Exhaustive Exercise Increases Spontaneous but Not fMLP-Induced Production of Reactive Oxygen Species by Circulating Phagocytes in Amateur Sportsmen

Strenuous exercise alters the oxidative response of blood phagocytes to various agonists. However, little is known about spontaneous post exercise oxidant production by these cells. In this cross-over trial, we tested whether an exhaustive treadmill run at a speed corresponding to 70% of VO2max affects spontaneous and fMLP-provoked oxidant production by phagocytes in 18 amateur sportsmen. Blood was collected before, just after, and 1, 3, 5 and 24 h post exercise for determination of absolute and normalized per phagocyte count spontaneous (a-rLBCL, rLBCL) and fMLP-induced luminol-enhanced whole blood chemiluminescence (a-fMLP-LBCL, fMLP-LBCL). a-rLBCL and rLBCL increased by 2.5- and 1.5-times just after exercise (p < 0.05) and then returned to baseline or decreased by about 2-times at the remaining time-points, respectively. a-fMLP-LBCL increased 1.7- and 1.6-times just after and at 3 h post-exercise (p < 0.05), respectively, while fMLP-LBCL was suppressed by 1.5- to 2.3-times at 1, 3, 5 and 24 h post-exercise. No correlations were found between elevated post-exercise a-rLBCL, a-fMLP-LBCL and run distance to exhaustion. No changes of oxidants production were observed in the control arm (1 h resting instead of exercise). Exhaustive exercise decreased the blood phagocyte-specific oxidative response to fMLP while increasing transiently spontaneous oxidant generation, which could be a factor inducing secondary rise in antioxidant enzymes activity.

Effect of Multiple-Nutrient Supplement on Muscle Damage, Liver, and Kidney Function After Exercising Under Heat: Based on a Pilot Study and a Randomised Controlled Trial

Objective: This study explored the effect of multiple-nutrient supplementation on muscle damage and liver and kidney function after vigorous exercise under heat.Methods: After an initial pilot trial comprising 89 male participants, 85 participants were recruited and assigned into three groups: a multiple-nutrient (M) group, a glucose (G) group, and a water (W) group. Multiple-nutrient supplements contain glucose, fructose, maltose, sodium, potassium, vitamin B1, vitamin B2, vitamin C, vitamin K, and taurine. Participants were organised to take a 3-km running test (wet-bulb globe temperature 32°C) after a short-term (7 days) supplement. Blood samples were obtained to detect biochemical parameters [glucose (GLU), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), uric acid (UA), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid], inflammation factors [interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)], and oxidative stress biomarkers [superoxide dismutase (SOD) and 8-iso-prostaglandin F (2alpha) (8-iso-PGF2α)].Results: In the pilot trial, BUN decreased significantly in the M and G groups immediately after the running test. AST, Cr, and UA were significantly reduced 24 h after the running test with single-shot multiple-nutrient supplementation. In the short-term trial, multiple nutrients further prevented the elevation of CK (p = 0.045) and LDH (p = 0.033) levels 24 h after strenuous exercise. Moreover, we found that multiple nutrients significantly reduced IL-6 (p = 0.001) and TNF-α (p = 0.015) elevation immediately after exercise. Simultaneously, SOD elevation was significantly higher in the M group immediately after exercising than in the other two groups (p = 0.033). 8-iso-PGF2α was reduced in the M group 24 h after exercise (p = 0.036).Conclusions: This study found that multiple-nutrient supplementation promoted the recovery of muscle damage and decreased liver and kidney function caused by strenuous exercise in a hot environment, probably through the inhibition of secondary damage induced by increased inflammatory reactions and oxidative stress. In this respect, the current study has important implications for the strategy of nutritional support to accelerate recovery and potentially prevent heat-related illness. This study was prospectively registered on clinicaltrials.gov on June 21, 2019 (ID: ChiCTR1900023988).

