Hemoconcentration induced by exercise: Revisiting the Dill and Costill equation.

The Dill and Costill equation is used to estimate the exercise-induced hemoconcentration. However, this calculation requires drawing an extra whole-blood sample, which cannot be frozen and has to be analyzed with dedicate instrumentation in a relative short time. The aim of the present study was to explore the usefulness of some serum biochemical parameters to estimate hemoconcentration induced by exhaustive exercise. Fourteen healthy male subjects (19-34 years) performed a15-min running test at 110% of anaerobic threshold speed. Hemoglobin, hematocrit, brain natriuretic peptide (BNP), creatinine, gamma-glutamyltransferase (GGT), total-proteins, albumin, total calcium (Ca), K(+), Na(+), and Cl(-) were determined in blood samples taken before, after exercise, and after a 30-min recovery period. Plasma volume loss (ΔPV) was calculated by Dill and Costill equation. At post-exercise and after recovery, the percentage increments of total-proteins, albumin, GGT and Ca correlated significantly with ΔPV. Bland-Altman analyses showed that correcting BNP, creatinine, and K(+) concentration by Ca percentage increments yield biases and limits of agreement that are acceptable when compared with Dill and Costill equation correction. Ca concentration may be used as a hemoconcentration biomarker in high-intensity exercise, which would allow scientists and physicians avoid extra costs, facilitate in-field research, and delayed estimation of hemoconcentration using stored serum samples.

Allopurinol prevents cardiac and skeletal muscle damage in professional soccer players.

Xanthine oxidase (XO), a free radical-generating enzyme, is involved in tissue damage produced during exhaustive exercise. Our aim was to test whether allopurinol, a powerful inhibitor of XO, may be effective in preventing exercise-induced tissue damage in soccer players. Twelve soccer players were randomized into two experimental groups. One received allopurinol, before a match of the premier Spanish Football League, and the other placebo. Allopurinol prevented the exercise-induced increase in all the markers of skeletal muscle damage analyzed: creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and myoglobin. Creatine kinase-MB isoenzyme and highly sensitive troponin T, specific biomarkers of myocardial injury, increased significantly in the placebo but not in the allopurinol-treated group after the football match. We also found that the exercise-induced lipid peroxidation, as reflected by malondialdehyde measurements, was prevented after allopurinol administration. However, inhibition of XO did not prevent the increment in the activity of alanine aminotransferase found after the match. No changes in the serum gamma glutamyltransferase activity was found after the match on either the placebo and the allopurinol groups. These two enzymes were determined as biomarkers of liver injury. Allopurinol represents an effective and inexpensive pharmacological agent to prevent tissue damage in soccer players.

Exercise effects on erythrocyte deformability in exercise-induced arterial hypoxemia.

Exercise-induced arterial hypoxemia (EIAH) is often found in endurance-trained subjects at high exercise intensity. The role of erythrocyte deformability (ED) in EIAH has been scarcely explored. We aimed to explore the role of erythrocyte properties and lactate accumulation in the response of ED in EIAH. ED was determined in 10 sedentary and in 16 trained subjects, both before and after a maximal incremental test, and after recovery, along with mean corpuscular volume (MCV) and red blood cell lactate concentrations. EIAH was found in 6 trained subjects (∆SaO2=-8.25±4.03%). Sedentary and non-EIAH trained subjects showed reduced ED after exercise, while no effect on ED was found in EIAH trained subjects. After exercise, lactate concentrations rose and MCV increased equally in all groups. ED is strongly driven by cell volume, but the different ED response to exercise in EIAH shows that other cellular mechanisms may be implicated. Interactions between membrane and cytoskeleton, which have been found to be O2-regulated, play a role in ED. The drop in SaO2 in EIAH subjects can improve ED response to exercise. This can be an adaptive mechanism that enhances muscular and pulmonary perfusion, and allows the achievement of high exercise intensity in EIAH despite lower O2 arterial transport.

