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Background Sarcopenia is the progressive loss of muscle mass and strength that occurs with advancing age and plays a pivotal role in the causal pathway leading to frailty, disability and, eventually, to death among older persons. As oxidative damage of muscle proteins has been shown to be a relevant contributory factor, in this study we hypothesized that uric acid (UA), a powerful endogenous antioxidant, might exert a protective effect on muscle function in the oldest old and we tested our hypothesis in a group of nonagenarians who participated in the Mugello Study. Methods 239 subjects, 73 men and 166 women, mean age 92.8 years ± SD 3.1, underwent the assessment of UA serum level and isometric handgrip strength, a widely used clinical measure of sarcopenia. Results Mean UA serum level was 5.69 mg/dL ± SD 1.70 and mean handgrip strength was 15.0 kg ± SD 6.9. After adjusting for relevant confounders, higher UA serum levels remained independent positive predictors of isometric handgrip strength (β 1.24 ± SE(β) 0.43, p = 0.005). Conclusion Our results show that higher UA serum levels are associated with better muscle function in the oldest old and, accordingly, might slow down the progression of sarcopenia.

Vascular calcification (VC) represents a recognized adverse predictor for cardiovascular morbidity and mortality. Previously considered passive and degenerative, VC is now recognized as an active process that resembles bone formation, and shares a number of histopathological features, mineral composition, and initiation mechanisms with bone development and metabolism. Oxidative stress and inflammation are key factors in both VC and osteoporosis (OP). Biochemical factors known to be primarily involved in the healthy bone metabolism also regulate VC. These biomarkers include vitamin D, osteoprotegerin, osteopontin, matrix Gla protein, cathepsin K, fibroblast growth factor-23, and fetuin-A. A better understanding of this highly controlled regulatory network, with multiple, nested feedback loops and cross talk between organs, may help to decrease the growing prevalence of calcific vasculopathy as well as OP in the aging population, and to advance in common preventive and therapeutic interventions targeted at both conditions.

We read with interest the manuscript by Lee et al. [(1)][1], which reports statin use impact on coronary plaque features. Statins increase coronary artery calcification, reducing local inflammation, changing phenotypic plaque composition, and lowering the high-risk plaques, as also observed in

Free radicals are produced during aerobic cellular metabolism and have key roles as regulatory mediators in signaling processes. Oxidative stress reflects an imbalance between production of reactive oxygen species and an adequate antioxidant defense. This adverse condition may lead to cellular and tissue damage of components, and is involved in different physiopathological states, including aging, exercise, inflammatory, cardiovascular and neurodegenerative diseases, and cancer. In particular, the relationship between exercise and oxidative stress is extremely complex, depending on the mode, intensity, and duration of exercise. Regular moderate training appears beneficial for oxidative stress and health. Conversely, acute exercise leads to increased oxidative stress, although this same stimulus is necessary to allow an up-regulation in endogenous antioxidant defenses (hormesis). Supporting endogenous defenses with additional oral antioxidant supplementation may represent a suitable noninvasive tool for preventing or reducing oxidative stress during training. However, excess of exogenous antioxidants may have detrimental effects on health and performance. Whole foods, rather than capsules, contain antioxidants in natural ratios and proportions, which may act in synergy to optimize the antioxidant effect. Thus, an adequate intake of vitamins and minerals through a varied and balanced diet remains the best approach to maintain an optimal antioxidant status. Antioxidant supplementation may be warranted in particular conditions, when athletes are exposed to high oxidative stress or fail to meet dietary antioxidant requirements. Aim of this review is to discuss the evidence on the relationship between exercise and oxidative stress, and the potential effects of dietary strategies in athletes. The differences between diet and exogenous supplementation as well as available tools to estimate effectiveness of antioxidant intake are also reported. Finally, we advocate the need to adopt an individualized diet for each athlete performing a specific sport or in a specific period of training, clinically supervised with inclusion of blood analysis and physiological tests, in a comprehensive nutritional assessment.

