Gender differences in macrophage antiviral function following exercise stress

INTRODUCTION: In male mice, exhaustive exercise increases susceptibility to respiratory infection following intranasal inoculation with herpes simplex virus-1 (HSV-1), whereas moderate exercise decreases the risk of infection. These responses have been linked with altered macrophage antiviral resistance, among other immune mechanisms. Female mice appear to be better protected from death than male mice following HSV-1 infection, although their response to exercise stress is similar. The possible immune mechanisms, however, have not been explored. PURPOSE: This study was conducted to examine gender differences in macrophage antiviral resistance following repeated moderate and exhaustive treadmill exercise. METHODS: Male (M, N = 36) and female (F, N = 36) CD-1 mice were randomly assigned to moderate exercise (Mod), exhaustive exercise (Exh), or control (C) groups. Exercise was done daily for 3 d; moderate exercise consisted of treadmill running for 90 min, whereas exhaustive exercise consisted of running to volitional fatigue (approximately 50 min). RESULTS: Females had greater macrophage antiviral resistance to HSV-1 than males in C and Mod (P < 0.05), but not Exh; Mod increased resistance, whereas Exh decreased resistance similarly in both genders (P < 0.001). CONCLUSIONS: These data suggest that altered macrophage antiviral resistance to HSV-1 may contribute to gender differences in in vivo resistance to HSV-1 respiratory infection at rest, as well as following moderate and exhaustive exercise.     

Decreased blood oxidative stress after repeated muscle-damaging exercise

PURPOSE: To examine the effect of repeated muscle-damaging exercise on the time-course changes in several indices of muscle damage, and to compare them with changes in blood oxidative stress indices. METHODS: Twelve females underwent an isokinetic exercise session consisting of 75 lengthening knee flexions, which was repeated after 3 wk. Isometric torque, range of movement (ROM), delayed-onset muscle soreness (DOMS), creatine kinase (CK), reduced glutathione (GSH), oxidized glutathione (GSSG), thiobarbituric acid-reactive substances (TBARS), protein carbonyls, catalase, uric acid, bilirubin, and total antioxidant capacity (TAC) in blood were measured before, immediately after, and 1, 2, 3, 4, and 7 d after lengthening contractions. RESULTS: All muscle damage indices (torque, ROM, DOMS, and CK) changed significantly after exercise. The concentration of all oxidative stress indices changed significantly in a way indicating increased oxidative stress in the blood (GSH and GSH/GSSG decreased, whereas GSSG, TBARS, protein carbonyls, catalase, uric acid, bilirubin, and TAC increased), peaking in all but bilirubin at 3 d and returning to baseline values by 7 d after exercise. The repeated bout of lengthening contractions induced significantly less changes in indices of muscle damage and blood oxidative stress than the first bout. In general, from the increasing or decreasing area under the curve calculated for each oxidative stress index, the second bout produced 1.8- to 6.1-fold less changes in oxidative stress than after the first bout. CONCLUSION: A repeated bout of lengthening contractions attenuated muscle damage and blood oxidative stress compared with the first bout.     

Gender differences in the progression of metabolic responses during incremental exercise

AIM: The present investigation was undertaken to elucidate the differences in the progression of metabolic responses during incremental exercise between men and women of similar maximal aerobic capacity. METHODS: Twenty males and 20 females served as subjects for the study. Each subject was randomly assigned to perform a graded exercise test on either a cycle ergometer or a treadmill. Of the 20 subjects within each gender, 10 were tested on the cycle ergometer, whereas the other half was tested on the treadmill. During each test, absolute VO2, relative VO2, and HR were recorded during the last 15 seconds of every minute throughout the test. These variables were then plotted separately as a function of work rate so that a best-fit linear regression equation was generated for each of the three plots. RESULTS: Under the cycle condition, we found no difference in slope of increment in absolute VO2 between genders. However, the slope of increment in relative VO2 and HR was greater (P<0.05) in women than men. A negative correlation (r=-0.858, P<0.05) was found between body mass and slope of increment in relative VO2 in men and women combined. Under the treadmill condition, the slope for absolute VO2 were greater (P<0.05) in men than women. However, in terms of relative VO2 and HR, no between-gender differences were observed in the slope of increment. A positive correlation (r=0.769, P<0.05) was found between body mass and slope of increment in absolute VO2 in men and women combined. CONCLUSIONS: These results indicate that the progression of metabolic responses during incremental exercise differs between men and women despite a similar fitness. These gender differences may be further attributed to body mass that seems to play a distinctive role when the incremental exercise is conducted on a cycle ergometer and treadmill.     

