Host cell glutamine metabolism as a potential antiviral target.

A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in glutamine utilization and metabolism. Glutamine metabolism generates ATP and precursors for the synthesis of macromolecules to assemble progeny viruses. Some compounds derived from glutamine are used in the synthesis of purines and pyrimidines. These latter compounds are precursors for the synthesis of nucleotides. Inhibitors of glutamine transport and metabolism are potential candidate antiviral drugs. Glutamine is also an essential nutrient for the functions of leukocytes (lymphocyte, macrophage, and neutrophil), including those in virus-infected patients. The increased glutamine requirement for immune cell functions occurs concomitantly with the high glutamine utilization by host cells in virus-infected patients. The development of antiviral drugs that target glutamine metabolism must then be specifically directed at virus-infected host cells to avoid negative effects on immune functions. Therefore, the aim of this review was to describe the landscape of cellular glutamine metabolism to search for potential candidates to inhibit glutamine transport or glutamine metabolism.

Regulation of Gene Expression by Exercise-Related Micrornas.

Gene expression control by microRNAs (miRs) is an important mechanism for maintenance of cellular homeostasis in physiological and pathological conditions as well as in response to different stimuli including nutritional factors and exercise. MiRs are involved in regulation of several processes such as growth and development, fuel metabolism, insulin secretion, immune function, miocardium remodeling, cell proliferation, differenciation, survival, and death. These molecules have also been proposed to be potential biomarkers and/or therapeutical targets in obesity, type 2 diabetes mellitus, cardiovascular diseases, metabolic syndrome, and cancer. MiRs are released by most cells and potentially act on intercellular communication to borderer or distant cells. Various studies have been performed to elucidate the involvement of miRs in exercise-induced effects. The aims of this review are: 1) to bring up the main advances for the comprehension of the mechanisms of action of miRs; 2) to present the main results on miR involvement in physical exercise; 3) to discuss the physiological effects of miRs modified by exercise. The state of the art and the perspectives on miRs associated with physical exercise will be presented. Thus, this review is important for updating recent advances and driving further strategies and studies on the exercise-related miR research.

Chronic inflammation and neutrophil activation as possible causes of joint diseases in ballet dancers.

UNLABELLED: Herein, we investigated the effects of a ballet class on the kinetic profiles of creatine kinase (CK) and lactate dehydrogenase (LDH) activities, cytokines, complement component 3 (C3), and the concentrations of immunoglobulin (Ig), IgA and IgM, in ballerinas. We also verified neutrophil death and ROS release. Blood samples were taken from 13 dancers before, immediately after, and 18 hours after a ballet class. The ballet class increased the plasma activities of CK-total (2.0-fold) immediately after class, while the activities of CK-cardiac muscle (1.0-fold) and LDH (3.0-fold) were observed to increase 18 hours after the class. Levels of the TNF-α , IL-1ß, IgG, and IgA were not affected under the study conditions. The exercise was found to induce neutrophil apoptosis (6.0-fold) 18 hours after the ballet class. Additionally, immediately after the ballet class, the neutrophils from the ballerinas were found to be less responsive to PMA stimulus. CONCLUSION: Ballet class was found to result in inflammation in dancers. The inflammation caused by the ballet class remained for 18 hours after the exercise. These findings are important in preventing the development of chronic lesions that are commonly observed in dancers, such as those with arthritis and synovitis.

Generation of reactive oxygen species by leukocytes of Prochilodus lineatus.

Prochilodus lineatus (curimbatá), from the Procholodontidae family, is a Brazilian freshwater fish, which is important commercially, nutritionally and ecologically. It is encountered in the Rio da Prata Bay in Southern South America. Studies on the immune system of this fish are scarce, but the physiological mechanisms of the species are analogous to those of other vertebrates. Thus, this work discusses the present study, which correlates P. lineatus leukocytes and the generation of reactive oxygen species after modulatory stimuli. Leukocytes were characterized by light and electron transmission microscopy and investigated by the generation of H2O2 and O2 (-), using phenol red, flow-cytometry and electron transmission histochemistry. The study determined that monocytes and neutrophils are the main cells responsible for generating O2 after stimulation with phorbol myristate acetate. Superoxide dismutase successfully inhibited the generation of reactive oxygen species in neutrophils and monocytes, but stimulated generation when in association with phorbol myristate acetate. Fish leukocyte samples from P. lineatus showed cross-reactivity with antibodies directed against human NADPH-oxidase antibody subunits (p47(phox) and p67(phox)). Thus, catalase enhanced the presence of p47(phox). Neutrophil mitochondria were shown to be generators of H2O2 (charged by cerium precipitate), being enlarged and changing their format. The present study contributes to a better understanding of the respiratory burst pathways in this species and suggests mitochondria as the organelle responsible for generation of reactive oxygen species.

