The natural history of nonalcoholic fatty liver disease: mortality rates and liver enzymes

Nonalcoholic fatty liver disease (NAFLD) has emerged as an important health issue of the modern world, due to the dramatic increase in its prevalence, which has doubled and in some regions tripled in the past decade. Epidemiological studies, including national health surveys, are remarkable instruments for indirectly measuring the health status of the general population, as well as providing estimations of the mortality and morbidity associated with major diseases and delineating global risk factors.Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Gamma-glutamyl transferase level predicts the development of hypertension in Hong Kong Chinese

Introduction: Liver enzymes are elevated in cardiometabolic diseases, particularly when there is non-alcoholic fatty liver disease. We therefore investigated if hypertension is associated with elevated levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase and γ-glutamyl transferase (GGT). Methods: We included 235 hypertensive and 708 normotensive subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000-2004 who had fewer than one alcoholic drink a week. In the follow-up study in 2005-2008 (CRISPS-3), 126 out of the 708 subjects had developed hypertension. Results: In CRISPS-2, plasma ALT (OR=1.31 per SD of log-transformed level, P=0.005) and GGT (OR=1.52 per SD of log-transformed level, P<0.001) were significantly associated with prevalent hypertension after adjusting for age, sex and body mass index (BMI). Among subjects not on anti-hypertensive medication, plasma ALP and GGT were significantly associated with both systolic blood pressure (beta=0.141, P<0.001 for ALP and beta=0.096, P=0.004 for GGT) and diastolic blood pressure (beta=0.131, P<0.001 for ALP and beta=0.102, P=0.004 for GGT). In forward stepwise logistic regression analysis of subjects normotensive at CRISPS-2, the highest tertile of plasma GGT level was an independent predictor of the development of hypertension in CRISPS-3 (OR=2.40, P=0.010), together with age, BMI, systolic blood pressure and plasma CRP at baseline, and change in BMI. The other liver enzymes were not significantly predictors of new-onset hypertension. Conclusions: Among the four liver enzymes, elevated GGT level is the strongest risk factor for hypertension in Hong Kong Chinese. Acknowledgement: This study was funded by Hong Kong Research Grant Council grants (HKU7229/01M and HKU7626/07M) and the Sun Chieh Yeh Heart Foundation.published_or_final_versio

Frazioni della gamma-glutammiltrasferasi plasmatica: valori di riferimento, correlazioni con fattori di rischio cardiovascolare, alterazioni indotte dall'abuso di alcool

