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1

Effect of alanine on D-galactosamine-induced acute liver failure in rats  

Microsoft Academic Search

The effect of high-dose alanine on survival and liver function in rats with acute liver failure caused by a lethal dose of D-galactosamine (D-gal) was studied. Greater than 90% of control animals died within 5 days after D-gal injection, but alanine significantly decreased mortality, even when treatment was started at 12 hours after D-gal injection. Alanyl-glutamine had a slight effect,

K Maezono; K Mawatari; K Kajiwara; A Shinkai; T Maki

1996-01-01

2

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

Microsoft Academic Search

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

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

2005-01-01

3

Liver function tests in viremic and nonviremic chronic hepatitis B virus-infected pregnant women: importance of alanine aminotransferase/sodium ratio.  

PubMed

The major risk factor of perinatal transmission of Hepatitis B virus (HBV) infection is the level of maternal HBV-deoxyribonucleic acid (DNA) during the third trimester of pregnancy. The primary aim of this study was to evaluate the hematological and biochemical status in Hepatitis B e-antigen (HBeAg)-negative chronic HBV-infected pregnant women and to correlate the findings with the presence or absence of viremia. Ninety-five consecutive chronic HBV-infected pregnant women were evaluated between the 28th and 32nd week of gestation. Viral load was determined by using the COBAS TaqMan HBV test. Sixty-nine women were evaluated and 14 of them exhibited HBV-DNA levels higher than 2000 IU·ml. In this study, viremic women exhibited significantly higher alanine aminotransferase (ALT), creatinine, and uric acid values as well as significantly lower white blood cell count compared with nonviremic women. There was also a significant statistical difference concerning ALT/sodium ratio between viremic and nonviremic women (0.20 ± 0.22 vs. 0.10 ± 0.09, respectively, p= .024). The optimal cutoff points discriminating those women with a high probability to have detectable serum HBV-DNA were 0.092 for ALT/sodium ratio (sensitivity = 73.0%, specificity = 61.5%, area under the receiver operating characteristic curve [AUC] = 71.05%) and 12.8 IU/L for ALT (sensitivity = 73.0%, specificity = 63.0%, AUC = 72.2%). Chronic HBV-infected pregnant women with ALT/sodium ratio ? 0.11 had the higher probability of having serum HBV-DNA levels higher than 2000 IU/ml (sensitivity = 76.92%, specificity = 58%, AUC = 62.38%). Presence of HBV-DNA in maternal blood during the third trimester of pregnancy is significantly associated with maternal serum ALT levels in HBeAg-negative chronic HBV-infected pregnant women. Women with an ALT/sodium ratio greater than 0.092 have the higher probability of HBV-DNA presence in maternal blood whereas an ALT/sodium ratio greater than 0.11 could discriminate those women with HBV-DNA levels higher than 2000 IU/ml. PMID:24304526

Elefsiniotis, Ioannis S; Tsoumakas, Konstantinos; Kapritsou, Maria; Magaziotou, Ioanna; Derdemezi, Angeliki; T, Mariolis-Sapsakos; Katsoulas, Th; Konstantinou, Evangelos A

2013-01-01

4

L-alanine uptake by rat liver parenchymal and haematopoietic cells during the perinatal period.  

PubMed Central

Alanine disposal by liver parenchymal and haematopoietic cells from 21-day fetuses, newborns and adult rats was studied. Preparations selectively enriched in either haematopoietic cells or hepatocytes were obtained by direct perfusion of fetal- and neonatal-rat livers. L-Alanine transport into liver parenchymal cells was best fitted to two Na(+)-dependent saturable systems. The high-affinity system showed a much higher activity (Vmax.) in hepatocytes from fetuses and newborns than in those from adult rats (2.4, 4.3 and 0.3 nmol/8 min per 10(6) cells for fetuses, newborns and adults respectively). Vmax. for the low-affinity component was slightly lower during the perinatal period than in the adult (about 30 nmol/8 min per 10(6) cells for hepatocytes from fetuses and newborns, versus 48 nmol/8 min per 10(6) cells for adult rat parenchymal cells). Haematopoietic cells from fetal-rat livers showed significant Na(+)-dependent L-alanine uptake which was completely abolished after birth. These results show that the transport systems involved in L-alanine uptake by liver parenchymal cells are fully developed before birth. This probably contributes to fulfilling the high requirement for neutral amino acids for protein synthesis during development. Haematopoietic cells may play an important role in liver amino acid metabolism during fetal life.

Martinez-Mas, J V; Casado, J; Felipe, A; Marin, J J; Pastor-Anglada, M

1993-01-01

5

Functional Characterization of Alanine Racemase from Schizosaccharomyces pombe: a Eucaryotic Counterpart to Bacterial Alanine Racemase  

PubMed Central

Schizosaccharomyces pombe has an open reading frame, which we named alr1+, encoding a putative protein similar to bacterial alanine racemase. We cloned the alr1+ gene in Escherichia coli and purified the gene product (Alr1p), with an Mr of 41,590, to homogeneity. Alr1p contains pyridoxal 5?-phosphate as a coenzyme and catalyzes the racemization of alanine with apparent Km and Vmax values as follows: for l-alanine, 5.0 mM and 670 ?mol/min/mg, respectively, and for d-alanine, 2.4 mM and 350 ?mol/min/mg, respectively. The enzyme is almost specific to alanine, but l-serine and l-2-aminobutyrate are racemized slowly at rates 3.7 and 0.37% of that of l-alanine, respectively. S. pombe uses d-alanine as a sole nitrogen source, but deletion of the alr1+ gene resulted in retarded growth on the same medium. This indicates that S. pombe has catabolic pathways for both enantiomers of alanine and that the pathway for l-alanine coupled with racemization plays a major role in the catabolism of d-alanine. Saccharomyces cerevisiae differs markedly from S. pombe: S. cerevisiae uses l-alanine but not d-alanine as a sole nitrogen source. Moreover, d-alanine is toxic to S. cerevisiae. However, heterologous expression of the alr1+ gene enabled S. cerevisiae to grow efficiently on d-alanine as a sole nitrogen source. The recombinant yeast was relieved from the toxicity of d-alanine.

Uo, Takuma; Yoshimura, Tohru; Tanaka, Naotaka; Takegawa, Kaoru; Esaki, Nobuyoshi

2001-01-01

6

Alanine Aminotransferase Elevation in Obese Infants and Children: A Marker of Early Onset Non Alcoholic Fatty Liver Disease  

PubMed Central

Background: Elevated aminotransferases serve as surrogate markers of non-alcoholic fatty liver disease, a feature commonly associated with the metabolic syndrome. Studies on the prevalence of fatty liver disease in obese children comprise small patient samples or focus on those patients with liver enzyme elevation. Objectives: We have prospectively analyzed liver enzymes in all overweight and obese children coming to our tertiary care centre. Patients and Methods: In a prospective study 224 healthy, overweight or obese children aged 1 - 12 years were examined. Body Mass Index-Standard Deviation Score, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl-transpeptidase were measured. Results: Elevated alanine aminotransferase was observed in 29% of children. 26 % of obese and 30 % of overweight children had liver enzyme elevations. Obese children had significantly higher alanine aminotransferase levels than overweight children (0.9 vs. 0.7 times the Upper Limit of Normal; P = 0.04). Conclusions: Elevation of liver enzymes appears in 29 % obese children in a tertiary care centre. Absolute alanine aminotransferase levels are significantly higher in obese than in overweight children. Even obese children with normal liver enzymes show signs of fatty liver disease as demonstrated by liver enzymes at the upper limit of normal.

Engelmann, Guido; Hoffmann, Georg Friedrich; Grulich-Henn, Juergen; Teufel, Ulrike

2014-01-01

7

Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase  

PubMed Central

AIM: To identify the proportion, causes and the nature of drug-induced liver injury (DILI) in patients with notably elevated alanine aminotransferase (ALT). METHODS: All the inpatients with ALT levels above 10 times upper limit of normal range (ULN) were retrospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT elevations were examined for each patient, including biliary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed using the Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors. RESULTS: A total of 129 cases with ALT > 10 ULN were identified. Hemodynamic injury (n = 46, 35.7%), DILI (n = 25, 19.4%) and malignancy (n = 21, 16.3%) were the top three causes of liver injury. Peak ALT values were lower in DILI patients than in patients with hemodynamic injury (14.5 ± 5.6 ULN vs 32.5 ± 30.7 ULN, P = 0.001). Among DILI patients, one (4%) case was classified as definite, 19 (76%) cases were classified as probable and 5 (20%) as possible according to the CIOMS scale. A hepatocellular pattern was observed in 23 (92%) cases and mixed in 2 (8%). The extent of severity of liver injury was mild in 21 (84%) patients and moderate in 4 (16%). Before discharge, 10 (40%) patients were recovered and the other 15 (60%) were improved. The improved patients tended to have a higher peak ALT (808 ± 348 U/L vs 623 ± 118 U/L, P = 0.016) and shorter treatment duration before discharge (8 ± 6 d vs 28 ± 12 d, P = 0.008) compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILI. Antibacterials were the most common agents causing DILI in 8 (32%) cases, followed by glucocorticoids in 6 (24%) cases. Twenty-four (96%) cases received treatment of DILI with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs (e.g., glycyrrhizinate), antioxidants (e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin), polyene phosphatidyl choline and herbal extracts (e.g., protoporphyrin disodium and silymarin). Diagnosis of DILI was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgical wards had a higher risk of missed diagnosis in discharge letter [odds ratio (OR) 32.7, 95%CI (2.8-374.1), and OR 58.5, 95%CI (4.6-746.6), respectively]. CONCLUSION: DILI is mostly caused by use of antibacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT > 10 ULN. DILI is underdiagnosed frequently.

Xu, Hui-Min; Chen, Yan; Xu, Jie; Zhou, Quan

2012-01-01

8

Studies on a unique organelle localization of a liver enzyme, serine:pyruvate (or alanine:glyoxylate) aminotransferase  

PubMed Central

Serine:pyruvate (or alanine:glyoxylate) aminotransferase (SPT or AGT) in the liver is unique in that its subcellular distribution is entirely peroxisomal in man and herbivores, and largely mitochondrial in carnivores. In rats, this enzyme is located in both mitochondria and peroxisomes and only the mitochondrial activity is markedly induced by glucagon. The mechanism of the species-specific dual organelle localization is either transcription of the gene from two different start sites or loss of upstream translation initiation ATG codon by mutations. In herbivores, peroxisomal localization of SPT appears to be indispensable to prevent excessive oxalate production by removing glyoxylate, an immediate precursor of oxalate, formed from glycolate in this organelle. In carnivores, its mitochondrial localization appears to be needed to metabolize glyoxylate formed from L-hydroxyproline in mitochondria. In addition, SPT contributes substantially to gluconeogenesis from serine in rabbit, human and dog livers, irrespective of its mitochondrial or peroxisomal localization.

ICHIYAMA, Arata

2011-01-01

9

?-alanine supplementation improves tactical performance but not cognitive function in combat soldiers  

PubMed Central

Background There are no known studies that have examined ?-alanine supplementation in military personnel. Considering the physiological and potential neurological effects that have been reported during sustained military operations, it appears that ?-alanine supplementation may have a potential benefit in maintaining physical and cognitive performance during high-intensity military activity under stressful conditions. The purpose of this study was to examine the effect of 28 days of ?-alanine ingestion in military personnel while fatigued on physical and cognitive performance. Methods Twenty soldiers (20.1?±?0.9 years) from an elite combat unit were randomly assigned to either a ?-alanine (BA) or placebo (PL) group. Soldiers were involved in advanced military training, including combat skill development, navigational training, self-defense/hand-to-hand combat and conditioning. All participants performed a 4-km run, 5-countermovement jumps using a linear position transducer, 120-m sprint, a 10-shot shooting protocol with assault rifle, including overcoming a misfire, and a 2-min serial subtraction test to assess cognitive function before (Pre) and after (Post) 28 days of supplementation. Results The training routine resulted in significant increases in 4-km run time for both groups, but no between group differences were seen (p?=?0.597). Peak jump power at Post was greater for BA than PL (p?=?0.034), while mean jump power for BA at Post was 10.2% greater (p?=?0.139) than PL. BA had a significantly greater (p?=?0.012) number of shots on target at Post (8.2?±?1.0) than PL (6.5?±?2.1), and their target engagement speed at Post was also significantly faster (p?=?0.039). No difference in serial subtraction performance was seen between the groups (p?=?0.844). Conclusion Results of this study indicate that 4-weeks of ?-alanine ingestion in young, healthy soldiers did not impact cognitive performance, but did enhance power performance, marksmanship and target engagement speed from pre-ingestion levels.

2014-01-01

10

Functionalization of single-walled carbon nanotubes with uracil, guanine, thymine and L-alanine  

NASA Astrophysics Data System (ADS)

Experimental investigation of functionalization of oxidized single-walled carbon nanotubes (OSWCNTs) with three nucleic acid bases such as uracil, guanine, thymine and one amino acid, L-alanine is carried out. Initially, the SWCNTs are oxidized by acid treatment. Further, the oxidized SWCNTs are effectively functionalized with aforementioned biological compounds by ultrasonication. The diameter of OSWCNTs has increased after the adsorption of biological compounds. The cumulative ?-? stacking, hydrogen bond and polar interaction are the key factors to realize the adsorption. The amount of adsorption of each biological compound is estimated. The adsorption of guanine is more among all the four biological compounds.

Silambarasan, D.; Iyakutti, K.; Vasu, V.

2014-06-01

11

The effects of the stress caused by experimental procedures on alanine aspartate, glutamate and glutamine in rat liver  

PubMed Central

Rats were stressed by intravenous injection, tail-warming or moderate restraint for 30s, i.e. by stresses imposed by normal handling during experiment. Liver glutamate concentrations were greatly affected. The results were substantially the same in two varieties of rat (Wistar and Sprague–Dawley), in two laboratories, in experiments carried out by two sets of workers, and after all three stresses. The following detailed results refer to Wistar rats. 1. In starved rats at 20°C and 30°C and in post-absorptive rats at 20°C stress by injection raised liver glutamate concentrations from 1.54, 1.57 and 1.88?mol/g wet wt. 30s after injection to 3.4, 2.7 and 3.6?mol/g wet wt. respectively a few minutes later. In starved rats at 20°C the concentration then fell slowly to 2.3?mol/g wet wt., in starved rats at 30°C it remained steady, and in post-absorptive rats at 20°C it rose slowly to about 4.3?mol/g wet wt. The final values seemed fairly steady and corresponded to an `alert' state. 2. In starved rats at 20°C anaesthesia, with or without injection or cannulation during it, raised glutamate concentrations to the `alert' values, which were maintained for 2–3h. 3. Liver alanine concentration in post-absorptive rats initially fell from 1.5 to 0.8?mol/g, and then stayed fairly constant. 4. Aspartate and glutamine concentrations altered only in starved rats, and proportionately much less than those of glutamate. 5. The necessity for knowing the time-dependence of glutamate concentrations after experimental handling is emphasized. 6. There is no wholly satisfactory explanation of the observations.

Heath, D. F.; George, D. R.; Rose, J. G.

1971-01-01

12

Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation.  

PubMed

Ischemia/reperfusion (IR) injury in transplanted livers contributes to organ dysfunction and failure and is characterized in part by loss of NO bioavailability. Inhalation of NO is nontoxic and at high concentrations (80 ppm) inhibits IR injury in extrapulmonary tissues. In this prospective, blinded, placebo-controlled study, we evaluated the hypothesis that administration of inhaled NO (iNO; 80 ppm) to patients undergoing orthotopic liver transplantation inhibits hepatic IR injury, resulting in improved liver function. Patients were randomized to receive either placebo or iNO (n = 10 per group) during the operative period only. When results were adjusted for cold ischemia time and sex, iNO significantly decreased hospital length of stay, and evaluation of serum transaminases (alanine transaminase, aspartate aminotransferase) and coagulation times (prothrombin time, partial thromboplastin time) indicated that iNO improved the rate at which liver function was restored after transplantation. iNO did not significantly affect changes in inflammatory markers in liver tissue 1 hour after reperfusion but significantly lowered hepatocyte apoptosis. Evaluation of circulating NO metabolites indicated that the most likely candidate transducer of extrapulmonary effects of iNO was nitrite. In summary, this study supports the clinical use of iNO as an extrapulmonary therapeutic to improve organ function following transplantation. PMID:17717604

Lang, John D; Teng, Xinjun; Chumley, Phillip; Crawford, Jack H; Isbell, T Scott; Chacko, Balu K; Liu, Yuliang; Jhala, Nirag; Crowe, D Ralph; Smith, Alvin B; Cross, Richard C; Frenette, Luc; Kelley, Eric E; Wilhite, Diana W; Hall, Cheryl R; Page, Grier P; Fallon, Michael B; Bynon, J Steven; Eckhoff, Devin E; Patel, Rakesh P

2007-09-01

13

Liver Function among Neoprene Production Workers.  

National Technical Information Service (NTIS)

Liver function was tested in neoprene (9010984) production workers. Blood samples from 81 workers at the Denka Chemical Company (SIC-2822) in Houston, Texas were analyzed for various proteins and enzymes related to liver function. The authors suggest that...

E. B. Whorton I. Schoen J. B. Ward P. R. Gilmer

1980-01-01

14

Liver function impairment in liver transplantation and after extended hepatectomy  

PubMed Central

Extended hepatectomy, or liver transplantation of reduced-size graft, can lead to a pattern of clinical manifestations, namely “post-hepatectomy liver failure” and “small-for-size syndrome” respectively, that can range from mild cholestasis to irreversible organ non-function and death of the patient. Many mechanisms are involved in their occurrence but in the recent past, high portal blood flow through a relatively small liver vascular bed has taken a central role. Therefore, several techniques of inflow modulation have been attempted in cases of portal hyperperfusion first in liver transplantation, such as portocaval shunt, mesocaval shunt, splenorenal shunt, splenectomy or ligation of the splenic artery. However, high portal flow is not the only factor responsible, and before major liver resections, preoperative assessment of the residual liver function is necessary. Techniques such as portal vein embolization or portal vein ligation can be adopted to increase the future liver volume, preventing post-hepatectomy liver failure. More recently, a new surgical procedure, that combines in situ splitting of the liver and portal vein ligation, has gradually come to light, inducing remarkable hypertrophy of the healthy liver in just a few days. Further studies are needed to confirm this hypothesis and overcome one of the biggest issues in the field of liver surgery.

Serenari, Matteo; Cescon, Matteo; Cucchetti, Alessandro; Pinna, Antonio Daniele

2013-01-01

15

Molecular Structure of Alanine  

NSDL National Science Digital Library

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

2002-08-20

16

Effect of chronic consumption of Piliostigma thonningii on activities of alanine aminotransferase and aspartate aminotransferase in serum and liver in Rattus novergicus.  

PubMed

The effect of chronic consumption of Piliostigma thonningii on the activities of Aspartate Aminotransferases (AST) and Alanine Aminotransferases (ALT) on serum and liver of Rattus novergicus was investigated in this research. The aim of this study was to check the possible effect of chronic consumption of Piliostigma thonningii on the activities of the liver biomarkers (ALT and AST) in Rattus novergicus. The results from this study revealed that the activities of aspartate aminotransferase (AST) in serum, showed a significant increase (34.20 +/- 12.9*) at (p < 0.05) upon chronic consumption of ethanolic extract of P. thonningii when compared with that of the control B (18.02 +/- 1.54). The result also showed that the liver AST was significantly increased (32.75 +/- 5.89*) when compared to that of the control B (17.01 +/- 1.81) at (p < 0.05). The results from the study also revealed that there was a significant increase in the activity of alanine aminotransferase in the liver (17.01 +/- 5.86*) when compared with that of the control B (5.1 +/- 1.11) at (p < 0.05). There was a corresponding increase in serum activity of the enzyme ALT (13.65 +/- 3.79*) when compared with that of the control B (9.4 +/- 1.98) at (p < 0.05). The results from this research has shown that chronic consumption of P. thonningii may cause liver injury thereby, increasing the liver enzyme activity (17.01 +/- 5.86*). This was shown in the corresponding increase in the serum level. Excessive consumption of the extract of P. thonningii has a toxicity potential on the liver and possibly other organs and tissues. PMID:24517031

Awhin, E P; Jeroh, E; Anigboro, A A; Rachael, Nwaoroko

2013-12-15

17

Evaluation of factors influencing liver function test in on-pump coronary artery bypass graft surgery.  

PubMed

Background: Liver dysfunction during on-pump coronary artery bypass graft surgery (CABG) is a rare complication but is associated with significant morbidity and mortality. The ability to identify high-risk patients may be helpful in planning appropriate management strategies. We aimed to evaluate the factors influencing liver function tests during on-pump CABG. Methods: In 146 patients scheduled for on-pump CABG, the liver function test was done preoperatively and on the first postoperative day. Some preoperative and intraoperative risk factors were checked and then the postoperative liver function tests were compared with the preoperative ones. Probable relationships between these changes and the preoperative and intraoperative risk factors were studied. Results: A medical history of diabetes had a significant relationship with the changes in direct bilirubin. Preoperative central venous pressure had a significant relationship with the changes in aspartate aminotransferase and alanine aminotransferase. Use of intra-aortic balloon pump and duration of aortic cross-clamp were significantly related to the changes in the liver function tests except for alanine aminotransferase and alkaline phosphatase. Conclusion: It seems that the techniques for the reduction of cardiopulmonary bypass and aortic cross-clamp duration may be useful to protect liver function. We recommend that a larger population of patients be studied to confirm these findings. PMID:24293784

Shahbazi, Shahrbano; Panah, Ashkan; Sahmeddini, Mohammad Ali

2013-12-01

18

Evaluation of abnormal liver function tests.  

PubMed

Interpretation of abnormalities in liver function tests is a common problem faced by clinicians. This has become more common with the introduction of automated routine laboratory testing. Not all persons with one or more abnormalities in these tests actually have liver disease. The various biochemical tests, their pathophysiology, and an approach to the interpretation of abnormal liver function tests are discussed in this review. PMID:12840117

Limdi, J K; Hyde, G M

2003-06-01

19

Development of laminin receptor agonists: identification of important functional residues by alanine scanning.  

PubMed

An antagonist of cellular adhesion and motility, acetyl-C-[S-Acm]-VIGYSGDRC-[S-Acm]-NH(2) (mEGF(33-42)), shares homology with the agonist sequence CDPGYIGSR-NH(2). It has been proposed that the latter peptide binds to the high affinity 67 kDa laminin receptor. Both peptides have equal affinities for the receptor and similar conformations have been derived for both. We have examined the importance of individual non-homologous residues with respect to receptor binding and antagonistic properties of mEGF(33-42). Alanine scanning of non-conserved residues in the N-terminal half of mEGF(33-42) caused loss of biological activity with respect to cell attachment, receptor binding and migratory response. Substitution of alanine for serine (position 6) caused loss of laminin-specific cell attachment and receptor binding activities. However, the peptide did stimulate migration suggesting that this peptide may be a non-specific stimulator of migration. In contrast, alanine substitution for the C-terminal Cys-S-Acm had no apparent effect on the attachment or receptor binding activities of the peptide but generated an agonist from the antagonist parent. Comparison of the modelled folds of the alanine containing peptides revealed the presence of significant helical content in those peptides capable of stimulating migration and suggests that a reduction in bulk in the N-terminal residues is not conducive to adopting a productive binding conformation. PMID:10962089

Scott, W N; McFerran, N V; Harriott, P; Walker, B; Nelson, J

2000-08-31

20

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

PubMed Central

objective Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Methods and Procedures Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m2) were randomized to “control (CO)” = 100% energy requirements; “CR” = 25%; “caloric restriction and increased structured exercise (CR+EX)”= 12.5% CR + 12.5% increase in energy expenditure through exercise; or “low-calorie diet (LCD)” = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. Results At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. Discussion CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.

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

2009-01-01

21

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

PubMed Central

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.

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

22

Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology  

Microsoft Academic Search

Background\\/Aims: The significance of abnormal liver function tests in the absence of diagnostic serology is unclear. The aim of this study was to report liver biopsy findings in a large group of patients with unexplained abnormal liver biochemistry. Methods: Histological findings were examined in 354 patients who underwent liver biopsy to investigate abnormal liver function tests. Results: Six percent of

Maeve M. Skelly; Peter D. James; Stephen D. Ryder

23

Metabolism of 7-ethyoxycoumarin by Isolated Perfused Rainbow Trout Livers  

EPA Science Inventory

Isolated trout livers were perfused using methods designed to preserve tissue viability and function. Liver performance was evaluated by measuring O2 consumption, vascular resistance, K+ leakage, glucose flux, lactate flux, alanine aminotransferase leakage, and metabolic clearanc...

24

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

Microsoft Academic Search

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

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

2001-01-01

25

Liver-Spleen Scintigrams, Epigastric Sonograms and Liver Function Scintigram for Comparative Studies of Various Cases of Liver Cirrhosis.  

National Technical Information Service (NTIS)

23 patients where liver cirrhosis was established were subjected to an epigastric sonogram, a liver-spleen scintigram, a liver-function scintigram, and to various relevant laboratory tests. The liver-spleen scintigram was evaluated for size of the liver, ...

R. Geiger

1983-01-01

26

Monitoring of Total and Regional Liver Function after SIRT.  

PubMed

Selective internal radiation therapy (SIRT) is a promising treatment modality for advanced hepatocellular carcinoma or metastatic liver cancer. SIRT is usually well tolerated. However, in most patients, SIRT will result in a (temporary) decreased liver function. Occasionally patients develop radioembolization-induced liver disease (REILD). In case of a high tumor burden of the liver, it could be beneficial to perform SIRT in two sessions enabling the primary untreated liver segments to guarantee liver function until function in the treated segments has recovered or functional hypertrophy has occurred. Clinically used liver function tests provide evidence of only one of the many liver functions, though all of them lack the possibility of assessment of segmental (regional) liver function. Hepatobiliary scintigraphy (HBS) has been validated as a tool to assess total and regional liver function in liver surgery. It is also used to assess segmental liver function before and after portal vein embolization. HBS is considered as a valuable quantitative liver function test enabling assessment of segmental liver function recovery after regional intervention and determination of future remnant liver function. We present two cases in which HBS was used to monitor total and regional liver function in a patient after repeated whole liver SIRT complicated with REILD and a patient treated unilaterally without complications. PMID:24982851

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

2014-01-01

27

Monitoring of Total and Regional Liver Function after SIRT  

PubMed Central

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

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

2014-01-01

28

Environmental modulation of microcystin and ?-N-methylamino-l-alanine as a function of nitrogen availability.  

PubMed

The most significant modulators of the cyanotoxins microcystin and ?-N-methylamino-l-alanine in laboratory cyanobacterial cultures are the concentration of growth-medium combined nitrogen and nitrogen uptake rate. The lack of field studies that support these observations led us to investigate the cellular content of these cyanotoxins in cyanobacterial bloom material isolated from a freshwater impoundment and to compare these to the combined nitrogen availability. We established that these toxins typically occur in an inverse relationship in nature and that their presence is mainly dependent on the environmental combined nitrogen concentration, with cellular microcystin present at exogenous combined nitrogen concentrations of 29 ?M and higher and cellular BMAA correlating negatively with exogenous nitrogen at concentrations below 40 ?M. Furthermore, opposing nutrient and light gradients that form in dense cyanobacterial blooms may result in both microcystin and BMAA being present at a single sampling site. PMID:24878376

Scott, L L; Downing, S; Phelan, R R; Downing, T G

2014-09-01

29

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

PubMed

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

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

1993-12-01

30

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

PubMed Central

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

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

1993-01-01

31

Toxicity Effect of Nigella Sativa on the Liver Function of Rats  

PubMed Central

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

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

2013-01-01

32

Electrical impedimetric biosensors for liver function detection.  

PubMed

In this study, electrical impedimetric biosensors composed of Au-electrodes were fabricated for the quantitative detection of human serum albumin (HSA), an essential biomarker of liver function. The Au-electrodes were fabricated via a single-step photolithography process, and can be easily integrated in biochips for assessing liver function in the future. The glass sensing surface between two adjacent Au-electrodes was modified with 3-aminopropyltriethoxysilane (APTES) to improve the biocompatibility for its subsequent binding to anti-human serum albumin (AHSA). The sensing surface without AHSA binding was blocked using skim milk powders, preventing possible non-specific bonding HSA conjugation. Biosensors were used to measure HSA concentration for liver function detection. The impedance between two adjacent Au-electrodes of the biosensors applied with various HSA concentrations was directly measured, and quantified using an electrochemical impedance spectroscopy system under AC conditions. The results of plotting both values in log scales indicated the impedance increased linearly with HSA conjugation increase. The limit of HSA detection was about 2'10(-4)mg/ml using the electrochemical impedimetric biosensor proposed in this work. This study demonstrates the feasibility of using electrochemical impedimetry as a bio-sensing mechanism to quantify human serum albumin concentration. The sensor proposed in this work also displays great potential for assessing liver function because of its simple detection mechanism, ease of biochip integration, and low cost. PMID:21840200

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

2011-10-15

33

Hepatectomy: Preoperative Analysis of Hepatic Function and Postoperative Liver Failure  

Microsoft Academic Search

Most authors reporting on hepatectomy stress the importance of preoperative assessment of liver function and functional reserve to minimize the surgical risk, especially in patients with liver cirrhosis, jaundice or those undergoing prolonged chemotherapy [1] since it is these patients who have a markedly increased risk of developing liver failure [2–5]. According to a recent review, liver failure is the

Heinz Zimmermann; Jürg Reichen

1998-01-01

34

[Monitoring of liver function in the critically ill].  

PubMed

Liver failure and hepatic dysfunction represent diagnostic and therapeutic challenges for the intensivist. Besides acute liver failure, hypoxic hepatitis, sepsis and (secondary) sclerosing cholangitis may lead to massive liver dysfunction with subsequent multiorgan dysfunction syndrome that limits survival. Among classical laboratory parameters (so-called static liver parameters) liver function tests may help with the diagnosis to allow early treatment or prevention of liver dysfunction. The aim of this article is to present the current aspects of liver function monitoring and to provide guidelines to the intensivist for diagnosing liver dysfunction in the intensive care setting. PMID:24997165

Sponholz, C; Gonnert, F A; Kortgen, A; Bauer, M

2014-07-01

35

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

PubMed

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

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

2013-09-01

36

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

PubMed Central

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

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

2013-01-01

37

Optimization of an Isolated Perfused Rainbow Trout Liver Model: Clearance Studies with 7-Ethoxycoumarin  

EPA Science Inventory

Isolated trout livers were perfused using methods designed to preserve tissue viability and function. Liver performance was evaluated by measuring O2 consumption (VO2), vascular resistance, K+ leakage, glucose flux, lactate flux, alanine aminotransferase (ALT) leakage, and meta...

38

Liver Function Profile Anomalies in HIV Seropositive Tuberculosis.  

PubMed

Background: The Human Immunodeficiency Virus (HIV) and the Tuberculosis (TB) co infection are contributory to each other in causing a progressive decline in the cell mediated immunity and a damage to the hepatobiliary system. The aim of our study was to estimate the extent of liver damage which was caused by these infections before the start of the therapy with hepatotoxic drugs like Antiretroviral Therapy (ART) and Antitubercular Drugs (ATD). Methods: One hundred and ninty three confirmed HIV positive cases were enrolled in this study. The cases were divided into 2 groups; Group 1-100 subjects with TB and Group 2-93 subjects without TB.80 age and sex matched controls were also included (Group 0). Some parameters of the serum Liver Function Test (LFT) were estimated biochemically by using an auto analyzer (ERBA XL600,Transasia). Results: The serum total bilirubin, Alanine Transaminase (ALT), Aspartate Transaminase (AST) and the Alkaline Phosphatase (ALK-P) levels were significantly higher in the cases as compared to those in the controls, more so in the cases with the associated TB co infection, except the AST levels. The Group 1subjects had lower serum total protein and albumin levels and altered albumin/globulin ratios as compared to the controls. A statistically significant difference was absent in the serum total protein levels between the Group 2 cases and the Group 0 controls. No significant differences were observed when the values for serum total protein, albumin and globulin and the albumin: globulin ratios among the two case groups (1 and 2) were compared. Conclusion: The results have shown the importance of estimating some LFT parameters, prior to the start of ATD and ART in these cases. Hence, a mandatory performance of LFT is recommended, as it is simple and cost effective. PMID:23905105

Dey, Subir Kumar; Ghosh, Indranath; Bhattacharjee, Debojyoti; A, Praveen; Jha, Sumanta; Dasgupta, Anindya; Dey, Sukanta Kumar

2013-06-01

39

Liver Function Profile Anomalies in HIV Seropositive Tuberculosis  

PubMed Central

Background: The Human Immunodeficiency Virus (HIV) and the Tuberculosis (TB) co infection are contributory to each other in causing a progressive decline in the cell mediated immunity and a damage to the hepatobiliary system. The aim of our study was to estimate the extent of liver damage which was caused by these infections before the start of the therapy with hepatotoxic drugs like Antiretroviral Therapy (ART) and Antitubercular Drugs (ATD). Methods: One hundred and ninty three confirmed HIV positive cases were enrolled in this study. The cases were divided into 2 groups; Group 1-100 subjects with TB and Group 2-93 subjects without TB.80 age and sex matched controls were also included (Group 0). Some parameters of the serum Liver Function Test (LFT) were estimated biochemically by using an auto analyzer (ERBA XL600,Transasia). Results: The serum total bilirubin, Alanine Transaminase (ALT), Aspartate Transaminase (AST) and the Alkaline Phosphatase (ALK-P) levels were significantly higher in the cases as compared to those in the controls, more so in the cases with the associated TB co infection, except the AST levels. The Group 1subjects had lower serum total protein and albumin levels and altered albumin/globulin ratios as compared to the controls. A statistically significant difference was absent in the serum total protein levels between the Group 2 cases and the Group 0 controls. No significant differences were observed when the values for serum total protein, albumin and globulin and the albumin: globulin ratios among the two case groups (1 and 2) were compared. Conclusion: The results have shown the importance of estimating some LFT parameters, prior to the start of ATD and ART in these cases. Hence, a mandatory performance of LFT is recommended, as it is simple and cost effective.

Dey, Subir Kumar; Ghosh, Indranath; Bhattacharjee, Debojyoti; A., Praveen; Jha, Sumanta; Dasgupta, Anindya; Dey, Sukanta Kumar

2013-01-01

40

Molecular Insight into the Synergism between the Minor Allele of Human Liver Peroxisomal Alanine:Glyoxylate Aminotransferase and the F152I Mutation*  

PubMed Central

Human liver peroxisomal alanine:glyoxylate aminotransferase (AGT) is a pyridoxal 5?-phosphate (PLP)-dependent enzyme that converts glyoxylate into glycine. AGT deficiency causes primary hyperoxaluria type 1 (PH1), a rare autosomal recessive disorder, due to a marked increase in hepatic oxalate production. Normal human AGT exists as two polymorphic variants: the major (AGT-Ma) and the minor (AGT-Mi) allele. AGT-Mi causes the PH1 disease only when combined with some mutations. In this study, the molecular basis of the synergism between AGT-Mi and F152I mutation has been investigated through a detailed biochemical characterization of AGT-Mi and the Phe152 variants combined either with the major (F152I-Ma, F152A-Ma) or the minor allele (F152I-Mi). Although these species show spectral features, kinetic parameters, and PLP binding affinity similar to those of AGT-Ma, the Phe152 variants exhibit the following differences with respect to AGT-Ma and AGT-Mi: (i) pyridoxamine 5?-phosphate (PMP) is released during the overall transamination leading to the conversion into apoenzymes, and (ii) the PMP binding affinity is at least 200–1400-fold lower. Thus, Phe152 is not an essential residue for transaminase activity, but plays a role in selectively stabilizing the AGT-PMP complex, by a proper orientation of Trp108, as suggested by bioinformatic analysis. These data, together with the finding that apoF152I-Mi is the only species that at physiological temperature undergoes a time-dependent inactivation and concomitant aggregation, shed light on the molecular defects resulting from the association of the F152I mutation with AGT-Mi, and allow to speculate on the responsiveness to pyridoxine therapy of PH1 patients carrying this mutation.

Cellini, Barbara; Montioli, Riccardo; Paiardini, Alessandro; Lorenzetto, Antonio; Voltattorni, Carla Borri

2009-01-01

41

Proposal of Noninvasive Liver Function Measurement Method via Saliva  

NASA Astrophysics Data System (ADS)

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

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

42

Factors regulating amino acid release from extrasplanchnic tissues in the rat. Interactions of alanine and glutamine.  

PubMed Central

1. Factors regulating the release of alanine and glutamine in vivo were investigated in starved rats by removing the liver from the circulation and monitoring blood metabolite changes for 30 min. 2. Alanine and glutamine were the predominant amino acids released into the circulation in this preparation. 3. Dichloroacetate, an activator of pyruvate dehydrogenase, inhibited net alanine release: it also interfered with the metabolism of the branched-chain amino acids valine, leucine and isoleucine. 4. L-Cycloserine, an inhibitor of alanine aminotransferase, decreased alanine accumulation by 80% after functional hepatectomy, whereas methionine sulphoximine, an inhibitor of glutamine synthetase, decreased glutamine accumulation by the same amount. 5. It was concluded that: (a) the alanine aminotransferase and the glutamine synthetase pathways respectively were responsible for 80% of the alanine and glutamine released into the circulation by the extrasplanchnic tissues, and extrahepatic proteolysis could account for a maximum of 20%; (b) alanine formation by the peripheral tissues was dependent on availability of pyruvate and not of glutamate; (c) glutamate availability could influence glutamine formation subject, possibly, to renal control.

Blackshear, P J; Holloway, P A; Alberti, K G

1975-01-01

43

Molecular Determinants for Functional Differences between Alanine-Serine-Cysteine Transporter 1 and Other Glutamate Transporter Family Members*  

PubMed Central

The ASCTs (alanine, serine, and cysteine transporters) belong to the solute carrier family 1 (SLC1), which also includes the human glutamate transporters (excitatory amino acid transporters, EAATs) and the prokaryotic aspartate transporter GltPh. Despite the high degree of amino acid sequence identity between family members, ASCTs function quite differently from the EAATs and GltPh. The aim of this study was to mutate ASCT1 to generate a transporter with functional properties of the EAATs and GltPh, to further our understanding of the structural basis for the different transport mechanisms of the SLC1 family. We have identified three key residues involved in determining differences between ASCT1, the EAATs and GltPh. ASCT1 transporters containing the mutations A382T, T459R, and Q386E were expressed in Xenopus laevis oocytes, and their transport and anion channel functions were investigated. A382T and T459R altered the substrate selectivity of ASCT1 to allow the transport of acidic amino acids, particularly l-aspartate. The combination of A382T and T459R within ASCT1 generates a transporter with a similar profile to that of GltPh, with preference for l-aspartate over l-glutamate. Interestingly, the amplitude of the anion conductance activated by the acidic amino acids does not correlate with rates of transport, highlighting the distinction between these two processes. Q386E impaired the ability of ASCT1 to bind acidic amino acids at pH 5.5; however, this was reversed by the additional mutation A382T. We propose that these residues differences in TM7 and TM8 combine to determine differences in substrate selectivity between members of the SLC1 family.

Scopelliti, Amanda J.; Ryan, Renae M.; Vandenberg, Robert J.

2013-01-01

44

Molecular determinants for functional differences between alanine-serine-cysteine transporter 1 and other glutamate transporter family members.  

PubMed

The ASCTs (alanine, serine, and cysteine transporters) belong to the solute carrier family 1 (SLC1), which also includes the human glutamate transporters (excitatory amino acid transporters, EAATs) and the prokaryotic aspartate transporter GltPh. Despite the high degree of amino acid sequence identity between family members, ASCTs function quite differently from the EAATs and GltPh. The aim of this study was to mutate ASCT1 to generate a transporter with functional properties of the EAATs and GltPh, to further our understanding of the structural basis for the different transport mechanisms of the SLC1 family. We have identified three key residues involved in determining differences between ASCT1, the EAATs and GltPh. ASCT1 transporters containing the mutations A382T, T459R, and Q386E were expressed in Xenopus laevis oocytes, and their transport and anion channel functions were investigated. A382T and T459R altered the substrate selectivity of ASCT1 to allow the transport of acidic amino acids, particularly l-aspartate. The combination of A382T and T459R within ASCT1 generates a transporter with a similar profile to that of GltPh, with preference for l-aspartate over l-glutamate. Interestingly, the amplitude of the anion conductance activated by the acidic amino acids does not correlate with rates of transport, highlighting the distinction between these two processes. Q386E impaired the ability of ASCT1 to bind acidic amino acids at pH 5.5; however, this was reversed by the additional mutation A382T. We propose that these residues differences in TM7 and TM8 combine to determine differences in substrate selectivity between members of the SLC1 family. PMID:23393130

Scopelliti, Amanda J; Ryan, Renae M; Vandenberg, Robert J

2013-03-22

45

Role of liver function enzymes in diagnosis of choledocholithiasis in biliary colic patients.  

PubMed

Liver functional tests due to inflammatory process which induced by cholecystitis might changed and some clinicians suggested that these changes might help us to stone prediction in common bile ducts and decrease hazards of performing ERCP and other invasive procedures. Present study was performed for assessment of role of liver functional test in diagnosis of common bile duct stone in patients with cholecystitis and help in their management. Present prospective study was performed between April 2010 and March 2011 on 350 patients who come to our hospital with cholecystitis or biliary colic diagnosis. Patients with cholesistitis diagnosis were underwent operation for removing gall bladder stone and retrograde cholangiopancreatography (ERCP) was performed for patients with suspicious to biliary colic and common bile duct (CBD) stones. Ultrasonography, aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline phosphatase (ALP) and direct and total serum bilirubin were measured for all of participated patients. Mean of AST. ALT, ALP and total and direct bilirubin were had no significant differences between two study groups. In logistic regression analysis, after entering into the model only CBD diameter (OR: 20; P=0.00) and elevated serum level of ALT (OR: 2; P=0.04) were remained into the model and were known as independent predictor of cholelithiasis. Elevated level of liver enzymes had not main role in CBD diagnosis and ERCP had no to perform for suspicious CBD stone only with elevated liver enzyme and even with normal ultrasonography findings. Endosonography as non invasive procedure recommend for patients before ERCP. PMID:22071641

Zare, Mohammad; Kargar, Saeed; Akhondi, Mohsen; Mirshamsi, Mohammad Hussein

2011-01-01

46

Bioluminescence imaging allows measuring CD8 T cell function in the liver.  

PubMed

In vivo evaluation of CD8 T cell effector (cytotoxic T lymphocyte [CTL]) function in peripheral organs such as the liver is currently not possible but would greatly improve our understanding of local immune regulation, because simple determination of antigen-specific CTL numbers does not predict the outcome of immune responses. In particular, measurement of alanine aminotransferase serum levels is not sensitive enough to detect T cell immunity against low numbers of target hepatocytes. We developed a procedure that detects virus-specific effector function of CTLs in the liver after simultaneous adenoviral transfer of reporter and immune target genes into hepatocytes, followed by bioluminescence imaging of reporter genes. Bioluminescence imaging enabled detection of as few as 10,000 infected hepatocytes in vivo, and even more importantly, quantification of antiviral effector function of as few as 50,000 CTLs. Conclusion: Our results provide evidence that low numbers of antigen-specific CTLs are sufficient to control viral gene expression and eliminate viral infection from hepatocytes. The experimental system established here is a highly sensitive method to simultaneously detect viral infection of hepatocytes and to quantify antiviral CTL function in the liver in vivo and will help in characterizing principles of hepatic immune regulation. PMID:20373369

Stabenow, Dirk; Frings, Marianne; Trück, Christina; Gärtner, Katja; Förster, Irmgard; Kurts, Christian; Tüting, Thomas; Odenthal, Margarete; Dienes, Hans-Peter; Cederbrant, Karin; Protzer, Ulrike; Knolle, Percy A

2010-04-01

47

?-Alanine Biosynthesis in Methanocaldococcus jannaschii.  