Nutrition and Exercise Interventions on Skeletal Muscle Physiology, Injury and Recovery: From Mechanisms to Therapy.

Interventional strategies involving nutrition and physical exercise have been widely proposed to positively modulate skeletal muscle function, in both physiological and pathological states, such as obesity, T2DM, inflammatory diseases, cardiovascular diseases, aging, and sarcopenia [...].

Changes in lymphocyte and neutrophil function induced by a marathon race.

The aim of this study was to investigate the changes in lymphocyte and neutrophil selected functions before and after a marathon race. Fifteen professional athletes were recruited, and the following parameters were measured: plasma concentrations of IL-1ra, IL-6, IL-8, IL-10, TNF-α and C-reactive protein (CRP); neutrophil phagocytic capacity; cytokine production by neutrophils and lymphocytes and signs of neutrophil and lymphocyte death. The marathon race had no effect on CRP levels, but plasma concentrations of IL-6 and IL-1ra were increased. Although no effect was observed on the production of IL-6, IL1-ra, TNF-α, IL-1ß and IL-8 by unstimulated or stimulated neutrophils, a decrease in neutrophil phagocytic activity was observed immediately following the marathon. A high percentage of neutrophils undergoing apoptosis was observed due to the intense training regimen, whereas the percentages of apoptotic neutrophils were reduced after the race. The production of IL-2, TNF-α, IL-1ß and IL-10 by lymphocytes was decreased by 50%-80%, and the percentage of apoptotic and necrotic lymphocytes was increased by 42% and fourfold, respectively, as a result of the race. In conclusion, the increase in plasma levels of IL-6, IL-8, IL-1ra and IL-10 after the race was not due to the production of the cytokines by neutrophils or lymphocytes. In fact, the marathon led to a decrease in lymphocyte and neutrophil function, and the diminished function was more pronounced in lymphocytes, indicating an impairment in acquired immunity.

Effects of DHA-rich fish oil supplementation on lymphocyte function before and after a marathon race.

PURPOSE: To investigate the effects of docosahexaenoic-(DHA)-rich fish oil (FO) supplementation on lymphocyte function before and after a marathon race. METHODS: Twenty-one athletes participated in this study. Eight marathon runners were supplemented with 3 g of FO daily for 60 d (FO group), and 13 athletes were not supplemented (C group). The following measures of lymphocytes were taken before and after the marathon: cell proliferation, cytokine production (IL-2, IL-10, TNF-α, and IL-4), and signs of cell death. RESULTS: In the C group, the marathon had no effect on lymphocyte proliferation, DNA fragmentation, or mitochondrial membrane polarization; however, the marathon increased phosphatidylserine externalization (by 2.5-fold), induced a loss of plasma membrane integrity (by 20%), and decreased IL-2, TNF-α, and IL-10 production (by 55%, 95%, and 50%, respectively). FO supplementation did not prevent lymphocyte death induced by the marathon, as indicated by cell viability, DNA fragmentation, and phosphatidylserine externalization. However, FO supplementation increased lymphocyte proliferation before and after the marathon, and before the race, FO supplementation decreased IL-2, TNF-α, and IL-10 production in concanavalin-A-stimulated lymphocytes (by 55%, 95%, and 58%, respectively) compared with cells from the C group. The production of cytokines was not altered before or after the race in the FO group. CONCLUSIONS: DHA-rich FO supplementation increased lymphocyte proliferation and prevented a decrease in cytokine production, but it did not prevent lymphocyte death induced by participation in the marathon. Overall, DHA rich-FO supplementation has beneficial effects in preventing some of the changes in lymphocyte function induced by marathon participation.

Fish Oil Supplementation Improves the Repeated-Bout Effect and Redox Balance in 20-30-Year-Old Men Submitted to Strength Training.

