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Sample records for liver function test

  1. Liver Function Tests

    MedlinePlus

    ... herbal supplements you are taking. What are normal ranges for liver function tests? Normal ranges for liver function tests can vary by age, ... other factors. Laboratory test results usually provide normal ranges for each liver function test with your results. ...

  2. Liver Function Tests

    MedlinePlus

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

  3. Abnormality on Liver Function Test

    PubMed Central

    2013-01-01

    Children with abnormal liver function can often be seen in outpatient clinics or inpatients wards. Most of them have respiratory disease, or gastroenteritis by virus infection, accompanying fever. Occasionally, hepatitis by the viruses causing systemic infection may occur, and screening tests are required. In patients with jaundice, the tests for differential diagnosis and appropriate treatment are important. In the case of a child with hepatitis B virus infection vertically from a hepatitis B surface antigen positive mother, the importance of the recognition of immune clearance can't be overstressed, for the decision of time to begin treatment. Early diagnosis changes the fate of a child with Wilson disease. So, screening test for the disease should not be omitted. Non-alcoholic fatty liver disease, which is mainly discovered in obese children, is a new strong candidate triggering abnormal liver function. Muscular dystrophy is a representative disease mimicking liver dysfunction. Although muscular dystrophy is a progressive disorder, and early diagnosis can't change the fate of patients, it will be better to avoid parent's blame for delayed diagnosis. PMID:24511518

  4. Evaluation of abnormal liver function tests.

    PubMed

    Agrawal, Swastik; Dhiman, Radha K; Limdi, Jimmy K

    2016-04-01

    Incidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests. PMID:26842972

  5. Tests for Liver Cancer

    MedlinePlus

    ... cancer Next Topic Liver cancer stages Tests for liver cancer If you have some of the signs ... cancer has come back (recurred). Other blood tests Liver function tests (LFTs): Because liver cancer often develops ...

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

    PubMed Central

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

    2014-01-01

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

  7. Liver Function Tests Following Irreversible Electroporation of Liver Tumors: Experience in 174 Procedures.

    PubMed

    Froud, Tatiana; Venkat, Shree R; Barbery, Katuzka J; Gunjan, Arora; Narayanan, Govindarajan

    2015-09-01

    Irreversible electroporation (IRE) is a relatively new ablation modality that uses electric currents to cause cell death. It is commonly used to treat primary and secondary liver tumors in patients with normal liver function and preexisting cirrhosis. Retrospective analysis of 205 procedures sought to evaluate changes in liver function after IRE. Liver function tests (LFTs) results before and after IRE were evaluated from 174 procedures in 124 patients. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALKP), and total bilirubin levels were analyzed. The study was Health Insurance Portability and Accountability Act compliant and institutional review board approved. Informed consent was waived. Changes in LFT results after IRE were compared with baseline and were followed up over time to see if they resolved. Changes were compared with volume of ablation. The greatest perturbations were in transaminase levels. The levels increased sharply within 24 hours after IRE in 129 (74.1%) procedures to extreme levels (more than 20 times the upper limit of normal in one-third of cases). Resolution occurred in 95% and was demonstrated to have occurred by a mean of approximately 10 weeks, many documented as early as 7 days after procedure. ALKP levels elevated in 10% procedures, was slower to increase, and was less likely to resolve. Total bilirubin level demonstrated 2 different patterns of elevation--early and late--and similar to ALKP, it was more likely to remain elevated. There was no increased risk in patients with cirrhosis or cholangiocarcinoma. There was no correlation of levels with volume of ablation. IRE results in significant abnormalities in LFT results, but in most of the cases, these are self-limiting, do not preclude treatment, and are similar to the changes seen after radiofrequency and cryoablation in the liver. PMID:26365543

  8. Developing a Causal Model from Liver Function Test Data

    NASA Astrophysics Data System (ADS)

    Inada, Masanori; Terano, Takao

    As Active Mining is a new concept among data mining and/or knowledge discovery in databases communities, in order to validate the effectiveness, it is important to carry out empirical studies using practical data. Based on the concept of Active User Reaction, this paper develops a causal model from liver function test data in a medical domain. To develop the model, we have set a problem to predict the values of ICG (indocyanine green) test from given observation data and experts' background knowledge. We therefore employ a framework of meta-learning and structural equation modeling. In this paper meta-learning means learning about mined results from multiple data-mining techniques. Structural equation modeling enables us to describe flexible models from background knowledge. The construction of the causal model contains two phases: meta-learning and the model building. The meta-learning phase utilizes both the linear regression and the neural network as data mining techniques, then examines the predictability on the given data set. Mining models are n-folded learned from the training data set. Each of the prediction accuracy of the mining models is compared using with the testing data. On the model building phase, we use structural equation modeling to develop a causal model based on results of meta-learning and background knowledge. We again compare the accuracy of the causal model with each of the mining models. Consequently we have developed the causal model, which is comprehensible and have good predictive performance, via the meta-learning phase. Through the empirical study, we have got the conclusion that the framework of meta-learning is effective in data mining in a difficult medical domain.

  9. How to interpret liver function tests in heart failure patients?

    PubMed

    Çağlı, Kumral; Başar, Fatma Nurcan; Tok, Derya; Turak, Osman; Başar, Ömer

    2015-05-01

    Cardiac hepatopathy has generally been used to describe any liver damage caused by cardiac disorders in the absence of other possible causes of liver damage. Although there is no consensus on the terminology used, cardiac hepatopathy can be examined as congestive hepatopathy (CH) and acute cardiogenic liver injury (ACLI). CH is caused by passive venous congestion of the liver that generally occurs in the setting of chronic cardiac conditions such as chronic HF, constrictive pericarditis, tricuspid regurgitation, or right-sided heart failure (HF) of any cause, and ACLI is most commonly associated with acute cardiocirculatory failure resulting from acute myocardial infarction, acute decompensated HF, or myocarditis. Histologically, CH is characterized by sinusoidal dilation, replacement of hepatocytes with red blood cells extravasating from the sinusoids, and necrosis/apoptosis of zone 3 of the Rappaport acinus, and it could progress to cirrhosis in advanced cases. In ACLI, however, massive necrosis of zone 3 is the main histological finding. Primary laboratory findings of CH are elevated serum cholestasis markers including bilirubin, alkaline phosphatase, and γ-glutamyl-transpeptidase levels, whereas those of ACLI are a striking elevation in transaminase and lactate dehydrogenase levels. Both CH and ACLI have a prognostic value for identifying cardiovascular events and mortality and have some special implications in the management of patients undergoing ventricular assist device implantation or cardiac transplantation. There is no specific treatment for CH or ACLI other than treatment of the underlying cardiac disorder. PMID:26006191

  10. Application of the Liver Maximum Function Capacity Test in Acute Liver Failure: A Helpful Tool for Decision-Making in Liver Transplantation?

    PubMed Central

    Vondran, Florian Wolfgang Rudolf; Schumacher, Carsten; Johanning, Kai; Hartleben, Björn; Knitsch, Wolfgang; Wiesner, Olaf; Jaeckel, Elmar; Manns, Michael Peter; Klempnauer, Juergen; Bektas, Hueseyin; Lehner, Frank

    2016-01-01

    Background. Despite aggressive intensive medical management acute liver failure (ALF) may require high-urgency liver transplantation (LTx). Available prognostic scores do not apply for all patients; reliable tools to identify individuals in need of LTx are highly required. The liver maximum function capacity test (LiMAx) might represent an appropriate option. Referring to a case of ALF after Amanita phalloides-intoxication the potential of the LiMAx-test in this setting is discussed. Presentation of Case. LiMAx was performed in a 27-year-old patient prior to and after high-urgency LTx. In accordance with clinical appearance of hepatic encephalopathy, coagulopathy, and acute kidney failure, the LiMAx-test constituted a fulminant course of ALF with hardly any detectable metabolic activity. Following LTx with a marginal donor organ (95% hepatosteatosis), uptake of liver function was demonstrated by postoperative increase of the LiMAx-value. The patient was discharged from hospital on postoperative day 26. Discussion. ALF often is associated with a critical state of the patient that requires almost immediate decision-making regarding further therapy. Application of a noninvasive liver function test might help to determine the prognosis of ALF and support decision-making for or against LTx as well as acceptance of a critical donor organ in case of a critically ill patient. PMID:27274881

  11. Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome

    PubMed Central

    Vootla, Vamshidhar R.; Daniel, Myrta

    2015-01-01

    Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome. PMID:26351414

  12. Deranged liver function tests in pregnancy: the importance of postnatal follow-up

    PubMed Central

    Stone, Sophia; Girling, Joanna C

    2009-01-01

    We report an asymptomatic 40-year-old woman with persistently deranged liver function tests found incidentally in the first trimester of her second pregnancy. No cause was apparent clinically, serologically or with imaging studies until a new finding of hepatomegaly led to a repeat ultrasound scan six weeks following delivery. A mass in the region of the common hepatic duct was confirmed to be a cholangiocarcinoma, with vascular invasion precluding curative surgical resection. This case highlights the need for close vigilance of patients with unexplained and persistently abnormal liver function tests, antenatally and postdelivery.

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

    PubMed Central

    Cappello, Maria; Randazzo, Claudia; Bravatà, Ivana; Licata, Anna; Peralta, Sergio; Craxì, Antonio; Almasio, Piero Luigi

    2014-01-01

    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. PMID:24966712

  14. Assessment of liver function in dogs using the 13C-galactose breath test.

    PubMed

    Silva, S; Wyse, C A; Goodfellow, M R; Yam, P S; Preston, T; Papasouliotis, K; Hall, E J

    2010-08-01

    The aim of this study was to evaluate the application of the 13C-galactose breath test (13C-GBT) in assessing canine liver function by applying it to a group of healthy dogs, and to a group with clinicopathological evidence of liver dysfunction. Breath samples were collected 30 min before ingestion of 13C-galactose, and then at regular intervals thereafter for 6 h. The proportion of 13CO2/12CO2 in the breath samples was measured by isotope-ratio mass spectrometry. There was no significant difference in recovery of 13CO2 in the diseased group, compared to the healthy controls, but there was considerable inter-subject variation in both groups, possibly due to differences in the rate of gastric emptying, which could preclude detection of alterations in hepatic metabolism of galactose. The results of this study do not support the application of the 13C-GBT for assessment of canine liver function. PMID:19546016

  15. Liver function tests and urinary albumin in house painters with previous heavy exposure to organic solvents.

    PubMed

    Lundberg, I; Nise, G; Hedenborg, G; Högberg, M; Vesterberg, O

    1994-05-01

    The serum activities or concentrations of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), albumin, gamma-glutamyl transpeptidase (GGT), bilirubin (BIL), cholic acid (CHOL), chenodeoxycholic acid (CHENO), and transferrin with isoelectric point 5.7, and the urinary excretion of albumin were determined among male current or former house painters (n = 135) and house carpenters (n = 71) who had worked in their trades for at least 10 years before 1970. Workers who showed a value above the 90th percentile among the carpenters in at least one of the tests ASAT, ALAT, GGT, BIL, CHOL, or CHENO were regarded as showing "possible signs of liver dysfunction". Each participant's lifetime solvent exposure was evaluated by interview. The painters were divided into categories with low, intermediate, and heavy cumulative exposure during life (LTSE) or during the most exposed year (MEYSE). All participants stated none or slight recent exposure. The prevalence of possible signs of liver dysfunction increased with solvent exposure category according to LTSE as well as MEYSE with a numerically higher risk estimate in the heavy exposure category for MEYSE than for LTSE. ALP activity increased with exposure category according to both exposure estimates. This increase seemed to be due to an interaction between exposure to solvents and current or previous long term intake of medicines potentially toxic to the liver. None of these results was affected by whether or not the subjects had been exposed to solvents during the year before the investigation. The exposure to solvents was not significantly related to any other outcome variable. It is concluded that long term heavy exposure to solvents may elicit changes in conventional liver function tests indicative of a mild chronic effect on the liver. The findings also suggest that heavy solvent exposure during short time periods is a more likely cause of the findings than lifetime cumulative

  16. 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

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

    2014-01-01

    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 μmol/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

  17. Dynamic carbon 13 breath tests for the study of liver function and gastric emptying.

    PubMed

    Bonfrate, Leonilde; Grattagliano, Ignazio; Palasciano, Giuseppe; Portincasa, Piero

    2015-02-01

    In gastroenterological practice, breath tests (BTs) are diagnostic tools used for indirect, non-invasive assessment of several pathophysiological metabolic processes, by monitoring the appearance in breath of a metabolite of a specific substrate. Labelled substrates originally employed radioactive carbon 14 ((14)C) and, more recently, the stable carbon 13 isotope ((13)C) has been introduced to label specific substrates. The ingested (13)C-substrate is metabolized, and exhaled (13)CO2 is measured by mass spectrometry or infrared spectroscopy. Some (13)C-BTs evaluate specific (microsomal, cytosolic, and mitochondrial) hepatic metabolic pathways and can be employed in liver diseases (i.e. simple liver steatosis, non-alcoholic steato-hepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug and alcohol effects). Another field of clinical application for (13)C-BTs is the assessment of gastric emptying kinetics in response to liquids ((13)C-acetate) or solids ((13)C-octanoic acid in egg yolk or in a pre-packed muffin or the (13)C-Spirulina platensis given with a meal or a biscuit). Studies have shown that (13)C-BTs, used for gastric emptying studies, yield results that are comparable to scintigraphy and can be useful in detecting either delayed- (gastroparesis) or accelerated gastric emptying or changes of gastric kinetics due to pharmacological effects. Thus, (13)C-BTs represent an indirect, cost-effective and easy method of evaluating dynamic liver function and gastric kinetics in health and disease, and several other potential applications are being studied. PMID:25339354

  18. Dynamic carbon 13 breath tests for the study of liver function and gastric emptying

    PubMed Central

    Bonfrate, Leonilde; Grattagliano, Ignazio; Palasciano, Giuseppe; Portincasa, Piero

    2015-01-01

    In gastroenterological practice, breath tests (BTs) are diagnostic tools used for indirect, non-invasive assessment of several pathophysiological metabolic processes, by monitoring the appearance in breath of a metabolite of a specific substrate. Labelled substrates originally employed radioactive carbon 14 (14C) and, more recently, the stable carbon 13 isotope (13C) has been introduced to label specific substrates. The ingested 13C-substrate is metabolized, and exhaled 13CO2 is measured by mass spectrometry or infrared spectroscopy. Some 13C-BTs evaluate specific (microsomal, cytosolic, and mitochondrial) hepatic metabolic pathways and can be employed in liver diseases (i.e. simple liver steatosis, non-alcoholic steato-hepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug and alcohol effects). Another field of clinical application for 13C-BTs is the assessment of gastric emptying kinetics in response to liquids (13C-acetate) or solids (13C-octanoic acid in egg yolk or in a pre-packed muffin or the 13C-Spirulina platensis given with a meal or a biscuit). Studies have shown that 13C-BTs, used for gastric emptying studies, yield results that are comparable to scintigraphy and can be useful in detecting either delayed- (gastroparesis) or accelerated gastric emptying or changes of gastric kinetics due to pharmacological effects. Thus, 13C-BTs represent an indirect, cost-effective and easy method of evaluating dynamic liver function and gastric kinetics in health and disease, and several other potential applications are being studied. PMID:25339354

  19. The Role of Cea and Liver Function Tests in the Detection of Hepatic Metastases From Colo-Rectal Cancer

    PubMed Central

    Bombelli, Luigia; Bozzetti, F.; Doci, R.; Gennari, L.; Koukouras, D.

    1990-01-01

    Carcinoembryonic antigen and some liver function tests (alkaline phosphatase, gamma-glutamyl-transpeptidase, lactic dehydrogenase and cholinesterase) were evaluated in patients with primary colorectal cancer in order to define their role in the pre-operative detection of liver metastases. The records of 278 consecutive patients admitted to the Istituto Nazionale Tumori of Milan between January 1982 and December 1983 who were suffering from primary invasive colo-rectal cancer and who underwent laparotomy were retrospectively analyzed. At laparotomy, liver metastases were found in 38 pts (13.7%). Considering single tests, CEA was the most sensitive (71%); no single test was found to be reliably predictive, when the result was abnormal. On the contrary, the normal value of each test was associated with a good prediction. When we considered all the five tests together in the single patient their predictive value, when abnormal, proved to be quite good only if four or five results were abnormal. On the other hand, liver metastases in the presence of all normal tests were found only in two patients, so giving a negative predictive value of about 97%. So we conclude that, in the lack of an infallable imaging technique for liver evaluation, in the presence of all normal tests any other investigation on the liver could be avoided. However, when liver tests are pathologic, some other imaging technique should be performed in order to supply the surgeon with information about the extent and the spread of the metastases. PMID:2090187

  20. 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

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

    2007-01-01

    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

  1. A GWAS Study on Liver Function Test Using eMERGE Network Participants

    PubMed Central

    Namjou, Bahram; Marsolo, Keith; Lingren, Todd; Ritchie, Marylyn D.; Verma, Shefali S.; Cobb, Beth L.; Perry, Cassandra; Kitchner, Terrie E.; Brilliant, Murray H.; Peissig, Peggy L.; Borthwick, Kenneth M.; Williams, Marc S.; Grafton, Jane; Jarvik, Gail P.; Holm, Ingrid A.; Harley, John B.

    2015-01-01

    Introduction Liver enzyme levels and total serum bilirubin are under genetic control and in recent years genome-wide population-based association studies have identified different susceptibility loci for these traits. We conducted a genome-wide association study in European ancestry participants from the Electronic Medical Records and Genomics (eMERGE) Network dataset of patient medical records with available genotyping data in order to identify genetic contributors to variability in serum bilirubin levels and other liver function tests and to compare the effects between adult and pediatric populations. Methods The process of whole genome imputation of eMERGE samples with standard quality control measures have been described previously. After removing missing data and outliers based on principal components (PC) analyses, 3294 samples from European ancestry were used for the GWAS study. The association between each single nucleotide polymorphism (SNP) and total serum bilirubin and other liver function tests was tested using linear regression, adjusting for age, gender, site, platform and ancestry principal components (PC). Results Consistent with previous results, a strong association signal has been detected for UGT1A gene cluster (best SNP rs887829, beta = 0.15, p = 1.30x10-118) for total serum bilirubin level. Indeed, in this region more than 176 SNPs (or indels) had p<10−8 spanning 150Kb on the long arm of chromosome 2q37.1. In addition, we found a similar level of magnitude in a pediatric group (p = 8.26x10-47, beta = 0.17). Further imputation using sequencing data as a reference panel revealed association of other markers including known TA7 repeat indels (rs8175347) (p = 9.78x10-117) and rs111741722 (p = 5.41x10-119) which were in proxy (r2 = 0.99) with rs887829. Among rare variants, two Asian subjects homozygous for coding SNP rs4148323 (G71R) were identified. Additional known effects for total serum bilirubin were also confirmed including organic anion

  2. Scope for some enzymic tests and for radionuclide hepatography in the diagnosis of early changes in liver function

    SciTech Connect

    Vlakhov, N.; Angelov, G.; Georgiev, P.; Zhelyazkova, T

    1985-06-01

    This paper studies the sensitivity of some enzymic tests and of radionuclide scanning for the purpose of detecting the earliest and mildest changes in hepatic function after tetrachloromethane poisoning. Fifteen days after rabbits were given tetrachloromethane (CCL/sub 4/) to induce liver damage, they were killed and pieces of different parts of the liver were removed for histological investigation, by classical methods. It is clear that after liver damage by CCL/sub 4/ considerable changes in plasma enzyme activity were found in the livers after 48 h. Changes reflected in a lower curve were recorded: a reduced vascular segment and a more prolonged maximum of accumulation of the radioactive colloid, exceeding 16-20 min. The phenomenon described can be explained by disturbed functional activity of the reticuloendothelial cells as a result of their toxic damage by CCL/sub 4/.

  3. The utility of pulmonary function testing in predicting outcomes following liver transplantation.

    PubMed

    Kia, Leila; Cuttica, Michael J; Yang, Amy; Donnan, Erica N; Whitsett, Maureen; Singhvi, Ajay; Lemmer, Alexander; Levitsky, Josh

    2016-06-01

    Although pulmonary function tests (PFTs) are routinely performed in patients during the evaluation period before liver transplantation (LT), their utility in predicting post-LT mortality and morbidity outcomes is not known. The aim of this study was to determine the impact of obstructive and/or restrictive lung disease on post-LT outcomes. We conducted a retrospective analysis of patients who had pre-LT PFTs and underwent a subsequent LT (2007-2013). We used statistical analyses to determine independent associations between PFT parameters and outcomes (graft/patient survival, time on ventilator, and hospital/intensive care unit [ICU] length of stay [LOS]). A total of 415 LT recipients with available PFT data were included: 65% of patients had normal PFTs; 8% had obstructive lung disease; and 27% had restrictive lung disease. There was no difference in patient and graft survival between patients with normal, obstructive, and restrictive lung disease. However, restrictive lung disease was associated with longer post-LT time on ventilator and both ICU and hospital LOS (P < 0.05). More specific PFT parameters (diffusing capacity of the lungs for carbon monoxide, total lung capacity, and residual volume) were all significant predictors of ventilator time and both ICU and hospital LOS (P < 0.05). Although pre-LT PFT parameters may not predict post-LT mortality, restrictive abnormalities correlate with prolonged post-LT ventilation and LOS. Efforts to identify and minimize the impact of restrictive abnormalities on PFTs might improve such outcomes. Liver Transplantation 22 805-811 2016 AASLD. PMID:26929108

  4. Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings

    PubMed Central

    Verstuyft, Céline; Corruble, Emmanuelle; Perlemuter, Gabriel; Colle, Romain

    2016-01-01

    Background Concerning the risk of antidepressant induced liver injury, it is not clear whether psychiatrists perform a liver function test (LFT) and whether an increase in aminotransferase levels should contraindicate antidepressant treatment. Aim To evaluate LFT availability, the prevalence of LFT abnormalities and the probable cause of an altered LFT in patients with a major depressive episode (MDE) requiring an antidepressant drug. Methods We studied LFT evaluation in a real world psychiatric setting, in a sample of 321 consecutive patients with a current major depressive episode (MDE) requiring an antidepressant drug treatment, but without current alcohol or drug dependence or unstable medical disease. Results An LFT is performed in 36.1% (116/321) of depressed patients. One fifth of antidepressant-treated patients who had an LFT evaluation had abnormal results. The most frequent causes of LFT abnormalities were: NAFLD (nonalcoholic fatty liver disease) (7/321; 2.1%), acute alcohol consumption (4/321; 1.2%), antidepressant-induced liver injury (3/321; 0.9%), hepatitis C virus infection (2/321; 0.6%) and heart failure (1/321; 0.3%). The cause of LFT abnormalities was unknown in 32% of patients (8/25) due to the absence of etiological investigations. Conclusion These results demonstrate that an LFT is infrequently performed by psychiatrists in depressed patients requiring an antidepressant drug. Baseline LFT assessment and observations during the first six months of antidepressant treatment may be useful for detection of patients with pre-existing liver disease such as NAFLD, and early identification of cases of antidepressant-induced liver injury. An increase in aminotransferase levels may be related to an underlying liver disease, but does not contraindicate antidepressant treatment. PMID:27171561

  5. Serum Basal Paraoxonase 1 Activity as an Additional Liver Function Test for the Evaluation of Patients with Chronic Hepatitis

    PubMed Central

    Halappa, Chandrakanth K; Pyati, Sudharani A; Nagaraj; Wali, Vinod

    2015-01-01

    Background The diagnostic accuracy of currently available standard panel of liver function tests is not satisfactory for the reliable diagnosis of chronic liver disorders. Earlier studies have reported that serum basal paraoxonase 1 (PON1) activity measurement may add a significant contribution to the liver function tests. Aim To assess whether the measurement of serum basal paraoxonase 1 (PON1) activity would be useful as an index of liver function status in chronic hepatitis patients. Materials and Methods The study included 50 chronic hepatitis patients and 50 apparently healthy controls based on inclusion & exclusion criteria. In all the subjects, standard liver function tests were analysed by using standard methods. Basal PON1 activity was estimated using spectrophotometric method by the hydrolysis of p-nitrophenylacetate. Student t-test, Pearson’s correlation coefficient, diagnostic validity tests and ROC curve analysis were the methods used for the statistical analysis of the data. Results The serum basal PON1 activity was significantly decreased in chronic hepatitis cases when compared to controls (p< 0.001). Also basal PON1 activity was positively correlated with serum total protein and albumin, and negatively correlated with serum total bilirubin, alanine amino transferase (ALT), and alkaline phosphatase (ALP) (p< 0.001) in chronic hepatitis cases but not in healthy controls. Diagnostic validity tests showed, basal PON1 activity was a better discriminator of chronic hepatitis than total protein, albumin and ALP with sensitivity of 68%, specificity of 100%, positive predictive value of 100% and negative predictive value of 75%. ROC curve analysis demonstrated highest diagnostic accuracy for ALT (AUC = 0.999) followed by PON1 (AUC = 0.990), total bilirubin (AUC = 0.977), ALP (AUC = 0.904), total protein (AUC = 0.790) and albumin (AUC = 0.595). Conclusion Diagnostic accuracy of serum PON1 activity is better than total bilirubin, total protein, albumin and

  6. Toxicological studies of "Chondrokola Rosh", an Ayurvedic preparation on liver function tests of rats.

    PubMed

    Nasrin, S; Bachar, S C; Choudhuri, M S K

    2011-01-01

    Chondrokola Rosh (CKR) is a traditional metallic Ayurvedic preparation widely used by the rural and ethnic people of Bangladesh in dysuria. It is a preparation of various roasted metals (Hg and Cu), non-metal (sulphur and Mica) and medicinal herbs. Considering the controversy over the risk of toxic heavy metals in Ayurvedic herbo-mineral preparations, toxicological parameters on liver functions were investigated. A single dose of 100mg/kg body weight of the preparation was administered orally to the rats of both sexes for ninety days. In this evaluation a statistically significant (p<0.001) increase of serum albumin levels in male (17%) and female (15%) rat groups were observed. On the other hand, the plasma bilirubin level was decreased 50% and 28% respectively in both rats groups. But no remarkable differences were observed in plasma protein, sGPT, sGOT and ALP activities from their corresponding control values. This study showed that CKR had no remarkable toxic effect on liver of the animals despite the presence of traces of transformed heavy metals. PMID:22754071

  7. Monitoring of Total and Regional Liver Function after SIRT

    PubMed Central

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

    2014-01-01

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

  8. Risperidone rechallenge for marked liver function test abnormalities in an autistic child.

    PubMed

    Copur, Mazlum; Erdogan, Ayten

    2011-09-01

    Risperidone have been reported to commonly lead to asymptomatic elevation of liver enzymes in adult population, and recently in children and adolescents. Results from controlled clinical trials, reports of spontaneous adverse events, and published studies/ case reports suggest that severe hepatotoxicity may be rare but can occur in the pediatric population. In the following case report, we describe a 5-year-old male patient diagnosed as autism with severe distruptive behavior. Substantial improvement was achieved with risperidone therapy. Increase in liver enzymes at the beginning of the risperidone treatment was successfully managed with multidisciplinary approach as the treatment was initially withdrawn, afterwards restarted and carefully continued. We demonstrated that risperidone may be cautiously rechallenged in selected pediatric patients who showed marked psychiatric improvement with risperidone on the face of liver enzymes elevation. Some important patents on risperidone delivery and their use for the treatment of autism are also outlined. PMID:21913889

  9. Loss of brain function - liver disease

    MedlinePlus

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

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

    PubMed Central

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

    2013-01-01

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

  11. Hepatic (Liver) Function Panel

    MedlinePlus

    ... AST). This enzyme, which plays a role in processing proteins, is found in the liver, heart, muscles, ... doctor. © 1995- The Nemours Foundation. All rights reserved. Images provided by The Nemours Foundation, iStock, Getty Images, ...

  12. The inhomogeneous distribution of liver function: possible impact on the prediction of post-operative remnant liver function

    PubMed Central

    Nilsson, Henrik; Karlgren, Silja; Blomqvist, Lennart; Jonas, Eduard

    2015-01-01

    Background Previous studies have shown that liver function is inhomogeneously distributed in diseased livers, and this uneven distribution cannot be compensated for if a global liver function test is used for the prediction of post-operative remnant liver function. Dynamic Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) can assess segmental liver function, thus offering the possibility to overcome this problem. Methods In 10 patients with liver cirrhosis and 10 normal volunteers, the contribution of individual liver segments to total liver function and volume was calculated using dynamic Gd-EOB-DTPA-enhanced MRI. Remnant liver function predictions using a segmental method and global assessment were compared for a simulated left hemihepatectomy. For the prediction based on segmental functional MRI assessment, the estimated function of the remnant liver segments was added. Results Global liver function assessment overestimated the remnant liver function in 9 out of 10 patients by as much as 9.3% [median −3.5% (−9.3–3.5%)]. In the normal volunteers there was a slight underestimation of remnant function in 9 out of 10 cases [median 1.07% (−0.7–2.5%)]. Discussion The present study underlines the necessity of a segmental liver function test able to compensate for the non-homogeneous nature of liver function, if the prediction of post-operative remnant liver function is to be improved. PMID:25297934

  13. Non-Invasive Assessment of Liver Function

    PubMed Central

    Helmke, Steve; Colmenero, Jordi; Everson, Gregory T.

    2015-01-01

    Purpose of review It is our opinion that there is an unmet need in Hepatology for a minimally- or noninvasive test of liver function and physiology. Quantitative liver function tests (QLFTs) define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high affinity hepatic transporters exhibit high “first-pass” hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways. Recent Findings We highlight one QLFT, the dual cholate test, and introduce the concept of a disease severity index (DSI) linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting. Summary It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy. PMID:25714706

  14. [Peranal bleeding and elevated liver function tests in a 33‑year-old refugee from Nigeria].

    PubMed

    Argirovic, N; Caselitz, M; Mohren, W; Cruz Cordero, F; Huber, J; Wagner, S

    2016-08-01

    A 33-year-old refugee from Nigeria, who had been living in Germany for 1 year, was admitted to the hospital due to pelvic pain, peranal hemorrhage, and an unexplained increase in transaminase levels. As the liver screening tests, sonography findings, and colonoscopy were normal, a liver biopsy was performed that revealed Schistosoma mansoni worm eggs as an unexpected diagnostic finding. Serological tests for specific antibodies and parasitological egg detection in the stool confirmed the diagnosis. After only temporary response to a short-term and low-dose treatment with praziquantel, a 3-day high-dose (40 mg/kg body weight) treatment with praziquantel finally led to long-lasting symptom relief. PMID:27167633

  15. [Liver cirrhosis: pulmonary function].

    PubMed

    Marichal, I; Dublet, P; Medrano, G; Hinestrosa, H; Tálamo, C; Korchoff, W; Alvarado, R; Quirós, E

    1991-01-01

    We performed a functional respiratory examination which consisted of arterial gasometry, spirometry, diffusion capacity to CO2, alveolo-arterial gradient of O2 and pulmonary volumes to 8 patients with cirrhosis diagnosed by clinical history, laboratory exams, abdominal ultrasound and histology. Our results showed a slight obstructive pattern of peripheric airways (FMM: 88.87 +/- 8.7%) in the spirometry, no difference in arterial gases at upright and recumbent position was observed, with low values of apO2 (75.51 +/- 1.16 upright and 75.87 +/- 2.16 mmHg recumbent) without statistic significance. The gradient G(Aa) O2 increased to (30.89 +/- 1.06 mmHg). Besides there was a diffusion abnormality with a DLCO2/VA of (71.87 +/- 6.05%). Breathing 100% O2, did not change the gradient which allows us to postulate the existence of an abnormality of gaseous interchange due to shunts. We found no relationship between albumin levels and DLCO2/VO neither with pO2 in upright position; there was a relationship at recumbent position between the hepatic disorder and the arterial desaturation. We concluded that there is no significant hypoxia even with position changes, there is increase of G (Aa) O2 by shunt type disorders and that this is probably related with albumin levels. PMID:1843958

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

    PubMed Central

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

    2013-01-01

    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. PMID:23403453

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

    SciTech Connect

    Stadalnik, R.C.

    1993-03-25

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

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

    PubMed

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

    2013-08-01

    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

  19. Life-threatening postpartum hemolysis, elevated liver functions tests, low platelets syndrome versus thrombocytopenic purpura – Therapeutic plasma exchange is the answer

    PubMed Central

    Nasa, Prashant; Dua, J. M.; Kansal, Sudha; Chadha, Geeta; Chawla, Rajesh; Manchanda, Manav

    2011-01-01

    The differential diagnosis of life-threatening microangiopathic disorders in a postpartum female includes severe preeclampsia–eclampsia, hemolysis, elevated liver functions tests, low platelets syndrome and thrombotic thrombocytopenic purpura. There is considerable overlapping in the clinical and laboratory findings between these conditions, and hence an exact diagnosis may not be always possible. However, there is considerable maternal mortality and morbidity associated with these disorders. This case underlines the complexity of pregnancy-related microangiopathies regarding their differential diagnosis, multiple organ dysfunction and role of therapeutic plasma exchange in their management. PMID:21814380

  20. Quantitative Liver Function Tests Improve the Prediction of Clinical Outcomes in Chronic Hepatitis C: Results from the HALT-C Trial

    PubMed Central

    Everson, Gregory T.; Shiffman, Mitchell L.; Hoefs, John C.; Morgan, Timothy R.; Sterling, Richard K.; Wagner, David A.; Lauriski, Shannon; Curto, Teresa M.; Stoddard, Anne; Wright, Elizabeth C.

    2011-01-01

    Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C. We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred twenty seven participants in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.5 years for clinical outcomes. QLFTs were repeated in 196 patients at month 24 and in 165 patients at month 48. Caffeine elimination rate (k), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, and perfused hepatic mass (PHM) and liver and spleen volumes (SPECT) were measured. Baseline QLFTs were significantly worse (p=0.0017 to <0.0001) and spleen volumes larger (p<0.0001) in the 54 patients who subsequently experienced clinical outcomes. QLFT cutoffs that characterized patients as “low” and “high risk” for clinical outcome yielded hazard ratios ranging from 2.21 (95%CI 1.29–3.78) for GEC to 6.52 (95%CI 3.63–11.71) for CA Cloral. QLFTs independently predicted outcome in models with Ishak fibrosis score, platelet count, and standard laboratory tests. In serial studies, patients with “high risk” results for CA Cloral or PHM had a nearly 15-fold increase in risk for clinical outcome. Less than 5% of patients with “low risk” QLFTs experienced a clinical outcome. Conclusion QLFTs independently predict risk for future clinical outcomes. By improving risk assessment, QLFTs could enhance noninvasive monitoring, counseling, and management of patients with chronic hepatitis C. PMID:22030902

  1. [Nuclear medicine for evaluation of liver functions].

    PubMed

    Yamamoto, K

    1994-05-01

    The clinical usefulness of colloid liver scintigraphy to detect space occupying lesions in the liver has been reduced by X-ray CT and ultrasonography. However, scintigraphic examinations have potentials for characteristic diagnosis of liver tumors, such as 99mTc RBC SPECT for hepatic hemangioma, 99mTc PMT for positive imaging of hepatocellular carcinoma and its extrahepatic metastasis, and radioimmunoscintigraphy for metastatic tumors. Moreover, prediction of the prognosis and monitoring therapeutic effect to liver cancer can be made by the use of nuclear medicine techniques. Recently, 99mTc galactosyl serum albumin (GSA), a newly developed radiotracer to evaluate hepatocyte function, has become commercially available. Quantitative parameters of liver functions can be obtained by analysis of time-activity curve in blood and liver after 99mTc-GSA administration. In several cases, 99mTc-GSA study showed intrahepatic unevenness of function, which could not be depicted by other imaging examinations. Positron emission tomography (PET) with 18F-fluoro-2-deoxy glucose (FDG) is useful to detect malignant tumors in the liver. Since PET can provide absolutely quantitative data in better resolution, it is expected that regional true metabolic functions in the liver may be able to be quantitatively evaluated with PET in near future. PMID:8028225

  2. Use of liver breath tests to assess severity of nonalcoholic fatty liver disease.

    PubMed

    Furnari, Manuele; Savarino, Vincenzo; Giannini, Edoardo G

    2014-01-01

    As the prevalence of obesity and insulin-resistance continues to increase in the general population, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions, thus becoming one of the leading causes of chronic liver disease worldwide. It may present as simple steatosis (NAFL) or steatohepatitis (NASH), which in turn may develop fibrosis and ultimately cirrhosis. Conventional biochemical liver test and radiological investigations are not able to provide reliable information on liver functional reserve, and liver biopsy remains the gold standard to stage NAFLD, differentiate simple steatosis from NASH, and grade fibrosis. However, liver biopsy has some limitations, and is not preferred by patients due to its invasiveness. Thus, non-invasive assessment of disease stage by using liver breath tests - which are based on hepatic clearance of non-radioactive stable (13)C-labelled drugs - may be of interest to stage disease and assess patients prognosis due to good accuracy and repeatability. These substrates are orally administered and are cleaved by enzymes specifically located in the liver thus reflecting either the microsomal, cytosolic, or mitochondrial functions. (13)C-Breath Tests have been initially oriented to differentiate broad categories of patients and more recently to refine stage differentiation in patients with early stages of liver disease. In NAFLD patients, (13)C-BTs were able to distinguish simple steatosis from NASH and had good correlation with both histological fibrosis stage and biochemical markers of fibrogenesis. Although promising results have been achieved in this field, their use in clinical practice is still restricted to a specialized niche. However, concordant data from literature conferred to (13)C-Breath Tests a potential role in providing punctual and longitudinal evaluation of patients, identifying those patients where liver biopsy may selectively be performed to stage disease, monitoring and predicting therapeutic

  3. A Randomized Controlled Trial of the Effects of an Almond-enriched, Hypocaloric Diet on Liver Function Tests in Overweight/Obese Women

    PubMed Central

    Abazarfard, Zohreh; Eslamian, Ghazaleh; Salehi, Mousa; Keshavarzi, Sareh

    2016-01-01

    Background: Gradual weight reduction has been shown to be associated with improvements in liver enzymes. However, some evidence demonstrated that liver enzymes may transiently increase immediately after a diet-induced weight loss. Objectives: This study was designed to assess the effects of a hypocaloric, almond-enriched diet (AED) compared with a hypocaloric nut-free diet (NFD) on liver function tests in the context of a three-month weight reduction program in overweight/obese women. Patients and Methods: This randomized controlled clinical trial was registered at Iranian Registry of Clinical Trials with ID number of IRCT2013062313751N1. Overweight and obese Iranian women [n = 108; age = 42.7 y, body mass index = 29.6 kg/m2] were randomly assigned to consume an AED or NFD. The carefully planned hypocaloric diets were identical for both groups except for the AED group who consumed 50 grams of almonds daily for three months. Anthropometric measurements and laboratory measurements including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) were assessed before and immediately after the intervention. Results: Of 108 participants, 50 women in AED group and 50 women in NFD group completed the protocol of the study (response rate: 92.6 %). The AED led to a median weight loss of 3.79 kg (interquartile range: 4.4 kg). Significant decreases within AED and NFD were observed in ALT (-16.6 ± 16.3 and -11.7 ± 16.8, P < 0.001, respectively). Similar significant decreases were observed in AST (-13.6 ± 15.7 and -7.7 ± 16.1; P < 0.001, respectively). The decrease in GGT was also significant in both groups (-11.4 ± 21.6 and -6.2 ± 19.8; P < 0.001 respectively). ALT, AST and GGT decreased significantly in the AED group compared to the NFD group (P < 0.001). Conclusions: AED improved liver enzymes in obese women. However, mild, transient increases in ALT and AST values can be observed immediately after

  4. 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

    2011-01-01

    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

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

    PubMed Central

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

    2015-01-01

    Background Sarcopenia, obesity and sarcopenic obesity have been linked to impaired outcome after liver surgery. Preoperative liver function of sarcopenic, obese and sarcopenic-obese patients might be reduced, possibly leading to more post-operative morbidity. The aim of this study was to explore whether liver function and volume were influenced by body composition in patients undergoing liver resection. Methods In 2011 and 2012, all consecutive patients undergoing the methacetin breath liver function test were included. Liver volumetry and muscle mass analysis were performed using preoperative CT scans and Osirix® software. Muscle mass and body-fat% were calculated. Predefined cut-off values for sarcopenia and the top two body-fat% quintiles were used to identify sarcopenia and obesity, respectively. Histologic assessment of the resected liver gave insight in background liver disease. Results A total number of 80 patients were included. Liver function and volume were comparable in sarcopenic(-obese) and non-sarcopenic(-obese) patients. Obese patients showed significantly reduced liver function [295 (95–508) vs. 358 (96–684) µg/kg/h, P = 0.018] and a trend towards larger liver size [1694 (1116–2685) vs. 1533 (869–2852) mL, P = 0.079] compared with non-obese patients. Weight (r = −0.40), body surface area (r = −0.32), estimated body-fat% (r = −0.43) and body mass index (r = −0.47) showed a weak but significant negative (all P < 0.05) correlation with liver function. Moreover, body-fat% was identified as an independent factor negatively affecting the liver function. Conclusion Sarcopenia and sarcopenic obesity did not seem to influence liver size and function negatively. However, obese patients had larger, although less functional, livers, indicating dissociation of liver function and volume in these patients. PMID:26136191

  6. Optimizing global liver function in radiation therapy treatment planning

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  7. Optimizing global liver function in radiation therapy treatment planning.

    PubMed

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

    2016-09-01

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

  8. Multiphoton microscopy in defining liver function

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  9. Immunological functions of liver sinusoidal endothelial cells.

    PubMed

    Knolle, Percy A; Wohlleber, Dirk

    2016-05-01

    Liver sinusoidal endothelial cells (LSECs) line the liver sinusoids and separate passenger leukocytes in the sinusoidal lumen from hepatocytes. LSECs further act as a platform for adhesion of various liver-resident immune cell populations such as Kupffer cells, innate lymphoid cells or liver dendritic cells. In addition to having an extraordinary scavenger function, LSECs possess potent immune functions, serving as sentinel cells to detect microbial infection through pattern recognition receptor activation and as antigen (cross)-presenting cells. LSECs cross-prime naive CD8 T cells, causing their rapid differentiation into memory T cells that relocate to secondary lymphoid tissues and provide protection when they re-encounter the antigen during microbial infection. Cross-presentation of viral antigens by LSECs derived from infected hepatocytes triggers local activation of effector CD8 T cells and thereby assures hepatic immune surveillance. The immune function of LSECs complements conventional immune-activating mechanisms to accommodate optimal immune surveillance against infectious microorganisms while preserving the integrity of the liver as a metabolic organ. PMID:27041636

  10. Complete blood counts, liver function tests, and chest x-rays as routine screening in early-stage breast cancer: value added or just cost?

    PubMed

    Louir, Raphael J; Tonneson, Jennifer E; Gowarty, Minda; Goodney, Philip P; Barth, Richard J; Rosenkranz, Kari M

    2015-11-01

    Current National Comprehensive Cancer Network guidelines for breast cancer staging include pre-treatment complete blood count (CBC) and liver function tests (LFT) to screen for occult metastatic disease. To date, the relevance of these tests in detecting metastatic disease in asymptomatic women with early-stage breast cancer (Stage I/II) has not been demonstrated. Although chest x-rays are no longer recommended in the NCCN guidelines, many centers continue to include this imaging as part of their screening process. We aim to determine the clinical and financial impact of these labs and x-rays in the evaluation of early-stage breast cancer patients. A single institution IRB-approved retrospective chart review was conducted of patients with biopsy-proven invasive breast cancer treated from January 1, 2005–December 31, 2009. We collected patient demographics, clinical and pathologic staging, chest x-ray, CBC, and LFT results at the time of referral. Patients were stratified according to radiographic stage at the time of diagnosis. We obtained Medicare reimbursement fees for cost analysis. From 2005 to 2009, 1609 patients with biopsy-proven invasive breast cancer were treated at our institution. Of the 1082 patients with radiographic stage I/II disease, 27.3 % of patients had abnormal CBCs. No additional testing was performed to evaluate these abnormalities. In the early-stage population, 24.7 % of patients had elevated LFTs, resulting in 84 additional imaging studies. No metastatic disease was detected. The cost of CBC, LFTs and chest x-rays was $110.20 per patient, totaling $106,410.99. Additional tests prompted by abnormal results cost $58,143.30 over the five-year period. We found that pre-treatment CBCs, LFTs, and chest x-rays did not improve detection of occult metastatic disease but resulted in additional financial costs. Avoiding routine ordering of these tests would save the US healthcare system $25.7 million annually. PMID:26467045

  11. A comparative analysis of liver transcriptome suggests divergent liver function among human, mouse and rat.

    PubMed

    Yu, Yao; Ping, Jie; Chen, Hui; Jiao, Longxian; Zheng, Siyuan; Han, Ze-Guang; Hao, Pei; Huang, Jian

    2010-11-01

    The human liver plays a vital role in meeting the body's metabolic needs and maintaining homeostasis. To address the molecular mechanisms of liver function, we integrated multiple gene expression datasets from microarray, MPSS, SAGE and EST platforms to generate a transcriptome atlas of the normal human liver. Our results show that 17396 genes are expressed in the human liver. 238 genes were identified as liver enrichment genes, involved in the functions of immune response and metabolic processes, from the MPSS and EST datasets. A comparative analysis of liver transcriptomes was performed in humans, mice and rats with microarray datasets shows that the expression profile of homologous genes remains significantly different between mouse/rat and human, suggesting a functional variance and regulation bias of genes expressed in the livers. The integrated liver transcriptome data should provide a valuable resource for the in-depth understanding of human liver biology and liver disease. PMID:20800674

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

    PubMed Central

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

    2016-01-01

    AIM: To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. METHODS: Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient. RESULTS: At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to ½ of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures

  13. Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI

    PubMed Central

    Nilsson, Henrik; Blomqvist, Lennart; Douglas, Lena; Nordell, Anders; Jonas, Eduard

    2010-01-01

    Objectives Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) is a gadolinium-based hepatocyte-specific contrast agent for magnetic resonance imaging (MRI). The aim of this study was to determine whether the hepatic uptake and excretion of Gd-EOB-DTPA differ between patients with primary biliary cirrhosis (PBC) and healthy controls, and whether differences could be quantified. Methods Gd-EOB-DTPA-enhanced liver MRI was performed in 20 healthy volunteers and 12 patients with PBC. The uptake of Gd-EOB-DTPA was assessed using traditional semi-quantitative parameters (Cmax, Tmax and T1/2), as well as model-free parameters derived after deconvolutional analysis (hepatic extraction fraction [HEF], input-relative blood flow [irBF] and mean transit time [MTT]). In each individual, all parameters were calculated for each liver segment and the median of the segmental values was used to define a global liver median (GLM). Results Although the PBC patients had relatively mild disease according to their Model for End-stage Liver Disease (MELD), Child–Pugh and Mayo risk scores, they had significantly lower HEF and shorter MTT values compared with the healthy controls. These differences significantly increased with increasing MELD and Child–Pugh scores. Conclusions Dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) has a potential role as an imaging-based liver function test. The high spatial resolution of MRI enables hepatic function to be assessed on segmental and sub-segmental levels. PMID:20887325

  14. Circadian Clock Control of Liver Metabolic Functions.

    PubMed

    Reinke, Hans; Asher, Gad

    2016-03-01

    The circadian clock is an endogenous biological timekeeping system that synchronizes physiology and behavior to day/night cycles. A wide variety of processes throughout the entire gastrointestinal tract and notably the liver appear to be under circadian control. These include various metabolic functions such as nutrient uptake, processing, and detoxification, which align organ function to cycle with nutrient supply and demand. Remarkably, genetic or environmental disruption of the circadian clock can cause metabolic diseases or exacerbate pathological states. In addition, modern lifestyles force more and more people worldwide into asynchrony between the external time and their circadian clock, resulting in a constant state of social jetlag. Recent evidence indicates that interactions between altered energy metabolism and disruptions in the circadian clock create a downward spiral that can lead to diabetes and other metabolic diseases. In this review, we provide an overview of rhythmic processes in the liver and highlight the functions of circadian clock genes under physiological and pathological conditions; we focus on their roles in regulation of hepatic glucose as well as lipid and bile acid metabolism and detoxification and their potential effects on the development of fatty liver and nonalcoholic steatohepatitis. PMID:26657326

  15. Loss of brain function - liver disease

    MedlinePlus

    ... of chronic liver damage. Common causes of chronic liver disease in the United States are: Chronic hepatitis B ... hepatitis Bile duct disorders Some medicines Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) Once you have ...

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

    PubMed Central

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

    2015-01-01

    Background Schistosomiasis mansoni is a chronic liver disease, in which some patients (5–10%) progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients. Methodology/Principal Findings Forty-five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55). Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1. Conclusion/Significance This study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status. PMID:26267788

  17. Astaxanthin as a Potential Protector of Liver Function: A Review

    PubMed Central

    Chen, Jui-Tung; Kotani, Kazuhiko

    2016-01-01

    Protecting against liver damage, such as non-alcoholic fatty liver disease, is currently considered to be important for the prevention of adverse conditions, such as cardiovascular and cancerous diseases. Liver damage often occurs in relation to oxidative stress with metabolic disorders, including cellular lipid accumulation. Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′dione), a xanthophyll carotenoid, is a candidate for liver protection. Here, we briefly review astaxanthin as a potential protector against liver damage. In particular, studies have reported antioxidative effects of astaxanthin in liver tissues. Astaxanthin treatment is also reported to improve hyperlipidemia, which indirectly induces the antioxidative effects of astaxanthin on liver pathologies. Furthermore, astaxanthin may alleviate liver damage independent of its antioxidative effects. Of note, there are still insufficient human data to observe the effect of astaxanthin treatment on liver function in clinical conditions. More studies investigating the relevance of astaxanthin on liver protection are necessary.

  18. The relationship between aminopyrine breath test and severity of liver disease in cirrhosis

    SciTech Connect

    Morelli, A.; Narducci, F.; Pelli, M.A.; Farroni, F.; Vedovelli, A.

    1981-08-01

    Twenty-two patients with cirrhosis were evaluated by the 2 hr.-(C14)-aminopyrine breath test, the conventional liver tests and two systems for grading the severity of liver disease. Twenty-three patients with noncirrhotic liver disease and 15 controls were also studied. Reduced 14CO2 values were found in 21 of the 22 cirrhotic patients and seven of those had noncirrhotic liver disease associated with severe functional reserve impairment. The values in patients with minor liver diseases or cholestasis were normal. In the cirrhotic patients 2 hr.-(C14)-aminopyrine breath test scores correlated with prothrombin time, retention of bromosulfalein, fasting serum bile acid, albumin, bilirubin, serum aspartate aminotransferase and, above all, with the scores of the two clinical rating systems. The 2 hr.-(C14)-aminopyrine breath test was superior to conventional tests in quantifying the degree of hepatic functional reserve and forecasting the prognosis.

  19. Extraocular muscle function testing

    MedlinePlus

    Extraocular muscle function testing examines the function of the eye muscles. A health care provider observes the movement of ... evaluate weakness or other problem in the extraocular muscles. These problems may result in double vision or ...

  20. Functional Task Test (FTT)

    NASA Technical Reports Server (NTRS)

    Bloomberg, Jacob J.; Mulavara, Ajitkumar; Peters, Brian T.; Rescheke, Millard F.; Wood, Scott; Lawrence, Emily; Koffman, Igor; Ploutz-Snyder, Lori; Spiering, Barry A.; Feeback, Daniel L.; Platts, Steven H.; Stenger, Michael B.; Lee, Stuart M.C.; Arzeno, Natalia; Feiveson, Alan H.; Ryder, Jeffrey; Garcia, Yamil; Guilliams, Mark E.

    2009-01-01

    This slide presentation reviews the Functional Task Test (FTT), an interdisciplinary testing regimen that has been developed to evaluate astronaut postflight functional performance and related physiological changes. The objectives of the project are: (1) to develop a set of functional tasks that represent critical mission tasks for the Constellation Program, (2) determine the ability to perform these tasks after space flight, (3) Identify the key physiological factors that contribute to functional decrements and (4) Use this information to develop targeted countermeasures.

  1. [The diagnostic value of the aminophenazone breath test in chronic liver diseases].

    PubMed

    Sensing, H; Treutler, J; Haustein, K O; Hüller, G

    1991-09-01

    In 230 patients (90 females, 140 males aged between 20 and 73 years, average age 47.8 years) with and without exception histologically and/or laparoscopically ascertained chronic liver diseases (degenerative damages of liver parenchyma in 45, fatty liver stage I in 28, fatty liver stage II in 36, cholangiohepatitis in 4, chronic persisting hepatitis in 31, chronic active hepatitis in 57 and liver cirrhosis in 59 cases) the incorporation of the aminophenazon breathing test in the so-called laboratory chemical liver spectrum was controlled. The restriction of the microsomal biotransformation established by means of the aminophenazon breathing test behaved parallel to the degree of severity of the disease. The aminophenazon breathing test was performed in the modification after Haustein and Schenker (1985). The largest delays in the decomposition were found in the complete cirrhotic transformation of the liver. The unequivocally pathologic result of the aminophenazon breathing test in severe irreversible damages of the liver parenchyma was confirmed by the formation of correlations with parameters of the conventional laboratory spectrum of the liver. Thus the restriction of the performance of the synthesis of the liver for coagulation factors and albumins was parallel to the loss of function of the mixed functional oxidases. In all patients with chronic liver diseases a connection between the value of the thromboplastin time (Quick's test) and result of the breathing test was found. Positive linear correlation between serum albumin and results of the breathing test could also be proved particularly in the group of the severe chronic inflammatory liver diseases. In chronic fibrosing liver diseases there were positive inverse correlations between gamma-globulin concentration in the serum and thymol turbidity test on the one hand as well as the aminophenazon breathing test on the other. There were no correlations between liver enzyme and aminophenazon breathing test. The

  2. Pulmonary Function Tests

    PubMed Central

    Ranu, Harpreet; Wilde, Michael; Madden, Brendan

    2011-01-01

    Pulmonary function tests are valuable investigations in the management of patients with suspected or previously diagnosed respiratory disease. They aid diagnosis, help monitor response to treatment and can guide decisions regarding further treatment and intervention. The interpretation of pulmonary functions tests requires knowledge of respiratory physiology. In this review we describe investigations routinely used and discuss their clinical implications. PMID:22347750

  3. Platelet Function Tests

    MedlinePlus

    ... of the clotting process in the body ( in vivo ). A person with normal platelet function test results may still experience excessive bleeding or inappropriate clotting during and after a surgery. Most samples for platelet function testing are only stable for a very short period ...

  4. Sperm function test

    PubMed Central

    Talwar, Pankaj; Hayatnagarkar, Suryakant

    2015-01-01

    With absolute normal semen analysis parameters it may not be necessary to shift to specialized tests early but in cases with borderline parameters or with history of fertilization failure in past it becomes necessary to do a battery of tests to evaluate different parameters of spermatozoa. Various sperm function tests are proposed and endorsed by different researchers in addition to the routine evaluation of fertility. These tests detect function of a certain part of spermatozoon and give insight on the events in fertilization of the oocyte. The sperms need to get nutrition from the seminal plasma in the form of fructose and citrate (this can be assessed by fructose qualitative and quantitative estimation, citrate estimation). They should be protected from the bad effects of pus cells and reactive oxygen species (ROS) (leukocyte detection test, ROS estimation). Their number should be in sufficient in terms of (count), structure normal to be able to fertilize eggs (semen morphology). Sperms should have intact and functioning membrane to survive harsh environment of vagina and uterine fluids (vitality and hypo-osmotic swelling test), should have good mitochondrial function to be able to provide energy (mitochondrial activity index test). They should also have satisfactory acrosome function to be able to burrow a hole in zona pellucida (acrosome intactness test, zona penetration test). Finally, they should have properly packed DNA in the nucleus to be able to transfer the male genes (nuclear chromatic decondensation test) to the oocyte during fertilization. PMID:26157295

  5. Sperm function test.

    PubMed

    Talwar, Pankaj; Hayatnagarkar, Suryakant

    2015-01-01

    With absolute normal semen analysis parameters it may not be necessary to shift to specialized tests early but in cases with borderline parameters or with history of fertilization failure in past it becomes necessary to do a battery of tests to evaluate different parameters of spermatozoa. Various sperm function tests are proposed and endorsed by different researchers in addition to the routine evaluation of fertility. These tests detect function of a certain part of spermatozoon and give insight on the events in fertilization of the oocyte. The sperms need to get nutrition from the seminal plasma in the form of fructose and citrate (this can be assessed by fructose qualitative and quantitative estimation, citrate estimation). They should be protected from the bad effects of pus cells and reactive oxygen species (ROS) (leukocyte detection test, ROS estimation). Their number should be in sufficient in terms of (count), structure normal to be able to fertilize eggs (semen morphology). Sperms should have intact and functioning membrane to survive harsh environment of vagina and uterine fluids (vitality and hypo-osmotic swelling test), should have good mitochondrial function to be able to provide energy (mitochondrial activity index test). They should also have satisfactory acrosome function to be able to burrow a hole in zona pellucida (acrosome intactness test, zona penetration test). Finally, they should have properly packed DNA in the nucleus to be able to transfer the male genes (nuclear chromatic decondensation test) to the oocyte during fertilization. PMID:26157295

  6. [Function of zinc in liver disease].

