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Grossini E.,University of Piemonte Orientale | Molinari C.,University of Piemonte Orientale | Pollesello P.,Orion Pharma | Bellomo G.,Laboratory Analysis | And 6 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2012

Ischemia/reperfusion (I/R) injury is an important cause of acute renal failure because of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine any possible protective effects of levosimendan in an in vivo pig model of renal I/R injury. In 40 anesthetized pigs (eight groups of five pigs each), I/R was induced by clamping-reopening the left renal artery. During ischemia, in three groups of pigs, levosimendan and the multiorgan preservation solution Custodiol, alone or in combination with levosimendan, were infused in the renal artery. In two other groups of animals, levosimendan in combination with Custodiol was administered after the intrarenal nitric-oxide (NO) synthase blocker Nω-nitro-L-arginine methyl ester (L-NAME) or the mitochondrial ATP-sensitive K+channel (K ATP channel) inhibitor 5-hydroxydecanoate (5-HD). In the other animals, saline, L-NAME, or 5-HD were administered alone. Throughout the experiments, urinary N-acetyl-β-glucosaminidase (NAG) release was measured, and renal function was assessed. Moreover, renal biopsy samples were taken for the detection of apoptosis and tissue peroxidation. In pigs treated with levosimendan or the combination of levosimendan and Custodiol, NAG, peroxidation, and apoptotic markers were lower than in animals treated with Custodiol alone. In addition, renal function was better preserved, and cell survival and antioxidant systems were more activated. All beneficial effects were prevented by L-NAME and 5-HD. In conclusion, levosimendan alone or in combination with Custodiol exerted better protection against renal I/R injuries than Custodiol alone through antioxidant, antiapoptotic, and prosurvival actions depending on mitochondrial KATP channels and NO-related mechanisms. Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics.

Foppiani L.,Endocrinology | Maffe A.,Laboratory Analysis | Forzano F.,Genetics
Andrologia | Year: 2010

Summary Coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies (CHARGE) syndrome is a genetic syndrome in which hypogonadism is a frequent feature. A causative mutation within the chromodomain helicase DNA-binding protein-7 gene, which plays an important role in the embryonic development, is present in 2/3 of affected patients. We describe the clinical, hormonal and molecular characteristics of a young man from Ecuador who was diagnosed as having CHARGE syndrome at an adult age. The patient showed several phenotypic features of the syndrome, associated with a prepubertal state and cryptorchidism; hypogonadotrophic hypogonadism with undetectable testosterone levels not responsive to hCG testing and severe osteoporosis were ascertained. Molecular evaluation of the CHD7 gene showed the novel frameshift truncating heterozygous mutation p.Tyr1046Glyfs*23 in exon 12. Magnetic resonance imaging revealed mild hypoplasia of the pituitary gland and hypoplasia of the posterior cranial fossa. Parenteral testosterone therapy led to sexual development over time and, in combination with diphophonate therapy and calcium-vitamin D supplementation, significantly improved bone mineralisation. Early proper hormonal treatment of hypogonadism in patients with complex genetic syndromes is important to achieve normal sexual maturation, improve quality of life and avoid significant comorbidities, such as osteoporosis. © 2010 Blackwell Verlag GmbH.

Feola M.,Cardiovascular Rehabilitation Heart Failure Unit | Garrone O.,Nuclear Medicine Service | Occelli M.,Nuclear Medicine Service | Francini A.,Nuclear Medicine Service | And 4 more authors.
International Journal of Cardiology | Year: 2011

Anthracyclines are among the most active drugs in breast cancer patients. We planned to evaluate the early and 2-year modification of left ventricular ejection fraction (LVEF) and the effects of chemotherapy on troponin I and neurohormonal assessment. Methods: Patients with early breast cancer surgically treated and eligible to adjuvant chemotherapy were enrolled. All patients underwent clinical assessment, radionuclide ventriculography, troponin I and brain natriuretic peptide (BNP) measurements at baseline and one-month (T1), one year (T2) and 2-year (T3) after chemotherapy. Reductions of LVEF ≥ 10% or an overt heart failure were considered cardiovascular events. Results: 53 patients, 52 females and 1 male, age 55.3 years were included and followed at T3. A significant reduction of LVEF was observed (from 62 ± 5.5% to 59.3 ± 8.6%, p = 0.04) at T3; BNP increased (from 33.4 ± 41.5 pg/ml to 62.7 ± 94.7 pg/ml, p = 0.005) at T1. Troponin I augmented at T1 (from 0.006 ± 0.01 ng/ml to 0.05 ± 0.04 ng/ml, p = 0.0001) but normalized at T2 (0.005 ± 0.08 ng/ml; p = 0.9). Only baseline BNP was nearly to be significantly correlated with T3 LVEF (p = 0.07 HR 0.96-1) at multivariate analysis. In 13/53 patients (32.1%) LVEF showed ≥ 10% reduction at T3 (group A); in 40/53 patients (67.9%) LVEF was unchanged (group B). Patients in group A demonstrated higher baseline plasma BNP (p = 0.02) and lower haemoglobin concentration (p = 0.007) compared to patients in group B. Conclusions: LVEF and BNP modified early after anthracycline chemotherapy and LVEF did not recover at T3. In patients who developed left ventricular systolic dysfunction, a subclinical activation of neurohormonal profile was observed. © 2009 Elsevier Ireland Ltd.