PubMed

One efficient approach to assigning function to unannotated genes is to establish the enzymes that are missing in known biosynthetic pathways. One group of such pathways is those involved in coenzyme biosynthesis. In the case of the methanogenic archaeon Methanocaldococcus jannaschii as well as most methanogens, none of the expected enzymes for the biosynthesis of the ?-alanine and pantoic acid moieties required for coenzyme A are annotated. To identify the gene(s) for ?-alanine biosynthesis, we have established the pathway for the formation of ?-alanine in this organism after experimentally eliminating other known and proposed pathways to ?-alanine from malonate semialdehyde, l-alanine, spermine, dihydrouracil, and acryloyl-coenzyme A (CoA). Our data showed that the decarboxylation of aspartate was the only source of ?-alanine in cell extracts of M. jannaschii. Unlike other prokaryotes where the enzyme producing ?-alanine from l-aspartate is a pyruvoyl-containing l-aspartate decarboxylase (PanD), the enzyme in M. jannaschii is a pyridoxal phosphate (PLP)-dependent l-aspartate decarboxylase encoded by MJ0050, the same enzyme that was found to decarboxylate tyrosine for methanofuran biosynthesis. A Km of ?0.80 mM for l-aspartate with a specific activity of 0.09 ?mol min(-1) mg(-1) at 70°C for the decarboxylation of l-aspartate was measured for the recombinant enzyme. The MJ0050 gene was also demonstrated to complement the Escherichia coli panD deletion mutant cells, in which panD encoding aspartate decarboxylase in E. coli had been knocked out, thus confirming the function of this gene in vivo. PMID:24891443

Wang, Yu; Xu, Huimin; White, Robert H

2014-08-01

48

Liver function assessment in workers exposed to vinyl chloride  

Microsoft Academic Search

Objective: To investigate liver function in vinyl chloride workers and assess its relation with current\\/past occupational exposure\\u000a to vinyl chloride monomer (VCM). Methods: A medical examination including the execution of liver function tests (LFTs) and liver ultrasonography was executed in a\\u000a group of 757 workers with a long-standing service in the production of VCM\\/polyvinylchloride (PVC). Cumulative and maximum\\u000a VCM exposures

Marco Maroni; Anna Clara Fanetti

2006-01-01

49

The effects of beta-alanine supplementation and high-intensity interval training on neuromuscular fatigue and muscle function  

Microsoft Academic Search

The purpose of this study was to determine the effects of beta-alanine supplementation and high-intensity interval training\\u000a (HIIT) on electromyographic fatigue threshold (EMGFT) and efficiency of electrical activity (EEA). A total of 46 men completed four, 2-min work bouts on a cycle ergometer. Using\\u000a bipolar surface electrodes, the EMG amplitude was averaged and plotted over the 2-min. The resulting slopes

Abbie E. Smith; Jordan R. Moon; Kristina L. Kendall; Jennifer L. Graef; Christopher M. Lockwood; Ashley A. Walter; Travis W. Beck; Joel T. Cramer; Jeffrey R. Stout

2009-01-01

50

The liver-spleen scan as a quantitative liver function test: Correlation with liver severity at peritoneoscopy  

Microsoft Academic Search

Sulfur colloid distribution on liver-spleen scan is determined by the perfused Kupffer cell mass. The perfused Kupffer cell mass is proportional to the perfused hepatocyte mass, but is less affected by acute changes in hepatocyte function. Thus, sulfur colloid distribution parameters (precisely measured by quantitative liver-spleen scan [QLSS]) may be an excellent test of the perfused hepatic mass. Although no

John C. Hoefs; Felix Wang; Gary Kanel; Philip Braunstein

1995-01-01

51

Liver Function Test Abnormalities in Patients with Inflammatory Bowel Diseases: A Hospital-based Survey  

PubMed Central

BACKGROUND AND AIMS Inflammatory bowel diseases (IBD) are frequently associated with altered liver function tests (LFTs). The causal relationship between abnormal LFTs and IBD is unclear. The aim of our study was to evaluate the prevalence and etiology of LFTs abnormalities and their association with clinical variables in a cohort of IBD patients followed up in a single center. MATERIALS AND METHODS A retrospective review was undertaken of all consecutive IBD in- and outpatients routinely followed up at a single referral center. Clinical and demographic parameters were recorded. Subjects were excluded if they had a previous diagnosis of chronic liver disease. LFT abnormality was defined as an increase in aspartate aminotransferase, (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), or total bilirubin. RESULTS A cohort of 335 patients (179 males, mean age 46.0 ± 15.6 years) was analyzed. Abnormal LFTs were detected in 70 patients (20.9%). In most cases, the alterations were mild and spontaneously returned to normal values in about 60% of patients. Patients with abnormal LFTs were less frequently on treatment with aminosalicylates (22.8 vs. 36.6%, P = 0.04). The most frequent cause for transient abnormal LFTs was drug-induced cholestasis (34.1%), whereas fatty liver was the most frequent cause of persistent liver damage (65.4%). A cholestatic pattern was found in 60.0% of patients and was mainly related to older age, longer duration of disease, and hypertension. CONCLUSIONS The prevalence of LFT abnormalities is relatively high in IBD patients, but the development of severe liver injury is exceptional. Moreover, most alterations of LFTs are mild and spontaneously return to normal values. Drug-induced hepatotoxicity and fatty liver are the most relevant causes of abnormal LFTs in patients with IBD.

Cappello, Maria; Randazzo, Claudia; Bravata, Ivana; Licata, Anna; Peralta, Sergio; Craxi, Antonio; Almasio, Piero Luigi

2014-01-01

52

Long-term effects of radium exposure in female dial workers: Liver function and liver disease  

Microsoft Academic Search

The question of the long-term effects of ..cap alpha..-emitting radionuclides on the liver is of considerable interest. Liver function test results and data on the prevalence of and mortality from diseases of the liver and biliary tract were examined among women who were first employed before 1930 in the US radium watch-dial painting industry, and who had a radium body-burden

A. Polednak

1979-01-01

53

Nonalcoholic fatty liver disease associated with impairment of kidney function in nondiabetes population  

PubMed Central

Background Nonalcoholic fatty liver disease (NAFLD) is associated with the increased burden of kidney. However, there is still no large population study to explore the potential relationship between NAFLD and mild kidney function damage (MKFD) after adjusted for confounding factors. This study is to test the hypothesis that NAFLD is associated with MKFD under controlling the effects of confounding factors. Materials and methods: Levels of serum fasting glucose, creatinine, cholesterol, triglyceride, alanine aminotransferase and aspartate aminotransferase were analyzed from 1412 Chinese Han adults. Questionnaire and physical examination were performed to explore the potential association of NAFLD with kidney function. Results: NAFLD was associated with impairment of kidney function. Multivariate-adjusted odds ratio illustrated that, compared to subjects with normal liver, NAFLD subjects had a significantly higher risk of MKFD with or without adjusted for blood glucose and other covariates (P = 0.041). Further results from multi-interaction analysis demonstrated that the underlying mechanisms linked NAFLD with impaired kidney function may be that they share common risk factors and similar pathological processes. Conclusions: The most striking finding of this study is that NAFLD is negatively associated with kidney function, in nondiabetic population. NAFLD and MKFD may share similar risk factors and/or pathological processes.

Li, Guolin; Shi, Wang; Hu, Hui; Chen, Yaqin; Liu, Li; Yin, Dazhong

2012-01-01

54

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

Microsoft Academic Search

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

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

2009-01-01

55

Evaluation of Alanine Transaminase and Hepatitis B Virus DNA to Predict Liver Cirrhosis in Hepatitis B e Antigen-Negative Chronic Hepatitis B Using Transient Elastography  

Microsoft Academic Search

BACKGROUND AND AIMS:We aimed to investigate the relationship between serum hepatitis B virus (HBV) DNA and alanine transaminase (ALT) levels and the risk of cirrhosis in a large cohort of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients based on transient elastography.METHODS:We prospectively studied treatment-naive HBeAg-negative patients recruited based on territory-wide referrals. We defined possible cirrhosis and probable

Grace Lai-Hung Wong; Vincent Wai-Sun Wong; Paul Cheung-Lung Choi; Anthony Wing-Hung Chan; Angel Mei-Ling Chim; Karen Ka-Lam Yiu; Hoi-Yun Chan; Francis Ka-Leung Chan; Joseph Jao-Yao Sung; Henry Lik-Yuen Chan

2008-01-01

56

What are the best reference values for a normal serum alanine transaminase activity (ALT)? Impact on the presumed prevalence of drug induced liver injury (DILI)  

Microsoft Academic Search

BackgroundIn clinical research, the definition of the upper limit of normal (ULN) is rarely detailed. For alanine transaminase (ALT), there are several definitions of ULN-ALT but no recognized global reference. Furthermore the inter-laboratory variability of results expressed using ULN-ALT is higher than using the actual value of ULN expressed in IU\\/L. Regulatory agencies still use ULN-ALT for the definition of

Helmi M’Kada; Mona Munteanu; Hugo Perazzo; Yen Ngo; Nittia Ramanujam; Françoise Imbert-Bismut; Vlad Ratziu; Dominique Bonnefont-Rousselot; Bernard Souberbielle; Ina Schuppe-Koistinen; Thierry Poynard

2011-01-01

57

Gd-EOB-DTPA-enhanced MRI for the assessment of liver function and volume in liver cirrhosis  

PubMed Central

Objective: The aims of this study were to use dynamic hepatocyte-specific contrast-enhanced MRI to evaluate liver volume and function in liver cirrhosis, correlate the results with standard scoring models and explore the inhomogeneous distribution of liver function in cirrhotic livers. Methods: 10 patients with liver cirrhosis and 20 healthy volunteers, serving as controls, were included. Hepatic extraction fraction (HEF), input relative blood flow and mean transit time were calculated on a voxel-by-voxel basis using deconvolutional analysis. Segmental and total liver volumes as well as segmental and total hepatic extraction capacity, expressed in HEFml, were calculated. An incongruence score (IS) was constructed to reflect the uneven distribution of liver function. The Mann–Whitney U-test was used for group comparison of the quantitative liver function parameters, liver volumes and ISs. Correlations between liver function parameters and clinical scores were assessed using Spearman rank correlation. Results: Patients had larger parenchymal liver volume, lower hepatocyte function and more inhomogeneous distribution of function compared with healthy controls. Conclusion: The study demonstrates the non-homogeneous nature of liver cirrhosis and underlines the necessity of a liver function test able to compensate for the heterogeneous distribution of liver function in patients with diseased liver parenchyma. Advances in knowledge: The study describes a new way to quantitatively assess the hepatic uptake of gadoxetate or gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid in the liver as a whole as well as on a segmental level.

Blomqvist, L; Douglas, L; Nordell, A; Janczewska, I; Naslund, E; Jonas, E

2013-01-01

58

Can Quantitative Tests of Liver Function Discriminate Between Different Etiologies of Liver Cirrhosis?  

Microsoft Academic Search

Studies comparing quantitative testing of liver function (QTLF) in large numbers of patients with defined etiology of cirrhosis are lacking. In all 316 patients with proven cirrhosis underwent QTLF, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol (SCI), and indocyanine green clearance (ICG). Values were correlated with the Child-Pugh classification (CP) and the etiology of liver cirrhosis. Fifty-five

Christoph Herold; Sabine Regn; Marion Ganslmayer; Matthias Ocker; Eckhart G. Hahn; Detlef Schuppan

2002-01-01

59

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

PubMed Central

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

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

2013-01-01

60

Effects of maternal undernutrition during late pregnancy on the development and function of ovine fetal liver.  

PubMed

This study investigated the effects of maternal undernutrition during late pregnancy on the development and function of ovine fetal liver. Eighteen ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.175MJMEkgBW(-0.75)d(-1), n=6), Restricted Group 2 (RG2, 0.33MJMEkgBW(-0.75)d(-1), n=6) and a Control Group (CG, ad libitum, 0.67MJMEkgBW(-0.75)d(-1), n=6). Fetuses were recovered at slaughter on d 140. Fetuses in the RG1 group exhibited decreased (P<0.05) liver weight, total antioxidant capacity (T-AOC), superoxide dismutase activity (SOD), cholinesterase (CHE), total protein (TP), globulin (GLB), and alanine transaminase (ALT). In addition, intermediate changes were found in the RG2 fetuses, including decreased liver weight, T-AOC and CHE (P<0.05). In contrast, increases in fetal hepatic collagen fibers and reticular fibers, glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOs), monoamine oxidase (MAO), albumin (ALB)/GLB, aspartate transaminase (AST), and AST/ALT were found in the RG1 fetuses (P<0.05). The RG2 fetuses had increased fetal hepatic collagen fibers, NOs and MAO (P<0.05) relative to the control fetuses. These results indicate that impaired fetal hepatic growth, fibrosis, antioxidant imbalance and dysfunction were associated with maternal undernutrition. PMID:24852270

Gao, Feng; Liu, Yingchun; Li, Lingyao; Li, Ming; Zhang, Chongzhi; Ao, Changjin; Hou, Xianzhi

2014-06-30

61

Liver function test abnormalities in murine typhus in Greece: a retrospective study of 165 cases.  

PubMed

The aim of this study was to analyse data relating to the liver function profile during acute infection from murine typhus in the city of Chania in the island of Crete (Greece). A retrospective study of the files of all the cases with a diagnosis of murine typhus admitted to the Saint George General Hospital of Chania over a 15-year period (1993-2008) was performed. Variations in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels were recorded from three consecutive examined serum samples. A total of 165 patients were diagnosed with murine typhus during the above time period. Serum aminotransferase and lactate dehydrogenase were abnormal in most of the first examined samples. Remarkably on admission, serum levels of AST, ALT, and LDH recorded an increase above the cut-off point in 142 (86%), 114 (69%) and 136 (82.4%) patients respectively. More than two out of every ten patients presented hepatomegaly. In conclusion, liver dysfunction occurs frequently in patients with murine typhus. A high level of physicians' awareness is required for the liver biochemical abnormalities caused by this worldwide zoonotic disease, especially in endemic areas such as Greece. PMID:24008853

Anyfantakis, Dimitrios; Doukakis, Stephanos; Papadakis, Michael; Triantafyllidou, Domniki; Bambili, Konstantina; Polimili, Georgia; Kastanakis, Serafim

2013-09-01

62

Mesenchymal Stem Cell-Derived Hepatocytes for Functional Liver Replacement  

PubMed Central

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

Christ, Bruno; Stock, Peggy

2012-01-01

63

The effects of beta-alanine supplementation and high-intensity interval training on neuromuscular fatigue and muscle function.  

PubMed

The purpose of this study was to determine the effects of beta-alanine supplementation and high-intensity interval training (HIIT) on electromyographic fatigue threshold (EMG(FT)) and efficiency of electrical activity (EEA). A total of 46 men completed four, 2-min work bouts on a cycle ergometer. Using bipolar surface electrodes, the EMG amplitude was averaged and plotted over the 2-min. The resulting slopes were used to calculate EMG(FT) and EEA. Following initial testing, all participants were randomly assigned to either placebo (PL; n = 18), beta-alanine (BA; n = 18) or control groups (CON; n = 10). Following randomization, participants engaged in 6 weeks of HIIT training. Significant improvements in EMG(FT) and EEA resulted for both training groups. In conclusion, HIIT appeared to be the primary stimulus effecting EMG(FT) or EEA, suggesting adaptations from HIIT may be more influential than increasing skeletal muscle carnosine levels on delaying fatigue in recreationally active men. PMID:18989693

Smith, Abbie E; Moon, Jordan R; Kendall, Kristina L; Graef, Jennifer L; Lockwood, Christopher M; Walter, Ashley A; Beck, Travis W; Cramer, Joel T; Stout, Jeffrey R

2009-02-01

64

Association of body burden of mercury with liver function test status in the U.S. population.  

PubMed

The majority of mercury (Hg) exposure in the US population is from consumption of fish contaminated with methylmercury (MeHg). Since inorganic Hg is the predominant form excreted in the feces and urine, hepatic biotransformation is a critical step in its normal clearance. This study was set to test the hypothesis that compromised liver function is associated with body burden of Hg as indirectly reflected by Hg sampled in blood and urine. From the National Health and Nutrition Examination Survey (NHANES, 2003-2008), 3769 adults aged 20years and above were selected for analysis. Hepatic function was inferred from the three standard serum liver-related enzyme activities, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and ?-glutamyltransferase (GGT). Multivariate regression models were used to examine the associations of interest. Although urinary Hg was significantly correlated with serum Hg, the blood-urinary Hg relationship was influenced by liver function, which is also a function of demographic and lifestyle factors (e.g., gender). Although the results were only marginally significant for examined enzymes (p=0.06-0.08), urinary Hg tended to be lower among subjects with elevated liver enzymes, as compared to those with normal enzyme measurements. Conversely, MeHg generally represents a higher fraction of the total circulating Hg among those with elevated liver enzyme levels, especially among participants with elevations in all three enzymes (p=0.01). In conclusion, this population-based study identified an association between liver function, serum Hg and urinary Hg. Urinalysis may not be the optimal approach to monitor Hg elimination toxicokinetics or Hg exposure, since the majority of Hg excretion is fecal and the fidelity of urinary excretion may depend on healthy liver function. Future prospective studies are warranted to expand these findings. PMID:24908642

Lin, Yu-Sheng; Ginsberg, Gary; Caffrey, James L; Xue, Jianping; Vulimiri, Suryanarayana V; Nath, Raghu G; Sonawane, Babasaheb

2014-09-01

65

Dosimetric applications of ?-alanine  

Microsoft Academic Search

Irradiation of solid polycrystalline alanine creates a free radical, whose concentration can be measured from its ESR signal. The radical CH3HCOO– of practically unlimited stability at room temperature shows an electronic absorption spectrum in the UV. Modern methods of diffuse reflectance spectrophotometry allow to measure the radical concentration which is proportional to the absorbed dose of radiation. The alanine dosimeter

Z. P. Zagórski

1994-01-01

66

Favorable effects of flaxseed supplemented diet on liver and kidney functions in hypertensive Wistar rats.  

PubMed

Hypertension is a major risk factor for cardiovascular diseases and is detrimental to several organs including the liver and kidneys. The flaxseed-derived polyunsaturated fatty acids including the omega-3 and omega-6 essential fatty acids have been shown to blunt the effects of hypertension. It is however, unclear whether the flaxseed, which is rich in these essential fatty acids, could improve the liver and kidney dysfunctions observed in the hypertensive condition. To test this, functional markers of the liver and kidneys, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), uric acid (UA), creatinine, and renin were examined in hypertensive male Wistar rats fed a flaxseed diet. Normotensive rats maintained on a standard diet were rendered hypertensive with a daily administration of cyclosporin A (CYS) (25 mg/kg) for 4 weeks. Subsequently, hypertensive rats were either fed a standard diet alone or a flaxseed-supplemented standard diet (FLX; 10% W/W) for 8 weeks. Compared to normotensive rats, standard diet-fed hypertensive rats had significantly elevated blood pressure, altered lipid profile, and increased plasma levels of tissue markers measured immediately following the CYS treatment and thereafter at 4 and 8 week intervals. On the other hand, rats fed the FLX-supplemented diet had significantly lower blood pressure, an improved lipid profile and decreased tissue marker levels measured after 4 and 8 week durations. The data demonstrate for the first time the favourable effects of FLX in improving liver and kidney functions in the hypertensive condition. These effects are likely to be mediated by the alpha-linolenic acid (ALA) and linoleic acid (LA) contents of flaxseed oil due to its demonstrated ability to lower the blood pressure. PMID:24005015

Al-Bishri, Widad M

2013-01-01

67

Peroxisomal alanine: glyoxylate aminotransferase AGT1 is indispensable for appressorium function of the rice blast pathogen, Magnaporthe oryzae.  

PubMed

The role of ?-oxidation and the glyoxylate cycle in fungal pathogenesis is well documented. However, an ambiguity still remains over their interaction in peroxisomes to facilitate fungal pathogenicity and virulence. In this report, we characterize a gene encoding an alanine, glyoxylate aminotransferase 1 (AGT1) in Magnaporthe oryzae, the causative agent of rice blast disease, and demonstrate that AGT1 is required for pathogenicity of M. oryzae. Targeted deletion of AGT1 resulted in the failure of penetration via appressoria; therefore, mutants lacking the gene were unable to induce blast symptoms on the hosts rice and barley. This penetration failure may be associated with a disruption in lipid mobilization during conidial germination as turgor generation in the appressorium requires mobilization of lipid reserves from the conidium. Analysis of enhanced green fluorescent protein expression using the transcriptional and translational fusion with the AGT1 promoter and open reading frame, respectively, revealed that AGT1 expressed constitutively in all in vitro grown cell types and during in planta colonization, and localized in peroxisomes. Peroxisomal localization was further confirmed by colocalization with red fluorescent protein fused with the peroxisomal targeting signal 1. Surprisingly, conidia produced by the ?agt1 mutant were unable to form appressoria on artificial inductive surfaces, even after prolonged incubation. When supplemented with nicotinamide adenine dinucleotide (NAD(+))+pyruvate, appressorium formation was restored on an artificial inductive surface. Taken together, our data indicate that AGT1-dependent pyruvate formation by transferring an amino group of alanine to glyoxylate, an intermediate of the glyoxylate cycle is required for lipid mobilization and utilization. This pyruvate can be converted to non-fermentable carbon sources, which may require reoxidation of NADH generated by the ?-oxidation of fatty acids to NAD(+) in peroxisomes. Therefore, it may provide a means to maintain redox homeostasis in appressoria. PMID:22558413

Bhadauria, Vijai; Banniza, Sabine; Vandenberg, Albert; Selvaraj, Gopalan; Wei, Yangdou

2012-01-01

68

Function of GATA Factors in the Adult Mouse Liver  

PubMed Central

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

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

2013-01-01

69

Drug metabolism and liver function after methyldopa withdrawal.  

PubMed Central

1 The effects of methyldopa withdrawal on liver function and drug metabolism were investigated in ten elderly females suffering from the drug-induced orthostatic reaction and resistant hypertension. 2 There was a significant increase in serum albumin level, antipyrine metabolism and urinary excretion of D-glucaric acid 6 months after the methyldopa withdrawal. 3 The results suggest that patients treated with methyldopa might show a reduced metabolizing ability in spite of normal liver function tests.

Ylikallio, A; Sotaniemi, E A

1980-01-01

70

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

Microsoft Academic Search

Objective:Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids

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

2008-01-01

71

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

PubMed Central

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

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

2014-01-01

72

Biomechanics and functionality of hepatocytes in liver cirrhosis.  

PubMed

Cirrhosis is a life-threatening condition that is generally attributed to overproduction of collagen fibers in the extracellular matrix that mechanically stiffens the liver. Chronic liver injury due to causes including viral hepatitis, inherited and metabolic liver diseases and external factors such as alcohol abuse can result in the development of cirrhosis. Progression of cirrhosis leads to hepatocellular dysfunction. While extensive studies to understand the complexity underlying liver fibrosis have led to potential application of anti-fibrotic drugs, no such FDA-approved drugs are currently available. Additional studies of hepatic fibrogenesis and cirrhosis primarily have focused on the extracellular matrix, while hepatocyte biomechanics has received limited attention. The role of hepatocyte biomechanics in liver cirrhosis remains elusive, and how the cell stiffness is correlated with biological functions of hepatocytes is also unknown. In this study, we demonstrate that the biomechanical properties of hepatocytes are correlated with their functions (e.g., glucose metabolism), and that hepatic dysfunction can be restored through modulation of the cellular biomechanics. Furthermore, our results indicate the hepatocyte functionality appears to be regulated through a crosstalk between the Rho and Akt signaling. These novel findings may lead to biomechanical intervention of hepatocytes and the development of innovative tissue engineering for clinical treatment to target liver cells rather than exclusively focusing on the extracellular matrix alone in liver cirrhosis. PMID:24262849

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

2014-06-27

73

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

PubMed Central

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

Kowalczyk, Wojciech; Krasuska-Slawinska, Ewa; Dadalski, Maciej; Kostewicz, Krzysztof; Pawlowska, Joanna

2014-01-01

74

Liver function from Y to Z  

PubMed Central

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

Arias, Irwin M.

2012-01-01

75

Hepatic Mitochondrial Function Analysis Using Needle Liver Biopsy Samples  

PubMed Central

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

Hosking, Alexander W. G.; MacDonald, Julia R.; Bartlett, Adam S. J. R.; Hickey, Anthony J. R.

2013-01-01

76

What is the best strategy for investigating abnormal liver function tests in primary care? Implications from a prospective study  

PubMed Central

Objective Evaluation of predictive value of liver function tests (LFTs) for the detection of liver-related disease in primary care. Design A prospective observational study. Setting 11 UK primary care practices. Participants Patients (n=1290) with an abnormal eight-panel LFT (but no previously diagnosed liver disease). Main outcome measures Patients were investigated by recording clinical features, and repeating LFTs, specific tests for individual liver diseases, and abdominal ultrasound scan. Patients were characterised as having: hepatocellular disease; biliary disease; tumours of the hepato-biliary system and none of the above. The relationship between LFT results and disease categories was evaluated by stepwise regression and logistic discrimination, with adjustment for demographic and clinical factors. True and False Positives generated by all possible LFT combinations were compared with a view towards optimising the choice of analytes in the routine LFT panel. Results Regression methods showed that alanine aminotransferase (ALT) was associated with hepatocellular disease (32 patients), while alkaline phosphatase (ALP) was associated with biliary disease (12 patients) and tumours of the hepatobiliary system (9 patients). A restricted panel of ALT and ALP was an efficient choice of analytes, comparing favourably with the complete panel of eight analytes, provided that 48 False Positives can be tolerated to obtain one additional True Positive. Repeating a complete panel in response to an abnormal reading is not the optimal strategy. Conclusions The LFT panel can be restricted to ALT and ALP when the purpose of testing is to exclude liver disease in primary care.

Lilford, Richard J; Bentham, Louise M; Armstrong, Matthew J; Neuberger, James; Girling, Alan J

2013-01-01

77

Kinetics of liver function tests after a hepatectomy for colorectal liver metastases predict post-operative liver failure as defined by the International Study Group for Liver Surgery  

PubMed Central

Background Post-hepatectomy liver failure (PHLF) has been defined by the International Study Group for Liver Surgery (ISGLS). The purpose of the present study was to examine the kinetics of conventional liver function tests (LFT) after a major liver resection and is the first to examine their utility in predicting PHLF in groups defined by the ISGLS. Methods Consecutive patients undergoing a major liver resection for colorectal liver metastases were stratified into ISGLS groups and their LFT up to 1 year after surgery compared. Receiving-operating characteristic (ROC) analysis of LFT identified optimal thresholds in predicting category C liver failure. Results In total, 32, 22 and 19 patients belonged to ISGLS groups A, B and C, respectively. The median international normalized ratio (INR) and bilirubin values on post-operative days 1, 3, 5 and 7 were significantly different among the groups (all P-values <0.05). ROC analysis of day 1 INR (AUC 0.813) and day 5 bilirubin (AUC 0.798) revealed thresholds of 1.35 and 52 ?mol/l to have sensitivities of 85% and 81% and specificities of 63% and 73%, respectively, to predict group C liver failure. Discussion Post-operative LFT after a major liver resection differs significantly among the three ISGLS groups. Thresholds of bilirubin and INR can be used to identify patients who are at a maximum risk of complications.

Roberts, Keith J; Bharathy, Kishore GS; Lodge, J Peter A

2013-01-01

78

Improvement of liver function in humans using a mixture of schisandra fruit extract and sesamin.  

PubMed

This was a randomized, parallel, and placebo-controlled study. Forty subjects were divided into a test group and a placebo group. The study was focused on the potential effects of a mixture of Schisandra fruit extract and sesamin (hereinafter called 'SCH') in the subjects with borderline high levels (40-60 U/L) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Twenty subjects taking SCH (four tablets per day) and 20 subjects taking a placebo (four tablets per day) were studied. The effects of SCH on ALT, AST, total bilirubin, direct bilirubin, free radical levels, total antioxidant status, glutathione peroxidase, glutathione reductase, and the lag time for low-density lipoprotein oxidation were determined. The total test period was 5?months. Intervention of SCH clearly reduced the levels of ALT and AST, but it made no change in the total bilirubin and direct bilirubin. Intake of SCH also greatly increased the antioxidant capacity and decreased the values of thiobarbituric acid reactive substances, total free radicals, and superoxide anion radicals in the plasma. The activities of glutathione peroxidase and reductase in the erythrocytes were significantly increased. In addition, the lag time for low-density lipoprotein oxidation, an inflammatory marker, was evidently increased. Fatty liver was found to have been significantly improved in this study. SCH proved to have the effects of antioxidation and improving liver function. PMID:22610748

Chiu, Hui-Fang; Chen, Tzy-Yen; Tzeng, Yu-Te; Wang, Chin-Kun

2013-03-01

79

Beta-alanine synthesis in Escherichia coli.  

PubMed Central

The enzyme, aspartate 1-decarboxylase (L-aspartate 1-carboxy-lyase; EC 4.1.1.15), that catalyzes the reaction aspartate leads to beta-alanine + CO2 was found in extracts of Escherichia coli. panD mutants of E. coli are defective in beta-alanine biosynthesis and lack aspartate 1-decarboxylase. Therefore, the enzyme functions in the biosynthesis of the beta-alanine moiety of pantothenate. The genetic lesion in these mutants is closely linked to the other pantothenate (pan) loci of E. coli K-12. Images

Cronan, J E

1980-01-01

80

Bilirubin binding with liver cystatin induced structural and functional changes.  

PubMed

Cysteine proteinases and their inhibitors play a significant role in the proteolytic environment of the cells. Inhibitors of cysteine proteinases regulate the activity of these enzymes helping in checking the degdration activity of cathepsins. The bilirubin secreated by liver cells can bind to cystatin present in the liver resulting in its functional inactivation, which may further lead to the increase in cathepsins level causing liver cirrhosis. In case of some pathophysiological conditions excess bilirubin gets accumulated e.g. in presence of Fasciola hepatica (liver fluke) in mammals and humans, leading to liver cirrhosis and possibly jaundice or normal blockade of bile duct causing increased level of bilirubin in blood. Protease-cystatin imbalance causes disease progression. In the present study, Bilirubin (BR) and liver cystatin interaction was studied to explore the cystatin inactivation and structural alteration. The binding interaction was studied by UV-absorption, FT-IR and fluorescence spectroscopy. The quenching of protein fluorescence confirmed the binding of BR with buffalo liver cystatin (BLC). Stern-Volmer analysis of BR-BLC system indicates the presence of static component in the quenching mechanism and the number of binding sites to be close to 1. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR-cystatin complex formation. FTIR analysis of BR-Cystatin complex revealed change in the secondary structure due to perturbation in the microenvironment further confirmed by the decreased caseinolytic activity of BLC against papain. Fluorescence measurements also revealed quenching of fluorescence and shift in peak at different time intervals and at varying pH values. Photo-illumination of BR-cystatin complex causes change in the surrounding environment of liver cystatin as indicated by red-shift. The binding constant for BR-BLC complex was found to be 9.279?×?10(4) M(-1). The cystatin binding with bilirubin has a significant biophysical and pathophysiological significance, hence our effort to study the same. PMID:24711081

Mustafa, Mir Faisal; Bano, Bilqees

2014-05-01

81

Different proton transfer channels for the transformation of zwitterionic alanine-(H?O)(n=2-4) to nonzwitterionic alanine-(H?O)(n=2-4): a density functional theory study.  

PubMed

We report here the various possibilities of proton transfer between the zwitterionic and the non-zwetterionic form of alanine (Ala) via (H?O)(n=2-4) clusters by calculating the transition state structures of zwitterionic alanine (ZAla)-(H?O)(n=2-4) and non-zwitterionic alanine (Ala)-(H?O)(n=2-4) complexes at B3LYP/6-311++G(d,p) and CAM-B3LYP/6-311++G(d,p) level of theory. In order to determine the most feasible channel for proton transfer, the barrier energy corresponding to each channel was calculated. For the transformation of ZAla-(H?O)(n=2) to Ala-(H?O)(n=2), we identified eight channels for proton transfer. The lowest barrier energy (2.57 kcal mol?¹) channel, where ZAla-(H?O)(n=2) transforms to Ala-(H?O)(n=2) via triple proton transfer, is said to be the energetically most feasible channel. The values of barrier energy corresponding to the least energy pathway for proton transfer were calculated to be 1.14 and 9.82 kcal mol?¹ for n?=?3 and n?=?4 complexes, respectively, at B3LYP/6-311++G(d,p) level of theory. For complex n?=?3, the structure where proton transfer takes place directly from -NH?? to -COO? has the lowest energy pathway. However, the complexes for n?=?2 and 3--the channels where proton transferred from -NH?? to -COO? via two water molecules have the lowest barrier energy. For each n, the values of barrier energy calculated at CAM-B3LYP/6-311++G(d,p) level of theory were always less compared those calculated at B3LYP/6-311++G(d,p) level of theory. The value of rate constants corresponding to each proton transfer channel was also calculated. PMID:24573496

Ojha, Animesh K; Bhunia, Snehasis

2014-03-01

82

Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver  

Microsoft Academic Search

Background & Aims: Based on a recently cloned rat liver organic anion transporter, we attempted to clone the corresponding human liver organic anion transporting polypeptide. Methods: A human liver complementary DNA library was screened with a specific rat liver complementary DNA probe. The human liver transporter was cloned by homology with the rat protein and functionally characterized in Xenopus laevis

Gerd A. Kullak-Ublick; Bruno Hagenbuch; Bruno Stieger; Claudio D. Schteingart; Alan F. Hofmann; Allan W. Wolkoff; Peter J. Meier

1995-01-01

83

Sex Hormone-Related Functions in Regenerating Male Rat Liver  

PubMed Central

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

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

2011-01-01

84

High-dose naltrexone and liver function safety.  

PubMed

Studies have found naltrexone useful in the treatment of diseases other than opiate addiction in which endogenous opioids presumably play a role, such as alcoholism and eating disorders. Some of these studies involve high doses (100-200 mg bid). Because investigational studies with high doses (300 mg/day) reported clinically significant increases in liver enzyme levels, the authors measured a spectrum of liver function parameters in response to high doses of naltrexone in a double-blind, crossover trial (100 mg bid) followed by an open-label period (200 mg bid). They observed no adverse clinical or laboratory changes in liver function in association with high-dose naltrexone therapy in eating disorders. PMID:9097868

Marrazzi, M A; Wroblewski, J M; Kinzie, J; Luby, E D

1997-01-01

85

Prolonged Observations on the Liver Function Tests in Infectious Hepatitis.  

National Technical Information Service (NTIS)

Standard liver function tests were analyzed in 215 patients with infectious hepatitis who had a mean hospitalization of 56 days. In 189 patients there was the usual (or typical) progressive decrease in the SGOT and SGPT. Twenty-four of the other 26 patien...

G. T. Strickland D. O. Castell R. A. Kronmal

1971-01-01

86

Effect of Rifampicin and Isoniazid on Liver Function  

Microsoft Academic Search

The effects of rifampicin and isoniazid on liver function have been studied in 63 patients with pulmonary tuberculosis; 29% showed abnormalities of serum aspartate aminotransferase (SGOT) and a similar percentage abnormalities of serum bilirubin. These usually occurred during the first 12 weeks of therapy. The average duration of the abnormalities was 14½ days, irrespective of whether treatment was interrupted or

Satinder Lal; S. N. Singhal; D. M. Burley; G. Crossley

1972-01-01

87

Generation of quinoneimine intermediates in the bioactivation of 3-(N-phenylamino)alanine (PAA) by human liver microsomes: a potential link between eosinophilia-myalgia syndrome and toxic oil syndrome.  

PubMed

Eosinophilia-myalgia syndrome (EMS) was an intoxication episode that occurred in the US in 1989 and affected 1,500 people. EMS was associated with the ingestion of manufactured L-tryptophan, and 3-(N-phenylamino)alanine (PAA) was identified as one of the contaminants present in the L-tryptophan batches responsible for intoxication. In previous studies (Martínez-Cabot et al., Chem Res. Toxicol., in press), we have shown that the incubation of 3-(N-phenylamino)propane-1,2-diol (PAP), a toxic biomarker of the oil batches that caused Toxic Oil Syndrome in Spain, with human liver microsomes generates a reactive quinoneimine intermediate. The structural similarity between PAA and PAP led Mayeno and co-workers (Mayeno et al. (1995) Chem. Res. Toxicol. 8, 911-916) to hypothesize that both xenobiotics could be linked to a common etiologic agent. We thus set about to study the bioactivation of PAA by human liver microsomes. Under these conditions, PAA is converted to its 4'-hydroxy derivative, an unstable intermediate that is rapidly transformed into the final metabolites 4-aminophenol and formylglycine, which were identified in the incubations by GC/MS using the H2(18)O-labeled medium. We also provide evidence that 4-aminophenol and formylglycine are formed from a quinoneimine intermediate via a pathway similar to that demonstrated for PAP bioactivation. This quinoneimine, in the absence of nucleophiles in the incubation medium, could isomerize to give the corresponding imine, which could undergo hydrolysis to yield the aforementioned final products. These findings establish that EMS and TOS are linked by a common toxic metabolite (4-aminophenol) and that they may be further linked by the concomitant release of potentially hazardous carbonyl species. PMID:17892268

Martínez-Cabot, Anna; Messeguer, Angel

2007-10-01

88

Liver function test abnormalities and pruritus in a patient treated with atorvastatin: case report and review of the literature.  

PubMed

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as statins) are associated with elevated transaminase levels in 1-3% of patients. Therapy with these drugs requires monitoring of alanine aminotransferase (ALT) levels because animal studies and premarketing clinical trials showed signs of hepatotoxicity that were primarily minor elevations of ALT. Nevertheless, postmarketing experience suggests that hepatotoxicity is rare, and that elevated ALT levels are reversible with continued therapy and probably are related to cholesterol lowering. Based on the low occurrence of ALT elevations and the lack of clinical evidence of hepatotoxicity, some clinicians are calling for a change in the current practice of monitoring liver function tests. We report, however, the case of a 71-year-old woman who was receiving atorvastatin and experienced elevated transaminase levels on two occasions, and developed pruritus on rechallenge with the drug. Thus, clinicians should be aware of asymptomatic elevations in liver function tests in patients receiving atorvastatin who do not have known risk factors for liver damage. PMID:14740794

Gershovich, Olga E; Lyman, Alfred E

2004-01-01

89

Impact of serum chemerin levels on liver functional reserves and platelet counts in patients with hepatocellular carcinoma.  

PubMed

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

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

2014-01-01

90

Biochemical parameters of liver function in artisans occupationally exposed to "vat dyes"  

PubMed Central

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

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

2007-01-01

91

Proliferation and function of microbodies in the nematophagous fungus Arthrobotrys oligospora during growth on oleic acid or D-alanine as the sole carbon source  

Microsoft Academic Search

The nematophagous fungus Arthrobotrys oligospora is able to grow on oleic acid or D-alanine as the sole carbon source. During growth on oleic acid, activities of enzymes of the ?-oxidation pathway, but not catalase, were induced. In the presence of D-alanine, both D-amino acid oxidase and catalase activities were enhanced. Biochemically and cytochemically, the activities of the above enzymes were

Jan Dijksterhuis; Wim Harder; Marten Veenhuis

1993-01-01

92

Dilated common bile duct and deranged liver function tests associated with ketamine use in two HIV-positive MSM.  

PubMed

We report here the first two cases of hepatobiliary pathology in HIV-positive men following recreational use of ketamine: >1?g/day over a 12-month period while on ritonavir-based antiretroviral therapy. Presentation in each case was acute with nausea, vomiting and epigastric pain. Alanine aminotransferase was raised at 3.2× and 10.1?×?upper limit of normal and alkaline phosphatase was raised at 1.7× and 2.5?×?ULN for cases 1 and 2, respectively. Magnetic resonance cholangiopancreatography showed dilatation of the common bile duct; case 1, 18?mm and case 2, 14?mm with no ductal obstruction on endoscopic retrograde cholangiopancreatography. The symptoms resolved, common bile duct dilatation and liver function improved on discontinuation of ketamine use. Time to development of symptoms is shorter than reported in HIV-negative cases (12 months vs. 4 years) which may be explained by an interaction between ketamine and ritonavir. PMID:23970577

Zhou, Judith; Shaw, Simon G; Gilleece, Yvonne

2013-08-01

93

Functional significance of an evolutionarily conserved alanine (GCA) resume codon in tmRNA in Escherichia coli.  

PubMed

Occasionally, ribosomes stall on mRNAs prior to the completion of the polypeptide chain. In Escherichia coli and other eubacteria, tmRNA-mediated trans-translation is a major mechanism that recycles the stalled ribosomes. The tmRNA possesses a tRNA-like domain and a short mRNA region encoding a short peptide (ANDENYALAA in E. coli) followed by a termination codon. The first amino acid (Ala) of this peptide encoded by the resume codon (GCN) is highly conserved in tmRNAs in different species. However, reasons for the high evolutionary conservation of the resume codon identity have remained unclear. In this study, we show that changing the E. coli tmRNA resume codon to other efficiently translatable codons retains efficient functioning of the tmRNA. However, when the resume codon was replaced with the low-usage codons, its function was adversely affected. Interestingly, expression of tRNAs decoding the low-usage codon from plasmid-borne gene copies restored efficient utilization of tmRNA. We discuss why in E. coli, the GCA (Ala) is one of the best codons and why all codons in the short mRNA of the tmRNA are decoded by the abundant tRNAs. PMID:21602351

Kapoor, Suman; Samhita, Laasya; Varshney, Umesh

2011-07-01

94

Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications  

PubMed Central

Human hepatic peroxisomal AGT (alanine:glyoxylate aminotransferase) is a PLP (pyridoxal 5?-phosphate)-dependent enzyme whose deficiency causes primary hyperoxaluria Type I, a rare autosomal recessive disorder. To acquire experimental evidence for the physiological function of AGT, the Keq,overall of the reaction, the steady-state kinetic parameters of the forward and reverse reactions, and the pre-steady-state kinetics of the half-reactions of the PLP form of AGT with L-alanine or glycine and the PMP (pyridoxamine 5?-phosphate) form with pyruvate or glyoxylate have been measured. The results indicate that the enzyme is highly specific for catalysing glyoxylate to glycine processing, thereby playing a key role in glyoxylate detoxification. Analysis of the reaction course also reveals that PMP remains bound to the enzyme during the catalytic cycle and that the AGT–PMP complex displays a reactivity towards oxo acids higher than that of apoAGT in the presence of PMP. These findings are tentatively related to possible subtle rearrangements at the active site also indicated by the putative binding mode of catalytic intermediates. Additionally, the catalytic and spectroscopic features of the naturally occurring G82E variant have been analysed. Although, like the wild-type, the G82E variant is able to bind 2 mol PLP/dimer, it exhibits a significant reduced affinity for PLP and even more for PMP compared with wild-type, and an altered conformational state of the bound PLP. The striking molecular defect of the mutant, consisting in the dramatic decrease of the overall catalytic activity (?0.1% of that of normal AGT), appears to be related to the inability to undergo an efficient transaldimination of the PLP form of the enzyme with amino acids as well as an efficient conversion of AGT–PMP into AGT–PLP. Overall, careful biochemical analyses have allowed elucidation of the mechanism of action of AGT and the way in which the disease causing G82E mutation affects it.

Cellini, Barbara; Bertoldi, Mariarita; Montioli, Riccardo; Paiardini, Alessandro; Borri Voltattorni, Carla

2007-01-01

95

Improvement of liver function parameters in patients with type 2 diabetes treated with thiazolidinediones  

Microsoft Academic Search

To increase our understanding of the effect of thiazolidinediones, a new class of antidiabetic drugs, on liver function as well as glycemic control, we investigated liver function before, during, and after treatment with troglitazone and pioglitazone.A total of 32 patients with type 2 diabetes were studied. Glycemic control and liver function were measured before, during, and after 4 to 12

Masaya Ono; Hiroshi Ikegami; Tomomi Fujisawa; Koji Nojima; Yumiko Kawabata; Masanori Nishino; Hidenori Taniguchi; Michiko Itoi-Babaya; Naru Babaya; Kaori Inoue; Toshio Ogihara

2005-01-01

96

Biochemical Parameters for Longitudinal Monitoring of Liver Function in Rat Models of Partial Hepatectomy Following Liver Injury  

PubMed Central

Background While evaluation of liver function in preclinical animal studies is commonly performed at selected time-points by invasive determination of the liver/body weight ratio and histological analyses, the validation of longitudinal measurement tools for monitoring liver function are of major interest. Aims To longitudinally evaluate serum cholinesterase (CHE) and total serum bilirubin (TSB) levels as non-invasive markers to determine injury- and partial hepatectomy (PHx)-induced alterations of liver function in rats. Methods Male and female Lewis rats were subjected to either methionine/choline deficient (MCD) diet or treatment with FOLFOX chemotherapy prior to PHx. Body weight and CHE/TSB levels are determined weekly. Following PHx and at the study end, histological analyses of liver tissue are performed. Results Following MCD diet, but not after FOLFOX chemotherapy treatment, results indicate gender-specific alterations in serum CHE levels and gender-independent alterations in TSB levels. Likewise, histological analyses of resected liver parts indicate significant liver injury following MCD-diet, but not following FOLFOX treatment. While TSB levels rapidly recover following MCD diet/FOLFOX treatment combined with a PHx, serum CHE levels are subject to significant model- and gender-specific differences, despite full histopathological recovery of liver tissue. Conclusions Longitudinal measurements of serum CHE levels and TSB levels in rats are highly complementary as non-invasive parameters for evaluation of liver injury and/or recovery.

Boeykens, Nele; Ponsaerts, Peter; Ysebaert, Dirk; De Greef, Kathleen

2013-01-01

97

Serum Perfluorooctanoate (PFOA) and Perfluorooctane Sulfonate (PFOS) Concentrations and Liver Function Biomarkers in a Population with Elevated PFOA Exposure  

PubMed Central

Background: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) persist in the environment and are found in relatively high concentrations in animal livers. Studies in humans have reported inconsistent associations between PFOA and liver enzymes. Objectives: We examined the cross-sectional association between serum PFOA and PFOS concentrations with markers of liver function in adults. Methods: The C8 Health Project collected data on 69,030 persons; of these, a total of 47,092 adults were included in the present analysis. Linear regression models were fitted for natural log (ln)-transformed values of alanine transaminase (ALT), ?-glutamyltransferase (GGT), and direct bilirubin on PFOA, PFOS, and potential confounders. Logistic regression models were fitted comparing deciles of PFOA or PFOS in relation to high biomarker levels. A multilevel analysis comparing the evidence for association of PFOA with liver function at the individual level within water districts to that at the population level between water districts was also performed. Results: ln-PFOA and ln-PFOS were associated with ln-ALT in linear regression models [PFOA: coefficient, 0.022; 95% confidence interval (CI): 0.018, 0.025; PFOS: coefficient, 0.020; 95% CI: 0.014, 0.026] and with raised ALT in logistic regression models [with a steady increase in the odds ratio (OR) estimates across deciles of PFOA and PFOS; PFOA: OR = 1.10; 95% CI: 1.07, 1.13; PFOS: OR = 1.13; 95% CI: 1.07, 1.18]. There was less consistent evidence of an association of PFOA and GGT or bilirubin. The relationship with bilirubin appears to rise at low levels of PFOA and to fall again at higher levels. Conclusions: These results show a positive association between PFOA and PFOS concentrations and serum ALT level, a marker of hepatocellular damage.

