrosis level. Combining LSM with a blood fibrosis test improves mortality risk assessment. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
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Basic Aspects of Deep Soil Mixing Technology Control
NASA Astrophysics Data System (ADS)
Egorova, Alexandra A.; Rybak, Jarosław; Stefaniuk, Damian; Zajączkowski, Przemysław
2017-10-01
Improving a soil is a process of increasing its physical/mechanical properties without changing its natural structure. Improvement of soil subbase is reached by means of the knitted materials, or other methods when strong connection between soil particles is established. The method of DSM (Deep Soil Mixing) columns has been invented in Japan in 1970s. The main reason of designing cement-soil columns is to improve properties of local soils (such as strength and stiffness) by mixing them with various cementing materials. Cement and calcium are the most commonly used binders. However new research undertaken worldwide proves that apart from these materials, also gypsum or fly ashes can also be successfully implemented. As the Deep Soil Mixing is still being under development, anticipating mechanical properties of columns in particular soils and the usage of cementing materials in formed columns is very difficult and often inappropriate to predict. That is why a research is carried out in order to find out what binders and mixing technology should be used. The paper presents several remarks on the testing procedures related to quality and capacity control of Deep Soil Mixing columns. Soil improvement methods, their advantages and limitations are briefly described. The authors analyse the suitability of selected testing methods on subsequent stages of design and execution of special foundations works. Chosen examples from engineering practice form the basis for recommendations for the control procedures. Presented case studies concerning testing the on capacity field samples and laboratory procedures on various categories of soil-cement samples were picked from R&D and consulting works offered by Wroclaw University of Science and Technology. Special emphasis is paid to climate conditions which may affect the availability of performing and controlling of DSM techniques in polar zones, with a special regard to sample curing.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Stepinski, Dominique C.; Abdul, Momen; Youker, Amanda J.
2016-06-01
Argonne National Laboratory has developed a Mo-recovery and -purification system for the SHINE medical technologies process, which uses a uranyl sulfate solution for the accelerator-driven production of Mo-99. The objective of this effort is to reduce the processing time for the acidification of the Mo-99 product prior to loading onto a concentration column and concentration of the Mo-99 product solution. Two methods were investigated: (1) the replacement of the titania concentration column by an anion-exchange column to decrease processing time and increase the radioiodine-decontamination efficiency and (2) pretreatment of the titania sorbent to improve its effectiveness for the Mo-recovery andmore » -concentration columns. Promising results are reported for both methods.« less
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Analysis of Slab-column Shearwall Structure of 6000 Tons Cold Storage
NASA Astrophysics Data System (ADS)
He, Dongqing; Song, Pengwei; Jie, Pengyu
2018-05-01
Combining with the functional requirements, the site conditions and the 6000 tons load characteristics of cold storage, so determine its structure system for the slab-column-shear wall structure. The paper recommends the design of foundation, the settings of column cap, the arrangement of shear wall, the punching shear of floor slab and the analysis and calculation results of main structure. By addition shear wall in slab-column structure to increase the overall stiffness of structure and improve the seismic performance of structure. Take the detached form between the main structure and the external wall insulation, while set anchorage beam between in the main floor and the ring beam along the axis of the column grid to enhance the overall stability of the external wall insulation.
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Reducing liver transplant length of stay: a Lean Six Sigma approach.
Toledo, Alexander H; Carroll, Tracy; Arnold, Emily; Tulu, Zeynep; Caffey, Tom; Kearns, Lauren E; Gerber, David A
2013-12-01
Organ transplant centers are under increasing scrutiny to maintain outcomes while controlling cost in a challenging population of patients. Throughout health care and transplant specifically, length of stay is used as a benchmark for both quality and resource utilization. To decrease our length of stay for liver transplant by using Lean Six Sigma methods. The Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) method was used to systematically analyze our process from transplant listing to hospital discharge after transplant, identifying many factors affecting length of stay. Adult, single-organ, primary liver transplant recipients between July 2008 and June 2012 were included in the study. Recipients with living donors or fulminant liver failure were excluded. Multiple interventions, including a clinical pathway and enhanced communication, were implemented. Length of stay after liver transplant and readmission after liver transplant.R ESULTS: Median length of stay decreased significantly from 11 days before the intervention to 8 days after the intervention. Readmission rate did not change throughout the study. The improved length of stay was maintained for 24 months after the study. Using a Lean Six Sigma approach, we were able to significantly decrease the length of stay of liver transplant patients. These results brought our center's outcomes in accordance with our goal and industry benchmark of 8 days. Clear expectations, improved teamwork, and a multidisciplinary clinical pathway were key elements in achieving and maintaining these gains.
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Effect of growth hormone on fatty liver in panhypopituitarism
Takano, S.; Kanzaki, S.; Sato, M.; Kubo, T.; Seino, Y.
1997-01-01
Accepted 10 March 1997 A 17 year old boy was admitted because of short stature and hepatomegaly. He was diagnosed with panhypopituitarism and fatty liver. The fatty liver improved, not with hydrocortisone or levothyroxine treatment, but with growth hormone administration. The fatty liver in this patient was attributable to a growth hormone deficient state. PMID:9245856
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Gritti, Fabrice; Gilar, Martin; Jarrell, Joseph A
2016-04-29
A cylindrical vacuum chamber (inner diameter 5 cm) housing a narrow-bore 2.1 mm×100 mm column packed with 1.8 μm HSS-T3 fully porous particles was built in order to isolate thermally the chromatographic column from the external air environment. Consistent with statistical physics and the mean free path of air molecules, the experimental results show that natural air convection and conduction are fully eliminated for housing air pressures smaller than 10(-4) Torr. Heat radiation is minimized by wrapping up the column with low-emissivity aluminum-tape (emissivity coefficient ϵ=0.03 vs. 0.28 for polished stainless steel 316). Overall, the heat flux at the column wall is reduced by 96% with respect to standard still-air ovens. From a practical viewpoint, the efficiency of the column run at a flow rate of 0.6 mL/min at a constant 13,000 psi pressure drop (the viscous heat power is around 9 W/m) is improved by up to 35% irrespective of the analyte retention. Models of heat and mass transfer reveal that (1) the amplitude of the radial temperature gradient is significantly reduced from 0.30 to 0.01 K and (2) the observed improvement in resolution power stems from a more uniform distribution of the flow velocity across the column diameter. The eddy dispersion term in the van Deemter equation is reduced by 0.8±0.1 reduced plate height unit, a significant gain in column performance. Copyright © 2016 Elsevier B.V. All rights reserved.
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Gao, Jin-Hang; Wen, Shi-Lei; Tong, Huan; Wang, Chun-Hui; Yang, Wen-Juan; Tang, Shi-Hang; Yan, Zhao-Ping; Tai, Yang; Ye, Cheng; Liu, Rui; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Tang, Cheng-Wei
2016-06-01
Inflammatory transport through the gut-liver axis may facilitate liver cirrhosis. Cyclooxygenase-2 (COX-2) has been considered as one of the important molecules that regulates intestinal epithelial barrier function. This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α, and IL-6, it significantly enhanced T cell subsets reduced by TAA. As a result, liver fibrosis induced by TAA was significantly alleviated in the celecoxib group. These data indicated that celecoxib improved the integrity of intestinal epithelial barrier, blocked inflammatory transport through the dysfunctional gut-liver axis, and ameliorated the progress of liver cirrhosis. Copyright © 2016 the American Physiological Society.
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Babata, Lucas K. R.; Pedrosa, Maria M. D.; Garcia, Rosângela F.; Peicher, Márcia V.; de Godoi, Vilma Aparecida Ferreira
2014-01-01
Background. As the liver is important for blood glucose regulation, this study aimed at relating liver glucose release stimulated by glucagon and adrenaline to in vivo episodes of hypoglycaemia. Methods. The blood glucose profile during an episode of insulin-induced hypoglycaemia in exercised and nonexercised male Wistar control (GC) and food-restricted (GR, 50%) rats and liver glucose release stimulated by glucagon and adrenaline were investigated. Results. In the GR, the hypoglycaemic episodes showed severe decreases in blood glucose, persistent hypoglycaemia, and less complete glycaemic recovery. An exercise session prior to the episode of hypoglycaemia raised the basal blood glucose, reduced the magnitude of the hypoglycaemia, and improved the recovery of blood glucose. In fed animals of both groups, liver glucose release was activated by glucagon and adrenaline. In fasted GR rats, liver glycogenolysis activated by glucagon was impaired, despite a significant basal glycogenolysis, while an adrenaline-stimulated liver glucose release was recorded. Conclusions. The lack of liver response to glucagon in the GR rats could be partially responsible for the more severe episodes of hypoglycaemia observed in vivo in nonexercised animals. The preserved liver response to adrenaline can partially account for the less severe hypoglycaemia in the food-restricted animals after acute exercise. PMID:24719616
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[Schizophrenia and Liver Transplantation: Case Report].
Diana, Restrepo B; Marle, Duque G; Carlos, Cardeño C
2012-09-01
Liver transplantation is a treatment available for many patients with liver cirrhosis who find in this treatment a way to improve life expectancy and quality of life. Paranoid schizophrenia affects 1% of the general population, produces psychotic symptoms, and runs a chronic course in some cases with significant deterioration in all areas of life. To discuss the case of a patient with liver cirrhosis diagnosed with paranoid schizophrenia during the evaluation protocol for liver transplantation. Case report. We report the case of a 47-year-old woman with liver cirrhosis whose only alternative to improve life expectancy and quality of life was access to liver transplantation. During routine evaluations the liaison psychiatrist observed first-order psychotic symptoms and documented a life story that confirmed the presence of paranoid schizophrenia. Paranoid schizophrenia is a psychiatric disorder common in the general population that can be a part of the medical comorbidities of patients requiring liver transplantation and is not an absolute contraindication to its completion. We are unaware of similar cases of liver transplantation in patients with schizophrenia in our country. We believe this is a big step on the road to overcome the stigma that mental illness imposes on patients. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.
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Hepatitis C and liver transplantation
NASA Astrophysics Data System (ADS)
Brown, Robert S.
2005-08-01
Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.
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Tan, Cher Heng; Venkatesh, Sudhakar Kundapur
2016-09-15
Recent advances in the noninvasive imaging of chronic liver disease have led to improvements in diagnosis, particularly with magnetic resonance imaging (MRI). A comprehensive evaluation of the liver may be performed with the quantification of the degree of hepatic steatosis, liver iron concentration, and liver fibrosis. In addition, MRI of the liver may be used to identify complications of cirrhosis, including portal hypertension, ascites, and the development of hepatocellular carcinoma. In this review article, we discuss the state of the art techniques in liver MRI, namely, magnetic resonance elastography, hepatobiliary phase MRI, and liver fat and iron quantification MRI. The use of these advanced techniques in the management of chronic liver diseases, including nonalcoholic fatty liver disease, will be elaborated.
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Tan, Cher Heng; Venkatesh, Sudhakar Kundapur
2016-01-01
Recent advances in the noninvasive imaging of chronic liver disease have led to improvements in diagnosis, particularly with magnetic resonance imaging (MRI). A comprehensive evaluation of the liver may be performed with the quantification of the degree of hepatic steatosis, liver iron concentration, and liver fibrosis. In addition, MRI of the liver may be used to identify complications of cirrhosis, including portal hypertension, ascites, and the development of hepatocellular carcinoma. In this review article, we discuss the state of the art techniques in liver MRI, namely, magnetic resonance elastography, hepatobiliary phase MRI, and liver fat and iron quantification MRI. The use of these advanced techniques in the management of chronic liver diseases, including non-alcoholic fatty liver disease, will be elaborated. PMID:27563019
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Zhu, Lin; Brown, William C.; Cai, Qing; Krust, Andrée; Chambon, Pierre; McGuinness, Owen P.; Stafford, John M.
2013-01-01
Pathway-selective insulin resistance where insulin fails to suppress hepatic glucose production but promotes liver fat storage may underlie glucose and lipid abnormalities after menopause. We tested the mechanisms by which estrogen treatment may alter the impact of a high-fat diet (HFD) when given at the time of ovariectomy (OVX) in mice. Female C57BL/6J mice underwent sham operation, OVX, or OVX with estradiol (E2) treatment and were fed an HFD. Hyperinsulinemic-euglycemic clamps were used to assess insulin sensitivity, tracer incorporation into hepatic lipids, and liver triglyceride export. OVX mice had increased adiposity that was prevented with E2 at the time of OVX. E2 treatment increased insulin sensitivity with OVX and HFD. In sham and OVX mice, HFD feeding induced fatty liver, and insulin reduced hepatic apoB100 and liver triglyceride export. E2 treatment reduced liver lipid deposition and prevented the decrease in liver triglyceride export during hyperinsulinemia. In mice lacking the liver estrogen receptor α, E2 after OVX limited adiposity but failed to improve insulin sensitivity, to limit liver lipid deposition, and to prevent insulin suppression of liver triglyceride export. In conclusion, estrogen treatment may reverse aspects of pathway-selective insulin resistance by promoting insulin action on glucose metabolism but limiting hepatic lipid deposition. PMID:22966069
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Improvement of Liver Cell Therapy in Rats by Dietary Stearic Acid
Goradel, Nasser Hashemi; Eghbal, Mohammad Ali; Darabi, Masoud; Roshangar, Leila; Asadi, Maryam; Zarghami, Nosratollah; Nouri, Mohammad
2016-01-01
Background: Stearic acid is known as a potent anti-inflammatory lipid. This fatty acid has profound and diverse effects on liver metabolism. The aim of this study was to investigate the effect of stearic acid on markers of hepatocyte transplantation in rats with acetaminophen (APAP)-induced liver damage. Methods: Wistar rats were randomly assigned to 10-day treatment. Stearic acid was administered to the rats with APAP-induced liver damage. The isolated liver cells were infused intraperitoneally into rats. Blood samples were obtained to evaluate the changes in the serum liver enzymes, including activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and the level of serum albumin. To assess the engraftment of infused hepatocytes, rats were euthanized, and the liver DNA was used for PCR using sex-determining region Y (SRY) primers. Results: The levels of AST, ALT and ALP in the serum of rats with APAP-induced liver injury were significantly increased and returned to the levels in control group by day six. The APAP-induced decrease in albumin was significantly improved in rats through cell therapy, when compared with that in the APAP-alone treated rats. SRY PCR analysis showed the presence of the transplanted cells in the liver of transplanted rats. Conclusion: Stearic acid-rich diet in combination with cell therapy accelerates the recovering of hepatic dysfunction in a rat model of liver injury. PMID:27090202
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Belaz, Kátia Roberta A; Pereira-Filho, Edenir Rodrigues; Oliveira, Regina V
2013-08-01
In this work, the development of two multidimensional liquid chromatography methods coupled to a fluorescence detector is described for direct analysis of microsomal fractions obtained from rat livers. The chiral multidimensional method was then applied for the optimization of the in vitro metabolism of albendazole by experimental design. Albendazole was selected as a model drug because of its anthelmintics properties and recent potential for cancer treatment. The development of two fully automated achiral-chiral and chiral-chiral high performance liquid chromatography (HPLC) methods for the determination of albendazole (ABZ) and its metabolites albendazole sulphoxide (ABZ-SO), albendazole sulphone (ABZ-SO2) and albendazole 2-aminosulphone (ABZ-SO2NH2) in microsomal fractions are described. These methods involve the use of a phenyl (RAM-phenyl-BSA) or octyl (RAM-C8-BSA) restricted access media bovine serum albumin column for the sample clean-up, followed by an achiral phenyl column (15.0×0.46cmI.D.) or a chiral amylose tris(3,5-dimethylphenylcarbamate) column (15.0×0.46cmI.D.). The chiral 2D HPLC method was applied to the development of a compromise condition for the in vitro metabolism of ABZ by means of experimental design involving multivariate analysis. Copyright © 2013 Elsevier B.V. All rights reserved.
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Pulsed electric field processing for fruit and vegetables
USDA-ARS?s Scientific Manuscript database
This month’s column reviews the theory and current applications of pulsed electric field (PEF) processing for fruits and vegetables to improve their safety and quality. This month’s column coauthor, Stefan Toepfl, is advanced research manager at the German Institute of Food Technologies and professo...
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David, Stefan; Hamilton, James P
2011-01-01
Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but pre-existing liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. PMID:21874146
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Camus, Christophe; Lavoué, Sylvain; Gacouin, Arnaud; Le Tulzo, Yves; Lorho, Richard; Boudjéma, Karim; Jacquelinet, Christian; Thomas, Rémi
2006-11-01
To assess the usefulness of dialysis with the molecular adsorbent recirculating system (MARS) in patients with acute liver failure who fulfil criteria for liver transplantation. Observational cohort study. ICU at a liver transplantation centre. Twenty-two patients (23 episodes) received MARS dialysis. They were either listed for LT (n=14), delayed (n=1), or not listed (contra-indication, n=7). A total of 56 MARS treatments (median per patient 2; mean duration 7.6+/-2.6h) were performed on haemodialysis. Clinical and biological variables were assessed before and 24[Symbol: see text]h after MARS therapy. The rate of recovery of liver function without transplantation was compared with an expected rate and survival was analysed. Following MARS dialysis, we observed an improvement in the grade of hepatic encephalopathy (P=0.02) and the Glasgow coma score (P=0.02), a decrease in conjugated bilirubin (P=0.05) and INR (P=0.006), and an increase in prothrombin index (P=0.005). Overall, liver function improved in seven patients (32%): four listed patients in whom transplantation could be avoided and three patients among those not listed due to contra-indications. The transplant-free recovery rate in listed patients was 29% (vs. expected 9%, P=0.036). Listed patients (n=14) had a higher 30-day survival rate [86% (12/14) vs 38% (3/8), P=0.05] and a higher long-term survival rate (P=0.02). A statistically significant improvement of liver function was observed after MARS therapy. Transplant-free recovery was more frequent than expected. The apparent benefit of MARS dialysis to treat acute liver failure needs to be confirmed by a controlled study.
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Pandey, Anuradha; Raj, Priyank; Goru, Santosh Kumar; Kadakol, Almesh; Malek, Vajir; Sharma, Nisha; Gaikwad, Anil Bhanudas
2017-08-01
Non-alcoholic fatty liver disease (NAFLD), a chronic metabolic disorder is associated with oxidative stress, inflammation and fibrotic cascades. In this study, we aimed to examine the effects of Esculetin, a well-known anti-oxidant on TGF-β1 mediated liver fibrosis and FoxO1 activity. A non-genetic murine model for NAFLD was developed by chronic high fat diet (HFD) (58% calories from fats) feeding in Wistar rats. The plasma biochemical parameters, liver function tests, oxidative stress, and histopathological alterations were assessed. The alterations in extracellular matrix (ECM) deposition and FoxO1 activity were assessed by immunohistochemistry. The aberrations in plasma parameters, liver functioning, morphometric and microscopic changes in liver structure of HFD fed rats were significantly improved by treatment with Esculetin. Liver fibrosis, identified in the form of collagen deposition and expression of fibrotic proteins like TGF-β1 and fibronectin was also markedly controlled by Esculetin. The expression of phospho-FoxO1 was found to be reduced in HFD fed rats' liver, showing an increase in activation of FoxO1 under insulin resistant and hyperglycemic states. Esculetin treatment could improve phospho-FoxO1 expression, thus showing its ability to act on Akt/PI3K/FoxO1 pathway. As per the previous studies, a potential therapy for NAFLD may be the one with multi-faceted actions on insulin resistance, oxidative stress, inflammation and fibrosis. This study demonstrates the efficiency of Esculetin in improving liver fibrosis in HFD induced NAFLD. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
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Khalesi, Saman; Johnson, David Wayne; Campbell, Katrin; Williams, Susan; Fenning, Andrew; Saluja, Sonia; Irwin, Christopher
2017-11-08
The gut-liver interaction suggests that modification of gut bacterial flora using probiotics and synbiotics may improve liver function. This systematic review and meta-analysis aimed to clarify the effect of probiotics and synbiotics consumption on the serum concentration of liver function enzymes. PubMed (MEDLINE), Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library (Central) were searched from 1980 to August 2017 for studies where adults consumed probiotics and/or synbiotics in controlled trials and changes in liver function enzymes were examined. A total of 17 studies (19 trials) were included in the meta-analysis. Random effects meta-analyses were applied. Probiotics and synbiotics significantly reduced serum alanine aminotransferase [- 8.05 IU/L, 95% confidence interval (CI) - 13.07 to - 3.04; p = 0.002]; aspartate aminotransferase (- 7.79 IU/L, 95% CI: - 13.93 to - 1.65; p = 0.02) and gamma-glutamyl transpeptidase (- 8.40 IU/L, 95% CI - 12.61 to - 4.20; p < 0.001). Changes in the serum concentration of alkaline phosphatase and albumin did not reach a statistically significant level. Changes to bilirubin levels were in favour of the control group (0.95 μmol/L, 95% CI 0.48-1.42; p < 0.001). Subgroup analysis suggested the existence of liver disease at baseline, synbiotics supplementation and duration of supplementation ≥ 8 weeks resulted in more pronounced improvement in liver function enzymes than their counterparts. Probiotics and synbiotics may be suggested as supplements to improve serum concentration of liver enzymes, especially when synbiotics administered for a period ≥ 8 weeks and in individuals with liver disease.
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El Baz, Hanan; Demerdash, Zeinab; Kamel, Manal; Atta, Shimaa; Salah, Faten; Hassan, Salwa; Hammam, Olfat; Khalil, Heba; Meshaal, Safa; Raafat, Inas
2018-02-01
Liver transplant is the cornerstone line of treatment for chronic liver diseases; however, the long list of complications and obstacles stand against this operation. Searching for new modalities for treatment of chronic liver illness is a must. In the present research, we aimed to compare the effects of transplant of undifferentiated human mesenchymal stem cells, in vitro differentiated mesenchymal stem cells, and adult hepatocytes in an experimental model of chronic liver failure. Undifferentiated human cord blood mesenchymal stem cells were isolated, pro-pagated, and characterized by morphology, gene expression analysis, and flow cytometry of surface markers and in vitro differentiated into hepatocyte-like cells. Rat hepatocytes were isolated by double perfusion technique. An animal model of chronic liver failure was developed, and undifferentiated human cord blood mesenchymal stem cells, in vitro hepato-genically differentiated mesenchymal stem cells, or freshly isolated rat hepatocytes were transplanted into a CCL4 cirrhotic experimental model. Animals were killed 3 months after transplant, and liver functions and histopathology were assessed. Compared with the cirrhotic control group, the 3 cell-treated groups showed improved alanine aminotransferase, aspartate aminotransferase, albumin, and bilirubin levels, with best results shown in the hepatocyte-treated group. Histopathologic examination of the treated groups showed improved fibrosis, with best results obtained in the undifferentiated mesenchymal stem cell-treated group. Both adult hepatocytes and cord blood mesenchymal stem cells proved to be promising candidates for cell-based therapy in liver regeneration on an experimental level. Improved liver function was evident in the hepatocyte-treated group, and fibrosis control was more evident in the undifferentiated mesenchymal stem cell-treated group.
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Chen, H-L; Tung, Y-T; Tsai, C-L; Lai, C-W; Lai, Z-L; Tsai, H-C; Lin, Y-L; Wang, C-H; Chen, C-M
2014-09-01
Fatty liver disease is commonly associated with obesity, insulin resistance and diabetes. Severe fatty liver is sometimes accompanied by steatohepatitis and may lead to the development of hepatocellular carcinoma. At present, there is no effective treatment for non-alcoholic fatty liver disease (NAFLD); thus, recent investigations have focused on developing effective therapeutics to treat this condition. This study aimed to evaluate the effects of kefir on the hepatic lipid metabolism of ob/ob mice, which are commonly used to model fatty liver disease. In this study, we used leptin receptor-deficient ob/ob mice as an animal disease model of NAFLD. Six-week-old ob/ob mice were orally administered the dairy product kefir (140 mg kg(-1) of body weight (BW) per day) for 4 weeks. The data demonstrated that kefir improved fatty liver syndrome on BW, energy expenditure and basal metabolic rate by inhibiting serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities (P<0.05) and by decreasing the triglyceride (TG) and total cholesterol (TC) contents of the liver (P<0.05). Oral kefir administration also significantly reduced the macrovesicular fat quantity in liver tissue. In addition, kefir markedly decreased the expression of the genes sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (P<0.05) but not the expression of peroxisome proliferator-activated receptor α (PPARα) or hepatic carnitine palmitoyltransferase-1α (CPT1α) in the livers of ob/ob mice. On the basis of these results, we conclude that kefir improves NAFLD on BW, energy expenditure and basal metabolic rate by inhibiting the lipogenesis pathway and that kefir may have the potential for clinical application to the prevention or treatment of NAFLD.
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D'Avola, Delia; Fernández-Ruiz, Verónica; Carmona-Torre, Francisco; Méndez, Miriam; Pérez-Calvo, Javier; Prósper, Felipe; Andreu, Enrique; Herrero, José Ignacio; Iñarrairaegui, Mercedes; Fuertes, Carmen; Bilbao, José Ignacio; Sangro, Bruno; Prieto, Jesús; Quiroga, Jorge
2017-10-01
The aim of this nonrandomized, open label, phase 1 clinical trial was to evaluate the safety and the feasibility of the treatment with autologous bone marrow-derived endothelial progenitor cells (EPC) in decompensated liver cirrhosis. In addition, the changes in liver function and hepatic venous pressure gradient (HVPG) and their relation with the characteristics of the cellular product were analyzed. Twelve patients with Child-Pugh ≥8 liver cirrhosis underwent bone marrow harvest for ex vivo differentiation of EPC. The final product was administered through the hepatic artery in a single administration. Patients underwent clinical and radiologic follow-up for 12 months. The phenotype and the ability to produce cytokines and growth factors of the final cellular suspension were analyzed. Eleven patients were treated (feasibility 91%). No treatment-related severe adverse events were observed as consequence of any study procedure or treatment. Model for end-stage liver disease score improved significantly (P 0.042) in the first 90 days after cells administration and 5 of the 9 patients alive at 90 days showed a decreased of HVPG. There was a direct correlation between the expression of acetylated-low density lipoprotein and von Willebrand factor in the cellular product and the improvement in liver function and HVPG. The treatment with EPCs in patients with decompensated liver cirrhosis is safe and feasible and might have therapeutic potential. Patients receiving a higher amount of functionally active EPC showed an improvement of liver function and portal hypertension suggesting that the potential usefulness of these cells for the treatment of liver cirrhosis deserves further evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.
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Bridges, John Fp; Gallego, Gisselle; Blauvelt, Barri M
2011-07-28
Liver cancer is the fifth most common cancer in men and the seventh for women. Usually because of late diagnosis, the prognosis for liver cancer remains poor, resulting in liver cancer being the third most common cause of death from cancer. While some countries have treatment guidelines, little is known or understood about the strategies needed for liver cancer control internationally. To explore leading liver cancer clinician's perceptions of the current public policy needs to control liver cancer internationally. Key informant interviews were conducted with a range of liver cancer clinicians involved in policy in eleven countries. Interviews were digitally recorded, transcribed verbatim, translated (where necessary), de-identified and analyzed by two researchers using a constant comparative method. Twenty in-depth semi-structured interviews were conducted in: Australia, China, France, Germany, Italy, Japan, Spain, South Korea, Taiwan, Turkey and the United States. Nine themes were identified and cluster into three groups: 1) Promoting prevention via early risk assessment, focusing on viral hepatitis and other lifestyle factors; 2) Increasing political, public and medical community awareness; and 3) Improving funding for screening, liver cancer surveillance and treatment. This study is an important step towards developing an evidence-based approach to assessing preparedness for implementing comprehensive liver cancer control strategies. Evaluation mechanisms to assess countries' performance on the needs described are needed. Future research will concentrate of understanding how these needs vary across countries and the optimal strategies to improve the diagnosis and prognosis of patients with liver cancer internationally.
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Zhu, Xian-Sheng; Wang, Sha-Sha; Cheng, Qi; Ye, Chuang-Wen; Huo, Feng; Li, Peng
2016-02-01
Extracorporeal membrane oxygenation (ECMO) has been used to support brain-dead donors for liver procurement. This study investigated the potential role of ultrasonographic monitoring of hepatic perfusion as an aid to improve the viability of liver transplants obtained from brain-dead donors who are supported on ECMO. A total of 40 brain-dead patients maintained on ECMO served as the study population. Hepatic blood flow was monitored using ultrasonography, and perioperative optimal perfusion was maintained by calibrating ECMO. Liver function tests were performed to assess the viability of the graft. The hepatic arterial blood flow was well maintained with no significant changes observed before and after ECMO (206 ± 32 versus 241 ± 45 mL/minute; P = 0.06). Similarly, the portal venous blood flow was also maintained throughout (451 ± 65 versus 482 ± 77 mL/minute; P = 0.09). No significant change in levels of total bilirubin, alanine transaminase, and lactic acid were reported during ECMO (P = 0.17, P = 0.08, and P = 0.09, respectively). Before the liver is procured, ultrasonographic monitoring of hepatic blood flow could be a valuable aid to improve the viability of a liver transplant by allowing for real-time calibration of ECMO perfusion in brain-dead liver donors. In our study, ultrasonographic monitoring helped prevent warm ischemic injury to the liver graft by avoiding both overperfusion and underperfusion of the liver. © 2015 American Association for the Study of Liver Diseases.
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Entrapment of hepatocyte spheroids in a hollow fiber bioreactor as a potential bioartificial liver.
Wu, F J; Peshwa, M V; Cerra, F B; Hu, W S
1995-01-01
A bioartificial liver (BAL) employing xenogeneic hepatocytes has been developed as a potential interim support for patients in hepatic failure. For application in human therapy, the BAL requires a substantial increase in liver-specific functions. Cultivation of hepatocytes as spheroids leads to enhanced liver specific functions. We explored the possibility of entrapping spheroids into the BAL in order to improve device performance. Rat hepatocyte spheroids were entrapped in collagen gel within the lumen fibers of the BAL. The morphology and ultrastructure of collagen-entrapped spheroids resembled those of suspended spheroids formed on petri dishes. Albumin synthesis and P-450 enzyme activity were measured as markers of liver specific functions of spheroids entrapped in the BAL. At least a 4-fold improvement in these functions was observed compared to BAL devices entrapped with dispersed hepatocytes in collagen gels.
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[Complex program for the recovery of the vertebral column motor function].
Kukareko, V P; Furmanov, A G
2011-01-01
This paper addresses the problems pertinent to the improvement of the efficacy of restoration of the vertebral column motor function based on the implementation of a comprehensive therapeutic program including massage, thermal procedures, and physical exercises. The program was realized in three phases, viz. preparatory, basic, and consolidating. The results of integral estimation of the whole body and vertebral column condition were taken into consideration. The experiment lasted 6 months and confirmed high efficiency of the comprehensive program.
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Yang, Yang; Zhang, Yongmin; Wei, Chong; Li, Jing; Sun, Wenji
2018-09-01
Silver ion chromatography, utilizing columns packed with silver ions bonded to silica gel, has proved to be an invaluable technique for the analysis of some positional isomers. In this work, silver ion chromatography by combination with online heart-cutting LC-LC technique for the preparative separation of two sesquiterpenes positional isomers from a natural product was investigated. On the basis of the evaluation that silver ion content impacts on the separation, the laboratory-made silver ion columns, utilizing silica gel impregnated with 15% silver nitrate as column packing materials, were used for peak resolution improvement of these two isomers and the preparative separation of them in heart-cutting LC-LC. The relationship among the maximal sample load, flow rate and peak resolution in the silver ion column were optimized, and the performance of the silver ion column was compared with conventional C 18 column and silica gel column. Based on the developed chromatographic conditions, online heart-cutting LC-LC chromatographic separation system in combination with a silica gel column and a silver ion column that was applied to preparative separation of these two isomers from a traditional Chinese medicine, Inula racemosa Hook.f., was established. The results showed that the online heart-cutting LC-LC technique by combination of a silica gel column and a silver ion column for the preparative separation of these two positional isomers from this natural plant was superior to the preparative separation performed on a single-column system with C 18 column or silica gel column. Copyright © 2018 Elsevier B.V. All rights reserved.
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Barakat, Omar; Skolkin, Mark D; Toombs, Barry D; Fischer, John H; Ozaki, Claire F; Wood, R Patrick
2008-01-01
Background Morbid obesity strongly predicts morbidity and mortality in surgical patients. However, obesity's impact on outcome after major liver resection is unknown. Case presentation We describe the management of a large hepatocellular carcinoma in a morbidly obese patient (body mass index >50 kg/m2). Additionally, we propose a strategy for reducing postoperative complications and improving outcome after major liver resection. Conclusion To our knowledge, this is the first report of major liver resection in a morbidly obese patient with hepatocellular carcinoma. The approach we used could make this operation nearly as safe in obese patients as it is in their normal-weight counterparts. PMID:18783621
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Direct peritoneal resuscitation improves obesity-induced hepatic dysfunction after trauma.
Matheson, Paul J; Franklin, Glen A; Hurt, Ryan T; Downard, Cynthia D; Smith, Jason W; Garrison, Richard N
2012-04-01
The metabolic syndrome and associated fatty liver disease are thought to contribute to poor outcomes in trauma patients. Experimentally, obesity compromises liver blood flow. We sought to correlate the effect of obesity, injury severity, and liver dysfunction with trauma outcomes. We hypothesized that obesity-related liver dysfunction could be mitigated with the novel technique of adjunctive direct peritoneal resuscitation (DPR). This study has clinical and experimental arms. The clinical study was a case-controlled retrospective analysis of ICU trauma patients (n = 72 obese, n = 187 nonobese). The experimental study was a hemorrhagic shock model in obese rats to assess the effect of DPR on liver blood flow, liver function, and inflammatory mediators. In trauma patients, univariate and multivariate analyses demonstrated increasing mortality (p < 0.05), septic complications (p < 0.05), liver dysfunction (p < 0.001), and renal impairment (p < 0.05) with increasing body mass index and injury severity score. Obesity in rats impairs liver blood flow, liver function, renal function, and inflammation (interleukin [IL]-1β, IL-6, high mobility group protein B1[HMGB-1]). The addition of DPR to shock resuscitation restores liver blood flow, improves organ function, and reverses the systemic proinflammatory response. Our clinical review substantiates that obesity worsens trauma outcomes regardless of injury severity. Obesity-related liver and renal dysfunction is aggravated by injury severity. In an obese rat model of resuscitated hemorrhagic shock, the addition of DPR abrogates trauma-induced liver, renal, and inflammatory responses. We conclude that the addition of DPR to the clinical resuscitation regimen will benefit the obese trauma patient. Published by Elsevier Inc.
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Asgharzadeh, Fereshteh; Bargi, Rahimeh; Beheshti, Farimah; Hosseini, Mahmoud; Farzadnia, Mehdi; Khazaei, Majid
2017-01-01
Liver fibrosis is the primary sign of chronic liver injury induced by various causes. Thymoquinone (TQ) is the major ingredient of Nigella sativa with several beneficial effects on the body. In the present study, we aimed to investigate the effect of TQ on liver fibrosis in a lipopolysaccharide (LPS)-induced inflammation in male rats. Fifty male Wistar rats were randomly divided into five groups (n=10 in each group) as follow: (1) control; (2) LPS (1 mg/kg/day; i.p); (3) LPS+TQ 2 mg/kg/day (i.p) (LPs+TQ2); (4) LPS+TQ 5 mg/kg/day (LPS+TQ5); (5) LPS+ TQ 10 mg/kg/day (LPS+ TQ10). After three weeks, blood samples were taken for evaluation of liver function tests. Then, the livers were harvested for histological evaluation of fibrosis and collagen content and measurement of oxidative stress markers including malondialdehyde (MDA), total thiol groups, superoxide dismutase (SOD) and catalase activity in tissue homogenates. LPS group showed higher levels of fibrosis and collagen content stained by Masson's trichrome in liver tissue with impaired liver function test and increased oxidative stress markers (p<0.05). Treatment by TQ restored liver fibrosis, improved liver function tests and increased the levels of anti-oxidative enzymes (SOD and catalase), while reduced MDA concentration (p<0.05). Treatment by TQ restores inflammation-induced liver fibrosis possibly through affecting oxidative stress status. It seems that administration of TQ can be considered as a part of liver fibrosis management.
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Lin, Chih-Wen; Zhang, Hao; Li, Min; Xiong, Xiwen; Chen, Xi; Chen, Xiaoyun; Dong, Xiaocheng C; Yin, Xiao-Ming
2013-05-01
Pharmacological approaches can potentially improve fatty liver condition in alcoholic and non-alcoholic fatty liver diseases. The salutary effects of reducing lipid synthesis or promoting lipid oxidation have been well reported, but the benefits of increasing lipid degradation have yet to be well explored. Macroautophagy is a cellular degradation process that can remove subcellular organelles including lipid droplets. We thus investigated whether pharmacological modulation of macroautophagy could be an effective approach to alleviate fatty liver condition and liver injury. C57BL/6 mice were given ethanol via intraperitoneal injection (acute) or by a 4-week oral feeding regime (chronic), or high fat diet for 12 weeks. An autophagy enhancer, carbamazepine or rapamycin, or an autophagy inhibitor, chloroquine, was given before sacrifice. Activation of autophagy, level of hepatic steatosis, and blood levels of triglycerides, liver enzyme, glucose and insulin were measured. In both acute and chronic ethanol condition, macroautophagy was activated. Carbamazepine, as well as rapamycin, enhanced ethanol-induced macroautophagy in hepatocytes in vitro and in vivo. Hepatic steatosis and liver injury were exacerbated by chloroquine, but alleviated by carbamazepine. The protective effects of carbamazepine and rapamycin in reducing steatosis and in improving insulin sensitivity were also demonstrated in high fat diet-induced non-alcoholic fatty liver condition. These findings indicate that pharmacological modulation of macroautophagy in the liver can be an effective strategy for reducing fatty liver condition and liver injury. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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Liver transplant in ethylmalonic encephalopathy: a new treatment for an otherwise fatal disease.
Dionisi-Vici, Carlo; Diodato, Daria; Torre, Giuliano; Picca, Stefano; Pariante, Rosanna; Giuseppe Picardo, Sergio; Di Meo, Ivano; Rizzo, Cristiano; Tiranti, Valeria; Zeviani, Massimo; De Ville De Goyet, Jean
2016-04-01
Ethylmalonic encephalopathy is a fatal, rapidly progressive mitochondrial disorder caused by ETHE1 mutations, whose peculiar clinical and biochemical features are due to the toxic accumulation of hydrogen sulphide and of its metabolites, including thiosulphate. In mice with ethylmalonic encephalopathy, liver-targeted adeno-associated virus-mediated ETHE1 gene transfer dramatically improved both clinical course and metabolic abnormalities. Reasoning that the same achievement could be accomplished by liver transplantation, we performed living donor-liver transplantation in an infant with ethylmalonic encephalopathy. Unlike the invariably progressive deterioration of the disease, 8 months after liver transplantation, we observed striking neurological improvement with remarkable achievements in psychomotor development, along with dramatic reversion of biochemical abnormalities. These results clearly indicate that liver transplantation is a viable therapeutic option for ETHE1 disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Comparison of two different modes of molecular adsorbent recycling systems for liver dialysis.
Soo, Euan; Sanders, Anja; Heckert, Karlheinz; Vinke, Tobias; Schaefer, Franz; Schmitt, Claus Peter
2016-11-01
In children acute liver failure is a rare but life-threatening condition from which two-thirds do not recover with supportive therapy. Treatment is limited by the availability of liver transplants. Molecular adsorbent recirculating system (MARS) dialysis is a bridge to transplantation that enhances the chances of survival during the waiting period for a transplant, although it cannot improve survival. Open albumin dialysis (OPAL) is a new mode of albumin dialysis developed to further improve dialysis efficiency. We report a paediatric case of acute-on-chronic liver failure and compare the two modes of albumin dialysis, namely, the MARS and OPAL, used to treat this patient's cholestatic pruritus. Removal of total and direct bilirubin, ammonia and bile acids were measured by serial blood tests. There was an increased removal of bile acids with the OPAL mode, whereas the removal of total and direct bilirubin and ammonia was similar in both modes. The patient reported better improvement in pruritus following OPAL compared to dialysis with the MARS. OPAL may offer a better solution than the MARS in the treatment of refractory pruritus in liver failure.
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Peripheral nerve field stimulation in chronic abdominal pain.
Paicius, Richard M; Bernstein, Clifford A; Lempert-Cohen, Cheryl
2006-07-01
Spinal Cord Stimulation (SCS) has become an accepted therapeutic modality for the treatment of intractable pain syndromes, primarily used today in the settings of failed back surgery syndrome, neuropathic back and limb pain. The use of spinal cord stimulators for peripheral nerve field electrostimulation is becoming increasingly recognized as a safe, effective alternative for chronic pain conditions that are refractory to medical management and do not respond to traditional dorsal column stimulation. Advances in technology have allowed for minimally invasive percutaneous placement of multipolar leads with complex programmable systems to provide patient- controlled relief of pain in precisely targeted regions. With these improvements in hardware, the use of Peripheral Nerve Field Stimulation (PNFS) appears to have an untapped potential for providing patients with pain relief for a wider range of underlying conditions than was previously believed possible. We present three cases, each with a different etiology of chronic abdominal pain: one with inguinal neuralgia, one with chronic pancreatitis, and one with pain following liver transplant. Each patient was refractory to conventional medical approaches. For all three patients, PNFS provided significant relief from pain, enabling patients to decrease or discontinue their opioid medications and to enjoy significant improvement in their quality of life. We conclude that PNFS is a safe, effective and minimally invasive treatment that may be used successfully for a wide variety of indications including chronic abdominal pain.
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Adjunctive traditional Chinese medicine therapy improves survival of liver cancer patients.
Liao, Yueh-Hsiang; Lin, Cheng-Chieh; Lai, Hsueh-Chou; Chiang, Jen-Huai; Lin, Jaung-Geng; Li, Tsai-Chung
2015-12-01
Traditional Chinese medicine (TCM) is an alternative treatment for cancer with its effect by stimulating host immune response for cytotoxic activity against liver cancer. No studies evaluated TCM treatment on survival of liver cancer patients. This study determined whether the combination of TCM and conventional cancer treatment affects the survival of liver cancer patients. A retrospective cohort study was conducted in 127 237 newly diagnosed liver cancer patients from 2000 to 2009 in the National Health Insurance Program database. Among these patients, 30 992 (24.36%) used TCM for liver cancer care. All patients were followed up until 2011. The mean follow-up was 5.67 years (SD 1.47) for TCM users and 5.49 years (SD 3.64) for non-TCM users. Compared with patients without TCM use, patients with TCM use were significantly associated with a decreased risk of death [hazard ratio (HR) = 0.65, 95% confidence interval (CI) = 0.64-0.66] with multivariate adjustment. A similar significant protective effect of TCM use across various subgroups of chronic liver diseases was also observed. Jia Wei Xiao Yao San (HR = 0.89, 95% CI = 0.81-0.96) and Chai Hu Shu Gan Tang (HR = 0.86, 95% CI = 0.78-0.95) were the most effective TCM agents that improved survival. This cohort study provided information that adjunctive therapy with TCM may improve the survival in liver cancer patients. Further studies are needed to confirm the potential role of TCM in HCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Characterisation of RPLC columns packed with porous sub-2 microm particles.
