Abstract: Many epidemiological studies have demonstrated that level of exercise is associated with reduced colorectal cancer risk. Treadmill training can decrease Apc(Min/+) mouse intestinal polyp number and size, but the mechanisms remain unclear. Understanding the molecular changes in the tumor following exercise training may provide insight on the mechanism by which exercise decreases Apc(Min/+) mouse polyp formation and growth. The purpose of this study was to determine if exercise can modulate Apc(Min/+) mouse intestinal polyp cellular signaling related to tumor formation and growth. Male Apc(Min/+) mice were randomly assigned to Control (n=20) or Exercise (n=20) treatment groups. Exercised mice ran on a treadmill at a moderate intensity (18 m/min, 60 min, 6 d/wk, 5% grade) for 9 weeks. Polyps from Apc(Min/+) mice were used to quantify markers of polyp inflammation, apoptosis, and beta-catenin signaling. Exercise decreased the number of macrophages in large polyps by 35%. Related to apoptosis, exercise decreased the number of TUNEL positive cells by 73% in all polyps. Bax protein expression in polyps was decreased 43% by exercise. B-catenin phosphorylation was elevated 3.3-fold in polyps from exercised mice. Moderate-intensity exercise training alters cellular pathways in Apc(Min/+) mouse polyps and these changes may be related to the exercise-induced reduction in polyp formation and growth. Key words: COLON CANCER, INFLAMMATION, PHYSICAL ACTIVITY, -CATENIN.

Abstract: Downhill running is associated with fiber damage, inflammation, delayed-onset muscle soreness, and various functional deficits. Curcumin, a constituent of the Indian spice turmeric has been investigated for its anti-inflammatory activity and may offset some of the damage and functional deficits associated with downhill running. This study examined the effects of curcumin on inflammation and recovery of running performance following downhill running in mice. Male mice were assigned to downhill placebo (Down-Plac), downhill curcumin (Down-Cur), uphill placebo (Up-Plac), or uphill curcumin (Up-Cur) groups and run on a treadmill at 22 m/min at -14% or +14% grade, for 150 min. At 48 h or 72 h after the up/downhill run, mice (experiment 1) underwent a treadmill performance run to fatigue. Another subset of mice was placed in voluntary activity wheel cages following the up/downhill run (experiment 2) and their voluntary activity (distance, time and peak speed) was recorded. Additional mice (experiment 3) were killed at 24 h and 48 h following the up/downhill run, and the soleus muscle was harvested for analysis of inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), and plasma was collected for creatine kinase analysis. Downhill running decreased both treadmill run time to fatigue (48 h and 72 h) and voluntary activity (24 h) (P < 0.05), and curcumin feedings offset these effects on running performance. Downhill running was also associated with an increase in inflammatory cytokines (24 h and 48 h) and creatine kinase (24 h) (P < 0.05) that were blunted by curcumin feedings. These results support the hypothesis that curcumin can reduce inflammation and offset some of the performance deficits associated with eccentric exercise-induced muscle damage.

Abstract: Immune changes following 2 h of intensive cycling with or without rest intervals were measured in trained cyclists (n = 12) who functioned as their own controls during two test sessions that were separated by two weeks. Subjects cycled for 2.0 h at approximately 64 % Watts(max) continuously (C) or with 3-min rest intervals (R) interspersed every 10 min (2.6 h total time), with the order of the sessions randomized. Blood samples were collected 30-min pre-exercise, and immediately and 1-h postexercise, and assayed for blood leukocyte subset counts, plasma IL-6, IL-10, IL-1ra, IL-8, PHA-induced lymphocyte proliferation, and natural killer cell activity (NKCA). Significant time effects were measured for all immune measures, but no significant differences in the pattern of change were found between C and R exercise trials. In conclusion, immune changes induced by 2 h of intense and prolonged exercise paralleled those measured when athletes rested 3 min every 10 min of exercise.

Abstract: Fatiguing exercise has been associated with a decrease in certain functions of neutrophils, whereas moderate exercise has generally been associated with an increase. Consumption of oat beta-glucan (ObetaG), a soluble fiber and mild immune system enhancer, may offset the immunosuppression associated with intense training and perhaps further enhance the benefits of moderate exercise. PURPOSE: To test the effects of ObetaG consumption on neutrophil function and number after both moderate and fatiguing exercise. METHODS: Male mice were assigned to one of six treatment groups. Fatiguing exercise mice (Ftg-ObetaG and Ftg-H2O) ran to volitional fatigue on a treadmill for three consecutive days, and moderate exercise mice (Mod-ObetaG and Mod-H2O) ran for six consecutive days for 1 h. Control mice (Con-ObetaG and Con-H2O) were exposed to the treadmill environment but did not run. ObetaG was consumed in the drinking water (approximately 0.6 mL x d(-1)) for 10 consecutive days. After rest or exercise on the last day of training, mice were given a 1-mL i.p. injection of thioglycollate. Mice were sacrificed 3 h later; neutrophils were harvested from the peritoneal cavity and counted, and their respiratory burst activity was measured using flow cytometry. RESULTS: Both moderate exercise and ObetaG increased neutrophil burst activity, whereas fatiguing exercise had no effect. Neutrophil number was increased by fatiguing exercise and ObetaG, but not moderate exercise. There were no additive effects of exercise and ObetaG on either of these variables. CONCLUSION: These data suggest that although not additive in their effects, both ObetaG and exercise can alter overall neutrophil respiratory burst activity (number and/or function), but only ObetaG increased both number and function, which may have important ramifications for defense against infection.

Abstract: Exhaustive exercise has been associated with an increased risk for upper respiratory tract infections in mice and humans. We have previously shown (Brown AS, Davis JM, Murphy AE, Carmichael MD, Ghaffer A, Mayer EP. Med Sci Sports Exerc 36: 1290-1295, 2004) that female mice are better protected from the lethal effects of herpes simplex virus type 1 (HSV-1) infection, both at rest and following exercise stress, but little is known about possible mechanisms. This study tested the effects of estrogen on HSV-1 infection and macrophage antiviral resistance following repeated exhaustive exercise. Female mice were assigned to either exercise (Ex) or control (C): intact female (I-C or I-Ex), ovariectomized female (O-C or O-Ex), or ovariectomized estrogen-supplemented female (E-C or E-Ex). Exercise consisted of treadmill running to volitional fatigue ( approximately 125 min) for 3 consecutive days. Intact female mice had a later time to death than O and E (P < 0.05) and fewer deaths than both O and E (P < 0.05). Exercise stress was associated with increased time to sickness (P < 0.05) and symptom severity at days 6 and 12-21 postinfection (P < 0.05) and decreased macrophage antiviral resistance (P < 0.001) in all groups. E had increased symptom severity at days 6 and 13-21 postinfection (P < 0.05). Results indicate that intact female mice are better protected from the lethal effects of HSV-1 infection and that exercise stress had a similar negative impact in all groups. This protective effect was lost in ovariectomized mice, but it was not reinstated by 17beta-estradiol replacement. This indicates that other ovarian factors, alone or in combination with estrogen, are responsible for the protective effects in females.

Abstract: PURPOSE: To investigate the effects of quercetin supplementation on incidence of upper respiratory tract infections (URTI) and exercise-induced changes in immune function. METHODS: Trained male cyclists (N=40) were randomized to quercetin (N=20) or placebo (N=20) groups and, under double-blind procedures, received 3 wk quercetin (1000 mg.d(-1)) or placebo before, during, and for 2 wk after a 3-d period in which subjects cycled for 3 h.d(-1) at approximately 57% Wmax. Blood and saliva samples were collected before and after each of the three exercise sessions and assayed for natural killer cell activity (NKCA), PHA-stimulated lymphocyte proliferation (PHA-LP), polymorphonuclear oxidative-burst activity (POBA), and salivary IgA output (sIgA). RESULTS: Pre- to postexercise changes in NKCA, PHA-LP, POBA, and sIgA did not differ significantly between quercetin and placebo groups. URTI incidence during the 2-wk postexercise period differed significantly between groups (quercetin=1/20 vs placebo=9/20, Kaplan-Meier analysis statistic=8.31, P=0.004). CONCLUSION: Quercetin versus placebo ingestion did not alter exercise-induced changes in several measures of immune function, but it significantly reduced URTI incidence in cyclists during the 2-wk period after intensified exercise.