RIASSUNTO La determinazione sierica dell'attività dell'enzima gamma-glutamiltrasferasi (GGT) è un test di laboratorio di basso costo, sensibile ed accurato, frequentemente utilizzato come indice di disfunzione epatobiliare e di abuso di alcool. Valori di GGT nell'intervallo di riferimento correlano positivamente con il rischio di insorgenza ed evoluzione del processo aterosclerotico, malattie ad esso correlate, ipertensione, diabete mellito di tipo 2 e sindrome metabolica. La rilevanza del valore predittivo della GGT sierica è stata recentemente incrementata da studi che hanno mostrato il ruolo di quest'enzima nella prognosi di malattia renale, malattia epatobiliare e tumori, confermando così un valore della GGT come predittore indipendente di mortalità. La GGT è considerato anche un marcatore di stress ossidativo e la sua attività è in grado di modulare alcuni importanti elementi cellulari tra cui fattori di trascrizione e proteine di membrana. Sebbene il test di laboratorio comunemente utilizzato per la sua determinazione sia altamente riproducibile e sensibile, la GGT possiede comunque una scarsa specificità, che ne limita il valore diagnostico e prognostico. È noto che l'attività totale di GGT sierica è dovuta a numerosi complessi molecolari contenenti GGT; una migliore comprensione della natura, del significato fisiopatologico e delle correlazioni cliniche di questi complessi, di diversa natura e dotati di distinte proprietà chimico-fisiche, potrebbe migliorare l'utilizzo della determinazione della GGT. I metodi utilizzati fino ad ora per analizzare le diverse frazioni di GGT sono scarsamente sensibili e riproducibili e inoltre hanno portato a risultati contrastanti riguardo al numero stesso di frazioni presenti nel plasma; in più consentono la determinazione delle frazioni soltanto in presenza di alti valori di GGT e ciò in tutte quelle situazioni (ad esempio malattie epatobiliari) in cui è noto un aumento dei valori dell'enzima, ma non in presenza di valori nell'intervallo di riferimento. Recentemente è stato messo a punto un nuovo metodo per la separazione e la quantificazione delle frazioni circolanti di GGT nel siero o nel plasma. Tale tecnica prevede l'utilizzo della cromatografia per esclusione molecolare per separare le frazioni in base al loro peso molecolare ed una reazione enzimatica post-colonna specifica per la GGT. Questo metodo consente la determinazione, con elevata sensibilità e riproducibilità, di quattro frazioni di GGT (b-, m-, s-, ed f-GGT). Lo scopo della mia tesi è stato quello di studiare il potenziale clinico di questo metodo e cercare così di stabilire valori di riferimento e determinanti fisiopatologiche delle frazioni di GGT in un gruppo di soggetti sani (200 soggetti, 100 uomini e 100 donne) reclutati all'interno di una popolazione di donatori di sangue e in un gruppo di trenta alcolisti. I risultati di questa analisi mostrano che all'interno dei soggetti sani tutte le quattro frazioni sono significativamente più rappresentate negli uomini rispetto alle donne; la f-GGT è la frazione prominente in soggetti con bassi valori di GGT, ma all'aumentare degli stessi si accompagna principalmente l'aumento dalle frazioni s- e b-GGT. Tutte le frazioni correlano positivamente con ALT (P <0,01), ma la b-GGT è la frazione che più di tutte correla con i già noti fattori di rischio cardivascolare in entrambi i generi (indice di massa corporea, pressione diastolica, acido urico, colesterolo LDL); m- e f-GGT correlano con colesterolo LDL mentre solo la f-GGT correla significativamente con i valori di trigliceridi negli uomini (P <0,01). Nel gruppo degli alcolisti si sono riscontrati valori significativamente più elevati in tutte le frazioni, ma la s-GGT si è dimostrata di gran lunga la maggiore responsabile dell'aumento dei valori di GGT rispetto alla popolazione sana. In conclusione l'analisi delle quattro frazioni con la cromatografia ad esclusione molecolare è un metodo riproducibile e sensibile che può migliorare la bassa specificità dell'attuale saggio standard di laboratorio e permettere così nella pratica clinica uno studio più approfondito sull'effetivo ruolo di questo enzima in molte delle condizioni fisiopatologiche sopra menzionate

Hepatitis induced by noni juice from Morinda citrifolia: A rare cause of hepatotoxicity or the tip of the iceberg?

A 24-year-old female patient presented to her community hospital with mild elevations of serum transaminase and bilirubin levels. Because of multiple sclerosis, she was treated with interferon beta-la for 6 weeks. After exclusion of viral hepatitis due to hepatitis A-E, interferon beta-la was withdrawn under the suspicion of drug-induced hepatitis. One week later, she was admitted again to her community hospital with severe icterus. The transaminase and bilirubin levels were highly elevated, and a beginning impairment of the liver synthesis was expressed by a reduced prothrombin time. The confinement to our department occurred with a fulminant hepatitis and the suspicion of beginning acute liver failure. There was no evidence for hepatitis due to potentially hepatotoxic viruses, alcoholic hepatitis, Budd-Chiari syndrome, hemochromatosis, and Wilson's disease. In her serum there were high titers of liver-kidney microsomal type 1 autoantibody; the serum gamma globulin levels were in the normal range. Fine-needle aspiration biopsy of the liver ruled out an autoimmune hepatitis but showed signs of drug-induced toxicity. During the interview, she admitted that for `general immune system stimulation' she had been drinking Noni juice, a Polynesian herbal remedy made from a tropical fruit (Morinda citrifolia), during the past 4 weeks. After cessation of the Noni juice ingestion, her transaminase levels normalized quickly and were in the normal range within 1 month. Copyright (c) 2006 S. Karger AG, Basel