    PubMed

    Katayama, Kazuhiro

    2016-07-01

    Zinc deficiency is highly prevalent in cirrhotic patients, and contributes to several clinical symptoms such as hepatic encephalopathy and liver fibrosis. Ammonia is detoxified in liver to urea through urea cycle, and is also detoxified in extrahepatic tissue to glutamine through glutamine synthetase. The reduced ability of ammonia detoxification in liver cirrhosis is ascribed to zinc deficiency, because a member of urea cycle, ornithine transcarbamylase is a zinc enzyme. In this condition, glutamine synthesis is enhanced, which enables the body, at least temporarily, to suppress the increase of ammonia. However, the glutamine is metabolized predominantly in enterocyte to ammomia and glutamate, indicating that a vicious cycle in glutamine synthesis and glutamine breakdown occurs in liver cirrhosis. Attention should be given to the clinical significance of zinc in liver diseases. PMID:27455801

  7. Liver trauma grading and biochemistry tests.

    PubMed

    Arslan, Gozde; Gemici, Aysegul Akdogan; Yirgin, Inci Kizildag; Gulsen, Esma; Inci, Ercan

    2013-10-01

    Among solid organ blunt traumas, the liver and spleen are mostly subject to injury. In addition, the liver is also commonly injured in penetrating traumas because of its size, location, and the ease of injury to the "Glisson Capsule". Several enzymes are known to be elevated following trauma. In our study, we evaluated the correlation between the levels of serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and gamma-glutamyl transpeptidase in 57 patients with blunt trauma to the liver and compared these values to the American Association for the Surgery of Trauma trauma grading system. Additionally, we compared the enzyme level elevations in these patients to the enzyme levels of 29 healthy subjects. As expected, we found significant elevations in enzyme levels of trauma patients compared to the control group. The calculated point estimates were not significantly different between grades 1 and 2 trauma. However, grade 3 trauma group showed a significant increase in enzyme levels. PMID:23793528

  8. Mesenchymal Stem Cell-Derived Hepatocytes for Functional Liver Replacement

    PubMed Central

    Christ, Bruno; Stock, Peggy

    2012-01-01

    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. PMID:22737154

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Prevalence of abnormal liver function tests and comorbid psychiatric disorders among patients with anorexia nervosa and eating disorders not otherwise specified in the anorexia nervosa DSM-IV criteria

    PubMed Central

    Goh, Kye Hock Robin; Lee, Ee Lian

    2015-01-01

    INTRODUCTION Anorexia nervosa (AN) and eating disorders not otherwise specified (EDNOS) are on the rise in Singapore. Abnormal liver function tests have been reported for up to 12.2% of patients with AN. These patients are also known to present with comorbid psychiatric disorders. This study aims to investigate the correlation between body mass index (BMI) and the severity of abnormal liver function tests, and between BMI and the presence of comorbid psychiatric disorders. METHODS A retrospective cohort analysis of 373 patients diagnosed with AN or EDNOS at a tertiary hospital was performed. The clinical course of transaminitis and comorbid psychiatric disorders was correlated with the patient’s BMI. RESULTS Patients with a BMI of ≥ 16.6 kg/m2 at their first consult had a significantly lower risk of having comorbid psychiatric disorders (χ2 = 32.08, p < 0.001). These patients were five times less likely to have comorbid psychiatric disorders as compared to patients from the other BMI groups (odds ratio [OR] 0.21). On the other hand, patients with a BMI of < 14.6 kg/m2 had a significantly higher risk of having transaminitis (χ2 = 72.5, p < 0.001). They were 11.1 times more likely to develop transaminitis as compared to patients with a BMI of ≥ 14.6 kg/m2 (OR 11.05). CONCLUSION Severity of BMI can be used by clinicians as an indicator to assess for secondary psychiatric comorbidities and/or transaminitis during the first consultation. This could help reduce the morbidity and mortality rates in patients with AN or EDNOS. PMID:26451050

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

    PubMed Central

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

    2016-01-01

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

  13. Function of GATA Factors in the Adult Mouse Liver

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  15. Hepatic encephalopathy: effects of liver failure on brain function.

    PubMed

    Felipo, Vicente

    2013-12-01

    Liver failure affects brain function, leading to neurological and psychiatric alterations; such alterations are referred to as hepatic encephalopathy (HE). Early diagnosis of minimal HE reveals an unexpectedly high incidence of mild cognitive impairment and psychomotor slowing in patients with liver cirrhosis - conditions that have serious health, social and economic consequences. The mechanisms responsible for the neurological alterations in HE are beginning to emerge. New therapeutic strategies acting on specific targets in the brain (phosphodiesterase 5, type A GABA receptors, cyclooxygenase and mitogen-activated protein kinase p38) have been shown to restore cognitive and motor function in animal models of chronic HE, and NMDA receptor antagonists have been shown to increase survival in acute liver failure. This article reviews the latest studies aimed at understanding how liver failure affects brain function and potential ways to ameliorate these effects. PMID:24149188

  16. True versus mild hyperthermia during isolated hepatic perfusion: effects on melphalan pharmacokinetics and liver function.

    PubMed

    Pilati, Pierluigi; Mocellin, Simone; Rossi, Carlo R; Ori, Carlo; Innocente, Federico; Scalerta, Romano; Ceccherini, Mauro; Da Pian, Pier Paolo; Nitti, Donato; Lise, Mario

    2004-08-01

    Hyperthermic antiblastic isolated hepatic perfusion (IHP) with melphalan has been recently proposed as an alternative therapeutic option for patients with unresectable liver tumors. Although melphalan-heat antiblastic synergism is at a maximum at temperatures higher than 41 degrees C, IHP has so far been performed in humans at lower temperatures. In this experimental work, we compared IHP under mild versus true hyperthermic conditions in terms of drug pharmacokinetics and liver function. Ten pigs were submitted to IHP with melphalan 1.5 mg/kg at a mean temperature of 40 degrees C (group A, n = 5) or 42 degrees C (group B, n = 5). After a 60-minute perfusion, a 15-minute washout was performed. Perfusate-to-plasma leakage was monitored using scintigraphy. Throughout perfusion, samples from the systemic blood, perfusate, and liver parenchyma were obtained to measure melphalan concentrations. Liver function was assessed using standard blood tests and the indocyanine green-based test. No deaths related to the IHP procedure were recorded. All animals had transient liver function impairment, with all liver function test results returning to normal within the observation period. At histologic examination, liver damage was similar under both hyperthermic conditions. Melphalan levels in the perfusate were not significantly different in the two study groups (the mean perfusate/plasma area under the curve from 0 to 60 minutes ratios were 463 and 501, respectively). These results correlated well with those obtained using the scintigraphic method. Liver drug concentrations remained unchanged after true hyperthermia IHP. Under true hyperthermic conditions, neither an increase in liver parenchyma toxicity nor changes in melphalan pharmacokinetics were observed. These findings support the use of true hyperthermia in the clinical setting to exploit fully the antitumor synergism between melphalan and heat. PMID:15457357

  17. Development of a mechanical testing assay for fibrotic murine liver

    SciTech Connect

    Barnes, Stephanie L.; Lyshchik, Andrej; Washington, Mary K.; Gore, John C.; Miga, Michael I.

    2007-11-15

    In this article, a novel protocol for mechanical testing, combined with finite element modeling, is presented that allows the determination of the elastic modulus of normal and fibrotic murine livers and is compared to an independent mechanical testing method. The novel protocol employs suspending a portion of murine liver tissue in a cylindrical polyacrylamide gel, imaging with a microCT, conducting mechanical testing, and concluding with a mechanical property determination via a finite element method analysis. More specifically, the finite element model is built from the computerized tomography (CT) images, and boundary conditions are imposed in order to simulate the mechanical testing conditions. The resulting model surface stress is compared to that obtained during mechanical testing, which subsequently allows for direct evaluation of the liver modulus. The second comparison method involves a mechanical indentation test performed on a remaining liver lobe for comparison. In addition, this lobe is used for histological analysis to determine relationships between elasticity measurements and tissue health. This complete system was used to study 14 fibrotic livers displaying advanced fibrosis (injections with irritant), three control livers (injections without irritant), and three normal livers (no injections). The moduli evaluations for nondiseased livers were estimated as 0.62{+-}0.09 kPa and 0.59{+-}0.1 kPa for indenter and model-gel-tissue (MGT) assay tests, respectively. Moduli estimates for diseased liver ranged from 0.6-1.64 kPa and 0.96-1.88 kPa for indenter and MGT assay tests, respectively. The MGT modulus, though not equivalent to the modulus determined by indentation, demonstrates a high correlation, thus indicating a relationship between the two testing methods. The results also showed a clear difference between nondiseased and diseased livers. The developed MGT assay system is quite compact and could easily be utilized for controlled evaluation of

  18. Adrenal function testing.

    PubMed

    Dluhy, R G

    1978-12-01

    Glucocorticoid stimulation and suppression tests are essential to the definitive diagnosis of diseases of the hypothalamic-pituitary-adrenal axis, because they document abnormal physiologic control of hormonal secretion. Similarly, diseases of the renin-angiotensin-aldosterone axis are diagnosed by mineralocorticoid stimulation and suppression testing. [Ed. Note: See Moore TJ, Williams GH: Adrenal causes of hypertension, in this issue.] Unlike tests of glucocorticoid function, testing of the renin-angiotension-aldosterone system is more complicated, because knowledge of posture and dietary sodium are necessary to interpret the results. However, measurement of the tropic hormone renin and plasma levels of aldosterone can be accurately made, allowing precise definition of this system. Errors are most commonly encountered when dynamic tests of cortisol output are performed in patients taking medications that may interfere with the assays or with the metabolism of the administered compounds, such as dexamethasone or metyrapone. Abnormal, spurious values may also be obtained in some individuals who do not have adrenocortical hyperfunction if they are very obese or if testing is performed in a setting of clinical stress. Careful attention to these pitfalls will avoid errors and allow the clinician to arrive at the correct diagnosis. PMID:216524

  19. Adverse Outcome Pathways and Drug-Induced Liver Injury Testing.

    PubMed

    Vinken, Mathieu

    2015-07-20

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis, and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This review evaluates these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  20. Adverse outcome pathways and drug-induced liver injury testing

    PubMed Central

    Vinken, Mathieu

    2015-01-01

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This paper reviews these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

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

    PubMed Central

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

    2016-01-01

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

  2. Functions of autophagy in normal and diseased liver

    PubMed Central

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

    2013-01-01

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

  3. Liver morphology and function in visceral leishmaniasis (Kala-azar).

    PubMed Central

    el Hag, I A; Hashim, F A; el Toum, I A; Homeida, M; el Kalifa, M; el Hassan, A M

    1994-01-01

    AIM--To study the morphology and function of the liver in visceral leishmaniasis (Kala-azar). METHODS--Percutaneous liver biopsy specimens from 18 patients with confirmed visceral leishmaniasis were examined under light and electron microscopy before and after treatment with pentovalent antimony. The tissue was also examined for hepatitis B surface and core antigens using immunoperoxidase staining. Liver function was investigated in nine patients before and after treatment. RESULTS--Specimens before treatment showed Kupffer cells and macrophages colonised by leishmania parasites in 40% of cases. A chronic mononuclear cell infiltrate had affected the portal tracts and lobules. Ballooning degeneration of the hepatocytes, fibrosis of the terminal hepatic venules, and pericellular fibrosis were common findings. The fibrosis was related to Ito cells transforming to fibroblast-like cells. None of the patients had hepatitis B infection. All patients had biochemical evidence of liver dysfunction before treatment. Liver function improved after treatment. CONCLUSION--Visceral leishmaniasis causes morphological and functional disturbance in the liver. Focal fibrosis rather than cirrhosis occurs. The exact aetiology of hepatic damage is unclear but may have an immunological basis. Images PMID:8063939

  4. Pediatric Arm Function Test

    PubMed Central

    Uswatte, Gitendra; Taub, Edward; Griffin, Angi; Rowe, Jan; Vogtle, Laura; Barman, Joydip

    2012-01-01

    Objective Although there are several validated upper-extremity measures in young children with cerebral palsy (CP), none primarily assess capacity to carry out actions and tasks with the more-affected arm. To address this need, we developed the Pediatric Arm Function Test (PAFT), which involves behavioral observation of how children use their more-affected arm during structured play in the laboratory or clinic. This paper evaluates the reliability and validity of the PAFT Functional Ability scale. Design In Study 1, 20 children between 2–8 years with a wide range of upper-extremity hemiparesis due to CP completed the PAFT on two occasions separated by three weeks. In Study 2, 41 children between 2–6 years with similar characteristics completed the PAFT and received a grade reflecting severity of more-affected arm motor impairment. Results In Study 1, the PAFT test-retest reliability correlation coefficient was 0.74. In Study 2, convergent validity was supported by a strong, inverse correlation (r = −0.6, p < .001) between PAFT scores and grade of impairment. Conclusions The PAFT Functional Ability scale is a reliable and valid measure of more-affected arm motor capacity in children with CP between 2–6 years. It can be employed to measure upper-extremity neurorehabilitation outcome. PMID:23103486

  5. Characteristics and outcomes of chronic liver disease patients with acute deteriorated liver function by severity of underlying liver disease

    PubMed Central

    Hong, Yun Soo; Sinn, Dong Hyun; Gwak, Geum-Youn; Cho, Juhee; Kang, Danbee; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

    2016-01-01

    AIM: To analyze characteristics and outcome of patients with acute-on-chronic liver failure (ACLF) according to the severity of underlying liver disease. METHODS: One hundred and sixty-seven adult patients with chronic liver disease and acute deteriorated liver function, defined by jaundice and coagulopathy, were analyzed. Predisposition, type of injury, response, organ failure, and survival were analyzed and compared between patients with non-cirrhosis (type A), cirrhosis (type B) and cirrhosis with previous decompensation (type C). RESULTS: The predisposition was mostly hepatitis B in type A, while it was alcoholic liver disease in types B and C. Injury was mostly hepatic in type A, but was non-hepatic in type C. Liver failure, defined by CLIF-SOFA, was more frequent in types A and B, and circulatory failure was more frequent in type C. The 30-d overall survival rate (85.3%, 81.1% and 83.7% for types A, B and C, respectively, P = 0.31) and the 30-d transplant-free survival rate (55.9%, 65.5% and 62.5% for types A, B and C, respectively P = 0.33) were not different by ACLF subtype, but 1-year overall survival rate were different (85.3%, 71.7% and 58.7% for types A, B and C, respectively, P = 0.02). CONCLUSION: There were clear differences in predisposition, type of injury, accompanying organ failure and long-term mortality according to spectrum of chronic liver disease, implying classifying subtype according to the severity of underlying liver disease is useful for defining, clarifying and comparing ACLF. PMID:27076763

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

    PubMed

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

    2015-11-01

    The long-term implications of making-weight daily on musculoskeletal health and functioning of the kidney and liver remain unknown. This study aimed to investigate musculoskeletal health and kidney and liver function in a group of retired jockeys. 28 retired male jockeys (age 50-70 years) provided fasting blood samples for markers of bone metabolism and kidney and liver function. A dual-energy x-ray absorptiometry (DXA) scan was performed for the assessment of bone mineral density (BMD). Established reference ranges were used for interpretation of results. Comparisons were made between retired jockeys based on the professional racing licence held: Flat, National Hunt or Dual. Mean whole-body osteopenia was reported, with no differences between groups. Bone markers, micronutrients, electrolytes and associated hormones, and markers for kidney and liver function were within clinical normative ranges. No differences existed between groups. Results indicate the retired jockeys in this study do not demonstrate compromised bone health or kidney and liver function. However, the retired jockeys may not have undergone chronic weight cycling in the extreme manner evident in present-day jockeys, indicating the next generation of jockeys may face more of a problem. Jockeys should be tracked longitudinally throughout their racing career and beyond. PMID:26212243

  7. Systems proteomics of liver mitochondria function.

    PubMed

    Williams, Evan G; Wu, Yibo; Jha, Pooja; Dubuis, Sébastien; Blattmann, Peter; Argmann, Carmen A; Houten, Sander M; Amariuta, Tiffany; Wolski, Witold; Zamboni, Nicola; Aebersold, Ruedi; Auwerx, Johan

    2016-06-10

    Recent improvements in quantitative proteomics approaches, including Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS), permit reproducible large-scale protein measurements across diverse cohorts. Together with genomics, transcriptomics, and other technologies, transomic data sets can be generated that permit detailed analyses across broad molecular interaction networks. Here, we examine mitochondrial links to liver metabolism through the genome, transcriptome, proteome, and metabolome of 386 individuals in the BXD mouse reference population. Several links were validated between genetic variants toward transcripts, proteins, metabolites, and phenotypes. Among these, sequence variants in Cox7a2l alter its protein's activity, which in turn leads to downstream differences in mitochondrial supercomplex formation. This data set demonstrates that the proteome can now be quantified comprehensively, serving as a key complement to transcriptomics, genomics, and metabolomics--a combination moving us forward in complex trait analysis. PMID:27284200

  8. Functional and histopathologic changes in the liver during sepsis.

    PubMed

    Caruana, J A; Montes, M; Camara, D S; Ummer, A; Potmesil, S H; Gage, A A

    1982-05-01

    Although liver failure from sepsis is a frequent occurrence in serious ill, hospitalized patients, little information is available on the histologic changes of the liver. We examined the histopathology of the liver of 19 patients who died of clinical sepsis and attempted to relate certain features of the illness or treatment to the observed histopathologic changes. The most striking finding was midzonal and peripheral necrosis of a moderate to marked degree in 11 of 19 patients. Other important changes were acute inflammation and cholestasis. The severity of hepatocellular necrosis did not appear to be influenced by the premortem circulating pathogen, by the nutritional support administered or by the arterial blood pressure. It is suggested that hepatocellular necrosis is characteristic of sepsis and may be caused by loss of specific factors which normally maintain liver function and structure. PMID:6803371

  9. Pathological and ultrastructural observations and liver function analysis of Eimeria stiedai-infected rabbits.

    PubMed

    Jing, Jin; Liu, Chun; Zhu, Shun-Xing; Jiang, Ying-Mei; Wu, Liu-Cheng; Song, Hong-Yan; Shao, Yi-Xiang

    2016-06-15

    To study the pathogenicity of Eimeria stiedai, sporulated oocysts were given orally to coccidian-free two-month-old New Zealand rabbits(1000±20g). After 30days, blood samples from the rabbit hearts were collected for routine blood tests, liver functions and four characteristics of blood coagulation. Additionally, specimens of the liver, bile duct and duodenum were collected to observe the changes in pathology and ultrastructure. E. stiedai severely restricted the growth and development of rabbits. Blood tests showed that glutamine transferase (GGT) and serum cholinesterase (ChE) were significantly different from the non-infected controls. Other extremely significant differences were observed in the biochemical indices of routine blood tests, liver function and four blood coagulation characteristics, indicating that the liver functions were significantly affected. Staining showed that, compared with the negative control group, the liver, bile duct and duodenum contained significant numbers of lesions, and organs and cell structures suffered severe damage in ultrastructure, which greatly affecting bodily functions. E. stiedai-infected rabbits model was successfully established, which might provide a theoretical basis for research on the pathogenesis of rabbit coccidia, and the diagnosis and prevention of coccidiosis in rabbits. PMID:27198796

  10. A novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo

    PubMed Central

    Reebye, V.; Sætrom, P.; Mintz, P.J.; Huang, K.W.; Swiderski, P.; Peng, L.; Liu, C.; Liu, X.X.; Jensen, S.; Zacharoulis, D.; Kostomitsopoulos, N.; Kasahara, N.; Nicholls, J.P.; Jiao, L.R.; Pai, M.; Mizandari, M.; Chikovani, T.; Emara, M.M.; Haoudi, A.; Tomalia, D.A.; Rossi, J.J.; Habib, N.A.; Spalding, D.R.

    2015-01-01

    Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here, we show an innovative RNA-based targeted approach to enhance endogenous albumin production whilst reducing liver tumour burden. We designed short-activating RNAs (saRNA) to enhance expression of C/EBPα (CCAAT/enhancer-binding protein-α), a transcriptional regulator and activator of albumin gene expression. Increased levels of both C/EBPα and albumin mRNA in addition to a 3-fold increase in albumin secretion and 50% decrease in cell proliferation was observed in C/EBPα-saRNA transfected HepG2 cells. Intravenous injection of C/EBPα-saRNA in a cirrhotic rat model with multifocal liver tumours increased circulating serum albumin by over 30% showing evidence of improved liver function. Tumour burden decreased by 80% (p = 0.003) with a 40% reduction in a marker of pre-neoplastic transformation. Since C/EBPα has known anti-proliferative activities via retinoblastoma, p21 and cyclins; we used mRNA expression liver cancer specific microarray in C/EBPα-saRNA transfected HepG2 cells to confirm down-regulation of genes strongly enriched for negative regulation of apoptosis, angiogenesis and metastasis. Up-regulated genes were enriched for tumour suppressors and positive regulators of cell differentiation. A quantitative PCR and Western-blot analysis of C/EBPα-saRNA transfected cells suggested that in addition to the known anti-proliferative targets of C/EBPα, we also observed suppression of IL6R, c-Myc and reduced STAT3 phosphorylation. Conclusion We demonstrate for the first time that a novel injectable saRNA-oligonucleotide that enhances C/EBPα expression successfully reduces tumour burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model. PMID:23929703

  11. Effects of simulated heliox diving at high altitudes on blood cells, liver functions and renal functions.

    PubMed

    Hu, Hui-Jun; Fan, Dan-Feng; Lv, Yan; Zhang, Yu; Yang, Chen; Zhao, Ling; Zhao, Ru-Gang; Pan, Xiao-Wen

    2013-01-01

    The aim of the present study was to examine the effects of simulated heliox diving at high altitudes on divers' blood cells, liver functions and renal functions. In this experiment, four divers lived for nine consecutive days in a dual-function high-low pressure chamber, which simulated air pressure at an altitude of 3,000 meters and at a 30-meter depth; an altitude of 4,000 meters and 30-meter depth; and at an altitude of 5,200 meters and 30 meters and 50 meters in depth. Total time underwater was 60 minutes. The subjects breathed heliox (with oxygen at 40% and helium at 60%) during the simulated 30-meter dive from zero altitude to 30 meters and while remaining underwater; they breathed air while ascending from 30 meters to 18. They breathed heliox (with oxygen at 26.7% and helium at 73.3%) in the simulated dive from zero altitude to 50 meters underwater, in remaining underwater and in ascending from 50 meters to 29; air while ascending from 29 meters to 18. Pure oxygen was breathed while ascending from 18 meters to the surface; then air. Results indicated: (1) the correlating indices of routine blood, liver and renal functions, and urine routine were all within normal reference ranges; and (2) the indices tested at other periods of time were not significantly different (p > 0.05) from the results at zero-meter level and 3,000-meter level. The study suggests that the heliox diving processes at different high altitudes simulated in this experiment have no significant impact upon divers' blood routine, liver functions and renal functions. PMID:23957203

  12. Assessment of Liver Function Using 99mTc-Mebrofenin Hepatobiliary Scintigraphy in ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy)

    PubMed Central

    Cieslak, Kasia P.; Olthof, Pim B.; van Lienden, Krijn P.; Besselink, Marc G.; Busch, Olivier R.C.; van Gulik, Thomas M.; Bennink, Roelof J.

    2015-01-01

    ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a new surgical technique for patients in whom conventional treatment is not feasible due to insufficient future remnant liver (FRL). During the first stage of ALPPS, accelerated hypertrophy of the FRL is induced by ligation of the portal vein and in situ split of the liver. In the second stage, the deportalized liver is removed when the FRL volume has reached ≥25% of total liver volume. However, FRL volume does not necessarily reflect FRL function. 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) with SPECT-CT is a quantitative test enabling regional assessment of parenchymal uptake function using a validated cut-off value for the prediction of postoperative liver failure (2.7%/min/m2). This paper describes the changes in FRL function and FRL volume in a 79-year-old patient diagnosed with metachronous colonic liver metastases who underwent ALPPS. We have observed a substantial difference between the increase in FRL volume and FRL function suggesting that HBS with SPECT-CT enables monitoring of the FRL function and could be a useful tool in the timing of resection in the second stage of the ALPPS procedure. PMID:26675783

  13. Cognitive functions in patients with liver cirrhosis: A tendency to commit more memory errors

    PubMed Central

    Ciećko-Michalska, Irena; Wójcik, Jan; Senderecka, Magdalena; Wyczesany, Mirosław; Binder, Marek; Szewczyk, Jakub; Dziedzic, Tomasz; Słowik, Agnieszka; Mach, Tomasz

    2013-01-01

    Background Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy (HE). For diagnostic purposes, 2 alternative batteries of psychometric screening tests are recommended. They differ from each other in terms of the cognitive domains assessed. The research was designed to provide a profile of cognitive functioning in patients with liver cirrhosis, using an assessment that covers a wider range of cognitive functions than the usual screening battery. Material/Methods We examined 138 persons, including 88 with liver cirrhosis and 50 healthy volunteers. The Mini Mental State Examination (MMSE) was used for screening and excluding advanced cognitive impairment. Then, to assess cognitive functions in more detail, the following tests were used: Auditory Verbal Learning Test (AVLT), Letter and Semantic Fluency Tests (LF and SF), Trail Making Test (TMT A&B), Digit Symbol Test (DST), Block Design Test (BDT), and Mental Rotation Test (MRT). The MRT task has not been used in MHE diagnosis so far. Finally, 57 patients and 48 controls took part in the entire study. Results Patients with liver cirrhosis commit significantly more errors of intrusions in the AVLT during the delayed free recall trial. Results significantly deviating from the norm in at least 2 tests were found only in 7 cirrhosis patients. Conclusions The results do not provide any specific profile of cognitive disturbances in MHE, but suggest that cirrhosis patients have a tendency to commit more memory errors, probably due to subtle impairments of executive function. PMID:23598598

  14. Glycation of Liver Cystatin: Implication on its Structure and Function.

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2016-09-01

    The increased level of reducing sugars and their derivatives in a diabetic condition has been the main cause of protein related complications. The changes in native state of proteins upon glycation induce loss in the function and structure of proteins. This further leads to cell damage and accumulation of immune system inducing AGE formation. Here in the present study cystatin was purified from liver (BLC) through affinity chromatography and was incubated with glucose, fructose and ribose. Changes were observed in the intensity of Trp absorption at 280 nm as well as AGE's specific fluorescence at 435 nm upon excitation at 370 nm to monitor the formation of BLC-sugar adducts. Protein intrinsic fluorescence showed marked conformational changes when BLC was incubated with D-ribose, glucose and fructose. Glycation with D-ribose induces BLC to misfold rapidly into an intermediate state retaining a low percentage of α-helical content compared to fructose and glucose as revealed by far-UV CD data. Furthermore, a caseinolytic assay of papain in presence of glycated liver cystatin showed decreased activity in the protein induced by these reducing sugars. Ribose had more effect on the structure as well as the function of liver cystatin followed by fructose and least for glucose. Absorption spectroscopy shows change in BLC and formation of AGE's. These results shows that liver cystatin-cathepsin imbalance is compromised in diabetic state which may lead to improper balance of proteinases leading to cirrhosis or liver damage. PMID:27351669

  15. Thyroid Function Tests.

    ERIC Educational Resources Information Center

    Glover, Irving T.

    1979-01-01

    Describes two tests, T-4 and T-3, for hypothyroid based on the binding of the hormones by proteins. The tests were performed in courses for physicians, clinical chemists, laboratory technicians, and undergraduate science students by the individuals involved and on their own sera. These tests are commercially available in kit form. (GA)

  16. Bioreactor Technologies to Support Liver Function In Vitro

    PubMed Central

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

    2014-01-01

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

  17. Functional Blood Progenitor Markers in Developing Human Liver Progenitors.

    PubMed

    Goldman, Orit; Cohen, Idan; Gouon-Evans, Valerie

    2016-08-01

    In the early fetal liver, hematopoietic progenitors expand and mature together with hepatoblasts, the liver progenitors of hepatocytes and cholangiocytes. Previous analyses of human fetal livers indicated that both progenitors support each other's lineage maturation and curiously share some cell surface markers including CD34 and CD133. Using the human embryonic stem cell (hESC) system, we demonstrate that virtually all hESC-derived hepatoblast-like cells (Hep cells) transition through a progenitor stage expressing CD34 and CD133 as well as GATA2, an additional hematopoietic marker that has not previously been associated with human hepatoblast development. Dynamic expression patterns for CD34, CD133, and GATA2 in hepatoblasts were validated in human fetal livers collected from the first and second trimesters of gestation. Knockdown experiments demonstrate that each gene also functions to regulate hepatic fate mostly in a cell-autonomous fashion, revealing unprecedented roles of fetal hematopoietic progenitor markers in human liver progenitors. PMID:27509132

  18. Alcoholic liver disease

    MedlinePlus

    ... blood count (CBC) Liver biopsy Liver function tests Coagulation studies Tests to rule out other diseases include: ... over-the-counter medicines. MEDICINES FROM YOUR DOCTOR "Water pills" (diuretics) to get rid of fluid build- ...

  19. Bilirubin binding with liver cystatin induced structural and functional changes.

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

    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

  20. Structural and functional hepatocyte polarity and liver disease

    PubMed Central

    Gissen, Paul; Arias, Irwin M.

    2015-01-01

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

  1. Pulmonary Function Tests

    MedlinePlus

    ... enters your body. The most common PFT’s are spirometry (spy-RAH-me-tree), diffusion studies and body ... on the day of your test. What is spirometry? Spirometry is one of the most commonly ordered ...

  2. Thyroid function tests

    MedlinePlus

    ... free T4 (the main thyroid hormone in your blood) TSH (the hormone from the pituitary gland that stimulates the thyroid to produce T4) T3 (also included sometimes) Other thyroid tests include: T3 resin uptake Thyroid scan

  3. [Endothelial function test].

    PubMed

    Tomiyama, Hirofumi

    2015-11-01

    Endothelial dysfunction is thought to have pivotal roles for the development of hypertension, initiation/progression of hypertensive organ damages, and prognosis. In clinical setting, flow-mediated vasodilatation (FMD) of brachial artery is used as a marker of endothelial function. However, well-trained sonographer is needed to conduct FMD measurement, and therefore, FMD has not been fully standardized (i.e., the reference value of FMD has not been established). Even so, FMD predicts future cardiovascular events. Lifestyle modifications (i.e., smoking cessation, exercise, or weight loss) and antihypertensive medication provide beneficial effects on endothelial function. Thus, FMD have a potential as a useful surrogate marker for the management of hypertension. PMID:26619655

  4. Pulmonary Function Testing in Children

    MedlinePlus

    ... are s pirometry and airway resistance tests . What is spirometry? Spirometry is the most common lung function test done. ... follow very specific instructions. Most children can do spirometry by age 6, though some preschoolers are able ...

  5. Redox Control of Liver Function in Health and Disease

    PubMed Central

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

    2010-01-01

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

  6. Factors Affecting Exercise Test Performance in Patients After Liver Transplantation

    PubMed Central

    Kotarska, Katarzyna; Wunsch, Ewa; Jodko, Lukasz; Raszeja-Wyszomirska, Joanna; Bania, Izabela; Lawniczak, Malgorzata; Bogdanos, Dimitrios; Kornacewicz-Jach, Zdzislawa; Milkiewicz, Piotr

    2016-01-01

    Background Cardiovascular diseases are a leading cause of morbidity and mortality in solid organ transplant recipients. In addition, low physical activity is a risk factor for cardiac and cerebrovascular complications. Objectives This study examined potential relationships between physical activity, health-related quality of life (HRQoL), risk factors for cardiovascular disease, and an exercise test in liver-graft recipients. Patients and Methods A total of 107 participants (62 men/45 women) who had received a liver transplantation (LT) at least 6 months previously were evaluated. Physical activity was assessed using three different questionnaires, while HRQoL was assessed using the medical outcomes study short form (SF)-36 questionnaire, and health behaviors were evaluated using the health behavior inventory (HBI). The exercise test was performed in a standard manner. Results Seven participants (6.5%) had a positive exercise test, and these individuals were older than those who had a negative exercise test (P = 0.04). A significant association between a negative exercise test and a higher level of physical activity was shown by the Seven-day physical activity recall questionnaire. In addition, HRQoL was improved in various domains of the SF-36 in participants who had a negative exercise test. No correlations between physical activity, the exercise test and healthy behaviors, as assessed via the HBI were observed. Conclusions Exercise test performance was affected by lower quality of life and lower physical activity after LT. With the exception of hypertension, well known factors that affect the risk of coronary artery disease had no effect on the exercise test results. PMID:27226801

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

    PubMed

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

    2016-09-01

    Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. PMID:27288631

  8. Tests of gastric neuromuscular function.

    PubMed

    Parkman, Henry P; Jones, Michael P

    2009-05-01

    Tests of gastric neuromuscular function are used to evaluate patients with symptoms referable to the upper digestive tract. These symptoms can be associated with alterations in the rates of gastric emptying, impaired accommodation, heightened gastric sensation, or alterations in gastric myoelectrical function and contractility. Management of gastric neuromuscular disorders requires an understanding of pathophysiology and treatment options as well as the appropriate use and interpretation of diagnostic tests. These tests include measures of gastric emptying; contractility; electrical activity; regional gastric motility of the fundus, antrum, and pylorus; and tests of sensation and compliance. Tests are also being developed to improve our understanding of the afferent sensory pathways from the stomach to the central nervous system that mediate gastric sensation in health and gastric disorders. This article reviews tests of gastric function and provides a basic description of the tests, the methodologies behind them, descriptions of the physiology that they assess, and their clinical utility. PMID:19293005

  9. When Your Child Needs a Liver Transplant

    MedlinePlus

    ... Your Child for Surgery Hepatitis Hereditary Hemochromatosis Digestive System Blood Test: Hepatic (Liver) Function Panel What Happens in the Operating Room? Hepatitis Your Liver Your Digestive System Anesthesia - ...

  10. Organotypic liver culture models: Meeting current challenges in toxicity testing

    PubMed Central

    LeCluyse, Edward L.; Witek, Rafal P.; Andersen, Melvin E.; Powers, Mark J.

    2012-01-01

    Prediction of chemical-induced hepatotoxicity in humans from in vitro data continues to be a significant challenge for the pharmaceutical and chemical industries. Generally, conventional in vitro hepatic model systems (i.e. 2-D static monocultures of primary or immortalized hepatocytes) are limited by their inability to maintain histotypic and phenotypic characteristics over time in culture, including stable expression of clearance and bioactivation pathways, as well as complex adaptive responses to chemical exposure. These systems are less than ideal for longer-term toxicity evaluations and elucidation of key cellular and molecular events involved in primary and secondary adaptation to chemical exposure, or for identification of important mediators of inflammation, proliferation and apoptosis. Progress in implementing a more effective strategy for in vitro-in vivo extrapolation and human risk assessment depends on significant advances in tissue culture technology and increasing their level of biological complexity. This article describes the current and ongoing need for more relevant, organotypic in vitro surrogate systems of human liver and recent efforts to recreate the multicellular architecture and hemodynamic properties of the liver using novel culture platforms. As these systems become more widely used for chemical and drug toxicity testing, there will be a corresponding need to establish standardized testing conditions, endpoint analyses and acceptance criteria. In the future, a balanced approach between sample throughput and biological relevance should provide better in vitro tools that are complementary with animal testing and assist in conducting more predictive human risk assessment. PMID:22582993

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

    PubMed Central

    Kurnath, Patrice; Dearing, M. Denise

    2013-01-01

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

  12. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes.

    PubMed

    Shi, Xiao-Lei; Gao, Yimeng; Yan, Yupeng; Ma, Hucheng; Sun, Lulu; Huang, Pengyu; Ni, Xuan; Zhang, Ludi; Zhao, Xin; Ren, Haozhen; Hu, Dan; Zhou, Yan; Tian, Feng; Ji, Yuan; Cheng, Xin; Pan, Guoyu; Ding, Yi-Tao; Hui, Lijian

    2016-02-01

    Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system. PMID:26768767

  13. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes

    PubMed Central

    Shi, Xiao-Lei; Gao, Yimeng; Yan, Yupeng; Ma, Hucheng; Sun, Lulu; Huang, Pengyu; Ni, Xuan; Zhang, Ludi; Zhao, Xin; Ren, Haozhen; Hu, Dan; Zhou, Yan; Tian, Feng; Ji, Yuan; Cheng, Xin; Pan, Guoyu; Ding, Yi-Tao; Hui, Lijian

    2016-01-01

    Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system. PMID:26768767

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

    NASA Astrophysics Data System (ADS)

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

    2000-04-01

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

  15. Function of Autophagy in Nonalcoholic Fatty Liver Disease.

    PubMed

    Czaja, Mark J

    2016-05-01

    Autophagy is a lysosomal degradative pathway that functions to promote cell survival by supplying energy in times of stress or by removing damaged organelles and proteins after injury. The involvement of autophagy in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) was first suggested by the finding that this pathway mediates the breakdown of intracellular lipids in hepatocytes and therefore may regulate the development of hepatic steatosis. Subsequent studies have demonstrated additional critical functions for autophagy in hepatocytes and other hepatic cell types such as macrophages and stellate cells that regulate insulin sensitivity, hepatocellular injury, innate immunity, fibrosis, and carcinogenesis. These findings suggest a number of possible mechanistic roles for autophagy in the development of NAFLD and progression to NASH and its complications. The functions of autophagy in the liver, together with findings of decreased hepatic autophagy in association with conditions that predispose to NAFLD such as obesity and aging, suggest that autophagy may be a novel therapeutic target in this disease. PMID:26725058

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. Effects of a Fusarium toxin-contaminated triticale, either untreated or treated with sodium metabisulphite (Na2S2O5, SBS), on weaned piglets with a special focus on liver function as determined by the 13C-methacetin breath test.

    PubMed

    Dänicke, Sven; Beineke, Andreas; Goyarts, Tanja; Valenta, Hana; Beyer, Marita; Humpf, Hans-Ulrich

    2008-08-01

    The aim of the present experiment was to test the effects of a wet preservation of triticale contaminated mainly with deoxynivalenol (DON) with sodium metabisulphite (Na2S2O5, SBS) on growth performance, liver function, clinical-chemical plasma parameters and organ histopathology of piglets. For this purpose both the uncontaminated control triticale and the DON contaminated triticale were included in the piglet diet either untreated (CON, FUS) or SBS-treated (CON-SBS, FUS-SBS) and fed for 28 d starting from weaning. The dietary concentrations of DON and DON sulfonate (DONS), the DON derivative resulting from the SBS treatment, amounted to 0.156, 0.084, 2.312 and 0.275 mg DON per kg CON, CON-SBS, FUS and FUS-SBS diet, and to <0.05, <0.05, <0.05 and 1.841 mg/kg diet, respectively. Feeding the FUS diet significantly reduced the feed intake compared to the other three groups as indicated by the significant interactions between triticale source and SBS treatment when the whole experimental period of 28 d was considered (p = 0.014) while live weight gain and feed to gain ratio remained unaffected. The total plasma protein concentration was significantly depressed due to feeding the contaminated diets whereas SBS treatment exerted an increasing effect at the same time (45.4, 49.5, 40.7 and 46.5 g/l for piglets fed the CON, CON-SBS, FUS and FUS-SBS diet, respectively). The liver function was tested by the 13C-methacetin breath test (MBT) allowing evaluation of the cytochrome P4501A2 activity. MBT results, expressed as cumulative percentage dose recovery after 360 min (cPDR360) revealed a slight stimulation of liver function due to SBS treatment (p = 0.052) (37.5, 39.4, 37.4 and 55.1% for piglets fed the CON, CON-SBS, FUS and FUS-SBS diet, respectively). Liver weight and histopathological scoring were only weakly related to the MBT results. Further histopathological examinations of kidneys, pancreas and heart revealed no treatment effects. It was concluded that the SBS

  20. [Problems and prospects of creation of extracorporal systems for support of functional livers status].

    PubMed

    Ryabinin, V E

    2015-01-01

    The review considers features of efferent therapy employing extracorporeal systems, the devices known as "artificial liver" and "bioartificial liver" in the treatment of liver insufficiency. Analysis of literature data shows the need for further development of these biomedical studies and the search for optimal solutions in the selection of the source of hepatocytes, the development of bioreactors and biomaterials forming the basis of devices like "bioartificial liver". Taking into consideration certain advantages and disadvantages typical for various methods of extracorporeal support of the functional state of the liver one can evaluate prior experience in the treatment of liver diseases and approaches to the development of new, more effective medical technologies. PMID:26539863

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Zhang, Dong; Song, Xiao-Jing; Li, Shun-Yue; Wang, Shu-You; Chen, Bing-Jun; Bai, Xiao-Dong; Tang, Li-Mei

    2016-01-01

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

  3. Comparison of the promutagenic activity of liver homogenates from fish and rat in the Ames test

    SciTech Connect

    Yamashita, M.; Kinae, N.; Tomita, I.; Kimura, I.

    1987-04-01

    Several mutagenic assay systems using bacteria have been developed as pre-screening methods for the detection of carcinogens from the industrial and the environmental materials. A liver homogenate, so-called S9 (supernatant at 9000 x g), prepared from the livers of rat, mouse or golden hamster is used for the metabolic activation in these systems. Recently, it was demonstrated that the activity of microsomal mixed function oxidase and the content of cytochrome P-450 in fish was increased by exposure to chemicals and environmental pollutants as observed in mammals. Several mutagenic and carcinogenic substances were isolated from samples of sediment, sea water and marine fish from the estuary area in which a high incidence of croaker nibe (Nibea mitsukurii) skin tumors were observed. But, the incidences of other fish diseases in the coastal area were not significant from those of the control areas. These results suggest that nibe has a high metabolic potency against the xenobiotics and are induced the tumor by these materials. In this paper, the authors report the comparison of liver microsomal enzymic activities of nibe and carp (Cyprinus carpio), freshwater fish, as well as that of rat or without PCB administration. They also describe an application of liver homogenates to the bacterial mutagenicity test developed by Ames.

  4. Characterization of liver-specific structure and function during hepatocyte spheroid self-assembly: Implications for a bioartificial liver device

    NASA Astrophysics Data System (ADS)

    Friend, Julie Renee

    A hollow fiber bioreactor containing collagen-entrapped hepatocytes has been developed as a bioartificial liver device. For clinical application, further scale-up of the device is desirable. This may be achieved through the use of hepatocyte spheroids, which are compacted aggregates that exhibit prolonged viability, higher liver-specific function and a more tissue-like ultrastructure compared to hepatocytes cultured as monolayers. In order to gain a better understanding of structural changes in spheroids over the course of their self-assembly, confocal microscopy was used to optically section spheroids and monitor changes in situ. Channels within spheroids hypothesized to be bile canaliculi were first evaluated by monitoring the diffusion of a fluorescent tracer, FITC-dextran, into spheroids. Three-dimensional reconstruction of spheroids showed that a continuous network of channels was forming within spheroids. Functionality of these channels as bile canaliculi was demonstrated by monitoring secretion of a fluorescently tagged bile acid, FITC-glycocholate, by hepatocytes in spheroids. Secretion of FITC-glycocholate could be seen in both rat and porcine hepatocyte spheroids. To elucidate changes in metabolism occurring during spheroid self-assembly, metabolic flux analysis was applied to hepatocyte spinner cultures. Glucose, lactate, amino acid, albumin and urea concentration in culture medium were measured and used to estimate intracellular fluxes within hepatocytes. Metabolism before and after spheroid formation was compared. Overall, little difference was seen in metabolism before and after spheroid self-assembly. As the BAL approaches clinical trials, methods of bioreactor storage for shipping and inventory purposed need to be developed. Storage conditions were tested in various hepatocyte culture systems. A protocol for storing reactors for 24 hours without significant loss in function was developed. Further optimization will be necessary for storage for longer

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

    PubMed

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

    1996-01-01

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

  6. Platelet Function Tests in Bleeding Disorders.

    PubMed

    Lassila, Riitta

    2016-04-01

    Functional disorders of platelets can involve any aspect of platelet physiology, with many different effects or outcomes. These include platelet numbers (thrombocytosis or thrombocytopenia); changes in platelet production or destruction, or capture to the liver (Ashwell receptor); altered adhesion to vascular injury sites and/or influence on hemostasis and wound healing; and altered activation or receptor functions, shape change, spreading and release reactions, procoagulant and antifibrinolytic activity. Procoagulant membrane alterations, and generation of thrombin and fibrin, also affect platelet aggregation. The above parameters can all be studied, but standardization and quality control of assay methods have been limited despite several efforts. Only after a comprehensive clinical bleeding assessment, including family history, information on drug use affecting platelets, and exclusion of coagulation factor, and tissue deficits, should platelet function testing be undertaken to confirm an abnormality. Current diagnostic tools include blood cell counts, platelet characteristics according to the cell counter parameters, peripheral blood smear, exclusion of pseudothrombocytopenia, whole blood aggregometry (WBA) or light transmission aggregometry (LTA) in platelet-rich plasma, luminescence, platelet function analysis (PFA-100) for platelet adhesion and deposition to collagen cartridges under blood flow, and finally transmission electron microscopy to exclude rare structural defects leading to functional deficits. The most validated test panels are included in WBA, LTA, and PFA. Because platelets are isolated from their natural environment, many simplifications occur, as circulating blood and interaction with vascular wall are omitted in these assays. The target to reach a highly specific platelet disorder diagnosis in routine clinical management can be exhaustive, unless needed for genetic counseling. The elective overall assessment of platelet function disorder

  7. Mitochondrial respiratory function and antioxidant capacity in normal and cirrhotic livers following partial hepatectomy.

    PubMed

    Yang, S; Tan, T M C; Wee, A; Leow, C K

    2004-01-01

    For many liver malignancies, major hepatectomy is the usual therapy. Although a normal liver has a tremendous capacity for regeneration, liver hepatectomy in humans is usually carried out on a diseased liver and, in such cases, liver regeneration takes place in a cirrhotic remnant. Mitochondrial function in cirrhotic livers shows a variety of changes compared to control livers. This study investigated how mitochondrial respiratory function and antioxidant capacity change following partial hepatectomy of cirrhotic livers, because liver regeneration requires greater energy demands and control of oxidative stress. Cirrhosis was induced in male Wistar-Furth rats by administration of thioacetamide. NADH-cytochrome c reductase activity, mitochondrial glutathione peroxidase activity and mitochondrial GSH levels were all significantly lowered in cirrhotic livers and in the cirrhotic remnants up to 72 h after 70% hepatectomy when compared to the corresponding controls. Lower respiratory control ratios with succinate as substrate were also observed from 6 to 48 h post-hepatectomy. At 24 h post-hepatectomy, higher levels of lipid peroxidation were observed. We conclude that, compared to the controls, cirrhotic livers have diminished oxidative phosphorylation capabilities due to changes in NADH and FADH(2)-linked respiration as well as impaired antioxidant defenses following partial hepatectomy. Both of these factors, if critical, could then impede liver regeneration. PMID:14745500

  8. Effects of exercise and ethanol on liver mitochondrial function

    SciTech Connect

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

    1987-03-16

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

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

    PubMed Central

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

    2009-01-01

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

  10. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.

    PubMed

    Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

    2016-07-01

    Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD. PMID:26946466

  11. The functional role of some tomato products on lipid profile and liver function in adult rats.

    PubMed

    Ibrahim, Hoda Salama; Ahmed, Lamiaa Ali; El-din, Maha Mohamed Essam

    2008-09-01

    This study was carried out to investigate the functional role of lycopene obtained from powder prepared from fresh tomato, tomato paste, and ketchup that contained equal amounts of lycopene based on levels of intake on body weight gain (BWG), feed intake, feed efficiency ratio (FER), lipid profiles, atherogenic index, and liver enzymes of hyperlipidemic rats. Forty-eight male albino rats were divided into two main groups: the first group (n = 6 rats) was kept on the basal diet as a normal control, while the second group (n = 42 rats) was fed a hyperlipidemic diet for 5 weeks to induce hyperlipidemia. The latter group was divided into seven subgroups: the first subgroup was the positive control group, while the others were supplemented with one of the tomato products at one of two levels (10 or 20 mg of lycopene/kg of diet). BWG, feed intake, and FER were calculated, and blood samples were collected to determine total lipids, total cholesterol, triglycerides, lipoprotein fractions, atherogenic index, and liver function in sera. Relative organ weights were also calculated. Results revealed that administration of various tomato products produced a significant reduction in feed intake except for the hyperlipidemic group that supplemented with the lower lycopene level from tomato paste. In addition, BWG and FER were not influenced by addition of tomato products at any level of intake. Hyperlipidemic rats supplemented with tomato powder, tomato paste, or ketchup showed significant improvement in almost all the parameters studied compared to the positive control group. Results showed that the higher lycopene level from tomato paste produced significant improvement in all lipid parameters, followed by 10 mg of lycopene/kg from tomato paste, which caused significant elevation in high-density lipoprotein cholesterol comparable to that of the negative control group. The lowest atherogenic index was achieved by addition of the lower lycopene level from tomato paste followed by

  12. Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers.

    PubMed

    Banan, Babak; Watson, Rao; Xu, Min; Lin, Yiing; Chapman, William

    2016-07-01

    Donor organ shortages have led to an increased interest in finding new approaches to recover organs from extended criteria donors (ECD). Normothermic extracorporeal liver perfusion (NELP) has been proposed as a superior preservation method to reduce ischemia/reperfusion injury (IRI), precondition suboptimal grafts, and treat ECD livers so that they can be successfully used for transplantation. The aim of this study was to investigate the beneficial effects of a modified NELP circuit on discarded human livers. Seven human livers that were rejected for transplantation were placed on a modified NELP circuit for 8 hours. Perfusate samples and needle core biopsies were obtained at hourly intervals. A defatting solution that contained exendin-4 (50 nM) and L-carnitine (10 mM) was added to the perfusate for 2 steatotic livers. NELP provided normal temperature, electrolytes, and pH and glucose levels in the perfusate along with physiological vascular flows and pressures. Functional, biochemical, and microscopic evaluation revealed no additional injuries to the grafts during NELP with an improved oxygen extraction ratio (>0.5) and stabilized markers of hepatic injury. All livers synthesized adequate amounts of bile and coagulation factors. We also demonstrated a mild reduction (10%) of macroglobular steatosis with the use of the defatting solution. Histology demonstrated normal parenchymal architecture and a minimal to complete lack of IRI at the end of NELP. In conclusion, a modified NELP circuit preserved hepatocyte architecture, recovered synthetic functions, and hepatobiliary parameters of ECD livers without additional injuries to the grafts. This approach has the potential to increase the donor pool for clinical transplantation. Liver Transplantation 22 979-993 2016 AASLD. PMID:27027254

  13. Effect of delayed CNI-based immunosuppression with Advagraf® on liver function after MELD-based liver transplantation [IMUTECT

    PubMed Central

    2014-01-01

    Background MELD-based allocation for liver transplantation follows the “sickest-patient-first” strategy. The latter patients present with both, decreased immune competence and poor kidney function which is further impaired by immunosuppressants. Methods/Design In this prospective observational study, 50 patients with de novo low-dose standard Advagraf®-based immunosuppression consisting of Advagraf®, Mycophenolat-mofetil and Corticosteroids after liver transplantation will be evaluated. Advagraf® trough levels of 7-10 μg/l will be reached at the end of the first postoperative week. Immunostatus, infectious complications, graft and kidney function are compared between patients with a pretransplant calculated MELD-score of ≤20 and >20. Each group comprises of 25 consecutive patients. Prior to liver transplantation and on the postoperative days 1, 3 and 7, the patients’ graft function (LiMAx test) will be evaluated. On the postoperative days 3, 5 and 7 the patients’ immune status will be evaluated by the measurement of their monocytic HLA-DR status. Infectious complications (CMV-reactivation, wound infection, urinary tract infection, and pneumonia), graft- and kidney function will be analysed on day 0, within the first week, and 1, 3, 6, 9 and 12 months after liver transplantation. Discussion This study was designed to assess the effect of a standard low-dose Calcineurin inhibitor-based immunosuppression regime with Advagraf® on the rate of infectious complications, graft and renal function after liver transplantation. Trial registration The trial is registered at “Clinical Trials” (http://www.clinicaltrials.gov), NCT01781195. PMID:25178675

  14. Characterization of Liver-Specific Functions of Human Fetal Hepatocytes in Culture.

    PubMed

    Chinnici, Cinzia Maria; Timoneri, Francesca; Amico, Giandomenico; Pietrosi, Giada; Vizzini, Giovanni; Spada, Marco; Pagano, Duilio; Gridelli, Bruno; Conaldi, Pier Giulio

    2015-01-01

    This study was designed to assess liver-specific functions of human fetal liver cells proposed as a potential source for hepatocyte transplantation. Fetal liver cells were isolated from livers of different gestational ages (16-22 weeks), and the functions of cell preparations were evaluated by establishing primary cultures. We observed that 20- to 22-week-gestation fetal liver cell cultures contained a predominance of cells with hepatocytic traits that did not divide in vitro but were functionally competent. Fetal hepatocytes performed liver-specific functions at levels comparable to those of their adult counterpart. Moreover, exposure to dexamethasone in combination with oncostatin M promptly induced further maturation of the cells through the acquisition of additional functions (i.e., ability to store glycogen and uptake of indocyanine green). In some cases, particularly in cultures obtained from fetuses of earlier gestational ages (16-18 weeks gestation), cells with mature hepatocytic traits proved to be sporadic, and the primary cultures were mainly populated by clusters of proliferating cells. Consequently, the values of liver-specific functions detected in these cultures were low. We observed that a low cell density culture system rapidly prompted loss of the mature hepatocytic phenotype with downregulations of all the liver-specific functions. We found that human fetal liver cells can be cryopreserved without significant loss of viability and function and evaluated up to 1 year in storage in liquid nitrogen. They might, therefore, be suitable for cell banking and allow for the transplantation of large numbers of cells, thus improving clinical outcomes. Overall, our results indicate that fetal hepatocytes could be used as a cell source for hepatocyte transplantation. Fetal liver cells have been used so far to treat end-stage liver disease. Additional studies are needed to include these cells in cell-based therapies aimed to treat liver failure and inborn

  15. Liver.

    PubMed

    Kim, W R; Lake, J R; Smith, J M; Skeans, M A; Schladt, D P; Edwards, E B; Harper, A M; Wainright, J L; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    The median waiting time for patients with MELD ≥ 35 decreased from 18 days in 2012 to 9 days in 2014, after implementation of the Share 35 policy in June 2013. Similarly, mortality among candidates listed with MELD ≥ 35 decreased from 366 per 100 waitlist years in 2012 to 315 in 2014. The number of new active candidates added to the pediatric liver transplant waiting list in 2014 was 655, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) continued to decline, 401 active and 173 inactive. The number of deceased donor pediatric liver transplants peaked at 542 in 2008 and was 478 in 2014. The number of living donor liver pediatric transplants was 52 in 2014; most were from donors closely related to the recipients. Graft survival continued to improve among pediatric recipients of deceased donor and living donor livers. PMID:26755264

  16. GALACSI integration and functional tests

    NASA Astrophysics Data System (ADS)

    La Penna, P.; Ströbele, S.; Aller Carpentier, E.; Argomedo, J.; Arsenault, R.; Conzelmann, R. D.; Delabre, B.; Donaldson, R.; Duchateau, M.; Fedrigo, E.; Gago, F.; Hubin, N.; Quentin, J.; Jolley, P.; Kiekebusch, M.; Kirchbauer, J. P.; Klein, B.; Kolb, J.; Kuntschner, H.; Le Louarn, M.; Lizon, J. L.; Madec, P.-.; Manescau, A.; Mehrgan, L.; Sedghi, B.; Suarez Valles, M.; Soenke, C.; Tordo, S.; Vernet, J.; Zampieri, S.