Abstract: Trained male cyclists (n = 40) ingested quercetin (Q; n = 20) (1,000 mg/day) or placebo (P; n = 20) supplements under randomized, double-blinded methods for 3 wk before and during a 3-day period in which subjects cycled for 3 h/day at approximately 57% maximal work rate. Blood samples were collected before and after each exercise session and assayed for plasma IL-6, IL-10, IL-1ra, IL-8, TNF-alpha, and monocyte chemoattractant protein 1, and leukocyte IL-10, IL-8, and IL-1ra mRNA. Muscle biopsies were obtained before and after the first and third exercise sessions and assayed for NF-kappaB and cyclooxygenase-2 (COX-2), IL-6, IL-8, IL-1beta, and TNF-alpha mRNA. Postexercise increases in plasma cytokines did not differ between groups, but the pattern of change over the 3-day exercise period tended to be lower in Q vs. P for IL-8 and TNF-alpha (P = 0.094 for both). mRNA increased significantly postexercise for each cytokine measured in blood leukocyte and muscle samples. Leukocyte IL-8 and IL-10 mRNA were significantly reduced in Q vs. P (interaction effects, P = 0.019 and 0.012, respectively) with no other leukocyte or muscle mRNA group differences. Muscle NF-kappaB did not increase postexercise and did not differ between Q and P. Muscle COX-2 mRNA increased significantly postexercise but did not differ between Q and P. In summary, 1 g/day quercetin supplementation by trained cyclists over a 24-day period diminished postexercise expression of leukocyte IL-8 and IL-10 mRNA, indicating that elevated plasma quercetin levels exerted some effects within the blood compartment. Quercetin did not, however, influence any of the muscle measures, including NF-kappaB content, cytokine mRNA, or COX-2 mRNA expression across a 3-day intensified exercise period.

Abstract: 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.

Abstract: Brain cytokines, induced by various inflammatory challenges, have been linked to sickness behaviors, including fatigue. However, the relationship between brain cytokines and fatigue after exercise is not well understood. Delayed recovery of running performance after muscle-damaging downhill running is associated with increased brain IL-1beta concentration compared with uphill running. However, there has been no systematic evaluation of the direct effect of brain IL-1beta on running performance after exercise-induced muscle damage. This study examined the specific role of brain IL-1beta on running performance (either treadmill or wheel running) after uphill and downhill running by manipulating brain IL-1beta activity via intracerebroventricular injection of either IL-1 receptor antagonist (ra; downhill runners) or IL-1beta (uphill runners). Male C57BL/6 mice were assigned to the following groups: uphill-saline, uphill-IL-1beta, downhill-saline, or downhill-IL-1ra. Mice initially ran on a motor-driven treadmill at 22 m/min and -14% or +14% grade for 150 min. After the run, at 8 h (wheel cage) or 22 h (treadmill), uphill mice received intracerebroventricular injections of IL-1beta (900 pg in 2 microl saline) or saline (2 microl), whereas downhill runners received IL-1ra (1.8 microg in 2 microl saline) or saline (2 microl). Later (2 h), running performance was measured (wheel running activity and treadmill run to fatigue). Injection of IL-1beta significantly decreased wheel running activity in uphill runners (P<0.01), whereas IL-1ra improved wheel running in downhill runners (P<0.05). Similarly, IL-1beta decreased and Il-1ra increased run time to fatigue in the uphill and downhill runners, respectively (P<0.01). These results support the hypothesis that increased brain IL-1beta plays an important role in fatigue after muscle-damaging exercise.

Abstract: The influence of carbohydrate compared with placebo ingestion on changes in immune cell counts and functions following 2 h intensive cycling was studied in 12 trained cyclists who functioned as their own controls. The subjects performed two tests 2 weeks apart where they cycled for 2 h at approximately 64% Watts(max) while receiving 4 mL x kg(-1) x 15 min(-1) carbohydrate (6%) (Cho) or placebo (Pla) beverages. Blood samples were collected 30 min preexercise, and immediately and 1 h postexercise. The samples were assayed for plasma cortisol and epinephrine, blood leukocyte subset counts, PHA-induced lymphocyte proliferation, and natural killer cell activity (NKCA). Compared with Pla ingestion, Cho attenuated exercise-induced changes in plasma cortisol, blood neutrophil, and monocyte counts, but not in total blood lymphocyte, T cell, and NK cell counts, PHA-induced lymphocyte proliferation, and NKCA. Thus despite a strong attenuating influence of carbohydrate ingestion on exercise-induced changes in plasma cortisol and blood neutrophil and monocyte counts, other immune measures related to lymphocyte subset counts, and function were unaffected.

Abstract: The primary purpose of this project was to study exercise-induced leukocyte cytokine mRNA expression. Changes in plasma cytokine levels and blood leukocyte mRNA expression for interleukin-6 (IL-6), IL-8, IL- 10, and IL-1 receptor antagonist (IL-1Ra) were measured in 12 athletes following 2 h of intensive cycling ( approximately 64% Watts(max)) while ingesting a carbohydrate or placebo beverage (randomized and double blinded). Blood samples were collected 30 min preexercise and immediately and 1 h postexercise. Carbohydate compared with placebo ingestion attenuated exercise-induced changes in plasma cortisol (8.8% vs. 62%, respectively), epinephrine (-9.2% vs. 138%), IL-6 (10-fold vs. 40-fold), IL-10 (8.9-fold vs. 26-fold, and IL-1Ra (2.1-fold vs. 5.6-fold). Significant time effects were measured for blood leukocyte IL-8 (2.4-fold increase 1 h postexercise), IL-10 (2.7-fold increase), IL-1Ra (2.2-fold increase), and IL-6 (0.8-fold decrease) mRNA content, with no significant differences between Cho and Pla test conditions. In summary, gene expression for IL-8, IL-10, and IL-1Ra, but not IL-6, is increased in blood leukocytes taken from athletes following 2 h of intensive cycling and is not influenced by carbohydrate compared with placebo ingestion. mRNA expression was high enough to indicate a substantial contribution of blood leukocytes to plasma levels of IL-8, IL-10, and IL-1Ra during prolonged exercise.

Abstract: PURPOSE: This study was designed to examine the effect of carbohydrate (CHO) feedings on physical and central nervous system (CNS) function during intermittent high-intensity exercise with physical demands similar to those of team sports such as basketball. METHODS: Twenty active men (N = 10) and women (N = 10), with experience competing in team sports, performed three practice sessions before two experimental trials during which they were fed either a 6% CHO solution or a flavored placebo (PBO). Experimental trials consisted of four 15-min quarters of shuttle running with variable intensities ranging from walking (30% VO(2max)), to running (120% VO(2max)), to maximal sprinting, and 40 jumps at a target hanging at 80% of their maximum vertical jump height. Subjects received 5 mL.kg(-1) of fluid before exercise and 3 mL.kg(-1) after exercise, in addition to 3 mL.kg(-1) over a 5-min span after the first and third quarters, and 8 mL.kg(-1) during a 20-min halftime. During each break, the subjects performed a battery of tests measuring peripheral and CNS function, including 20-m sprints, a 60-s maximal jumping test, internal and external mood evaluation, cognitive function, force sensation, tests of motor skills, and target-jumping accuracy. RESULTS: Compared with PBO, CHO feedings during exercise resulted in faster 20-m sprint times and higher average jump height in the fourth quarter (P < 0.05). CHO feedings also reduced force sensation, enhanced motor skills, and improved mood late in exercise versus PBO (P < 0.05). CONCLUSION: These results suggest that CHO feedings during intermittent high-intensity exercise similar to that of team sports benefited both peripheral and CNS function late in exercise compared with a flavored placebo.

