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Petta S.,University of Palermo | Valenti L.,University of Milan | Bugianesi E.,University of Turin | Targher G.,University of Verona | And 23 more authors.
Digestive and Liver Disease | Year: 2016

The prevalence of fatty liver (steatosis) in the general population is rapidly increasing worldwide. The progress of knowledge in the physiopathology of fatty liver is based on the systems biology approach to studying the complex interactions among different physiological systems. Similarly, translational and clinical research should address the complex interplay between these systems impacting on fatty liver. The clinical needs drive the applications of systems medicine to re-define clinical phenotypes, assessing the multiple nature of disease susceptibility and progression (e.g. the definition of risk, prognosis, diagnosis criteria, and new endpoints of clinical trials). Based on this premise and in light of recent findings, the complex mechanisms involved in the pathology of fatty liver and their impact on the short- and long-term clinical outcomes of cardiovascular, metabolic liver diseases associated with steatosis are presented in this review using a new "systems medicine" approach. A new data set is proposed for studying the impairments of different physiological systems that have an impact on fatty liver in different subsets of subjects and patients. © 2015 Editrice Gastroenterologica Italiana S.r.l.

Giovanardi P.,Internal Cardiovascular Medicine | Stefanelli G.,Unit of Cardiosurgery | Turrini F.,Internal Cardiovascular Medicine | Sarti L.,Internal Cardiovascular Medicine | And 5 more authors.
Minerva Cardioangiologica | Year: 2014

Aim. Aim of this study was to better understand interactions between left ventricular (LV) and right ventricular (RV) systolic and diastolic function echocardiographic indexes in stable cardiovascular diseased patients and in subjects with cardiovascular risk factors. Methods. The study enrolled 683 stable patients who were submitted to standard transthoracic echocardiography with evaluation of left ventricular ejection fraction (LVEF) (Simpson biplane method), LV and RV systolic peak on Doppler tissue imaging (LVSys and RVSys), tricuspid annulus plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), and multiparameter evaluation of LV and RV diastolic function utilizing E and A peak, their ratio, E peak deceleration time, E′ and A′ peak on Doppler tissue imaging, their ratio, and E/E′ ratio. Results. Part of the considered indexes had interactions but only LVEF and TAPSE were related to all the others (LVEF P<0.001 with all the considered parameters; TAPSE P<0.001 with all parameters except with PASP=0.003). Unexpectedly TAPSE seems to have, such as LVEF, a pivotal position among LV and RV function. Conclusion. The study demonstrates the existence of interactions between LV and RV function indexes; these results may be considered as a piece of evidence in favor of heart seen as a single structure.

Michot C.,University of Paris Descartes | Hubert L.,University of Paris Descartes | Romero N.B.,University Pierre and Marie Curie | Gouda A.,National Research Center of Egypt | And 21 more authors.
Journal of Inherited Metabolic Disease | Year: 2012

Background: Recessive LPIN1 mutations were identified as a cause of severe rhabdomyolysis in pediatric patients. The human lipin family includes two other closely related members, lipin-2 and 3, which share strong homology and similar activity. The study aimed to determine the involvement of the LPIN family genes in a cohort of pediatric and adult patients (n = 171) presenting with muscular symptoms, ranging from severe (CK >10 000 UI/L) or moderate (CK <10 000 UI/L) rhabdomyolysis (n = 141) to exercise-induced myalgia (n = 30), and to report the clinical findings in patients harboring mutations. Methods: Coding regions of LPIN1, LPIN2 and LPIN3 genes were sequenced using genomic or complementary DNAs. Results: Eighteen patients harbored two LPIN1 mutations, including a frequent intragenic deletion. All presented with severe episodes of rhabdomyolysis, starting before age 6 years except two (8 and 42 years). Few patients also suffered from permanent muscle symptoms, including the eldest ones (≥40 years). Around 3/4 of muscle biopsies showed accumulation of lipid droplets. At least 40% of heterozygous relatives presented muscular myalgia. Nine heterozygous SNPs in LPIN family genes were identified in milder phenotypes (mild rhabdomyolysis or myalgia). These variants were non-functional in yeast complementation assay based on respiratory activity, except the LPIN3-P24L variant. Conclusion: LPIN1-related myolysis constitutes a major cause of early-onset rhabdomyolysis and occasionally in adults. Heterozygous LPIN1 mutations may cause mild muscular symptoms. No major defects of LPIN2 or LPIN3 genes were associated with muscular manifestations. © 2012 SSIEM and Springer.

Patel J.V.,Metabolic Medicine | Patel J.V.,University of Birmingham | Hughes E.A.,Metabolic Medicine | Lip G.Y.H.,University of Birmingham | Gill P.S.,University of Birmingham
BMC Cardiovascular Disorders | Year: 2011

Background: Coronary heart disease (CHD) is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk.Methods/Design: The Diabetes Health, Residence & Metabolism in Asians (DHRMA) study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI) supply of chapatti (bread), stone ground, high protein wheat flour and white basmati rice (high bran, unpolished) or commercially available (leading brand) versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner.Discussion: It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive) for South Asian ethnic communities.Trial registration. Current Controlled Trials ISRCTN02839188. © 2011 Patel et al; licensee BioMed Central Ltd.

Salerno A.,Clinical Cardiology Heart Failure Clinic | Fragasso G.,Clinical Cardiology Heart Failure Clinic | Esposito A.,Diagnostic Radiology | Esposito A.,Vita-Salute San Raffaele University | And 11 more authors.
Acta Diabetologica | Year: 2015

Background and aims: We wanted to assess the effects of short-term changes in serum free fatty acids (FFAs) on left ventricular (LV) energy metabolism and function in patients with heart failure and whether they correlated with circulating markers of inflammation. Methods and results: LV function and phosphocreatine (PCr)/ATP ratio were assessed using MR imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) in 11 men with chronic heart failure in two experimental conditions 7 days apart. Study 1: MRI and 31P-MRS were performed before and 3–4 h after i.v. bolus + continuous heparin infusion titrated to achieve a serum FFA concentration of 1.20 mM. Study 2: The same protocol was performed before and after the oral administration of acipimox titrated to achieve a serum FFA concentration of 0.20 mM. Serum concentrations of IL6, TNF-α, PAI-1, resistin, visfatin and leptin were simultaneously assessed. Serum glucose and insulin concentrations were not different between studies. The PCr/ATP ratio (percent change from baseline: +6.0 ± 16.9 and −16.6 ± 16.1 % in Study 1 and Study 2, respectively; p = 0.005) and the LV ejection fraction (−1.5 ± 4.0 and −6.9 ± 6.3 % in Study 1 and Study 2, respectively; p = 0.044) were reduced during low FFA when compared to high FFA. Serum resistin was higher during Study 1 than in Study 2 (p < 0.05 repeated measures ANOVA); meanwhile, the other adipocytokines were not different. Conclusion: FFA deprivation, but not excess, impaired LV energy metabolism and function within hours. Cautions should be used when sudden iatrogenic modulation of energy substrates may take place in vulnerable patients. © 2014, Springer-Verlag Italia.

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