Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid (Aβ), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of α-syn interactions with Aβ or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral α-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet. Herein, the content of α-syn, Aβ, tau, and of their heterocomplexes was determined in red blood cells (RBCs) of healthy subjects (sedentary and athletes). Such parameters were related to the extent of the antioxidant capability (AOC), a key marker of oxidative stress in aging-related pathologies, and to physical exercise, which is known to play an important preventive role in NDs and to modulate oxidative stress. Tau content and plasma AOC toward hydroxyl radicals were both reduced in older or sedentary subjects; in contrast, α-syn and Aβ accumulated in elderly subjects and showed an inverse correlation with both hydroxyl AOC and the level of physical activity. For the first time, α-syn heterocomplexes with Aβ or tau were quantified and demonstrated to be inversely related to hydroxyl AOC. Furthermore, α-syn/Aβ aggregates were significantly reduced in athletes and inversely correlated with physical activity level, independent of age. The positive correlation between antioxidant capability/physical activity and reduced protein accumulation was confirmed by these data and suggested that peripheral α-syn heterocomplexes may represent new indicators of ND-related protein misfolding.
Objective: The aim of the present study was to evaluate the effect of clinical hypothyroidism on cardiovascular autonomic function and ventricular repolarization. Design and methods: We studied 31 patients (22 females and 9 males; mean age 53.6G11.8 years) with overt hypothyroidism (TSHZ56.2G14.7 mU/ml, low free thyroxine (T 4 ), free tri-iodothyronine (T 3 )) and 31 euthyroid controls, to investigate the dispersion of the QT interval in electrocardiogram (ECG) (an index of inhomogeneity of repolarization) and heart rate variability (HRV; a measure of cardiac autonomic modulation). The hypothyroid patients and controls underwent a full medical examination, standard 12-lead ECG, and 24-h ambulatory ECG monitoring. The hypothyroid patients were re-examined after 6 months of treatment with L-T 4 . Results: Patients with hypothyroidism showed higher QT dispersion and lower HRV measures than controls (P!0.01 or P!0.001). In hypothyroid patients, standard deviation of all R-R intervals was inversely related (by simple regression) to serum (log)TSH levels (rZK0.47, PZ0.008), while QT dispersion (rZ0.50, PZ0.004) and QTc dispersion (rZ0.46, PZ0.008) were directly related to (log)TSH. Parameters of HRV improved after 6 months of L-T 4 treatment, with the correction of hypothyroidism, becoming comparable with those of the control subjects, whereas the QT and QTc dispersion results were found to be only partially restored, remaining higher than the controls.
Conclusions:The results of the study demonstrate that hypothyroidism is associated with a decreased sympatho-vagal modulation of the heart rate and with an increased inhomogeneity of ventricular recovery times. The assessment of HRV and QT dispersion in patients with overt hypothyroidism may represent a useful tool in monitoring the cardiovascular risks.European Journal of Endocrinology 158 85-90
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