Abstract: Moderate-intensity treadmill running can alter male Apc(Min/+) mouse polyp formation. This purpose of this study was to examine whether exercise mode differentially affects Apc(Min/+) mouse intestinal polyp development in male and female mice. Male and female Apc(Min/+) mice were randomly assigned to control, treadmill (18 m/min; 60 min/day; 6 days/wk), or voluntary wheel running (24-h access) groups. Nine weeks of training decreased total intestinal polyps by 29% in male treadmill runners (66 +/- 9; P = 0.038) compared with male controls (93 +/- 7). The number of large polyps (>/=1-mm diameter) were also reduced by 38% in male treadmill runners (49 +/- 6; P = 0.005) compared with male controls (79 +/- 6). Treadmill running in female Apc(Min/+) mice and wheel running in both genders did not affect polyp number or size. Spleen weight decreased in male treadmill runners (91 +/- 9 mg; P = 0.011) and wheel runners (75 +/- 6 mg; P = 0.004) compared with controls (141 +/- 13 mg). Plasma IL-6 was reduced by 96% in male treadmill runners (1.2 +/- 0.6 pg/ml) and 78% in male wheel runners (6.6 +/- 3.3 pg/ml) compared with control mice (27.9 +/- 2.8 pg/ml; P < 0.05). Female mice responded similarly with an 86% decrease in plasma IL-6 with treadmill running (3.2 +/- 1.2 pg/ml) and 90% decrease with wheel running (2.9 +/- 2.0 pg/ml) compared with control mice (21.1 +/- 5.3 pg/ml; P < 0.05). The crypt depth-to-villus height ratio in the intestine, an indirect marker of intestinal inflammation, decreased by 21 (P = 0.024) and 24% (P = 0.029), respectively, in male and female treadmill runners but not wheel runners. Physical activity-induced attenuation of intestinal polyp number and size is dependent on exercise mode and differs between genders. The modulation of systemic and intestinal inflammation may also depend on exercise mode.

Abstract: Recovery following muscle-damaging downhill running is associated with increased muscle inflammatory cytokines. Various inflammatory challenges can also increase cytokines in the brain, which have been linked to sickness behaviors, including fatigue, but little is known about the brain cytokine response to stressful exercise. We used a downhill running model to determine the relationship between brain IL-1beta and recovery of running performance. Male C57BL/6 mice were assigned to: downhill (DH), uphill (UH), or non-running control (Con) groups and run on a treadmill at 22 m/min and -14% or 14% grade, for 150 min. Following the run, a subset of DH and UH was placed into activity wheel cages where voluntary running activity was measured for 7 days. A second subset was run to fatigue on a motorized treadmill at 36 m/min, 8% grade at 24, 48, and 96 h post-up/downhill run. A third subset of DH, UH, and Con mice had brains dissected and assayed for IL-1beta at 24 and 48 h. DH resulted in delayed recovery of both voluntary wheel-running and treadmill running to fatigue as compared to UH (p < .05). DH was also associated with increased IL-1beta concentrations in cortex (at 24 and 48 h) and cerebellum (24 h) as compared to UH and Con. UH was not different than Con in any brain region. Eccentric-biased downhill running results in an increase in plasma CK and delayed recovery in running performance, as compared to the more metabolically demanding uphill running, and this was associated with increased concentrations of IL-1beta in regions of the brain responsible for movement, coordination, motivation, perception of effort, and pain.

Abstract: PURPOSE: To study the effect of carbohydrate compared to placebo ingestion on plasma cytokines and muscle cytokine mRNA following 2.5 h of intensive cycling in 15 trained cyclists. METHODS: Fifteen trained cyclists cycled for 2.5 h at 60% Wmax on two occasions while receiving 4 mL.kg.15 min carbohydrate (6%) (CHO) or placebo (PLA) beverages in a randomized, counterbalanced design. Blood and vastus lateralis muscle biopsy samples were collected before and after exercise and 12 h postexercise and compared to samples taken from five cyclists who rested in the lab during the exercise sessions. Blood cell counts were determined, and plasma was analyzed for interleukin (IL)-6, IL-10, IL-1 receptor antagonist (ra), IL-8, cortisol, epinephrine, glucose, and insulin. Muscle was analyzed for glycogen content and relative gene expression of four cytokines, IL-6, IL-8, tumor necrosis factor (TNF) alpha, and IL-1beta, using real-time quantitative reverse transcriptase polymerase chain reaction. RESULTS: Plasma glucose and insulin were higher, and epinephrine, cortisol, IL-6, IL-10, and IL-1ra, but not IL-8, were significantly lower postexercise in CHO versus PLA. Muscle glycogen content decreased 68% immediately postexercise and the pattern of change did not differ between CHO and PLA. Muscle IL-6, IL-8, TNF-alpha, but not IL-1beta mRNA increased immediately postexercise compared to controls, with no differences between CHO and PLA. CONCLUSION: CHO compared to PLA beverage ingestion attenuated the increase in plasma cortisol, epinephrine, IL-6, IL-10, and IL-1ra, but not muscle IL-6, IL-8, and TNF-alpha mRNA in athletes cycling 2.5 h at 60% Wmax.

Abstract: Both moderate exercise and the soluble fiber beta-glucan can have beneficial effects on the initiation and growth of tumors, but the data are limited, and there is no information on their combined effects. This study tested the independent and combined effects of short-term moderate-exercise training and the soluble oat fiber beta-glucan (ObetaG) on the metatastic spread of injected tumor cells and macrophage antitumor cytotoxicity. Male C57BL/6 mice were assigned to one of four groups: exercise (Ex)-H2O, Ex-ObetaG, control (Con)-H2O, or Con-ObetaG. ObetaG was fed in the drinking water for 10 days before tumor administration and death. Exercise consisted of treadmill running (1 h/day) for 6 days. After rest or exercise on the last day of training, syngeneic B16 melanoma cells (2 x 10(5)) were administered via intravenous injection (n = 8-11 per group). Lungs were removed 14 days later, and tumor foci were counted. Additional mice (n = 8 per group) were killed, and peritoneal macrophages were assayed for cytotoxicity against the same mouse tumor cell line at various effector-to-target ratios. Both moderate exercise and ObetaG decreased lung tumor foci and increased macrophage cytotoxicity. However, there were no differences in lung tumor foci and macrophage cytotoxicity between Ex-ObetaG and either Ex-H2O or Con-ObetaG. These data suggest that, although not additive in their effects, both short-term moderate-exercise training and consumption of the soluble ObetaG can decrease the metatastic spread of injected B16 melanoma cells, and these effects may be mediated in part by an increase in macrophage cytotoxicity to B16 melanoma.

Abstract: Both moderate exercise and the soluble oat fiber beta-glucan can increase immune function and decrease risk of infection, but no information exists on their possible combined effects. This study tested the effects of moderate exercise and oat beta-glucan on respiratory infection, macrophage antiviral resistance, and natural killer (NK) cell cytotoxicity. Mice were assigned to four groups: exercise and water, exercise and oat beta-glucan, control water, or control oat beta-glucan. Oat beta-glucan was fed in the drinking water for 10 days before intranasal inoculation of herpes simplex virus type 1 (HSV-1) or euthanasia. Exercise consisted of treadmill running (1 h/day) for 6 days. Macrophage resistance to HSV-1 was increased with both exercise and oat beta-glucan, whereas NK cell cytotoxicity was only increased with exercise. Exercise was also associated with a 45 and 38% decrease in morbidity and mortality, respectively. Mortality was also decreased with oat beta-glucan, but this effect did not reach statistical significance. No additive effects of exercise and oat beta-glucan were found. These data confirm a positive effect of both moderate exercise and oat beta-glucan on immune function, but only moderate exercise was associated with a significant reduction in the risk of upper respiratory tract infection in this model.