Gallo, Valentina; Leonardi, Giovanni; Genser, Bernd; Lopez-Espinosa, Maria-Jose; Frisbee, Stephanie J.; Karlsson, Lee; Ducatman, Alan M.

2012-01-01

98

The effect of ursodeoxycholic acid in liver functional restoration of patients with obstructive jaundice after endoscopic treatment: a prospective, randomized, and controlled study  

PubMed Central

Background In patients with obstructive jaundice, multi-organ dysfunction may develop. Methods/Design This trial is a prospective, open-label, randomized, and controlled study with the objective to evaluate the effect of ursodeoxycholic acid in liver functional restoration in patients with obstructive jaundice after endoscopic treatment. The aim of this study is to evaluate the effect of ursodeoxycholic acid in liver functional restoration of patients with obstructive jaundice after endoscopic treatment. The hypothesis of this trial is that patients with obstructive jaundice, in which will be administered UDCA, in the early phase after endoscopic intervention will have better and faster functional restoration of the liver than patients in the control group. Patients with obstructive jaundice, randomly, will be divided into two groups: (A) test group in which will be administered ursodeoxycholic acid twenty-four hours after endoscopic procedure and will last fourteen days, and (B) control group. Serum-testing will include determination of bilirubin, alanine transaminase, aspartate transaminase, gama-glutamil transpeptidase, alkaline phosphatase, albumin, and cholesterol levels. These parameters will be determined one day prior endoscopic procedure, and on the third, fifth, seventh, tenth, twelfth and fourteenth days after endoscopic intervention. Discussion This trial is a prospective, open-label, randomized, and controlled study to asses the effect of ursodeoxycholic acid in liver functional restoration of patients with obstructive jaundice in the early phase after endoscopic treatment. Trial registration ClinicalTrials.gov, NCT01688375

2013-01-01

99

Functional hyposplenism in alcoholic liver disease: a toxic effect of alcohol?  

Microsoft Academic Search

Functional hyposplenism, seen in some patients with alcoholic liver disease, may contribute to the increased susceptibility to infections. As hyposplenism does not complicate non-alcohol related chronic liver disease, it is probably secondary to a toxic effect of alcohol. Over a two year period the case notes of 82 patients with alcoholic liver disease, whose splenic function had been assessed by

A F Muller; P J Toghill

1994-01-01

100

In vitro evaluation of metabolic functions of a bioartificial liver.  

PubMed

The purpose of this study is to develop a bioartificial liver (BAL) with such a simple structure that it can be prepared within several hours and through which whole blood can be perfused as in current hemodialyzers. Hepatocytes were isolated from 37 pigs; each liver weighed 300 to 400 g. The average yield of hepatocytes was 2.4 +/- 0.6 x 10(10) cells per liver, with a cell viability of 89.6 +/- 3.9%. To prepare a BAL device, a cartridge, composed of hollow fibers made of cellulose diacetate was used. Nominal cut-off molecular weight of the hollow fibers was 68 kDa, and the internal diameter was 195 microm. One hundred milliliters of hepatocyte suspension, containing 1 x 10(10) cells, was inoculated into the inner space of the hollow fibers, and both the inlet and outlet of the hollow fiber cartridge were closed. It took only 3 hrs from administration of the pig's anesthesia to the start of an in vitro evaluation of the prepared BAL device. To evaluate the functions of this BAL quantitatively, using a pharmacokinetic method, a mixture of fresh human blood and Dulbecco's modified Eagle medium was circulated in the shell space of the hollow fibers at 200 ml/min. Chemicals (lidocaine, ammonia, and galactose) were then loaded into the perfusion medium. The average intrinsic clearance of the BAL device was found to be 46 ml/min for lidocaine and 8.8 ml/min for ammonia. The galactose elimination capacity of the BAL device was 1.34 mg/min. The metabolic function of the BAL device decreased by 81%, 49%, and 64% of the initial function for lidocaine, ammonia, and galactose, respectively, after 10 days of in vitro circulation. PMID:10445735

Iwata, H; Sajiki, T; Maeda, H; Park, Y G; Zhu, B; Satoh, S; Uesugi, T; Ikai, I; Yamaoka, Y; Ikada, Y

1999-01-01

101

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

PubMed

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

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

2013-05-01

102

Controlled therapy by imaging of functional structures of intact liver  

NASA Astrophysics Data System (ADS)

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

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

2000-04-01

103

Folding and Function of a T4 Lysozyme Containing 10 Consecutive Alanines Illustrate the Redundancy of Information in an Amino Acid Sequence  

NASA Astrophysics Data System (ADS)

Single and multiple Xaa -> Ala substitutions were constructed in the ?-helix comprising residues 39-50 in bacteriophage T4 lysozyme. The variant with alanines at 10 consecutive positions (A40-49) folds normally and has activity essentially the same as wild type, although it is less stable. The crystal structure of this polyalanine mutant displays no significant change in the main-chain atoms of the helix when compared with the wild-type structure. The individual substitutions of the solvent-exposed residues Asn-40, Ser-44, and Glu-45 with alanine tend to increase the thermostability of the protein, whereas replacements of the buried or partially buried residues Lys-43 and Leu-46 are destabilizing. The melting temperature of the lysozyme in which Lys-43 and Leu-46 are retained and positions 40, 44, 45, 47, and 48 are substituted with alanine (i.e., A40-42/44-45/47-49) is increased by 3.1^circC relative to wild type at pH 3.0, but reduced by 1.6^circC at pH 6.7. In the case of the charged amino acids Glu-45 and Lys-48, the changes in melting temperature indicate that the putative salt bridge between these two residues contributes essentially nothing to the stability of the protein. The results clearly demonstrate that there is considerable redundancy in the sequence information in the polypeptide chain; not every amino acid is essential for folding. Also, further evidence is provided that the replacement of fully solvent-exposed residues within ?-helices with alanines may be a general way to increase protein stability. The general approach may permit a simplification of the protein folding problem by retaining only amino acids proven to be essential for folding and replacing the remainder with alanine.

Heinz, Dirk W.; Baase, Walt A.; Matthews, Brian W.

1992-05-01

104

Liver and kidney function tests amongst paint factory workers in Nkpor, Nigeria.  

PubMed

Lead, cadmium, nickel and other industrial metals used as part of paint varnishes have been reported to have adverse health implications. An evaluation study on some toxicological effects of occupational exposure to paint, among 25 occupationally exposed artisans and 25 students (control) of Ichi Technical College, Ichi Ekwusigo Local Government Area, Anambra State, Nigeria was carried out. Heavy metals were analysed by atomic absorption spectrophotometry and standard assay procedures were employed for biochemical parameters. The biochemical indices used include serum electrolytes urea, creatinine, alanine (ALT) and aspartate aminotransferases (AST), alkaline phosphatase (ALP), conjugated and total bilirubin. Others include blood lead, serum cadmium and nickel. Our results showed that occupational exposure of humans to paints increased the blood lead (39 +/- 4 microg/dL), serum cadmium (13 +/- 1 microg/dL) and nickel (63 +/- 1 microg/dL), when compared with non-paint factory workers (PFW) lead (17 +/- 4 microg/dL), serum cadmium (9 +/- microg/dL) and nickel (25 +/- 44 microg/dL), significantly at P < 0.05 lower values were observed for serum sodium (138.96 +/- 0.58 mmol/L), bicarbonate (26.88 +/- 0.39 mmol/L), urea (3.15 +/- 0.13 mmol/L) and creatinine (80.48 +/- 1.04 micromol/L) for paints factory workers when compared with non-paint factory workers, sodium (139.84 +/- 0.62 mmol/L), bicarbonate (26.20 +/- 0.22 mmol/L), urea (3.44 +/- 0.11 mmol/L) and creatinine (80.40 +/- 1.55 micromol/L); at P > 0.05. The activities of AST (10.36 +/- 0.58 micro/L), ALT(8.76 +/- 0.47 micro/L) and ALP (47.12 +/- 3.33 micro/L) in PFW were slightly elevated compared with non-PFW. Our result indicates that occupational exposure of humans to heavy metals in paints may have long term deleterious effects on liver and renal functions. In conclusion, it should be noted that occupational exposure to cadmium or lead among PFW, may compromise the liver and renal functions in man. PMID:18220158

Orisakwe, O E; Nwachukwu, E; Osadolor, H B; Afonne, O J; Okocha, C E

2007-04-01

105

[Functional restructurings of the mononuclear phagocyte system in experimental liver cirrhosis].  

PubMed

In rats with CCl4-induced liver cirrhosis the clearance rate of colloid carbon particles was more than 2 times lower than in control animals. Simultaneously the uptake capacity of liver Kupffer calls falls. The number of phagocytizing liver macrophages decreased. Along with the diminished functional activity of liver macrophages in cirrhotic liver, the total number of lung and spleen macrophages increased 1.5-fold, with their uptake capacity increasing 10- and 3-fold, respectively. The nitroblue tetrazolium dye reduction and methacrylate particles uptake by alveolar macrophages in vitro rises. The liver, lung, spleen and peritoneal macrophages during liver fibrosis become less sensitive to zymosan stimulation. The incidence of zymosan-induced liver infiltrates decreases 50-fold, while in the lungs they do not develop at all. Such a decreased macrophage reactivity may be closely linked with progressing, poorly reversible liver fibrosis. PMID:3349155

Maianski?, D N; Shvarts, Ia Sh; Tsyrendorzhiev, D D; Kutina, S N

1988-02-01

106

Effect of carbamazepine on serum lipids and liver function tests.  

PubMed

We prospectively studied the effect of carbamazepine (CBZ) therapy on serum lipids and liver function tests in 28 patients and 28 age and sex matched controls. The mean age of patients was 8.29 years, duration of therapy with CBZ 10.3 months and dose of CBZ 13.1 mg/dL. The patients and controls were comparable in weight, height and BMI. Mean +/- SD of cholesterol 162 +/- 25.8 mg/dL in patients was significantly more than controls 131+/- 25.2 mg/dL. Mean LDL cholesterol and HDL cholesterol were also significantly raised in patients. Values of mean VLDL, triglycerides, ratio of LDL HDL, TC HDLC bilirubin and SGPT were not significantly different in two groups. Blood Levels of alkaline phosphatase were significantly more in patients compared to controls. The long term implications of these findings need to be studied. PMID:16208051

Aggarwal, Anju; Kumar, Manish; Faridi, M M A

2005-09-01

107

Effects of exercise and ethanol on liver mitochondrial function  

SciTech Connect

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

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

1987-03-16

108

In vitro evaluation of donor liver preservation fluids on human hepatocyte function  

Microsoft Academic Search

Successful liver transplantation depends on adequate preservation of cellular function. We therefore tested the effects of two currently used liver preservation fluids, Euro-Collins (EC) solution and University of Wisconsin (UW) solution, on the viability and some functional activities of hepatocytes isolated from human livers. Cells in primary culture were maintained under hypoxic (95% N2\\/5% CO2) and hypothermic (4°C) conditions for

Pascal Thomas; Georges de Sousa; Florence Nicolas; Yves P. Le Treut; Jean-Robert Delpero; Pierre Fuentes; Michel Placidi; Roger Rahmani

1995-01-01

109

The effects of high-intensity resistance exercise on the blood lipid profile and liver function in hypercholesterolemic hamsters.  

PubMed

It is well established that atherogenic dyslipidemia, characterized by high levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol, constitutes important risk factors for cardiovascular disease. Regular exercise has been associated with a reduced risk for metabolic diseases. However, studies supporting the concept that resistance exercise is a modifier of blood lipid parameters are often contradictory. The aim of this study was to investigate the effects of high-intensity resistance exercise on the serum levels of TG, TC, HDL and non-HDL cholesterol, glucose, and the liver function enzymes alanine aminotransferase (ALT, EC 2.6.1.2) and aspartate aminotransferase (AST, EC 2.6.1.1) in golden Syrian hamsters (Mesocricetus auratus (Waterhouse, 1839)) fed a hypercholesterolemic diet. Sedentary groups (S) and exercise groups (E) were fed a standard diet (SS and ES) or a cholesterol-enriched diet (standard plus 1% cholesterol, SC and EC). Resistance exercise was performed by jumps in the water, carrying a load strapped to the chest, representing 10 maximum repetitions (10 RM, 30 s rest, five days per week for five weeks). Mean blood sample comparisons were made by ANOVA + Tukey or ANOVA + Kruskal-Wallis tests (p < 0.05) to compare parametric and nonparametric samples, respectively. There were no differences in blood lipids between the standard diet groups (SS and ES) (p > 0.05). However, the EC group increased the glucose, non-HDL, and TC levels in comparison with the ES group. Moreover, the EC group increased the TG levels versus the SC group (p < 0.05). In addition, the ALT levels were increased only by diet treatment. These findings indicated that high-intensity resistance exercise contributed to dyslipidemia in hamsters fed a hypercholesterolemic diet, whereas liver function enzymes did not differ in regards to the exercise protocol. PMID:22494106

Frajacomo, Fernando Tadeu Trevisan; Demarzo, Marcelo Marcos Piva; Fernandes, Cleverson Rodrigues; Martinello, Flávia; Bachur, José Alexandre; Uyemura, Sérgio Akira; Perez, Sérgio Eduardo de Andrade; Garcia, Sérgio Britto

2012-06-01

110

Functional Characterization of Seven ?-Glutamylpolyamine Synthetase Genes and the bauRABCD Locus for Polyamine and ?-Alanine Utilization in Pseudomonas aeruginosa PAO1 ?  

PubMed Central

Pseudomonas aeruginosa and many other bacteria can utilize biogenic polyamines, including diaminopropane (DAP), putrescine (Put), cadaverine (Cad), and spermidine (Spd), as carbon and/or nitrogen sources. Transcriptome analysis in response to exogenous Put and Spd led to the identification of a list of genes encoding putative enzymes for the catabolism of polyamines. Among them, pauA1 to pauA6, pauB1 to pauB4, pauC, and pauD1 and pauD2 (polyamine utilization) encode enzymes homologous to Escherichia coli PuuABCD of the ?-glutamylation pathway in converting Put into GABA. A series of unmarked pauA mutants was constructed for growth phenotype analysis. The results revealed that it requires specific combinations of pauA knockouts to abolish utilization of different polyamines and support the importance of ?-glutamylation for polyamine catabolism in P. aeruginosa. Another finding was that the list of Spd-inducible genes overlaps almost completely with that of Put-inducible ones except the pauA3B2 operon and the bauABCD operon (?-alanine utilization). Mutation analysis led to the conclusion that pauA3B2 participate in catabolism of DAP, which is related to the aminopropyl moiety of Spd, and that bauABCD are essential for growth on ?-alanine derived from DAP (or Spd) catabolism via the ?-glutamylation pathway. Measurements of the pauA3-lacZ and bauA-lacZ expression indicated that these two promoters were differentially induced by Spd, DAP, and ?-alanine but showed no apparent response to Put, Cad, and GABA. Induction of the pauA3 and bauA promoters was abolished in the bauR mutant. The recombinant BauR protein was purified to demonstrate its interactions with the pauA3 and bauA regulatory regions in vitro. In summary, the present study support that the ?-glutamylation pathway for polyamine utilization is evolutionarily conserved in E. coli and Pseudomonas spp. and is further expanded in Pseudomonas to accommodate a more diverse metabolic capacity in this group of microorganisms.

Yao, Xiangyu; He, Weiqing; Lu, Chung-Dar

2011-01-01

111

Liver function in asymptomatic adult individuals with severe alpha1-antitrypsin deficiency (Pi Z).  

PubMed

Eleven adult individuals (aged 24 to 66 years) with severe alpha1-antitrypsin deficiency, Pi Z, and with no clinical signs of liver disease, were investigated with a broad spectrum of liver function tests. Except for low alpha1-antitrypsin levels, no evidence of abnormal hepatic protein synthesis was found. Neither could any biochemical signs of liver cell necrosis or increased liver cell regeneration be disclosed. In spite of the well-known pronounced distension of hepatic endoplasmic reticulum (E.R.) by aggregated asialo-alpha1-antitrypsin in this disease, the function of the E.R. tested with the aminopyrine breath test was not found to be impaired. PMID:303370

Larsson, C; Eriksson, S

1977-01-01

112

Toxicological evaluation of the effect of water contaminated with lead, phenol and benzene on liver, kidney and colon of Albino rats  

Microsoft Academic Search

The effect of water contaminated with phenol, benzene and lead on rats cellular system was investigated. Selected enzyme activity of the kidney and colon of rats was carried out. Standard enzyme assays were also conducted for selected liver enzymes such as alkaline and acid phosphatases, alanine and aspartate transaminases, and gamma glutamyl transpeptidase. Serum indices of liver and kidney function

O. Adeyemi; J. O. Ajayi; A. M. Olajuyin; O. B. Oloyede; A. T. Oladiji; O. M. Oluba; I. A. Ololade; E. A. Adebayo

2009-01-01

113

Liver Panel  

MedlinePLUS

... Hepatitis , Hemochromatosis , Wilson Disease , Cirrhosis Elsewhere On The Web American Liver Foundation MayoClinic.com: Liver function tests KidsHealth from Nemours: Hepatic [Liver] Function Panel National ...

114

Liver Function and Regeneration in Rats X Irradiated at Birth.  

National Technical Information Service (NTIS)

Radiation injury to the liver, an organ considered to be radioresistant, can be demonstrated by stimulating cell division through partial hepatectomy of hepatotoxic agents. The mitotic figures resulting from this induced cell proliferation are for the mos...

G. F. Leong R. L. Pessotti J. S. Krebs M. L. Albright

1967-01-01

115

Pivotal role of ADAMTS13 function in liver diseases  

Microsoft Academic Search

The liver is a major source of clotting and fibrinolytic proteins, and plays a central role in thrombo-regulation. Patients\\u000a with advanced liver diseases tend to bleed because of reduced plasma levels of several clotting factors and thrombocytopenia,\\u000a but they do also exhibit thrombotic complications. ADAMTS13 is a metalloproteinase, produced exclusively in hepatic stellate\\u000a cells, and specifically cleaves highly multimeric von

Masahito Uemura; Yoshihiro Fujimura; Saiho Ko; Masanori Matsumoto; Yoshiyuki Nakajima; Hiroshi Fukui

2010-01-01

116

Peptide-functionalized gold nanorods increase liver injury in hepatitis.  

PubMed

Targeted nanomedicine holds enormous potential for advanced diagnostics and therapy. Although it is known that nanoparticles accumulate in liver in vivo, the impact of cell-targeting particles on the liver, especially in disease conditions, is largely obscure. We had previously demonstrated that peptide-conjugated nanoparticles differentially impact macrophage activation in vitro. We thus comprehensively studied the distribution of gold nanorods (AuNR) in mice in vivo and assessed their hepatotoxicity and impact on systemic and hepatic immune cells in healthy animals and experimental liver disease models. Gold nanorods were stabilized with either cetyltrimethylammonium bromide or poly(ethylene glycol) and additional bioactive tripeptides RGD or GLF. Gold nanorods mostly accumulated in liver upon systemic injection in mice, as evidenced by inductively coupled plasma mass spectrometry from different organs and by non-invasive microcomputerized tomography whole-body imaging. In liver, AuNR were only found in macrophages by seedless deposition and electron microscopy. In healthy animals, AuNR did not cause significant hepatotoxicity as evidenced by biochemical and histological analyses, even at high AuNR doses. However, flow cytometry and gene expression studies revealed that AuNR polarized hepatic macrophages, even at low doses, dependent on the respective peptide sequence, toward M1 or M2 activation. While peptide-modified AuNR did not influence liver scarring, termed fibrosis, in chronic hepatic injury models, AuNR-induced preactivation of hepatic macrophages significantly exacerbated liver damage and disease activity in experimental immune-mediated hepatitis in mice. Bioactively targeted gold nanoparticles are thus potentially harmful in clinically relevant settings of liver injury, as they can aggravate hepatitis severity. PMID:22994679

Bartneck, Matthias; Ritz, Thomas; Keul, Heidrun A; Wambach, Mona; Bornemann, Jörg; Gbureck, Uwe; Ehling, Josef; Lammers, Twan; Heymann, Felix; Gassler, Nikolaus; Lüdde, Tom; Trautwein, Christian; Groll, Jürgen; Tacke, Frank

2012-10-23

117

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

NASA Astrophysics Data System (ADS)

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

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

2014-03-01

118

Morphology and function of cells of human embryonic liver in monolayer culture.  

PubMed

A system for culturing human fetal liver cells in monolayers is described and the effects of various conditions of growth on the morphology and function of the cultured cells are presented. The addition of 10% calf serum or 1% human serum to the growth medium accelerated the proliferation of the liver cells, with subsequent loss of characteristic morphology and specific functional activity. In the absence of serum, the cultured liver cells retained their morphology and their function for at least 4 wk, as evidenced by secretion of serum albumin and storage of glycogen and iron. PMID:4104969

Bissell, D M; Tilles, J G

1971-07-01

119

MORPHOLOGY AND FUNCTION OF CELLS OF HUMAN EMBRYONIC LIVER IN MONOLAYER CULTURE  

PubMed Central

A system for culturing human fetal liver cells in monolayers is described and the effects of various conditions of growth on the morphology and function of the cultured cells are presented. The addition of 10% calf serum or 1% human serum to the growth medium accelerated the proliferation of the liver cells, with subsequent loss of characteristic morphology and specific functional activity. In the absence of serum, the cultured liver cells retained their morphology and their function for at least 4 wk, as evidenced by secretion of serum albumin and storage of glycogen and iron.

Bissell, D. Montgomery; Tilles, Jeremiah G.

1971-01-01

120

Alteration of liver function due to H1N1 infection: a case report  

PubMed Central

H1N1 virus is known to affect the respiratory tract. The majority of healthcare providers focus on the respiratory complications attributed to H1N1 infection, overlooking possible multi-organ involvement. We present a rare case of abnormal liver function in a child who was admitted for respiratory illness due to the H1N1 virus. There was a marked elevation in liver function tests concurrent with the respiratory disease. Our patient was treated with oseltamavir for the H1N1 infection, and the liver function levels decreased dramatically in 72 hours.

Alhammadi, Ahmed H; Hendaus, Mohamed A; Kayoum, Anas A

2013-01-01

121

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

PubMed

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

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

2011-01-01

122

Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function  

PubMed Central

Background Interindividual differences in liver functions such as protein synthesis, lipid and carbohydrate metabolism and drug metabolism are influenced by epigenetic factors. The role of the epigenetic machinery in such processes has, however, been barely investigated. 5-hydroxymethylcytosine (5hmC) is a recently re-discovered epigenetic DNA modification that plays an important role in the control of gene expression. Results In this study, we investigate 5hmC occurrence and genomic distribution in 8 fetal and 7 adult human liver samples in relation to ontogeny and function. LC-MS analysis shows that in the adult liver samples 5hmC comprises up to 1% of the total cytosine content, whereas in all fetal livers it is below 0.125%. Immunohistostaining of liver sections with a polyclonal anti-5hmC antibody shows that 5hmC is detected in most of the hepatocytes. Genome-wide mapping of the distribution of 5hmC in human liver samples by next-generation sequencing shows significant differences between fetal and adult livers. In adult livers, 5hmC occupancy is overrepresented in genes involved in active catabolic and metabolic processes, whereas 5hmC elements which are found in genes exclusively in fetal livers and disappear in the adult state, are more specific to pathways for differentiation and development. Conclusions Our findings suggest that 5-hydroxymethylcytosine plays an important role in the development and function of the human liver and might be an important determinant for development of liver diseases as well as of the interindividual differences in drug metabolism and toxicity.

2013-01-01

123

Functional Relationships between Lipid Metabolism and Liver Regeneration.  

PubMed

The regenerative capacity of the liver is well known, and the mechanisms that regulate this process have been extensively studied using experimental model systems including surgical resection and hepatotoxin exposure. The response to primary mitogens has also been used to investigate the regulation of hepatocellular proliferation. Such analyses have identified many specific cytokines and growth factors, intracellular signaling events, and transcription factors that are regulated during and necessary for normal liver regeneration. Nevertheless, the nature and identities of the most proximal events that initiate hepatic regeneration as well as those distal signals that terminate this process remain unknown. Here, we review the data implicating acute alterations in lipid metabolism as important determinants of experimental liver regeneration and propose a novel metabolic model of regeneration based on these data. We also discuss the association between chronic hepatic steatosis and impaired regeneration in animal models and humans and consider important areas for future research. PMID:22319652

Rudnick, David A; Davidson, Nicholas O

2012-01-01

124

Functional Relationships between Lipid Metabolism and Liver Regeneration  

PubMed Central

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

Rudnick, David A.; Davidson, Nicholas O.

2012-01-01

125

Renal and liver functions and muscle injuries during training and after competition in Thai boxers  

PubMed Central

OBJECTIVE: To observe whether there are any injuries to muscle and deleterious effects on the liver and kidneys during training and after competition in Thai boxers. METHODS: Serum levels of intracellular enzymes and specific markers in the urine were measured during training and after fighting in Thai boxers. RESULTS: During the training period, the activities of muscle enzymes were significantly increased whereas those of the liver enzymes and creatinine clearance were not changed. After a match, on the other hand, both liver and muscle enzyme activities were elevated but renal function was decreased. CONCLUSIONS: The training protocol for Thai boxers has virtually no deleterious effect on liver and renal function, but damage to skeletal muscle cells may occur. However, competition may cause muscle injury without any obvious damage to the liver and kidneys. ???

Saengsirisuwan, V.; Phadungkij, S.; Pholpramool, C.

1998-01-01

126

Enhanced in vivo targeting of murine nonparenchymal liver cells with monophosphoryl lipid a functionalized microcapsules.  

PubMed

A broad spectrum of infectious liver diseases emphasizes the need of microparticles for targeted delivery of immunomodulatory substances to the liver. Microcapsules (MCs) are particularly attractive for innovative drug and vaccine formulations, enabling the combination of antigen, drugs, and adjuvants. The present study aimed to develop microcapsules characterized by an enhanced liver deposition and accelerated uptake by nonparenchymal liver cells (NPCs). Initially, two formulations of biodegradable microcapsules were synthesized from either hydroxyethyl starch (HES) or mannose. Notably, HES-MCs accumulated primarily in the liver, while mannose particles displayed a lung preference. Functionalization of HES-MCs with anti-CD40, anti-DEC205, and/or monophosphoryl lipid A (MPLA) enhanced uptake of MCs by nonparenchymal liver cells in vitro. In contrast, only MPLA-coated HES-MCs promoted significantly the in vivo uptake by NPCs. Finally, HES-MCs equipped with MPLA, anti-CD40, and anti-DEC205 induced the secretion of TNF-?, IL-6 by Kupffer cells (KCs), and IFN-? and IL-12p70 by liver dendritic cells (DCs). The enhanced uptake and activation of KCs by MPLA-HES-MCs is a promising approach to prevent or treat infection, since KCs are exploited as an entry gate in various infectious diseases, such as malaria. In parallel, loading and activating liver DCs, usually prone to tolerance, bears the potential to induce antigen specific, intrahepatic immune responses necessary to prevent and treat infections affecting the liver. PMID:24901387

Pietrzak-Nguyen, Anette; Fichter, Michael; Dedters, Marvin; Pretsch, Leah; Gregory, Stephen H; Meyer, Claudius; Doganci, Aysefa; Diken, Mustafa; Landfester, Katharina; Baier, Grit; Gehring, Stephan

2014-07-14

127

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

PubMed Central

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

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

2014-01-01

128

[The effect of chronic internal irradiation from incorporated radionuclides on liver function].  

PubMed

On chronic supply to the body of a mixture of nuclear division products lanthanum-140, barium-140, tellurium-132, neodymium-147, neptunium-239, zirconium-95, niobium-95, iodine-131, cerium-141, -144, cesium-134, -137, and ruthenium-103 are detectable in liver tissue within the first months. In the 2 to 4 years following the disaster, liver tissue primarily accumulates cerium-144, radium-226, thorium-228, -232, ruthenium-106, antimony-125, and europium-154. Within the first periods the liver radionuclide content was 19 to 31% higher than that in the blood, and in the following years it was 24 to 38% higher. The radionuclides indicated were actively excreted with the bile into the gastrointestinal lumen. Within the first months after the chronic internal radiation the functional liver disorders were detectable in 30 to 40% of the patients. Later on diverse acute and chronic diseases of the liver, gallbladder and pancreas were detectable in 20 to 30% of the patients. The radionuclide content in the body was found to be in parallel with functional liver disorders. Acceleration of radionuclide excretion from the body results in liver function improvement. PMID:2084889

Dedenko, I K; Zakharash, M P; Ganich, O N; Siksa?, L T; Shnitser, R I; Sofienko, G I; Bytsa?, N N; Zemskov, V S; Trunov, V I; Bukanov, V N

1990-01-01

129

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

SciTech Connect

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

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

2013-01-01

130

Vascularized and functional human liver from an iPSC-derived organ bud transplant.  

PubMed

A critical shortage of donor organs for treating end-stage organ failure highlights the urgent need for generating organs from human induced pluripotent stem cells (iPSCs). Despite many reports describing functional cell differentiation, no studies have succeeded in generating a three-dimensional vascularized organ such as liver. Here we show the generation of vascularized and functional human liver from human iPSCs by transplantation of liver buds created in vitro (iPSC-LBs). Specified hepatic cells (immature endodermal cells destined to track the hepatic cell fate) self-organized into three-dimensional iPSC-LBs by recapitulating organogenetic interactions between endothelial and mesenchymal cells. Immunostaining and gene-expression analyses revealed a resemblance between in vitro grown iPSC-LBs and in vivo liver buds. Human vasculatures in iPSC-LB transplants became functional by connecting to the host vessels within 48?hours. The formation of functional vasculatures stimulated the maturation of iPSC-LBs into tissue resembling the adult liver. Highly metabolic iPSC-derived tissue performed liver-specific functions such as protein production and human-specific drug metabolism without recipient liver replacement. Furthermore, mesenteric transplantation of iPSC-LBs rescued the drug-induced lethal liver failure model. To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells. Although efforts must ensue to translate these techniques to treatments for patients, this proof-of-concept demonstration of organ-bud transplantation provides a promising new approach to study regenerative medicine. PMID:23823721

Takebe, Takanori; Sekine, Keisuke; Enomura, Masahiro; Koike, Hiroyuki; Kimura, Masaki; Ogaeri, Takunori; Zhang, Ran-Ran; Ueno, Yasuharu; Zheng, Yun-Wen; Koike, Naoto; Aoyama, Shinsuke; Adachi, Yasuhisa; Taniguchi, Hideki

2013-07-25

131

Functions of c-Jun in Liver and Heart Development  

Microsoft Academic Search

Mice lacking the AP-1 transcription factor c-Jun die around embryonic day E13.0 but little is known about the cell types affected as well as the cause of embryonic lethality. Here we show that a fraction of mutant E13.0 fetal livers exhibits extensive apoptosis of both hematopoietic cells and hepatoblasts, whereas the expression of 15 mRNAs, including those of albumin, keratin

Robert Eferl; Maria Sibilia; Frank Hilberg; Andrea Fuchsbichler; Iris Kufferath; Barbara Guertl; Rainer Zenz; Erwin F. Wagner; Kurt Zatloukal

1999-01-01

132

The Association of Alanine Transaminase With Aging, Frailty, and Mortality  

PubMed Central

The relationships between blood tests of liver function and injury (alanine transaminase [ALT], gamma-glutamyl transferase, bilirubin, and albumin) with age, frailty, and survival were investigated in 1,673 community-dwelling men aged 70 years or older. ALT was lower in older participants. Those participants with ALT below the median at baseline had reduced survival (hazard ratio 2.10, 95% confidence interval [CI] 1.53–2.87) up to 4.9 years. Older age, frailty, low albumin, low body mass index, and alcohol abstinence also were associated with reduced survival, with age and frailty being the most powerful predictors. Low ALT was associated with frailty (odds ratio 3.54, 95% CI 2.45–5.11), and the relationship between ALT and survival disappeared once frailty and age were included in the survival analysis. Low ALT activity is a predictor of reduced survival; however, this seems to be mediated by its association with frailty and increasing age. ALT has potential value as a novel biomarker of aging.

Blyth, Fiona M.; Creasey, Helen M.; Handelsman, David J.; Naganathan, Vasi; Sambrook, Philip N.; Seibel, Markus J.; Waite, Louise M.; Cumming, Robert G.

2010-01-01

133

Choline's role in maintaining liver function: new evidence for epigenetic mechanisms  

PubMed Central

Purpose of review Humans eating diets low in choline develop fatty liver and liver damage. Rodents fed choline–methionine-deficient diets not only develop fatty liver, but also progress to develop fibrosis and hepatocarcinoma. This review focuses on the role of choline in liver function, with special emphasis on the epigenetic mechanisms of action. Recent findings Dietary intake of methyl donors like choline influences the methylation of DNA and histones, thereby altering the epigenetic regulation of gene expression. The liver is the major organ within which methylation reactions occur, and many of the hepatic genes involved in pathways for the development of fatty liver, hepatic fibrosis, and hepatocarcinomas are epigenetically regulated. Summary Dietary intake of choline varies over a three-fold range and many humans have genetic polymorphisms that increase their demand for choline. Choline is an important methyl donor needed for the generation of S-adenosylmethionine. Dietary choline intake is an important modifier of epigenetic marks on DNA and histones, and thereby modulates the gene expression in many of the pathways involved in liver function and dysfunction.

Mehedint, Mihai G.; Zeisel, Steven H.

2013-01-01

134

Attenuation of Kupffer Cell Function in Acute on Chronic Liver Injury Enhanced Engraftment of Transplanted Hepatocytes  

Microsoft Academic Search

Background  The present study was designed to elucidate the relationship of engraftment efficiency of transplanted cells and Kupffer cell\\u000a function in mice with acute on chronic liver injury and acute liver injury.\\u000a \\u000a \\u000a \\u000a Methods  The recipient dipeptidyl peptidase IV knockout (DPPIV–\\/–) mice were divided into two groups: (1) the acute on chronic liver injury group (CCl4\\/APAP group) that received CCl4 (1 ml\\/kg) twice

Ray-Hwang Yuan; Hui-Ling Chen; Huey-Ling Chen; Ming-Kung Hsu; Po-Huang Lee; Mei-Hwei Chang

2007-01-01

135

Thyroid function tests in chronic liver disease: evidence for multiple abnormalities despite clinical euthyroidism  

Microsoft Academic Search

To further evaluate thyroid function in patients with liver disease, we have measured total and free T3 and T4, thyroxine binding globulin, basal and thyrotropin releasing hormone-stimulated thyrotropin and thyroglobulin antibodies in 33 patients with liver cirrhosis, in 22 with chronic hepatitis and in 30 healthy controls. All the patients but one were clinically euthyroid. T3, FT3, T3\\/thyroxine binding globulin

M Borzio; R Caldara; F Borzio; V Piepoli; P Rampini; C Ferrari

1983-01-01

136

Hepatic function testing can assist in treatment planning for liver cancer patients  

Cancer.gov

Monitoring the hepatic function of unresectable liver cancer patients, measured by 99mTc-labeled iminodiacetic acid (HIDA) via single-photon emission computed tomography (SPECT) prior to and during radiation therapy, provides vital information that could guide more customized treatment plans and reduce risks of liver injury, according to University of Michigan research being presented at the 2013 Cancer Imaging and Radiation Therapy Symposium. The University of Michigan is home to the University of Michigan Comprehensive Cancer Center.

137

Glycyrrhetinic acid-functionalized degradable micelles as liver-targeted drug carrier  

Microsoft Academic Search

Recently, many efforts have been devoted to investigating the application of functionalized micelles as targeted drug delivery\\u000a carriers. In this study, glycyrrhetinic acid (GA, a liver targeting ligand) modified poly(ethylene glycol)-b-poly(?-benzyl l-glutamate) micelles were prepared and evaluated as a potential liver-targeted drug carrier. The aggregation behavior, stability,\\u000a size and morphology of the micelles were investigated. Anticancer drug doxorubicin (DOX) was

Wei Huang; Wei Wang; Ping Wang; Chuang-Nian Zhang; Qin Tian; Yue Zhang; Xiu-Hua Wang; Rui-Tao Cha; Chun-Hong Wang; Zhi Yuan

2011-01-01

138

Liver functional reserve estimation: state of the art and relevance for local treatments  

Microsoft Academic Search

More than 90% of cases of hepatocellular carcinoma (HCC) develop as a consequence of underlying liver disease (most commonly\\u000a viral hepatitis), often resulting in impaired liver function. In such cases, transplantation is an appealing alternative as\\u000a it can potentially cure both the malignancy and the underlying disease. When transplant is not readily available due to organ\\u000a scarcity, borderline cases must

Fotini Manizate; Spiros P. Hiotis; Daniel Labow; Sasan Roayaie; Myron Schwartz

2010-01-01

139

PedsQL(TM) Cognitive Functioning Scale in Pediatric Liver Transplant Recipients: Feasibility, Reliability and Validity  

PubMed Central

Objective The PedsQL™ (Pediatric Quality of Life Inventory™) is a modular instrument designed to measure health-related quality of life and disease-specific symptoms. The PedsQL™ Cognitive Functioning Scale was developed as a brief generic symptom-specific instrument to measure cognitive functioning. The objective of the present study was to determine the feasibility, reliability, and validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients. Methods The 6-item PedsQL™ Cognitive Functioning Scale and the PedsQL™ 4.0 Generic Core Scales were completed by pediatric liver transplant recipients ages 8–18 years (n = 215) and parents of pediatric liver transplant recipients ages 2–18 years (n = 502). Both patient self-report and parent proxy-report were available for 212 cases. The 72-item Behavior Rating Inventory of Executive Function (BRIEF), a widely validated measure of executive functioning, was completed by 100 parents and 56 teachers on a subset of patients. Results The PedsQL™ Cognitive Functioning Scale demonstrated minimal missing responses (0.0%, child report, 0.67%, parent report), achieved excellent reliability (? = 0.88 child report, 0.94 parent report), distinguished between pediatric patients with liver transplants and healthy children supporting discriminant validity, and was significantly correlated with the PedsQL™ 4.0 Generic Core Scales and the BRIEF supporting construct and concurrent validity, respectively. Pediatric liver transplants recipients experienced cognitive functioning comparable to long-term pediatric cancer survivors. Conclusions The results demonstrate the feasibility, reliability, discriminant, construct and concurrent validity of the PedsQL™ Cognitive Functioning Scale in pediatric liver transplant recipients.

Varni, James W.; Limbers, Christine A.; Sorensen, Lisa G.; Neighbors, Katie; Martz, Karen; Bucuvalas, John C.; Alonso, Estella M.

2013-01-01

140

Modulating influence of cytochrome P-450 MspI polymorphism on serum liver function profiles in coke oven workers  

PubMed Central

OBJECTIVES: It was reported previously that topside oven workers with heavy exposure to coke oven emissions had increased serum activities of hepatic aminotransferase in one coke oven plant. This study was conducted to investigate the modifying effect of CYP1A1 MspI polymorphism on liver function profiles in coke oven workers. METHODS: 88 coke oven workers from a large steel company in Taiwan were studied in 1995-6. Exposure was categorised by work area: topside oven workers and sideoven workers. Liver function profiles including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), r-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (BIL) were examined in the morning after personal exposure measurements. The MspI polymorphism was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: Five of 23 (22%) topside oven workers and seven of 65 (11%) sideoven workers had the CYP1A1 MspI homozygous variant genotype. With sideoven workers with the combined wild type and heterozygous variant as the reference group in multiple regression models, it was found that topside oven workers with the combined traits had mean AST and ALT activities that were 21% and 46% higher (95% confidence interval (95% CI) 4% to 42% and 12% to 91%, respectively) than the reference group after adjusting for appropriate confounders. Also, topside oven workers with the homozygous variant trait had mean AST, ALT, and GGT activities that were 59%, 68%, and 157% higher (95% CI 21% to 109%, 6% to 168%, and 39% to 374%, respectively) than the reference group. The prevalence of an abnormal hepatocellular pattern (AST > 37 IU/l or ALT > 39 IU/l) was more common in the topside oven workers with the homozygous variant than in the sideoven workers with the other combined genotypes (adjusted odds ratio 9.9, 95% CI 1.2 to 82.3) after adjusting for appropriate confounders. CONCLUSIONS: The CYP1A1 MspI polymorphism may modify the biotransformation of coke oven emissions, which results in hepatocellular damage in coke oven workers.  

Wu, M. T.; Ho, C. K.; Huang, S. L.; Yeh, Y. F.; Liu, C. L.; Mao, I. F.; Christiani, D. C.

1999-01-01

141

Genistein Modifies Liver Fibrosis and Improves Liver Function by Inducing uPA Expression and Proteolytic Activity in CCl4Treated Rats  

Microsoft Academic Search

Aim: To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats. Methods: 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)

Alfonso Leija Salas; Tania Díaz Montezuma; German Garrido Fariña; Jorge Reyes-Esparza; Lourdes Rodríguez-Fragoso

2008-01-01

142

Functional characterization of peripheral circulating and liver recruited neutrophils in endotoxic rats  

Microsoft Academic Search

Neutrophil accumulation in tissues is a hallmark of inflammation and is associated with a variety of pathological conditions. In bacterial infection neu- trophils are selectively attracted in large numbers to phagocytose and kill invading microorganisms. However, activated neutrophibs can also cause injury to tissues. To investigate functional alterations in liver recruited neu- trophibs (PMNs), we studied the functional characteris- tics

J. A. Spitzer; P. Zhang; A. M. S. Mayer

1994-01-01

143

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

PubMed

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

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

2014-05-14

144

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

PubMed Central

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

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

2014-01-01

145

Manipulation of nitric oxide in an animal model of acute liver injury. The impact on liver and intestinal function  

Microsoft Academic Search

Background: Nitric oxide may have a protective effect on the liver during endotoxemia and chronic inflammation. There is evidence that it maintains liver and intestinal tissue integrity during inflammatory processes. We evaluated the impact of altering nitric oxide release on acute liver injury, the associated gut injury and bacterial translocation, at different time intervals. Methods: An acute rat liver injury

Diya Adawi; F Behzad Kasravi; Göran Molin

146

Prediction of liver disease in patients whose liver function tests have been checked in primary care: model development and validation using population-based observational cohorts  

PubMed Central

Objective To derive and validate a clinical prediction model to estimate the risk of liver disease diagnosis following liver function tests (LFTs) and to convert the model to a simplified scoring tool for use in primary care. Design Population-based observational cohort study of patients in Tayside Scotland identified as having their LFTs performed in primary care and followed for 2?years. Biochemistry data were linked to secondary care, prescriptions and mortality data to ascertain baseline characteristics of the derivation cohort. A separate validation cohort was obtained from 19 general practices across the rest of Scotland to externally validate the final model. Setting Primary care, Tayside, Scotland. Participants Derivation cohort: LFT results from 310?511 patients. After exclusions (including: patients under 16?years, patients having initial LFTs measured in secondary care, bilirubin >35??mol/L, liver complications within 6?weeks and history of a liver condition), the derivation cohort contained 95?977 patients with no clinically apparent liver condition. Validation cohort: after exclusions, this cohort contained 11?653 patients. Primary and secondary outcome measures Diagnosis of a liver condition within 2?years. Results From the derivation cohort (n=95?977), 481 (0.5%) were diagnosed with a liver disease. The model showed good discrimination (C-statistic=0.78). Given the low prevalence of liver disease, the negative predictive values were high. Positive predictive values were low but rose to 20–30% for high-risk patients. Conclusions This study successfully developed and validated a clinical prediction model and subsequent scoring tool, the Algorithm for Liver Function Investigations (ALFI), which can predict liver disease risk in patients with no clinically obvious liver disease who had their initial LFTs taken in primary care. ALFI can help general practitioners focus referral on a small subset of patients with higher predicted risk while continuing to address modifiable liver disease risk factors in those at lower risk.

McLernon, David J; Donnan, Peter T; Sullivan, Frank M; Roderick, Paul; Rosenberg, William M; Ryder, Steve D; Dillon, John F

2014-01-01

147

Kinetics of lymphocyte subpopulations and their functions in cases of amoebic liver abscess.  