Petersson, Patrik; Euerby, Melvin R
2007-08-01
Eight commercially available sub-2 microm octadecyl silane columns (C18 columns) have been characterised by the Tanaka protocol. The columns can be grouped into two groups that display large differences in selectivity and peak shape due to differences in hydrophobicity, degree of surface coverage and silanol activity. Measurements of particle size distributions were made using automated microscopy and electrical sensing zone measurements. Only a weak correlation could be found between efficiency and particle size. Large differences in column backpressure were observed. These differences are not related to particle size distribution. A more likely explanation is differences in packing density. In order to take full advantage of 100-150 mm columns packed with sub-2 microm particles, it is often necessary to employ not only an elevated pressure but also an elevated temperature. A comparison between columns packed with sub-2, 3 and 5 microm versions of the same packing indicates potential method transferability problems for several of the columns due to selectivity differences. Currently, the best alternative for fast high-resolution LC is the use of sub-2 microm particles in combination with elevated pressure and temperature. However, as shown in this study additional efforts are needed to improve transferability as well as column performance.
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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.
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Investigation of Gas Holdup in a Vibrating Bubble Column
NASA Astrophysics Data System (ADS)
Mohagheghian, Shahrouz; Elbing, Brian
2015-11-01
Synthetic fuels are part of the solution to the world's energy crisis and climate change. Liquefaction of coal during the Fischer-Tropsch process in a bubble column reactor (BCR) is a key step in production of synthetic fuel. It is known from the 1960's that vibration improves mass transfer in bubble column. The current study experimentally investigates the effect that vibration frequency and amplitude has on gas holdup and bubble size distribution within a bubble column. Air (disperse phase) was injected into water (continuous phase) through a needle shape injector near the bottom of the column, which was open to atmospheric pressure. The air volumetric flow rate was measured with a variable area flow meter. Vibrations were generated with a custom-made shaker table, which oscillated the entire column with independently specified amplitude and frequency (0-30 Hz). Geometric dependencies can be investigated with four cast acrylic columns with aspect ratios ranging from 4.36 to 24, and injector needle internal diameters between 0.32 and 1.59 mm. The gas holdup within the column was measured with a flow visualization system, and a PIV system was used to measure phase velocities. Preliminary results for the non-vibrating and vibrating cases will be presented.
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Hydrodynamic flow in capillary-channel fiber columns for liquid chromatography.
Stanelle, Rayman D; Sander, Lane C; Marcus, R Kenneth
2005-12-23
The flow characteristics of capillary-channel polymer (C-CP) fiber liquid chromatographic (LC) columns have been investigated. The C-CP fibers are manufactured with eight longitudinal grooves (capillary channels) extending the length of the fibers. Three C-CP fiber examples were studied, with fiber dimensions ranging from approximately 35 microm to 65 microm, and capillary-channel dimensions ranging from approximately 6 microm to 35 microm. The influence of fiber packing density and column inner diameter on peak asymmetry, peak width, and run-to-run reproducibility have been studied for stainless steel LC columns packed with polyester (PET) and polypropylene (PP) C-CP fibers. The van Deemter A-term was evaluated as a function of fiber packing density (approximately 0.3 g/cm(3)-0.75 g/cm(3)) for columns of 4.6 mm inner diameter (i.d.) and at constant packing densities for 1.5 mm, 3.2 mm, 4.6 mm, and 7.7 mm i.d. columns. Although column diameter had little influence on the eluting peak widths, peak asymmetry increased with increasing column diameter. The A-terms for the C-CP fiber packed columns are somewhat larger than current commercial, microparticulate-packed columns, and means for improvement are discussed. Applications in the area of protein (macromolecule) separations appear the most promising at this stage of the system development.
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NASA Astrophysics Data System (ADS)
Darezereshki, E.; Schaffie, M.; Lotfalian, M.; Seiedbaghery, S. A.; Ranjbar, M.
2011-04-01
Bioleaching was examined for copper extraction from a low grade ore using mesophilic and moderate thermophilic bacteria. Five equal size columns were used for the leaching of the ore. Sulfuric acid solution with a flow rate of 3.12 L·m-2·h-1 and pH 1.5 passed through each column continuously for 90 d. In the first and the second column, bioleaching was performed without agglomeration of the ore and on the agglomerated ore, respectively. 28wt% of the copper was extracted in the first column after 40 d, while this figure was 38wt% in the second column. After 90 d, however, the overall extractions were almost the same for both of them. Bioleaching with mesophilic bacteria was performed in the third column without agglomeration of the ore and in the fourth column on the agglomerated ore. After 40 d, copper extractions in the third and the fourth columns were 62wt% and 70wt%, respectively. Copper extractions were 75wt% for both the columns after 90 d. For the last column, bioleaching was performed with moderate thermophilic bacteria and agglomerated ore. Copper extractions were 80wt% and 85wt% after 40 and 90 d, respectively. It was concluded that crushing and agglomeration of the ore using bacteria could enhance the copper extraction considerably.
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Zhan, Xi; Zhang, Zhiqing; Huang, Hanfei; Zhang, Yujun; Zeng, Zhong
2018-06-01
To investigate the effect of heme oxygenase-1 (HO-1) on the ischemic reperfusion injury (IRI) of bile duct in rat models after liver transplantation. 320 SD rats were equally and randomly divided into 5 groups, which were group A receiving injection of 3×10 8 /pfu/ml adenovirus (adv), group B with donor receiving Adv-HO-1 and recipient receiving Adv-HO-1-siRNA, group C with donor and recipient both receiving Adv-HO-1, group D with donor receiving Adv-HO-1-siRNA and recipient receiving Adv-HO-1, and group E with donor and recipient both receiving Adv-HO-1-siRNA at 24h before liver transplantation. Donor liver was stored in UW liquid at 4°C followed by measuring HO-1 level by western blot before transplantation. On d1, d3, d7 and d14, serum and liver was isolated for analysis of liver function, inflammatory cell infiltration by H&E staining, ultrastructure of liver by transmission electron microscopy as well as the expression of HO-1, Bsep, Mrp2 and Ntcp by western blot. Compared with group D and E, group B and C displayed improved liver function as demonstrated by lower level of ALT, AST, LDH, TBIL, ALP and GGT, increased secretion of TBA and PL as well as expression of transporter proteins (Bsep, Mrp2 and Ntcp), reduced inflammatory cells infiltration and liver injury. Our study demonstrated that overexpression of HO-1 in donor liver can ameliorate the damage to bile duct and liver, and improved liver function, suggesting HO-1 might be a new therapeutic target in the treatment of IRI after liver transplantation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Yamamoto, Naoki; Okano, Keiichi; Oshima, Minoru; Akamoto, Shitaro; Fujiwara, Masao; Tani, Joji; Miyoshi, Hisaaki; Yoneyama, Hirohito; Masaki, Tsutomu; Suzuki, Yasuyuki
2015-12-01
We aimed to assess the short-term outcomes of laparoscopic splenectomy (LS) and liver function at 1 year after splenectomy in the patients with liver cirrhosis. Forty-five patients with liver cirrhosis and hypersplenism underwent LS. We reviewed electronic medical records regarding the liver functional reserve, the etiology of liver cirrhosis, and the presence of hepatocellular carcinoma and esophago-gastric varices. Prospectively collected data of perioperative variables, postoperative complications, and long-term liver function were analyzed. Forty-five patients had a chronic liver disease classified into Child-Pugh classes (A/B/C: 23/20/2). The etiologies of disease were hepatitis C virus infection in 34 patients, hepatitis B virus infection in 4, and others in 7. Fourteen patients underwent procedures in addition to LS, including hepatectomy (n = 7) and devascularization for esophagogastric varices (n = 8). Postoperative complications occurred in 11 patients (24%). Neither postoperative liver failure nor in-hospital mortality occurred. White blood cell and platelet counts determined 7 days, 1 month, and 1 year after LS doubled or increased more than twice compared with the preoperative values (P < .001). One year after LS, patients who had been classified preoperatively into Child-Pugh class B had decreased total serum bilirubin levels (P = .03), and increased prothrombin activity (P = 003) and decreased Child-Pugh scores (P = .001). The Child-Pugh classifications improved in 14 of 18 patients (78%) who had Child-Pugh class B preoperatively. LS is a safe and feasible procedure for hypersplenism in patients with liver cirrhosis. In addition, LS most likely ameliorates liver function at 1 year after LS in patients with Child-Pugh class B liver cirrhosis. Copyright © 2015 Elsevier Inc. All rights reserved.
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Philips, Cyriac Abby; Kumar, Lijesh; Augustine, Philip
2017-09-01
Large spontaneous portosystemic shunts (SPSS) are seen in a subset of patients with liver disease and medically refractory recurrent/persistent hepatic encephalopathy (MRHE). Shunt occlusion has been shown to improve clinical outcomes. We retrospectively analyzed patient characteristics, SPSS attributes, procedural features, baseline clinical and investigational parameters, neurological outcomes, adverse effects (procedure and portal hypertension related), and risk factors predicting outcomes in liver disease patients undergoing shunt occlusion procedure for MRHE. Between October 2016 and July 2017, 21 patients (Child-Pugh score, CTP 6 to 13) with mean model of end-stage liver disease (MELD) and MELD-sodium scores 15.7 and 19.3 respectively with MRHE [3-cirrhotic Parkinsonism (CP)] were diagnosed to have single or multiple large SPSSs. A total of 29 shunts were occluded (1 surgical, 20 non-surgical). Recurrent and persistent HE and CP markedly improved in the short (n=20, 1 to 3 months), intermediate (n=12, 3 to 6 months), and long (n=7, 6 to 9 months) follow up. None had spontaneous or persistent HE at a median follow up 105 (30 to 329) days (p<0.05). Motor, speech, sleep abnormalities, daily activities of living, and liver disease severity scores improved significantly on follow up. Baseline arterial ammonia showed a statistically significant reduction in all time periods of follow up after shunt occlusion (p<0.05). CTP >11 predicted mortality post shunt occlusion (p=0.04). Embolization of large SPSS in liver disease patients with MRHE and modestly preserved liver function is safe and efficacious and associated with improved quality of life and can function as a bridge to liver transplantation in accurately selected patients.
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Iwasa, Junpei; Shimizu, Masahito; Shiraki, Makoto; Shirakami, Yohei; Sakai, Hiroyasu; Terakura, Yoichi; Takai, Koji; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka
2010-02-01
Obesity and related metabolic abnormalities, including insulin resistance, are risk factors for hepatocellular carcinoma in non-alcoholic steatohepatitis as well as in chronic viral hepatitis. Branched-chain amino acids (BCAA), which improve insulin resistance, inhibited obesity-related colon carcinogenesis in a rodent model, and also reduced the incidence of hepatocellular carcinoma in obese patients with liver cirrhosis. In the present study, we determined the effects of BCAA on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in obese C57BL/KsJ-db/db (db/db) mice with diabetes mellitus. Male db/db mice were given tap water containing 40 ppm DEN for an initial 2 weeks and thereafter they received a basal diet containing 3.0% of BCAA or casein, which served as a nitrogen content-matched control of BCAA, throughout the experiment. Supplementation with BCAA significantly reduced the total number of foci of cellular alteration, a premalignant lesion of the liver, and the expression of insulin-like growth factor (IGF)-1, IGF-2, and IGF-1 receptor in the liver when compared to the casein supplementation. BCAA supplementation for 34 weeks also significantly inhibited both the development of hepatocellular neoplasms and the proliferation of hepatocytes in comparison to the basal diet or casein-fed groups. Supplementation with BCAA improved liver steatosis and fibrosis and inhibited the expression of alpha-smooth muscle actin in the DEN-treated db/db mice. The serum levels of glucose and leptin decreased by dietary BCAA, whereas the value of the quantitative insulin sensitivity check index increased by this agent, indicating the improvement of insulin resistance and hyperleptinemia. In conclusion, oral BCAA supplementation improves insulin resistance and prevents the development of liver tumorigenesis in obese and diabetic mice.
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Ursodeoxycholic acid in chronic liver disease.
de Caestecker, J S; Jazrawi, R P; Petroni, M L; Northfield, T C
1991-01-01
The hydrophilic bile acid ursodeoxycholic acid has recently been shown to reduce biochemical markers of both cholestasis and hepatocellular damage in patients with chronic liver diseases. The most compelling evidence available is for chronic cholestatic liver diseases, in particular primary biliary cirrhosis, primary sclerosing cholangitis, and cholestasis associated with cystic fibrosis. The effects may be less beneficial in patients with advanced liver disease from these conditions. Data from placebo controlled trials are now available in support of earlier uncontrolled observations, but it is not yet clear whether short term benefit results in an improvement in longterm prognosis. The mechanism of action of the compound seems to reside in its displacement of toxic hydrophobic bile acids from both the bile acid pool and hepatocellular membranes. There may be an independent effect on bile flow, which could be of particular importance in cystic fibrosis, and possibly an effect on the immune system. Ursodeoxycholic acid should now be regarded as occupying a central place in the medical management of chronic cholestatic liver diseases, in particular primary biliary cirrhosis, because it improves cholestasis and reduces hepatocellular damage and it is not toxic. Research should now be targeted on whether treatment with ursodeoxycholic acid, initiated early in cholestatic liver conditions, improves the long-term outcome. PMID:1916492
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Talwar, Sahil; Jagani, Hitesh V; Nayak, Pawan G; Kumar, Nitesh; Kishore, Anoop; Bansal, Punit; Shenoy, Rekha R; Nandakumar, Krishnadas
2013-06-06
Based on the reported antioxidant and anti-inflammatory potential of Terminalia paniculata, the bark aqueous extract (TPW) was investigated against liver damage. Intrinsic cytotoxicity was tested on normal human liver (Chang) cell lines, followed by acute and sub-chronic toxicity studies in mice. TPW was then evaluated against CCl4-induced liver toxicity in rats. Liver enzymes (AST, ALT, and ALP) and antioxidant markers were assessed. The effect of TPW on isolated hepatic cells, post-CCl4 administration, was assessed by isolated mitochondrial membrane staining. The actions of TPW on apoptotic pathway in CCl4-treated Chang cells were also elucidated. TPW was found to be safe at all doses tested in both in vitro and in vivo toxicity studies. TPW (400 mg/kg, p.o.) significantly (*p <0.05) improved liver enzyme activity as compared to CCl4. Also, it improved antioxidant status (GSH, GST, MDA and total thiol) and preserved hepatic cell architecture. TPW pre-treatment significantly attenuated the levels of phospho-p53, p53, cleaved caspase-3, phospho-Bad, Bad and cleaved PARP in CCl4-treated Chang cells, improving the viability considerably. The findings support a protective role for Terminalia paniculata in pathologies involving oxidative stress.
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The evidence for the use of nutritional support in liver disease.
Koretz, Ronald L
2014-03-01
Although there is a well established association between malnutrition and poorer clinical outcomes in patients with liver disease, that fact alone does not prove that improving the malnutrition will improve outcome. The best way to determine if nutritional interventions are effective is to compare them to untreated control groups in well designed and executed randomized clinical trials. A recent systematic review assessed 37 trials that compared parenteral nutrition, enteral nutrition, or nutritional supplements to no nutritional therapy in patients with a variety of liver diseases. Since the publication of that review, an additional three trials have become available. Whereas all but one of the trials did have methodologic shortcomings that may have allowed the introduction of bias (which usually results in an overestimation of benefit), the trials failed to show much, if any, benefit. In fact, the single trial at low risk of bias found that more deaths occurred in the recipients of the supplements. Although malnutrition may be associated with a poor outcome, the current best evidence indicates that the provision of adjunctive nutritional support (parenteral or enteral nutrition, or nutritional supplements) to patients with a variety of liver diseases (alcoholic hepatitis, cirrhosis, hepatocellular carcinoma, liver surgery, liver transplantation, obstructive jaundice, hepatitis C antiviral treatment) does not improve clinical outcomes.
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Guan, Lianyue; Liu, Hongyu; Fu, Peiyao; Li, Zhuonan; Li, Peidong; Xie, Lijuan; Xin, Mingang; Wang, Zhanpeng
2016-01-01
The aim of this study was to explore the protective effects of ulinastatin (urinary trypsin inhibitor, UTI) on liver ischemia-reperfusion injury (IRI) and graft survival. We employed mouse liver cold IRI and orthotopic liver transplantation (OLTx) models. UTI was added to lactated Ringer's (LR) solution for liver perfusion and preservation in vitro or combined with UTI injection intraperitoneally to the liver graft recipient. Our results indicated that UTI supplementation protected the liver from cold IRI in a dose-dependent manner and prolonged liver graft survival from extended cold preserved liver donors significantly. The underlying mechanism of UTI on liver IRI may be mediated by inhibition of proinflammatory cytokine release, increasing the expression of the antiapoptotic gene Bcl-2 and decreasing the expression of the proapoptosis genes of Caspase-3 and Bax, and further protects hepatocytes from apoptotic death and improves liver function. PMID:26783413
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Guan, Lianyue; Liu, Hongyu; Fu, Peiyao; Li, Zhuonan; Li, Peidong; Xie, Lijuan; Xin, Mingang; Wang, Zhanpeng; Li, Wei
2016-01-01
The aim of this study was to explore the protective effects of ulinastatin (urinary trypsin inhibitor, UTI) on liver ischemia-reperfusion injury (IRI) and graft survival. We employed mouse liver cold IRI and orthotopic liver transplantation (OLTx) models. UTI was added to lactated Ringer's (LR) solution for liver perfusion and preservation in vitro or combined with UTI injection intraperitoneally to the liver graft recipient. Our results indicated that UTI supplementation protected the liver from cold IRI in a dose-dependent manner and prolonged liver graft survival from extended cold preserved liver donors significantly. The underlying mechanism of UTI on liver IRI may be mediated by inhibition of proinflammatory cytokine release, increasing the expression of the antiapoptotic gene Bcl-2 and decreasing the expression of the proapoptosis genes of Caspase-3 and Bax, and further protects hepatocytes from apoptotic death and improves liver function.
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Rácz, Norbert; Kormány, Róbert; Fekete, Jenő; Molnár, Imre
2015-04-10
Column technology needs further improvement even today. To get information of batch-to-batch repeatability, intelligent modeling software was applied. Twelve columns from the same production process, but from different batches were compared in this work. In this paper, the retention parameters of these columns with real life sample solutes were studied. The following parameters were selected for measurements: gradient time, temperature and pH. Based on calculated results, batch-to-batch repeatability of BEH columns was evaluated. Two parallel measurements on two columns from the same batch were performed to obtain information about the quality of packing. Calculating the average of individual working points at the highest critical resolution (R(s,crit)) it was found that the robustness, calculated with a newly released robustness module, had a success rate >98% among the predicted 3(6) = 729 experiments for all 12 columns. With the help of retention modeling all substances could be separated independently from the batch and/or packing, using the same conditions, having high robustness of the experiments. Copyright © 2015 Elsevier B.V. All rights reserved.
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Wang, Qiqin; Peng, Kun; Chen, Weijia; Cao, Zhen; Zhu, Peijie; Zhao, Yumei; Wang, Yuqiang; Zhou, Haibo; Jiang, Zhengjin
2017-01-06
This study described a simple synthetic methodology for preparing biomembrane mimicking monolithic column. The suggested approach not only simplifies the preparation procedure but also improves the stability of double chain phosphatidylcholine (PC) functionalized monolithic column. The physicochemical properties of the optimized monolithic column were characterized by scanning electron microscopy, energy-dispersive X-ray spectrometry, and nano-LC. Satisfactory column permeability, efficiency, stability and reproducibility were obtained on this double chain PC functionalized monolithic column. It is worth noting that the resulting polymeric monolith exhibits great potential as a useful alternative of commercial immobilized artificial membrane (IAM) columns for in vitro predication of drug-membrane interactions. Furthermore, the comparative study of both double chain and single chain PC functionalized monoliths indicates that the presence or absence of glycerol backbone and the number of acyl chains are not decisive for the predictive ability of IAM monoliths on drug-membrane interactions. This novel PC functionalized monolithic column also exhibited good selectivity for a protein mixture and a set of pharmaceutical compounds. Copyright © 2016 Elsevier B.V. All rights reserved.
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Wang, Y; Zeng, Z; Guan, N; Cheng, J
2001-07-01
A novel open-tubular capillary electrochromatography (OT-CEC) column coated with 2,6-dibutyl-beta-cyclodextrin (DB-beta-CD) was prepared using sol-gel technique. In the sol-gel approach, owing to the three-dimensional network of sol-gel and the strong chemical bond between the stationary phase and the surface of capillary columns, good chromatographic characteristics and unique selectivity in separating isomers were shown. We achieved high efficiencies of 5-14 x 10(4) plates/m for the isomeric nitrophenols using the sol-gel-derived DB-beta-CD columns. The migration time reproducibility of the separation of the isomeric nitrophenols was better than 2.2% over five runs and 4.5% from column to column. These sol-gel-coated DB-beta-CD columns have shown improved separations of isomeric aminophenols, isomeric dihydroxybenzenes and isomeric nitrophenols, in comparison with the sol-gel matrix capillary column. The influences of buffer pH and methanol solvent on separation were investigated. The chiral resolution of enantiomers such as ibuprofen and binaphthol was explored primarily.
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Interpretation of the lime column penetration test
NASA Astrophysics Data System (ADS)
Liyanapathirana, D. S.; Kelly, R. B.
2010-06-01
Dry soil mix (DSM) columns are used to reduce the settlement and to improve the stability of embankments constructed on soft clays. During construction the shear strength of the columns needs to be confirmed for compliance with technical assumptions. A specialized blade shaped penetrometer known as the lime column probe, has been developed for testing DSM columns. This test can be carried out as a pull out resistance test (PORT) or a push in resistance test (PIRT). The test is considered to be more representative of average column shear strength than methods that test only a limited area of the column. Both PORT and PIRT tests require empirical correlations of measured resistance to an absolute measure of shear strength, in a similar manner to the cone penetration test. In this paper, finite element method is used to assess the probe factor, N, for the PORT test. Due to the large soil deformations around the probe, an Arbitrary Lagrangian Eulerian (ALE) based finite element formulation has been used. Variation of N with rigidity index and the friction at the probe-soil interface are investigated to establish a range for the probe factor.
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Conceição, E P S; Moura, E G; Soares, P N; Ai, X X; Figueiredo, M S; Oliveira, E; Lisboa, P C
2016-06-01
Obesity is related to diabetes, higher oxidative stress and nonalcoholic fatty liver disease, and dietetic therapies, for instance calcium-rich diet, can improve these dysfunctions. Rats raised in small litters (SL) had increased fat depots and insulin resistance at adulthood associated with higher liver oxidative stress and microsteatosis. Thus, we evaluated if dietary calcium can improve these changes. In PN3, litter size was adjusted to 3 pups (SL group) to induce overfeeding, while controls had 10 pups until weaning. At PN120, SL group was randomly divided into: rats fed with standard chow or fed with calcium supplementation (SL-Ca group, 10 g/kg chow) for 60 days. At PN180, dietary calcium normalized food consumption, visceral fat, plasma aspartate aminotransferase (AST) and glycaemia. Concerning oxidative balance, calcium restored both higher hepatic lipid peroxidation and protein carbonylation as well as higher plasma lipid peroxidation. Higher fatty acid synthase (FAS) content, steatosis and lower protein kinase B (Akt) in SL group were normalized by dietary calcium and SL-Ca rats had lower hepatic cholesterol. Thus, calcium supplementation improved the insulin sensitivity, redox balance and steatosis in the liver. Therefore, dietary calcium can be a promising therapy for liver disease in the metabolic syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Exposure to liver toxicants can result in or exacerbate fatty liver disease. Recent evidence suggests that serum-derived microRNAs (miRs) may improve identification of chemical-induced fatty liver disease relative to traditional protein-based biomarkers alone. Historical serum sa...
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BrahmaNaidu, Parim; Nemani, Harishankar; Meriga, Balaji; Mehar, Santosh Kumar; Potana, Sailaja; Ramgopalrao, Sajjalaguddam
2014-09-25
An increased risk of obesity has become a common public health concern as it is associated with hypertension, diabetes, osteoarthritis, heart diseases, liver steatosis etc. Pharmacological intervention with natural product-based drugs is considered a healthier alternative to treat obesity. This study was aimed to evaluate anti-obesity effects of piperine on high fat diet (HFD) induced obesity in rats. Piperine was isolated from methanolic extract of Piper nigrum by using column chromatography and confirmed by LC-MS analysis. Male SD rats were fed HFD initially for 15weeks to induce obesity. After induction of obesity, piperine was supplemented in different doses (20, 30 and 40mg/kgb.wt) through HFD for 42days to experimental rats. HFD induced changes in body weight, body composition, fat percentage, adiposity index, blood pressure, plasma levels of glucose, insulin resistance, leptin, adiponectin, plasma and tissue lipid profiles, liver antioxidants were explained. The activities of lipase, amylase and lipid metabolic marker enzymes such as HMG-CoA reductase, carnitine palmitoyl transferase (CPT), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), lecithin-cholesterol acyl transferase (LCAT) and lipoprotein lipase (LPL) were assessed in experimental rats. Supplementation of piperine at a dose of 40mg/kgb.wt has significantly (p<0.05) reversed the HFD-induced alterations in experimental rats in a dose dependant manner, the maximum therapeutic effect being noted at a dose of 40mg/kgb.wt. Our study concludes that piperine can be well considered as an effective bioactive molecule to suppress of body weight, improve insulin and leptin sensitivity, ultimately leading to regulate obesity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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Kaiser, Philipp; Surmann, Peter; Fuhrmann, Herbert
2009-01-01
Astaxanthin shows peak deformation and reduced peak area response when eluted with methanol and methyl tert-butyl ether on nonendcapped polymeric C30-bonded HPLC phases. The present study tested different column manufacturers, column batches, and ten mobile phase additives including acids, bases, buffers, complexing and antioxidant agents for improvement of peak shape and peak area response. Concerning chromatographic benefits and feasibility, ammonium acetate was found to be the best additive followed by triethylamine for all columns tested. Variation of the mobile phase pH equivalent and the column temperature showed no synergistic effects on peak shape and peak area response. Results indicate that peak tailing and variation of peak area response are due to different on-column effects. Possible mechanisms of the observed phenomenon will be discussed.
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Living donor liver transplant (LDLT) is the way forward in Asia.
Rela, Mohamed; Reddy, Mettu Srinivas
2017-03-01
Living donor liver transplantation (LDLT) is currently the commonest form of liver transplantation in Asia. Efforts to improve the number of deceased donor liver transplantation have not been uniformly successful. We believe that THE unique combination of demographic, social, economic and political factors that exist in Asia will ensure that LDLT will continue to remain the predominant form of liver transplantation. While efforts to increase deceased donation rates should continue and intensify, progress in LDLT should also be supported and encouraged, as it will be the main workhorse of liver transplantation in Asia in the near and medium-term future.
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Human Hepatocyte Growth Factor (hHGF)-Modified Hepatic Oval Cells Improve Liver Transplant Survival
Li, Li; Ran, Jiang-Hua; Li, Xue-Hua; Liu, Zhi-Heng; Liu, Gui-Jie; Gao, Yan-Chao; Zhang, Xue-Li; Sun, Hiu-Dong
2012-01-01
Despite progress in the field of immunosuppression, acute rejection is still a common postoperative complication following liver transplantation. This study aims to investigate the capacity of the human hepatocyte growth factor (hHGF) in modifying hepatic oval cells (HOCs) administered simultaneously with orthotopic liver transplantation as a means of improving graft survival. HOCs were activated and isolated using a modified 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH) model in male Lewis rats. A HOC line stably expressing the HGF gene was established following stable transfection of the pBLAST2-hHGF plasmid. Our results demonstrated that hHGF-modified HOCs could efficiently differentiate into hepatocytes and bile duct epithelial cells in vitro. Administration of HOCs at the time of liver transplantation induced a wider distribution of SRY-positive donor cells in liver tissues. Administration of hHGF-HOC at the time of transplantation remarkably prolonged the median survival time and improved liver function for recipients compared to these parameters in the other treatment groups (P<0.05). Moreover, hHGF-HOC administration at the time of liver transplantation significantly suppressed elevation of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) levels while increasing the production of IL-10 and TGF-β1 (P<0.05). HOC or hHGF-HOC administration promoted cell proliferation, reduced cell apoptosis, and decreased liver allograft rejection rates. Furthermore, hHGF-modified HOCs more efficiently reduced acute allograft rejection (P<0.05 versus HOC transplantation only). Our results indicate that the combination of hHGF-modified HOCs with liver transplantation decreased host anti-graft immune responses resulting in a reduction of allograft rejection rates and prolonging graft survival in recipient rats. This suggests that HOC-based cell transplantation therapies can be developed as a means of treating severe liver injuries. PMID:23028627
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Cuthbertson, Daniel J; Shojaee-Moradie, Fariba; Sprung, Victoria S; Jones, Helen; Pugh, Christopher J A; Richardson, Paul; Kemp, Graham J; Barrett, Mark; Jackson, Nicola C; Thomas, E Louise; Bell, Jimmy D; Umpleby, A Margot
2016-01-01
Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR. © 2016 Authors; published by Portland Press Limited.
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Buechter, Matthias; Gerken, Guido; Hoyer, Dieter P; Bertram, Stefanie; Theysohn, Jens M; Thodou, Viktoria; Kahraman, Alisan
2018-06-20
Acute liver failure (ALF) is a life-threatening entity particularly when infectious complications worsen the clinical course. Urgent liver transplantation (LT) is frequently the only curative treatment. However, in some cases, recovery is observed under conservative treatment. Therefore, prognostic tools for estimating course of the disease are of great clinical interest. Since laboratory parameters sometimes lack sensitivity and specificity, enzymatic liver function measured by liver maximum capacity (LiMAx) test may offer novel and valuable additional information in this setting. We here report the case of a formerly healthy 20-year old male caucasian patient who was admitted to our clinic for ALF of unknown origin in December 2017. Laboratory parameters confirmed the diagnosis with an initial MELD score of 28 points. Likewise, enzymatic liver function was significantly impaired with a value of 147 [> 315] μg/h/kg. Clinical and biochemical analyses for viral-, autoimmune-, or drug-induced hepatitis were negative. Liver synthesis parameters further deteriorated reaching a MELD score of 40 points whilst clinical course was complicated by septic pneumonia leading to severe hepatic encephalopathy grade III-IV, finally resulting in mechanical ventilation of the patient. Interestingly, although clinical course and laboratory data suggested poor outcome, serial LiMAx test revealed improvement of the enzymatic liver function at this time point increasing to 169 μg/h/kg. Clinical condition and laboratory data slowly improved likewise, however with significant time delay of 11 days. Finally, the patient could be dismissed from our clinic after 37 days. Estimating prognosis in patients with ALF is challenging by use of the established scores. In our case, improvement of enzymatic liver function measured by the LiMAx test was the first parameter predicting beneficial outcome in a patient with ALF complicated by sepsis.
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Tian, Juan; Wen, Hua; Lu, Xing; Liu, Wei; Wu, Fan; Yang, Chang-Geng; Jiang, Ming; Yu, Li-Juan
2018-01-01
This study aimed to determine the effects of supplementing the diet of adult Nile tilapia Oreochromis niloticus with phosphatidylcholine (PC) on growth performance, body composition, fatty acid composition and gene expression. Genetically Improved Farmed Tilapia fish with an initial body weight of 83·1 (sd 2·9) g were divided into six groups. Each group was hand-fed a semi-purified diet containing 1·7 (control diet), 4·0, 6·5, 11·5, 21·3 or 41·0 g PC/kg diet for 68 d. Supplemental PC improved the feed efficiency rate, which was highest in the 11·5 g PC/kg diet. Weight gain and specific growth rate were unaffected. Dietary PC increased PC content in the liver and decreased crude fat content in the liver, viscera and body. SFA and MUFA increased and PUFA decreased in muscle with increasing dietary PC. Cytoplasmic phospholipase A 2 and secreted phospholipase A 2 mRNA expression were up-regulated in the brain and heart in PC-supplemented fish. PC reduced fatty acid synthase mRNA expression in the liver and visceral tissue but increased expression in muscle. Hormone-sensitive lipase and lipoprotein lipase expression increased in the liver with increasing dietary PC. Growth hormone mRNA expression was reduced in the brain and insulin-like growth factor-1 mRNA expression in liver reduced with PC above 6·5 g/kg. Our results demonstrate that dietary supplementation with PC improves feed efficiency and reduces liver fat in adult Nile tilapia, without increasing weight gain, representing a novel dietary approach to reduce feed requirements and improve the health of Nile tilapia.
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Wong, Weng-Yew; Ward, Leigh C; Fong, Chee Wai; Yap, Wei Ney; Brown, Lindsay
2017-02-01
This study tested the hypothesis that γ- and δ-tocotrienols are more effective than α-tocotrienol and α-tocopherol in attenuating the signs of diet-induced metabolic syndrome in rats. Five groups of rats were fed a corn starch-rich (C) diet containing 68 % carbohydrates as polysaccharides, while the other five groups were fed a diet (H) high in simple carbohydrates (fructose and sucrose in food, 25 % fructose in drinking water, total 68 %) and fats (beef tallow, total 24 %) for 16 weeks. Separate groups from each diet were supplemented with either α-, γ-, δ-tocotrienol or α-tocopherol (85 mg/kg/day) for the final 8 of the 16 weeks. H rats developed visceral obesity, hypertension, insulin resistance, cardiovascular remodelling and fatty liver. α-Tocopherol, α-, γ- and δ-tocotrienols reduced collagen deposition and inflammatory cell infiltration in the heart. Only γ- and δ-tocotrienols improved cardiovascular function and normalised systolic blood pressure compared to H rats. Further, δ-tocotrienol improved glucose tolerance, insulin sensitivity, lipid profile and abdominal adiposity. In the liver, these interventions reduced lipid accumulation, inflammatory infiltrates and plasma liver enzyme activities. Tocotrienols were measured in heart, liver and adipose tissue showing that chronic oral dosage delivered tocotrienols to these organs despite low or no detection of tocotrienols in plasma. In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. The most important mechanism of action is likely to be reduction in organ inflammation.
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Park, Sin Young; Cheong, Won Jo
2015-09-01
This study introduces a preparation method for polymer-encased monolith frits with improved durability for liquid chromatography columns. The inner surface of the polyether ether ketone tubing is pretreated with sulfuric acid in the presence of catalysts (vanadium oxide and sodium sulfate). The tubing was rinsed with water and acetone, flushed with nitrogen, and treated with glycidyl methacrylate. After washing, the monolith reaction mixture composed of lauryl methacrylate, ethylene glycol dimethacrylate, initiator, and porogenic solvent was filled in the tubing and subjected to in situ polymerization. The tubing was cut into thin slices and used as frits for microcolumns. To check their durability, the frit slices were placed in a vial and a heavy impact was applied on the vial by a vortex mixer for various periods. The frits made in the presence of catalysts were found to be more durable than those made without catalysts. Furthermore, when the monolith-incorporated tubing was used as a chromatography column, the column prepared in the presence of catalysts resulted in a better separation efficiency. The separation performance of the columns installed with the polyether ether ketone encased monolith frits was comparable to that of the columns installed with the commercial stainless-steel screen frits. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Wright, Bob W; Wright, Cherylyn W
2012-10-26
A novel method is described for the evaluation of irreversible adsorption and column bleed in gas chromatographic (GC) columns using a tandem GC approach. This work specifically determined the degree of irreversible adsorption behavior of specific sulfur and phosphorous containing test probe compounds at levels ranging from approximately 50 picograms (pg) to 1 nanogram (ng) on selected gas chromatographic columns. This method does not replace existing evaluation methods that characterize reversible adsorption but provides an additional tool. The test compounds were selected due to their ease of adsorption and their importance in the specific trace analytical detection methodology being developed. Replicate chromatographic columns with 5% phenylmethylpolysiloxane (PMS), polyethylene glycol (wax), trifluoropropylpolysiloxane (TFP), or 78% cyanopropylpolysiloxane stationary phases from a variety of vendors were evaluated. As expected, the results demonstrate that the different chromatographic phases exhibit differing degrees of irreversible adsorption behavior. The results also indicate that all manufacturers do not produce equally inert columns nor are columns from a given manufacturer identical. The wax-coated columns for the test probes used were more inert as a group than 5% PMS coated columns, and they were more reproducibly manufactured. Both TFP and 78% cyanopropylpolysiloxane columns displayed superior inertness to the test compounds compared to either 5% PMS- or wax-coated columns. Irreversible adsorption behavior was characterized for a limited range of stationary phase film thicknesses. In addition, the method was shown effective for characterizing column bleed and methods to remove bleed components. This method is useful in screening columns for demanding applications and to obtain diagnostic information related to improved preparation methods. Copyright © 2012 Elsevier B.V. All rights reserved.
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Improving the Amazonian Hydrologic Cycle in a Coupled Land-Atmosphere, Single Column Model
NASA Astrophysics Data System (ADS)
Harper, A. B.; Denning, S.; Baker, I.; Prihodko, L.; Branson, M.
2006-12-01
We have coupled a land-surface model, the Simple Biosphere Model (SiB3), to a single column of the Colorado State University General Circulation Model (CSU-GCM) in the Amazon River Basin. This is a preliminary step in the broader goal of improved simulation of Basin-wide hydrology. A previous version of the coupled model (SiB2) showed drought and catastrophic dieback of the Amazon rain forest. SiB3 includes updated soil hydrology and root physiology. Our test area for the coupled single column model is near Santarem, Brazil, where measurements from the km 83 flux tower in the Tapajos National Forest can be used to evaluate model output. The model was run for 2001 using NCEP2 Reanalysis as driver data. Preliminary results show that the updated biosphere model coupled to the GCM produces improved simulations of the seasonal cycle of surface water balance and precipitation. Comparisons of the diurnal and seasonal cycles of surface fluxes are also being made.
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Yan, Yaping; Wang, Junfeng; Duan, Yanchao; Li, Shanshan; Yan, Li; Wang, Hong; Chen, Bingbing; Sang, Xiongbo; Ji, Weizhi
2018-01-01
Liver fibrosis is a disease that causes high morbidity and has become a major health problem. Liver fibrosis can lead to the end stage of liver diseases (livercirrhosisand hepatocellularcarcinoma). Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, the shortage of organ donors, high cost of medical surgery, immunological rejection and transplantation complications severely hamper liver transplantation therapy. Mesenchymal stem cells (MSCs) have been regarded as promising cells for clinical applications in stem cell therapy in the treatment of liver diseases due to their unique multipotent differentiation capacity, immunoregulation and paracrine effects. Although liver fibrosis improvements by MSC transplantation in preclinical experiments as well as clinical trials have been reported, the in vivo fate of MSCs after transportation and their therapeutic mechanisms remain unclear. In this present study, we isolated MSCs from the bone marrow of rhesus macaques. The cells exhibited typical MSC markers and could differentiate into chondrocytes, osteocytes, and adipocytes, which were not affected by labeling with enhanced green fluorescent protein (EGFP). The harvested MSCs respond to interferon-γ stimulation and have the ability to inhibit lymphocyte proliferation in vitro. EGFP-labeled MSCs (1 × 106 cells) were transplanted into mice with carbon tetrachloride-induced liver fibrosis via tail vein injection. The ability of the heterogenic MSC infusion to ameliorate liver fibrosis in mice was evaluated by a blood plasma chemistry index, pathological examination and liver fibrosis-associated gene expression. Additionally, a small number of MSCs that homed and engrafted in the mouse liver tissues were evaluated by immunofluorescence analysis. Our results showed that the transplantation of heterogenic MSCs derived from monkey bone marrow can be used to treat liver fibrosis in the mouse model and that the paracrine effects of MSCs may play an important role in the improvement of liver fibrosis. PMID:29456886
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Usefulness of granular BCAA after hepatectomy for liver cancer complicated with liver cirrhosis.
Togo, Shinji; Tanaka, Kuniya; Morioka, Daisuke; Sugita, Mitsutaka; Ueda, Michio; Miura, Yasuhiko; Kubota, Toru; Nagano, Yasuhiko; Matsuo, Kenichi; Endo, Itaru; Sekido, Hitoshi; Shimada, Hiroshi
2005-04-01
Nutritional disturbances such as ascites and hypoalbuminemia frequently arise after hepatectomy for liver cancer with liver cirrhosis. We examined the possibility of maintaining a favorable state of nutrition by outpatient administration of branched-chain amino acid (BCAA) granules. Forty-three patients who had gross liver cirrhosis complicated by liver cancer and underwent surgery up to May 2002 were given BCAA granules (n = 21, BCAA group) or no granules (n = 22, control group). 1) Background details such as age, sex, surgical technique, blood loss, and duration of surgery showed no significant differences. 2) Among objective findings, improvement of ascites and edema tended to occur sooner in the BCAA group, but without a significant difference. 3) Although serum albumin recovered its preoperative value 9 mo after surgery in the control group, only 6 mo was required for recovery in the BCAA group. Total protein showed similar changes, but neither group showed any difference in changes of aspartate aminotransferase, alanine transferase, or platelets. 4) One year postoperatively, the change from the preoperative indocyanine green retention rate at 15 min after intravenous administration tended to be worse in the control group, but not significantly so. 5) In the BCAA group, hyaluronic acid and type IV collagen 7S improved significantly sooner than in the control group. BCAA supplementation after hepatectomy promotes rapid improvement in protein metabolism and inhibits progression to liver cirrhosis. Administration of BCAA after hepatectomy is considered beneficial to a patient's nutritional state.
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[Construction and characterization of a cDNA library from human liver tissue of cirrhosis].
Chen, Xiao-hong; Chen, Zhi; Chen, Feng; Zhu, Hai-hong; Zhou, Hong-juan; Yao, Hang-ping
2005-03-01
To construct a cDNA library from human liver tissue of cirrhosis. The total RNA from human liver tissue of cirrhosis was extracted using Trizol method, and the mRNA was purified using mRNA purification kit. SMART technique and CDSIII/3' primer were used for first-strand cDNA synthesis. Long distance PCR was then used to synthesize the double-strand cDNA that was then digested by proteinase K and Sfi I, and was fractionated by CHOMA SPIN-400 column. The cDNA fragments longer than 0.4 kb were collected and ligated to lambdaTripl Ex2 vector. Then lambda-phage packaging reaction and library amplification were performed. The qualities of both unamplified and amplified cDNA libraries was strictly checked by conventional titer determination. Eleven plaques were randomly picked and tested using PCR with universal primers derived from the sequence flanking the vector. The titers of unamplifed and amplified libraries were 1.03 x 10(6) pfu/ml and 1.36 x 10(9) pfu/ml respectively. The percentages of recombinants from both libraries were 97.24 % in unamplified library and 99.02 % in amplified library. The lengths of the inserts were 1.02 kb in average (36.36 % 1 approximately equals 2 kb and 63.64 % 0.5 approximately equals 1.0 kb). A high quality cDNA library from human liver tissue of cirrhosis was constructed successfully, which can be used for screening and cloning new special genes associated with the occurrence of cirrhosis.
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Seibert, Cathrin; Davidson, Brian R; Fuller, Barry J; Patterson, Laurence H; Griffiths, William J; Wang, Yuqin
2009-04-01
Here we report the identification and approximate quantification of cytochrome P450 (CYP) proteins in human liver microsomes as determined by nano-LC-MS/MS with application of the exponentially modified protein abundance index (emPAI) algorithm during database searching. Protocols based on 1D-gel protein separation and 2D-LC peptide separation gave comparable results. In total, 18 CYP isoforms were unambiguously identified based on unique peptide matches. Further, we have determined the absolute quantity of two CYP enzymes (2E1 and 1A2) in human liver microsomes using stable-isotope dilution mass spectrometry, where microsomal proteins were separated by 1D-gel electrophoresis, digested with trypsin in the presence of either a CYP2E1- or 1A2-specific stable-isotope labeled tryptic peptide and analyzed by LC-MS/MS. Using multiple reaction monitoring (MRM) for the isotope-labeled tryptic peptides and their natural unlabeled analogues quantification could be performed over the range of 0.1-1.5 pmol on column. Liver microsomes from four individuals were analyzed for CYP2E1 giving values of 88-200 pmol/mg microsomal protein. The CYP1A2 content of microsomes from a further three individuals ranged from 165 to 263 pmol/mg microsomal protein. Although, in this proof-of-concept study for CYP quantification, the two CYP isoforms were quantified from different samples, there are no practical reasons to prevent multiplexing the method to allow the quantification of multiple CYP isoforms in a single sample.
