Usos del micofenolato de mofetilo en condiciones distintas de las autorizadas: nefritis lúpica / Off-lable uses of mycophenolate mofetil: lupus nephritis

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Expression of TLR3, 4, 7 and 9 in cutaneous malignant melanoma: relationship with clinicopathological characteristics and prognosis.

Toll-like receptors (TLRs) have achieved an extraordinary amount of interest in cancer research due to their role in tumor progression. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4, 7 and 9 in cutaneous malignant melanoma (CMM). The expression levels of TLR3, 4, 7 and 9 were analyzed in tumors from 30 patients with CMM. The analysis was performed by immunohistochemistry, and the results were correlated with various clinicopathological findings and with relapse-free survival. Our results indicate that there was a wide variability in the immunostaining score values for each receptor. Positive staining for TLRs was generally found in tumor cells, especially for TLR4 and TLR9. Nevertheless, a significant percentage of tumors also showed TLR4 expression in mononuclear inflammatory cells (62.1 %) and in fibroblast-like cells (34.5 %). Our results showed no significant association between score values for each TLR and clinicopathological characteristics of patients. However, our results demonstrated that high TLR4 expression was significantly associated with a shortened relapse-free survival (p = 0.001). Therefore, TLR4 expression may be a new prognostic factor of unfavorable evolution in cutaneous malignant melanoma.

Physical Activity as Healthy Intervention Against Severe Oxidative Stress in Elderly Population.

Severe oxidative stress is a relevant risk factor for major deleterious health-related events in older people and is thought to be an important contributor to age-related disease. Literature has suggested oxidative stress as a therapeutic target for mitigating the biological decline and attenuating the occurrence of adverse clinical events in aged individuals. However, definitive treatments are not known. Regular and moderate physical activity has been proposed as possible intervention for slowing age-related decline. This healthy strategy presents a wide range of beneficial aspects for elderly, from the reduction of morbidity, disability, frailty and mortality rates to treatment of many age-related disorders. Importantly, the global benefits on health are not shared by any other strategies. Nevertheless, the physiological basis by which exercise produces its benefits to the organism is not fully understood. This review summarizes the evidence for the role of physical activity as potential healthy intervention for mitigating the negative aspects of aging through the modulation of the oxidative mechanisms.

p73 cooperates with Ras in the activation of MAP kinase signaling cascade.

The p73 gene is capable of inducing cell cycle arrest, apoptosis, senescence, differentiation and to cooperate with oncogenic Ras in cellular transformation. Ras can be considered as a branch point in signal transduction, where diverse extracellular stimuli converge. The intensity of the mitogen-activated protein kinase (MAPK) cascade activation influences the cellular response to Ras. Despite the fundamental role of p53 in Ras-induced growth arrest and senescence, it remains unclear how the Ras/MEK/ERK pathway induces growth arrest in the absence of p53. We report here that oncogenic Ras stabilizes p73 resulting in p73 accumulation and enhancement of its activity. p73, in turn, induces a sustained activation of the MAP kinase cascade synergizing with oncogenic Ras. We also found that inhibition of p73 function modifies the cellular outcome to Ras activation inhibiting Ras-dependent differentiation. Here, we show for the first time that there is a signaling loop between Ras-dependent MAPK cascade activation and p73 function.

Upper body aerobic fitness comparison between two groups of competitive surfboard riders.

The aim of the present study was to evaluate and compare the upper-body aerobic fitness characteristics in 2 groups of competitive surfers with different performance levels. Thirteen male competitive surfers performed an incremental dry-land board paddling test to determine specific peak oxygen uptake (VO2peak), peak power output (Wpeak) and the exercise intensity (%VO2peak) that elicits a blood lactate concentration of 4 mmol x L(-1) (LT4). As a measure of surfing performance, surfers were ranked according to their competitive season performance (RANK) and divided into 2 groups based on their performance level; European top-level competitive surfers (ELS) (n = 7) and regional level competitive surfers (RLS) (n = 6). ELS reached significantly higher values than RLS for Wpeak (154.71 +/- 36.82 W vs. 117.70 +/- 27.14 W: P = 0.04) and LT4 (95.18 +/- 3.42 %VO2peak vs. 88.89 +/- 5.01 %VO2peak; P = 0.02) but not VO2peak (3.34 +/- 0.31 L x min(-1) vs. 3.40 +/- 0.37 L x min(-1); P = 0.77). Spearman-rank order correlation analysis revealed that RANK was inversely correlated with Wpeak (r = -0.65, P = 0.01) and LT4 (r = -0.58, P = 0.03). These findings identify that better surfers have higher upper body aerobic fitness scores.