Abstract: The purpose of this research was to provide more definitive support for the hypothesis that prolonged muscle activation at high intensities increases voluntary activation deficits. Interpolated twitch responses were evoked during maximal and sub-maximal voluntary contractions of the soleus muscle in 10 college-aged students. Maximal voluntary contractions (MVC), maximal muscle twitches, and interpolated twitch responses were measured before, during, and after fatiguing isometric exercise, five bouts of 20 intermittent MVCs. The relationship between voluntary activation and force was studied by evoking interpolated twitches during sub-maximal voluntary contractions on Day 1 and pre-post fatigue on Day 2. Intraclass reliability coefficients for the MVC, maximal muscle twitch, and interpolated twitch responses were adequate across trials and days (R > or = .80). MVC force and maximal twitch force decreased after the fatiguing exercise bouts by 28% and 32%, respectively (p < .05). Voluntary activation of the fatigue-resistant soleus muscle decreased by 10% after the first five min of maximal exercise with a subsequent decrease of 9% occurring after 25 min of maximal exercise (p < .05). At the end of the experimental session, approximately 30 min after the end of the fatiguing exercise, decreases in 100% MVC force, maximal muscle twitch force, and voluntary activation were still evident: 22%, 23%, and 11%, respectively (p < .05). Post-fatigue, there were also changes in neural strategies for voluntary activation of the soleus muscle at the higher sub-maximal efforts, > or = 70% MVC target levels (p < .05). These data demonstrate the cumulative effects of prolonged exercise on voluntary activation.

Abstract: Thirty strength-trained subjects were randomized to carbohydrate (CHO) or placebo (Pla) groups and lifted weights for 2 h (10 exercises, 4 sets each, 10 repetitions, with 2- to 3-min rest intervals). Subjects received 10 ml x kg(-1) x h(-1) CHO (6%) or Pla beverages during the weight training bout. Blood, saliva, and vastus lateralis muscle biopsy samples were collected before and after exercise. Blood cell counts were determined, and plasma was analyzed for IL-6, IL-10, IL-1 receptor antagonist (IL-1ra), IL-8, and cortisol. Muscle was analyzed for glycogen content and relative gene expression of 13 cytokines (IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-gamma, TNF-alpha) by use of real-time quantitative RT-PCR. Significant but modest increases were measured for plasma IL-6, IL-10, IL-1ra, and IL-8, but the pattern of increase did not differ between CHO and Pla groups. The rate of decrease in muscle glycogen content did not differ between CHO and Pla (P = 0.463). Muscle cytokine mRNA was detected preexercise for IL-1beta, IL-6, IL-15, IL-8, and TNF-alpha, and of these, IL-1beta, IL-6, IL-8, and TNF-alpha were significantly increased after the 2-h weight training bout. The increase in mRNA (fold difference from preexercise) did not differ between CHO and Pla groups. In summary, CHO vs. Pla ingestion did not alter modest increases measured for plasma IL-6, IL-10, IL-1ra, and IL-8, and muscle gene expression for IL-1beta, IL-6, IL-8, and TNF-alpha in strength-trained subjects lifting weights intensively for 2 h.

Abstract: 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.

Abstract: Fatiguing exercise can increase susceptibility to respiratory infection after intranasal inoculation with herpes simplex virus-1 (HSV-1) in male mice. Although gender differences in susceptibility to certain pathogens do exist, it is unknown whether female mice will respond differently than males in response to strenuous exercise and HSV-1 infection. PURPOSE: To test the effects of gender on susceptibility to HSV-1 respiratory infection after repeated exhaustive exercise. METHODS: Male (N = 86) and female (N = 89) CD-1 mice (approximately 60 d old) were randomly assigned to exercise (Ex) or control (C) groups. Exercise consisted of 3 d of treadmill running at 36 m x min(-1) at 8% grade until volitional fatigue (135 +/- 5min). Fifteen minutes after the last bout of exercise, Ex and C mice were inoculated intranasally with a standard dose (LD30) of HSV-1. Mice were monitored for 21 d for morbidity (time to sickness and symptom severity) and mortality. RESULTS: Run time to fatigue was significantly longer in females than males (P = 0.027). Significant gender differences in susceptibility to infection were found after exercise stress. In males, exercise stress resulted in increased morbidity (66%, P < 0.05) and mortality (30%, P < 0.05) whereas in females, exercise stress only resulted in increased morbidity (66%, P < 0.05). CONCLUSION: Results suggest that although males and females have similar morbidity rates after infection and exercise stress, females recover to a greater extent and are ultimately better protected from death.

Abstract: Moderate exercise training is associated with a decreased risk for upper respiratory tract infection in human and animal studies, but the mechanisms have not been elucidated. Lung macrophages play an important role in resistance to respiratory infection, and moderate exercise can enhance macrophage antiviral resistance, but no studies have directly tested the role of lung macrophages in this response. This study tested the effect of lung macrophage depletion on susceptibility to infection following short-term moderate exercise training. Mice were assigned to one of four groups: exercise (Ex) and resting controls (Con) with and without clodronate encapsulated liposomes (CL(2)MDP-lip). Ex mice ran for 1 h on a treadmill for 6 days at 36 m/min, 8% grade. Fifteen minutes following exercise or rest on the last day of training, mice were intranasally inoculated with a standardized dose of herpes simplex virus type 1. Clodronate (Ex-CL(2)MDP-lip and Con-CL(2)MDP-lip) or PBS liposomes (Ex-PBS-lip and Con-PBS-lip) (100 microl) were intranasally administered following exercise or rest on the 4th day of training and again on the 4th day postinfection. Morbidity, mortality, and symptom severity were monitored for 21 days. Exercise decreased morbidity by 36%, mortality by 61%, and symptom severity score on days 5-7 (P < 0.05). Depletion of lung macrophages negated the beneficial effects of moderate exercise. This was indicated by no differences between Ex-CL(2)MDP-lip and Con-PBS-lip in morbidity (89 vs. 95%), mortality (79 vs. 95%), or symptom severity. Results indicate that lung macrophages play an important role in mediating the beneficial effects of moderate exercise on susceptibility to respiratory infection.

Abstract: The role of creatine supplementation in altering the physiological parameters regulating cardiac muscle's functional capacity through the initiation of cardiac hypertrophy and altered contractile protein expression has not been determined. The purpose of this study was to determine the effect of creatine supplementation, with and without exercise stress, on physiological parameters regulating functional capacity through alterations in rat cardiac mass and contractile-protein expression. Thirty male Sprague-Dawley rats were subjected to 30 min of exercise stress 5 days/week for 3 weeks with 2% of total body mass attached to the tail. Animals were randomly assigned to one of four treatment groups: group 1 (Con) received (1 ml/day) sucrose water by intubation tube (n=8); group 2 (Cr) received (1 ml/day) sucrose/creatine solution (n=6); group 3 (EX) received 1 ml/day sucrose water and the exercise stimulus (n=8), and group 4 (Cr/EX) received (1 ml/day) sucrose/creatine solution and the exercise stimulus (n=8). At the conclusion of the 21-day exercise-training period, the heart was collected and weighed for determination of wet weight, total protein, total RNA, and myosin heavy chain protein expression. RNA concentration decreased significantly (13%) in the EX group, but not in the CR/EX group, indicating an interactive effect of creatine and exercise. Total RNA significantly decreased (15%) in the EX group. Protein concentration significantly increased (9%) in the exercising treatments, while total protein did not change. Cardiac myosin heavy chain expression significantly shifted towards a predominant expression of the beta-isoform in the Cr/EX group [54.53% (3.42) beta]. These results indicate an interaction of creatine supplementation and swimming exercise stress that potentially alters cardiac protein synthesis and demonstrates a possible mechanism through which the combination of creatine supplementation and swimming stress stimuli act to alter the physiological parameters regulating cardiac functional capacity.

