Vascular oxidative stress-induced senescence is minimized by melatonin intake in ApoE-deficient mice

Aging is a natural process that produces deleterious changes in all tissues of the organism. One leading theory about the cause of aging suggest that oxidative stress play a fundamental role in pathogenesis. Oxidative stress induces intracellular damage that affects all biological components, including, DNA, lipids, sugars and proteins. Therefore, the imbalance between intracellular reactive oxygen species (ROS) and antioxidant defence mechanisms results in harmful oxidative stress. One of the most widely considered strategies for preventing aging and for treating age-related disease is the use of natural anti-oxidant agents, such as melatonin and resveratrol. Melatonin is a potent endogenous anti-oxidant neurohormone, which acts through various mechanisms to ameliorate the toxic effects of ROS. However, little is known about the mechanisms of signalling pathways through which melatonin acts to reverse the effects of ROS. In the present study we treated ApoE-deficient mice, a well-known senescence model, from 6th week to 15th week of life, with a specific melatonin formulation: Armonia Retard (kindly provided by Nathura s.r.l, Reggio Emilia, Italy), with an extended-release pharmacokinetic, at different progressive doses 0.04, 0.1, 10 mg/kg/day. We used the same treatment in C57BL6 mice, as control group. Vascular alterations were evaluated in aorta by morphology and immunofluorescence analysis was focused on pleiotropic inflammatory markers, such as interleukins (IL) 6 and 10, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α). We observed in ApoE-deficient mice endothelial cell detachment and  IL-6, IL-10, iNOS and TNF-α overexpression. Melatonin treatment improved not only the endothelial damage, but also the overall vascular cytoarchitecture and reduced inflammation and macrophages infiltration. In particular, melatonin Retard at the highest dose, recovered all the above markers to the levels of C57BL6 mice. These results outline the anti-inflammatory and anti-oxidant properties of melatonin and its beneficial anti-aging and anti-atherosclerotic effects, especially in extended-release formulation

Sirtuin 6 localization at cortical brain level of young diabetic mice

The metabolic syndrome, characterized by visceral obesity, dyslipidaemia, hyperglycaemia and hypertension, has become one of the major public-health challenges worldwide and it is strictly associated with the development of type II diabetes and neurodegenerative diseases (Alberti et al. 2005; Panza et al. 2010). Increased metabolic flux to the brain during overnutrition can orchestrate stress response, blood-brain barrier alteration, microglial cells activation and neuroinflammation (Nerurkar et al., 2011). The protein sirtuin family is a class of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that act on a variety of targets and so play a key role in central physiological regulation (Sebastian et al., 2012; Wang et al., 2012). To assess the physiopathological significance of sirtuin6 (SIRT6) at brain cortical level, we analysed its specific expression and subcellular localization in young db/db mice, animal model of type II diabetes mellitus, and respective control lean mice. In particular, we analysed the cytoarchitecture of the brain cortex, evaluated SIRT6 expression and its localization by immunohistochemistry comparing young db/db mice to lean control mice, distinguishing among the six cortical layers and between motor and somatosensory cortex. We observed that SIRT6 is mainly localized in the nucleus of both lean and db/db mice. Diabetic mice showed few SIRT6 positive cells respect to lean control mice in all cortical layers without significant differences between motor and somatosensory cortex. No morphological alteration have been find. In conclusion, our findings contribute to further understand SIRT6 protein expression in the early steps of type II diabetes mellitus and suggest its implication in the pathogenic processes of diabetes mellitus and diabetes–induced neurodegeneration