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Lambropoulou, Dimitra A; Konstantinou, Ioannis K; Albanis, Triantafyllos A
2006-07-28
In the present study a combined analytical method involving ultrasonic extraction (USE), sulfuric acid clean-up and headspace solid-phase microextraction (HS-SPME) was developed for the determination of chlorinated pesticides (CPs) in bird livers. Extraction of CPs from 1g of liver was performed by ultrasonication for 30 min using 20 mL of solvent mixture (n-hexane:acetone (4:1, v/v)). The extract was subsequently subjected to a clean-up step for lipid removal. A comparative study on several clean-up procedures prior to the HS-SPME enrichment step was performed in order to achieve maximum recovery and optimal clean-up efficiency, which would provide suitable limits of detection in the gas chromatographic analysis. For this purpose, destructive (sulfuric acid or sodium hydroxide treatment) and non-destructive (alumina column) clean-up procedures has been assayed. The treatment of the extract with 40% (v/v) H2SO4 prior to HS-SPME process showed the best performance since lower detection limits and higher extraction efficiencies were obtained. The method detection limit ranged from 0.5 to 1.0 ng g(-1) wet weight and peak areas were proportional to analyte concentrations (r2>0.990) in the range of 5-500 ng g(-1) wet wt. The method was found to be reproducible (R.S.D.<10%) and effective under the operational conditions proposed and was applied successfully to the analysis of CPs in liver tissues of various bird species from Greece.
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Seibert, Cathrin; Davidson, Brian R.; Fuller, Barry J.; Patterson, Laurence H.; Griffiths, William J.; Wang, Yuqin
2009-01-01
Here we report the identification and approximate quantification of cytochrome P450 (CYP) proteins in human liver microsomes as determined by nano-LC-MS/MS with application of the exponentially modified protein abundance index (emPAI) algorithm during database searching. Protocols based on 1D-gel protein separation and 2D-LC peptide separation gave comparable results. In total 18 CYP isoforms were unambiguously identified based on unique peptide matches. Further, we have determined the absolute quantity of two CYP enzymes (2E1 and 1A2) in human liver microsomes using stable-isotope dilution mass spectrometry, where microsomal proteins were separated by 1D-gel electrophoresis, digested with trypsin in the presence of either a CYP2E1- or 1A2-specific stable-isotope labelled tryptic peptide and analysed by LC-MS/MS. Using multiple reaction monitoring (MRM) for the isotope-labelled tryptic peptides and their natural unlabelled analogues quantification could be performed over the range of 0.1 – 1.5 pmol on column. Liver microsomes from four individuals were analysed for CYP2E1 giving values of 88 - 200 pmol/mg microsomal protein. The CYP1A2 content of microsomes from a further three individuals ranged from 165 – 263 pmol/mg microsomal protein. Although, in this proof-of-concept study for CYP quantification, the two CYP-isoforms were quantified from different samples, there are no practical reasons to prevent multiplexing the method to allow the quantification of multiple CYP-isoforms in a single sample. PMID:19714871
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Shin, Seung Kak; Kim, Jeong Han; Park, Hyeonsu; Kwon, Oh Sang; Lee, Hyun Jung; Yeon, Jong Eun; Byun, Kwan Soo; Suh, Sang Jun; Yim, Hyung Joon; Kim, Yun Soo; Kim, Ju Hyun
2015-12-01
Entecavir (ETV) induces biochemical and histologic improvement of the liver in patients with chronic hepatitis B. This study aimed to confirm that 2 years of ETV treatment improves liver function and non-invasive fibrosis markers in patients with hepatitis B virus (HBV)-associated cirrhosis. A total 472 naïve patients with HBV-associated cirrhosis was treated with ETV for at least 2 years, between March 2007 and December 2012. Model for end-stage liver disease and Child-Pugh (CP) score were used to evaluate the improvement of liver function. Aspartate transaminase to platelet ratio index, FIB-4 index, and fibrosis index were used to evaluate the improvement of fibrosis. The final 370 of 472 patients with HBV-associated cirrhosis were enrolled. Mean age was 51 ± 10 years, and 240 patients (64.9%) were men. The distribution of CP class was 71.1% in A, 24.6% in B, and 4.3% in C. Mean end-stage liver disease and CP score changed over the study period from 8.5 ± 4.6 to 6.2 ± 4.2 (P < 0.001) and from 6.2 ± 1.6 to 5.6 ± 0.9 (P < 0.001), respectively. Aspartate transaminase to platelet ratio index, FIB-4 index, and fibrosis index changed from 3.6 ± 4.5 to 1.5 ± 1.5 (P < 0.001), from 7.0 ± 6.2 to 3.9 ± 2.8 (P < 0.001), and from 3.3 ± 0.9 to 2.5 ± 1.1 (P < 0.001), respectively. After 2 years of treatment, ETV improves liver function and non-invasive fibrosis markers in patients with HBV-associated cirrhosis. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
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Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review
Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R.; Partovi, Nilufar; Yoshida, Eric M.
2016-01-01
Abstract Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present. PMID:27777888
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Fernández del Río, R.; O'Hara, M.E.; Holt, A.; Pemberton, P.; Shah, T.; Whitehouse, T.; Mayhew, C.A.
2015-01-01
Background The burden of liver disease in the UK has risen dramatically and there is a need for improved diagnostics. Aims To determine which breath volatiles are associated with the cirrhotic liver and hence diagnostically useful. Methods A two-stage biomarker discovery procedure was used. Alveolar breath samples of 31 patients with cirrhosis and 30 healthy controls were mass spectrometrically analysed and compared (stage 1). 12 of these patients had their breath analysed after liver transplant (stage 2). Five patients were followed longitudinally as in-patients in the post-transplant period. Results Seven volatiles were elevated in the breath of patients versus controls. Of these, five showed statistically significant decrease post-transplant: limonene, methanol, 2-pentanone, 2-butanone and carbon disulfide. On an individual basis limonene has the best diagnostic capability (the area under a receiver operating characteristic curve (AUROC) is 0.91), but this is improved by combining methanol, 2-pentanone and limonene (AUROC curve 0.95). Following transplant, limonene shows wash-out characteristics. Conclusions Limonene, methanol and 2-pentanone are breath markers for a cirrhotic liver. This study raises the potential to investigate these volatiles as markers for early-stage liver disease. By monitoring the wash-out of limonene following transplant, graft liver function can be non-invasively assessed. PMID:26501124
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Inoue, K; Watanabe, T; Maruoka, N; Kuroki, Y; Takahashi, H; Yoshiba, M
2010-12-01
The Japanese style of intensive medical care for acute liver failure has yielded high survival rates. The care system comprises artificial liver support (ALS) together with treatment for the underlying disease. Plasma exchange in combination with high-volume hemodiafiltration using an high performance membrane has become the standard ALS system. It is safe, efficiently removing more low and middle molecular weight toxic substances than other methods because of the large volumes of buffer (more than 200 L per session), resulting in recovery from coma in patients with severe fulminant hepatitis, a status comparable with the ahepatic state. This ALS is therefore an effective tool to sustain patients with fulminant hepatitis in a favorable condition until liver function recovers or liver transplantation becomes available. The accompanying treatment for underlying disease serves to limit the liver destruction that hampers regeneration. The treatment has remarkably improved the prognosis for patients with subacute types of fulminant hepatitis, which generally carry a less favorable prognosis than the acute type. This treatment system thus provides more time for physicians to assess the indications for liver transplantation as well as giving the patient a greater chance of undergoing transplantation. Copyright © 2010 Elsevier Inc. All rights reserved.
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Size mismatch in liver transplantation.
Fukazawa, Kyota; Nishida, Seigo
2016-08-01
Size mismatch is an unique and inevitable but critical issue in live donor liver transplantation. Unmatched metabolic demand of recipient as well as physiologic mismatch aggravates the damage to liver graft, inevitably leading to graft failure on recipient. Also, an excessive resection of liver graft for better recipient outcome in live donor liver transplant may jeopardize the healthy donor well-being and even put donor life in danger. There is a fine balance between resected graft volume required to meet the recipient's metabolic demand and residual graft volume required for donor safety. The obvious clinical necessity of finding that balance has prompted a clinical need and promoted the improvement of knowledge and development of management strategies for size-mismatched transplants. The development of the size-matching methodology has significantly improved graft outcome and recipient survival in live donor liver transplants. On the other hand, the effect of size mismatch in cadaveric transplants has never been observed as being so pronounced. The importance of matching of the donor recipient size has been unrecognized in cadaveric liver transplant. In this review, we attempt to summarize the current most updated knowledge on the subject, particularly addressing the definition and complications of size-mismatched cadaveric liver transplant, as well as management strategies. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
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Kawashima, Hiroto; Suto, Momoka; Suto, Nana
2018-05-20
Liquid chromatography/isotope ratio mass spectrometry (LC/IRMS) has been used to authenticate and trace products such as honey, wine, and lemon juice, and compounds such as caffeine and pesticides. However, LC/IRMS has several disadvantages, including the high cost of the CO 2 membrane and blocking by solidified sodium persulfate. Here, we developed an improved system for determining carbon isotope ratios by LC/IRMS. The main improvement was the use of a post-column pump. Using the improved system, we determined δ 13 C values for glucose with high accuracy and precision (0.1‰ and 0.1‰, respectively; n = 3). The glucose, fructose, disaccharide, trisaccharide, and organic acid constituents of the honey samples were analyzed by LC/IRMS. The δ 13 C values for glucose, fructose, disaccharides, trisaccharides, and organic acids ranged from -27.0 to -24.2‰, -26.8 to -24.0‰, -28.8 to -24.0‰, -27.8 to -22.8‰, and -30.6 to -27.4‰, respectively. The analysis time was 1/3-1/2 the times required for analysis by previously reported methods. The column flow rate could be arbitrarily adjusted with the post-column pump. We applied the improved method to 26 commercial honey samples. Our results can be expected to be useful for other researchers who use LC/IRMS. This article is protected by copyright. All rights reserved.
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Bahitham, Wesam; Watts, Russell; Nelson, Randal; Lian, Jihong; Lehner, Richard
2016-05-01
Ces1g/Es-x deficiency in mice results in weight gain, insulin resistance, fatty liver and hyperlipidemia through upregulation of de novo lipogenesis and oversecretion of triacylglycerol (TG)-rich lipoproteins. Here, we show that restoration of Ces1g/Es-x expression only in the liver significantly reduced hepatic TG concentration accompanied by decreased size of lipid droplets, reduced secretion of very low-density lipoproteins and improved insulin-mediated signal transduction in the liver. Collectively, these results demonstrate that hepatic Ces1g/Es-x plays a critical role in limiting hepatic steatosis, very low-density lipoprotein assembly and in augmenting insulin sensitivity. Copyright © 2016 Elsevier B.V. All rights reserved.
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Park, C H; Okos, M R; Wankat, P C
1990-06-20
Acetone-butanol-ethanol (ABE) fermentation was performed continuously in an immobilized cell, trickle bed reactor for 54 days without, degeneration by maintaining the pH above 4.3. Column clogging was minimized by structured packing of immobilization matrix. The reactor contained two serial glass columns packed with Clostridium acetobutylicum adsorbed on 12- and 20-in.-long polyester sponge strips at total flow rates between 38 and 98.7 mL/h. Cells were initially grown at 20 g/L glucose resulting in low butanol (1.15 g/L) production encouraging cell growth. After the initial cell growth phase a higher glucose concentration (38.7 g/L) improved solvent yield from 13.2 to 24.1 wt%, and butanol production rate was the best. Further improvement in solvent yield and butanol production rate was not observed with 60 g/L of glucose. However, when the fresh nutrient supply was limited to only the first column, solvent yield increased to 27.3 wt% and butanol selectivity was improved to 0.592 as compared to 0.541 when fresh feed was fed to both columns. The highest butanol concentration of 5.2 g/L occurred at 55% conversion of the feed with 60 g/L glucose. Liquid product yield of immobilized cells approached the theoretical value reported in the literature. Glucose and product concentration profiles along the column showed that the columns can be divided into production and inhibition regions. The length of each zone was dependent upon the feed glucose concentration and feed pattern. Unlike batch fermentation, there was no clear distinction between acid and solvent production regions. The pH dropped, from 6.18-6.43 to 4.50-4.90 in the first inch of the reactor. The pH dropped further to 4.36-4.65 by the exit of the column. The results indicate that the strategy for long term stable operation with high solvent yield requires a structured packing of biologically stable porous matrix such as polyester sponge, a pH maintenance above 4.3, glucose concentrations up to 60 g/L and nutrient supply only to the inlet of the reactor.
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Sun, Baoguo; Chen, Yan; Xiang, Ting; Zhang, Lei; Chen, Zexiong; Zhang, Shijun; Zhou, Houming; Chen, Shuqing
2015-01-01
Traditional Chinese Medicine Jianpijiedu decoction (JPJD) could improve the general status of liver cancer patients in clinics, especially the symptoms of decreased food intake and diarrhea. In this study, our results showed that the survival rate of the liver cancer with food restriction and diarrhea (FRD-LC) rats was lower than the liver cancer (LC) rats, and the tumor volume of the FRD-LC rats was higher than the LC rats. It was also shown that the high dose of JPJD significantly improved the survival rate, weight, and organ weight when compared with FRD-LC-induced rats. Moreover, JPJD administration upregulated the mRNA and protein levels of ABCC2 and downregulated the mRNA and protein levels of OATP1B2 in liver tissues. However, opposite results were observed in the cancer tissues. In conclusion, the study indicated that the Chinese Medicine JPJD could contribute to the rats with liver cancer which were pretreated with food restriction and diarrhea by regulating the expression of ABCC2 and OATP1B2 in liver tissues and cancer tissues. PMID:26665149
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Taimr, Pavel; Jongerius, Vivian L; Pek, Chulja J; Krak, Nanda C; Hansen, Bettina E; Janssen, Harry L A; Metselaar, Herold J; van Eijck, Casper H J
2015-12-01
The aim of this study is to provide a diagnostic performance evaluation of contrast-enhanced ultrasonography (CEUS) in detecting liver metastases in patients with suspected of pancreatic or periampullary cancer. Computed tomography (CT) is often insufficient for detection of liver metastases, but their presence plays a crucial role in the choice of therapy. Eighty-nine patients with suspected pancreatic or periampullary cancer were included in this prospective study with retrospective analysis. Patients underwent an abdominal CT and CEUS. Fifteen patients had liver metastases. The CT sensitivity was 73.3% (11/15), the specificity 93.2% (69/74), the positive predictive value (PPV) 68.8% (11/16) and the negative predictive value (NPV) 94.6% (69/73). Based on CEUS, the sensitivity was 80% (12/15), specificity 98.6% (73/74), PPV 92.3% (12/13) and NPV 96.1% (73/76). CEUS improved characterization of liver lesions in patients with suspected pancreatic or periampullary cancer compared with CT. CEUS can better detect benign liver lesions and distinguish false-positive or indeterminate CT results. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
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Panyod, Suraphan; Wu, Wei-Kai; Ho, Chi-Tang; Lu, Kuan-Hung; Liu, Chun-Ting; Chu, Yung-Lin; Lai, Yi-Syuan; Chen, Wei-Cheng; Lin, Yu-En; Lin, Shih-Hang; Sheen, Lee-Yan
2016-09-28
This study investigated the liver-protective effects of allicin, an active compound in fresh garlic, against alcoholic fatty liver disease (AFLD) and liver inflammation. Its effects were investigated in an AFLD model in male C57BL/6 mice, which were fed Lieber-DeCarli liquid diet containing ethanol. Allicin (5 and 20 mg/kg bw/day) was orally administered daily in the AFLD mice for 4 weeks. The results indicate that allicin promotes hepatoprotection by significantly reducing aspartate transaminase (AST) and alanine transaminase (ALT) levels (p < 0.05) in the plasma, which are key indicators of liver damage. Allicin reduced fat accumulation, increased glutathione and catalase levels, and decreased microsomal protein cytochrome P450 2E1 (CYP2E1) expression (p < 0.05) in the livers of the AFLD mice. Furthermore, allicin supplementation significantly decreased the levels of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 and suppressed the expression of sterol regulatory element-binding protein-1 (SREBP-1) (p < 0.05). Additionally, it improved the hepatic alcohol dehydrogenase (ADH) activity (p < 0.05). Collectively, these findings demonstrate that allicin attenuates liver oxidative stress and inflammation.
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Movsesyan, Nina; Platt, Frances M.
2017-01-01
In this case series, we demonstrate that Ursodeoxycholic acid (UDCA) improves liver dysfunction in Niemann-Pick type C (NPC) and may restore a suppressed cytochrome p450 system. NPC disease is a progressive neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 genes. Liver disease is a common feature presenting either acutely as cholestatic jaundice in the neonatal period, or in later life as elevated liver enzymes indicative of liver dysfunction. Recently, an imbalance in bile acid synthesis in a mouse model of NPC disease was linked to suppression of the P450 detoxification system and was corrected by UDCA treatment. UDCA (3α, 7β-dihydroxy-5β-cholanic acid), a hydrophilic bile acid, is used to treat various cholestatic disorders. In this report we summarise the findings from four independent cases of NPC, three with abnormal liver enzyme levels at baseline, that were subsequently treated with UDCA. The patients differed in age and clinical features, they all tolerated the drug well, and in those with abnormal liver function, there were significant improvements in their liver enzyme parameters. PMID:29119141
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Heavy metal adsorption changes of EAF steel slag after phosphorus adsorption.
Song, Guanling; Cao, Lijing; Chen, Xiao; Hou, Wenhua; Wang, Qunhui
2012-01-01
A kind of electric arc furnace (EAF) steel slag was phosphated, and its isothermal and dynamic adsorptions of copper, cadmium, and lead ions were measured to determine if heavy metal adsorption changes after phosphorus adsorption. The surface area increased greatly after the slag was phosphated. Isothermal adsorption experiments showed that the theoretical Q(max) of the EAF steel slag on Cu(2+), Cd(2+), and Pb(2+) improved 59, 50, and 89% respectively after it was phosphated. Dynamic adsorption results showed that the greatest adsorption capacities of unit volume of Cu(2+), Cd(2+), and Pb(2+) were 2.2, 1.8, and 1.8 times that of the column packed with original EAF steel slag when the column was packed with phosphate EAF steel slag at the same heavy metal ion concentration. The breakthrough time, the exhaustion time and elution efficiency of the column also increased when the column was packed with phosphated EAF steel slag compared with that packed with original EAF steel slag. Phosphorus adsorption could further improve the heavy metal ion adsorption of the EAF steel slag.
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Axial thermal gradients in microchip gas chromatography.
Wang, Anzi; Hynynen, Sampo; Hawkins, Aaron R; Tolley, Samuel E; Tolley, H Dennis; Lee, Milton L
2014-12-29
Fabrication technologies for microelectromechanical systems (MEMS) allow miniaturization of conventional benchtop gas chromatography (GC) to portable, palm-sized microfabricated GC (μGC) devices, which are suitable for on-site chemical analysis and remote sensing. The separation performance of μGC systems, however, has not been on par with conventional GC. Column efficiency, peak symmetry and resolution are often compromised by column defects and non-ideal injections. The relatively low performance of μGC devices has impeded their further commercialization and broader application. In this work, the separation performance of μGC columns was improved by incorporating thermal gradient gas chromatography (TGGC). The analysis time was ∼20% shorter for TGGC separations compared to conventional temperature-programmed GC (TPGC) when a wide sample band was introduced into the column. Up to 50% reduction in peak tailing was observed for polar analytes, which improved their resolution. The signal-to-noise ratios (S/N) of late-eluting peaks were increased by 3-4 fold. The unique focusing effect of TGGC overcomes many of the previous shortcomings inherent in μGC analyses. Copyright © 2014 Elsevier B.V. All rights reserved.
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Neuberger, James M; Bechstein, Wolf O; Kuypers, Dirk R J; Burra, Patrizia; Citterio, Franco; De Geest, Sabina; Duvoux, Christophe; Jardine, Alan G; Kamar, Nassim; Krämer, Bernhard K; Metselaar, Herold J; Nevens, Frederik; Pirenne, Jacques; Rodríguez-Perálvarez, Manuel L; Samuel, Didier; Schneeberger, Stefan; Serón, Daniel; Trunečka, Pavel; Tisone, Giuseppe; van Gelder, Teun
2017-04-01
Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of recipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient modifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes.COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across Europe. The group's remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant.The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting.
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Xu, Bei; Lin, Lanyi; Xu, Guoguang; Zhuang, Yan; Guo, Qing; Liu, Yunye; Wang, Hui; Zhou, Xiaqiu; Wu, Shanming; Bao, Shisan; Cai, Wei; Xie, Qing
2015-02-01
Antiviral therapy is important in advanced liver fibrosis/cirrhosis with chronic hepatitis B (AdLF-CHB) patients, but complete regression of cirrhosis remains to be the challenge. We aimed to investigate whether up to 10 years lamivudine treatment achieves liver fibrosis/cirrhosis regression in AdLF-CHB patients. Improvement of hepatic fibrosis/cirrhosis, virological response and disease progression were evaluated in 28 AdLF-CHB patients with up to 10 years lamivudine treatment. Liver biopsy was performed in all of the 28 patients at baseline, but only 19 patients had second biopsy at year 10. There were 24 hepatitis B e antigen (HBeAg)-positive and 4 HBeAg-negative patients within the original 28 AdLF-CHB patients. At the end of 10 years lamivudine treatment, 20 of the 24 HBeAg-positive patients had HBeAg loss. HBeAg seroconversion was detected in 10 of these 20 HBeAg loss patients. HBsAg loss was observed in 4 of the original 28 patients. Among these four HBsAg loss patients, three had HBsAg seroconversion. All patients achieved hepatitis B virus DNA (HBV DNA) undetectable. Histopathology was evaluated between paired original and final liver biopsies among 19 patients as follows: 4/19 achieved complete liver fibrosis/cirrhosis regression; 9/19 improved in Ishak fibrosis score; whereas 6/19 showed no fibrosis improvement. About 75% patients achieved inflammatory/fibrotic improvement. No significant disease progression was observed in 24/28 patients. Furthermore, no significant difference in histopathology improvement, cirrhosis regression, disease progression between non-resistance and rescue for resistance was observed. Long-term lamivudine therapy achieves regression of fibrosis/cirrhosis and improvement of histological and disease progression in AdLF-CHB patients. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
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Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery
NASA Astrophysics Data System (ADS)
Rudolph, Karl Lenhard; Chang, Sandy; Millard, Melissa; Schreiber-Agus, Nicole; DePinho, Ronald A.
2000-02-01
Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR-/- mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of ``telomerase therapy'' for such diseases.
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Martino, Rodrigo B; Júnior, Eserval Rocha; Manuel, Valdano; Rocha-Santos, Vinicius; D'Albuquerque, Luis Augusto C; Andraus, Wellington
2017-10-11
BACKGROUND Adequate portal venous flow is required for successful liver transplantation. Reduced venous flow and blood flow 'steal' by collateral vessels are a concern, and when there is a prominent splenorenal shunt present, ligation of the left renal vein has been recommended to improve portal venous blood flow. CASE REPORT A 51-year-old man who had undergone right nephrectomy in childhood required liver transplantation for liver cirrhosis and hepatocellular carcinoma due to hepatitis C virus (HCV) infection. The patient had no other comorbidity and no history of hepatorenal syndrome. At transplantation surgery, portal venous flow was poor and did not improve with ligation of shunt veins, but ligation of the left renal vein improved portal venous flow. On the first and fifth postoperative days, the patient was treated with basiliximab, a chimeric monoclonal antibody to the IL-2 receptor, and methylprednisolone. The calcineurin inhibitor, tacrolimus, was introduced on the fifth postoperative day. On the sixteenth postoperative day, renal color Doppler ultrasound showed normal left renal parenchyma; hepatic Doppler ultrasound showed good portal vein flow and preserved hepatic parenchyma in the liver transplant. CONCLUSIONS This case report has shown that in a patient with a single left kidney, left renal vein ligation is feasible and safe in a patient with no other risk factors for renal impairment following liver transplantation. Modification of postoperative immunosuppression to avoid calcineurin inhibitors in the very early postoperative phase may be important in promoting good recovery of renal function and to avoid the need for postoperative renal dialysis.
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Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial.
Bomhof, Marc R; Parnell, Jill A; Ramay, Hena R; Crotty, Pam; Rioux, Kevin P; Probert, Chris S; Jayakumar, Saumya; Raman, Maitreyi; Reimer, Raylene A
2018-05-19
In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota. Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease. Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted. This trial was registered at Clinicaltrials.com as NCT03184376.
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Salvage liver transplantation for hepatic gas gangrene.
Birnbaum, David Jérémie; Grégoire, Emilie; Hardwigsen, Jean; Le Treut, Yves Patrice
2012-09-01
Hepatic gas gangrene is an uncommon situation mainly due to bacterial infection by Clostridium perfringens. It remains a life-threatening condition associated with a high mortality rate. Quick diagnosis and aggressive therapy including liver transplantation should be proposed to improve the outcome. This report describes a rare case of hepatic gas gangrene on native liver, secondary to iatrogenic hepatic artery thrombosis and instrumental biliary tree infection, which was successfully treated by liver transplantation.
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HAART and the liver: friend or foe?
2010-01-01
The overall effect of HAART on the liver is the result of the balance between hepatotoxicity and the consequences of immunoreconstitution on the evolution of HIV-associated liver diseases, particularly viral hepatitis. HAART may lead to the emergence of acute toxic hepatitis, steatosis, steatohepatitis, liver fibrosis, and noncirrhotic portal hypertension. On the other hand, HAART use has been associated with slower fibrosis progression in HIV/HCV-coinfected patients in most studies dealing with this issue. As well, an improvement of the clinical outcome of liver disease has been reported in patients taking HAART. For these reasons, the short- and mid-term effects of HAART on the liver are mostly beneficial. PMID:20452892
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Experimental Evaluation of Beam to Diamond Box Column Connection with Through Plate in Moment Frames
NASA Astrophysics Data System (ADS)
Keshavarzi, Farhad; Mirghaderi, Rasoul; Torabian, Shahabeddin; Imanpour, Ali
2008-07-01
Moment resisting frames with built up section have very enhanced features due to high bending stiffness and strength characteristics in two principal axes and access to column faces for beam to column easy connections. But due to proper transfer of beam stresses to column faces there were always some specific controvertibly issues that how to make the load transfer through and in plane manner in order to mobilize the forces in column faces. Using diamond column instead of box column provide possibility to mobilize the load transfer mechanism in column faces. This section as a column has considerable benefit such as high plastic to elastic section modulus ratio which is an effective factor for force controlled components. Typical connection has no chance to be applied with diamond column. This paper elucidates the seismic behavior of through-plates moment connections to diamond box columns for use in steel moment resisting frames. This connection has a lot of economical benefits such as no need to horizontal continuity plates and satisfying the weak beam—strong column criteria in the connection region. They might serve as panel zone plates as well. According to high shear demand in panel zone of beam to column joint one should use the doublers plates in order to decrease the shear strength demand in this sensitive part of structure but these plates have no possibility to mobilize the load transfer mechanism in column web and transfer them to column flanges. In this type of connection, column faces have effective role in order to decrease the demands on through plate and they are impressive factors for improving the performance of the connection. Experimental analysis was conducted to elucidate the seismic behavior of this connection. The results of Experimental analysis established the effectiveness of the through plate in mitigating local stress concentrations and forming the plastic hinge zone in the beam away from the beam to column interface. The moment-rotation graphs form sub-assemblage show a desirable seismic performance of this connection
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Butt, Zeeshan; Parikh, Neehar D.; Skaro, Anton; Ladner, Daniela; Cella, David
2013-01-01
Purpose of review In this review, we briefly summarize three fruitful, emerging areas in liver transplantation research: quality of life; risk assessment; and patient safety. Our goal is to highlight recent findings in these areas, with a call for increased integration of social scientists and transplant clinicians to address how best to shape policy and improve outcomes. Recent findings After liver transplantation, recipients generally experience clinically significant, sustained improvement in their physical, social and emotional well-being. However, a sizeable minority of patients do experience excess morbidity that may benefit from ongoing surveillance and/or intervention. There is growing body of research that describes risks associated with liver transplantation, which can be useful aids to better inform decision making by patients, clinicians, payers, and policy makers. In contrast, there has been a relative lack of empirical data on transplant patient safety vulnerabilities, placing the field of surgery in stark contrast to other high risk industries, where such assessments inform continuous process improvement. Summary Health services and outcomes research has grown in importance in the liver transplantation literature, but several important questions remain unanswered that merit programmatic, interdisciplinary research. PMID:22476225
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Wakamatsu, Jun-ichi; Murakami, Naoko; Nishimura, Takanori
2015-05-01
The objective of this study was to obtain fundamental data for improving the color of meat products by using animal by-products. We investigated zinc protoporphyrin IX (ZnPP)-forming properties of various internal organs from pigs and chickens. ZnPP was formed in the liver, heart and kidney, whereas the porcine spleen and bile, which are involved in the metabolism of heme, did not have ZnPP-forming properties. The optimum pH values were different among the internal organs and the ZnPP-forming properties of porcine organs were better than those of chicken organs. The porcine liver showed the greatest ZnPP-forming properties among all of the internal organs investigated in this study. The optimum pH value for ZnPP formation in the liver was lower than that of skeletal muscle. Oxygen did not inhibit the formation of ZnPP in the liver, unlike in skeletal muscle. Animal by-products such as the liver have good ability for the formation of ZnPP and might be useful for improving the color of meat products. © 2014 Japanese Society of Animal Science.
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Intraportal islet transplantation: the impact of the liver microenvironment.
Delaune, Vaihere; Berney, Thierry; Lacotte, Stéphanie; Toso, Christian
2017-03-01
The portal vein remains the preferred site for pancreatic islet transplantation due to its easy access and low morbidity. However, despite great progress in isolation and transplantation protocols over the past few years, it is still associated with the early loss of some 50-70% of transplanted islets. The complex liver microenvironment itself presumably plays an important role in this loss. The present review focuses on the specifics of the liver microenvironment, notably the localized hepatic ischemia/reperfusion injury following transplantation, the low oxygenation of the portal vein, the instant blood-mediated inflammatory reaction, the endogenous liver immune system, and the gut-liver axis, and how they can each have an impact on the transplanted islets. It identifies the potential, or already applied, clinical interventions for improving intraportal islet survival, and pinpoints those promising areas still lacking preclinical research. Future interventions on clinical intraportal islet transplantation need to take into account the global context of the liver microenvironment, with multi-point interventions being most likely to improve early islet survival and engraftment. © 2017 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.
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Li, Wenping; Shi, Jingshan; Papa, Fabrizio; Maggi, Filippo; Chen, Xiuping
2016-01-01
Isofuranodiene is a natural sesquiterpene rich occurring in Smyrnium olusatrum, a forgotten culinary herb which was marginalised after the domestication of the improved form of celery. Our recent data showed that isofuranodiene inhibited the proliferation and induced apoptosis in cancer cells. In this study, we investigated its protective effect on d-galactosamine/lipopolysacchride (GalN/LPS)-induced liver injury in SD rats. Oral administration of isofuranodiene (20 and 50 mg/kg) dramatically inhibited GalN/LPS-induced serum elevation of aspartate aminotransferase, alanine aminotransferase and malondialdehyde levels, and significantly ameliorated liver injury as evidenced by the histological improvement in H&E staining. Furthermore, isofuranodiene treatment significantly inhibited GalN/LPS-induced mRNA expression of IL-1β, IL-6 and inducible nitric oxide synthase in liver tissues. The results from this study showed that isofuranodiene protects GalN/LPS-induced liver injury in SD rats and suggested that it may be a potential functional food ingredient for the prevention and treatment of liver diseases.
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Taut, F J H; Schmidt, H; Zapletal, C M; Thies, J C; Grube, C; Motsch, J; Klar, E; Martin, E
2001-01-01
In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P ≤ 0·02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment. PMID:11422213
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Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C.; Takei, Yoshiyuki
2013-01-01
Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183
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Li, Hanmin; Ye, Zhihua; Gao, Xiang; Zhang, Lisheng; Yao, Xin; Gu, Jianxun; Lu, Dingbo; Wan, Ming; Xiao, Lin; Cai, Wangxi; Yan, Xuesheng; Zhao, Binbin; Wu, Yu; Zhang, Jinrong
2018-01-01
The number of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) has shown a significant upward trend in recent years. However, antiviral drugs are not very effective. Regulation of liver regeneration by traditional Chinese medicine is an important way to improve clinical efficacy. This randomized controlled trial assessed the efficacy and safety of DWYG in patients with HBeAg-negative CHB. Overall, 130 subjects were randomized to (A) DWYG 1.2 g three times daily (n = 44), (B) entecavir 0.5 mg/day (n = 43) in combination with DWYG or (C) entecavir 0.5 mg/day (n = 43). The liver histological response rate was assessed as the primary efficacy endpoint. The results showed that the liver histological response rate in the combination treatment group was significantly higher than that in the group with entecavir (71.43% versus 22.22%; P = 0.036) after 48 weeks of treatment. And the pathological progression rate of liver in the group with DWYG was significantly lower than that of the entecavir group during 228 weeks of follow-up (0% versus 60.00%; P = 0.019). No significant adverse events occurred during the study. In conclusion, treating HBeAg-negative CHB with DWYG is safe and effective to improve liver histological response.
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Particle detector spatial resolution
Perez-Mendez, V.
1992-12-15
Method and apparatus for producing separated columns of scintillation layer material, for use in detection of X-rays and high energy charged particles with improved spatial resolution is disclosed. A pattern of ridges or projections is formed on one surface of a substrate layer or in a thin polyimide layer, and the scintillation layer is grown at controlled temperature and growth rate on the ridge-containing material. The scintillation material preferentially forms cylinders or columns, separated by gaps conforming to the pattern of ridges, and these columns direct most of the light produced in the scintillation layer along individual columns for subsequent detection in a photodiode layer. The gaps may be filled with a light-absorbing material to further enhance the spatial resolution of the particle detector. 12 figs.
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Nie, Feng; Hao, Liang; Gao, Mei; Wu, Yingchun; Li, Xinsheng; Yu, Sha
2011-01-01
The Cu(2+)-imprinted cross-linked chitosan resin was synthesized and the binding characteristic of the resin to Cu(2+) was evaluated. The prepared resin was packed into a micro-glass column and used as micro-separating column. The micro-separating column was connected into the chemiluminescence flow system and placed in front of the window of the photomultiplier tube. Based on the luminol-hydrogen peroxide chemiluminescence system, a flow injection online chemiluminescence method for determination of trace copper was developed and trace Cu(2+) in complex samples was successfully determined. The proposed method improved the shortcomings of chemiluminescence method's poor selectivity. Copyright © 2010 John Wiley & Sons, Ltd.
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Particle detector spatial resolution
Perez-Mendez, Victor
1992-01-01
Method and apparatus for producing separated columns of scintillation layer material, for use in detection of X-rays and high energy charged particles with improved spatial resolution. A pattern of ridges or projections is formed on one surface of a substrate layer or in a thin polyimide layer, and the scintillation layer is grown at controlled temperature and growth rate on the ridge-containing material. The scintillation material preferentially forms cylinders or columns, separated by gaps conforming to the pattern of ridges, and these columns direct most of the light produced in the scintillation layer along individual columns for subsequent detection in a photodiode layer. The gaps may be filled with a light-absorbing material to further enhance the spatial resolution of the particle detector.
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Xiang, Junxi; Liu, Peng; Zheng, Xinglong; Dong, Dinghui; Fan, Shujuan; Dong, Jian; Zhang, Xufeng; Liu, Xuemin; Wang, Bo; Lv, Yi
2017-10-01
Weak mechanical property and unstable degradation rate limited the application of decellularized liver matrix in tissue engineering. The aim of this study was to explore a new method for improving the mechanical properties, anti-degeneration and angiogenic capability of decellularized liver matrix. This was achieved by a novel approach using riboflavin/ultraviolet A treatment to induce collagen cross-linking of decellularized matrix. Histological staining and scanning electron microscope showed that the diameter of cross-linked fibers significantly increased compared with the control group. The average peak load and Young's modulus of decellularized matrix were obviously improved after cross-linking. Then we implanted the modified matrix into the rat hepatic injury model to test the anti-degeneration and angiogenic capability of riboflavin/UVA cross-linked decellularized liver scaffolds in vivo. The results indicated that cross-linked scaffolds degrade more slowly than those in the control group. In the experiment group, average microvessel density in the implanted matrix was higher than that in the control group since the first week after implantation. In conclusion, we initiated the method to improve the biomechanical properties of decellularized liver scaffolds by riboflavin/UVA cross-linking, and more importantly, its improvement on anti-degeneration and angiogenesis was identified. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2662-2669, 2017. © 2017 Wiley Periodicals, Inc.
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Experimental analysis of robot-assisted needle insertion into porcine liver.
Wang, Wendong; Shi, Yikai; Goldenberg, Andrew A; Yuan, Xiaoqing; Zhang, Peng; He, Lijing; Zou, Yingjie
2015-01-01
How to improve placement accuracy of needle insertion into liver tissue is of paramount interest to physicians. A robot-assisted system was developed to experimentally demonstrate its advantages in needle insertion surgeries. Experiments of needle insertion into porcine liver tissue were performed with conic tip needle (diameter 8 mm) and bevel tip needle (diameter 1.5 mm) in this study. Manual operation was designed to compare the performance of the presented robot-assisted system. The real-time force curves show outstanding advantages of robot-assisted operation in improving the controllability and stability of needle insertion process by comparing manual operation. The statistics of maximum force and average force further demonstrates robot-assisted operation causes less oscillation. The difference of liver deformation created by manual operation and robot-assisted operation is very low, 1 mm for average deformation and 2 mm for maximum deformation. To conclude, the presented robot-assisted system can improve placement accuracy of needle by stably control insertion process.
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Sheridan, David A; Aithal, Guru; Alazawi, William; Allison, Michael; Anstee, Quentin; Cobbold, Jeremy; Khan, Shahid; Fowell, Andrew; McPherson, Stuart; Newsome, Philip N; Oben, Jude; Tomlinson, Jeremy; Tsochatzis, Emmanouil
2017-10-01
Guidelines for the assessment of non-alcoholic fatty liver disease (NAFLD) have been published in 2016 by National Institute for Health and Care Excellence and European Associations for the study of the Liver-European Association for the study of Diabetes-European Association for the study of Obesity. Prior to publication of these guidelines, we performed a cross-sectional survey of gastroenterologists and hepatologists regarding NAFLD diagnosis and management. An online survey was circulated to members of British Association for the Study of the Liver and British Society of Gastroenterology between February 2016 and May 2016. 175 gastroenterologists/hepatologists responded, 116 completing the survey, representing 84 UK centres. 22% had local NAFLD guidelines. 45% received >300 referrals per year from primary care for investigation of abnormal liver function tests (LFTs). Clinical assessment tended to be performed in secondary rather than primary care including body mass index (82% vs 26%) and non-invasive liver screen (86% vs 32%) and ultrasound (81% vs 37%). Widely used tools for non-invasive fibrosis risk stratification were aspartate transaminase (AST)/alanine transaminase (ALT) ratio (53%), Fibroscan (50%) and NAFLD fibrosis score (41%). 78% considered liver biopsy in selected cases. 50% recommended 10% weight loss target as first-line treatment. Delivery of lifestyle interventions was mostly handed back to primary care (56%). A minority have direct access to community weight management services (22%). Follow-up was favoured by F3/4 fibrosis (72.9%), and high-risk non-invasive fibrosis tests (51%). Discharge was favoured by simple steatosis at biopsy (30%), and low-risk non-invasive scores (25%). The survey highlights areas for improvement of service provision for NAFLD assessment including improved recognition of non-alcoholic steatohepatitis in people with type 2 diabetes, streamlining abnormal LFT referral pathways, defining non-invasive liver fibrosis assessment tools, use of liver biopsy, managing metabolic syndrome features and improved access to lifestyle interventions.