PubMed

This study shows the relationship between lymphocyte subpopulations and their response to non-specific stimulant phytohaemagglutinin (PHA) and specific stimulant (amoebic antigen) in cases of amoebic liver abscess in relation to the duration of disease, based on the first appearance of symptoms and/or signs, 26 patients with amoebic liver abscess and 20 normal, healthy controls were studied. Five of the patients gave a history of alcohol intake for the last 10 to 15 years. Eight had a solitary abscess and five had multiple abscesses, as seen on liver scan. No change in the B cell count was noticed in any of the patients. Depression of the T cell number and function was noticed from two weeks onwards. A history of alcohol intake made no difference. Cases with multiple liver abscesses were more immunologically depressed than were those with a solitary abscess. PMID:6977210

Ganguly, N K; Mahajan, R C; Gill, N J; Koshy, A

1981-01-01

148

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

PubMed

The effects of a hydroalcoholic extract of Agaricus brasiliensis (A. blazei) on functional parameters in the perfused rat liver were examined with emphasis on its content of nucleotides and nucleosides. Several nucleosides and nucleotides were identified in the A. brasiliensis extract, which was active on several liver functions. A significant part of the effects is the result of the purinergic action of nucleosides and nucleotides: pressure increment, glycogenolysis stimulation, transient inhibition of oxygen consumption, and redox state changes. Other phenomena such as the stimulation of gluconeogenesis, ureogenesis, and oxygen consumption are more likely consequences of the metabolic transformation of substrates contained within the extract, especially amino acids. It seems apparent that consumption of A. brasiliensis represents not only the ingestion of metabolic precursors but also the ingestion of substances that, even at low concentrations, can exert important signaling functions in the liver as well as in the organism as a whole. PMID:20507067

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

2010-06-23

149

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

PubMed Central

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

Donnan, Peter T; McLernon, David; Steinke, Douglas; Ryder, Stephen; Roderick, Paul; Sullivan, Frank M; Rosenberg, William; Dillon, John F

2007-01-01

150

Maintenance of Human Hepatocyte Function In Vitro by Liver-Derived Extracellular Matrix Gels  

PubMed Central

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

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

2010-01-01

151

Characterization of the Regulation and Function of Zinc-Dependent Histone Deacetylases During Mouse Liver Regeneration  

PubMed Central

The studies reported here were undertaken to define the regulation and functional importance of zinc-dependent histone deacetylase (Zn-HDAC) activity during liver regeneration using the mouse partial hepatectomy (PH) model. The results showed that hepatic HDAC activity was significantly increased in nuclear and cytoplasmic fractions following PH. Further analyses showed isoform-specific effects of PH on HDAC mRNA and protein expression, with increased expression of the class I HDACs, 1 and 8, and class II HDAC4 in regenerating liver. Hepatic expression of (class II) HDAC5 was unchanged after PH; however HDAC5 exhibited transient nuclear accumulation in regenerating liver. These changes in hepatic HDAC expression, subcellular localization, and activity coincided with diminished histone acetylation in regenerating liver. The significance of these events was investigated by determining the effects of suberoylanilide hydroxyamic acid (SAHA, a specific inhibitor of Zn-HDAC activity) on hepatic regeneration. The results showed that SAHA-treatment suppressed the effects of PH on histone deacetylation and hepatocellular BrdU incorporation. Further examination showed that SAHA blunted hepatic expression and activation of cell cycle signals downstream of induction of cyclin D1 expression in mice subjected to PH. Conclusion The data reported here demonstrate isoform-specific regulation of Zn-HDAC expression, subcellular localization, and activity in regenerating liver. These studies also indicate that HDAC activity promotes liver regeneration by regulating hepatocellular cell cycle progression at a step downstream of cyclin D1 induction.

Huang, Jiansheng; Barr, Emily; Rudnick, David A.

2013-01-01

152

Characterization of the regulation and function of zinc-dependent histone deacetylases during rodent liver regeneration.  

PubMed

The studies reported here were undertaken to define the regulation and functional importance of zinc-dependent histone deacetylase (Zn-HDAC) activity during liver regeneration using the mouse partial hepatectomy (PH) model. The results showed that hepatic HDAC activity was significantly increased in nuclear and cytoplasmic fractions following PH. Further analyses showed isoform-specific effects of PH on HDAC messenger RNA (mRNA) and protein expression, with increased expression of the class I HDACs, 1 and 8, and class II HDAC4 in regenerating liver. Hepatic expression of (class II) HDAC5 was unchanged after PH; however, HDAC5 exhibited transient nuclear accumulation in regenerating liver. These changes in hepatic HDAC expression, subcellular localization, and activity coincided with diminished histone acetylation in regenerating liver. The significance of these events was investigated by determining the effects of suberoylanilide hydroxyamic acid (SAHA, a specific inhibitor of Zn-HDAC activity) on hepatic regeneration. The results showed that SAHA treatment suppressed the effects of PH on histone deacetylation and hepatocellular bromodeoxyuridine (BrdU) incorporation. Further examination showed that SAHA blunted hepatic expression and activation of cell cycle signals downstream of induction of cyclin D1 expression in mice subjected to PH. Conclusion: The data reported here demonstrate isoform-specific regulation of Zn-HDAC expression, subcellular localization, and activity in regenerating liver. These studies also indicate that HDAC activity promotes liver regeneration by regulating hepatocellular cell cycle progression at a step downstream of cyclin D1 induction. PMID:23258575

Huang, Jiansheng; Barr, Emily; Rudnick, David A

2013-05-01

153

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

PubMed Central

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

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

2012-01-01

154

Vibrational dynamics of crystalline L-alanine  

SciTech Connect

The authors report a new, complete vibrational analysis of L-alanine and L-alanine-d{sub 4} which utilizes IINS intensities in addition to frequency information. The use of both isotopomers resulted in a self-consistent force field for and assignment of the molecular vibrations in L-alanine. Some details of the calculation as well as a comparison of calculated and observed IINS spectra are presented. The study clarifies a number of important issues on the vibrational dynamics of this molecule and presents a self-consistent force field for the molecular vibrations in crystalline L-alanine.

Bordallo, H.N.; Eckert, J. [Los Alamos National Lab., NM (United States); Barthes, M. [Univ. Montpellier II (France)

1997-11-01

155

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

SciTech Connect

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

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

2012-09-28

156

Changes in Liver Function correlate with the Improvement of Lipid Profile after Restoration of Euthyroidism in Patients with Subclinical Hypothyroidism  

Microsoft Academic Search

Overt hypothyroidism frequently leads to liver dysfunction. Subclinical hypothyroidism (SCH) is linked to abnormalities of lipoprotein metabolism, however, data on liver function are lacking. We analyzed the effects of L-thyroxine (L-T4) therapy on liver function and their association with changes of serum lipoproteins in SCH as part of a prospective, double-blind study. 66 women with SCH were randomly assigned to

Mirjam Christ-Crain; Christian Meier; Jardena Puder; Jean-Jacques Staub; Peter R. Huber; Ulrich Keller; Beat Müller

157

Specific, functional effector\\/memory CD8 + T cells are found in the liver post-vaccination  

Microsoft Academic Search

Background: The liver efficiently eliminates activated CD8+ T blasts. It is unknown if vaccine-primed CD8+ T blasts migrate to and establish functional CD8+ T cell immunity in the liver post-immunization.Aims: We tested, if functional CD8+ T cell populations can be detected in the liver post-vaccination.Methods: Murine CD8+ T cells with different epitope\\/restriction specificities were primed by intramuscular injection of protein-

Nektarios Dikopoulos; Ieva Jomantaite; Reinhold Schirmbeck; Jörg Reimann

2003-01-01

158

Exposure to mixtures of solvents among paint workers and biochemical alterations of liver function  

Microsoft Academic Search

The objective of this study was to determine biochemical alterations of liver function among paint manufacturers and sprayers associated with exposure to organic solvents. Two paint manufacturing factories and 22 various kinds of spray painting factories (16 car painting, two aircraft painting, three video terminal painting; and one trailer painting) were included. Air concentrations of organic solvents were collected by

J D Chen; J D Wang; J P Jang; Y Y Chen

1991-01-01

159

Graves' disease, celiac disease and liver function abnormalities in a patient - clinical manifestation and diagnostic difficulties.  

PubMed

Autoimmune diseases due to probable common pathogenesis tend to coexist in some patients. Complex clinical presentation with diverse timing of particular symptoms and sophisticated treatment with numerous side effects, may cause diagnostic difficulties, especially in children. The paper presents diagnostic difficulties and pitfalls in a child with Graves' disease, celiac disease and liver function abnormalities. PMID:24904927

Góra-G?bka, Magdalena; Wo?niak, Ma?gorzata; Cielecka-Kuszyk, Joanna; Korpal-Szczyrska, Maria; Sznurkowska, Katarzyna; Zagierski, Maciej; Jankowska, Irena; Plata-Nazar, Katarzyna; Kami?ska, Barbara; Liberek, Anna

2014-01-01

160

Non-invasive assessment of choledocholithiasis in patients with gallstones and abnormal liver function  

PubMed Central

AIM: To find a non-invasive strategy for detecting choledocholithiasis before cholecystectomy, with an acceptable negative rate of endoscopic retrograde cholangiopancreatography. METHODS: All patients with symptomatic gallstones were included in the study. Patients with abnormal liver functions and common bile duct abnormalities on ultrasound were referred for endoscopic retrograde cholangiopancreatography. Patients with normal ultrasound were referred to magnetic resonance cholangiopancreatography. All those who had a negative magnetic resonance or endoscopic retrograde cholangiopancreatography underwent laparoscopic cholecystectomy with intraoperative cholangiography. RESULTS: Seventy-eight point five percent of patients had laparoscopic cholecystectomy directly with no further investigations. Twenty-one point five percent had abnormal liver function tests, of which 52.8% had normal ultrasound results. This strategy avoided unnecessary magnetic resonance cholangiopancreatography in 47.2% of patients with abnormal liver function tests with a negative endoscopic retrograde cholangiopancreatography rate of 10%. It also avoided un-necessary endoscopic retrograde cholangiopancreatography in 35.2% of patients with abnormal liver function. CONCLUSION: This strategy reduces the cost of the routine use of magnetic resonance cholangiopancreatography, in the diagnosis and treatment of common bile duct stones before laparoscopic cholecystectomy.

Al-Jiffry, Bilal O; Elfateh, Abdeen; Chundrigar, Tariq; Othman, Bassem; AlMalki, Owaid; Rayza, Fares; Niyaz, Hashem; Elmakhzangy, Hesham; Hatem, Mohammed

2013-01-01

161

Relationship Between Some Serum Enzyme Activities, Liver Functions and Body Weight in Growing Local Chickens  

Microsoft Academic Search

2 Abstract: An experiment was conducted to detect the relationship between some serum enzyme activities, i.e. lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) enzymes and liver functions, as well as evaluating the difference in some physiological parameters in relation to body weight in six body weight lines of Golden Montazah (GM) chickens. A total of 288 GM chickens 4-wk old

S. F. Hassaan; S. A. Abdel-Fattah; A. E. Elsalmoney; M. S. H. Hassan

2009-01-01

162

Chronic pancreatitis prevalence in liver cirrhosis. Morphological and functional study.  

PubMed

Ductal pancreatic changes and functional exocrine assessment have been studied, in a group of 60 cirrhotic patients. In these patients the aetiology of cirrhosis was alcoholism in 35, hepatitis B virus-hepatitis C virus infection in 19, primary biliary cirrhosis in 2 and not determinable in 4. Eighteen patients (30%) showed an endoscopic retrograde pancreatography picture consistent with chronic pancreatitis (14 mild, 2 moderate and 2 severe). Mild pancreatographic changes were present in 7 alcoholic (20%) and in 7 non-alcoholic cirrhosis patients (28%). Moderate and severe abnormalities were present only in alcoholic cirrhosis (4 patients, 11.4%). No correlation was found between presence or pancreatopathy degree and Child-Pugh score or cirrhosis duration. Functional exocrine tests were abnormal only in severe endoscopic retrograde pancreatography picture. Mild type ductal lesions can mimic either age-dependent changes or chronic pancreatitis. The absence of impaired functional tests makes it impossible to discriminate between these two possibilities. These findings emphasize that in our cirrhotic group the prevalence of chronic pancreatitis (with a moderate or severe endoscopic retrograde pancreatography picture) is low (6.6%) and alcoholism is always present. Possibly, cirrhosis with secretion of high-volume low protein concentration juice confers a protective effect on the pancreas. PMID:8782001

Caradonna, P; Costamagna, G; Benedetti, G; Gentiloni, N; Gasbarrini, G B

1996-01-01

163

Probing alanine transaminase catalysis with hyperpolarized 13CD3-pyruvate  

NASA Astrophysics Data System (ADS)

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

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

2013-03-01

164

The Utility of Liver Function Tests for Mortality Prediction within One Year in Primary Care Using the Algorithm for Liver Function Investigations (ALFI)  

PubMed Central

Background Although liver function tests (LFTs) are routinely measured in primary care, raised levels in patients with no obvious liver disease may trigger a range of subsequent expensive and unnecessary management plans. The aim of this study was to develop and validate a prediction model to guide decision-making by general practitioners, which estimates risk of one year all-cause mortality in patients with no obvious liver disease. Methods In this population-based historical cohort study, biochemistry data from patients in Tayside, Scotland, with LFTs performed in primary care were record-linked to secondary care and prescription databases to ascertain baseline characteristics, and to mortality data. Using this derivation cohort a survival model was developed to predict mortality. The model was assessed for calibration, discrimination (using the C-statistic) and performance, and validated using a separate cohort of Scottish primary care practices. Results From the derivation cohort (n?=?95 977), 2.7% died within one year. Predictors of mortality included: age; male gender; social deprivation; history of cancer, renal disease, stroke, ischaemic heart disease or respiratory disease; statin use; and LFTs (albumin, transaminase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase). The C-statistic for the final model was 0.82 (95% CI 0.80–0.84), and was similar in the validation cohort (n?=?11 653) 0.86 (0.79–0.90). As an example of performance, for a 10% predicted probability cut-off, sensitivity?=?52.8%, specificity?=?94.0%, PPV?=?21.0%, NPV?=?98.5%. For the model without LFTs the respective values were 43.8%, 92.8%, 15.6%, 98.1%. Conclusions The Algorithm for Liver Function Investigations (ALFI) is the first model to successfully estimate the probability of all-cause mortality in patients with no apparent liver disease having LFTs in primary care. While LFTs added to the model's discrimination and sensitivity, the clinical utility of ALFI remains to be established since LFTs did not improve an already high NPV for short term mortality and only modestly improved a very low PPV.

McLernon, David J.; Dillon, John F.; Sullivan, Frank M.; Roderick, Paul; Rosenberg, William M.; Ryder, Stephen D.; Donnan, Peter T.

2012-01-01

165

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

PubMed Central

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

Camps, Jordi; Marsillach, Judit; Joven, Jorge

2009-01-01

166

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

PubMed

Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxidized cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes. PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels have been reported in a variety of diseases involving oxidative stress including chronic liver diseases. Measurement of serum PON1 activity has been proposed as a potential test for the evaluation of liver function. However, this measurement is still restricted to research and has not been extensively applied in routine clinical chemistry laboratories. The reason for this restriction is due to the problem that the substrate commonly used for PON1 measurement, paraoxon, is toxic and unstable. The recent development of new assays with non-toxic substrates makes this proposal closer to a practical development. The present editorial summarizes PON1 biochemistry and function, its involvement with chronic liver impairment, and some aspects related to the measurement of PON1 activity in circulation. PMID:19399923

Camps, Jordi; Marsillach, Judit; Joven, Jorge

2009-04-28

167

Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases  

PubMed Central

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

Abdelmegeed, Mohamed A.; Song, Byoung-Joon

2014-01-01

168

Indocyanine green clearance in evaluating the recovery of liver reserve function after superselective transarterial chemoembolization.  

PubMed

Transarterial chemoembolization (TACE) may ravage normal liver tissues apart from the neoplastic nodules which offset the anti-tumor effect. This study aimed to evaluate the recovery of liver reserve function (LRF) after TACE by indocyanine green (ICG) clearance test and other routine liver function tests. Forty-six newly diagnosed HCC patients who had undergone TACE as the initial treatment from January 2011 to January 2012 were enrolled in this study. The effects of age, basic ICG clearance rate and interval time between two assessments on the recovery of LRF were analyzed. We found that ICG retention rate at the 15 minutes (ICGR15) was significantly increased after TACE (12.3+/-8.1% vs 16.8+/-12.1%, P<0.01) in all the 46 patients. In particular, the ICGR15 value was increased in older patients (age>55 years, 20.3+/-12.5% vs 13.7+/-7.2%, P<0.01). The interval of ICG test also affected the ICGR15 value (?47 days, 17.8+/-11.4% after vs 12.1+/-7.1% before TACE, P<0.01). Our data suggested that TACE decreased LRF, especially in older patients. ICG test was more sensitive to evaluate the recovery of LRF after TACE than the Child-Pugh grade and routine liver function tests. PMID:24322753

Chen, Xin; Zhang, Hai-Bing; Li, Zhong-Qi; Yu, Xiong-Fei; Yang, Mei-Fang; Wang, Hao-Hao; Teng, Li-Song

2013-12-01

169

Importance of intrahepatic mechanisms to gluconeogenesis from alanine during exercise and recovery  

SciTech Connect

These studies were performed to assess the importance of intrahepatic mechanisms to gluconeogenesis in the dog during 150 min of treadmill exercise and 90 min of recovery. Sampling catheters were implanted in an artery and portal and hepatic veins 16 days before experimentation. Infusions of (U-/sup 14/C)alanine, (3-/sup 3/H)glucose, and indocyanine green were used to assess gluconeogenesis. During exercise, a decline in arterial and portal vein plasma alanine and in hepatic blood flow led to a decrease in hepatic alanine delivery. During recovery, hepatic blood flow was restored to basal, causing an increase in hepatic alanine delivery beyond exercise rates but still below resting rates. Hepatic fractional alanine extraction increased from 0.26 +/- 0.02 at rest to 0.64 +/- 0.03 during exercise and remained elevated during recovery. Net hepatic alanine uptake was 2.5 +/- 0.2 mumol.kg-1.min-1 at rest and remained unchanged during exercise but was increased during recovery. The conversion rate of (/sup 14/C)alanine to glucose had increased by 248 +/- 38% by 150 min of exercise and had increased further during recovery. The efficiency with which alanine was channeled into glucose in the liver was accelerated to a rate of 338 +/- 55% above basal by 150 min of exercise but declined slightly during recovery. In conclusion, 1) gluconeogenesis from alanine is accelerated during exercise, due to an increase in the hepatic fractional extraction of the amino acid and through intrahepatic mechanisms that more efficiently channel it into glucose.

Wasserman, D.H.; Williams, P.E.; Lacy, D.B.; Green, D.R.; Cherrington, A.D.

1988-04-01

170

CT evaluations of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis: relationship between imaging appearance and baseline liver function  

PubMed Central

This study aimed to assess the imaging appearances of focal liver reactions following stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) and to examine relationships between imaging appearance and baseline liver function. We retrospectively studied 50 lesions in 47 patients treated with SBRT (30–40 Gy in 5 fractions) for HCC, who were followed up for more than 6 months. After SBRT, all patients underwent regular follow-ups with blood tests and dynamic CT scans. At a median follow-up of 18.1 months (range 6.2–43.7 months), all lesions but one were controlled. 3 density patterns describing focal normal liver reactions around HCC tumours were identified in pre-contrast, arterial and portal-venous phase scans: iso/iso/iso in 4 patients (Type A), low/iso/iso in 8 patients (Type B) and low/iso (or high)/high in 38 patients (Type C). Imaging changes in the normal liver surrounding the treated HCC began at a median of 3 months after SBRT, peaked at a median of 6 months and disappeared 9 months later. Liver function, as assessed by the Child–Pugh classification, was the only factor that differed significantly between reactions to treatment showing “non-enhanced” (Type A and B) and “enhanced” (Type C) appearances in CT. Hence, liver tissue with preserved function is more likely to be well enhanced in the delayed phase of a dynamic contrast-enhanced CT scan. The CT appearances of normal liver seen in reaction to the treatment of an HCC by SBRT were therefore related to background liver function and should not be misread as recurrence of HCC.

Sanuki-Fujimoto, N; Takeda, A; Ohashi, T; Kunieda, E; Iwabuchi, S; Takatsuka, K; Koike, N; Shigematsu, N

2010-01-01

171

Depressed function of Kupffer cells in rats with CCl4-induced liver cirrhosis.  

PubMed

In the present study, the Kupffer cell function of rats with CCl4-induced liver cirrhosis was tested by analyzing the changes in the host defense system. In rats without liver cirrhosis injected with CCl4 for 3 weeks concomitant with the high opsonic activity the endocytic index was significantly increased. Rats treated for 9 and 13 weeks developed cirrhosis, and their endocytic indices were not increased despite the rise in their opsonic activity. Particularly, the endocytic index of 13-week-treated rats with advanced liver cirrhosis was significantly lower than that of the other groups. The organic distribution of 51Cr-endotoxin injected intravenously exhibited characteristic changes in 9-week- and 13-week-treated rats: decreased hepatic uptake and increased splenic uptake. In contrast, pulmonary uptake was increased in all CCl4-treated rats. The superoxide production by Kupffer cells from 13-week-treated rats was greatly reduced, accompanied by the decreased superoxide dismutase activity of liver homogenate. Thus, results of this study suggest that Kupffer cell dysfunction is one of the main factors affecting host defenses in liver cirrhosis. PMID:2164243

Arii, S; Monden, K; Itai, S; Sasaoki, T; Adachi, Y; Funaki, N; Higashitsuji, H; Tobe, T

1990-01-01

172

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

PubMed

Background: Patients with chronic liver disease (CLD) have been reported to have sexual dysfunction irrespective of etiology. There is little or no report from Nigeria on this disorder. This study looked at sexual dysfunction among male patients with CLD. Materials and Methods: Patients with chronic viral hepatitis B, liver cirrhosis (LC) and hepatocellular carcinoma (HCC) were interviewed using the international index of erectile function questionnaire. Their responses were compared with an age and sex matched healthy controls. Bio-data and body mass index were obtained for both groups and liver disease severity was graded for patients using the Child-Pugh score. Analysis was done using SPSS (SPSS Inc., Chicago, IL, USA, 2004) for frequencies and means while comparison of means was done using Student's t-test. Significance level was put at P < 0.05. Results: There were 120 subjects consisting of 60 patients aged from 28 to 71 years; mean (SD) 45. 3 ± 9.4 and 60 controls aged from 29 to 79 years with mean (SD) 45.5 ± 10.1 years. Sexual dysfunctions were seen in patients with HCC and LC in the domains of sexual desire and sexual satisfaction respectively when compared with controls. When patients were divided into the various liver disease severities, patients in Child-Pugh Grade B scored low in the domain of arousal, whereas the domains of erectile functions, orgasm, resolution and satisfaction were affected in patients in Grade C when compared with controls. Conclusions: Male patients with CLD have significant sexual dysfunctions when compared with controls. The dysfunctions are more pronounced in those with Grade C liver disease. Sexual concerns of CLD should be inquired of in those with advanced liver disease. PMID:24705113

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

2014-01-01

173

Domino versus deceased donor liver transplantation: association with early graft function and perioperative bleeding.  

PubMed

This study sought to evaluate the potential impact of domino liver transplantation (DLT) on initial graft function and early postoperative outcome in patients with cirrhosis in a Portuguese liver transplantation center. A retrospective comparative analysis was performed between 77 domino recipients (from familial amyloidotic polyneuropathy donors) and 91 deceased donor recipients, all submitted to primary elective whole liver transplantation, using the piggyback technique, in a 42-month period. Outcome parameters included graft dysfunction (defined as either primary nonfunction or initial poor function, according to the Ploeg-Maring criteria) and Clavien II-IV complications in the first postoperative week. Domino and deceased donor recipients had similar preoperative severity indices (Child-Pugh classification and Model for End-Stage Liver Disease score) and immediate postoperative severity scores (APACHE II [Acute Physiology and Chronic Health Evaluation II] and SAPS II [Simplified Acute Physiology Score II]). In DLT, donors were younger, cold ischemia time was shorter, and intraoperative transfusion requirements of packed red blood cells and fresh-frozen plasma were significantly lower. Graft dysfunction incidence was 3.4-fold lower in DLT: 5.2% (only 4 cases of initial poor function) versus 18.0% (1 primary nonfunction and 15 cases of initial poor function), P = 0.010. Postoperative bleeding was the most frequent early Clavien II-IV complication (n = 29, 17.3%), with an incidence 2.2-fold lower in domino recipients. A statistically significant difference was not found in the other analyzed Clavien II-IV complications, intensive care unit stay, mechanical ventilation time, intensive care unit mortality, and 1-year survival rate. In conclusion, in this study the younger donors and shorter ischemic time associated with DLT may provide a protective role in regards to graft dysfunction and perioperative bleeding, which are 2 important determinants of early morbidity after liver transplantation. PMID:21384509

Bispo, Miguel; Marcelino, Paulo; Marques, Hugo Pinto; Martins, Américo; Perdigoto, Rui; Aguiar, Maria João; Mourão, Luís; Barroso, Eduardo

2011-03-01

174

Mechanisms of itch evoked by ?-alanine  

PubMed Central

?-alanine, a popular supplement for muscle building, induces itch and tingling after consumption, but the underlying molecular and neural mechanisms are obscure. Here we show that, in mice, ?-alanine elicited itch-associated behavior that requires MrgprD, a G protein-coupled receptor expressed by a subpopulation of primary sensory neurons. These neurons exclusively innervate the skin, respond to ?-alanine, heat and mechanical noxious stimuli but do not respond to histamine. In humans, intradermally injected ?-alanine induced itch but neither wheal nor flare suggesting that the itch was not mediated by histamine. Thus, the primary sensory neurons responsive to ?-alanine are likely part of a histamine-independent itch neural circuit and a target for treating clinical itch that is unrelieved by anti-histamines.

Liu, Qin; Sikand, Parul; Ma, Chao; Tang, Zongxiang; Han, Liang; Li, Zhe; Sun, Shuohao; LaMotte, Robert H.; Dong, Xinzhong

2012-01-01

175

Complete resection of unresectable liver metastases from colorectal cancer without deterioration of liver function after cetuximab and irinotecan: two case reports.  

PubMed

Complete resection for colorectal metastases is the only treatment that can provide long-term survival and may lead to cure. Recent reports have shown that liver resection following systemic chemotherapy in patients with initially unresectable metastases from colorectal cancer may also result in a good long-term survival, and rescue surgery after chemotherapy has become a strategy of choice. A 29-year-old male and a 35-year-old female with unresectable liver metastases from colorectal cancer underwent complete resection after administration of third-line combination therapy of cetuximab and irinotecan. Although systemic chemotherapy may decrease liver function, which may make liver resection unfeasible, in the two cases reported, liver function did not deteriorate after cetuximab plus irinotecan. The indocyanine green retention rate at 15 minutes, which is useful in deciding the safe limit of hepatectomy, was optimal after the administration of cetuximab plus irinotecan in both patients. Cetuximab plus irinotecan may be beneficial as neoadjuvant chemotherapy for metastatic colorectal cancer, not only because of its oncological efficacy but also for preservation of liver function. PMID:21443115

Karasaki, Takahiro; Sano, Keiji; Takamoto, Taketumi; Kinoshita, Hiroto; Tateishi, Ryosuke; Takemura, Tamiko; Makuuchi, Masatoshi

2010-01-01

176

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

PubMed

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

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

2014-08-01

177

Resonant inelastic charge transfer in short alanine bridges  

NASA Astrophysics Data System (ADS)

We investigate theoretically the effect of atomic vibrations on the electron tunneling in polyalanine bridges. The inelastic-scattering processes in the bridge are included using a nonequilibrium Green’s function formalism with the density-functional Hamiltonian. With this method we analyze the inelastic charge transfer in polyalanine. We find that electron tunneling across alanine exhibits a resonant behavior and that atomic vibrations substantially change the charge-transfer rate across the bridge by providing additional scattering channels.

Sergueev, Nikolai; Demkov, Alexander A.

2010-01-01

178

Decrease in functional albumin mRNA during estrogen-induced vitellogenin biosynthesis in avian liver.  

PubMed Central

Translation of rooster liver RNA in a wheat germ extract is shown to yield albumin as one of the cell-free products. Quantitation of albumin mRNA by the translation assay indicates that functional albumin mRNA represents 10% of total liver mRNA activity in control roosters. After estrogen administration, this level decreases in a continuous fashion until functional albumin mRNA represents 5% of total mRNA activity at 12 days. This decrease in functional albumin mRNA was correlated with several parameters of vitellogenin induction. Functional vitellogenin mRNA increases to a maximum at 4 days after hormone treatment and returns to control levels by 12 days. A similar pattern is seen for the hormone-stimulated increase in total mRNA activity. The decrease in functional albumin mRNA, therefore, persists after the vitellogenic response of the liver has been completed. These results suggest that the decrease in hepatic albumin synthesis after hormone treatment is due to an estrogen-mediated decrease in the content of albumin mRNA.

Williams, D L; Wang, S Y; Klett, H

1978-01-01

179

Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans.  

PubMed

During fetal life, human liver sinusoids, which differentiate between 4 and 12 weeks of gestation from capillaries of the septum transversum, must support an important hematopoietic function and acquire the structural and functional characteristics of adult sinusoids. To gain insight into their differentiation process, we studied the expression of (1) markers of continuous endothelia, absent from adult sinusoidal endothelial cells (PECAM-1, CD34, and 1F10); (2) functional markers of adult sinusoidal endothelial calls (CD4, 1CAM-1, CD32, and CD14); and (3) extracellular matrix components (laminin, tenascin, fibronectin, and thrombospondin) in 37 fetuses of different gestational ages. We identified two successive differentiation events. (1) An early structural differentiation, occurring from 5 to 12 weeks of gestation, was characterized by the loss of continuous endothelial cell markers and a reduction in the perisinusoidal amount of laminin and in the deposition of tenascin, fibronectin, and thrombospondin; at the end of this process, fetal liver sinusoids present structural characteristics comparable to those of the sinuses in adult hematopoietic bone marrow. (2) A later functional differentiation was characterized by the acquisition of the markers of adult sinusoidal endothelial cells, initiating at 10 weeks of gestation and completed by 20 weeks of gestation; this process likely contributes to adapt liver sinusoids to the specific functions of the adult hepatic tissue. PMID:8639825

Couvelard, A; Scoazec, J Y; Dauge, M C; Bringuier, A F; Potet, F; Feldmann, G

1996-06-01

180

Oat prevents obesity and abdominal fat distribution, and improves liver function in humans.  

PubMed

Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our recent report suggested that oat, rich in beta-glucan, had a metabolic-regulating and liver-protecting effect in an animal model. In this study, we performed a clinical trial to further confirm the effect of oat. Subjects with BMI ?27 and aged 18-65, were randomly divided into a control (n=18) and an oat-treated (n=16) group, taking a placebo or beta glucan-containing oat cereal, respectively, for 12 weeks. Our data showed that consumption of oat reduced body weight, BMI, body fat and the waist-to-hip ratio. Profiles of hepatic function, including AST, but especially ALT, were useful resources to help in the evaluation of the liver, since both showed decrements in patients with oat consumption. Nevertheless, anatomic changes were still not observed by ultrasonic image analysis. Ingestion of oat was well tolerated and there was no adverse effect during the trial. In conclusion, consumption of oat reduced obesity, abdominal fat, and improved lipid profiles and liver functions. Taken as a daily supplement, oat could act as an adjuvant therapy for metabolic disorders. PMID:23371785

Chang, Hong-Chou; Huang, Chien-Ning; Yeh, Da-Ming; Wang, Shing-Jung; Peng, Chiung-Huei; Wang, Chau-Jong

2013-03-01

181

Liver injury in hypervitaminosis A: Evidence for activation of Kupffer cell function  

SciTech Connect

The most important and novel finding of this work was enhanced liver Kupffer cell phagocytic and metabolic function by hypervitaminosis A. An animal model of hypervitaminosis A was developed in male Sprague-Dawley rats gavaged with 250,000 I.U. retinol/kg body weight/day for 3 weeks. Presence of hypervitaminosis A was indicated by characteristic changes in the fur coat, presence of brittle bones and spontaneous fractures and a significant increase in plasma and liver concentrations of retinyl palmitate while retinol levels remained the same as in controls. Hypervitaminosis A did not cause severe liver abnormalities as reflected by normal plasma glutamate pyruvate transaminase activity and bilirubin. The main change was a marked increase in size of the fat or Vitamin A storing cells. Measurement of clearance from blood of indocyanine green and {sup 99m}Tc-disofenin indicated this hepatocyte function was normal. Kupffer cell phagocytic function was enhanced in hypervitaminosis A as determined by clearance from blood of {sup 99m}Tc-sulfur colloid. In vitro, there was also evidence that treatment with high doses of Vitamin A activated or enhanced Kupffer cell function. Kupffer cells from control and Vitamin A treated rats were isolated by enzymatic dispersion, purified by centrifugal elutriation, and placed in culture. Activation was indicated by (1) increased phagocytosis of {sup 51}Cr-labeled opsonized sheep red blood cells (2) enhanced release of superoxide anion and (3) enhanced production of tumor cytolytic factor by Kupffer cells from Vitamin A treated rats.

Sim, W.L.W.

1988-01-01

182

Morphological and functional characterization of non-alcoholic fatty liver disease induced by a methionine-choline-deficient diet in C57BL/6 mice  

PubMed Central

Background: Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), appears to be increasingly common worldwide. Its histopathology and the effects of nutrition on liver function have not been fully determined. Aim: To elucidate the cellular mechanisms of NAFLD induced by a methionine-choline-deficient (MCD) diet in mice. Particular focus was placed on the role of phagocytic cells. Methods: Male C57BL/6 mice were fed an MCD diet for 30 weeks. A recovery model was also established wherein a normal control diet was provided for 2 weeks after a period of 8, 16, or 30 weeks. Results: Mice fed the MCD diet for ?2 weeks exhibited severe steatohepatitis with elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Steatohepatitis was accompanied by the infiltration of CD68-positive macrophages (Kupffer cells). The severity of steatohepatitis increased in the first 16 weeks but was seen to lessen by week 30. Fibrosis began to develop at 10 weeks and continued thereafter. Steatohepatitis and elevated serum hepatic enzyme concentrations returned to normal levels after switching the diet back to the control within the first 16 weeks, but fibrosis and CD68-positive macrophages remained. Conclusions: The histopathological changes and irreversible fibrosis seen in this model were caused by prolonged feeding of an MCD diet. These results were accompanied by changes in the activity of CD68-positive cells with temporary elevation of CCL-2, MMP-13, and MMP-9 levels, all of which may trigger early steatohepatitis and late fibrosis through phagocytosis-associated MMP induction.

Itagaki, Hiroko; Shimizu, Kazuhiko; Morikawa, Shunichi; Ogawa, Kenji; Ezaki, Taichi

2013-01-01

183

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

SciTech Connect

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

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

2002-03-15

184

Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh  

PubMed Central

Background Chronic arsenic exposure has been shown to cause liver damage. However, serum hepatic enzyme activity as recognized on liver function tests (LFTs) showing a dose-response relationship with arsenic exposure has not yet been clearly documented. The aim of our study was to investigate the dose-response relationship between arsenic exposure and major serum enzyme marker activity associated with LFTs in the population living in arsenic-endemic areas in Bangladesh. Methods A total of 200 residents living in arsenic-endemic areas in Bangladesh were selected as study subjects. Arsenic concentrations in the drinking water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The study subjects were stratified into quartile groups as follows, based on concentrations of arsenic in the drinking water, as well as in subjects' hair and nails: lowest, low, medium and high. The serum hepatic enzyme activities of alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) were then assayed. Results Arsenic concentrations in the subjects' hair and nails were positively correlated with arsenic levels in the drinking water. As regards the exposure-response relationship with arsenic in the drinking water, the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates. With internal exposure markers (arsenic in hair and nails), the ALP, AST and ALT activity profiles assumed a similar shape of dose-response relationship, with very few differences seen in the higher groups compared to the lowest group, most likely due to the temporalities of exposure metrics. Conclusions The present study demonstrated that arsenic concentrations in the drinking water were strongly correlated with arsenic concentrations in the subjects' hair and nails. Further, this study revealed a novel exposure- and dose- response relationship between arsenic exposure metrics and serum hepatic enzyme activity. Elevated serum hepatic enzyme activities in the higher exposure gradients provided new insights into arsenic-induced liver toxicity that might be helpful for the early prognosis of arsenic-induced liver diseases.

2011-01-01

185

Expression of an epidermal keratin protein in liver of transgenic mice causes structural and functional abnormalities  

Microsoft Academic Search

To examine the role of keratin intermediate filament proteins in cell structure and function, trans- genie mice were isolated that express a modified form of the human K14 keratin protein in liver hepatoeytes. A modified K14 eDNA (K14.P) sequence was linked downstream of the mouse transthyretin (TTR) gene promoter and enhancer elements to achieve targeted expression in hepatocytes. Hepatoeytes expressing

Kathryn M. Albers; Frankie E. Davis; Teresa N. Perrone; Eun Y. Lee; Yong Liu; Mary Vore

1995-01-01

186

Ribavirin pharmacokinetics in renal and liver transplant patients: evidence that it depends on renal function  

Microsoft Academic Search

Background: Ribavirin is approved for the treatment of chronic hepatitis C virus (HCV) infection. However, no recommendation exists for dosing patients with impaired renal function. Methods: The authors performed a pharmacokinetic study in 21 HCV-positive renal or liver transplant patients. The mean creatinine clearance (ClCr) calculated by the Cockcroft-Gault equation was 57 mL\\/min (0.95 mL\\/s; range, 17 to 89 mL\\/min

Nassim Kamar; Etienne Chatelut; Efthymios Manolis; Thierry Lafont; Jacques Izopet; Lionel Rostaing

2004-01-01

187

Extrahepatic biliary atresia: Correlation of histopathology and liver function tests with surgical outcomes  

PubMed Central

Aims: To correlate the age at surgery, liver function tests, and hepatic and portal tract histo-pathological changes with surgical outcome in the form of disappearance of jaundice in extrahepatic biliary atresia (EHBA). Materials and Methods: This is a retrospective study of 39 cases of EHBA. There were 19 males and 10 females. Kasai's portoenterostomy (KPE) along with liver biopsy was performed in these patients; for purpose of correlation this biopsy was considered to be the preoperative biopsy. These patients were divided into three groups based upon surgical outcome: (A) disappearance of jaundice; (B) initial disappearance of jaundice with recurrence after 3 months; and (C) persistence of jaundice. Postoperatively, liver function tests and liver biopsies were repeated at 3 months after the KPE. Results: There were 11 patients in group A (28%), 21 patients in group B (54%), and seven patients in group C (18%). The age at surgery was comparable in all the three groups. The postoperative levels of serum bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGTP) showed statistically significant improvement as compared with the preoperative levels in group A and B patients. Patients belonging to group C showed no improvement in the liver functions following surgery. The preoperative hepatic histopathological changes (hepatocellular alteration, cholestasis, bile ductular proliferation, and bile duct inflammation) showed a significant difference among the three groups; patients with lesser degrees of pre-existing histopathological changes had better outcome following surgery. Fibrosis was seen in all the three groups preoperatively but the difference was not statistically significant. Group C had significant fibrosis in more than 50% patients. Additional findings, viz. ductal plate malformation (9 patients, 23%) and giant cell transformation (19 patients, 49%) did not show any correlation with surgical outcomes. Conclusions: The liver function tests and the histopathological features appeared to affect the final surgical outcome of these patients. Higher degree of cholestasis, hepatocellular alteration, bile ductule proliferation, bile duct inflammation showed definite correlation with poor surgical outcome. High grade hepatic fibrosis and portal edema showed a trend towards poor outcome but did not achieve statistical significance.

Gupta, Lucky; Gupta, Siddhartha D.; Bhatnagar, Veereshwar

2012-01-01

188

Development of tyrosine aminotransferase in perinatal rat liver: changes in function messenger RNA and the role of inducing hormones  

Microsoft Academic Search

Expression of the hepatic enzyme tyrosine aminotranferase was analyzed in the perinatal period of development in the rat, when this expression undergoes significant changes associated with hepatocyte differentiation. In late prenatal liver both enzyme and functional mRNA gene products are present at levels 10- to 15-fold below those in the fully differentiated adult liver. This low level of expression in

S. T. Perry; R. Rothrock; K. R. Isham; K. L. Lee; F. T. Kenney

1983-01-01

189

Differential expression and function of CYP2C isoforms in human intestine and liver.  

PubMed

This study aimed to characterize the intestinal and hepatic expression and function of CYP2C enzymes in the same set of subjects. CYP2C isoform-specific quantitative reverse transcription-polymerase chain reaction assays, Western immunoblotting and marker reactions of CYP2C8, CYP2C9 and CYP2C19 activities were employed to investigate expression and activity of the CYP2C isoforms in samples of small intestine and liver obtained from 15 patients undergoing gastrectomy or pancreatoduodenectomy. The rank order for CYP2C mRNA expression in the intestine was CYP2C9 = CYP2C18 > CYP2C19 > CYP2C8, whereas that in the liver was CYP2C9 > CYP2C8 > CYP2C18 > CYP2C19. The rank order for expression of CYP2C protein in the intestine was CYP2C9 > CYP2C19 > CYP2C8 (content below limit of quantification) > CYP2C18 (not detected) and that in the liver was CYP2C9 > CYP2C8 > CYP2C19 > CYP2C18 (not detected). The CYP2C9 protein content was approximately 10-fold higher in the liver than in the intestine (P < 0.001). The CLint for the formation of D-703 from verapamil (marker of CYP2C8 activity) was 7.6-fold higher (P < 0.001) and that for the diclofenac 4'-hydroxylation (marker of CYP2C9 activity) was 6.1-fold higher (P < 0.001) in the liver than in the intestine. Apart from a borderline positive correlation (r = 0.58, P = 0.0504) between the intestinal and hepatic CLint for the diclofenac 4'-hydroxylation, no intra-individual relationships between these tissues with respect to expression or activity of different CYP2C isoforms were found. Collectively, these results show that CYP2C8, CYP2C9 and CYP2C19 are expressed as functional enzymes in the human small intestine, and further suggest that CYP2C genes are independently regulated in human intestine and liver. Although, overall, the expression and activity of CYP2C enzymes is lower in the gut than in the liver, the surface area of the proximal small intestine is large and intestinal CYP2C9 and CYP2C19 may well contribute to the first-pass metabolism of their substrate drugs. PMID:12972955

Läpple, Florian; von Richter, Oliver; Fromm, Martin F; Richter, Tanja; Thon, Klaus P; Wisser, Hermann; Griese, Ernst-Ulrich; Eichelbaum, Michel; Kivistö, Kari T

2003-09-01

190

Changes in plasma hormones profile and liver function in cows naturally exposed to lead and cadmium around different industrial areas.  

PubMed

The present study was carried out to assess the endocrine status and liver function in adult cows reared in polluted environment around different industrial units in India. The effect on endocrine system was examined by determination of plasma level of thyroid hormones, thyroxin (T4) (n=269) and triidothyronin (T3) (n=269), stress hormone cortisol (n=266), and reproductive hormones such as estradiol (n=84) and progesterone (n=84) in cows (>3 years) reared around different polluted industrial and non-polluted areas. The respective blood lead and cadmium concentration was also determined in all the cows. The mean plasma levels of both T3 and T4 were significantly (P<0.05) higher around lead zinc smelter (2.43+/-0.26 and 41.1+/-2.9nmol/L) and closed lead cum operational zinc smelter (1.81+/-0.16 and 42.4+/-6.2nmol/L), where the mean blood lead level (0.86+/-0.06 and 0.51+/-0.09mug/ml) was also significantly higher than that of cows (0.07+/-0.01mug/ml) from unpolluted areas. Regression analysis of data from 269 cows revealed a significant (P<0.01) positive correlation between the blood lead and plasma T3 (r=0.287) and T4 (r=0.173). The correlation between thyroidal hormones and the blood cadmium concentration (r=-0.079 and -0.48; P>0.05) was not significant. Plasma cortisol level had also a non-significant (P>0.05) correlation (r=-0.092) with blood lead level.However, the mean cortisol level (4.02+/-1.96nmol/L) of cows in phosphate rock mining areas was significantly (P<0.05) higher than that of controls (1.98+/-0.70nmol/L). The mean plasma estradiol level was significantly (P<0.05) higher in cows around closed lead cum operational zinc smelter (47.1+/-19.5pg/ml) than that of the control animals (21.8+/-3.9pg/ml) and in rest of the areas, the difference did not reach the statistical significance (P>0.05). The serum biochemical analysis in 36 cows around lead-zinc smelter with the highest mean blood lead level (0.86+/-0.06mug/ml) amongst all the industrial/urban areas surveyed, and in 15 animals from non-polluted areas revealed a significant positive correlation between blood lead and serum ALT (alanine transaminase) (r=0.688, P<0.01) and AST (aspartate transaminase) (r=0.390, P<0.01) and a negative correlation with serum total lipids (r=-0.337, P<0.05), total protein (r=-0.449, P<0.01) and albumin(r=-0.662, P<0.01). It is concluded from the study that the natural exposure to lead in polluted environments disturbs the endocrine profile and the higher blood lead level alters serum biochemical parameters indicative of liver functions. PMID:16822533

Swarup, D; Naresh, Ram; Varshney, V P; Balagangatharathilagar, M; Kumar, P; Nandi, D; Patra, R C

2007-02-01

191

Beta-alanine supplementation in high-intensity exercise.  