Inconsistency in circulating irisin levels: what is really happening?

The discovery of irisin as a novel and promising peptidic hormone for the treatment of obesity and diabetes has recently been reported. As a result, great hopes have been raised based on this finding, hypothesizing that irisin might provide additional benefits, not only for obesity and diabetes, but also for a wide range of pathological conditions requiring therapeutical and clinical attention. However, controversial results and conclusions on circulating irisin concentrations and correlations with other variables, including its role in metabolism, have recently been reported. Although laboratory assessment of irisin by ELISA is easily available and may provide interesting information for therapeutics and clinical practice, the heterogeneous and often discrepant results published so far, raise serious concerns about its measurement, indicating that it may still not be ready for use or whether irisin really exists. We highlight here some aspects on these discrepancies and contradictions, and put forward their implications.

Impact of exercise training on neuroplasticity-related growth factors in adolescents.

OBJECTIVES: We aimed to determine the effect of exercise training on plasma levels of brain-derived neurotrophic factor (BDNF), and serum insulin-like growth factor-1 (IGF-1) as well as cAMP response element-binding (CREB) activation in peripheral blood mononuclear cells (PBMCs) in adolescents. METHODS: Nine trained and seven sedentary male adolescents, matched in age (14.0±2.2 years), were recruited for the study. Trained boys performed higher physical activity levels (expressed both as total energy expenditure and as physical activity energy expenditure) and showed significant bradycardia when compared with sedentary ones. RESULTS: We found that BDNF and IGF-1 levels were significantly higher in trained adolescents than in sedentary ones. However, no effect of training was found in the activation of CREB in PBMCs. CONCLUSIONS: We demonstrated the increase of neuroplasticity-related proteins due to exercise training in adolescents. Our results emphasize the significance and impact of exercise in this developmental period.

Increased average longevity among the "Tour de France" cyclists.

It is widely held among the general population and even among health professionals that moderate exercise is a healthy practice but long term high intensity exercise is not. The specific amount of physical activity necessary for good health remains unclear. To date, longevity studies of elite athletes have been relatively sparse and the results are somewhat conflicting. The Tour de France is among the most gruelling sport events in the world, during which highly trained professional cyclists undertake high intensity exercise for a full 3 weeks. Consequently we set out to determine the longevity of the participants in the Tour de France, compared with that of the general population. We studied the longevity of 834 cyclists from France (n=465), Italy (n=196) and Belgium (n=173) who rode the Tour de France between the years 1930 and 1964. Dates of birth and death of the cyclists were obtained on December 31 (st) 2007. We calculated the percentage of survivors for each age and compared them with the values for the pooled general population of France, Italy and Belgium for the appropriate age cohorts. We found a very significant increase in average longevity (17%) of the cyclists when compared with the general population. The age at which 50% of the general population died was 73.5 vs. 81.5 years in Tour de France participants. Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners. Our findings underpin the importance of exercising without the fear that becoming exhausted might be bad for one's health.

Desmopresssin and hemodilution: implications in doping.

Blood doping improves physical performance in sport. This is the reason why the antidoping authorities subject athletes to blood tests. Plasma volume expanders are prohibited agents used to reduce an artificial increase in hematological values using different illegal practices. The aim of our study was to test whether desmopressin (DDAVP)-induced hemodilution would alter the concentration of hematological parameters used to detect blood doping in sports. This was an intra-subject crossover study. Venous blood samples were obtained from eight physically active males on two occasions. On the first occasion the subjects ingested 1.5 L of mineral water and 4.3 microg/kg of DDAVP. On the second occasion the subjects ingested 1.5 L of mineral water. The samples were analyzed for hematocrit, hemoglobin, reticulocytes, OFF Hr-Score, glucose, albumin, creatinine and total proteins. After treatment with DDAVP we found a significant decrease in the hematocrit, hemoglobin and in the OFF Hr-Score values. We also found a significant decrease in glucose, albumin, creatinine and total proteins concentration; however, in this case, all the values were significantly below the physiological levels. Treatment with DDAVP has a very effective hemodilution effect. We consider that this substance should be included in the WADA's prohibited list.