Effects of oat beta-glucan on innate immunity and infection after exercise stress

PURPOSE: To test the effects of oat beta-glucan (ObetaG) on respiratory infection, macrophage antiviral resistance, and NK cytotoxicity. METHODS: Mice were randomly assigned to one of four groups: Ex-H2O, Ex-ObetaG, Con-H2O, or Con-ObetaG. ObetaG was fed in the drinking water for 10 d before intranasal inoculation of HSV-1 or sacrifice. Exercise consisted of treadmill running to volitional fatigue (approximately 140 min) for three consecutive days. Fifteen minutes after the last bout of exercise or rest, mice (N = 24) were intranasally inoculated with a standardized dose of HSV-1. Mice were monitored twice daily for morbidity and mortality. Additional mice were sacrificed after exercise, peritoneal macrophages were obtained via i.p. lavage and assayed for antiviral resistance to HSV-1 (N = 18), and spleens were harvested and assayed for NK cell cytotoxicity (N = 12). RESULTS: Exercise stress was associated with a 28% increase in morbidity (P = 0.036) and 18% increase in mortality (P = 0.15). Ingestion of ObetaG before infection prevented this increase in morbidity (P = 0.048) and mortality (P = 0.05). Exercise stress was associated with a decrease in macrophage antiviral resistance (P = 0.007), which was blocked by ingestion of ObetaG (P < 0.001). There were no effects of exercise or ObetaG on NK cytotoxicity. CONCLUSION: These data suggest that daily ingestion of ObetaG may offset the increased risk of URTI associated with exercise stress, which may be mediated, at least in part, by an increase in macrophage antiviral resistance.     

Glucocorticoid receptor and ubiquitin expression after repeated eccentric exercise

INTRODUCTION/PURPOSE: Eccentric exercise causes muscle proteolysis that may be attenuated with repeated exercise. Therefore, this study determined the effect of repeated bouts of eccentric exercise on ubiquitin (UBI), ubiquitin conjugating enzyme (E2), and 20S proteasome (20S) and glucocorticoid receptor (GR) mRNA and protein expression, myofibrillar protein content, DNA content, caspase-3 activity, serum skeletal muscle troponin-I (sTnI) and cortisol (CORT), and muscle strength. METHODS: Nine males underwent two identical eccentric exercise bouts (BT1 and BT2) 3 wk apart involving seven sets of 10 repetitions at 150% one-repetition maximum of the dominant knee extensors. Blood and muscle biopsy samples were obtained before and at 6 and 24 h postexercise whereas muscle strength was assessed before and at 24, 48, and 72 h postexercise. Data were analyzed with separate 2 x 3 and 2 x 4 factorial ANOVA (P < 0.05). RESULTS: Decrements in strength and increased soreness occurred at 24 and 48 h postexercise for both bouts (P < 0.05); however, the changes for BT1 were greater than BT2. Serum CORT and sTnI were greater immediately after and at 6, 24, and 48 h postexercise for both bouts; however, the differences in BT1 were greater than BT2 (P < 0.05). Caspase-3 activity and the mRNA and protein levels of UBI, E2, 20S, and GR were increased at 6 and 24 h postexercise, and these differences were greater for BT1 than BT2 (P < 0.05). For BT1, DNA and myofibrillar protein content decreases were apparent at 24 h postexercise (P < 0.05) but not in BT2. CONCLUSION: These results indicate that muscle injury occurring from an initial bout of eccentric exercise seems to decrease muscle strength and myofibrillar protein, possibly due to apoptosis and up-regulation of glucocorticoid receptor mediated increases in UBI-proteolytic pathway activity, all of which appear to be tempered with a repeated eccentric exercise bout.     