Herein, we investigated the effect of fish oil supplementation combined with a strength-training protocol, for 6 weeks, on muscle damage induced by a single bout of strength exercise in untrained young men. Sixteen men were divided into two groups, supplemented or not with fish oil, and they were evaluated at the pre-training period and post-training period. We investigated changes before and 0, 24, and 48 h after a single hypertrophic exercise session. Creatine kinase (CK) and lactate dehydrogenase (LDH) activities, plasma interleukin-6 (IL-6) and C-reactive protein (CRP) levels, and the redox imbalance were increased in response to the single-bout session of hypertrophic exercises at baseline (pre-training period) and decreased during the post-training period in the control group due to the repeated-bout effect (RBE). The fish oil supplementation exacerbated this reduction and improved the redox state. In summary, our findings demonstrate that, in untrained young men submitted to a strength-training protocol, fish oil supplementation is ideal for alleviating the muscle injury, inflammation, and redox imbalance induced by a single session of intense strength exercises, highlighting this supplementation as a beneficial strategy for young men that intend to engage in strength-training programs.

Hydrolyzed whey protein enriched with glutamine dipeptide attenuates skeletal muscle damage and improves physical exhaustion test performance in triathletes.

Purpose: To investigate the effects of hydrolyzed whey protein enriched with glutamine dipeptide on the percentage of oxygen consumption, second ventilatory threshold, duration and total distance covered, and skeletal muscle damage during an exhaustion test in elite triathletes. Methods: The study was a randomized, double-blinded, placebo-controlled, crossover trial. Nine male triathletes performed a progressive incremental test on a treadmill ergometer (1.4 km h-1·3 min-1) 30 min after ingesting either 50 g of maltodextrin plus four tablets of 700 mg hydrolyzed whey protein enriched with 175 mg of glutamine dipeptide diluted in 250 ml of water (MGln) or four tablets of 700 mg maltodextrin plus 50 g maltodextrin diluted in 250 ml of water (M). Each athlete was submitted to the two dietary treatments and two corresponding exhaustive physical tests with an interval of one week between the interventions. The effects of the two treatments were then compared within the same athlete. Maximal oxygen consumption, percentage of maximal oxygen consumption, second ventilatory threshold, and duration and total distance covered were measured during the exhaustion test. Blood was collected before and immediately after the test for the determination of plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration (also measured 6, 10, and 15 min after the test). Plasma cytokines (IL-6, IL-1ß, TNF-α, IL-8, IL-10, and IL-1ra) and C-reactive protein levels were also measured. Results: A single dose of MGln increased the percentage of maximal oxygen consumption, second ventilatory threshold duration, and total distance covered during the exhaustion test and augmented plasma lactate levels 6 and 15 min after the test. MGln also decreased plasma LDH and CK activities indicating muscle damage protection. Plasma cytokine and C-reactive protein levels did not change across the study periods. Conclusion: Conditions including overnight fasting and a single dose of MGln supplementation resulted in exercising at a higher percentage of maximal oxygen consumption, a higher second ventilatory threshold, blood lactate levels, and reductions in plasma markers of muscle damage during an exhaustion test in elite triathletes. These findings support oral glutamine supplementation's efficacy in triathletes, but further studies require.

Chronic Low or High Nutrient Intake and Myokine Levels.

Inadequate nutrient availability has been demonstrated to be one of the main factors related to endocrine and metabolic dysfunction. We investigated the role of inadequate nutrient intakes in the myokine levels of runners. Sixty-one amateur runners participated in this study. The myokine levels were determined using the Human Magnetic Bead Panel from plasma samples collected before and after the marathon. Dietary intake was determined using a prospective method of three food records. The runners with lower carbohydrate and calcium intakes had higher percentages of fat mass (p < 0.01). The runners with a sucrose intake comprising above 10% of their energy intake and an adequate sodium intake had higher levels of BDNF (p = 0.027 and p = 0.031). After the race and in the recovery period, the runners with adequate carbohydrate intakes (g/kg) (>5 g/kg/day) had higher levels of myostatin and musclin (p < 0.05). The runners with less than 45% of carbohydrate of EI had lower levels of IL-15 (p = 0.015) and BNDF (p = 0.013). The runners with higher cholesterol intakes had lower levels of irisin (p = 0.011) and apelin (p = 0.020), and those with a low fiber intake had lower levels of irisin (p = 0.005) and BDNF (p = 0.049). The inadequate intake influenced myokine levels, which promoted cardiometabolic tissue repair and adaptations to exercise.

