Catholic University of Rome Sacro Cuore

San Vito sullo Ionio, Italy

Catholic University of Rome Sacro Cuore

San Vito sullo Ionio, Italy

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Cao J.,Chinese PLA General Hospital | Cao J.,University of Toledo | Vecoli C.,Sant'Anna School of Advanced Studies | Vecoli C.,Johns Hopkins University | And 12 more authors.
Frontiers in Physiology | Year: 2012

Myocardial dysfunction and coronary macro/microvascular alterations are the hallmarks of diabetic cardiomyopathy and are ascribed to increased oxidative stress and altered nitric oxide synthase (NOS) activity. We hypothesize that pre-treatment by cobalt-protoporphyrin IX (CoPP) ameliorates both myocardial function and coronary circulation in streptozotocin (STZ)-induced diabetic rats. Isolated hearts from diabetic rats in Langendorff configuration displayed lower left ventricular function and higher coronary resistance (CR) compared to hearts from control animals. CoPP treatment of diabetic animals (0.3mg/100g body weight i.p., once a week for 3 weeks) significantly increased all the contractile/relaxation indexes (p < 0.01), while decreasing CR (p < 0.01). CoPP enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the significant (p < 0.05) decrease in heart % GSSG, 0 2 -, and malondialdehyde (MDA) levels. CoPP increased adiponectin levels and phosphorylation of AKT and AMPK and reversed the eNOS/iNOS expression imbalance observed in the untreated diabetic heart. Furthermore, after CoPP treatment, a rise in malonyl-CoAas well as a decrease in acetyl-CoAwas observed in diabetic hearts. In this experimental model of diabetic cardiomyopathy, CoPP treatment improved both cardiac function and coronary flow by blunting oxidative stress, restoring eNOS/iNOS expression balance and increasing HO-1 levels, thereby favoring improvement in both endothelial function and insulin sensitivity. © 2012 Cao, Vecoli, Neglia, Tavazzi, Lazzarino, Novelli, Masiello, Wang, Puri, Paolocci, L'Abbate and Abraham.


Amorini A.M.,Catholic University of Rome Sacro Cuore | Giorlandino C.,Artemisia Fetal Maternal Medical Center | Longo S.,University of Catania | D'Urso S.,Catholic University of Rome Sacro Cuore | And 8 more authors.
Molecular and Cellular Biochemistry | Year: 2012

Physiologic concentration in amniotic fluid (AF) of several metabolites has not been established with certainty. In this study, we initially assayed purines, pyrimidines, and amino compounds in 1,257 AF withdrawn between the 15th and the 20th week of gestation from actually normal pregnancies (normal gestations, normal offspring). Results allowed to determine physiologic reference intervals for 45 compounds. In these AF, not all purines and pyrimidines were detectable and uric acid (238.35 ± 76.31 μmol/l) had the highest concentration. All amino compounds were measurable, with alanine having the highest concentration (401.10 ± 88.47 μmol/l). In the second part of the study, we performed a blind metabolic screening of AF to evaluate the utility of this biochemical analysis as an additional test in amniocenteses. In 1,295 additional AF from normal pregnancies, all metabolites fell within the confidence intervals determined in the first part of the study. In 24 additional AF from women carrying Down's syndrome-affected fetuses, glutamate, glutamine, glycine, taurine, valine, isoleucine, leucine, ornithine, and lysine were different from physiologic reference values. One AF sample showed phenylalanine level of 375.54 μmol/l (mean value in normal AF = 65.07 μmol/l) and was from a woman with unreported phenylketonuria with mild hyperphenylalaninemia (serum phenylalanine = 360.88 μmol/l), carrying the IVS 4 + 5 G-T and D394A mutations. The fetus was heterozygote for the maternal D394A mutation. An appropriate diet maintained the mother phenylalanine in the range of normality during pregnancy, avoiding serious damage in fetal and neonatal development. These results suggest that the metabolic screening of AF might be considered as an additional biochemical test in amniocenteses useful to highlight anomalies potentially related to IEM. © 2011 Springer Science+Business Media, LLC.


Di Pietro V.,Southampton General Hospital | Amin D.,Southampton General Hospital | Pernagallo S.,University of Edinburgh | Lazzarino G.,University of Catania | And 4 more authors.
Journal of Neurotrauma | Year: 2010

Traumatic brain injury (TBI) is the one of the most common forms of head trauma, and it remains a leading cause of death and disability. It is known that the initial mechanical axonal injury triggers a complex cascade of neuroinflammatory and metabolic events, the understanding of which is essential for clinical, translational, and pharmacological research. These can occur even in mild TBI, and are associated with several post-concussion manifestations, including transiently heightened vulnerability to a second insult. Recent studies have challenged the tenet that ischemia is the ultimate modality of tissue damage following TBI, as metabolic dysfunction can develop in the presence of normal perfusion and before intracranial hypertension. In order to elucidate the cellular and molecular changes occurring in TBI as a direct result of neuronal injury and in the absence of ischemic damage, we performed a microarray analysis of expressed genes and molecular interaction pathways for different levels of severity of trauma using an in-vitro model. A stretch injury, equivalent to human diffuse axonal injury, was delivered to rat organotypic hippocampal slice cultures, and mRNA levels following a 10% (mild) and 50% (severe) stretch were compared with controls at 24h. More genes were differentially expressed following 10% stretch than 50% stretch, indicating the early activation of complex cellular mechanisms. The data revealed remarkable differential gene expression following mTBI, even in the absence of cell damage. Pathway analysis revealed that molecular interactions in both levels of injury were similar, with IL-1β playing a central role. Additional pathways of neurodegeneration involving RhoA (ras homolog gene family, member A) were found in 50% stretch. © 2010, Mary Ann Liebert, Inc.


PubMed | Catholic University of Rome Sacro Cuore
Type: Journal Article | Journal: Molecular and cellular biochemistry | Year: 2011

Physiologic concentration in amniotic fluid (AF) of several metabolites has not been established with certainty. In this study, we initially assayed purines, pyrimidines, and amino compounds in 1,257 AF withdrawn between the 15th and the 20th week of gestation from actually normal pregnancies (normal gestations, normal offspring). Results allowed to determine physiologic reference intervals for 45 compounds. In these AF, not all purines and pyrimidines were detectable and uric acid (238.3576.31 mol/l) had the highest concentration. All amino compounds were measurable, with alanine having the highest concentration (401.1088.47 mol/l). In the second part of the study, we performed a blind metabolic screening of AF to evaluate the utility of this biochemical analysis as an additional test in amniocenteses. In 1,295 additional AF from normal pregnancies, all metabolites fell within the confidence intervals determined in the first part of the study. In 24 additional AF from women carrying Downs syndrome-affected fetuses, glutamate, glutamine, glycine, taurine, valine, isoleucine, leucine, ornithine, and lysine were different from physiologic reference values. One AF sample showed phenylalanine level of 375.54 mol/l (mean value in normal AF=65.07 mol/l) and was from a woman with unreported phenylketonuria with mild hyperphenylalaninemia (serum phenylalanine=360.88 mol/l), carrying the IVS 4+5 G-T and D394A mutations. The fetus was heterozygote for the maternal D394A mutation. An appropriate diet maintained the mother phenylalanine in the range of normality during pregnancy, avoiding serious damage in fetal and neonatal development. These results suggest that the metabolic screening of AF might be considered as an additional biochemical test in amniocenteses useful to highlight anomalies potentially related to IEM.

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