Feola M.,Cardiovascular Rehabilitation Heart Failure Unit | Valeri L.,SS Annunziata Hospital | Menditto E.,Cardiovascular Rehabilitation Heart Failure Unit | Nervo E.,Cardiovascular Rehabilitation Heart Failure Unit | And 4 more authors.
Journal of Endocrinological Investigation | Year: 2010

This study compared two different methods, namely the immunoradiometric (IRMA) and fluorimetric (FIA), in order to determine plasma brain natriuretic peptide (BNP) in congestive heart failure (CHF) patients. Methods: CHF in-patients underwent echocardiography and plasma BNP determination using both two methods. The echocardiograms analysed left ventricular end-systolic (LVESV) and end-diastolic (LVEDV) volumes and systolic dysfunction [left ventricular ejection fraction (LVEF) <50%]. Results: Seventy-three (71% males, age 67±9.6 yr) patients were enrolled, 31.5% affected by valvular heart disease. The mean LVEF was 39.8±14.1%; in 26 (35%) a hypertensive etiology emerged. The immunoradiometric assay (IRMA) BNP was found to be significantly lower than the FIA determination 116.5±149 pg/ml vs 267.3±285.6 pg/ml; p=0.0001) and the two methods were closely correlated (r=0.89; p=0.00001). Logistic regression demonstrated a significant correlation between BNP, LVEF, and LVESV/LVEDV (r=-0.45, p=0.0003; r=-0.48, p=0.00001; r=0.22 p=0.003; r=0.34 p=0.0001; r=0.13 p=0.02; r=0.28 p=0.001 IRMA and FIA, respectively). IRMA BNP and FIA BNP significantly increased according to the worsening functional class [from 34.3±60.2 pg/ml in NYHA (New York Heart Association) I to 555.5±273.1 pg/ml in NYHA IV; from 86.1±162.1 pg/ml in NYHA I to 1070±42.2 pg/ml in NYHA IV, respectively]. In severe systolic dysfunction (LVEF<30%), receiver operating characteristic analysis revealed a satisfactorily sensitivity and specificity using a cut-off point of 50.6 pg/ml with IRMA and 243 pg/ml with FIA. In mild systolic dysfunction (LVEF<50%), a good sensitivity and specificity using a cut-off point of 42 pg/ml with IRMA and 182 pg/ml with FIA emerged. Conclusions: In CHF patients both BNP methods correlated with NYHA class, LVEF, and ventricular volumes. ©2010, Editrice Kurtis.

Radicioni M.,Neonatal Intensive Care | Bruni A.,Neonatal Intensive Care | Bini V.,University of Perugia | Villa A.,Laboratory Analysis | Ferri C.,Laboratory Analysis
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2015

Objective: To delineate thromboelastographic profiles of the premature infants with and without intracranial hemorrhage during the first 21 days of life. Methods: In this study, 49 premature infants (24 female; 25 male) were consecutively admitted at our neonatal intensive care unit during a 6 months period were subject to thromboelastography and standard coagulation assessments at birth and weekly up to 21 days. Sixteen out of 49 infants developed intracranial hemorrhage at birth. Results: The test results of 127/196 were considered eligible for analysis. Overall significant changes of the main thromboelastographic parameters were observed shortly after birth. Newborns with intracranial hemorrhage showed increased thromboelastogram-defined thrombin generation (shorter R and time to maximum amplitude times) from birth onward, suggesting a hypercoagulable state. No significant differences concerning thromboelastographic and coagulation assays parameters were found at birth between infants with and without intracranial hemorrhage, except for higher plasma D-Dimer concentration (p = 0.002) in the former infants. Finally, a positive correlation between clot lysis time and gestational age (Spearman's rho = 0.502, p = 0.002) was observed. Conclusions: Thromboelastographic profiles of the premature infants suggest an effective hemostatic function during the first post-natal weeks. Further study is needed to determine whether thromboelastography may be more useful than coagulation assays to reflect the bleeding risk of the premature infants. © 2014 Informa UK Ltd. All rights reserved.

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