Interleukin-6 expression after repeated bouts of eccentric exercise

Plasma interleukin-6 (IL-6) is known to increase in response to eccentric exercise due to an acute-phase immune response. However, the severity of muscle injury is reduced with repeated bouts of eccentric exercise, possibly as a result of decreases in plasma IL-6. This study determined the response of IL-6 mRNA and IL-6, troponin-I (sTnI), muscle strength, and soreness as a result of repeated bouts of eccentric exercise. Eight males underwent two eccentric exercise bouts (3 wk apart) involving 7 sets of 10 repetitions at 150 % of the isotonic 1-RM of the dominant knee extensors. Blood samples were taken before, after and 2, 4, 6, 24, 48 and 96 h post-exercise. Strength and soreness ratings were assessed before and at 24, 48 and 96 h-post. Data were analyzed with 2 x 4 and 2 x 8 ANOVAs and the non-parametric Friedman test (p < 0.05). Both IL-6 mRNA and IL-6 underwent peak increases (p < 0.05) at 4 h-post and 6 h-post, respectively, but were not different between bouts. However, there were significant changes (p < 0.05) in sTnI, strength, and soreness that were greater after the first bout than the second, characteristic of the repeated bout effect. These results indicate that changes in sTnI, strength and soreness were less with the second eccentric exercise bout whereas the changes in both IL-6 mRNA and protein were not effected between bouts.     

Creatine kinase and muscle soreness after repeated isometric exercise

This study examined adaptation to isometric exercise with regard to changes in serum creatine kinase (CK) activity and muscle soreness. Forty-five college-age males were placed into six groups, each performing two bouts of strenuous isometric exercise of the knee extensors. In experiment 1 (N = 27), after performing the first bout of exercise, groups A, B, and C performed the second bout 3, 6, and 9 wk later, respectively. In experiment 2 (N = 18), groups D, E, and F performed the second exercise bout 1, 2, and 3 wk after the first bout, respectively. In experiment 3, group D performed two additional exercise bouts; thus, this group performed a total of four bouts spaced 1 wk apart. Muscle soreness and CK were assessed prior to and 6, 18, and 24 (or 42) h following each exercise. In experiment 1, no significant difference in soreness or serum CK was found between bouts 1 and 2. In experiment 2, a significant decrease in the CK and soreness responses was found on bout 2 compared with bout 1 (P less than 0.05). In experiment 3, serum CK and soreness responses were highest following bout 1 while bouts 2, 3, and 4 were not significantly different from one another. Performance of this isometric exercise results in an adaptation that lasts approximately 3 wk, with the greatest adaptation occurring after one bout.     

Sympathoadrenergic mechanisms in reduced hemodynamic stress responses after exercise

PURPOSE: This study examines the acute effects of moderate aerobic exercise on 1) hemodynamic and sympathetic activity during behavioral stress and 2) beta-adrenergic receptor responsivity in a biracial sample of 24 sedentary adults. METHODS: Before and after exercise, blood pressure (BP), impedance-derived cardiovascular measures, and plasma norepinephrine (NE) and epinephrine (EPI) were assessed during mental arithmetic and active speech tasks, and beta-adrenergic receptor responsivity was assessed using a standard isoproterenol challenge procedure. RESULTS: After exercise, BP, NE, and EPI responses to stress were reduced (0.0001 < P < 0.08), preejection period (PEP) was elongated (P < 0.0001), and beta(1)- and beta(2)-receptor responsivity (P < 0.02) was enhanced. Approximately 65% of the prepost exercise mean arterial pressure response difference could be accounted for by changes in sympathetic factors, with change in NE and PEP being the single best predictors. CONCLUSIONS: Reduced BP responses to stress after acute exercise are strongly linked to a decrease in sympathetic drive, as evidenced by reduced NE responses and elongation of the PEP. Coincident with this overall dampening of the hemodynamic response to stress, increases in cardiac and vascular beta-adrenergic receptor responsivity occur. These findings may have important implications for future translational studies that seek to articulate the mechanisms through which regular aerobic exercise reduces the risks of hypertensive and coronary heart disease.     