Abstract: Caffeine ingestion can delay fatigue during exercise, but the mechanisms remain elusive. This study was designed to test the hypothesis that blockade of central nervous system (CNS) adenosine receptors may explain the beneficial effect of caffeine on fatigue. Initial experiments were done to confirm an effect of CNS caffeine and/or the adenosine A(1)/A(2) receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) on spontaneous locomotor activity. Thirty minutes before measurement of spontaneous activity or treadmill running, male rats received caffeine, NECA, caffeine plus NECA, or vehicle during four sessions separated by approximately 1 wk. CNS caffeine and NECA (intracerebroventricular) were associated with increased and decreased spontaneous activity, respectively, but caffeine plus NECA did not block the reduction induced by NECA. CNS caffeine also increased run time to fatigue by 60% and NECA reduced it by 68% vs. vehicle. However, unlike the effects on spontaneous activity, pretreatment with caffeine was effective in blocking the decrease in run time by NECA. No differences were found after peripheral (intraperitoneal) drug administration. Results suggest that caffeine can delay fatigue through CNS mechanisms, at least in part by blocking adenosine receptors.

Abstract: PURPOSE: To observe the effects of exercise training on plasminogen activator inhibitor, type-1 (PAI-1), tissue plasminogen activator (tPA), and associated metabolic variables in sedentary men and women. METHODS: A randomized, controlled experimental design was used to examine the influence of 10 d of moderate-intensity exercise training on measures of fibrinolysis. Sixteen men and 16 women between the ages of 50 and 70 yr were randomly assigned to exercise (EX) and control groups (CON) that were balanced for gender and hormone replacement therapy. Blood samples were collected on days 1, 2, 11, and 12 for measurement of plasma PAI-1, tPA, insulin, glucose, and triglyceride. Subjects in EX performed 50 min of treadmill walking at an intensity corresponding to 65% of heart rate reserve each day for 10 consecutive days. RESULTS: There were no significant changes in PAI-1, tPA, or associated metabolic variables between EX and CON during the intervention period. Within EX subjects, those with higher body fatness had a significant decrease in insulin and triglyceride compared with those with lower body fatness. However, no changes in fibrinolytic measures were observed within these subgroups. CONCLUSIONS: Short-term exercise training does not change PAI-1 levels in normal, asymptomatic men and women. In addition, modest decreases in insulin and triglyceride in individuals with elevated body fatness do not result in changes in PAI-1 after short-term training. It appears likely that decreases in PAI-1 with exercise training require decreases in adiposity and/or marked changes in metabolic variables.

Abstract: PURPOSE: This study was designed to examine the effects of carbohydrate-electrolyte ingestion on physical and mental function associated with the performance of intermittent high-intensity (IHI) exercise similar to many common competitive sporting events. METHODS: Physically active men (N = 5) and women (N = 5), experienced in competitive soccer or basketball, completed three practice sessions and two experimental trials of an IHI shuttle running protocol designed to closely stimulate the demands of an actual competitive sporting event such as basketball. The experimental trials consisted of four 15-min quarters (QTR) of intermittent shuttle running at various percentages of .VO(2max) (walking, jogging, running, sprinting and jumping), separated by a 20-min halftime rest period (HALF) and followed by a shuttle run to fatigue. Various tests of physical and mental function (shuttle run to fatigue, 20-m maximal sprint, 10-repetition maximal vertical jumping, whole body motor skill test (MS-Test), profile of mood states (POMS), and Stroop Color-Word Test) were performed throughout the experimental trial. Carbohydrate-electrolyte (CHO) or placebo (P) drinks were consumed before exercise (5 mL.kg(-1); 6% solution) and at halftime (5 mL.kg(-1); 18% solution). Smaller volumes (3 mL.kg(-1); 6% solution) were given after QTR-1, HALF, QTR-3, and QTR-4. RESULTS: CHO ingestion resulted in a 37% longer run time to fatigue and faster 20-m sprint time during QTR-4 (P < 0.05). MS-Test performance was also improved during the latter stages of exercise along with self-reported perceptions of fatigue (subscale of POMS) (P < 0.05) in CHO versus P. CONCLUSION: These results suggest a beneficial role of carbohydrate-electrolyte ingestion on physical and mental function during intermittent exercise similar to that of many competitive team sports.

Abstract: The purpose of this study was to determine if differences exist between the effects of acute treadmill running and restraint stress on corticotropin-releasing hormone (CRH) release within the amygdala of rats. Extracellular CRH immunoreactivity (CRH-IR) was measured in microdialysate collected from the central nucleus of the amygdala (CeA) during exposure to an inactivated treadmill (TC), during 1 h treadmill running to exhaustion (RUN), and 1 h restraint (RES). Extracellular CRH-IR increased from control levels during the first 20-min period for TC, RUN, and RES, with the largest increase during RES. During the second 20-min period, only RES maintained levels higher than control values. CRH release was higher than control during the third 20-min period of RES and RUN. A second experiment consisted of four groups of either cage controls (CC), TC, RUN, or RES. Immediately following the 60-min treatment, brains were removed and trunk blood collected for analysis of tissue CRH-IR and plasma corticosterone. While amygdala tissue CRH-IR was not different in the CC, TC and RUN rats, these groups had significantly lower levels than the RES animals. Hypothalamic tissue CRH-IR was not different between the CC and TC rats, but the levels were significantly higher in the RES and RUN rats than in the two control groups. Plasma corticosterone levels were elevated only in RES and RUN rats. Results from tissue analysis indicate that increased tissue CRH-IR in the amygdala and hypothalamus can be elicited by RES, while only the hypothalamus shows an increase following RUN. Further, extracellular CRH release in the CeA is increased throughout the period of RES, when rats are placed on the treadmill, and when the animals are approaching physical exhaustion. No increase is observed during the running period between placement on the treadmill and intense exertion. Overall, the data suggest that amygdala CRH release is regulated differently during treadmill running and restraint.

Abstract: Exercise can increase plasma inflammatory cytokine concentrations in humans, but tissue responses are not well studied. We examined plasma concentrations and tissue expression of TNFalpha, IL-1beta, and IL-6 following treadmill running in mice. C57B1/6 mice were randomly assigned to: non-exercise control (CON), sacrifice at 0 or 1.5 h after 60 min running (MOD0, MOD 1.5), sacrifice at 0, 1.5, or 3 h after fatiguing running (approximately 3 h) (EX0, EX1.5, EX3), or lipopolysaccharide (25 microg) with no exercise (LPS). Lung, liver, muscle, and brain mRNA expression was analyzed (n = 4-6/group) using reverse transcriptase-rapid polymerase chain reaction (RT-RPCR). Plasma cytokine concentrations were determined (n =4-10/group) by ELISA. Plasma IL-6 was higher in EX1.5, and lung TNFalpha mRNA was higher in EX1.5 and EX3 compared to CON (P < 0.05). No significant increases in plasma cytokine concentrations or tissue cytokine expression were found in other EX groups. LPS significantly increased these cytokine measures in tissues and plasma, with the exception of plasma IL-1beta which was undetectable. The source of the plasma IL-6 following exercise does not appear to be lung, liver, muscle, or brain tissue, and remains to be determined. These data also suggest that tissue level cytokine expression may not necessarily lead to increased plasma cytokine concentrations.