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Zhu, Shu Yun; Dong, Ying; Tu, Jie; Zhou, Yue; Zhou, Xing Hua; Xu, Bin
2014-01-01
Background: Silybum marianum has been used as herbal medicine for the treatment of liver disease, liver cirrhosis, and to prevent liver cancer in Europe and Asia since ancient times. Silybum marianum oil (SMO), a by-product of silymarin production, is rich in essential fatty acids, phospholipids, sterols, and vitamin E. However, it has not been very good development and use. Objective: In the present study, we used olive oil as a control to investigate the antioxidant and anti-aging effect of SMO in D-galactose (D-gal)-induced aging mice. Materials and Methods: D-gal was injected intraperitoneally (500 mg/kg body weight daily) for 7 weeks while SMO was simultaneously administered orally. The triglycerides (TRIG) and cholesterol (CHOL) levels were estimated in the serum. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), monoamine oxidase (MAO), malondialdehyde (MDA), caspase-3, and Bcl-2 were determined in the liver and brain. The activities of Na+-K+-adenosine triphosphatase (ATPase), Ca2+-Mg2+-ATPase, membrane potential (ΔΨm), and membrane fluidity of the liver mitochondrial were estimated. Results: SMO decreased levels of TRIG and CHOL in aging mice. SMO administration elevated the activities of SOD, GSH-Px, and T-AOC, which are suppressed by aging. The levels of MAO and MDA in the liver and brain were reduced by SMO administration in aging mice. Enzyme linked immunosorbent assay showed that SMO significantly decreased the concentration of caspase-3 and improved the activity of Bcl-2 in the liver and brain of aging mice. Furthermore, SMO significantly attenuated the D-gal induced liver mitochondrial dysfunction by improving the activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, membrane potential (ΔΨm), and membrane fluidity. Conclusion: These results indicate that SMO effectively attenuated oxidative damage and improved apoptosis related factors as well as liver mitochondrial dysfunction in aging mice. PMID:24914315
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Improved outcomes in the non-operative management of liver injuries
Saltzherr, Teun Peter; van der Vlies, Cees H; van Lienden, Krijn P; Beenen, Ludo F M; Ponsen, Kees Jan; van Gulik, Thomas M; Goslings, J Carel
2011-01-01
Objectives Non-operative management has become the treatment of choice in the majority of liver injuries. The aim of this study was to assess the changes in primary treatment and outcomes in a single Dutch Level 1 trauma centre with wide experience in angio-embolisation (AE). Methods The prospective trauma registry was retrospectively analysed for 7-year periods before (Period 1) and after (Period 2) the introduction of AE. The primary outcome was the failure rate of primary treatment defined as liver injury-related death or re-bleeding requiring radiologic or operative (re)interventions. Secondary outcomes were liver injury-related intra-abdominal complications. Results Despite an increase in high-grade liver injuries, the incidence of primary non-operative management more than doubled over the two periods, from 33% (20 of 61 cases) in Period 1 to 72% (84 of 116 cases) in Period 2 (P < 0.001). The failure rate of primary treatment in Period 1 was 18% (11/61), compared with 11% (13/116) in Period 2 (P = 0.21). Complication rates were 23% (14/61) and 16% (18/116) in Periods 1 and 2, respectively (P = 0.22). Liver-related mortality rates were 10% (6/61) and 3% (4/116) in Periods 1 and 2, respectively (P = 0.095). The increase in the frequency of non-operative management was even higher in high-grade injuries, in which outcomes were improved. In high-grade injuries in Periods 1 and 2, failure rates decreased from 45% (9/20) to 20% (11/55) (P = 0.041), liver-related mortality decreased from 30% (6/20) to 7% (4/55) (P = 0.019) and complication rates fell from 60% (12/20) to 27% (15/55) (P = 0.014). Liver infarction or necrosis and abscess formation seemed to occur more frequently with AE. Conclusions Overall, liver-related mortality, treatment failure and complication rates remained constant despite an increase in non-operative management. However, in high-grade injuries outcomes improved after the introduction of AE. PMID:21492335
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Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Mizuno, Kazuyuki; Sone, Yasuhiro; Kataoka, Saki; Hashinokuchi, Shinichi
2017-12-01
There is insufficient research on whether direct-acting antiviral (DAA) therapy can improve liver fibrosis in patients with chronic hepatitis C virus (HCV). We evaluated sequential changes in liver stiffness using shear wave elastography in patients with HCV who received DAA therapy. A total of 210 patients with HCV who received daclatasvir and asunaprevir therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness, as evaluated by shear wave elastography, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), and at 24 weeks after EOT (SVR24). Alanine aminotransferase levels (ALT) decreased over time, and there were significant differences between baseline and EOT and between EOT and SVR24. Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to SVR24. The median (interquartile range) liver stiffness values at baseline, EOT, and SVR24 were 10.2 (7.7-14.7), 8.8 (7.1-12.1), and 7.6 (6.3-10.3) kPa, respectively (P < 0.001, baseline vs EOT; P < 0.001, EOT vs SVR24). Additionally, in patients with ALT ≤ 30 (indicating low necroinflammatory activity in the liver) and Fibrosis-4 index > 2.0 (n = 75), the liver stiffness values at baseline, EOT, and SVR24 were 9.6 (7.7-15.2), 9.2 (7.3-12.1), and 7.7 (6.3-10.1) kPa, respectively (P < 0.001, baseline vs EOT; P < 0.001, EOT vs SVR24). These results suggest that early improvement of liver stiffness starts during the administration of DAAs in patients who achieve SVR, and this effect is particularly pronounced in patients with progressive liver fibrosis. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
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Zhang, Qing; Guan, Yanxing; Xiang, Tianxin; Liu, Shaozheng; Chen, Qingjie; Zhang, Qing
2017-02-01
The treatment of hyperthyroidism associated with severe liver dysfunction (LD) is a clinical challenge, and there has been no unified examination of this problem. The objective of this study was to assess the efficacy and safety of radioiodine ( 131 I) in combination with a molecular adsorbent recirculating system (MARS) for the treatment of hyperthyroidism complicated by severe liver LD. A total of 116 hyperthyroidism patients with concomitant LD who received MARS treatment were studied retrospectively. The patients were grouped according to whether or not they also received 131 I treatment: Group 1 (59 patients) received 131 I following MARS treatment, while Group 2 (57 cases) received only MARS. Clinical outcomes, including thyroid hormone levels, liver function parameters, and therapeutic efficacy were calculated. The overall response rate was significantly greater in Group 1 than in Group 2 (P<.01). The clinical indicators improved significantly in both groups 3 months after treatment compared with before treatment (P<.05), but Group 1 showed a greater improvement. Compared with Group 1, patients in Group 2 had a longer stay in hospital (P<.05), and received more frequent MARS treatments (P<.05). The combination of MARS and 131 I for the treatment of hyperthyroidism complicated by severe LD was effective and safe. The use of this system could rapidly improve liver function and metabolism, allowing 131 I therapy to be applied as early as possible with a shortened recovery time of liver function. ALSS = artificial liver support system ALT = alanine transaminase AST = aspartate transaminase ATD = antithyroid drugs DBil = direct bilirubin FT3 = free tri-iodothyronine FT4 = free thyroxine 131 I = radioiodine INR = international normalized ratio LD = liver dysfunction MARS = molecular adsorbent recirculating system MELD = model for end-stage liver disease PT = prothrombin time TBil = total bilirubin TSH = thyroid-stimulating hormone.
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Edlund, Per Olof; Baranczewski, Pawel
2004-03-10
The metabolism of the 5HT2c agonist BVT.2938, 1-(3-[2-[(2-ethoxy-3-pyridinyl)oxy]ethoxy]-2-pyrazinyl)-2(R)-methylpiperazine, was studied in vitro by incubation with rat, monkey and human liver microsomes as well as cryopreserved hepatocytes, followed by liquid chromatography/mass spectrometry (LC/MS) and LC/MS/MS analysis on a quadrupole-time of flight mass spectrometer for structural elucidation. Deuterium exchange on column was used to differentiate between hydroxylation and N-oxidation. Liver microsomes were incubated in two different buffer systems with optimum conditions for cytochrome P450 activity or UDP-glucuronosyltransferase activity. The major phase I metabolites of BVT.2938 originated from O-deethylation of the pyridine ring, O-dealkylation of the ethylene bridge, pyrazine ring hydroxylation, hydroxylation of pyridine ring and piperazine ring N-hydroxylation. When a hydrogen carbonate buffer system was supplemented with UDPGA, the piperazine carbamoyl-glucuronide from the parent compound was identified together with several glucuronides of the phase I metabolites. The metabolite pattern in hepatocytes was similar to microsomes except that the sulphate at the N-position of the piperazine ring of BVT.2938 was identified, while the carbamoyl-glucuronide was missing. Excellent correlation was obtained between radioactivity detection and the chemiluminescent nitrogen detector when the nitrogen content of the analytes was taken into account.
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Zhu, Pingping; Yue, Zhenfeng; Zheng, Zongkun; Zhang, Yi; Li, Wenyin; Zhao, Fengjuan; Xiao Chengui; Bai, Runye; Lin, Wei
2015-05-01
A method was developed for the determination of 19 perfluoroalkyl acids (PFAs) in lamb liver by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS) combined with dispersive solid phase extraction. The sample was extracted with acidified acetonitrile, and then cleaned-up by a mixture of N-propylethylenediamine (PSA), C18 and graphitized carbon black (GCB) sorbents. The 19 PFAs were analyzed by HPLC-MS/MS with a C18 chromatographic column, adopting the multiple reaction monitoring (MRM) mode with negative electrospray ionization. The effects of the dosages of hydrochloric acid and the sorbents on the recoveries of the 19 PFAs were studied. For accurate quantitative analysis, the isotope internal standard method was used. The calibration curves were linear with the correlation coefficients over 0.998 in the range of 0.05-20 µg/kg for the 19 PFAs. The limits of detection were 0.004-0.111 µg/kg. The limits of quantification were 0.012-0.370 µg/kg. The mean recoveries of the 19 PFAs at spiked levels of 0.5, 1.0, 2.0 µg/kg were in the range from 80% to 128% with the relative standard deviations of 0.31%-11.1%. The developed method is rapid, simple, accurate. It is suitable for the determination of the 19 PFAs in large quantities of lamb liver samples.
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NASA Astrophysics Data System (ADS)
Ma, Weiwei; Wan, Xiuquan; Wang, Zhankun; Liu, Yulong; Wan, Kai
2017-12-01
The influence of high-frequency atmospheric forcing on the formation of a well-mixed summer warm water column in the central Bohai Sea is investigated comparing model simulations driven by daily surface forcing and those using monthly forcing data. In the absence of high-frequency atmospheric forcing, numerical simulations have repeatedly failed to reproduce this vertically uniform column of warm water measured over the past 35 years. However, high-frequency surface forcing is found to strongly influence the structure and distribution of the well-mixed warm water column, and simulations are in good agreement with observations. Results show that high frequency forcing enhances vertical mixing over the central bank, intensifies downward heat transport, and homogenizes the water column to form the Bohai central warm column. Evidence presented shows that high frequency forcing plays a dominant role in the formation of the well-mixed warm water column in summer, even without the effects of tidal and surface wave mixing. The present study thus provides a practical and rational way of further improving the performance of oceanic simulations in the Bohai Sea and can be used to adjust parameterization schemes of ocean models.
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McGettigan, Brett M; McMahan, Rachel H; Luo, Yuhuan; Wang, Xiaoxin X; Orlicky, David J; Porsche, Cara; Levi, Moshe; Rosen, Hugo R
2016-10-28
Bile acid sequestrants are synthetic polymers that bind bile acids in the gut and are used to treat dyslipidemia and hyperphosphatemia. Recently, these agents have been reported to lower blood glucose and increase insulin sensitivity by altering bile acid signaling pathways. In this study, we assessed the efficacy of sevelamer in treating mice with non-alcoholic fatty liver disease (NAFLD). We also analyzed how sevelamer alters inflammation and bile acid signaling in NAFLD livers. Mice were fed a low-fat or Western diet for 12 weeks followed by a diet-plus-sevelamer regimen for 2 or 12 weeks. At the end of treatment, disease severity was assessed, hepatic leukocyte populations were examined, and expression of genes involved in farnesoid X receptor (FXR) signaling in the liver and intestine was analyzed. Sevelamer treatment significantly reduced liver steatosis and lobular inflammation. Sevelamer-treated NAFLD livers had notably fewer pro-inflammatory infiltrating macrophages and a significantly greater fraction of alternatively activated Kupffer cells compared with controls. Expression of genes involved in FXR signaling in the liver and intestine was significantly altered in mice with NAFLD as well as in those treated with sevelamer. In a mouse model of NAFLD, sevelamer improved disease and counteracted innate immune cell dysregulation in the liver. This study also revealed a dysregulation of FXR signaling in the liver and intestine of NAFLD mice that was counteracted by sevelamer treatment. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
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[Therapeutic effect of saxagliptin in rat models of nonalcoholic fatty liver and type 2 diabetes].
Liu, Yan; Zhang, Zhen; Chen, Rongping; Sun, Jia; Chen, Hong
2014-06-01
To observe the therapeutic effect of saxagliptin in a rat model of nonalcoholic fatty liver and type 2 diabetes and investigate the possible mechanism. Rats models of nonalcoholic fatty liver and type 2 diabetes established by feeding on a high glucose and fat diet and streptozotocin injection were treated with saxagliptin (daily dose of 10 mg/kg) gavage for 8 weeks, using saline as the control. After the treatment, fasting blood glucose, serum insulin, blood lipids, liver function, liver oxidative indices, and hepatic pathologies were evaluated in all the rats, and the expressions of Bcl-2 and Bax in the liver tissue were detected with immunohistochemistry and Western blotting. Compared with the model group, saxagliptin intervention significantly reduced blood glucose and HOMA-IR, improved the liver function and SOD activity (P<0.01), lowered the liver weight, liver index (P<0.01) and MDA level (P<0.05), and slightly lowered the body weight and blood lipids (P>0.05); AST level was similar between the normal control group and saxagliptin intervention group (P>0.05). HE and oil red staining showed obvious hepatic pathologies in the model group, and saxagliptin intervention significantly reduced lipid droplets in the hepatocytes and improved the structural damage of the liver. Hepatic Bax expression significantly increased and Bcl-2 expression decreased in the model group, and these changes were reversed by saxagliptin. Saxagliptin shows good therapeutic effect in rat models of nonalcoholic fatty liver and type 2 diabetes possibly by controlling blood glucose, lowering insulin resistance, alleviating hepatic oxidative stress and hepatocyte damage, and regulating the expression of apoptosis-related proteins.
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Compagnon, Philippe; Levesque, Eric; Hentati, Hassen; Disabato, Mara; Calderaro, Julien; Feray, Cyrille; Corlu, Anne; Cohen, José Laurent; Ben Mosbah, Ismail; Azoulay, Daniel
2017-07-01
Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. Cardiac arrest was induced in female large white pigs by intravenous injection of potassium chloride. After 60 minutes of WI, livers were flushed in situ with histidine-tryptophan-ketoglutarate and subsequently preserved either by simple cold storage (WI-SCS group) or HMP (WI-HMP group) using Belzer-MPS solution. Liver grafts procured from heart-beating donors and preserved by SCS served as controls. After 4 hours of preservation, all livers were transplanted. All recipients in WI-SCS group died within 6 hours after transplantation. In contrast, the HMP device fully protected the liver against lethal ischemia/reperfusion injury, allowing 100% survival rate. A postreperfusion syndrome was observed in all animals of the WI-SCS group but none of the control or WI-HMP groups. After reperfusion, HMP-preserved livers functioned better and showed less hepatocellular and endothelial cell injury, in agreement with better-preserved liver histology relative to WI-SCS group. In addition to improved energy metabolism, this protective effect was associated with an attenuation of inflammatory response, oxidative load, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. This study demonstrates for the first time the efficacy of the HMP Airdrive system to protect liver grafts from lethal ischemic damage before transplantation in a clinically relevant DCD model.
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Yu, Haoyong; Jia, Weiping; Guo, ZengKui
2014-09-01
Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. eight non-diabetic obese adults were restricted for daily energy intake (800 kcal) and low carbohydrate (<10%) for 8 weeks. Body compositions, liver fat and hepatic glucose production (HGP) and peripheral glucose disposal before and after the intervention were determined. the caloric restriction reduced liver fat content by 2/3 (p = 0.004). Abdominal subcutaneous and visceral fat, body weight, BMI, waist circumference and fasting plasma triglyceride and free fatty acid concentrations all significantly decreased (p < 0.05). The suppression of post-load HGP was improved by 22% (p = 0.002) whereas glucose disposal was not affected (p = 0.3). Fasting glucose remained unchanged and the changes in the 2-hour plasma glucose and insulin concentration were modest and statistically insignificant (p > 0.05). Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment.
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Haufe, Sven; Haas, Verena; Utz, Wolfgang; Birkenfeld, Andreas L; Jeran, Stephanie; Böhnke, Jana; Mähler, Anja; Luft, Friedrich C; Schulz-Menger, Jeanette; Boschmann, Michael; Jordan, Jens; Engeli, Stefan
2013-11-01
Weight loss reduces abdominal and intrahepatic fat, thereby improving metabolic and cardiovascular risk. Yet, many patients regain weight after successful diet-induced weight loss. Long-term changes in abdominal and liver fat, along with liver test results and insulin resistance, are not known. We analyzed 50 overweight to obese subjects (46 ± 9 years of age; BMI, 32.5 ± 3.3 kg/m2; women, 77%) who had participated in a 6-month hypocaloric diet and were randomized to either reduced carbohydrates or reduced fat content. Before, directly after diet, and at an average of 24 (range, 17-36) months follow-up, we assessed body fat distribution by magnetic resonance imaging and markers of liver function and insulin resistance. Body weight decreased with diet but had increased again at follow-up. Subjects also partially regained abdominal subcutaneous and visceral adipose tissue. In contrast, intrahepatic fat decreased with diet and remained reduced at follow-up (7.8 ± 9.8% [baseline], 4.5 ± 5.9% [6 months], and 4.7 ± 5.9% [follow-up]). Similar patterns were observed for markers of liver function, whole-body insulin sensitivity, and hepatic insulin resistance. Changes in intrahepatic fat und intrahepatic function were independent of macronutrient composition during intervention and were most effective in subjects with nonalcoholic fatty liver disease at baseline. A 6-month hypocaloric diet induced improvements in hepatic fat, liver test results, and insulin resistance despite regaining of weight up to 2 years after the active intervention. Body weight and adiposity measurements may underestimate beneficial long-term effects of dietary interventions.
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Koch, Wendelin; Forcisi, Sara; Lehmann, Rainer; Schmitt-Kopplin, Philippe
2014-09-26
The application of ammonia acetate buffered liquid chromatography (LC) eluents is known to concomitantly lead to ion suppression when electrospray ionization mass spectrometry (ESI-MS) detection is used. In negative ESI mode, post column infusion of 2-(2-methoxyethoxy)ethanol (2-MEE) was shown in the literature to help to compensate this adverse effect occurring in reversed phase liquid chromatography mass spectrometry (RP-LC-MS) analyses. Here a setup of direct infusion and hydrophilic interaction chromatography (HILIC) post-column infusion experiments was established in order to investigate systematically the beneficial effects of 2-MEE. We demonstrate that, 2-MEE can help to improve ESI-MS sensitivity in HILIC too and reveal analyte structure specific behaviors. Our study indicates that 2-MEE especially improves ESI response for small and polar molecules. The ESI response of stable isotope labeled amino acids spiked into biological matrices increases up to 50-fold (i.e. D5-l-glutamic acid) when post column infusion of 2-MEE is applied. A non-targeted analysis of a pooled urine sample via HILIC-ESI-QTOF-MS supports this hypothesis. In direct infusion, the combined application of an ammonia acetate buffered solution together with 2-MEE results in an improved ESI response compared to a non-buffered solution. We observed up to 60-fold increased ESI response of l-lysine. We propose this effect is putatively caused by the formation of smaller ESI droplets and stripping of positive charge from ESI droplets due to evaporation of acetic acid anions. In summary, post-column infusion of 2-MEE especially enhances ESI response of small and polar molecules. Therefore it can be regarded as a valuable add-on in targeted or non-targeted metabolomic HILIC-MS studies since this method sets a focus on this molecule category. Copyright © 2014 Elsevier B.V. All rights reserved.
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Improving Standoff Bombing Capacity in the Face of Anti-Access Area Denial Threats
2015-09-01
Make a charitable contribution Limited Electronic Distribution Rights This document and trademark(s) contained herein are protected by law as...of the RAND Corporation. CHILDREN AND FAMILIES EDUCATION AND THE ARTS ENERGY AND ENVIRONMENT HEALTH AND HEALTH CARE INFRASTRUCTURE AND...Variables With (Left Column) and Without ( Right Column) Natural Log Transformation
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Critical Thinking: Strategies for Improving Student Learning, Part II
ERIC Educational Resources Information Center
Paul, Richard; Elder, Linda
2008-01-01
In the last column we focused (as a primary goal of instruction) on the importance of teaching so that students learn to think their way into and through content. We stressed the need for well-designed daily structures and tactics for fostering deep learning, offering three strategies as examples. In this column, we provide four additional…
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Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention.
Otten, J; Mellberg, C; Ryberg, M; Sandberg, S; Kullberg, J; Lindahl, B; Larsson, C; Hauksson, J; Olsson, T
2016-05-01
Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention. An ad libitum Paleolithic diet (PD) was compared with a conventional low-fat diet (LFD). Seventy healthy, obese, postmenopausal women were randomized to either a PD or a conventional LFD. Diet intakes were ad libitum. Liver fat was measured with proton magnetic resonance spectroscopy. Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as homeostasis model assessment-insulin resistance (HOMA-IR)/liver insulin resistance (Liver IR) index for hepatic insulin sensitivity and oral glucose insulin sensitivity (OGIS)/Matsuda for peripheral insulin sensitivity. All measurements were performed at 0, 6 and 24 months. Forty-one women completed the examinations for liver fat and were included. Liver fat decreased after 6 months by 64% (95% confidence interval: 54-74%) in the PD group and by 43% (27-59%) in the LFD group (P<0.01 for difference between groups). After 24 months, liver fat decreased 50% (25-75%) in the PD group and 49% (27-71%) in the LFD group. Weight reduction between baseline and 6 months was correlated to liver fat improvement in the LFD group (rs=0.66, P<0.01) but not in the PD group (rs=0.07, P=0.75). Hepatic insulin sensitivity improved during the first 6 months in the PD group (P<0.001 for Liver IR index and HOMA-IR), but deteriorated between 6 and 24 months without association with liver fat changes. A PD with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional LFD at 6 months. This difference may be due to food quality, for example, a higher content of mono- and polyunsaturated fatty acids in the PD. Changes in liver fat did not associate with alterations in insulin sensitivity.
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Hepatic Resection for Liver Metastases from Cervical Cancer Is Safe and May Have Survival Benefit.
Bacalbasa, Nicolae; Balescu, Irina; Dima, Simona; Popescu, Irinel
2016-06-01
The goal of this study was to evaluate the single-centre experience with hepatectomy for liver metastases from cervical cancer (CCLM). Fifteen patients who underwent such surgery at the Fundeni Clinical Hospital between January 2002 and April 2014 were retrospectively reviewed. Liver lesions diagnosed at more than 6 months from cervical cancer diagnosis were classified as metachronous lesions, while lesions occurring within the first 6 months were considered synchronous lesions. Two patients were diagnosed with synchronous CCLM, while the other 13 patients had metachronous. Early postoperative death occurred in a single patient with metachronous liver metastases and pelvic recurrence, but this was not related to liver surgery. The median overall survival for the entire cohort was 18 months from the time of liver resection; patients with metachronous lesions had an improved outcome when compared to those with synchronous lesions. In patients with metachronous liver metastases, prognostic factors associated with an improved outcome were the general biological status of the patient, grade of tumoural differentiation and absence of other abdomino-pelvic recurrences. In multivariate analysis, only the grade of differentiation was statistically significant. In conclusion, hepatic resection for liver metastases from cervical cancer can be performed safely, may prove effective, and should be part of the multimodal treatment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
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Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen
2012-01-01
Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664
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High intensity interval training improves liver and adipose tissue insulin sensitivity.
Marcinko, Katarina; Sikkema, Sarah R; Samaan, M Constantine; Kemp, Bruce E; Fullerton, Morgan D; Steinberg, Gregory R
2015-12-01
Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine-alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.
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Matthiesen, T h; Sallmann, H P; Heimann, W; Kunstýr, I
1976-01-01
In newborn guinea pigs the structural development of the liver was studied with emphasis on changes in the lipid content as related to biochemical parameters. The livers of 149 guinea pigs (strain PIRBRIGHT) up to an age of 21 days were examined. The mothers were grouped in cages and kept as usual (room temperature 22 degrees C, air humidity 60-70%, natural light-dark rhythm and commercial standard diet ad libitum, sawdust and straw as bedding). Pregnant animals were placed in individual cages being left there together with their offspring until weaning or sacrification. In this period additional uptake of solid diet was allowed to the guinea pigs. The animals were bleeded to death in anesthesia (by head stroke). For histological examination tissue samples from the Lobes sinister lateralis were fixed in Barker's formol or absolute alcohol. The following staining reactions were applied (paraffin embedding or frozen sections): haemalum-eosin stain; PAS-reaction; Sudan III; Sudan black; Best's carmine (for details on the techniques see ROMEIS 1968). In biochemical analysis the total lipids of the liver were determined by the isolation methods reported by FOLCH et al.(1957). Moreover, in modification of the analytical procedures earlier described (SALLMANN 1972 a, b) several fractions of the liver total lipids could be isolated. By dialysis against a rubber membrane a dialysable lipid component (hydrocarbons, triglycerides, incomplete glycerides, cholesterol and free lipid acids) was isolated from the phosphatide fractions. Further separation of the "dialysable" lipids on Florisil columns yielded purified glyceride fractions. The total lipids as well as all components isolated from these were determined gravimetrically after removal of the solvents concerned. In biochemical analysis the livers of fetuses 10-12 days ante partum and of young animals up to 53 days were included. Results (see also table 1): The relative liver weight--related to the body weight reduced for that of the gastrointestinal tract--is highest at birth. It is lowered independent of the development of the gastrointestinal tract within a short period, then it remains fairly constant during the rest of the time of observation. On the 1st day abundant lipids are regularly distributed throughout the whole liver lobule (fig. 1). Beginning with the 3rd day the central parts of the lobules are nearly free from lipids, only in the peripheral zones of the lobules lipid augmentation was still observed. Consequently the marked decrease in liver weight is due to the rapid reduction of lipids within the first 3 days of life. These observations are in accordance with the biochemical findings: about 10 days ante partum noticeable storage of lipids occurs in the liver reaching its peak 2 to 3 days after birth (physiological fatty infiltration of the liver during the last days of intrauterine life). In fetal liver tissue predominantly tryglycerides are augmented.
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Improved Signal Chains for Readout of CMOS Imagers
NASA Technical Reports Server (NTRS)
Pain, Bedabrata; Hancock, Bruce; Cunningham, Thomas
2009-01-01
An improved generic design has been devised for implementing signal chains involved in readout from complementary metal oxide/semiconductor (CMOS) image sensors and for other readout integrated circuits (ICs) that perform equivalent functions. The design applies to any such IC in which output signal charges from the pixels in a given row are transferred simultaneously into sampling capacitors at the bottoms of the columns, then voltages representing individual pixel charges are read out in sequence by sequentially turning on column-selecting field-effect transistors (FETs) in synchronism with source-follower- or operational-amplifier-based amplifier circuits. The improved design affords the best features of prior source-follower-and operational- amplifier-based designs while overcoming the major limitations of those designs. The limitations can be summarized as follows: a) For a source-follower-based signal chain, the ohmic voltage drop associated with DC bias current flowing through the column-selection FET causes unacceptable voltage offset, nonlinearity, and reduced small-signal gain. b) For an operational-amplifier-based signal chain, the required bias current and the output noise increase superlinearly with size of the pixel array because of a corresponding increase in the effective capacitance of the row bus used to couple the sampled column charges to the operational amplifier. The effect of the bus capacitance is to simultaneously slow down the readout circuit and increase noise through the Miller effect.
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Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie
Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulatingmore » glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver. ► Nrf2 deficiency improves glucose tolerance by influencing Fgf21 and insulin signaling.« less
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Hou, Jin-Lin; Xu, Daozheng; Shi, Guangfeng; Wan, Mobin; Goodman, Zachary; Tan, Deming; Xie, Qing; Chen, Chengwei; Wei, Lai; Niu, Junqi; Wang, Qinhuan; Ren, Hong; Wang, Yuming; Jia, Jidong; Bao, Weibin; Dong, Yuhong; Trylesinski, Aldo; Naoumov, Nikolai V
2015-08-01
The long-term goal of chronic hepatitis B (CHB) treatment is improvement of liver disease and prevention of cirrhosis. The aim of this study was to assess whether prolonged telbivudine treatment improves liver inflammation and fibrosis. The primary objective was to evaluate the proportion of patients with absence/minimal inflammation (Knodell necroinflammatory score ≤3) on liver biopsy at Year 5. Fifty-seven patients aged 16-70 years with a clinical history of CHB and active viral replication (38 hepatitis B e antigen [HBeAg] positive and 19 HBeAg negative) were followed for 6 years: 33 received telbivudine 600 mg/day continuously for 5 years; 24 received lamivudine 100 mg/day for 2 years and then telbivudine for 3 years. Liver biopsies were taken pre-treatment and after 5 years of treatment. At baseline, mean (standard deviation) serum hepatitis B virus (HBV) DNA load was 8.5 (1.7) log10 copies/mL, Knodell necroinflammatory score was 7.6 (2.9), and Ishak fibrosis score was 2.2 (1.1). After antiviral treatment (median duration: 261 weeks), liver histology improved with increased proportions of patients with absence/minimal liver inflammation (Knodell necroinflammatory score ≤3), from 16% (9/57) at baseline to 98% (56/57), and absence/minimal fibrosis (Ishak score ≤1), from 25% (14/57) at baseline to 84% (48/57). At Year 5, HBV DNA load was <300 copies/mL for all patients; cumulative HBeAg loss and seroconversion rates were 88% and 77%, respectively. At Year 6, 95% of patients with abnormal baseline glomerular filtration rate (60-90 mL/min/1.73 m(2)) improved to normal GFR (>90 mL/min/1.73 m(2)). Long-term telbivudine treatment with profound and durable viral suppression significantly improved liver histology, thus achieving the long-term goals of CHB treatment. FibroScan(®) results after 5 and 6 years of treatment (in almost 20% of patients) were consistent with this information. Novartis and National Science and Technology Major Project (2012ZX10002003). ClinicalTrials.gov # NCT00877149.
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Quantification of Liver Iron with MRI: State of the Art and Remaining Challenges
Hernando, Diego; Levin, Yakir S; Sirlin, Claude B; Reeder, Scott B
2015-01-01
Liver iron overload is the histological hallmark of hereditary hemochromatosis and transfusional hemosiderosis, and can also occur in chronic hepatopathies. Iron overload can result in liver damage, with the eventual development of cirrhosis, liver failure and hepatocellular carcinoma. Assessment of liver iron levels is necessary for detection and quantitative staging of iron overload, and monitoring of iron-reducing treatments. This article discusses the need for non-invasive assessment of liver iron, and reviews qualitative and quantitative methods with a particular emphasis on MRI. Specific MRI methods for liver iron quantification include signal intensity ratio as well as R2 and R2* relaxometry techniques. Methods that are in clinical use, as well as their limitations, are described. Remaining challenges, unsolved problems, and emerging techniques to provide improved characterization of liver iron deposition are discussed. PMID:24585403
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Wadhawan, Manav; Anand, Anil C
2016-03-01
Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality.
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Surgical anatomy of segmental liver transplantation.
Deshpande, R R; Heaton, N D; Rela, M
2002-09-01
The emergence of split and living donor liver transplantation has necessitated re-evaluation of liver anatomy in greater depth and from a different perspective than before. Early attempts at split liver transplantation were met with significant numbers of vascular and biliary complications. Technical innovations in this field have evolved largely by recognizing anatomical anomalies and variations at operation, and devising novel ways of dealing with them. This has led to increasing acceptance of these procedures and decreased morbidity and mortality rates, similar to those observed with whole liver transplantation. The following review is based on clinical experience of more than 180 split and living related liver transplantations in adults and children, performed over a 7-year period from 1994 to 2001. A comprehensive understanding and application of surgical anatomy of the liver is essential to improve and maintain the excellent results of segmental liver transplantation.
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Yang, Lijun; Hu, Qiaoru; Guo, Wei; Liu, Yumin; Song, Xiaohua; Zhang, Pengcheng
2011-05-01
A method for the simultaneous determination of 7 arsenic species was developed with high performance liquid chromatography and inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The sample was extracted with artificial gastric juice. The HPLC separation was performed on an anion analytical column utilizing a gradient elution program of ammonium carbonate and water as the mobile phase. Identification and quantification were achieved by ICP-MS. Good linearities of 7 arsenic species were observed in the range from 1 microg/kg to 50 microg/kg with the correlation coefficients greater than 0.999. The average recoveries of 7 arsenic species spiked at the three levels of 1, 2 and 10 microg/kg ranged from 84.3% to 106.6% with the relative standard deviations of 1.4%-4.2%. The quantification limits of 7 arsenic species were 1 microg/kg. The method was proved to be good reproducibility, high sensitivity and simple preprocessing. This method is suitable for the simultaneous determination of 7 arsenic species in chicken muscle and chicken liver.
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[Medical assessments and measurements in ELSA-Brasil].
Mill, Jose Geraldo; Pinto, Karina; Griep, Rosane Härter; Goulart, Alessandra; Foppa, Murilo; Lotufo, Paulo A; Maestri, Marcelo K; Ribeiro, Antonio Luiz; Andreão, Rodrigo Varejão; Dantas, Eduardo Miranda; Oliveira, Ilka; Fuchs, Sandra C; Cunha, Roberto de Sá; Bensenor, Isabela M
2013-06-01
The article describes assessments and measurements performed in the Brazilian Longitudinal Study for Adult Health (ELSA-Brasil). Some assessments including anthropometric assessment, casual blood pressure measurement, and ankle-brachial index have an established clinical application while others including pulse wave velocity, heart rate variability, and carotid intima-media thickness have no established application and do not have reference values for healthy Brazilian population but may be important predictors of cardiovascular outcomes. Blood pressure measurement following postural change maneuver was included in the ELSA-Brasil because it has not been much tested in epidemiological studies. Innovative approaches were developed for assessing the ankle-brachial index using an automatic device instead of the mercury column to measure blood pressure and for assessing the anterior-posterior diameter of the right lobe of the liver by ultrasound for quantitative assessment of nonalcoholic fatty liver disease. All ELSA-Brasil subjects were younger (35 years or more) than those included in other cohorts studying subclinical atherosclerosis. The inclusion of younger individuals and a variety of assessments make the ELSA-Brasil a relevant epidemiology study nationwide and worldwide.
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Supercooling Preservation Of The Rat Liver For Transplantation
Bruinsma, Bote G.; Berendsen, Tim A.; Izamis, Maria-Louisa; Yeh, Heidi; Yarmush, Martin L.; Uygun, Korkut
2015-01-01
The current standard for liver preservation is limited in duration. Employing a novel subzero preservation technique that includes supercooling and machine perfusion can significantly improve preservation and prolong storage times. By loading rat livers with cryoprotectants to prevent both intra- and extracellular ice formation and protect against hypothermic injury, livers can be cooled to −6 °C without freezing and kept viable for up to 96 hours. Here, we describe the procedures of loading cryoprotectants by means of subnormothermic machine perfusion (SNMP), controlled cooling to a supercooled state, followed by SNMP recovery and orthotopic liver transplantation. PMID:25692985
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Firu, S G; Streba, C T; Firu, D; Tache, D E; Rogoveanu, I
2015-01-01
Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker. To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis. We have searched through current literature and analyzed all significant full text articles on this topic. NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed.
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Improvement of Shear Wave Motion Detection Using Harmonic Imaging in Healthy Human Liver.
Amador, Carolina; Song, Pengfei; Meixner, Duane D; Chen, Shigao; Urban, Matthew W
2016-05-01
Quantification of liver elasticity is a major application of shear wave elasticity imaging (SWEI) to non-invasive assessment of liver fibrosis stages. SWEI measurements can be highly affected by ultrasound image quality. Ultrasound harmonic imaging has exhibited a significant improvement in ultrasound image quality as well as for SWEI measurements. This was previously illustrated in cardiac SWEI. The purpose of this study was to evaluate liver shear wave particle displacement detection and shear wave velocity (SWV) measurements with fundamental and filter-based harmonic ultrasound imaging. In a cohort of 17 patients with no history of liver disease, a 2.9-fold increase in maximum shear wave displacement, a 0.11 m/s decrease in the overall interquartile range and median SWV and a 17.6% increase in the success rate of SWV measurements were obtained when filter-based harmonic imaging was used instead of fundamental imaging. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
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Bosch-Barrera, Joaquim; Corominas-Faja, Bruna; Cuyàs, Elisabet; Martin-Castillo, Begoña; Brunet, Joan; Menendez, Javier A
2014-08-01
Silibinin exerts hepatoprotective, anti-inflammatory and anti-fibrotic effects. Several pre-clinical studies have shown anti-tumoral activity of silibinin in breast cancer cell lines. We present the case of a heavily pre-treated breast cancer patient with extensive liver infiltration. The patient presented with progressive liver failure despite several chemotherapy treatments, including paclitaxel, capecitabine and vinorelbine. After four cycles of a fourth-line chemotherapy treatment consisting of carboplatin and gemcitabine, the patient's liver blood test results deteriorated to life-threatening levels. The compassionate use of Legasil®, a new commercially available nutraceutical product containing a new silibinin formulation, was offered to the patient according to article 37 of the 2013 Declaration of Helsinki. After treatment initiation, the patient presented clinical and liver improvement, which permitted the patient to continue palliative chemotherapy. This is the first case report of a clinical benefit of silibinin administration in a breast cancer patient. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
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Gounder, Prabhu P; Haering, Celia; Bruden, Dana J T; Townshend-Bulson, Lisa; Simons, Brenna C; Spradling, Philip R; McMahon, Brian J
2018-01-01
The aspartate aminotransferase-to-platelet ratio index (APRI) and a fibrosis index calculated using platelets (FIB-4) have been proposed as noninvasive markers of liver fibrosis. To determine APRI/FIB-4 accuracy for predicting histologic liver fibrosis and evaluate whether incorporating change in index improves test accuracy in hepatitis C virus (HCV)-infected Alaska Native persons. Using liver histology as the gold standard, we determined the test characteristics of APRI to predict Metavir ≥F2 fibrosis and FIB-4 to predict Metavir ≥F3 fibrosis. Index discrimination was measured as the area under the receiver operator characteristic curve. We fit a logistic regression model to determine whether incorporating change in APRI/FIB-4 over time improved index discrimination. Among 283 participants, 46% were female, 48% had a body mass index >30, 11% had diabetes mellitus, 8% reported current heavy alcohol use. Participants were infected with HCV genotypes 1 (68%), 2 (17%), or 3 (15%). On liver histology, 30% of study participants had ≥F2 fibrosis and 15% had ≥F3 fibrosis. The positive predictive value of an APRI>1.5/FIB-4>3.25 for identifying fibrosis was 77%/78%. The negative predictive value of an APRI<0.5/FIB-4<1.45 was 91%/87%. The area under the receiver operator characteristic curve of an APRI/FIB-4 for identifying fibrosis was 0.82/0.84. Incorporating change in APRI/FIB-4 did not improve index discrimination. The accuracy of APRI/FIB-4 for identifying liver fibrosis in HCV-infected Alaska Native persons is similar to that reported in other populations and could help prioritize patients for treatment living in areas without access to liver biopsy. Change in APRI/FIB-4 was not predictive of degree of fibrosis.
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Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan
2017-12-14
To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. A CCl 4 -induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo . Functionally, the transplantation of hUC-MSCs to CCl 4 -treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl 4 -induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.
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Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan
2017-01-01
AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. METHODS A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. RESULTS We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of hUC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. CONCLUSION Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis. PMID:29290652
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Rostami-Nejad, Mohammad; Haldane, Thea; AlDulaimi, David; Alavian, Seyed Moayed; Zali, Mohammad Reza; Rostami, Kamran
2013-01-01
Context Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet. Evidence Acquisition PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified. Results Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders. Conclusions Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia. PMID:24348636
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Improved rat liver decellularization by arterial perfusion under oscillating pressure conditions.
Struecker, Benjamin; Butter, Antje; Hillebrandt, Karl; Polenz, Dietrich; Reutzel-Selke, Anja; Tang, Peter; Lippert, Steffen; Leder, Anne; Rohn, Susanne; Geisel, Dominik; Denecke, Timm; Aliyev, Khalid; Jöhrens, Korinna; Raschzok, Nathanael; Neuhaus, Peter; Pratschke, Johann; Sauer, Igor M
2017-02-01
One approach of regenerative medicine to generate functional hepatic tissue in vitro is decellularization and recellularization, and several protocols for the decellularization of livers of different species have been published. This appears to be the first report on rat liver decellularization by perfusion under oscillating pressure conditions, intending to optimize microperfusion and minimize damage to the ECM. Four decellularization protocols were compared: perfusion via the portal vein (PV) or the hepatic artery (HA), with (+P) or without (-P) oscillating pressure conditions. All rat livers (n = 24) were perfused with 1% Triton X-100 and 1% sodium dodecyl sulphate, each for 90 min with a perfusion rate of 5 ml/min. Perfusion decellularization was observed macroscopically and the decellularized liver matrices were analysed by histology and biochemical analyses (e.g. levels of DNA, glycosaminoglycans and hepatocyte growth factor). Livers decellularized via the hepatic artery and under oscillating pressure showed a more homogeneous decellularization and less remaining DNA, compared with the livers of the other experimental groups. The novel decellularization method described is effective, quick (3 h) and gentle to the extracellular matrix and thus represents an improvement of existing methodology. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.
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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. PMID:26225262
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Wang, Jing-Zhang; Xiong, Nan-Yan; Zhao, Li-Zhen; Hu, Jin-Tian; Kong, De-Cheng; Yuan, Jiang-Yong
2018-06-07
The epidemiological trend in liver diseases becomes more serious worldwide. Several recent articles published by International Journal of Surgery in 2018 particularly emphasized the encouraging clinical benefits of hepatectomy, liver regeneration and liver transplantation, however, there are still many technical bottlenecks underlying these therapeutic approaches. Remarkably, a few preliminary studies have shown some clues to the role of three-dimensional (3D) printing in improving traditional therapy for liver diseases. Here, we concisely elucidated the curative applications of 3D-printing (no cells) and 3D Bio-printing (with hepatic cells), such as 3D-printed patient-specific liver models and devices for medical education, surgical simulation, hepatectomy and liver transplantation, 3D Bio-printed hepatic constructs for liver regeneration and artificial liver, 3D-printed liver tissues for evaluating drug's hepatotoxicity, and so on. Briefly, 3D-printed liver models and bioactive tissues may facilitate a lot of key steps to cure liver disorders, predictably bringing promising clinical benefits. This work further provides novel insights into facilitating treatment of hepatic carcinoma, promoting liver regeneration both in vivo and in vitro, expanding transplantable liver resources, maximizing therapeutic efficacy as well as minimizing surgical complications, medical hepatotoxicity, operational time, economic costs, etc. Copyright © 2018. Published by Elsevier Ltd.
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Jeong, Jong Seok; Mkhoyan, K Andre
2016-06-01
Acquiring an atomic-resolution compositional map of crystalline specimens has become routine practice, thus opening possibilities for extracting subatomic information from such maps. A key challenge for achieving subatomic precision is the improvement of signal-to-noise ratio (SNR) of compositional maps. Here, we report a simple and reliable solution for achieving high-SNR energy-dispersive X-ray (EDX) spectroscopy spectrum images for individual atomic columns. The method is based on standard cross-correlation aided by averaging of single-column EDX maps with modifications in the reference image. It produces EDX maps with minimal specimen drift, beam drift, and scan distortions. Step-by-step procedures to determine a self-consistent reference map with a discussion on the reliability, stability, and limitations of the method are presented here.
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Target biomarker profile for the clinical management of paracetamol overdose
Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W
2015-01-01
Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366
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Pommergaard, Hans-Christian; Rostved, Andreas Arendtsen; Adam, René; Thygesen, Lau Caspar; Salizzoni, Mauro; Gómez Bravo, Miguel Angel; Cherqui, Daniel; De Simone, Paolo; Boudjema, Karim; Mazzaferro, Vincenzo; Soubrane, Olivier; García-Valdecasas, Juan Carlos; Fabregat Prous, Joan; Pinna, Antonio D; O'Grady, John; Karam, Vincent; Duvoux, Christophe; Rasmussen, Allan
2018-05-01
Locoregional treatment while on the waiting list for liver transplantation (Ltx) for hepatocellular carcinoma (HCC) has been shown to improve survival. However, the effect of treatment type has not been investigated. We investigate the effect of locoregional treatment type on survival after Ltx for HCC. We investigated patients registered in the European Liver Transplant Registry database using multivariate Cox regression survival analysis. Information on locoregional therapy was registered for 4978 of 23 124 patients and was associated with improved overall survival [hazard ratio (HR) 0.84 (0.73-0.96)] and HCC-specific survival [HR 0.76 (0.59-0.98)]. Radiofrequency ablation (RFA) was the one monotherapy associated with improved overall survival [HR 0.51 (0.40-0.65)]. In addition, the combination of RFA and transarterial chemoembolization also improved survival [HR 0.74 (0.55-0.99)]. Adjusting for factors related to prognosis, disease severity, and tumor aggressiveness, RFA was highly beneficial for overall and HCC-specific survival. The effect may represent a selection of patients with favorable tumor biology; however, the treatment may be effective per se by halting tumor progression. Clinicaltrials.gov number: NCT02995096. © 2018 Steunstichting ESOT.