Exercise Induced-Cytokines Response in Marathon Runners: Role of ACE I/D and BDKRB2 +9/-9 Polymorphisms.

Renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) have a different site of interaction and modulate vascular tone and inflammatory response as well on exercise adaptation, which is modulated by exercise-induced cytokines. The aim of the study was to evaluate the role of ACE I/D and BDKRB2 +9/-9 polymorphism on exercise-induced cytokine response. Seventy-four male marathon finishers, aged 30 to 55 years, participated in this study. Plasma levels of exercise-induced cytokines were determined 24 h before, immediately after, and 24 h and 72 h after the São Paulo International Marathon. Plasma concentrations of MCP-1, IL-6 and FGF-21 increased after marathon in all genotypes of BDKRB2. IL-10, FSTL and BDNF increased significantly after marathon in the genotypes with the presence of the -9 allele. FSTL and BDNF concentrations were higher in the -9/-9 genotype compared to the +9/+9 genotype before (p = 0.006) and after the race (p = 0.023), respectively. Apelin, IL-15, musclin and myostatin concentrations were significantly reduced after the race only in the presence of -9 allele. Marathon increased plasma concentrations of MCP1, IL-6, BDNF and FGF-21 in all genotypes of ACE I/D polymorphism. Plasma concentrations of IL-8 and MIP-1alpha before the race (p = 0.015 and p = 0.031, respectively), of MIP-1alpha and IL-10 after the race (p = 0.033 and p = 0.047, respectively) and VEGF 72 h after the race (p = 0.018) were lower in II homozygotes compared to runners with the presence of D allele. One day after the race we also observed lower levels of MIP-1alpha in runners with II homozygotes compared to DD homozygotes (p = 0.026). Before the marathon race myostatin concentrations were higher in DD compared to II genotypes (p = 0.009). Myostatin, musclin, IL-15, IL-6 and apelin levels decreased after race in genotypes with the presence of D allele. After the race ACE activity was negatively correlated with MCP1 (r = -56, p < 0.016) and positively correlated with IL-8, IL-10 and MIP1-alpha (r = 0.72, p < 0.0007, r = 0.72, p < 0.0007, r = 0.47, p < 0.048, respectively). The runners with the -9/-9 genotype have greater response in exercise-induced cytokines related to muscle repair and cardioprotection indicating that BDKRB2 participate on exercise adaptations and runners with DD genotype have greater inflammatory response as well as ACE activity was positively correlated with inflammatory mediators. DD homozygotes also had higher myostatin levels which modulates protein homeostasis.

Leukocyte metabolism in obese type 2 diabetic individuals associated with COVID-19 severity.

Recent studies show that the metabolic characteristics of different leukocytes, such as, lymphocytes, neutrophils, and macrophages, undergo changes both in the face of infection with SARS-CoV-2 and in obesity and type 2 diabetes mellitus (DM2) condition. Thus, the objective of this review is to establish a correlation between the metabolic changes caused in leukocytes in DM2 and obesity that may favor a worse prognosis during SARS-Cov-2 infection. Chronic inflammation and hyperglycemia, specific and usual characteristics of obesity and DM2, contributes for the SARS-CoV-2 replication and metabolic disturbances in different leukocytes, favoring the proinflammatory response of these cells. Thus, obesity and DM2 are important risk factors for pro-inflammatory response and metabolic dysregulation that can favor the occurrence of the cytokine storm, implicated in the severity and high mortality risk of the COVID-19 in these patients.

Molecular and cellular mechanisms involved in tissue-specific metabolic modulation by SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is triggered by the SARS-CoV-2, which is able to infect and cause dysfunction not only in lungs, but also in multiple organs, including central nervous system, skeletal muscle, kidneys, heart, liver, and intestine. Several metabolic disturbances are associated with cell damage or tissue injury, but the mechanisms involved are not yet fully elucidated. Some potential mechanisms involved in the COVID-19-induced tissue dysfunction are proposed, such as: (a) High expression and levels of proinflammatory cytokines, including TNF-α IL-6, IL-1ß, INF-α and INF-ß, increasing the systemic and tissue inflammatory state; (b) Induction of oxidative stress due to redox imbalance, resulting in cell injury or death induced by elevated production of reactive oxygen species; and (c) Deregulation of the renin-angiotensin-aldosterone system, exacerbating the inflammatory and oxidative stress responses. In this review, we discuss the main metabolic disturbances observed in different target tissues of SARS-CoV-2 and the potential mechanisms involved in these changes associated with the tissue dysfunction.