To evaluate whether the route of estrogen therapy (ET) may affect the levels of different vasoactive factors in healthy recent post-menopausal women.We conducted a cross-over study in 20 healthy nonsmoking women in recent postmenopause (1.8+/-0.1 years). Women received either 1-month oral-ET (O-ET, 2 mg oral micronized 17beta estradiol daily) or transdermal-ET regimen (T-ET, 17beta estradiol 1.5 mg gel daily) with a 1-month wash-out interval. Blood pressure, plasma levels of endothelin-1 (ET), 6-ketoPGF1a (6-ketoPG, prostacyclin metabolite), nitrite/nitrate (NOx), epinephrine (E) and norepinephrine (NE) and lipid profile were measured at baseline and after each treatment.Both regimens significantly reduced E (p0.01) and NE levels (p0.05). O-ET reduced low-density lipoproteins (LDL) levels (p0.05) and increased NOx values (p0.01). Neither regimen caused significant changes of ET or 6-ketoPG.Our results, obtained in healthy women in recent menopause, indicate that the ratio between vasodilator (NOx and prostacyclin) and vasoconstrictor (ET) bioavailability shifted towards the previous ones after O-ET, while it remained unchanged after T-ET; moreover, catecholamines levels were reduced by both treatments already from 1 month of therapy. These changes might represent very early beneficial effects evoked by ET on the cardiovascular system.

The risk of cardiovascular disease significantly increases after menopause. Accordingly, many evidences suggest that estrogens may positively affect the production of different vasoactive factors, such as nitric oxide, prostacyclin, endothelin-1 and catecholamines and induce favourable changes in lipid profile. However, although observational data indicate that hormone replacement therapy (HRT) reduces significantly the cardiovascular risk, recent results have added controversial data to the institution of HRT in postmenopausal women. These last studies present numerous bias, related to inclusion of a single combination HRT regimen, recruitment women of older age groups who began treatment years after menopause and generally with pre-existing coronary artery disease. In fact, it is known that aging and atherosclerotic injury may induce estrogen receptors depletion, endothelial dysfunction and thrombosis, thus potentially decreasing HRT efficacy. Therefore, particular attention must be paid to the age of the woman and the complexity of atheroscleriotic lesions as determinants of the response to HRT for each patient. Moreover, the maintenance of an healthy and normal functioning endothelium after menopause emerges as a major target to retain maximal cardiovascular benefit from this treatment.

Direct measurement of oxidative stress in biological fluids requires complex laboratory instruments and extraction procedures. Aim of the study was to analyse a new colorimetric assay and to evaluate its utility in the clinical setting. Forty-four unselected outpatients were studied. Stress oxidative levels were analysed with a colorimetric determination of oxygen free radicals, the dROMs test while serum total antioxidant capability was determined by OXY-adsorbent assay. In nine patients, ELISA 8-iso-PGF 2α plasma level determinations were obtained. The lower limit of sensitivity of dROMs test resulted 4.96 mg % H 2 O 2 . The assay was found to be linear over the range of oxidative stress levels 0–500 mg % H 2 O 2 , with correlation coefficients greater than 0.99. According to dROMs, the exposition to oxygen radical in the studied population was of moderate entity. Variation on replicate samples within or between days were lower than 5.5% and free radical levels were directly correlated with serum glucose concentration. A high significant inverse correlation between oxidative stress and total serum antioxidant levels was observed. 8-iso-PGF 2α plasma levels were positively correlated with serum free radical levels and inversely with serum concentration of antioxidant. The present data indicate that the analysis of serum free radicals with d-ROMs test is a rapid, no expensive method with good sensitivity and reproducibility.

