Regular physical exercise prevents nitrosative stress caused by ageing in elderly athletes

Ageing is associated with an increased susceptibility to free radical-induced tissue damage. One of the most important classes of free radicals generated in living systems is represented by reactive nitrogen species (RNS), responsible for the so-called nitrosative stress. It has been shown that physical activity is able to induce up-regulation of antioxidant systems contributing to prevent oxidative stress. The aim of the present study was to assess whether regular physical activity is able to counteract age-induced nitrosative stress. Thirty male endurance athletes (average age 70.8 ± 6.1 years, VO2max 59.07 ± 8.5 ml/kg/min) and thirty age-sex-matched sedentary controls ( average age 71.5 ± 4.3 years, VO2max 25.6 ± 8.2 ml/kg/min) were studied. Plasma free radicals antioxidant capacity against peroxynitrite, one of the most important RNS, was evaluated as Total Oxyradical Scavenging Capacity (TOSC) units. Results. Plasma TOSC values against peroxynitrite were higher in athletes than in sedentary controls (22.94 ± 1.85 vs 15.41 ± 1.24 units/ml, p < 0.001). In the athletes group, TOSC values were related to VO2max (r = 0.44, p < 0.05). In conclusion, these results suggest that regular physical activity is associated with increased antioxidant defences in elderly athletes. In athletes, a direct correlation between the scavenger scavenger of the plasma and the VO2max (r = 0.44, p <0.05) was also observed. These results confirm that regular physical activity practised for many years can determine the best response to nitrosative stress induced by peroxynitrite

Carotid integrated backscatter analysis in patients with subclinical hypothyroidism

OBJECTIVE: The aim of the present study was to determine whether integrated backscatter (IBS) analysis combined with conventional ultrasonography could differentiate the tissue characteristics of carotid artery intimal hyperplasia in patients with subclinical hypothyroidism (SH). METHODS: Forty-one patients with SH, as judged by elevated serum TSH levels and free thyroid hormones within the normal range, and 31 sex- and age-matched euthyroid volunteers underwent two-dimensional conventional ultrasonography and IBS analysis of the carotid wall. Carotid intima-media thickness (IMT) and corrected IBS (C-IBS), an index of arterial wall degeneration and fibrosis, were evaluated. RESULTS: Mean IMT as well C-IBS values were higher in SH than in controls (P < 0.0001 for both), whereas the carotid diameter was not significantly different between the two groups. The distribution of C-IBS values in each group showed that regions with higher C-IBS values were found more frequently in SH patients than in control subjects. The percentage of regions that could be considered as fibromatous (C-IBS value from -18 to -21 dB) was 28% in SH and 9% in euthyroid subjects (P < 0.0001). In the SH group, C-IBS values were significantly and positively associated with plasma TSH (r = 0.32, P < 0.05 and r = 0.59, P < 0.0001, respectively) and with both total cholesterol (r = 0.46, P = 0.01) and low density lipoprotein (LDL)-cholesterol (r = 0.55, P = 0.001). CONCLUSIONS: Carotid IMT in subclinically hypothyroid patients is higher than that in euthyroid controls. This is characterized by increased IBS values, which are related to the collagen content of the arterial wall. The severity of this remodelling process seems to be related to TSH and cholesterol levels

Effect of L-thyroxine treatment on left ventricular function in subclinical hypothyroidism

Aim of this study was to investigate the effects of thyroxine treatment on myocardial regional left ventricular (LV) systolic and diastolic function in patients with subclinical hypothyroidism (SH) by tissue Doppler imaging (TDI). Forty-two patients (29 women and 13 men; mean age 52.2 +/- 15.1 years) with SH, as judged by elevated serum thyroid-stimulating hormone (TSH) levels (> 3.6 mIU/l; range, 3.8-12.0) and free thyroid hormones (FT4 and FT3) within the normal range, and 30 euthyroid volunteers (21 women and nine men; mean age 50.4 +/- 17.1 years) underwent standard echocardiography and TDI-derived early (E-m) and late (A(m)) diastolic velocities, systolic (S-m) velocity, and isovolumetric relaxation time (IVRTm). Patients were randomly assigned to receive or not L-thyroxine replacement therapy. All patients returned after 6 months to repeat thyroid function tests and the evaluation of all parameters. No significant differences were seen in the Sm peak between SH and control groups. Respect to controls, SH patients exhibited a lower E-m, a higher A(m), and, subsequently, a reduced E-m/A(m) ratio of both lateral wall (LW) and interventricular septum (IVS) (P < 0.001 for both). The IVRTm was distinctly longer in SH patients, as compared to controls (P < 0.001). At 6 months, L-thyroxine-treated patients showed a significant increase of E-m (P < 0.01) and a subsequent increase of the E-m/A(m) ratio (P < 0.01), whereas IVRTm significantly reduced (P < 0.05). No significant change in any of these parameters was observed in the untreated group. Our data suggest that SH is associated with a subtle, reversible impairment of myocardial function. TDI analysis detects and extends these functional defects by displaying alterations in regional myocardial function. L-T-4 replacement therapy should be advised for these patients with the aim to correct preclinical cardiac dysfunction and prevent the development of clinically significant myocardial dysfunction. (c) 2006 Elsevier SAS. All rights reserved

