Influence of age and physical exercise on sirtuin activity in humans.

Sirtuins are NAD+-dependent lysine deacetylases. Sirtuins acquired worldwide attention because of their ability to increase yeast, flies, worms and mice lifespan. Recently, this assumption has been challenged. However, their beneficial role on the quality of ageing is widely accepted. In this work we aimed to study how and if sirtuins expression and activity levels varies in function of age and, in the case of young subjects, of exercise. Fifteen blood donors of different ages and fifteen athletes of the Italian rowing male team were enrolled and peripheral blood mononuclear cells (PBMCs) isolated from blood samples. Our results show that sirtuins deacetylases activity measured in PBMCs increases from 18 to 40 years of age and then decreases during the following 20 years. Moreover, physical exercise in professional athletes can upregulate sirtuin activity. Thus, for the first time in humans, we demonstrate that sirtuin activity is a function of age and can be altered through physical exercise.

Cold exposure increases exercise-induced oxidative stress.

AIM: We determined the combined effects of cold and exercise on oxidative stress during submaximal exercise. METHODS: Sixteen amateur male cyclists pedaled at a constant speed corresponding to 85% of maximal HR as determined in normal conditions. Eight athletes pedaled indoors at 23 °C while 8 athletes pedaled outdoors at a temperature of 4-6 °C. We then evaluated the levels of reactive oxygen metabolites and plasma levels of antioxidants after exercise. RESULTS: Performing a physical task in cold conditions increased the free radical production, as demonstrated by the augmented levels of reactive oxygen metabolites and the concomitant decrease of plasma levels of antioxidants in outdoors cyclists as compared to indoors cyclists. The overall ANOVA and the post-hoc comparisons revealed a significant exercise and temperature effect. The mean level of reactive oxygen metabolites in athletes who exercised indoors was significantly lower than that of the outdoor athletes. Moreover, the outdoors group presented plasma levels of antioxidants significantly lower than those of the indoors group. CONCLUSION: Since several sports are performed outdoors during the winter season, the increased risk of oxidative stress in cold conditions must be considered in these disciplines. Cyclists, football and rugby players, and runners are all affected by the elevation in oxygen radicals induced by cold and should take appropriate precautions, such as specific antioxidant integration.

Endothelial (dys)function: the target of physical exercise for prevention and treatment of cardiovascular disease.

AIM: Endothelial dysfunction has been recognized as the early event and the common feature of chronic disorders associated with increased risk for atherosclerotic heart diseases. While the beneficial effects of aerobic, moderate-intensity exercise on endothelial function are very well assessed, an intriguing doubt exists about the effects of long-term high-intensity physical activity. The aim of the present study was to compare recent findings of our group concerning homocysteine levels in athletes to available data in literature in order to clarify the meaning of such apparent metabolic paradox. METHODS: The studied population included 185 athletes: 180 healthy age and sex matched subjects served as control group. The assessed variables included homocysteine, folate, vitamin B12, total and HDL cholesterol, LDH, CPK and IL-6. Results were compared to available data in literature. RESULTS: The prevalence of hyperhomocysteinemia (>15 µmol/L) in athletes and controls was 55% and 15%, respectively. In the studied population, no correlation was found between homocysteine and all the other investigated variables. CONCLUSION: The present results suggest that intensive physical training could induce a pathological increase of homocysteine levels. With this regard, it has been suggested that the observed increases of cardio-vascular risk factors in athletes could represent an adaptative feature marker of muscle demand but would not actually lead to endothelial damage. This remains, however, a speculative hypothesis and further analysis are needed in order to clarify the clinical significance of those observations in order to better preserve the athletes immediate and future health.

Assessment of body fluid balance and voluntary drinking in ultimate players during a match.

AIM: Ultimate is a sport played by hundreds of thousands of people in more than 42 countries; however, it is still mainly known as a recreational more than a team sport, and further studies are needed to define its physical load. Particularly, since no studies relating Ultimate to hydration have been performed, we aimed to determine body fluid balance, voluntary water intake and the most reliable method for assessing the hydration status of players after a typical 80-minute Ultimate match. METHODS: bioimpedance, urine specific gravity and body mass changes to asses the hydration level of the players were measured. RESULTS: It was observed that not all of the methods are adequate to determine dehydration in Ultimate players, and that measurement of body mass changes represents a reliable and accurate technique. CONCLUSIONS: These findings demonstrate that ultimate as an intense sport that can induce significant fluid loss, which is not always replaced by individual drinking.