Abstract: The purpose of this research was to describe further the effects of exercise-induced muscle damage on reflex sensitivity. The subjects were eight physically active, but untrained males, between the ages of 18 and 29 years. The effects of eccentric and concentric exercise on patellar tendon reflex responses were determined. The 8 week experiment consisted of two, 5 day, test protocols with a 6 week wash-out period between test protocols. Each 5 day test protocol consisted of the following six test sessions: (1) day 1--baseline, (2) day 2 baseline, (3) day 2--immediate post-exercise, and (4-6) days 3-5: 24, 48, and 72 h post-exercise. On day 2, the subjects made either 100 fatiguing concentric or eccentric isotonic contractions using the right leg at 75% of the corresponding repetition maximum values. During each test session, the electromyogram (EMG) and force-time characteristics of basic and conditioned patellar tendon reflex responses were measured. The reflex amplitudes of basic and conditioned patellar tendon reflex responses were decreased following fatiguing concentric exercise. There were no immediate effects of fatiguing eccentric exercise on the basic and conditioned patellar tendon reflex responses, but the EMG amplitudes of these reflex responses were reduced on the days following eccentric exercise. The amount of conditioned patellar tendon reflex facilitation was decreased following the concentric exercise protocol and at 48 h post-eccentric exercise. Our conditioned reflex data suggest that post-exercise changes to the physiological mechanisms that modulate the recruitment gain of the alpha-motoneuron pool may depend upon the type of fatiguing exercise.

Abstract: Saliva immunoglobulins (sIgA, sIgG, and sIgM) and upper respiratory tract infection (URTI) rates were evaluated in 20 elite female rowers and 19 nonathletes. Also, the influence of carbohydrate versus placebo beverage consumption on saliva immunoglobulin responses to rowing training sessions was measured in 15 rowers and in 5 non-exercising rowers. Saliva samples were collected 1 day before, and 5-10 min and 1.5 h after rowing or rest. Pre-exercise sIgA (but not sIgG or sIgM) concentration was 77% higher in the rowers compared to nonathletes (P < 0.001). Health records kept over 2 months revealed mean 5.2 (SEM 1.2) and 3.3 (SEM 1.1) days with URTI symptoms for the rowers and controls, respectively. For all 39 subjects, and for the 20 rowers separately, no significant correlation was found between URTI symptoms or insulin, cortisol, and growth hormone concentrations and pre-exercise or exercise-related changes in saliva immunoglobulin concentrations or secretion rates. The patterns of change in saliva immunoglobulin concentration and secretion rate did not differ between the carbohydrate and placebo rowing trials, or between exercised and rested athletes. These data indicated an increased sIgA concentration in the female elite rowers compared to the nonathletes, no association between saliva immunoglobulins and URTI, and no effect of a normal 2-hour training session or carbohydrate ingestion on saliva immunoglobulin concentrations or secretion rates.

Abstract: Purpose: This study was designed to test the hypothesis that addition of chromium (Cr) to a carbohydrate-electrolyte drink would enhance the reported benefits of carbohydrate on exercise capacity during intermittent high-intensity shuttle running. Methods: Eight physically active men performed 3 exercise trials while ingesting 6% carbohydrate-electrolyte (CHO), CHO plus chromium picolinate (400 mg) (CHO + Cr+3), or placebo (P) using a double-blind, counterbalanced design. Each trial consisted of 5 3 15 min bouts of shuttle running (walk, sprint, and run at 95 and 55% of estimated VáO2max, separated by 3-min rest). This was followed by a fatigue test (running alternating 20-m lengths at 55 and 95% of estimated VáO2 until fatigue). Results: During the standardized shuttle running, blood glucose was higher with both CHO and CHO + Cr+3 than P. Plasma free fatty acid was higher in P than both CHO and CHO + Cr+3 at 75 min of exercise and at fatigue. In the fatigue test, subjects ran longer with both CHO and CHO + Cr+3 than P. Conclusions: The data confirm an ergogenic benefit of ingesting CHO during exercise designed to imitate sports like basketball, soccer, and hockey, but do not support the hypothesis that the addition of Cr would enhance this effect.

Abstract: PURPOSE: This study examined the influence of carbohydrate (C) versus placebo (P) beverage ingestion on the phagocytic and cytokine responses to normal rowing training by 15 elite female rowers. METHODS: Athletes received C or P before, during and after, two, 2-h bouts of rowing performed on consecutive days. Blood was collected before and 5-10 min and 1.5 h after rowing. Metabolic measures indicated that training was performed at moderate intensities, with some high-intensity intervals interspersed throughout the sessions. RESULTS: Concentrations of blood neutrophils and monocytes, phagocytic activity, and plasma IL-1ra were significantly lower postexercise after C versus P ingestion. No differences were observed for oxidative burst activity, IL-6, IL-8, or TNFalpha. Glucose was significantly higher after 2 h of rowing with C ingestion; however, cortisol, growth hormone, epinephrine, norepinephrine, and CRP were not affected by carbohydrate. CONCLUSIONS: These data indicate that carbohydrate compared with placebo ingestion attenuated the moderate rise in blood neutrophils, monocytes, phagocytosis, and plasma IL-1ra concentrations that followed 2-h bouts of training in elite female rowers. No changes in blood hormone concentrations were found.

Abstract: Fatigue from voluntary muscular effort is a complex phenomenon involving the central nervous system (CNS) and muscle. An understanding of the mechanisms within muscle that cause fatigue has led to the development of nutritional strategies to enhance performance. Until recently, little was known about CNS mechanisms of fatigue, even though the inability or unwillingness to generate and maintain central activation of muscle is the most likely explanation of fatigue for most people during normal daily activities. A possible role of nutrition in central fatigue is receiving more attention with the development of theories that provide a clue to its biological mechanisms. The focus is on the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] because of its role in depression, sensory perception, sleepiness, and mood. Nutritional strategies have been designed to alter the metabolism of brain 5-HT by affecting the availability of its amino acid precursor. Increases in brain 5-HT concentration and overall activity have been associated with increased physical and perhaps mental fatigue during endurance exercise. Carbohydrate (CHO) or branched-chain amino acid (BCAA) feedings may attenuate increases in 5-HT and improve performance. However, it is difficult to distinguish between the effects of CHO on the brain and those on the muscles themselves, and most studies involving BCAA show no performance benefits. It appears that important relations exist between brain 5-HT and central fatigue. Good theoretical rationale and data exist to support a beneficial role of CHO and BCAA on brain 5-HT and central fatigue, but the strength of evidence is presently weak.

Abstract: Epidemiological evidence suggests that physical activity may be protective against the development of colon cancer. Potential mechanisms remain largely unexplored due to the paucity of appropriate experimental models. PURPOSE: The purpose of this study was to examine the effect of exercise training on polyp development in an induced mutant mouse strain predisposed to multiple intestinal neoplasia (Min mouse). METHODS: Three-week-old male and female heterozygotes were randomly assigned to control (CON; 10 males, 6 females) or exercise (EX; 11 males, 11 females) groups. In the first week, EX mice were acclimated to treadmill running at 10-18 m x min(-1) for 15-60 min x d(-1). From 4-10 wk of age, mice ran at 18-21 m x min(-1) for 60 min. CON mice sat in Plexiglas lanes suspended above the treadmill for the same time periods. At 10 wk of age, the mice were sacrificed and the intestines removed, opened, and counted for polyps. RESULTS: Skeletal muscle oxidative capacity increased with training as shown by a 64% increase in citrate synthase activity in the gastrocnemius/soleus muscle of EX compared with CON (P = 0.009). There were no significant effects of exercise in the males and females combined on small intestine, colon, or total intestinal polyps (P > 0.05). When analyzed separately, however, there were fewer colon and total polyps in the EX than in the CON males, although the difference was not statistically significant (P = 0.06). CONCLUSIONS: These results suggest that seven weeks of exercise training do not affect the development of intestinal polyps in the Min mouse. Further studies are required to determine if a true sex difference exists or if variations on the current training protocol may affect tumor outcomes.

