Increased formation of distinct F2 isoprostanes in hypercholesterolemia

BACKGROUND: F2 isoprostanes are stable, free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. METHODS AND RESULTS: Specific assays were developed by use of mass spectrometry for the F2 isoprostanes iPF2alpha-III and iPF2alpha-VI and arachidonic acid (AA). Urinary excretion of the 2 F2 isoprostanes was significantly increased in hypercholesterolemic patients, whereas substrate AA in urine did not differ between the groups. iPF2alpha-III (pmol/mmol creatinine) was elevated (P<0.0005) in homozygous familial hypercholesterolemic (HFH) patients (85+/-5. 5; n=38) compared with age- and sex-matched normocholesterolemic control subjects (58+/-4.2; n=38), as were levels of iPF2alpha-VI (281+/-22 versus 175+/-13; P<0.0005). Serum cholesterol correlated with urinary iPF2alpha-III (r=0.41; P<0.02) and iPF2alpha-VI (r=0. 39; P<0.03) in HFH patients. Urinary excretion of iPF2alpha-III (81+/-10 versus 59+/-4; P<0.05) and iPF2alpha-VI (195+/-18 versus 149+/-20; P<0.05) was also increased in moderately hypercholesterolemic subjects (n=24) compared with their controls. Urinary excretion of iPF2alpha-III and iPF2alpha-VI was correlated (r=0.57; P<0.0001; n=106). LDL iPF2alpha-III levels (ng/mg arachidonate) were elevated (P<0.01) in HFH patients (0.32+/-0.08) compared with controls (0.09+/-0.02). The concentrations of iPF2-III in LDL and urine were significantly correlated (r=0.42; P<0.05) in HFH patients. CONCLUSIONS: Asymptomatic patients with moderate and severe hypercholesterolemia have evidence of oxidant stress in vivo

Two siblings with a homozygous MTHFR C677T (G80A-RFC1) mutation and stroke

Background: Stroke is a rare disorder in childhood; among its risk factors, C677T mutations in the methylenetetrahydrofolate reductase (MTHFR) gene with secondary hyperhomocysteinemia are considered. Patients and methods: We report on a family in which two brothers had arterial ischemic stroke (AIS). One of these siblings came to our observation at the age of 4 years because of decreased motility of the right arm, mild hypotrophy of the right limbs, and frequent falls: brain magnetic resonance imaging revealed a large left AIS. Family history revealed that his older brother had died at the age of 7 due to AIS. An extensive metabolic investigation revealed a homozygous C677T [G80A-reduced folate carrier 1 (RFC1)] mutation in the MTHFR gene in both the affected siblings and in their healthy older brother and heterozygous mutations in the parents. None of these family members presented hyperhomocysteinemia. Conclusions: To the best of our knowledge, this is the first family with multiple AIS patients harboring homozygous MTHFR gene C677T (G80A-RFC1) mutations without associated hyperhomocysteinemia (the latter factor is usually considered as effector of vascular damage in patients with MTHFR C677T mutations). The pathogenic hypotheses of stroke in this family are considered

Catalogo Prestazionale dei Manti Bituminosi Superficiali

La pavimentazione stradale riveste oggi peculiare rilevanza in relazione al soddisfacimento di istanze primarie ed assolutamente generali quali la sicurezza della locomozione e la ecocompatibilit\ue0 del moto, soprattutto per ci\uf2 che concerne le caratteristiche dello strato superficiale. La logica che presiede al processo di attribuzione dei requisiti si \ue8 nel contempo sempre pi\uf9 caratterizzata in termini di esigenza di \u201cprestazioni\u201d (aderenza, regolarit\ue0, portanza, ridotta contribuzione vibro-sonora, etc.), rendendo di fatto meno prioritario e cogente il sistema di vincoli compositivo-esecutivi, diffusamente usato finora nei tradizionali Capitolati Speciali d\u2019Appalto. In tale ottica, condivisa in ambito scientifico, tecnologico e giuridico, cospicua importanza hanno acquisito i \u201ccapitolati prestazionali\u201d, con i quali \ue8 possibile governare, in un mercato dalle regole di accesso e permanenza in continua evoluzione, i rapporti tra Committenze (sempre pi\uf9 identificate in Enti Locali) ed Imprese Esecutrici, sulla base di codici di \u201csussistenza prestazionale\u201d, fondati su di un insieme di indicatori funzionali. Essi, con riferimento al piano di via, rivestono un ruolo fondamentale poich\ue9 attengono a propriet\ue0 che sono in grado di condizionare tutti i fenomeni connessi al contatto tra pneumatico e superficie di rotolamento, i cui effetti interferiscono con la sicurezza del moto, con il comfort di marcia, nonch\ue9 con la compatibilit\ue0 ambientale del trasporto su gomma, tanto in termini di inquinamenti (rumore e vibrazioni) che di costi energetici (consumo di carburanti e pneumatici). Presupposto per\uf2 indispensabile per la validit\ue0 del sistema \u201cprestazionale\u201d di rapporti tra Committenze ed Esecutori \ue8 che, a valle delle richieste di \u201cperformances\u201d avanzate dalle Prime, i Secondi abbiano riferimenti sicuri su quali strumenti (materiali, accortezze compositive, processi di messa in opera, etc.) consentiranno loro di rispondere con successo. In tale articolato scenario, caratterizzato dalla inconsueta contemporaneit\ue0 tra innalzamento e diversificazione delle prestazioni richieste, trasferimento di oneri di possesso e manutenzione agli Enti Locali, affinamento delle tecniche di indagine sperimentale e cospicuo incremento dei costi delle strumentazioni di prova, si avverte l\u2019esigenza di chiare ed affidabili regole di corrispondenza tra aspetti compositivo-esecutivi e prestazioni ottenute. Sensibili a tali istanze, nel 2001 \ue8 stato cofinanziato, ed ad oggi completato, un progetto di rilevante interesse nazionale dal titolo \u201cIstituzione di un catalogo prestazionale dei manti bituminosi per pavimentazioni stradali\u201d, il cui obiettivo era proprio la formalizzazione, a valle di una cospicua attivit\ue0 di sperimentazione, di un catalogo dei rivestimenti superficiali ove risultasse possibile accertare la corrispondenza fra protocolli di composizione, produzione e messa in opera da un lato e prestazioni risultanti dall\u2019altro