Autonomic and psychological adaptations in Olympic rowers.

AIM: Power spectral analysis of heart rate variability has been used to assess the time course of neurovegetative adaptations to training. This study was undertaken: 1) to evaluate whether and which indicator(s) of autonomic cardiac regulation and psychophysical stress can identify successful athletes during a training season culminating with the Olympic Games and 2) to evaluate the feasibility of a quasi-on-line assessment of autonomic cardiac regulation from training field, by a telematic approach. METHODS: This study was conducted on the group of male athletes composing the Italian national team of rowing (n=34), in the season preceding the 2004 Olympic Games. Complete results are from 18 subjects (age 25.3+/-0.5 years), who were selected to participate to the Athens' Olympic games. Athletes were studied while partially detrained, at mid-training season and close to the games. The RR interval was obtained through a miniature transtelephonic-ECG recorder in the supine and standing posture, thus allowing the evaluation of cardiovascular responses to a sympathetic challenge. Data were downloaded through a telephone line, to the referral center where RR-interval variability data were analyzed with the autoregressive method. Also, in each study sessions, athletes filled a self-administered questionnaire of stress perception and somatic symptoms (4S-Q). RESULTS: All ECG recordings were transmitted successfully by phone to the referral center. No significant difference was detected in any marker of autonomic cardiac regulation between athletes who won a medal at the Olympic Games and those who did not. However, respiratory rate was faster in medal winners (P=0.02), while the questionnaire addressing stress (4S-Q) provided greater scores in the group that did not win a medal (F=5.55, P<0.022) at mid-training season and close to the Olympic Games. CONCLUSIONS: The results of this study would suggest the possibility of an early detection of psychosomatic symptoms resulting from long duration and elevated stress of preparing for top level competitions, whose better handling might identify the most successful athletes. In addition, it indicates the feasibility of a quasi-on-line assessment of autonomic cardiac adaptations to strenuous training directly from field to be possibly used for improving individual training programs, allowing athletes evaluation in their natural environment.

1-beta-D-arabinofuranosylcytosine nucleotide inhibition of sialic acid metabolism in WI-38 cells.

Because cytidine nucleotides have been demonstrated to affect activity of sialytransferases of both normal and malignant cells, we have investigated the effects of nucleotides of 1-beta-D-arabinofuranosylcytosine (ara-C) [1-beta-D-arabinofuranosylcytosine 5'-monophosphate and 1-beta-D-arabinofuranosycytosine 5'-triphosphate (ara-CTP)] on synthesis of sialoglycoproteins. Normal human diploid fibroblasts (WI-38 cells) were used in culture at confluency, when fewer than 1% of the cells were synthesizing DNA. 1-beta-D-Arabinofuranosylcytosine 5'-monophosphate was inhibitory to both sialytransferase activity of the intact cell and total cell homogenate transferase activity. The enzymes which synthesize and degrade the substrate of sialyltransferases, cytidine 5'-monophosphate-N-acetylneuraminic acid (CMP-AcNeu), were also tested for inhibition by nucleotides of ara-C. Synthesis of CMP-AcNeu was competitively inhibited by ara-CTP; however, formation of CMP-AcNeu when ara-CTP was supplied as substrate could not be detected. Hydrolysis of CMP-AcNeu was inhibited more severely by cytidine 5'-triphosphate than by ara-CTP or 1-beta-D-arabinofuranosylcytosine 5'-monophosphate. Confluent cultures of WI-38 cells exposed to ara-C have decreased amounts of glycoprotein sialic acid, suggesting that ara-C nucleotides may reach sufficient intracellular concentrations to affect the enzyme systems described.

Sialyltransferase activities of aging diploid fibroblasts.

Sialyltransferase activity and cell-cell adhesion rates of aging WI-38 cells were studied to determine the possible basis for a previously described decrease in membrane bound sialic acid and loss of proliferation of senescent cells. Ectosialyltransferase was demonstrated on the surface of both young and old WI-38 cells. The sialyltransferase assays consist of an enzyme source which is either the surface of intact cells (ectoenzyme) or a Triton X-100 cell homogenate, the nucleotide sialic acid donor (cytidine monophosphate-N-acetylneuraminic acid), and an asialo-acceptor which may be endogenous to the enzyme preparation or may be added exogenously. When sialyltransferase activity is measured in the absence of exogenous acceptors, there is a greater amount of sialic acid transferred by odl cells. However, when exogenous acceptors are provided, the amount of transfer is stimulated to a greater extent in young cells equalizing the amount of sialic acid incorporated into young and old cells. This suggests that there are fewer asialoglycoproteins and that acceptor concentration is a limiting factor in assays of young cell sialyltransferase. The end result of this may be the previously described decreased amount of membrane-bound sialic acid of old cells. A change in the adhesiveness of old cells is described which may be related to the altered cell surface.