Abstract: This randomized, double-blind, placebo-controlled study was designed to determine the influence of exercise mode, and 6% carbohydrate (C) versus placebo (P) beverage ingestion, on ratings of perceived exertion (RPE) and hormonal regulation to 2.5 h of high-intensity running and cycling (approximately 75% maximum oxygen uptake) by ten triathletes who acted as their own controls. Statistical significance was set at P < or = 0.05. The pattern of change in RPE over time was significantly different between C and P ingestion (P < 0.001) and between running and cycling modes (P = 0.001). The lowest RPE values were seen in the C-cycling sessions and the highest in the P-running sessions. The pattern of change in the respiratory exchange ratio and fat and carbohydrate oxidation rates were significantly different between the C and P conditions but not between the running and cycling modes. C relative to P ingestion (but not exercise mode) was associated with higher plasma levels of glucose and insulin and lower plasma cortisol and growth hormone levels. The pattern of change in plasma levels of catecholamines and lactate did not differ between the C and P conditions. These data indicate that a lower RPE was associated with a higher level of carbohydrate oxidation, higher plasma glucose and insulin levels, and lower plasma cortisol and growth hormone levels during cycle exercise following C supplementation as compared to P feeding. These findings support a physiological link between RPE and carbohydrate substrate availability as well as selected hormonal regulation during cycle exercise.

Abstract: Epidemiological evidence suggests a link between the intensity of exercise and infectious and neoplastic disease. One likely way by which exercise exerts its effect on cancer and infection is by altering the function of the immune system. Cells of the innate immune system (i.e., macrophage [Mphi], natural killer [NK] cell, and polymorphonuclear neutrophils [PMN]) are first-line defenders against cancer and infectious disease by nature of their phagocytic, cytolytic, and antimicrobial properties. The purpose of this review is to define the role of cells of the innate immune system (i.e., Mphi, PMN, and NK cells) in infection and cancer, present current information regarding the effects of acute and chronic exercise on the quantification and functional activities of these cells, and briefly to discuss potential mechanisms as to how exercise affects these cells and describe how these changes may potentially affect susceptibility to infection and cancer. The effects of exercise on the number, functions, and characteristics of cells of the innate immune system are complex and are dependent several factors, including 1) the cell function or characteristic being analyzed; 2) the intensity, duration and chronicity of exercise; 3) the timing of measurement in relation to the exercise bout; 4) the dose and type of immunomodulator used to stimulate the cell in vitro or in vivo; and 5) the site of cellular origin. Further studies are needed to determine whether the exercise-induced changes in immune function alter incidence or progression of disease. Likewise, the mechanisms as to how exercise alters innate immune function are as yet unresolved.

Abstract: The influence of exercise mode and 6% carbohydrate (C) versus placebo (P) beverage ingestion on lymphocyte proliferation, natural killer cell cytotoxicity (NKCA), Interleukin (IL)-1beta production, and hormonal responses to 2.5 hr of intense running and cycling (approximately 75% VO2max) was measured in 10 triathletes serving as their own controls. The C versus P condition (but not exercise mode) resulted in higher plasma glucose concentrations, lower plasma cortisol concentrations, reduced postexercise lymphocytosis and NKCA, and a lessened T-cell reduction during recovery, No condition or mode effects were observed for concanavalin A and phytohemagglutinin-induced lymphocyte proliferation. Significant mode (but not condition) effects were observed for lipopolysaccharide-induced IL-1beta production over time. However, when expressed per monocyte, the mode effect was abolished and a sustained suppression in IL-1beta/monocyte was observed in all sessions throughout recovery. These data indicate that carbohydrate ingestion significantly affects plasma glucose and cortisol concentrations, blood lymphocyte counts, and NKCA, whereas exercise mode has no effect on these parameters.

Abstract: Experimental support for the hypothesized benefits of BCAA supplements on endurance performance is limited. However, it is theorized that the benefits may be enhanced if 1) BCAA are taken along with a pre-event carbohydrate meal as well as during exercise, and 2) the exercise is intermittent in nature. This study tested the effects of ingesting carbohydrate beverages with and without BCAA before and during intermittent high-intensity running to fatigue. Eight subjects performed 3 exercise trials consisting of intermittent shuttle running (walking, sprinting, and running) to fatigue. Subjects drank either carbohydrate drinks given 1 h before (5 mL/kg, 18% carbohydrate) and during exercise (2 mL/kg, 6% carbohydrate) (CHO), carbohydrate drinks with BCAA (7 g) added to the portions consumed 1 h before and immediately before exercise (CHO+BCAA), or flavored water placebos (P). Subjects ran longer when fed either CHO or CHO+BCAA as compared to P, with no differences between CHO and CHO+BCAA. CHO and CHO+BCAA also had higher plasma glucose and insulin, and lower FFA (p < 0.05). These findings confirm a beneficial effect of carbohydrate feedings on fatigue during exercise designed to mimic the activity pattern that occurs in sports like soccer, basketball, and hockey. They do not, however, support the hypothesis of an added benefit of BCAA supplements.

Abstract: The influence of carbohydrate (C) versus placebo (P) beverage consumption on the immune and hormonal responses to normal rowing training sessions was measured in 15 elite female rowers residing at the U.S. Olympic Training Center. In a randomized, counterbalanced design, the athletes received C or P beverages (double-blind) before, during, and after two 2-hour bouts of rowing (one day apart). Blood samples were collected before, and 5-10 minutes and 1.5 hours after rowing. Metabolic measures indicated that training was performed at moderate intensities, with some high intensity intervals interspersed throughout the sessions (mean oxygen uptake of 2,307+/-169 m x min(-1), 57% of VO2max). Glucose and insulin were significantly lower after two hours of rowing with ingestion of P compared to C. The patterns of change in cortisol, growth hormone, epinephrine, and norepinephrine did not differ between C and P rowing trials. Blood neutrophil cell counts and the neutrophililymphocyte ratio were significantly higher following P versus C rowing sessions. The patterns of change in blood lymphocyte and lymphocyte subset counts, and lymphocyte proliferative responses did not differ between P and C trials, except for a slight difference in NK cell counts and activity. In summary, minimal changes in blood hormonal and immune measures were found following two-hour bouts of training in elite female rowers. Carbohydrate compared to placebo ingestion attenuated the moderate rise in blood neutrophil counts, but had slight or no effects on other immune parameters.

Abstract: The influence of exercise mode and 6% carbohydrate (C) vs. placebo (P) beverage ingestion on granulocyte and monocyte phagocytosis and oxidative burst activity (GMPOB) after prolonged and intensive exertion was measured in 10 triathletes. The triathletes acted as their own controls and ran or cycled for 2.5 h at approximately 75% maximal O2 uptake, ingesting C or P (4 total sessions, random order, with beverages administered in double-blind fashion). During the 2. 5-h exercise bouts, C or P (4 ml/kg) was ingested every 15 min. Five blood samples were collected (15 min before exercise, immediately after exercise, and 1.5, 3, and 6 h after exercise). The pattern of change over time for GMPOB was significantly different between C and P conditions (P </= 0.05), with postexercise values lower during the C trials. Little difference was measured between running and cycling modes. C relative to P ingestion (but not exercise mode) was associated with higher plasma levels of glucose and insulin, lower plasma levels of cortisol and growth hormone, and lower blood neutrophil and monocyte cell counts. These data indicate that C vs. P ingestion is associated with higher plasma glucose levels, an attenuated cortisol response, and lower GMPOB.