    2014-07-01

    GALACSI is the Adaptive Optics (AO) modules of the ESO Adaptive Optics Facility (AOF) that will correct the wavefront delivered to the MUSE Integral Field Spectrograph. It will sense with four 40×40 subapertures Shack-Hartmann wavefront sensors the AOF 4 Laser Guide Stars (LGS), acting on the 1170 voice-coils actuators of the Deformable Secondary Mirror (DSM). GALACSI has two operating modes: in Wide Field Mode (WFM), with the four LGS at 64" off axis, the collected energy in a 0.2"×0.2" pixel will be enhanced by a factor 2 at 750 nm over a Field of View (FoV) of 1'×1' using the Ground Layer AO (GLAO) technique. The other mode, the Narrow Field Mode (NFM), provides an enhanced wavefront correction (Strehl Ratio (SR) of 5% (goal 10%) at 650 nm) but in a smaller FoV (7.5"×7.5"), using Laser Tomography AO (LTAO), with the 4 LGS located closer, at 10" off axis. Before being shipped to Paranal, GALACSI will be first integrated and fully tested in stand-alone, and then moved to a dedicated AOF facility to be tested with the DSM in Europe. At present the module is fully assembled, its main functionalities have been implemented and verified, and AO system tests with the DSM are starting. We present here the main system features and the results of the internal functional tests of GALACSI.

  17. Generation and functional significance of CXC chemokines for neutrophil-induced liver injury during endotoxemia.

    PubMed

    Dorman, Robert B; Gujral, Jaspreet S; Bajt, Mary Lynn; Farhood, Anwar; Jaeschke, Hartmut

    2005-05-01

    The hypothesis that the neutrophil chemoattractant CXC chemokines KC and macrophage inflammatory protein-2 (MIP-2) are involved in neutrophil transmigration and liver injury was tested in C3Heb/FeJ mice treated with galactosamine (Gal, 700 mg/kg), endotoxin (ET, 100 microg/kg), or Gal + ET (Gal/ET). Hepatic KC and MIP-2 mRNA levels and plasma CXC chemokine concentrations were dramatically increased 1.5 h after Gal/ET or ET alone and gradually declined up to 7 h. Murine recombinant cytokines (TNF-alpha, IL-1 alpha, and IL-1 beta), but not Gal/ET, induced CXC chemokine formation in the ET-resistant C3H/HeJ strain. To assess the functional importance of KC and MIP-2, C3Heb/FeJ mice were treated with Gal/ET and control IgG or a combination of anti-KC and anti-MIP-2 antibodies. Anti-CXC chemokine antibodies did not attenuate hepatocellular apoptosis, sinusoidal neutrophil sequestration and extravasation, or liver injury at 7 h. Furthermore, there was no difference in liver injury between BALB/cJ wild-type and CXC receptor-2 gene knockout (CXCR2-/-) mice treated with Gal/ET. The higher neutrophil count in livers of CXCR2-/- than in wild-type mice after Gal/ET was caused by the elevated number of neutrophils located in sinusoids of untreated CXCR2-/- animals. The pancaspase inhibitor Z-Val-Ala-Asp-fluoromethylketone eliminated Gal/ET-induced apoptosis and neutrophil extravasation and injury but not CXC chemokine formation. Thus Gal/ET induced massive, cytokine-dependent CXC chemokine formation in the liver. However, neutrophil extravasation and injury occurred in response to apoptotic cell injury at 6-7 h and was independent of CXC chemokine formation. PMID:15576625

  18. In vitro gene regulatory networks predict in vivo function of liver

    PubMed Central

    2010-01-01

    Background Evolution of toxicity testing is predicated upon using in vitro cell based systems to rapidly screen and predict how a chemical might cause toxicity to an organ in vivo. However, the degree to which we can extend in vitro results to in vivo activity and possible mechanisms of action remains to be fully addressed. Results Here we use the nitroaromatic 2,4,6-trinitrotoluene (TNT) as a model chemical to compare and determine how we might extrapolate from in vitro data to in vivo effects. We found 341 transcripts differentially expressed in common among in vitro and in vivo assays in response to TNT. The major functional term corresponding to these transcripts was cell cycle. Similarly modulated common pathways were identified between in vitro and in vivo. Furthermore, we uncovered the conserved common transcriptional gene regulatory networks between in vitro and in vivo cellular liver systems that responded to TNT exposure, which mainly contain 2 subnetwork modules: PTTG1 and PIR centered networks. Interestingly, all 7 genes in the PTTG1 module were involved in cell cycle and downregulated by TNT both in vitro and in vivo. Conclusions The results of our investigation of TNT effects on gene expression in liver suggest that gene regulatory networks obtained from an in vitro system can predict in vivo function and mechanisms. Inhibiting PTTG1 and its targeted cell cyle related genes could be key machanism for TNT induced liver toxicity. PMID:21073692

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

    SciTech Connect

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

    2014-06-15

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

  20. Synthesis and application of lactosylated, 99mTc chelating albumin for measurement of liver function.

    PubMed

    Chaumet-Riffaud, Philippe; Martinez-Duncker, Ivan; Marty, Anne-Laure; Richard, Cyrille; Prigent, Alain; Moati, Frederic; Sarda-Mantel, Laure; Scherman, Daniel; Bessodes, Michel; Mignet, Nathalie

    2010-04-21

    Neogalactosylated and neolactosylated albumins are currently used as radiopharmaceutical agents for imaging the liver asialoglycoprotein receptors, which allows the quantification of hepatic liver function in various diseases and also in healthy liver transplant donors. We developed an original process for synthesizing a chelating neolactosylated human albumin using maleimidopropyl-lactose and maleimidopropyl-diethylene triamine pentaacetic acid (DTPA) derivatives. The lactosylated protein (LACTAL) conjugate showed excellent liver uptake compared to nonlactosylated protein and a very high signal-to-noise ratio, based on functional assessment of biodistribution in mice using (99m)Tc-scintigraphy. PMID:20201600

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

    PubMed Central

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

    2015-01-01

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

  2. [Effect of hepatophyt on the choleretic function of the liver damaged by tetracycline].

    PubMed

    Nikolaev, S M; Sambueva, Z G; Chekhirova, G V; Tsyrenzhalov, A V

    2003-01-01

    In experimental injury of the liver in Wistar-line white rats induced by tetracycline the course therapeutic and prophylatic administration of the dry extract "Hepatophyt" in a dose of 0.1 g/kg inhibits the negative effect of tetracycline and promotes stimulation of choleretic and antitoxic functions of the liver. The dry extract was derived from the herbal mix of the same name, used in the practice of Tibetan medicine against liver diseases. PMID:13677134

  3. [Exercise test and respiratory muscle function test].

    PubMed

    Akashiba, Tsuneto

    2011-10-01

    Dyspnea on exertion is a chief complaint of patients with COPD, and it has a major effect on the quality of their lives. Dyspnea is, by definition, subjective, but objective approaches are needed for a comprehensive understanding of these patients' conditions. Thus, measuring changes in cardiopulmonary variables during exercise can be very helpful when evaluating patients with COPD. The main purpose of exercise testing is to evaluate exercise tolerance and to identify the factors limiting exercise. Although incremental exercise testing is ideal for these purposes, simple walking tests such as 6-minute walking test, are also useful. PMID:22073578

  4. Functional Nanoparticles Activate a Decellularized Liver Scaffold for Blood Detoxification.

    PubMed

    Xu, Fen; Kang, Tianyi; Deng, Jie; Liu, Junli; Chen, Xiaolei; Wang, Yuan; Ouyang, Liang; Du, Ting; Tang, Hong; Xu, Xiaoping; Chen, Shaochen; Du, Yanan; Shi, Yujun; Qian, Zhiyong; Wei, Yuquan; Deng, Hongxin; Gou, Maling

    2016-04-01

    Extracorporeal devices have great promise for cleansing the body of virulence factors that are caused by venomous injuries, bacterial infections, and biological weaponry. The clinically used extracorporeal devices, such as artificial liver-support systems that are mainly based on dialysis or electrostatic interaction, are limited to remove a target toxin. Here, a liver-mimetic device is shown that consists of decellularized liver scaffold (DLS) populated with polydiacetylene (PDA) nanoparticles. DLS has the gross shape and 3D architecture of a liver, and the PDA nanoparticles selectively capture and neutralize the pore-forming toxins (PFTs). This device can efficiently and target-orientedly remove PFTs in human blood ex vivo without changing blood components or activating complement factors, showing potential application in antidotal therapy. This work provides a proof-of-principle for blood detoxification by a nanoparticle-activated DLS, and can lead to the development of future medical devices for antidotal therapy. PMID:26914158

  5. Functional Immune Anatomy of the Liver-As an Allograft.

    PubMed

    Demetris, A J; Bellamy, C O C; Gandhi, C R; Prost, S; Nakanuma, Y; Stolz, D B

    2016-06-01

    The liver is an immunoregulatory organ in which a tolerogenic microenvironment mitigates the relative "strength" of local immune responses. Paradoxically, necro-inflammatory diseases create the need for most liver transplants. Treatment of hepatitis B virus, hepatitis C virus, and acute T cell-mediated rejection have redirected focus on long-term allograft structural integrity. Understanding of insults should enable decades of morbidity-free survival after liver replacement because of these tolerogenic properties. Studies of long-term survivors show low-grade chronic inflammatory, fibrotic, and microvascular lesions, likely related to some combination of environment insults (i.e. abnormal physiology), donor-specific antibodies, and T cell-mediated immunity. The resultant conundrum is familiar in transplantation: adequate immunosuppression produces chronic toxicities, while lightened immunosuppression leads to sensitization, immunological injury, and structural deterioration. The "balance" is more favorable for liver than other solid organ allografts. This occurs because of unique hepatic immune physiology and provides unintended benefits for allografts by modulating various afferent and efferent limbs of allogenic immune responses. This review is intended to provide a better understanding of liver immune microanatomy and physiology and thereby (a) the potential structural consequences of low-level, including allo-antibody-mediated injury; and (b) how liver allografts modulate immune reactions. Special attention is given to the microvasculature and hepatic mononuclear phagocytic system. PMID:26848550

  6. DEVELOPMENT OF A TOXICITY TEST SYSTEM USING PRIMARY RAT LIVER CELLS

    EPA Science Inventory

    A model in vitro rat liver parenchymal cellular toxicity system employing cells obtained by the in situ collagenase perfusion technique has been developed to detect potential liver toxicants. The initial evaluation of this test system was accomplished using cadmium chloride, chro...

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  8. Hepatic function in hypothermically stored porcine livers: comparison of hypothermic machine perfusion vs cold storage.

    PubMed

    Jain, S; Lee, C Y; Baicu, S; Duncan, H; Xu, H; Jones, J W; Clemens, M G; Brassil, J; Taylor, M J; Brockbank, K G M

    2005-01-01

    Hypothermic machine perfusion (HMP) has a potential to relieve the current donor liver crisis by providing an improved and extended preservation method. This study examined the effect of HMP on hepatocellular functions, using a prototype liver transporter capable of preserving livers for 24 hours. Livers obtained from adult farm pigs (28 to 32 kg body weight) were divided into three groups: fresh control, HMP, and simple cold storage (n = 4 each). A 4-hour normothermic reperfusion of livers was conducted to assess hepato-metabolic and cellular functions. The hepatic transport function, as indicated by canalicular excretion of indocyanine green, was improved in the HMP group than in the SCS group. The overall tissue viability, as indicated by oxygen consumption levels, was notably improved in HMP and control livers as compared to the SCS group. Higher bile production in both the preserved groups as compared to the fresh control livers could be a result of biliary edema and leakage of plasma into the canaliculus. The hepato-cellular injury, measured by ALT, release was significantly greater in the SCS group as compared to the HMP and control groups. These findings suggest that HMP could be a better method to preserve hepatic function and overall tissue viability as compared to SCS. Improved hepatic functions are indirect indicators of superior microcirculation and sinusoidal endothelial cell functions. Further studies in progress will evaluate these functions to confirm the significance of these observations. PMID:15808637

  9. Functional Task Test: Data Review

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita

    2014-01-01

    After space flight there are changes in multiple physiological systems including: Cardiovascular function; Sensorimotor function; and Muscle function. How do changes in these physiological system impact astronaut functional performance?

  10. Cognitive function in patients with alcoholic and nonalcoholic chronic liver disease.

    PubMed

    Brodersen, Carlos; Koen, Eduardo; Ponte, Alicia; Sánchez, Silvina; Segal, Eduardo; Chiapella, Alberto; Fernández, Maria; Torres, Maria; Tripodi, Valeria; Lemberg, Abraham

    2014-01-01

    The aim of the present study was to characterize the neurophysiological profile of cognitive impairment associated with patients with chronic alcoholic and nonalcoholic liver disease. The authors evaluated 43 patients with cirrhotic liver disease: 19 patients with chronic alcohol ingestion and 24 nonalcoholic patients who had been infected with hepatitis B or C virus. Eleven healthy subjects were included as control subjects. A battery of 12 psychological tests was used to investigate cognitive deficits in the patients with chronic liver disease. It was observed that alcoholic patients with chronic liver disease showed a more important cognitive deterioration than those affected by hepatitis B or C virus. PMID:25093764

  11. Liver involvement in systemic infection

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2014-01-01

    The liver is often involved in systemic infections, resulting in various types of abnormal liver function test results. In particular, hyperbilirubinemia in the range of 2-10 mg/dL is often seen in patients with sepsis, and several mechanisms for this phenomenon have been proposed. In this review, we summarize how the liver is involved in various systemic infections that are not considered to be primarily hepatotropic. In most patients with systemic infections, treatment for the invading microbes is enough to normalize the liver function tests. However, some patients may show severe liver injury or fulminant hepatic failure, requiring intensive treatment of the liver. PMID:25276279

  12. 14 CFR 35.40 - Functional test.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Functional test. 35.40 Section 35.40... STANDARDS: PROPELLERS Tests and Inspections § 35.40 Functional test. The variable-pitch propeller system must be subjected to the applicable functional tests of this section. The same propeller system used...

  13. 14 CFR 35.40 - Functional test.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Functional test. 35.40 Section 35.40... STANDARDS: PROPELLERS Tests and Inspections § 35.40 Functional test. The variable-pitch propeller system must be subjected to the applicable functional tests of this section. The same propeller system used...

  14. 14 CFR 35.40 - Functional test.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Functional test. 35.40 Section 35.40... STANDARDS: PROPELLERS Tests and Inspections § 35.40 Functional test. The variable-pitch propeller system must be subjected to the applicable functional tests of this section. The same propeller system used...

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

    PubMed Central

    2013-01-01

    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. PMID:23958281

  16. [Respiratory functional impairment in patients with liver cirrhosis].

    PubMed

    Siemieniako, Andrzej; Łapiński, Tadeusz Wojciech; Flisiak, Robert

    2010-04-01

    Liver pathologies have negative influence on numerous organs including pulmonary system. Liver failure, which often results from cirrhosis, may lead to the hepatopulmonary syndrome and portopulmonary hypertension. The hepatopulmonary syndrome is characterized by increased alveolar-capillary oxygen gradient, presence of intrapulmonary leak and diminished retention of the carbon dioxide from arterial blood. Two types of the hepatopulmonary syndrome are distinguished: the type 1 connected with pre-capillary and capillaries extension, what shortens the time of the blood flow by the pulmonary vessels. The type 2 hepatopulmonary syndrome results from the formation of arteriovenous anastomoses and anatomical "shunt" connections. Most patients with hepatopulmonary syndrome demonstrate both types. Patients with liver failure may develop portopulmonary hypertension, independently from hepatopulmonary syndrome. If not treated, hypertension might lead to the death of 50 to 90% patients in the 5-year follow up. The patients with the serious damage of the liver have hiperdynamic circulation with the increased heart capacity and lowered systemic vascular resistance. The hepatopulmonary syndrome is characterized by the growth of the pulmonary artery pressure and the presence of portal hypertension. The mechanism how the portal hypertension leads to the pulmonary hypertension is not clear. PMID:20491346

  17. Influence of black cohosh (Cimicifuga racemosa) use by postmenopausal women on total hepatic perfusion and liver functions.

    PubMed

    Nasr, Ahmed; Nafeh, Hanan

    2009-11-01

    In this prospective longitudinal clinical trial, 87 postmenopausal women receiving for 12 consecutive months a daily dose of 40 mg of a dry extract preparation of Cimicifuga racemosa (Klimadynon) for relief of vasomotor symptoms were followed up by evaluation of total hepatic blood flow, assessed by color Doppler ultrasound, as well as prothrombin time and concentration, serum albumin, bilirubin, gamma-glutamyltransferase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Because no significant changes in total hepatic blood flow or any of the liver functions tested were reported, we concluded that use of C. racemosa for 1 year by healthy postmenopausal women without evidence of liver disease does not seem to influence the liver. PMID:19539907

  18. 14 CFR 35.40 - Functional test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the endurance test (§ 35.39) must be used in the functional tests and must be driven by a representative engine on a test stand or on an airplane. The propeller must complete these tests without evidence of failure or malfunction. This test may be combined with the endurance test for accumulation...

  19. Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting.

    PubMed

    Nielsen, Signe Marie Borch; Vinther-Jensen, Tua; Nielsen, Jørgen E; Nørremølle, Anne; Hasholt, Lis; Hjermind, Lena E; Josefsen, Knud

    2016-03-15

    Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- and cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity indicated by the Unified Huntington's disease rating scale-Total Functional Capacity Score (UHDRS-TFC). For gamma-glutamyl transferase, elevated levels were more frequent in the manifest groups than in both the HD gene-expansion negative controls and premanifest HD gene-expansion carriers. Finally, the manifest HD gene-expansion carriers displayed moderate increases in total cholesterol and blood glucose relative to the premanifest HD gene-expansion carriers, as well as increased C-reactive protein relative to HD gene-expansion negative controls. Our results show that LFT values are elevated more frequently in manifest compared to premanifest HD gene-expansion carriers and controls. The majority of the manifest HD gene-expansion carriers receive medication, and it is possible that this can influence the liver function tests performed in this study. PMID:26944172

  20. Quantitative liver function in patients with rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study.

    PubMed

    Beyeler, C; Reichen, J; Thomann, S R; Lauterburg, B H; Gerber, N J

    1997-03-01

    The objectives were to determine quantitative liver function prospectively in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX), to search for risk factors for a loss of quantitative liver function and to assess the relationship between quantitative liver function and histological staging. A total of 117 patients with RA (ACR criteria, 85 women, mean age 59 yr) had measurements of galactose elimination capacity (GEC), aminopyrine breath test (ABT) and liver enzymes [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (AP), 7-glutamyl transferase (GGT), bile acids, bilirubin, albumin] before treatment with weekly i.m. MTX injections and every year thereafter. In 16 patients, liver biopsies were performed. Before the introduction of MTX, mean GEC was 6.6 mg/min/kg [5th to 95th percentile (5-95 PC) 5.1-8.5; reference range 6.0-9.1] and mean ABT was 0.80% kg/mmol (5-95 PC 0.42-1.30: reference range 0.6-1.0). During treatment with MTX [mean weekly dose 11.8 mg (5-95 PC 5.4-20.2), mean observation period 3.8 yr (5-95 PC 0.4-6.9)], significant declines of GEC (-0.12 mg/min/kg per year. t = 3.30, P < 0.002) and ABT (-0.06% kg/mmol per year, t = 4.81, P < 0.001) were observed. Negative correlations were found between the annual change in GEC and GEC at baseline (Rs = -0.40, P < 0.0001), and the annual change in ABT and ABT at baseline (Rs = -0.43, P < 0.0001). No correlations were found between the annual change in GEC or ABT and weekly MTX dose, age or percentage of increased liver enzymes, and no effect of a history of alcohol consumption > 30 g/week became evident. Two patients with Roenigk grade III had impaired quantitative liver function, while 14 patients with Roenigk grades I and II exhibited a high variability of GEC and ABT from normal to abnormal values. The continuous declines in GEC and ABT observed deserve attention in patients with prolonged treatment. Patients with a low GEC or ABT at

  1. Functional Implications of Biochemical and Molecular Characteristics of Donation After Circulatory Death Livers

    PubMed Central

    Masuzaki, Ryota; Yu, Hui; Kingsley, Philip; Marnett, Lawrence; Zhao, Zhongming; Karp, Seth J.

    2015-01-01

    Background In aggregate, livers donated after circulatory death (DCD) provide lower rates of graft and patient survival compared to brain dead donors (DBD). A method to identify DCD livers likely to perform well would lead to better decision-making regarding which livers to use and which to discard and is an important unmet clinical need. We hypothesized that the ischemic time between extubation and cold perfusion in the donor leads to immediate and unique biochemical and molecular changes that could be used to predict subsequent function. Methods Biopsies from normal perfused liver, immediately after cold perfusion during DCD or DBD liver procurement, and during subsequent cold storage were analyzed and compared. Biochemical analysis included adenosine triphosphate (ATP), adenosine diphosphate, adenosine monophosphate, hypoxanthine, xanthine, inosine, nicotinamide adenine dinucleotide, and flavin adenine dinucleotide. Levels of these metabolites were compared to peak posttransplant aspartate aminotransferase as a marker of ischemic injury. Molecular analysis was performed by transcriptional profiling using high throughput sequencing. Results Immediately after cold perfusion in the donor, biochemical analysis revealed lower levels of ATP and adenosine diphosphate in DCD versus DBD liver samples (P < 0.01 in both cases). The ATP levels showed high negative correlation with peak aspartate aminotransferase levels in recipients (P = 0.029). Four hundred seventy genes showed differential expression in DCD but not DBD samples immediately after cold perfusion compared with normal liver samples. Upregulated genes function in inflammation and immunity, whereas downregulated genes function in translation. During cold storage, samples were transcriptionally inactive with no consistent changes in messenger RNA expression. Conclusion The ATP content of liver samples taken immediately postperfusion correlates with ischemic injury. Transcriptional profiling identifies biological

  2. (14C)Aminopyrine breath test in chronic liver disease: preliminary diagnostic implications

    SciTech Connect

    Burnstein, A.V.; Galambos, J.T.

    1981-12-01

    The (14C)aminopyrine breath test (APBT) score, an estimate of hepatic mixed-oxidase function, was evaluated in 21 consecutive patients wih active nonalcoholic chronic liver diseases. Ten had primary biliary cirrhosis (PBC) and 11 had chronic active hepatitis (CAH). The APBT score was normal or elevated in patients with PBC (P less than 0.001), and lower than normal in CAH patients (P less than 0.01); 10.5 +/- 1.6 and 3.5 +/- 1.86, respectively, vs control 7.65 +/- 1.15 (mean +/- SD). The 11 patients with CAH included two middle-aged women who displayed ambiguous severe intrahepatic cholestasis. There was no overlap between the APBT scores of the 10 PBC and 11 CAH patients. These initial data suggest that the APBT may be helpful in the differentiation of PBC and CAH, including misleading cholestatic forms of CAH.

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

    SciTech Connect

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. Track/train dynamics test procedure transfer function test

    NASA Technical Reports Server (NTRS)

    Vigil, R. A.

    1975-01-01

    A transfer function vibration test was made on an 80 ton open hopper freight car in an effort to obtain validation data on the car's nonlinear elastic model. Test configuration, handling, test facilities, test operations, and data acquisition/reduction activities necessary to meet the conditions of test requirements are given.

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

    PubMed

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

    2016-07-01

    The progression of liver fibrosis, an intrinsic response to chronic liver injury, is associated with hepatic hypoxia, angiogenesis, abnormal inflammation, and significant matrix deposition, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Due to the complex pathogenesis of liver fibrosis, antifibrotic drug development has faced the challenge of efficiently and specifically targeting multiple pathogenic mechanisms. Therefore, CXCR4-targeted nanoparticles (NPs) were formulated to deliver siRNAs against vascular endothelial growth factor (VEGF) into fibrotic livers to block angiogenesis during the progression of liver fibrosis. AMD3100, a CXCR4 antagonist that was incorporated into the NPs, served dual functions: it acted as a targeting moiety and suppressed the progression of fibrosis by inhibiting the proliferation and activation of hepatic stellate cells (HSCs). We demonstrated that CXCR4-targeted NPs could deliver VEGF siRNAs to fibrotic livers, decrease VEGF expression, suppress angiogenesis and normalize the distorted vessels in the fibrotic livers in the carbon tetrachloride (CCl4) induced mouse model. Moreover, blocking SDF-1α/CXCR4 by CXCR4-targeted NPs in combination with VEGF siRNA significantly prevented the progression of liver fibrosis in CCl4-treated mice. In conclusion, the multifunctional CXCR4-targeted NPs delivering VEGF siRNAs provide an effective antifibrotic therapeutic strategy. PMID:27224003

  7. [Clinical Application of Non-invasive Diagnostic Tests for Liver Fibrosis].

    PubMed

    Shin, Jung Woo; Park, Neung Hwa

    2016-07-25

    The diagnostic assessment of liver fibrosis is an important step in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard to assess necroinflammation and fibrosis. However, recent technical advances have introduced numerous serum biomarkers and imaging tools using elastography as noninvasive alternatives to biopsy. Serum markers can be direct or indirect markers of the fibrosis process. The elastography-based studies include transient elastography, acoustic radiation force imaging, supersonic shear wave imaging and magnetic resonance elastography. As accumulation of clinical data shows that noninvasive tests provide prognostic information of clinical relevance, non-invasive diagnostic tools have been incorporated into clinical guidelines and practice. Here, the authors review noninvasive tests for the diagnosis of liver fibrosis. PMID:27443617

  8. Tributyltin chloride leads to adiposity and impairs metabolic functions in the rat liver and pancreas.

    PubMed

    Bertuloso, Bruno D; Podratz, Priscila L; Merlo, Eduardo; de Araújo, Julia F P; Lima, Leandro C F; de Miguel, Emilio C; de Souza, Leticia N; Gava, Agata L; de Oliveira, Miriane; Miranda-Alves, Leandro; Carneiro, Maria T W D; Nogueira, Celia R; Graceli, Jones B

    2015-05-19

    Tributyltin chloride (TBT) is an environmental contaminant used in antifouling paints of boats. Endocrine disruptor effects of TBT are well established in animal models. However, the adverse effects on metabolism are less well understood. The toxicity of TBT in the white adipose tissue (WAT), liver and pancreas of female rats were assessed. Animals were divided into control and TBT (0.1 μg/kg/day) groups. TBT induced an increase in the body weight of the rats by the 15th day of oral exposure. The weight gain was associated with high parametrial (PR) and retroperitoneal (RP) WAT weights. TBT-treatment increased the adiposity, inflammation and expression of ERα and PPARγ proteins in both RP and PR WAT. In 3T3-L1 cells, estrogen treatment reduced lipid droplets accumulation, however increased the ERα protein expression. In contrast, TBT-treatment increased the lipid accumulation and reduced the ERα expression. WAT metabolic changes led to hepatic inflammation, lipid accumulation, increase of PPARγ and reduction of ERα protein expression. Accordingly, there were increases in the glucose tolerance and insulin sensitivity tests with increases in the number of pancreatic islets and insulin levels. These findings suggest that TBT leads to adiposity in WAT specifically, impairing the metabolic functions of the liver and pancreas. PMID:25819109

  9. What Are Lung Function Tests?

    MedlinePlus

    ... COPD How the Lungs Work Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... caused by conditions such as pulmonary fibrosis and sarcoidosis (sar-koy-DOE-sis). Also, these tests might ...

  10. Functional Assays for Neurotoxicity Testing

    EPA Science Inventory

    Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

  11. Functional Assays for Neurotoxicity Testing*

    EPA Science Inventory

    Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

  12. Liver function in acute viral hepatitis as determined by a hepatocyte-specific ligand: 99mTc-galactosyl-neoglycoalbumin.

    PubMed

    Virgolini, I; Müller, C; Höbart, J; Scheithauer, W; Angelberger, P; Bergmann, H; O'Grady, J; Sinzinger, H

    1992-04-01

    Twelve patients with recently diagnosed acute viral hepatitis underwent serial 99mTc-galactosyl neoglycoalbumin scanning of the liver (for up to 8 mo). Injection of 99mTc-galactosyl neoglycoalbumin (150 mBq) at a rate of 3.5 mg (50 nmol; 1 ml) revealed that the liver is the exclusive site of tracer uptake. Simulation of 99mTc-galactosyl neoglycoalbumin kinetics allowed quantification of galactosyl neoglycoalbumin binding to human hepatic binding protein. Return of liver function test scores to normal values was associated in two patients with hepatitis A, in four patients with hepatitis B and in two patients with non-A, non-B hepatitis virus infection, with increases in hepatic binding protein concentration (up to three times the initial concentration), binding rate constant and hepatic blood flow. In the other four patients (three patients with hepatitis B and one patient with cytomegalovirus infection) a prolonged course of disease was monitored. In the mean, hepatic binding protein increased from 0.41 +/- 0.11 mumol/L after onset of acute hepatitis (n = 12) to 0.78 +/- 0.21 mumol/L after 6 mo of follow-up (n = 10) (p less than 0.001). During this period, binding rate constant (72.4 +/- 12.6 vs. 82 +/- 11.5 mumol/L/sec; p less than 0.05) and hepatic blood flow (0.027 +/- 0.0051 vs. 0.031 +/- 0.0083 L/sec; p less than 0.05) increased. Hepatic binding protein concentration correlated highly with actual laboratory test results for liver function (r = 0.98; p = 0.0001). We conclude that scintigraphic evaluation of functional liver cell mass using the new receptor-tracer 99mTc-galactosyl neoglycoalbumin could provide an in vivo diagnostic means of quantifying liver function and assessing liver morphology. In addition, our findings suggest that changes in hepatic binding protein-receptor concentration are likely to occur in vivo. PMID:1551636

  13. Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

    PubMed

    Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

    2015-09-01

    Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. PMID:25857839

  14. The Evaluation of Liver Function and Surgical Influence by ICGR15 after Chemotherapy for Colorectal Liver Metastases

    PubMed Central

    Hiwatashi, Kiyokazu; Ueno, Shinichi; Sakoda, Masahiko; Iino, Satoshi; Minami, Koji; Mori, Shinichiro; Kita, Yoshiaki; Baba, Kenji; Kurahara, Hiroshi; Mataki, Yuko; Maemura, Kosei; Shinchi, Hiroyuki; Natsugoe, Shoji

    2016-01-01

    Background; Approximately 60% of patients with colorectal cancer develop liver metastasis at some point after diagnosis. The aim of this study is to investigate whether the evaluation of ICGR15 preoperatively is a useful clinical indicator of hepatic injury following chemotherapy and to investigate the influence of multiple chemotherapies on liver function. Results; Mean ICGR15 values were higher in patients ≥65 years (P = 0.047) and in patients with ≥3 cycles (P = 0.022) and ≥6 cycles (P = 0.001) of systemic chemotherapy. ICGR15 values tended to be higher in patients with postoperative complications (P = 0.085). Patients receiving systemic chemotherapy for ≥6 cycles had higher levels of AST (P = 0.003), ALT (P = 0.015), and alkaline phosphatase (ALP) (P = 0.041). Patients receiving systemic chemotherapy for ≥3 cycles had higher levels of AST (P = 0.015) and ALP (P = 0.015). Conclusions; Because the pathological diagnosis is usually established only after operation, preoperative evaluation such as the identification of sinusoidal injury is difficult. Based on this study, higher ICGR15 values may provide an indication of surgical complications and be a predictor of liver dysfunction following frequent cycles of chemotherapy. Hepatectomy should be performed with the utmost care in such patients, and the number of cycles of preoperative chemotherapy should probably be as low as possible. PMID:27053958

  15. Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: a randomized controlled trial.

    PubMed

    Hallsworth, Kate; Thoma, Christian; Hollingsworth, Kieren G; Cassidy, Sophie; Anstee, Quentin M; Day, Christopher P; Trenell, Michael I

    2015-12-01

    Although lifestyle changes encompassing weight loss and exercise remain the cornerstone of non-alcoholic fatty liver disease (NAFLD) management, the effect of different types of exercise on NAFLD is unknown. This study defines the effect of modified high-intensity interval training (HIIT) on liver fat, cardiac function and metabolic control in adults with NAFLD. Twenty-three patients with NAFLD [age 54±10 years, body mass index (BMI) 31±4 kg/m(2), intra-hepatic lipid >5%) were assigned to either 12 weeks HIIT or standard care (controls). HIIT involved thrice weekly cycle ergometry for 30-40 min. MRI and spectroscopy were used to assess liver fat, abdominal fat and cardiac structure/function/energetics. Glucose control was assessed by oral glucose tolerance test and body composition by air displacement plethysmography. Relative to control, HIIT decreased liver fat (11±5% to 8±2% compared with 10±4% to 10±4% P=0.019), whole-body fat mass (35±7 kg to 33±8 kg compared with 31±9 kg to 32±9 kg, P=0.013), alanine (52±29 units/l to 42±20 units/l compared with 47±22 units/l to 51±24 units/l, P=0.016) and aspartate aminotransferase (AST; 36±18 units/l to 33±15 units/l compared with 31±8 units/l to 35±8 units/l, P=0.017) and increased early diastolic filling rate (244±84 ml/s to 302±107 ml/s compared with 255±82 ml/s to 251±82 ml/s, P=0.018). There were no between groups differences in glucose control. Modified HIIT reduces liver fat and improves body composition alongside benefits to cardiac function in patients with NAFLD and should be considered as part of the broader treatment regimen by clinical care teams. ISRCTN trial ID: ISRCTN78698481. PMID:26265792

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  17. Radiofrequency Ablation (RFA): Development of a Flow Model for Bovine Livers for Extensive Bench Testing

    SciTech Connect

    Lubienski, Andreas Bitsch, Rudi G.; Lubienski, Katrin; Kauffmann, Guenter; Duex, Markus

    2006-12-15

    Purpose. To develop a flow model for bovine livers for extensive bench testing of technical improvements or procedure-related developments of radiofrequency ablation excluding animal experiments. Methods. The perfusion of bovine livers directly from the slaughterhouse was simulated in a liver perfusion tank developed for the experimental work. The liver perfusion medium used was a Tyrode solution prepared in accordance with physiologic criteria (as for liver transplants) which was oxygenated by an oxygenator and heated to 36.5 deg. C. Portal vein circulation was regulated via a flow- and pressure-controlled pump and arterial circulation using a dialysis machine. Flow rate and pressure were adjusted as for the physiology of a human liver converted to bovine liver conditions. The fluid discharged from the liver was returned into the perfusion system through the vena cava. Extendable precision swivel arms with the radiofrequency probe attached were mounted on the liver perfusion tank. RFA was conducted with the RF3000 generator and a 2 cm LeVeen needle (Boston Scientific, Ratingen, Germany) in a three-dimensional grid for precise localization of the generated thermolesions. Results. Four bovine livers weighing 8.4 {+-} 0.4 kg each were prepared, connected to the perfusion system, and consecutively perfused for the experiments. Mean arterial flow was 569 {+-} 43 ml/min, arterial pressure 120 mmHg, portovenous flow 1440 {+-} 305 ml/min, and portal pressure 10 mmHg. Macroscopic evaluation after the experiments revealed no thrombi within the hepatic vessels. A total of 136 RF thermolesions were generated with an average number of 34 per liver. Mean RF duration was 2:59 {+-} 2:01 min:sec with an average baseline impedance of 28.2 {+-} 3.4 ohms. The mean diameter of the thermolesions along the puncture channel was 22.98 {+-} 4.34 mm and perpendicular to the channel was 23.27 {+-} 4.82 mm. Conclusion. Extracorporeal perfusion of bovine livers with consecutive standardized RF

  18. What Is Liver Cancer?

    MedlinePlus

    ... Topic Key statistics about liver cancer What is liver cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  19. Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

    PubMed Central

    Honda, Koichi; Seike, Masataka; Oribe, Junya; Endo, Mizuki; Arakawa, Mie; Syo, Hiroki; Iwao, Masao; Tokoro, Masanori; Nishimura, Junko; Mori, Tetsu; Yamashita, Tsutomu; Fukuchi, Satoshi; Muro, Toyokichi; Murakami, Kazunari

    2016-01-01

    AIM: To identify factors that influence long-term liver function following radiofrequency ablation (RFA) in patients with viral hepatitis-related hepatocellular carcinoma. METHODS: A total of 123 patients with hepatitis B virus- or hepatitis C virus-related hepatocellular car-cinoma (HCC) (n = 12 and n = 111, respectively) were enrolled. Cumulative rates of worsening Child-Pugh (CP) scores (defined as a 2-point increase) were examined. RESULTS: CP score worsening was confirmed in 22 patients over a mean follow-up period of 43.8 ± 26.3 mo. Multivariate analysis identified CP class, platelet count, and aspartate aminotransferase levels as signi-ficant predictors of a worsening CP score (P = 0.000, P = 0.011 and P = 0.024, respectively). In contrast, repeated RFA was not identified as a risk factor for liver function deterioration. CONCLUSION: Long-term liver function following RFA was dependent on liver functional reserve, the degree of fibrosis present, and the activity of the hepatitis condition for this cohort. Therefore, in order to maintain liver function for an extended period following RFA, suppression of viral hepatitis activity is important even after the treatment of HCC. PMID:27168872

  20. [Liver and artificial liver].

    PubMed

    Chamuleau, R A

    1998-06-01

    Despite good results of orthotopic liver transplantation in patients with fulminant hepatic failure the need still exists for an effective and safe artificial liver, able to temporarily take over the complex liver function so as to bridge the gap with transplantation or regeneration. Attempts to develop non-biological artificial livers have failed, mostly when controlled clinical trials were performed. In the last decade several different types of bioartificial livers have been devised, in which the biocomponent consists of freshly isolated porcine hepatocytes or a human hepatoblastoma cell line. The majority use semipermeable hollow fibers known from artificial kidney devices. The liver cells may lie either inside or outside the lumen of these fibers. In vitro analysis of liver function and animal experimental work showing that the bioartificial liver increases survival justify clinical application. Bioartificial livers are connected to patients extracorporeally by means of plasmapheresis circuit for periods of about 6 hours. In different trials about 40 patients with severe liver failure have been treated. No important adverse effects have not been reported in these phase I trials. Results of controlled studies are urgently needed. As long as no satisfactory immortalised human liver cell line with good function is available, porcine hepatocytes will remain the first choice, provided transmission of porcine pathogens to man is prevented. PMID:9752034

  1. Differences in cognitive function between patients with viral and alcoholic compensated liver cirrhosis.

    PubMed

    Lee, Yunhyeong; Kim, Chulho; Suk, Ki Tae; Choi, Hui Chul; Bang, Chang Seok; Yoon, Jai Hoon; Baik, Gwang Ho; Kim, Dong Joon; Jang, Min Uk; Sohn, Jong Hee

    2016-04-01

    As alcohol induces change in frontal cortex primarily involved in cognition, cognitive function may be different between viral and alcoholic liver cirrhosis (LC). This study aimed to determine the differences of cognitive function between viral and alcoholic compensated LC. From October 2011 to March 2013, 80 patients (viral: 37; alcohol: 43) with compensated LC were prospectively enrolled. Neuropsychological functions including attention, language, visuospatial, verbal memory, visual memory, and frontal/executive function were evaluated between two groups and compared with age-matched normal group (n = 1000). Cumulative incidence rate of overt hepatic encephalopathy (HE) was calculated. In the comparison with normal group, both two groups showed decreased memory function, frontal/executive function, and Korea-Mini Mental Status Examination. In the analysis of two groups, memory function by Verbal Learning Test (recognition: 20.1 ± 3.6 and 17.8 ± 4.8, p = 0.022), visuospatial function by Ray-Complex Figure Copy Test (recognition: 19.0 ± 2.6 and 17.3 ± 4.0, p = 0.043), frontal/executive function by Controlled Oral Ward Association (semantic: 17.1 ± 6.9 and 12.7 ± 6.9, p = 0.004), and the Korea-Mini Mental Status Examination (27.5 ± 1.9 and 26.2 ± 3.1, p = 0.03) showed low scores in alcoholic compensated LC patients. The 1-, 2-, and 3-year cumulative incidence rates of overt HE were 23 %, 26 %, and 26 % and 33 %, 43 %, and 49 % in the viral and alcoholic compensated LC group, respectively (p = 0.033). Impaired memory and frontal lobe executive functions and early development of overt HE were more common in patients with alcoholic LC. For patients with alcoholic LC, more integrated tests for early detection of minimal HE and intensive treatment should be considered to prevent overt HE. PMID:26563125

  2. HEALTH SIGNIFICANCE OF PULMONARY FUNCTION TESTS

    EPA Science Inventory

    As the sensitivity and precision of functional tests improves, we become increasingly able to measure responses to pollutant exposures with little, if any, demonstrable health significance. Proper interpretation of such functional responses generally requires an ability to evalua...

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

    PubMed

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

    2016-03-01

    Normothermic extracorporeal liver perfusion (NELP) can decrease ischemia/reperfusion injury to the greatest degree when cold ischemia time is minimized. Warm perfusion of cold-stored livers results in hepatocellular damage, sinusoidal endothelial cell (SEC) dysfunction, and Kupffer cell activation. However, the logistics of organ procurement mandates a period of cold preservation before NELP. The aim of this study was to determine the beneficial effects of gradual rewarming of cold-stored livers by placement on NELP. Three female porcine livers were used for each group. In the immediate NELP group, procured livers were immediately placed on NELP for 8 hours. In the cold NELP group, livers were cold-stored for 4 hours followed by NELP for 4 hours. In rewarming groups, livers were cold-stored for 4 hours, then gradually rewarmed in different durations to 38°C and kept on NELP for an additional 4 hours. For comparison purposes, the last 4 hours of NELP runs were considered to be the evaluation phase. Immediate NELP livers had significantly lower concentrations of liver transaminases, hyaluronic acid, and β-galactosidase and had higher bile production compared to the other groups. Rewarming livers had significantly lower concentrations of hyaluronic acid and β-galactosidase compared to the cold NELP livers. In addition, there was a significant decline in international normalized ratio values, improved bile production, reduced biliary epithelial cell damage, and improved cholangiocyte function. Thus, if a NELP machine is not available at the procurement site and livers will need to undergo a period of cold preservation, a gradual rewarming protocol before NELP may greatly reduce damages that are associated with reperfusion. In conclusion, gradual rewarming of cold-preserved livers upon NELP can minimize the hepatocellular damage, Kupffer cell activation, and SEC dysfunction. PMID:26439190

  4. Integrative fascial release and functional testing.

    PubMed

    Hammer, W

    2000-03-01

    Soft tissue techniques, including Integrative Myofascial Release (IFR) can be more effective if the area of treatment can be determined by functional testing. The patient's source of pain may not necessarily be located at the area of complaint and functional testing helps in pinpointing the source. Post-treatment functional testing will provide feedback to both the patient and the doctor as to whether the technique was effective. This paper will describe some typical functional tests and treatment using IFR of the posterior cervical/thoracolumbar fascia. PMID:17987166

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

    PubMed Central

    Vesin, P.; Traverso, H.

    1975-01-01

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

  6. [Mutagenic Activity of Four Aminoazo Compounds with Different Carcinogenicity for Rat Liver in the Ames Test].

    PubMed

    Frolova, T S; Sinitsyna, O I; Kaledin, V I

    2015-01-01

    In this paper in the bacterial Ames test we compared the mutagenicity of four aminoazo compounds, previously studied by other researchers and used for activation of rat liver enzymes, with the carcinogenicity in the rat liver. It was found that in the Ames test they have mutagenic activity, however, this activity does not correlate quantitatively with rat sensitivity to their hepatocarcinogenic action. Thus, the most active carcinogen 3'-methyl-4-dimethylaminoazobenzene causes mutations almost 2.5 times less than weakly carcinogenic ortho-aminoazotoluene, and exactly the same number of mutations as non-carcinogenic N,N-diethyl-4-aminoazobenzene. PMID:26591610

  7. Personalized management of cirrhosis by non-invasive tests of liver fibrosis.

    PubMed

    Wong, Grace Lai-Hung; Espinosa, Wendell Zaragoza; Wong, Vicnent Wai-Sun

    2015-09-01

    Owing to the high prevalence of various chronic liver diseases, cirrhosis is one of the leading causes of morbidity and mortality worldwide. In recent years, the development of non-invasive tests of fibrosis allows accurate diagnosis of cirrhosis and reduces the need for liver biopsy. In this review, we discuss the application of these non-invasive tests beyond the diagnosis of cirrhosis. In particular, their role in the selection of patients for hepatocellular carcinoma surveillance and varices screening is highlighted. PMID:26523265

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

    PubMed Central

    Dai, Xin; Wang, Bangmao

    2015-01-01

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

  9. Human precision-cut liver slices as a model to test antifibrotic drugs in the early onset of liver fibrosis.

    PubMed

    Westra, Inge M; Mutsaers, Henricus A M; Luangmonkong, Theerut; Hadi, Mackenzie; Oosterhuis, Dorenda; de Jong, Koert P; Groothuis, Geny M M; Olinga, Peter

    2016-09-01

    Liver fibrosis is the progressive accumulation of connective tissue ultimately resulting in loss of organ function. Currently, no effective antifibrotics are available due to a lack of reliable human models. Here we investigated the fibrotic process in human precision-cut liver slices (PCLS) and studied the efficacy of multiple putative antifibrotic compounds. Our results demonstrated that human PCLS remained viable for 48h and the early onset of fibrosis was observed during culture, as demonstrated by an increased gene expression of Heat Shock Protein 47 (HSP47) and Pro-Collagen 1A1 (PCOL1A1) as well as increased collagen 1 protein levels. SB203580, a specific inhibitor of p38 mitogen-activated protein kinase (MAPK) showed a marked decrease in HSP47 and PCOL1A1 gene expression, whereas specific inhibitors of Smad 3 and Rac-1 showed no or only minor effects. Regarding the studied antifibrotics, gene levels of HSP47 and PCOL1A1 could be down-regulated with sunitinib and valproic acid, while PCOL1A1 expression was reduced following treatment with rosmarinic acid, tetrandrine and pirfenidone. These results are in contrast with prior data obtained in rat PCLS, indicating that antifibrotic drug efficacy is clearly species-specific. Thus, human PCLS is a promising model for liver fibrosis. Moreover, MAPK signaling plays an important role in the onset of fibrosis in this model and transforming growth factor beta pathway inhibitors appear to be more effective than platelet-derived growth factor pathway inhibitors in halting fibrogenesis in PCLS. PMID:27235791

  10. Liver fibrosis markers in alcoholic liver disease

    PubMed Central

    Chrostek, Lech; Panasiuk, Anatol

    2014-01-01

    Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients. PMID:25009372

  11. ELEFUNT. Tests of Fortran Elementary Functions

    SciTech Connect

    Cody, W.J.

    1980-03-14

    ELEFUNT is an aggressive test of one or more of the elementary function subroutines generally supplied with the support library accompanying a FORTRAN compiler. Functions tested are ALOG/ALOG10, ASIN/ACOS, ATAN, EXP, POWER, SIN/COS, SINH/COSH, SQRT, TAN/COTAN, and TANH.

  12. The ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers.

    PubMed

    Takeshita, T; Yang, X; Morimoto, K

    2000-06-01

    A highly prevalent, atypical genotype in low Km aldehyde dehydrogenase (ALDH2) may influence alcohol-induced liver injury because of higher production of acetaldehyde in the liver. In the present study, we examined relationships between the ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers. Study subjects were 385 male workers in a metal plant in Japan, who were free from hepatic viruses and did not have higher aminotransferase activities (<100). The subjects completed a questionnaire on alcohol drinking habits and other lifestyles. The ALDH2 genotype was determined by the PCR method followed by restriction-enzyme digestion. In the moderately and heavily drinking groups, those with ALDH2*1/*2 exhibited significantly lower levels than those with ALDH2*1/*1 for all three parameters of liver function, whereas no such differences were observed in the least-drinking group. Multiple linear-regression analysis, adjusting for age, obesity, and smoking habits, revealed that aspartate aminotransferase activity was positively associated with alcohol intake only in those with ALDH2*1/*1. On the other hand, alanine transferase activity was negatively associated with alcohol intake only in those with ALDH2*1/*2. The present study indicates that effects of alcohol intake on liver-function biomarkers are likely to be modified by the ALDH2 genotype in adult males. PMID:10942105

  13. Assessment of Preoperative Liver Function in Patients with Hepatocellular Carcinoma – The Albumin-Indocyanine Green Evaluation (ALICE) Grade

    PubMed Central

    Kokudo, Takashi; Hasegawa, Kiyoshi; Amikura, Katsumi; Uldry, Emilie; Shirata, Chikara; Yamaguchi, Takamune; Arita, Junichi; Kaneko, Junichi; Akamatsu, Nobuhisa; Sakamoto, Yoshihiro; Takahashi, Amane; Sakamoto, Hirohiko; Makuuchi, Masatoshi; Matsuyama, Yutaka; Demartines, Nicolas; Malagó, Massimo; Kokudo, Norihiro; Halkic, Nermin

    2016-01-01

    Background Most patients with hepatocellular carcinoma (HCC) have underlying liver disease, therefore, precise preoperative evaluation of the patient’s liver function is essential for surgical decision making. Methods We developed a grading system incorporating only two variables, namely, the serum albumin level and the indocyanine green retention rate at 15 minutes (ICG R15), to assess the preoperative liver function, based on the overall survival of 1868 patients with HCC who underwent liver resection. We then tested the model in a European cohort (n = 70) and analyzed the predictive power for the postoperative short-term outcome. Results The Albumin-Indocyanine Green Evaluation (ALICE) grading system was developed in a randomly assigned training cohort: linear predictor = 0.663 × log10ICG R15 (%)−0.0718 × albumin (g/L) (cut-off value: -2.20 and -1.39). This new grading system showed a predictive power for the overall survival similar to the Child-Pugh grading system in the validation cohort. Determination of the ALICE grade in Child-Pugh A patients allowed further stratification of the postoperative prognosis. This result was reproducible in the European cohort. Determination of the ALICE grade allowed better prediction of the risk of postoperative liver failure and mortality (ascites: grade 1, 2.1%; grade 2, 6.5%; grade 3, 16.0%; mortality: grade 1, 0%; grade 2, 1.3%; grade 3, 5.3%) than the previously reported model based on the presence/absence of portal hypertension. Conclusions This new grading system is a simple method for prediction of the postoperative long-term and short-term outcomes. PMID:27434062

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

    PubMed Central

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

    2015-01-01

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

  15. Changes in portal blood flow and liver functions in cirrhotics during Ramadan fasting in the summer; a pilot study

    PubMed Central

    Mohamed, Salem Y; Emara, Mohamed H; Hussien, Hala IM; Elsadek, Hany M

    2016-01-01

    Aim: Assessment of short term changes in portal blood flow and long term changes in liver functions in cirrhotic patients who chose to fast during the month of Ramadan in summer. Background: During Ramadan, healthy Muslims obligated to fast from predawn to sunset. Patients and methods: Forty cirrhotic patients intended to fast during the month of Ramadan in the year 2014, were examined by Congestion index (CI) as a non-invasive indicator of short term changes in the portal blood flow, while liver function tests were determined as an indicator of long term changes in liver functions. Results: A total of 38 patients completed the whole month fasting and two patients discontinued fasting due to variceal bleeding. The complicated patients were 7. CI showed a statistically significant increase from fasting to postprandial status (P<0.001), with statistically significant increases from fasting to postprandial status in Child class A (P<0.001), and B (P<0.001). We did not find a statistical significance between patients with complications and those without complications (P=0.6). There was a statistically significant rise in the serum bilirubin after Ramadan. Deterioration noticed as advanced Child classes, development of lower limb edema, increasing ascites, increasing jaundice and overt encephalopathy. Conclusion: Cirrhotic patients showed significant short-term changes in the portal blood flow. However, these changes are not linked to complications or deterioration of liver functions and accommodated especially in patients with Child class A and B. Child class C patients should not fast. PMID:27458510

  16. Patterns and predictors of sexual function after liver donation: The Adult-to-Adult Living Donor Liver Transplantation Cohort study.

    PubMed

    DiMartini, Andrea F; Dew, Mary Amanda; Butt, Zeeshan; Simpson, Mary Ann; Ladner, Daniela P; Smith, Abigail R; Hill-Callahan, Peg; Gillespie, Brenda W

    2015-05-01

    Although sexual functioning is an important facet of a living donor's quality of life, it has not received an extensive evaluation in this population. Using data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, we examined donor sexual functioning across the donation process from the predonation evaluation to 3 months and 1 year after donation. Donors (n = 208) and a comparison group of nondonors (n = 155) completed self-reported surveys with specific questions on sexual desire, satisfaction, orgasm, and (for men) erectile function. Across the 3 time points, donor sexual functioning was lower at the evaluation phase and 3 months after donation versus 1 year after donation. In the early recovery period, abdominal pain was associated with difficulty reaching orgasm [odds ratio (OR), 3.98; 95% confidence interval (CI), 1.30-12.16], concerns over appearance were associated with lower sexual desire (OR, 4.14; 95% CI, 1.02-16.79), and not feeling back to normal was associated with dissatisfaction with sexual life (OR, 3.58; 95% CI, 1.43-8.99). Efforts to educate donors before the surgery and prepare them for the early recovery phase may improve recovery and reduce distress regarding sexual functioning. PMID:25779554

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

    PubMed Central

    Nantasanti, Sathidpak; Toussaint, Mathilda J. M.; Youssef, Sameh A.; Tooten, Peter C. J.; de Bruin, Alain

    2016-01-01

    The tumor suppressors Retinoblastoma (Rb) and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC) or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). DDC is metabolized mainly by cytochrome P450 (Cyp)3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC. PMID:26967735

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

    SciTech Connect

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

    2012-09-28

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

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

    PubMed

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

    2011-02-01

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

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

    PubMed Central

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

    2010-01-01

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

  1. Recommended protocols for the liver micronucleus test: Report of the IWGT working group.

    PubMed

    Uno, Yoshifumi; Morita, Takeshi; Luijten, Mirjam; Beevers, Carol; Hamada, Shuichi; Itoh, Satoru; Ohyama, Wakako; Takasawa, Hironao

    2015-05-01

    At the 6th International Workshop on Genotoxicity Testing (IWGT), the liver micronucleus test working group discussed practical aspects of the in vivo rodent liver micronucleus test (LMNT). The group members focused on the three methodologies currently used, i.e., a partial hepatectomy (PH) method, a juvenile/young rat (JR) method, and a repeated-dose (RD) method in adult rodents. Since the liver is the main organ that metabolizes chemicals, the LMNT is expected to detect clastogens, especially those that need metabolic activation in the liver, and aneugens. Based on current data the three methods seem to have a high sensitivity and specificity, but more data, especially on non-genotoxic but toxic substances, would be needed to fully evaluate the test performance. The three methods can be combined with the micronucleus test (MNT) using bone marrow (BM) and/or peripheral blood (PB). The ability of the PH method to detect both clastogens and aneugens has already been established, but the methodology is technically challenging. The JR method is relatively straightforward, but animal metabolism might not be fully comparable to adult animals, and data on aneugens are limited. These two methods also have the advantage of a short testing period. The RD method is also straightforward and can be integrated into repeated-dose (e.g. 2 or 4 weeks) toxicity studies, but again data on aneugens are limited. The working group concluded that the LMNT could be used as a second in vivo test when a relevant positive result in in vitro mammalian cell genotoxicity tests is noted (especially under the condition of metabolic activation), and a negative result is observed in the in vivo BM/PB-MNT. The group members discussed LMNT protocols and reached consensus about many aspects of test procedures. However, data gaps as mentioned above remain, and further data are needed to fully establish the LMNT protocol. PMID:25953396

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

    PubMed Central

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

    2013-01-01

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

  3. [Liver function tests after a 6-month deposiston therapy].