PubMed

Glycolysis involves the oxidation of two neutral hydroxyl groups on each glycosyl (or glucosyl) unit metabolised, yielding two carboxylic acid groups. During low-intensity exercise these, along with the remainder of the carbon skeleton, are further oxidised to CO(2) and water. But during high-intensity exercise a major portion (and where blood flow is impaired, then most) is accumulated as lactate anions and H(+). The accumulation of H(+) has deleterious effects on muscle function, ultimately impairing force production and contributing to fatigue. Regulation of intracellular pH is achieved over time by export of H(+) out of the muscle, although physicochemical buffers in the muscle provide the first line of defence against H(+) accumulation. In order to be effective during high-intensity exercise, buffers need to be present in high concentrations in muscle and have pK(a)s within the intracellular exercise pH transit range. Carnosine (?-alanyl-L-histidine) is ideal for this role given that it occurs in millimolar concentrations within the skeletal muscle and has a pK(a) of 6.83. Carnosine is a cytoplasmic dipeptide formed by bonding histidine and ?-alanine in a reaction catalysed by carnosine synthase, although it is the availability of ?-alanine, obtained in small amounts from hepatic synthesis and potentially in greater amounts from the diet that is limiting to synthesis. Increasing muscle carnosine through increased dietary intake of ?-alanine will increase the intracellular buffering capacity, which in turn might be expected to increase high-intensity exercise capacity and performance where this is pH limited. In this study we review the role of muscle carnosine as an H(+) buffer, the regulation of muscle carnosine by ?-alanine, and the available evidence relating to the effects of ?-alanine supplementation on muscle carnosine synthesis and the subsequent effects of this on high-intensity exercise capacity and performance. PMID:23075550

Harris, Roger C; Sale, Craig

2012-01-01

192

Tissue-specific Function of Farnesoid X Receptor in Liver and Intestine  

PubMed Central

Nuclear receptors (NRs) are ligand-activated transcriptional factors that are involved in various physiological, developmental, and toxicological processes. Farnesoid X receptor (FXR) is a NR that belongs to the NR superfamily. The endogenous ligands of FXR are bile acids. FXR is essential in regulating a network of genes involved in maintaining bile acid and lipid homeostasis. It is clear that FXR is critical for liver and intestinal function. In mice FXR deficiency leads to the development of cholestasis, gallstone disease, nonalcoholic steatohepatitis, liver tumor, and colon tumor. Using mouse models where FXR is deleted either in the whole-body, or selectively in hepatocytes or enterocytes, we start to reveal the importance of tissue-specific FXR function in regulating bile acid and lipid homeostasis. However, a great challenge exists for developing tissue-specific FXR modulators to prevent and treat diseases associated with bile acid or lipid disorders. With further understanding of FXR function in both rodents and humans, this nuclear receptor may emerge as a novel target to prevent and treat liver, gastrointestinal and systemic diseases.

Zhu, Yan; Li, Fei; Guo, Grace L.

2011-01-01

193

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

PubMed

Bioartificial liver (BAL) system is promising as an alternative treatment for liver failure. We have developed a bioreactor with stacked sandwich culture plates for the application of BAL. This bioreactor design addresses some of the persistent problems in flat-bed bioreactors through increasing cell packing capacity, eliminating dead flow, regulating shear stress, and facilitating the scalability of the bioreactor unit. The bioreactor contained a stack of twelve double-sandwich-culture plates, allowing 100 million hepatocytes to be housed in a single cylindrical bioreactor unit (7 cm of height and 5.5 cm of inner diameter). The serial flow perfusion through the bioreactor increased cell-fluid contact area for effective mass exchange. With the optimal perfusion flow rate, shear stress was minimized to achieve high and uniform cell viabilities across different plates in the bioreactor. Our results demonstrated that hepatocytes cultured in the bioreactor could re-establish cell polarity and maintain liver-specific functions (e.g. albumin and urea synthesis, phase I&II metabolism functions) for seven days. The single bioreactor unit can be readily scaled up to house adequate number of functional hepatocytes for BAL development. PMID:22889484

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

2012-11-01

194

Changes of mitochondrial respiratory functions and superoxide dismutase activity during liver regeneration.  

PubMed

The general objective of this study was to examine the relationship between mitochondrial respiratory function and liver regeneration in the rat. The role that free radicals may play in the process was also evaluated. It was found that the respiratory control and ADP/O ratios were concomitantly decreased to the lowest level at 6 hr after hepatectomy and gradually recovered thereafter. Both ratios were significantly increased at 48 hr and quickly reached plateau levels. Assays of mitochondrial respiratory functions revealed that the activities of Complex I+III, Complex II+III and Complex IV all decreased drastically at 6 hr after hepatectomy and then gradually returned to the original level during 18-24 hr after hepatectomy. Interestingly, the activities of all these enzyme complexes continuously increased and were elevated significantly above the normal levels (145-200%). In contrast, the liver mitochondrial electron transport activities of sham-operated rats returned only to the original level after recovering from the operation-induced decline at 6 hr post-hepatectomy. We measured the superoxide dismutase (SOD) activity of liver mitochondria of the hepatectomized and sham-operated rats. The results showed that the Mn-SOD activity started to increase after hepatectomy, reached a maximum (900% of control) at 6 hr, and then returned to normal levels at 24 hr after operation. The Cu, Zn-SOD activity was increased 9-fold in hepatectomized rats and about 3-fold in sham-operated rats as compared with control rats. The maximum activity of Mn-SOD was found to be about 4 times higher than that of Cu, Zn-SOD after hepatectomy. The amount of lipoperoxides in the liver mitochondria was found to be increased to 140% in hepatectomized rats and to 120% in sham-operated rats as compared with that of the control rats. Taken together these results suggest that the changes in mitochondrial respiratory functions in the early phase of hepatectomy are due to tissue damage caused by the transient elevation of free radicals. These free radicals are then quickly disposed of by the ever-increasing activities of the Mn-SOD and Cu, Zn-SOD in the liver mitochondria, thereby protecting the liver from further damage and gearing the organ to the regeneration process. PMID:1333766

Tsai, J L; King, K L; Chang, C C; Wei, Y H

1992-10-01

195

Adrenal insufficiency as a cause of acute liver failure: a case report.  

PubMed

Introduction. Many diseases and conditions can contribute to elevated liver enzymes. Common causes include viral and autoimmune hepatitis, fatty liver, and bile duct diseases, but, in uncommon cases like liver involvement in endocrine disorders, liver failure is also seen. Adrenal insufficiency is the rarest endocrine disorder complicating the liver. In the previously reported cases of adrenal insufficiency, mild liver enzymes elevation was seen but we report a case with severe elevated liver enzymes and liver failure due to adrenal insufficiency. Based on our knowledge, this is the first report in this field. Case Report. A 39-year-old woman was referred to emergency ward due to drowsiness and severe fatigue. Her laboratory tests revealed prothrombin time: 21 sec, alanine aminotransferase (ALT): 2339?IU/L, aspartate aminotransferase (AST): 2002?IU/L, and ALP: 90?IU/L. No common cause of liver involvement was discovered, and eventually, with diagnosis of adrenal insufficiency and corticosteroid therapy, liver enzymes and function became normal. Finally, the patient was discharged with good general condition. Conclusion. With this report, we emphasize adrenal insufficiency (primary or secondary) as a reason of liver involvement in unexplainable cases and recommend that any increase in the liver enzymes, even liver failure, in these patients should be observed. PMID:23533837

Vafaeimanesh, Jamshid; Bagherzadeh, Mohammad; Parham, Mahmoud

2013-01-01

196

Adrenal Insufficiency as a Cause of Acute Liver Failure: A Case Report  

PubMed Central

Introduction. Many diseases and conditions can contribute to elevated liver enzymes. Common causes include viral and autoimmune hepatitis, fatty liver, and bile duct diseases, but, in uncommon cases like liver involvement in endocrine disorders, liver failure is also seen. Adrenal insufficiency is the rarest endocrine disorder complicating the liver. In the previously reported cases of adrenal insufficiency, mild liver enzymes elevation was seen but we report a case with severe elevated liver enzymes and liver failure due to adrenal insufficiency. Based on our knowledge, this is the first report in this field. Case Report. A 39-year-old woman was referred to emergency ward due to drowsiness and severe fatigue. Her laboratory tests revealed prothrombin time: 21 sec, alanine aminotransferase (ALT): 2339?IU/L, aspartate aminotransferase (AST): 2002?IU/L, and ALP: 90?IU/L. No common cause of liver involvement was discovered, and eventually, with diagnosis of adrenal insufficiency and corticosteroid therapy, liver enzymes and function became normal. Finally, the patient was discharged with good general condition. Conclusion. With this report, we emphasize adrenal insufficiency (primary or secondary) as a reason of liver involvement in unexplainable cases and recommend that any increase in the liver enzymes, even liver failure, in these patients should be observed.

Bagherzadeh, Mohammad; Parham, Mahmoud

2013-01-01

197

[Effect of administration of Escherichia coli Nissle (Mutaflor) on intestinal colonisation, endo-toxemia, liver function and minimal hepatic encephalopathy in patients with liver cirrhosis].  

PubMed

The purpose of the study was to verify effects of Escherichia coli Nissle (Mutaflor) on intestinal colonisation, endotoxin levels, hepatic encephalopathy and liver function in patients with liver cirrhosis. The study involved 39 patients (22 taking Mutaflor and 17 taking placebo). Even though the number combination test showed extended reaction time in patients with described minimal hepatic encephalopathy the drop was not significant in the trend evaluation. However, the treated group displayed significant improvement of intestinal colonisation (p < 0.001) and a trend towards significant reduction of endotoxin levels on day 42 (p = 0.07) and improvement of liver function assessed with the Child-Pugh classification on days 42 and 84 (p = 0.06). Probiotic preparations can therefore represent a significant contribution to this group therapy. PMID:16722152

Lata, J; Juránková, J; Príbramská, V; Fric, P; Senkyrík, M; Díte, P; Kroupa, R

2006-03-01

198

The metabolism of histamine in the Drosophila optic lobe involves an ommatidial pathway: ?-alanine recycles through the retina.  

PubMed

Flies recycle the photoreceptor neurotransmitter histamine by conjugating it to ?-alanine to form ?-alanyl-histamine (carcinine). The conjugation is regulated by Ebony, while Tan hydrolyses carcinine, releasing histamine and ?-alanine. In Drosophila, ?-alanine synthesis occurs either from uracil or from the decarboxylation of aspartate but detailed roles for the enzymes responsible remain unclear. Immunohistochemically detected ?-alanine is present throughout the fly's entire brain, and is enhanced in the retina especially in the pseudocone, pigment and photoreceptor cells of the ommatidia. HPLC determinations reveal 10.7 ng of ?-alanine in the wild-type head, roughly five times more than histamine. When wild-type flies drink uracil their head ?-alanine increases more than after drinking l-aspartic acid, indicating the effectiveness of the uracil pathway. Mutants of black, which lack aspartate decarboxylase, cannot synthesize ?-alanine from l-aspartate but can still synthesize it efficiently from uracil. Our findings demonstrate a novel function for pigment cells, which not only screen ommatidia from stray light but also store and transport ?-alanine and carcinine. This role is consistent with a ?-alanine-dependent histamine recycling pathway occurring not only in the photoreceptor terminals in the lamina neuropile, where carcinine occurs in marginal glia, but vertically via a long pathway that involves the retina. The lamina's marginal glia are also a hub involved in the storage and/or disposal of carcinine and ?-alanine. PMID:22442379

Borycz, Janusz; Borycz, Jolanta A; Edwards, Tara N; Boulianne, Gabrielle L; Meinertzhagen, Ian A

2012-04-15

199

Cardiac Structural and Functional Alterations in Infants and Children with Biliary Atresia, Listed for Liver Transplantation  

PubMed Central

Background & Aims Cirrhotic liver diseases are associated with abnormalities in cardiac geometry and function in adults (cirrhotic cardiomyopathy), but rarely explored in cirrhotic infants or children. We proposed that features of cirrhotic cardiomyopathy are present in infants with cirrhosis due to biliary atresia (BA) as early as the time of evaluation for liver transplantation and will correlate with mortality and post-operative morbidity. Methods Two-dimensional echocardiography (2DE) of infants with BA (n=40, median age 8 months), listed for transplantation at the Texas Children’s Hospital from 2004 to 2010, were reviewed and compared to age- and sex-matched infants without cardiac or liver disease (controls). Length of stay and correlation with 2DE results were assessed. Results Compared to controls, children with BA had significant increases in multiple 2DE parameters, notably left ventricle (LV) wall thickness (23% increase), LV mass indexed to body surface area (51% increase) and LV shortening fraction (8% increase). Overall, features of cirrhotic cardiomyopathy were observed in most infants (29/40; 72%); 17 had hyperdynamic contractility and 24 had altered LV geometry. After liver transplantation (33), infants with abnormal 2DE results had longer stays in the intensive care unit (median 6 vs 4 days) and the hospital (21 vs 11 days), compared with infants who had normal 2DE reports. On univariate analysis, the length of hospital stay correlated with LV mass index. Conclusions Cardiomyopathy is a prevalent condition in infants with end-stage cirrhotic liver disease due to BA (>70%). This under-recognized condition likely contributes to the prolongation of post-transplant hospitalization.

Desai, Moreshwar S.; Zainuer, Shabier; Kennedy, Curtis; Kearney, Debra; Goss, John; Karpen, Saul J.

2013-01-01

200

Solved? The reductive radiation chemistry of alanine.  

PubMed

The structural changes throughout the entire reductive radiation-induced pathway of l-?-alanine are solved on an atomistic level with the aid of periodic DFT and nudged elastic band (NEB) simulations. This yields unprecedented information on the conformational changes taking place, including the protonation state of the carboxyl group in the "unstable" and "stable" alanine radicals and the internal transformation converting these two radical variants at temperatures above 220 K. The structures of all stable radicals were verified by calculating EPR properties and comparing those with experimental data. The variation of the energy throughout the full radiochemical process provides crucial insight into the reason why these structural changes and rearrangements occur. Starting from electron capture, the excess electron quickly localizes on the carbon of a carboxyl group, which pyramidalizes and receives a proton from the amino group of a neighboring alanine molecule, forming a first stable radical species (up to 150 K). In the temperature interval 150-220 K, this radical deaminates and deprotonates at the carboxyl group, the detached amino group undergoes inversion and its methyl group sustains an internal rotation. This yields the so-called "unstable alanine radical". Above 220 K, triggered by the attachment of an additional proton on the detached amino group, the radical then undergoes an internal rotation in the reverse direction, giving rise to the "stable alanine radical", which is the final stage in the reductive radiation-induced decay of alanine. PMID:24356118

Pauwels, Ewald; De Cooman, Hendrik; Waroquier, Michel; Hole, Eli O; Sagstuen, Einar

2014-02-14

201

In vitro gene regulatory networks predict in vivo function of liver  

PubMed Central

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

2010-01-01

202

Comparative Effects of Oyster Mushrooms on Lipid Profile, Liver and Kidney Function in Hypercholesterolemic Rats  

PubMed Central

Comparative effects of oyster mushrooms on plasma and fecal lipid profiles and on liver and kidney function were evaluated in hyper and normocholesterolemic rats. Feeding of hypercholesterolemic rats a 5% powder of oyster mushrooms (Pleurotus ostreatus, P. sajor-caju and P. florida) reduced the plasma total cholesterol level by 37%, 21% and 16%, respectively and reduced the triglyceride level by 45%, 24% and 14%, respectively. LDL/HDL ratio decreased by 64%, 45% and 41% for P. sajor-caju, P. ostreatus and P. florida fed rats, respectively. Mushroom feeding also reduced body weight in hypercholesterolemic rats. However, it had no adverse effect on plasma bilirubin, creatinin and urea nitrogen level. Mushroom feeding also increased the total lipid and cholesterol excretion in the feces. The present study reveals that feeding of 5% oyster mushroom powder does not have detrimental effects on the liver and kidneys rather may provide health benefits for the cardiovascular-related complication by decreasing the atherogenic lipid profiles.

Alam, Nuhu; Amin, Ruhul; Khan, Asaduzzaman; Ara, Ismot; Shim, Mi Ja; Lee, Min Woong; Lee, U Youn

2009-01-01

203

Lipid Profiling and Transcriptomic Analysis Reveals a Functional Interplay between Estradiol and Growth Hormone in Liver  

PubMed Central

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

Fernandez-Perez, Leandro; Santana-Farre, Ruyman; de Mirecki-Garrido, Mercedes; Garcia, Irma; Guerra, Borja; Mateo-Diaz, Carlos; Iglesias-Gato, Diego; Diaz-Chico, Juan Carlos; Flores-Morales, Amilcar; Diaz, Mario

2014-01-01

204

Lipid Profiling and Transcriptomic Analysis Reveals a Functional Interplay between Estradiol and Growth Hormone in Liver.  

PubMed

17?-estradiol (E2) may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2, through its interaction with the estrogen receptor, exerts direct effects on liver. Hypothyroidism also affects endocrine and metabolic functions of the liver, rendering a metabolic phenotype with features that mimic deficiencies in E2 or GH. In this work, we combined the lipid and transcriptomic analysis to obtain comprehensive information on the molecular mechanisms of E2 effects, alone and in combination with GH, to regulate liver functions in males. We used the adult hypothyroid-orchidectomized rat model to minimize the influence of internal hormones on E2 treatment and to explore its role in male-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. The combination of E2 and GH decreased transcriptional immune responses. E2 decreased the hepatic content of saturated fatty acids and induced a transcriptional program that seems to be mediated by the activation of PPAR?. In contrast, GH inhibited fatty acid oxidation. Both E2 and GH replacements reduced hepatic CHO levels and increased the formation of cholesterol esters and triacylglycerols. Notably, the hepatic lipid profiles were endowed with singular fingerprints that may be used to segregate the effects of different hormonal replacements. In summary, we provide in vivo evidence that E2 has a significant impact on lipid content and transcriptome in male liver and that E2 exerts a marked influence on GH physiology, with implications in human therapy. PMID:24816529

Fernández-Pérez, Leandro; Santana-Farré, Ruymán; de Mirecki-Garrido, Mercedes; García, Irma; Guerra, Borja; Mateo-Díaz, Carlos; Iglesias-Gato, Diego; Díaz-Chico, Juan Carlos; Flores-Morales, Amilcar; Díaz, Mario

2014-01-01

205

Fas (CD95, APO1) antigen expression and function in murine liver endothelial cells: implications for the regulation of apoptosis in liver endothelial cells  

Microsoft Academic Search

The Fas (CD95, APO-1) receptor is a membrane-associated polypeptide that can mediate apoptosis in various cell types. Although Fas receptor is expressed in endothelial cells (EC), little is known about its function in these cells. The expression of Fas by liver endothelial cells (LEC) suggests that upon stimulation, apoptosis may occur in these cells. We show that Fas is highly

TARA SCHULTE; HEIDE KAMMER; JENNY KWAK; MARISABEL CARDIER

206

Functional central rhythmicity and light entrainment, but not liver and muscle rhythmicity, are Clock independent.  

PubMed

The circadian rhythmicity of hormone secretion, body temperature, and sleep/wakefulness results from an endogenous rhythm of neural activity generated by clock genes in the suprachiasmatic nucleus (SCN). One of these genes, Clock, has been considered essential for the generation of cellular rhythmicity centrally and in the periphery; however, melatonin-proficient Clock(Delta19) + MEL mutant mice retain melatonin rhythmicity, suggesting that their central rhythmicity is intact. Here we show that melatonin production in these mutants was rhythmic in constant darkness and could be entrained by brief single daily light pulses. Under normal light-dark conditions, per2 and prokineticin2 (PK2) mRNA expression was rhythmic in the SCN of Clock(Delta19) + MEL mice. Expression of Bmal1 and npas2 was not altered, whereas per1 expression was arrhythmic. In contrast to the SCN, per1 and per2 expression, as well as Bmal1 expression in liver and skeletal muscle, together with plasma corticosterone, was arrhythmic in Clock(Delta19) + MEL mutant mice in normal light-dark conditions. npas2 mRNA was also arrhythmic in liver but rhythmic in muscle. The Clock(Delta19) mutation does not abolish central rhythmicity and light entrainment, suggesting that a functional Clock homolog, possibly npas2, exists in the SCN. Nevertheless, the SCN of Clock(Delta19) + MEL mutant mice cannot maintain liver and muscle rhythmicity through rhythmic outputs, including melatonin secretion, in the absence of functional Clock expression in the tissues. Therefore, liver and muscle, but not SCN, have an absolute requirement for CLOCK, with as yet unknown Clock-independent factors able to generate the latter. PMID:16709646

Kennaway, David J; Owens, Julie A; Voultsios, Athena; Varcoe, Tamara J

2006-10-01

207

?-Alanine Supplementation for Athletic Performance: An Update.  

PubMed

Bellinger, PM. ?-alanine supplementation for athletic performance: An update. J Strength Cond Res 28(6): 1751-1770, 2014-?-alanine supplementation has become a common practice among competitive athletes participating in a range of different sports. Although the mechanism by which chronic ?-alanine supplementation could have an ergogenic effect is widely debated, the popular view is that ?-alanine supplementation augments intramuscular carnosine content, leading to an increase in muscle buffer capacity, a delay in the onset of muscular fatigue, and a facilitated recovery during repeated bouts of high-intensity exercise. ?-alanine supplementation appears to be most effective for exercise tasks that rely heavily on ATP synthesis from anaerobic glycolysis. However, research investigating its efficacy as an ergogenic aid remains equivocal, making it difficult to draw conclusions as to its effectiveness for training and competition. The aim of this review was to update, summarize, and critically evaluate the findings associated with ?-alanine supplementation and exercise performance with the most recent research available to allow the development of practical recommendations for coaches and athletes. A critical review of the literature reveals that when significant ergogenic effects have been found, they have been generally shown in untrained individuals performing exercise bouts under laboratory conditions. The body of scientific data available concerning highly trained athletes performing single competition-like exercise tasks indicates that this type of population receives modest but potentially worthwhile performance benefits from ?-alanine supplementation. Recent data indicate that athletes may not only be using ?-alanine supplementation to enhance sports performance but also as a training aid to augment bouts of high-intensity training. ?-alanine supplementation has also been shown to increase resistance training performance and training volume in team-sport athletes, which may allow for greater overload and superior adaptations compared with training alone. The ergogenic potential of ?-alanine supplementation for elite athletes performing repeated high-intensity exercise bouts, either during training or during competition in sports which require repeated maximal efforts (e.g., rugby and soccer), needs scientific confirmation. PMID:24276304

Bellinger, Phillip M

2014-06-01

208

First principles investigation of L-alanine in terahertz region.  

PubMed

Terahertz absorption spectrum (0.5-4.0 THz) of L-alanine in the solid phase was measured by terahertz time-domain spectroscopy at room temperature. Simulations utilizing gaseous-state and solid-state theory were performed to determine the origins of the observed vibrational features. Our calculations showed that the measured features in solid-state materials could be well understood by considering the crystal packing interactions in a solid-state density functional theory calculation. Furthermore, intermolecular vibrations of L-alanine are found to be the dominating contributions to these measured spectral features in the range of 0.5-4.0 THz, except that located at 3.11 THz. PMID:23729906

Zheng, Zhuan-Ping; Fan, Wen-Hui

2012-06-01

209

Phenotypic and in vivo functional characterization of immortalized human fetal liver cells  

PubMed Central

We report the establishment and characterization of immortalized human fetal liver progenitor cells by expression of the Simian virus 40 large T (SV40 LT) antigen. Well-characterized cells at various passages were transplanted into nude mice with acute liver injury and tested for functional capacity. The SV40LT antigen-immortalized fetal liver cells showed a morphology similar to primary cells. Cultured cells demonstrated stable phenotypic expression in various passages, of hepatic markers such as albumin, CK 8, CK18, transcription factors HNF-4? and HNF-1? and CYP3A/7. The cells did not stain for any of the tested cancer-associated markers. Albumin, HNF-4? and CYP3A7 expression was confirmed by reverse transcription polymerase chain reaction (RT-PCR). Flow cytometry showed expression of some progenitor cell markers. In vivo study showed that the cells expressed both fetal and differentiated hepatocytes markers. Our study suggests new approaches to expand hepatic progenitor cells, analyze their fate in animal models aiming at cell therapy of hepatic diseases.

Patil, Pradeep B.; Begum, Setara; Joshi, Meghnad; Kleman, Marika I; Olausson, Michael

2014-01-01

210

The pharmacokinetics of Casodex enantiomers in subjects with impaired liver function.  

PubMed Central

1. Casodex is a novel non-steroidal antiandrogen being developed for the treatment of prostatic cancer. The antiandrogenic activity is predominantly in the R(-) enantiomer with little, if any, activity in the S(+) enantiomer. 2. The pharmacokinetics of the enantiomers of Casodex have been investigated over 28 days following a single oral dose of Casodex (50 mg) to 10 male subjects with histologically verified liver cirrhosis or fatty liver with fibrosis. Ten age matched male subjects with normal hepatic function served as a control group. 3. For both groups plasma concentrations of (S)-Casodex were lower than those for (R)-Casodex; this difference was about 10-fold at early time points and increased to about 25-fold by 24 h after dosage. 4. The kinetics of (R)-Casodex were similar in subjects with and without liver disease (Cmax: 750 vs 848 ng ml(-1); tmax: 24 - 30 h; t(1/2): 7.40 vs 7.22 days; AUC: 182 vs 225 microg ml(-1) h). 5. The kinetics of (S)-Casodex could not be described in the majority of subjects; in the remainder the mean terminal phase half-life for both groups was less than 1 day.

Cockshott, I D; Sotaniemi, E A; Cooper, K J; Jones, D C

1993-01-01

211

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort  

PubMed Central

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population.

2011-01-01

212

Biochemical markers of liver and kidney function are influenced by thyroid function-a case-controlled follow up study in Indian hypothyroid subjects  

Microsoft Academic Search

Thyroid hormones regulate the renal hemodynamics and basal metabolic rate of most cells. This hospital-based case-control\\u000a study was done to evaluate the changes in biochemical markers of liver and kidney function in hypothyroid subjects before\\u000a and after treatment. The study included 176 subjects randomly selected from Thyroid clinics. Serum T3, T4, TSH, Liver and Kidney Function tests were analysed using

Sarika Arora; Ranjna Chawla; Devika Tayal; Vinod K. Gupta; Jagdeep S. Sohi; V. Mallika

2009-01-01

213

Liver Test Results Do Not Identify Liver Disease in Adults with ?-1 Antitrypsin Deficiency  

PubMed Central

BACKGROUND & AIMS Liver disease is a significant cause of mortality among adults with ?-1 antitrypsin (AAT) deficiency. Age and male sex are reported risk factors for liver disease. In the absence of adequate risk stratification, current recommendations are to intermittently test AAT-deficient adults for liver function. We evaluated this recommendation in a large group of adults with AAT deficiency, to determine the prevalence of increased levels of alanine aminotransferase (ALT) and identify risk factors for liver disease. METHODS We used the Alpha-1 Foundation DNA and Tissue Bank to identify a cross-section of AAT-deficient adults (n=647) with and without liver disease; individuals without AAT-deficiency were used as controls (n=152). Results from ALT tests were compared between groups. RESULTS The prevalence of liver disease among individuals with ATT-deficiency was 7.9%; an increased level of ALT was observed in 7.8% of ATT-deficient individuals, which did not differ significantly from controls. Mean levels of ALT fell within normal range for all groups. An increased level of ALT identified patients with liver disease with 11.9% sensitivity. The level of only ?- glutamyl transpeptidase was significantly higher in the AAT-deficient group than in controls (43 vs 30 IU/ml; P<.003). A childhood history of liver disease and male sex were risk factors for adult liver disease in the multivariate analysis. CONCLUSIONS An increased level of ALT does not identify adults with AAT deficiency who have liver disease. Male sex and liver disease during childhood might help identify those at risk.

Clark, Virginia C.; Dhanasekaran, Renumathy; Brantly, Mark; Rouhani, Farshid; Schreck, Pamela; Nelson, David R.

2012-01-01

214

Lanthanum associated abnormal liver function tests in two patients on dialysis: a case report  

PubMed Central

Lanthanum (La) is a phosphate binder used in patients on dialysis in the UK. As it has only recently been in use, there are no long-term data about safety of this rare metal in human subjects with renal failure on renal replacement therapy. La has not been previously reported to cause any adverse reactions apart from nausea, sickness, dialysis graft occlusion and abdominal pain. We report here La induced abnormal liver function tests in a male and a female patient of 70 and 44 years old each, on peritoneal dialysis (PD) and haemodialysis (HD) respectively, the first report of such an adverse reaction to this agent.

2009-01-01

215

Effects of occupational exposure to 1,4-dichlorobenzene on hematologic, kidney, and liver functions  

Microsoft Academic Search

Purpose  To investigate the effects of 1,4-dichlorobenzene (1,4-DCB) on kidney, liver, and hematological functions of workers in insect\\u000a repellent factories in Taiwan.\\u000a \\u000a \\u000a \\u000a Methods  A cross-sectional study was performed comparing 46 exposed workers and 29 non-exposed workers. Health information was collected\\u000a using questionnaires and biochemical tests. The concentration of urinary 2,5-dichlorophenol (2,5-DCP), the major metabolite\\u000a of 1,4-DCB, was analyzed by gas chromatography with

Pao-Kuei Hsiao; Yi-Chang Lin; Tung-Sheng Shih; Yin-Mei Chiung

2009-01-01

216

Pharmacokinetic analysis verifies P450 function during in vitro and in vivo application of a bioartificial liver.  

PubMed

Lidocaine is a sensitive substrate for evaluating liver P450 function. In this study, metabolism of lidocaine by xenogeneic hepatocytes in a hollow fiber, bioartificial liver was measured under in vitro conditions (n = 6) and in an anhepatic rabbit model. Animals in the treatment group (n = 6) received hemoperfusion by a bioartificial liver that contained 100 million rat hepatocytes. Other anhepatic rabbits received no hemoperfusion (n = 3) or a bioartificial liver with no cells (n = 3). Lidocaine clearance was 7.0 +/- 0.6 ml/min, and the half-life of lidocaine was 5.6 +/- 0.8 hr under in vitro conditions. Conversion of lidocaine to 3-hydroxy-lidocaine was confirmed in vitro and accounted for 46% of lidocaine elimination in the hepatocyte bioartificial liver. During in vivo application of the bioartificial liver, pharmacokinetic parameters of lidocaine metabolism, including drug half-life and metabolite formation, were significantly improved in anhepatic rabbits. 3-Hydroxy-lidocaine profiles verified the activity of a P450 isozyme expressed preferentially by rat hepatocytes in the bioartificial liver. We conclude that hepatic P450 activity was provided by xenogeneic hepatocytes during in vitro and in vivo applications of a bioartificial liver. PMID:8268538

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

1993-01-01

217

Human solute carrier SLC6A14 is the ?-alanine carrier  

PubMed Central

The ?-alanine carrier was characterized functionally in the 1960s to 1980s at the luminal surface of the ileal mucosal wall and is a Na+- and Cl?-dependent transporter of a number of essential and non-essential cationic and dipolar amino acids including lysine, arginine and leucine. ?-Alanine carrier-like function has not been demonstrated by any solute carrier transport system identified at the molecular level. A series of experiments were designed to determine whether solute carrier SLC6A14 is the molecular correlate of the intestinal ?-alanine carrier, perhaps the last of the classical intestinal amino acid transport systems to be identified at the molecular level. Following expression of the human SLC6A14 transporter in Xenopus laevis oocytes, the key functional characteristics of the ?-alanine carrier, identified previously in situ in ileum, were demonstrated for the first time. The transport system is both Na+ and Cl? dependent, can transport non-?-amino acids such as ?-alanine with low affinity, and has a higher affinity for dipolar and cationic amino acids such as leucine and lysine. N-methylation of its substrates reduces the affinity for transport. These observations confirm the hypothesis that the SLC6A14 gene encodes the transport protein known as the ?-alanine carrier which, due to its broad substrate specificity, is likely to play an important role in absorption of essential nutrients and drugs in the distal regions of the human gastrointestinal tract.

Anderson, Catriona M H; Ganapathy, Vadivel; Thwaites, David T

2008-01-01

218

Risk of elevated liver enzymes associated with TNF inhibitor utilisation in patients with rheumatoid arthritis  

Microsoft Academic Search

ObjectiveLiver function test (LFT) elevations are reported with the use of tumour necrosis factor inhibitors (TNF-Is). The aim of this study was to compare LFT elevations in patients with rheumatoid arthritis receiving adalimumab (ADA), etanercept (ETN) or infliximab (INF) enrolled in the Consortium of Rheumatology Researchers of North America from October 2001 to March 2007.MethodsAlanine aminotransferase (ALT) and\\/or aspartate aminotransferase

Jeremy Sokolove; Vibeke Strand; Jeffrey D Greenberg; Jeffrey R Curtis; Arthur Kavanaugh; Joel M Kremer; Alina Anofrei; George Reed; Leonard Calabrese; Michele Hooper; Scott Baumgartner; Daniel E Furst

2010-01-01

219

The effect of anterograde persufflation on energy charge and hepatocyte function in donation after cardiac death livers unsuitable for transplant.  

PubMed

Donation after cardiac death (DCD) livers are considered to be marginal organs for solid organ and cell transplantation. Low energy charge (EC) and low purine quantity within the liver parenchyma has been associated with poor outcome after liver transplantation. The aim of this work was to assess the effect of anterograde persufflation (A-PSF) using an electrochemical concentrator on DCD liver energy status and hepatocyte function. Organs utilized for research were DCD livers considered not suitable for transplant. Each liver was formally split, and the control non-persufflated (non-PSF) section was stored in University of Wisconsin (UW) solution at 4°C. The A-PSF liver section was immersed in UW solution on ice, and A-PSF was performed via the portal vein with 40% oxygen. Tissue samples were taken 2 hours after A-PSF from the A-PSF and control non-PSF liver sections for snap freezing. Purine analysis was performed with photodiode array detection. Hepatocytes were isolated from A-PSF and control non-PSF liver sections using a standard organs utilized for research were DCD livers considered not suitable for transplant collagenase perfusion technique. Hepatocyte function was assessed using mitochondrial dehydrogenase activity {3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyl tetrazolium bromide (MTT)} and the sulforhodamine B (SRB) assay for cell attachment. In DCD livers with <30% steatosis (n?=?6), A-PSF increased EC from 0.197?±?0.025 to 0.23?±?0.035 (P?=?0.04). In DCD livers with >30% steatosis (n?=?4), A-PSF had no beneficial effect. After isolation (n=4, <30% steatosis), A-PSF was found to increase MTT from 0.92?±?0.045 to 1.19?±?0.55 (P?function of isolated hepatocytes from DCD livers with <30% steatosis. PMID:24604782

Khorsandi, Shirin Elizabeth; Jitraruch, Suttiruk; Fairbanks, Lynette; Cotoi, Corina; Jassem, Wayel; Vilca-Melendez, Hector; Prachalias, Andreas; Dhawan, Anil; Heaton, Nigel; Srinivasan, Parthi

2014-06-01

220

Alanine Aminotransferase-Old Biomarker and New Concept: A Review  

PubMed Central

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

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

2014-01-01

221

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

PubMed Central

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

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

2014-01-01

222

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

PubMed Central

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

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

1988-01-01

223

An analysis of imaging studies and liver function tests to detect hepatic neoplasia  

Microsoft Academic Search

A retrospective study was conducted to determine the sensitivity, specificity, and accuracy of scintigraphy, ultrasound, and CT scanning in conjunction with biochemical tests in the detection of liver neoplasia. Sixty-three patients with metastatic liver disease and 45 patients with nonmalignant liver disease received a total of 46 liver\\/spleen scan, 61 ultrasounds, and 49 CT scans. The sensitivities of liver\\/spleen scan,

Thomas J. McGarrity; Todd Samuels; Frederick A. Wilson

1987-01-01

224

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

SciTech Connect

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

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

1986-01-01

225

Deletion of Smad2 in mouse liver reveals novel functions in hepatocyte growth and differentiation.  

PubMed

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

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

2006-01-01

226

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

PubMed Central

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

2014-01-01

227

Possible Relations Between Thyroid Function, Endothelium, and Kidney and Liver Function in Kidney Allograft Recipients  

Microsoft Academic Search

BackgroundRenal function affects the thyroid gland in many ways. Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these two processes.

J. Malyszko; K. Pawlak; M. Mysliwiec

2006-01-01

228

Preoperative estimation of operative risk in liver surgery, with special reference to functional reserve of the remnant liver following major hepatic resection  

Microsoft Academic Search

Hepatic functional reserve was evaluated in 76 patients with known liver, biliary tract or pancreas diseases using kinetic\\u000a analysis of removal of indocyanine green (ICG) with special reference to maximal removal rate (Rmax).\\u000a \\u000a In surgery other than hepatectomy, if ICG Rmax is below 0.4 mg\\/kg\\/min the operative risk should be considered high. In hepatic\\u000a surgery, even if ICG Rmax is

Ryuji Mizumoto; Yoshifumi Kawarada; Takashi Noguchi

1979-01-01

229

Decreased Circulating Endothelial Progenitor Cell Levels and Function in Patients with Nonalcoholic Fatty Liver Disease  

PubMed Central

Objectives Nonalcoholic fatty liver disease (NAFLD) is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs), and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD) might have decreased endothelial progenitor cell (EPC) levels and attenuated EPC function. Methods and Results A total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34+, CD34+KDR+, and CD34+KDR+CD133+) in peripheral blood samples was used to assess circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P<0.05), attenuated EPC functions, and enhanced systemic inflammation compared to controls. Multivariate logistic regression analysis showed that circulating EPC level (CD34+KDR+ [cells/105 events]) was an independent reverse predictor of NAFLD (Odds ratio: 0.78; 95% confidence interval: 0.69–0.89, P<0.001). Conclusions NAFLD patients have decreased circulating EPC numbers and functions than those without NAFLD, which may be one of the mechanisms to explain atherosclerotic disease progression and enhanced cardiovascular risk in patients with NAFLD.

Chiang, Chia-Hung; Huang, Po-Hsun; Chung, Fa-Po; Chen, Zu-Yin; Leu, Hsin-Bang; Huang, Chin-Chou; Wu, Tao-Cheng; Chen, Jaw-Wen; Lin, Shing-Jong

2012-01-01

230

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

PubMed

This study was designed to investigate the functional roles of histamine and histamine H1-receptor agonist and antagonist in the development of liver function impairment in immunized rabbits. The study comprised of six groups containing 18 rabbits each. Group III-VI received histamine (100 ?g/kg, s.c.), H1R-agonist (HTMT, 10 ?g/kg, s.c.), H1R-antagonist (pheniramine, 10 mg/kg, i.m.), and H1R-antagonist (pheniramine, 10 mg/kg, i.m.) plus histamine (100 ?g/kg, s.c.), respectively, b.i.d. for 10 days. Group I (negative control) and group II (positive control) received sterile distilled water intramuscularly b.i.d. for 10 days. Groups II-VI were immunized on day 3 with intravenous injection of SRBC (1 × 10(9) cells/ml). Blood samples were collected on pre-immunization day 0, as well as on days 7-, 14-, 21-, 28-, and 58-post-immunization. Biochemical parameters AST, ALT, alkaline phosphatase and bilirubin [total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB)] were determined. On each experimental day, the mean values of serum enzymes and bilirubin in group I and group II showed no significant changes while in group III, IV, V, and VI, these enzymes and bilirubin levels showed significant changes (p < 0.05), when compared with their experimental values within the group. The levels of serum enzymes and bilirubin showed significant difference (p < 0.05) in group III, IV, V, and VI on each experimental day, when compared with the corresponding values of each other, and also compared with the corresponding values of group I and II. Histamine, HTMT, pheniramine, and combination of histamine + pheniramine cause hepatic function impairment in terms of altered serum enzymes and bilirubin levels. The present findings suggest that HTMT causes moderate liver function impairment while others show mild impairment. PMID:23961154

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

2011-10-01

231

Effect of etonogestrel implant on serum lipids, liver function tests and hemoglobin levels  

Microsoft Academic Search

BackgroundThis study aimed to assess the possible effects of etonogestrel implant (Implanon®, Organon, Oss, The Netherlands) on total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Hb levels in a sample of Turkish population.

Berna Dilbaz; Ozlem Ozdegirmenci; Eray Caliskan; Serdar Dilbaz; Ali Haberal

2010-01-01

232

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

SciTech Connect

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

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

1981-12-15

233

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

SciTech Connect

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

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

1981-12-15

234

Effect of various alanine analogues on the L-alanine-adding enzyme from Escherichia coli.  

PubMed

An extract from Escherichia coli containing the L-alanine-adding enzyme with a high specific activity was prepared. Several compounds structurally related to L-alanine were tested as inhibitors of this activity. Intact amino and carboxyl groups were necessary for an interaction with the enzyme. Certain halogenated (haloalanines) or unsaturated (L-vinylglycine, L-propargylglycine, 3-cyano-L-alanine) amino acids were good inhibitors. Radioactive glycine, serine and 1-aminoethylphosphonic acid were tested as substrates. Whereas glycine or L-serine gave rise to the formation of the corresponding nucleotide product, no synthesis of UDP-N-acetylmuramyl-L-1-aminoethylphosphonic acid could be detected. PMID:1855644

Liger, D; Blanot, D; van Heijenoort, J

1991-05-01

235

Quantitative proteomic and functional analysis of liver mitochondria from high fat diet (HFD) diabetic mice.  

PubMed

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

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

2013-12-01

236

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

Microsoft Academic Search

AIM: To investigate the relationship of changes in expression of marker genes in functional categories or molecular networks comprising one functional category or multiple categories in progression of hepatic fibrosis in hepatitis C (HCV) patients. METHODS: Marker genes were initially identified using DNA microarray data from a rat liver fibrosis model. The expression level of each fibrosis associated marker gene

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

2010-01-01

237

Liver in systemic disease  

PubMed Central

Potential causes of abnormal liver function tests include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function test results might be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

Shimizu, Yukihiro

2008-01-01

238

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

PubMed Central

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

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

2011-01-01

239

Vancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution.  

PubMed

The molecular structure of the D-alanine:D-alanine ligase of the ddlB gene of Escherichia coli, co-crystallized with an S,R-methylphosphinate and adenosine triphosphate, was determined by x-ray diffraction to a resolution of 2.3 angstroms. A catalytic mechanism for the ligation of two D-alanine substrates is proposed in which a helix dipole and a hydrogen-bonded triad of tyrosine, serine, and glutamic acid assist binding and deprotonation steps. From sequence comparison, it is proposed that a different triad exists in a recently discovered D-alanine:D-lactate ligase (VanA) present in vancomycin-resistant enterococci. A molecular mechanism for the altered specificity of VanA is suggested. PMID:7939684

Fan, C; Moews, P C; Walsh, C T; Knox, J R

1994-10-21

240

Interference by branched-chain amino acids in the assay of alanine with alanine dehydrogenase.  

PubMed Central

Commercial preparations of alanine dehydrogenase from Bacillus subtilis are contaminated to varying extents with activity towards branched-chain amino acids. The Km values for these amino acids are of the same order as for L-alanine (about 10(-3)M). The branched-chain amino acid dehydrogenase activity is lost on dialysis for 2--4h against water or 2mM-EDTA.

Lund, P; Baverel, G

1978-01-01

241

Functional and ultrastructural features of ethanol\\/bile salts interaction in the isolated perfused rat liver  

Microsoft Academic Search

We investigated whether bile salts (BS) with different hydrophobic-hydrophilic properties interact with ethanol on bile secretion, enzyme (aspartate transaminase [AST], lactate dehydrogenase [Ldh]) release in the perfusate, liver ultrastructure, and vesicular exocytosis in the isolated perfused rat liver. Ethanol (0.1 or 1%) promoted a rapid decrease of bile flow and BS secretion in livers perfused with taurocholate (TCA), the physiologic

Domenico Alvaro; Antonio Benedetti; Alessandro Gigliozzi; Adriano Bini; Paola Della Guardia; Tiziana La Rosa; Anne Marie Jezequel; Livio Capocaccia

1995-01-01

242

[Studies on the antilipid peroxidation of nine sorts of Chinese herbal medicines with the function of protecting liver].  

PubMed

The antilipid peroxidation of nine sorts of Chinese herbal medicines with the function of protecting liver, including Salivia miltiorrhiza, Hypericum japonicum, Scutellaria baicalensis, Callicarpa cathayana, Chrysanthemum indicum, Paeonia latiflora, Lysimachia christinae, Ligustrum lucidum (L1), Patrinia villosa (Pv) on hepatic homogenate of rat were tested. It was found that all tested medicines showed inhibition with dose-effect relationship, the inhibitory rate of L1 and Pv were lower than the other's. All results showed that these Chinese herbal medicines have strong antilipid peroxidation and are natural oxidation inhibitor. It was suggested that their function of protecting liver and others have relationship with the antioxidation. PMID:12572505

Jiang, H; Huang, X; Yang, Y; Zhang, Q

1997-12-01

243

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

PubMed Central

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

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

2013-01-01

244

Role of cystatin C and renal resistive index in assessment of renal function in patients with liver cirrhosis  

PubMed Central

AIM: To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis. METHODS: We conducted a study of 63 patients with liver cirrhosis. A control group comprised of 30 age and gender-matched healthy persons. Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made. Estimated glomerular filtration rate from serum creatinine (GFRCr) and cystatin C (GFRCys) was calculated. RESULTS: We confirmed significant differences in values of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh (P = 0.01), and a significant correlation with model of end stage liver disease (MELD) score (rs = 0.527, P < 0.001). More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr (P < 0.001). Significantly higher renal resistive index was noted in Child-Pugh C than in A (P < 0.001) and B stage (P = 0.001). Also, a significant correlation between renal resistive index and MELD score was observed (rs = 0.607, P < 0.001). Renal resistive index correlated significantly with cystatin C (rs = 0.283, P = 0.028) and showed a negative correlation with GFRCys (rs = -0.31, P = 0.016). CONCLUSION: Cystatin C may be a more reliable marker for assessment of liver insufficiency. Additionally, cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.