Effect of intermittent hypoxia on hematological parameters after recombinant human erythropoietin administration.

Recent publications reflect the anti-doping authorities' concern about the use of altitude simulator systems as violating the spirit of sport criterion (Levine 2006; Loland and Murray 2007; Spriggs 2005). The aim of our study was to determine whether intermittent hypoxic treatments could modify the hemoglobin, hematocrit, reticulocytes, and erythropoietic stimulation index (OFF-Hr Score) values after administration of rHuEPO-alpha. Although these hematological parameters are of secondary nature some international sport federations currently exclude athletes who show aberrant values of these parameters from competition. Ten young male Wistar rats were treated, three times a week for 2 weeks, with 500 IU of rHuEPO-alpha. After the treatment, the animals were randomly divided into two groups: normoxic and hypoxic. The normoxic group was maintained at 21% O(2) 24 h a day for 23 days. The hypoxic group was maintained 12 h at 21% O(2) and 12 h at 12% O(2) (~4,000 m) the same time period. After the rHuEPO-alpha treatment, the hypoxic group of animals had a faster recovery rate in the reticulocyte count, elevated concentrations of hemoglobin and hematocrit and a significant increase in the endogenous EPO levels when compared with the normoxic group of animals. These changes led to significant modifications in the OFF-Hr Score between the hypoxic and normoxic animals. Intermittent hypoxic treatments after rHuEPO administration can significantly modify the main hematological parameters tested by the anti-doping authorities. Our results in an animal model suggest checking the described phenomena in humans in order to reach major conclusions.

Epidemiology and clinics of mushroom poisoning in Northern Italy: A 21-year retrospective analysis.

BACKGROUND: Limited information exists about epidemiology and management of mushroom poisoning. We analyzed and described epidemiology, clinical presentation, and clinical course of mushroom-poisoned patients admitted to emergency departments (EDs) of the Province of Parma, Italy. METHODS: Data from the database of mycological service were matched with clinical information retrieved from hospitals' database, from January 1, 1996 to December 31, 2016. RESULTS: Mycologist consultation was obtained in 379/443 identified mushroom poisonings. A remarkable seasonality was found, with significant peak in autumn. Thanks to the collaboration, the implicated species could be identified in 397 cases (89.6%); 108 cases (24.4%) were due to edible mushrooms, Boletus edulis being the most represented (63 cases). Overall, 408 (92%) cases presented with gastrointestinal toxicity. Twenty cases of amatoxin poisoning were recorded (11 Amanita phalloides and 9 Lepiota brunneoincarnata). One liver transplantation was needed. We observed 13 cases of cholinergic toxicity and 2 cases of hallucinogenic toxicity. Finally, 46 cases were due to "mixed" toxicities, and a total of 69 needed hospitalization. CONCLUSIONS: Early identification and management of potentially life-threatening cases is challenging in the ED, so that a mycologist service on call is highly advisable, especially during periods characterized by the highest incidence of poisoning.

Response rate to the treatment of Waldenström macroglobulinemia: A meta-analysis of the results of clinical trials.