Modulatory effect of fatty acids on fungicidal activity, respiratory burst and TNF-α and IL-6 production in J774 murine macrophages.

The reported effects of different families of fatty acids (FA; SFA, MUFA, n-3 and n-6 PUFA) on human health and the importance of macrophage respiratory burst and cytokine release to immune defence led us to examine the influence of palmitic acid (PA), oleic acid (OA), linoleic acid, arachidonic acid, EPA and DHA on macrophage function. We determined fungicidal activity, reactive oxygen species (ROS) and cytokine production after the treatment of J774 cells with non-toxic concentrations of the FA. PA had a late and discrete stimulating effect on ROS production, which may be associated with the reduced fungicidal activity of the cells after treatment with this FA. OA presented a sustained stimulatory effect on ROS production and increased fungicidal activity of the cells, suggesting that enrichment of diets with OA may be beneficial for pathogen elimination. The effects of PUFA on ROS production were time- and dose-dependently regulated, with no evident differences between n-3 and n-6 PUFA. It was worth noting that most changes induced after stimulation of the cells with lipopolysaccharide were suppressed by the FA. The present results suggest that supplementation of the diet with specific FA, not classes of FA, might enable an improvement in host defence mechanisms or a reduction in adverse immunological reactions.

Time Course and Role of Exercise-Induced Cytokines in Muscle Damage and Repair After a Marathon Race.

Endurance exercise induces an increase in the expression of exercise-induced peptides that participate in the repair and regeneration of skeletal muscles. The present study aimed to evaluate the time course and role of exercise-induced cytokines in muscle damage and repair after a marathon race. Fifty-seven Brazilian male amateur marathon finishers, aged 30-55 years, participated in this study. The blood samples were collected 24 h before, immediately after, and 24 and 72 h after the São Paulo International Marathon. The leukogram and muscle damage markers were analyzed using routine automated methodology in the clinical laboratory. The plasma levels of the exercise-induced cytokines were determined using the Human Magnetic Bead Panel or enzyme-linked immunosorbent assays [decorin and growth differentiation factor 15 (GDF-15)]. A muscle damage was characterized by an increase in plasma myocellular proteins and immune changes (leukocytosis and neutrophilia). Running the marathon increased interleukin (IL)-6 (4-fold), IL-8 (1.5-fold), monocyte chemoattractant protein-1 (2.4-fold), tumor necrosis factor alpha (TNF-α) (1.5-fold), IL-10 (11-fold), decorin (1.9-fold), GDF-15 (1.8-fold), brain-derived neurotrophic factor (BDNF) (2.7-fold), follistatin (2-fold), and fibroblast growth factor (FGF-21) (3.4-fold) plasma levels. We also observed a reduction in musclin, myostatin, IL-15, and apelin levels immediately after the race (by 22-36%), 24 h (by 26-52%), and 72 h after the race (by 25-53%). The changes in BDNF levels were negatively correlated with the variations in troponin levels (r = -0.36). The variations in IL-6 concentrations were correlated with the changes in follistatin (r = 0.33) and FGF-21 (r = 0.31) levels after the race and with myostatin and irisin levels 72 h after the race. The changes in IL-8 and IL-10 levels had positive correlation with variation in musclin (p < 0.05). Regeneration of exercise-induced muscle damage involves the participation of classical inflammatory mediators, as well as GDF-15, BDNF, follistatin, decorin, and FGF-21, whose functions include myogenesis, mytophagia, satellite cell activation, and downregulation of protein degradation. The skeletal muscle damage markers were not associated to myokines response. However, BDNF had a negative correlation with a myocardial damage marker. The classical anti-inflammatory mediators (IL-10, IL-8, and IL-6) induced by exercise are associated to myokines response immediately after the race and in the recovery period and may affect the dynamics of muscle tissue repair.

Relationship between children physical activity, inflammatory mediators and lymphocyte activation: possible impact of social isolation (COVID-19).

