Individuals with familial hypercholesterolemia and cardiovascular events have higher circulating Lp(a) levels

BACKGROUND: Cardiovascular disease (CVD) is a major cause of mortality and morbidity. Increased low-density lipoprotein cholesterol (LDL-C) level is its major risk factor. Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated LDL-C since birth and subsequent premature CVD. There is a heterogeneity in the CVD onset in patients with FH. This is potentially due to the presence of other independent risk factors. Lipoprotein(a) [Lp(a)] is an LDL-like particle and represents a strong risk factor for CVD. OBJECTIVE: Our objective was to understand the contribution of Lp(a) in the susceptibility to CVD in individuals with genetic diagnosis of FH. METHODS: We measured Lp(a) levels in 2 independent and well-characterized genetic-FH cohorts: the FH-Gothenburg cohort (n = 190) and the FH-CEGP Milan cohort (n = 160). The genetic diagnosis was performed by targeted next-generation sequencing (FH-Gothenburg and part of the FH-CEGP Milan cohort), or by Sanger sequencing. RESULTS: We show that among individuals with genetic diagnosis of FH, those with previous CVD had higher Lp(a) levels. In addition, analyzing the response to the lipid-lowering therapies, we have also shown that statins had the same LDL-C-lowering effect irrespective of the type of FH-causative mutation. However, when we examined the lipid-lowering effect of proprotein convertase subtilisin/kexin type 9 inhibition by antibodies, we observed a trend in a better reduction of the LDL-C level in carriers of nonsense mutations. CONCLUSION: In conclusion, our results suggest that Lp(a) contributes to CVD onset in individuals with genetic diagnosis of FH. Our finding supports the importance to identify an efficacious therapy to lower Lp(a) in patients with FH to prevent CVD onset or recurrence

Identification and characterization of two novel mutations in the LPL gene causing type I hyperlipoproteinemia

Background Type 1 hyperlipoproteinemia is a rare autosomal recessive disorder most often caused by mutations in the lipoprotein lipase (LPL) gene resulting in severe hypertriglyceridemia and pancreatitis. Objectives The aim of this study was to identify novel mutations in the LPL gene causing type 1 hyperlipoproteinemia and to understand the molecular mechanisms underlying the severe hypertriglyceridemia. Methods Three patients presenting classical features of type 1 hyperlipoproteinemia were recruited for DNA sequencing of the LPL gene. Pre-heparin and post-heparin plasma of patients were used for protein detection analysis and functional test. Furthermore, in\ua0vitro experiments were performed in HEK293\ua0cells. Protein synthesis and secretion were analyzed in lysate and medium fraction, respectively, whereas medium fraction was used for functional assay. Results We identified two novel mutations in the LPL gene causing type 1 hyperlipoproteinemia: a two base pair deletion (c.765_766delAG) resulting in a frameshift at position 256 of the protein (p.G256TfsX26) and a nucleotide substitution (c.1211\ua0T\ua0>\ua0G) resulting in a methionine to arginine substitution (p.M404\ua0R). LPL protein and activity were not detected in pre-heparin or post-heparin plasma of the patient with p.G256TfsX26 mutation or in the medium of HEK293\ua0cells over-expressing recombinant p.G256TfsX26 LPL. A relatively small amount of LPL p.M404\ua0R was detected in both pre-heparin and post-heparin plasma and in the medium of the cells, whereas no LPL activity was detected. Conclusions We conclude that these two novel mutations cause type 1 hyperlipoproteinemia by inducing a loss or reduction in LPL secretion accompanied by a loss of LPL enzymatic activity

Retinoid and carotenoid status in serum and liver among patients at high-risk for liver cancer

BACKGROUND: Approximately 2.7 million Americans are chronically infected with hepatitis C virus (HCV). HCV patients with cirrhosis form the largest group of persons at high risk for hepatocellular carcinoma (HCC). Increased oxidative stress is regarded as a major mechanism of HCV-related liver disease progression. Deficiencies in retinoid and carotenoid antioxidants may represent a major modifiable risk factor for disease progression. This study aims to identify key predictors of serum antioxidant levels in patients with HCV, to examine the relationship between retinoid/carotenoid concentrations in serum and hepatic tissue, to quantify the association between systemic measures of oxidative stress and antioxidant status, and to examine the relationship between retinoids and stellate cell activation. METHODS: Patients undergoing liver biopsy (n = 69) provided fasting blood, fresh tissue, urine and completed a diet history questionnaire. Serum and questionnaire data from healthy volunteers (n = 11), normal liver tissue from public repositories and patients without liver disease (n = 11) were also collected. Urinary isoprostanes, serum and tissue retinoid concentrations were obtained by UHPLC-MS-MS. Immunohistochemistry for αSMA was performed on FFPE sections and subsequently quantified via digital image analysis. Associations between urinary isoprostanes, αSMA levels, and retinoids were assessed using Spearman correlation coefficients and non-parametric tests were utilized to test differences among disease severity groups. RESULTS: There was a significant inverse association between serum retinol, lycopene, and RBP4 concentrations with fibrosis stage. Serum β-carotene and lycopene were strongly associated with their respective tissue concentrations. There was a weak downward trend of tissue retinyl palmitate with increasing fibrosis stage. Tissue retinyl palmitate was inversely and significantly correlated with hepatic αSMA expression, a marker for hepatic stellate cell activation (r = −0.31, P < 0.02). Urinary isoprostanes levels were inversely correlated with serum retinol, β-carotene, and RBP4. CONCLUSIONS: A decrease in serum retinol, β-carotene, and RBP4 is associated with early stage HCV. Retinoid and carotenoid levels decline as disease progresses, and our data suggest that this decline occurs early in the disease process, even before fibrosis is apparent. Measures of oxidative stress are associated with fibrosis stage and concurrent antioxidant depletion. Vitamin A loss is accompanied by stellate cell activation in hepatic tissue. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12876-016-0432-5) contains supplementary material, which is available to authorized users