Marathon-Induced Cardiac Strain as Model for the Evaluation of Diagnostic microRNAs for Acute Myocardial Infarction

Background: The current gold standard biomarker for myocardial infarction (MI), cardiac troponin (cTn), is recognized for its high sensitivity and organ specificity; however, it lacks diagnostic specificity. Numerous studies have introduced circulating microRNAs as potential biomarkers for MI. This study investigates the MI-specificity of these serum microRNAs by investigating myocardial stress/injury due to strenuous exercise. Methods: MicroRNA biomarkers were retrieved by comprehensive review of 109 publications on diagnostic serum microRNAs for MI. MicroRNA levels were first measured by next-generation sequencing in pooled sera from runners (n = 46) before and after conducting a full competitive marathon. Hereafter, reverse transcription quantitative real-time PCR (qPCR) of 10 selected serum microRNAs in 210 marathon runners was performed (>10,000 qPCR measurements). Results: 27 potential diagnostic microRNA for MI were retrieved by the literature review. Eight microRNAs (miR-1-3p, miR-21-5p, miR-26a-5p, miR-122-5p, miR-133a-3p, miR-142-5p, miR-191-5p, miR-486-3p) showed positive correlations with cTnT in marathon runners, whereas two miRNAs (miR-134-5p and miR-499a-5p) showed no correlations. Upregulation of miR-133a-3p (p = 0.03) and miR-142-5p (p = 0.01) went along with elevated cTnT after marathon. Conclusion: Some MI-associated microRNAs (e.g., miR-133a-3p and miR-142-5p) have similar kinetics under strenuous exercise and MI as compared to cTnT, which suggests that their diagnostic specificity could be limited. In contrast, several MI-associated microRNAs (miR-26a-5p, miR-134-5p, miR-191-5p) showed different release behavior; hence, combining cTnT with these microRNAs within a multi-marker strategy may add diagnostic accuracy in MI.

Is strenuous exercise harmful in the era of COVID-19 vaccination and may increase the risk of the rare adverse effects of myocarditis and thrombosis in recently vaccinated young people? The secret is IL-6. A retrospective and prospective observational study.

Interleukin 6 (IL-6) is a type of interleukin that functions as both a pro-inflammatory and anti-inflammatory cytokine. It is encoded by the IL6 gene in humans. Both COVID-19 infection and S-Protein Based Vaccines for COVID-19 were found to induce the production of proinflammatory IL-6, and also, strenuous exercise was found to induce IL-6 secretion by the skeletal muscles via lactate. Exercise causes skeletal muscle cells to release IL-6, and it raises the plasma concentration of IL-6 100 times higher than at rest . Exercise-induced IL-6 release is highly correlated with exercise intensity and duration; thus, IL-6 is regarded as an energy sensor released by contracting muscles. Although, COVID-19 infection and S-Protein Based Vaccines for COVID-19 have similar pathological effects, such as myocardial infarction, thrombotic and coagulation abnormalities (deep thrombosis), but these adverse effects are rarely associated with S-Protein Based Vaccines for COVID-19. Recently, it was showed that most patients who experienced myocarditis after COVID-19 vaccine were young male youth aged 16 to 29 years had the highest incidence of myocarditis. Interestingly, It was observed that IL-6 was linked to adverse effects such as thrombosis and myocarditis, both of which are similar to that was caused by COVID-19 infection, and that S-Protein based vaccines for COVID-19. Here, we propose a testable hypothesis that strenuous exercise could be a risk and cofactor helping in the existing of these adverse effects in young people such as myocarditis and thrombosis via induction the secretion of proinflammatory IL-6. In our retrospective and prospective observational study we will assess the possible correlation among the strenuous exercise , IL-6, myocarditis and thrombosis. The study will be multi-center and will involve young patient who will be vaccinated with first ,second and third dose of S-Protein Based Vaccines for COVID-19 (Moderna and Pfizer-BioNTech vaccine). Pfizer and BioNTech have successfully developed the BNT162b2 mRNA vaccine, which consists of the full-length S glycoprotein with the K986P and V987P mutation sites. Also, Moderna's mRNA-1273 vaccine contains the coding sequence for a S glycoprotein stabilized by a pair of proline substitutions (K986P/V987P), a transmembrane anchor, and an intact S1-S2 cleavage site .