OBJECTIVE: Lifestyle and body composition may be simultaneously responsible for immune response modulation. This study aimed to compare plasmatic adipokines concentration and lymphocyte cytokine production in children with different daily steps (DS) range, as well as to discuss the potential negative impact of the social isolation during COVID-19 pandemic in this context. DS can be a useful and low-cost way of monitoring children's health status. STUDY DESIGN: Fifty children were classified into clusters based in DS measured by pedometer: Sedentary Group (DS = 9338 ± 902 steps) and Active Group (DS = 13,614 ± 1003 steps). Plasma and lymphocytes were isolated and cultured to evaluate cytokine production. RESULTS: Sedentary group presented lower adiponectin (7573 ± 232 pg/mL), higher leptin (16,250 ± 1825 pg/mL) plasma concentration, and higher lymphocyte production of IL-17, IFN-gamma, TNF-, IL-2 in relation to active group, suggesting predominance of Th1 response. Otherwise, the active group presented higher lymphocyte supernatant concentration of IL-10 and higher regulatory T cell (Treg) percentage. CONCLUSION: These results indicate that lymphocytes of children performing higher DS have an anti-inflammatory profile, especially of Treg. Besides, the prolonged social isolation in children during the COVID-19 pandemic, limiting physical mobility and exercise, reduces DS and increases adiposity, which could impair the immune system function and raise the susceptibility to inflammatory diseases.

Association Between Hematological Parameters and Iron Metabolism Response After Marathon Race and ACTN3 Genotype.

α-Actinin-3 (ACTN3 R577X, rs.1815739) polymorphism is a genetic variation that shows the most consistent influence on metabolic pathway and muscle phenotype. XX genotype is associated with higher metabolic efficiency of skeletal muscle; however, the role of ACTN3 polymorphism in oxygen transport and utilization system has not yet been investigated. Therefore, the aim of this study was to determine the influence of ACTN3 polymorphisms on hematological and iron metabolism response induced by marathon race. Eighty-one Brazilian amateur male endurance runners participated in the study. Blood samples and urine were collected before; immediately after; and 1, 3, and 15 days after the marathon race. Urine, hematological parameters, iron metabolism, and ACTN3 genotyping analyses were performed. The marathon race induced a decrease in erythrocytes, Hb, and Ht, and an increase in hematuria, creatinine, myoglobin, red cell distribution width, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, direct and indirect bilirubin and erythropoietin. Moreover, an elevation immediately or 1 day after the marathon race follows a reduction 3 or 15 days after the marathon race were observed on transferrin saturation and iron and transferrin levels. Hematological parameters and iron metabolism changes induced by marathon race were not observed in XX genotypes. Hematuria and decreased erythrocytes, Hb, Ht, and iron and transferrin levels were observed only in RR and/or RX genotypes but not in XX genotypes. The percentage of runners with hematuria, leukocyturia, iron deficiency, creatinine, myoglobin, and bilirubin imbalance was higher in RR compared to XX genotypes. ACTN3 polymorphism is associated with iron metabolism and hematological responses after endurance exercise. Despite these results being based on a small sample, they highlight a protective role of the XX genotype on hematological and renal changes induced by long-distance exercise. Therefore, these findings should be further replicated.

Angiotensin-Converting Enzyme Related-Polymorphisms on Inflammation, Muscle and Myocardial Damage After a Marathon Race.