Cardiac involvement in chronic progressive external ophthalmoplegia

Myocardial involvement has not been extensively investigated in mitochondrial myopathies. The aim of the study was to assess the myocardial morpho-functional changes in patients with chronic progressive external ophthalmoplegia (PEO). Twenty patients with PEO and 20 controls underwent standard echocardiography with tissue Doppler imaging (TDI) and integrated backscatter (IBS) analyses. These techniques are capable of providing non-invasively the early, subtle structural and functional changes of the myocardium. TDI myocardial systolic (Sm) and early (Em) and late (Am) diastolic velocities of left ventricular walls were determined. The systo-diastolic variation of IBS was also determined. Patients with PEO exhibited lower Sm, lower Em, and higher Am, and a reduced Em/Am ratio than controls (p<0.001 for all) at interventricular septum and lateral wall levels. In PEO patients, septal and posterior wall cyclic variations of IBS were significantly lower than those in controls (p<0.001). Patients with PEO showed myocardial wall remodeling characterized by increased fibrosis and early left ventricular systo-diastolic function abnormalities. Although cardiac involvement in PEO is generally considered to be limited to the cardiac conduction system, left ventricular dysfunction may be present and should receive more attention in the management of these patients

Effect of physical activity on heart rate variability and carotid intima-media thickness in older people

We investigated the effect of physical activity on heart rate variability (HRV) and carotid intima-media thickness (IMT) in elderly subjects and the relationship between HRV and IMT. Thirty-two elderly sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring IMT, and 24-h ECG monitoring for measuring HRV. Elderly athletes had evidence of increased vagal activity in the time (SDANN, rMSSD, and pNN50; p < 0. 01) and frequency domain (HF and LF/HF ratio, p < 0. 01) with respect to sedentary subjects. Moreover, athletes showed lower IMT than control subjects (p < 0. 01). In the whole population SDNN was inversely related to IMT, respectively (r = -0. 60 and r = -0. 58, p < 0. 0001), while LF/HF ratio related positively to IMT. In conclusion, this study demonstrated that in aging HRV is negatively associated with IMT, a putative index of atherosclerosis, confirming cardiac autonomic neuropathy as part of the pathophysiological pathway for atherosclerosis. It confirms that the regular physical activity represents a valuable strategy to counter age-related impairments of cardiac autonomic activity and artery structural changes. © 2013 SIMI

Effect of a nanostructured dendrimer-naloxonazine complex on endogenous opioid peptides mu(1) receptor-mediated post-ictal antinociception

The aim of this study was to investigate the capacity of the host dendrimer DAB-Am-16 as a drug carrier to reduce the time required for the encapsulated naloxonaxine to establish an irreversible covalent bond with mu(1)-opioid receptor (resulting in a pharmacologically selective effect). The efficacy of dendrimer-naloxonazine nanocomplex (DNC) was studied in antinociception induced by convulsions elicited by intraperitoneal (IP) administration of pentylenetetrazole, and analgesia was measured by the tail-flick test. We found that animals showed increased tail-flick latencies following convulsions. Furthermore, acute pre-treatment (10 minutes) with DNC, but not with naloxonazine alone, antagonized post-ictal analgesia in comparison with control pre-treatment. However, naloxonazine treatment 24 hours before PTZ decreased post-ictal antinociception, but DNC failed to antagonize tonic-clonic seizure-induced analgesia. In addition, according to Racine's index of seizure severity, naloxonazine, DAB-Am-16 dendrimer or DNC did not influence seizure severity when administered either 10 minutes or 24 hours before PTZ.From the Clinical Editor: This study characterizes the effect of a dendrimer-naloxonazine complex on mu(1) receptor-mediated post-ictal antinociception in an animal model of seizure disorder. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field