Clinical significance of abnormal electrocardiographic patterns in trained athletes.

BACKGROUND-The prevalence, clinical significance, and determinants of abnormal ECG patterns in trained athletes remain largely unresolved. METHODS AND RESULTS-We compared ECG patterns with cardiac morphology (as assessed by echocardiography) in 1005 consecutive athletes (aged 24+/-6 years; 75% male) who were participating in 38 sporting disciplines. ECG patterns were distinctly abnormal in 145 athletes (14%), mildly abnormal in 257 (26%), and normal or with minor alterations in 603 (60%). Structural cardiovascular abnormalities were identified in only 53 athletes (5%). Larger cardiac dimensions were associated with abnormal ECG patterns: left ventricular end-diastolic cavity dimensions were 56. 0+/-5.6, 55.4+/-5.7, and 53.7+/-5.7 mm (P<0.001) and maximum wall thicknesses were 10.1+/-1.4, 9.8+/-1.3, and 9.3+/-1.4 mm (P<0.001) in distinctly abnormal, mildly abnormal, and normal ECGs, respectively. Abnormal ECGs were also most associated with male sex, younger age (<20 years), and endurance sports (cycling, rowing/canoeing, and cross-country skiing). A subset of athletes (5% of the 1005) showed particularly abnormal or bizarre ECG patterns, but no evidence of structural cardiovascular abnormalities or an increase in cardiac dimensions. CONCLUSIONS-Most athletes (60%) in this large cohort had ECGs that were completely normal or showed only minor alterations. A variety of abnormal ECG patterns occurred in 40%; this was usually indicative of physiological cardiac remodeling. A small but important subgroup of athletes without cardiac morphological changes showed striking ECG abnormalities that suggested cardiovascular disease; however, these changes were likely an innocent consequence of long-term, intense athletic training and, therefore, another component of athlete heart syndrome. Such false-positive ECGs represent a potential limitation to routine ECG testing as part of preparticipation screening.

Role of exercise stress test in master athletes.

BACKGROUND: The effectiveness of cardiovascular screening in minimising the risk of athletic field deaths in master athletes is not known. OBJECTIVE: To evaluate the prevalence and clinical significance of ST segment depression during a stress test in asymptomatic apparently healthy elderly athletes. METHODS: A total of 113 male subjects aged over 60 were studied (79 trained and 34 sedentary); 88 of them (62 trained and 26 sedentary) were followed up for four years (mean 2.16 years for athletes, 1.26 years for sedentary subjects), with a resting 12 lead electrocardiogram (ECG), symptom limited exercise ECG on a cycle ergometer, echocardiography, and 24 hour ECG Holter monitoring. RESULTS: A significant ST segment depression at peak exercise was detected in one athlete at the first evaluation. A further case was seen during the follow up period in a previously "negative" athlete. Both were asymptomatic, and single photon emission tomography and/or stress echocardiography were negative for myocardial ischaemia. The athletes remained symptom-free during the period of the study. One athlete died during the follow up for coronary artery disease: he showed polymorphous ventricular tachycardia during both the exercise test and Holter monitoring, but no significant ST segment depression. CONCLUSIONS: The finding of false positive ST segment depression in elderly athletes, although still not fully understood, may be related to the physiological cardiac remodelling induced by regular training. Thus athletes with exercise induced ST segment depression, with no associated symptoms and/or complex ventricular arrhythmias, and no adverse findings at second level cardiological testing, should be considered free from coronary disease and safe to continue athletic training.

Absence of left ventricular wall thickening in athletes engaged in intense power training.