Exercise-Induced Cardiac Fatigue in Soldiers Assessed by Echocardiography

Background: Echocardiographic signs of exercise-induced cardiac fatigue (EICF) have been described after strenuous endurance exercise. Nevertheless, few data are available on the effects of repeated strenuous exercise, especially when associated with other constraints as sleep deprivation or mental stress which occur during military selection boot camps. Furthermore, we aimed to study the influence of experience and training level on potential EICF signs.Methods: Two groups of trained soldiers were included, elite soldiers from the French Navy Special Forces (elite; n = 20) and non-elite officer cadets from a French military academy (non-elite; n = 38). All underwent echocardiography before and immediately after exposure to several days of uninterrupted intense exercise during their selection boot camps. Changes in myocardial morphology and function of the 4 cardiac chambers were assessed.Results: Exercise-induced decrease in right and left atrial and ventricular functions were demonstrated with 2D-strain parameters in both groups. Indeed, both atrial reservoir strain, RV and LV longitudinal strain and LV global constructive work were altered. Increase in LV mechanical dispersion assessed by 2D-strain and alteration of conventional parameters of diastolic function (increase in E/e' and decrease in e') were solely observed in the non-elite group. Conventional parameters of LV and RV systolic function (LVEF, RVFAC, TAPSE, s mitral, and tricuspid waves) were not modified.Conclusions: Alterations of myocardial functions are observed in soldiers after uninterrupted prolonged intense exercise performed during selection boot camps. These alterations occur both in elite and non-elite soldiers. 2D-strain is more sensitive to detect EICF than conventional echocardiographic parameters.

Urine proteomics as a non-invasive approach to monitor exertional rhabdomyolysis during military training

Exertional rhabdomyolysis (ERM), a condition often associated with strenuous exercise, a common practice in the military activities, can be defined as the process of injury and rupture of muscle cell membranes, with leakage of its components into the blood stream. Creatine kinase (CK) has been extensively used for ERM diagnosis, albeit several studies reported the discrepancy between CK levels and clinical signs or symptoms. In this study, we analyzed the biochemical profile of the blood, and the urinary proteome of ten marine soldiers in a special training course. The samples were collected in two periods, M1 and M2, which correspond to the lowest and highest CK levels during training, respectively. Quantitative urinary proteome profile of M1 and M2 was determined showing changes with highest significance in immune system and cell adhesion-related pathways after strenuous physical exercise. Changes in the abundance of several proteins was observed in individuals carrying genetic polymorphisms related to greater risk for muscle damage. Remarkably, we identified a panel of proteins (CTSH, PIK3IP1, DEFB1, ITGB1, BCAN, and TNFRSF10C) that present high correlation with three classical blood biochemical markers of ERM and AGT MET235Thr and ACE I/D polymorphisms. These proteins represent potential urine markers of muscle damage due to intense physical conditions such as military training activities.

Repetitions of Strenuous Exercise Consistently Increase Paraoxonase 1 Concentration and Activity in Plasma of Average-Trained Men