Muscle damage is one of the most important factors that affect muscle fatigue during endurance exercise. Recent evidence suggests that the renin-angiotensin system impacts on skeletal muscle wasting. The aim of this study was to determine association between the AGT Met235Thr, ACE I/D and BDKRB2 -9/+9 polymorphisms with inflammation, myocardial and muscle injury induced by endurance exercise. Eighty-one Brazilian male runners participated in this study and completed the International Marathon of Sao Paulo. Muscle and myocardial damage markers (alanine transaminase, ALT, aspartate transaminase, AST, lactic dehydrogenase, LDH, creatine kinase, CK, Troponin, pro BNP, myoglobin, and CK-MB) and inflammatory mediators (IL-6, IL-8, IL-10, IL12p70, IL1ß, and TNF-α) were determined one day before, immediately after, one day after, and three days after the event. Muscle damage was also determined fifteen days after race and angiotensinogen (AGT) Met235Thr, angiotensin-converting enzyme (ACE) I/D, and Bradykinin B2 receptor (BDKRB2) -9/+9 polymorphisms were determined. Marathon race participation induced an increase in all muscle damage and inflammatory markers evaluated (p < 0.0001). The muscle damage markers, troponin and pro BNP, CK and LDH and inflammatory markers, IL-6, IL-8, IL-1ß and IL-10 were also higher in ACE II genotype immediately after race, compared to DD genotype. The percentage of runners higher responders (>500U/I) to CK levels was higher for II genotypes (69%) compared to DD and ID genotypes (38% and 40%, respectively) immediately after. Troponin, pro BNP and IL-1ß, IL-8 levels were also elevated in AGT MM genotype compared to TT genotype athletes after and/or one day after race. BDKRB2 -9/-9 had pronounced response to LDH, CK, CK-MB and ALT and AST activities, myoglobin, troponin, IL-6, IL-8 levels immediately, one day and/or three days after race. The percentage of runners higher responders (>500U/I) to CK levels was greater for -9-9 and -9+9 genotypes (46 and 48%, respectively) compared to +9+9 genotypes (31%) immediately after. ACE II, AGT MM, and BDKRB2 -9-9 genotypes may increase the susceptibility to inflammation, muscle injury after endurance exercise and could be used to predict the development of clinical conditions associated with muscle damage and myocardial injury.

New insights on the regulation of cancer cachexia by N-3 polyunsaturated fatty acids.

Cancer cachexia is a multifactorial syndrome that develops during malignant tumor growth. Changes in plasma levels of several hormones and inflammatory factors result in an intense catabolic state, decreased activity of anabolic pathways, anorexia, and marked weight loss, leading to cachexia development and/or accentuation. Inflammatory mediators appear to be related to the control of a highly regulated process of muscle protein degradation that accelerates the process of cachexia. Several mediators have been postulated to participate in this process, including TNF-α, myostatin, and activated protein degradation pathways. Some interventional therapies have been proposed, including nutritional (dietary, omega-3 fatty acid supplementation), hormonal (insulin), pharmacological (clenbuterol), and nonpharmacological (physical exercise) therapies. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid, are recognized for their anti-inflammatory properties and have been used in therapeutic approaches to treat or attenuate cancer cachexia. In this review, we discuss recent findings on cellular and molecular mechanisms involved in inflammation in the cancer cachexia syndrome and the effectiveness of n-3 PUFAs to attenuate or prevent cancer cachexia.

Impairment on Cardiopulmonary Function after Marathon: Role of Exhaled Nitric Oxide.

BACKGROUND: The endurance exercise is capable of inducing skeletal muscle, heart, and respiratory fatigue, evidenced by morphofunctional cardiac changes, release of myocardial injury biomarkers, and reduction of maximal voluntary ventilation and oxygen consumption (VO2) at peak exercise. PURPOSE: The aim of this study was to investigate whether marathoners present cardiac fatigue after marathon and whether it correlates with pulmonary levels of exhaled nitric oxide (eNO) and pulmonary inflammation. METHODS: 31 male marathoners, age 39 ± 9 years, were evaluated by cardiopulmonary exercise test three weeks before and between three and 15 days after a marathon; eNO analysis and spirometry were evaluated before, immediately after, and 24 and 72 hours after the marathon, and sputum cellularity and cytokine level were assessed before and after the marathon. RESULTS: Marathon induced an increase in the percentage of macrophages, neutrophils (from 0.65% to 4.28% and 6.79% to 14.11%, respectively), and epithelial cells and a decrease in cytokines in induced sputum, followed by an increase in eNO concentration (20 ± 11 to 35 ± 19 ppb), which presented a significant reduction 24 and 72 hours after marathon (9 ± 12 e 12 ± 9 ppb, p < 0.05). We observed a decrease in the spirometry parameters in all time points assessed after the marathon (p < 0.05) as well as in cardiopulmonary capacity, evidenced by a reduction in VO2 and ventilation peaks (57 ± 6 to 55 ± 6 mL·min-1·Kg-1 and 134 ± 19 to 132 ± 18 Lpm, respectively, p < 0.05). Finally, we observed a negative correlation between the decrease in forced expiratory volume and decrease in eNO 24 and 72 hours after marathon (r = -0.4, p = 0.05). CONCLUSION: Reduction in eNO bioavailability after marathon prevents the reduction in cardiopulmonary capacity induced by acute inflammatory pattern after marathon.