Culafic, ?or?e; Stulic, Milos; Obrenovic, Radmila; Miletic, Danijela; Mijac, Dragana; Stojkovic, Milica; Jovanovic, Marija; Culafic, Milica

2014-01-01

245

On the existence of 'L-alanine cadmium bromide'.  

PubMed

It is argued that the recently reported nonlinear optical crystal L-alanine cadmium bromide, grown by slow solvent evaporation method at room temperature [P. Ilayabarathi, J. Chandrasekaran, Spectrochim. Acta 96A (2012) 684-689] is the well-known L-alanine crystal. The isolation of L-alanine crystal is explained due to fractional crystallization. PMID:23973284

Srinivasan, Bikshandarkoil R

2013-12-01

246

Characterization of the Alanine Racemases from Pseudomonas aeruginosa PAO1  

Microsoft Academic Search

Alanine racemases are ubiquitous, almost uniquely prokaryotic enzymes catalyzing the racemization between l- and d-alanine. The requirement for d-alanine as a necessary component of the bacterial cell wall makes this class of enzymes a logical target for the development of novel antibiotics. In an effort to better understand the structure and mechanism of these enzymes, we have cloned the two

Ulrich Strych; Hung-Chung Huang; Kurt L. Krause; Michael J. Benedik

2000-01-01

247

Potential energy surface of alanine polypeptide chains  

Microsoft Academic Search

The multidimensional potential energy surfaces of the peptide chains consisting of three and six alanine (Ala) residues have\\u000a been studied with respect to the degrees of freedom related to the twist of these molecules relative to the peptide backbone\\u000a (these degrees of freedom are responsible for the folding of such peptide molecules and proteins). The potential energy surfaces\\u000a have been

I. A. Solov’yov; A. V. Yakubovitch; A. V. Solov’yov; W. Greiner

2006-01-01

248

MRI-based estimation of liver function: Gd-EOB-DTPA-enhanced T1 relaxometry of 3T vs. the MELD score  

PubMed Central

Gd-EOB-DTPA is a hepatocyte-specific MRI contrast agent. Due to its hepatocyte-specific uptake and paramagnetic properties, functioning areas of the liver exhibit shortening of the T1 relaxation time. We report the potential use of T1 relaxometry of the liver with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) for estimating the liver function as expressed by the MELD score. 3 T MRI relaxometry was performed before and 20?min after Gd-EOB-DTPA administration. A strong correlation between changes in the T1 relaxometry and the extent of liver disease, expressed by the MELD score, was documented. Reduced liver function correlates with decreased Gd-EOB-DTPA accumulation in the hepatocytes during the hepatobiliary phase. MRI-based T1 relaxometry with Gd-EOB-DTPA may be a useful method for assessing overall and segmental liver function.

Haimerl, Michael; Verloh, Niklas; Fellner, Claudia; Zeman, Florian; Teufel, Andreas; Feigl, Stefan Fichtner-; Schreyer, Andreas G.; Stroszczynski, Christian; Wiggermann, Philipp

2014-01-01

249

Patients with hepatitis C infection and normal liver function: an evaluation of cognitive function  

PubMed Central

Purpose of the study Hepatitis C virus (HCV) is associated with neuropsychiatric complaints. Previous studies have associated cognitive alterations with HCV infection but have often included confounding factors in their samples. This study compares the cognitive performance between patients with HCV infection (HCV patients) and a control group while excluding other factors that may cause cognitive impairment. Study design This cross-sectional study was conducted from March 2010 through June 2011. HCV infected patients and healthy individuals between the ages of 18 and 80?years were considered eligible. The exclusion criteria included well established causes of cognitive impairment such as depression and cirrhosis. Study participants underwent neuropsychological testing involving measures of attention, memory, abstraction, visuoconstructive abilities, and executive function. Results Of 138 initial patients, 47 were excluded because of their medical records, three refused to participate, 23 did not attend the consultation, and 32 were excluded because of having Beck Depression Inventory (BDI) scores >11. In all, 33 patients underwent neuropsychological testing; however, three were excluded because of having hypothyroidism, and one was excluded because of having a cobalamin deficiency. For the control group, of the 33 healthy individuals that were selected, four were excluded because of having BDI scores >11. Thus, the final analysis included 29 HCV patients and 29 control participants. The groups did not differ in education, age, or gender. No statistically significant differences were found between the groups regarding cognitive performance. Conclusions In this study using strict selection criteria, there was no evidence of an association between HCV infection and cognitive impairment.

Abrantes, Jefferson; Torres, Daniel Simplicio; de Mello, Carlos Eduardo Brandao

2013-01-01

250

Abundant stage-dependent Ly49E expression by liver NK cells is not essential for their differentiation and function.  

PubMed

The NKR Ly49E has several unique characteristics. Unlike most NKRs, Ly49E is highly expressed on fetal NK cells, whereas expression is decreased on bone marrow-derived NK cells in adult mice. To investigate a possible role for Ly49E in NK cell differentiation and function, we have generated an Ly49E KO mouse. Our results show that bone marrow and splenic NK cells are present in normal numbers in Ly49E KO mice, expressing an unaltered panel of NKRs and differentiation markers. Furthermore, cytokine production and cytotoxicity by these cells are unaffected. Surprisingly, WT DX5(-) liver NK cells express high Ly49E levels in fetal and adult mice. Ly49E(+)DX5(-) liver NK cells transferred into Rag-2(-/-)/gc(-/-) mice maintain high Ly49E expression in the liver and differentiate into DX5(+) NK cells in spleen and bone marrow. Ly49E expression is not crucial for liver NK cell differentiation during ontogeny, as the DX5(-)/DX5(+) ratio, the NKR repertoire, and the granzyme B and TRAIL levels are comparable in Ly49E KO versus WT mice, except for lower TRAIL expression on DX5(-) liver NK cells in 20-day-old mice. The TRAIL-, perforin-, and FasL-mediated cytolysis by liver NK cells is unaffected in Ly49E KO mice. Collectively, we show that in addition to high Ly49E expression on fetal NK cells versus low Ly49E expression on conventional NK cells in adult life, Ly49E remains highly expressed on DX5(-) liver NK cells. However, Ly49E expression does not have a crucial role in differentiation and/or function of these NK cells. PMID:23475576

Filtjens, Jessica; Taveirne, Sylvie; Van Acker, Aline; Van Ammel, Els; Vanhees, Mandy; Kerre, Tessa; Taghon, Tom; Vandekerckhove, Bart; Plum, Jean; Leclercq, Georges

2013-05-01

251

Cardiorespiratory Fitness, Waist Circumference and Alanine Aminotransferase in Youth  

PubMed Central

Non-alcoholic fatty liver disease (NAFLD) is considered the liver component of the metabolic syndrome and is strongly associated with cardiometabolic diseases. In adults, cardiorespiratory fitness (CRF) is inversely associated with alanine aminotransferase (ALT), a blood biomarker for NAFLD. However, information regarding these associations is scarce for youth. Purpose To examine associations between CRF, waist circumference (WC) and ALT in youth. Methods Data were obtained from youth (n=2844, 12-19 years) in the National Health and Nutrition Examination Survey (NHANES) 2001-2004. CRF was dichotomized into youth FITNESSGRAM® categories of “low” and “adequate” CRF. Logistic and quantile regression were used for a comprehensive analysis of associations, and variables with previously-reported associations with ALT were a priori included in the models. Results Results from logistic regression suggested that youth with low CRF had 1.5 times the odds of having an ALT>30 than youth with adequate CRF, although the association was not statistically significant (P=0.09). However, quantile regression demonstrated that youth with low CRF had statistically significantly higher ALT (+1.04, +1.05, and +2.57 U/L) at the upper end of the ALT distribution (80th, 85th, and 90th percentiles, respectively) than youth with adequate CRF. For every 1-cm increase in WC, the odds of having an ALT>30 increased by 1.06 (P<0.001), and the strength of this association increased across the ALT distribution. Conclusions Future studies should examine whether interventions to improve CRF can decrease hepatic fat and liver enzyme concentrations in youth with ALT ?80th percentile or in youth diagnosed with NAFLD.

Trilk, Jennifer L.; Ortaglia, Andrew; Blair, Steven N.; Bottai, Matteo; Church, Timothy S.; Pate, Russell R.

2012-01-01

252

Lipid Modulation and Liver Function Tests: A Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH)  

Microsoft Academic Search

Background Statin drugs are known to cause dose-dependent abnormalities in liver function tests (LFTs), with elevations three times the upper limits of normal of the aminotransferase enzymes in up to 2.5% of patients on the highest prescribable doses. The Program on the Surgical Control of the Hyperlipidemias (POSCH) trial employed no hypocholesterolaemic drugs and used a surgical procedure, partial ileal

Henry Buchwald; Stanley E. Williams; John P. Matts; James R. Boen

2002-01-01

253

Glutamine and alanine metabolism in NIDDM.  

PubMed

Gluconeogenesis is increased in NIDDM. We therefore examined the metabolism of glutamine and alanine, the most important gluconeogenic amino acids, in 14 postabsorptive NIDDM subjects and 18 nondiabetic volunteers using a combination of isotopic ([6-3H]glucose (20 microCi, 0.2 microCi/min), [U-14C]glutamine (20 microCi, 0.2 microCi/min), [3-13C]alanine (99% 13C, 2 mmol, 20 micromol/min), [ring-2H5]phenylalanine (99% 2H, 2 micromol/kg, 0.03 micromol x kg(-1) x min(-1)), and limb balance techniques. Alanine turnover (4.54 +/- 0.24 vs. 5.64 +/- 0.33 micromol x kg(-1) x min(-1)), de novo synthesis (3.00 +/- 0.25 vs. 4.01 +/- 0.33 micromol x kg(-1) x min(-1)), and conversion to glucose (1.02 +/- 0.09 vs. 1.56 +/- 0.17 micromol x kg(-1) x min(-1)) were increased in NIDDM subjects (all P < 0.01), while its forearm release (0.45 +/- 0.04 vs. 0.39 +/- 0.04 micromol x kg(-1) x min(-1)) was unaltered. Although glutamine turnover (4.81 +/- 0.23 vs. 4.40 +/- 0.31 micromol x kg(-1) x min(-1)) was unaltered in NIDDM, its conversion to glucose (0.57 +/- 0.04 vs. 1.08 +/- 0.10 micromol x kg(-1) x min(-1)) and to alanine (0.10 +/- 0.01 vs. 0.34 +/- 0.04 micromol x kg(-1) x min(-1)) (both P = 0.001) was increased while its oxidation (2.84 +/- 0.27 vs. 1.84 +/- 0.15 micromol x kg(-1) x min(-1), P = 0.03) and forearm release (0.77 +/- 0.05 vs. 0.62 +/- 0.09 micromol x kg(-1) x min(-1), P < 0.008) were both reduced. Our results thus demonstrate that there are substantial alterations of glutamine and alanine metabolism in NIDDM. Conversion of both amino acids to glucose and the proportion of their turnover used for gluconeogenesis are increased; release of both amino acids from tissues other than skeletal muscle seems to be increased. Finally, the reduction in glutamine oxidation, possibly the result of competition with glucose and free fatty acids as fuels, makes more glutamine available for gluconeogenesis without a change in its turnover. PMID:8666134

Stumvoll, M; Perriello, G; Nurjhan, N; Bucci, A; Welle, S; Jansson, P A; Dailey, G; Bier, D; Jenssen, T; Gerich, J

1996-07-01

254

Functional imaging biomarkers for assessing response to treatment in liver and lung metastases  

PubMed Central

Abstract Management of patients with metastatic cancer and development of new treatments rely on imaging to provide non-invasive biomarkers of tumour response and progression. The widely used size-based criteria have increasingly become inadequate where early measures of response are required to avoid toxicity of ineffective treatments, as biological, physiologic, and molecular modifications in tumours occur before changes in gross tumour size. A multiparametric approach with the current range of imaging techniques allows functional aspects of tumours to be simultaneously interrogated. Appropriate use of these imaging techniques and their timing in relation to the treatment schedule, particularly in the context of clinical trials, is fundamental. There is a lack of consensus regarding which imaging parameters are most informative for a particular disease site and the best time to image so that, despite an increasing body of literature, open questions on these aspects remain. In addition, standardization of these new parameters is required. This review summarizes the published literature over the last decade on functional and molecular imaging techniques in assessing treatment response in liver and lung metastases.

O'Flynn, Elizabeth A.M.; deSouza, Nandita M.

2013-01-01

255

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

SciTech Connect

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

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

2007-05-15

256

Partial liver transplantation.  

PubMed

Partial liver transplantation, including reducedsize liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud's anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situ to ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations-including anatomical, liver volume, and liver function evaluations-is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society. PMID:21681668

Gong, Nianqiao; Chen, Xiaoping

2011-03-01

257

Effect of beta-alanine supplementation on muscle carnosine concentrations and exercise performance.  

PubMed

High-intensity exercise results in reduced substrate levels and accumulation of metabolites in the skeletal muscle. The accumulation of these metabolites (e.g. ADP, Pi and H(+)) can have deleterious effects on skeletal muscle function and force generation, thus contributing to fatigue. Clearly this is a challenge to sport and exercise performance and, as such, any intervention capable of reducing the negative impact of these metabolites would be of use. Carnosine (beta-alanyl-L-histidine) is a cytoplasmic dipeptide found in high concentrations in the skeletal muscle of both vertebrates and non-vertebrates and is formed by bonding histidine and beta-alanine in a reaction catalysed by carnosine synthase. Due to the pKa of its imidazole ring (6.83) and its location within skeletal muscle, carnosine has a key role to play in intracellular pH buffering over the physiological pH range, although other physiological roles for carnosine have also been suggested. The concentration of histidine in muscle and plasma is high relative to its K (m) with muscle carnosine synthase, whereas beta-alanine exists in low concentration in muscle and has a higher K (m) with muscle carnosine synthase, which indicates that it is the availability of beta-alanine that is limiting to the synthesis of carnosine in skeletal muscle. Thus, the elevation of muscle carnosine concentrations through the dietary intake of carnosine, or chemically related dipeptides that release beta-alanine on absorption, or supplementation with beta-alanine directly could provide a method of increasing intracellular buffering capacity during exercise, which could provide a means of increasing high-intensity exercise capacity and performance. This paper reviews the available evidence relating to the effects of beta-alanine supplementation on muscle carnosine synthesis and the subsequent effects on exercise performance. In addition, the effects of training, with or without beta-alanine supplementation, on muscle carnosine concentrations are also reviewed. PMID:20091069

Sale, Craig; Saunders, Bryan; Harris, Roger C

2010-07-01

258

Metabolic liver disease.  

PubMed

Diagnosis of metabolic liver disease requires a high level of diagnostic suspicion. Diet is usually the primary treatment for metabolic liver disease. Where indicated, liver transplantation provides lifelong functional correction of liver-based metabolic defects. Liver cell therapy warrants further study for the future treatment of metabolic liver disease. All families should receive genetic advice and pre-emptive management of future affected siblings. PMID:22521124

McKiernan, Pat

2012-06-01

259

Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function  

PubMed Central

A critical regulator of autophagy is the Class III PI3K Vps34 (also called PIK3C3). Although Vps34 is known to play an essential role in autophagy in yeast, its role in mammals remains elusive. To elucidate the physiological function of Vps34 and to determine its precise role in autophagy, we have generated Vps34f/f mice, in which expression of Cre recombinase results in a deletion of exon 4 of Vps34 and a frame shift causing a deletion of 755 of the 887 amino acids of Vps34. Acute ablation of Vps34 in MEFs upon adenoviral Cre infection results in a diminishment of localized generation of phosphatidylinositol 3-phosphate and blockade of both endocytic and autophagic degradation. Starvation-induced autophagosome formation is blocked in both Vps34-null MEFs and liver. Liver-specific Albumin-Cre;Vps34f/f mice developed hepatomegaly and hepatic steatosis, and impaired protein turnover. Ablation of Vps34 in the heart of muscle creatine kinase-Cre;Vps34f/f mice led to cardiomegaly and decreased contractility. In addition, while amino acid-stimulated mTOR activation was suppressed in the absence of Vps34, the steady-state level of mTOR signaling was not affected in Vps34-null MEFs, liver, or cardiomyocytes. Taken together, our results indicate that Vps34 plays an essential role in regulating functional autophagy and is indispensable for normal liver and heart function.

Jaber, Nadia; Dou, Zhixun; Chen, Juei-Suei; Catanzaro, Joseph; Jiang, Ya-Ping; Ballou, Lisa M.; Selinger, Elzbieta; Ouyang, Xiaosen; Lin, Richard Z.; Zhang, Jianhua; Zong, Wei-Xing

2012-01-01

260

Puerarin improves metabolic function leading to hepatoprotective effects in chronic alcohol-induced liver injury in rats.  

PubMed

Puerarin (PR), an active component extracted from the kudzu root, has been widely used as an ethno-medicine to treat hepatopathy in China. Therefore, the aim of the present study was to investigate the hepatoprotective action of PR in chronic alcohol-induced liver injury in rats. Data showed that the serum levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were elevated following PR administration. In addition, the levels of endogenous CYP2E1, CYP1A2, and CYP3A proteins in liver tissue were also gradually decreased following PR treatment. Histopathological examinations suggested that alcohol-induced hepatocellular lesions were mitigated by PR treatment. Collectively, these data indicate that PR contributes to cytoprotection against alcohol-induced liver lesions through improving metabolic function. PMID:23669266

Chen, Xu; Li, Rong; Liang, Tao; Zhang, Kefeng; Gao, Ya; Xu, Lingyuan

2013-07-15

261

A molecular dynamics study of the dielectric properties of aqueous solutions of alanine and alanine dipeptide  

NASA Astrophysics Data System (ADS)

Molecular dynamics simulations were used to compute the frequency-dependent dielectric susceptibility of aqueous solutions of alanine and alanine dipeptide. We studied four alanine solutions, ranging in concentration from 0.13-0.55 mol/liter, and two solutions of alanine dipeptide (0.13 and 0.27 mol/liter). In accord with experiment we find a strong dielectric increment for both solutes, whose molecular origin is shown to be the zwitterionic nature of the solutes. The dynamic properties were analyzed based on a dielectric component analysis into solute, a first hydration shell, and all remaining (bulk) waters. The results of this three component decomposition were interpreted directly, as well as by uniting the solute and hydration shell component to a ``suprasolute'' component. In both approaches three contributions to the frequency-dependent dielectric properties can be discerned. The quantitatively largest and fastest component arises from bulk water [i.e., water not influenced by the solute(s)]. The interaction between waters surrounding the solute(s) (the hydration shell) and bulk water molecules leads to a relaxation process occurring on an intermediate time scale. The slowest relaxation process originates from the solute(s) and the interaction of the solute(s) with the first hydration shell and bulk water. The primary importance of the hydration shell is the exchange of shell and bulk waters; the self-contribution from bound water molecules is comparatively small. While in the alanine solutions the solute-water cross-terms are more important than the solute self-term, the solute contribution is larger in the dipeptide solutions. In the latter systems a much clearer separation of time scales between water and alanine dipeptide related properties is observed. The similarities and differences of the dielectric properties of the amino acid/peptide solutions studied in this work and of solutions of mono- and disaccharides and of the protein ubiquitin are discussed.

Boresch, Stefan; Willensdorfer, Martin; Steinhauser, Othmar

2004-02-01

262

[Assessment of protein synthesizing function of the liver in experimental hepatitis].  

PubMed

Liver protein synthesis was estimated comparing the levels of prothrombin and its inactive form PIVKA-prothrombin. The latter indicates liver dysfunction. These diagnostic tests allow monitoring the effectiveness of the commonly applied preparation "Essentiale Forte" and that of the liposomal form of the biologically active additive (BAA) FLP-MD based on phospholipids of various origin. PMID:21800650

Hryshchenko, V A; Tomchuk, V A; Lytvynenko, O M; Chernyshenko, V O; Hryshchuk, V I; Platonova, T M

2011-01-01

263

Early septic shock induces loss of oxidative phosphorylation yield plasticity in liver mitochondria.  

PubMed

We aimed to study the change in mitochondrial oxidative phosphorylation efficiency occurring at the early stage of septic shock in an experimental model. Thirty-six male Wistar rats were divided into two groups. In the first group, a cecal ligation and puncture (CLP) was carried out to induce septic shock for 5 h. The second group includes sham-operated rats and constitutes the control group. Blood gas analysis, alanine amino transferase, and lactic acid dosages were assayed 5 h after surgery. Liver mitochondria were isolated for in vitro functional characterization, including mitochondrial respiratory parameters, oxidative phosphorylation efficiency, oxi-radical production, membrane potential, and cytochrome c oxidase activity and content. Liver interleukin 1? (IL-1?) and tumor necrosis ? mRNA levels were determined. Septic shock induced a severe hypotension occurring 180 min after CLP in association with a metabolic acidosis, an increase in plasma alanine amino transferase, liver IL-1? gene expression, and mitochondrial reactive oxygen species production. The rates of mitochondrial oxygen consumption and the activity and content of cytochrome c oxidase were significantly decreased while no alterations in the oxidative phosphorylation efficiency and inner membrane integrity were found. These results show that contrary to what was expected, liver mitochondria felt to adjust their oxidative phosphorylation efficiency in response to the decrease in the mitochondrial oxidative activity induced by CLP. This loss of mitochondrial bioenergetics plasticity might be related to mitochondrial oxidative stress and liver cytokines production. PMID:24570093

Eyenga, Pierre; Roussel, Damien; Morel, Jérôme; Rey, Benjamin; Romestaing, Caroline; Teulier, Loic; Sheu, Shey-Shing; Goudable, Joelle; Négrier, Claude; Viale, Jean Paul

2014-06-01

264

Ameliorative effect of Partysmart in rat model of alcoholic liver disease.  

PubMed

Present study was designed to investigate the effect of polyherbal formulation PartySmart in experimental model of alcoholic liver disease in male Wistar strain rats. Alcohol plus fish oil were administered to animals for 8 weeks to induce liver injury. PartySmart was administered at doses of 250 and 500 mg/kg body weight. After 8 weeks, parameters such as liver weight, liver function serum markers alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) and lipid peroxidation were studied. Livers from all the groups were subjected for histological evaluation. Treatment with PartySmart at the dose of 500 mg/kg body weight showed significant reduction in the levels of serum ALT, AST and ALP with a decrease in liver weight as compared to ethanol-fed rats. A significant decrease was also observed in malondialdehyde levels following treatment with PartySmart at 500 mg/kg body weight. Histological profile of liver tissue in PartySmart-treated animals showed lesser vacuolar degeneration and intactness of hepatic architecture along with improved glycogen deposition as demonstrated by PAS staining. PartySmart ameliorated alcohol-induced liver injury by preventing cell membrane disturbances, reduction of oxidative stress by free radical scavenging and antioxidant activity and normalization of altered intracellular redox status. Thus, PartySmart can be beneficial in the treatment of alcohol-induced liver damage. PMID:18335812

Gopumadhavan, S; Rafiq, Mohammed; Azeemuddin, M; Mitra, S K

2008-02-01

265

Core level study of alanine and threonine.  

PubMed

Core level X-ray photoemission spectra (XPS) and near edge X-ray absorption fine structure (NEXAFS) spectra of alanine and threonine in the gas phase have been measured at the carbon, nitrogen, and oxygen K edges and interpreted in the light of theoretical calculations. For the computations, a set of approximations is made which allows sufficiently accurate calculations of several conformers to be performed in reasonable computing time. The accuracy has been checked by comparing results obtained for proline to our previous, higher level calculations. The photoemission spectra at the carbon and oxygen edges are assigned and compared. The nitrogen 1s photoemission peaks show anomalous broadening which we relate to the populations and types of conformers. The carbon K-edge NEXAFS spectra of alanine and threonine are compared with our previous data on glycine and resonances assigned accordingly. The nitrogen K-edge NEXAFS spectra of alanine and threonine do not show measurable effects due to the population of conformers, in contrast to the photoemission results. At the oxygen K edge, the spectra of these amino acids are similar with two prominent peaks assigned to transitions of O 1s electrons from the oxo and hydroxyl groups to vacant pi* and sigma* orbitals and additional intensity for threonine due to the second OH group. Conformer effects are observable in photoemission but appear to be more difficult to resolve in photoabsorption. We explain this by energetic shifts of opposite sign for the core hole states and unoccupied orbitals, which causes partial cancelation in NEXAFS but not in photoemission. PMID:18671382

Feyer, Vitaliy; Plekan, Oksana; Richter, Robert; Coreno, Marcello; Prince, Kevin C; Carravetta, Vincenzo

2008-08-28

266

Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study  

PubMed Central

Background Liver function tests (LFTs) can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees. Methods We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits. Results Coffee consumption was closely related to male gender, high body mass index (BMI), alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST). On multivariable analyses, smoking raised serum ?-glutamyl transferase (GGT) level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking. Conclusions Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.

2012-01-01

267

Fistuloclysis Improves Liver Function and Nutritional Status in Patients with High-Output Upper Enteric Fistula  

PubMed Central

Background. We aimed to determine the efficacy of fistuloclysis in patients with high-output upper enteric fistula (EF). Methods. Patients were assigned into the fistuloclysis group (n = 35, receiving fistuloclysis plus total enteral nutrition (TEN)) and the control group (n = 60, receiving TEN). Laboratory variables were measured during the four-week treatment. Results. At baseline, variables were similar between the two groups. Delta value was defined as the changes from baseline to day 28. Compared with the control group, the fistuloclysis group showed greater improvements in liver function (Delta total bilirubin (TB): 20.3 ± 9.7 in the fistuloclysis group versus 15.6 ± 6.3 in the control group, P = 0.040; Delta direct bilirubin (DB): 12.5 ± 3.4 versus 10.0 ± 3.6, P = 0.011; Delta alkaline phosphatase (ALP): 98.4 ± 33.5 versus 57.6 ± 20.9, P < 0.001); nutritional status (Delta total protein: 21.8 ± 8.7 versus 10.7 ± 2.1, P < 0.001; Delta albumin: 11.3 ± 2.5 versus 4.2 ± 1.3, P < 0.001). In the fistuloclysis subgroups, biliary fistula patients had the maximum number of variables with the greatest improvements. Conclusions. Fistuloclysis improved hepatic and nutritional parameters in patients with high-output upper EF, particularly in biliary fistula patients.

Wu, Yin; Ren, Jianan; Wang, Gefei; Zhou, Bo; Ding, Chao; Gu, Guosheng; Chen, Jun; Liu, Song; Li, Jieshou

2014-01-01

268

Fingolimod (FTY720) in severe hepatic impairment: pharmacokinetics and relationship to markers of liver function.  

PubMed

The authors assessed the impact of severe hepatic impairment on the disposition of fingolimod--a sphingosine-1-phosphate receptor immunomodulator primarily metabolized by CYP4F2--in 6 patients and 6 matched healthy controls who received a single 5-mg oral dose. Compared with healthy controls, severe hepatic-impaired subjects had a doubled area under the concentration time curve (AUC) and 50% prolonged elimination half-life but a similar peak blood concentration. When these data were combined with those from a previous study in mild and moderate hepatic-impaired subjects, there were significant positive correlations between fingolimod AUC versus bilirubin (r = 0.683) and prothrombin time (r = 0.777) and a significant negative correlation versus albumin (r = 0.578), confirming the importance of liver function for fingolimod clearance. For patients with severe hepatic impairment (Child-Pugh class C), a standard first dose of fingolimod could be given followed by a maintenance dose that is reduced by half from the normal maintenance dose. PMID:16432266

Kovarik, John M; Schmouder, Robert L; Hartmann, Stefan; Riviere, Gilles-Jacques; Picard, Franck; Voss, Brigitta; Weiss, Markus; Wagner, Frank; Schmidt, Hartmut H-J

2006-02-01

269

Effect of green tea extracts on liver functions in Wistar rats.  

PubMed

An herbal medicinal product (Exolise) containing as active ingredient an hydro-alcoholic extract of green tea named AR25 (standardized to 25% catechins) has been implicated in hepatic failures, leading to the withdrawal of the marketing authorization. The active ingredient of Exolise being manufactured with 80% ethanol, the question to know whether the extraction solvent could introduce some toxic components was hypothesized. Two investigations were conducted in Wistar rats to determine if repeated oral administration of different green tea extracts could corroborate the reported hepatotoxicity in humans. In a preliminary 6 week-study, experimental groups (n=9/group) received either the vehicle or a methylene chloride extract (2500 mg/kg body weight) where potential non-polar hepatotoxin(s) could be concentrated. In a second experiment (12 week-study), rats were divided in three groups (n=10/group) and treated with either the vehicle, or an aqueous extract (1400 mg/kg) or AR25 green tea extract (2000 mg/kg). Rat liver functions were assessed by serum biochemistry of hepatotoxicity markers. No sign of evidence of characteristic hepatotoxicity was found in rats treated with very high amount of different green tea extracts in these two experiments (respectively a daily dosage, which was about 900 and 80 times higher to the therapeutic daily dosage of Exolise. PMID:16487645

Bun, S S; Bun, H; Guédon, D; Rosier, C; Ollivier, E

2006-07-01

270

Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia.  

PubMed

The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult-to-adult LDLT grafts without anatomical, immunological or hepatitis-related issues were included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH-20) was used to characterize PGD. DFH-20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH-20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PT-INR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH-20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH-20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality. PMID:22494784

Ikegami, T; Shirabe, K; Yoshizumi, T; Aishima, S; Taketomi, Y A; Soejima, Y; Uchiyama, H; Kayashima, H; Toshima, T; Maehara, Y

2012-07-01

271

Characterization and functional studies on rat liver fat-storing cell line and freshly isolated hepatocyte coculture system.  

PubMed Central

We developed and characterized a coculture system composed of a fat-storing cell clone (CFSC-2G) and freshly isolated hepatocytes that can reproduce in vitro some of the physical and functional relationships observed in vivo. Hepatocytes in the coculture are polarized, are smaller in size than hepatocytes plated on plastic, maintain a cuboidal shape, and have a tendency to form cords. Fat-storing cells, which are initially extended, retract and leave spaces that resemble liver sinusoids. Both cell types in the coculture system are functional for at least two weeks as determined by the expression of high levels of liver-specific protein mRNAs as well as by the production and secretion of liver-specific proteins into the culture medium. The hepatocytes maintain relatively high levels of asialoglycoprotein receptor on their cell surface and form functional gap junctional complexes with fat-storing cells. Hence, this coculture system retains a number of differentiated functions of hepatocytes, making it a useful model to study cell-cell interactions in culture and to analyze regulation of hepatocyte functions. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10

Rojkind, M.; Novikoff, P. M.; Greenwel, P.; Rubin, J.; Rojas-Valencia, L.; de Carvalho, A. C.; Stockert, R.; Spray, D.; Hertzberg, E. L.; Wolkoff, A. W.

1995-01-01

272

Liver Transplant  

MedlinePLUS

... Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about liver ... substances from your blood. What is a liver transplant? A liver transplant is the process of replacing ...

273

Purification and properties of L-alanine dehydrogenase of the phototrophic bacterium Rhodobacter capsulatus E1F1.  

PubMed Central

In the phototrophic nonsulfur bacterium Rhodobacter capsulatus E1F1, L-alanine dehydrogenase aminating activity functions as an alternative route for ammonia assimilation when glutamine synthetase is inactivated. L-Alanine dehydrogenase deaminating activity participates in the supply of organic carbon to cells growing on L-alanine as the sole carbon source. L-Alanine dehydrogenase is induced in cells growing on pyruvate plus nitrate, pyruvate plus ammonia, or L-alanine under both light-anaerobic and dark-heterotrophic conditions. The enzyme has been purified to electrophoretic and immunological homogeneity by using affinity chromatography with Red-120 agarose. The native enzyme was an oligomeric protein of 246 kilodaltons (kDa) which consisted of six identical subunits of 42 kDa each, had a Stokes' radius of 5.8 nm, an s20.w of 10.1 S, a D20,w of 4.25 x 10(-11) m2 s-1, and a frictional quotient of 1.35. The aminating activity was absolutely specific for NADPH, whereas deaminating activity was strictly NAD dependent, with apparent Kms of 0.25 (NADPH), 0.15 (NAD+), 1.25 (L-alanine), 0.13 (pyruvate), and 16 (ammonium) mM. The enzyme was inhibited in vitro by pyruvate or L-alanine and had two sulfhydryl groups per subunit which were essential for both aminating and deaminating activities.

Caballero, F J; Cardenas, J; Castillo, F

1989-01-01

274

Antimicrobial activity of antihypertensive food-derived peptides and selected alanine analogues.  

PubMed

This study evaluated four food-derived peptides with known antihypertensive activities for antimicrobial activity against pathogenic microorganisms, and assessed structure-function relationships using alanine analogues. The peptides (EVSLNSGYY, barley; PGTAVFK, soybean; TTMPLW, ?-casein; VHLPP, ?-zein) and the six alanine substitution peptides of PGTAVFK were synthesised, characterised and evaluated for antimicrobial activity using the bacteria, Escherichia coli, Staphylococcus aureus, and Micrococcus luteus and the yeast, Candida albicans. The peptides TTMPLW and PGTAVFK inhibited growth of all four microorganisms tested, with activities of a similar order of magnitude to ampicillin and ethanol controls. EVSLNSGYY inhibited the growth of the bacteria, but VHLPP showed no antimicrobial activity. The alanine analogue, PGAAVFK showed the highest overall antimicrobial activity and PGTAVFA showed no activity; overall, the activities of the analogues were consistent with their structures. Some peptides with antihypertensive activity also show antimicrobial activity, suggesting that food-derived peptides may exert beneficial effects via a number of mechanisms. PMID:24176365

McClean, Stephen; Beggs, Louise B; Welch, Robert W

2014-03-01

275

Solvation structure, thermodynamics, and conformational dependence of alanine dipeptide in aqueous solution analyzed with reference interaction site model theory  

Microsoft Academic Search

With the CHARMM22 (Chemistry at Harvard Macromolecular Mechanics) all-atom nonbonded potential parameters for alanine dipeptide solute and the transferable intermolecular potential model water for the solvent, the reference interaction site model (RISM) integral equations with the hypernetted chain closure are solved to obtain all the atomic solvent-solute radial distribution functions. The solvation structures of alanine dipeptide in its seven conformations:

Qizhi Cui; Vedene H. Smith

2003-01-01

276

Single and repeated dose pharmacokinetics of dexketoprofen trometamol in patients with impaired liver function.  

PubMed

Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. They received 25 mg dexketoprofen (equivalent to 37 mg of its tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8 hours for a total of 10 doses). Dexketoprofen concentrations were determined in plasma and urine by reverse-phase high performance liquid chromatography (HPLC). Model-independent pharmacokinetic parameters were obtained. All subjects completed the study. No serious adverse events were recorded. Following the single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects), 2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B). Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33-1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and 3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9 ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/- 0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration, similar results were obtained showing no drug accumulation. As related to the administered dose, median excretions of unchanged and conjugated dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy volunteers (median and 95% CI for differences: -5.4% [-19.9% to 2.0%] and -19.4% [-45.6% to 0.4%]). Conservatively, a dose adjustment of dexketoprofen trometamol in patients with impaired hepatic function is recommended. PMID:16801990

Valles, J; Artigas, R; Bertolotti, M; Crea, A; Muller, F; Paredes, I; Capriati, A

2006-06-01

277

[Activity of alanine aminopeptidase in blood and in urine of smoking and non-smoking smelters].  

PubMed

The human body is constantly exposed to xenobiotics. This will include exogenous substances from environmental pollution such as heavy metals and lifestyle such as smoking, which may lead to impaired functioning of many organs. The liver and kidney are the critical organs in the case of a long-term occupational or environmental exposure to heavy metals and tobacco smoke. In diagnostics of liver and kidney damage useful are the methods which determine the activity of enzymes such as alanine aminopeptidase (AAP). AAP is a marker for early detection of acute kidney damage, and presence of AAP derive mainly from proximal tubular brush-border. Activity of AAP in urine allows to assess the damage resulting from the nephrotoxic exposure to heavy metals. In the serum AAP is mainly from hepatic. Activity of AAP may be useful to identify liver cancer. The investigation was shown, that AAP activity in the blood is used to detect hepatic cholestasis and congestive jaundice. The aim of present study was to assess the influence of occupational exposure of copper-foundry workers to heavy metals (arsenic, cadmium, lead) on activity of alanine aminopeptidase in blood and urine. The investigations were performed in blood and urine of 166 subjects: 101 male copper smelters and 65 non-exposed male subjects. The study protocol was approved by Local Bioethics Committee of Wroclaw Medical University (KB No: 469/2008). The data on smoking which had been obtained from a direct personal interview were verified by determination of serum cotinine concentrations. Biological material collected from the control group and smelters was divided into subgroups of nonsmokers and smokers. The concentrations of lead and cadmium were determined in whole blood, whilst the level of arsenic and cadmium were determined in urine using FAAS method (Flame Atomic Absorption Spectrometry) in the acetylate flame on the SOLAAR M6. The activity of AA was determined in blood and in urine. The results showed a 9-fold increase in the concentration of lead and 10-fold elevation of arsenic level in all groups of smelters in comparison to the control group. The highest cadmium, lead and arsenic concentrations were observed in blood and urine of smoking smelters. We have observed a significant increase in the concentrations of lead and cadmium in blood of smoking persons from control group in comparison to the non-smoking persons from this group, which suggest, that tobacco smoking increase the heavy metals concentrations in the organisms. Occupational exposure to heavy metals resulted in an increase of AAP activity in blood and urine of all groups of smelters in comparison to corresponding control groups. The highest value of AAP was observed in serum and urine of smoking smelters. Tobacco smoke also increases the AAP activity the blood and urine of smoking smelters and control group compared to the non-smoking smelters and nonsmoking control group, appropriate. The study was shown that occupational exposure to heavy metals and tobacco. PMID:21360924

Bizo?, Anna; Stasiak, Karolina; Milnerowicz, Halina

2010-01-01

278

Protective effect of aqueous extract of Feronia elephantum correa leaves on thioacetamide induced liver necrosis in diabetic rats  

PubMed Central

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.

Sharma, Prashant; Bodhankar, Subhash L; Thakurdesai, Prasad A

2012-01-01

279

Living with Your Liver  

NSDL National Science Digital Library

Students learn the function of the liver and how biomedical engineers can use liver regeneration to help people. Students test the effects of toxic chemicals on a beef liver by adding hydrogen peroxide to various liver and salt solutions. They observe, record and graph their results.

Integrated Teaching And Learning Program

280

MicroRNA Function in the Profibrogenic Interplay upon Chronic Liver Disease  

PubMed Central

In chronic liver disease leading to fibrosis, hepatic stellate cells (HSC) differentiate into myofibroblasts. Myofibroblastic HSC have taken center stage during liver fibrogenesis, due to their remarkable synthesis of extracellular matrix proteins, their secretion of profibrogenic mediators and their contribution to hypertension, due to elevated contractility. MicroRNAs (miRNAs) are small, noncoding RNA molecules of 19–24 nucleotides in length. By either RNA interference or inhibition of translational initiation and elongation, each miRNA is able to inhibit the gene expression of a wide panel of targeted transcripts. Recently, it was shown that altered miRNA patterns after chronic liver disease highly affect the progression of fibrosis by their potential to target the expression of extracellular matrix proteins and the synthesis of mediators of profibrogenic pathways. Here, we underline the role of miRNAs in the interplay of the profibrogenic cell communication pathways upon myofibroblastic differentiation of hepatic stellate cells in the chronically injured liver.

Huang, Jia; Yu, Xiaojie; Fries, Jochen W. U.; Zhang, Li'ang; Odenthal, Margarete

2014-01-01

281

[Physiologic regeneration and functional activity of hepatocytes in normobaric hypoxia].  

PubMed

It was studied the effects of dosed normobaric hypoxia during 14 and 28 days on physiological regeneration and functional activity liver of parenhima fenomenas of adult rats. It was shown that after completion of experiment at rats increase sizes nucleus, the area of cytoplasm decrease, and also is increase the hepatocytes amount on tissue area unit. Concentration albumin increased after 14 days ofnormobaric hypoxia. Activity alanine aminotranferease increased and aspartate aminotransferase activity decreased after 28 days of dosed normobaric hypoxia. Thus our study suggested that normobaric hypoxia stimulante morphological marcers functional action and regenerator liver ability. PMID:20799634

Ianko, R V

2010-01-01

282

Stimulation of liver functions in hierarchical co-culture of bone marrow cells and hepatocytes  

Microsoft Academic Search

A hierarchial co-culture, in which rat hepatocytes and non-parenchymal liver cells (NPLCs) were separated by a collagen layer and which was designed to mimic the in vivo microenvironment, was carried out with the aim of developing a module for bio-artificial liver support. Compared with a monolayer co-culture and hepatocytes cultured alone in a monolayer, higher urea synthesis activity was maintained

Kiyohito Yagi; Nobuaki Sumiyoshi; Yumiko Nakashima; Nobuyasu Michibayashi; Masaya Kawase; Yoshiharu Miura; Tadashi Mizoguchi

1998-01-01

283

Characterization of the alanine racemases from two Mycobacteria  

Microsoft Academic Search

D-Alanine is a necessary precursor in the biosynthesis of the bacterial peptidoglycan. The naturally occurring L-alanine isomer is racemized to its D-form through the action of a class of enzymes called alanine racemases. These enzymes are ubiquitous among prokaryotes, and with very few exceptions are absent in eukaryotes, making them a logical target for the development of novel antibiotics. The

Ulrich Strych; Rebecca L Penland; Margarita Jimenez; Kurt L Krause; Michael J Benedik

2001-01-01

284

Hepatic stellate cells undermine the allostimulatory function of liver myeloid dendritic cells via STAT3-dependent induction of IDO  

PubMed Central

Hepatic stellate cells (HSCs) are critical for hepatic wound repair and tissue remodeling. They also produce cytokines and chemokines that may contribute to the maintenance of hepatic immune homeostasis and the inherent tolerogenicity of the liver. The functional relationship between HSCs and the professional migratory APCs in the liver, i.e. dendritic cells (DCs), has not been evaluated. Here, we report that murine liver DCs co-localize with HSCs in vivo under normal, steady-state conditions, and cluster with HSCs in vitro. In vitro, HSCs secrete high levels of DC chemoattractants, such as MIP1? and MCP-1, as well as cytokines that modulate DC activation, including TNF?, IL-6 and IL-1?. Culture of HSCs with conventional liver myeloid (m) DCs resulted in increased IL-6 and IL-10 secretion compared to that of either cell population alone. Co-culture also resulted in enhanced expression of co-stimulatory (CD80, CD86) and co-inhibitory (B7-H1) molecules on mDCs. HSC-induced mDC maturation required cell-cell contact and could be blocked, in part, by neutralizing MIP1? or MCP-1. HSC-induced mDC maturation was dependent on activation of STAT3 in mDCs and in part on HSC-secreted IL-6. Despite up-regulation of co-stimulatory molecules, mDCs conditioned by HSCs demonstrated impaired ability to induce allogeneic T cell proliferation, which was independent of B7-H1, but dependent upon HSC-induced STAT3 activation and subsequent up-regulation of IDO. In conclusion, by promoting IDO expression, HSCs may act as potent regulators of liver mDCs and function to maintain hepatic homeostasis and tolerogenicity.

Sumpter, Tina L.; Dangi, Anil; Matta, Benjamin M.; Huang, Chao; Stolz, Donna B.; Vodovotz, Yoram; Thomson, Angus W.; Gandhi, Chandrashekhar R.