Objective To evaluate whether obesity and smoking habit may accelerate the age-related increase of oxidative stress. Methods The Oxidative-INDEX, a score reflecting both oxidative and antioxidant counterparts, was estimated in 179 subjects (50 males, aged 16–79 years). Results Oxidative stress results were elevated in obese and smoker subjects. Adjusted logistic regression analysis indicated obesity and smoking as independent variables for elevated Oxidative-INDEX (odds ratio = 4.8 and 3.1, respectively). Oxidative-INDEX steadily rises at a mean rate of 5.3% (0.017 AU) per year in the overall population, showing twice and three times higher annual rate increase in smokers and obese subjects. Conclusion Our results suggest the pro-ageing effects of cigarette smoking and obesity by a more rapid and sharp elevation of the oxidative stress status.

Objectives. This study sought to assess the value of dipyridamole echocardiography in predicting reinfarction in patients evaluated early after uncomplicated acute myocardial infarction. Background. The identification of future nonfatal reinfarction seems an elusive target for physiologic testing. However, a large sample population is needed to detect minor differences in phenomena with a low event rate. Methods. We assessed the value of dipyridamole echocardiography in predicting reinfarction in 1,080 patients (mean [±SD] age 56 ± 9 years; 926 men, 154 women) evaluated early (10 ± 5 days) after uncomplicated acute myocardial infarction and followed up for 14 ± 10 months. Results. Submaximal studies due to limiting side effects occurred in 14 patients (1.3%); these test results were included in the analysis. Results of dipyridamole echocardiography were positive in 475 patients (44%). During follow-up, there were 50 reinfarctions: 45 nonfatal, 5 fatal (followed by cardiac death ≤4 days after reinfarction). Reinfarction (either nonfatal or fatal) occurred in 30 patients with positive and 20 with negative results (6.3% vs. 3.3%, p Conclusions. Dipyridamole echocardiographic positivity identifies patients evaluated early after uncomplicated acute myocardial infarction at higher risk of reinfarction, especially fatal reinfarction.

The aim of this study was to evaluate whether hydroperoxide levels, an index of oxidative stress, predict cardiac and total death in patients with cardiovascular disease. Serum hydroperoxide levels were measured in 157 consecutive inpatients, followed during a mean follow-up of 20+/-0.3 months. Elevated oxidative stress resulted in an independent predictors for cardiac death, suggesting that hydroperoxide evaluation could provide an adjunctive estimate in the evaluation of prognosis in the cardiovascular clinical setting.

F. Bamonti1, L. Vigna2, C. Novembrino1, R. De Giuseppe1, F. De Liso1, C. Vassalle3. 1Dip. Scienze Mediche, Universita degli Studi di Milano, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Fondazione IRCCS, Milano, Italy; 2Dip Medicina Preventiva Clinica e del Lavoro, U.O. Medicina del Lavoro I, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Fondazione IRCCS, Milano, Italy; 3Fondazione Toscana G. Monasterio, Istituto Fisiologia Clinica, CNR, Pisa, Italy E-mail: fabrizia.bamonti@unimi.it

losses of 0.6 to 1.2 g/kg per day have been reported. There is a marked reduction in key micronutrient levels in fevers (vitamin B2), tuberculosis (vitamins A, D, C and E, zinc and iron) and cancer (vitamin C, B2, B6, B12 and D, magnesium and zinc). Almost any nutritional deficiency can further compromise the immune functionality, impacting health outcome, quality of life and recovery from illness. It is therefore, essential to replace the nutritional losses sustained during illness as well as provide additional allowances for convalescence. Increased protein requirements of up to 2 g/day and micronutrient intakes to at least the recommended allowances or higher are indicated. Studies report positive effects of optimal nutritional support with significant increases in body weight, total lean mass and grip strength in TB subjects. Cancer subjects reported improved nutritional status, body weight, un-interrupted course of radiation (in case of subjects undergoing radiotherapy), reduced postoperative complications and improved quality of life as a result of nutrition intervention. Nutritional support should therefore be an integral part of the comprehensive care to optimise treatment for illness like fevers, TB and cancer.