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Talavera-Urquijo, Eider; Rodríguez-Navarro, Sarai; Beisani, Marc; Salcedo-Allende, Maria Teresa; Chakkur, Aisha; Arús-Avilés, Marc; Cremades, Manel; Augustin, Salvador; Martell, María; Balibrea, José M
2018-01-01
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease and is found in 70% of obese people. The evidence available to date suggests that bariatric surgery could be an effective treatment by reducing weight and also by improving metabolic complications in the long term. This work aimed to compare, in a diet-induced NAFLD animal model, the effect of both sleeve gastrectomy (SG) and very-low calorie diet (VLCD). Thirty-five Wistar rats were divided into control rats (n = 7) and obese rats fed a high-fat diet (HFD). After 10 weeks, the obese rats were subdivided into four groups: HFD (n = 7), VLCD (n = 7), and rats submitted to either a sham operation (n = 7) or SG (n = 7). Both liver tissue and blood samples were processed to evaluate steatosis and NASH changes in histology (Oil Red, Sirius Red and H&E); presence of endothelial damage (CD31, Moesin/p-Moesin, Akt/p-Akt, eNOS/p-eNOS), oxidative stress (iNOS) and fibrosis (αSMA, Col1, PDGF, VEGF) proteins in liver tissue; and inflammatory (IL6, IL10, MCP-1, IL17α, TNFα), liver biochemical function, and hormonal (leptin, ghrelin, visfatin and insulin) alterations in plasma. Both VLCD and SG improved histology, but only SG induced a significant weight loss, improved endothelial damage, and a decreased cardiovascular risk by reducing insulin resistance (IR), leptin, total cholesterol, and triglyceride levels. There were no relevant variations in the inflammatory and fibrosis markers. Our study suggests a slight superiority of SG over VLCD by improving not only the histology but also the IR and cardiovascular risk markers related to NAFLD.
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Delmastro-Greenwood, Meghan M.; Marré, Meghan L.; O’Connor, Erin C.; Novak, Elizabeth A.; Vincent, Garret; Mollen, Kevin P.; Lee, Sojin; Dong, H. Henry; Piganelli, Jon D.
2017-01-01
Oxidative stress and persistent inflammation are exaggerated through chronic over-nutrition and a sedentary lifestyle, resulting in insulin resistance. In type 2 diabetes (T2D), impaired insulin signaling leads to hyperglycemia and long-term complications, including metabolic liver dysfunction, resulting in non-alcoholic fatty liver disease (NAFLD). The manganese metalloporphyrin superoxide dismustase (SOD) mimetic, manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnP), is an oxidoreductase known to scavenge reactive oxygen species (ROS) and decrease pro-inflammatory cytokine production, by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. We hypothesized that targeting oxidative stress-induced inflammation with MnP would assuage liver complications and enhance insulin sensitivity and glucose tolerance in a high-fat diet (HFD)-induced mouse model of T2D. During 12 weeks of feeding, we saw significant improvements in weight, hepatic steatosis, and biomarkers of liver dysfunction with redox modulation by MnP treatment in HFD-fed mice. Additionally, MnP treatment improved insulin sensitivity and glucose tolerance, while reducing serum insulin and leptin levels. We attribute these effects to redox modulation and inhibition of hepatic NF-κB activation, resulting in diminished ROS and pro-inflammatory cytokine production. This study highlights the importance of controlling oxidative stress and secondary inflammation in obesity-mediated insulin resistance and T2D. Our data confirm the role of NF-κB-mediated inflammation in the development of T2D, and demonstrate the efficacy of MnP in preventing the progression to disease by specifically improving liver pathology and hepatic insulin resistance in obesity. PMID:29104232
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Tang, Rui; Ma, Long-Fei; Rong, Zhi-Xia; Li, Mo-Dan; Zeng, Jian-Ping; Wang, Xue-Dong; Liao, Hong-En; Dong, Jia-Hong
2018-04-01
Augmented reality (AR) technology is used to reconstruct three-dimensional (3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the virtual images onto a view of the surgical field. In liver surgery, these superimposed virtual images help the surgeon to visualize intrahepatic structures and therefore, to operate precisely and to improve clinical outcomes. The keywords "augmented reality", "liver", "laparoscopic" and "hepatectomy" were used for searching publications in the PubMed database. The primary source of literatures was from peer-reviewed journals up to December 2016. Additional articles were identified by manual search of references found in the key articles. In general, AR technology mainly includes 3D reconstruction, display, registration as well as tracking techniques and has recently been adopted gradually for liver surgeries including laparoscopy and laparotomy with video-based AR assisted laparoscopic resection as the main technical application. By applying AR technology, blood vessels and tumor structures in the liver can be displayed during surgery, which permits precise navigation during complex surgical procedures. Liver transformation and registration errors during surgery were the main factors that limit the application of AR technology. With recent advances, AR technologies have the potential to improve hepatobiliary surgical procedures. However, additional clinical studies will be required to evaluate AR as a tool for reducing postoperative morbidity and mortality and for the improvement of long-term clinical outcomes. Future research is needed in the fusion of multiple imaging modalities, improving biomechanical liver modeling, and enhancing image data processing and tracking technologies to increase the accuracy of current AR methods. Copyright © 2018 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.
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Hashem, Reem M; Mahmoud, Mona F; El-Moselhy, Mohamed A; Soliman, Hala M
2008-10-01
Fatty liver disease is commonly associated with diabetes mellitus (DM). Insulin resistance (IR) as an investigative biomarker is only concerned with fatty liver that results from DM type 2 associated with metabolic syndrome. Irrespective of IR, DM is generally characterized by overproduction of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), whereas action of the latter is modulated by the anti-inflammatory cytokine interleukin-10 (IL-10). The aim of this study was to investigate the efficacy of using TNF-alpha alone or IL-10/TNF-alpha ratio compared to IR, as a promising biomarker for fatty liver assessment in DM. Furthermore, we hypothesized that using garlic as an immunomodulator may decrease TNF-alpha and increase IL-10 production to improve steatohepatitis. DM was induced metabolically by a high-fat diet to bring about IR, or chemically by alloxan, producing insulin deficiency, in male albino rats. Garlic powder was supplemented (15 mg/kg per day) for 3 weeks. Fatty liver was depicted histologically and biochemically (aspartic aminotransferase, alanine aminotransferase, HOMA-IR, TNF-alpha, IL-10, IL-10/TNF-alpha ratio). We found that, in contrast to obese rats, garlic decreased IL-10/TNF-alpha ratio, despite decreasing TNF-alpha in alloxan diabetic rats in agreement with the histology, which revealed more prominent improvement in the obese group. Moreover, the effect of garlic was not linked to improvement of IR in obese rats. We conclude that IL-10/TNF-alpha ratio may be considered as a convenient biomarker for investigation of fatty liver of different grades, apart from being associated with IR, and immunomodulation of this ratio in favor of increasing it may exert significant improvement.
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Physician perspectives on the management of viral hepatitis and hepatocellular carcinoma in Myanmar
Kim, Yoona A.; Trinh, Sam; Thura, Si; Kyi, Khin Pyone; Lee, Thomas; Sze, Stan; Richards, Adam; Aronsohn, Andrew; Wong, Grace L. H.; Tanaka, Yasuhito; Dusheiko, Geoffrey
2017-01-01
Background In Myanmar, over five million people are infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). Hepatitis has been a recent focus with the development of a National Strategic Plan on Hepatitis and plans to subsidize HCV treatment. Methods During a two-day national liver disease symposium covering HCV, HBV, hepatocellular (HCC), and end-stage liver disease (ESLD), physician surveys were administered using the automated response system (ARS) to assess physician knowledge, perceptions of barriers to screening and treatment, and proposed solutions. Multivariate logistic regression was used to estimate odds ratio (OR) relating demography and practice factors with higher provider knowledge and improvement. Results One hundred two physicians attending from various specialty areas (31.0% specializing in gastroenterology/hepatology and/or infectious disease) were of mixed gender (46.8% male), were younger than or equal to 40 years old (51.1% 20 to 40 years), had less experience (61.6% with ≤10 years of medical practice), were from the metropolitan area of Yangon (72.1%), and saw <10 liver disease patients per week (74.3%). The majority of physicians were not comfortable with treating or managing patients with liver disease. The post-test scores demonstrated an improvement in liver disease knowledge (9.0% ± 27.0) compared to the baseline pre-test scores; no variables were associated with significant improvement in hepatitis knowledge. Physicians identified the cost of diagnostic blood tests and treatment as the most significant barrier to treatment. Top solutions proposed were universal screening policies (46%), removal of financial barriers for treatment (29%), patient education (14%) and provider education (11%). Conclusions Physician knowledge improved after this symposium, and many other needs were revealed by the physician input on barriers to care and their solutions. These survey results are important in guiding the next steps to improve liver disease management and future medical education efforts in Myanmar. PMID:28797080
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Physician perspectives on the management of viral hepatitis and hepatocellular carcinoma in Myanmar.
Kim, Yoona A; Trinh, Sam; Thura, Si; Kyi, Khin Pyone; Lee, Thomas; Sze, Stan; Richards, Adam; Aronsohn, Andrew; Wong, Grace L H; Tanaka, Yasuhito; Dusheiko, Geoffrey; Nguyen, Mindie H
2017-01-01
In Myanmar, over five million people are infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). Hepatitis has been a recent focus with the development of a National Strategic Plan on Hepatitis and plans to subsidize HCV treatment. During a two-day national liver disease symposium covering HCV, HBV, hepatocellular (HCC), and end-stage liver disease (ESLD), physician surveys were administered using the automated response system (ARS) to assess physician knowledge, perceptions of barriers to screening and treatment, and proposed solutions. Multivariate logistic regression was used to estimate odds ratio (OR) relating demography and practice factors with higher provider knowledge and improvement. One hundred two physicians attending from various specialty areas (31.0% specializing in gastroenterology/hepatology and/or infectious disease) were of mixed gender (46.8% male), were younger than or equal to 40 years old (51.1% 20 to 40 years), had less experience (61.6% with ≤10 years of medical practice), were from the metropolitan area of Yangon (72.1%), and saw <10 liver disease patients per week (74.3%). The majority of physicians were not comfortable with treating or managing patients with liver disease. The post-test scores demonstrated an improvement in liver disease knowledge (9.0% ± 27.0) compared to the baseline pre-test scores; no variables were associated with significant improvement in hepatitis knowledge. Physicians identified the cost of diagnostic blood tests and treatment as the most significant barrier to treatment. Top solutions proposed were universal screening policies (46%), removal of financial barriers for treatment (29%), patient education (14%) and provider education (11%). Physician knowledge improved after this symposium, and many other needs were revealed by the physician input on barriers to care and their solutions. These survey results are important in guiding the next steps to improve liver disease management and future medical education efforts in Myanmar.
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Elattar, Samah; Estaphan, Suzanne; Mohamed, Enas A; Elzainy, Ahmed; Naguib, Mary
2017-10-01
There is an accumulating evidence suggesting an immunomodulatory role of 1α,25(OH) 2 D3. Altered 1α,25(OH) 2 D3 level may play a role in the development of T2DM and contribute to the pathogenesis of liver diseases. Our study was designed to study and compare the effect of metformin and 1α,25(OH) 2 D3 supplementation on liver injury in type 2 diabetic rat. Sixty male Albino rats were divided into 5 groups; group 1: control rats. the remaining rats were fed high fat diet for 2 weeks and injected with streptozotocin (35mg/kg BW, i.p.) to induce T2DM and were divided into: group 2: untreated diabetic rats, group 3: diabetic rats treated by metformin (100mg/kgBW/d, orally), group 4: diabetic rats supplemented by 1α,25(OH) 2 D3 (0.5μg/kg BW, i.p.) 3 times weekly and group 5: supplemented by both 1α,25(OH) 2 D3 and metformin. Eight weeks later, serum glucose and insulin levels were measured, HOMA IR was calculated, lipid profile, Ca2+, ALT and AST were estimated. Liver specimens were taken to investigate PPAR-α (regulator of lipid metabolism), NF-κB p65, caspase 3 and PCNA (proliferating cell nuclear antigen) and for histological examination. The liver enzymes were elevated in the diabetic rats and the histological results revealed an injurious effect of diabetes on the liver. 1α,25(OH) 2 D3, metformin and both drugs treatment significantly improved liver enzymes as compared to the untreated rats. The improvement was associated with a significant improvement in the glycemic control, lipid profile and serum Ca2+ with a significant reduction in NF-κB p65 and caspase 3 and increased PPAR-α, and PCNA expression as compared to the untreated group. 1α,25(OH) 2 D3 induced a slightly better effect as compared to metformin. Both agents together had a synergistic action and almost completely protected the liver. Histological results confirmed the biochemical findings. Our results showed a protective effect of 1α,25(OH) 2 D3 and metformin on liver in diabetic rats as indicated by an improvement of the level of the liver enzymes, decreased apoptosis and increased proliferation and this was confirmed histologically, with modulating NFkB and PPAR-α. Both agents together had a synergistic effect. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A.; Thomson, Angus W.
2016-01-01
The surgically-demanding mouse orthotopic liver transplant model was first described in 1991. It has proved a powerful research tool for investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, since the mouse genome is well-characterized and there is much greater availability of both genetically-modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice has provided valuable mechanistic insights into the immuno- and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/ immune-mediated events in the hepatic environment and systemically. Conclusion: Orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology and allograft tolerance that may result in therapeutic innovation in liver and other diseases. PMID:26709949
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Jellestad, Lena; Fink, Tobias; Pradarutti, Sascha; Kubulus, Darius; Wolf, Beate; Bauer, Inge; Thiemermann, Chris; Rensing, Hauke
2014-02-05
Ischemia and reperfusion may cause liver injury and are characterized by hepatic microperfusion failure and a decreased hepatocellular function. Inhibition of glycogen synthase kinase (GSK)-3β, a serine-threonine kinase that has recently emerged as a key regulator in the modulation of the inflammatory response after stress events, may be protective in conditions like sepsis, inflammation and shock. Therefore, aim of the study was to assess the role of GSK-3β in liver microcirculation and hepatocellular function after hemorrhagic shock and resuscitation (H/R). Anesthetized male Sprague-Dawley rats underwent pretreatment with Ringer´s solution, vehicle (DMSO) or TDZD-8 (1 mg/kg), a selective GSK-3β inhibitor, 30 min before induction of hemorrhagic shock (mean arterial pressure 35±5 mmHg for 90 min) and were resuscitated with shed blood and Ringer´s solution (2h). 5h after resuscitation hepatic microcirculation was assessed by intravital microscopy. Propidium iodide (PI) positive cells, liver enzymes and alpha-GST were measured as indicators of hepatic injury. Liver function was estimated by assessment of indocyanine green plasma disappearance rate. H/R led to a significant decrease in sinusoidal diameters and impairment of liver function compared to sham operation. Furthermore, the number of PI positive cells in the liver as well as serum activities of liver enzymes and alpha-GST increased significantly after H/R. Pretreatment with TDZD-8 prevented the changes in liver microcirculation, hepatocellular injury and liver function after H/R. A significant rise in the plasma level of IL-10 was observed. Thus, inhibition of GSK-3β before hemorrhagic shock modulates the inflammatory response and improves hepatic microcirculation and hepatocellular function. Copyright © 2013 Elsevier B.V. All rights reserved.
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Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation.
Xiong, Xi; Ren, Yuqian; Cui, Yun; Li, Rui; Wang, Chunxia; Zhang, Yucai
2017-12-01
Cholestasis, as a main manifestation, induces liver injury during sepsis. The farnesoid X receptor (FXR) plays an important role in regulating bile acid homeostasis. Whether FXR activation by its agonist obeticholic acid (OCA) is contributed to improve sepsis-induced liver injury remains unknown. The aim of the present study was to investigate the effect of OCA on lipopolysaccharide (LPS)-induced acute liver injury in mice. 8-week old male C57BL/6J mice were randomly divided into control group, LPS group, oral OCA group and LPS plus oral OCA (LPS + OCA) group. The serum and livers were collected for further analysis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and total bilirubin (TBIL) were measured at indicated time after LPS administration. Liver sections were stained with hematoxylin & eosin (H&E). Orally OCA pretreatment stimulated the expression of FXR and BSEP in livers and protected mice from LPS-induced hepatocyte apoptosis and inflammatory infiltration. Consistently, LPS-induced higher serum levels of ALT, AST, TBA and TBIL were significantly reversed by OCA administration. Meanwhile, the mRNA levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) and IL-6 were decreased in livers of mice in LPS + OCA group compared with LPS group. Further investigation indicated that the higher expression of ATF4 and LC3II/I were associated with the protective effect of OCA on LPS-induced liver injury. Orally OCA pretreatment protects mice from LPS-induced liver injury possibly contributed by improved bile acid homeostasis, decreased inflammatory factors and ATF4-mediated autophagy activity in hepatocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Xu, Ting-Ting; Jiang, Miao-Na; Li, Cong; Che, Ying; Jia, Yu-Jie
2007-03-01
To explore the antifibrotic effect of traditional Chinese medicine compound Gan-fu-kang (GFK) on CCl(4)-induced liver fibrosis in rats and its probable mechanisms. The effects of GFK on CCl(4)-induced liver fibrosis were tested in rats. The liver histopathology was examined by light microscope, polaring microscope and electron microscope. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed and the content of albumin (ALB) and hydroxyproline in the liver was measured. The expression of transforming growth factor-beta(1) (TGF-beta(1)) and laminin (LN) was determined by immunohistochemistry. Semi-quantitive computation of collagen types I and III and laminin was done. The expression of MMP-2 and TIMP-1 was assayed by reverse transcription polymerase chain reaction (RT-PCR). Upon pathological examination, GFK treatment had significantly reversed liver fibrosis. Hepatic extracellular matrix (ECM) deposition was significantly reduced, as evidenced by the reduction of the content of hydroxyproline, collagen types I and III, and laminin. Hepatic function was improved by GFK treatment, as evidenced by the increase of plasma ALB and A/G, and by the decrease of serum ALT and AST. TGF-beta(1) in liver was significantly reduced. A significant expression of MMP-2 and TIMP-1 mRNA in liver were downregulated after GFK treatment. The traditional Chinese medicine compound recipe GFK has an antifibrotic effect on CCl(4)-induced liver fibrosis in rats, which improves hepatic function and lessens the deposition of collagen in the liver. The probable antifibrotic mechanisms were: inhibiting the expression of TGF-beta(1) and decreasing expressions of MMP-2 and TIMP-1.
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D'Argenio, Giuseppe; Cariello, Rita; Tuccillo, Concetta; Mazzone, Giovanna; Federico, Alessandro; Funaro, Annalisa; De Magistris, Laura; Grossi, Enzo; Callegari, Maria L; Chirico, Marilena; Caporaso, Nicola; Romano, Marco; Morelli, Lorenzo; Loguercio, Carmela
2013-05-01
Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P < 0.001 in all cases). Circulating levels of pro-inflammatory cytokine TNF-α were significantly increased in rats with liver fibrosis as compared with normal rats, while symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-β, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis. © 2013 John Wiley & Sons A/S.
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The liver sieve and atherosclerosis.
Fraser, Robin; Cogger, Victoria C; Dobbs, Bruce; Jamieson, Hamish; Warren, Alessandra; Hilmer, Sarah N; Le Couteur, David G
2012-04-01
The 'liver sieve' is a term developed to describe the appearance and the role of fenestrations in the liver sinusoidal endothelial cell (LSEC). LSECs are gossamer-thin cells that line the hepatic sinusoid and they are perforated with pores called fenestrations clustered in sieve plates. There is growing evidence that fenestrations act like a permselective ultrafiltration system which is important for the hepatic uptake of many substrates, particularly chylomicron remnant lipoproteins. The liver sieve is a very efficient exchange system, however in conditions such as hepatic cirrhosis and fibrosis, diabetes mellitus and old age, there is defenestration of the liver sieve. Such defenestration has been shown to influence the hepatic uptake of various substrates including lipoproteins. In the future, pharmacological manipulation of the liver sieve may play a number of therapeutic roles including the management of dyslipidaemia; increasing the efficiency of liver-targeted gene therapy; and improving regeneration of old livers. (C) 2012 Royal College of Pathologists of Australasia.
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Soufi, Nisreen; Chambers, Kari T.; Chen, Zhouji; Schweitzer, George G.; McCommis, Kyle S.; Erion, Derek M.; Graham, Mark J.; Su, Xiong; Finck, Brian N.
2014-01-01
Monoacylglycerol acyltransferase (MGAT) enzymes convert monoacylglycerol to diacylglycerol (DAG), a lipid that has been linked to the development of hepatic insulin resistance through activation of protein kinase C (PKC). The expression of genes that encode MGAT enzymes is induced in the livers of insulin-resistant human subjects with nonalcoholic fatty liver disease, but whether MGAT activation is causal of hepatic steatosis or insulin resistance is unknown. We show that the expression of Mogat1, which encodes MGAT1, and MGAT activity are also increased in diet-induced obese (DIO) and ob/obmice. To probe the metabolic effects of MGAT1 in the livers of obese mice, we administered antisense oligonucleotides (ASOs) against Mogat1 to DIO and ob/ob mice for 3 weeks. Knockdown of Mogat1 in liver, which reduced hepatic MGAT activity, did not affect hepatic triacylglycerol content and unexpectedly increased total DAG content. Mogat1 inhibition also increased both membrane and cytosolic compartment DAG levels. However, Mogat1 ASO treatment significantly improved glucose tolerance and hepatic insulin signaling in obese mice. In summary, inactivation of hepatic MGAT activity, which is markedly increased in obese mice, improved glucose tolerance and hepatic insulin signaling independent of changes in body weight, intrahepatic DAG and TAG content, and PKC signaling. PMID:24595352
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Marinho, Polyana C; Vieira, Aline B; Pereira, Priscila G; Rabelo, Kíssila; Ciambarella, Bianca T; Nascimento, Ana L R; Cortez, Erika; Moura, Aníbal S; Guimarães, Fernanda V; Martins, Marco A; Barquero, Gonzalo; Ferreira, Rodrigo N; de Carvalho, Jorge J
2018-01-01
Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of liver dysfunction worldwide and is commonly associated with obesity. Evidences suggest that NAFLD might be a mitochondrial disease, which contributes to the hepatic steatosis, oxidative stress, cytokine release, and cell death. Capybara oil (CO) is a rich source of polyunsaturated fatty acids (PUFA), which is known to improve inflammation and oxidative stress. In order to determine the effects of CO on NAFLD, C57Bl/6 mice were divided into 3 groups and fed a high-fat diet (HFD) (NAFLD group and NAFLD + CO group) or a control diet (CG group) during 16 weeks. The CO (1.5 g/kg/daily) was administered by gavage during the last 4 weeks of the diet protocol. We evaluated plasma liver enzymes, hepatic steatosis, and cytokine expression in liver as well as hepatocyte ultrastructural morphology and mitochondrial function. CO treatment suppressed hepatic steatosis, attenuated inflammatory response, and decreased plasma alanine aminotransferase (ALT) in mice with NAFLD. CO was also capable of restoring mitochondrial ultrastructure and function as well as balance superoxide dismutase and catalase levels. Our findings indicate that CO treatment has positive effects on NAFLD improving mitochondrial dysfunction, steatosis, acute inflammation, and oxidative stress.
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Organ allocation for chronic liver disease: model for end-stage liver disease and beyond.
Asrani, Sumeet K; Kim, W Ray
2010-05-01
Implementation of the model for end-stage liver disease (MELD) score has led to a reduction in waiting list registration and waitlist mortality. Prognostic models have been proposed to either refine or improve the current MELD-based liver allocation. The model for end-stage liver disease - sodium (MELDNa) incorporates serum sodium and has been shown to improve the predictive accuracy of the MELD score. However, laboratory variation and manipulation of serum sodium is a concern. Organ allocation in the United Kingdom is now based on a model that includes serum sodium. An updated MELD score is associated with a lower relative weight for serum creatinine coefficient and a higher relative weight for bilirubin coefficient, although the contribution of reweighting coefficients as compared with addition of variables is unclear. The D-MELD, the arithmetic product of donor age and preoperative MELD, proposes donor-recipient matching; however, inappropriate transplantation of high-risk donors is a concern. Finally, the net benefit model ranks patients according to the net survival benefit that they would derive from the transplant. However, complex statistical models are required and unmeasured characteristics may unduly affect the model. Despite their limitations, efforts to improve the current MELD-based organ allocation are encouraging.
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Ogawa, Yasuhiro; Murata, Yoriko; Saibara, Toshiji; Nishioka, Akihito; Kariya, Shinji; Yoshida, Shoji
2003-01-01
One-third of the breast cancer patients who underwent tamoxifen intake showed less than 0.9 of their liver/spleen CT (computed tomography) ratio on their annual CT study, and were diagnosed as having fatty liver (hepatic steatosis). Among them, patients who showed a lower liver/spleen CT ratio of less than 0.5 were recommended to undergo needle biopsy of the liver in order to obtain histopathological confirmation of non-alcoholic steatohepatitis (NASH), with 15 patients undergoing needle biopsy of the liver. As a result, 14 out of the 15 patients were diagnosed as having NASH, and these patients were additionally administered bezafibrate in order to prevent possible progressive changes of NASH into liver cirrhosis. In this study, we show the changes of follow-up CT findings of 6 patients with histopathologically-proven NASH who continued to undergo bezafibrate intake after the diagnosis of NASH. Two patients showed almost complete improvement as indicated by the liver/spleen CT ratio several months after completion of a tamoxifen intake of 5 years, and another 3 showed partial improvement on their liver/spleen CT ratio by bezafibrate intake in spite of continuing tamoxifen intake. Another patient with diabetes mellitus (type II) showed a continually decreasing liver/spleen CT ratio during adjuvant tamoxifen in spite of bezafibrate intake. Therefore, we concluded that the progression of NASH could be prevented by bezafibrate without any interruption of adjuvant tamoxifen treatment. For patients with diabetes mellitus, critical follow-up using CT study and laboratory tests is considered essential.
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Kawaguchi, T; Yamagishi, S; Sata, M
2009-01-01
Recent clinical studies have shown that patients with chronic liver disease are insulin resistant. Of all etiologies of chronic liver disease including non-alcoholic fatty liver disease, the one that causes the most sever insulin resistance is hepatitis C virus (HCV) infection. Since insulin resistance promotes inflammatory and fibrogenic reactions in the liver, thus leading to the development of liver cirrhosis and hepatocellular carcinoma (HCC) in patients with HCV infection, amelioration of insulin sensitivity may inhibit the progression of HCV-associated liver disease, and could improve the survival of these patients. HCV directly causes insulin resistance through HCV core protein-elicited proteasomal degradation of insulin receptor substrates and subsequent inactivation of intracellular insulin signaling molecules such as Akt. Furthermore, tumor necrosis factor-alpha (TNF-alpha) and/or triglyceride accumulation-induced nuclear factor-kappaB (NF-kappaB) activation in the liver is shown to play a role in insulin resistance in patients with HCV-related chronic liver disease as well. We, along with others, have recently found that branched-chain amino acids (BCAAs) and pigment epithelium-derived factor (PEDF) could improve the HCV-associated insulin resistance via suppression of NF-kappaB and preservation of insulin signaling pathway. In this review, we discuss the mechanisms for the actions of BCAAs and PEDF, and their clinical implications in insulin resistance of chronic liver disease in patients with HCV infection. We also discuss here which chemical structures could contribute to insulin-sensitization in patients with HCV infection.
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Bioartificial liver devices: Perspectives on the state of the art.
Ding, Yi-Tao; Shi, Xiao-Lei
2011-03-01
Acute liver failure remains a significant cause of morbidity and mortality. Bioartificial liver (BAL) devices have been in development for more than 20 years. Such devices aim to temporarily take over the metabolic and excretory functions of the liver until the patients' own liver has recovered or a donor liver becomes available for transplant. The important issues include the choice of cell materials and the design of the bioreactor. Ideal BAL cell materials should be of good viability and functionality, easy to access, and exclude immunoreactive and tumorigenic cell materials. Unfortunately, the current cells in use in BAL do not meet these requirements. One of the challenges in BAL development is the improvement of current materials; another key point concerning cell materials is the coculture of different cells. The bioreactor is an important component of BAL, because it determines the viability and function of the hepatocytes within it. From the perspective of bioengineering, a successful and clinically effective bioreactor should mimic the structure of the liver and provide an in vivo-like microenvironment for the growth of hepatocytes, thereby maintaining the cells' viability and function to the maximum extent. One future trend in the development of the bioreactor is to improve the oxygen supply system. Another direction for future research on bioreactors is the application of biomedical materials. In conclusion, BAL is, in principle, an important therapeutic strategy for patients with acute liver failure, and may also be a bridge to liver transplantation. It requires further research and development, however, before it can enter clinical practice.
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Anno, Takatoshi; Kaneto, Hideaki; Shigemoto, Ryo; Kawasaki, Fumiko; Kawai, Yasuhiro; Urata, Noriyo; Kawamoto, Hirofumi; Kaku, Kohei; Okimoto, Niro
2018-01-01
Hypoglycemia is induced by many causes, especially over-dose of insulin or oral hypoglycemic agents in diabetic subjects. In such a case, hyperinsulinemic hypoglycemia is usually observed. On the other hand, it is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia. Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in clinical practice. Herein, we experienced similar 2 cases of non-diabetic hypoinsulinemic hypoglycemia. Both of them were elderly subjects with low body weight. Furthermore, it is likely that hypoinsulinemic hypoglycemia in both subjects was triggered by severe liver injury, at least in part, due to possible limited liver glycogen store. In elderly subjects with low body weight and/or malnutrition, metabolism in the liver is reduced and glycogen accumulation is decreased. Such alteration brings out acute and marked liver injury, which finally leads to the onset of severe hypoglycemia. It is known that not only liver injury but also multiple organ failure could be induced due to extreme emaciation in subjects. It is likely that in elderly subjects with low body weight and/or malnutrition, multiple organ failure including liver failure could be induced due to the similar reason. Therefore, we should be very careful of such subjects in order to avoid the development of multiple organ failure which leads to life-threatening situations. In conclusion, we should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly or starving subjects with low body weight and limited liver glycogen stores. It is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia.Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in everyday clinical practice.Herein, we reported similar 2 cases of hypoinsulinemic hypoglycemia without diabetes presumably triggered by severe liver injury.In both cases, hypoglycemia was improved by glucose infusion, although their liver injury was not improved.We should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly subjects with low body weight.
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Haufe, Sven; Haas, Verena; Utz, Wolfgang; Birkenfeld, Andreas L.; Jeran, Stephanie; Böhnke, Jana; Mähler, Anja; Luft, Friedrich C.; Schulz-Menger, Jeanette; Boschmann, Michael; Jordan, Jens; Engeli, Stefan
2013-01-01
OBJECTIVE Weight loss reduces abdominal and intrahepatic fat, thereby improving metabolic and cardiovascular risk. Yet, many patients regain weight after successful diet-induced weight loss. Long-term changes in abdominal and liver fat, along with liver test results and insulin resistance, are not known. RESEARCH DESIGN AND METHODS We analyzed 50 overweight to obese subjects (46 ± 9 years of age; BMI, 32.5 ± 3.3 kg/m2; women, 77%) who had participated in a 6-month hypocaloric diet and were randomized to either reduced carbohydrates or reduced fat content. Before, directly after diet, and at an average of 24 (range, 17–36) months follow-up, we assessed body fat distribution by magnetic resonance imaging and markers of liver function and insulin resistance. RESULTS Body weight decreased with diet but had increased again at follow-up. Subjects also partially regained abdominal subcutaneous and visceral adipose tissue. In contrast, intrahepatic fat decreased with diet and remained reduced at follow-up (7.8 ± 9.8% [baseline], 4.5 ± 5.9% [6 months], and 4.7 ± 5.9% [follow-up]). Similar patterns were observed for markers of liver function, whole-body insulin sensitivity, and hepatic insulin resistance. Changes in intrahepatic fat und intrahepatic function were independent of macronutrient composition during intervention and were most effective in subjects with nonalcoholic fatty liver disease at baseline. CONCLUSIONS A 6-month hypocaloric diet induced improvements in hepatic fat, liver test results, and insulin resistance despite regaining of weight up to 2 years after the active intervention. Body weight and adiposity measurements may underestimate beneficial long-term effects of dietary interventions. PMID:23963894
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Wang, Kun; Li, Yuwen; Zhu, Tiantian; Zhang, Yongting; Li, Wenting; Lin, Wenyu; Li, Jun; Zhu, Chuanlong
2017-07-05
Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has emerged as a novel therapy for acute liver failure (ALF). However, the homing efficiency of BMSCs to the injured liver sites appears to be poor. In this study, we aimed to determine if overexpression of c-Met in BMSCs could promote the homing ability of BMSCs to rat livers affected by ALF. Overexpression of c-Met in BMSCs (c-Met-BMSCs) was attained by transfection of naive BMSCs with the lenti-c-Met-GFP. The impact of transplanted c-Met-BMSCs on both homing and repair of ALF was evaluated and compared with lenti-GFP empty vector transfected BMSCs (control BMSCs). After cells were transfected with the lenti-c-Met-GFP vector, the BMSCs displayed very high expression of c-Met protein as demonstrated by Western blot. In addition, in vitro transwell migration assays showed that the migration ability of c-Met-BMSCs was significantly increased in comparison with that of control BMSCs (P < 0.05), and was dependent on hepatocyte growth factor (HGF). Furthermore, rats with ALF that received transplanted c-Met-BMSCs showed significantly improved homing ability to the injured liver; this was accompanied by elevated survival rates and liver function in the ALF rats. Parallel pathological examination further confirmed that transplantation of c-Met-BMSCs ameliorated liver injury with reduced hepatic activity index (HAI) scores, and that the effects of c-Met-BMSCs were more profound than those of control BMSCs. Overexpression of c-Met promotes the homing of BMSCs to injured hepatic sites in a rat model of ALF, thereby improving the efficacy of BMSC therapy for ALF repair.
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Carrión, José A; Navasa, Miquel; García-Retortillo, Montserrat; García-Pagan, Juan Carlos; Crespo, Gonzalo; Bruguera, Miquel; Bosch, Jaime; Forns, Xavier
2007-05-01
Recurrence of hepatitis C virus (HCV) infection is a relevant problem of liver transplantation programs. We evaluated the effect of antiviral therapy on disease progression in 81 HCV-infected liver transplantation recipients. Patients with mild hepatitis C recurrence (fibrosis stage F0 to F2, n = 54) were randomized to no treatment (group A, n = 27) or peginterferon alfa-2b/ribavirin for 48 weeks (group B, n = 27). Patients with severe recurrence (F3 to F4, cholestatic hepatitis) were treated (group C, n = 27). All patients (n = 81) underwent a liver biopsy at baseline and after follow-up; paired hepatic venous pressure gradient (HVPG) measurements were available in 51 patients. Thirteen (48%) patients of group B and 5 (18.5%) of group C achieved sustained virological response. Liver fibrosis progressed > or =1 stage in 40 (49%) of 81 patients: 19 (70%) of group A versus 7 (26%) of group B (P = .001) and in 14 (54%) of group C. HVPG increased (6.5 to 13 mm Hg, P < .01) in patients in whom fibrosis worsened, whereas it decreased (5 to 3.5 mm Hg, P = .017) or remained unchanged in those with fibrosis improvement or stabilization, respectively. The only variable independently associated with fibrosis improvement/stabilization was treatment (odds ratio [OR] =3.7, 95% confidence interval [CI] 1.3 to 10, P = .009). Among treated patients, alanine aminotransferase (ALT) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization (OR 5.3, 95% CI 1.5 to 18, P < .01; OR 7.4, 95% CI 1.4 to 38, P = .01; respectively). Our data demonstrate that in liver transplantation recipients, antiviral therapy slows disease progression (particularly in sustained virological responders), as shown by its effects on liver histology and on HVPG.
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Catani, Lucia; Sollazzo, Daria; Bianchi, Elisa; Ciciarello, Marilena; Antoniani, Chiara; Foscoli, Licia; Caraceni, Paolo; Giannone, Ferdinando Antonino; Baldassarre, Maurizio; Giordano, Rosaria; Montemurro, Tiziana; Montelatici, Elisa; D'Errico, Antonia; Andreone, Pietro; Giudice, Valeria; Curti, Antonio; Manfredini, Rossella; Lemoli, Roberto Massimo
2017-12-01
Growing evidence supports the therapeutic potential of bone marrow (BM)-derived stem/progenitor cells for end-stage liver disease (ESLD). We recently demonstrated that CD133 + stem/progenitor cell (SPC) reinfusion in patients with ESLD is feasible and safe and improve, albeit transiently, liver function. However, the mechanism(s) through which BM-derived SPCs may improve liver function are not fully elucidated. Here, we characterized the circulating SPCs compartment of patients with ESLD undergoing CD133 + cell therapy. Next, we set up an in vitro model mimicking SPCs/liver microenvironment interaction by culturing granulocyte colony-stimulating factor (G-CSF)-mobilized CD133 + and LX-2 hepatic stellate cells. We found that patients with ESLD show normal basal levels of circulating hematopoietic and endothelial progenitors with impaired clonogenic ability. After G-CSF treatment, patients with ESLD were capable to mobilize significant numbers of functional multipotent SPCs, and interestingly, this was associated with increased levels of selected cytokines potentially facilitating SPC function. Co-culture experiments showed, at the molecular and functional levels, the bi-directional cross-talk between CD133 + SPCs and human hepatic stellate cells LX-2. Human hepatic stellate cells LX-2 showed reduced activation and fibrotic potential. In turn, hepatic stellate cells enhanced the proliferation and survival of CD133 + SPCs as well as their endothelial and hematopoietic function while promoting an anti-inflammatory profile. We demonstrated that the interaction between CD133 + SPCs from patients with ESLD and hepatic stellate cells induces significant functional changes in both cellular types that may be instrumental for the improvement of liver function in cirrhotic patients undergoing cell therapy. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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90Y Liver Radioembolization Imaging Using Amplitude-Based Gated PET/CT.
Osborne, Dustin R; Acuff, Shelley; Neveu, Melissa; Kaman, Austin; Syed, Mumtaz; Fu, Yitong
2017-05-01
The usage of PET/CT to monitor patients with hepatocellular carcinoma following Y radioembolization has increased; however, image quality is often poor because of low count efficiency and respiratory motion. Motion can be corrected using gating techniques but at the expense of additional image noise. Amplitude-based gating has been shown to improve quantification in FDG PET, but few have used this technique in Y liver imaging. The patients shown in this work indicate that amplitude-based gating can be used in Y PET/CT liver imaging to provide motion-corrected images with higher estimates of activity concentration that may improve posttherapy dosimetry.
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Effect of Weight Loss, Diet, Exercise, and Bariatric Surgery on Nonalcoholic Fatty Liver Disease.
Hannah, William N; Harrison, Stephen A
2016-05-01
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD is the most common liver disease in developed countries. Weight reduction of 3% to 5% is associated with improved steatosis; reductions of 5% to 7% are necessary for decreased inflammation; with 7% to 10%, individuals may experience NAFLD/NASH remission and regression of fibrosis. No specific dietary intervention has proven beneficial beyond calorie restriction. Physical activity without weight loss seems to decrease hepatic steatosis. Bariatric surgery is associated with decreased cardiovascular risk and improved overall mortality in addition to reduction in hepatic steatosis, inflammation, and fibrosis. Published by Elsevier Inc.
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Park, Sin Young; Cheong, Won Jo
2016-05-01
Tiny polyether ether ketone encased monolith frits have been prepared by modified catalytic sulfonation of the inner surface of polyether ether tubing (1.6 mm od, 0.25 mm id) followed by modified formation of organic monolith and cutting of the tubing into slices. The frit was placed below the central hole of the column outlet union and supported by a combination of a silica capillary (0.365 mm od, 0.05 mm id) and a polyether ether ketone sleeve (1.6 mm od, 0.38 mm id) tightened with a nut and a ferrule when the column was packed to prevent sinking of the frit element into the union hole (0.25 mm opening) otherwise. The column packed this way with the frits investigated in this study has shown better separation performance owing to the reduced frit volume in comparison to the column packed with a commercial stainless-steel screen frit. This study establishes the strategy of disposable microcolumns in which cheap disposable frits are used whenever the column is re-packed to yield columns of even better chromatographic performance than the columns with commercial frits. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Supramolecular Affinity Chromatography for Methylation-Targeted Proteomics.
Garnett, Graham A E; Starke, Melissa J; Shaurya, Alok; Li, Janessa; Hof, Fraser
2016-04-05
Proteome-wide studies of post-translationally methylated species using mass spectrometry are complicated by high sample diversity, competition for ionization among peptides, and mass redundancies. Antibody-based enrichment has powered methylation proteomics until now, but the reliability, pan-specificity, polyclonal nature, and stability of the available pan-specific antibodies are problematic and do not provide a standard, reliable platform for investigators. We have invented an anionic supramolecular host that can form host-guest complexes selectively with methyllysine-containing peptides and used it to create a methylysine-affinity column. The column resolves peptides on the basis of methylation-a feat impossible with a comparable commercial cation-exchange column. A proteolyzed nuclear extract was separated on the methyl-affinity column prior to standard proteomics analysis. This experiment demonstrates that such chemical methyl-affinity columns are capable of enriching and improving the analysis of methyllysine residues from complex protein mixtures. We discuss the importance of this advance in the context of biomolecule-driven enrichment methods.
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[Column chromatography purification and analysis of biodiesel by transesterification].
Liu, Yang; Yi, Huai-feng; Chen, Yu; Wu, Yu-long; Yang, Ming-de; Chen, Zeng; Tong, Jun-mao
2012-02-01
In the present paper, crude biodiesel prepared with sorbifolia oil as raw material by transesterification was purified by column chromatography, then the composition of biodiesel was analyzed by gas chromatography, FTIR, GC-MS and 1H NMR. Column chromatography can separate the crude biodiesel into two fractions: petroleum ether eluted fraction (A1) and methanol eluted fraction (A2). Petroleum ether eluted fraction was mainly biodiesel fraction, which was produced from sorbifolia oil by transesterification, including methyl linoleate, methyl cis-9-octadecenoate and so on; methanol eluted fraction was mainly glycerol fraction, which came from the side reaction of transesterification. The results show that the purity of refined biodiesel increased from 77.51% to 93.872, and the product recovery rate reached up to 91.04% after the purification by column chromatography. The results obtained by FTIR and 1H NMR further showed that the column chromatography can effectively improve the purity of biodiesel. This paper provides a basis for industrialization of purification of biodiesel.
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Maliken, Bryan D; Avrin, William F; Nelson, James E; Mooney, Jody; Kumar, Sankaran; Kowdley, Kris V
2012-01-01
There is an ongoing clinical need for novel methods to measure hepatic iron content (HIC) noninvasively. Both magnetic resonance imaging (MRI) and superconducting quantum interference device (SQUID) methods have previously shown promise for estimation of HIC, but these methods can be expensive and are not widely available. Room-temperature susceptometry (RTS) represents an inexpensive alternative and was previously found to be strongly correlated with HIC estimated by SQUID measurements among patients with transfusional iron overload related to thalassemia. The goal of the current study was to examine the relationship between RTS and biochemical HIC measured in liver biopsy specimens in a more varied patient cohort. Susceptometry was performed in a diverse group of patients with hyperferritinemia due to hereditary hemochromatosis (HHC) (n = 2), secondary iron overload (n = 3), nonalcoholic fatty liver disease (NAFLD) (n = 2), and chronic viral hepatitis (n = 3) within one month of liver biopsy in the absence of iron depletion therapy. The correlation coefficient between HIC estimated by susceptometry and by biochemical iron measurement in liver tissue was 0.71 (p = 0.022). Variance between liver iron measurement and susceptometry measurement was primarily related to reliance on the patient's body-mass index (BMI) to estimate the magnetic susceptibility of tissue overlying the liver. We believe RTS holds promise for noninvasive measurement of HIC. Improved measurement techniques, including more accurate overlayer correction, may further improve the accuracy of liver susceptometry in patients with liver disease.
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High intensity interval training improves liver and adipose tissue insulin sensitivity
Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.