There is a widely held perception that power training increases left ventricular (LV) wall thickness. Consequently, in individual power-trained athletes, confusion may legitimately occur with regard to the differential diagnosis of athlete's heart and nonobstructive hypertrophic cardiomyopathy. To investigate the effects of systematic strength training on cardiac dimensions (particularly absolute LV wall thickness), 100 relatively young and highly conditioned athletes participating in weight and power lifting, wrestling, bobsledding and weight-throwing events for 3 to 24 years (mean 7) were studied by echocardiography. No athlete showed a maximal absolute LV wall thickness that exceeded the generally accepted upper limits of normal (i.e., 12 mm; range 8 to 12). When compared with 26 normal, sedentary control subjects of similar age and body surface area, maximal septal thickness was mildly but significantly greater in athletes (9.6 +/- 0.8 vs 9.0 +/- 0.5 mm; p < 0.001), as was the calculated LV mass index (96 +/- 12 vs 81 +/- 8 g/m2; p < 0.001); LV end-diastolic cavity dimension was similar in athletes and controls (55 +/- 4 and 54 +/- 3, respectively; p > 0.05). Consequently, echocardiographic data in this selected group of purely strength-trained athletes show that whereas this form of conditioning is associated with increased LV mass and a disproportionate increase in wall thickness in relation to cavity dimension, only modest alterations in absolute wall thickness occur (which do not exceed upper normal limits). Therefore, in highly conditioned, strength-trained, competitive athletes, the presence of substantial LV wall thickening (> 13 mm) should suggest alternative explanations, such as the diagnosis of pathologic hypertrophy (i.e., hypertrophic cardiomyopathy).

Morphology of the "athlete's heart" assessed by echocardiography in 947 elite athletes representing 27 sports.

In the present study, we used echocardiography to investigate the morphologic adaptations of the heart to athletic training in 947 elite athletes representing 27 sports who achieved national or international levels of competition. Cardiac morphology was compared for these sports, using multivariate statistical models. Left ventricular (LV) diastolic cavity dimension above normal (> 54 mm, ranging up to 66 mm) was identified in 362 (38%) of the 947 athletes. LV wall thickness above normal (> 12 mm, ranging up to 16 mm) was identified in only 16 (1.7%) of the athletes. Athletes training in the sports examined showed considerable differences with regard to cardiac dimensions. Endurance cyclists, rowers, and swimmers had the largest LV diastolic cavity dimensions and wall thickness. Athletes training in sports such as track sprinting, field weight events, and diving were at the lower end of the spectrum of cardiac adaptations to athletic training. Athletes training in sports associated with larger LV diastolic cavity dimensions also had higher values for wall thickness. Athletes training in isometric sports, such as weightlifting and wrestling, had high values for wall thickness relative to cavity dimension, but their absolute wall thickness remained within normal limits. Analysis of gender-related differences in cardiac dimensions showed that female athletes had smaller LV diastolic cavity dimension (average 2 mm) and smaller wall thickness (average 0.9 mm) than males of the same age and body size who were training in the same sport.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of correlation between ventricular late potentials and left ventricular mass in top-level male athletes.

PURPOSE: The aim of this study was to establish: 1) the prevalence of abnormal signal-averaged electrocardiogram (SAECG) in a large population of top-level athletes and 2) the relationship between SAECG parameters and left ventricular mass. One-hundred and fifty-three elite male athletes without apparent heart disease, symptoms, or arrhythmias were studied. METHODS: Fifty-six athletes (37%) had increased left ventricular mass (> 134 g.m(-2)). All athletes underwent time-domain SAECG on 300-400 heart beats recorded at rest from three bipolar orthogonal tests with a filter setting of 40-250 Hz. Criteria for abnormality were 1) filtered QRS duration > 114 ms, 2) duration of low-amplitude signals > 38 ms, or 3) root mean square voltage of the last 40 ms of the filtered QRS < 20 microV. RESULTS: The prevalence of abnormal SAECG was 7.2% (abnormality of one parameter), 6.5% (abnormality of two parameters), and 5.8%(abnormality of three parameters). The prevalence of abnormal SAECG was similar in athletes with or without increased left ventricular mass. CONCLUSIONS: In conclusion, this study showed: 1) the low rate of positive results of SAECG parameters in top-level male athletes, similar to that found in healthy sedentary subjects; and 2) the lack of correlation between left ventricular mass and overall SAECG parameters.

The electrocardiographic T wave changes in highly trained athletes during training. An old problem revisited.