Il crollo del vento

Ogni volta che si ritiene necessario migliorare e rendere maggiormente adeguato all'evoluzione della tecnologia e del mercato il sistema normativo e incentivante relativo alle fonti rinnovabili, introducendo cambiamenti radicali, si determina una contrazione degli investimenti della durata variabile, ma mediamente - sino all'ultimo provvedimento legislativo, almeno per quanto riguarda l'eolico - di circa un paio d'anni. In linea di massima, la motivazione di tale rallentamento nella diffusione dell'eolico è ascrivibile alla necessità da parte dei potenziali investitori e degli istituti di credito di comprendere appieno il disposto legislativo, la sua portata e i margini di rischio. Ora, invece, con la normativa attuale -e precisamente con il Decreto Legislativo del 3 marzo 2011 e del susseguente decreto attuativo del 6 luglio 2012 - la situazione è drasticamente peggiorata sia per le previsioni sulla durata degli effetti negativi, sinora registrati e, soprattutto, per l'entità degli stessi, nettamente superiore alle ipotesi più pessimistiche

PRODUZIONE ESTIVA DI PLEUROTUS SAJOR-CAJU (FR.) SINGER SU RESIDUI LEGNOSI IN STRUTTURE AZIENDALI

LE CARATTERISTICHE DEL PLEUROTUS SAJOR-CAJU HANNO CONSENTITO LO SVILUPPO DI FRUTTIFICAZIONI NELL'INTERVALLO DI TEMPERATURA 16-26°C, SU SUBSTRATI COSTITUITI DA TRINCIATO DI PIOPPO, PAGLIA DI GRANO E RELATIVE MISCELE, ANCHE NON STERILIZZATI, CON CONSEGUENTE POSSIBILE RIDUZIONE DEI COSTI DI PRODUZION

Indagine anemologica in quaranta siti della Sardegna

SIGLEITItal

High prevalence of genetic determined familial hypercholesterolemia in premature coronary artery disease

Carlo Pirazzi,1 Lina H&aring;kansson,1 Carola Gustafsson,1 Elmir Omerovic,1,2 Olov Wiklund,2 Rosellina Margherita Mancina21Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden; 2Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, SwedenBackground: Premature coronary artery disease (CAD) is a major cause of mortality and morbidity. Increased low-density lipoprotein-cholesterol (LDL-C) level is a major risk factor for CAD and thus the main target for its prevention. Familial Hypercholesterolemia (FH) is a genetic inherited disorder characterized by high LDL-C, and subsequent premature CAD development. Early drug treatment with lipid-lowering medications in FH prevents cardiovascular disease onset.&nbsp; &nbsp;The FH prevalence in the Northern European general population is 0.3%, and it is estimated that it explains 20% of premature CAD cases in individuals with familial clustering. Despite the wide number of papers showing the prevalence of clinical FH in cardiovascular disease, the prevalence of genetic FH in individuals with premature CAD is not yet well known. Here, we examined the prevalence of genetically determined FH in individuals with premature CAD.Patients and methods: 66 patients who underwent coronary angiography with suspected premature acute coronary syndrome (age &lt;50 years for men and &lt;55 years for women) underwent genetic screening to identify FH-causing mutations. All patients underwent physical and clinical examinations. Information about family and personal history, drug therapy and habits were also collected.Results: We found FH-causative mutations in 3/66 (4.5%) screened individuals with premature CAD. When considering individuals with confirmed CAD after coronary angiography, the FH mutation prevalence was 6.1% (3/49). After excluding individuals with classical risk factors for CAD other than hypercholesterolemia, the FH mutation prevalence raised to 15.8% (3/19).Conclusion: In conclusion, we found that individuals with premature CAD have a more than 15-fold increased prevalence of FH mutations compared to the general population.Keywords: young, myocardial infarction, CAD, acute coronary event, F