Blood lactate and heart rate during national and international women's basketball.

AIM: In order to measure game intensity in female basketball players, 2 teams (Olympic National Team - I -and a team at 1(st) National Division - N) were studied for a total of 12 games (10 official competitions and 2 practice games -P). METHODS: Both blood lactate concentration ([La](b)) and mean heart rate (HR) were measured during the games and then compared with a progressive field test where maximal blood lactate (max[La](b)), individual lactate threshold and maximal heart rate (HR max) values were obtained. All different categories (International, National and Practice) and positions (Guard, Forward and Center) were taken into account in this study. RESULTS: Differences (p<0.05) in HR were found between all positions (Guard=185+/-5.9; Forward=175+/-11 and Center=167+/-12 beats x min(-1)) and between the International team and the rest of the categories (International=186+/-6; National=175+/-13 and Practice=170+/-11 beats x min(-1)). The [La](b) differed between the Guard and the other 2 positions (Guard=5.7+/-2.1; Forward=4.2+/-2.1 and Center=3.9+/-2.0 mmol x L(-1)) and between Practice and the rest of the categories (International=5.0+/-2.3; National=5.2+/-2.0 and Practice=2.7+/-1.2 mmol x L(-1)). The game intensity of International players reached 94.6% of their maximum HR value, whereas National players reached 90.8%, this percentage descending to 89.8% during Practice. International games reached the individual lactate threshold at 89.2% of the maximum HR; National games at 88.6%. CONCLUSION: We can conclude that the game intensity of female basketball increases according to the level of competition. It may also differ according to playing position, being greatest in guards. The game intensity at international level surpasses the individual lactate threshold, whereas it reaches a lower level in training games.

The response of sexual and stress hormones of male pro-cyclists during continuous intense competition.

The aim of this study was to compare hormonal changes in plasma total testosterone (T), cortisol (C), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (P) in two world-class teams, both consisting of 9 top male pro-cyclists, during a real sports situation (the 1998 "Vuelta a España", a 3-week multi-stage international cycling competition). Venous blood samples were taken the day before the race (S0), after 1 week (S1), after 2 weeks (S2) and at the end of the race (S3). The S0 T level was significantly lower in the team with more racing days in the previous month. There was a significant basal T decrease (p < 0.05) during the race in comparison with the initial value, in spite of the difference in S0 T level between teams. However, there was no difference between teams in the mean decrease in T level. C decreased significantly between S0 and S1 and between S1 and S2, but not between S2 and S3. There were no differences in P concentration between teams or throughout the study, except for a significant increase between S2 and S3. There were no initial differences in LH nor FSH concentration between the teams, nor at any of the study follow-up times. We conclude that in professional top-level athletes S0 T values depend on the number of competition days of the previous month. We observed a similar decrease in the T levels in both teams, independent of the absolute S0 values. In both teams C decreased during long-lasting cycling competition.

Physiological differences and rating of perceived exertion (RPE) in professional, amateur and young cyclists.

BACKGROUND: The aim of this study is to measure and compare the physiological characteristics and the rating of perceived exertion (RPE) in 72 high level road cyclists of 3 different categories. METHODS: These cyclists were divided in 3 groups according to their age (24 professionals, mean age 26 years, 22 amateurs, 22 years and 26 juniors, 18 years). MEASURES: they carried out a progressive test to exhaustion in a specific cycloergometer, starting with a power output of 100 watts and increasing 50 watts each 4 min. VO2 was measured continuously. At the end of each one of the 4 min steps the subject was asked about his RPE using the 6-20 Borg's scale. RESULTS: Professional cyclists showed a VO2max, VO2 x kg(-1) and a maximum power output significant higher than other groups, while there were no significant differences between amateurs and juniors. VO2 and RPE were significantly different, in all the categories, during high work loads. No significant differences were found between RPE and %VO2max. RPE and heart rate (HR) were significantly different between professionals and juniors. RPE and %HR max were significantly different with low loads, but no with high loads. In the same way, RPE/w and RPE/(w x kg(-1) were significantly different in all categories. CONCLUSIONS: We conclude that professional road cyclists reached a VO2max, VO2max x kg(-1) and a maximum power higher than the other categories; so, therefore, these parameters are good as performance indicators, and RPE is of practical value to prescribe exercise training intensities in each category.

Genetic variation in the renin-angiotensin system and athletic performance.