    PubMed

    Brügmann, E; Göretzlehner, G; Töwe, J; Rehpenning, W

    1975-01-01

    18 women were treated with Deposition (4th, 11th and 18th cycle day each 1 mg 17alpha-Ethynyl-3isopropylsulfonyloxy-Estradiol, 25th cycle day 10 mg norethisterone acetate). When these medicines were taken the activities of aminotransferases, alkaline phosphatase and alpha-amylase, the contents cholesterol, total bilirubin and proteins of the serum and the paperelectric solution, TTT and indocyanine green half worth time. A little significant decrease of the activity of alaninamino-transferase (GPT) was to be stated. Whereas at the end of the 6th cycle the TTT as well as the contents of total proteins and albumin, showed a little significant decrease and the contents of alpha2-globulin, beta-globulin as well as cholesterol were statistically shown to grow. The indocyanine green elimation was longer at the end of the 6th cycle without any pathological worth from clinical point of view being proved. PMID:1189758

  4. Binomial test statistics using Psi functions

    SciTech Connect

    Bowman, Kimiko o

    2007-01-01

    For the negative binomial model (probability generating function (p + 1 - pt){sup -k}) a logarithmic derivative is the Psi function difference {psi}(k + x) - {psi}(k); this and its derivatives lead to a test statistic to decide on the validity of a specified model. The test statistic uses a data base so there exists a comparison available between theory and application. Note that the test function is not dominated by outliers. Applications to (i) Fisher's tick data, (ii) accidents data, (iii) Weldon's dice data are included.

  5. The current status of alternatives to animal testing and predictive toxicology methods using liver microfluidic biochips.

    PubMed

    Prot, Jean Matthieu; Leclerc, Eric

    2012-06-01

    In this paper, we will consider new in vitro cell culture platforms and the progress made, based on the microfluidic liver biochips dedicated to pharmacological and toxicological studies. Particular emphasis will be given to recent developments in the microfluidic tools dedicated to cell culture (more particularly liver cell culture), in silico opportunities for Physiologically Based PharmacoKinetic (PBPK) modelling, the challenge of the mechanistic interpretations offered by the approaches resulting from "multi-omics" data (transcriptomics, proteomics, metabolomics, cytomics) and imaging microfluidic platforms. Finally, we will discuss the critical features regarding microfabrication, design and materials, and cell functionality as the key points for the future development of new microfluidic liver biochips. PMID:22160577

  6. Prep1 Controls Insulin Glucoregulatory Function in Liver by Transcriptional Targeting of SHP1 Tyrosine Phosphatase

    PubMed Central

    Oriente, Francesco; Iovino, Salvatore; Cabaro, Serena; Cassese, Angela; Longobardi, Elena; Miele, Claudia; Ungaro, Paola; Formisano, Pietro; Blasi, Francesco; Beguinot, Francesco

    2011-01-01

    OBJECTIVE We investigated the function of the Prep1 gene in insulin-dependent glucose homeostasis in liver. RESEARCH DESIGN AND METHODS Prep1 action on insulin glucoregulatory function has been analyzed in liver of Prep1-hypomorphic mice (Prep1i/i), which express 2–3% of Prep1 mRNA. RESULTS Based on euglycemic hyperinsulinemic clamp studies and measurement of glycogen content, livers from Prep1i/i mice feature increased sensitivity to insulin. Tyrosine phosphorylation of both insulin receptor (IR) and insulin receptor substrate (IRS)1/2 was significantly enhanced in Prep1i/i livers accompanied by a specific downregulation of the SYP and SHP1 tyrosine phosphatases. Prep1 overexpression in HepG2 liver cells upregulated SYP and SHP1 and inhibited insulin-induced IR and IRS1/2 phosphorylation and was accompanied by reduced glycogen content. Consistently, overexpression of the Prep1 partner Pbx1, but not of p160MBP, mimicked Prep1 effects on tyrosine phosphorylations, glycogen content, and on SYP and SHP1 expression. In Prep1 overexpressing cells, antisense silencing of SHP1, but not that of SYP, rescued insulin-dependent IR phosphorylation and glycogen accumulation. Both Prep1 and Pbx1 bind SHP1 promoter at a site located between nucleotides −2,113 and −1,778. This fragment features enhancer activity and induces luciferase function by 7-, 6-, and 30-fold, respectively, in response to Prep1, Pbx1, or both. CONCLUSIONS SHP1, a known silencer of insulin signal, is a transcriptional target of Prep1. In liver, transcriptional activation of SHP1 gene by Prep1 attenuates insulin signal transduction and reduces glucose storage. PMID:20864515

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

    PubMed Central

    TANAKA, Hiroshi; TAKEO, Shun; ABE, Takahito; KIN, Airi; SHIRASUNA, Koumei; KUWAYAMA, Takehito; IWATA, Hisataka

    2016-01-01

    The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts. PMID:26832309

  8. All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver.

    PubMed

    Tripathy, Sasmita; Chapman, John D; Han, Chang Y; Hogarth, Cathryn A; Arnold, Samuel L M; Onken, Jennifer; Kent, Travis; Goodlett, David R; Isoherranen, Nina

    2016-05-01

    All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. The liver is the main storage organ of vitamin A, but activation of the retinoic acid receptors (RARs) in mouse liver and in human liver cell lines has also been shown. AlthoughatRA treatment improves mitochondrial function in skeletal muscle in rodents, its role in modulating mitochondrial function in the liver is controversial, and little data are available regarding the human liver. The aim of this study was to determine whetheratRA regulates hepatic mitochondrial activity.atRA treatment increased the mRNA and protein expression of multiple components of mitochondrialβ-oxidation, tricarboxylic acid (TCA) cycle, and respiratory chain. Additionally,atRA increased mitochondrial biogenesis in human hepatocytes and in HepG2 cells with and without lipid loading based on peroxisome proliferator activated receptor gamma coactivator 1αand 1βand nuclear respiratory factor 1 mRNA and mitochondrial DNA quantification.atRA also increasedβ-oxidation and ATP production in HepG2 cells and in human hepatocytes. Knockdown studies of RARα, RARβ, and PPARδrevealed that the enhancement of mitochondrial biogenesis andβ-oxidation byatRA requires peroxisome proliferator activated receptor delta. In vivo in mice,atRA treatment increased mitochondrial biogenesis markers after an overnight fast. Inhibition ofatRA metabolism by talarozole, a cytochrome P450 (CYP) 26 specific inhibitor, increased the effects ofatRA on mitochondrial biogenesis markers in HepG2 cells and in vivo in mice. These studies show thatatRA regulates mitochondrial function and lipid metabolism and that increasingatRA concentrations in human liver via CYP26 inhibition may increase mitochondrial biogenesis and fatty acidβ-oxidation and provide therapeutic benefit in diseases associated with mitochondrial dysfunction. PMID:26921399

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

    PubMed

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

    2016-06-17

    The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts. PMID:26832309

  10. Micronucleus test in rodent tissues other than liver or erythrocytes: Report of the IWGT working group.

    PubMed

    Uno, Yoshifumi; Morita, Takeshi; Luijten, Mirjam; Beevers, Carol; Hamada, Shuichi; Itoh, Satoru; Ohyama, Wakako; Takasawa, Hironao

    2015-05-01

    At the 6th International Workshop on Genotoxicity Testing, the liver micronucleus test (MNT) working group briefly discussed the MNT using tissues other than liver/erythrocytes. Many tissues other than liver/erythrocytes have been studied, primarily for research purposes. They have included the colon and intestinal epithelium, skin, spleen, lung, stomach, bladder, buccal mucosa, vagina, and fetal/neonatal tissues. These tissues were chosen because they were target sites of carcinogens, and/or relevant to a specific route of exposure. Recently, there has been particular focus on the gastrointestinal (GI) tract as it is a contact site associated with high exposure following oral gavage. Furthermore GI tumors are observed with high frequency in human populations. A collaborative study of the rat glandular stomach and colon MNT was conducted in conjunction with a collaborative study of the repeated-dose liver MNT. Based on limited data currently available, the rodent MNT using the glandular stomach and/or colon seems to detect genotoxic carcinogens with GI tract target-organ specificity. The working group concluded that the GI tract MNT would be a promising method to examine clastogenicity or aneugenicity of test chemicals in the stomach and/or colon. Further data will be needed to fully establish the methods, and to identify the sensitivity and specificity of the GI tract MNT. PMID:25953397

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

    NASA Astrophysics Data System (ADS)

    Yazdani, Farshad; Fattahi, Bahare; Azizi, Najmodin

    2016-05-01

    The aim of this research was the preparation of functionalized magnetite nanoparticles to use as a liver targeting contrast agent in magnetic resonance imaging (MRI). For this purpose, Fe3O4 nanoparticles were synthesized via the co-precipitation method. The synthesized nanoparticles were coated with silica via the Stober method and finally the coated nanoparticles were functionalized with mebrofenin. Formation of crystalline magnetite particles was confirmed by X-ray diffraction (XRD) analysis. The Fourier transform infrared spectroscopy (FTIR) and energy dispersive X-ray analyzer (EDX) of the final product showed that silica had been effectively bonded onto the surface of the magnetite nanoparticles and the coated nanoparticles functionalized with mebrofenin. The magnetic resonance imaging of the functional nanoparticles showed that the Fe3O4-SiO2-mebrofenin composite is an effective MRI contrast agent for liver targeting.

  12. Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology

    PubMed Central

    2014-01-01

    The liver is a central immunological organ. Liver resident macrophages, Kupffer cells (KC), but also sinusoidal endothelial cells, dendritic cells (DC) and other immune cells are involved in balancing immunity and tolerance against pathogens, commensals or food antigens. Hepatic stellate cells (HSCs) have been primarily characterized as the main effector cells in liver fibrosis, due to their capacity to transdifferentiate into collagen-producing myofibroblasts (MFB). More recent studies elucidated the fundamental role of HSC in liver immunology. HSC are not only the major storage site for dietary vitamin A (Vit A) (retinol, retinoic acid), which is essential for proper function of the immune system. This pericyte further represents a versatile source of many soluble immunological active factors including cytokines [e.g., interleukin 17 (IL-17)] and chemokines [C-C motif chemokine (ligand) 2 (CCL2)], may act as an antigen presenting cell (APC), and has autophagy activity. Additionally, it responds to many immunological triggers via toll-like receptors (TLR) (e.g., TLR4, TLR9) and transduces signals through pathways and mediators traditionally found in immune cells, including the Hedgehog (Hh) pathway or inflammasome activation. Overall, HSC promote rather immune-suppressive responses in homeostasis, like induction of regulatory T cells (Treg), T cell apoptosis (via B7-H1, PDL-1) or inhibition of cytotoxic CD8 T cells. In conditions of liver injury, HSC are important sensors of altered tissue integrity and initiators of innate immune cell activation. Vice versa, several immune cell subtypes interact directly or via soluble mediators with HSC. Such interactions include the mutual activation of HSC (towards MFB) and macrophages or pro-apoptotic signals from natural killer (NK), natural killer T (NKT) and gamma-delta T cells (γδ T-cells) on activated HSC. Current directions of research investigate the immune-modulating functions of HSC in the environment of liver

  13. Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

    PubMed Central

    Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2014-01-01

    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. PMID:24876909

  14. In situ patterned micro 3D liver constructs for parallel toxicology testing in a fluidic device.

    PubMed

    Skardal, Aleksander; Devarasetty, Mahesh; Soker, Shay; Hall, Adam R

    2015-09-01

    3D tissue models are increasingly being implemented for drug and toxicology testing. However, the creation of tissue-engineered constructs for this purpose often relies on complex biofabrication techniques that are time consuming, expensive, and difficult to scale up. Here, we describe a strategy for realizing multiple tissue constructs in a parallel microfluidic platform using an approach that is simple and can be easily scaled for high-throughput formats. Liver cells mixed with a UV-crosslinkable hydrogel solution are introduced into parallel channels of a sealed microfluidic device and photopatterned to produce stable tissue constructs in situ. The remaining uncrosslinked material is washed away, leaving the structures in place. By using a hydrogel that specifically mimics the properties of the natural extracellular matrix, we closely emulate native tissue, resulting in constructs that remain stable and functional in the device during a 7-day culture time course under recirculating media flow. As proof of principle for toxicology analysis, we expose the constructs to ethyl alcohol (0-500 mM) and show that the cell viability and the secretion of urea and albumin decrease with increasing alcohol exposure, while markers for cell damage increase. PMID:26355538

  15. PULMONARY FUNCTION TESTING IN SMALL LABORATORY MAMMALS

    EPA Science Inventory

    The lung is the primary organ likely to be exposed by inhalation studies and, therefore, measurement of changes in lung function are of particular interest to the pulmonary physiologist and toxicologist. Tests of pulmonary function have been developed which can be used with small...

  16. Analysis of the serine protease function of porcine factor I produced by liver cells for xenotransplantation.

    PubMed

    Nakahata, Kengo; Matsunami, Katsuyoshi; Kobayashi, Chizuko; Omori, Takeshi; Xu, Hengjie; Firdawes, Sabere; Fukuzawa, Masahiro; Miyagawa, Shuji

    2008-04-01

    The use of a bioartificial liver with pig liver cells in the treatment of fulminant hepatic failure has already begun as a clinical trial in several countries. Therefore, studies on plasma complement regulatory proteins of the pig are necessary, because the liver produces them. Complement factor I is a serine protease that cleaves C3b and C4b. The DNA sequences of factor I have been reported in many species, with the noted exception of pigs. In this study, porcine factor I was cloned and an open reading frame of 1794 base pairs were identified. The predicted amino acid sequence maintained a relatively high homology compared to those of other mammals, especially in the serine protease (SP) region. The cell membrane-bound forms of the porcine and the human SP domain of factor I were constructed. Amelioration of complement-mediated cell lysis by these molecules was then tested, using several kinds of sera and Chinese hamster ovary (CHO) cell transfectants. Both molecules had a suppressing effect on pig, human and dog complements, indicating little species-specificity. Further studies of other plasma complement regulatory proteins produced from pig liver cells will need to be considered as the primary feature of the pig bioartificial liver. PMID:18346635

  17. Human Ex-Vivo Liver Model for Acetaminophen-induced Liver Damage

    PubMed Central

    Schreiter, Thomas; Sowa, Jan-Peter; Schlattjan, Martin; Treckmann, Jürgen; Paul, Andreas; Strucksberg, Karl-Heinz; Baba, Hideo A.; Odenthal, Margarete; Gieseler, Robert K.; Gerken, Guido; Arteel, Gavin E.; Canbay, Ali

    2016-01-01

    Reliable test systems to identify hepatotoxicity are essential to predict unexpected drug-related liver injury. Here we present a human ex-vivo liver model to investigate acetaminophen-induced liver injury. Human liver tissue was perfused over a 30 hour period with hourly sampling from the perfusate for measurement of general metabolism and clinical parameters. Liver function was assessed by clearance of indocyanine green (ICG) at 4, 20 and 28 hours. Six pieces of untreated human liver specimen maintained stable liver function over the entire perfusion period. Three liver sections incubated with low-dose acetaminophen revealed strong damage, with ICG half-lives significantly higher than in non-treated livers. In addition, the release of microRNA-122 was significantly higher in acetaminophen-treated than in non-treated livers. Thus, this model allows for investigation of hepatotoxicity in human liver tissue upon applying drug concentrations relevant in patients. PMID:27550092

  18. Biliary reconstruction in living donor liver transplantation with dye injection leakage test and without stent use.

    PubMed

    Ikegami, T; Nishizaki, T; Kishikawa, K; Nomoto, K; Uchiyama, H; Ohta, R; Hiroshige, S; Sugimachi, K

    2001-01-01

    Biliary complication remains a significant source of morbidity and mortality in living donor liver transplantation. From October 1996 to December 1999, 34 patients underwent 35 living donor liver transplantations at Kyushu University Hospital. In the initial twenty cases, anastomotic internal stents were placed. In the most recent fifteen cases, no internal stent was inserted and routine postreconstruction dye injection leakage tests were administered. In recipient biliary reconstruction, hepaticojejunostomy was performed using interrupted sutures without an anastomotic stent. After an intestinal clamp was applied at the anal side of the hepaticojejunostomy, leakage test was done using diluted indigocarmine solution injected into the jejunal loop lumen. Two (13%) of the fifteen recent patients suffered from biliary complications, whereas eight patients (40%) from the former twenty patients suffered from biliary complications. We conclude that the use of the stent was not useful, but the application of the dye injection leakage test was useful. PMID:11813578

  19. Comparison of clinical tests of olfactory function.

    PubMed

    Reden, J; Draf, C; Frank, R A; Hummel, T

    2016-04-01

    To assess olfactory function, various measures are used in clinical routine. In this study, the Sniff Magnitude Test (SMT), a test considering the sniff response to an odor, was applied to patients with olfactory dysfunction (n = 49) and to a control group without subjective olfaction disorder (n = 21). For comparison, the validated "Sniffin' Sticks" test battery, a psychophysical olfactory test consisting of tests for phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification was performed. Analyses indicated that the SMT showed significant differences between patients and controls (p = 0.003). Furthermore, results from the SMT and the "Sniffin' Sticks" correlated significantly (p < 0.001). In conclusion, the SMT appears to be a useful addition to the battery of available clinical tests to assess olfactory function. PMID:26050222

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2010-01-01

    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

  2. Complete and rapid response to FOLFIRI plus bevacizumab in a patient presenting with impaired liver function and poor performance status from colon cancer liver metastases.

    PubMed

    Belda-Iniesta, Cristóbal; Sáenz, Enrique Casado; de Castro-Carpeño, Javier; Hernández, Elena; Barón, Manuel González

    2009-04-01

    Impaired liver function is a final complication of hepatic metastases from colon cancer. This disease status is of critical importance at first clinical presentation because of the tight therapeutic window for chemotherapy. A rapid response to treatment is required as other means of supportive care for hepatic function are limited. New targeted therapies including monoclonal antibodies directed against several proteins with key roles in colon cancer biology are now available, allowing new treatment options for this group of patients. Here, we present a patient with highly impaired liver function secondary to hepatic metastases from colon cancer that showed clinical and radiological improvement after systemic treatment including bevacizumab. PMID:19352108

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

    PubMed Central

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

    2015-01-01

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

  4. HepatoProteomics: Applying Proteomic Technologies to the Study of Liver Function and Disease

    SciTech Connect

    Diamond, Deborah L.; Proll, Sean; Jacobs, Jon M.; Chan, Eric Y.; Camp, David G.; Smith, Richard D.; Katze, Michael G.

    2006-08-01

    The wealth of human genome sequence information now available, coupled with technological advances in robotics, nanotechnology, mass spectrometry, and information systems, has given rise to a method of scientific inquiry known as functional genomics. By using these technologies to survey gene expression and protein production on a near global scale, the goal of functional genomics is to assign biological function to genes with currently unknown roles in physiology. This approach carries particular appeal in disease research, where it can uncover the function of previously unknown genes and molecular pathways that are directly involved in disease progression. With this knowledge may come improved diagnostic techniques, prognostic capabilities, and novel therapeutic approaches. In this regard, the continuing evolution of proteomic technologies has resulted in an increasingly greater impact of proteome studies in many areas of research and hepatology is no exception. Our laboratory has been extremely active in this area, applying both genomic and proteomic technologies to the analysis of virus-host interactions in several systems, including the study of hepatitis C virus (HCV) infection and HCV-associated liver disease. Since proteomic technologies are foreign to many hepatologists (and to almost everyone else), this article will provide an overview of proteomic methods and technologies and describe how they're being used to study liver function and disease. We use our studies of HCV infection and HCV-associated liver disease to present an operational framework for performing high throughput proteome analysis and extracting biologically meaningful information.

  5. Evaluation of Liver Function After Proton Beam Therapy for Hepatocellular Carcinoma

    SciTech Connect

    Mizumoto, Masashi; Okumura, Toshiyuki; Hashimoto, Takayuki; Fukuda, Kuniaki; Oshiro, Yoshiko; Fukumitsu, Nobuyoshi; Abei, Masato; Kawaguchi, Atsushi; Hayashi, Yasutaka; Ohkawa, Ayako; Hashii, Haruko; Kanemoto, Ayae; Moritake, Takashi; Tohno, Eriko; Tsuboi, Koji; Sakae, Takeji; Sakurai, Hideyuki

    2012-03-01

    Purpose: Our previous results for treatment of hepatocellular carcinoma with proton beam therapy (PBT) revealed excellent local control. In this study, we focused on the impact of PBT on normal liver function. Methods and Materials: The subjects were 259 patients treated with PBT at University of Tsukuba between January 2001 and December 2007. We evaluated the Child-Pugh score pretreatment, on the final day of PBT, and 6, 12, and 24 months after treatment with PBT. Patients who had disease progression or who died with tumor progression at each evaluation point were excluded from the analysis to rule out an effect of tumor progression. An increase in the Child-Pugh score of 1 or more was defined as an adverse event. Results: Of the 259 patients, 241 had no disease progression on the final day of PBT, and 91 had no progression within 12 months after PBT. In univariate analysis, the percentage volumes of normal liver receiving at least 0, 10, 20, and 30 GyE in PBT (V0, 10, 20, and 30) were significantly associated with an increase of Child-Pugh score at 12 months after PBT. Of the 91 patients evaluated at 12 months, 66 had no increase of Child-Pugh score, 15 had a 1-point increase, and 10 had an increase of {>=}2 points. For the Youden index, the optimal cut-offs for V0, V10, V20, and V30 were 30%, 20%, 26%, and 18%, respectively. Conclusion: Our findings indicate that liver function after PBT is significantly related to the percentage volume of normal liver that is not irradiated. This suggests that further study of the relationship between liver function and PBT is required.

  6. Leakage tests reduce the frequency of biliary fistulas following hydatid liver cyst surgery

    PubMed Central

    Kayaalp, Cuneyt; Aydin, Cemalettin; Olmez, Aydemir; Isik, Sevil; Yilmaz, Sezai

    2011-01-01

    BACKGROUND AND AIM: Biliary fistulas are the most common morbidity (8.2-26%) following hydatid liver surgery. The aim of our study was to reduce the incidence of postoperative biliary fistulas after the suturing of cystobiliary communications by applying a bile leakage test. PATIENTS AND METHODS: A total of 133 hydatid liver cysts from 93 patients were divided into two groups, according to whether the test was performed. Tests were performed on 56 cysts from 34 patients, and the remaining 77 cysts from 59 patients were treated without the test. In both groups, all visible biliary orifices in the cysts were suture ligated, and drains were placed in all cysts. The visibility of the biliary orifices and postoperative biliary drainage through the drains were recorded. Patients in both groups were also compared with respect to the number of days living with the drains, the length of the hospital stay, and secondary interventions related to biliary complications. RESULTS: Biliary orifices were more visible in the tested cysts (13% vs. 48%; P <0.001). Fewer biliary complications occurred in the tested patients (8.8% vs. 27.7%, P = 0.033). The mean drain removal time (4.1±3.3 days vs. 6.8±8.9 days, P<0.05) and the length of the hospital stay (6.7±2.7 days vs. 9.7±6.3 days, P<0.01) were shorter for the tested patients. None of the patients in the test group required postoperative Endoscopic retrograde cholangiopancreaticography (ERCP) or nasobiliary drainage (0.0% vs. 8.4%, P  =  0.09). There were no long-term biliary complications for either group after three years of follow-up. CONCLUSIONS: Identification of biliary orifices with a bile leakage test and the suturing of cystobiliary communications significantly reduced postoperative biliary complications following hydatid liver surgery. PMID:21552666

  7. Pulmonary function testing in small laboratory mammals.

    PubMed Central

    O'Neil, J J; Raub, J A

    1984-01-01

    The lung is the primary organ likely to be exposed by inhalation studies and, therefore, measurement of changes in lung function are of particular interest to the pulmonary physiologist and toxicologist. Tests of pulmonary function have been developed which can be used with small animals to measure spirometry (lung volumes), mechanics, distribution of ventilation, gas exchange or control of ventilation. These tests were designed on the basis of similar tests which are used in humans to diagnose and manage patients with lung disease. A major difference is that many of the measurements are performed in anesthetized animals, while human pulmonary function is usually measured in awake cooperating individuals. In addition, the measurement of respiratory events in small animals requires sensitive and rapidly responding equipment, because signals may be small and events can occur quickly. In general, the measurements described provide information on the change in normal lung function which results primarily from structural changes. These tests of pulmonary function can be repetitively and routinely accomplished and the results appear to be highly reproducible. Although some are quite sophisticated, many can be undertaken with relatively inexpensive equipment and provide useful information for toxicological testing. PMID:6434299

  8. Liver biopsy

    MedlinePlus

    ... Test is Performed The biopsy helps diagnose many liver diseases . The procedure also helps assess the stage (early, advanced) of liver disease. This is especially important in hepatitis C infection. ...

  9. Liver transplant - series (image)

    MedlinePlus

    The liver is in the right upper abdomen. The liver serves many functions, including the detoxification of substances delivered ... A liver transplant may be recommended for: liver damage due to alcoholism (Alcoholic cirrhosis) primary biliary cirrhosis long-term ( ...

  10. [Evaluating new tests for liver damage: still a long way to go].

    PubMed

    Bossuyt, P M M

    2007-07-01

    Because of its limitations and risks, alternatives are being developed for liver biopsy as the first-line method for evaluating liver injury. Many markers and several imaging methods have been developed as non-invasive alternatives. Although these methods have been evaluated in studies published in peer-reviewed journals, the methodological rigor of the design, execution and analysis of these studies leaves much to be desired. In addition, some of the inventors of these methods, who have become shareholders of the companies that market these tests, can be found frequently in the list of authors. The way in which new medical tests are evaluated can be improved, as well as the level of independence from conflicting interests. PMID:17763807

  11. Estimating Functional Liver Reserve Following Hepatic Irradiation: Adaptive Normal Tissue Response Models

    PubMed Central

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

    2014-01-01

    Purpose To estimate the limit of functional liver reserve for safe application of hepatic irradiation using changes in indocyanine green, an established assay of liver function. Materials and Methods From 2005–2011, 60 patients undergoing hepatic irradiation were enrolled in a prospective study assessing the plasma retention fraction of indocyanine green at 15-min (ICG-R15) prior to, during (at 60% of planned dose), and after radiotherapy (RT). The limit of functional liver reserve was estimated from the damage fraction of functional liver (DFL) post-RT [1−(ICG-R15pre-RT/ICG-R15post-RT)] where no toxicity was observed using a beta distribution function. Results Of 48 evaluable patients, 3 (6%) developed RILD, all within 2.5 months of completing RT. The mean ICG-R15 for non-RILD patients pre-RT, during-RT and 1-month post-RT was 20.3%(SE 2.6), 22.0%(3.0), and 27.5%(2.8), and for RILD patients was 6.3%(4.3), 10.8%(2.7), and 47.6%(8.8). RILD was observed at post-RT damage fractions of ≥78%. Both DFL assessed by during-RT ICG and MLD predicted for DFL post-RT (p<0.0001). Limiting the post-RT DFL to 50%, predicted a 99% probability of a true complication rate <15%. Conclusion The DFL as assessed by changes in ICG during treatment serves as an early indicator of a patient’s tolerance to hepatic irradiation. PMID:24813090

  12. Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs

    SciTech Connect

    Westra, Inge M.; Oosterhuis, Dorenda; Groothuis, Geny M.M.; Olinga, Peter

    2014-01-15

    Induction of fibrosis during prolonged culture of precision-cut liver slices (PCLS) was reported. In this study, the use of rat PCLS was investigated to further characterize the mechanism of early onset of fibrosis in this model and the effects of antifibrotic compounds. Rat PCLS were incubated for 48 h, viability was assessed by ATP and gene expression of PDGF-B and TGF-β1 and the fibrosis markers Hsp47, αSma and Pcol1A1 and collagen1 protein expressions were determined. The effects of the antifibrotic drugs imatinib, sorafenib and sunitinib, PDGF-pathway inhibitors, and perindopril, valproic acid, rosmarinic acid, tetrandrine and pirfenidone, TGFβ-pathway inhibitors, were determined. After 48 h of incubation, viability of the PCLS was maintained and gene expression of PDGF-B was increased while TGF-β1 was not changed. Hsp47, αSma and Pcol1A1 gene expressions were significantly elevated in PCLS after 48 h, which was further increased by PDGF-BB and TGF-β1. The increased gene expression of fibrosis markers was inhibited by all three PDGF-inhibitors, while TGFβ-inhibitors showed marginal effects. The protein expression of collagen 1 was inhibited by imatinib, perindopril, tetrandrine and pirfenidone. In conclusion, the increased gene expression of PDGF-B and the down-regulation of fibrosis markers by PDGF-pathway inhibitors, together with the absence of elevated TGF-β1 gene expression and the limited effect of the TGFβ-pathway inhibitors, indicated the predominance of the PDGF pathway in the early onset of fibrosis in PCLS. PCLS appear a useful model for research of the early onset of fibrosis and for testing of antifibrotic drugs acting on the PDGF pathway. - Highlights: • During culture, fibrosis markers increased in precision-cut liver slices (PCLS). • Gene expression of PDGF-β was increased, while TGFβ was not changed in rat PCLS. • PDGF-pathway inhibitors down-regulated this increase of fibrosis markers. • TGFβ-pathway inhibitors had only

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

    SciTech Connect

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

    2002-03-15

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

  14. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis.

    PubMed

    Karsdal, Morten A; Manon-Jensen, Tina; Genovese, Federica; Kristensen, Jacob H; Nielsen, Mette J; Sand, Jannie Marie B; Hansen, Niels-Ulrik B; Bay-Jensen, Anne-Christine; Bager, Cecilie L; Krag, Aleksander; Blanchard, Andy; Krarup, Henrik; Leeming, Diana J; Schuppan, Detlef

    2015-05-15

    Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated. The aims of this review are to 1) explore key structural and functional components of the ECM as exemplified by monogenetic disorders leading to severe pathologies, 2) discuss selected pathological posttranslational modifications of ECM proteins resulting in altered functional (signaling) properties from the original structural proteins, and 3) discuss how these findings support the novel concept that an increasing number of components of the ECM harbor signaling functions that can modulate fibrotic liver disease. The ECM entails functions in addition to anchoring cells and modulating their migratory behavior. Key ECM components and their posttranslational modifications often harbor multiple domains with different signaling potential, in particular when modified during inflammation or wound healing. This signaling by the ECM should be considered a paracrine/endocrine function, as it affects cell phenotype, function, fate, and finally tissue homeostasis. These properties should be exploited to establish novel biochemical markers and antifibrotic treatment strategies for liver fibrosis as well as other fibrotic diseases. PMID:25767261

  15. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

    PubMed Central

    Manon-Jensen, Tina; Genovese, Federica; Kristensen, Jacob H.; Nielsen, Mette J.; Sand, Jannie Marie B.; Hansen, Niels-Ulrik B.; Bay-Jensen, Anne-Christine; Bager, Cecilie L.; Krag, Aleksander; Blanchard, Andy; Krarup, Henrik; Leeming, Diana J.; Schuppan, Detlef

    2015-01-01

    Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated. The aims of this review are to 1) explore key structural and functional components of the ECM as exemplified by monogenetic disorders leading to severe pathologies, 2) discuss selected pathological posttranslational modifications of ECM proteins resulting in altered functional (signaling) properties from the original structural proteins, and 3) discuss how these findings support the novel concept that an increasing number of components of the ECM harbor signaling functions that can modulate fibrotic liver disease. The ECM entails functions in addition to anchoring cells and modulating their migratory behavior. Key ECM components and their posttranslational modifications often harbor multiple domains with different signaling potential, in particular when modified during inflammation or wound healing. This signaling by the ECM should be considered a paracrine/endocrine function, as it affects cell phenotype, function, fate, and finally tissue homeostasis. These properties should be exploited to establish novel biochemical markers and antifibrotic treatment strategies for liver fibrosis as well as other fibrotic diseases. PMID:25767261

  16. Vicarious liver visualization in solitary functioning kidney with technetium-99m ethylenedicysteine renal scintigraphy

    PubMed Central

    Jain, Tarun Kumar; Phulsunga, Rohit Kumar; Gupta, Nitin; Sood, Ashwani; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2015-01-01

    We present a case of 3-year-old boy who was incidentally diagnosed to have single left kidney on ultrasonography. Dynamic technetium-99m ethylenedicysteine renal scintigraphy was acquired for assessing the existing kidney function showed the tracer localization in bilateral renal fossae during the entire study. The single-photon emission computerized tomography/computerized tomography study revealed activity in the right renal fossa to be in the enlarged right lobe of the liver, which was mimicking as impaired functioning right kidney in planar images. The hybrid imaging helped in accurate delineation of tracer uptake by confirming it to be the false appearance of the right kidney in planar imaging. This case report also highlights the possible mechanism of renal tracer uptake in the liver parenchyma. PMID:26170576

  17. Procollagen III peptide and fibronectin in alcohol-related chronic liver disease: correlations with morphological features and biochemical tests.

    PubMed

    Gabrielli, G B; Faccioli, G; Casaril, M; Capra, F; Bonazzi, L; Falezza, G; Tomba, A; Baracchino, F; Corrocher, R

    1989-02-22

    In order to clarify the significance of procollagen III peptide (PIIIP) and fibronectin (FN) blood concentration in alcohol related chronic liver disease (ALD), we have investigated their relationships with histological liver features and biochemical liver tests in 44 ALD patients. PIIIP was measured in serum by radioimmunoassay whereas FN was determined in plasma using an immunonephelometric method. In each liver biopsy, steatosis, portal infiltrate, lobular necro-inflammation, portal fibrosis and lobular fibrosis were semiquantitatively assessed by scoring from 0 to 3. A close correlation of PIIIP was found with morphological features of fibrosis (both of lobular and portal type), but not with necro-inflammation or steatosis. PIIIP was also positively correlated with ALP and GGT and exhibited a good diagnostic value in liver fibrosis. On the contrary, FN did not distinguish between normals and patients and was not correlated with any morphological liver feature or biochemical liver test. We also conclude that serum NP3P effectively reflects liver fibrosis, whereas plasma FN seems not related to any of the main histological aspects of liver damage in ALD. PMID:2714004

  18. An automated system for pulmonary function testing

    NASA Technical Reports Server (NTRS)

    Mauldin, D. G.

    1974-01-01

    An experiment to quantitate pulmonary function was accepted for the space shuttle concept verification test. The single breath maneuver and the nitrogen washout are combined to reduce the test time. Parameters are defined from the forced vital capacity maneuvers. A spirometer measures the breath volume and a magnetic section mass spectrometer provides definition of gas composition. Mass spectrometer and spirometer data are analyzed by a PDP-81 digital computer.

  19. Track/train dynamics test report transfer function test. Volume 1: Test

    NASA Technical Reports Server (NTRS)

    Vigil, R. A.

    1975-01-01

    A description is presented of the transfer function test performed on an open hopper freight car loaded with 80 tons of coal. Test data and a post-test update of the requirements document and test procedure are presented. Included are a statement of the test objective, a description of the test configurations, test facilities, test methods, data acquisition/reduction operations, and a chronological test summary. An index to the data for the three test configurations (X, Y, and Z-axis tests) is presented along with test sequence, run number, test reference, and input parameters.

  20. Long Term Liver Engraftment of Functional Hepatocytes Obtained from Germline Cell-Derived Pluripotent Stem Cells

    PubMed Central

    Fagoonee, Sharmila; Famulari, Elvira Smeralda; Silengo, Lorenzo; Tolosano, Emanuela; Altruda, Fiorella

    2015-01-01

    One of the major hurdles in liver gene and cell therapy is availability of ex vivo-expanded hepatocytes. Pluripotent stem cells are an attractive alternative. Here, we show that hepatocyte precursors can be isolated from male germline cell-derived pluripotent stem cells (GPSCs) using the hepatoblast marker, Liv2, and induced to differentiate into hepatocytes in vitro. These cells expressed hepatic-specific genes and were functional as demonstrated by their ability to secrete albumin and produce urea. When transplanted in the liver parenchyma of partially hepatectomised mice, Liv2-sorted cells showed regional and heterogeneous engraftment in the injected lobe. Moreover, approximately 50% of Y chromosome-positive, GPSC-derived cells were found in the female livers, in the region of engraftment, even one month after cell injection. This is the first study showing that Liv2-sorted GPSCs-derived hepatocytes can undergo long lasting engraftment in the mouse liver. Thus, GPSCs might offer promise for regenerative medicine. PMID:26323094

  1. [Functional activity of the liver in immersion and effects of the countermeasures].

    PubMed

    Solov'eva, A A; Sedova, E A; Tomilovskaia, E S; Shigueva, T A; Afonin, B V

    2014-01-01

    Two groups of male volunteers for 4-day dry immersion with and w/o countermeasures (support load imitator (SLI) or high-frequency electrostimulator) underwent ultrasonic investigation (USI) of the liver, gastroduodenal organs and vessels, and blood biochemical analysis. Two other groups of volunteers performed the 13C-methacetin breath test (13C-MBT) to study the effects of immersion and SLI on the liver detox activity and metabolic capacity. In immersion, USI diagnosed slowdown of blood flow along the hepatic vein and signs of plethora in the abdominal venous system. In addition, immersion was accompanied by increases in blood pepsinogen, pancreatic amylase, total bilirubin, the "indirect" fraction specifically, insulin and C-peptide. 13C-MBT detected deceleration of 13C-methacetin inactivation and diminution of the liver metabolic capacity. Administration of the countermeasures did not improve the ultrasonic image of hemodynamic alterations in the liver and abdomen significantly. High-frequency electrostimulation cancelled out changes in all biochemical parameters except C-peptide; SLI was favorable to recovery of pepsinogen and amylase baseline values only. Besides, the SLI wearing prevented loss of the 13C-methacetin inactivation rate but was not effective enough against diminution of the hepatic metabolic capacity. PMID:25087407

  2. [Structuro-functional changes in dog liver and regional lymph node lysosomes in toxic hepatitis].

    PubMed

    Borodin, Iu I; Korolenko, T A; Malygin, A E; Pupyshev, A B; Sharaĭkina, E O

    1978-10-01

    Structural and functional changes in the dog liver and regional lymph nodes lysosomes were studied during toxic hepatitis induced by CCl4 administration (single and repeated). Total activity of lysosomal enzymes (acid RNA-ase and beta-galactosidase) was higher in the regional lymph nodes than in the liver, reflecting the barrier, protective function of the organ. During acute toxic hepatitis the specific activities of acid RNA-ase and cathepsin D displayed a sharp rise. No normalization of the indices under study occurred during the observation period (from 8 to 30 days). At the same time there was a rise of the regional lymph node weight and an elevation of the relative macrophage and neutrophil content in the sinuses. The increased activity of the lysosome enzymes in the regional lymph nodes in injury of the liver was connected with greater functional load on the lymph nodes effecting hydrolysis of biopolymeres which penetrated into the regional lymphatic node with the lymph. PMID:708870

  3. Text Messaging Improves Participation in Laboratory Testing in Adolescent Liver Transplant Patients

    PubMed Central

    McKenzie, Rebecca B.; Berquist, William E.; Foley, Megan A.; Park, KT; Windsheimer, Jered E.; Litt, Iris F.

    2015-01-01

    Background In solid organ transplant patients, non-participation in all aspects of the medical regimen is a prevalent problem associated with adverse consequences particularly in the adolescent and young adult (AYA) age group. This study is the first to evaluate the feasibility, utility and impact of a text messaging (TM) intervention to improve participation in laboratory testing in adolescent liver transplant patients. Methods AYA patients, aged 12 to 21 years, were recruited for a prospective pilot trial evaluating a TM intervention delivered over a 1-year period. The intervention involved automated TM reminders with feedback administered according to a prescribed laboratory testing frequency. Participation rate in laboratory testing after the intervention was compared to the year prior. Patient responses and feedback by text and survey were used to assess feasibility, acceptability and use of the intervention. Results Forty-two patients were recruited and 33 patients remained enrolled for the study duration. Recipients of the TM intervention demonstrated a significant improvement in participation rate in laboratory testing from 58% to 78% (P<.001). This rate was also significantly higher than in non-intervention controls (P=.003). There was a high acceptability, response rate and a significant correlation with reported versus actual completion of laboratory tests by TM. Conclusions TM reminders significantly improved participation in laboratory testing in AYA liver transplant patients. The intervention demonstrated feasibility, acceptability, and use with a high proportion of patients who engaged in and perceived a benefit from using this technology. PMID:26213633

  4. Gas Test Loop Functional and Technical Requirements

    SciTech Connect

    Glen R. Longhurst; Soli T. Khericha; James L. Jones

    2004-09-01

    This document defines the technical and functional requirements for a gas test loop (GTL) to be constructed for the purpose of providing a high intensity fast-flux irradiation environment for developers of advanced concept nuclear reactors. This capability is needed to meet fuels and materials testing requirements of the designers of Generation IV (GEN IV) reactors and other programs within the purview of the Advanced Fuel Cycle Initiative (AFCI). Space nuclear power development programs may also benefit by the services the GTL will offer. The overall GTL technical objective is to provide developers with the means for investigating and qualifying fuels and materials needed for advanced reactor concepts. The testing environment includes a fast-flux neutron spectrum of sufficient intensity to perform accelerated irradiation testing. Appropriate irradiation temperature, gaseous environment, test volume, diagnostics, and access and handling features are also needed. This document serves to identify those requirements as well as generic requirements applicable to any system of this kind.

  5. Variability of routine pulmonary function tests.

    PubMed Central

    Hruby, J; Butler, J

    1975-01-01

    Pulmonary function tests sometimes indicate a progressive deterioration and at other times a 'stepwise' worsening which may be followed by improvement. Interpretation depends on the extent of random or diurnal variations in function. Routing pulmonary function tests (VC, FEV1, FRC, and airway resistance (Raw)) were repeatedly measured in normal subjects, patients with stable irreversible airways obstruction, and patients with stable restrictive disease. In all groups there was a significant (P less than 0.001) diurnal variation in Raw, with high values in the morning, low values at noon, and rising values in the evening. The midday Raw values were about 80% of the highest daily values. The considerable random and diurnal variability seen in all tests is reflected in the range of high and low values (% of mean individual response) in individuals. The largest variation in an individual between measurements taken at two different times was 81% in Raw (range: 40% above to 41% below the mean). There was less variation in FEV1 (29%), FRC (62%), and VC (30%). Thus the finding of a stepwise change in function could reflect its natrual variability. When repeated studies are done to assess progress or the effects of therapy on disease, there are many factors, including the time of day at which the tests are performed, which should be standardized as far as possible. PMID:1198395

  6. Metabolic alterations in liver and testes of adult and newborn rats following cadmium administration

    SciTech Connect

    Agarwal, A.K.

    1988-04-01

    A large number of studies have been conducted to understand the effect of cadmium on cellular intermediary metabolism. Although, most of the metal is stored in liver and kidney, the organ affected most in acute toxicity is testis. Increased lipid peroxidation and decreased mitochondrial respiration along with other cellular enzyme activities have been reported to take place due to cadmium administration. The present experiment was designed to study the effect of acute cadmium administration on the activities of some of the tissue enzyme systems that provide the reducing equivalent NADPH. The levels of NADH and NADPH were also measured. All the measurements were conducted in two tissues: liver and testes. The effect of simultaneous administration of zinc on cadmium induced changes was also determined. Newborn animals have been found to be resistant to many effects of cadmium. The present studies were also conducted in newborn rat liver and testes. The purpose of the study is to compare the effects of cadmium on adult and new born rats.

  7. [Liver replacement therapy. Reliable indications in acute liver failure].

    PubMed

    Rifai, K; Ott, M; Bahr, M M; Schneider, A; Manns, M P

    2003-12-01

    Extracorporeal liver support devices aim at improving the therapeutical options for liver failure. Numerous artificial and bioartificial devices have been tested to reduce the high mortality of this dynamic disease. In particular, the detoxification function of the liver should be upheld, by means of a number of different procedures, either until liver function is restored or until transplantation. Both purely artificial, machine-based procedures including different forms of dialysis and hemoadsorption as well as bioartificial procedures based on hepatocytes are being tested, as are different types of extracorporeal liver perfusion. This paper provides an overview of the different methods and devices and their clinical evidence in order to give a recommendation for the handling of the expensive devices. There is no current indication for the application of liver support devices outside of clinical studies at specialised centres. PMID:14689190

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

    PubMed Central

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

    2014-01-01

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

  9. Function of the liver and bile ducts in humans exposed to lead.

    PubMed

    Kasperczyk, A; Dziwisz, M; Ostałowska, A; Swietochowska, E; Birkner, E

    2013-08-01

    Lead is very common in the environment, and it is therefore important to characterize its possible adverse health effects. The aim of this study was to evaluate the impact of lead exposure on selected functions of the liver and bile ducts in people who are chronically exposed to the metal because of their occupations. To provide this information, the activity of specific enzymes and the bilirubin concentration were determined in blood serum, and morphological parameters of the liver and bile ducts were evaluated using the ultrasonic imaging method. Healthy male employees of a lead-zinc processing facility (n = 145) who were occupationally exposed to lead were divided into two subgroups as a function of the lead concentrations in blood (PbB): low lead exposure (PbB = 20-35 μg/dl; n = 57) and high lead exposure (PbB = 35-60 μg/dl; n = 88). Human exposure to lead compounds was found to cause liver enlargement and to activate inflammatory reactions with the characteristics of moderate cholestasis within the bile ducts, while no characteristics of necrotic damage of hepatic cells were noted. It seems that lipid peroxidation can be one of the toxic mechanisms of lead which induce moderate cholestasis. The effects depend on the extent of the lead exposure and were greater in subjects with higher exposure levels, particularly subjects with PbB values greater than 35 μg/dl. PMID:23529799

  10. Platelet function tests: a comparative review

    PubMed Central

    Paniccia, Rita; Priora, Raffaella; Alessandrello Liotta, Agatina; Abbate, Rosanna

    2015-01-01

    In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation – adhesion, shape change, release reaction, and aggregation – have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT) dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]). POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well-tried and innovative platelet function tests and their methodological features and clinical applications are considered. PMID:25733843

  11. Co-associations between insulin sensitivity and measures of liver function, subclinical inflammation, and hematology.

    PubMed

    Godsland, Ian F; Johnston, Desmond G

    2008-09-01

    Clustering of risk factors for coronary heart disease and diabetes is well established, particularly in relation to insulin resistance. To determine whether evaluation of risk factor clustering will contribute to risk assessment, it is first necessary to discriminate co-association between risk factors from correlation. We undertook this in a large homogenous group, using a sophisticated measure of insulin sensitivity and a broad range of risk factors. Cross-sectional analysis of an occupational cohort using regression and factor analyses was performed. Subjects were 472 apparently healthy white men. The main outcome measures were insulin sensitivity, S(I), by minimal model analysis of the intravenous glucose tolerance test plus liver function and hematologic variables, including the inflammation indices, leukocyte count, and erythrocyte sedimentation rate. The S(I) correlated independently with serum gamma-glutamyl transferase (GGT), aspartate transaminase, and alkaline phosphatase activities; blood pressure; leukocyte count; and erythrocyte sedimentation rate (P < .01). On factor analysis, the factor that explained the greatest proportion of the variance (56.7%) included, in decreasing order of factor loading, triglycerides, S(I) (negative), body mass index, high-density lipoprotein cholesterol (negative), insulin, uric acid, and GGT activity (loadings >0.40). Mean arterial pressure was not a feature (loading 0.29), neither were indices of subclinical inflammation. In apparently healthy men, blood pressure and indices of subclinical inflammation do not cluster with other insulin resistance-related risk factors, despite correlating with insulin sensitivity. In contrast, both GGT activity and uric acid concentrations correlated with insulin sensitivity and co-associated with insulin resistance-related risk factors and are therefore components of a true risk factor cluster. PMID:18702943

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

    PubMed Central

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

    2014-01-01

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

  13. Screening for Wilson Disease in Acute Liver Failure: A Comparison of Currently Available Diagnostic Tests

    PubMed Central

    Korman, Jessica D.; Volenberg, Irene; Balko, Jody; Webster, Joe; Schiodt, Frank V.; Squires, Robert H.; Lee, William M.; Schilsky, Michael L.

    2013-01-01

    Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD (ALF-WD), data and serum were collected from 140 ALF patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp <20 mg/dL by the oxidase method provided a diagnostic sensitivity of 21% and specificity of 84% while, by nephelometry, a sensitivity of 56% and specificity of 63%. Serum copper levels exceeded 200 g/dL in all ALF-WD patients measured (13/16), but were also elevated in non-WD ALF. An alkaline phosphatase (AP) to total bilirubin (TB) ratio <4 yielded a sensitivity of 94%, specificity of 96%, and a likelihood ratio of 23 for diagnosing fulminant WD. In addition, an AST:ALT ratio > 2.2 yielded a sensitivity of 94%, a specificity of 86%, and a likelihood ratio of 7 for diagnosing fulminant WD. Combining the tests provided a diagnostic sensitivity and specificity of 100%. In conclusion, conventional WD testing utilizing serum ceruloplasmin and/or serum copper levels are less sensitive and specific in identifying patients with ALF-WD than other available tests. More readily available laboratory tests including alkaline phosphatase, bilirubin and serum aminotransferases by contrast provides the most rapid and accurate method for diagnosis of ALF due to WD. PMID:18798336

  14. Liver disease alters high-density lipoprotein composition, metabolism and function.

    PubMed

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk. PMID:27106140

  15. The relationship between serology of hepatitis E virus with liver and kidney function in kidney transplant patients

    PubMed Central

    Zeraati, Abbas Ali; Nazemian, Fatemeh; Takalloo, Ladan; Sahebkar, Amirhossein; Heidari, Elahe; Yaghoubi, Mohammad Ali

    2016-01-01

    Although hepatitis E virus (HEV) is well known to cause acute hepatitis, there are reports showing that HEV may also be responsible for progression of acute to chronic hepatitis and liver cirrhosis in patients receiving organ transplantation. In this study, we aimed to evaluate the prevalence of HEV in patients with kidney transplantation. In this study, 110 patients with kidney transplantation were recruited, and anti-HEV IgG, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and estimated glomerular filtration rate (eGFR) in the first, third and sixth months after renal transplantation were measured. The mean serum anti-HEV IgG titers in the study participants was 1.36 (range 0.23 to 6.3). Twenty-three patients were found to be seropositive for HEV Ab defined as anti-HEV IgG titer > 1.1. The difference in liver and renal function tests (creatinine, eGFR, AST, ALT and ALP) at different intervals was not significant between patients with HEV Ab titers higher and lower than 1.1 (p > 0.05). However, an inverse correlation was observed between HEV Ab and eGFR values in the first (p = 0.047, r = -0.21), third (p = 0.04, r = -0.20) and sixth (p = 0.04, r = -0.22) months after renal transplantation in patients with HEV Ab < 1.1 but not in the subgroup with HEV Ab > 1.1. Also, a significant correlation between age and HEV Ab levels was found in the entire study population (p = 0.001, r = 0.33). Our findings showed a high prevalence of seropositivity for anti-HEV IgG in patients receiving renal transplants. However, liver and renal functions were not found to be significantly different seropositive and seronegative patients by up to 6 months post-transplantation. PMID:27366144

  16. The relationship between serology of hepatitis E virus with liver and kidney function in kidney transplant patients.

    PubMed

    Zeraati, Abbas Ali; Nazemian, Fatemeh; Takalloo, Ladan; Sahebkar, Amirhossein; Heidari, Elahe; Yaghoubi, Mohammad Ali

    2016-01-01

    Although hepatitis E virus (HEV) is well known to cause acute hepatitis, there are reports showing that HEV may also be responsible for progression of acute to chronic hepatitis and liver cirrhosis in patients receiving organ transplantation. In this study, we aimed to evaluate the prevalence of HEV in patients with kidney transplantation. In this study, 110 patients with kidney transplantation were recruited, and anti-HEV IgG, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and estimated glomerular filtration rate (eGFR) in the first, third and sixth months after renal transplantation were measured. The mean serum anti-HEV IgG titers in the study participants was 1.36 (range 0.23 to 6.3). Twenty-three patients were found to be seropositive for HEV Ab defined as anti-HEV IgG titer > 1.1. The difference in liver and renal function tests (creatinine, eGFR, AST, ALT and ALP) at different intervals was not significant between patients with HEV Ab titers higher and lower than 1.1 (p > 0.05). However, an inverse correlation was observed between HEV Ab and eGFR values in the first (p = 0.047, r = -0.21), third (p = 0.04, r = -0.20) and sixth (p = 0.04, r = -0.22) months after renal transplantation in patients with HEV Ab < 1.1 but not in the subgroup with HEV Ab > 1.1. Also, a significant correlation between age and HEV Ab levels was found in the entire study population (p = 0.001, r = 0.33). Our findings showed a high prevalence of seropositivity for anti-HEV IgG in patients receiving renal transplants. However, liver and renal functions were not found to be significantly different seropositive and seronegative patients by up to 6 months post-transplantation. PMID:27366144

  17. Parasitaemia and Its Relation to Hematological Parameters and Liver Function among Patients Malaria in Abs, Hajjah, Northwest Yemen.

    PubMed

    Al-Salahy, Mohamed; Shnawa, Bushra; Abed, Gamal; Mandour, Ahmed; Al-Ezzi, Ali

    2016-01-01

    Plasmodium falciparum malaria is the most common infection in Yemen. The present study aims to investigate changes in hematological and hepatic function indices of P. falciparum infected individuals. This study included 67 suspected falciparum malarial patients attended in clinics and rural Abs Hospital (Tehama, Hajjah), Yemen, from October 2013 to April 2014. The diagnosis of malaria was confirmed by thick and thin film with Giemsa staining of malaria parasite. Hematological parameters and serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin (total and direct) as test indicators of liver function were studied. Patients with parasitaemia tended to have significantly lower hemoglobin, hematocrit, white blood cell count, lymphocytes, and platelets, compared with healthy normal subjects. Neutrophils levels were significantly higher in cases of falciparum malaria in comparison to healthy normal subjects. Serums AST, ALT, ALP, and bilirubin (total and direct) in falciparum malaria patients were significantly higher (p < 0.0001) than those of falciparum malaria of free individuals. Hematological and liver dysfunctions measured parameters were seen associated with moderate and severe parasitaemia infection. This study concludes that hematological and hepatic dysfunction parameters could be indicator of malaria in endemic regions. PMID:27051422

  18. Parasitaemia and Its Relation to Hematological Parameters and Liver Function among Patients Malaria in Abs, Hajjah, Northwest Yemen

    PubMed Central

    Al-Salahy, Mohamed; Shnawa, Bushra; Abed, Gamal; Mandour, Ahmed

    2016-01-01

    Plasmodium falciparum malaria is the most common infection in Yemen. The present study aims to investigate changes in hematological and hepatic function indices of P. falciparum infected individuals. This study included 67 suspected falciparum malarial patients attended in clinics and rural Abs Hospital (Tehama, Hajjah), Yemen, from October 2013 to April 2014. The diagnosis of malaria was confirmed by thick and thin film with Giemsa staining of malaria parasite. Hematological parameters and serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin (total and direct) as test indicators of liver function were studied. Patients with parasitaemia tended to have significantly lower hemoglobin, hematocrit, white blood cell count, lymphocytes, and platelets, compared with healthy normal subjects. Neutrophils levels were significantly higher in cases of falciparum malaria in comparison to healthy normal subjects. Serums AST, ALT, ALP, and bilirubin (total and direct) in falciparum malaria patients were significantly higher (p < 0.0001) than those of falciparum malaria of free individuals. Hematological and liver dysfunctions measured parameters were seen associated with moderate and severe parasitaemia infection. This study concludes that hematological and hepatic dysfunction parameters could be indicator of malaria in endemic regions. PMID:27051422

  19. Relation of inflammation and liver function with the plasma cortisol response to adrenocorticotropin in early lactating dairy cows.