Myocardial stress after competitive exercise in professional road cyclists

PURPOSE: Based on the determination of cardiac troponin (cTnT), brain natriuretic peptide (BNP), and echocardiographic measurements, recent investigations have reported myocardial damage and reversible cardiac dysfunction after prolonged endurance exercise in apparently healthy subjects. In the present study, we investigated the myocardial stress reaction in professional endurance athletes after strenuous competitive physical exercise. METHODS: Eleven highly trained male professional road cyclists (age 27 +/- 4 yr; .VO2peak 67 +/- 5 mL.kg-1.min-1; training workload 34,000 +/- 2,500 km.yr-1) were examined. The following parameters were determined before and after one stage of a 5-d professional cycling race: BNP, cTnT (third-generation assay that shows no cross reactivity with skeletal TnT), creatine kinase (CK), creatine kinase MB (CKMB), myoglobin (Myo), and urea. All participants were submitted to a careful cardiac examination including echocardiography and stress ECG. RESULTS: None of the athletes showed pathological findings in the cardiac examination. CK (P < 0.01), CKMB (P < 0.05), and Myo (P < 0.01) were increased after the race. Normal postexercise cTnT levels indicate that the increase in CK, CKMB, and Myo was of noncardiac origin. In contrast, BNP rose significantly from 47.5 +/- 37.5 to 75.3 +/- 55.3 pg.mL-1 (P < 0.01). Pre- and postexercise values of BNP as well as the individual exercise-induced increase in BNP were significantly correlated with age (R2 = 0.68, R2 = 0.66, and R2 = 0.58, respectively; P < 0.05). CONCLUSION: Strenuous endurance exercise in professional road cyclists does not result in structural myocardial damage. The rise in BNP in older athletes may reflect a reversible, mainly diastolic left ventricular dysfunction. This needs to be confirmed by larger trials including different intensities, sports, and age groups.     

Obesity exacerbates oxidative stress levels after acute exercise

INTRODUCTION/PURPOSE: This study compared oxidative stress levels and antioxidant capacity in nonobese and obese participants after acute resistance (RX) and aerobic exercise (AX). METHODS: Blood samples were collected from 28 nonobese (mean = 20.8% body fat) and obese (mean = 35.0% body fat) participants pre- and immediately post-RX and AX. Lipid hydroperoxides (PEROX), malondialdehyde (TBARS) and total antioxidant status (TAS) were measured. Oxygen consumption (VO2) and minute ventilation (VE) values were determined during each exercise session. RESULTS: In both groups, PEROX and TBARS were elevated post-RX and AX, with the greater elevations occurring in the obese group in each case (P < 0.05). In the obese, TBARS increased by 42% and 41% post-RX and AX, respectively, compared with 7.1% and 26.9% in the nonobese group. PEROX increased by 100% and 70% post-RX and AX, respectively, in the obese, and by 85% and 62% in the nonobese. TAS was 17% higher (P < 0.05) post-RX in the nonobese compared with the obese, whereas TAS values were not different post-AX. Peak and average VE, and relative VO2). rates were higher in the obese post-AX compared with the nonobese (P < 0.05) Correlations existed between the exercise-induced change in PEROX and body fat, vitamin C and A intake, peak oxygen consumption, and exercise ventilation rates in the obese group (r = 0.784-0.776, P < 0.05). In both groups, the exercise-induced changes in PEROX were associated with vitamin C intake, exercise ventilation rates, VO2peak, and plasma triglycerides (r = 0.669-0.558, P < 0.05). CONCLUSION: Lipid peroxidation is elevated in both RX and AX, and it is exacerbated in the obese. The mechanisms underlying this response in each exercise may be different but could involve plasma triglycerides, oxygen consumption, and antioxidant intake.     

Gender differences in outcome after anterior cruciate ligament reconstruction with hamstring tendon autograft

BACKGROUND: It is now well documented that women are more likely to suffer anterior cruciate ligament injuries than are men. A few studies have examined gender differences in the outcome of anterior cruciate ligament reconstruction with patellar tendon graft and hamstring tendon with EndoButton fixation, but no well-controlled studies have specifically compared men and women after anterior cruciate ligament reconstruction with hamstring tendon graft and interference screw fixation. HYPOTHESIS: There is no difference in outcome between men and women after anterior cruciate ligament reconstruction with hamstring tendon autograft and interference screw fixation. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: There were 100 men and 100 women who underwent isolated anterior cruciate ligament reconstruction by a single surgeon. Patients were assessed preoperatively and at 1, 2, and 7 years after surgery. Variables were compared between female and male patients. RESULTS: Laxity on physical evaluation was greater in women than in men on Lachman (P = .04), pivot-shift (P = .05), and mean manual maximum testing (P = .05) at 7 years. However, the magnitude of this difference was small. No patient had a greater than grade 1 Lachman or pivot-shift test result, and the mean difference between men and women was 0.6 mm on instrumented testing. Anterior cruciate ligament graft rupture occurred in 11 men and 10 women. There was no difference between male and female patients for self-reported knee function or symptoms of instability or radiologic examination. CONCLUSION: Anterior cruciate ligament reconstruction using hamstring tendon autograft affords excellent self-reported and objective results in both men and women after 7 years. Although significantly greater laxity on physical examination was present in female patients than in male patients, the magnitude of this difference was small and had no effect on activity level, graft failure, or subjective or functional assessment.