Twisting 4-manifolds along RP^2

We prove that the Dolgachev surface E(1)_{2,3} (which is an exotic copy of the elliptic surface E(1)=CP^2 # 9(-CP^2)) can be obtained from E(1) by twisting along a simple "plug", in particular it can be obtained from E(1) by twisting along an RP^2.Comment: 5 papes, 5 figures. Appeared in Proceedings of GGT

Self-powered microfluidic chips for multiplexed protein assays from whole blood

We report herein on a self-powered, self-contained microfluidic-based chip designed to separate plasma from whole blood, and then execute an assay of a multiplexed panel of plasma biomarker proteins. The power source is based upon a chemical reaction that is catalytically triggered by the push of a button on the chip. We demonstrate assays of a dozen blood-based protein biomarkers using this automated, self-contained device. This platform can potentially permit high throughput, accurate, multiplexed blood diagnostic measurements in remote locations and by minimally trained individuals

Potential for gene-flow from cultivated Irish grasses and cereals

End of project reportThe importance of gene movement from cultivated plants has been highlighted in regard to minimising the movement of seed and/or pollen between GM and non-GM crops (i.e. gene flow). Although ryegrass covers in excess of 90% of Ireland’s agricultural area, very little is known about gene flow from ryegrass populations from an Irish context. The goal of this project was to address this lack of data by measuring the degree of pollen-mediated gene-flow between two Lolium spp. in a field environment. Ryegrass (esp. Lolium perenne) was selected because as the dominant pasture grass it is critical for the livestock industry as well as being a current target for novel improvements. The results from this research indicate that the potential for pollen-mediated gene flow from perennial ryegrass decreases exponentially with increased distance from the pollen source, with hybridisation events recorded out at 192m. In parallel to this research, a separate study was conducted to assess the degree of genetic diversity within feral and wild Lolium spp across Ireland and also within the important crop weed Avena fatua (‘wild oats’); thereby providing an insight into the degree of historic gene flow that has occurred within each species and in regard to the latter, identifying the potential for non-native A. fatua to colonise the Irish agrienvironment

Bus Rapid Transit: A Handbook for Partners, MTI Report 06-02

In April 2005, the Caltrans Division of Research and Innovation (DRI) asked MTI to assist with the research for and publication of a guidebook for use by Caltrans employees who work with local transit agencies and jurisdictions in planning, designing, and operating Bus Rapid Transit (BRT) systems that involve state facilities. The guidebook was also to assist to transit operators, local governments, community residents, and other stakeholders dealing with the development of BRT systems. Several areas in the state have experienced such projects ( San Diego , Los Angeles , San Francisco , and Alameda County ) and DRI wished to use that experience to guide future efforts and identify needed changes in statutes, policies, and other state concerns. Caltrans convened a Task Team from the Divisions of Research and Innovation, Mass Transportation, and Operations, together with stakeholders representing many of those involved with the BRT activities around the state. Prior to MTI’s involvement, this group produced a white paper on the topic, a series of questions, and an outline of the guidebook that MTI was to write. The MTI team conducted case studies of the major efforts in California, along with less developed studies of some of the other BRT programs under development or in early implementation phases around the state. The purpose was to clarify those issues that need to be addressed in the guidebook, as well as to compile information that would identify items needing legislative or regulatory action and items that Caltrans will need to address through district directives or other internal measures. A literature scan was used to develop a bibliography for future reference. The MTI team also developed a draft Caltrans director’s policy document, which provides the basis for Caltrans’ actions. This ultimately developed to be a project within a project. MTI submitted a draft document to Caltrans as a final product from the Institute. Task team members and Caltrans staff and leadership provided extensive review of the draft Bus Rapid Transit: A Handbook for Partners. Caltrans adopted a new Director’s Policy and published the document, BRT Caltrans. The MTI “wraparound” report presented below discusses in more detail the process that was followed to produce the draft report. The process was in many ways as much a project as the report itself