The D allele at the angiotensin-I-converting enzyme (ACE)-insertion/deletion polymorphism has been associated with an increased risk of developing several pathological processes, such as coronary heart disease and ventricular hypertrophy. Individuals with the DD genotype show a significantly increased left-ventricular mass in response to physical training, compared to the II genotype (which would be associated with the lowest plasma ACE levels) and the ID genotype. The II genotype has been linked to a greater anabolic response. In accordance with a role for ACE in the response to rigorous physical training, a higher frequency of the I allele has been reported to exist among elite rowers and high-altitude mountaineers. Sixty elite (professional) athletes (25 cyclists, 20 long-distance runners, and 15 handball players), and 400 healthy controls were genotyped for the DNA polymorphisms of the ACE, angiotensinogen (Ang) and angiotensin receptor type 1 (AT1) genes. Plasma ACE levels showed a strong correlation with the I/D genotype in our population. The I-allele occurred at a significantly higher frequency in athletes compared to controls (P = 0.0009). Gene and genotype frequencies for the Ang and AT1 polymorphisms did not differ between athletes and controls. Since the frequency of the ACE I allele was significantly increased among our elite athletes, we conclude that the ACE polymorphism represents a genetic factor that contributes to the development of an elite athlete.

Intensity of exercise during road race pro-cycling competition.

PURPOSE: The aim of this study was to quantify the intensity of competition during two professional bicycle stage races: the Tour de France (Tour) and Vuelta a España (Vuelta). METHODS: The HR responses of 18 world class cyclists were recorded during the races and compared with HR ranges that corresponded to four intensities of exercise that were measured in the laboratory with an incremental test to exhaustion 2 wk before each race. The four intensities were: Anaerobic (AN) over the individual anaerobic threshold, which was over 90% of VO2max; intense aerobic (IA), which was between 70 and 90% of VO2max; moderate aerobic (MA), which was between 50 and 70% of VO2max; and recovery (RE), which was < 50% of VO2max. The stages were divided in individual time trial (ITT), flat, or mountain. RESULTS: The mean HR of the Vuelta and Tour were, respectively, 133.8 +/- 17.9 and 134 +/- 18.6 beats x min(-1). The mean total time of each stage was 269.6 +/- 122 and 259.4 +/- 119.9 min. The mean stage time over IAT was 17.5 +/- 15.7 and 24.7 +/- 26 min; the IA time was 75.2 +/- 47.6 and 79.6 +/- 48.3 min; the MA was 97.2 +/- 57.4 and 89.5 +/- 54.9 min. Finally the RE time was 79.6 +/- 60.5 and 65.4 +/- 69.7 min. The percentage of participation related to total time of the race was, respectively, in the Vuelta and the Tour, 12.99 and 16.8% in AN exercise intensity, 29.5 and 29.2% in IA, 32.4 and 31.9% in MA, and 25.1 and 25.2% in RE. There are no differences in AN time among flat, mountain, and ITT stages in each race, except for the mountain stages in the Tour. CONCLUSION: Cycling is a high intensity sport because approximately 93 min in flat and 123 min in mountain stages were above 70% of VO2max. In addition, the time spent at IAT was roughly 20 min regardless of stage type, suggesting that the anaerobic capacity limits performance.

Importance of wash riding in kayaking training and competition.

PURPOSE: The use of different wash-riding techniques is common during kayak training and competition. Changes in wash-riding positions could imply a different exercise intensity. The aim of this study, therefore, was to quantify the energy savings made when a kayaker is "wash riding." METHODS: Eight male international flat water kayakers, who performed a field test of 2000 m in each of the four wash-riding positions, head (H), right wave (RW), left wave (LW), and end position (V), were studied. The data investigated were: time, stroke rate, blood lactate (BL), heart rate (HR), and rate of perceived exertion (RPE). Under laboratory conditions kayakers performed the same intensity of exercise in a kayak ergometer, and HR, oxygen uptake (VO2), BL, mean power output (W), and RPE were measured. RESULTS: The results show significant differences (P < 0.05) among H, RW/LW, and V. The mean values for BL (P < 0.05) were 4.2, 2.0, 2.2, and 1.5 mmol.L-1, for H, RW, LW, and V, respectively. RPE also revealed differences, with values of 15, 12.6, 12.6, and 9.7 for H, RW, LW, and V, respectively. Mean power output gave values of 190.3 (H), 155.6 (RW and LW), and 129.5 (V) W. HR was different between H and V (172 and 151), while stroke rate was different among the parameters H, RW, and V (93.7, 88.8, and 87.6, respectively). The VO2 in the kayak ergometer test showed a difference between H and V (3.78 and 2.23 L.min-1). CONCLUSIONS: We conclude that "wash riding" involves a saving in energy cost of between 18% and 31.9%, depending on the position. This conclusion is of importance for the quantification and calibration of kayak training and competition.