    PubMed

    Trevisi, E; Bertoni, G; Lombardelli, R; Minuti, A

    2013-09-01

    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 β-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

  20. Individualized Immunosuppressive Protocol of Liver Transplant Recipient Should be Made Based on Splenic Function Status

    PubMed Central

    Song, Ji-Yong; Du, Guo-Sheng; Xiao, Li; Chen, Wen; Suo, Long-Long; Gao, Yu; Feng, Li-Kui; Shi, Bing-Yi

    2016-01-01

    Background: Lymphocyte subsets play important roles in rejection in liver transplant recipients, and the effect of splenic function on these roles remains unknown. The aim of this study was to explore the feasibility to adjust immunosuppressive agents based on splenic function status through detecting the lymphocyte subsets in liver transplant recipients. Methods: The lymphocyte subsets of 49 liver transplant recipients were assessed in the 309th Hospital of Chinese People's Liberation Army between June 2014 and August 2015. The patients were divided into splenectomy group (n = 9), normal splenic function group (n = 24), and hypersplenism group (n = 16). The percentages and counts of CD4+ T, CD8+ T, natural killer (NK) cell, B-cell, regulatory B-cell (Breg), and regulatory T-cell (Treg) were detected by flow cytometer. In addition, the immunosuppressive agents, histories of rejection and infection, and postoperative time of the patients were compared among the three groups. Results: There was no significant difference of clinical characteristics among the three groups. The percentage of CD19+CD24+CD38+ Breg was significantly higher in hypersplenism group than normal splenic function group and splenectomy group (3.29 ± 0.97% vs. 2.12 ± 1.08% and 1.90 ± 0.99%, P = 0.001). The same result was found in CD4+CD25+FoxP3+ Treg percentage (0.97 ± 0.39% vs. 0.54 ± 0.31% and 0.56 ± 0.28%, P = 0.001). The counts of CD8+ T-cell, CD4+ T-cell, and NK cell were significantly lower in hypersplenism group than normal splenic function group (254.25 ± 149.08 vs. 476.96 ± 225.52, P = 0.002; 301.69 ± 154.39 vs. 532.50 ± 194.42, P = 0.000; and 88.56 ± 63.15 vs. 188.33 ± 134.51, P = 0.048). Moreover, the counts of CD4+ T-cell and NK cell were significantly lower in hypersplenism group than splenectomy group (301.69 ± 154.39 vs. 491.89 ± 132.31, P = 0.033; and 88.56 ± 63.15 vs. 226.00 ± 168.85, P = 0.032). Conclusion: Splenic function status might affect the immunity of

  1. Risk factors for damaged liver function after chemotherapy in hepatitis B virus carriers with non-Hodgkin lymphoma.

    PubMed

    Li, X; Fan, X W; Liu, W; Guo, L; Li, Y; Hu, X; Liang, X; Ma, X P; Yang, S E

    2015-01-01

    The goal of this study was to investigate damaged liver function after chemotherapy in hepatitis B virus (HBV) carriers with non-Hodgkin lymphoma (NHL) and to evaluate risk factors associated with a high risk of damaged liver function. Clinical histories of 134 HBV carriers with NHL who were treated with chemotherapy were obtained and analyzed for the occurrence of damaged liver function and other related high-risk factors. Analysis showed that 76 patients (56.7%) had damaged liver function after chemotherapy: 6 patients (7.9%) had I degree, 17 patients (22.4%) had II degree, 20 patients (26.3%) had III degree, and 33 patients (43.4%) had IV degree damage. After treatment, 18 patients (23.7%) continued to receive chemotherapy according to their original schedule, 39 patients (51.3%) delayed chemotherapy, 16 patients (21.1%) stopped chemotherapy, and 3 patients (3.9%) died. Analysis of a binary multivariate logistic regression model showed that administration of steroids was a high-risk factor for damaged liver function after chemotherapy in NHL patients. The incidence of damaged liver function after chemotherapy is high among HBV carriers with NHL; therefore, administration of steroid chemotherapy is a high-risk factor. PMID:25867413

  2. Establishing population distribution of drug-metabolizing enzyme activities for the use of salivary caffeine as a dynamic liver function marker in a Singaporean Chinese population.

    PubMed

    Chia, Hazel Yiting; Yau, Wai-Ping; Ho, Han Kiat

    2016-04-01

    The salivary paraxanthine/caffeine molar ratio has been proposed as a novel dynamic liver function test to guide dose adjustments of drugs hepatically cleared by CYP1A2. Its usability requires an established population norm as well as the factors influencing the ratio and actual concentrations. To address this knowledge gap, salivary caffeine and paraxanthine concentrations were measured at 4 h post caffeine dose in healthy Chinese individuals who had undergone 24 h of caffeine abstinence. The metabolic ratio was calculated and statistical analysis was performed. From the 52 participants (26 males; 30 regular caffeine consumers) recruited, the salivary paraxanthine/caffeine molar ratio was normally distributed with a mean and SD of 0.5 ± 0.2. No statistically significant factors (BMI, body weight, gender and regularity of caffeine intake) affecting the metabolic ratio were found. The caffeine concentration and total caffeine plus paraxanthine concentrations were lower in males than in females, and lower in regular caffeine consumers than in non-regular caffeine consumers. The 4 h salivary metabolic ratio (mean: 0.5) was generally not significantly different from the literature reported salivary, serum and plasma ratios measured at 4-9 h in healthy individuals (mean range 0.4-0.7) but was significantly higher than the literature reported 6 h plasma ratio and salivary ratios measured at 1-6 h in patients with liver disease or mild abnormal liver function tests (mean range 0.03-0.2). Overall, the population norm of the salivary metabolic ratio in a Singaporean Chinese population established in this study is distinct from individuals with liver disease or mild abnormal liver function tests and provides the benchmark for dosage adjustments of drugs metabolized by CYP1A2. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26862045

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-03-01

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

  5. Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease

    PubMed Central

    Pacifico, Lucia; Di Martino, Michele; Anania, Caterina; Andreoli, Gian Marco; Bezzi, Mario; Catalano, Carlo; Chiesa, Claudio

    2015-01-01

    AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease (NAFLD). METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction (HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue (VAT), pancreatic fat fraction (PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance (HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index (WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either: (1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/dL to < 126 mg/dL; (2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/dL and < 200 mg/dL; or (3) hemoglobin A1c value of ≥ 5.7% to < 6.5%. RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index (BMI)-SD score, and VAT. In multiple regression analysis with WBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI (standardized coefficient B, -0.398; P = 0.001) as well as HOMA-IR (0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained

  6. Successful expansion of functional and stable regulatory T cells for immunotherapy in liver transplantation

    PubMed Central

    Safinia, Niloufar; Vaikunthanathan, Trishan; Fraser, Henrieta; Thirkell, Sarah; Lowe, Katie; Blackmore, Laura; Whitehouse, Gavin; Martinez-Llordella, Marc; Jassem, Wayel; Sanchez-Fueyo, Alberto; Lechler, Robert I.; Lombardi, Giovanna

    2016-01-01

    Strategies to prevent organ transplant rejection whilst minimizing long-term immunosuppression are currently under intense investigation with regulatory T cells (Tregs) nearing clinical application. The clinical trial, ThRIL, recently commenced at King's College London, proposes to use Treg cell therapy to induce tolerance in liver transplant recipients, the success of which has the potential to revolutionize the management of these patients and enable a future of drug-free transplants. This is the first report of the manufacture of clinical grade Tregs from prospective liver transplant recipients via a CliniMACS-based GMP isolation technique and expanded using anti-CD3/CD28 beads, IL-2 and rapamycin. We report the enrichment of a pure, stable population of Tregs (>95% CD4+CD25+FOXP3+), reaching adequate numbers for their clinical application. Our protocol proved successful in, influencing the expansion of superior functional Tregs, as compared to freshly isolated cells, whilst also preventing their conversion to Th17 cells under pro-inflammatory conditions. We conclude with the manufacture of the final Treg product in the clinical research facility (CRF), a prerequisite for the clinical application of these cells. The data presented in this manuscript together with the much-anticipated clinical results from ThRIL, will undoubtedly inform the improved management of the liver transplant recipient. PMID:26788992

  7. Contraception with subdermal ST-1435 capsules: side-effects, endocrine profiles and liver function related to different lengths of capsules.

    PubMed

    Kurunmäki, H; Toivonen, J; Lähteenmäki, P; Luukkainen, T

    1985-03-01

    One Silastic capsule of 15 mm, 20 mm or 30 mm length was inserted subcutaneously into the ventral aspect of the left forearm or upper arm of 28 healthy women during menstrual bleeding or not later than on the seventh day of the menstrual cycle. A new capsule of the same length was inserted after six months and both capsules were removed twelve months after the first insertion. Side-effects, including changes in body weight, blood pressure, menstrual bleeding and liver function test results, were registered. Blood samples were taken from selected subjects twice a week during the 1st, 2nd, 3rd, 6th, 7th and 12th month of use. Plasma concentrations of ST-1435 were measured by radioimmunoassay and the effects of treatment on pituitary and ovarian function were determined by assaying plasma concentrations of LH, FSH, estradiol and progesterone. There were no differences in hormonal side-effects between subjects who had a 30 mm capsule or subjects who had 20 mm or 15 mm capsules, but subjects who had 20 or 15 mm capsules had significantly longer bleeding or spotting periods in comparison with subjects who had a 30 mm capsule. There were no changes in blood pressure, body weight or liver function test results in comparison with pre-insertion values. The plasma level of ST-1435 was not significantly higher during the use of 30 mm capsules than during the use of 20 or 15 mm capsules. During the use of the shorter ST-1435 capsules, plasma estradiol elevation and slightly suppressed FSH were seen, while the use of longer capsules resulted in a slight suppression of LH. Progesterone concentrations during monitored cycles indicated anovulation. No pregnancies occurred during the study period of one year. The continuation rate at one year was 71% in the 30 mm capsule group and 57% in the 20 and 15 mm capsule groups taken together. PMID:3922676

  8. Liver functions in silica-exposed workers in Egypt: possible role of matrix remodeling and immunological factors

    PubMed Central

    Zawilla, Nermin; Taha, Fatma; Ibrahim, Yasser

    2014-01-01

    Background: Brick manufacturing constitutes an important industrial sector in Egypt with considerable exposure to silica. Objectives: We aimed for evaluating hepatic functions in silica-exposed workers in the clay brick industry, and the possible role of matrix remodeling and immunological factors. Methods: A case–control study, 87 workers as exposed and 45 as control subjects. Questionnaire, clinical examination, and laboratory investigations: liver functions, matrix metalloproteinase-9, immunoglobulins G and E, and anti-liver kidney microsomal antibody. Results: In the exposed workers, mean levels of liver functions, matrix metalloproteinase-9 (MMP-9), and IgG and IgE were significantly higher. In the silicotic subgroup the mean level of GGT was almost twice the level in the non-silicotic subjects. Logistic regression showed that abnormal GGT and ALT were associated with production workers. Conclusion: Workers in the clay brick industry showed evidence of liver disease that could be related to matrix remodeling. PMID:24999850

  9. Metabolic liver function after stereotactic body radiation therapy for hepatocellular carcinoma.

    PubMed

    Dreher, Constantin; Høyer, Katrine I; Fode, Mette Marie; Habermehl, Daniel; Combs, Stephanie E; Høyer, Morten

    2016-07-01

    Purpose The time course of changes of the liver function after stereotactic body radiotherapy (SBRT) was analyzed in patients treated for non-resectable hepatocellular carcinoma (HCC). Patients and methods Twenty-six patients with non-resectable HCC treated with SBRT were included in this study. Clinical, biochemical and treatment-related parameters were retrospectively collected. S-albumin, s-bilirubin, s-alkaline phosphatase (AP) and s-alanine transaminase (ALAT) at 0, 3, 6, and 12 months after radiotherapy were analyzed. Results Seventeen and nine patients were Child-Pugh class A and B, respectively. The liver was exposed to relatively high radiation doses with mean doses of 1.9-26 Gy. None of the patients developed classic radiotherapy-induced liver disease (RILD), but two patients developed non-classic RILD. Two patients developed grade 3 ascites and no grade 4-5 toxicities were observed. Six patients declined in Child-Pugh class. The s-albumin decreased significantly from a pretreatment median of 37.4-34.36 g/l at three months after SBRT and stabilized thereafter. S-bilirubin, s-AP and s-ALAT did not change significantly over the study period. Conclusion Despite the fact that patients received high radiation dose to the liver, there was only moderate morbidity related to the treatment. The s-albumin decreases over three months after SBRT reflecting minor to moderate hepatic toxicity. S-albumin should be observed in the follow-up of HCC patients treated with SBRT. PMID:26878669

  10. Renal Function in Kidney and Liver Transplant Recipients After A 130-km Road Cycling Race

    PubMed Central

    Mosconi, Giovanni; Roi, Giulio Sergio; Totti, Valentina; Zancanaro, Marco; Tacconi, Alessandra; Todeschini, Paola; Ramazzotti, Eric; Di Michele, Rocco; Trerotola, Manuela; Donati, Carlo; Nanni Costa, Alessandro

    2015-01-01

    Abstract Background A few patients, after receiving solid organ transplantation, return to performing various sports and competitions; however, at present, data no study had evaluated the effects of endurance cycling races on their renal function. Methods Race times and short form (36) health survey questionnaires of 10 kidney transplant recipients (KTR) and 8 liver transplant recipients (LTR) transplanted recipients involved in a road cycling race (130 km) were compared with 35 healthy control subjects (HCS), also taking laboratory blood and urine tests the day before the race, at the end of the race, and 18 to 24 hours after competing. Results The 3 groups showed similar race times (KTR, 5 hours 59 minutes ± 0 hours 39 minutes; LTR, 6 hours 20 minutes ± 1 hour 11 minutes; HCS, 5 hours 40 minutes ± 1 hour 28 minutes), similar short form (36) health survey scores, and similar trend of laboratory parameters which returned to baseline after 18 to 24 hours. After the race, there was an increase in creatinine (0.24 mg/dL; effect size [ES] = 0.78; P < 0.001), urea (22 mg/dL; ES = 1.42; P < 0.001), and a decrease of estimated glomerular filtration rate (−17 mL/min; ES = 0.85; P < 0.001). The increase of blood uric acid was more remarkable in HCS and KTR (2.3 mg/dL; ES = 1.39; P < 0.001). The KTR showed an increase of microalbuminuria (167.4 mg/L; ES = 1.20; P < 0.001) and proteinuria (175 mg/mL; ES = 0.97; P < 0.001) similar to LTR (microalbuminuria: 176.0 mg/L; ES = 1.26; P < 0.001; proteinuria: 213 mg/mL; ES = 1.18; P < 0.001), with high individual variability. The HCS had a nonsignificant increase of microalbuminuria (4.4 mg/L; ES = 0.03; P = 0.338) and proteinuria (59 mg/mL; ES = 0.33; P = 0.084). Conclusions Selected and well-trained KTR and LTR patients can participate to an endurance cycling race showing final race times and temporary modifications of kidney function similar to those of HCS group, despite some differences related to baseline clinical

  11. Protective effect of salvianolic acid B on NASH rat liver through restoring intestinal mucosal barrier function

    PubMed Central

    Wang, Ying-Chun; Jin, Qing-Mei; Kong, Wei-Zong; Chen, Juan

    2015-01-01

    Aim: To investigate the effect of Salvianolic acid B (Sal B) on the disease progress of NASH and change of intestinal barrier function. Methods: Sixty Sprague-Dawley (SD) rats were randomly divided into control group, model group and treated group, with the former given normal diet and the latter 2 groups rats fed high-fat diet. In treated group, rats were infused through the stomach with 1 mg/ml Sal B every day at a dose of 20 mL/kg body weight. All animals were killed at the 24th week and plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), endotoxin (ET) and diamine oxdase (DAO) were analyzed using the blood samples. The histopathology of liver was observed by H&E staining. The expression changes of tight junction protein occludin and ZO-1 were analyzed by immunocytochemistry. Ultrastructural morphology of small intestinal tissues was investigated by transmission electron microscopy. Results: Plasma levels of ALT, AST, TG, TC, ET and DAO were significantly higher in model group than those in both control group and group treated with Sal B. In model group, vacuolated swelling of the cytoplasm with aggregates of chronic inflammatory cells was observed in the liver tissue but not in Sal B-treated group. NAFLD Activity Score in the treated group was significantly lower than that in model group. Immunohistochemical staining showed that Sal B administration recovered the expression of occludin and ZO-1, which was downregulated in the model group. Transmission electron microscopy analysis demonstrated that cell surface microvilli and major intercellular junctional complex including tight junction, gap junction and adherens junction were restored in Sal B-treated group. Conclusion: Sal B exerted protective function against high-fat diet-induced liver damage by restoring healthy barrier function of intestine in NASH rat model. PMID:26191218

  12. Enterocyte Fatty Acid Binding Proteins (FABPs): Different Functions of Liver- and Intestinal- FABPs in the Intestine

    PubMed Central

    Gajda, Angela M.; Storch, Judith

    2014-01-01

    SUMMARY Fatty acid binding proteins (FABP) are highly abundant cytosolic proteins that are expressed in most mammalian tissues. In the intestinal enterocyte, both Liver- (LFABP; FABP1) and Intestinal-fatty acid binding proteins (IFABP; FABP2) are expressed. These proteins display high affinity binding for long chain fatty acids (FA) and other hydrophobic ligands, thus they are believed to be involved with uptake and trafficking of lipids in the intestine. In vitro studies have identified differences in ligand binding stoichiometry and specificity, and in mechanisms of FA transfer to membranes, and it has been hypothesized that LFABP and IFABP have difference functions in the enterocyte. Studies directly comparing LFABP- and IFABP-null mice have revealed markedly different phenotypes, indicating that these proteins indeed have different functions in intestinal lipid metabolism and whole body energy homeostasis. In this review, we discuss the evolving knowledge of the functions of LFABP and IFABP in the intestinal enterocyte. PMID:25458898

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

    PubMed

    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

    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 < 0.001) and SRB from 2.53 ± 0.12 to 3.2 ± 0.95 (P < 0.001). In conclusion, A-PSF can improve the EC and function of isolated hepatocytes from DCD livers with <30% steatosis. PMID:24604782

  14. Expression of Wilms' tumor suppressor in the liver with cirrhosis: relation to hepatocyte nuclear factor 4 and hepatocellular function.

    PubMed

    Berasain, Carmen; Herrero, José-Ignacio; García-Trevijano, Elena R; Avila, Matías A; Esteban, Juan Ignacio; Mato, José M; Prieto, Jesús

    2003-07-01

    The Wilms' tumor suppressor WT1 is a transcriptional regulator present in the fetal but not in the mature liver. Its expression and functional role in liver diseases remains unexplored. In this study, we analyzed WT1 expression by reverse-transcription polymerase chain reaction (RT-PCR) and by immunohistochemistry in normal and diseased livers. In addition, we performed in vitro studies in isolated rat hepatocytes to investigate WT1 regulation and function. We detected WT1 messenger RNA (mRNA) in 18% of normal livers, 17% of chronic hepatitis with minimal fibrosis, 49% of chronic hepatitis with bridging fibrosis, and 71% of cirrhotic livers. In cirrhosis, WT1 immunoreactivity was localized to the nucleus of hepatocytes. WT1 mRNA abundance correlated inversely with prothrombin time (P =.04) and directly with serum bilirubin (P =.002) and with the MELD score (P =.001) of disease severity. In rats, WT1 expression was present in fetal hepatocytes and in the cirrhotic liver but not in normal hepatic tissue. In vitro studies showed that isolated primary hepatocytes express WT1 when stimulated with transforming growth factor beta (TGF-beta) or when the cells undergo dedifferentiation in culture. Moreover, we found that WT1 down-regulates hepatocyte nuclear factor 4 (HNF-4), a factor that is essential to maintain liver function and metabolic regulation in the mature organ. Hepatic expression of HNF-4 was impaired in advanced human cirrhosis and negatively correlated with WT1 mRNA levels (P =.001). In conclusion, we show that WT1 is induced by TGF-beta and down-regulates HNF-4 in liver cells. WT1 is reexpressed in the cirrhotic liver in relation to disease progression and may play a role in the development of hepatic insufficiency in cirrhosis. PMID:12829997

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

    PubMed

    Zhang, Yan; Zhang, Yi; Chen, Min; Zhou, Yan; Lang, Meidong

    2014-08-01

    The lack of pendant functional groups on the PCL backbone has been a great challenge for surface bioactivation of poly(ε-caprolactone) (PCL). In the present study, covalently galactosylated PCL (GPCL) was developed through coupling between the amino-functionalized PCL (NPCL) and the lactobionic acid (LA) and its potential application in maintenance of physiological functions of HepG2 cells was further evaluated. The structure and properties of GPCL were explored by (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

  16. Uses of esophageal function testing: dysphagia.

    PubMed

    Yazaki, Etsuro; Woodland, Philip; Sifrim, Daniel

    2014-10-01

    Esophageal function testing should be used for differential diagnosis of dysphagia. Dysphagia can be the consequence of hypermotility or hypomotility of the muscles of the esophagus. Decreased esophageal or esophagogastric junction distensibility can provoke dysphagia. The most well established esophageal dysmotility is achalasia. Other motility disorders can also cause dysphagia. High-resolution manometry (HRM) is the gold standard investigation for esophageal motility disorders. Simultaneous measurement of HRM and intraluminal impedance can be useful to assess motility and bolus transit. Impedance planimetry measures distensibility of the esophageal body and gastroesophageal junction in patients with achalasia and eosinophilic esophagitis. PMID:25216909

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

    PubMed Central

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

    2012-01-01

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

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

    SciTech Connect

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

    1986-01-01

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

  19. Functional Task Test: 2. Spaceflight-Induced Cardiovascular Change and Recovery During NASA's Functional Task Test

    NASA Technical Reports Server (NTRS)

    Phillips, Tiffany; Arzeno, Natalia M.; Stenger, Michael; Lee, Stuart M. C.; Bloomberg, Jacob J.; Platts, Steven H.

    2011-01-01

    The overall objective of the functional task test (FTT) is to correlate spaceflight-induced physiological adaptations with changes in performance of high priority exploration mission-critical tasks. This presentation will focus on the recovery from fall/stand test (RFST), which measures the cardiovascular response to the transition from the prone posture (simulated fall) to standing in normal gravity, as well as heart rate (HR) during 11 functional tasks. As such, this test describes some aspects of spaceflight-induced cardiovascular deconditioning and the course of recovery in Space Shuttle and International Space Station (ISS) astronauts. The sensorimotor and neuromuscular components of the FTT are described in two separate abstracts: Functional Task Test 1 and 3.

  20. [Liver parameters in intensive care medicine].

    PubMed

    Penndorf, V; Saner, F; Gerken, G; Canbay, A

    2013-12-01

    Elevated liver function tests in ICU-bound patients are associated with a greater risk of mor-tality. Chronic liver diseases as well as acute events and complications of therapy are among the causes. The disorder could further be investigated by assessment of liver cell integrity markers (AST, ALT and GLDH), cholestasis parameters -(bilirubin, GGT, ALP) and liver synthethic function (albumin, coagulation profile). Ultrasound and elastography are cheap and mobile options to evaluate chronic liver disease, cholestasis or perfusion of the liver. The interpretation of the results should include the medical history on the ICU. Liver injury could be due to septic or isch-aemic complications as well as toxic side effects or parenteral nutrition. The main therapeutic option is to identify the cause of the liver dysfuntion and to eliminate it as far as possible. PMID:22565500

  1. Efficacy of liver graft washout as a function of the perfusate, pressure, and temperature.

    PubMed

    Post, Ivo C J H; Dirkes, Marcel C; Heger, Michal; Verheij, Joanne; de Bruin, Kora M; de Korte, Dirk; Bennink, Roelof J; van Gulik, Thomas M

    2013-08-01

    Donor graft washout can be impaired by colloids in organ preservation solutions that increase the viscosity and agglutinative propensity of red blood cells (RBCs) and potentially decrease organ function. The colloid-induced agglutinative effects on RBCs and RBC retention after liver washout with Ringer's lactate (RL), histidine tryptophan ketoglutarate solution, University of Wisconsin solution, and Polysol were determined as a function of the washout pressure (15 or 100 mm Hg) and temperature (4 or 37°C) in a rat liver washout model with (99m) Tc-pertechnetate-labeled RBCs. Colloids (polyethylene glycol in Polysol and hydroxyethyl starch in University of Wisconsin) induced RBC agglutination, regardless of the solution's composition. RL was associated with the lowest degree of (99m) Tc-pertechnetate-labeled RBC retention after simultaneous arterial and portal washout at 37°C and 100 mm Hg. RL washout was also associated with the shortest washout time. A single portal washout with any of the solutions did not result in differences in the degree of RBC retention, regardless of the temperature or pressure. In conclusion, no differences were found in portal washout efficacy between colloidal solutions, histidine tryptophan ketoglutarate, and RL. Simultaneous arterial and portal washout with RL at 37°C and 100 mm Hg resulted in the least RBC retention and the shortest washout time. PMID:23696414

  2. Optical nanoscopy to reveal structural and functional properties of liver cells (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    McCourt, Peter; Huser, Thomas R.; Sørensen, Karen K.; Øie, Cristina I.; Mönkemöller, Viola; Ahluwalia, Balpreet S.

    2015-08-01

    The advent of optical nanoscopy has provided an opportunity to study fundamental properties of nanoscale biological functions, such as liver sinusoidal endothelial cells (LSEC) and their fenestrations. The fenestrations are nano-pores (50-200 nm) on the LSEC plasma membrane that allow free passage of molecules through cells. The fenestrated LSEC also hase a voracious appetite for waste molecules, viruses and nanoparticles. LSEC daily remove huge amounts of waste, nanoparticles and virus from the blood. Pharmaceuticals also need to pass through these fenestrations to be activated (e.g. cholesterol reducing statins) or detoxified by hepatocytes. And, when we age, our LSEC fenestrations become smaller and fewer. Today, we study these cells and structures using either conventional light microscopy on living cells, or high-resolution (but static) methods such as transmission and scanning electron microscopy on fixed (i.e. dead) tissue. Such methods, while very powerful, yield no real time information about the uptake of virus or nanoparticles, nor any information about fenestration dynamics. Therefore, to study LS-SEC, we are now using optical nanoscopy methods, and developing our own, to map their functions in 4 dimensions. Attaining this goal will shed new light on the cell biology of the liver and how it keeps us alive. This paper describes the challenges of studying LS-SEC with light microscopy, as well as current and potential solutions to this challenge using optical nanoscopy.

  3. Impact of combined treatment with rosuvastatin and antidepressants on liver and kidney function in rats

    PubMed Central

    HERBET, MARIOLA; GAWROŃSKA-GRZYWACZ, MONIKA; IZDEBSKA, MAGDALENA; PIĄTKOWSKA-CHMIEL, IWONA; JAGIEŁŁO-WÓJTOWICZ, EWA

    2016-01-01

    Depression is among the most prevalent and life-threatening forms of mental illness, and is also a risk factor for cardiovascular disorders, diabetes and metabolic syndrome. Elderly patients commonly receive statins for the prevention of cardiovascular diseases, and antidepressant drugs for the treatment of depression. It should be noted that long-term polypharmacotherapy may lead to potential drug interactions and disorders of the organs. The aim of the present study was to determine whether, and to what extent, combined treatment with rosuvastatin and antidepressants (amitriptyline or fluoxetine) influences the biochemical markers of liver and kidney function in a rat model. For this purpose, the activity levels of aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and the concentrations of total protein, urea, creatinine and β2-microglobulin were determined. The results of the study indicated that combined treatment with rosuvastatin and the antidepressants amitriptyline and fluoxetine for 14 days altered the activity levels of ALT and GGT, and the concentrations of urea and creatinine in the serum compared with groups of rats receiving rosuvastatin or either antidepressant alone. These observed changes in biochemical parameters may suggest the possibility of impaired liver and kidney function during the continuous combined exposure to the drugs. However, further clinical and animal studies are required in order to further elucidate this process. PMID:27073465

  4. Exploration of steroidogenesis-related genes in testes, ovaries, adrenals, liver and adipose tissue in pigs.

    PubMed

    Robic, Annie; Feve, Katia; Louveau, Isabelle; Riquet, Juliette; Prunier, Armelle

    2016-08-01

    To explore the metabolism of steroids in the pig species, a qualitative PCR analysis was performed for the main transcript of 27 genes involved in steroid metabolism. We compared samples of testes, adipose tissue and liver from immature and peripubertal males, adrenal cortex from peripubertal males, ovaries from cyclic females and adipose tissue from peripubertal females. Some genes were shown to have a tissue-specific expression. Two of them were expressed only in testes, ovaries and adrenals: CYP11A1 and CYP11B. The CYP21 and HSD17B3 genes, were expressed respectively only in adrenals and only in testes. Very few differences were observed between transcriptional patterns of peripubertal testes and adrenal glands as well as between male and female fat tissues. However, the expression of genes involved in the sulfonation of steroids was higher in testes than in adrenals from males. Main differences between ovaries and testes were observed for HSD17B1/2/3, AKR1C-pig6 and sulfotransferase genes (SULT2A1/SULT2B1). The present study shows that the SRD5A2 and CYP21 genes were not involved in the testicular biosynthesis of androstenone. It also shows that porcine adrenal glands produce essentially corticosteroids and that fat tissue is unable to produce de novo steroids. PMID:27436769

  5. Parkin regulates mitophagy and mitochondrial function to protect against alcohol-induced liver injury and steatosis in mice.

    PubMed

    Williams, Jessica A; Ni, Hong-Min; Ding, Yifeng; Ding, Wen-Xing

    2015-09-01

    Alcoholic liver disease claims two million lives per year. We previously reported that autophagy protected against alcohol-induced liver injury and steatosis by removing damaged mitochondria. However, the mechanisms for removal of these mitochondria are unknown. Parkin is an evolutionarily conserved E3 ligase that is recruited to damaged mitochondria to initiate ubiquitination of mitochondrial outer membrane proteins and subsequent mitochondrial degradation by mitophagy. In addition to its role in mitophagy, Parkin has been shown to have other roles in maintaining mitochondrial function. We investigated whether Parkin protected against alcohol-induced liver injury and steatosis using wild-type (WT) and Parkin knockout (KO) mice treated with alcohol by the acute-binge and Gao-binge (chronic plus acute-binge) models. We found that Parkin protected against liver injury in both alcohol models, likely because of Parkin's role in maintaining a population of healthy mitochondria. Alcohol caused greater mitochondrial damage and oxidative stress in Parkin KO livers compared with WT livers. After alcohol treatment, Parkin KO mice had severely swollen and damaged mitochondria that lacked cristae, which were not seen in WT mice. Furthermore, Parkin KO mice had decreased mitophagy, β-oxidation, mitochondrial respiration, and cytochrome c oxidase activity after acute alcohol treatment compared with WT mice. Interestingly, liver mitochondria seemed able to adapt to alcohol treatment, but Parkin KO mouse liver mitochondria had less capacity to adapt to Gao-binge treatment compared with WT mouse liver mitochondria. Overall, our findings indicate that Parkin is an important mediator of protection against alcohol-induced mitochondrial damage, steatosis, and liver injury. PMID:26159696

  6. Parkin regulates mitophagy and mitochondrial function to protect against alcohol-induced liver injury and steatosis in mice

    PubMed Central

    Williams, Jessica A.; Ni, Hong-Min; Ding, Yifeng

    2015-01-01

    Alcoholic liver disease claims two million lives per year. We previously reported that autophagy protected against alcohol-induced liver injury and steatosis by removing damaged mitochondria. However, the mechanisms for removal of these mitochondria are unknown. Parkin is an evolutionarily conserved E3 ligase that is recruited to damaged mitochondria to initiate ubiquitination of mitochondrial outer membrane proteins and subsequent mitochondrial degradation by mitophagy. In addition to its role in mitophagy, Parkin has been shown to have other roles in maintaining mitochondrial function. We investigated whether Parkin protected against alcohol-induced liver injury and steatosis using wild-type (WT) and Parkin knockout (KO) mice treated with alcohol by the acute-binge and Gao-binge (chronic plus acute-binge) models. We found that Parkin protected against liver injury in both alcohol models, likely because of Parkin's role in maintaining a population of healthy mitochondria. Alcohol caused greater mitochondrial damage and oxidative stress in Parkin KO livers compared with WT livers. After alcohol treatment, Parkin KO mice had severely swollen and damaged mitochondria that lacked cristae, which were not seen in WT mice. Furthermore, Parkin KO mice had decreased mitophagy, β-oxidation, mitochondrial respiration, and cytochrome c oxidase activity after acute alcohol treatment compared with WT mice. Interestingly, liver mitochondria seemed able to adapt to alcohol treatment, but Parkin KO mouse liver mitochondria had less capacity to adapt to Gao-binge treatment compared with WT mouse liver mitochondria. Overall, our findings indicate that Parkin is an important mediator of protection against alcohol-induced mitochondrial damage, steatosis, and liver injury. PMID:26159696

  7. Integrated Locomotor Function Tests for Countermeasure Evaluation

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Landsness, E. C.; Black, F. O.

    2005-01-01

    Following spaceflight crewmembers experience locomotor dysfunction due to inflight adaptive alterations in sensorimotor function. Countermeasures designed to mitigate these postflight gait alterations need to be assessed with a new generation of tests that evaluate the interaction of various sensorimotor sub-systems central to locomotor control. The goal of the present study was to develop new functional tests of locomotor control that could be used to test the efficacy of countermeasures. These tests were designed to simultaneously examine the function of multiple sensorimotor systems underlying the control of locomotion and be operationally relevant to the astronaut population. Traditionally, gaze stabilization has been studied almost exclusively in seated subjects performing target acquisition tasks requiring only the involvement of coordinated eye-head movements. However, activities like walking involve full-body movement and require coordination between lower limbs and the eye-head-trunk complex to achieve stabilized gaze during locomotion. Therefore the first goal of this study was to determine how the multiple, interdependent, full-body sensorimotor gaze stabilization subsystems are functionally coordinated during locomotion. In an earlier study we investigated how alteration in gaze tasking changes full-body locomotor control strategies. Subjects walked on a treadmill and either focused on a central point target or read numeral characters. We measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, shank and foot, accelerations along the vertical axis at the head and the shank, and the vertical forces acting on the support surface. In comparison to the point target fixation condition, the results of the number reading task showed that compensatory head pitch movements increased, peak head acceleration was reduced and knee flexion at heel-strike was increased. In a more recent study we investigated the

  8. Association Between Pulmonary Function and Nonalcoholic Fatty Liver Disease in the NHANES III Study

    PubMed Central

    Peng, Tao-Chun; Kao, Tung-Wei; Wu, Li-Wei; Chen, Ying-Jen; Chang, Yaw-Wen; Wang, Chung-Ching; Tsao, Yu-Tzu; Chen, Wei-Liang

    2015-01-01

    Abstract Emerging evidence indicates that nonalcoholic fatty liver disease (NAFLD) is associated with a wide variety of extrahepatic complications. However, the potential association between impaired pulmonary function and NAFLD has been less investigated. This study examined the relationship between pulmonary function and hepatic steatosis in 9976 adults participating in a cross-sectional analysis of the Third National Health and Nutrition Examination Survey (NHANES III). NAFLD was defined as hepatic steatosis presented on ultrasound examinations in the absence of other known liver diseases. The associations between predicted forced expiratory volume in 1 second (FEV1)% or predicted forced vital capacity (FVC)% and NAFLD were examined using multivariable linear regression while controlling for confounders. The association between obstructive or restrictive spirometry patterns and NAFLD was also evaluated using multivariable logistic regression analysis. After adjustment for multiple covariates, predicted FEV1% and FVC% were significantly and inversely associated with the degree of hepatic steatosis (P for trend <0.001 for both). The restrictive lung pattern was significantly related to participants with moderate and severe hepatic steatosis as compared with those without steatosis (OR 1.65, 95% CI 1.14–2.39 and OR 1.85, 95% CI 1.13–2.82), whereas the obstructive lung pattern was not associated with the presence of hepatic steatosis. Individuals with a greater degree of hepatic steatosis were at greater risk for poor pulmonary function, especially in restrictive pattern. These novel findings demonstrate that impaired pulmonary function is also an extrahepatic complication of NAFLD. PMID:26020401

  9. Unique functions of Gata4 in mouse liver induction and heart development.

    PubMed

    Borok, Matthew J; Papaioannou, Virginia E; Sussel, Lori

    2016-02-15

    Gata4 and Gata6 are closely related transcription factors that are essential for the development of a number of embryonic tissues. While they have nearly identical DNA-binding domains and similar patterns of expression, Gata4 and Gata6 null embryos have strikingly different embryonic lethal phenotypes. To determine whether the lack of redundancy is due to differences in protein function or Gata4 and Gata6 expression domains, we generated mice that contained the Gata6 cDNA in place of the Gata4 genomic locus. Gata4(Gata6/Gata6) embryos survived through embryonic day (E)12.5 and successfully underwent ventral folding morphogenesis, demonstrating that Gata6 is able to replace Gata4 function in extraembryonic tissues. Surprisingly, Gata6 is unable to replace Gata4 function in the septum transversum mesenchyme or the epicardium, leading to liver agenesis and lethal heart defects in Gata4(Gata6/Gata6) embryos. These studies suggest that Gata4 has evolved distinct functions in the development of these tissues that cannot be performed by Gata6, even when it is provided in the identical expression domain. Our work has important implications for the respective mechanisms of Gata function during development, as well as the functional evolution of these essential transcription factors. PMID:26687508

  10. Myocardial perfusion imaging is an effective screening test for coronary artery disease in liver transplant candidates.

    PubMed

    Baker, Sally; Chambers, Charles; McQuillan, Patrick; Janicki, Piotr; Kadry, Zakiyah; Bowen, Daniel; Bezinover, Dmitri

    2015-04-01

    A reliable screening test for coronary artery disease (CAD) in liver transplant (LT) candidates with end-stage liver disease is essential because a high percentage of perioperative mortality and morbidity is CAD-related. In this study, the effectiveness of myocardial perfusion imaging (MPI) for identification of significant CAD in LT candidates was evaluated. Records of 244 patients meeting criteria for MPI were evaluated: 74 met inclusion criteria; 40 had a positive MPI and cardiology follow-up; 27 had a negative MPI and underwent LT; and seven had a negative MPI and then had coronary angiography or a significant cardiac event. A selective MPI interpretation strategy was established where MPI-positive patients were divided into high, intermediate, and low CAD risk groups. The overall incidence of CAD in this study population was 5.1% and our strategy resulted in PPV 20%, NPV 94%, sensitivity 80%, and specificity 50% for categorizing CAD risk. When applied only to the subset of patients categorized as high CAD risk, the strategy was more effective, with PPV 67%, NPV 97%, sensitivity 80%, and specificity 94%. We determined that renal dysfunction was an independent predictive factor for CAD (p < 0.0001, odds ratio = 8.1), and grades of coronary occlusion correlated significantly with chronic renal dysfunction (p = 0.0079). PMID:25604507

  11. Survival Benefits of Small Anatomical Resection of the Liver for Patients with Hepatocellular Carcinoma and Impaired Liver Function, Based on New-Era Imaging Studies

    PubMed Central

    Sakoda, Masahiko; Ueno, Shinichi; Iino, Satoshi; Hiwatashi, Kiyokazu; Minami, Koji; Kawasaki, Yota; Kurahara, Hiroshi; Mataki, Yuko; Maemura, Kosei; Shinchi, Hiroyuki; Natsugoe, Shoji

    2016-01-01

    Background: It has been reported that anatomical resection of the liver may be preferred for primary hepatocellular carcinoma (HCC), and is at least recommended for systematic removal of a segment confined by tumor-bearing portal tributaries. However, nonanatomical resection (NAR) is often selected because of the patient's background, impairment of liver function, and tumor factors. The aims of the present study were to retrospectively compare the recurrence-free survival (RFS) rates for cases of partial resection (PR) and for small anatomical resection (SAR), which is regarded as NAR for primary HCC with impaired liver function. Patients and Methods: So-called NAR was performed for a primary and solitary (≤ 5cm) HCC in 47 patients; the patients were classified into PR (n=25) and SAR (n=22) groups. Clinicopathological factors, survival data, and recurrence patterns were compared between groups. Results: There were no significant differences in the preoperative characteristics between the two groups. Operative time was significantly longer in the SAR group than in the PR group. There was no significant difference in the postoperative morbidity and tumor pathological characteristics between the two groups. The RFS of the SAR group was significantly better than those of the PR group. Although there was no significant difference in the pattern of recurrence between the two groups, the rate of intrahepatic recurrence in the same segment as the initial tumor tended to be higher in the PR group than in the SAR group. Multivariate analysis revealed that only the PR operative procedure was significant independent risk factor for poorer RFS. Conclusion: Compared with PR, SAR effectively improves the rate of RFS after surgery for a primary and solitary HCC with impaired liver function. PMID:27326244

  12. Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function.

    PubMed

    Takami, Taro; Yamasaki, Takahiro; Saeki, Issei; Matsumoto, Toshihiko; Suehiro, Yutaka; Sakaida, Isao

    2016-08-28

    Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis. PMID:27621572

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

    PubMed

    Calmus, Yvon; Poupon, Raoul

    2014-10-01

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

  14. Expression Profile and Function Analysis of LncRNAs during Priming Phase of Rat Liver Regeneration

    PubMed Central

    Jin, Wei; Qin, Yanli; Zhao, Weiming; Chang, Cuifang; Xu, Cunshuan

    2016-01-01

    Emerging evidences have revealed that long non-coding RNAs (lncRNAs) functioned in a wide range of physiological and pathophysiological processes including rat liver regeneration, and could regulate gene expression in the transcriptional and post-transcriptional levels. However, the underlying mechanism for lncRNAs participation in liver regeneration is largely unknown. To define the mechanisms how the lncRNAs regulate LR, we performed bio-chip technology, high-throughput sequencing and RT-PCR to detect the expression of lncRNAs at 0, 2 and 6 h during LR after 2/3 hepatectomy (PH). The results indicated that 28 lncRNAs were involved in LR. Bioinformatics analysis predicated 465 co-expression target genes including 10 regulatory genes were related to these 28 lncRNAs. Ingenuity Pathway Analysis (IPA) was employed to analyze the signaling pathways and physiological activities that regulated by these genes, and the results suggested that these genes were potentially related to ILK, SAPK/JNK and ERK/MAPK signaling pathways, and possibly regulate many important physiological activities in LR in terms of cell proliferation, cell differentiation, cell survival, apoptosis and necrosis. PMID:27326854

  15. Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function

    PubMed Central

    Takami, Taro; Yamasaki, Takahiro; Saeki, Issei; Matsumoto, Toshihiko; Suehiro, Yutaka; Sakaida, Isao

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis. PMID:27621572

  16. Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function

    PubMed Central

    Bjursell, Magnus K.; Blom, Henk J.; Cayuela, Jordi Asin; Engvall, Martin L.; Lesko, Nicole; Balasubramaniam, Shanti; Brandberg, Göran; Halldin, Maria; Falkenberg, Maria; Jakobs, Cornelis; Smith, Desiree; Struys, Eduard; von Döbeln, Ulrika; Gustafsson, Claes M.; Lundeberg, Joakim; Wedell, Anna

    2011-01-01

    Four inborn errors of metabolism (IEMs) are known to cause hypermethioninemia by directly interfering with the methionine cycle. Hypermethioninemia is occasionally discovered incidentally, but it is often disregarded as an unspecific finding, particularly if liver disease is involved. In many individuals the hypermethioninemia resolves without further deterioration, but it can also represent an early sign of a severe, progressive neurodevelopmental disorder. Further investigation of unclear hypermethioninemia is therefore important. We studied two siblings affected by severe developmental delay and liver dysfunction. Biochemical analysis revealed increased plasma levels of methionine, S-adenosylmethionine (AdoMet), and S-adenosylhomocysteine (AdoHcy) but normal or mildly elevated homocysteine (Hcy) levels, indicating a block in the methionine cycle. We excluded S-adenosylhomocysteine hydrolase (SAHH) deficiency, which causes a similar biochemical phenotype, by using genetic and biochemical techniques and hypothesized that there was a functional block in the SAHH enzyme as a result of a recessive mutation in a different gene. Using exome sequencing, we identified a homozygous c.902C>A (p.Ala301Glu) missense mutation in the adenosine kinase gene (ADK), the function of which fits perfectly with this hypothesis. Increased urinary adenosine excretion confirmed ADK deficiency in the siblings. Four additional individuals from two unrelated families with a similar presentation were identified and shown to have a homozygous c.653A>C (p.Asp218Ala) and c.38G>A (p.Gly13Glu) mutation, respectively, in the same gene. All three missense mutations were deleterious, as shown by activity measurements on recombinant enzymes. ADK deficiency is a previously undescribed, severe IEM shedding light on a functional link between the methionine cycle and adenosine metabolism. PMID:21963049

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

    PubMed Central

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

    2011-01-01

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

  18. Correlation between the presence of tRNA His GUG and the erythropoietic function in foetal sheep liver.

    PubMed Central

    Landin, R M; Boisnard, M; Petrissant, G

    1979-01-01

    Histidyl-tRNAs from foetal and adult sheep liver were compared to their reticulocyte counterparts. The combination of various techniques revealed the existence of two histidyl-tRNA species in reticulocytes, one of which was not retained on acetylated DBAE-cellulose columns and was guanylatable. Three histidyl-tRNA isoacceptors were identified in foetal liver. Two of these species were not adsorbed on acetylated DBAE-cellulose but only one was found to be guanylatable. An identical chromatographic behaviour on RPC-5 columns was observed for guanylated histidyl-tRNAs from both origins. These results suggest the occurrence of a GUG anticodon in these guanine-accepting tRNAs. In foetal liver the amount of guanylatable histidyl-tRNA was estimated to be 7% of the total tRNA population. This observation is in agreement with the erythropoietic function of liver during the foetal life. Images PMID:503863

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

    NASA Astrophysics Data System (ADS)

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

    2005-05-01

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

  20. Hanford tanks initiative test facility functions and requirements

    SciTech Connect

    Krieg, S.A., Fluor Daniel Hanford

    1997-03-01

    This document presents the functions and requirements for a test facility for testing single-shell tank waste retrieval equipment and systems for the Hanford Tanks Initiative (HTI) project. This effort includes review of previous test facility functions and requirements and conducting a workshop to develop specific functions and requirements for HTI testing needs. Functions and requirements for testing future retrieval systems that follow HTI are also identified.

  1. Formal functional test designs with a test representation language

    NASA Technical Reports Server (NTRS)

    Hops, J. M.

    1993-01-01

    The application of the category-partition method to the test design phase of hardware, software, or system test development is discussed. The method provides a formal framework for reducing the total number of possible test cases to a minimum logical subset for effective testing. An automatic tool and a formal language were developed to implement the method and produce the specification of test cases.

  2. Functional analysis of the effect of monoclonal antibodies on monkey liver phenylalanine hydroxylase.

    PubMed Central

    Jennings, I G; Russell, R G; Armarego, W L; Cotton, R G

    1986-01-01

    An analysis of the effect of eleven monoclonal antibodies on the functional characteristics of monkey liver phenylalanine hydroxylase is presented. These eleven antibodies have been found to react with eight distinct regions on the phenylalanine hydroxylase protein. PH1 antibody inhibits enzyme activity, is dependent on phenylalanine for its binding, and appears to be related to structural changes occurring during phenylalanine activation of the enzyme activity. PH2 and PH3 antibodies stimulate enzyme activity, their binding is inhibited by lysolecithin and this group apparently is recognizing structures involved in lysolecithin activation of the enzyme activity. PH5, PH10, PH12 and PH6 recognise sites on phenylalanine hydroxylase affected by lysolecithin activation. PMID:2427069

  3. Low-dose propranolol for multiple hepatic and cutaneous hemangiomas with deranged liver function.

    PubMed

    Tan, Swee Thong; Itinteang, Tinte; Leadbitter, Philip

    2011-03-01

    We report here the case of an infant with multiple hepatic and cutaneous infantile hemangiomas (IHs) associated with deranged liver function who was treated successfully with low-dose propranolol. We also discuss our recent data that show that IH is a developmental anomaly of hemogenic endothelium derived from primitive mesoderm with a neural crest-cell phenotype. We previously presented evidence that this hemogenic endothelium is governed by the renin-angiotensin system, which we propose can account for both the action of propranolol and the process of spontaneous involution of IH. We further speculate on the possibility of using inhibitors of angiotensin-converting enzyme and that of angiotensin II receptor 2 as potential alternative therapies. PMID:21357335

  4. Effects on the hemostatic system and liver function in relation to Implanon and Norplant. A prospective randomized clinical trial.

    PubMed

    Egberg, N; van Beek, A; Gunnervik, C; Hulkko, S; Hirvonen, E; Larsson-Cohn, U; Bennink, H C

    1998-08-01

    In this prospective randomized clinical trial, two long-term contraceptive implants were studied with respect to hemostasis and liver function in 86 healthy young women. The two implants used were Implanon, containing the progestagen etonogestrel (the biologically active metabolite of desogestrel) and Norplant, the implant containing the progestagen levonorgestrel. The results of the trial showed that both implants had similar small effects on the hemostatic system that are not suggestive of a tendency towards thrombosis. The effect on liver function was characterized by increases in total bilirubin and gamma-glutamyl transferase and decreases in alanine aminotransferase and aspartate aminotransferase. PMID:9773263

  5. Treatment to Improve Nutrition and Functional Capacity Evaluation in Liver Transplant Candidates

    PubMed Central

    Dasarathy, Srinivasan

    2014-01-01

    Opinion Statement Liver transplantation is the definitive therapy for cirrhosis and malnutrition is the most frequent complication in these patients. Sarcopenia or loss of muscle mass is the major component of malnutrition in cirrhotics and adversely affects their outcome. In addition to the metabolic consequences, functional consequences of sarcopenia include reduced muscle strength and deconditioning. Despite nearly universal occurrence of sarcopenia and its attendant complications there are no established therapies to prevent or reverse the same. Major reasons for this deficiency include the lack of established standardized definitions or measures to quantify muscle mass and paucity of mechanistic studies or identified molecular targets to develop specific therapeutic interventions. Anthropometric evaluation, bioelectrical impedance analysis, DEXA scans are relatively imprecise measures of muscle mass and recent data on imaging measures to determine muscle mass accurately is likely to allow well defined outcome responses to treatments. Resurgence of interest in the mechanisms of muscle loss in liver disease has been directly related to the rapid advances in the field of muscle biology. Metabolic tracer studies on whole body kinetics have been complemented by direct studies on the skeletal muscle of cirrhotics. Hypermetabolism and anabolic resistance contribute to sarcopenia. Reduced protein synthesis and increased autophagy have been reported in cirrhotic skeletal muscle while the contribution of the ubiquitin-proteasome pathway is controversial. Increased plasma concentration and skeletal muscle expression of myostatin, a TGFβ superfamily member that causes reduction in muscle mass, have been reported in cirrhosis. Hyperammonemia and TNFα have been reported to increase myostatin expression and may be responsible for sarcopenia in cirrhosis. Nutriceutical interventions with leucine enriched amino acid mixtures, myostatin antagonists and physical activity hold

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-12-01

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

  8. Ezetimibe markedly attenuates hepatic cholesterol accumulation and improves liver function in the lysosomal acid lipase-deficient mouse, a model for cholesteryl ester storage disease.

    PubMed

    Chuang, Jen-Chieh; Lopez, Adam M; Posey, Kenneth S; Turley, Stephen D

    2014-01-17

    Lysosomal acid lipase (LAL) plays a critical role in the intracellular handling of lipids by hydrolyzing cholesteryl esters (CE) and triacylglycerols (TAG) contained in newly internalized lipoproteins. In humans, mutations in the LAL gene result in cholesteryl ester storage disease (CESD), or in Wolman disease (WD) when the mutations cause complete loss of LAL activity. A rat model for WD and a mouse model for CESD have been described. In these studies we used LAL-deficient mice to investigate how modulating the amount of intestinally-derived cholesterol reaching the liver might impact its mass, cholesterol content, and function in this model. The main experiment tested if ezetimibe, a potent cholesterol absorption inhibitor, had any effect on CE accumulation in mice lacking LAL. In male Lal(-/-) mice given ezetimibe in their diet (20 mg/day/kg bw) for 4 weeks starting at 21 days of age, both liver mass and hepatic cholesterol concentration (mg/g) were reduced to the extent that whole-liver cholesterol content (mg/organ) in the treated mice (74.3±3.4) was only 56% of that in those not given ezetimibe (133.5±6.7). There was also a marked improvement in plasma alanine aminotransferase (ALT) activity. Thus, minimizing cholesterol absorption has a favorable impact on the liver in CESD. PMID:24370824

  9. Validation of AshTest as a Non-Invasive Alternative to Transjugular Liver Biopsy in Patients with Suspected Severe Acute Alcoholic Hepatitis

    PubMed Central

    Rudler, Marika; Mouri, Sarah; Charlotte, Frederic; Cluzel, Philippe; Ngo, Yen; Munteanu, Mona; Lebray, Pascal; Ratziu, Vlad; Thabut, Dominique; Poynard, Thierry

    2015-01-01

    Background/Aims According to guidelines, the histological diagnosis of severe alcoholic steatohepatitis (ASH) can require liver biopsy if a specific treatment is needed. The blood test AshTest (BioPredictive, Paris, France) has been initially validated for the non-invasive diagnosis of ASH in a large population of heavy drinkers. The aim was to validate the AshTest accuracy in the specific context of use of patients with suspected severe ASH, in order to reduce the need for transjugular biopsy before deciding treatment. Methods The reference was liver biopsy, performed using the transjugular route, classified according to its histological severity as none, minimal, moderate or severe. Biopsies were assessed by the same experienced pathologist, blinded to simultaneous AshTest results. Results A total of 123 patients with severe clinical ASH (recent jaundice and Maddrey function greater or equal to 32) were included, all had cirrhosis and 80% had EASL histological definition of ASH. 95% of patients received prednisolone; and the 2-year mortality was 63%. The high AshTest performance was confirmed both for the binary outcome [AUROC = 0.803 (95%CI 0.684–0.881)] significantly higher than the AST/ALT AUROC [0.603 (0.462–0.714); P<0.001], and for the severity of ASH-score system by the Obuchowski measures for [mean (SE) 0.902 (0.017) vs. AST/ALT 0.833 (0.023); P = 0.01], as well as for the diagnosis and severity of ballooning, PMN and Mallory bodies. According to attributability of discordances, AshTest had a 2–7% risk of 2 grades misclassification. Conclusion These results confirmed the diagnostic performance of AshTest in cirrhotic patients with severe clinical ASH, in the specific context of use of corticosteroid treatment. AshTest is an appropriate non-invasive alternative to transjugular liver biopsy. PMID:26252713

  10. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

  11. Ammonia Test

    MedlinePlus

    ... be ordered, along with other tests such as glucose , electrolytes , and kidney and liver function tests , to help diagnose the cause of ... Pages tab.) An increased ammonia level and decreased glucose ... may indicate that severe liver or kidney damage has impacted the body's ability ...