Waldenström macroglobulinemia (WM) is a malignant lymphoproliferative disorder characterized by the presence of a high level of serum monoclonal IgM and a lymphoplasmacytic infiltrate in the bone marrow. This meta-analysis sought to assess the effectiveness of the different treatments for WM tested in published trials using the response rate (RR) as the main outcome measure. Forty-six articles (1409 patients) identified were entered in a variable effects model meta-analysis of proportions (rates and sample sizes). A greater response to treatment was produced in patients treated with a combination of 2+ drugs (RR=73%; 95%CI: 62, 83; p<0.01) than in those receiving monotherapy with rituximab (RR=44%; 95%CI: 34, 55; p<0.01) or a purine analogue [61% (95%CI: 43, 78; p<0.01) for cladribine and 53% (95%CI: 34, 72; p<0.01) for fludarabine]. The combination rituximab+cladribine emerged as particularly effective (RR=87%; 95%CI: 78, 94; p<0.01), slightly more effective than rituximab+bortezomib/dexamethasone (RR=84%; 95%CI: 79, 88; p<0.01) and rituximab+cyclophosphamide/dexamethasone [RR=81% (95%CI: 72, 88; p<0.01)]. Our results are in overall agreement with treatment recommendations from the seventh International Workshops on WM. Our findings are limited by the fact that we could not analyze progression-free survival (PFS). More phase II/III trials are needed to corroborate promising recent findings with bendamustine and carfilzomib and further research are needed to standardize recommendations based on maximum treatment efficacy combined with lowest toxicity, differentiation between first vs second line treatment, or long-term follow up after treatment.

Effects of an acute high-intensity interval training protocol on plasma viscosity.

AIM: High-intensity interval training (HIT) is an exercise model that has been seen to cause similar muscle adaptations and improvements in exercise performance to other traditional exercise models. This study aimed to examine the effects of low-volume HIT exercise on plasma viscosity (PV). METHODS: Ten healthy male subjects (25.80±3.39 years) randomly performed a HIT running protocol (2-min warm up at 8 km/h, 5x2-min bouts at 90% maximal heart rate, separated by 2-min at 8 km/h, finished with another 2-min period at 8 km/h) or an aerobic (AER) running exercise (60'at 55% VO2max). Blood samples were drawn before and after exercise, and after 30-minute recovery. PV, hematocrit (Hct), fibrinogen, total proteins, triglycerides, total-cholesterol and glucose levels were analyzed. Plasma volume loss during exercise was calculated. RESULTS: PV rose after HIT (P<0.05) while Hct rose after both protocols. Plasma volume loss was higher after HIT (-6.35±3.47%) than after AER (-3.11±2.49%) (P=0.045). Total-proteins (P<0.001), triglycerides (P=0.013), total-cholesterol (P<0.001) and glucose (P=0.001) concentrations increased after HIT. After AER no statistically significant differences were found in plasma constituents concentrations. CONCLUSION: A low-volume HIT session causes a sufficient loss in plasma volume that leads to significantly incremented plasma constituents' concentrations and, therefore, a mild transient rise in PV.

Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches?

Intensive muscular activity can trigger oxidative stress, and free radicals may hence be generated by working skeletal muscle. The role of the enzyme xanthine oxidase as a generating source of free radicals is well documented and therefore is involved in the skeletal muscle damage as well as in the potential transient cardiovascular damage induced by high-intensity physical exercise. Allopurinol is a purine hypoxanthine-based structural analog and a well-known inhibitor of xanthine oxidase. The administration of the xanthine oxidase inhibitor allopurinol may hence be regarded as promising, safe, and an economic strategy to decrease transient skeletal muscle damage (as well as heart damage, when occurring) in top-level athletes when administered before a competition or a particularly high-intensity training session. Although continuous administration of allopurinol in high-level athletes is not recommended due to its possible role in hampering training-induced adaptations, the drug might be useful in non-athletes. Exertional rhabdomyolysis is the most common form of rhabdomyolysis and affects individuals participating in a type of intense exercise to which they are not accustomed. This condition can cause exercise-related myoglobinuria, thus increasing the risk of acute renal failure and is also associated with sickle cell trait. In this manuscript, we have reviewed the recent evidence about the effects of allopurinol on exercise-induced muscle damage. More research is needed to determine whether allopurinol may be useful for preventing not only exertional rhabdomyolysis and acute renal damage but also skeletal muscle wasting in critical illness as well as in immobilized, bedridden, sarcopenic or cachectic patients.