OBJECTIVE: To evaluate the T-wave pattern alterations during vigorous training in elite athletes. SETTING: Institute of Sport Science in Rome and National Rowing Center in Piediluco, Italy. STUDY POPULATION: Nine male and 7 female rowers of the national team were examined prospectively at different times of their conditioning period. METHODS: All athletes underwent electrocardiography and echocardiography; the ecg was analyzed for QRS voltages and axis, T-wave pattern and QTc interval; from echocardiography the left ventricular (LV) cavity dimension, wall thickness and mass were calculated. From Doppler-echocardiography the transmitral diastolic LV filling pattern was evaluated. RESULTS: Variation of T-wave voltages was seen in all the athletes. Specifically, during the low-intensity training period the T-wave pattern was positive and increased in voltage (T-wave max amplitude in V6 increased to 130% in male and 100% in female than pretraining values). During the peak training a variety of patterns was observed, and a transient flattening was present in 50% of subjects. No concomitant alteration of heart rate, QRS and T-wave axis and QTc duration were observed. No significant changes of cavity dimension, wall thickness, LV mass index and Doppler-derived diastolic peak flow velocities were detected during the study period. CONCLUSIONS: Transient changes of T-wave pattern may occur in athletes as an effect of athletic conditioning, without changes of cardiac dimension or alteration of indexes of LV function. This finding supports the role of ecg monitoring to follow-up the individual athletes response to training exercise load.

Effects of aerobic exercise training on 24 hr profile of heart rate variability in female athletes.

BACKGROUND: The aim of this study was to investigate the effects of exercise training on autonomic regulation of heart rate under daily life conditions. METHODS: Twenty-six healthy female athletes (age 24.5 +/- 1.9 yrs) involved in regular physical activity were recruited during a period of yearly rest and randomly assigned to a five-week aerobic exercise training program (n = 13) or to a non-exercise control group (n = 13). MEASURES: Before and after the five-week training, all subjects underwent a bycicle ergometer stress test and a 24-hour dynamic ECG monitoring. Autonomic regulation of heart rate has been investigated by means of both time and frequency domain analyses of heart rate variability (HRV). Spectral analysis of R-R interval variability (autoregressive algorithm) provided markers of sympathetic (low frequency, LF, 0.10 Hz) and parasympathetic (high frequency, HF, 0.25 Hz) modulation of the sinus node. RESULTS: Trained subjects showed a reduced heart rate response to submaximal workload. Before training there was no significant difference between the two groups. After training resting heart rate did not significantly differ between trained and untrained subjects. No significant differences were observed in the different time domain indexes of heart rate variability. The day-night difference in SD and SDRR were significantly less in the trained as compared to the untrained group. Normalized LF and HF components did not significantly differ between trained and untrained subjects, during the awake period. The decrease in the LF and the increase in the HF component during nighttime were significantly less in the trained group. The LF/HF ratio was significantly decreased during the night in the untrained group whereas it was not significantly different from the awake state in the trained group. CONCLUSIONS: These findings of the relative night-time increase in LF and the decrease in the day-night difference in time domain indexes of heart rate variability suggest that, in young female athletes, exercise training is able to induce an increase in the sympathetic modulation of the sinus node which may coexist with signs of relatively reduced, or unaffected, vagal modulation.

The natural course of bicuspid aortic valve in athletes.

The purpose of this study was to evaluate the impact of a long-term athletic training on the clinical course of bicuspid aortic valve. A group of 81 athletes (73 M, 8 F, 22.7 +/- 5.6 years) with bicuspid aortic valve was collected. Based on clinical and echocardiographic criteria, athletes were initially divided into 2 groups: the low-risk (51 athletes) and the high-risk group (30 athletes). The high-risk athletes were disqualified from training and competitions after the first evaluation. Over the follow-up period, all of them showed significant worsening of morphologic and hemodynamic features of bicuspid aortic valve; two underwent surgical valvular repair and one of them died suddenly. Over the same period, six of the initially low-risk athletes (7%) showed significant worsening of morphologic features of bicuspid aortic valve and/or incidence of symptoms which led to their disqualification from competition. At the end of follow-up, we observed that in high-risk subjects the progression of valvular disease occurred independently from the former athletic activity and that the majority of athletes with mild bicuspid aortic valve had a benign clinical course. However, athletes with bicuspid aortic valve should be viewed with caution, and continued clinical surveillance would be mandatory.

Atypical cutaneous manifestation of HSV-2 with Candida albicans co-infection in a patient with HIV-1.

Herpes simplex virus type 2 (HSV-2) infection was one of the first opportunistic infections identified among patients with AIDS. In the literature there are many data suggesting that the natural history of HSV-2 infection is altered in HIV-HSV-2 co-infected patients. Furthermore, a relationship between HIV seropositivity and HBV infection because of their analogous way of transmission is also described. We report the case of a 37-year-old patient who suffered from multiple painful ulcerative lesions of the perianal region. Laboratory examination showed positivity for HIV and HBV infections. In HIV-positive patients perianal HSV-2 can have atypical manifestations, especially if co-infection by Candida albicans occurs.