  12. Supplementation of Eurycoma longifolia Jack Extract for 6 Weeks Does Not Affect Urinary Testosterone: Epitestosterone Ratio, Liver and Renal Functions in Male Recreational Athletes

    PubMed Central

    Chen, Chee Keong; Mohamad, Wan Mohd Zahiruddin Wan; Ooi, Foong Kiew; Ismail, Shaiful Bahari; Abdullah, Mohamad Rusli; George, Annie

    2014-01-01

    Background: Eurycoma longifolia Jack (ElJ) has been shown to elevate serum testosterone and increased muscle strength in humans. This study investigated the effects of Physta® a standardized water extract of ElJ (400 mg/day for 6 weeks) on testosterone: epitestosterone (T:E) ratio, liver and renal functions in male recreational athletes. Methods: A total of 13 healthy male recreational athletes were recruited in this double blind, placebo-controlled, cross-over study. The participants were required to consume either 400 mg of ElJ or placebo daily for 6 weeks in the first supplementation regimen. Following a 3 week wash-out period, the participants were requested to consume the other supplement for another 6 weeks. Mid-stream urine samples and blood samples were collected prior to and after 6 weeks of supplementation with either ElJ or placebo. The urine samples were subsequently analyzed for T:E ratio while the blood samples were analyzed for liver and renal functions. Results: T:E ratio was not significantly different following 6 weeks supplementation of either ElJ or placebo compared with their respective baseline values. Similarly, there were no significant changes in both the liver and renal functions tests following the supplementation of ElJ. Conclusions: Supplementation of ElJ i.e. Physta® at a dosage of 400 mg/day for 6 weeks did not affect the urinary T:E ratio and hence will not breach any doping policies of the International Olympic Committee for administration of exogenous testosterone or its precursor. In addition, the supplementation of ElJ at this dosage and duration was safe as it did adversely affect the liver and renal functions. PMID:25013692

  13. Preoperative Estimation of Future Remnant Liver Function Following Portal Vein Embolization Using Relative Enhancement on Gadoxetic Acid Disodium-Enhanced Magnetic Resonance Imaging

    PubMed Central

    Matsushima, Shigeru; Inaba, Yoshitaka; Sano, Tsuyoshi; Yamaura, Hidekazu; Kato, Mina; Shimizu, Yasuhiro; Senda, Yoshiki; Ishiguchi, Tsuneo

    2015-01-01

    Objective To retrospectively evaluate relative enhancement (RE) in the hepatobiliary phase of gadoxetic acid disodium-enhanced magnetic resonance (MR) imaging as a preoperative estimation of future remnant liver (FRL) function in a patients who underwent portal vein embolization (PVE). Materials and Methods In 53 patients, the correlation between the indocyanine green clearance (ICG-K) and RE imaging was analyzed before hepatectomy (first analysis). Twenty-three of the 53 patients underwent PVE followed by a repeat RE imaging and ICG test before an extended hepatectomy and their results were further analyzed (second analysis). Whole liver function and FRL function were calculated on the MR imaging as follows: RE x total liver volume (RE Index) and FRL-RE x FRL volume (Rem RE Index), respectively. Regarding clinical outcome, posthepatectomy liver failure (PHLF) was evaluated in patients undergoing PVE. Results Indocyanine green clearance correlated with the RE Index (r = 0.365, p = 0.007), and ICG-K of FRL (ICG-Krem) strongly correlated with the Rem RE Index (r = 0.738, p < 0.001) in the first analysis. Both the ICG-Krem and the Rem RE Index were significantly correlated after PVE (r = 0.508, p = 0.013) at the second analysis. The rate of improvement of the Rem RE Index from before PVE to after PVE was significantly higher than that of ICG-Krem (p = 0.014). Patients with PHLF had a significantly lower Rem RE Index than patients without PHLF (p = 0.023). Conclusion Relative enhancement imaging can be used to estimate FRL function after PVE. PMID:25995681

  14. A novel NADPH:(bound) NADP+ reductase and NADH:(bound) NADP+ transhydrogenase function in bovine liver catalase.

    PubMed

    Gaetani, Gian F; Ferraris, Anna M; Sanna, Paola; Kirkman, Henry N

    2005-02-01

    Many catalases have the shared property of containing bound NADPH and being susceptible to inactivation by their own substrate, H2O2. The presence of additional (unbound) NADPH effectively prevents bovine liver and human erythrocytic catalase from becoming compound II, the reversibly inactivated state of catalase, and NADP+ is known to be generated in the process. The function of the bound NADPH, which is tightly bound in bovine liver catalase, has been unknown. The present study with bovine liver catalase and [14C]NADPH and [14C]NADH revealed that unbound NADPH or NADH are substrates for an internal reductase and transhydrogenase reaction respectively; the unbound NADPH or NADH cause tightly bound NADP+ to become NADPH without becoming tightly bound themselves. This and other results provide insight into the function of tightly bound NADPH. PMID:15456401

  15. Role of the 13C-methacetin breath test in the assessment of acute liver injury in a rat model

    PubMed Central

    Zhu, Dong; Zhang, Hui; Mao, Jing-Yi; Wang, Hong-Yan; Li, Xin; Xu, You-Qing

    2014-01-01

    AIM: To evaluate the role of the 13C-methacetin breath test (13C-MBT) in the assessment of acute liver injury in a rat model. METHODS: Acute liver injury in rats was induced by a single intraperitoneal injection of D-galactosamine (D-GalN). Forty-eight male Sprague-Dawley rats were randomly assigned to a control group (n = 8) and five model groups (each n = 8), and acute liver injury was assessed at different time points (6, 12, 24, 48 and 72 h) after D-GalN injection. The 13C-MBT, biochemical tests, 15-min retention rate of indocyanine green (ICGR15), and liver biopsy were performed and compared between the control and model groups. Correlations between parameters of the 13C-MBT (Tmax, MVmax, CUM120 and DOBmax), biochemical tests, ICGR15 and liver necrosis score were also analyzed using Spearman’s correlation analysis. RESULTS: Tmax, MVmax, CUM120 and DOBmax, as well as most of the traditional methods, correlated with the liver necrosis score (r = 0.493, P < 0.05; r = -0.731, P < 0.01; r = -0.618, P < 0.01; r = -0.592, P < 0.01, respectively). MVmax, CUM120 and DOBmax rapidly decreased and were lower than those in the controls as early as 6 h after D-GalN injection (3.84 ± 0.84 vs 5.06 ± 0.78, P < 0.01; 3.35 ± 0.72 vs 4.21 ± 1.44, P < 0.05; 52.3 ± 20.58 vs 75.1 ± 9.57, P < 0.05, respectively) and reached the lowest point 24 h after D-GalN injection. MVmax, CUM120 and DOBmax returned to normal levels 72 h after D-GalN injection and preceded most of the traditional methods, including liver biopsy. CONCLUSION: The 13C-MBT is a sensitive tool for the timely detection of acute liver injury and early prediction of recovery in a rat model. Further clinical studies are warranted to validate its role in patients with acute liver injury. PMID:25170215

  16. Human immunodeficiency virus infection and the liver

    PubMed Central

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

    2012-01-01

    Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries. PMID:22489261

  17. Transplantation vs resection for hepatocellular carcinoma with compensated liver function after downstaging therapy

    PubMed Central

    Lei, Jian-Yong; Yan, Lu-Nan; Wang, Wen-Tao

    2013-01-01

    AIM: Our study aimed to compare the results of liver transplantation (LT) and liver resection (LR) in patients with hepatocellular carcinoma (HCC) that met the Milan criteria after successful downstaging therapy. METHODS: From February 2004 to August 2010, a consecutive series of 102 patients were diagnosed with advanced-stage HCC that met the modified UCSF down-staging protocol inclusion criteria. All of the patients accepted various down-staging therapies. The types and numbers of treatments were tailored to each patient according to the tumor characteristics, location, liver function and response. After various downstaging therapies, 66 patients had tumor characteristics that met the Milan criteria; 31 patients accepted LT in our center, and 35 patients accepted LR. The baseline characteristics, down-staging protocols, postoperative complications, overall survival and tumor free survival rate, and tumor recurrence rate were compared between the two groups. Kaplan-Meier analyses were used to estimate the long-term overall survival and tumor-free survival rate. Meanwhile, a Cox proportional hazards model was used for the multivariate analyses of overall survival and disease-free survival rate. RESULTS: No significant difference was observed between the LT and LR groups with respect to the down-staging protocol, target tumor characteristics, and baseline patient characteristics. Fifteen patients suffered various complications after LT, and 8 patients had complications after LR. The overall complication rate for the LT group was 48.4%, which was significantly higher than the LR group (22.9%) (P = 0.031). The overall in-hospital mortality in hospital for the LT group was 12.9% vs 2.9% for the LR group (P = 0.172). The overall patient survival rates at 1-, 3- and 5-years were 87.1%, 80.6% and 77.4%, respectively, after LT and 91.4%, 77.1% and 68.6%, respectively, after LR (P = 0.498). The overall 1-, 3- and 5-year tumor recurrence-free rates were also comparable (P

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

    PubMed Central

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

    2015-01-01

    Liver transplantation is the ultimate treatment for severe hepatic failure to date. However, the limited supply of donor organs has severely hampered this treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to replenish the hepatic cell population have been shown; nevertheless, there still is a lack of an optimal three-dimensional scaffold for generation of well-transplantable hepatic tissues. In this study, we utilized a cryo-chemical decellularization method which combines physical and chemical approach to generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS provides a biomimetic three-dimensional environment to support hepatic differentiation of MSCs, evidenced by expression of hepatic-associated genes and marker protein, glycogen storage, albumin secretion, and urea production. It is also found that hepatic differentiation of MSCs within the ALS is much more efficient than two-dimensional culture in vitro. Importantly, the hepatic-like tissues (HLT) generated by repopulating ALS with MSCs are able to act as functional grafts and rescue lethal hepatic failure after transplantation in vivo. In summary, the cryo-chemical method used in this study is suitable for decellularization of liver and create acellular scaffolds that can support hepatic differentiation of MSCs and be used to fabricate functional tissue-engineered liver constructs. PMID:24462361

  19. Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus

    PubMed Central

    Pakharukova, Mariya Y.; Vavilin, Valentin A.; Sripa, Banchob; Laha, Thewarach; Brindley, Paul J.; Mordvinov, Viatcheslav A.

    2015-01-01

    The basic metabolic cytochrome P450 (CYP) system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene. The role of this enzyme in the physiology and biochemistry of helminths is not known. The flukes and tapeworms are the etiologic agents of major neglected tropical diseases of humanity. Three helminth infections (Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium) are considered by the International Agency for Research on Cancer (IARC) as definite causes of cancer. We focused our research on the human liver fluke Opisthorchis felineus, an emerging source of biliary tract disease including bile duct cancer in Russia and central Europe. The aims of this study were (i) to determine the significance of the CYP activity for the morphology and survival of the liver fluke, (ii) to assess CYP ability to metabolize xenobiotics, and (iii) to localize the CYP activity in O. felineus tissues. We observed high constitutive expression of CYP mRNA (Real-time PCR) in O. felineus. This enzyme metabolized xenobiotics selective for mammalian CYP2E1, CYP2B, CYP3A, but not CYP1A, as determined by liquid chromatography and imaging analyses. Tissue localization studies revealed the CYP activity in excretory channels, while suppression of CYP mRNA by RNA interference was accompanied by morphological changes of the excretory system and increased mortality rates of the worms. These results suggest that the CYP function is linked to worm metabolism and detoxification. The findings also suggest that the CYP enzyme is involved in vitally important processes in the organism of parasites and is a potential drug target. PMID:26625139

  20. Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus.

    PubMed

    Pakharukova, Mariya Y; Vavilin, Valentin A; Sripa, Banchob; Laha, Thewarach; Brindley, Paul J; Mordvinov, Viatcheslav A

    2015-12-01

    The basic metabolic cytochrome P450 (CYP) system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene. The role of this enzyme in the physiology and biochemistry of helminths is not known. The flukes and tapeworms are the etiologic agents of major neglected tropical diseases of humanity. Three helminth infections (Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium) are considered by the International Agency for Research on Cancer (IARC) as definite causes of cancer. We focused our research on the human liver fluke Opisthorchis felineus, an emerging source of biliary tract disease including bile duct cancer in Russia and central Europe. The aims of this study were (i) to determine the significance of the CYP activity for the morphology and survival of the liver fluke, (ii) to assess CYP ability to metabolize xenobiotics, and (iii) to localize the CYP activity in O. felineus tissues. We observed high constitutive expression of CYP mRNA (Real-time PCR) in O. felineus. This enzyme metabolized xenobiotics selective for mammalian CYP2E1, CYP2B, CYP3A, but not CYP1A, as determined by liquid chromatography and imaging analyses. Tissue localization studies revealed the CYP activity in excretory channels, while suppression of CYP mRNA by RNA interference was accompanied by morphological changes of the excretory system and increased mortality rates of the worms. These results suggest that the CYP function is linked to worm metabolism and detoxification. The findings also suggest that the CYP enzyme is involved in vitally important processes in the organism of parasites and is a potential drug target. PMID:26625139

  1. The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity.

    PubMed

    Pacifico, Lucia; Bonci, Enea; Andreoli, Gian Marco; Di Martino, Michele; Gallozzi, Alessia; De Luca, Ester; Chiesa, Claudio

    2016-01-01

    The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m². Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m² was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001). The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001). Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16-5.57); p < 0.05) independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease. PMID:27472326

  2. The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity

    PubMed Central

    Pacifico, Lucia; Bonci, Enea; Andreoli, Gian Marco; Di Martino, Michele; Gallozzi, Alessia; De Luca, Ester; Chiesa, Claudio

    2016-01-01

    The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m2. Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m2 was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001). The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001). Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16–5.57); p < 0.05) independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease. PMID:27472326

  3. Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo: clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver.

    PubMed Central

    Griffen, S C; Russell, S M; Katz, L S; Nicoll, C S

    1987-01-01

    The functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver has not been established. Previous studies indicated that insulin does not acutely regulate glucose metabolism by a direct hepatic effect. More recent observations suggest that the role of insulin in regulating body growth may be mediated, at least in part, by the liver. Our experiments were designed to test whether insulin can promote body growth and regulate glucose metabolism by a direct hepatic action in vivo. Rats were made diabetic by injections of streptozotocin, and insulin or solvent was infused into the jugular vein (JV) or the hepatic portal vein (HPV) for 14 days using catheters that were attached to osmotic minipumps. Infusion of a low dose of insulin (2 units per kg per day) into the JV had no effects on the hyperglycemia, body weight gain, tail growth, tibial epiphysial cartilage plate thickness, or serum levels of somatomedin C in the diabetic rats. However, the same dose given into the HPV caused a 30% reduction of blood glucose and stimulated a significant degree of growth, as determined by all indices. Infusion of a higher dose of insulin (5 units per kg per day) into either vein caused full restoration of body weight gain and tail growth and it restored the glycemic status almost to normal. However, it did not increase the tibial epiphysial plate width or serum somatomedin C levels above those of the rats given the low dose of the hormone into the HPV. These results indicate that insulin can act directly on the liver to promote body growth and to regulate glucose metabolism. The significance of direct delivery of insulin from the pancreatic beta cells to the liver may be as much for growth control as for glucose homeostasis. Images PMID:3313390

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

    PubMed

    Góra-Gębka, Magdalena; Woźniak, Małgorzata; Cielecka-Kuszyk, Joanna; Korpal-Szczyrska, Maria; Sznurkowska, Katarzyna; Zagierski, Maciej; Jankowska, Irena; Plata-Nazar, Katarzyna; Kamińska, Barbara; Liberek, Anna

    2014-01-01

    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

  5. Effect of in utero exposure of Toddy (coconut palm wine) on liver function and lipid metabolism in rat fetuses.

    PubMed

    Lal, J J; Sreeranjit Kumar, C V; Suresh, M V; Indira, M; Vijayammal, P L

    1998-01-01

    The objective of this study was to determine the effects of a country liquor Toddy (Coconut palm wine) and an equivalent quantity of ethanol on liver function and lipid metabolism in utero. Female albino rats with an average weight of 125 +/- 5 g were exposed to Toddy from coconut palm (24.5 ml/kg body weight/day) and ethanol (0.52 ml/kg body weight/day) for 15 days before conception and during pregnancy. On day 13 and day 19 of gestation, altered liver function and hyperlipidemia were seen in the fetuses of both the treated groups. Altered liver function was evidenced by the increased activity of alcohol dehydrogenase, aldehyde dehydrogenase, glutamic oxaloacetic transaminase (aspartate amino transferase (GOT)), glutamic pyruvic transaminase (alanine amino transferase (GPT)). Hyperlipidemia was caused by increased biosynthesis since the incorporation of 14C acetate into lipids and activities of HMG CoA reductase and lipogenic enzymes were elevated. Toddy treated fetuses were more severely affected than those exposed to an equivalent quantity of ethanol. Toddy seemed to potentiate the toxicity induced by alcohol suggesting the role of non alcoholic components. Hepatic functions of the day 13 fetuses were effected to a lesser degree than those in the day 19 hepatic liver. PMID:9950082

  6. Novel immortalized human fetal liver cell line, cBAL111, has the potential to differentiate into functional hepatocytes

    PubMed Central

    Deurholt, Tanja; van Til, Niek P; Chhatta, Aniska A; ten Bloemendaal, Lysbeth; Schwartlander, Ruth; Payne, Catherine; Plevris, John N; Sauer, Igor M; Chamuleau, Robert AFM; Elferink, Ronald PJ Oude; Seppen, Jurgen; Hoekstra, Ruurdtje

    2009-01-01

    Background A clonal cell line that combines both stable hepatic function and proliferation capacity is desirable for in vitro applications that depend on hepatic function, such as pharmacological or toxicological assays and bioartificial liver systems. Here we describe the generation and characterization of a clonal human cell line for in vitro hepatocyte applications. Results Cell clones derived from human fetal liver cells were immortalized by over-expression of telomerase reverse transcriptase. The resulting cell line, cBAL111, displayed hepatic functionality similar to the parental cells prior to immortalization, and did not grow in soft agar. Cell line cBAL111 expressed markers of immature hepatocytes, like glutathione S transferase and cytokeratin 19, as well as progenitor cell marker CD146 and was negative for lidocaine elimination. On the other hand, the cBAL111 cells produced urea, albumin and cytokeratin 18 and eliminated galactose. In contrast to hepatic cell lines NKNT-3 and HepG2, all hepatic functions were expressed in cBAL111, although there was considerable variation in their levels compared with primary mature hepatocytes. When transplanted in the spleen of immunodeficient mice, cBAL111 engrafted into the liver and partly differentiated into hepatocytes showing expression of human albumin and carbamoylphosphate synthetase without signs of cell fusion. Conclusion This novel liver cell line has the potential to differentiate into mature hepatocytes to be used for in vitro hepatocyte applications. PMID:19845959

  7. The alteration of profile analysis to accommodate testing functions

    NASA Technical Reports Server (NTRS)

    Myers, R. H.

    1979-01-01

    The development of a methodology was studied for testing differences among several pilot functions, where the data points represent averages at various frequencies. Topics discussed include: basic assumptions, hypothesis, profile analysis, alteration of profile analysis to accommodate testing functions, test and procedures, and power of tests.

  8. Generation of a functional liver tissue mimic using adipose stromal vascular fraction cell-derived vasculatures

    PubMed Central

    Nunes, S. S.; Maijub, J. G.; Krishnan, L.; Ramakrishnan, V. M.; Clayton, L. R.; Williams, S. K.; Hoying, J. B.; Boyd, N. L.

    2013-01-01

    One of the major challenges in cell implantation therapies is to promote integration of the microcirculation between the implanted cells and the host. We used adipose-derived stromal vascular fraction (SVF) cells to vascularize a human liver cell (HepG2) implant. We hypothesized that the SVF cells would form a functional microcirculation via vascular assembly and inosculation with the host vasculature. Initially, we assessed the extent and character of neovasculatures formed by freshly isolated and cultured SVF cells and found that freshly isolated cells have a higher vascularization potential. Generation of a 3D implant containing fresh SVF and HepG2 cells formed a tissue in which HepG2 cells were entwined with a network of microvessels. Implanted HepG2 cells sequestered labeled LDL delivered by systemic intravascular injection only in SVF-vascularized implants demonstrating that SVF cell-derived vasculatures can effectively integrate with host vessels and interface with parenchymal cells to form a functional tissue mimic. PMID:23828203

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

    SciTech Connect

    Moreira, Paula I.; Custodio, Jose B.A.; Nunes, Elsa; Moreno, Antonio; Seica, Raquel; Oliveira, Catarina R.; Santos, Maria S. . E-mail: mssantos@ci.uc.pt

    2007-05-15

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

  10. Metabolic liver disease.

    PubMed

    McKiernan, Pat

    2012-06-01

    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

  11. Trans-generational exposure to low levels of rhodamine B does not adversely affect litter size or liver function in murine mucopolysaccharidosis type IIIA.

    PubMed

    Roberts, Ainslie L K; Fletcher, Janice M; Moore, Lynette; Byers, Sharon

    2010-01-01

    MPS IIIA is a lysosomal storage disorder caused by mutations in the sulphamidase gene, resulting in the accumulation of heparan sulphate glycosaminoglycans (HS GAGs). Symptoms predominantly manifest in the CNS and there is no current therapy that effectively addresses neuropathology in MPS IIIA patients. Recent studies in MPS IIIA mice have shown that rhodamine B substrate deprivation therapy (SDT) (also termed substrate reduction therapy/SRT) inhibits GAG biosynthesis and, improves both somatic and CNS disease pathology. Acute overexposure to high doses of rhodamine B results in liver toxicity and is detrimental to reproductive ability. However, the long-term effects of decreasing GAG synthesis, at the low dose sufficient to alter neurological function are unknown. A trans-generational study was therefore initiated to evaluate the continuous exposure of rhodamine B treatment in MPS IIIA mice over 4 generations, including treatment during pregnancy. No alterations in litter size, liver histology or liver function were observed. Overall, there are no long-term issues with the administration of rhodamine B at the low dose tested and no adverse effects were noted during pregnancy in mice. PMID:20650670

  12. Pharmacogenetic testing in idiosyncratic drug-induced liver injury: current role in clinical practice.

    PubMed

    Aithal, Guruprasad P

    2015-07-01

    In contrast to the studies that have explored association of genetic variants with other complex traits, those investigating hepatotoxicity have identified risk alleles with substantially higher risk ratios for the susceptibility to drug-induced liver injury (DILI). In addition, a relatively small number of human leukocyte antigen (HLA) alleles have overlapping associations with a variety of adverse reactions including DILI, cutaneous hypersensitivity and drug-induced pancreatitis. However, if used as a test prior to prescription to prevent potential adverse reaction, genotyping would have a very high negative predictive value, yet a low positive predictive value based on the low incidence of DILI. One potential consideration is to treat all relevant HLA genotypes as one panel covering different forms of adverse drug reactions, thereby improving the positive predictive value of the panel and widen its application. The majority of HLA alleles associated with DILI have a very high negative predictive value; therefore, they can be used to rule out hepatotoxicity caused by particular drugs. A high negative predictive value of a genetic test can be used to identify the correct agent underlying DILI when the patient had been exposed to two concomitant medications with a potential to cause DILI. Inclusion of genetic tests in the causality assessment of an event, where DILI is suspected, may improve consistency and precision of causality assessment tools. A recent clinical trial used N-acetyltransferase 2 genotyping to determine the appropriate dose of isoniazid in an anti-tuberculosis therapeutic regimen and demonstrated that pharmacogenetic-based clinical algorithms have the potential to improve efficacy of a drug and to reduce DILI. PMID:25809692

  13. Liver Panel

    MedlinePlus

    ... liver; the best test for detecting hepatitis Alkaline phosphatase (ALP) – an enzyme related to the bile ducts ... only moderately elevated or close to normal. Alkaline phosphatase (ALP) ALP may be significantly increased with obstructed ...

  14. Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments

    PubMed Central

    Altrichter, Jens; Haubner, Cristof; Pertschy, Annette; Wild, Thomas; Doß, Fanny; Thomsen, Maren; Ehler, Johannes; Henschel, Jörg; Doß, Sandra; Koch, Stephanie; Richter, Georg; Mitzner, Steffen R.

    2016-01-01

    Purpose. Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients. Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results. The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged. PMID:27433475

  15. Herbal Compound Songyou Yin and Moderate Swimming Suppress Growth and Metastasis of Liver Cancer by Enhancing Immune Function.

    PubMed

    Zhang, Quan-Bao; Meng, Xiang-Ting; Jia, Qing-An; Bu, Yang; Ren, Zheng-Gang; Zhang, Bo-Heng; Tang, Zhao-You

    2016-09-01

    Objective Both the Chinese herbal compound Songyou Yin (SYY) and swimming exercise have been shown to have protective effects against liver cancer in animal models. In this study, we investigated whether SYY and moderate swimming (MS) have enhanced effect on suppressing progression of liver cancer by immunomodulation. Methods C57BL/6 mice were transplanted with Hepa1-6 murine liver cancer cell lines and received treatment with SYY alone or SYY combined with MS. The green fluorescent protein (GFP)-positive metastatic foci in lungs were imaged with a stereoscopic fluorescence microscope. Flow cytometry was used to test the proportion of CD4 +, CD8 + T cells in peripheral blood and the proportions of CD4 + CD25 + Foxp3 + Treg cells in peripheral blood, spleen, and tumor tissues. Cytokine transforming growth factor (TGF)-β1 level in serum was detected by ELISA. Results SYY plus MS significantly suppressed the growth and lung metastasis of liver cancer and prolonged survival in tumor-burdened mice. SYY plus MS markedly raised the CD4 to CD8 ratio in peripheral blood and lowered the serum TGF-β1 level and the proportions of Treg cells in peripheral blood, spleen, and tumor tissue. The effects of the combined intervention were significantly superior to SYY or MS alone. Conclusion The combined application of SYY and MS exerted an enhanced effect on suppressing growth and metastasis of liver cancer by strengthening immunity. PMID:26699805

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

    PubMed Central

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

    2016-01-01

    Reproduction is thought to come at a cost to longevity. Based on the assumption that increased energy expenditure during reproduction is associated with increased free-radical production by mitochondria, oxidative damage has been suggested to drive this trade-off. We examined the impact of reproduction on liver mitochondrial function by utilizing post-reproductive and non-reproductive house mice (Mus musculus) living under semi-natural conditions. The age-matched post-reproductive and non-reproductive groups were compared after the reproductive females returned to a non-reproductive state, so that both groups were in the same physiological state at the time the liver was collected. Despite increased oxidative damage (p = 0.05) and elevated CuZnSOD (p = 0.002) and catalase (p = 0.04) protein levels, reproduction had no negative impacts on the respiratory function of liver mitochondria. Specifically, in a post-reproductive, maintenance state the mitochondrial coupling (i.e., respiratory control ratio) of mouse livers show no negative impacts of reproduction. In fact, there was a trend (p = 0.059) to suggest increased maximal oxygen consumption by liver mitochondria during the ADP stimulated state (i.e., state 3) in post-reproduction. These findings suggest that oxidative damage may not impair mitochondrial respiratory function and question the role of mitochondria in the trade-off between reproduction and longevity. In addition, the findings highlight the importance of quantifying the respiratory function of mitochondria in addition to measuring oxidative damage. PMID:27537547

  17. Repeated dose liver micronucleus assay using adult mice with multiple genotoxicity assays concurrently performed as a combination test.

    PubMed

    Hagio, Soichiro; Furukawa, Satoshi; Abe, Masayoshi; Kuroda, Yusuke; Hayashi, Seigo; Ogawa, Izumi

    2014-06-01

    Recently, the liver micronucleus (MN) assay using young adult rats with repeated administrations has been investigated by employing a new method without partial hepatectomy or in situcollagenase perfusion as the repeated dose liver MN (RDLMN) assay by Narumi et al. (2012). In our study, in order to investigate the possibility of the RDLMN assay using young adult mice instead of rats and the feasibility of employing some genotoxicity assays along with the RDLMN assay as a combination test, two genotoxic carcinogens (N,N-diethylnitrosoamine (DEN) and cisplatin (CIS)) and a nongenotoxic carcinogen (phenobarbital sodium (PHE)) were administered to mice for 15 or 29 days. Then, the liver MN assay, peripheral blood (PB) MN assay and comet assay using the liver and kidney were concurrently performed as a combination test. DEN showed positive responses to all endpoints except MN induction in PB after 15 days of repeat administration. A cross-linking agent, CIS, showed MN induction in liver after 29 days of repeat administration, and in PB after 15 and 29 days of repeat administration, although the comet assay yielded negative responses for both organs at both sampling times. PHE yielded negative responses for all endpoints. In conclusion, it is suggested that the RDLMN assay using mice is a feasible method to be integrated into the general repeated toxicity test along with the combination assays, i.e., comet assay or PB MN assay, which would help in risk assessment for carcinogenicity by comparing the results of combination assays with each other. PMID:24849678

  18. Identification of two functional nuclear localization signals mediating nuclear import of liver receptor homologue-1.

    PubMed

    Yang, Feng-Ming; Lin, Yu-Chi; Hu, Meng-Chun

    2011-04-01

    Liver receptor homologue-1 (LRH-1) is a member of the nuclear receptor superfamily. We characterized two functional nuclear localization signals (NLSs) in LRH-1. NLS1 (residues 117-168) overlaps the second zinc finger in the DNA binding domain. Mutagenesis showed that the zinc finger structure and two basic clusters on either side of the zinc finger loop are critical for nuclear import of NLS1. NLS2 (residues 169-204) is located in the Ftz-F1 box that contains a bipartite signal. In full-length LRH-1, mutation of either NLS1 or NLS2 had no effect on nuclear localization, but disruption of both NLS1 and NLS2 resulted in the cytoplasmic accumulation of LRH-1. Either NLS1 or NLS2 alone was sufficient to target LRH-1 to the nucleus. Both NLS1 and NLS2 mediate nuclear transport by a mechanism involving importin α/β. Finally, we showed that three crucial basic clusters in the NLSs are involved in the DNA binding and transcriptional activities of LRH-1. PMID:20853131

  19. Maintenance of liver functions in rat hepatocytes cultured as spheroids in a rotating wall vessel.

    PubMed

    Brown, Lanika A; Arterburn, Linda M; Miller, Ana P; Cowger, Nancy L; Hartley, Sonya M; Andrews, Annette; Silber, Paul M; Li, Albert P

    2003-01-01

    Rat hepatocytes were cultured initially as spheroids on culture plates and then transferred into a rotating wall vessel (high-aspect ratio vessel [HARV]) for further culturing. Morphological evaluation based on electron microscopy showed that hepatocyte spheroids cultured for 30 d in the HARV had a compact structure with tight cell-cell junctions, numerous smooth and rough endoplasmic reticulum, intact mitochondria, and bile canaliculi lined with microvilli. The viability and differentiated properties of the hepatocytes cultured in the HARV were further substantiated by the presence of both phase I oxidation and phase II conjugation drug-metabolizing enzyme activities, as well as albumin synthesis. Homogenates prepared from freshly isolated hepatocytes and hepatocytes cultured in the HARV showed similar cytochrome P450 2B activities measured as pentoxyresorufin-O-dealkylase and testosterone 16beta-hydroxylase. Further, intact hepatocytes cultured in the HARV were found to metabolize chlorzoxazone to 6-hydroxychlorzoxazone; dextromethorphan to dextrorphan, 3-methoxymorphinan, and 3-hydroxymorphinan; midazolam to 1-hydroxymidazolam and 4-hydroxymidazolam; and 7-hydroxycoumarin to its glucuronide and sulfate conjugates. In conclusion, we found that hepatocyte spheroids could be cultured in a HARV to retain cellular and physiological properties of the intact liver, including drug-metabolizing enzyme activities, plasma protein production, and long-term (1 mo) maintenance of viability and cellular function. PMID:12892522

  20. Inhibition of mixed function oxidases in rat liver by trans- and cis-1,2-dichloroethylene.

    PubMed

    Freundt, K J; Macholz, J

    1978-06-01

    A single 8-h exposure to trans-1,2-dichloroethylene (t-DCE) or cis-1,2-dichloroethylene (c-DCE) at 200 ppm (hygienic standard in workplaces) resulted in a significant increase in the hexobarbital sleeping time, the zoxazolamine paralysis time, and the metabolic formation of 4-aminoantipyrine from aminopyrine in adult female Wistar rats. Higher DCE concentrations caused a dose-dependent and substantial enhancement of these effects, the effects of c-DCE being stronger than that of t-DCE. In the course of enzyme-kinetic measurements in isolated rat liver microsomes, t-DCE proved to be a competitive inhibitor of the oxidative N-demethylation of aminopyrine and of the O-demethylation of p-nitroanisole. It is concluded from the results that the inhibition of hepatic drug metabolism is caused by a competitive and reversible interaction of the 2 DCE isomers with the mixed-function oxidase system, the interaction possibly operating at the type I binding site. PMID:684758

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

    PubMed Central

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

    2014-01-01

    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. PMID:24719613

  2. Protective effects of dietary avocado oil on impaired electron transport chain function and exacerbated oxidative stress in liver mitochondria from diabetic rats.

    PubMed

    Ortiz-Avila, Omar; Gallegos-Corona, Marco Alonso; Sánchez-Briones, Luis Alberto; Calderón-Cortés, Elizabeth; Montoya-Pérez, Rocío; Rodriguez-Orozco, Alain R; Campos-García, Jesús; Saavedra-Molina, Alfredo; Mejía-Zepeda, Ricardo; Cortés-Rojo, Christian

    2015-08-01

    Electron transport chain (ETC) dysfunction, excessive ROS generation and lipid peroxidation are hallmarks of mitochondrial injury in the diabetic liver, with these alterations also playing a role in the development of non-alcoholic fatty liver disease (NAFLD). Enhanced mitochondrial sensitivity to lipid peroxidation during diabetes has been also associated to augmented content of C22:6 in membrane phospholipids. Thus, we aimed to test whether avocado oil, a rich source of C18:1 and antioxidants, attenuates the deleterious effects of diabetes on oxidative status of liver mitochondria by decreasing unsaturation of acyl chains of membrane lipids and/or by improving ETC functionality and decreasing ROS generation. Streptozocin-induced diabetes elicited a noticeable increase in the content of C22:6, leading to augmented mitochondrial peroxidizability index and higher levels of lipid peroxidation. Mitochondrial respiration and complex I activity were impaired in diabetic rats with a concomitant increase in ROS generation using a complex I substrate. This was associated to a more oxidized state of glutathione, All these alterations were prevented by avocado oil except by the changes in mitochondrial fatty acid composition. Avocado oil did not prevented hyperglycemia and polyphagia although did normalized hyperlipidemia. Neither diabetes nor avocado oil induced steatosis. These results suggest that avocado oil improves mitochondrial ETC function by attenuating the deleterious effects of oxidative stress in the liver of diabetic rats independently of a hypoglycemic effect or by modifying the fatty acid composition of mitochondrial membranes. These findings might have also significant implications in the progression of NAFLD in experimental models of steatosis. PMID:26060181

  3. Acyl ghrelin acts in the brain to control liver function and peripheral glucose homeostasis in male mice.

    PubMed

    Stark, Romana; Reichenbach, Alex; Lockie, Sarah H; Pracht, Corinna; Wu, Qunli; Tups, Alexander; Andrews, Zane B

    2015-03-01

    Recent evidence suggests that peripheral ghrelin regulates glucose metabolism. Here, we designed experiments to examine how central acyl ghrelin infusion affects peripheral glucose metabolism under pair-fed or ad libitum feeding conditions. Mice received intracerebroventricular (icv) infusion of artificial cerebrospinal fluid (aCSF), ghrelin, and allowed to eat ad libitum (icv ghrelin ad lib) or ghrelin and pair-fed to the aCSF group (icv ghrelin pf). Minipumps delivered acyl ghrelin at a dose of 0.25 μg/h at 0.5 μL/h for 7 days. There was no difference in daily blood glucose, insulin, glucagon, triglycerides, or nonesterified fatty acids. Body weight gain and food intake was significantly higher in icv ghrelin ad lib mice. However, both icv ghrelin ad lib and icv ghrelin pf groups exhibited heavier white adipose mass. Icv ghrelin pf mice exhibited better glucose tolerance than aCSF or icv ghrelin ad lib mice during a glucose tolerance test, although both icv ghrelin ad lib and icv ghrelin pf increased insulin release during the glucose tolerance test. Central acyl ghrelin infusion and pair feeding also increased breakdown of liver glycogen and triglyceride, and regulated genes involved in hepatic lipid and glucose metabolism. Icv ghrelin pf mice had an increase in plasma blood glucose during a pyruvate tolerance test relative to icv ghrelin ad lib or aCSF mice. Our results suggest that under conditions of negative energy (icv ghrelin pf), central acyl ghrelin engages a neural circuit that influences hepatic glucose function. Metabolic status affects the ability of central acyl ghrelin to regulate peripheral glucose homeostasis. PMID:25535832

  4. OAIS Functional Model Conformance Test: A Proposed Measurement

    ERIC Educational Resources Information Center

    Laughton, Paul

    2012-01-01

    Purpose: The purpose of this paper is to develop a test for data centres, repositories and archives to determine OAIS functional model conformance. The test developed was carried out among the World Data Centre (WDC) member data centres. The method used to develop the OAIS functional model conformance test is discussed, along with the test…

  5. Functional Literacy in Schoolchildren. Definition and Criteria of Test Selection.

    ERIC Educational Resources Information Center

    Bessemer, David W.; Spencer, Mary L.

    As part of the development of a functional literacy test for fourth through eigth grade children in Title I compensatory education programs, this report defines functional literacy for children and enumerates criteria for evaluating existing tests. Criteria for selection of a test include: (1) content, empirical, and construct validity; (2)…

  6. 20 CFR 718.103 - Pulmonary function tests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (MVV) is reported, the results of such test shall be obtained independently rather than calculated from the results of the FEV1. (b) All pulmonary function test results submitted in connection with a claim... within 10% of each other shall be sufficient. Pulmonary function test results developed in...

  7. Ubiquitin C-terminal hydrolase 1: A novel functional marker for liver myofibroblasts and a therapeutic target in chronic liver disease

    PubMed Central

    Wilson, Caroline L.; Murphy, Lindsay B.; Leslie, Jack; Kendrick, Stuart; French, Jeremy; Fox, Christopher R.; Sheerin, Neil S.; Fisher, Andrew; Robinson, John H.; Tiniakos, Dina G.; Gray, Douglas A.; Oakley, Fiona; Mann, Derek A.

    2016-01-01

    Background & Aims Ubiquitination is a reversible protein modification involved in the major cellular processes that define cell phenotype and behaviour. Ubiquitin modifications are removed by a large family of proteases named deubiquitinases. The role of deubiquitinases in hepatic stellate cell (HSC) activation and their contribution to fibrogenesis are poorly defined. We have identified that the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) is highly induced following HSC activation, determined its function in activated HSC and its potential as a therapeutic target for fibrosis. Methods Deubiquitinase expression was determined in day 0 and day 10 HSC. Increased UCHL1 expression was confirmed in human HSC and in an alcoholic liver disease (ALD) patient liver. The importance of UCHL1 in hepatic fibrosis was investigated in CCl4 and bile duct ligation injured mice using a pharmacological inhibitor (LDN 57444). The effects of UCHL1 inhibition on HSC proliferation were confirmed by Western blot and 3H thymidine incorporation. Results Here we report that pharmacological inhibition of UCHL1 blocks progression of established fibrosis in CCl4 injured mice. UCHL1 siRNA knockdown, LDN 57444 treatment, or HSC isolated from UCHL1–/– mice show attenuated proliferation in response to the mitogen, platelet-derived growth factor. Additionally, we observed changes in the phosphorylation of the cell cycle regulator retinoblastoma protein (Rb) in the absence of UCHL1 highlighting a potential mechanism for the reduced proliferative response. Conclusions UCHL1 expression is highly upregulated upon HSC activation and is involved in the regulation of HSC proliferation. This study highlights therapeutic opportunities for pharmacological targeting of UCHL1 in chronic liver disease. PMID:26264933

  8. Magnesium isoglycyrrhizinate inhibits inflammatory response through STAT3 pathway to protect remnant liver function

    PubMed Central

    Tang, Guang-Hua; Yang, Hua-Yu; Zhang, Jin-Chun; Ren, Jin-Jun; Sang, Xin-Ting; Lu, Xin; Zhong, Shou-Xian; Mao, Yi-Lei

    2015-01-01

    AIM: To investigate the protective effect of magnesium isoglycyrrhizinate (MgIG) on excessive hepatectomy animal model and its possible mechanism. METHODS: We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond’s method, in which the left, middle, right upper, and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups, and were injected intraperitoneally with 3 mL saline (control group), 30 mg/kg (low-dose group) and 60 mg/kg (high-dose group) of MgIG, respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl endopeptidase, total bilirubin (TBil), direct bilirubin (DBil), total protein, albumin, blood glucose (Glu), hyper-sensitivity C-reactive protein, prothrombin time (PT), and thrombin time (TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines (IL-1, IL-6, IL-10, and iNOS) was analyzed by ELISA. STAT3 protein and mRNA were analyzed by Western blot and quantitative reverse-transcription PCR, respectively. RESULTS: The high-dose group demonstrated a significantly prolonged survival time, compared with both the control and the low-dose groups (22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h, P = 0.018). There were significant differences among the groups in ALT, Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the MgIG treated groups than in the control group. Both Glu and PT levels were significantly higher in the MgIG treated groups than in the control group. At 12 h, ALT, AST, TBil, DBil and TT levels showed significant differences between the MgIG treated groups and the control group. No significant

  9. Human Liver Progenitor Cells for Liver Repair

    PubMed Central

    Lombard, Catherine A.; Prigent, Julie; Sokal, Etienne M.

    2013-01-01

    Because of their high proliferative capacity, resistance to cryopreservation, and ability to differentiate into hepatocyte-like cells, stem and progenitor cells have recently emerged as attractive cell sources for liver cell therapy, a technique used as an alternative to orthotopic liver transplantation in the treatment of various hepatic ailments ranging from metabolic disorders to end-stage liver disease. Although stem and progenitor cells have been isolated from various tissues, obtaining them from the liver could be an advantage for the treatment of hepatic disorders. However, the techniques available to isolate these stem/progenitor cells are numerous and give rise to cell populations with different morphological and functional characteristics. In addition, there is currently no established consensus on the tests that need to be performed to ensure the quality and safety of these cells when used clinically. The purpose of this review is to describe the different types of liver stem/progenitor cells currently reported in the literature, discuss their suitability and limitations in terms of clinical applications, and examine how the culture and transplantation techniques can potentially be improved to achieve a better clinical outcome. PMID:26858860

  10. Autoimmune liver disease panel

    MedlinePlus

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider diagnose ...

  11. Patterns and Predictors of Sexual Function After Liver Donation: the Adult to Adult Living Donor Liver Transplantation Cohort Study (A2ALL)

    PubMed Central

    DiMartini, AF.; Dew, MA.; Butt, Z.; Simpson, MA.; Ladner, DP.; Smith, AR.; Hill-Callahan, P.; Gillespie, BW.

    2015-01-01

    Although sexual functioning is an important facet of living donor quality of life, it has not received extensive evaluation in this population. Using data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, we examined donor sexual functioning across the donation process from the predonation evaluation to 3 months and 1 year postdonation. Donors (n=208) and a comparison group of non-donors (n=155) completed self-reported surveys with specific questions on sexual desire, satisfaction, orgasm, and (for men) erectile function. Across the three time points, donor sexual functioning was lower at the evaluation phase and 3 months postdonation than at one year postdonation. In the early recovery period, abdominal pain was associated with difficulty reaching orgasm (OR = 3.98, 95% CI 1.30–12.16), concerns over appearance with lower sexual desire (OR = 4.14, 95% CI 1.02–16.79), and not feeling back to normal was associated with dissatisfaction with sexual life (OR 3.58, 95% CI 1.43–8.99). Efforts to educate donors before the surgery and prepare them for the early recovery phase may improve recovery and reduce distress regarding sexual functioning. PMID:25779554

  12. Controlled formation of heterotypic hepatic micro-organoids in anisotropic hydrogel microfibers for long-term preservation of liver-specific functions.

    PubMed

    Yamada, Masumi; Utoh, Rie; Ohashi, Kazuo; Tatsumi, Kohei; Yamato, Masayuki; Okano, Teruo; Seki, Minoru

    2012-11-01

    We have developed a hydrogel-based cell cultivation platform for forming 3D restiform hepatic micro-organoids consisting of primary rat hepatocytes and feeder cells (Swiss 3T3 cells). Sodium alginate solutions containing hepatocytes/3T3 cells were continuously introduced into a microfluidic channel to produce cell-incorporating anisotropic Ba-alginate hydrogel microfibers, where hepatocytes at the center were closely sandwiched by 3T3 cells. Hydrogel fiber-based cultivation under high oxygen tension enabled the formation of heterotypic micro-organoids with a length of up to 1 mm and a diameter of ∼50 μm, mimicking the hepatic cord structures found in the liver, while maintaining a high hepatocyte viability (∼80%) over 30 days. Long-term observation of up to 90 days revealed a significant enhancement of hepatic functions because of heterotypic and homotypic cell-cell interactions, including albumin secretion and urea synthesis as well as expression of hepatocyte-specific genes, compared with conventional monolayer culture and single cultivation in the hydrogel fibers. The encapsulated hepatic constructs were recovered as scaffold-free micro-organoids by enzymatically digesting the hydrogel matrices using alginate lyase. This technique for creating heterotypic micro-organoids with precisely ordered multiple cell types will be useful for the development of a new liver tissue engineering approach and may be applicable to the fabrication of extracorporeal bioartificial liver (BAL) devices and assessment tools for drug development and testing. PMID:22906609

  13. Modification of the association of bisphenol A with abnormal liver function by polymorphisms of oxidative stress-related genes.

    PubMed

    Kim, Jin Hee; Lee, Mee-Ri; Hong, Yun-Chul

    2016-05-01

    Some studies suggested oxidative stress as a possible mechanism for the relation between exposure to bisphenol A (BPA) and liver damage. Therefore, we evaluated modification of genetic polymorphisms of cyclooxygenase 2 (COX2 or PTGS2), epoxide hydrolase 1 (EPHX1), catalase (CAT), and superoxide dismutase 2 (SOD2 or MnSOD), which are oxidative stress-related genes, on the relation between exposure to BPA and liver function in the elderly. We assessed the association of visit-to-visit variations in BPA exposure with abnormal liver function by each genotype or haplotype after controlling for age, sex, BMI, alcohol consumption, exercise, urinary cotinine levels, and low density lipoprotein cholesterol using a GLIMMIX model. A significant association of BPA with abnormal liver function was observed only in participants with COX2 GG genotype at rs5277 (odds ratio (OR)=3.04 and p=0.0231), CAT genotype at rs769218 (OR=4.16 and p=0.0356), CAT CT genotype at rs769217 (OR=4.19 and p=0.0348), SOD2 TT genotype at rs4880 (OR=2.59 and p=0.0438), or SOD2 GG genotype at rs2758331 (OR=2.57 and p=0.0457). Moreover, we also found higher OR values in participants with a pair of G-G haplotypes for COX2 (OR=2.81 and p=0.0384), G-C-A haplotype for EPHX1 (OR=4.63 and p=0.0654), A-T haplotype for CAT (OR=4.48 and p=0.0245), or T-G-A haplotype for SOD2 (OR=2.91 and p=0.0491) compared with those with the other pair of haplotypes for each gene. Furthermore, the risk score composed of 4 risky pair of haplotypes showed interactive effect with BPA on abnormal liver function (p=0.0057). Our study results suggest that genetic polymorphisms of COX2, EPHX1, CAT, and SOD2 modify the association of BPA with liver function. PMID:26922413

  14. Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis.

    PubMed

    Iff, Joël; Wang, Wei; Sajic, Tatjana; Oudry, Nathalie; Gueneau, Estelle; Hopfgartner, Gérard; Varesio, Emmanuel; Szanto, Ildiko

    2009-10-01

    Increased inflammatory signaling is a key feature of metabolic disorders. In this context, the role of increased pro-inflammatory signals has been extensively studied. By contrast, no efforts have been dedicated to study the contrasting scenario: the attenuation of anti-inflammatory signals and their role in metabolic homeostasis. IL-4 and IL-13 are anti-inflammatory cytokines signaling through the Signal Transducer and Activator of Transcription 6 (STAT6). Our study was aimed at evaluating the lack of STAT6 signaling on liver homeostasis. To this end we analyzed the liver proteome of wild type and STAT6 knock-out mice using 2D nanoscale LC-MS/MS with iTRAQ labeling technique. The coordinated changes in proteins identified by this quantitative proteome analysis indicated disturbed lipid homeostasis and a state of hepatocellular stress. Most significantly, the expression of the liver fatty acid binding protein (FABP1) was increased in the knock-out mice. In line with the elevated FABP1 expression we found latent liver lipid accumulation in the STAT6-deficient mice which was further aggravated when mice were challenged by a high fat diet. In conclusion, our study revealed a so far uncharacterized role for STAT6 in regulating liver lipid homeostasis and demonstrates the importance of anti-inflammatory signaling in the defense against the development of liver steatosis. PMID:19663508

  15. A Comparison of Statistical Significance Tests for Selecting Equating Functions

    ERIC Educational Resources Information Center

    Moses, Tim

    2009-01-01

    This study compared the accuracies of nine previously proposed statistical significance tests for selecting identity, linear, and equipercentile equating functions in an equivalent groups equating design. The strategies included likelihood ratio tests for the loglinear models of tests' frequency distributions, regression tests, Kolmogorov-Smirnov…

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

    PubMed Central

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

    2012-01-01

    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 MIP1α and MCP-1, as well as cytokines that modulate DC activation, including TNFα, IL-6 and IL-1β. 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 MIP1α 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. PMID:22962681

  17. Liver Regeneration

    PubMed Central

    Michalopoulos, George K.

    2009-01-01

    Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other. PMID:17559071

  18. Axial force measurement for esophageal function testing.

    PubMed

    Gravesen, Flemming H; Funch-Jensen, Peter; Gregersen, Hans; Drewes, Asbjørn Mohr

    2009-01-14

    The esophagus serves to transport food and fluid from the pharynx to the stomach. Manometry has been the "golden standard" for the diagnosis of esophageal motility diseases for many decades. Hence, esophageal function is normally evaluated by means of manometry even though it reflects the squeeze force (force in radial direction) whereas the bolus moves along the length of esophagus in a distal direction. Force measurements in the longitudinal (axial) direction provide a more direct measure of esophageal transport function. The technique used to record axial force has developed from external force transducers over in-vivo strain gauges of various sizes to electrical impedance based measurements. The amplitude and duration of the axial force has been shown to be as reliable as manometry. Normal, as well as abnormal, manometric recordings occur with normal bolus transit, which have been documented using imaging modalities such as radiography and scintigraphy. This inconsistency using manometry has also been documented by axial force recordings. This underlines the lack of information when diagnostics are based on manometry alone. Increasing the volume of a bag mounted on a probe with combined axial force and manometry recordings showed that axial force amplitude increased by 130% in contrast to an increase of 30% using manometry. Using axial force in combination with manometry provides a more complete picture of esophageal motility, and the current paper outlines the advantages of using this method. PMID:19132762

  19. Testing the functional significance of tail streamers

    PubMed Central

    Evans, M. R.; Thomas, A. L. R.

    1997-01-01

    Studies of the evolution of elaborate ornaments have concentrated on their role in increasing attractiveness to mates. The classic examples of such sexually selected structures are the elongated tails of some bird species. Elongated tails can be divided into three categories: graduated tails, pin tails and streamers. There seems to be little debate about whether graduated and pin tails are ornaments; i.e. costly signals used in mate choice. However, in the case of streamers there is considerable discussion about their function. It has been suggested that tail streamers could be (i) entirely naturally selected, (ii) entirely sexually selected, (iii) partly naturally and partly sexually selected. The prime example of a species with tail streamers is the swallow (Hirundo rustica) in which both sexes have tail streamers. In this paper we discuss the aerodynamic consequences of different types of manipulation of the streamer and/or outer tail feather. We make qualitative predictions about the aerodynamic performance of swallows with manipulated tail streamers; these predictions differ depending on whether streamers have a naturally or sexually selected function. We demonstrate that these hypotheses can only be separated if tail streamers are shortened and changes in aerodynamic performance measured during turning flight.

  20. Effects of acute exercise on liver function and blood redox status in heavy drinkers

    PubMed Central

    GEORGAKOULI, KALLIOPI; MANTHOU, EIRINI; FATOUROS, IOANNIS G.; DELI, CHARIKLIA K.; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.; KOURETAS, DEMETRIOS; KOUTEDAKIS, YIANNIS; THEODORAKIS, YANNIS; JAMURTAS, ATHANASIOS Z.

    2015-01-01

    Excessive alcohol consumption can induce oxidative stress, resulting in the development of several diseases. Exercise has been reported to prevent and/or improve a number of health issues through several mechanisms, including an improvement in redox status. It has also been previously suggested that exercise can help individuals with alcohol use disorders reduce their alcohol intake; however, research in this field is limited. The aim of the present study was to investigage the effects of acute exercise of moderate intensity on the liver function and blood redox status in heavy drinkers. For this purpose, a total of 17 heavy drinkers [age, 31.6±3.2 years; body mass index (BMI), 27.4±0.8 kg/m2; experimental group (EG)] and 17 controls [age, 33.5±1.3 years; BMI, 26.1±1.4 kg/m2; control group (CG), who did not exceed moderate alcohol consumption], underwent one trial of acute exercise of moderate intensity (50–60% of the heart rate reserve) for 30 min on a cycle ergometer, following an overnight fast, and abstaining from smoking and alcohol consumption. Blood samples were obtained before and immediately after exercise for later determination of the indices of liver function and blood redox status. The subjects in the EG had significantly higher (p<0.05) baseline γ-glutamyl transferase (γ-GT) levels compared to the subjects in the CG. Exercise thus resulted in significantly higher γ-GT levels (p<0.005) only in the EG. No significant differences in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) baseline levels were observed between the 2 groups. Following exercise, the AST levels increased significantly (p<0.001) in both groups, whereas the ALT levels increased significantly (p<0.01) only in the EG. The baseline glutathione (GSH) levels were significantly lower (p<0.05) and remained low following exercise in the EG. In addition, we observed a trend for higher (p=0.07) baseline levels of thiobarbituric acid-reactive substances (TBARS), which

  1. Fibrosis progression under maintenance interferon in hepatitis C is better detected by blood test than liver morphometry.

    PubMed

    Calès, P; Zarski, J P; Chapplain, J Marc; Bertrais, S; Sturm, N; Michelet, C; Babany, G; Chaigneau, J; Eddine Charaf, M

    2012-02-01

    We evaluated whether quantitative measurements of liver fibrosis with recently developed diagnostics outperform histological staging in detecting natural or interferon-induced changes. We compared Metavir staging, morphometry (area and fractal dimension) and six blood tests in 157 patients with chronic hepatitis C from two trials testing maintenance interferon for 96 weeks. Paired liver biopsies and blood tests were available for 101 patients, and there was a significant improvement in Metavir activity and a significant increase in blood tests reflecting fibrosis quantity in patients treated with interferon when compared with controls - all per cent changes in histological fibrosis measures were significantly increased in F1 vs F2-4 stages only in the interferon group. For the whole population studied between weeks 0 and 96, there was significant progression only in the area of fibrosis (AOF) (P = 0.026), FibroMeter (P = 0.020) and CirrhoMeter (P = 0.003). With regards to dynamic reproducibility, agreement was good (r(ic) ≥ 0.72) only for Metavir fibrosis score, FibroMeter and CirrhoMeter. The per cent change in AOF was significantly higher than that of fractal dimension (P = 0.003) or Metavir fibrosis score (P = 0.015). CirrhoMeter was the only blood test with a change significantly higher than that of AOF (P = 0.039). AOF and two blood tests, reflecting fibrosis quantity, have high sensitivity and/or reproducibility permitting the detection of a small progression in liver fibrosis over two years. A blood test reflecting fibrosis quantity is more sensitive and reproducible than morphometry. The study also shows that maintenance interferon does not improve fibrosis, whatever its stage. PMID:22239512

  2. [The effect of altan on the functional activity of the liver mitochondria and microsomes from rats with toxic hepatitis].

    PubMed

    Gordienko, A D; Iakovleva, L V

    1999-01-01

    In in vitro experiments althan had no effect on the respiration of intact mitochondria in state 4 according to Chance and produced a high antioxidant effect in fermentative and ascorbate-dependent lipid peroxidation in intact microsomes isolated from the rat liver. In ethanol-induced toxic hepatitis althan restored the functional activity of mitochondria to the level of that in intact animals and increased microsome hydroxylase activity in CCl4-hepatitis. PMID:10513340

  3. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.

    PubMed

    Inoue, Kenji; Ochi, Akimu; Koda, Akira; Wako, Yumi; Kawasako, Kazufumi; Doi, Takaaki

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs. PMID:24768639

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    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

    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. PMID:23519077

  6. Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver

    PubMed Central

    Nakajima, Mayuka; Arimatsu, Kei; Kato, Tamotsu; Matsuda, Yumi; Minagawa, Takayoshi; Takahashi, Naoki; Ohno, Hiroshi; Yamazaki, Kazuhisa

    2015-01-01

    Although periodontitis has been implicated as a risk factor for various systemic diseases, the precise mechanisms by which periodontitis induces systemic disease remain to be elucidated. We have previously revealed that repeated oral administration of Porphyromonas gingivalis elicits endotoxemia via changes in the gut microbiota of the ileum, and thereby induces systemic inflammation and insulin resistance. However, it is not clear to what extent a single administration of P. gingivalis could affect gut microbiota composition, gut barrier function, and subsequent influx of gut microbiota into the liver. Therefore, in the present study, C57BL/6 mice were orally administered P. gingivalis (strain W83) once and compared to sham-inoculated mice. The phylogenetic structure and diversity of microbial communities in the gut and liver were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum endotoxin activity was determined by a Limulus amebocyte lysate test. Gene expression in the intestine and expression of 16S rRNA genes in the blood and liver were examined by quantitative polymerase chain reaction. Administration of P. gingivalis significantly altered gut microbiota, with an increased proportion of phylum Bacteroidetes, a decreased proportion of phylum Firmicutes, and increased serum endotoxin levels. In the intestinal tissues, gene expression of tjp-1 and occludin, which are involved in intestinal permeability, were downregulated. Higher amounts of bacterial DNA were detected in the liver of infected mice. Importantly, changes in gut microbiota preceded systemic inflammatory changes. These results further support the idea that disturbance of the gut microbiota composition by orally derived periodontopathic bacteria may be a causal mechanism linking periodontitis and systemic disease. PMID:26218067

  7. Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and Impaired Barrier Function Leading to Dissemination of Enterobacteria to the Liver.