Sirtuin 6 localization at cortical brain level of young diabetic mice

The metabolic syndrome, characterized by visceral obesity, dyslipidaemia, hyperglycaemia and hypertension, has become one of the major public-health challenges worldwide and it is strictly associated with the development of type II diabetes and neurodegenerative diseases (Alberti et al. 2005; Panza et al. 2010). Increased metabolic flux to the brain during overnutrition can orchestrate stress response, blood-brain barrier alteration, microglial cells activation and neuroinflammation (Nerurkar et al., 2011). The protein sirtuin family is a class of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that act on a variety of targets and so play a key role in central physiological regulation (Sebastian et al., 2012; Wang et al., 2012). To assess the physiopathological significance of sirtuin6 (SIRT6) at brain cortical level, we analysed its specific expression and subcellular localization in young db/db mice, animal model of type II diabetes mellitus, and respective control lean mice. In particular, we analysed the cytoarchitecture of the brain cortex, evaluated SIRT6 expression and its localization by immunohistochemistry comparing young db/db mice to lean control mice, distinguishing among the six cortical layers and between motor and somatosensory cortex. We observed that SIRT6 is mainly localized in the nucleus of both lean and db/db mice. Diabetic mice showed few SIRT6 positive cells respect to lean control mice in all cortical layers without significant differences between motor and somatosensory cortex. No morphological alteration have been find. In conclusion, our findings contribute to further understand SIRT6 protein expression in the early steps of type II diabetes mellitus and suggest its implication in the pathogenic processes of diabetes mellitus and diabetes–induced neurodegeneration

Effect of initial levothyroxine dose on neurodevelopmental and growth outcomes in children with congenital hypothyroidism

We designed a multicentre open prospective randomized trial to evaluate the risk-benefit profile of two different initial treatment schemes with levothyroxine (L-T4), 10-12.5 μg/kg/day vs 12.6-15 μg/kg/day, on growth and neurodevelopmental outcomes in children with congenital hypothyroidism (CH) detected by neonatal screening to identify the best range dose to achieve optimal neurocognitive development

Gross hematuria caused by a congenital intrarenal arteriovenous malformation: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report the case of a woman who presented with gross hematuria and was treated with a percutaneous embolization.</p> <p>Case presentation</p> <p>A 48-year-old Caucasian woman presented with gross hematuria, left flank pain, and clot retention. The patient had no history of renal trauma, hypertension, urolithiasis, or recent medical intervention with percutaneous instrumentation. The patient did not report any bleeding disorder and was not taking any medication. Her systolic and diastolic blood pressure values were normal at presentation. The patient had anemia (8 mg/dL) and tachycardia (110 bpm). She underwent color and spectral Doppler sonography, multi-slice computed tomography, and angiography of the kidneys, which showed a renal arteriovenous malformation pole on top of the left kidney.</p> <p>Conclusions</p> <p>The feeding artery of the arteriovenous malformation was selectively embolized with a microcatheter introduced using a right transfemoral approach. By using this technique, we stopped the bleeding, preserved renal parenchymal function, and relieved the patient's symptoms. The hemodynamic effects associated with the abnormality were also corrected.</p

Lipoprotein(a) and family history for cardiovascular disease in paediatric patients: A new frontier in cardiovascular risk stratification. Data from the LIPIGEN paediatric group

Background and aims: Little is known about the role of Lp(a) in the assessment of cardiovascular risk in the paediatric population. Trying to clarify the clinical relevance of Lp(a) in risk stratification, the aim of the study is to evaluate the association between Lp(a) plasma levels in children with familial hypercholesterolaemia (FH) and positive family history for premature cardiovascular disease (pCVD) in first-and second-degree relatives. Methods: 653 Caucasian children and adolescents (334 females and 319 males), aged 2-17 years, with diagnosis of FH from a paediatric cohort included in the LIPIGEN Network, were selected. We compared family history of pCVD, lipid and genetic profile in two groups based on Lp(a) levels below or above 30 mg/dL. To determine the independent predictors of pCVD, a multivariate logistic regression was used, with all clinical characteristics and blood measurements as predictors. Results: Subjects with Lp(a) > 30 mg/dl more frequently reported positive family history of pCVD compared to subjects with Lp(a) 30 mg/dl was an independent predictor of family history of pCVD. Comparing subjects with or without family history of pCVD, we reported significant differences for Lp(a) > 30 mg/dl (46.25% vs 17.65%, p 30 mg/dl where more likely to have a positive family history of pCVD. Lp(a) screening in children and adolescents with FH may enhance risk assessment and help identify those subjects, children and relatives, at increased pCVD risk

Thymus and aging: morphological, radiological, and functional overview.

5reservedmixedRezzani R.; Nardo L.; Favero G.; Peroni M.; Rodella L.F.Rezzani, Rita; Nardo, L.; Favero, Gaia; Peroni, M.; Rodella, Luigi Fabrizi