2015-01-01
Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307
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Cai, S R; Motoyama, K; Shen, K J; Kennedy, S C; Flye, M W; Ponder, K P
2000-01-01
Liver insufficiency occurs when the liver cannot perform critical functions such as ammonia metabolism, gluconeogenesis, or production of coagulation factors The hypothesis of this study was that decreased function of existing hepatocytes may contribute to hepatic failure, and that the function of these cells might be increased pharmacologically. Lovastatin is a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor that inhibits cholesterol biosynthesis and affects the activity of some signal transduction pathways and liver transcription factors. Changes in hepatic transcription factors during liver regeneration might result in decreased liver functions, and lovastatin might prevent these changes Rats received 90% partial hepatectomy (90% PH), and either lovastatin or vehicle alone daily. Survival and liver functions were assessed. Lovastatin increased survival to 58% (vs. 6% in controls that received 90% PH without drug), decreased the peak ammonia level to 427 microM (vs. 846 microM in controls), increased the nadir of glucose to 88 mg/dl (vs. 57 mg/dl in controls), decreased the peak prothrombin time to 23 s (vs 29 s in controls), and decreased the peak activated partial thromboplastin time to 29 s (vs. 39 s in controls). The full survival and metabolic benefits were observed when lovastatin was started at 30 min after 90% PH, but lovastatin was less efficacious when started at later times. Lovastatin increases the function of existing hepatocytes and might be used to improve liver function after extensive hepatic resection.
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Zhang, Rong; Watson, David G; Wang, Lijie; Westrop, Gareth D; Coombs, Graham H; Zhang, Tong
2014-10-03
It has been reported that HILIC column chemistry has a great effect on the number of detected metabolites in LC-HRMS-based untargeted metabolite profiling studies. However, no systematic investigation has been carried out with regard to the optimisation of mobile phase characteristics. In this study using 223 metabolite standards, we explored the retention mechanisms on three zwitterionic columns with varied mobile phase composition, demonstrated the interference from poor chromatographic peak shapes on the output of data extraction, and assessed the quality of chromatographic signals and the separation of isomers under each LC condition. As expected, on the ZIC-cHILIC column the acidic metabolites showed improved chromatographic performance at low pH which can be attributed to the opposite arrangement of the permanently charged groups on this column in comparison with the ZIC-HILIC column. Using extracts from the protozoan parasite Leishmania, we compared the numbers of repeatedly detected LC-HRMS features under different LC conditions with putative identification of metabolites not amongst the standards being based on accurate mass (±3ppm). Besides column chemistry, the pH of the mobile phase plays a key role in not only determining the retention mechanisms of solutes but also the output of the LC-HRMS data processing. Fast evaporation of ammonium carbonate produced less ion suppression in ESI source and consequently improved the detectability of the metabolites in low abundance in comparison with other ammonium salts. Our results show that the combination of a ZIC-pHILIC column with an ammonium carbonate mobile phase, pH 9.2, at 20mM in the aqueous phase or 10mM in both aqueous and organic mobile phase components, provided the most suitable LC conditions for LC-HRMS-based untargeted metabolite profiling of Leishmania parasite extracts. The signal reliability of the mass spectrometer used in this study (Exactive Orbitrap) was also investigated. Copyright © 2014 Elsevier B.V. All rights reserved.
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Novel hybrid columns made of ultra-high performance concrete and fiber reinforced polymers
NASA Astrophysics Data System (ADS)
Zohrevand, Pedram
The application of advanced materials in infrastructure has grown rapidly in recent years mainly because of their potential to ease the construction, extend the service life, and improve the performance of structures. Ultra-high performance concrete (UHPC) is one such material considered as a novel alternative to conventional concrete. The material microstructure in UHPC is optimized to significantly improve its material properties including compressive and tensile strength, modulus of elasticity, durability, and damage tolerance. Fiber-reinforced polymer (FRP) composite is another novel construction material with excellent properties such as high strength-to-weight and stiffness-to-weight ratios and good corrosion resistance. Considering the exceptional properties of UHPC and FRP, many advantages can result from the combined application of these two advanced materials, which is the subject of this research. The confinement behavior of UHPC was studied for the first time in this research. The stress-strain behavior of a series of UHPC-filled fiber-reinforced polymer (FRP) tubes with different fiber types and thicknesses were tested under uniaxial compression. The FRP confinement was shown to significantly enhance both the ultimate strength and strain of UHPC. It was also shown that existing confinement models are incapable of predicting the behavior of FRP-confined UHPC. Therefore, new stress-strain models for FRP-confined UHPC were developed through an analytical study. In the other part of this research, a novel steel-free UHPC-filled FRP tube (UHPCFFT) column system was developed and its cyclic behavior was studied. The proposed steel-free UHPCFFT column showed much higher strength and stiffness, with a reasonable ductility, as compared to its conventional reinforced concrete (RC) counterpart. Using the results of the first phase of column tests, a second series of UHPCFFT columns were made and studied under pseudo-static loading to study the effect of column parameters on the cyclic behavior of UHPCFFT columns. Strong correlations were noted between the initial stiffness and the stiffness index, and between the moment capacity and the reinforcement index. Finally, a thorough analytical study was carried out to investigate the seismic response of the proposed steel-free UHPCFFT columns, which showed their superior earthquake resistance, as compared to their RC counterparts.
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Results of the eruptive column model inter-comparison study
Costa, Antonio; Suzuki, Yujiro; Cerminara, M.; Devenish, Ben J.; Esposti Ongaro, T.; Herzog, Michael; Van Eaton, Alexa; Denby, L.C.; Bursik, Marcus; de' Michieli Vitturi, Mattia; Engwell, S.; Neri, Augusto; Barsotti, Sara; Folch, Arnau; Macedonio, Giovanni; Girault, F.; Carazzo, G.; Tait, S.; Kaminski, E.; Mastin, Larry G.; Woodhouse, Mark J.; Phillips, Jeremy C.; Hogg, Andrew J.; Degruyter, Wim; Bonadonna, Costanza
2016-01-01
This study compares and evaluates one-dimensional (1D) and three-dimensional (3D) numerical models of volcanic eruption columns in a set of different inter-comparison exercises. The exercises were designed as a blind test in which a set of common input parameters was given for two reference eruptions, representing a strong and a weak eruption column under different meteorological conditions. Comparing the results of the different models allows us to evaluate their capabilities and target areas for future improvement. Despite their different formulations, the 1D and 3D models provide reasonably consistent predictions of some of the key global descriptors of the volcanic plumes. Variability in plume height, estimated from the standard deviation of model predictions, is within ~ 20% for the weak plume and ~ 10% for the strong plume. Predictions of neutral buoyancy level are also in reasonably good agreement among the different models, with a standard deviation ranging from 9 to 19% (the latter for the weak plume in a windy atmosphere). Overall, these discrepancies are in the range of observational uncertainty of column height. However, there are important differences amongst models in terms of local properties along the plume axis, particularly for the strong plume. Our analysis suggests that the simplified treatment of entrainment in 1D models is adequate to resolve the general behaviour of the weak plume. However, it is inadequate to capture complex features of the strong plume, such as large vortices, partial column collapse, or gravitational fountaining that strongly enhance entrainment in the lower atmosphere. We conclude that there is a need to more accurately quantify entrainment rates, improve the representation of plume radius, and incorporate the effects of column instability in future versions of 1D volcanic plume models.
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Multi-Column Xe/Kr Separation with AgZ-PAN and HZ-PAN
DOE Office of Scientific and Technical Information (OSTI.GOV)
Greenhalgh, Mitchell Randy; Garn, Troy Gerry; Welty, Amy Keil
Previous multi-column xenon/krypton separation tests have demonstrated the capability of separating xenon from krypton in a mixed gas feed stream. The results of this initial testing with AgZ-PAN and HZ-PAN indicated that an excellent separation of xenon from krypton could be achieved. Building upon these initial results, a series of additional multi-column testing were performed in FY-16. The purpose of this testing was to scale up the sorbent beds, test a different composition of feed gas and attempt to improve the accuracy of the analysis of the individual capture columns’ compositions. Two Stirling coolers were installed in series to performmore » this testing. The use of the coolers instead of the cryostat provided two desired improvements, 1) removal of the large dilution due to the internal volume of the cryostat adsorption chamber, and 2) ability to increase the sorbent bed size for scale-up. The AgZ-PAN sorbent, due to its xenon selectivity, was loaded in the first column to capture the xenon while allowing the krypton to flow through and be routed to a second column containing the HZ-PAN for capture and analysis. The gases captured on both columns were sampled with evacuated sample bombs and subsequently analyzed via GC-MS for both krypton and xenon. The results of these tests can be used to develop the scope of future testing and analysis using this test bed for demonstrating the capture and separation of xenon and krypton using sorbents, for demonstrating desorption and regeneration of the sorbents, and for determining compositions of the desorbed gases. They indicate a need for future desorption studies in order to better quantify co-adsorbed species and final krypton purity.« less
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NASA Astrophysics Data System (ADS)
Geng, Guannan; Zhang, Qiang; Martin, Randall V.; Lin, Jintai; Huo, Hong; Zheng, Bo; Wang, Siwen; He, Kebin
2017-03-01
Spatial proxies used in bottom-up emission inventories to derive the spatial distributions of emissions are usually empirical and involve additional levels of uncertainty. Although uncertainties in current emission inventories have been discussed extensively, uncertainties resulting from improper spatial proxies have rarely been evaluated. In this work, we investigate the impact of spatial proxies on the representation of gridded emissions by comparing six gridded NOx emission datasets over China developed from the same magnitude of emissions and different spatial proxies. GEOS-Chem-modeled tropospheric NO2 vertical columns simulated from different gridded emission inventories are compared with satellite-based columns. The results show that differences between modeled and satellite-based NO2 vertical columns are sensitive to the spatial proxies used in the gridded emission inventories. The total population density is less suitable for allocating NOx emissions than nighttime light data because population density tends to allocate more emissions to rural areas. Determining the exact locations of large emission sources could significantly strengthen the correlation between modeled and observed NO2 vertical columns. Using vehicle population and an updated road network for the on-road transport sector could substantially enhance urban emissions and improve the model performance. When further applying industrial gross domestic product (IGDP) values for the industrial sector, modeled NO2 vertical columns could better capture pollution hotspots in urban areas and exhibit the best performance of the six cases compared to satellite-based NO2 vertical columns (slope = 1.01 and R2 = 0. 85). This analysis provides a framework for information from satellite observations to inform bottom-up inventory development. In the future, more effort should be devoted to the representation of spatial proxies to improve spatial patterns in bottom-up emission inventories.
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NASA Astrophysics Data System (ADS)
Cahyono, Bambang; Maduwu, Ratna Dewi; Widayat, Suzery, Meiny
2015-12-01
Commercial silica gel only used once by many researchers and affected high cost for purification process, also less support the green chemistry program. This research focused in regeneration silica gel that used purification of temulawak's extracts (Curcuma xanthorrhiza Roxb) by vacuum column chromatography. Sample extracts (contains 10.1195±0.5971% of curcuminoids) was purified by vacuum column chromatography (pressure: 45 kPa, column: 100mm on length and 16mm on diameter). Ethanol 96% and acetone were compared as eluent. The amount of solvent and yield of curcuminoids used as indicator purification. The silica gel was regenerated with heating in 600°C for 8 hours The silica gels were analyzed by IR spectroscopy and X-ray diffraction. Furthermore, regenerated silica gel was used as the stationary phase in vacuum column chromatography under the same conditions with the previous purification. All the purification experiments were performed in three repetitions. Based on regression equation, y=0.132x+0.0011 (r2=0.9997) the yield of curcuminoids on purified products using ethanol as the eluent was improved 4.26% (to 14.3724±0.5749%) and by acetone was improved 3,03% (to 13.1450 ±0.6318%). The IR spectrum of both silica gel showed the same vibration profile and also there were three crystallinity peaks missing on its X-ray diffraction. Regenerated silica gel has the same performance with new silica gel in purification of temulawak's extract: by ethanol has increased 4.08% (14.1947±0.7415%) and 2.93% (13.0447±0.4822) by acetone. In addition, all purification products showed similar TLC profiles. Purification using regenerated silica gel as the adsorbent on vacuum column chromatography has exactly same potential with the new silica gel.
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Hepatic stellate cells in liver development, regeneration, and cancer
Yin, Chunyue; Evason, Kimberley J.; Asahina, Kinji; Stainier, Didier Y.R.
2013-01-01
Hepatic stellate cells are liver-specific mesenchymal cells that play vital roles in liver physiology and fibrogenesis. They are located in the space of Disse and maintain close interactions with sinusoidal endothelial cells and hepatic epithelial cells. It is becoming increasingly clear that hepatic stellate cells have a profound impact on the differentiation, proliferation, and morphogenesis of other hepatic cell types during liver development and regeneration. In this Review, we summarize and evaluate the recent advances in our understanding of the formation and characteristics of hepatic stellate cells, as well as their function in liver development, regeneration, and cancer. We also discuss how improved knowledge of these processes offers new perspectives for the treatment of patients with liver diseases. PMID:23635788
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Approach to the patient with abnormal liver tests.
Mahl, T C
1998-01-01
Patients with abnormal liver blood tests are frequently encountered by primary care practitioners. An understanding of the cellular implications of these abnormalities is helpful in determining the etiology of liver injury. Elevated serum aminotransferases suggest injury of hepatocytes. Elevations in alkaline phosphatase suggest injury to any part of the biliary tree. Neither of these enzymes measures liver function. Serum bilirubin and albumin levels, as well as prothrombin time, do measure function and can be used in conjunction with the physical examination and the specific etiology of the patient's disorder to determine a patient's prognosis. Many diverse disorders result in similar biochemical patterns of liver injury. The history, physical examination, and use of specific disease markers (hepatitis serology, autoimmune markers, and so forth) help to narrow the differential diagnosis. The definitive diagnosis of all liver diseases usually rests on histology: the liver biopsy is the gold standard. With the advent of treatments for liver disease, identifying and accurately diagnosing patients with liver disorders will result in improved quality of life and survival.
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Deng, Xiuling; Wang, Jiliang; Jiao, Li; Utaipan, Tanyarath; Tuma-Kellner, Sabine; Schmitz, Gerd; Liebisch, Gerhard; Stremmel, Wolfgang; Chamulitrat, Walee
2016-05-01
PLA2G6 or GVIA calcium-independent PLA2 (iPLA2β) is identified as one of the NAFLD modifier genes in humans, and thought to be a target for NAFLD therapy. iPLA2β is known to play a house-keeping role in phospholipid metabolism and remodeling. However, its role in NAFLD pathogenesis has not been supported by results obtained from high-fat feeding of iPLA2β-null (PKO) mice. Unlike livers of human NAFLD and genetically obese rodents, fatty liver induced by high-fat diet is not associated with depletion of hepatic phospholipids. We therefore tested whether iPLA2β could regulate obesity and hepatic steatosis in leptin-deficient mice by cross-breeding PKO with ob/ob mice to generate ob/ob-PKO mice. Here we observed an improvement in ob/ob-PKO mice with significant reduction in serum enzymes, lipids, glucose, insulin as well as improved glucose tolerance, and reduction in islet hyperplasia. The improvement in hepatic steatosis measured by liver triglycerides, fatty acids and cholesterol esters was associated with decreased expression of PPARγ and de novo lipogenesis genes, and the reversal of β-oxidation gene expression. Notably, ob/ob livers contained depleted levels of lysophospholipids and phospholipids, and iPLA2β deficiency in ob/ob-PKO livers lowers the former, but replenished the latter particularly phosphatidylethanolamine (PE) and phosphatidylcholine (PC) that contained arachidonic (AA) and docosahexaenoic (DHA) acids. Compared with WT livers, PKO livers also contained increased PE and PC containing AA and DHA. Thus, iPLA2β deficiency protected against obesity and ob/ob fatty liver which was associated with hepatic fatty-acyl phospholipid remodeling. Our results support the deleterious role of iPLA2β in severe obesity associated NAFLD. Copyright © 2016 Elsevier B.V. All rights reserved.
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Ye, Xiaowei; Lu, Dongyan; Chen, Xinlin; Li, Suihui; Chen, Yao; Deng, Li
2016-06-01
Shuangbai San is a Chinese herb preparation used externally to treat pain. There have been few randomized controlled trials addressing the safety and usefulness of Shuangbai San, such as its effect on pain relief and quality of life (QOL) improvement. This study was conducted to evaluate the effect of Shuangbai San on relieving pain and improving QOL in primary liver cancer patients with cancer pain. A total of 134 primary liver cancer patients with mild pain (numerical rating scale [NRS] ≤ 3), either locally in the liver or in the upper abdomen, were enrolled and randomly allocated to the group receiving Shuangbai San or the control group (receiving placebo). The primary outcome measures were the NRS score and QOL scales, including the QOL scale for patients with liver cancer, version 2.0 and the European Organization for Research and Treatment of Cancer QOL Questionnaire-C30. The secondary outcome measures included the Karnofsky Performance Status score, blood indicators, and liver and kidney function before and after treatment. The NRS scores decreased more significantly in the Shuangbai San group than in the placebo group (P < 0.05) at the corresponding time points. The changes in the scores for the physical function, psychological function, and symptoms/adverse effects domains of the QOL scale for patients with liver cancer, version 2.0 and the physical, emotional, and cognitive domains of the European Organization for Research and Treatment of Cancer QOL Questionnaire-C30 were significantly greater in the Shuangbai San group than in the placebo group (P < 0.05). The changes in the scores for the other domains were not significantly different (P > 0.05). The use of Shuangbai San can relieve mild pain in liver cancer patients and improve their QOL. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
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Deformable Dose Reconstruction to Optimize the Planning and Delivery of Liver Cancer Radiotherapy
NASA Astrophysics Data System (ADS)
Velec, Michael
The precise delivery of radiation to liver cancer patients results in improved control with higher tumor doses and minimized normal tissues doses. A margin of normal tissue around the tumor requires irradiation however to account for treatment delivery uncertainties. Daily image-guidance allows targeting of the liver, a surrogate for the tumor, to reduce geometric errors. However poor direct tumor visualization, anatomical deformation and breathing motion introduce uncertainties between the planned dose, calculated on a single pre-treatment computed tomography image, and the dose that is delivered. A novel deformable image registration algorithm based on tissue biomechanics was applied to previous liver cancer patients to track targets and surrounding organs during radiotherapy. Modeling these daily anatomic variations permitted dose accumulation, thereby improving calculations of the delivered doses. The accuracy of the algorithm to track dose was validated using imaging from a deformable, 3-dimensional dosimeter able to optically track absorbed dose. Reconstructing the delivered dose revealed that 70% of patients had substantial deviations from the initial planned dose. An alternative image-guidance technique using respiratory-correlated imaging was simulated, which reduced both the residual tumor targeting errors and the magnitude of the delivered dose deviations. A planning and delivery strategy for liver radiotherapy was then developed that minimizes the impact of breathing motion, and applied a margin to account for the impact of liver deformation during treatment. This margin is 38% smaller on average than the margin used clinically, and permitted an average dose-escalation to liver tumors of 9% for the same risk of toxicity. Simulating the delivered dose with deformable dose reconstruction demonstrated the plans with smaller margins were robust as 90% of patients' tumors received the intended dose. This strategy can be readily implemented with widely available technologies and thus can potentially improve local control for liver cancer patients receiving radiotherapy.
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Ursodeoxycholic acid for cystic fibrosis-related liver disease.
Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L
2014-12-15
Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies.Date of the most recent search of the Group's trials register: 29 May 2014. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. Ten trials have been identified, of which three trials involving 118 participants were included; the dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30 participants from two trials. Improvement in biliary excretion was reported in only one trial and no significant change after treatment was shown. There were no data available for analysis for long-term outcomes such as death or need for liver transplantation. There are few trials assessing the effectiveness of ursodeoxycholic acid. There is insufficient evidence to justify its routine use in cystic fibrosis.
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[Correlation between red blood cell count and liver function status].
Xie, Xiaomeng; Wang, Leijie; Yao, Mingjie; Wen, Xiajie; Chen, Xiangmei; You, Hong; Jia, Jidong; Zhao, Jingmin; Lu, Fengmin
2016-02-01
To investigate the changes in red blood cell count in patients with different liver diseases and the correlation between red blood cell count and degree of liver damage. The clinical data of 1427 patients with primary liver cancer, 172 patients with liver cirrhosis, and 185 patients with hepatitis were collected, and the Child-Pugh class was determined for all patients. The differences in red blood cell count between patients with different liver diseases were retrospectively analyzed, and the correlation between red blood cell count and liver function status was investigated. The Mann-Whitney U test, Kruskal-Wallis H test, rank sum test, Spearman rank sum correlation test, and chi-square test were performed for different types of data. Red blood cell count showed significant differences between patients with chronic hepatitis, liver cancer, and liver cirrhosis and was highest in patients with chronic hepatitis and lowest in patients with liver cirrhosis (P < 0.05). In the patients with liver cirrhosis, red blood cell count tended to decrease in patients with a higher Child-Pugh class (P < 0.05). For patients with liver cirrhosis, red blood cell count can reflect the degree of liver damage, which may contribute to an improved liver function prediction model for these patients.
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Segmentation of liver region with tumorous tissues
NASA Astrophysics Data System (ADS)
Zhang, Xuejun; Lee, Gobert; Tajima, Tetsuji; Kitagawa, Teruhiko; Kanematsu, Masayuki; Zhou, Xiangrong; Hara, Takeshi; Fujita, Hiroshi; Yokoyama, Ryujiro; Kondo, Hiroshi; Hoshi, Hiroaki; Nawano, Shigeru; Shinozaki, Kenji
2007-03-01
Segmentation of an abnormal liver region based on CT or MR images is a crucial step in surgical planning. However, precisely carrying out this step remains a challenge due to either connectivities of the liver to other organs or the shape, internal texture, and homogeneity of liver that maybe extensively affected in case of liver diseases. Here, we propose a non-density based method for extracting the liver region containing tumor tissues by edge detection processing. False extracted regions are eliminated by a shape analysis method and thresholding processing. If the multi-phased images are available then the overall outcome of segmentation can be improved by subtracting two phase images, and the connectivities can be further eliminated by referring to the intensity on another phase image. Within an edge liver map, tumor candidates are identified by their different gray values relative to the liver. After elimination of the small and nonspherical over-extracted regions, the final liver region integrates the tumor region with the liver tissue. In our experiment, 40 cases of MDCT images were used and the result showed that our fully automatic method for the segmentation of liver region is effective and robust despite the presence of hepatic tumors within the liver.
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Polyploidization without mitosis improves in vivo liver transduction with lentiviral vectors.
Pichard, Virginie; Couton, Dominique; Desdouets, Chantal; Ferry, Nicolas
2013-02-01
Lentiviral vectors are efficient gene delivery vehicles for therapeutic and research applications. In contrast to oncoretroviral vectors, they are able to infect most nonproliferating cells. In the liver, induction of cell proliferation dramatically improved hepatocyte transduction using all types of retroviral vectors. However, the precise relationship between hepatocyte division and transduction efficiency has not been determined yet. Here we compared gene transfer efficiency in the liver after in vivo injection of recombinant lentiviral or Moloney murine leukemia viral (MoMuLV) vectors in hepatectomized rats treated or not with retrorsine, an alkaloid that blocks hepatocyte division and induces megalocytosis. Partial hepatectomy alone resulted in a similar increase in hepatocyte transduction using either vector. In retrorsine-treated and partially hepatectomized rats, transduction with MoMuLV vectors dropped dramatically. In contrast, we observed that retrorsine treatment combined with partial hepatectomy increased lentiviral transduction to higher levels than hepatectomy alone. Analysis of nuclear ploidy in single cells showed that a high level of transduction was associated with polyploidization. In conclusion, endoreplication could be exploited to improve the efficiency of liver-directed lentiviral gene therapy.
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Polyploidization Without Mitosis Improves In Vivo Liver Transduction With Lentiviral Vectors
Couton, Dominique; Desdouets, Chantal; Ferry, Nicolas
2013-01-01
Abstract Lentiviral vectors are efficient gene delivery vehicles for therapeutic and research applications. In contrast to oncoretroviral vectors, they are able to infect most nonproliferating cells. In the liver, induction of cell proliferation dramatically improved hepatocyte transduction using all types of retroviral vectors. However, the precise relationship between hepatocyte division and transduction efficiency has not been determined yet. Here we compared gene transfer efficiency in the liver after in vivo injection of recombinant lentiviral or Moloney murine leukemia viral (MoMuLV) vectors in hepatectomized rats treated or not with retrorsine, an alkaloid that blocks hepatocyte division and induces megalocytosis. Partial hepatectomy alone resulted in a similar increase in hepatocyte transduction using either vector. In retrorsine-treated and partially hepatectomized rats, transduction with MoMuLV vectors dropped dramatically. In contrast, we observed that retrorsine treatment combined with partial hepatectomy increased lentiviral transduction to higher levels than hepatectomy alone. Analysis of nuclear ploidy in single cells showed that a high level of transduction was associated with polyploidization. In conclusion, endoreplication could be exploited to improve the efficiency of liver-directed lentiviral gene therapy. PMID:23249390
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2018-06-06
Stage I Adult Liver Cancer; Stage I Colorectal Cancer; Stage IA Gastric Cancer; Stage IA Pancreatic Cancer; Stage IB Gastric Cancer; Stage IB Pancreatic Cancer; Stage II Adult Liver Cancer; Stage IIA Colorectal Cancer; Stage IIA Gastric Cancer; Stage IIA Pancreatic Cancer; Stage IIB Colorectal Cancer; Stage IIB Gastric Cancer; Stage IIB Pancreatic Cancer; Stage IIC Colorectal Cancer; Stage III Pancreatic Cancer; Stage IIIA Adult Liver Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Adult Liver Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Adult Liver Cancer; Stage IIIC Colorectal Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer; Stage IVA Colorectal Cancer; Stage IVA Liver Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Liver Cancer; Stage IVB Pancreatic Cancer
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Lee-Montiel, Felipe T; George, Subin M; Gough, Albert H; Sharma, Anup D; Wu, Juanfang; DeBiasio, Richard; Vernetti, Lawrence A; Taylor, D Lansing
2017-10-01
This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS). In addition, the oxygen tension was measured using a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2'-bipyridyl) dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa 488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea secretion and Zone 3 biased functions of glycolysis, α1AT secretion, Cyp2E1 expression and acetaminophen toxicity were demonstrated in the respective Zone 1 and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus MicroPhysiology System included improved performance of selected nonparenchymal cells, the inclusion of a porcine liver extracellular matrix to model the Space of Disse, as well as an improved media to support both hepatocytes and non-parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System is most amenable to low to medium throughput, acute through chronic studies, including liver disease models, prioritizing compounds for preclinical studies, optimizing chemistry in structure activity relationship (SAR) projects, as well as in rising dose studies for initial dose ranging. Impact statement Oxygen zonation is a critical aspect of liver functions. A human microphysiology system is needed to investigate the impact of zonation on a wide range of liver functions that can be experimentally manipulated. Because oxygen zonation has such diverse physiological effects in the liver, we developed and present a method for computationally modeling and measuring oxygen that can easily be implemented in all MPS models. We have applied this method in a liver MPS in which we are then able to control oxygenation in separate devices and demonstrate that zonation-dependent hepatocyte functions in the MPS recapitulate what is known about in vivo liver physiology. We believe that this advance allows a deep experimental investigation on the role of zonation in liver metabolism and disease. In addition, modeling and measuring oxygen tension will be required as investigators migrate from PDMS to plastic and glass devices.
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Lee-Montiel, Felipe T; George, Subin M; Sharma, Anup D; Wu, Juanfang; DeBiasio, Richard; Vernetti, Lawrence A; Taylor, D Lansing
2017-01-01
This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS). In addition, the oxygen tension was measured using a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2′-bipyridyl) dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa 488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea secretion and Zone 3 biased functions of glycolysis, α1AT secretion, Cyp2E1 expression and acetaminophen toxicity were demonstrated in the respective Zone 1 and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus MicroPhysiology System included improved performance of selected nonparenchymal cells, the inclusion of a porcine liver extracellular matrix to model the Space of Disse, as well as an improved media to support both hepatocytes and non-parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System is most amenable to low to medium throughput, acute through chronic studies, including liver disease models, prioritizing compounds for preclinical studies, optimizing chemistry in structure activity relationship (SAR) projects, as well as in rising dose studies for initial dose ranging. Impact statement Oxygen zonation is a critical aspect of liver functions. A human microphysiology system is needed to investigate the impact of zonation on a wide range of liver functions that can be experimentally manipulated. Because oxygen zonation has such diverse physiological effects in the liver, we developed and present a method for computationally modeling and measuring oxygen that can easily be implemented in all MPS models. We have applied this method in a liver MPS in which we are then able to control oxygenation in separate devices and demonstrate that zonation-dependent hepatocyte functions in the MPS recapitulate what is known about in vivo liver physiology. We believe that this advance allows a deep experimental investigation on the role of zonation in liver metabolism and disease. In addition, modeling and measuring oxygen tension will be required as investigators migrate from PDMS to plastic and glass devices. PMID:28409533
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Wang, Xiaoyang; Wang, Mi; Zhang, Keyu; Hou, Ting; Zhang, Lifang; Fei, Chenzong; Xue, Feiqun; Hang, Taijun
2018-06-01
A reliable UPLC-MS/MS method with high sensitivity was developed and validated for the determination of virginiamycin M1 in muscle, fat, liver, and kidney samples of chicken and swine. Analytes were extracted using acetonitrile and extracts were defatted by N-hexane. Chromatographic separation was performed on a BEH C18 liquid chromatography column. The analytes were then detected using triplequadrupole mass spectrometry in positive electrospray ionization and multiple reaction monitoring mode. Calibration plots were constructed using standard working solutions and showed good linearity. Limits of quantification ranged from 2 to 60 ng mL -1 . Copyright © 2018 Elsevier Ltd. All rights reserved.
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Klammt, Sebastian; Mitzner, Steffen R; Stange, Jan; Loock, Jan; Heemann, Uwe; Emmrich, Jörg; Reisinger, Emil C; Schmidt, Reinhard
2008-09-01
Extracorporeal albumin dialysis (ECAD) enables the elimination of albumin bound substances and is used as artificial liver support system. Albumin binding function for the benzodiazepine binding site specific marker Dansylsarcosine was estimated in plasma samples of 22 patients with cirrhosis and hyperbilirubinaemia (ECAD: n = 12; control: n = 10) during a period of 30 days in a randomized controlled clinical ECAD trial. Albumin Binding Capacity (ABiC) at baseline was reduced to 31.8% (median; range 24%-74%) and correlated to the severity of liver disease. Within two weeks a significant improvement of ABiC and a reduction of the albumin bound markers bilirubin and bile acids were observed in the ECAD group. During single treatments a significant decrease of albumin bound substances (bilirubin and bile acids) as well as an increase in ABiC was observed. In the control group, baseline ABiC was significantly lower in patients who died during study period (34.2% vs. 41.7%; P < 0.028), whereas no significant differences were observed for CHILD, coagulation factors, albumin, bile acids nor bilirubin. At baseline 13 patients had a severely impaired ABiC (<40%), improvement of ABiC was more frequent in the ECAD group (5/6) than in the SMT group (2/7). Reduced albumin binding function is present in decompensated liver failure and is related to severity and 30 day survival. ABiC can be improved by ECAD. The beneficial effect of this treatment may be related to the improvement of albumin binding function more than to the elimination of specific substances. Characterization of albumin function by the ABiC test may help to evaluate different liver support systems and other therapeutic measures.
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Saito, Tetsuo; Nishida, Miyako; Saito, Masafumi; Tanabe, Akari; Eitsuka, Takahiro; Yuan, Shi-Hua; Ikekawa, Nobuo; Nishida, Hiroshi
2016-10-01
Obesity-associated insulin resistance is a major risk factor for most metabolic diseases, including dyslipidemia and type 2 diabetes. Acanthopanax senticosus (Rupr. et Maxim.) Harms (Goka) root has been used in traditional Chinese medicine for treatment of diabetes and other conditions; however, little is known about the effects of Goka fruit (GF). Goka fruit is rich in anthocyanin, which has beneficial effects on obesity and insulin resistance via activation of adenosine monophosphate-activated protein kinase (AMPK). We hypothesized that GF can improve obesity-associated insulin resistance. The aim of the present study was to investigate whether GF improves insulin resistance in high-fat diet (HFD)-induced obese mice. High-fat diet mice treated with GF (500 and 1000 mg/kg) for 12 weeks showed an improved glucose tolerance and insulin sensitivity, as well as reduced plasma insulin and liver lipid accumulation. Moreover, GF administration to HFD mice resulted in down-regulation of fatty acid synthase expression and up-regulation of cholesterol 7-alpha-hydroxylase expression in the liver. Notably, AMPK phosphorylation in the liver increased after GF administration. In summary, GF supplementation improved obesity-associated insulin resistance and hepatic lipid accumulation through modulation of AMPK activity and lipid metabolism-associated gene expression. Copyright © 2016 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Chouhan, Manil D.; Bainbridge, Alan; Atkinson, David; Punwani, Shonit; Mookerjee, Rajeshwar P.; Lythgoe, Mark F.; Taylor, Stuart A.
2017-02-01
Liver dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling could be useful in the assessment of diffuse liver disease and focal liver lesions, but is compromised by errors in arterial input function (AIF) sampling. In this study, we apply cardiac output correction to arterial input functions (AIFs) for liver DCE MRI and investigate the effect on dual-input single compartment hepatic perfusion parameter estimation and reproducibility. Thirteen healthy volunteers (28.7 ± 1.94 years, seven males) underwent liver DCE MRI and cardiac output measurement using aortic root phase contrast MRI (PCMRI), with reproducibility (n = 9) measured at 7 d. Cardiac output AIF correction was undertaken by constraining the first pass AIF enhancement curve using the indicator-dilution principle. Hepatic perfusion parameters with and without cardiac output AIF correction were compared and 7 d reproducibility assessed. Differences between cardiac output corrected and uncorrected liver DCE MRI portal venous (PV) perfusion (p = 0.066), total liver blood flow (TLBF) (p = 0.101), hepatic arterial (HA) fraction (p = 0.895), mean transit time (MTT) (p = 0.646), distribution volume (DV) (p = 0.890) were not significantly different. Seven day corrected HA fraction reproducibility was improved (mean difference 0.3%, Bland-Altman 95% limits-of-agreement (BA95%LoA) ±27.9%, coefficient of variation (CoV) 61.4% versus 9.3%, ±35.5%, 81.7% respectively without correction). Seven day uncorrected PV perfusion was also improved (mean difference 9.3 ml min-1/100 g, BA95%LoA ±506.1 ml min-1/100 g, CoV 64.1% versus 0.9 ml min-1/100 g, ±562.8 ml min-1/100 g, 65.1% respectively with correction) as was uncorrected TLBF (mean difference 43.8 ml min-1/100 g, BA95%LoA ±586.7 ml min-1/ 100 g, CoV 58.3% versus 13.3 ml min-1/100 g, ±661.5 ml min-1/100 g, 60.9% respectively with correction). Reproducibility of uncorrected MTT was similar (uncorrected mean difference 2.4 s, BA95%LoA ±26.7 s, CoV 60.8% uncorrected versus 3.7 s, ±27.8 s, 62.0% respectively with correction), as was and DV (uncorrected mean difference 14.1%, BA95%LoA ±48.2%, CoV 24.7% versus 10.3%, ±46.0%, 23.9% respectively with correction). Cardiac output AIF correction does not significantly affect the estimation of hepatic perfusion parameters but demonstrates improvements in normal volunteer 7 d HA fraction reproducibility, but deterioration in PV perfusion and TLBF reproducibility. Improved HA fraction reproducibility maybe important as arterialisation of liver perfusion is increased in chronic liver disease and within malignant liver lesions.
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Zhang, Shichang; Zhang, Bo; Chen, Xia; Chen, Li; Wang, Zhengguo; Wang, Yingjie
2014-12-01
Tissue-engineered liver using primary hepatocytes has been considered a valuable new therapeutic modality as an alternative to whole organ liver transplantation for different liver diseases. The development of clinically feasible liver tissue engineering approaches, however, has been hampered by the poor engraftment efficiency of hepatocytes. We developed a three-dimensional (3D) culture system using a microgravity bioreactor (MB), biodegradable scaffolds and growth-factor-reduced Matrigel to construct a tissue-engineered liver for transplantation into the peritoneal cavity of non-obese diabetic severe combined immunodeficient mice. The number of viable cells in the hepatic tissue constructs was stably maintained in the 3D MB culture system. Hematoxylin-eosin staining and zonula occludens-1 expression revealed that neonatal mouse liver cells were reorganized to form tissue-like structures during MB culture. Significantly upregulated hepatic functions (albumin secretion, urea production and cytochrome P450 activity) were observed in the MB culture group. Post-transplantation analysis indicated that the engraftment efficiency of the hepatic tissue constructs prepared in MB cultures was higher than that of those prepared in the static cultures. Higher level of hepatic function in the implants was confirmed by the expression of albumin. These findings suggest that 3D MB culture systems may offer an improved method for creating tissue-engineered liver because of the higher engraftment efficiency and the reduction of the initial cell function loss.
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DPP-4 inhibitors improve liver dysfunction in type 2 diabetes mellitus.
Kanazawa, Ippei; Tanaka, Ken-ichiro; Sugimoto, Toshitsugu
2014-09-17
Dipeptidyl peptidase-4 (DPP-4) inhibitors might have pleiotropic effects because receptors for incretin exist in various tissues, including liver. We examined whether DPP-4 inhibitors affect liver function in patients with type 2 diabetes. A retrospective review of 459 patients with type 2 diabetes who were prescribed DPP-4 inhibitors was performed. After exclusion of patients with hepatitis B or C, steroid use, and other diseases that might affect liver function and diabetes status, 224 patients were included in the analysis. Forty-four patients (19.6%) with liver injury defined by aspartate transaminase (AST) or alanine transaminase (ALT) over the normal level of 40 U/L. In the patients with liver injury, AST and ALT were significantly decreased after 6 months from the first date of DPP-4 prescription, with mean changes of -6.2 U/L [95% confidence interval (CI) -10.9 to -1.4, p=0.012] and of -11.9 U/L (95%CI -19.5 to -4.2, p=0.003), respectively. Percent changes in AST were significantly and negatively correlated with baseline AST and ALT (r=-0.27, p<0.001 and r=-0.23, p=0.002, respectively), and percent changes in ALT were also negatively correlated with them (r=-0.23, p=0.001 and r=-0.27, p<0.001, respectively). DPP-4 inhibitors improved liver dysfunction in patients with type 2 diabetes.
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Scottoni, Federico; Crowley, Claire; Fiadeiro, Rebeca; Maghsoudlou, Panagiotis; Pellegata, Alessandro Filippo; Mazzacuva, Francesca; Gjinovci, Asllan; Lyne, Anne-Marie; Zulini, Justine; Little, Daniel; Mosaku, Olukunbi; Kelly, Deirdre; De Coppi, Paolo; Gissen, Paul
2017-01-01
Liver transplantation is the definitive treatment of liver failure but donor organ shortage limits its availability. Stem cells are highly expandable and have the potential to differentiate into any specialist cell. Use of patient-derived induced Pluripotent Stem Cells (hiPSCs) has the additional advantage for organ regeneration therapies by removing the need for immunosuppression. We compared hepatocyte differentiation of human embryonic stem cells (hESCs) and hiPSCs in a mouse decellularised liver scaffold (3D) with standard in vitro protocol (2D). Mouse livers were decellularised preserving micro-architecture, blood vessel network and extracellular matrix. hESCs and hiPSCs were primed towards the definitive endoderm. Cells were then seeded either in 3D or 2D cultures and the hepatocyte differentiation was continued. Both hESCs and hiPSCs differentiated more efficiently in 3D than in 2D, with higher and earlier expression of mature hepatocyte marker albumin, lipid and glycogen synthesis associated with a decrease in expression of fetal hepatocyte marker alpha-fetoprotein. Thus we conclude that stem cell hepatocyte differentiation in 3D culture promotes faster cell maturation. This finding suggests that optimised 3D protocols could allow generation of mature liver cells not achieved so far in standard 2D conditions and lead to improvement in cell models of liver disease and regenerative medicine applications. PMID:29261712
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Multidisciplinary management of hepatoblastoma in children: Experience from a developing country.
Shanmugam, Naresh; Scott, Julius Xavier; Kumar, Vimal; Vij, Mukul; Ramachandran, Priya; Narasimhan, Gomathy; Reddy, Mettu Srinivas; Kota, Venugopal; Munirathnam, Deenadayalan; Kelgeri, Chayarani; Sundaram, Karthick; Rela, Mohamed
2017-03-01
Advances in chemotherapy, liver resection techniques, and pediatric liver transplantation have vastly improved survival in children with hepatoblastoma (HB). These are best managed by a multidisciplinary team (MDT) in a setting where all treatment options are available. Until recently, this was difficult to achieve in India. All children (<16 years) with HB treated in a pediatric liver surgery and transplantation unit between January 2011 and July 2016 were reviewed. Data regarding the clinical presentation, preoperative management, surgical treatment, postoperative course, and outcomes were extracted from a prospectively managed database. Thirty children were treated for HB during the study period. Nine children were PRETEXT 4, 7 were PRETEXT 3, 13 were PRETEXT 2, and 1 was PRETEXT 1 (where PRETEXT is pretreatment extension). All children received a neoadjuvant chemotherapy before surgery followed by an adjuvant chemotherapy. Nineteen children had complete resection, while six underwent primary living donor liver transplantation. There were six mortalities including five children who poorly responded to chemotherapy with progressive tumor extension. At a median follow-up of 30 months, two children who underwent resection and one child who underwent liver transplant had disease recurrence. Improved outcomes can be achieved in children with HB even in countries with limited resources when they are managed by MDTs with expertise in pediatric oncology, liver resection, and liver transplantation. © 2016 Wiley Periodicals, Inc.
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Wan, D-L; Li, M-X; Bao, L; Zhang, L-L; Zhang, L; Chen, Q-Y; Lin, S-Z
2018-04-01
With the continuous improvement of liver transplantation technology, the survival rate of liver transplantation has been improved, but recurrent or de novo malignancy remains one of the major factors affecting the long-term survival of liver transplant recipients. A 45-year-old Chinese man had a plastic biliary stent placed on account of biliary anastomotic stenosis after 3 years of piggyback liver transplantation. He came to our hospital because of recurrent fever and jaundice for 2 weeks, and his carcinoembryonic antigen-199 had increased. The patient's duodenal papillary was cauliflower-like at endoscopic retrograde cholangiopancreatography to replace the biliary stent. He was initially suspected of having duodenal papillary carcinoma after liver transplantation. However, the pathology from endoscopic retrograde cholangiopancreatography and endoscopic ultrasound-guided biopsy showed inflammation. While awaiting the result of biopsy, his CA-199 decreased significantly after anti-infection and symptomatic treatment. The patient was diagnosed with biliary anastomotic stenosis and duodenal papillitis. He was discharged uneventfully; to date, there is no evidence of malignant tumor. We report this case to provide helpful information to clinicians about the management of the duodenal papilla cauliflower-like neoplasm after liver transplantation, which should be considered as inflammatory first. Perhaps our view can avoid the risk of bringing an excessive medical treatment and unnecessary economic burden to patients and their families. Copyright © 2018 Elsevier Inc. All rights reserved.