2012-01-01

285

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

PubMed

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

Harris, Roger C; Stellingwerff, Trent

2013-01-01

286

Investigation of the Potential Relationships Between Plasma Voriconazole Concentrations and Visual Adverse Events or Liver Function Test Abnormalities  

Microsoft Academic Search

This study investigated the relationship between plasma voriconazole concentrations (pVC) and risk of visual adverse events (VAEs) or liver function test (LFT) abnormalities using longitudinal logistic regression. Seven-day mean pVC were calculated from 2925 plasma samples (1053 patients); in each 7-day period, the presence or absence of VAEs\\/abnormal LFTs was analyzed as a binary outcome variable. There was a relationship

Keith Tan; Nigel Brayshaw; Konrad Tomaszewski; Peter Troke; Nolan Wood

2006-01-01

287

Changes in plasma hormones profile and liver function in cows naturally exposed to lead and cadmium around different industrial areas  

Microsoft Academic Search

The present study was carried out to assess the endocrine status and liver function in adult cows reared in polluted environment around different industrial units in India.The effect on endocrine system was examined by determination of plasma level of thyroid hormones, thyroxin (T4) (n=269) and triidothyronin (T3) (n=269), stress hormone cortisol (n=266), and reproductive hormones such as estradiol (n=84) and

D. Swarup; Ram Naresh; V. P. Varshney; M. Balagangatharathilagar; P. Kumar; D. Nandi; R. C. Patra

2007-01-01

288

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

PubMed

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

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

2014-03-01

289

Evaluation of inhibitory guanine nucleotide regulatory protein G i function in hepatocyte and liver membranes from obese Zucker (fa\\/fa) rats and their lean (Fa\\/?) littermates  

Microsoft Academic Search

Summary  Previous studies have shown that hepatocyte and liver membranes from insulin resistant animals exhibit an impairment of inhibitory guanine nucleotide binding regulatory protein, Gi function, such that a Gi defect may contribute towards the diabetic syndrome. In the current studies, it is shown that the demonstration of Gi activity in liver and hepatocyte membranes is dependent critically on the membrane

P. Young; D. M. Kirkham; G. J. Murphy; M. A. Cawthorne

1991-01-01

290

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

PubMed

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

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

2014-01-01

291

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

PubMed Central

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

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

2014-01-01

292

Effect of portal vein ligation on tumor growth and liver regeneration in rat cirrhotic liver lobes  

PubMed Central

The aim of the present study was to investigate the effect of portal vein ligation (PVL) on the tumor growth rate and liver regeneration in rat cirrhotic liver lobes. A total of 45 male Wistar rats were randomly divided into PVL, hepatic tumor (HT) and HT + PVL groups (n=15 per group). Liver regeneration and tumor growth in ligated and non-ligated lobes were evaluated prior to and following PVL. In addition, serum alanine transaminase, total bilirubin levels and liver tissue samples were evaluated. The results indicated that PVL induced apparent hypertrophy in normal and HT rats. However, the ratio of non-ligated lobes to total liver weight or body weight in the HT + PVL group was significantly lower when compared with the PVL group (P<0.05). Compared with the HT group, the tumor growth rate in the ligated lobes of the HT + PVL group significantly increased (P<0.05). However, tumor growth in the non-ligated lobes exhibited no statistically significant difference between the HT and HT + PVL groups. In addition, Knodell scores indicated that fibrosis was more apparent in the non-ligated lobes of the HT + PVL group when compared with the HT group (P<0.05). Therefore, tumor growth was accelerated in ligated lobes following PVL, but not in non-ligated lobes. PVL also induced liver regeneration in cirrhotic liver lobes with lower efficiency than that in the non-cirrhotic lobes. However, hypertrophy in the contralateral cirrhotic lobes appeared to be non-functional.

XU, RUI; YUAN, YU-FENG; AYAV, AHMET; JIANG, CHONG-QING; BRESLER, LAURENT; LIU, ZHI-SU; TRAN, NGUYEN

2014-01-01

293

Breath tests with novel 13c-substrates for clinical studies of liver mitochondrial function in health and disease.  

PubMed

Mitochondrial dysfunction determines the onset and progression of chronic deleterious conditions including liver diseases. The in vivo assessment of mitochondrial function, by providing more insight into the pathogenesis of liver diseases, would be a helpful tool to study specific functions and to develop diagnostic, prognostic and therapeutic strategies. The application of breath tests in the clinical setting to evaluate mitochondrial fitness may elegantly and noninvasively overcome the difficulties due to previous complex techniques and may provide clinically relevant information, i.e the effects of drugs presenting mitochondrial liabilities. Substrates meeting this requirement include alpha-ketoisocaproic acid and methionine, both decarboxylated by mitochondria. Long and medium chain fatty acids that are metabolized through the Krebs cycle and benzoic acid, which undergoes glycine conjugation, may also reflect the mitochondrial performance. This review focuses on the utility of breath tests to assess mitochondrial function in humans, thus contributing to unravel potential mechanisms associated with the dysfunction of this organelle network in the pathophysiology of liver diseases. PMID:24443072

Grattagliano, I; Bonfrate, L; Oliveira, P J; Castorani, L; Ruggiero, V; Valenzano, A T; Ascensão, A; Buzoianu, A; Portincasa, P

2013-12-01

294

Rhinacanthus nasutus Improves the Levels of Liver Carbohydrate, Protein, Glycogen, and Liver Markers in Streptozotocin-Induced Diabetic Rats  

PubMed Central

The present study was designed to investigate the total carbohydrate, total protein, and glycogen levels in the liver and to measure functional liver markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in streptozotocin-(STZ-) induced diabetic rats after treatment with methanolic extract of Rhinacanthus nasutus (R. nasutus). The methanolic extract of R. nasutus was orally administered at 200?mg/kg/day while glibenclamide was administered at 50?mg/kg/day. All animals were treated for 30 days before being sacrificed. The amounts of carbohydrate, glycogen, proteins, and liver markers (AST and ALT) were measured in the liver tissue of the experimental animals. The levels of carbohydrate, glycogen, and proteins were significantly reduced in the diabetic rats but were augmented considerably after 30 days of R. nasutus treatment. The elevated AST and ALT levels in diabetic rats showed a significant decline after treatment with R. nasutus for 30 days. These results show that the administration of R. nasutus ameliorates the altered levels of carbohydrate, glycogen, proteins, and AST and ALT observed in diabetic rats and indicate that R. nasutus restores overall metabolism and liver function in experimental diabetic rats. In conclusion, the outcomes of the present study support the traditional belief that R. nasutus could ameliorate the diabetic state.

Visweswara Rao, Pasupuleti; Madhavi, K.; Dhananjaya Naidu, M.; Gan, Siew Hua

2013-01-01

295

Loss of Survivin influences liver regeneration and is associated with impaired Aurora B function  

PubMed Central

The chromosomal passenger complex (CPC) acts as a key regulator of mitosis, preventing asymmetric segregation of chromosomal material into daughter cells. The CPC is composed of three non-enzymatic components termed Survivin, the inner centromere protein (INCENP) and Borealin, and an enzymatic component, Aurora B kinase. Survivin is necessary for the appropriate separation of sister chromatids during mitosis and is involved in liver regeneration, but its role in regenerative processes is incompletely elucidated. Whether Survivin, which is classified as an inhibitor of apoptosis protein (IAP) based on domain composition, also has a role in apoptosis is controversial. The present study examined the in vivo effects of Survivin ablation in the liver and during liver regeneration after 70% hepatectomy in a hepatocyte-specific knockout mouse model. The absence of Survivin caused a reduction in the number of hepatocytes in the liver, together with an increase in cell volume, macronucleation and polyploidy, but no changes in apoptosis. During liver regeneration, mitosis of hepatocytes was associated with mislocalization of the members of the CPC, which were no longer detectable at the centromere despite an unchanged protein amount. Furthermore, the loss of survivin in regenerating hepatocytes was associated with reduced levels of phosphorylated Histone H3 at serine 28 and abolished phosphorylation of CENP-A and Hec1 at serine 55, which is a consequence of decreased Aurora B kinase activity. These data indicate that Survivin expression determines hepatocyte number during liver development and liver regeneration. Lack of Survivin causes mislocalization of the CPC members in combination with reduced Aurora B activity, leading to impaired phosphorylation of its centromeric target proteins and inappropriate cytokinesis.

Hagemann, S; Wohlschlaeger, J; Bertram, S; Levkau, B; Musacchio, A; Conway, E M; Moellmann, D; Kneiseler, G; Pless-Petig, G; Lorenz, K; Sitek, B; Baba, H A

2013-01-01

296

Ketamine-Xylazine-Acepromazine Compared with Isoflurane for Anesthesia during Liver Transplantation in Rodents  

PubMed Central

Orthotopic liver transplantation in mice and rats is used to study a wide range of scientific questions. Inhalant anesthesia is widely used in liver transplantation models in rodents, but drawbacks of inhalant anesthetics include issues of cost, safety, and ease of use. The goal here was to find an effective injection anesthesia protocol that would not directly influence metabolic or functional parameters after liver transplantation. We compared intraperitoneal injection of a ketamine–xylazine–acepromazine cocktail (KXA) with isoflurane during 50% liver transplantation in mice and rats. Anesthesia with KXA had rapid induction (5 ± 3 min) and a long duration of surgical anesthesia (70 ± 10 min). The 2 methods of anesthesia produced no significant differences in liver injury (histology, serum alanine aminotransferase and total bilirubin concentrations), inflammation (IL6, TNF?, myeloperoxidase activity), regeneration (incorporation of 5-bromo-2?-deoxyuridine, mitotic index, restitution of liver weight), or 7-d survival. In conclusion, a KXA regimen is a safe and effective injectable anesthetic for rodent liver transplantation and is a suitable substitute for currently used inhalant anesthesia. Injectable anesthetics offer advantages in terms of cost, personal safety, and ease of use and will be particularly beneficial to microsurgeons during their training period in liver transplantation.

He, Songqing; Atkinson, Carl; Qiao, Fei; Chen, Xiaoping; Tomlinson, Stephen

2010-01-01

297

Heat Shock Protein 70 Expression is Increased in the Liver of Neonatal Intrauterine Growth Retardation Piglets  

PubMed Central

Intrauterine growth retardation (IUGR) leads to the dysfunction in digestive system, as well as the alteration in the expression of some functional proteins. Heat shock protein 70 (Hsp70) could be induced by various stress factors, but whether Hsp70 expression is changed in neonatal IUGR infants has not been demonstrated. This study was conducted to explore the expression of Hsp70 in the liver by using the IUGR piglet model. Liver and plasma samples were obtained from IUGR and normal birth weight (NBW) piglets at birth. The neonatal IUGR piglets had significantly lower liver weight than their counterparts. The activities of aspartate aminotransferase and alanine aminotransferase in serum were enhanced significantly in IUGR indicating liver dysfunction. The activities of superoxide dismutase (p<0.01), glutathione peroxidase (p<0.01) and catalase (p>0.05) were lower and the level of malondialdehybe was higher (p<0.05) in IUGR liver compared with in NBW. According to the results of histological tests, fatty hepatic infiltrates and cytoplasmic vacuolization were present in the liver of IUGR piglets, but not in NBW liver. The expression of Hsp70 protein was significantly higher (p<0.05) in IUGR piglet liver than in NBW. Similar to where the hepatic injuries were observed, location of Hsp70 was mostly in the midzonal hepatic lobule indicating that oxidative stress might be responsible for the increased expression of Hsp70.

Li, Wei; Zhong, Xiang; Zhang, Lili; Wang, Yuanxiao; Wang, Tian

2012-01-01

298

Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus: A case report  

PubMed Central

We present a case of fetal liver failure caused by the activation of lamivudine-resistant hepatitis B virus (HBV) nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decompensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase (ALT) decreased transiently. However, after the start of ?-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtL80I/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtL80I/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.

Suzuki, Yuka; Yotsuyanagi, Hiroshi; Okuse, Chiaki; Nagase, Yoshihiko; Takahashi, Hideaki; Moriya, Kyoji; Suzuki, Michihiro; Koike, Kazuhiko; Iino, Shiro; Itoh, Fumio

2007-01-01

299

Molecular characterization and clinical use of a polymorphic tandem repeat in an intron of the human alanine: Glyoxylate aminotransferase gene  

Microsoft Academic Search

The autosomal recessive disease primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). This paper concerns the identification, characterization and clinical use of an unusual discretely polymorphic tandem repeat sequence in the fourth intron of the human AGT gene (gene locus designation AGXT). In a random Caucasian population, three alleles could

Christopher J. Danpure; Graeme M. Birdsey; Gillian Rumsby; Michael J. Lumb; P. Edward Purdue; Jennifer Allsop

1994-01-01

300

Pharmacokinetics and safety of candesartan cilexetil in subjects with normal and impaired liver function  

Microsoft Academic Search

Objective: The influence of liver disease on the pharmacokinetics of candesartan, a long-acting selective AT1 subtype angiotensin II receptor antagonist was studied.\\u000a \\u000a \\u000a \\u000a Methods: Twelve healthy subjects and 12 patients with mild to moderate liver impairment received a single oral dose of 12?mg of candesartan\\u000a cilexetil on day 1 and once-daily doses of 12?mg on days 3–7. The drug was taken

J. F. W. Hoogkamer; C. H. Kleinbloesem; M. Ouwerkerk; A. Högemann; A. Nokhodian; W. Kirch; E. Weidekamm

1998-01-01

301

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

NASA Astrophysics Data System (ADS)

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

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

2013-04-01

302

Conditional knockout of heparin-binding epidermal growth factor-like growth factor in the liver accelerates carbon tetrachloride-induced liver injury in mice.  

PubMed

Aim:? We previously demonstrated that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is induced in response to several liver injuries. Because the HB-EGF knockout (KO) mice die in utero or immediately after birth due to cardiac defects, the loss of function study in vivo is limited. Here, we generated liver-specific HB-EGF conditional knockout mice using the interferon-inducible Mx-1 promoter driven cre recombinase transgene and investigated its role during acute liver injury. Methods:? We induced acute liver injury by a single i.p. injection of carbon tetrachloride (CCl4 ) in HB-EGF KO mice and wild-type mice and liver damage was assessed by biochemical and immunohistochemical analysis. We also used AML12 mouse hepatocyte cell lines to examine the molecular mechanism of HB-EGF-dependent anti-apoptosis and wound-healing process of the liver in vitro. Results:? HB-EGF KO mice exhibited a significant increase of alanine aminotransferase level and also showed a significant increase in the number of apoptotic hepatocytes assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining at 24?h after CCl4 injection. We also demonstrated that HB-EGF treatment inhibited tumor necrosis factor-?-induced apoptosis of AML12 mouse hepatocytes and promoted the wound-healing response of these cells. Conclusion:? This study showed that HB-EGF plays a protective role during acute liver injury. PMID:22882498

Takemura, Takayo; Yoshida, Yuichi; Kiso, Shinichi; Saji, Yukiko; Ezaki, Hisao; Hamano, Mina; Kizu, Takashi; Egawa, Mayumi; Chatani, Norihiro; Furuta, Kunimaro; Kamada, Yoshihiro; Iwamoto, Ryo; Mekada, Eisuke; Higashiyama, Shigeki; Hayashi, Norio; Takehara, Tetsuo

2013-04-01

303

Effects of horminone on liver mixed function mono-oxygenases and glutathione enzyme activities of Wistar rat.  

PubMed

The present study reports on the effects of horminone on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, on hepatic cytochrome P450 (P450) and cytochrome b5 (cyt b5) contents and on the activities of NADPH-cytochrome P450 reductase (NR), mixed function mono-oxygenases (MFO), glutathione-S-transferase (GST) and glutathione reductase (GR) of Wistar male rat. Horminone is a diterpenoid quinone (7,12-dihydroxyabiet-8,12-diene-11,14-dione) present in several species of the Labiatae family and used as medicinal plants in folk medicine. In this study, horminone was administered by the intraperitoneal route (i.p.) at a concentration of 1 or 10 mg/kg to each group of six mice, using water as a vehicle. On the one hand, results showed that horminone increased serum ALT and AST levels and cyt b5 content and induced the activities of ethylmorphine N-demethylase (EMD). On the other hand, horminone decreased P450 content and inhibited the activities of 7-ethoxyresorufin O-deethylase (ERD), 7-ethoxycoumarin O-deethylase (ECD), aniline 4-hydroxylase (AH) and NR. Based on these results, the possibility of toxic effects occurring after administration of plant extracts containing horminone must be considered. PMID:9324001

Ferreira, R; Candeias, F; Simões, F; Nascimento, J; Cruz Morais, J

1997-09-01

304

Molecular mechanism of inflammatory response in mouse liver caused by exposure to CeCl?.  

PubMed

To investigate the molecular mechanism of inflammatory response in the mouse liver caused by exposure to CeCl?, we measured the liver indices, and cerium content, evaluated the liver histopathological section, detected serum biochemical parameters of liver function, and the immunoglobulin M (IgM) content, analyzed the liver mRNA and protein expression levels of Toll-like receptor 2, 4 (TLR2, TLR4), and inflammatory cytokines in liver using real-time quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that exposure to CeCl? decreased body weight and caused cerium accumulation in the mouse liver and histopathological changes of liver (such as inflammatory cell infiltration). Furthermore, biochemical assays suggested that CeCl3 could promote the activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, pseudocholinesterase, and leucine aminopeptidase, decrease serum IgM, upregulate the levels of TLR2, TLR4, nuclear factor-?B (NF-?B), NF-?Bp52, NF-?Bp65, NF-?B-inducing kinase (NIK), I?B kinase ? (IKK-?), I?B kinase ? (IKK-?), and tumor necrosis factor-? (TNF-?) expression, and suppress NF-?B-inhibiting factor (I?B) and interleukin-2 (IL-2) expression in liver. Taken together, the inflammation of mice liver caused by exposure to CeCl? might be closely associated with the alteration of inflammatory cytokine expressions in the mouse liver, the signal-transducing events happening in CeCl?-induced macrophages of liver sequentially might occur via activation of TLRs?TNF-??NIK?I?B kinase (including IKK1, IKK2)?NF-?B (including NF-?BP52, NF-?BP65)? inflammation. PMID:21656643

Li, Na; Cheng, Jie; Cheng, Zhe; Hu, Renping; Cai, Jingwei; Gao, Guodong; Cui, Yaling; Wang, Ling; Hong, Fashui

2013-06-01

305

Protection of Liver as a Remote Organ after Renal Ischemia-Reperfusion Injury by Renal Ischemic Postconditioning  

PubMed Central

This study was designed to investigate the protective effects of local renal ischemic postconditioning (POC) on liver damage after renal ischemia-reperfusion (IR) injury. Male rats were divided into three groups??(n = 8). They underwent a right nephrectomy before induction of 45 minutes of left kidney ischemia or sham operation. POC was performed by four cycles of 10 seconds of ischemia and 10 seconds of reperfusion just at the beginning of 24 hours of reperfusion. Then blood and liver samples were collected to measure serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and liver oxidative stress parameters including superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Renal IR caused a significant increase in liver functional indices as demonstrated by increased serum AST and ALT compared to sham group. These parameters reduced significantly in POC group compared to IR group. Liver MDA levels increased and SOD activity decreased in IR group compared to sham group. Induction of POC reduced the elevated liver MDA levels and increased the reduced liver SOD activity. These results revealed that renal IR injury causes liver damage as a remote organ and POC protects liver from renal IR injury by a modification in the hepatic oxidative stress status.

Seifi, Behjat; Kadkhodaee, Mehri; Najafi, Atefeh; Mahmoudi, Atefeh

2014-01-01

306

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

Microsoft Academic Search

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

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

2003-01-01

307

Functional Characterization of Liver Enhancers That Regulate Drug-Associated Transporters  

PubMed Central

Little is known about how genetic variations in enhancers influence drug response. In this study, we investigated whether nucleotide variations in enhancers that regulate drug transporters can alter their expression levels. Using comparative genomics and liver-specific transcription factor binding site (TFBS) analyses, we identified evolutionary conserved regions (ECRs) surrounding nine liver membrane transporters that interact with commonly used pharmaceuticals. The top 50 ECRs were screened for enhancer activity in vivo, of which five—located around ABCB11, SLC10A1, SLCO1B1, SLCO1A2, and SLC47A1—exhibited significant enhancer activity. Common variants identified in a large ethnically diverse cohort (n = 272) were assayed for differential enhancer activity, and three variants were found to have significant effects on reporter activity as compared with the reference allele. In addition, one variant was associated with reduced SLCO1A2 mRNA expression levels in human liver tissues, and another was associated with increased methotrexate (MTX) clearance in patients. This work provides a general model for the rapid characterization of liver enhancers and identifies associations between enhancer variants and drug response.

Kim, MJ; Skewes-Cox, P; Fukushima, H; Hesselson, S; Yee, SW; Ramsey, LB; Nguyen, L; Eshragh, JL; Castro, RA; Wen, CC; Stryke, D; Johns, SJ; Ferrin, TE; Kwok, P-Y; Relling, MV; Giacomini, KM; Kroetz, DL; Ahituv, N

2011-01-01

308

Induced differentiation and maturation of newborn liver cells into functional hepatic tissue in macroporous alginate scaffolds  

Microsoft Academic Search

The present work explores cell cultiva- tion in macroporous alginate scaffolds as a means to reproduce hepatocyte terminal differentiation in vitro. Newborn rat liver cell isolates, consisting of proliferat- ing hepatocytes and progenitors, were seeded at high cell density of 125 106\\/cm3 within the scaffold and then cultivated for 6 wk in chemically defined medium. Within 3 days, the alginate-seeded

Mona Dvir-Ginzberg; Tsiona Elkayam; Smadar Cohen

2007-01-01

309

Effect of syrepar and oxaphenamide on liver function in experimental hypokinesia  

NASA Technical Reports Server (NTRS)

Experiments on albino rats showed that 30 day hypokinesia changes the reaction of the liver to cholagogues. The choleretic action of oxaphenamide as well as its inhibitory effect on synthesis of bile acids diminishes, while the influence of bilirubin secretion increases.

Skakun, L. N.

1980-01-01

310

Turner's syndrome with coeliac disease, thin bones and abnormal liver function tests  

PubMed Central

A patient is described with 45 XO Turner's syndrome and thin bones. It transpired that the patient had osteomalacia due to gluten sensitive enteropathy rather than the osteroporosis usually expected with Turner's syndrome. In addition, she had unexplained liver dysfunction. Causes for thin bones other than the osteoporosis associated with ovarian agenesis should be considered in patients with Turner's syndrome. ImagesFig. 1

Thatcher, N.; Stephens, A. D.; Besser, G. M.

1973-01-01

311

MicroRNA function in the profibrogenic interplay upon chronic liver disease.  

PubMed

In chronic liver disease leading to fibrosis, hepatic stellate cells (HSC) differentiate into myofibroblasts. Myofibroblastic HSC have taken center stage during liver fibrogenesis, due to their remarkable synthesis of extracellular matrix proteins, their secretion of profibrogenic mediators and their contribution to hypertension, due to elevated contractility. MicroRNAs (miRNAs) are small, noncoding RNA molecules of 19-24 nucleotides in length. By either RNA interference or inhibition of translational initiation and elongation, each miRNA is able to inhibit the gene expression of a wide panel of targeted transcripts. Recently, it was shown that altered miRNA patterns after chronic liver disease highly affect the progression of fibrosis by their potential to target the expression of extracellular matrix proteins and the synthesis of mediators of profibrogenic pathways. Here, we underline the role of miRNAs in the interplay of the profibrogenic cell communication pathways upon myofibroblastic differentiation of hepatic stellate cells in the chronically injured liver. PMID:24871365

Huang, Jia; Yu, Xiaojie; Fries, Jochen W U; Zhang, Li'ang; Odenthal, Margarete

2014-01-01

312

Foxo1 integrates insulin signaling with mitochondrial function in the liver  

Microsoft Academic Search

Type 2 diabetes is a complex disease that is marked by the dysfunction of glucose and lipid metabolism. Hepatic insulin resistance is especially pathogenic in type 2 diabetes, as it dysregulates fasting and postprandial glucose tolerance and promotes systemic dyslipidemia and nonalcoholic fatty liver disease. Mitochondrial dysfunction is closely associated with insulin resistance and might contribute to the progression of

Zhiyong Cheng; Shaodong Guo; Kyle Copps; Xiaochen Dong; Ramya Kollipara; Joseph T Rodgers; Ronald A Depinho; Pere Puigserver; Morris F White

2009-01-01

313

Pharmacokinetics of imidapril and its active metabolite imidaprilat following single dose and during steady state in patients with impaired liver function  

Microsoft Academic Search

Objective: The possible influence of impaired liver function on the pharmacokinetic disposition of imidapril, a novel prodrug type\\u000a angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite, imidaprilat, was investigated.\\u000a \\u000a \\u000a \\u000a Methods: Eight subjects with normal liver function and eight patients with liver dysfunction received an oral dose of 10?mg imidapril\\u000a once daily for 7 days.\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a Results: Plasma imidapril concentrations after single

J. F. W. Hoogkamer; C. H. Kleinbloesem; A. Nokhodian; M. J. A. Ouwerkerk; G. Lankhaar; W. Ungethüm; W. Kirch

1997-01-01

314

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

PubMed

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

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

2014-01-01

315

Zingiber officinale acts as a nutraceutical agent against liver fibrosis  

PubMed Central

Background/objective Zingiber officinale Roscoe (ginger) (Zingiberaceae) has been cultivated for thousands of years both as a spice and for medicinal purposes. Ginger rhizomes successive extracts (petroleum ether, chloroform and ethanol) were examined against liver fibrosis induced by carbon tetrachloride in rats. Results The evaluation was done through measuring antioxidant parameters; glutathione (GSH), total superoxide dismutase (SOD) and malondialdehyde (MDA). Liver marker enzymes; succinate and lactate dehydrogenases (SDH and LDH), glucose-6-phosphatase (G-6-Pase), acid phosphatase (AP), 5'- nucleotidase (5'NT) and liver function enzymes; aspartate and alanine aminotransferases (AST and ALT) as well as cholestatic markers; alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin were estimated. Liver histopathological analysis and collagen content were also evaluated. Treatments with the selected extracts significantly increased GSH, SOD, SDH, LDH, G-6-Pase, AP and 5'NT. However, MDA, AST, ALT ALP, GGT and total bilirubin were significantly decreased. Conclusions Extracts of ginger, particularly the ethanol one resulted in an attractive candidate for the treatment of liver fibrosis induced by CCl4. Further studies are required in order to identify the molecules responsible of the pharmacological activity.

2011-01-01

316

Characterization of a histidine- and alanine-rich protein showing interaction with calreticulin in rice  

Microsoft Academic Search

Calreticulin (CRT) is a major calcium-sequestering protein in the endoplasmic reticulum and has been implicated in a variety\\u000a of cellular functions. To analyze the function of CRT in rice, a yeast two-hybrid protein interaction assay was used for identifying\\u000a interacting proteins. Fourteen of 17 interacting cDNA clones found coded for a novel histidine- and alanine-rich protein (OsHARP)\\u000a of 342 amino

Setsuko Komatsu; Asad Jan; Yasunori Koga

2009-01-01

317

Long-term day-and-night rotating shift work poses a barrier to the normalization of alanine transaminase.  

PubMed

To evaluate the impact of day-and-night rotating shift work (RSW) on liver health, we performed a retrospective analysis of the association between long-term RSW exposure and the normalization of plasma alanine transaminase (ALT) levels over a five-year period. The data from physical examinations, blood tests, abdominal sonographic examinations, personal histories, and occupational records were collected from a cohort of workers in a semiconductor manufacturing company. The sample population was divided into three subgroups for analysis, according to self-reported shift work status over the five-year interval: persistent daytime workers, workers exposed intermittently to RSW (i-RSW), and workers exposed persistently to RSW (p-RSW). Records were analyzed for 1196 male workers with an initial mean age of 32.5 years (SD 6.0 years), of whom 821 (68.7%) were identified as rotating shift workers, including 374 i-RSW (31.3%) and 447 p-RSW workers (37.4%). At the beginning of the follow-up, 275 were found to have elevated ALT (e-ALT): 25.1% daytime workers, 23.0% i-RSW workers, and 21.3% p-RSW workers (p?=?0.098). Of those with e-ALT at the beginning, 101 workers showed normalized serum ALT levels at the end of five-year follow-up: 40 (10.7%) of 375 daytime workers, 32 (8.6%) of 374 i-RSW workers, and 29 (6.5%) of 447 p-RSW workers (p?=?0.016). Compared with the workers having persistent e-ALT at the end of follow-up, the workers normalized serum ALT levels had significantly lesser exposures to RSW during follow-up. By performing multivariate logistic regression analyses, and comparing with the persistent daytime co-workers, after controlling for confounding variables (age, occupational factors, educational levels, lifestyle factors, metabolic syndrome, hepatovirus infection, and fatty liver), analysis indicated that the workers exposed to p-RSW were 46% less likely (OR, 0.54; 95% CI, 0.30-0.95; p?=?0.03) to attain normal ALT levels within a five-year interval. These observations demonstrate that persistent day-and-night RSW pose a vigorous obstacle to the normalization of e-ALT among workers with preexisting abnormal liver function. We suggest that workers and managers approach with caution the consideration of assigning or accepting long-term day-and-night RSW when an employee health screening shows evidence of abnormal liver function. PMID:24354767

Lin, Yu-Cheng; Hsieh, I-Chun; Chen, Pau-Chung

2014-05-01

318

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

PubMed Central

Background & Aims There is a clinical need for methods that can quantify regional hepatic function noninvasively in patients with cirrhosis. Here we validate the use of 2-[18F]fluoro-2-deoxy-d-galactose (FDGal) PET/CT for measuring regional metabolic function for this purpose and apply the method to test the hypothesis of increased intrahepatic metabolic heterogeneity in cirrhosis. Methods Nine cirrhotic patients underwent dynamic liver FDGal PET/CT with blood samples from a radial artery and liver vein. Hepatic blood flow was measured by indocyanine green infusion/Fick’s principle. From blood measurements, hepatic systemic clearance (Ksyst, l blood/min) and hepatic intrinsic clearance (Vmax/Km, l blood/min) of FDGal were calculated. From PET data, hepatic systemic clearance of FDGal in liver parenchyma (Kmet, ml blood/ml liver tissue/min) was calculated. Intrahepatic metabolic heterogeneity was evaluated in terms of coefficient of variation (CoV, %) using parametric images of Kmet. Results Mean approximation of Ksyst to Vmax/Km was 86% which validates the use of FDGal as PET tracer of hepatic metabolic function. Mean Kmet was 0.157 ml blood/ml liver tissue/min, which was lower than 0.274 ml blood/ml liver tissue/min previously found in healthy subjects (p <0.001) in accordance with decreased metabolic function in cirrhotic livers. Mean CoV for Kmet in liver tissue was 24.4% in patients and 14.4% in healthy subjects (p <0.0001). The degree of intrahepatic metabolic heterogeneity correlated positively with HVPG (p <0.05). Conclusions A 20 min dynamic FDGal PET/CT with arterial sampling provides an accurate measure of regional hepatic metabolic function in patients with cirrhosis. This is likely to have clinical implications for assessment of patients with liver disease as well as treatment planning and monitoring.

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

2013-01-01

319

Are liver function tests, pancreatitis and cholecystitis predictors of common bile duct stones? Results of a prospective, population-based, cohort study of 1171 patients undergoing cholecystectomy  

PubMed Central

Objective: The purpose of this study was to explore the accuracy of elevated liver function values, age, gender, pancreatitis and cholecystitis as predictors of common bile duct stones (CBDS). Methods: All patients operated on for gallstone disease over a period of 3 years in a Swedish county of 302 564 citizens were registered prospectively. Intraoperative cholangiography (IOC) was used to detect CBDS. Results: A total of 1171 patients were registered; 95% of these patients underwent IOC. Common bile duct stones were found in 42% of patients with elevated liver function values, 20% of patients with a history of pancreatitis and 9% of patients with cholecystitis. The presence of CBDS was significantly predicted by elevated liver function values, but not by age, gender, history of acute pancreatitis or cholecystitis. A total of 93% of patients with normal liver function tests had a normal IOC. The best agreement between elevated liver function values and CBDS was seen in patients undergoing elective surgery without a history of acute pancreatitis or cholecystitis. Conclusions: Although alkaline phosphatase (ALP) and bilirubin levels represented the most reliable predictors of CBDS, false positive and false negative values were common, especially in patients with a history of cholecystitis or pancreatitis, which indicates that other mechanisms were responsible for elevated liver function values in these patients.

Videhult, Per; Sandblom, Gabriel; Rudberg, Claes; Rasmussen, Ib Christian

2011-01-01

320

Effect of oxidative stress on expression and function of human and rat organic anion transporting polypeptides in the liver.  

PubMed

Reactive oxygen species (ROS) have physiological function and involve alteration of physical state. However, it is not clear effect of oxidative stress on pharmacokinetics. Organic anion transporting polypeptides (human: OATPs, rodent: Oatps) are important for uptake of endogenous and exogenous compounds into hepatocytes. Thus, alteration of OATPs/Oatps expression level may affect pharmacokinetics of various drugs. In this study, we investigated the alteration of OATPs/Oatps expression levels and function by oxidative stress, and the effect of alteration of those on pharmacokinetics of a typical OATPs/Oatps substrate pravastatin. OATPs/Oatps expression levels and function were altered by H2O2-induced oxidative stress in in vitro experiments. The alteration of Oatps expression by oxidative stress also occurred in in vivo experiments. Oatp1a1, Oatp1a4 and Oatp1b2 expression in the liver were decreased in rats fed powdery diet containing 2% inosine, which induces oxidative stress through activation of xanthine oxidase, for 1 day. The decrease in Oatps expression levels by oxidative stress caused the suppression of pravastatin uptake to the liver, and resulted in high plasma concentration of pravastatin and low biliary excretion. In conclusion, oxidative stress induces alteration of OATPs/Oatps expression and function in hepatocytes, resulting in alteration of pharmacokinetics of their substrates. PMID:24409515

Tsujimoto, Takashi; Ogura, Jiro; Kuwayama, Kaori; Koizumi, Takahiro; Sasaki, Shunichi; Terada, Yusuke; Kobayashi, Masaki; Yamaguchi, Hiroaki; Iseki, Ken

2013-12-31

321

Prolonged, but transient, elevation of liver and biliary function tests in a healthy infant affected with breast milk jaundice.  

PubMed

Unconjugated hyperbilirubinaemia is a common finding in newborns. When it is exaggerated, it is usually investigated in order to exclude several diseases, such as newborn's haemolytic diseases, infections or hypothyroidism. Breast milk jaundice is a form of neonatal jaundice related to breast feeding and it is not usually associated with any clinical issue and/or other laboratory abnormalities. We describe a case of breast milk jaundice being associated, unexpectedly, to significant elevation of plasmatic liver and biliary enzymes. Despite the infant's good clinical condition and growth, several investigations were performed and these ruled out metabolic, infectious and autoimmune liver diseases. All liver function tests normalised by 6-7?months of life. We suggest that the finding of hypertransaminasaemia and hyper-?-glutamyl transpeptidase in a benign clinical context (similar to what we described) should be followed for 6-7?months before performing sophisticated and expensive diagnostic investigations which aim at excluding some unlikely and severe diseases in a completely asymptomatic infant. PMID:24872488

Poddighe, Dimitri; Castelli, Lucia; Marseglia, Gian Luigi; Bruni, Paola

2014-01-01

322

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

PubMed

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

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

2014-06-01

323

[The functional and morphological changes in the liver and kidneys of white rats treated with aluminum].  

PubMed

A total of 126 white male Wistar rats under subacute conditions were studied. Of them, 76 were perorally treated with AlCl3 in a dose of 3 mg/kg b.w. daily for 40 days. Activities of acid phosphatase (AP), succinate dehydrogenase (SDH), adenosine triphosphatase (ATP-ase) and the contents of glycogen, glucoproteins and RNA were dynamically followed-up in the liver and kidney. Serum activities of ASAT and ALAT were estimated by Borhringer's tests. Morphological changes were histochemically investigated. There was an initial elevation followed by reduction mostly manifested for SDH and ATP-ase and an increase of AP at the end of trial. Histochemical data argued for disorders of protein and carbohydrate metabolism. Morphological alterations more outlined in the liver became more severe until the end of the experiment. PMID:8713350

Nikolova, P; Softova, E; Kavaldzhieva, B; Boiadzhieva, S

1994-01-01

324

Frequent occurrence of high gamma-glutamyl transferase and alanine amino transferase among Nigerian patients with type 2 diabetes.  

PubMed

Liver function tests (LFTs) are commonly deranged in diabetic patients. There is, however, paucity of local data on actual prevalence and pattern of LFTs abnormality among diabetic patients. A case-control study was carried out to study the pattern of LFTs abnormality among patients with type 2 diabetes (DM). Ninety consecutive patients with type 2 diabetes attending Medical Outpatient Clinic of the University College Hospital, Ibadan, and 90 nondiabetic controls with comparable age and sex were recruited into the study. Serum albumin, alanine amino transferase (ALT) and Gamma glutamyl transpeptidase (GGT) were tested in all subjects. Data were analyzed using Student's t-test, chi-square test and Mann-Whitney U. Among the diabetic patients, 70% had at least one deranged LFTs. The ALT and GGT values were significantly higher (52.9 IU/L and 24.3 U/L respectively) in the diabetic group compared to the controls (34.4 IU/L and 9.2 U/L respectively). Also, the most predominant LFT abnormality in diabetic group was isolated elevation of GGT. This study has confirmed the reported common derangement of LFTs in patients with type 2 DM. In addition, isolated elevation of GGT and ALT are common in Nigerian type 2 diabetic patients. There is need for further study to determine the significance of high GGT and ALT in Nigerian type 2 diabetic population. PMID:18939403

Balogun, W O; Adeleye, J O; Akinlade, K S; Adedapo, K S; Kuti, M

2008-06-01

325

Clinical and virological characteristics of untreated patients with chronic hepatitis C who develop serum alanine aminotransferase flare-up.  

PubMed

Among patients with chronic hepatitis C virus (HCV) infection, serum alanine aminotransferase (ALT) rarely increases above 500 IU/L. We examined the clinical and virological features of untreated patients with serum ALT > or = 500 IU/L. One thousand seven hundred and sixty adult patients with chronic HCV infection were followed-up. Among these patients, 22 developed ALT flare-up (M:F=13:9, median age, 50.5 years). We evaluated liver function tests, genotype, and viral titer in these patients and 44 randomly selected age- and sex-matched control without ALT flare-up. In four patients with ALT flare-up, we examined changes in viral loads and sequential changes in amino acid sequences of the core region, hypervariable region 1 (HVR1), and interferon sensitivity determining region (ISDR) before and after ALT flare-up. Multivariate analysis identified genotype 2 as the only significant determinant of ALT flare-up. ALT flare-up occurred in three of four patients without increase in viral load. Several alterations in amino acids were noted in HVR1 before and within 6 months of ALT flare-up. One or two alterations in the core region and many alterations in HVR1 were noted after ALT flare-up in some patients. Genotype 2 is an important factor for ALT flare-up. However, we could not directly relate ALT flare-up to these alterations in amino acids of the core region, HVR1, and ISDR. PMID:15602722

Hiraga, Nobuhiko; Suzuki, Fumitaka; Akuta, Norio; Suzuki, Yoshiyuki; Sezaki, Hitomi; Hosaka, Tetsuya; Someya, Takashi; Kobayashi, Masahiro; Saitoh, Satoshi; Arase, Yasuji; Ikeda, Kenji; Kobayashi, Mariko; Matsuda, Marie; Watabiki, Sachiko; Satoh, Junko; Kumada, Hiromitsu

2005-02-01

326

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

PubMed

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

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

2013-06-01

327

Functional expression of carnitine/organic cation transporter OCTN1/SLC22A4 in mouse small intestine and liver.  

PubMed

Carnitine/organic cation transporter (OCTN1/SLC22A4) accepts various therapeutic agents as substrates in vitro and is expressed ubiquitously, although its function in most organs has not yet been examined. The purpose of the present study was to evaluate functional expression of OCTN1 in small intestine and liver, using octn1 gene knockout [octn1(-/-)] mice. After oral administration of [(3)H]ergothioneine ([(3)H]ERGO), a typical substrate of OCTN1, the amount of [(3)H]ERGO remaining in the small intestinal lumen was much higher in octn1(-/-) mice than in wild-type mice. In addition, uptake of [(3)H]ERGO by human embryonic kidney 293 cells heterologously expressing OCTN1 gene product and uptake of [(3)H]ERGO at the apical surface of intestinal everted sacs from wild-type mice were inhibited by OCTN1 substrates, tetraethylammonium and verapamil. Immunohistochemical analysis revealed that OCTN1 is localized on the apical surface of small intestine in mice and humans. These results suggest that OCTN1 is responsible for small intestinal absorption of [(3)H]ERGO. However, the plasma concentration of [(3)H]ERGO after oral administration was higher in octn1(-/-) mice than in wild-type mice, despite the lower absorption in octn1(-/-) mice. This was probably because of efficient hepatic uptake of [(3)H]ERGO, as revealed by integration plot analysis; the uptake clearance was close to the hepatic plasma flow rate. The uptake of [(3)H]ERGO by isolated hepatocytes was minimal, whereas [(3)H]ERGO uptake was observed in isolated nonparenchymal cells. This finding is consistent with immunostaining of OCTN1 in liver sinusoids. Thus, our results indicate that OCTN1 is functionally expressed in nonparenchymal liver cells. PMID:20601551

Sugiura, Tomoko; Kato, Sayaka; Shimizu, Takuya; Wakayama, Tomohiko; Nakamichi, Noritaka; Kubo, Yoshiyuki; Iwata, Daisuke; Suzuki, Kazuhiro; Soga, Tomoyoshi; Asano, Masahide; Iseki, Shoichi; Tamai, Ikumi; Tsuji, Akira; Kato, Yukio

2010-10-01

328

In vivo and in vitro effects of aluminum treatment on rat liver mitochondrial function  

Microsoft Academic Search

This study examines the effect on mitochondrial respiration and permeability of in vivo and in vitro aluminium (Al) exposure.\\u000a Rats were treated intraperitoneally with AlCl3 to achieve serum and liver Al concentrations comparable to those seen in Al-related disorders. Mitochondria isolated from\\u000a Al-treated rats had higher (pp<0.05) state 3 respiration, respiratory control (RCR), and ADP\\/O ratio (succinate substrate), and greater

Maria Burnatowska-Hledin; Karl V. Ebner; Gilbert H. Mayor

1986-01-01

329

[Exocrine function of the pancreas in patients with chronic hepatitis and liver cirrhosis of various etiologies].  

PubMed

Exocrinous performance of the pancreatic gland under secretin-pancreozymin stimulation was studied in 76 patients with chronic diffuse diseases of the liver who were distinguished into 6 groups: those who suffered from chronic persistent hepatitis of viral and alcohol origin, chronic active hepatitis of viral origin, cirrhosis of the liver of viral and alcohol origin, primary biliary hepatocirrhosis. The results obtained were correlated with those from 11 normal persons (controls). Out of 76 examinees the disorders of exocrinous performance of the pancreatic gland were revealed in 75 persons. The most characteristic features were: a decrease in the basal and an increase in the stimulated volume of the pancreatic juice; a reduction of both basal and stimulated production of bicarbonates; a decrease in the trypsin and amylase fasting levels and their increment in the stimulated juice of the pancreatic gland. Disorder in the production of bicarbonates was stated as a most characteristic feature in the patients both with viral and alcohol origin of the disease but it was mostly manifest in the patients with hepatocirrhosis. Pronounced elevation of the activity of amylase and trypsin in the pancreatic juice was observed in patients with very high activity of disease development and in the patients who continuously used large amounts of alcohol. The authors suspected that alcohol abuse and the effect of hepatitis virus had an equal pathogenic impact on the liver and pancreatic gland. PMID:8145501

Kataev, S S; Vasil'eva, N S; Avdeev, V G; Gil'var, L L; Starodvortseva, V G; Za?rat'iants, O V

1993-01-01

330

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

PubMed Central

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

1977-01-01

331

21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.  

Code of Federal Regulations, 2010 CFR

...false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section...1030 Alanine amino transferase (ALT/SGPT) test system. (a) Identification. An alanine amino transferase (ALT/SGPT) test system is a device intended...

2009-04-01

332

21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.  

Code of Federal Regulations, 2010 CFR

...false Alanine amino transferase (ALT/SGPT) test system. 862.1030 Section...1030 Alanine amino transferase (ALT/SGPT) test system. (a) Identification. An alanine amino transferase (ALT/SGPT) test system is a device intended...

2010-04-01

333

Transcriptome analysis of garlic-induced hepatoprotection against alcoholic fatty liver.  

PubMed

Fatty liver induced by alcohol abuse is a major worldwide health hazard leading to morbidity and mortality. Previous studies indicate antifatty liver properties of garlic. This study investigated the molecular mechanisms of garlic oil (GO) or diallyl disulfide (DADS) imparted hepatoprotection against alcohol induced fatty liver in C57BL/6 mice using microarray-based global gene expression analysis. Alcohol liquid diet resulted in severe fatty liver with increased levels of serum aspartate aminotransferease and alanine aminotransferease as well as triglycerides and decreased levels of liver glutathione and antioxidant enzymes. The major canonical pathways implicated by alcohol treatment are the metabolisms of xenobiotics by cytochrome P450, glutathione, and arachidonic acid. Treatment with DADS or GO normalized the serum aminotransferease levels and liver antioxidant enzymes and reduced the contents of triglycerides and cholesterol. The canonical pathways involved in the amelioration of liver include arachidonic acid metabolism, altered T cell and B cell signaling, tryptophan metabolism, antigen presentation pathway for DADS, metabolism of xenobiotics, mitotic roles of Polo-like kinase, fatty acid metabolism, LPS/IL-1 mediated inhibition of RXR function, and C21-steroid hormone metabolism for GO. PMID:23066854

Raghu, Rajasekaran; Liu, Chun-Ting; Tsai, Mong-Hsun; Tang, Xiaojia; Kalari, Krishna R; Subramanian, Subbaya; Sheen, Lee-Yan

2012-11-01

334

Rise in liver enzymes after laproscopic cholecystectomy: a transient phenomenon.  