Objectives. Oxidative stress, induced by physical activity, may stimulate the expression, release, and activity of certain antioxidant enzymes. We investigated the effect of three repeated bouts of strenuous exercise on paraoxonase 1 concentration (PON1c) and paraoxonase activity (PON). Methods. Eleven average-trained healthy men (age 34.0 ± 5.2 years) performed three strenuous exercise tests on a treadmill separated by 72 hours periods of resting. PON1c, PON, ferric-reducing activity of plasma (FRAP), lipid profile, C-reactive protein concentration (CRP), and lactate concentration were determined in plasma. Results. Each exercise bout resulted in similar PON1c, PON, FRAP, and high-density lipoprotein concentration (HDL-C) increments, while PON/HDL-C ratio remained stable in all repetitions. Percentage increments at the bout of each exercise were higher for PON1c (by 64.82% at the first, by 92.9% at the second, and by 77.02% at the third exercise) than for PON (by 6.49% at the first, 10.06% at the second, and by 12.32% at the third exercise). Association was found between preexercise PON and PON1c ( r = 0.56 , p = 0.029 ), pre- ( r = 0.87 , p = 0.00003 ) and postexercise HDL-C ( r = 0.6 , p = 0.0002 ), preexercise PON and cardiovascular fitness level of participants measured as VO2max ( r = 0.39 , p = 0.026 ), and postexercise PON and lactate concentration ( r = 0.44 , p = 0.01 ). Conclusions. PON1c and PON increase during strenuous exercise, yet the effect of exercise on PON1 concentration is more pronounced. PON1 does not show tolerance to physical activity. The enzyme may provide short-term protection from oxidative stress in each exercise bout. PON may depend on exercise load. Cardiovascular fitness levels may be associated with PON1 activity.

Succinyl-CoA-based energy metabolism dysfunctions in chronic heart failure

Heart failure (HF) is a leading cause of death and repeated hospitalizations1. HF progression generally involves mitochondrial dysfunction2-4. However, how mitochondria react to chronic HF remains unclear. Here, we show the molecular basis of mitochondrial dysfunction in chronic HF, which is characterized by altered succinyl-CoA metabolism. In myocardial mitochondria of coronary ligated mice, heme synthesis and ketolysis, and enzymes using succinyl-CoA in these events were upregulated, and enzymes synthesizing succinyl-CoA at the tricarboxylic acid (TCA) cycle were also increased. Intriguingly, the ADP-specific, but not the GDP-specific, subunit of succinyl-CoA synthetase, which uses succinyl-CoA in the TCA cycle, was decreased. Myocardial succinyl-CoA levels were significantly reduced in chronic HF, impairing mitochondrial oxidative phosphorylation (OXPHOS). Consequently, the administration of 5-aminolevulinic acid (ALA)5, an intermediate in the pathway from succinyl-CoA to heme synthesis, prevented HF progression in mice. Previous reports also support the presence of succinyl-CoA metabolism abnormalities in HF patients6,7. Our results indicated that changes in succinyl-CoA usage in various energy production systems in myocardial mitochondria is characteristic to chronic HF, and that although similar alterations occur in healthy conditions, such as during strenuous exercise, they may often occur irreversibly in HF. Moreover, nutritional interventions compensating the metabolic changes are likely to provide effective methods to treat HF.

Parsonage–Turner syndrome following coronavirus disease 2019 immunization with ChAdOx1-S vaccine: a case report and review of the literature

Background Parsonage–Turner syndrome is an acute peripheral neuropathy that affects the upper brachial plexus region. Previously published reports demonstrate that the condition can be triggered by surgery, infection, autoimmune diseases, strenuous exercise, trauma, radiation, and vaccination. Parsonage–Turner syndrome has already been reported in three other patients who were vaccinated against coronavirus disease 2019. Case presentation We report the case of a 51-year-old Caucasian man without comorbidities who received the first dose of the ChAdOx1-S recombinant vaccine (Vaxzevria, AstraZeneca, Oxford, UK) against coronavirus disease 2019 and was diagnosed with Parsonage–Turner syndrome. A few days after getting vaccinated, the patient reported a progressive increase in pain in the region of vaccine administration. One month later, the shoulder pain was followed by symptoms of hypoesthesia and muscle weakness on abduction and elevation of the left upper limb. Neurological examination revealed an atrophy of the proximal muscles of the left upper limb, accompanied by paresis of the left deltoid, biceps brachii, triceps brachii, and infraspinatus muscles. Electroneuromyography carried out 3 months after the onset of symptoms showed signs consistent with brachial plexus neuritis. The adverse reaction has been properly reported to the Italian Pharmacovigilance System (Italian Medicines Agency—Agenzia Italiana del Farmaco. Conclusion The increased awareness of such association is essential for early identification and diagnosis and, thus, better clinical outcomes.