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Bharti, Puja; Mittal, Deepti; Ananthasivan, Rupa
2016-04-19
Diffuse liver diseases, such as hepatitis, fatty liver, and cirrhosis, are becoming a leading cause of fatality and disability all over the world. Early detection and diagnosis of these diseases is extremely important to save lives and improve effectiveness of treatment. Ultrasound imaging, a noninvasive diagnostic technique, is the most commonly used modality for examining liver abnormalities. However, the accuracy of ultrasound-based diagnosis depends highly on expertise of radiologists. Computer-aided diagnosis systems based on ultrasound imaging assist in fast diagnosis, provide a reliable "second opinion" for experts, and act as an effective tool to measure response of treatment on patients undergoing clinical trials. In this review, we first describe appearance of liver abnormalities in ultrasound images and state the practical issues encountered in characterization of diffuse liver diseases that can be addressed by software algorithms. We then discuss computer-aided diagnosis in general with features and classifiers relevant to diffuse liver diseases. In later sections of this paper, we review the published studies and describe the key findings of those studies. A concise tabular summary comparing image database, features extraction, feature selection, and classification algorithms presented in the published studies is also exhibited. Finally, we conclude with a summary of key findings and directions for further improvements in the areas of accuracy and objectiveness of computer-aided diagnosis. © The Author(s) 2016.
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Liver transplantation: Current status and challenges
Jadlowiec, Caroline C; Taner, Timucin
2016-01-01
Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death (DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function. PMID:27182155
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Liver failure in total artificial heart therapy.
Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero; Spiliopoulos, Sotirios
2016-07-01
Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.
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van der Feen, Cathelijne; van der Doef, Hubert P J; van der Ent, Cornelis K; Houwen, Roderick H J
2016-11-01
Ursodeoxycholic acid (UDCA) might prevent progression of cystic fibrosis liver disease, but objective parameters for its effect are lacking. We used liver stiffness measurements to evaluate the effect of Ursodeoxycholic acid. Paired measurements of liver stiffness were done in 73 patients without UDCA and in 32 patients with UDCA. In the latter group, 6 patients had cirrhosis; in 15 patients, UDCA was started based on Colombo criteria, and in 11 patients for other reasons. In patients without UDCA, liver stiffness increased: 0.19 (-0.03 to 0.59)kPa/year. Liver stiffness also increased in patients with cirrhosis: 4.6 (0.67-12.4)kPa/year. In patients who had UDCA based on Colombo criteria, a decrease of liver stiffness was observed: 0.70 (-1.6 to 0.55)kPa/year (P=0.01). In patients on UDCA for other reasons, liver stiffness increased: 0.23 (-0.20 to 0.51)kPa/year. UDCA reduced liver stiffness in patients with well-defined, mild liver disease. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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The potential for geostationary remote sensing of NO2 to improve weather prediction
NASA Astrophysics Data System (ADS)
Liu, X.; Mizzi, A. P.; Anderson, J. L.; Fung, I. Y.; Cohen, R. C.
2017-12-01
Observations of surface winds remain sparse making it challenging to simulate and predict the weather in circumstances of light winds that are most important for poor air quality. Direct measurements of short-lived chemicals from space might be a solution to this challenge. Here we investigate the application of data assimilation of NO2 columns as will be observed from geostationary orbit to improve predictions and retrospective analysis of surface wind fields. Specifically, synthetic NO2 observations are sampled from a "nature run (NR)" regarded as the true atmosphere. Then NO2 observations are assimilated using EAKF methods into a "control run (CR)" which differs from the NR in the wind field. Wind errors are generated by introducing (1) errors in the initial conditions, (2) creating a model error by using two different formulations for the planetary boundary layer, (3) and by combining both of these effects. Assimilation of NO2 column observations succeeds in reducing wind errors, indicating the prospects for future geostationary atmospheric composition measurements to improve weather forecasting are substantial. We find that due to the temporal heterogeneity of wind errors, the success of this application favors chemical observations of high frequency, such as those from geostationary platform. We also show the potential to improve soil moisture field by assimilating NO2 columns.
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Antioxidant Capacity and Proanthocyanidin Composition of the Bark of Metasequoia glyptostroboides.
Chen, Fengyang; Zhang, Lin; Zong, Shuling; Xu, Shifang; Li, Xiaoyu; Ye, Yiping
2014-01-01
Metasequoia glyptostroboides Hu et Cheng is the only living species in the genus Metasequoia Miki ex Hu et Cheng (Taxodiaceae), which is well known as a "living fossil" species. In the Chinese folk medicine, the leaves and bark of M. glyptostroboides are used as antimicrobic, analgesic, and anti-inflammatory drug for dermatic diseases. This study is the first to report the free radical scavenging capacity, antioxidant activity, and proanthocyanidin composition of the bark of M. glyptostroboides. We observed total of six extracts and fractions, which were easily obtained by water-ethanol extraction and followed by a further separation with D101 resin column chromatography, had significant DPPH radical, superoxide anion radical, and hydroxyl radical scavenging capacity, total antioxidative capacity (T-AOC), lipid peroxidation inhibitory activity, and metal ions chelating capacity. The fraction MGEB, which was obtained by 60% ethanol extraction and followed by a further separation with D101 resin column chromatograph, possessed the highest proanthocyanidin content and the highest free radical scavenging and antioxidant activities. Furthermore, MGEB could significantly protect against CCl4 induced acute liver injury through inhibition of oxidative stress in mice. In addition, ten proanthocyanidins were isolated from MGEB, and six of them were firstly reported from this plant.
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Atmospheric Soundings from AIRS/AMSU in Partial Cloud Cover
NASA Technical Reports Server (NTRS)
Susskind, Joel; Atlas, Robert
2005-01-01
Simultaneous use of AIRS/AMSU-A observations allow for the determination of accurate atmospheric soundings under partial cloud cover conditions. The methodology involves the determination of the radiances AIRS would have seen if the AIRS fields of view were clear, called clear column radiances, and use of these radiances to infer the atmospheric and surface conditions giving rise to these clear column radiances. Susskind et al. demonstrate via simulation that accurate temperature soundings and clear column radiances can be derived from AIRS/AMSU-A observations in cases of up to 80% partial cloud cover, with only a small degradation in accuracy compared to that obtained in clear scenes. Susskind and Atlas show that these findings hold for real AIRS/AMSU-A soundings as well. For data assimilation purposes, this small degradation in accuracy is more than offset by a significant increase in spatial coverage (roughly 50% of global cases were accepted, compared to 3.6% of the global cases being diagnosed as clear), and assimilation of AIRS temperature soundings in partially cloudy conditions resulted in a larger improvement in forecast skill than when AIRS soundings were assimilated only under clear conditions. Alternatively, derived AIRS clear column radiances under partial cloud cover could also be used for data assimilation purposes. Further improvements in AIRS sounding methodology have been made since the results shown in Susskind and Atlas . A new version of the AIRS/AMSU-A retrieval algorithm, Version 4.0, was delivered to the Goddard DAAC in February 2005 for production of AIRS derived products, including clear column radiances. The major improvement in the Version 4.0 retrieval algorithm is with regard to a more flexible, parameter dependent, quality control. Results are shown of the accuracy and spatial distribution of temperature-moisture profiles and clear column radiances derived from AIRS/AMSU-A as a function of fractional cloud cover using the Version 4.0 algorithm. Use of the Version 4.0 AIRS temperature profiles increased the positive forecast impact arising from AIRS retrievals relative to what was shown in Susskind and Atlas .
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Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Córdoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jiménez, Wladimiro; Morales-Ruiz, Manuel
2017-11-01
Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl 4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl 4 -treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-β1 (TGF-β1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P < 0.05). The decrease of EndMT in cirrhotic livers correlated with a significant decrease in liver fibrosis ( P < 0.05) and an improvement in the vascular disorganization rate ( P < 0.05). We demonstrated the acquisition of the EndMT phenotype by a subpopulation of endothelial cells from cirrhotic livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-β1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization. Copyright © 2017 the American Physiological Society.
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Optimizing global liver function in radiation therapy treatment planning
NASA Astrophysics Data System (ADS)
Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.
2016-09-01
Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than \\ell \\text{EUD} model optimization does, the GLF model directly optimizes a more clinically relevant metric and can further improve fEUD plan quality.
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The effects of blueberry anthocyanins on histone acetylation in rat liver fibrosis
Zhan, Wei; Liao, Xin; Xie, Ru-Jia; Tian, Tian; Yu, Lei; Liu, Xing; Liu, Jing; Li, Po; Han, Bing; Yang, Ting; Zhang, Bei; Cai, Li-Jun; Li, Rui; Yang, Qin
2017-01-01
To determine the effects ofanthocyanins from blueberries on hepatic stellate cell (HSCs-T6) and on histone acetylation during liver fibrosis induced by CCl4 in rats. Fifty male SD rats weighing 180 ± 20g were randomly placed into a control group, a hepatic fibrosis group, a blueberry treatment group, a blueberry intervention group, and a natural recovery group. After the rats were sacrificed, the livers and the liver indexes were measured, and the pathological changes were observed by HE staining and Masson staining. The blood was analyzed for the four indexes of liver fibrosis and liver function; nucleoprotein from liver tissues and karyoplasm were isolated to determine the expression of acH3K9, acH3K14, and acH3K18 by Western blotting. Compared with the lethal rate of the control group, the median lethal rate of HSCs-T6 cells treated with a the 50μmol/L concentration was 66.94% (P < 0.05). The protein expression on α-SMA, type I collagen, TIMP1 significantly decreased (P < 0.05) following treatment with 50 ug/ml of anthocyanin for 36 h; moreover, the expression of acH3K9, acH3K14 and acH3K18 modification were up-regulated (P < 0.05). Furthermore, compared with the liver in the model group, the liver in the intervention group showed the most obvious improvement (P < 0.01), and its karyoplasm had increased expression of acH3K9, acH3K14 and acH3K18 (P<0.01). Regulating histone acetylation could improve liver function and liver fibrosis indexes in rats with hepatic fibrosis. The mechanism might be related to certain genes that promote apoptosis, so as to inhibit the effect of anti hepatic fibrosis. PMID:29228569
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Serum paraoxonase-1 as biomarker for improved diagnosis of fatty liver in dairy cows.
Farid, Ayman Samir; Honkawa, Kazuyuki; Fath, Eman Mohamed; Nonaka, Nariaki; Horii, Yoichiro
2013-04-11
Fatty liver is a major metabolic disorder in dairy cows and is believed to result in major economic losses in dairy farming due to decreased health status, reproductive performance and fertility. Currently, the definitive means for diagnosing fatty liver is determining the fat content of hepatic tissue by liver biopsy, which is an invasive and costly procedure, making it poorly suited to dairy farms. Therefore, the key aim of this study was to investigate the measurement of serum paraoxonase-1 (PON1), an enzyme exclusively synthesized by the liver, as a sensitive noninvasive biomarker for diagnosis of fatty liver in dairy cows. A comparative cohort study using serum specimens from Holstein-Friesian dairy cows (46 healthy and 46 fatty liver cases) was conducted. Serum PON1 (paraoxonase, lactonase and arylesterase) activity and other biochemical and hematological parameters were measured. We found that serum PON1 activity was lower (P<0.001) in cows suffering from fatty liver. The area under the receiver operating characteristic curve (AUC-ROC) of PON1 activity for diagnosis of fatty liver was 0.973-0.989 [95% confidence interval (CI) 0.941, 1.000] which was higher than the AUC-ROC of aspartate aminotransferase (AST), lecithin-cholesterol acyltransferase (LCAT), alkaline phosphatase (ALP), non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL). We found that adding serum PON1 measurement to different batteries of serum diagnostic panels showed a combination of high sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odd ratio (DOR) and overall diagnostic accuracy in diagnosing fatty liver. The present results indicate that addition of serum PON1 activity measurement to the biochemical profile could improve the diagnosis of fatty liver in dairy cows, which would have a considerable clinical impact and lead to greater profitability in the dairy industry.
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Replication fidelity improvement of PMMA microlens array based on weight evaluation and optimization
NASA Astrophysics Data System (ADS)
Jiang, Bing-yan; Shen, Long-jiang; Peng, Hua-jiang; Yin, Xiang-lin
2007-12-01
High replication fidelity is a prerequisite of high quality plastic microlens array in injection molding. But, there's not an economical and practical method to evaluate and improve the replication fidelity until now. Based on part weight evaluation and optimization, this paper presents a new method of replication fidelity improvement. Firstly, a simplified analysis model of PMMA micro columns arrays (5×16) with 200μm diameter was set up. And then, Flow (3D) module of Moldflow MPI6.0 based on Navier-Stokes equations was used to calculate the weight of the micro columns arrays in injection molding. The effects of processing parameters (melt temperature, mold temperature, injection time, packing pressure and packing time) on the part weight were investigated in the simulations. The simulation results showed that the mold temperature and the injection time have important effects on the filling of micro columns; the optimal mold temperature and injection time for better replication fidelity could be determined by the curves of mold temperature vs part weight and injection time vs part weight. At last, the effects of processing parameters on part weight of micro columns array were studied experimentally. The experimental results showed that the increase of melt temperature and mold temperature can make the packing pressure transfer to micro cavity more effectively through runner system, and increase the part weight. From the observation results of the image measuring apparatus, it was discovered that the higher the part weight, the better the filling of the microstructures. In conclusion, part weight can be used to evaluate the replication fidelity of micro-feature structured parts primarily; which is an economical and practical method to improve the replication fidelity of microlens arrays based on weight evaluation and optimization.
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Miura, Yasuo; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Tsudo, Mitsuru
2010-01-01
Iron chelation therapy (ICT) has been applied for the patients with iron overload-associated liver dysfunction since it is one of the causes of death in patients with intractable hematological diseases requiring multiple red blood cell transfusions. Recently, deferasirox (DSX), a novel, once-daily oral iron chelator, was demonstrated to have similar efficacy to the conventional continuous infusion of deferoxamine on a decrease in serum ferritin (SF) level in heavily transfused patients. We show three cases of transfusion-mediated iron-overloaded patients with an elevated serum alanine aminotransaminase (ALT). All three patients who received the ICT with DSX showed a decrease in ALT level in association with a decrease in SF level. It is suggested that DSX therapy could be considered to expect the improvement of liver damage for iron-overloaded patients with an abnormal ALT level. PMID:20592762
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Actinomyces naeslundii and Eikenella corrodens as rare causes of liver abscesses.
Jaqua, Nathan Thomas; Smith, Adam J; Shin, Terry T; Jahanmir, Jay
2013-07-17
A 48-year-old man with an unremarkable medical history was admitted with vague conditions of fever, chills, myalgias and malaise. Physical examination was remarkable for only scleral icterus. Laboratory evaluation revealed elevated aminotransferases, alkaline phosphatase and bilirubin. Imaging demonstrated two masses in the right lobe of his liver, which were ultimately drained and cultures demonstrated Actinomyces and Eikenella. He continued to have fever on broad-spectrum antibiotics until catheter drainage of the abscesses was performed. He was eventually discharged in improved condition on amoxicillin-clavulanate. His aminotransferases, alkaline phosphatase and bilirubin continued to improve and he remained afebrile and asymptomatic. A repeat CT 2 months after discharge demonstrated resolution of the abscesses. Actinomyces and Eikenella are rare causes of liver abscesses and treatment requires drainage and an extended course of antibiotics. The polymicrobial character typical of liver abscesses makes antibiotic therapy challenging when cultures reveal rare organisms such as Actinomyces and Eikenella.
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[Oligometastasized colorectal cancer-modern treatment strategies].
Binnebösel, M; Lambertz, A; Dejong, K; Neumann, U P
2018-06-05
The prognosis of colorectal cancer in UICC stage IV has been improved in the last decades by improvements in interdisciplinary treatment. Treatment strategies for oligometastasized colorectal cancer are developing more and more into an individualized treatment. An overview of the current literature of modern treatment concepts in oligometastasized colorectal cancer UICC stage IV is given. Surgery still has the supreme mandate in resectable colorectal liver metastases, as neoadjuvant and adjuvant treatment strategies to not provide any benefits for these patients. In marginal or non-resectable stages systemic treatment is superior in these patients depending on the prognostic parameters. Also in curative settings local treatment options should be considered as a reasonable additive tool. An interesting treatment approach for isolated liver metastases and non-resectable colorectal cancer is liver transplantation. Irrespective of new developments in treatment strategies for metastasized colorectal cancer, resection of colorectal liver metastases remains the gold standard whenever possible.
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Baimas-George, Maria; Baker, Erin; Kamionek, Michal; Salmon, J Stuart; Sastry, Amit; Levi, David; Vrochides, Dionisios
2018-04-05
Advances in the systemic treatment of stage IV colorectal cancer with liver metastases has offered improved survival rates for patients who otherwise face a dismal prognosis. However, a pathologically complete response (PCR) to chemotherapy for colorectal liver metastases is still rare, and its significance is not fully understood. In this case report, we describe a patient who achieved PCR after neoadjuvant immunotherapy with pembrolizumab and a left hepatectomy using an ex vivo resection technique. © 2018 S. Karger AG, Basel.
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The Global Burden of Liver Disease: The Major Impact of China
Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang
2016-01-01
Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus, HBV), nonalcoholic fatty liver disease and alcoholic liver disease affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its “leader in liver diseases” title by investing large amounts of money in funding research, vaccines and drug development for liver diseases, and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. PMID:25164003
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Dai, Zhaolai; Wu, Zhenlong; Jia, Sichao; Wu, Guoyao
2014-08-01
Studies of protein nutrition and biochemistry require reliable methods for analysis of amino acid (AA) composition in polypeptides of animal tissues and foods. Proteins are hydrolyzed by 6M HCl (110°C for 24h), 4.2M NaOH (105°C for 20 h), or proteases. Analytical techniques that require high-performance liquid chromatography (HPLC) include pre-column derivatization with 4-chloro-7-nitrobenzofurazan, 9-fluorenyl methylchloroformate, phenylisothiocyanate, naphthalene-2,3-dicarboxaldehyde, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, and o-phthaldialdehyde (OPA). OPA reacts with primary AA (except cysteine or cystine) in the presence of 2-mercaptoethanol or 3-mercaptopropionic acid to form a highly fluorescent adduct. OPA also reacts with 4-amino-1-butanol and 4-aminobutane-1,3-diol produced from oxidation of proline and 4-hydroxyproline, respectively, in the presence of chloramine-T plus sodium borohydride at 60°C, or with S-carboxymethyl-cysteine formed from cysteine and iodoacetic acid at 25°C. Fluorescence of OPA derivatives is monitored at excitation and emission wavelengths of 340 and 455 nm, respectively. Detection limits are 50 fmol for AA. This technique offers the following advantages: simple procedures for preparation of samples, reagents, and mobile-phase solutions; rapid pre-column formation of OPA-AA derivatives and their efficient separation at room temperature (e.g., 20-25°C); high sensitivity of detection; easy automation on the HPLC apparatus; few interfering side reactions; a stable chromatography baseline for accurate integration of peak areas; and rapid regeneration of guard and analytical columns. Thus, the OPA method provides a useful tool to determine AA composition in proteins of animal tissues (e.g., skeletal muscle, liver, intestine, placenta, brain, and body homogenates) and foods (e.g., milk, corn grain, meat, and soybean meal). Copyright © 2014 Elsevier B.V. All rights reserved.
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Semi-industrial experimental study on bauxite separation using a cell-column integration process
NASA Astrophysics Data System (ADS)
Zhang, Ning-ning; Zhou, Chang-chun; Cong, Long-fei; Cao, Wen-long; Zhou, You
2016-01-01
The cyclonic-static micro-bubble flotation column (FCSMC) is a highly efficient mineral processing equipment. In this study, a cell-column (FCSMC) integration process was investigated for the separation of bauxite and its feasibility was analyzed on a theoretical basis. The properties of low-grade bauxite ore from Henan Province, China were analyzed. Parameters such as reagent dosage, scraping bubble time, and pressure of the circulating pump during the sorting process were investigated and optimized to improve the flotation efficiency. On the basis of these parameters, continuous separation experiments were conducted. Bauxite concentrate with an aluminum-to-silicon (A/S) mass ratio of 6.37 and a 77.63wt% recovery rate were achieved via a flow sheet consisting of "fast flotation using a flotation cell, one roughing flotation and one cleaning flotation using flotation columns". Compared with the full-flotation-cells process, the cell-column integration process resulted in an increase of the A/S ratio by 0.41 and the recovery rate by 17.58wt%. Cell-column integration separation technology represents a new approach for the separation of middle-to-low-grade bauxite ore.
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Zhu, Manman; Zhang, Lingyi; Chu, Zhanying; Wang, Shulei; Chen, Kai; Zhang, Weibing; Liu, Fan
2018-07-01
An open tubular capillary liquid phase chromatographic column (1 m × 25 µm i.d.× 375 µm o.d.) was prepared by incorporating metal organic framework particles modified with vancomycin directly into zwitterionic polymer coating synthesized by the copolymerization of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide and N,N'-methylenebisacrylamide. The incorporation of IRMOF-3 (isoreticular metal organic framework-3) particles improved selectivity of zwitterionic polymer coating with absolute column efficiency reaching 79900 plates for p-xylene. Besides strong hydrophilic interaction, the separation of neutral, basic, and acidic compounds demonstrates that π-π stacking interaction and the coordination effect of unsaturated Zn 2+ of MOF also contribute to separation of various analytes. The RSD values (run-to-run, day-to-day, column-to-column, n = 3) of retention time of neutral compounds were less than 0.71%, 0.69% and 3.08% respectively, suggesting good repeatability. In addition, the column was applied to the analysis of the trypsin digest of bovine serum albumin, revealing the potential in separating biological samples. Copyright © 2018 Elsevier B.V. All rights reserved.
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Zhu, Ke-Xue; Nie, Shao-Ping; Tan, Le-He; Li, Chuan; Gong, De-Ming; Xie, Ming-Yong
2016-03-09
The present study was to evaluate the beneficial effect of polysaccharide isolated from Ganoderma atrum (PSG-1) on liver function in type 2 diabetic rats. Results showed that PSG-1 decreased the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), while increasing hepatic glycogen levels. PSG-1 also exerted strong antioxidant activities, together with upregulated mRNA expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), glucose transporter-4 (GLUT4), phosphoinositide 3-kinase (PI3K), and phosphorylated-Akt (p-Akt) in the liver of diabetic rats. Moreover, the concentrations of short-chain fatty acids (SCFA) were significantly higher in the liver, serum, and faeces of diabetic rats after treating with PSG-1 for 4 weeks. These results suggest that the improvement of PSG-1 on liver function in type 2 diabetic rats may be due to its antioxidant effects, SCFA excretion in the colon from PSG-1, and regulation of hepatic glucose uptake by inducing GLUT4 translocation through PI3K/Akt signaling pathways.
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Long-term outcomes and predictors in pediatric liver retransplantation.
Dreyzin, Alexandra; Lunz, John; Venkat, Veena; Martin, Lillian; Bond, Geoffrey J; Soltys, Kyle A; Sindhi, Rakesh; Mazariegos, George V
2015-12-01
Historically, 9-29% of pediatric liver transplant recipients have required retransplantation. Although outcomes have improved over the last decade, currently published patient and graft survival remain lower after retransplant than after primary transplant. Data from liver retransplantation recipients at our institution between 1991 and 2013 were retrospectively reviewed. Kaplan-Meier estimates were used to depict patient and graft survival. Predictors of survival were analyzed using a series of Cox proportional hazards models. Predictors were analyzed separately for patients who had "early" (≤ 30 days after primary transplant) and "late" retransplants. Eighty-four patients underwent retransplant at a median time of 241 days. Sixty percent had late retransplants. At one, five, and 10 yr, actuarial patient and graft survival were 73%/71%, 66%/63%, and 58%/53%, respectively. Since 2002, patient and graft survival improved to 86%/86% at one yr and 93%/87% at five yr. While operative complications were a common cause of death after earlier retransplants, since 2002, infection has been the only cause of death. Significant morbidities at five-yr follow-up include renal dysfunction (15%), diabetes (13%), hypertension (26%), chronic rejection (7%), and PTLD (2%). Current survival after pediatric liver retransplantation has improved significantly, but long-term immunosuppressant morbidity remains an opportunity for improvement. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Zhong, Wenhui; Qian, Kejian; Xiong, Jibin; Ma, Ke; Wang, Aizhong; Zou, Yan
2016-10-01
In many liver disorders, oxidative stress-related inflammation and apoptosis are important pathogenic components, finally resulting in acute liver failure. Erythropoietin and its analogues are well known to influence the interaction between apoptosis and inflammation in brain and kidney. The study is to clarify the effect of curcumin, a natural plant phenolic food additive, on lipopolysaccharides (LPS)-induced acute liver injury of mice with endotoxemia and associated molecular mechanism from inflammation, apoptosis and oxidative stress levels. And curcumin, lowered serum cytokines, including Interleukin 1beta (IL-1β), Interleukin 6 (IL-6) and tumor necrosis factor (TNF-α), and improved liver apoptosis through suppressing phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and inhibiting Cyclic AMP-responsive element-binding protein (CREB)/Caspase expression, and decreased oxidative stress-associated protein expression, mainly involving 2E1 isoform of cytochrome P450/nuclear factor E2-related factor 2/reactive oxygen species (CYP2E/Nrf2/ROS) signaling pathway, as well as liver nitric oxide (NO) production in LPS-induced mice. Moreover, curcumin regulated serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), accelerated liver antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-px) levels, and inhibited activation of the mitogen-activated protein kinases/c-Jun NH2-terminal kinase (P38/JNK) cascade in the livers of LPS-induced rats. Thus, curcumin treatment attenuates LPS-induced PI3K/AKT and CYP2E/Nrf2/ROS signaling and liver injury. Strategies to inhibit inflammation and apoptosis signaling may provide alternatives to the current clinical approaches to improve oxidative responses of endotoxemia. Copyright © 2016. Published by Elsevier Masson SAS.
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Xu, Xiao; Ling, Qi; Wang, Jianguo; Xie, Haiyang; Wei, Xuyong; Lu, Di; Hu, Qichao; Zhang, Xuanyu; Wu, Liming; Zhou, Lin; Zheng, Shusen
2016-02-01
Recurrence of hepatocellular carcinoma (HCC) is one of the leading causes of death after liver transplantation (LT). We aim to evaluate the association of donor and recipient single nucleotide polymorphisms (SNPs) with the risk of HCC recurrence after LT. A total of 155 adult patients who underwent primary LT for HCC were enrolled. Ten SNPs associated with HCC susceptibility were genotyped. Patients who received donor livers with the rs11614913 homozygous CC variant presented significantly higher recurrence rates of HCC (41.7 vs. 15.3%, p = 0.009) and lower cumulative tumor-free survival (p = 0.005) than those who received TT wild-type donor livers. The donor rs11614913 genetic variant was an independent risk factor for HCC recurrence (odds ratio = 2 per each C allele, p < 0.05) and could significantly improve the predictive abilities of clinical models (Milan, UCSF and Hangzhou criteria). Donor livers homozygous for rs11614913 CC were associated with a higher miR-196a expression than TT (p = 0.002). In a lentiviral infection of mouse liver and orthotopic mouse model of HCC, the liver miR-196a overexpression group showed a significantly larger tumor size than the control group (p = 0.001). There is a close association between the tumor size and expression of miR-196a in the liver (r = 0.693, p = 0.001). In conclusion, the donor miR-196a-2 rs11614913 polymorphism is associated with HCC recurrence after LT and improves the predictive value of clinical models. The overexpression of miR-196a in the liver might provide a tumor-favorable environment for the development of HCC. © 2015 UICC.
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Zhao, Tian-Yu; Su, Li-Ping; Ma, Chun-Ye; Zhai, Xiao-Han; Duan, Zhi-Jun; Zhu, Ying; Zhao, Gang; Li, Chun-Yan; Wang, Li-Xia; Yang, Dong
2015-07-08
Intestinal barrier dysfunction is not only the consequence of liver cirrhosis, but also an active participant in the development of liver cirrhosis. Previous studies showed that external administration of insulin-like growth factor 1 (IGF-1) improved intestinal barrier function in liver cirrhosis. However, the mechanism of IGF-1 on intestinal barrier in liver cirrhosis is not fully elucidated. The present study aims to investigate the mechanisms of IGF-1 improving intestinal barrier function via regulating tight junctions in intestines. We used carbon tetrachloride induced liver cirrhotic rats to investigate the effect of IGF-1 on intestinal claudin-1 and occludin expressions, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, severity of liver fibrosis, portal pressures, enterocytic apoptosis and lipopolysaccharides (LPS) levels in portal vein. The changes of IGF-1 in serum during the development of rat liver cirrhosis were also evaluated. Additionally, we assessed the effect of IGF-1 on claudin-1 and occludin expressions, changes of transepithelial electrical resistance (TEER) and apoptosis in Caco-2 cells to confirm in vivo findings. Serum IGF-1 levels were decreased in the development of rat liver cirrhosis, and external administration of IGF-1 restored serum IGF-1 levels. External administration of IGF-1 reduced serum ALT and AST levels, severity of liver fibrosis, LPS levels in portal vein, enterocytic apoptosis and portal pressure in cirrhotic rats. External administration of IGF-1 increased the expressions of claudin-1 and occludin in enterocytes, and attenuated tight junction dysfunction in intestines of cirrhotic rats. LPS decreased TEER in Caco-2 cell monolayer. LPS also decreased claudin-1 and occludin expressions and increased apoptosis in Caco-2 cells. Furthermore, IGF-1 attenuated the effect of LPS on TEER, claudin-1 expression, occludin expression and apoptosis in Caco-2 cells. Tight junction dysfunction develops during the development of liver cirrhosis, and endotoxemia will develop subsequently. Correspondingly, increased endotoxin in portal system worsens tight junction dysfunction via decreasing intestinal occludin and claudin-1 expressions and increasing enterocytic apoptosis. Endotoxemia and intestinal barrier dysfunction form a vicious circle. External administration of IGF-1 breaks this vicious circle. Improvement of tight junctions might be one possible mechanism of the restoration of intestinal barrier function mediated by IGF-1.
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Gulec, Seza A; Pennington, Kenneth; Hall, Michael; Fong, Yuman
2009-01-08
Extended liver resections are being performed more liberally than ever. The extent of resection of liver metastases, however, is restricted by the volume of the future liver remnant (FLR). An intervention that would both accomplish tumor control and induce compensatory hypertrophy, with good patient tolerability, could improve clinical outcomes. A 53-year-old woman with a history of cervical cancer presented with a large liver mass. Subsequent biopsy indicated poorly differentiated carcinoma with necrosis suggestive of squamous cell origin. A decision was made to proceed with pre-operative chemotherapy and Y-90 microsphere SIRT with the intent to obtain systemic control over the disease, downsize the hepatic lesion, and improve the FLR. A surgical exploration was performed six months after the first SIRT (three months after the second). There was no extrahepatic disease. The tumor was found to be significantly decreased in size with central and peripheral scarring. The left lobe was satisfactorily hypertrophied. A formal right hepatic lobectomy was performed with macroscopic negative margins. Selective internal radiation treatment (SIRT) with yttrium-90 (Y-90) microspheres has emerged as an effective liver-directed therapy with a favorable therapeutic ratio. We present this case report to suggest that the portal vein radiation dose can be substantially increased with the intent of inducing portal/periportal fibrosis. Such a therapeutic manipulation in lobar Y-90 microsphere treatment could accomplish the end points of PVE with avoidance of the concern regarding tumor progression.
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Yu, Hongwei; Li, Man; Tint, G Stephen; Chen, Jianliang; Xu, Guorong; Patel, Shailendra B
2007-04-04
Targeted disruption of the murine 3beta-hydroxysterol-Delta7-reductase gene (Dhcr7), an animal model of Smith-Lemli-Opitz syndrome, leads to loss of cholesterol synthesis and neonatal death that can be partially rescued by transgenic replacement of DHCR7 expression in brain during embryogenesis. To gain further insight into the role of non-brain tissue cholesterol deficiency in the pathophysiology, we tested whether the lethal phenotype could be abrogated by selective transgenic complementation with DHCR7 expression in the liver. We generated mice that carried a liver-specific human DHCR7 transgene whose expression was driven by the human apolipoprotein E (ApoE) promoter and its associated liver-specific enhancer. These mice were then crossed with Dhcr7+/- mutants to generate Dhcr7-/- mice bearing a human DHCR7 transgene. Robust hepatic transgene expression resulted in significant improvement of cholesterol homeostasis with cholesterol concentrations increasing to 80~90 % of normal levels in liver and lung. Significantly, cholesterol deficiency in brain was not altered. Although late gestational lung sacculation defect reported previously was significantly improved, there was no parallel increase in postnatal survival in the transgenic mutant mice. The reconstitution of DHCR7 function selectively in liver induced a significant improvement of cholesterol homeostasis in non-brain tissues, but failed to rescue the neonatal lethality of Dhcr7 null mice. These results provided further evidence that CNS defects caused by Dhcr7 null likely play a major role in the lethal pathogenesis of Dhcr7-/- mice, with the peripheral organs contributing the morbidity.
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Hydrodynamic Delivery of FGF21 Gene Alleviates Obesity and Fatty Liver in Mice Fed a High-fat Diet
Gao, Mingming; Ma, Yongjie; Cui, Ran; Liu, Dexi
2014-01-01
FGF21 is a secreted protein that plays critical roles in regulating glucose and lipid metabolism. In this study, we evaluated the effects of FGF21 gene transfer on C57BL/6 mice fed a high fat diet (HFD). We demonstrate that transfer of the FGF21 gene using a hydrodynamics-based procedure increased mRNA levels of FGF21 exclusively in the liver, consequently generating a sustained high level of FGF21 protein in blood that peaked at 500 ng/ml one day after injection, leading to a variety of beneficial effects including blockade of HFD-induced obesity, alleviation of fatty liver and improvement in glucose homeostasis. These effects were associated with altered expression of Ucp1, Dio2, Pgc1α, Pparγ2, Mgat1, F4/80, Mcp1 and Tnfα, which are involved in thermogenesis, lipogensis and chronic inflammation in the liver and adipose tissues. Transfer of the FGF21 gene in HFD-induced obese mice greatly increased expression of thermogenic genes in adipose tissue, resulting in similar improvements in systemic metabolism including reduction of adiposity, alleviation of fatty liver and attenuation of insulin resistance. Mechanistic studies on the effects of FGF21 gene transfer in lean mice revealed that mice transferred with FGF21 gene displayed suppressed lipogenesis in the liver and enhanced thermogenesis in brown adipose tissue which was coincident with a significant improvement in glucose tolerance. Collectively, our results suggest transfer of the FGF21 gene could be considered a promising approach for treating obesity and its complications. PMID:24747761
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Tzeng, Ching-Wei D; Aloia, Thomas A
2013-01-01
With modern multimodality therapy, patients with resected colorectal cancer (CRC) liver metastases (CLM) can experience up to 50-60 % 5-year survival. These improved outcomes have become more commonplace via achievements in multidisciplinary care, improved definition of resectability, and advances in technical skill. Even patients with synchronous and/or extensive bilateral disease have benefited from novel surgical strategies. Treatment sequencing of synchronous CRC with CLM can be simplified into the following three paradigms: (classic colorectal-first), simultaneous (combined), or reverse approach (liver-first). The decision of whether to treat the CLM or CRC first depends on which site dominates oncologically and symptomatically. Oxaliplatin with 5-fluorouracil/leucovorin (FOLFOX) and irinotecan with 5-fluorouracil/leucovorin (FOLFIRI) are the foundations of modern chemotherapy. Although each regimen has positively impacted survivals, both have the potential for negative effects on the non-tumor liver. Oxaliplatin is associated with vascular injury (sinusoidal ballooning, microvascular injury, nodular regenerative hyperplasia, and long-term fibrosis) but not steatosis. Irinotecan has been associated with steatohepatitis, especially in patients with obesity and diabetes. Steatohepatitis from irinotecan is the only chemotherapy-associated liver injury (CALI) associated with increased mortality from postoperative hepatic insufficiency. Extended duration of preoperative chemotherapy is also associated with CALI. To determine resectability and to prevent overtreatment with systemic therapy, all patients should receive high-quality cross-sectional imaging and be evaluated by a hepatobiliary surgeon before starting chemotherapy. Even as chemotherapy improves, liver surgeons will continue to play a central role in treatment planning by offering the best chance for prolonged survival-safe R0 resection with curative intent.
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Sharma, Prashant; Bodhankar, Subhash L; Thakurdesai, Prasad A
2012-01-01
Objective To evalueate hepatoprotective effects Feronia elephantum (F. elephantum) correa against thioacetamide (TA) induced liver necrosis in diabetic rats. Methods Male wistar rats were made diabetic with alloxan (160 mg/kg) on day 0 of the study. They were intoxicated with hepatotoxicant (thioacetamide, 300 mg/kg, ip) on day 9 of study to produce liver necrosis. Effects of 7 day daily once administration (day 2 to day 9) of EF (400 and 800 mg/kg, po) were evaluated on necorosis of liver in terms of mortality, liver volume, liver weight, serum aspartate aminotransferase (AST) and serum alanine transaminase (ALT), and histopathology of liver sections (for signs of necorosis and inflammation) on day-9 of the study. Separate groups of rats with treated only with alloxan (DA control), thioacetamide (TA control) and both (TA+DA control) were maintained. Results FE significantly lowered the mortality rate and showed improvement in liver function parameters in TA-induced diabetic rats without change in liver weight, volume and serum glucose levels. Conclusions FE showed promising activity against TA-induced liver necorsis in diabetic rats and so might be useful for prevention of liver complications in DM. PMID:23569996
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Lectin from embryos and oocytes of Xenopus laevis. Purification and properties.
Roberson, M M; Barondes, S H
1982-07-10
Soluble extracts of Xenopus laevis blastula stage embryos, oocytes, and adult liver contain lectin activities detected by agglutination of trypsinized, glutaraldehyde-fixed rabbit erythrocytes. Lectin from the embryos and oocytes was purified by affinity chromatography on a column derivatized with melibiose. Trace contaminants were removed either by preparative isoelectric focusing or by gel filtration. Based on its behavior on Sepharose 6B the purified oocyte lectin has an apparent molecular weight of approximately 480,000. On sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions there were two major bands with molecular weight ranges of about 43,000 and 45,000, with diffuse trails. Since the purified lectin contains about 20% saccharides by weight and since both bands are glycosylated, diffuseness might be due to variable glycosylation. Heterogeneity was indicated by isoelectric focusing in polyacrylamide gels, which showed four protein bands with isoelectric points ranging from 4.4 to 4.9. Lectins from both embryos and oocytes comprised about 1 to 2% of the total soluble protein and could not be distinguished by sodium dodecyl sulfate polyacrylamide gel electrophoresis. However, the specific hemagglutination activity of the purified oocyte lectin was, on the average, 7-fold higher. Levels in crude extracts of liver were 3 orders of magnitude lower than those from oocytes. The hemagglutination activities of the lectins from embryos, oocytes, and adult liver required Ca2+ and were blocked by similar concentrations of both alpha- and beta-galactosides.
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Current status and perspectives in split liver transplantation
Lauterio, Andrea; Di Sandro, Stefano; Concone, Giacomo; De Carlis, Riccardo; Giacomoni, Alessandro; De Carlis, Luciano
2015-01-01
Growing experience with the liver splitting technique and favorable results equivalent to those of whole liver transplant have led to wider application of split liver transplantation (SLT) for adult and pediatric recipients in the last decade. Conversely, SLT for two adult recipients remains a challenging surgical procedure and outcomes have yet to improve. Differences in organ shortages together with religious and ethical issues related to cadaveric organ donation have had an impact on the worldwide distribution of SLT. Despite technical refinements and a better understanding of the complex liver anatomy, SLT remains a technically and logistically demanding surgical procedure. This article reviews the surgical and clinical advances in this field of liver transplantation focusing on the role of SLT and the issues that may lead a further expansion of this complex surgical procedure. PMID:26494957
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Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) in HIV.
Rockstroh, Jürgen Kurt
2017-04-01
Abnormal liver enzymes (LE) are common in patients infected with the human immunodeficiency virus (HIV) even in the absence of viral hepatitis or alcohol abuse. With availability of antiretroviral combination therapy, life expectancy has improved dramatically and as a consequence the spectrum of liver disease is changing. Increased reports on the development of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in HIV coinfected patients raise questions around prevalence, clinical manifestations, and clinical outcome of these liver diseases in HIV coinfection. Moreover, the potential impact of combination antiretroviral therapy as well as direct HIV effects on the emergence of non-alcoholic fatty liver disease needs to be explored. This review summarizes the recent literature on NAFLD and NASH in HIV.
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NASA Astrophysics Data System (ADS)
Alhajjar, Bashar J.; Linn Gould, C.; Chesters, Gordon; Harkin, John M.
1990-12-01
The effects of phosphate (P) and zeolite (Z) -built detergents on leaching of N and P through sand columns simulating septic system drainfields were examined in laboratory columns. To simulate mound septic system drainfields, paired sets of columns were dosed intermittently with septic tank effluent from households using P- or Z-built detergent. Two other paired sets of columns were flooded with P- or Z-effluent to simulate new conventional septic system drainfields; after clogging mats or "crusts" developed at infiltration surface, the subsurfaces of the columns were aerated to simulate mature (crusted) conventional septic system drainfields. NO 3 loading in leachate was 1.1 times higher and ortho-P loading was 4.3 times lower when columns were dosed with Z- than with P-effluent. Dosed columns removed P poorly; total phosphorus (TP) loading in leachate was 81 and 19 g m -2 yr -1 with P- and Z-effluent, respectively. In flooded columns 1.3, 2.0 and 1.8 times more NH 4, organic nitrogen (ON) and total nitrogen (TN) respectively, were leached with Z- than with P-effluent; NO 3 leaching was similar. Flooded columns removed P efficiently; TP leached through flooded systems was 2.5 and 1.4 g m -2 yr -1 with P- and Z effluent, respectively. Crusted columns fed Z-effluent leached 1.2, 2.6, 1.4 and 2.1 times more NH 4, NO 3, ON and TN, respectively, than those with P-effluent but 1.8 times less TP. Crusted columns removed P satisfactorily: 8.2 and 4.6 g m -2 yr -1 TP with P- and Z-effluent, respectively. The P-built detergent substantially improves the efficiency of N removal with satisfactory P removal in columns simulating conventional septic system drainfield. Simultaneous removal of N and P under flooded conditions might be explained by precipitation of struvite-type minerals. Dosed system drainfields were less efficient in removing N and P compared to flooded and crusted system drainfelds.
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MicroRNA Silencing Improves the Tumor Specificity of Adenoviral Transgene Expression
Card, Paul B.; Hogg, Richard T.; del Alcazar, Carlos Gil
2012-01-01
Adenoviral technology has been thoroughly evaluated for delivering genetic material to tumor tissue and the surrounding microenvironment. Almost any gene can be cloned into an adenovirus (Ad) vector, which when combined with strong, constitutively active promoters permit up to a million-fold amplification of the transgene in a single adenoviral particle, thus facilitating their use in cancer therapy and imaging. However, widespread infection of the liver and other non-targeted tissues by Ad vectors is a substantial problem that often results in significant liver inflammation and hepatotoxicity at doses required to achieve efficient tumor transduction. miR-122 is a highly expressed liver-specific microRNA that provides a unique opportunity for down-regulating adenoviral transgene expression in liver tissue. The binding of endogenous miRNAs to complementary miRNA targeting elements (miRTs) incorporated into the 3′ untranslated region of adenoviral transgenes interferes with message stability and/or protein translation, and miRT elements against miR-122 (miRT-122) can selectively reduce adenoviral transgene expression in the liver. Previous studies using miR-122-based regulation, with and without other types of transcriptional targeting, have yielded promising preliminary results. However, investigations to date evaluating miRT-122 elements for improving tumor specificity have used either non-tumor bearing animals or direct intratumoral injection as the mode of delivery. In the present study, we confirmed the ability of miRT-122 sequences to selectively down-regulate adenoviral luciferase expression in the liver in vitro and in vivo, and show that this strategy can improve tumor specific transgene expression in a HT1080 human fibrosarcoma model. Rapid growth and the inefficient flow of blood through tumor neovasculature often results in profound hypoxia, which provides additional opportunities for targeting solid tumors and their microenvironment using vectors incorporating hypoxia-responsive promoters to drive transgene expression. We therefore employed a combinatorial approach using miRT-122 elements with hypoxia-responsive transcriptional targeting to further improve the tumor specific expression of an adenoviral reporter gene. Results from this investigation reveal that miRT122 elements alone decrease off-target liver expression and improve tumor specificity of adenoviral vectors. Furthermore, increased tumor specificity can be achieved by combining miRT-122 elements with hypoxia-responsive promoters. PMID:22555510
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Can paracetamol (acetaminophen) be administered to patients with liver impairment?