PubMed

The purpose of this study was to investigate the effect of laparoscopic surgery on liver function in humans and the possible mechanisms behind such effect. Blood samples from 30 patients who underwent laparoscopic cholecystectomy (LC) and 20 patients who underwent open cholecystectomy (OC) were tested for liver function by measuring the level of serum alanine aminotrasferase (ALT) and aspartate aminotrasferase (AST) before and after surgery. The level of serum ALT and AST increased significantly during the first 24 hours after surgery in laparoscopic cholecystectomy. However, no significant change of the serum liver enzymes was detected in open cholecystectomy patients. As a result, there was statistically significant difference in change of both ALT and AST levels between LC and OC patients. The effect was transient and reverted back to normal by the 7th day post operation. Transient elevation of hepatic transaminases occurred after laparoscopic surgery. The major causative factor seemed to be the CO2 pneumoperitoneum. In most of the laparoscopic surgery patients, the transient elevation of serum liver enzymes showed no apparent clinical implications. PMID:24047021

Koirala, R; Shakya, V C; Khania, S; Adhikary, S; Agrawal, C S

2012-09-01

335

Impact of the Removal of the Monthly Liver Function Test Requirement for Ambrisentan  

PubMed Central

Background The management of patients with pulmonary arterial hypertension (PAH) requires extensive coordination between patients, their support system, third-party payers, and healthcare professionals. For patients with PAH who are receiving endothelin receptor antagonists (ERAs), such cross-stakeholder coordination was needed to ensure compliance with a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) requirement for monthly liver function tests (LFTs). In March 2011, the FDA removed this requirement for ambrisentan (Letairis) in conjunction with a change to the product label. Objective This study sought to explore the impact of the ambrisentan label change on payers, providers who treat PAH, and specialty pharmacies. Methods This study, conducted in June and July 2011, involved telephone interviews with 5 medical/pharmacy directors in commercial health plans (representing 78,345,000 covered lives collectively); written surveys and telephone interviews with 6 nurses managing patients with PAH; and written surveys and telephone interviews with 4 staff members from specialty pharmacies to determine direct and indirect cost-savings associated with the removal of the monthly LFT requirement for ambrisentan. Qualitative telephone interviews with payer decision makers informed the cost-savings for payers. Direct cost-savings were calculated from the responses of the nurses managing PAH regarding the prescribing trends of their practices and the frequency of LFTs. Indirect cost-savings were calculated using time-savings data collected from the PAH-managing nurses and the specialty pharmacy staff, as well as from the US Bureau of Labor Statistics data regarding national wage averages for the respective staff. Results: Payers reported that REMS requirements did not play a large role in their plan's coverage or management of ERAs; although direct cost-savings resulting from the label change were an estimated $28 per patient per month, this amount is relatively small compared with the overall cost of PAH treatment for payers. The impact of the ambrisentan label change was more significant for providers and specialty pharmacies. The label change resulted in a significant, average 69% reduction in the frequency of LFTs for patients using ambrisentan. The average monthly time-savings realized by providers as a result of the label change was 12 minutes per patient receiving ambrisentan, and the average monthly direct and indirect cost-savings totaled $10.75 and $29.75, respectively, per patient taking ambrisentan. Telephone interviews with specialty pharmacies indicated that the average monthly time-savings for the 4 specialty pharmacies surveyed was 14 minutes per patient using ambrisentan, representing an 86.7% decrease in the amount of time specialty pharmacies spent on LFT-related administrative tasks for patients using ambrisentan. Conclusion Findings from this study indicate that the ambrisentan label change significantly reduced the number of LFTs for patients with PAH, resulting in time-savings or cost-savings for payers, providers, and specialty pharmacies.

Durst, Louise A.; Carlsen, John; Kuchinski, Megan; Harner, Lauren; Neves, Daniel; Harris, Stephanie J.; Traiger, Glenna L.

2012-01-01

336

Liver Cancer  

MedlinePLUS

... cancer has not spread, for some patients a liver transplant (replacement of the liver) may be an option. ... outlook for patients with liver cancer? A successful liver transplant will effectively cure liver cancer, but it is ...

337

Liver metastases  

MedlinePLUS

Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic ... Almost any cancer can spread to the liver. Cancers that may spread to the liver include: Breast cancer Colorectal cancer Esophageal ...

338

Preparation and Characterisation of Pva Doped with Beta Alanine  

NASA Astrophysics Data System (ADS)

Pure PVA has been doped with different amount of ? - alanine. Film has been prepared by Solution Casting Technique using water as a solvent. The Complex formation between the PVA and ? - alanine has been confirmed by FTIR. The Pure PVA conductivity is in the order 10-10 Scm-1 at ambient temperature. The conductivity has been found to increase to the order 10-6 when doped with 10% ? - alanine. In this paper characterization of a PVA doped with ?-ala has been studied using XRD, FTIR, AC impedance analysis and the results are reported.

Bhuvaneshwari, R.; Karthikeyan, S.; Rajeswari, N.; Selvasekarapandian, S.; Sanjeeviraja, C.

2013-07-01

339

Optical and Spectral Studies on ? Alanine Metal Halide Hybrid Crystals  

NASA Astrophysics Data System (ADS)

We have synthesized and grown ? alanine metal halide hybrid crystals viz. ? alanine cadmium chloride (BACC), an amino acid transition metal halide complex crystal and ? alanine potassium chloride (BAPC), an amino acid alkali metal halide complex crystal by slow evaporation method. The grown crystals were found to be transparent and have well defined morphology. The optical characteristics of the grown crystals were carried out with the help of UV-Vis Spectroscopy. The optical transmittances of the spectrums show that BAPC is more transparent than BACC. The Photoluminescence of the materials were determined by the Photoluminescent Spectroscopy

Sweetlin, M. Daniel; Selvarajan, P.; Perumal, S.; Ramalingom, S.

2011-10-01

340

Nucleation kinetics, growth and studies of ?-alanine single crystals  

NASA Astrophysics Data System (ADS)

Solubility and metastable zone width for the re-crystallized salt of ?-alanine was determined. Induction period measurement for the selected supersaturation ratios at room temperature (31 °C) was carried out for supersaturated aqueous solutions of ?-alanine and it is noticed that induction period decreases with increase of supersaturation ratio. The nucleation parameters such as Gibbs free energy change, radius and number of molecules of the critical nucleus, interfacial tension and the nucleation rate have been evaluated by classical nucleation theory. Single crystals of ?-alanine were grown using the optimized nucleation parameters by solution method and grown crystals have been subjected to various studies like XRD studies, FTIR, optical, thermal and SHG studies.

Shanthi, D.; Selvarajan, P.; HemaDurga, K. K.; Lincy Mary Ponmani, S.

2013-06-01

341

Effects of late evening snack including branched-chain amino acid on the function of hepatic parenchymal cells in patients with liver cirrhosis.  

PubMed

Aim:? A late evening snack (LES) improves protein-energy malnutrition due to overnight starvation and the catabolic state in patients with liver cirrhosis. Our aim was to examine whether LES including a branched-chain amino acid (BCAA) could maintain hepatic reserve and the function of hepatic parenchymal cells in patients with liver cirrhosis, including those in the early stage of disease. Methods:? Seventeen patients with liver cirrhosis received LES with a BCAA-enriched nutrient mixture. During the study period, each patient was instructed on energy and protein intake. Indicators of liver function measured at 6?months included maximum asialoscintigraphic removal (Rmax: indicator of total liver receptors), asialoscintigraphic imaging grade, serum albumin, ammonia, tyrosine and BTR (molar ratio of branched-chain amino acids to tyrosine). Results:? Serum albumin levels, BTR and tyrosine levels of the 17 patients were significantly improved after nutrient treatment. In patients with Rmax of 0.2 or higher, serum albumin level and tyrosine level were significantly improved. Conclusion:? LES with BCAA-enriched nutrient therapy can improve protein malnutrition in patients with liver cirrhosis, and is more useful in the early stages of liver cirrhosis in improving hepatic parenchymal cell mass. PMID:21518402

Koreeda, Chizu; Seki, Toshihito; Okazaki, Kazuichi; Ha-Kawa, Sang Kil; Sawada, Satoshi

2011-05-01

342

Biochemical and structural characterization of alanine racemase from Bacillus anthracis (Ames)  

PubMed Central

Background Bacillus anthracis is the causative agent of anthrax and a potential bioterrorism threat. Here we report the biochemical and structural characterization of B. anthracis (Ames) alanine racemase (AlrBax), an essential enzyme in prokaryotes and a target for antimicrobial drug development. We also compare the native AlrBax structure to a recently reported structure of the same enzyme obtained through reductive lysine methylation. Results B. anthracis has two open reading frames encoding for putative alanine racemases. We show that only one, dal1, is able to complement a D-alanine auxotrophic strain of E. coli. Purified Dal1, which we term AlrBax, is shown to be a dimer in solution by dynamic light scattering and has a Vmax for racemization (L- to D-alanine) of 101 U/mg. The crystal structure of unmodified AlrBax is reported here to 1.95 Å resolution. Despite the overall similarity of the fold to other alanine racemases, AlrBax makes use of a chloride ion to position key active site residues for catalysis, a feature not yet observed for this enzyme in other species. Crystal contacts are more extensive in the methylated structure compared to the unmethylated structure. Conclusion The chloride ion in AlrBax is functioning effectively as a carbamylated lysine making it an integral and unique part of this structure. Despite differences in space group and crystal form, the two AlrBax structures are very similar, supporting the case that reductive methylation is a valid rescue strategy for proteins recalcitrant to crystallization, and does not, in this case, result in artifacts in the tertiary structure.

Counago, Rafael M; Davlieva, Milya; Strych, Ulrich; Hill, Ryan E; Krause, Kurt L

2009-01-01

343

Metabolomics analysis identifies d-Alanine-d-Alanine ligase as the primary lethal target of d-Cycloserine in mycobacteria.  

PubMed

d-Cycloserine is an effective second line antibiotic used as a last resort to treat multi (MDR)- and extensively (XDR) drug resistant strains of Mycobacterium tuberculosis . d-Cycloserine interferes with the formation of peptidoglycan biosynthesis by competitive inhibition of alanine racemase (Alr) and d-alanine-d-alanine ligase (Ddl). Although the two enzymes are known to be inhibited, the in vivo lethal target is still unknown. Our NMR metabolomics work has revealed that Ddl is the primary target of DCS, as cell growth is inhibited when the production of d-alanyl-d-alanine is halted. It is shown that inhibition of Alr may contribute indirectly by lowering the levels of d-alanine, thus allowing DCS to outcompete d-alanine for Ddl binding. The NMR data also supports the possibility of a transamination reaction to produce d-alanine from pyruvate and glutamate, thereby bypassing Alr inhibition. Furthermore, the inhibition of peptidoglycan synthesis results in a cascading effect on cellular metabolism as there is a shift toward the catabolic routes to compensate for accumulation of peptidoglycan precursors. PMID:24303782

Halouska, Steven; Fenton, Robert J; Zinniel, Denise K; Marshall, Darrell D; Barletta, Raúl G; Powers, Robert

2014-02-01

344

FR167653 attenuates murine immunological liver injury  

Microsoft Academic Search

Abstract AIM: Tostudy the effect of FR167653 on immunological liver injury (ILI) in mice. METHODS: ILI was,established by tail vein injection of 2.5 mg Bacillus Calmette-Guerin(BCG), and 10 d later with 10 mg lipopolysaccharide (LPS) in 0.2 mL saline (BCG plus LPS). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) in sera,and,malondialdehyde (MDA), glutathione peroxidase (GSHpx) contents in liver homogenates,were,assayed,by spectrophotometry. The

Hong-wei Yao; Jun Li; Ji-qiang Chen; Zhejiang Respiratory Drugs

345

Liver Protective Effects of Morinda citrifolia (Noni)  

Microsoft Academic Search

This study evaluated the protective effects of Noni fruit juice on acute liver injury induced by carbon tetrachloride (CCl4) in female Sprague-Dawley (SD) rats. Liver damage (micro-centrilobular necrosis) was observed in animals pretreated with\\u000a 20% placebo (drinking water) + CCl4. However, pretreatment with 20% Noni juice in drinking water + CCl4 resulted in markedly decreased hepatotoxic lesions. Furthermore, serum alanine

Mian-Ying Wang; Diane Nowicki; Gary Anderson; Jarakae Jensen; Brett West

2008-01-01

346

Altered UDP-glucuronosyltransferase and sulfotransferase expression and function during progressive stages of human nonalcoholic fatty liver disease.  

PubMed

The UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) represent major phase II drug-metabolizing enzymes that are also responsible for maintaining cellular homeostasis by metabolism of several endogenous molecules. Perturbations in the expression or function of these enzymes can lead to metabolic disorders and improper management of xenobiotics and endobiotics. Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver damage ranging from steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Because the liver plays a central role in the metabolism of xenobiotics, the purpose of the current study was to determine the effect of human NAFLD progression on the expression and function of UGTs and SULTs in normal, steatosis, NASH (fatty), and NASH (not fatty/cirrhosis) samples. We identified upregulation of UGT1A9, 2B10, and 3A1 and SULT1C4 mRNA in both stages of NASH, whereas UGT2A3, 2B15, and 2B28 and SULT1A1, 2B1, and 4A1 as well as 3'-phosphoadenosine-5'-phosphosulfate synthase 1 were increased in NASH (not fatty/cirrhosis) only. UGT1A9 and 1A6 and SULT1A1 and 2A1 protein levels were decreased in NASH; however, SULT1C4 was increased. Measurement of the glucuronidation and sulfonation of acetaminophen (APAP) revealed no alterations in glucuronidation; however, SULT activity was increased in steatosis compared with normal samples, but then decreased in NASH compared with steatosis. In conclusion, the expression of specific UGT and SULT isoforms appears to be differentially regulated, whereas sulfonation of APAP is disrupted during progression of NAFLD. PMID:23223517

Hardwick, Rhiannon N; Ferreira, Daniel W; More, Vijay R; Lake, April D; Lu, Zhenqiang; Manautou, Jose E; Slitt, Angela L; Cherrington, Nathan J

2013-03-01

347

Immune dysfunction and liver damage of mice following exposure to lanthanoids.  

PubMed

In an effort to investigate the effects of exposure to lanthanoids (Ln) on the immune response and liver function, mice were orally exposed to LaCl3 , CeCl3 , and NdCl3 at 2, 10, and 20 mg/kg doses for 30 days, respectively; lymphocyte counts, serum IgM level, hematological indices, biochemical parameters of liver functions, and histopathological changes in Ln(3+) -treated mice were assessed. Indeed, 20 mg/kg Ln(3+) significantly inhibited mice growth and reduced the counts of white blood cells, platelets, and reticulocyte in mice blood. Specifically, in these Ln(3+) -treated mice, CD3+, CD4+, CD8+, CD19+ and NK cells, and CD4+/CD8+ ratio as well as serum IgM level were decreased. Furthermore, liver function was disrupted, as evidenced by the increased alanine aminotransferase, total bilirubin, total bile acid and triglycerides, and the decreased glucose and ratio of albumin to globulin. The cytoarchitecture damage and fatty degeneration in liver caused by Ln(3+) at 20 mg/kg dose were also observed. Our findings showed that exposure to Ln affected the cell and humoral immunity and disturbed liver function in mice. In addition, Ce(3+) was found to exhibit higher toxicity than La(3+) and Nd(3+). PMID:21928445

Cheng, Jie; Cheng, Zhe; Hu, Renping; Cui, Yaling; Cai, Jingwei; Li, Na; Gui, Suxing; Sang, Xuezi; Sun, Qingqing; Wang, Ling; Hong, Fashui

2014-01-01

348

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

PubMed Central

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

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

2008-01-01

349

Heap of stones: an unusual cause for biliary colic and elevated liver function tests.  

PubMed

A 40-year old woman presented with symptomatic intrahepatic gallstones in one liver segment only four years after cholecystectomy for cholelithiasis. Multiple small, yellow and round calculi were completely removed from the intrahepatic bile ducts via ERCP. The young age of the patient, recurrence of gallstones after cholecystectomy and intrahepatic gallstones suggested a subtype of the low-phospholipid associated cholelithiasis syndrome, a monogenic form of cholesterol cholelithiasis due to variations of the ABCB4 gene that encodes the canalicular phospholipid transporter MDR3. PMID:23619268

Wittenburg, Henning; Keim, Volker; Hoffmeister, Albrecht

2013-01-01

350

Short-Term Intravenous Fish Oil and Pediatric Intestinal Failure Associated Liver Disease: 3-year Follow-up on Liver Function and Nutrition  

PubMed Central

Intravenous fish oil (FO) has changed the management of intestinal failure associated liver disease (IFALD). This report describes two IFALD patients who received FO for 5 and 10 months, respectively and reports on their 3-year follow-up.

Calkins, Kara; Lowe, Allison; Shew, Stephen B.; Dunn, James C.Y.; Reyen, Laurie; Farmer, Douglas G.; Devaskar, Sherin U.; Venick, Robert

2012-01-01

351

Origin and Possible Significance of Alanine Production by Skeletal Muscle.  

National Technical Information Service (NTIS)

These experiments were undertaken to determine the source of alanine released by skeletal muscle and to clarify the possible relationships between this process and the degradation of branched chain amino acids, the release of glutamine, and protein turnov...

R. Odessey E. A. Khairallah A. L. Goldberg

1974-01-01

352

Histological and Clinical Characteristics of Patients with Chronic Hepatitis C and Persistently Normal Alanine Aminotransferase Levels  

PubMed Central

Patients with chronic hepatitis C virus (HCV) infection and persistently normal alanine aminotransferase (PNALT) are generally described to have mild liver disease. The aim of this study was to compare clinical and histological features in HCV-infected patients with PNALT and elevated ALT. Patients presenting to the University of Illinois Medical Center, Chicago, who had biopsy proven HCV, an ALT measurement at the time of liver biopsy, at least one additional ALT measurement over the next 12 months, and liver biopsy slides available for review were identified. PNALT was defined as ALT ? 30 on at least 2 different occasions over 12 months. Of 1200 patients with HCV, 243 met the study criteria. 13% (32/243) of patients had PNALT while 87% (211/243) had elevated ALT. Significantly more patients with PNALT had advanced fibrosis (F3 and F4) compared to those with elevated ALT (P = 0.007). There was no significant difference in the histology activity index score as well as mean inflammatory score between the two groups. In conclusion, in a well-characterized cohort of patients at a tertiary medical center, PNALT did not distinguish patients with mild liver disease.

Guzman, Grace

2014-01-01

353

Relation of inflammation and liver function with the plasma cortisol response to adrenocorticotropin in early lactating dairy cows.  

PubMed

In this study we examined the relationship between cortisol and inflammatory status in early lactating dairy cows after a stimulation test of the adrenal cortex. Twenty-four cows were grouped into quartiles (6 cows per each quartile) in accordance with the liver activity index (based on plasma concentration of negative acute phase proteins in early lactation); the quartiles were lower (LO; cows with the lowest liver functionality), intermediate lower, intermediate upper, and upper (UP; cows with the highest liver functionality). Each cow was injected i.v. with 20 µg of a synthetic analog of ACTH at 35 d in milk (DIM). Blood samples were taken to assess inflammatory status, and at 0, 30, and 60 min after ACTH challenge to measure total cortisol. The free cortisol fraction was analyzed in the LO and UP quartiles and the bound cortisol fraction was estimated as the difference between total and free cortisol. The LO, in comparison with the other quartiles, suffered a more severe inflammatory status, with the highest values of haptoglobin, reactive oxygen metabolites, and total nitric oxide metabolites and the lowest concentration of direct or indirect markers of negative acute phase proteins. The cows in the LO quartile had the highest values of plasma nonesterified fatty acids and ?-hydroxybutyrate at 7 DIM, suggesting a more severe body lipid mobilization. The LO quartile cows showed the highest frequency of health problems and the lowest milk yield in the first 35 DIM. Thirty minutes after the ACTH treatment, the concentration of total cortisol was lower in LO in comparison to other groups. Similarly, the bound cortisol fraction was lower in LO versus UP. The adrenal response appeared inversely related with health status after calving (e.g., lower in LO cows, experiencing the most severe inflammatory status). The lower increase in cortisol after the ACTH challenge in cows with greater inflammation (LO quartile) seems a consequence of the lower availability of cortisol-binding globulin synthetized by the liver, but other mechanisms can be involved (e.g., rate of cortisol production, secretion, and metabolic clearance). Our data provide evidence that inflammation and metabolic changes reduce the concentration of circulating plasma cortisol during an acute stress. Hence, the acute phase response in dairy cows should be taken into account to interpret the results obtained from stimulation tests of the adrenal cortex. PMID:23831090

Trevisi, E; Bertoni, G; Lombardelli, R; Minuti, A

2013-09-01

354

Non-Viral Related Liver Enzymes Elevation After Kidney Transplantation  

PubMed Central

Background: Liver enzymes elevations (LEE) can be observed after kidney transplantation due to multifactorial causes. Objectives: We performed a retrospective study on 1589 kidney transplants, 971 male and 618 female, who were hepatitis B surface antigen (HBsAg) and hepatitis C virus-antibody (HCV Ab) negative, and had no other liver diseases, to detect the prevalence of LEE and its risk factors in these patients between May 2008 and May 2010. Patients and methods: Liver enzymes and other biochemical parameters were measured in all recipients. Patients were divided into three groups, according to laboratory test time since transplantation: Group I, less than 3 months, Group II, 4 - 12 months after transplantation, and Group III, more than one year post-transplantation. Results: The highest LEE was more frequent in older patients (P < 0.001) and male individuals (P < 0.001). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were higher in patients who received kidneys from deceased donors (10.4% and 23.8%, respectively) as compared to living donor transplants (5.6% and 14.8%, respectively) (P < 0.001). The elevation of ALT was the liver enzyme abnormality after kidney transplantation with the highest prevalence (34.3%). The levels of ALT and AST were significantly elevated within the first 3 months after transplantation, followed by the 4-12 months period (P < 0.001). There was a reverse correlation between liver enzyme levels and renal allograft function in both univariate and linear regression analyses. This correlation increased over time. There was also a significant relation between cyclosporine blood levels and liver enzyme values in the univariate analysis. However, this relationship was attenuated over time. Elevated liver enzymes also correlated with anemia. Conclusions: The LEE is a common finding among kidney transplant recipients. Serial monitoring of aminotransferases, particularly ALT, should be performed in all patients after kidney transplantation.

Einollahi, Behzad; Ghadian, Alireza; Ghamar-Chehreh, Ebrahim; Alavian, Seyed Moayed

2014-01-01

355

A side reaction of alanine racemase: transamination of cycloserine.  

PubMed

Alanine racemase (EC 5.1.1.1) catalyzes the interconversion of alanine enantiomers, and thus represents the first committed step involved in bacterial cell wall biosynthesis. Cycloserine acts as a suicide inhibitor of alanine racemase and as such, serves as an antimicrobial agent. The chemical means by which cycloserine inhibits alanine racemase is unknown. Through spectroscopic assays, we show here evidence of a pyridoxal derivative (arising from either isomer of cycloserine) saturated at the C4' carbon position. We additionally report the L- and D-cycloserine inactivated crystal structures of Bacillus stearothermophilus alanine racemase, which corroborates the spectroscopy via evidence of a 3-hydroxyisoxazole pyridoxamine derivative. Upon the basis of the kinetic and structural properties of both the L- and D-isomers of the inhibitor, we propose a mechanism of alanine racemase inactivation by cycloserine. This pathway involves an initial transamination step followed by tautomerization to form a stable aromatic adduct, a scheme similar to that seen in cycloserine inactivation of aminotransferases. PMID:12741835

Fenn, Timothy D; Stamper, Geoffrey F; Morollo, Anthony A; Ringe, Dagmar

2003-05-20

356

Long-term impact of liver transplantation on respiratory function and nutritional status in children and adults with cystic fibrosis.  

PubMed

Early liver transplant (LT) has been advocated for patients with cystic fibrosis liver disease (CFLD) and evidence of deterioration in nutritional state and respiratory function to prevent further decline. However, the impact of single LT on long-term respiratory function and nutritional status has not been adequately addressed. We performed a retrospective analysis of the outcomes of 40 (21 adult/19 pediatric) patients with CFLD transplanted between 1987 and 2009 with median follow-up of 47.8 months (range 4-180). One and five-year actuarial survival rates were 85%/64% for adult and 90%/85% for pediatric LT cohorts, respectively. Lung function remained stable until 4 years (FEV(1) % predicted; pretransplant 48.4% vs. 45.9%, 4 years posttransplant) but declined by 5 years (42.4%). Up to 4 years posttransplant mean annual decline in FEV(1) % was lower (0.74%; p = 0.04) compared with the predicted 3% annual decline in CF patients with comorbidity including diabetes. Number of courses of intravenous antibiotics was reduced following LT, from 3.9/year pretransplant to 1.1/year, 5 years posttransplant. Body mass index was preserved posttransplant; 18.0 kg/m(2) (range 15-24.3) pretransplant versus 19.6 kg/m(2) (range 16.4-22.7) 5 years posttransplant. In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long-term lung function and preserving nutritional status. PMID:22225648

Dowman, J K; Watson, D; Loganathan, S; Gunson, B K; Hodson, J; Mirza, D F; Clarke, J; Lloyd, C; Honeybourne, D; Whitehouse, J L; Nash, E F; Kelly, D; van Mourik, I; Newsome, P N

2012-04-01

357

IL-27 Production and STAT3-Dependent Upregulation of B7-H1 Mediate Immune Regulatory Functions of Liver Plasmacytoid DC1  

PubMed Central

Plasmacytoid (p) dendritic cells (DC) are highly-specialized APC that, in addition to their well-recognized role in anti-viral immunity, also regulate immune responses. Liver-resident pDC are considerably less immunostimulatory than those from secondary lymphoid tissues and are equipped to promote immune tolerance/regulation through various mechanisms. IL-27 is an IL-12-family cytokine that regulates the function of both APC and T cells, although little is known about its role in pDC immunobiology. In this study, we show that mouse liver pDC express higher levels of IL-27p28 and EBV-induced protein (Ebi)3 compared to splenic pDC. Both populations of pDC express the IL-27R?/WSX-1; however, only liver pDC significantly upregulate expression of the co-regulatory molecule B7 homolog-1 (B7-H1) in response to IL-27. Inhibition of STAT3 activation completely abrogates IL-27-induced upregulation of B7-H1 expression on liver pDC. Liver pDC treated with IL-27 increase the percentage of CD4+Foxp3+ T cells in MLR, which is dependent upon expression of B7-H1. pDC from Ebi3-deficient mice lacking functional IL-27, show increased capacity to stimulate allogeneic T cell proliferation and IFN-? production in MLR. Liver but not spleen pDC suppress delayed-type hypersensitivity responses to OVA, an effect that is lost with Ebi3?/? and B7-H1?/? liver pDC compared to wild-type (WT) liver pDC. These data suggest that IL-27 signaling in pDC promotes their immunoregulatory function and that IL-27 produced by pDC contributes to their capacity to regulate immuneresponses in vitro and in vivo.

Matta, Benjamin M.; Raimondi, Giorgio; Rosborough, Brian R.; Sumpter, Tina L.; Thomson, Angus W.

2012-01-01

358

Reinterpreting the Mechanism of Inhibition of Mycobacterium tuberculosisd-Alanine:d-Alanine Ligase by d-Cycloserine  

PubMed Central

d-Cycloserine is a second-line drug approved for use in the treatment of patients infected with Mycobacterium tuberculosis, the etiologic agent of tuberculosis. The unique mechanism of action of d-cycloserine, compared with those of other clinically employed antimycobacterial agents, represents an untapped and exploitable resource for future rational drug design programs. Here, we show that d-cycloserine is a slow-onset inhibitor of MtDdl and that this behavior is specific to the M. tuberculosis enzyme orthologue. Furthermore, evidence is presented that indicates d-cycloserine binds exclusively to the C-terminal d-alanine binding site, even in the absence of bound d-alanine at the N-terminal binding site. Together, these results led us to propose a new model of d-alanine:d-alanine ligase inhibition by d-cycloserine and suggest new opportunities for rational drug design against an essential, clinically validated mycobacterial target.

2013-01-01

359

Reinterpreting the mechanism of inhibition of Mycobacterium tuberculosis D-alanine:D-alanine ligase by D-cycloserine.  

PubMed

d-Cycloserine is a second-line drug approved for use in the treatment of patients infected with Mycobacterium tuberculosis, the etiologic agent of tuberculosis. The unique mechanism of action of d-cycloserine, compared with those of other clinically employed antimycobacterial agents, represents an untapped and exploitable resource for future rational drug design programs. Here, we show that d-cycloserine is a slow-onset inhibitor of MtDdl and that this behavior is specific to the M. tuberculosis enzyme orthologue. Furthermore, evidence is presented that indicates d-cycloserine binds exclusively to the C-terminal d-alanine binding site, even in the absence of bound d-alanine at the N-terminal binding site. Together, these results led us to propose a new model of d-alanine:d-alanine ligase inhibition by d-cycloserine and suggest new opportunities for rational drug design against an essential, clinically validated mycobacterial target. PMID:24033232

Prosser, Gareth A; de Carvalho, Luiz Pedro S

2013-10-01

360

D-Amino acid dipeptide production utilizing D-alanine-D-alanine ligases with novel substrate specificity.  

PubMed

D-Alanine-D-alanine ligase (Ddl) is an important enzyme in the synthesis of bacterial peptidoglycan. The genes encoding Ddls from Escherichia coli K12 (EcDdlB), Oceanobacillus iheyensis JCM 11309 (OiDdl), Synechocystis sp. PCC 6803 (SsDdl) and Thermotoga maritima ATCC 43589 (TmDdl), the genomic DNA sequences of which have been determined, were cloned and the substrate specificities of these recombinant Ddls were investigated. Although OiDdl had a high substrate specificity for D-alanine; EcDdlB, SsDdl and TmDdl showed broad substrate specificities for D-serine, D-threonine, D-cysteine and glycine, in addition to D-alanine. Four D-amino acid dipeptides were produced using EcDdlB, and D-amino acid homo-dipeptides were successfully produced at high yields except for D-threonyl-D-threonine. PMID:16233841

Sato, Masaru; Kirimura, Kohtaro; Kino, Kuniki

2005-06-01

361

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

PubMed Central

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

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

2012-01-01

362

Expression of an L-alanine dehydrogenase gene in Zymomonas mobilis and excretion of L-alanine  

SciTech Connect

Gene alaD for L-alanine dehydrogenase from Bacillus sphaericus was cloned and introduced into Z. mobilis. Under the control of the strong promoter of the pyruvate decarboxylase (pdc) gene, the enzyme was expressed up to a specific activity of nearly 1 {mu}mol {center dot} min{sup {minus}1} {center dot} mg of protein{sup {minus}1} in recombinant cells. As a result of this high L-alanine dehydrogenase activity, growing cells excreted up to 10 mmol of alanine per 280 mmol of glucose utilized into a mineral salts medium. By the addition of 85 mM NH{sub 4}{sup +} to the medium, growth of the recombinant cells stopped, and up to 41 mmol of alanine was secreted. As alanine dehydrogenase competed with pyruvate decarboxylase (PDC) for the same substrate (pyruvate), PDC activity was reduced by starvation for the essential PDC cofactor thiamine PP{sub i}. A thiamine auxotrophy mutant of Z. mobilis which carried the alaD gene was starved for 40 h in glucose-supplemented mineral salts medium and then shifted to mineral salts medium with 85 mM NH {sub 4}{sup +} and 280 mmol of glucose. The recombinants excreted up to 84 mmol of alanine over 25 h. Alanine excretion proceeded at an initial velocity of 238 nmol {center dot} min{sup {minus}1} {center dot} mg(dry weight){sup {minus}1}. Despite this high activity, the excretion rate seemed to be a limiting factor, as the intracellular concentration of alanine was as high as 260 mM at the beginning of the excretion phase and decreased to 80 to 90 mM over 24 h.

Uhlenbusch, I.; Sahm, H.; Sprenger, G.A. (Inst. fur Biotechnologie 1, Julich (Germany))

1991-05-01

363

Expression of an L-alanine dehydrogenase gene in Zymomonas mobilis and excretion of L-alanine.  

PubMed Central

An approach to broaden the product range of the ethanologenic, gram-negative bacterium Zymomonas mobilis by means of genetic engineering is presented. Gene alaD for L-alanine dehydrogenase (EC 1.4.1.1.) from Bacillus sphaericus was cloned and introduced into Z. mobilis. Under the control of the strong promoter of the pyruvate decarboxylase (pdc) gene, the enzyme was expressed up to a specific activity of nearly 1 mu mol . min -1 . mg of protein -1 in recombinant cells. As a results of this high L-alanine dehydrogenase activity, growing cells excreted up to 10 mmol of alanine per 280 mmol of glucose utilized into a mineral salts medium. By the addition of 85 mM NH4+ to the medium, growth of the recombinant cells stopped, and up to 41 mmol alanine was secreted. As alanine dehydrogenase competed with pyruvate decarboxylase (PDC) (EC 4.1.1.1.) for the same substrate (pyruvate), PDC activity was reduced by starvation for the essential PDC cofactor thiamine PPi. A thiamine auxotrophy mutant of Z. mobilis which carried the alaD gene was starved for 40 h in glucose-supplemented mineral salts medium and then shifted to mineral salts medium with 85 mM NH4+ and 280 mmol of glucose. The recombinants excreted up to 84 mmol of alanine (7.5 g/liter) over 25 h. Alanine excretion proceeded at an initial velocity of 238 nmol . min-1 . mg [dry weight]-1. Despite this high activity, the excretion rate seemed to be a limiting factor, as the intracellular concentration of alanine was as high as 260 mM at the beginning of the excretion phase and decreased to 80 to 90 mM over 24 h.

Uhlenbusch, I; Sahm, H; Sprenger, G A

1991-01-01

364

[Effect of the diethylamide of nicotinic acid (cordiamine) on the hydroxylating function of the liver].  

PubMed

Diethylamide of nicotinic acid (subcutaneously, 40 and 120 mg/kg, once a day for 4 days) was shown to exert no influence on p-hydroxylation of aniline and to increase the rate of N-demethylation of amidopyrine and ethylmorphine in the rat liver microsomal fraction by 21 and 47% as compared with the control. At the same dose of 40 mg/kg and the same schedule of administration the drug was found to increase urine excretion of antipyrine metabolites: nor-antipyrine, 4-hydroxy-antipyrine and the sum of metabolites by 229, 89 and 80%, respectively, during the first 90 min of the experiment. Excretion of antipyrine, 3-hydroxymethyl-antipyrine and 3-carboxymethyl-antipyrine underwent no significant changes. The duration of hexobarbital-induced sleep of the rats was shown to be decreased by 26%. PMID:2806530

Bushma, M I; Zavodnik, L B; Lukienko, P I

1989-01-01

365

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

SciTech Connect

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

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

1991-08-01

366

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

PubMed Central

Twenty of 32 patients with either chronic cholestatic or hepatocellular liver disease had bone pain or recent fractures. On bone biopsy five patients had normal bone, 15 had osteomalacia, five had osteoporosis, and seven had a combination of osteomalacia and osteoporosis. In the presence of osteoporosis, osteomalacia was minimal or absent. There was no biochemical, radiological, or histological evidence of excess parathyroid activity. No significant correlations were demonstrated between the plasma and urinary biochemical findings and the presence of either osteoporosis or osteomalacia and bone biopsy was essential for correct diagnosis. There was no statistical relationship between low serum 25-hydroxy vitamin D values and the presence of osteomalacia. Bone disease was not prevented by regular intramuscular vitamin D2, although biochemical changes were improved. Drugs such as corticosteroids and cholestyramine may be important aetiological factors in hepatic osteodystrophy.

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

1978-01-01

367

Energy landscapes and global thermodynamics for alanine peptides  

NASA Astrophysics Data System (ADS)

We compare different approaches for computing the thermodynamics of biomolecular systems. Techniques based on parallel replicas evolving via molecular dynamics or Monte Carlo simulations produce overlapping histograms for the densities of states. In contrast, energy landscape methods employ a superposition partition function constructed from local minima of the potential energy surface. The latter approach is particularly powerful for systems exhibiting broken ergodicity, and it is usually implemented using a harmonic normal mode approximation, which has not been extensively tested for biomolecules. The present contribution compares these alternative approaches for small alanine peptides modelled using the CHARMM and AMBER force fields. Densities of states produced from canonical sampling using multiple temperature replicas provide accurate reference data to evaluate the effect of the harmonic normal mode approximation in the superposition calculations. This benchmarking lays foundations for the application of energy landscape methods to larger biomolecules. It will also provide well characterised model systems for developing enhanced sampling methods, and for the treatment of anharmonicity corresponding to individual local minima.

Somani, Sandeep; Wales, David J.

2013-09-01

368

Expression of constitutive androstane receptor splice variants in rat liver and lung and their functional properties.  

PubMed

The mammalian constitutive androstane receptor (CAR) is a transcription factor that participates in controlling the expression of xenobiotic metabolizing and transporting genes in response to xenobiotics in an organ-specific manner. In addition to the wild-type CAR (CAR WT) mRNA, mRNAs for five splice variants (SVs) could be detected in the liver of 7-week-old male Wistar rats by RT-PCR using primer pairs covering a full-length mRNA derived from 9 exons; insertion of 18 bp at the 5'-end of intron 8 with or without deletion of 3 bp from the 5'-end of exon 7 (CAR SV1 or SV2), deletion of 4 bp from the 5'-end of exon 8 (CAR SV3), insertion of 195 bp intron 7 (CAR SV4), and insertion of 91 bp intron 6 (CAR SV5). In contrast, only CAR SV5 was detected in lung. Due to the introduction of novel stop codons, all the SVs were considered to code for premature proteins. The liver homogenate gave two protein bands in the vicinity of 37 kDa on Western blotting. They were attributable to CAR WT and SV-complex, respectively, based on their putative molecular weights in descending order. Upon cotransfection with the reporter plasmid, only the cells transfected with the CAR SV4-expression plasmid showed enhanced luciferase activity similar to the WT-transfected cells, for which the further splicing of the remaining intron 7 seemed to be responsible. The transactivation-defective SVs downregulated CAR WT-induced luciferase activity to some extent in the cotransfection experiments. PMID:16272689

Kanno, Yuichiro; Aoki, Sho; Mochizuki, Megumi; Mori, Emi; Nakahama, Takayuki; Inouye, Yoshio

2005-11-01

369

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

PubMed Central

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

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

2013-01-01

370

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

PubMed

The lack of pendant functional groups on the PCL backbone has been a great challenge for surface bioactivation of poly(?-caprolactone) (PCL). In the present study, covalently galactosylated PCL (GPCL) was developed through coupling between the amino-functionalized PCL (NPCL) and the lactobionic acid (LA) and its potential application in maintenance of physiological functions of HepG2 cells was further evaluated. The structure and properties of GPCL were explored by (1)H NMR, FT-IR, GPC and DSC. Moreover, the incorporation of galactose ligands onto GPCL membranes not only promoted higher wettability, but also radically changed surface morphology in comparison with PCL and NPCL according to the contact angle measurement and atomic force microscopy. When HepG2 cells were seeded onto these membranes, the cells on GPCL membranes showed more pronounced cell adhesion and tended to form aggregates during the initial adhesion stage and then progressively grew into multi-layer structures compared to those without galactose ligands by the observation with fluorescence microscope and scanning electron microscopy. Furthermore, live-dead assay and functional tests demonstrated that HepG2 cells on GPCL membranes had superior viability and maintained better liver-specific functions. Collectively, GPCL has great potential for hepatic tissue engineering scaffolds. PMID:24907736

Zhang, Yan; Zhang, Yi; Chen, Min; Zhou, Yan; Lang, Meidong

2014-08-01

371

Post-operative elimination of sevoflurane anesthetic and hexafluoroisopropanol metabolite in exhaled breath: pharmacokinetic models for assessing liver function.  

PubMed

Sevoflurane (SEV), a commonly used anesthetic agent for invasive surgery, is directly eliminated via exhaled breath and indirectly by metabolic conversion to inorganic fluoride and hexafluoroisopropanol (HFIP), which is also eliminated in the breath. We studied the post-operative elimination of SEV and HFIP of six patients that had undergone a variety of surgeries lasting between 2.5 to 8.5 h using exhaled breath analysis. A classical three compartments pharmacokinetic model developed for the study of environmental contaminants was fitted to the breath data. We found that SEV kinetic behavior following surgery (for up to six days) is consistent across all subjects whereas the production and elimination of HFIP varies to some extent. We developed subject specific parameters for HFIP metabolism and interpreted the differences in the context of timing and dose of anesthesia, type of surgery, and specific host factors. We propose methods for assessing individual patient liver function using SEV as a probe molecule for assessing efficiency of liver metabolism to HFIP. This work is valuable not only for the clinical study of metabolism recovery, but potentially also for the study of the interaction of other manufactured and environmental compounds with human systems biology in controlled exposure and observational studies. PMID:23735676

Ghimenti, S; Di Francesco, F; Onor, M; Stiegel, M A; Trivella, M G; Comite, C; Catania, N; Fuoco, R; Pleil, J D

2013-09-01

372

Biochemical changes in liver and blood during liver fattening in rats.  

PubMed

Excessive fat accumulation in the liver is a common metabolic disorder seen in humans and animals. Fatty liver was induced in the rat by feeding the animals with a sucrose rich diet containing 1% orotic acid for 2-3 weeks. In the sera from fatty liver rats there were significant changes in the level of alanine aminotransferase (+ 68.7%), malic dehydrogenase (+ 77.8%), gamma-glutamyl transpeptidase (- 53.4%) and total lipids (+ 26.6%). There were small to no changes in the levels of aspartate aminotransferase, glucose-6-phosphate dehydrogenase, lactic dehydrogenase, aldolase, malic enzyme, 6-phosphogluconic acid dehydrogenase, alkaline phosphatase and albumin. In fatty liver, significant differences were seen in the levels of glucose 6-phosphate dehydrogenase (+ 235%), malic enzyme (+ 170%), gamma-glutamyl transpeptidase (+ 113%), 6-phosphogluconate dehydrogenase (+ 63%), aspartate aminotransferase (+ 35.6%), malic dehydrogenase (+ 38%), lactic dehydrogenase (+ 37%), and alanine aminotransferase (- 23%). Comparison of the non-fatty part with the fatty part of the fatty liver showed larger changes in the non-fatty part of the liver, suggesting that during the fattening process, there is an induction of enzymes in the liver reaching a peak prior to lipid accumulation, declining thereafter during liver fattening. The increase in NADPH-generating lipogenic enzymes suggests that accumulated fat in the liver is at least partially from de-novo increased synthesis in the liver. PMID:3772307

Bogin, E; Avidar, Y; Merom, M

1986-09-01

373

Surface interaction of L-alanine on hematite: an astrobiological implication.  

PubMed

In the present work, surface interaction of L-alanine (L-ala) has been investigated on hematite (?-Fe2O3), an abundant mineral on Mars, as a function of time (5 min-48 h), pH (4.0 and 6.20 ± 0.10) and concentration (1 × 10(-3) M-10 × 10(-3) M) with optical absorbance and energy-dispersive spectroscopy (EDS). Adsorption parameters (XM and KL) were calculated from Langmuir adsorption isotherms. L-alanine has maximum affinity (65.31 %) in its zwitterionic form at pH 6.20, while it is only 29.86 % adsorbed at pH 4.0. Possible astrobiological implications are discussed. PMID:24402033

Pandey, Pramod; Pant, Chandra Kala; Gururani, Kavita; Arora, Priyanka; Kumar, Sumit; Sharma, Yogesh; Pathak, Hari Datt; Mehata, Mohan Singh

2013-10-01

374

Rapid Crystallization of L-Alanine on Engineered Surfaces using Metal-Assisted and Microwave-Accelerated Evaporative Crystallization.  

PubMed

This study demonstrates the application of metal-assisted and microwave-accelerated evaporative crystallization (MA-MAEC) technique to rapid crystallization of L-alanine on surface engineered silver nanostructures. In this regard, silver island films (SIFs) were modified with hexamethylenediamine (HMA), 1-undecanethiol (UDET), and 11-mercaptoundecanoic acid (MUDA), which introduced -NH(2), -CH(3) and -COOH functional groups to SIFs, respectively. L-Alanine was crystallized on these engineered surfaces and blank SIFs at room temperature and using MA-MAEC technique. Significant improvements in crystal size, shape, and quality were observed on HMA-, MUDA- and UDET-modified SIFs at room temperature (crystallization time = 144, 40 and 147 min, respectively) as compared to those crystals grown on blank SIFs. Using the MA-MAEC technique, the crystallization time of L-alanine on engineered surfaces were reduced to 17 sec for microwave power level 10 (i.e., duty cycle 100%) and 7 min for microwave power level 1 (duty cycle 10%). Raman spectroscopy and powder x-ray diffraction (XRD) measurements showed that L-Alanine crystals grown on engineered surfaces using MA-MAEC technique had identical characteristic peaks of L-alanine crystals grown using traditional evaporative crystallization. PMID:22267957

Alabanza, Anginelle M; Pozharski, Edwin; Aslan, Kadir

2012-01-01

375

The immunologic outcome of enhanced function of mouse liver lymphocytes and Kupffer cells by high-fat and high-cholesterol diet.  

PubMed

Dietary lipids/cholesterol may modulate liver immune function. We have recently found that mouse F4/80 Kupffer cells