HCV infection is a risk factor for gallstone disease in liver cirrhosis: An Italian epidemiological survey

We assessed the prevalence of gallbladder disease (i.e. gallstones plus cholecystectomy) among patients with liver disease and its association with the severity and aetiology of hepatic injury. Subjects, referred to 79 Italian hospitals, were enrolled in a 6-month period. The independent effect of the severity and aetiology of liver disease on gallstone disease prevalence was assessed by multiple logistic regression analysis. Overall, 4867 subjects tested anti-hepatitis C virus (HCV) positive alone, 839 were hepatitis B virus surface antigen (HBsAg) alone, and 652 had an excessive alcohol intake. The prevalence of gallstone disease was 23.3% in anti-HCV-positive patients, 12.4% in HBsAg positive and 24.2% in subjects reporting excessive alcohol intake, respectively. Gallstone disease prevalence increased by age in each aetiological category. The proportion of patients with gallstone disease who had a cholecystectomy was the highest in HCV+ subjects. After adjusting for the confounding effect of age and body mass index, compared with patients with less severe liver disease, subjects with HCV-related cirrhosis, but not those with alcohol-related cirrhosis, were more likely to have gallstone disease. Subjects with HCV-related cirrhosis (OR 2.13, 95% CI: 1.38-3.26) were more likely to have gallstone disease when compared with those with HBV-related cirrhosis. HCV infection is a risk factor for gallstone disease. In Italy, the high prevalence of HCV infection among cirrhotic patients has important implications, as cholecystectomy in these subjects is associated with high risk of morbidity and mortality. \uc2\ua9 2007 The Authors

Glomerular filtration rate: A prognostic marker in atrial fibrillation-A subanalysis of the AntiThrombotic Agents Atrial Fibrillation.

OBJECTIVE An increased cardiovascular mortality and morbidity has been widely reported in patients with atrial fibrillation (AF). In this study, a subanalysis of the AntiThrombotic Agents Atrial Fibrillation (ATA-AF) is performed with the aim to evaluate estimated glomerular filtration rate (eGFR) as an independent prognostic marker of cardiovascular mortality and morbidity in patients with AF. METHODS AND RESULTS The ATA-AF study enrolled 7148 patients with AF, in 360 Italian centers. The eGFR was calculated from data reported in patient notes or hospital database. This post-hoc analysis included 1097 AF patients with eGFR data available and 1-year clinical follow-up. The endpoint was assessed as cardiovascular mortality and/or hospital admission for cardiovascular causes at follow-up. Patients were also divided in two groups according to the eGFR (<60 and ≥60 mL/min/1.73 m ). The Kaplan-Meyer curve for the mentioned endpoint showed a higher endpoint incidence in the group of patient with eGFR below 60 mL/min/1.73 m (P < 0.001). Using multivariate analysis (Cox regression), a trend toward a higher rate of occurrence of the primary endpoint was observed for eGFR below 60 mL/min/1.73 m without reaching the conventional level of statistical significance (hazard ratio [HR] 1.40; 95% confidence interval [CI] 0.99-1.99; P = 0.0572). When eGFR was included in the analysis as continuous variable a significant correlation was observed with the combined endpoint at the Cox regression (HR 0.99, 95% CI 0.98-0.99, P = 0.04). CONCLUSION The result of this post-hoc analysis indicates that an impaired eGFR is independently associated with worse prognosis among patients with AF