Hayward, Kelly L.; Powell, Elizabeth E.; Irvine, Katharine M.
2015-01-01
Although 60 years have passed since it became widely available on the therapeutic market, paracetamol dosage in patients with liver disease remains a controversial subject. Fulminant hepatic failure has been a well documented consequence of paracetamol overdose since its introduction, while short and long term use have both been associated with elevation of liver transaminases, a surrogate marker for acute liver injury. From these reports it has been assumed that paracetamol use should be restricted or the dosage reduced in patients with chronic liver disease. We review the factors that have been purported to increase risk of hepatocellular injury from paracetamol and the pharmacokinetic alterations in different pathologies of chronic liver disease which may affect this risk. We postulate that inadvertent under‐dosing may result in concentrations too low to enable efficacy. Specific research to improve the evidence base for prescribing paracetamol in patients with different aetiologies of chronic liver disease is needed. PMID:26460177
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Hepatic stem/progenitor cells and stem-cell transplantation for the treatment of liver disease.
Kakinuma, Sei; Nakauchi, Hiromitsu; Watanabe, Mamoru
2009-01-01
Allogeneic liver transplantation is still the only effective treatment available to patients with liver failure. However, because there is a serious shortage of liver donors, an alternative therapeutic approach is needed. Transplantation of mature hepatocytes has been evaluated in clinical trials, but the long-term efficacy remains unclear and the paucity of donor cells limits this strategy. Stem-cell transplantation is a more promising alternative approach. Several studies have provided information about the mechanism underlying the proliferation and differentiation of hepatic stem/progenitor cells. Moreover, in experimental models of liver disease, transplantation of hepatic stem/progenitor cells or hepatocyte-like cells derived from multipotent stem cells led to donor cell-mediated repopulation of the liver and improved survival rates. However, before stem-cell transplantation can be applied in the clinic to treat liver failure in humans, it will be necessary to overcome several difficulties associated with the technique.
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A review of drug-induced liver injury databases.
Luo, Guangwen; Shen, Yiting; Yang, Lizhu; Lu, Aiping; Xiang, Zheng
2017-09-01
Drug-induced liver injuries have been a major focus of current research in drug development, and are also one of the major reasons for the failure and withdrawal of drugs in development. Drug-induced liver injuries have been systematically recorded in many public databases, which have become valuable resources in this field. In this study, we provide an overview of these databases, including the liver injury-specific databases LiverTox, LTKB, Open TG-GATEs, LTMap and Hepatox, and the general databases, T3DB, DrugBank, DITOP, DART, CTD and HSDB. The features and limitations of these databases are summarized and discussed in detail. Apart from their powerful functions, we believe that these databases can be improved in several ways: by providing the data about the molecular targets involved in liver toxicity, by incorporating information regarding liver injuries caused by drug interactions, and by regularly updating the data.
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Dubois, M; Fluchard, D; Sior, E; Delahaut, P
2001-04-05
We present an electrospray high-performance liquid chromatographic tandem mass spectrometric (HPLC-MS-MS) method capable of determining in several tissues (muscle, kidney, liver), eggs and milk the following five macrolides: tylosin, tilmicosin, spiramycin, josamycin, erythromycin. Roxithromycin was used as an internal standard. The method uses extraction in a Tris buffer at pH 10.5, followed by protein precipitation with sodium tungstate and clean-up on an Oasis solid-phase extraction column. The HPLC separation was performed on a Purospher C18 column (125 x 3 mm I.D.) protected by a guard column, with a gradient of aqueous 0.1 M ammonium acetate-acetonitrile as the mobile phase at a flow-rate of 0.7 ml min(-1). Protonated molecules served as precursor ions for electrospray ionisation in the positive ion mode and four product ions were chosen for each analyte for multiple reaction monitoring (MRM). A validation study was conducted to confirm the five macrolides by MRM HPLC-MS-MS analysis of a negative control and fortified samples. All of the samples analysed were confirmed with four ions. The ion ratio reproducibility limit ranged from 2.4 to 15%. All compounds could be detected and quantified at half-maximum residue limits (MRLs). The method is specific, quantitative and reproducible enough to conform to European Union recommendations within the concentration range 0.5 MRL-2 MRL (accuracy: 80 to 110%, relative standard deviation: 2 to 13%). This whole method allows extraction and analysis of up to 50 samples per day.
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Leroy, P; Decolin, D; Nicolas, A; Archimbault, P
1994-12-01
A simple, selective and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the measurement of josamycin residues in four porcine tissues (i.e., muscle, liver, kidney and fat). The sample preparation consisted of a homogenization step in an acetonitrile-10 mmol l-1 phosphate buffer mixture, pH 6.0 (35 + 65), centrifugation and a liquid-liquid extractive clean-up of the resulting supernatant with isooctane. Pre-column derivatization of josamycin was performed using cyclohexa-1,3-dione in ammonium acetate buffer, pH 5.0 (90 degrees C for 2 h). The derivative was chromatographed in an isocratic reversed-phase HPLC system. A LiChrospher RP 18 end-capped (5 microns) column was eluted with an acetonitrile-methanol-10 mmol l-1 phosphate buffer mixture, pH 6.0 (45 + 5 + 50). The capacity factor of the josamycin derivative was 17.5. Detection was achieved using spectrofluorimetry (lambda ex = 375 nm; lambda em = 450 nm). The structure of the derivative was assessed by using mass spectrometry. Full selectivity was obtained in the HPLC system versus other macrolide antibiotics (tylosin, spiramycin and erythromycin), aldehydes (formaldehyde, acetaldehyde and benzaldehyde) and endogenous compounds. Linearity and repeatability were tested. Correlation coefficients, for calibration curves in the range of 0.1-3.2 micrograms g-1, were greater than 0.999 for all tissues and the relative standard deviation (S(r)) was 4.9% (1.6 micrograms g-1; n = 6); recovery was higher than 88%.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Unkelbach, J; Perko, Z; Wolfgang, J
Purpose: Stereotactic body radiotherapy (SBRT) has become an established treatment option for liver cancer. For patients with large tumors, the prescription dose is often limited by constraints on the mean liver dose, leading to tumor recurrence. In this work, we demonstrate that spatiotemporal fractionation schemes, ie delivering distinct dose distributions in different fractions, may allow for a 10% increase in biologically effective dose (BED) in the tumor compared to current practice where each fraction delivers the same dose distribution. Methods: We consider rotation therapy delivered with x-ray beams. Treatment plan optimization is performed using objective functions evaluated for the cumulativemore » BED delivered at the end of treatment. This allows for simultaneously optimizing multiple distinct treatment plans for different fractions. Results: The treatment that optimally exploits fractionation effects is designed such that each fraction delivers a similar dose bath to the uninvolved liver while delivering high single fraction doses to complementary parts of the target volume. Thereby, partial hypofractionation in the tumor is achieved along with near uniform fractionation in the surrounding liver - leading to an improvement in the therapeutic ratio. The benefit of such spatiotemporal fractionation schemes depends on tumor geometry and location as well as the number of fractions. For 5-fraction treatments (allowing for 5 distinct dose distributions) an improvement in the order of 10% is observed. Conclusion: Delivering distinct dose distributions in different fractions, purely motivated by fractionation effects rather than geometric changes, may improve the therapeutic ratio. For treatment sites where the prescriptions dose is limited by mean dose constraints in the surrounding organ, such as liver cancer, this approach may facilitate biological dose escalation and improved cure rates.« less
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Jahangiri, Azin; Barzegar-Jalali, Mohammad; Garjani, Alireza; Javadzadeh, Yousef; Hamishehkar, Hamed; Asadpour-Zeynali, Karim; Adibkia, Khosro
2016-01-20
Fixed-dose combination of atorvastatin calcium (ATV) and ezetimibe (EZT) provides a considerable advantage in the management of hyperlipidemia. However, both ATV and EZT suffer from the poor aqueous solubility, which can limit their oral bioavailability. The aim of the present study was to improve the in vitro performance and evaluate the in vivo efficiency of the improved (ATV/EZT) fixed-dose combination. The formulation was prepared through solid dispersion (SD)technique, using Polyvinylpyrrolidone K30 via solvent method. Solid-state analysis and the in vitro drug release of the prepared formulations were also assessed. In order to estimate the therapeutic efficiency of the prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were conducted. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) showed that the drugs crystallinity was notably decreased during the preparation process. All SDs showed enhanced release for both drugs compared to their binary mixture, drugs: polymer physical mixtures (PMs) and marketed product. Administration of ATV/EZT SD led to a remarkable decrease (P<0.05) in the serum levels of total cholesterol (TC) and LDL-C in the high fat diet-induced hyperlipidemic rats compared to the PM. Additionally, the histopathological examination of the liver tissue revealed the improved efficiency of the SDs on the liver steatosis. According to the obtained results, ATV/EZT SD with improved physicochemical characteristics, showed favorable effects on the serum lipid levels and liver steatosis. Copyright © 2015 Elsevier B.V. All rights reserved.
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Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice.
Mitchell, Sarah J; Bernier, Michel; Aon, Miguel A; Cortassa, Sonia; Kim, Eun Young; Fang, Evandro F; Palacios, Hector H; Ali, Ahmed; Navas-Enamorado, Ignacio; Di Francesco, Andrea; Kaiser, Tamzin A; Waltz, Tyler B; Zhang, Ning; Ellis, James L; Elliott, Peter J; Frederick, David W; Bohr, Vilhelm A; Schmidt, Mark S; Brenner, Charles; Sinclair, David A; Sauve, Anthony A; Baur, Joseph A; de Cabo, Rafael
2018-03-06
The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD + , is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD + nor NADP + was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects. Published by Elsevier Inc.
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Hepatocellular carcinoma: early-stage management challenges
Erstad, Derek J; Tanabe, Kenneth K
2017-01-01
Hepatocellular carcinoma (HCC) is a major cause of cancer death and is increasing in incidence. This review focuses on HCC surveillance and treatment of early-stage disease, which are essential to improving outcomes. Multiple societies have published HCC surveillance guidelines, but screening efforts have been limited by noncompliance and overall lack of testing for patients with undiagnosed chronic liver disease. Treatment of early-stage HCC has become increasingly complex due to expanding therapeutic options and better outcomes with established treatments. Surgical indications for HCC have broadened with improved preoperative liver testing, neoadjuvant therapy, portal vein embolization, and perioperative care. Advances in post-procedural monitoring have improved efficacies of transarterial chemoembolization and radiofrequency ablation, and novel therapies involving delivery of radiochemicals are being studied in small trials. Finally, advances in liver transplantation have allowed for expanded indications beyond Milan criteria with non-inferior outcomes. More clinical trials evaluating new therapies and multimodal regimens are necessary to help clinicians design better treatment algorithms and improve outcomes. PMID:28721349
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Computational Modeling in Liver Surgery
Christ, Bruno; Dahmen, Uta; Herrmann, Karl-Heinz; König, Matthias; Reichenbach, Jürgen R.; Ricken, Tim; Schleicher, Jana; Ole Schwen, Lars; Vlaic, Sebastian; Waschinsky, Navina
2017-01-01
The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery. PMID:29249974
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The global burden of liver disease: the major impact of China.
Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang
2014-12-01
Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its "leader in liver diseases" title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. © 2014 by the American Association for the Study of Liver Diseases.
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Shimizu, Masahito; Shirakami, Yohei; Hanai, Tatsunori; Imai, Kenji; Suetsugu, Atsushi; Takai, Koji; Shiraki, Makoto; Moriwaki, Hisataka
2014-01-01
The poor prognosis for patients with hepatocellular carcinoma (HCC) is associated with its high rate of recurrence in the cirrhotic liver. Therefore, more effective strategies need to be urgently developed for the chemoprevention of this malignancy. The malfunction of retinoid X receptor α, a retinoid receptor, due to phosphorylation by Ras/mitogen-activated protein kinase is closely associated with liver carcinogenesis and may be a promising target for HCC chemoprevention. Acyclic retinoid (ACR), a synthetic retinoid, can prevent HCC development by inhibiting retinoid X receptor α phosphorylation and improve the prognosis for this malignancy. Supplementation with branched-chain amino acids (BCAA), which are used to improve protein malnutrition in patients with liver cirrhosis, can also reduce the risk of HCC in obese cirrhotic patients. In experimental studies, both ACR and BCAA exert suppressive effects on HCC development and the growth of HCC cells. In particular, combined treatment with ACR and BCAA cooperatively inhibits the growth of HCC cells. Furthermore, ACR and BCAA inhibit liver tumorigenesis associated with obesity and diabetes, both of which are critical risk factors for HCC development. These findings suggest that pharmaceutical and nutraceutical approaches using ACR and BCAA may be promising strategies for preventing HCC and improving the prognosis of this malignancy. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Methods for Improving the Curvature of Steerable Needles in Biological Tissue
Adebar, Troy K.; Greer, Joseph D.; Laeseke, Paul F.; Hwang, Gloria L.; Okamura, Allison M.
2016-01-01
Robotic needle steering systems have the potential to improve percutaneous interventions such as radiofrequency ablation of liver tumors, but steering techniques described to date have not achieved sufficiently small radius of curvature in biological tissue to be relevant to this application. In this work, the impact of tip geometry on steerable needle curvature is examined. Finite-element simulations and experiments with bent-tip needles in ex vivo liver tissue demonstrate that selection of tip length and angle can greatly improve curvature, with radius of curvature below 5 cm in liver tissue possible through judicious selection of these parameters. Motivated by the results of this analysis, a new articulated-tip steerable needle is described, in which a distal section is actively switched by a robotic system between a straight tip (resulting in a straight path) and a bent tip (resulting in a curved path). This approach allows the tip length and angle to be increased, while the straight configuration allows the needle tip to still pass through an introducer sheath and rotate inside the body. Validation testing in liver tissue shows that the new articulated-tip steerable needle achieves smaller radius of curvature compared to bent-tip needles described in previous work. Steerable needles with optimized tip parameters, which can generate tight curves in liver tissue, increase the clinical relevance of needle steering to percutaneous interventions. PMID:26441438
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Huda, Kamrul A S M; Guo, Lei; Haga, Sanae; Murata, Hiroshi; Ogino, Tetsuya; Fukai, Moto; Yagi, Takahito; Iwagaki, Hiromi; Tanaka, Noriaki; Ozaki, Michitaka
2006-05-01
Signal transducer and activator of transcription-3 (STAT3) is one of the most important transcription factors for liver regeneration. This study was designed to examine the effects of constitutively activated STAT3 (STAT3-C) on post-transplant liver injury and regeneration in a rat 20% partial liver transplant (PLTx) model by ex vivo adenoviral gene transfer. Adenovirus encoding the STAT3-C gene was introduced intraportally into liver grafts and clamped for 30 min during cold preservation. After orthotopic PLTx, liver graft/body weights and serum biochemistry were monitored, and both a histological study and DNA binding assay were performed. STAT3-C protein expression and its binding to DNA in the liver graft were confirmed by Western blotting and electrophoretic mobility shift assay (EMSA), respectively. This treatment modality promoted post-Tx liver regeneration effectively and rapidly. The serum levels of alanine aminotransferase/aspartate aminotransferase (AST/ALT) and bilirubin decreased in rats with STAT3-C. However, albumin (a marker of liver function) did not. Ex vivo gene transfer of STAT3-C to liver grafts reduced post-Tx injury and promoted liver regeneration. Thus, the activation of STAT3 in the liver graft may be a potentially effective clinical strategy for improving the outcome of small-for-size liver transplantation.
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NASA Astrophysics Data System (ADS)
Uzunova, Yordanka; Prodanova, Krasimira; Spassov, Lubomir
2016-12-01
Orthotopic liver transplantation (OLT) is the only curative treatment for end-stage liver disease. Early diagnosis and treatment of infections after OLT are usually associated with improved outcomes. This study's objective is to identify reliable factors that can predict postoperative infectious morbidity. 27 children were included in the analysis. They underwent liver transplantation in our department. The correlation between two parameters (the level of blood glucose at 5th postoperative day and the duration of the anhepatic phase) and postoperative infections was analyzed, using univariate analysis. In this analysis, an independent predictive factor was derived which adequately identifies patients at risk of infectious complications after a liver transplantation.
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Huang, Cheng-Ze; Tung, Yu-Tang; Hsia, Shih-Min; Wu, Chi-Hao; Yen, Gow-Chin
2017-02-22
Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is closely associated with metabolic syndrome and refers to the accumulation of hepatic steatosis not due to excess alcohol consumption. Phyllanthus emblica L. is a rich source of gallic acid and many known medicinally phytochemicals such as tannins, lignans, flavonoids, alkaloids, vitamin C, mucic acid, and ellagic acid. Our previous study has revealed that P. emblica exhibits inhibitory effects on hepatic steatosis and liver fibrosis in vitro, as well as gallic acid improves high fat diet (HFD)-induced dyslipidaemia, hepatosteatosis, and oxidative stress in vivo. Therefore, the aim of this study was to investigate the hepatoprotective effect of the water extract of P. emblica L. fruit (WEPE) on NAFLD in an animal model. The results showed that WEPE could significantly decrease body weight, peritoneal fat and epididymal fat, enhance the antioxidant enzyme activities, and improve steatosis through elevating adiponectin in adipocytes and PPAR-α in the liver as well as lowering SREBP-1c in the liver of rats fed with a high fat diet (HFD). This might be an explanation for the hepatic fat deposition-lowering effect of WEPE. These results demonstrate that WEPE could be beneficial for the amelioration of HFD-induced steatosis.
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Vildhede, Anna; Wiśniewski, Jacek R; Norén, Agneta; Karlgren, Maria; Artursson, Per
2015-08-07
Freshly isolated human hepatocytes are considered the gold standard for in vitro studies of liver functions, including drug transport, metabolism, and toxicity. For accurate predictions of the in vivo outcome, the isolated hepatocytes should reflect the phenotype of their in vivo counterpart, i.e., hepatocytes in human liver tissue. Here, we quantified and compared the membrane proteomes of freshly isolated hepatocytes and human liver tissue using a label-free shotgun proteomics approach. A total of 5144 unique proteins were identified, spanning over 6 orders of magnitude in abundance. There was a good global correlation in protein abundance. However, the expression of many plasma membrane proteins was lower in the isolated hepatocytes than in the liver tissue. This included transport proteins that determine hepatocyte exposure to many drugs and endogenous compounds. Pathway analysis of the differentially expressed proteins confirmed that hepatocytes are exposed to oxidative stress during isolation and suggested that plasma membrane proteins were degraded via the protein ubiquitination pathway. Finally, using pitavastatin as an example, we show how protein quantifications can improve in vitro predictions of in vivo liver clearance. We tentatively conclude that our data set will be a useful resource for improved hepatocyte predictions of the in vivo outcome.
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Effect of concurrent training on risk factors and hepatic steatosis in obese adolescents
Antunes, Barbara de Moura M.; Monteiro, Paula Alves; Silveira, Loreana Sanches; Cayres, Suziane Ungari; da Silva, Camila Buonani; F., Ismael Forte
2013-01-01
OBJECTIVE To analyze the effects of a 20-week concurrent training on the variables of body composition, lipid profile, and fatty liver diagnosis in obese adolescents. METHODS An open clinical trial was carried out with 34 obese adolescents aged between 12 and 15 years. Total body fat, trunk fat mass, total cholesterol and its fractions (HDL, LDL and VLDL), and triglycerides were analyzed; an upper abdominal ultrasound was performed in order to diagnose fatty liver. The participants underwent concurrent training (association of weight training with aerobic training) three times per week, lasting one hour for 20 weeks. Statistical analysis included paired Studentâ€(tm)s t-test and frequency analysis in order to verify the relative and absolute reductions of fatty liver diagnosis, being significant p<0.05. RESULTS The studied adolescents showed statistically significant improvement in body composition, with a decrease of total body fat percentage, total fat mass, trunk fat, and an a increase in the lean body mass. They also presented reduced size of liver lobes, decrease in total cholesterol and in LDL-cholesterol, with a lower prevalence of fatty liver. CONCLUSIONS The concurrent training was effective for promoting significant improvements in body fat composition and lipid profile variables, besides reducing fatty liver prevalence rate. PMID:24142321
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An effective method for cirrhosis recognition based on multi-feature fusion
NASA Astrophysics Data System (ADS)
Chen, Yameng; Sun, Gengxin; Lei, Yiming; Zhang, Jinpeng
2018-04-01
Liver disease is one of the main causes of human healthy problem. Cirrhosis, of course, is the critical phase during the development of liver lesion, especially the hepatoma. Many clinical cases are still influenced by the subjectivity of physicians in some degree, and some objective factors such as illumination, scale, edge blurring will affect the judgment of clinicians. Then the subjectivity will affect the accuracy of diagnosis and the treatment of patients. In order to solve the difficulty above and improve the recognition rate of liver cirrhosis, we propose a method of multi-feature fusion to obtain more robust representations of texture in ultrasound liver images, the texture features we extract include local binary pattern(LBP), gray level co-occurrence matrix(GLCM) and histogram of oriented gradient(HOG). In this paper, we firstly make a fusion of multi-feature to recognize cirrhosis and normal liver based on parallel combination concept, and the experimental results shows that the classifier is effective for cirrhosis recognition which is evaluated by the satisfying classification rate, sensitivity and specificity of receiver operating characteristic(ROC), and cost time. Through the method we proposed, it will be helpful to improve the accuracy of diagnosis of cirrhosis and prevent the development of liver lesion towards hepatoma.
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Outcomes after liver transplantation of patients with Indo-Asian ethnicity.
Rocha, Chiara; Perera, M Thamara; Roberts, Keith; Bonney, Glenn; Gunson, Bridget; Nightingale, Peter; Bramhall, Simon R; Isaac, John; Muiesan, Paolo; Mirza, Darius F
2015-04-01
The impact of ethnicity on outcomes after orthotopic liver transplantation (OLT) is unclear. The British Indo-Asian population has a high incidence of liver disease but its contribution to the national deceased donor pool is small. We evaluated access to and outcomes of OLT in Indo-Asians. We compared 182 Indo-Asians with white patients undergoing OLT. Matching criteria were transplantation year, liver disease, age, sex. Donor and recipient characteristics, postoperative outcomes, including patient and graft survival, OLT era (early, 1987-2001; late, 2002-2011) were compared. Survival was also analyzed by underlying disease-acute liver failure (ALF) and chronic liver failure. Indo-Asians had higher diabetes incidence. There were no differences in waiting time for transplantation, despite smaller body size and more uncommon blood groups (B, AB) among Indo-Asians. In the early era, patient survival for Indo-Asians with ALF was worse when compared to whites. In the late era, graft and patient survival at 1, 2, and 5 years were similar between groups. This study demonstrates that Indo-Asian patients have equal access to OLT and comparable outcomes to whites in the United Kingdom. Survival has improved among Indo-Asian patients; this may be attributable to careful patient selection in case of ALF, though improvement of patient management may have contributed.
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Recurrent hepatitis C after liver transplant
deLemos, Andrew S; Schmeltzer, Paul A; Russo, Mark W
2014-01-01
End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5B polymerase inhibitors and NS5A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients. PMID:25152571
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Hsu, Huai-Che; Matsuno, Naoto; Machida, Noboru; Enosawa, Shin
2013-01-01
Demand for human primary hepatocytes is increasing, particularly for clinical trials of hepatocyte transplantation. However, due to the severe shortage of organ transplant donors, the source of cells for these endeavors is restricted to untransplantable livers, such as those from non-heart-beating donors and surgically resected liver tissues. To improve cell recovery from such sources after warm ischemia, we evaluated the efficacy of applying perfusion solutions, focusing on improvement of hepatocyte recovery. Warm ischemia was induced by clamping both portal vein and hepatic artery for 10 or 15 min in rats. The liver was perfused with either Euro-Collins (EC) or extracellular-type trehalose-containing Kyoto (ETK) solutions supplemented with an anticoagulant, either heparin or citrate phosphate dextrose solution (CPD), compared to Ca2+, Mg2+-free Hanks solution. While the viability of recovered cells was 81.5 ± 4.2% and cell yield was 2.27 ± 0.53 × 108 in nonwarm ischemia controls (n = 11), these values were only 74.7 ± 2.9% and 0.38 ± 0.17 × 108, respectively, in the 10-min warm ischemia group, using the Hanks as the perfusion solution. Although the addition of heparin increased the live cell number only twofold (0.71 ± 0.40 × 108, n = 4), the best improvement was achieved by adding CPD to EC. This resulted in a recovery of 1.41 ± 0.50 × 108 in the 10-min ischemia group (n = 7) and 1.37 ± 0.28 × 108 in the 15-min group (n = 3). Macroscopic observation showed that blood had been completely flushed out by the solution, suggesting good restoration of the microcirculation in ischemic liver. Using ETK instead of EC resulted in a slight decrease in efficacy. These results demonstrate that CPD, as opposed to heparin, is effective in ensuring liver microcirculation and flushing out the blood and that EC is the best perfusion solution for obtaining hepatocytes from ischemic liver. PMID:26858872
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Famurewa, Ademola C; Ufebe, Odomero G; Egedigwe, Chima A; Nwankwo, Onyebuchi E; Obaje, Godwin S
2017-03-01
The emerging health benefit of virgin coconut oil (VCO) has been associated with its potent natural antioxidants; however, the antioxidant and hepatoprotective effect of VCO against methotrexate-induced liver damage and oxidative stress remains unexplored. The study explored the antioxidant and hepatoprotective effects of VCO against oxidative stress and liver damage induced by anticancer drug methotrexate (MTX) in rats. Liver damage was induced in Wistar rats pretreated with dietary supplementation of VCO (5% and 15%) by intraperitoneal administration of MTX (20mg/kg bw) on day 10 only. After 12days of treatment, assays for serum liver biomarkers (aminotransferases), alkaline phosphatase, albumin and total protein as well as hepatic content of malondialdehyde, reduced glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) were carried out. Liver was used to examine histopathological changes. MTX administration induced significant increase in serum liver enzymes along with marked decrease in albumin and total protein compared to control group. Hepatic activities of antioxidant enzymes were significantly decreased, while malondialdehyde increased significantly. Treatment with VCO supplemented diet prior to MTX administration attenuated MTX-induced liver injury and oxidative stress evidenced by significant improvements in serum liver markers, hepatic antioxidant enzymes and malondialdehyde comparable to control group. Histopathological alterations were prevented and correlated well with the biochemical indices. The study suggests antioxidant and hepatoprotective effects of VCO supplementation against hepatotoxicity and oxidative damage via improving antioxidant defense system in rats. Our findings may have beneficial application in the management of hepatotoxicity associated with MTX cancer chemotherapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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Aliakbarian, Mohsen; Nikeghbalian, Saman; Ghaffaripour, Sina; Bahreini, Amin; Shafiee, Mohammad; Rashidi, Mohammad; Rajabnejad, Yaser
2017-08-01
One of the main concerns in liver transplant is the prolonged ischemia time, which may lead to primary graft nonfunction or delayed function. N-acetylcysteine is known as a hepato-protective agent in different studies, which may improve human hepatocyte viability in steatotic donor livers. This study investigated whether N-acetylcysteine can decrease the rate of ischemia-reperfusion syndrome and improve short-term outcome in liver transplant recipients. This was a double-blind, randomized, control clinical trial of 115 patients. Between April 2012 and January 2013, patients with orthotopic liver transplant were randomly divided into 2 groups; in 49 cases N-acetylcysteine was added to University of Wisconsin solution as the preservative liquid (experimental group), and in 66 cases standard University of Wisconsin solution was used (control group). We compared postreperfusion hypotension, inotrope requirement before and after portal reperfusion, intermittent arterial blood gas analysis and potassium measurement, pathological review of transplanted liver, in-hospital complications, morbidity, and mortality. There was no significant difference between the groups regarding time to hepatic artery reperfusion, hospital stay, vascular complications, inotrope requirement before and after portal declamping, and blood gas analysis. Hypotension after portal reperfusion was significantly more common in experimental group compared with control group (P = .005). Retransplant and in-hospital mortality were comparable between the groups. Preservation of the liver inside Univer-sity of Wisconsin solution plus N-acetylcysteine did not change the rate of ischemia reperfusion injury and short-term outcome in liver transplant recipients.
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Ion exchange purification of scandium
Herchenroeder, Laurie A.; Burkholder, Harvey R.
1990-10-23
An improvement in purification of scandium through ion exchange chromatography is disclosed in which the oxidation potential of the eluting solution is altered by the addition of potassium chlorate or ammonium chloride so that removal of contaminants is encouraged. The temperature, pH and concentration of the eluent HEDTA are controlled in order to maintain the scandium in the column while minimizing dilution of the scandium band. Recovery of scandium is improved by pumping dilute scandium over the column prior to stripping the scandium and precipitation. This eliminates the HEDTA ion and other monovalent cations contaminating the scandium band. This method maximizes recovery of scandium while maintaining purity.
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Ion exchange purification of scandium
Herchenroeder, L.A.; Burkholder, H.R.
1990-10-23
An improvement in purification of scandium through ion exchange chromatography is disclosed in which the oxidation potential of the eluting solution is altered by the addition of potassium chlorate or ammonium chloride so that removal of contaminants is encouraged. The temperature, pH and concentration of the eluent HEDTA are controlled in order to maintain the scandium in the column while minimizing dilution of the scandium band. Recovery of scandium is improved by pumping dilute scandium over the column prior to stripping the scandium and precipitation. This eliminates the HEDTA ion and other monovalent cations contaminating the scandium band. This method maximizes recovery of scandium while maintaining purity. 2 figs.
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Miyagi, Michiko; Yokoyama, Hirokazu; Hibi, Toshifumi
2007-07-01
An HPLC protocol for sugar microanalysis based on the formation of ultraviolet-absorbing benzoyl chloride derivatives was improved. Here, samples were prepared with a C-8 cartridge and analyzed with a high efficiency ODS column, in which porous spherical silica particles 3 microm in diameter were packed. These devices allowed us to simultaneously quantify multiple sugars and sugar alcohols up to 10 ng/ml and to provide satisfactory separations of some sugars, such as fructose and myo-inositol and sorbitol and mannitol. This protocol, which does not require special apparatuses, should become a powerful tool in sugar research.
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Improved Flow Modulator Construction for GC × GC with Quadrupole Mass Spectrometry.
Ston, Martin; Cabala, Radomir; Bierhanzl, Vaclav Matej; Krajicek, Jan; Bosakova, Zuzana
2016-08-18
Improvement and testing of a flow modulator for the application in comprehensive two-dimensional gas chromatography separations is the subject of the presented paper. This improved setup constructed from two independent capillary branches each consisting of a pressure regulator, a pressure sensor, a two-way solenoid valve and a microfluidic T-connector, allows an independent and easy settings of the pressures and flow velocities in the modulator and provides system flexibility in an operation without need of any component exchange. The estimated flow rates were 0.4 mL/min in the first column and 3.2 mL/min in the second column. This setup was compared with the commercial Zoex cryogenic modulator for the separation of 17 selected solvents at isothermal conditions. Modulator working conditions were optimized and its separation power was demonstrated on the analysis of a lavender extract under an application of two orthogonal capillary column sets (nonpolar-polar vs. polar-nonpolar) and temperature program. The results were evaluated by two commercial software packages and discussed with respect to the identification compliance. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Coconut water vinegar ameliorates recovery of acetaminophen induced liver damage in mice.
Mohamad, Nurul Elyani; Yeap, Swee Keong; Beh, Boon-Kee; Ky, Huynh; Lim, Kian Lam; Ho, Wan Yong; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu
2018-06-25
Coconut water has been commonly consumed as a beverage for its multiple health benefits while vinegar has been used as common seasoning and a traditional Chinese medicine. The present study investigates the potential of coconut water vinegar in promoting recovery on acetaminophen induced liver damage. Mice were injected with 250 mg/kg body weight acetaminophen for 7 days and were treated with distilled water (untreated), Silybin (positive control) and coconut water vinegar (0.08 mL/kg and 2 mL/kg body weight). Level of oxidation stress and inflammation among treated and untreated mice were compared. Untreated mice oral administrated with acetaminophen were observed with elevation of serum liver profiles, liver histological changes, high level of cytochrome P450 2E1, reduced level of liver antioxidant and increased level of inflammatory related markers indicating liver damage. On the other hand, acetaminophen challenged mice treated with 14 days of coconut water vinegar were recorded with reduction of serum liver profiles, improved liver histology, restored liver antioxidant, reduction of liver inflammation and decreased level of liver cytochrome P450 2E1 in dosage dependent level. Coconut water vinegar has helped to attenuate acetaminophen-induced liver damage by restoring antioxidant activity and suppression of inflammation.
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Combined heat and mass transfer device for improving separation process
Tran, Thanh Nhon
1999-01-01
A two-phase small channel heat exchange matrix simultaneously provides for heat transfer and mass transfer between the liquid and vapor phases of a multi-component mixture at a single, predetermined location within a separation column, significantly improving the thermodynamic efficiency of the separation process. The small channel heat exchange matrix is composed of a series of channels having a hydraulic diameter no greater than 5.0 millimeters for conducting a two-phase coolant. In operation, the matrix provides the liquid-vapor contacting surfaces within the separation column, such that heat and mass are transferred simultaneously between the liquid and vapor phases. The two-phase coolant allows for a uniform heat transfer coefficient to be maintained along the length of the channels and across the surface of the matrix. Preferably, a perforated, concave sheet connects each channel to an adjacent channel to facilitate the flow of the liquid and vapor phases within the column and to increase the liquid-vapor contacting surface area.
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Combined heat and mass transfer device for improving separation process
Tran, T.N.
1999-08-24
A two-phase small channel heat exchange matrix simultaneously provides for heat transfer and mass transfer between the liquid and vapor phases of a multi-component mixture at a single, predetermined location within a separation column, significantly improving the thermodynamic efficiency of the separation process. The small channel heat exchange matrix is composed of a series of channels having a hydraulic diameter no greater than 5.0 millimeters for conducting a two-phase coolant. In operation, the matrix provides the liquid-vapor contacting surfaces within the separation column, such that heat and mass are transferred simultaneously between the liquid and vapor phases. The two-phase coolant allows for a uniform heat transfer coefficient to be maintained along the length of the channels and across the surface of the matrix. Preferably, a perforated, concave sheet connects each channel to an adjacent channel to facilitate the flow of the liquid and vapor phases within the column and to increase the liquid-vapor contacting surface area. 12 figs.
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Bereman, Michael S.; Egertson, Jarrett D.; MacCoss, Michael J.
2012-01-01
Filter aided sample preparation (FASP) and a new sample preparation method using a modified commercial SDS removal spin column are quantitatively compared in terms of their performance for shotgun proteomic experiments in three complex proteomic samples: a Saccharomyces cerevisiae lysate (insoluble fraction), a Caenorhabditis elegans lysate (soluble fraction), and a human embryonic kidney cell line (HEK293T). The characteristics and total number of peptides and proteins identified are compared between the two procedures. The SDS spin column procedure affords a conservative 4-fold improvement in throughput, is more reproducible, less expensive (i.e., requires less materials), and identifies between 30–107% more peptides at a q≤0.01, than the FASP procedure. The peptides identified by SDS spin column are more hydrophobic than species identified by the FASP procedure as indicated by the distribution of GRAVY scores. Ultimately, these improvements correlate to as great as a 50% increase in protein identifications with 2 or more peptides. PMID:21656683
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Removing Chlorides From Metallurgical-Grade Silicon
NASA Technical Reports Server (NTRS)
Breneman, W. C.; Coleman, L. M.
1982-01-01
Process for making low-cost silicon for solar cells is further improved. Silane product recycled to feed stripper column converts some of heavy impurities to volatile ones that pass off at top of column with light wastes. Impurities--chlorides of arsenic, phosphorus, and boron-would otherwise be carried to subsequent distillations where they would be difficult to remove. Since only a small amount of silane is recycled, silicon production efficiency remains high.
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Pietrogrande, Maria Chiara; Dondi, Francesco; Ciogli, Alessia; Gasparrini, Francesco; Piccin, Antonella; Serafini, Mauro
2010-06-25
In this study, a comparative investigation was performed of HPLC Ascentis (2.7 microm particles) columns based on fused-core particle technology and Acquity (1.7 microm particles) columns requiring UPLC instruments, in comparison with Chromolith RP-18e columns. The study was carried out on mother and vegetal tinctures of Passiflora incarnata L. on one single or two coupled columns. The fundamental attributions of the chromatographic profiles are evaluated using a chemometric procedure, based on the AutoCovariance Function (ACVF). Different chromatographic systems are compared in terms of their separation parameters, i.e., number of total chemical components (m(tot)), separation efficiency (sigma), peak capacity (n(c)), overlap degree of peaks and peak purity. The obtained results show the improvements achieved by HPLC columns with narrow size particles in terms of total analysis time and chromatographic efficiency: comparable performance are achieved by Ascentis (2.7 microm particle) column and Acquity (1.7 microm particle) column requiring UPLC instruments. The ACVF plot is proposed as a simplified tool describing the chromatographic fingerprint to be used for evaluating and comparing chemical composition of plant extracts by using the parameters D% - relative abundance of the deterministic component - and c(EACF) - similarity index computed on ACVF. Copyright 2010 Elsevier B.V. All rights reserved.
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Study on Gas-liquid Falling Film Flow in Internal Heat Integrated Distillation Column
NASA Astrophysics Data System (ADS)
Liu, Chong
2017-10-01
Gas-liquid internally heat integrated distillation column falling film flow with nonlinear characteristics, study on gas liquid falling film flow regulation control law, can reduce emissions of the distillation column, and it can improve the quality of products. According to the distribution of gas-liquid mass balance internally heat integrated distillation column independent region, distribution model of heat transfer coefficient of building internal heat integrated distillation tower is obtained liquid distillation falling film flow in the saturated vapour pressure of liquid water balance, using heat transfer equation and energy equation to balance the relationship between the circulating iterative gas-liquid falling film flow area, flow parameter information, at a given temperature, pressure conditions, gas-liquid flow falling film theory makes the optimal parameters to achieve the best fitting value with the measured values. The results show that the geometric gas-liquid internally heat integrated distillation column falling film flow heat exchange area and import column thermostat, the average temperature has significant. The positive correlation between the heat exchanger tube entrance due to temperature difference between inside and outside, the heat flux is larger, with the increase of internal heat integrated distillation column temperature, the slope decreases its temperature rise, which accurately describes the internal gas-liquid heat integrated distillation tower falling film flow regularity, take appropriate measures to promote the enhancement of heat transfer. It can enhance the overall efficiency of the heat exchanger.
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Desferrioxamine in warm reperfusion media decreases liver injury aggravated by cold storage
Arthur, Peter G; Niu, Xian-Wa; Huang, Wen-Hua; DeBoer, Bastiaan; Lai, Ching Tat; Rossi, Enrico; Joseph, John; Jeffrey, Gary P
2013-01-01
AIM: To evaluate whether desferrioxamine decreases ischemia and perfusion injury aggravated by cold storage (CS) in a rat liver perfusion model. METHODS: Isolated rat livers were kept in CS in University of Wisconsin Solution for 20 h at 4 °C, then exposed to 25 min of warm ischemia (WI) at 37 °C followed by 2 h of warm perfusion (WP) at 37 °C with oxygenated (95% oxygen and 5% carbon dioxide) Krebs-Henseleit buffer. Desferrioxamine (DFO), an iron chelator, was added at different stages of storage, ischemia and perfusion: in CS only, in WI only, in WP only, in WI and perfusion, or in all stages. Effluent samples were collected after CS and after WI. Perfusate samples and bile were collected every 30 min (0, 0.5, 1, 1.5 and 2 h) during liver perfusion. Cellular injury was assessed by the determination of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) in the effluent and perfusate samples. Total iron was analysed in the perfusate samples. After WP, the liver was collected for the determination of liver swelling (wet to dry ratio) and liver morphological examination (hematoxylin and eosin staining). RESULTS: Increased CS time caused increased liver dysfunction during WP. After 2 h of WP, liver injury was indicated by increased release of AST (0.5 h CS: 9.4 ± 2.2 U/g liver vs 20 h CS: 45.9 ± 10.8 U/g liver, P < 0.05) and LDH (0.5 h CS: 59 ± 14 U/g liver vs 20 h CS: 297 ± 71 U/g liver, P < 0.05). There was an associated increase in iron release into the perfusate (0.5 h CS: 0.11 ± 0.03 μmoL/g liver vs 20 h CS: 0.58 ± 0.10 μmoL/g liver, P < 0.05) and reduction in bile flow (0.5 h CS: 194 ± 12 μL/g vs 20 h CS: 71 ± 8 μL/g liver, P < 0.05). When DFO was added during WI and WP following 20 h of CS, release of iron into the perfusate was decreased (DFO absent 0.58 ± 0.10 μmoL/g liver vs DFO present 0.31 ± 0.06 μmoL/g liver, P < 0.05), and liver function substantially improved with decreased release of AST (DFO absent 45.9 ± 10.8 U/g liver vs DFO present 8.1 ± 0.9 U/g liver, P < 0.05) and LDH (DFO absent 297 ± 71 U/g liver vs DFO present 56 ± 7 U/g liver, P < 0.05), and increased bile flow (DFO absent 71 ± 8 μL/g liver vs DFO present 237 ± 36 μL/g liver, P < 0.05). DFO was also shown to improve liver morphology after WP. Cellular injury (the release of LDH and AST) was significantly reduced with the addition of DFO in CS medium but to a lesser extent compared to the addition of DFO in WP or WI and perfusion. There was no effect on liver swelling or bile flow when DFO was only added to the CS medium. CONCLUSION: DFO added during WI and perfusion decreased liver perfusion injury aggravated by extended CS. PMID:23429835
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kostadinova, Radina; Boess, Franziska; Applegate, Dawn
2013-04-01
Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitromore » three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity observed in vivo. ► 3D liver co-cultures can detect species-specific drug toxicity observed in vivo. ► This in vitro model may improve assessment of human relevance of preclinical findings.« less
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Our Vision | Center for Cancer Research
Our Vision The mission of the NCI-CCR-LCP is to develop a multi-disciplinary program focused on the prevention, early detection, improved diagnosis and treatment of liver cancer. Liver cancer is the 2nd most common cause of cancer-related death worldwide.
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MacArthur, Katherine E; Brown, Hamish G; Findlay, Scott D; Allen, Leslie J
2017-11-01
Advances in microscope stability, aberration correction and detector design now make it readily possible to achieve atomic resolution energy dispersive X-ray mapping for dose resilient samples. These maps show impressive atomic-scale qualitative detail as to where the elements reside within a given sample. Unfortunately, while electron channelling is exploited to provide atomic resolution data, this very process makes the images rather more complex to interpret quantitatively than if no electron channelling occurred. Here we propose small sample tilt as a means for suppressing channelling and improving quantification of composition, whilst maintaining atomic-scale resolution. Only by knowing composition and thickness of the sample is it possible to determine the atomic configuration within each column. The effects of neighbouring atomic columns with differing composition and of residual channelling on our ability to extract exact column-by-column composition are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.