    PubMed

    Nakajima, Mayuka; Arimatsu, Kei; Kato, Tamotsu; Matsuda, Yumi; Minagawa, Takayoshi; Takahashi, Naoki; Ohno, Hiroshi; Yamazaki, Kazuhisa

    2015-01-01

    Although periodontitis has been implicated as a risk factor for various systemic diseases, the precise mechanisms by which periodontitis induces systemic disease remain to be elucidated. We have previously revealed that repeated oral administration of Porphyromonas gingivalis elicits endotoxemia via changes in the gut microbiota of the ileum, and thereby induces systemic inflammation and insulin resistance. However, it is not clear to what extent a single administration of P. gingivalis could affect gut microbiota composition, gut barrier function, and subsequent influx of gut microbiota into the liver. Therefore, in the present study, C57BL/6 mice were orally administered P. gingivalis (strain W83) once and compared to sham-inoculated mice. The phylogenetic structure and diversity of microbial communities in the gut and liver were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum endotoxin activity was determined by a Limulus amebocyte lysate test. Gene expression in the intestine and expression of 16S rRNA genes in the blood and liver were examined by quantitative polymerase chain reaction. Administration of P. gingivalis significantly altered gut microbiota, with an increased proportion of phylum Bacteroidetes, a decreased proportion of phylum Firmicutes, and increased serum endotoxin levels. In the intestinal tissues, gene expression of tjp-1 and occludin, which are involved in intestinal permeability, were downregulated. Higher amounts of bacterial DNA were detected in the liver of infected mice. Importantly, changes in gut microbiota preceded systemic inflammatory changes. These results further support the idea that disturbance of the gut microbiota composition by orally derived periodontopathic bacteria may be a causal mechanism linking periodontitis and systemic disease. PMID:26218067

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

    PubMed Central

    Hassan, Abeer; Tsuda, Yasuhiro; Asai, Akira; Yokohama, Keisuke; Nakamura, Ken; Sujishi, Tetsuya; Ohama, Hideko; Tsuchimoto, Yusuke; Fukunishi, Shinya; Abdelaal, Usama M.; Arafa, Usama A.; Hassan, Ali T.; Kassem, Ali M.; Higuchi, Kazuhide

    2015-01-01

    Transarterial chemoembolization (TACE) is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions. Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE. Results. The L-carnitine group maintained Child-Pugh (CP) score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P < 0.01). Conversely, the control group reported a significant CP score deterioration at 1 week (P < 0.05) and 12 weeks after TACE (P < 0.05). L-carnitine suppressed serum albumin deterioration at 1 week after TACE. There were significant differences between L-carnitine and control groups regarding mean serum albumin changes from baseline to 1 week (P < 0.05) and 4 weeks after TACE (P < 0.05). L-carnitine caused prothrombin time improvement from baseline to 1, 4 (P < 0.05), and 12 weeks after TACE. Total bilirubin mean changes from baseline to 1 week after TACE exhibited significant differences between L-carnitine and control groups (P < 0.05). The hepatoprotective effects of L-carnitine were enhanced by branched chain amino acids combination. Conclusion. L-carnitine maintained and improved liver functions after TACE. PMID:26664151

  9. Characterization of the effects of erythromycin estolate and erythromycin base on the excretory function of the isolated rat liver

    SciTech Connect

    Gaeta, G.B.; Utili, R.; Adinolfi, L.E.; Abernathy, C.O.; Giusti, G.

    1985-09-15

    To investigate the mechanisms of erythromycin cholestasis, the effects of erythromycin estolate (EE) on the excretory function of the isolated perfused rat liver and on liver plasma membrane (LM) preparations were studied and compared to those of erythromycin base (EB) and lauryl sulfate (LS), added alone or in combination. EE (at 125 to 200 microM) caused dose-dependent reductions of bile and perfusate flows, bile acid (BA) excretion, and biliary BA concentration. The alterations of the excretory function were only in part due to the decreased perfusate flow. In contrast, both 200 and 300 microM concentrations of EB elicited similar choleretic responses, which were presumably related to the osmotic activity of the drug excreted in the bile. LS did not affect hepatic excretory functions. However, the simultaneous addition of EB and LS resulted in a rate of bile flow lower than that observed with EB alone. EE, but not EB, increased canalicular permeability to (/sup 14/C)sucrose as measured by bile to plasma (B:P) ratio. Neither drugs altered (/sup 14/C)erythritol B:P ratio. In LM preparations both Na+,K+- and Mg2+-ATPase activities were inhibited in a dose-dependent manner by EE, but not by EB. The data suggest that EE could affect bile flow by inhibiting cotransport of Na+ and BA and by altering LM permeability and support the view that the effect of erythromycins on the liver may be related to their surface activity.

  10. Cement Dust Exposure and Perturbations in Some Elements and Lung and Liver Functions of Cement Factory Workers

    PubMed Central

    Richard, Egbe Edmund; Augusta Chinyere, Nsonwu-Anyanwu; Jeremaiah, Offor Sunday; Opara, Usoro Chinyere Adanna; Henrieta, Etukudo Maise; Ifunanya, Egbe Deborah

    2016-01-01

    Background. Cement dust inhalation is associated with deleterious health effects. The impact of cement dust exposure on the peak expiratory flow rate (PEFR), liver function, and some serum elements in workers and residents near cement factory were assessed. Methods. Two hundred and ten subjects (50 workers, 60 residents, and 100 controls) aged 18–60 years were studied. PEFR, liver function {aspartate and alanine transaminases (AST and ALT) and total and conjugated bilirubin (TB and CB)}, and serum elements {lead (Pb), copper (Cu), manganese (Mn), iron (Fe), cadmium (Cd), selenium (Se), chromium (Cr), zinc (Zn), and arsenic (As)} were determined using peak flow meter, colorimetry, and atomic absorption spectrometry, respectively. Data were analysed using ANOVA and correlation at p = 0.05. Results. The ALT, TB, CB, Pb, As, Cd, Cr, Se, Mn, and Cu were significantly higher and PEFR, Fe, and Zn lower in workers and residents compared to controls (p < 0.05). Higher levels of ALT, AST, and Fe and lower levels of Pb, Cd, Cr, Se, Mn, and Cu were seen in cement workers compared to residents (p < 0.05). Negative correlation was observed between duration of exposure and PEFR (r = −0.416, p = 0.016) in cement workers. Conclusions. Cement dust inhalation may be associated with alterations in serum elements levels and lung and liver functions while long term exposure lowers peak expiratory flow rate. PMID:26981118

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

    PubMed Central

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

    2015-01-01

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

  12. Effects of the pesticide methoxychlor on gene expression in the liver and testes of the male largemouth bass (Micropterus salmoides)

    PubMed Central

    Blum, Jason L.; Nyagode, Beatrice A.; James, Margaret O.; Denslow, Nancy D.

    2010-01-01

    The organochlorine pesticide methoxychlor (MXC) is an environmental estrogen known to stimulate the expression of the egg-yolk protein, vitellogenin (Vtg) in fish species. To begin to understand the underlying mechanisms for how MXC exerts its deleterious effects on the endocrine system, male largemouth bass (Micropterus salmoides) were treated with 2.5, 10, or 25 mg/kg MXC and compared to fish pair-treated with 1 mg/kg 17β-estradiol (E2), and vehicle control. Fish were sacrificed 24, 48, or 72 h following treatment. The liver and testes were then assayed for changes in expression of the three bass estrogen receptors (ERs α, βa, and βb) in tissues, as well as Vtg and cytochrome P450 (CYP) 3A isoform 68 in the liver and steroidogenic acute regulatory protein (StAR) in the testes. In the liver, significant increases in gene expression were seen for each of the genes measured by 24 h and each returned to the level of the vehicle by 72 h. Total testosterone 6β-hydroxylase activity, reflective of CYP3A activity, was also increased by 24 h for all of the exposures. In the testes, ERα was unaffected by any treatment, ERβa was upregulated only by MXC, peaking at 24 h for the 2.5 and 10 mg/kg MXC and at 48 h for the 25 mg/kg MXC treatment. By 72 h, the MXC effects had disappeared, while E2 significantly decreased the expression of ERβa mRNA. ERβb expression in the testes was stimulated by all concentrations of MXC by 24 h and the effect remained up to 72 h, whereas E2 had no effect. Finally, StAR expression was found to also be decreased by E2 and all MXC treatments. However, the effect on StAR expression by E2 occurred within 24 h, while the effect by all concentrations of MXC was not seen until 72 h after treatment. The stimulatory effects of E2 and 25 mg/kg MXC on the expression of the ERs in the liver were opposite to the responses seen in the testes, suggesting an inverted relationship between these two tissue types. These results provide a possible mechanism

  13. Genetic Variations in the Promoter of the APE1 Gene Are Associated with DMF-Induced Abnormal Liver Function: A Case-Control Study in a Chinese Population.

    PubMed

    Tong, Zhimin; Shen, Huanxi; Yang, Dandan; Zhang, Feng; Bai, Ying; Li, Qian; Shi, Jian; Zhang, Hengdong; Zhu, Baoli

    2016-01-01

    Acute or long-term exposure to N,N-dimethylformamide (DMF) can induce abnormal liver function. It is well known that DMF is mainly metabolized in the liver and thereby produces reactive oxygen species (ROS). The base excision repair (BER) pathway is regarded as a very important pathway involved in repairing ROS-induced DNA damage. Several studies have explored the associations between GSTM1, GSTT1, CYP2E1 polymorphisms and DMF-induced abnormal liver function; however, little is known about how common hOGG1, XRCC1 and APE1 polymorphisms and DMF induce abnormal liver function. The purpose of this study was to investigate whether the polymorphisms in the hOGG1 (rs159153 and rs2072668), XRCC1 (rs25487, rs25489, and rs1799782), APE1 (rs1130409 and 1760944) genes in the human BER pathway were associated with the susceptibility to DMF-induced abnormal liver function in a Chinese population. These polymorphisms were genotyped in 123 workers with DMF-induced abnormal liver function and 123 workers with normal liver function. We found that workers with the APE1 rs1760944 TG/GG genotypes had a reduced risk of abnormal liver function, which was more pronounced in the subgroups that were exposed to DMF for <10 years, exposed to ≥10 mg/m³ DMF, never smoked and never drank. In summary, our study supported the hypothesis that the APE1 rs1760944 T > G polymorphism may be associated with DMF-induced abnormal liver function in the Chinese Han population. PMID:27463724

  14. Genetic Variations in the Promoter of the APE1 Gene Are Associated with DMF-Induced Abnormal Liver Function: A Case-Control Study in a Chinese Population

    PubMed Central

    Tong, Zhimin; Shen, Huanxi; Yang, Dandan; Zhang, Feng; Bai, Ying; Li, Qian; Shi, Jian; Zhang, Hengdong; Zhu, Baoli

    2016-01-01

    Acute or long-term exposure to N,N-dimethylformamide (DMF) can induce abnormal liver function. It is well known that DMF is mainly metabolized in the liver and thereby produces reactive oxygen species (ROS). The base excision repair (BER) pathway is regarded as a very important pathway involved in repairing ROS-induced DNA damage. Several studies have explored the associations between GSTM1, GSTT1, CYP2E1 polymorphisms and DMF-induced abnormal liver function; however, little is known about how common hOGG1, XRCC1 and APE1 polymorphisms and DMF induce abnormal liver function. The purpose of this study was to investigate whether the polymorphisms in the hOGG1 (rs159153 and rs2072668), XRCC1 (rs25487, rs25489, and rs1799782), APE1 (rs1130409 and 1760944) genes in the human BER pathway were associated with the susceptibility to DMF-induced abnormal liver function in a Chinese population. These polymorphisms were genotyped in 123 workers with DMF-induced abnormal liver function and 123 workers with normal liver function. We found that workers with the APE1 rs1760944 TG/GG genotypes had a reduced risk of abnormal liver function, which was more pronounced in the subgroups that were exposed to DMF for <10 years, exposed to ≥10 mg/m3 DMF, never smoked and never drank. In summary, our study supported the hypothesis that the APE1 rs1760944 T > G polymorphism may be associated with DMF-induced abnormal liver function in the Chinese Han population. PMID:27463724

  15. Significance tests for functional data with complex dependence structure

    PubMed Central

    Lahiri, Soumen N.; Carroll, Raymond J.

    2015-01-01

    We propose an L2-norm based global testing procedure for the null hypothesis that multiple group mean functions are equal, for functional data with complex dependence structure. Specifically, we consider the setting of functional data with a multilevel structure of the form groups–clusters or subjects–units, where the unit-level profiles are spatially correlated within the cluster, and the cluster-level data are independent. Orthogonal series expansions are used to approximate the group mean functions and the test statistic is estimated using the basis coefficients. The asymptotic null distribution of the test statistic is developed, under mild regularity conditions. To our knowledge this is the first work that studies hypothesis testing, when data have such complex multilevel functional and spatial structure. Two small-sample alternatives, including a novel block bootstrap for functional data, are proposed, and their performance is examined in simulation studies. The paper concludes with an illustration of a motivating experiment. PMID:26023253

  16. Coaching patients during pulmonary function testing: A practical guide.

    PubMed

    Cheung, Heidi J; Cheung, Lawrence

    2015-01-01

    Pulmonary function tests are an important tool to assist in the diagnosis and management of patients with respiratory disease. Ensuring that the tests are of acceptable quality is vital. Acceptable pulmonary function test quality requires, among others, optimal patient performance. Optimal patient performance, in turn, requires adequate coaching from registered respiratory therapists (RRTs) and other pulmonary function laboratory personnel. The present article provides techniques and tips to help RRTs coach patients during testing. The authors briefly review the components of pulmonary function testing, then describe factors that may hinder a patient's performance, list common mistakes that patients make during testing, and provide tips that RRTs can use to help patients optimize their performance. PMID:26283871

  17. The effect of ZnO nanoparticles on liver function in rats

    PubMed Central

    Tang, Hua-Qiao; Xu, Min; Rong, Qian; Jin, Ru-Wen; Liu, Qi-Ji; Li, Ying-Lun

    2016-01-01

    Zinc oxide (ZnO) is widely incorporated as a food additive in animal diets. In order to optimize the beneficial effects of ZnO and minimize any resultant environmental pollution, ZnO nanoparticles are often used for delivery of the zinc. However, the possible toxic effects of ZnO nanoparticles, including effects on cytochrome P450 (CYP450) enzymes, have not been evaluated. In this study, we investigated the effect of ZnO nanoparticles, in doses used in animal feeds, on CYP450 enzymes, liver and intestinal enzymes, liver and kidney histopathology, and hematologic indices in rats. We found that liver and kidney injury occurred when the concentrations of ZnO nanoparticles in feed were 300–600 mg/kg. Also, liver mRNA expression for constitutive androstane receptor was suppressed and mRNA expression for pregnane X receptor was induced when feed containing ZnO nanoparticles was given at a concentration of 600 mg/kg. Although the expression of mRNA for CYP 2C11 and 3A2 enzymes was induced by ZnO nanoparticles, the activities of CYP 2C11 and 3A2 were suppressed. While liver CYP 1A2 mRNA expression was suppressed, CYP 1A2 activity remained unchanged at all ZnO nanoparticle doses. Therefore, it has been concluded that ZnO nanoparticles, in the doses customarily added to animal feed, changed the indices of hematology and blood chemistry, altered the expression and activity of hepatic CYP enzymes, and induced pathological changes in liver and kidney tissues of rats. These findings suggest that greater attention needs to be paid to the toxic effects of ZnO nanoparticles in animal feed, with the possibility that the doses of ZnO should be reduced. PMID:27621621

  18. The effect of ZnO nanoparticles on liver function in rats.

    PubMed

    Tang, Hua-Qiao; Xu, Min; Rong, Qian; Jin, Ru-Wen; Liu, Qi-Ji; Li, Ying-Lun

    2016-01-01

    Zinc oxide (ZnO) is widely incorporated as a food additive in animal diets. In order to optimize the beneficial effects of ZnO and minimize any resultant environmental pollution, ZnO nanoparticles are often used for delivery of the zinc. However, the possible toxic effects of ZnO nanoparticles, including effects on cytochrome P450 (CYP450) enzymes, have not been evaluated. In this study, we investigated the effect of ZnO nanoparticles, in doses used in animal feeds, on CYP450 enzymes, liver and intestinal enzymes, liver and kidney histopathology, and hematologic indices in rats. We found that liver and kidney injury occurred when the concentrations of ZnO nanoparticles in feed were 300-600 mg/kg. Also, liver mRNA expression for constitutive androstane receptor was suppressed and mRNA expression for pregnane X receptor was induced when feed containing ZnO nanoparticles was given at a concentration of 600 mg/kg. Although the expression of mRNA for CYP 2C11 and 3A2 enzymes was induced by ZnO nanoparticles, the activities of CYP 2C11 and 3A2 were suppressed. While liver CYP 1A2 mRNA expression was suppressed, CYP 1A2 activity remained unchanged at all ZnO nanoparticle doses. Therefore, it has been concluded that ZnO nanoparticles, in the doses customarily added to animal feed, changed the indices of hematology and blood chemistry, altered the expression and activity of hepatic CYP enzymes, and induced pathological changes in liver and kidney tissues of rats. These findings suggest that greater attention needs to be paid to the toxic effects of ZnO nanoparticles in animal feed, with the possibility that the doses of ZnO should be reduced. PMID:27621621

  19. Liver bioengineering

    PubMed Central

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

    2014-01-01

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

  20. Memory Hazard Functions: A Vehicle for Theory Development and Test

    ERIC Educational Resources Information Center

    Chechile, Richard A.

    2006-01-01

    A framework is developed to rigorously test an entire class of memory retention functions by examining hazard properties. Evidence is provided that the memory hazard function is not monotonically decreasing. Yet most of the proposals for retention functions, which have emerged from the psychological literature, imply that memory hazard is…

  1. Fialuridine Induces Acute Liver Failure in Chimeric TK-NOG Mice: A Model for Detecting Hepatic Drug Toxicity Prior to Human Testing

    PubMed Central

    Xu, Dan; Nishimura, Toshi; Nishimura, Sachiko; Zhang, Haili; Zheng, Ming; Guo, Ying-Ying; Masek, Marylin; Michie, Sara A.; Glenn, Jeffrey; Peltz, Gary

    2014-01-01

    Background Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU]) developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers. Methods and Findings Control and chimeric TK-NOG mice with humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by assessing liver histology, and by electron microscopy. After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in regions with human, but not mouse, hepatocytes. Electron micrographs revealed lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not develop in control mice that were treated with the same FIAU doses for 14 d. In contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44 mg/kg/d po) for 14 d, which did not cause liver toxicity in human trial participants, did not cause liver toxicity in mice with humanized livers. Conclusions FIAU-induced liver toxicity could be readily detected using chimeric TK-NOG mice with humanized livers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in human participants. The clinical features, laboratory abnormalities, liver histology, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treated human participants. The use of chimeric mice in

  2. A Generalized DIF Effect Variance Estimator for Measuring Unsigned Differential Test Functioning in Mixed Format Tests

    ERIC Educational Resources Information Center

    Penfield, Randall D.; Algina, James

    2006-01-01

    One approach to measuring unsigned differential test functioning is to estimate the variance of the differential item functioning (DIF) effect across the items of the test. This article proposes two estimators of the DIF effect variance for tests containing dichotomous and polytomous items. The proposed estimators are direct extensions of the…

  3. Effect of Multiple Testing Adjustment in Differential Item Functioning Detection

    ERIC Educational Resources Information Center

    Kim, Jihye; Oshima, T. C.

    2013-01-01

    In a typical differential item functioning (DIF) analysis, a significance test is conducted for each item. As a test consists of multiple items, such multiple testing may increase the possibility of making a Type I error at least once. The goal of this study was to investigate how to control a Type I error rate and power using adjustment…

  4. [Liver intervention].

    PubMed

    Oi, H

    2000-12-01

    Interventional radiology is now widely performed for the treatment of liver tumors, because surgery is sometimes limited by poor liver function. Transcatheter arterial chemoembolization(TACE) is an effective therapy for hepatocellular carcinoma. Lipiodol TACE shows a strong antitumor effect because of the overflow of excess iodized oil into the portal veins, and segmental TACE is recommended to avoid deteriorating liver function. Selective CT arteriography is performed in order to decide on the treatment area, and TACE under CT guidance leads to effective results in terms of dense accumulation of the chemotherapeutic drug in the individual tumors that are affected by the ischemic state and anticancer drugs. Percutaneous microwave or radiofrequency coagulation therapy is adequate for a few of the hypovascular tumors. Excessive coagulation through the needle tract is indispensable in these therapies, and precisely designed puncture is necessary to minimize damage to the liver parenchyma. Selective chemotherapy to the tumor-bearing organ is the first step in a number of liver tumors. Continuous intra-arterial infusion chemotherapy is performed for multiple liver metastases. The reservoir implantation technique is percutaneously achieved via the left subclavian artery under ultrasound guidance, without the exposure of an artery in the incision method, which can induce thrombus formation. PMID:11197832

  5. Changes in mixed-function oxidase system in the perfused liver of the cold-acclimated rat

    NASA Astrophysics Data System (ADS)

    Takano, T.; Miyazaki, Y.; Motohashi, Y.; Yamada, K.

    1986-09-01

    Changes in the hepatic cytochrome P-450-dependent drug-metabolizing system were studied in perfused livers obtained from cold-acclimated male Wistar rats after 30 days of cold exposure (4‡C) when using hexobarbital as a substrate. In fasted animals the cold-acclimated rats showed higher levels of hexobarbital metabolic rates compared to control rats, but there was no significant difference in fed animals. The maximum rates of hexobarbital metabolism produced by xylitol perfusion were also significantly higher in the perfused liver of cold-acclimated rats. It was concluded that the function of the cytochrome P-450 system for hexobarbital in cold-acclimated rats changed due to both an increase in the activity of the cytochrome P-450 system and to changes in regulation of the cytochrome P-450 system by the supply of reducing equivalents.

  6. Functional activity of sphingomyelin cycle in rat liver in chronic toxic hepatitis.

    PubMed

    Serebrov, V Yu; Kuzmenko, D I; Burov, P G; Novitsky, S V

    2008-12-01

    Activities of sphingomyelinase and ceramidase decreased in the liver in chronic toxic hepatitis and the balance between the levels of proapoptotic ceramide and antiapoptotic sphyngosine-1-phosphate shifts towards the latter substance. Pronounced changes in the qualitative and quantitative composition of fatty acids in the sphingomyelin cycle effector molecules were revealed. PMID:19513367

  7. Effect of syrepar and oxaphenamide on liver function in experimental hypokinesia

    NASA Technical Reports Server (NTRS)

    Skakun, L. N.

    1980-01-01

    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.

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

    PubMed

    Noga, Anna A; Vance, Dennis E

    2003-10-01

    Phosphatidylcholine (PC) is made in the liver by the CDP-choline pathway and via phosphatidylethanolamine N-methyltransferase (PEMT), which catalyzes the conversion of phosphatidylethanolamine to PC. Unexpectedly, hepatic apolipoprotein B-100 secretion is inhibited in male, but not female, Pemt-/- mice (Noga, A. A., Y. Zhao, and D. E. Vance. 2002. J. Biol. Chem. 277: 42358-42365; Noga, A. A., and D. E. Vance. 2003. J. Biol. Chem. 278: 21851-21859). To gain further insight into this process, we compared PC metabolism in male and female mice fed chow or a high-fat/high-cholesterol (HF/HC) diet. Immunoblot analyses demonstrated that twice as much PEMT2 was present in livers from female compared with male mice. In contrast, assays of CTP:phosphocholine cytidylyltransferase from livers of Pemt+/+ mice demonstrated more active cytidylyltransferase in male than in female mice. Secretion of PEMT-derived PC into lipoproteins was examined in vivo by injection of mice with [methyl-3H]methionine in the presence of Triton WR1339. The PEMT-derived PC shifts to smaller-sized particles in response to a HF/HC diet, but only in male mice. Secretion of PEMT-derived PC into bile was enhanced in mice fed a HF/HC diet. These results demonstrate that the synthesis and targeting of PC produced by the PEMT pathway in the livers of mice differs in a gender- and diet-specific manner. PMID:12837848

  9. Adhesion and function of rat liver cells adherent to silk fibroin/collagen blend films.

    PubMed

    Cirillo, B; Morra, M; Catapano, G

    2004-01-01

    Collagen is often used in bioartificial livers as a biomimetic coating to promote liver cell adhesion and differentiation. Animal proteins are expensive and expose the host to risks of cross-species infection due to contamination with prions. Silk fibroin (SF) is a biocompatible protein produced by Bombyx mori silk worms and possibly an alternative to collagen. We prepared SF-collagen blend films with different SF content adherent to the bottom of standard tissue culture dishes, and characterized their surface morphology by SEM, their wettability and examined them for their capacity to support rat liver cell adhesion and metabolism. Cell metabolism was characterized by estimating the rate at which cells eliminated ammonia and synthesized urea for up to 48h of culture. SF-containing films were smooth, clear and more wettable than collagen. Cells readily adhered, formed junctions and small size aggregates on all films. As many cells adhered on SF as on collagen films. Cell adhesion to high collagen content blend films could not be reliably estimated because cells dwelt in the large cavities in the film. The effect of SF on cell metabolism differed with the investigated metabolic pathway. However, cells on SF-containing films eliminated ammonia and synthesized urea at rates generally comparable to, for urea synthesis at times higher than, that of cells on collagen. These results suggest that silk fibroin is a suitable substratum for liver cell attachment and culture, and a potential alternative to collagen as a biomimetic coating. PMID:14984185

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

    PubMed Central

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

    2012-01-01

    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), γ-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. PMID:22289616

  11. Role of cytomegalovirus on the maturation and function of monocyte derived dendritic cells of liver transplant patients

    PubMed Central

    Karimi, Mohammad Hossein; Shariat, Afsoon; Yaghobi, Ramin; Mokhtariazad, Talat; Moazzeni, Seyed Mohammad

    2016-01-01

    AIM: To study the impact of association between cytomegalovirus (CMV) pathogenesis with dendritic cell (DC) maturation and function was evaluated in CMV reactivated liver transplanted patients in comparing with non-reactivated ones, and healthy controls. METHODS: Monocyte derived dendritic cells (MoDCs) was generated from collected ethylenediaminetetraacetic acid-treated blood samples from patient groups and controls. In these groups, expression rates and mean fluorescent intensity of DC markers were evaluated using flowcytometry technique. Secretion of cytokines including: interleukin (IL)-6, IL-12 and IL-23 were determined using enzyme-linked immunosorbent assay methods. The gene expression of toll-like receptor 2 (TLR2), TLR4 and IL-23 were analyzed using in-house real-time polymerase chain reaction protocols. RESULTS: Results have been shown significant decreases in: Expression rates of MoDC markers including CD83, CD1a and human leukocyte antigen DR (HLA-DR), the mean fluorescence intensitys for CD1a and HLA-DR, and secretion of IL-12 in CMV reactivated compared with non-reactivated liver transplanted patients. On the other hand, significant increases have been shown in the secretions of IL-6 and IL-23 and gene expression levels of TLR2, TLR4 and IL-23 from MoDCs in CMV reactivated compared with non-reactivated liver transplanted recipients. CONCLUSION: DC functional defects in CMV reactivated recipients, such as decrease in expression of DC maturation markers, increase in secretion of proinflammatory cytokines, and TLRs can emphasize on the importance of CMV infectivity in development of liver rejection in transplanted patients. PMID:27358779

  12. Overexpression of Peroxiredoxin 4 Affects Intestinal Function in a Dietary Mouse Model of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Noguchi, Hirotsugu; Mazaki, Yuichi; Kurahashi, Toshihiro; Izumi, Hiroto; Wang, Ke-Yong; Guo, Xin; Uramoto, Hidetaka; Kohno, Kimitoshi; Taniguchi, Hatsumi; Tanaka, Yoshiya; Fujii, Junichi; Sasaguri, Yasuyuki; Tanimoto, Akihide; Nakayama, Toshiyuki

    2016-01-01

    Background Accumulating evidence has shown that methionine- and choline-deficient high fat (MCD+HF) diet induces the development of nonalcoholic fatty liver disease (NAFLD), in which elevated reactive oxygen species play a crucial role. We have reported that peroxiredoxin 4 (PRDX4), a unique secretory member of the PRDX antioxidant family, protects against NAFLD progression. However, the detailed mechanism and potential effects on the intestinal function still remain unclear. Methods & Results Two weeks after feeding mice a MCD+HF diet, the livers of human PRDX4 transgenic (Tg) mice exhibited significant suppression in the development of NAFLD compared with wild-type (WT) mice. The serum thiobarbituric acid reactive substances levels were significantly lower in Tg mice. In contrast, the Tg small intestine with PRDX4 overexpression showed more suppressed shortening of total length and villi height, and more accumulation of lipid in the jejunum, along with lower levels of dihydroethidium binding. The enterocytes exhibited fewer apoptotic but more proliferating cells, and inflammation was reduced in the mucosa. Furthermore, the small intestine of Tg mice had significantly higher expression of cholesterol absorption-regulatory factors, including liver X receptor-α, but lower expression of microsomal triglyceride-transfer protein. Conclusion Our present data provide the first evidence of the beneficial effects of PRDX4 on intestinal function in the reduction of the severity of NAFLD, by ameliorating oxidative stress-induced local and systemic injury. We can suggest that both liver and intestine are spared, to some degree, by the antioxidant properties of PRDX4. PMID:27035833

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

    PubMed Central

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

    2012-01-01

    We examined the association between certain clinical factors and aflatoxin B1–albumin adduct (AF-ALB) levels in HIV-positive people. Plasma samples collected from 314 (155 HIV-positive and 159 HIV-negative) people were tested for AF-ALB levels, viral load, CD4+ T-cell count, liver function profile, malaria parasitaemia, and hepatitis B and C virus infections. HIV-positive participants were divided into high and low groups based on their median AF-ALB of 0.93 pmol mg−1 albumin and multivariable logistic and linear regression methods used to assess relationships between clinical conditions and AF-ALB levels. Multivariable logistic regression showed statistically significant increased odds of having higher HIV viral loads (OR=2.84; 95% CI=1.17–7.78) and higher direct bilirubin levels (OR=5.47; 95% CI=1.03–22.85) among HIV-positive participants in the high AF-ALB group. There were also higher levels of total bilirubin and lower levels of albumin in association with high AF-ALB. Thus, aflatoxin exposure may contribute to high viral loads and abnormal liver function in HIV-positive people and so promote disease progression. PMID:21749228

  14. Culture of HepG2 liver cells on three dimensional polystyrene scaffolds enhances cell structure and function during toxicological challenge

    PubMed Central

    Bokhari, Maria; Carnachan, Ross J; Cameron, Neil R; Przyborski, Stefan A

    2007-01-01

    Cultured cells are dramatically affected by the micro-environment in which they are grown. In this study, we have investigated whether HepG2 liver cells grown in three dimensional (3-D) cultures cope more effectively with the known cytotoxic agent, methotrexate, than their counterparts grown on traditional two dimensional (2-D) flat plastic surfaces. To enable 3-D growth of HepG2 cells in vitro, we cultured cells on 3-D porous polystyrene scaffolds previously developed in our laboratories. HepG2 cells grown in 3-D displayed excellent morphological characteristics and formed numerous bile canaliculi that were seldom seen in cultures grown on 2-D surfaces. The function of liver cells grown on 3-D supports was significantly enhanced compared to activity of cells grown on 2-D standard plasticware. Unlike their 2-D counterparts, 3-D cultures were less susceptible to lower concentrations of methotrexate. Cells grown in 3-D maintained their structural integrity, possessed greater viability, were less susceptible to cell death at higher levels of the cytotoxin compared to 2-D cultures, and appeared to respond to the drug in a manner more comparable to its known activity in vivo. Our results suggest that hepatotoxicity testing using 3-D cultures might be more likely to reflect true physiological responses to cytotoxic compounds than existing models that rely on 2-D culture systems. This technology has potential applications for toxicity testing and drug screening. PMID:17711423

  15. Culture of HepG2 liver cells on three dimensional polystyrene scaffolds enhances cell structure and function during toxicological challenge.

    PubMed

    Bokhari, Maria; Carnachan, Ross J; Cameron, Neil R; Przyborski, Stefan A

    2007-10-01

    Cultured cells are dramatically affected by the micro-environment in which they are grown. In this study, we have investigated whether HepG2 liver cells grown in three dimensional (3-D) cultures cope more effectively with the known cytotoxic agent, methotrexate, than their counterparts grown on traditional two dimensional (2-D) flat plastic surfaces. To enable 3-D growth of HepG2 cells in vitro, we cultured cells on 3-D porous polystyrene scaffolds previously developed in our laboratories. HepG2 cells grown in 3-D displayed excellent morphological characteristics and formed numerous bile canaliculi that were seldom seen in cultures grown on 2-D surfaces. The function of liver cells grown on 3-D supports was significantly enhanced compared to activity of cells grown on 2-D standard plasticware. Unlike their 2-D counterparts, 3-D cultures were less susceptible to lower concentrations of methotrexate. Cells grown in 3-D maintained their structural integrity, possessed greater viability, were less susceptible to cell death at higher levels of the cytotoxin compared to 2-D cultures, and appeared to respond to the drug in a manner more comparable to its known activity in vivo. Our results suggest that hepatotoxicity testing using 3-D cultures might be more likely to reflect true physiological responses to cytotoxic compounds than existing models that rely on 2-D culture systems. This technology has potential applications for toxicity testing and drug screening. PMID:17711423

  16. Liver disease in menopause

    PubMed Central

    Brady, Carla W

    2015-01-01

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

  17. Comparison of accuracy of fibrosis degree classifications by liver biopsy and non-invasive tests in chronic hepatitis C

    PubMed Central

    2011-01-01

    Background Non-invasive tests have been constructed and evaluated mainly for binary diagnoses such as significant fibrosis. Recently, detailed fibrosis classifications for several non-invasive tests have been developed, but their accuracy has not been thoroughly evaluated in comparison to liver biopsy, especially in clinical practice and for Fibroscan. Therefore, the main aim of the present study was to evaluate the accuracy of detailed fibrosis classifications available for non-invasive tests and liver biopsy. The secondary aim was to validate these accuracies in independent populations. Methods Four HCV populations provided 2,068 patients with liver biopsy, four different pathologist skill-levels and non-invasive tests. Results were expressed as percentages of correctly classified patients. Results In population #1 including 205 patients and comparing liver biopsy (reference: consensus reading by two experts) and blood tests, Metavir fibrosis (FM) stage accuracy was 64.4% in local pathologists vs. 82.2% (p < 10-3) in single expert pathologist. Significant discrepancy (≥ 2FM vs reference histological result) rates were: Fibrotest: 17.2%, FibroMeter2G: 5.6%, local pathologists: 4.9%, FibroMeter3G: 0.5%, expert pathologist: 0% (p < 10-3). In population #2 including 1,056 patients and comparing blood tests, the discrepancy scores, taking into account the error magnitude, of detailed fibrosis classification were significantly different between FibroMeter2G (0.30 ± 0.55) and FibroMeter3G (0.14 ± 0.37, p < 10-3) or Fibrotest (0.84 ± 0.80, p < 10-3). In population #3 (and #4) including 458 (359) patients and comparing blood tests and Fibroscan, accuracies of detailed fibrosis classification were, respectively: Fibrotest: 42.5% (33.5%), Fibroscan: 64.9% (50.7%), FibroMeter2G: 68.7% (68.2%), FibroMeter3G: 77.1% (83.4%), p < 10-3 (p < 10-3). Significant discrepancy (≥ 2 FM) rates were, respectively: Fibrotest: 21.3% (22.2%), Fibroscan: 12.9% (12.3%), FibroMeter2G: 5

  18. Exosomes in liver pathology.

    PubMed

    Sato, Keisaku; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco

    2016-07-01

    Exosomes are small (∼100nm) membrane-bound extracellular vesicles released by various types of cells into biological fluids. They contain proteins, mRNAs and miRNAs as cargo. Different cell types can take up exosomes by endocytosis and the cargo contained within them can be transferred horizontally to these recipient cells. Exosomal proteins and miRNAs can be functional and regulate physiological cell events modifying the microenvironment in target cells, a key event of liver pathology. Exosome-mediated cell-cell communication can alter tumor growth, cell migration, antiviral infection and hepatocyte regeneration, indicating that exosomes have great potential for development as diagnostic or therapeutic tools. Analyses of circulating total or exosomal miRNAs have identified a large number of candidate miRNAs that are regulated in liver diseases, and the diagnostic testing using single or multiple miRNAs shows good sensitivity and specificity. Some candidate miRNAs have been identified to play an important role in various liver disorders. This review summarizes recent findings on the role of extracellular vesicles in liver diseases and their diagnostic and therapeutic potential, mainly focusing on exosomes but also includes microvesicles in liver pathology. PMID:26988731

  19. Smoke alarm tests may not adequately indicate smoke alarm function.

    PubMed

    Peek-Asa, Corinne; Yang, Jingzhen; Hamann, Cara; Young, Tracy

    2011-01-01

    Smoke alarms are one of the most promoted prevention strategies to reduce residential fire deaths, and they can reduce residential fire deaths by half. Smoke alarm function can be measured by two tests: the smoke alarm button test and the chemical smoke test. Using results from a randomized trial of smoke alarms, we compared smoke alarm response to the button test and the smoke test. The smoke alarms found in the study homes at baseline were tested, as well as study alarms placed into homes as part of the randomized trial. Study alarms were tested at 12 and 42 months postinstallation. The proportion of alarms that passed the button test but not the smoke test ranged from 0.5 to 5.8% of alarms; this result was found most frequently among ionization alarms with zinc or alkaline batteries. These alarms would indicate to the owner (through the button test) that the smoke alarm was working, but the alarm would not actually respond in the case of a fire (as demonstrated by failing the smoke test). The proportion of alarms that passed the smoke test but not the button test ranged from 1.0 to 3.0%. These alarms would appear nonfunctional to the owner (because the button test failed), even though the alarm would operate in response to a fire (as demonstrated by passing the smoke test). The general public is not aware of the potential for inaccuracy in smoke alarm tests, and burn professionals can advocate for enhanced testing methods. The optimal test to determine smoke alarm function is the chemical smoke test. PMID:21747329

  20. Platelet Function Tests: A Review of Progresses in Clinical Application

    PubMed Central

    Choi, Jae-Lim; Li, Shuhua

    2014-01-01

    The major goal of traditional platelet function tests has been to screen and diagnose patients who present with bleeding problems. However, as the central role of platelets implicated in the etiology of arterial thrombotic diseases such as myocardial infarction and stroke became widely known, platelet function tests are now being promoted to monitor the efficacy of antiplatelet drugs and also to potentially identify patients at increased risk of thrombosis. Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, are mediators of inflammation, and have immunomodulatory activity. As new potential biomarkers and technologies arrive at the horizon, platelet functions testing appears to take on a new aspect. This review article discusses currently available clinical application of platelet function tests, placing emphasis on essential characteristics. PMID:24895576

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  2. A Semi-Automated Functional Test Data Analysis Tool

    SciTech Connect

    Xu, Peng; Haves, Philip; Kim, Moosung

    2005-05-01

    The growing interest in commissioning is creating a demand that will increasingly be met by mechanical contractors and less experienced commissioning agents. They will need tools to help them perform commissioning effectively and efficiently. The widespread availability of standardized procedures, accessible in the field, will allow commissioning to be specified with greater certainty as to what will be delivered, enhancing the acceptance and credibility of commissioning. In response, a functional test data analysis tool is being developed to analyze the data collected during functional tests for air-handling units. The functional test data analysis tool is designed to analyze test data, assess performance of the unit under test and identify the likely causes of the failure. The tool has a convenient user interface to facilitate manual entry of measurements made during a test. A graphical display shows the measured performance versus the expected performance, highlighting significant differences that indicate the unit is not able to pass the test. The tool is described as semiautomated because the measured data need to be entered manually, instead of being passed from the building control system automatically. However, the data analysis and visualization are fully automated. The tool is designed to be used by commissioning providers conducting functional tests as part of either new building commissioning or retro-commissioning, as well as building owners and operators interested in conducting routine tests periodically to check the performance of their HVAC systems.

  3. The Mind and Liver Test: A New Approach to the Diagnosis of Minimal Hepatic Encephalopathy in Resource-Poor Settings

    PubMed Central

    Ali, Sajjadh M. J.; Seward, James; Venkataraman, Jayanthi

    2014-01-01

    Background and Aims. Minimal hepatic encephalopathy (MHE) is diagnosed using neuropsychometric tests or neurophysiological tests that are either inapplicable to illiterate patient population in resource-poor settings or require sophisticated and expensive equipment. The available tests assess discrete domains of mental impairment. Our aim was (a) to design a neuropsychometric test that measures all domains of mental impairment in MHE using one metric; (b) to evaluate its sensitivity, specificity, and reproducibility. Methods. The mind and liver test (MALT), a psychometric test assessing cognition, memory, and psychometric impairment, each on a scale of 20, was designed keeping in mind the requirements of a universal test. 40 cirrhotics and 36 controls were subjected to critical flicker frequency (CFF) and MALT in same sitting. ROC curve was plotted for MALT using CFF as gold standard. Bland-Altman plot was used to find test-retest agreement. Results. CFF values and MALT scores varied significantly between the cases and the controls (P < 0.05). MALT was 94% sensitive and 83% specific. Using ROC with CFF as gold standard, the AUC for diagnosis of MHE using MALT score was 0.89. Test-retest agreement was high (ICC = 0.89). Conclusion. In this pilot study, MALT proved to be highly sensitive, specific, inexpensive, and reproducible. PMID:25548682

  4. The mind and liver test: a new approach to the diagnosis of minimal hepatic encephalopathy in resource-poor settings.

    PubMed

    Das, Saurav; Ali, Sajjadh M J; Seward, James; Venkataraman, Jayanthi

    2014-01-01

    Background and Aims. Minimal hepatic encephalopathy (MHE) is diagnosed using neuropsychometric tests or neurophysiological tests that are either inapplicable to illiterate patient population in resource-poor settings or require sophisticated and expensive equipment. The available tests assess discrete domains of mental impairment. Our aim was (a) to design a neuropsychometric test that measures all domains of mental impairment in MHE using one metric; (b) to evaluate its sensitivity, specificity, and reproducibility. Methods. The mind and liver test (MALT), a psychometric test assessing cognition, memory, and psychometric impairment, each on a scale of 20, was designed keeping in mind the requirements of a universal test. 40 cirrhotics and 36 controls were subjected to critical flicker frequency (CFF) and MALT in same sitting. ROC curve was plotted for MALT using CFF as gold standard. Bland-Altman plot was used to find test-retest agreement. Results. CFF values and MALT scores varied significantly between the cases and the controls (P < 0.05). MALT was 94% sensitive and 83% specific. Using ROC with CFF as gold standard, the AUC for diagnosis of MHE using MALT score was 0.89. Test-retest agreement was high (ICC = 0.89). Conclusion. In this pilot study, MALT proved to be highly sensitive, specific, inexpensive, and reproducible. PMID:25548682

  5. Safety and Function Test Report for the SWIFT Wind Turbine

    SciTech Connect

    Mendoza, I.; Hur, J.

    2013-01-01

    This test was conducted as part of the U.S. Department of Energy's (DOE) Independent Testing project. This project was established to help reduce the barriers of wind energy expansion by providing independent testing results for small turbines. Three turbines where selected for testing at the National Wind Technology Center (NWTC) as a part of round two of the Small Wind Turbine Independent Testing project. Safety and Function testing is one of up to 5 tests that may be performed on the turbines. Other tests include power performance, duration, noise, and power quality. The results of the testing will provide the manufacturers with reports that may be used for small wind turbine certification.

  6. Liver Cancer

    MedlinePlus

    ... body digest food, store energy, and remove poisons. Primary liver cancer starts in the liver. Metastatic liver ... and spreads to your liver. Risk factors for primary liver cancer include Having hepatitis B or C ...

  7. Liver scan

    MedlinePlus

    ... hyperplasia or adenoma of the liver Abscess Budd-Chiari syndrome Infection Liver disease (such as cirrhosis or ... Amebic liver abscess Cirrhosis Hepatic vein obstruction (Budd-Chiari) Hepatitis Liver cancer - hepatocellular carcinoma Liver disease Splenic ...

  8. A Functional Test Platform for the Community Land Model

    SciTech Connect

    Xu, Yang; Thornton, Peter E; King, Anthony Wayne; Steed, Chad A; Gu, Lianhong; Schuchart, Joseph

    2014-01-01

    A functional test platform is presented to create direct linkages between site measurements and the process-based ecosystem model within the Community Earth System Models (CESM). The platform consists of three major parts: 1) interactive user interfaces, 2) functional test model and 3) observational datasets. It provides much needed integration interfaces for both field experimentalists and ecosystem modelers to improve the model s representation of ecosystem processes within the CESM framework without large software overhead.

  9. TU-F-12A-04: Differential Radiation Avoidance of Functional Liver Regions Defined by 99mTc-Sulfur Colloid SPECT/CT with Proton Therapy

    SciTech Connect

    Bowen, S; Miyaoka, R; Kinahan, P; Sandison, G; Vesselle, H; Nyflot, M; Apisarnthanarax, S; Saini, J; Wong, T

    2014-06-15

    Purpose: Radiotherapy for hepatocellular carcinoma patients is conventionally planned without consideration of spatial heterogeneity in hepatic function, which may increase risk of radiation-induced liver disease. Pencil beam scanning (PBS) proton radiotherapy (pRT) plans were generated to differentially decrease dose to functional liver volumes (FLV) defined on [{sup 99m}Tc]sulfur colloid (SC) SPECT/CT images (functional avoidance plans) and compared against conventional pRT plans. Methods: Three HCC patients underwent SC SPECT/CT scans for pRT planning acquired 15 min post injection over 24 min. Images were reconstructed with OSEM following scatter, collimator, and exhale CT attenuation correction. Functional liver volumes (FLV) were defined by liver:spleen uptake ratio thresholds (43% to 90% maximum). Planning objectives to FLV were based on mean SC SPECT uptake ratio relative to GTV-subtracted liver and inversely scaled to mean liver dose of 20 Gy. PTV target coverage (V{sub 95}) was matched between conventional and functional avoidance plans. PBS pRT plans were optimized in RayStation for single field uniform dose (SFUD) and systematically perturbed to verify robustness to uncertainty in range, setup, and motion. Relative differences in FLV DVH and target dose heterogeneity (D{sub 2}-D{sub 98})/D50 were assessed. Results: For similar liver dose between functional avoidance and conventional PBS pRT plans (D{sub mean}≤5% difference, V{sub 18Gy}≤1% difference), dose to functional liver volumes were lower in avoidance plans but varied in magnitude across patients (FLV{sub 70%max} D{sub mean}≤26% difference, V{sub 18Gy}≤8% difference). Higher PTV dose heterogeneity in avoidance plans was associated with lower functional liver dose, particularly for the largest lesion [(D{sub 2}-D{sub 98})/D{sub 50}=13%, FLV{sub 90%max}=50% difference]. Conclusion: Differential avoidance of functional liver regions defined on sulfur colloid SPECT/CT is feasible with proton

  10. Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation

    PubMed Central

    Gadd, Victoria L.; Patel, Preya J.; Jose, Sara; Horsfall, Leigh

    2016-01-01

    Background and Aims Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence. Methods Peripheral blood monocyte surface marker (CD14, CD16, CD163, CSF1R, CCR2, CCR4, CCR5, CXCR3, CXCR4, CX3CR1, HLA-DR, CD62L, SIGLEC-1) expression and capacity for phagocytosis, oxidative burst and LPS-stimulated TNF production were assessed in patients with hepatitis C (HCV) (n = 39) or non-alcoholic fatty liver disease (NAFLD) (n = 34) (classified as non-advanced disease, compensated cirrhosis and decompensated cirrhosis) and healthy controls (n = 11) by flow cytometry. Results The selected markers exhibited similar monocyte-subset-specific expression patterns between patients and controls. Monocyte phenotypic signatures differed between NAFLD and HCV patients, with an increased proportion of CD16+ non-classical monocytes in NAFLD, but increased expression of CXCR3 and CXCR4 in HCV. In both cohorts, monocyte CCR2 expression was reduced and CCR4 elevated over controls. CD62L expression was specifically elevated in patients with decompensated cirrhosis and positively correlated with the model-for-end-stage-liver-disease score. Functionally, monocytes from patients with decompensated cirrhosis had equal phagocytic capacity, but displayed features of dysfunction, characterised by lower HLA-DR expression and blunted oxidative responses. Lower monocyte TNF production in response to LPS stimulation correlated with time to death in 7 (46%) of the decompensated patients who died within 8 months of recruitment. Conclusions Chronic HCV and NAFLD differentially affect circulating monocyte phenotype, suggesting specific injury-induced signals may contribute to hepatic monocyte recruitment and systemic activation state. Monocyte function, however, was similarly impaired in patients with both HCV and NAFLD, particularly in advanced disease, which

  11. Biochemical studies on the effect of different water resources in Hail region on liver and kidney functions of rats.

    PubMed

    Talkhan, Ola F A; Abd Elwahab, Safaa A E; Shalapy, Ebtessam M

    2016-08-01

    Low concentration of a heavy metal is toxic and can be classified as one of the pollution sources. Industrial and human waste can pollute water with heavy metals and soils breaking down under the effect of acidic rain, which release heavy metals into river, streams, lakes, and ground water. Bioaccumulation of heavy metals in vital organs of the human body damages these organs, including the liver and kidney, which are the main organs for metabolism, detoxification, and excretion. The present study aims to investigate into concentrations of such heavy metals (Fe, Cu, Zn, and Pb) in both ground and tap water samples collected from different areas in Hail region, KSA. Then, this study moves forward to examine the effects of such concentrations on the biochemistry of serum in rats. In this regard, the results demonstrate the presence of significant differences (p < 0.05) in the liver function parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total proteins, albumin, and globulin between all the studied groups that were exposed to heavy-metals-polluted water, when compared with the control group. In addition, there were significant differences (p < 0.05) in the kidney function parameters, uric acid, urea, and creatinine, when compared with the control group. Thence, and as this study indicates, heavy-metals-polluted water can cause disturbance in the liver and kidney function parameters, which highlights health risks of the water polluted with heavy metals. In this sense, the concerned authorities should regularly carry out survey and should monitor underground water, and people have to be aware of such risks. PMID:27461423

  12. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease

    PubMed Central

    Lucero, Catherine; Brown, Robert S.

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease.

  13. IDENTIFICATION AND CHARACTERIZATION OF DISEASE USING PULMONARY FUNCTION TESTS

    EPA Science Inventory

    Abstract
    Pulmonary function testing is used routinely in human medicine to objectively define functional deficits in individuals with respiratory disease. Despite the fact that respiratory disease is a common problem in veterinary medicine, evaluation of the small animal pa...

  14. Factors Predicting Health Related Quality of Life in Pediatric Liver Transplant Recipients in the Functional Outcomes Group

    PubMed Central

    Alonso, Estella M; Martz, Karen; Wang, Deli; Yi, Michael S.; Neighbors, Katie; Varni, James W; Bucuvalas, John C.

    2013-01-01

    Data from 997 pediatric liver transplant (LT) recipients were used to model demographic and medical variables as predictors of lower levels of health related quality of life (HRQOL). Data were collected through Studies of Pediatric Liver Transplantation (SPLIT) Functional Outcomes Group (FOG) project. Patients were between 2-18 years of age and survived LT by at least 12 months. Parents and children (age ≥ 8 years) completed PedsQL ™ 4.0 Generic Core and Cognitive Functioning Scales at one time point. Demographic and medical variables were obtained from SPLIT. HRQOL scores were categorized “poor” based on lower 25% of scores for each measure. Logistic regression models were generated. Single-parent households (OR 1.94, CI 1.13 – 3.33, p=0.017), anti-seizure medications (OR 3.99, CI 1.26 – 12.70, p=0.019) and number of days hospitalized (OR 1.03, CI 1.01 – 1.06, p=0.0067) were associated with lower self-reported HRQOL. Parent data identified increasing age at transplant, age 5-12 years at survey, hospitalization > 21 days at LT, re-operations, diabetes and growth failure at LT as additional predictors of generic HRQOL. Male gender, single-parent households, higher bilirubin levels at LT and use of anti-seizure medication predicted lower cognitive function scores. HRQOL following pediatric LT is related to medical and demographic variables. PMID:23902630

  15. Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450. Studies in rats and patients.

    PubMed Central

    Watkins, P B; Murray, S A; Winkelman, L G; Heuman, D M; Wrighton, S A; Guzelian, P S

    1989-01-01

    The major P-450IIIA gene family member present in human liver is HLp which, like its rat liver orthologue P-450p, is inducible by glucocorticoids and catalyzes erythromycin N-demethylation. To develop a practical method to estimate the amounts of HLp in patients [14C]N-methyl erythromycin was injected into rats that had been pretreated with dexamethasone or with inducers of other forms of cytochrome P-450. The rate of demethylation of this substrate, measured simply as 14CO2 in the breath, correlated well with the concentrations of immunoreactive P-450p protein (r = 0.70), holocytochrome P-450p (r = 0.70), or with erythromycin N-demethylase activity (r = 0.90) determined in the liver microsomes prepared from each rat. Next, [14C]N-methyl erythromycin was administered to 30 patients and there was a sixfold interindividual variation in breath 14CO2 production seemingly unrelated to medications, smoking status or age. However, the average breath test values were twofold greater in female as compared to male patients (P less than 0.01). Breath 14CO2 production rose in patients retested after treatment with the P-450IIIA inducers dexamethasone (P less than 0.05) or rifampicin (P less than 0.05) and was decreased after treatment with the HLp inhibitor triacetyloleandomycin (P less than 0.05). We conclude that the erythromycin breath test provides a convenient assay of P-450IIIA cytochromes in rats and in some patients. PMID:2913056

  16. Enterocyte fatty acid-binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine.

    PubMed

    Gajda, Angela M; Storch, Judith

    2015-02-01

    Fatty acid-binding proteins (FABP) are highly abundant cytosolic proteins that are expressed in most mammalian tissues. In the intestinal enterocyte, both liver- (LFABP; FABP1) and intestinal FABPs (IFABP; FABP2) are expressed. These proteins display high-affinity binding for long-chain fatty acids (FA) and other hydrophobic ligands; thus, they are believed to be involved with uptake and trafficking of lipids in the intestine. In vitro studies have identified differences in ligand-binding stoichiometry and specificity, and in mechanisms of FA transfer to membranes, and it has been hypothesized that LFABP and IFABP have different functions in the enterocyte. Studies directly comparing LFABP- and IFABP-null mice have revealed markedly different phenotypes, indicating that these proteins indeed have different functions in intestinal lipid metabolism and whole body energy homeostasis. In this review, we discuss the evolving knowledge of the functions of LFABP and IFABP in the intestinal enterocyte. PMID:25458898

  17. Improvement of liver function by the administration of oyster extract as a dietary supplement to habitual alcohol drinkers: A pilot study

    PubMed Central

    OSAKI, KENJI; SHIMIZU, YOSHIO; YAMAMOTO, TETSURO; MIYAKE, FUMIHARU; KONDO, SUMIO; YAMAGUCHI, HIDEYO

    2015-01-01

    Alcoholic liver disease (ALD) is characterized by elevated serum γ-glutamyltransferase (GGT) activity with hepatic steatosis, hepatitis or occasionally fibrosis that may progress to cirrhosis. The potential therapeutic role of oyster extract (OE) or OE-containing dietary supplements (OE supplement) in ALD has seldom been evaluated. In the present study, 84 adults who had an alcohol-drinking habit and marginally high serum GGT levels were enrolled in a randomized, double-blind, placebo-controlled feeding trial to study the effect on alcohol-impaired liver function as reflected by an increased serum level of GGT, as well as the safety, of an OE supplement. The subjects were randomized to receive either an OE supplement (OE group) or placebo (placebo group). There were 42 subjects (31 males and 11 females) in each group, and all the enrolled subjects entered the study. Four individuals (5%) dropped out for reasons unassociated with the study and 6 other subjects were excluded from the efficacy analysis because they did not maintain the required frequency of alcohol intake. As a result, 38 subjects in the placebo group and 36 in the OE group underwent efficacy assessment. Assays of GGT and other liver enzymes were performed at baseline (week 0) and at weeks 4, 8 and 12 of the intervention period. The mean serum levels of GGT in the placebo group gradually increased, while those in the OE group tended to decrease, although no significant within-group differences were observed for either group. A significant between-group difference in the change of mean GGT from baseline was, however, found at week 12 (P=0.049). No OE supplement-associated untoward side-effects nor any abnormal changes in routine laboratory tests and anthropometric parameters were observed throughout the 12-week intervention. An OE supplement shows promise in reducing risk factors associated with ALD in adults with an alcohol intake habit. PMID:26622379

  18. [Liver diseases in the elderly].

    PubMed

    Bruguera, Miguel

    2014-11-01

    Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. PMID:24951302

  19. Evaluation of 4-methylimidazole, in the Ames/Salmonella test using induced rodent liver and lung S9.

    PubMed

    Beevers, Carol; Adamson, Richard H

    2016-01-01

    4-methylimidazole (4-MeI) is formed by the interaction of ammonia with reducing sugars and low levels have been identified as a by-product in coffee, soy sauce, wine, dark beers, soft drinks, and caramel colors. The 4-MeI has been reported to induce alveolar/bronchiolar tumors in mice but not rats. Its mechanism of action is unlikely to be due to genotoxicity as 4-MeI does not induce mutation in Salmonella typhimurium and does not induce micronuclei in rodent peripheral erythrocytes or bone marrow cells. However, the question of whether genetically reactive intermediates could be formed via lung-specific metabolism has not previously been addressed. The 4-MeI was tested for its ability to induce mutation in five standard Ames strains of S. typhimurium using induced rat (F344/N) and mouse (B6C3F1) liver and lung S9 as a source of exogenous metabolism. The chemicals were tested in an OECD 471-compliant bacterial reverse mutation assay, using both plate-incorporation and pre-incubation methodologies, together with 10% S-9 metabolic activation. No induction of mutation (as measured by an increase in revertant colonies) was observed and it was concluded that 4-MeI was not mutagenic in S. typhimurium using either rodent liver or lung S9 for exogenous metabolism. PMID:26765635

  20. [Indexes of a functional condition of a liver with hemolytic disease of the newborn stipulated incompatibility between the mother and fetus].

    PubMed

    Khatiashvili, N A

    2006-06-01

    The hemolytic disease of the newborn, originating as a result of sensitization of the mother to the Rh-antigen of erythrocytes of the fetus (Rh-HDN) is one of the most important causes of the loss of a fetus and newborn. One of the pathogenetic mechanisms of Rh-HDN is the hyperbilirubinemia at the expense of the toxiferous fraction of a bilirubin negatively influencing many organs of the child, including the liver. The purpose of the work was the complex study of indexes of a functional condition of a liver newborn with a various degree of gravity Rh-HDN and definition of effectiveness of the conducted therapy. The direct association between severity of illness and indexes of pigmental, excretion and detoxication of the function of the liver in newborns with Rh-HDN has been found. There were found significant relations of ALT/AP, AST/AP, GT/AP, albumin and globulin factors with the degree of cholestasis and toxic damage of the liver. The lack of normalization of indexes of the peptide uptake and the excretion function of the liver on the background of treatment indicate to the necessity of further monitoring of functional condition of the liver and realization of the correction of therapy after discharge of children from the hospital, especially with the serious form of Rh- HDN. PMID:16905814

  1. SP-100 nuclear assembly test - Test assembly functional requirements and system arrangement

    NASA Astrophysics Data System (ADS)

    Fallas, T. T.; Gluck, Robert; Motwani, Kumar; Clay, Harold; O'Neill, Gerald

    This paper describes the functional requirements and the system that will be tested to validate the reactor, flight shield, and flight controller of the SP-100 Generic Flight System. The Nuclear Assembly Test consists of the test article (SP-100 reactor with control devices and the flight shield) and its supporting systems.

  2. Altered UDP-Glucuronosyltransferase and Sulfotransferase Expression and Function during Progressive Stages of Human Nonalcoholic Fatty Liver Disease

    PubMed Central

    Hardwick, Rhiannon N.; Ferreira, Daniel W.; More, Vijay R.; Lake, April D.; Lu, Zhenqiang; Manautou, Jose E.; Slitt, Angela L.

    2013-01-01

    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

  3. Effect of aqueous extract of Cochlospermum planchonii rhizome on some kidney and liver functional indicies of albino rats.

    PubMed

    Nafiu, Mo; Akanji, M A; Yakubu, M T

    2011-01-01

    Aqueous extract of Cochlospermum planchonii Hook. Ef. x Planch rhizome was investigated for its toxic effects in albino rats using some liver and kidney functional indices as 'markers'. Thirty six albino rats weighing 200.08 ± 10.21 were randomly assinged into six groups (A-F) of six animals each. Animals in groups A-E were orally administered on daily basis with 1 ml of the extract corresponding to 50 mg/kg body weight of the extract for 1, 3, 5, 10 and 15 days while those in the control group received orally 1 ml of distilled water. Rats in all the groups were sacrificed 24 hours after the completion of their respective doses. The extract significantly (P<0.05) decreased alkaline phosphatase (ALP) activities in the liver leading to 80.95% loss by the end of the experimental period. While there was no consistent pattern in the kidney ALP activity and serum bilirubin level, the serum enzyme compared well (P>0.05) with the control value. There was no effect (P>0.05) on the acid phosphatase activity of the tissues and serum of the animals. The extract also reduced the urea, albumin and creatinine content in the serum of the animals. The alterations in the biochemical parameters by the aqueous extract of Cochlospermum planchoni may have consequential effects on the normal functioning of the liver and kidney of the animals. Therefore, the 50 mg/kg body weight of the aqueous extract of Cochlospermum planchoni rhizome may not be completley safe as an oral remedy. PMID:22238479

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

    PubMed

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

    2000-06-01

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

  5. An automated miniaturized Haploscope for testing binocular visual function

    NASA Technical Reports Server (NTRS)

    Decker, T. A.; Williams, R. E.; Kuether, C. L.; Wyman-Cornsweet, D.

    1976-01-01

    A computer-controlled binocular vision testing device has been developed as one part of a system designed for NASA to test the vision of astronauts during spaceflight. The device, called the Mark III Haploscope, utilizes semi-automated psychophysical test procedures to measure visual acuity, stereopsis, phorias, fixation disparity and accommodation/convergence relationships. All tests are self-administered, yield quantitative data and may be used repeatedly without subject memorization. Future applications of this programmable, compact device include its use as a clinical instrument to perform routine eye examinations or vision screening, and as a research tool to examine the effects of environment or work-cycle upon visual function.

  6. A Liver Full of JNK: Signaling in Regulation of Cell Function and Disease Pathogenesis, and Clinical Approaches

    PubMed Central

    Seki, Ekihiro; Brenner, David A.; Karin, Michael

    2012-01-01

    c-Jun-N-terminal Kinase (JNK) is a mitogen-activated protein kinase (MAPK) family member that is activated by diverse stimuli, including cytokines (such as tumor necrosis factor and interleukin-1), reactive oxygen species (ROS), pathogens, toxins, drugs, endoplasmic reticulum stress, free fatty acids, and metabolic changes. Upon activation, JNK induces multiple biologic events through the transcription factor AP-1 and transcription-independent control of effector molecules. JNK isozymes regulate cell death and survival, differentiation, proliferation, ROS accumulation, metabolism, insulin signaling, and carcinogenesis in the liver. The biologic functions of JNK are isoform, cell-type, and context dependent. Recent studies using genetically engineered mice showed that loss or hyper-activation of the JNK pathway contributes to the development of inflammation, fibrosis, cancer growth, and metabolic diseases that include obesity, hepatic steatosis, and insulin resistance. We review the functions and pathways of JNK in liver physiology and pathology, and discuss findings from pre-clinical studies with JNK inhibitors. PMID:22705006

  7. Blood-Compatible Polymer for Hepatocyte Culture with High Hepatocyte-Specific Functions toward Bioartificial Liver Development.

    PubMed

    Hoshiba, Takashi; Otaki, Takayuki; Nemoto, Eri; Maruyama, Hiroka; Tanaka, Masaru

    2015-08-19

    The development of bioartificial liver (BAL) is expected because of the shortage of donor liver for transplantation. The substrates for BAL require the following criteria: (a) blood compatibility, (b) hepatocyte adhesiveness, and (c) the ability to maintain hepatocyte-specific functions. Here, we examined blood-compatible poly(2-methoxyethyl acrylate) (PMEA) and poly(tetrahydrofurfuryl acrylate) (PTHFA) (PTHFA) as the substrates for BAL. HepG2, a human hepatocyte model, could adhere on PMEA and PTHFA substrates. The spreading of HepG2 cells was suppressed on PMEA substrates because integrin contribution to cell adhesion on PMEA substrate was low and integrin signaling was not sufficiently activated. Hepatocyte-specific gene expression in HepG2 cells increased on PMEA substrate, whereas the expression decreased on PTHFA substrates due to the nuclear localization of Yes-associated protein (YAP). These results indicate that blood-compatible PMEA is suitable for BAL substrate. Also, PMEA is expected to be used to regulate cell functions for blood-contacting tissue engineering. PMID:26258689

  8. Effects of melatonin on liver function and lipid peroxidation in a rat model of hepatic ischemia/reperfusion injury

    PubMed Central

    DENG, WEN-SHENG; XU, QING; LIU, YE; JIANG, CHUN-HUI; ZHOU, HONG; GU, LEI

    2016-01-01

    The present study aimed to investigate the effects of melatonin (MT) on liver function and lipid peroxidation following hepatic ischemia-reperfusion injury (IRI). A total of 66 male Sprague-Dawley rats were randomly assigned into three groups: Normal control (N) group, ischemia-reperfusion (IR) group and the MT-treated group. A hepatic IRI model was developed by blocking the first porta hepatis, and subsequently restoring hepatic blood inflow after 35 min. Following reperfusion, changes in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were detected by a chemical method at various time points. In the MT group, the MDA levels were significantly reduced (P<0.05) at all time points, as compared with the IR group. Furthermore, SOD activity was significantly increased (P<0.05) in the MT group, as compared with the IR group at all time points; and the levels of GSH in the MT group were significantly higher (P<0.05) than those of the IR group at 2, 4, and 8 h post-reperfusion. The levels of ALT, AST and LDH were significantly reduced in the MT group at each time point, as compared with that of the IR group (P<0.05). In conclusion, MT exhibits potent antioxidant properties that may create favorable conditions for the recovery of liver function following IRI. PMID:27168834

  9. Testing for cognitive function in animals in a regulatory context.

    PubMed

    Bushnell, Philip J

    2015-01-01

    Superior cognitive functions have allowed the human species to proliferate in a world of incredible biological diversity. Threats to these essential capacities cannot be ignored, and a strategy is needed to evaluate the hazard posed by exposure to chemical and other agents. Because people exposed to chemicals often complain about confusion and forgetfulness, it is commonly thought that cognitive functions should be sensitive indicators of adverse consequences of chemical exposure. For these reasons, complex tests of cognitive function have been developed and deployed in experimental animal laboratories for decades. However, the results of these tests are rarely used as points of departure for chemical risk assessments. Due to their high cost in time, animals, and equipment, the efficacy and utility of these tests need to be evaluated in relation to cheaper and faster whole-animal screening methods. This review examines evidence for the assertions that cognitive functions represent uniquely sensitive indicators of chemical exposure, and that animal models of these functions are necessary to detect and quantify the neurotoxicity of chemicals. Studies conducted since the early 1980s to compare these approaches to assess the neurotoxicity of chemicals are reviewed for both adult and perinatal exposures in experimental rodents. Forty-one studies of 35 chemicals were found that directly compared acute effects using complex tests (i.e., tests that require training animals) with acute effects using screening tests (i.e., tests that do not require training animals) in adult rodents. Complex tests detected effects of three substances (bitertanol, iso-amyl nitrite, and Pfiesteria toxin) that had no effect on screening tests; for an additional five chemicals (carbaryl, deltamethrin, methyl mercury, tetraethyl tin, and Isopar-C), complex tests identified effects at lower doses than did screening tests. Fewer comparable cases were found for developmental exposures: screening and

  10. The organoid-initiating cells in mouse pancreas and liver are phenotypically and functionally similar

    PubMed Central

    Dorrell, Craig; Tarlow, Branden; Wang, Yuhan; Canaday, Pamela S; Haft, Annelise; Schug, Jonathan; Streeter, Philip R; Finegold, Milton J; Shenje, Lincoln T; Kaestner, Klaus H; Grompe, Markus

    2014-01-01

    Pancreatic Lgr5 expression has been associated with organoid-forming epithelial progenitor populations but the identity of the organoid-initiating epithelial cell subpopulation has remained elusive. Injury causes the emergence of an Lgr5+ organoid-forming epithelial progenitor population in the adult mouse liver and pancreas. Here, we define the origin of organoid-initiating cells from mouse pancreas and liver prior to Lgr5 activation. This clonogenic population was defined as MIC1-1C3+/CD133+/CD26− in both tissues and the frequency of organoid initiation within this population was approximately 5% in each case. The transcriptomes of these populations overlapped extensively and showed enrichment of epithelial progenitor-associated regulatory genes such as Sox9 and FoxJ1. Surprisingly, pancreatic organoid cells also had the capacity to generate hepatocyte-like cells upon transplantation to Fah-/- mice, indicating a differentiation capacity similar to hepatic organoids. Although spontaneous endocrine differentiation of pancreatic progenitors was not observed in culture, adenoviral delivery of fate-specifying factors Pdx1, Neurog3 and MafA induced insulin expression without glucagon or somatostatin. Pancreatic organoid cultures therefore preserve many key attributes of progenitor cells while allowing unlimited expansion, facilitating the study of fate determination. PMID:25151611

  11. The organoid-initiating cells in mouse pancreas and liver are phenotypically and functionally similar.

    PubMed

    Dorrell, Craig; Tarlow, Branden; Wang, Yuhan; Canaday, Pamela S; Haft, Annelise; Schug, Jonathan; Streeter, Philip R; Finegold, Milton J; Shenje, Lincoln T; Kaestner, Klaus H; Grompe, Markus

    2014-09-01

    Pancreatic Lgr5 expression has been associated with organoid-forming epithelial progenitor populations but the identity of the organoid-initiating epithelial cell subpopulation has remained elusive. Injury causes the emergence of an Lgr5(+) organoid-forming epithelial progenitor population in the adult mouse liver and pancreas. Here, we define the origin of organoid-initiating cells from mouse pancreas and liver prior to Lgr5 activation. This clonogenic population was defined as MIC1-1C3(+)/CD133(+)/CD26(-) in both tissues and the frequency of organoid initiation within this population was approximately 5% in each case. The transcriptomes of these populations overlapped extensively and showed enrichment of epithelial progenitor-associated regulatory genes such as Sox9 and FoxJ1. Surprisingly, pancreatic organoid cells also had the capacity to generate hepatocyte-like cells upon transplantation to Fah(-/-) mice, indicating a differentiation capacity similar to hepatic organoids. Although spontaneous endocrine differentiation of pancreatic progenitors was not observed in culture, adenoviral delivery of fate-specifying factors Pdx1, Neurog3 and MafA induced insulin expression without glucagon or somatostatin. Pancreatic organoid cultures therefore preserve many key attributes of progenitor cells while allowing unlimited expansion, facilitating the study of fate determination. PMID:25151611

  12. Effects of acute ethanol administration of female rat liver as a function of aging

    SciTech Connect

    Rikans, L.E.; Snowden, C.D. )

    1989-01-01

    Female Fischer 344 rats, aged 4, 14, and 25 months, received 4.0 g/kg of ethanol by intraperitoneal (i.p.) injection. Blood alcohol concentrations 2.5, 6 and 16 hr after ethanol injection were similar in the three age groups. Hepatic glutathione (GSH) levels were diminished 6 hr after ethanol injection, and there were no age-dependent differences in the depleted levels (3.2 {plus minus} 0.1, 3.5 {plus minus} 0.2, and 3.0 {plus minus} 0.5 {mu}g GSH/g liver). However, GSH contents in livers of young-adult rats approached control levels after 16 hr, whereas they remained depressed in older rats. Serum levels of hepatic enzymes were significantly elevated 6 hr after ethanol administration. The increases were greater in middle-aged and old rats than in young-adult rats. The results suggest that middle-aged and old rats are more susceptible than young rats to the acute toxicity of ethanol.

  13. Psychometric tests for assessment of brain function after solvent exposure.

    PubMed

    Rasmussen, K; Jeppesen, H J; Sabroe, S

    1993-11-01

    Psychometric testing is a key issue in neuropsychological toxicology assessment. Evaluation of methods for assessing general intellectual impairment is necessary as conventional neurology has been shown to be insensitive to the neurotoxic effects of solvents and metals. This study presents an analysis of a psychometric test battery from an investigation of psycho-organic syndrome in a historical cohort of 96 metal degreasers with long-term exposure to solvents, particularly trichloroethylene. The neuropsychological test battery was a combination of Wechsler Adult Intelligence Scale (WAIS), Luria, and tests developed in Scandinavia. Linear regression analysis showed a significant dose-response relation between increasing cumulative solvent exposure and impaired psychometric test performance in 9 out of 15 tests. Multivariate analysis, however, suggests that much of the variance was due to confounding variables, especially age, and to a lesser degree, primary intellectual function and word blindness. After control for confounding factors the strongest association with solvent exposure occurred for the following three tests: acoustic-motor function, Paced Auditory Serial Addition Test (PASAT), and the visual gestalt test. PMID:8266931

  14. Executive function on the Psychology Experiment Building Language tests.

    PubMed

    Piper, Brian J; Li, Victoria; Eiwaz, Massarra A; Kobel, Yuliyana V; Benice, Ted S; Chu, Alex M; Olsen, Reid H J; Rice, Douglas Z; Gray, Hilary M; Mueller, Shane T; Raber, Jacob

    2012-03-01

    The measurement of executive function has a long history in clinical and experimental neuropsychology. The goal of the present report was to determine the profile of behavior across the lifespan on four computerized measures of executive function contained in the recently developed Psychology Experiment Building Language (PEBL) test battery http://pebl.sourceforge.net/ and evaluate whether this pattern is comparable to data previously obtained with the non-PEBL versions of these tests. Participants (N = 1,223; ages, 5-89 years) completed the PEBL Trail Making Test (pTMT), the Wisconsin Card Sort Test (pWCST; Berg, Journal of General Psychology, 39, 15-22, 1948; Grant & Berg, Journal of Experimental Psychology, 38, 404-411, 1948), the Tower of London (pToL), or a time estimation task (Time-Wall). Age-related effects were found over all four tests, especially as age increased from young childhood through adulthood. For several tests and measures (including pToL and pTMT), age-related slowing was found as age increased in adulthood. Together, these findings indicate that the PEBL tests provide valid and versatile new research tools for measuring executive functions. PMID:21534005

  15. Functional Performance Testing After Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Abrams, Geoffrey D.; Harris, Joshua D.; Gupta, Anil K.; McCormick, Frank M.; Bush-Joseph, Charles A.; Verma, Nikhil N.; Cole, Brian J.; Bach, Bernard R.

    2014-01-01

    Background: When to allow an athlete to return to unrestricted sporting activity after anterior cruciate ligament (ACL) reconstruction remains controversial. Purpose: To report the results of functional performance testing reported in the literature for individuals at differing time points following ACL reconstruction and to examine differences between graft types. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of Medline, Scopus, and Cochrane Central Register of Controlled Trials was performed using PRISMA guidelines. Inclusion criteria were English-language studies that examined any functional rehabilitation test from 6 months to 2 years following ACL reconstruction. All patient-, limb-, and knee-specific demographics were extracted from included investigations. All functional rehabilitation tests were analyzed and compared when applicable. Results: The search term returned a total of 890 potential studies, with 88 meeting inclusion and exclusion criteria. A total of 4927 patients were included, of which 66% were male. The mean patient age was 26.5 ± 3.4 years. The predominant graft choices for reconstruction were bone–patellar tendon–bone (BPTB) autograft (59.8%) and hamstring autograft (37.9%). The most commonly reported functional tests were the hop tests. The results of these functional tests, as reported in the Limb Symmetry Index (LSI), improved with increasing time, with nearly all results greater than 90% at 1 year following primary ACL reconstruction. At 6 months postoperatively, a number of isokinetic strength measurements failed to reach 80% LSI, most commonly isokinetic knee extension testing in both BPTB and hamstring autograft groups. The knee flexion strength deficit was significantly less in the BPTB autograft group as compared with those having hamstring autograft at 1 year postoperatively, while no significant differences were found in isokinetic extension strength between the 2 groups. Conclusion: Hop

  16. [Diagnosis and examination for COPD. Pulmonary function tests].

    PubMed

    Kubota, Masaru

    2016-05-01

    Pulmonary function tests are essential for the diagnosis and management of COPD. It is important to understand the inspection method of tests and the interpretation of test results. The presence of a post-bronchodilator FEV1/FVC<0.70 confirms the presence of persistent airflow limitation and the diagnosis of COPD. On the other hand, the classification of severity of airflow limitation in COPD is based on %FEV1. In COPD patients, as airflow limitation worsens gas trapping and static hyperinflation occurs. These changes can be documented by lung volume measurement as increases in functional residual capacity, residual volume and total lung capacity. Measurement of diffusing capacity (DLco) provides information on the functional impact of emphysema in COPD. PMID:27254943

  17. SP-100 nuclear assembly test: Test assembly functional requirements and system arrangement

    NASA Astrophysics Data System (ADS)

    Fallas, T. Ted; Gluck, Robert; Motwani, Kumar; Clay, Harold; O'Neill, Gerald

    1991-01-01

    This paper describes the functional requirements and the system that will be tested to validate the reactor, flight shield, and flight controller of the SP-100 Generic Flight System (GFS). The Nuclear Assembly Test (NAT) consists of the test article (SP-100 reactor with control devices and the flight shield) and its supporting systems. The NAT test assembly is being designed by GE. Westinghouse Hanford Company (WHC) is designing the test cell and vacuum vessel system that will contain the NAT test assembly (Renkey et al. 1989). Preliminary design reviews have been completed and the final design is under way.

  18. Novel synergic antidiabetic effects of Astragalus polysaccharides combined with Crataegus flavonoids via improvement of islet function and liver metabolism.

    PubMed

    Cui, Kai; Zhang, Shaobo; Jiang, Xin; Xie, Weidong

    2016-06-01

    The present study investigated the synergic effects and potential mechanisms of action of Astragalus polysaccharides (APS) combined with Crataegus flavonoids (CF) in the treatment of type 1 diabetes. Diabetes was induced by intraperitoneal injection of 100 mg/kg streptozotocin in mice. Normal and untreated diabetic control mice were used, and CF‑treated (200 mg/kg/day), APS‑treated (200 mg/kg/day), APS + CF (AC)‑treated (200 mg/kg/day of each) and metformin‑treated (200 mg/kg/day) diabetic mice were orally administrated the appropriate therapeutic agent for 4 weeks. The results demonstrated that AC treatment significantly reduced the fasting blood glucose, food and water intake in the diabetic mice. The AC group demonstrated increased serum insulin levels and islet cell function was restored. Furthermore, the AC‑treated mice demonstrated significant increases in the protein expression levels of pancreatic and duodenal homeobox‑1 and phosphorylated adenosine 5'‑monophosphate‑activated protein kinase in the pancreatic and liver tissue samples, respectively. In addition, AC significantly increased the mRNA expression levels of neurogenin 3, v‑maf musculoaponeurotic fibrosarcoma oncogene family, protein A and insulin, and simultaneously decreased the expressions of interleukin 6, tumor necrosis factor‑α and chemokine (C‑C motif) ligand 2 in the pancreatic islet cells of diabetic mice. The anti‑inflammatory activity of APS and the islet‑restoring effect of CF may contribute to the improvement of islet function. AC exerted greater antidiabetic effects compared with APS or CF treatments alone. These results indicated that AC treatment had a synergic antidiabetic effect, which may involve improvements in islet function and liver metabolism. These effects of AC may facilitate the treatment of type 1 or 2 diabetes, as these patients frequently experience impaired islet function and disordered extrapancreatic metabolism. PMID

  19. [Problems of lung function testing in the laboratory].

    PubMed

    Tojo, Naoko

    2006-08-01

    Spirometry is indispensable for the screening test of general respiratory function, and measurements of lung volume and diffusing capacity play an important role in the assessment of disease severity, functional disability, disease activity and response to treatment. Pulmonary function testing requires cooperation between the subjects and the examiner, and the results obtained depend on technical as well as personal factors. In order to diminish the variability of results and improve measurement accuracy, the Japan Respiratory Society published the first guidelines on the standardization of spirometry and diffusing capacity for both technical and clinical staff in 2004. It is therefore essential to distribute the guidelines to both laboratory personnel and general physicians. Furthermore, training workshops are mandatory to improve their understanding of the basics of lung function testing. Recently, there has been increasing interest in noninvasive methods of lung function testing without requiring the patient's cooperation during spontaneous breathing. Three alternative techniques, i.e. the negative expiratory pressure (NEP) method to detect expiratory flow limitation, impulse oscillation system (IOS) to measure respiratory system resistance (Rrs) and reactance (Xrs), and interruption resistance (Rint) to measure respiratory resistance have been introduced. Further study is required to determine the advantage of these methods. PMID:16989403

  20. Pulmonary function testing: custom programs for manual equipment.

    PubMed

    Petrini, M F

    1984-01-01

    Pulmonary Function Laboratories with manual equipment can expedite calculations and make them more accurate by using a programmable calculator that will compute functions and predictive equations. However, a custom-made set of programs is better than calculator libraries available from the manufacturer. With custom-made programs, calculations remain as the staff is used to receiving them, programs can be stored in the memory and called independently and only those tests used routinely need to be available. PMID:6546910

  1. Characterization of membrane fraction lipid composition and function of cirrhotic rat liver. Role of S-adenosyl-L-methionine.

    PubMed

    Muriel, P; Mourelle, M

    1992-01-01

    The effect of S-adenosyl-L-methionine (SAM) administration on the lipid composition of the membrane fraction obtained from livers of cirrhotic rats was studied. Four groups of animals were used: group 1 received CCl4 for 8 weeks to induce cirrhosis. Animals in group 2 received 3 daily i.m. injections of SAM 20 mg/kg in addition to CCl4. Groups 3 and 4 were control groups of SAM and vehicles. Seventy-two h after the end of treatment all animals were killed and livers were studied to measure glycogen, cAMP contents and to isolate membrane fractions. The membrane activity of Na+,K(+)- and Ca(2+)-ATPases was measured and the lipid content was analyzed in extracts. Phospholipids were determined by thin-layer chromatography and fatty acids by gas chromatography. Chronic CCl4 treatment led to increases in cholesterol and in the cholesterol/phospholipid ratio. Analysis of phospholipids revealed an increase in phosphatidylserines. Saturated fatty acids increased, while unsaturated decreased significantly. The CCl4-treated group showed a decrease in glycogen and an increase in cAMP contents. Na+,K(+)- and Ca(2+)-ATPases activity were highly reduced in cirrhotic membranes. In the group receiving CCl4 + SAM the lipid composition and the function of liver membrane fraction showed no difference compared to normal controls, except for fatty acid composition which was similar to concentrations in the CCl4-treated group. Glycogen depletion was only partially prevented whereas cAMP levels were normalized in the CCl4 + SAM group. Our results showed that membrane lipid alterations were accompanied by changes in the activity of enzymes embedded in the membrane fraction derived from CCl4-cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1310704

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

    PubMed Central

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

    2012-01-01

    BACKGROUND Small-for-size syndrome (SFSS) may occur when graft volume is less than 45% of the standard liver volume, and it manifests as retarded growth and failure of the grafts and an increased mortality. However, its pathogenesis is poorly understood, and few effective interventions have been attempted. AIMS The present study aims to delineate the critical role of oxidant stress in SFSS and protective effects of a superoxide dismutase (SOD) mimetic, MnTBAP, on graft function, growth and survival in the recipient rats. METHODS Small size graft liver transplantation (SSGLT) was performed to determine the survival, graft injury and growth. MnTBAP was administered in SSGLT recipients (SSGLT+MnTBAP). RESULTS Serum ALT levels were sustained higher in SSGLT recipients, which were correlated with an increased apoptotic cell count and hepatocellular necrosis in liver sections. Malondialdehyde content, gene expression of TNF-α and IL-1β and DNA binding activity of NF-κB 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-κB signaling pathway contributes to SFS-associated graft failure, retarded graft growth and poor survival. MnTBAP effectively reversed the pathologic changes in SFS-associated graft failure. PMID:22955229

  3. Outcomes of Anatomical versus Functional Testing for Coronary Artery Disease

    PubMed Central

    Douglas, Pamela S.; Hoffmann, Udo; Patel, Manesh R.; Mark, Daniel B.; Al-Khalidi, Hussein R.; Cavanaugh, Brendan; Cole, Jason; Dolor, Rowena J.; Fordyce, Christopher B.; Huang, Megan; Khan, Muhammad Akram; Kosinski, Andrzej S.; Krucoff, Mitchell W.; Malhotra, Vinay; Picard, Michael H.; Udelson, James E.; Velazquez, Eric J.; Yow, Eric; Cooper, Lawton S.; Lee, Kerry L.

    2015-01-01

    BACKGROUND Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care. METHODS We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure. RESULTS The mean age of the patients was 60.8±8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3±21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P = 0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P = 0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001). CONCLUSIONS In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the

  4. Physiologic Dysfunction Scores and Cognitive Function Test Performance in United States Adults

    PubMed Central

    Kobrosly, Roni W; Seplaki, Christopher L; Jones, Courtney M; van Wijngaarden, Edwin

    2013-01-01

    Objective To investigate the relationship between a measure of cumulative physiologic dysfunction and specific domains of cognitive function. Methods We examined a summary score measuring physiological dysfunction, a multisystem measure of the body’s ability to effectively adapt to physical and psychological demands, in relation to cognitive function deficits in a population of 4511 adults aged 20 to 59 who participated in the third National Health and Nutrition Examination Survey (1988–1994). Measures of cognitive function comprised three domains: working memory, visuomotor speed, and perceptual-motor speed. ‘Physiologic dysfunction’ scores summarizing measures of cardiovascular, immunologic, kidney, and liver function were explored. We used multiple linear regression models to estimate associations between cognitive function measures and physiological dysfunction scores, adjusting for socioeconomic factors, test conditions, and self-reported health factors. Results We noted a dose-response relationship between physiologic dysfunction and working memory (coefficient = 0.207, 95% CI = (0.066, 0.348), p < 0.0001) that persisted after adjustment for all covariates (p = 0.03). We did not observe any significant relationships between dysfunction scores and visuomotor (p = 0.37) or perceptual-motor ability (p = 0.33). Conclusions Our findings suggest that multisystem physiologic dysfunction is associated with working memory. Future longitudinal studies are needed to clarify the underlying mechanisms and explore the persistency of this association into later life. We suggest that such studies should incorporate physiologic data, neuroendocrine parameters, and a wide range of specific cognitive domains. PMID:22155941

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

    SciTech Connect

    Gorczynska, E. ); Wegrzynowicz, R. )

    1991-08-01

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

  6. Repeated mobility testing for later artificial visual function evaluation

    NASA Astrophysics Data System (ADS)

    Velikay-Parel, M.; Ivastinovic, D.; Koch, M.; Hornig, R.; Dagnelie, G.; Richard, G.; Langmann, A.

    2007-03-01

    The study investigates the utility of a newly designed mobility test for repeated testing of visual function in patients with severe visual impairment and future application in evaluating functional progress in patients with artificial vision. Ten subjects divided into three groups based on visual acuity (VA) ranging from light perception to 20/200 and reduced visual field (VF) were included in the study. The mobility test consisted of using a set of four different but structurally similar and relatively short mazes having a constant number of obstacles of various sizes. The subjects, divided into three groups by acuity, passed through each course several times. In general, the patients with better VA had a larger extent of VF. Average speed and number of contacts were recorded as measures of performance. The average passing times of the groups through the courses were significantly different (p = 0.03), which was influenced by VA and VF. There was no significant difference in average number of contacts between the groups (p = 0.15). The mobility test proved to be appropriate for gaining statistically relevant results in repeated individual testing of patients with severe vision impairment. Results show promise for use this mobility test as a tool for assessing visual function of patients undergoing implantation of a visual prosthesis for artificial vision.

  7. Defining Normal Liver Stiffness Range in a Normal Healthy Chinese Population without Liver Disease

    PubMed Central

    Fung, James; Lee, Cheuk-kwong; Chan, Monica; Seto, Wai-kay; Wong, Danny Ka-ho; Lai, Ching-lung; Yuen, Man-fung

    2013-01-01

    Background For patients with chronic liver disease, different optimal liver stiffness cut-off values correspond to different stages of fibrosis, which are specific for the underlying liver disease and population. Aims To establish the normal ranges of liver stiffness in the healthy Chinese population without underlying liver disease. Methods This is a prospective cross sectional study of 2,528 healthy volunteers recruited from the general population and the Red Cross Transfusion Center in Hong Kong. All participants underwent a comprehensive questionnaire survey, measurement of weight, height, and blood pressure. Fasting liver function tests, glucose and cholesterol was performed. Abdominal ultrasound and transient elastography were performed on all participants. Results Of the 2,528 subjects, 1,998 were excluded with either abnormal liver parenchyma on ultrasound, chronic medical condition, abnormal blood tests including liver enzymes, fasting glucose, fasting cholesterol, high body mass index, high blood pressure, or invalid liver stiffness scan. The reference range for the 530 subjects without known liver disease was 2.3 to 5.9 kPa (mean 4.1, SD 0.89). The median liver stiffness was higher in males compared with females (4.3 vs 4.0 kPa respectively, p<0.001). There was also a decline in median Lliver stiffness in the older age group, from 4.2 kPa in those <25 years to 3.4 kPa for those >55 years (p=0.001). Conclusions The healthy reference range for liver stiffness in the Chinese population is 2.3 to 5.9 kPa. Female gender and older age group was associated with a lower median liver stiffness. PMID:24386446

  8. GROUND-WATER MODEL TESTING: SYSTEMATIC EVALUATION AND TESTING OF CODE FUNCTIONALITY AND PERFORMANCE

    EPA Science Inventory

    Effective use of ground-water simulation codes as management decision tools requires the establishment of their functionality, performance characteristics, and applicability to the problem at hand. This is accomplished through application of a systematic code-testing protocol and...

  9. Functional integrity of the interrenal tissue of yellow perch from contaminated sites tested in vivo

    SciTech Connect

    Girard, C.; Brodeur, J.C.; Hontela, A.

    1995-12-31

    The normal activation of the hypothalamo-pituitary-interrenal axis (HPI axis) in response to capture is disrupted in fish subjected to life-long exposure to heavy metals, PCBs and PAHs. The ability to increase plasma cortisol in yellow perch (Perca flavescens) from sites contaminated by heavy metals and organic compounds, and from a reference site was assessed by the Capture stress test and by the ACTH Challenge test, a new standardized in vivo method designed for field studies. The effects of seasonal factors, such as temperature and gonadal maturity on these tests were investigated. Measures of liver and muscle glycogen and histopathology were made to further characterize the biochemical and structural changes that may occur along with hormonal changes. The Capture stress test showed that an acute source of stress induced a lower cortisol response in fish from the highly contaminated site compared to the reference site, revealing a functional impairment of the HPI axis. The ACTH Challenge test showed that the hormonal responsiveness of the cortisol-secreting interrenal tissue, stimulated by a standard dose of ACTH injected i.p., was lower in fish from the highly contaminated site than the reference site. Spring is the season during which the impairment was the most evident. The possibility of using the reduced capacity of feral fish to respond to a standardized ACTH Challenge as an early bioindicator of toxic stress is discussed.

  10. Impact of hepatic function on serum procalcitonin for the diagnosis of bacterial infections in patients with chronic liver disease: A retrospective analysis of 324 cases.

    PubMed

    Qu, Junyan; Feng, Ping; Luo, Yan; Lü, Xiaoju

    2016-07-01

    Although procalcitonin (PCT) is a valid marker for early diagnosis of bacterial infections, it is unclear whether its accuracy in predicting bacterial infections is affected by impaired liver function. This study aimed to assess the impact of compromised liver function on the diagnostic value of PCT.This retrospective study was conducted between January 2013 and May 2015. A total of 324 patients with chronic liver disease were enrolled. Routine laboratory measurements and PCT were performed. Patients were divided into 3 groups according to clinical diagnosis: chronic hepatitis (group 1), decompensated cirrhosis (group 2), and acute-on-chronic liver failure/chronic liver failure (group 3). The correlation between PCT and liver function was analyzed. The area under the receiver operating characteristic (AUCROC) curve of PCT was analyzed according to infection status and liver function.PCT was more accurate than white blood cell count (P < 0.001) and percentage of neutrophils (P < 0.001) in detecting bacterial infections in patients with impaired liver function. In patients without infection, PCT had a moderate positive correlation with serum total bilirubin (TBIL) (r = 0.592), and a weak correlation with model for end-stage liver disease score (r = 0.483) and international normalized ratio (r = 0.389). The AUCROC and optimum thresholds of PCT and for predicting bacterial infections at different levels of TBIL were 0.907 (95% CI 0.828-0.958) and 0.38 ng/mL, respectively, for TBIL <5 mg/dL, 0.927 (95% CI 0.844-0.974) and 0.54 ng/mL (5 mg/dL ≤TBIL<10 mg/dL), 0.914 (95% CI 0.820-0.968) and 0.61 ng/mL (10 mg/dL ≤TBIL<20 mg/dL), 0.906 (95% CI 0.826-0.958) and 0.94 ng/mL (TBIL ≥20 mg/dL), respectively.This study demonstrated that PCT was a valuable marker of bacterial infection in patients with chronic liver diseases. TBIL affected PCT threshold, so different cut-offs should be used according to different TBIL values. PMID

  11. Kidney-to-liver ratio. A simple scintigraphic parameter for routine individual renal function assessment in children.

    PubMed

    Yung, B C; Sostre, S

    1994-03-01

    DTPA renography is commonly used for measuring relative renal function. However, in patients with bilateral renal disease or solitary kidneys, split function studies are of no value. Available techniques to quantify individual renal function are either time consuming or inaccurate. The authors validate the kidney-to-liver ratio at 3 minutes (K3/L3) as an index of renal function, showing excellent correlation with GFR. Normal K3/L3 ranges were then computed in 113 pediatric kidneys (age 2 days to 16 years) and 24 adults. Indicative of renal maturation, the K3/L3 rapidly rose from a value of 1.32 at birth to 2.02 at 6 months. Subsequently, it increased slowly to reach a peak of 2.34 at age 2, followed by gradual decline to adult values after age 5. This decrease is due likely to continued growth of the hepatic blood pool after renal maturation. GFR followed the same maturation pattern to reach a plateau around 2 years of age. K3/L3 reflects individual kidney function, and it requires no blood sampling or urine collection. By establishing normal values at different stages of maturity, this method provides identification and quantification of renal dysfunction in infants, children, and adults. PMID:8033475

  12. Development of an in vitro model to test antifibrotic drugs on primary human liver myofibroblasts.

    PubMed

    Aoudjehane, Lynda; Boelle, Pierre-Yves; Bisch, Grégoire; Delelo, Rolland; Paye, François; Scatton, Olivier; Housset, Chantal; Becquart, Jérôme; Calmus, Yvon; Conti, Filomena

    2016-06-01

    We have developed a culture model to assess antifibrotic drugs using normal human liver myofibroblasts (HLMFs) obtained from 31 subjects. Activation was evaluated in terms of α-smooth muscle actin (α-SMA) and collagen 1 (Coll1) expression using RT-PCR, and proliferation as the uptake of 5-ethynil-2'-deoxyuridine. Under analysis of variance, between-subject differences accounted for 70% of all variability and inter-experiment differences for 30%. The sensitivity of the model was determined by quantifying the effects in terms of relative expression, which were 0.74±0.03 for cyclosporine A (CsA) and 2.4±0.10 for transforming growth factor-beta (TGF-β) (P<0.0001 vs no treatment) for α-SMA expression. Inter-subject variations in α-SMA and Coll1 expression enabled the classification of subjects as potentially low or high fibrosers. Finally, we observed that pirfenidone (which has beneficial effects in vivo) significantly reduced the expressions of α-SMA and Coll1, whereas the angiotensin-converting enzyme inhibitor losartan (which has no effect in vivo) had no significant effect. Our model may thus detect the antifibrotic properties of drugs. Antifibrotic drugs with promising clinical relevance could possibly be selected using a bank of HLMFs from high fibrosers. PMID:26950484

  13. Thyroid hormone-induced cytosol-to-nuclear translocation of rat liver Nrf2 is dependent on Kupffer cell functioning.

    PubMed

    Videla, Luis A; Cornejo, Pamela; Romanque, Pamela; Santibáñez, Catherine; Castillo, Iván; Vargas, Romina

    2012-01-01

    L-3,3',5-triiodothyronine (T(3)) administration upregulates nuclear factor-E2-related factor 2 (Nrf2) in rat liver, which is redox-sensitive transcription factor mediating cytoprotection. In this work, we studied the role of Kupffer cell respiratory burst activity, a process related to reactive oxygen species generation and liver homeostasis, in Nrf2 activation using the macrophage inactivator gadolinium chloride (GdCl(3); 10 mg/kg i.v. 72 h before T(3) [0.1 mg/kg i.p.]) or NADPH oxidase inhibitor apocynin (1.5 mmol/L added to the drinking water for 7 days before T(3)), and determinations were performed 2 h after T(3). T(3) increased nuclear/cytosolic Nrf2 content ratio and levels of heme oxygenase 1 (HO-1), catalytic subunit of glutamate cysteine ligase, and thioredoxin (Western blot) over control values, proteins whose gene transcription is induced by Nrf2. These changes were suppressed by GdCl(3) treatment prior to T(3), an agent-eliciting Kupffer-cell depletion, inhibition of colloidal carbon phagocytosis, and the associated respiratory burst activity, with enhancement in nuclear inhibitor of Nrf2 kelch-like ECH-associated protein 1 (Keap1)/Nrf2 content ratios suggesting Nrf2 degradation. Under these conditions, T(3)-induced tumor necrosis factor-α (TNF-α) response was eliminated by previous GdCl(3) administration. Similar to GdCl(3), apocynin given before T(3) significantly reduced liver Nrf2 activation and HO-1 expression, a NADPH oxidase inhibitor eliciting abolishment of colloidal carbon-induced respiratory burst activity without altering carbon phagocytosis. It is concluded that Kupffer cell functioning is essential for upregulation of liver Nrf2-signaling pathway by T(3). This contention is supported by suppression of the respiratory burst activity of Kupffer cells and the associated reactive oxygen species production by GdCl(3) or apocynin given prior to T(3), thus hindering Nrf2 activation. PMID:22649286

  14. Fatty liver and hepatic function for residents with markedly high serum PCDD/Fs levels in Taiwan.

    PubMed

    Lee, Ching-Chang; Yao, Yei-Jen; Chen, Hsiu-Ling; Guo, Yue-Liang; Su, Huey-Jen

    2006-03-01

    This study was designed to examine the associations between serum polychtorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) levels and adverse hepatic-related health outcomes. Residents living in the vicinity of a closed pentachlorophenol (PCP) manufacturing factory (exposure area) and other areas nearby (control area) were identified from prior investigation of serum PCDD/Fs measurements. A total of 85 subjects were recruited for the study, 52 from exposure area and 33 from control, respectively. Average level of serum PCDD/Fs was 80.1 6 50.9 pg WHO-TEQ/g lipid for those residing in exposure area, and 25.5 6 18.2 in control area. Statistically higher odds ratio (ORs) for fatty liver and gamma-glutamyltransferase (GGT) activity was found in subjects with higher serum PCDD/Fs levels and high body mass index (BMI) as compared to those with lower PCDD/Fs levels and less BMI. Data suggest that dioxin exposure and high lipid content affect the prevalence of fatty liver in exposed subjects. Future study should be directed to prevent continuous exposure to environmental PCDD/Fs from the defunct PCP factory, and to characterize prospectively, with a larger study sample size, the potential long-term consequences on hepatic function associated with contaminant exposure. PMID:16455615

  15. Metabolism of benzene and phenol by a reconstituted purified phenobarbital induced rat liver mixed function oxidase system

    SciTech Connect

    Griffiths, J.C.

    1986-01-01

    Cytochrome P-450 and the electron-donor, NADPH-cytochrome c reductase were isolated from phenobarbital induced rat liver microsomes. Both benzene and its primary metabolite phenol, were substrates for the reconstituted purified phenobarbital induced rat liver mixed function oxidase system. Benzene was metabolized to phenol and the polyhydroxylated metabolites; catechol, hydroquinone and 1,2,4 benzenetriol. Benzene elicited a Type I spectral change upon its interaction with the cytochrome P-450 while phenol's interaction with the cytochrome P-450 produced a reverse Type I spectra. The formation of phenol showed a pH optimum of 7.0 compared with 6.6-6.8 for the production of the polyhyrdoxylated metabolites. Cytochrome P-450 inhibitors, such as metyrapone and SKF 525A, diminished the production of phenol from benzene but not the production of the polyhydroxylated metabolites from phenol. The radical trapping agents, DMSO, KTBA and mannitol, decreased the recovery of polyhydroxylated metabolites, from /sup 14/C-labeled benzene and/or phenol. As KTBA and DMSO interacted with OH. There was a concomitant release of ethylene and methane, which was measured. Desferrioxamine, an iron-chelator and catalase also depressed the recovery of polyhydroxylated metabolites. In summary, benzene and phenol were both substrates for this reconstituted purified enzyme system, but they differed in binding to cytochrome P-450, pH optima and mode of hydroxylation.

  16. Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model.

    PubMed

    Calattini, Sara; Fusil, Floriane; Mancip, Jimmy; Dao Thi, Viet Loan; Granier, Christelle; Gadot, Nicolas; Scoazec, Jean-Yves; Zeisel, Mirjam B; Baumert, Thomas F; Lavillette, Dimitri; Dreux, Marlène; Cosset, François-Loïc

    2015-09-18

    Lipoprotein components are crucial factors for hepatitis C virus (HCV) assembly and entry. As hepatoma cells producing cell culture-derived HCV (HCVcc) particles are impaired in some aspects of lipoprotein metabolism, it is of upmost interest to biochemically and functionally characterize the in vivo produced viral particles, particularly regarding how lipoprotein components modulate HCV entry by lipid transfer receptors such as scavenger receptor BI (SR-BI). Sera from HCVcc-infected liver humanized FRG mice were separated by density gradients. Viral subpopulations, termed HCVfrg particles, were characterized for their physical properties, apolipoprotein association, and infectivity. We demonstrate that, in contrast to the widely spread distribution of apolipoproteins across the different HCVcc subpopulations, the most infectious HCVfrg particles are highly enriched in apoE, suggesting that such apolipoprotein enrichment plays a role for entry of in vivo derived infectious particles likely via usage of apolipoprotein receptors. Consistent with this salient feature, we further reveal previously undefined functionalities of SR-BI in promoting entry of in vivo produced HCV. First, unlike HCVcc, SR-BI is a particularly limiting factor for entry of HCVfrg subpopulations of very low density. Second, HCVfrg entry involves SR-BI lipid transfer activity but not its capacity to bind to the viral glycoprotein E2. In conclusion, we demonstrate that composition and biophysical properties of the different subpopulations of in vivo produced HCVfrg particles modulate their levels of infectivity and receptor usage, hereby featuring divergences with in vitro produced HCVcc particles and highlighting the powerfulness of this in vivo model for the functional study of the interplay between HCV and liver components. PMID:26224633

  17. Use of extracorporeal liver assist device and auxiliary liver transplantation in fulminant hepatic failure.

    PubMed

    McCarthy, M; Ellis, A J; Wendon, J A; Heaton, N; Rela, M; Buxton-Thomas, M; Hughes, R D; Portmann, B C; Williams, R

    1997-04-01

    The case history of a 14-year-old boy with fulminant hepatic failure secondary to non-A, non-B hepatitis who fulfilled selection criteria for orthotopic liver transplantation is described. Two forms of liver support were used (extracorporeal liver assist device and an auxiliary partial orthotopic liver transplantation) to provide additional time to allow spontaneous recovery to occur. During the 66 h of extracorporeal haemoperfusion through the device, haemodynamic stability was maintained along with improvements in serum bilirubin (555 to 381 mumol/l), and international normalized ratio (INR) (3.7 to 2.9). Deterioration in these parameters was observed following cessation of treatment and 10 h later, after a donor liver had become available, an auxiliary transplant was performed. Clinical recovery, though initially slow, was eventually complete, with histopathological and scintigraphic evidence of full liver regeneration at 3 months. Withdrawal of his immunosuppressive drugs began at 6 months and was complete by 14 months after auxiliary transplantation. He has since remained well with normal liver function tests. Temporary liver support may provide additional time for spontaneous recovery of the native liver to occur in selected cases of fulminant hepatic failure, even when criteria are fulfilled for orthotopic liver grafting. PMID:9160207

  18. [Eosin Y-water test for sperm function examination].

    PubMed

    Zha, Shu-wei; Lü, Nian-qing; Xu, Hao-qin

    2015-06-01

    Based on the principles of the in vitro staining technique, hypotonic swelling test, and water test, the Eosin Y-water test method was developed to simultaneously detect the integrity of the sperm head and tail and sperm membrane structure and function. As a widely used method in clinical laboratories in China, the Eosin Y-water test is methodologically characterized by three advantages. Firstly, both the sperm head and tail can be detected at the same time, which allows easy and comprehensive assessment of membrane damage in different parts of sperm. Secondly, distilled water is used instead of the usual formula solution to simplify and standardize the test by eliminating any potential effects on the water molecules through the sperm membrane due to different osmotic pressure or different sugar proportions and electrolyte solutions. Thirdly, the test takes less time and thus can be repeated before and after treatment. This article focuses on the fundamental principles and modification of the Eosin Y-water test and its application in sperm function examination and routine semen analysis for male infertility, assessment of the quality of sperm retrieved by testicular fine needle aspiration, semen cryopreservation program development, and evaluation of sperm membrane integrity after microwave radiation. PMID:26242051

  19. Functional Integrity of the Chimeric (Humanized) Mouse Liver: Enzyme Zonation, Physiologic Spaces, and Hepatic Enzymes and Transporters.

    PubMed

    Chow, Edwin C Y; Wang, Jason Z Ya; Quach, Holly P; Tang, Hui; Evans, David C; Li, Albert P; Silva, Jose; Pang, K Sandy

    2016-09-01

    Chimeric mouse liver models are useful in vivo tools for human drug metabolism studies; however, liver integrity and the microcirculation remain largely uninvestigated. Hence, we conducted liver perfusion studies to examine these attributes in FRGN [Fah(-/-), Rag2(-/-), and Il2rg(-/-), NOD strain] livers (control) and chimeric livers repopulated with mouse (mFRGN) or human (hFRGN) hepatocytes. In single-pass perfusion studies (2.5 ml/min), outflow dilution profiles of noneliminated reference indicators ((51)Cr-RBC, (125)I-albumin, (14)C-sucrose, and (3)H-water) revealed preservation of flow-limited distribution and reduced water and albumin spaces in hFRGN livers compared with FRGN livers, a view supported microscopically by tightly packed sinusoids. With prograde and retrograde perfusion of harmol (50 µM) in FRGN livers, an anterior sulfation (Sult1a1) over the posterior distribution of glucuronidation (Ugt1a1) activity was preserved, evidenced by the 42% lower sulfation-to-glucuronidation ratio (HS/HG) and 14% higher harmol extraction ratio (E) upon switching from prograde to retrograde flow. By contrast, zonation was lost in mFRGN and hFRGN livers, with HS/HG and E for both flows remaining unchanged. Remnant mouse genes persisted in hFRGN livers (10%-300% those of FRGN). When hFRGN livers were compared with human liver tissue, higher UGT1A1 and MRP2, lower MRP3, and unchanged SULT1A1 and MRP4 mRNA expression were observed. Total Sult1a1/SULT1A1 protein expression in hFRGN livers was higher than that of FRGN livers, consistent with higher harmol sulfate formation. The composite data on humanized livers suggest a loss of zonation, lack of complete liver humanization, and persistence of murine hepatocyte activities leading to higher sulfation. PMID:27342868

  20. Viable RNaseH1 knockout mice show RNaseH1 is essential for R loop processing, mitochondrial and liver function

    PubMed Central

    Lima, Walt F.; Murray, Heather M.; Damle, Sagar S.; Hart, Christopher E.; Hung, Gene; De Hoyos, Cheryl Li; Liang, Xue-Hai; Crooke, Stanley T.

    2016-01-01

    Viable constitutive and tamoxifen inducible liver-specific RNase H1 knockout mice that expressed no RNase H1 activity in hepatocytes showed increased R-loop levels and reduced mitochondrial encoded DNA and mRNA levels, suggesting impaired mitochondrial R-loop processing, transcription and mitochondrial DNA replication. These changes resulted in mitochondrial dysfunction with marked changes in mitochondrial fusion, fission, morphology and transcriptional changes reflective of mitochondrial damage and stress. Liver degeneration ensued, as indicated by apoptosis, fibrosis and increased transaminase levels. Antisense oligonucleotides (ASOs) designed to serve as substrates for RNase H1 were inactive in the hepatocytes from the RNase H1 knockout mice and in vivo, demonstrating that RNase H1 is necessary for the activity of DNA-like ASOs. During liver regeneration, a clone of hepatocytes that expressed RNase H1 developed and partially restored mitochondrial and liver function. PMID:27131367

  1. Viable RNaseH1 knockout mice show RNaseH1 is essential for R loop processing, mitochondrial and liver function.

    PubMed

    Lima, Walt F; Murray, Heather M; Damle, Sagar S; Hart, Christopher E; Hung, Gene; De Hoyos, Cheryl Li; Liang, Xue-Hai; Crooke, Stanley T

    2016-06-20

    Viable constitutive and tamoxifen inducible liver-specific RNase H1 knockout mice that expressed no RNase H1 activity in hepatocytes showed increased R-loop levels and reduced mitochondrial encoded DNA and mRNA levels, suggesting impaired mitochondrial R-loop processing, transcription and mitochondrial DNA replication. These changes resulted in mitochondrial dysfunction with marked changes in mitochondrial fusion, fission, morphology and transcriptional changes reflective of mitochondrial damage and stress. Liver degeneration ensued, as indicated by apoptosis, fibrosis and increased transaminase levels. Antisense oligonucleotides (ASOs) designed to serve as substrates for RNase H1 were inactive in the hepatocytes from the RNase H1 knockout mice and in vivo, demonstrating that RNase H1 is necessary for the activity of DNA-like ASOs. During liver regeneration, a clone of hepatocytes that expressed RNase H1 developed and partially restored mitochondrial and liver function. PMID:27131367

  2. The Functional Task Test (FTT): An Interdisciplinary Testing Protocol to Investigate the Factors Underlying Changes in Astronaut Functional Performance

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Lawrence, E. L.; Arzeno, N. M.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Mulavara, A. P.; Peters, B. T.; Platts. S. H.; Ploutz-Snyder, L. L.; Reschke, M. F.; Ryder, J. W.; Spiering, B. A.; Stenger, M. B.; Taylor, L. C.; Wood, S. J.

    2011-01-01

    Exposure to space fligh