Abstract: OBJECTIVE AND METHODS: This randomized, double-blind, placebo-controlled study was designed to determine the influence of exercise mode and 6% carbohydrate (C) versus placebo (P) beverage ingestion, on blood cell counts, plasma glucose, hormone, and inflammatory cytokine responses (five total samples over 9 h) to 2.5 h of high-intensity running and cycling (approximately 75% VO2max) by 10 triathletes who acted as their own controls. Statistical significance was set at P < or = 0.05. RESULTS: C relative to P ingestion (but not exercise mode) was associated with higher plasma levels of glucose and insulin, lower plasma cortisol and growth hormone, and diminished perturbation in blood immune cell counts. The pattern of change over time for interleukin (IL)-6 was significantly different between C and P conditions (P = 0.021) and between running and cycling modes (P < 0.001), with the lowest postexercise values seen in the C-cycling sessions (10.7 +/- 1.8 pg x mL(-1)) and the highest in the P-running sessions (51.6 +/- 14.2 pg x mL(-1)). The pattern of change over time between C and P conditions (but not modes) was significantly different for IL-1 receptor antagonist (P = 0.003), with values once again lowest for the C-cycling sessions (1.5 h postexercise, 301 +/- 114 pg x mL(-1)) and highest for the P-running sessions (1171 +/- 439 pg x mL(-1)). CONCLUSION: These data indicate that carbohydrate versus placebo ingestion (4 mL x kg(-1) carbohydrate or placebo every 15 min of the 2.5-h exercise bout) is associated with higher plasma glucose levels, an attenuated cortisol response, and a diminished pro- and anti-inflammatory cytokine response.

Abstract: We hypothesized that a previously observed exercise-induced suppression of alveolar macrophage antiviral resistance results from increases in corticosterone and/or epinephrine. Mice (CD-1) were run to fatigue on a treadmill (exercise), or placed in Plexiglas lanes above the treadmill (control). The role of corticosterone was assessed by further dividing mice into groups receiving one of the following treatments; sham surgery, adrenalectomy, or adrenalectomy plus corticosterone replacement. Macrophage antiviral function was suppressed in the exercised mice compared to the control mice. However, macrophage antiviral function was not suppressed in the exercised mice that underwent adrenalectomy or adrenalectomy plus corticosterone replacement. We tested whether another adrenal factor (epinephrine) may be involved by dividing mice into exercise and control groups treated with either saline or propranolol. Macrophage antiviral function was again suppressed in the saline-treated exercised mice compared to saline-treated control mice, but no differences were found between the exercised mice receiving propranolol, control mice receiving propranolol, or saline-treated control mice. Isoproterenol, when added to alveolar macrophages in culture, also suppressed antiviral resistance. These findings suggest that decreased macrophage antiviral function following exercise may be due to increased release of adrenal catecholamines.

Abstract: Mice exercised to fatigue and exposed to herpes simplex virus type 1 (HSV-1) exhibit greater mortality than control mice. In this study, we examined lung macrophage resistance to HSV-1 after exercise in terms of both viral replication and interferon (IFN)-beta production. We utilized the reverse transcriptase-rapid polymerase chain reaction to measure the IFN-beta mRNA content in alveolar macrophages. IFN release was measured with a bioassay, and viral replication within the macrophage was assessed by plaque titration. Exercised (Ex) mice ran on a treadmill until fatigue while control (Con) mice remained in lanes above the treadmill. After exercise, alveolar macrophages were removed and incubated with HSV-1. Alveolar macrophage IFN-beta mRNA was greater in Ex than in Con mice. Culture supernatant from infected macrophages showed a higher degree of IFN release and a higher number of infectious viral particles in Ex vs. Con mice. It is likely that the increase in IFN-beta mRNA occurs in response to a higher degree of viral replication. These results suggest that macrophages from Ex mice are less resistant to infection with HSV-1.

Abstract: This study examined the effects of moderate and prolonged exercise on 1) lung tumor metastases and 2) alveolar macrophage antitumor response in vitro. C57B1/6 mice were assigned to either Ex-30 (30-min run), Ex-F (run to fatigue), Ex-F-24 h (run to fatigue 24 h before tumor injection), or Con (rested in lanes above the treadmill). Mice received intravenous injections of syngeneic B16 melanoma cells 30 min postexercise. Lungs were removed 7 or 10 days later, and tumor foci were counted. Ex-F had fewer tumors than either Ex-30 or Con, whereas Ex-F-24 h also showed a strong trend toward fewer tumors. The initial localization of tumor cells in the lungs after injection was not different among groups. For the in vitro experiment, mice were killed immediately after exercise or 8 h later. Alveolar macrophages were removed and cultured in vitro with B16 melanoma cells. The growth of the tumors cultured with macrophages from Ex-F was lower than Con after exercise and, to a lesser extent, 8 h later. In Ex-30, this effect was only found immediately after exercise. The data suggest that prolonged exercise has a protective effect on lung tumor metastases and enhances alveolar macrophage antitumor cytotoxicity.

Abstract: Extreme fatigue often accompanies infection and other diseases, but the causal mechanisms are unknown. Recent research has focused on various cytokines as potential immune system mediators of fatigue during illness. Interferon-alpha/beta (IFN-alpha/beta) has attracted the most interest in this regard. PURPOSE: The purpose of this research was to study the effect of IFN-alpha/beta on fatigue during treadmill running in mice. METHODS: Mice (male CD-1) were acclimated to treadmill running for 4 d before experimental sessions. In experiment 1 (EXP 1), mice were injected with either polyI:C (pI:C) (5 mg.kg-1 body weight) or saline (CON) 12 or 24 h before the exercise session. These sessions consisted of treadmill running to fatigue (approximately 3 h, 19-24 m.min-1, 5% grade, no shock). In experiment 2 (EXP 2), mice were injected 24 h before exercise with normal rabbit serum (CON), pI:C, or pI:C + anti-IFN-alpha/beta antibody (pI:C + Ab). RESULTS: The results of EXP 1 showed that the plasma IFN-alpha/beta titer was much higher at 24 h than at 12 h after pI:C injection (P < 0.001) and that run time to fatigue was significantly reduced only when the exercise occurred 24 h after injection (P < 0.05). In EXP 2, administration of the anti-IFN-alpha/beta antibody attenuated both the pI:C-induced increase in plasma IFN-alpha/beta (P < 0.001) and the decrease in run time to fatigue (r = -0.81, P < 0.001). CONCLUSIONS: These results suggest that immune system activation by pI:C was associated with early fatigue during prolonged treadmill exercise and that this effect may, at least partially, result from increased IFN-alpha/beta.

Abstract: Fatigue of voluntary muscular effort is a complex phenomenon. To date, relatively little attention has been placed on the role of the central nervous system (CNS) in fatigue during exercise despite the fact that the unwillingness to generate and maintain adequate CNS drive to the working muscle is the most likely explanation of fatigue for most people during normal activities. Several biological mechanisms have been proposed to explain CNS fatigue. Hypotheses have been developed for several neurotransmitters including serotonin (5-HT; 5-hydroxytryptamine), dopamine, and acetylcholine. The most prominent one involves an increase in 5-HT activity in various brain regions. Good evidence suggests that increases and decreases in brain 5-HT activity during prolonged exercise hasten and delay fatigue, respectively, and nutritional manipulations designed to attenuate brain 5-HT synthesis during prolonged exercise improve endurance performance. Other neuromodulators that may influence fatigue during exercise include cytokines and ammonia. Increases in several cytokines have been associated with reduced exercise tolerance associated with acute viral or bacterial infection. Accumulation of ammonia in the blood and brain during exercise could also negatively effect the CNS function and fatigue. Clearly fatigue during prolonged exercise is influenced by multiple CNS and peripheral factors. Further elucidation of how CNS influences affect fatigue is relevant for achieving optimal muscular performance in athletics as well as everyday life.

Abstract: Exercise effects on natural killer cell (NK) activity in men appear to be intensity dependent, but there is very little data in women. We tested the effect of high versus moderate-intensity exercise relative to non-exercising controls on NK cytolytic activity (NK activity) in women using oral contraceptives. Subjects (n = 8) participated in 3 treatments consisting of 25 min of cycle ergometer exercise at 80% (HI-INT) and 40% (MOD-INT) VO2max, and a 25 min control (CON) session in which the subject remained seated on the cycle ergometer, but did not exercise. Blood was obtained prior to exercise, immediately after, and at 90 min and 3 h after exercise. During CON, NK activity gradually increased and cortisol gradually decreased during the approximately 3.5 h experimental period. Relative to CON, HI-INT increased NK activity, %CD56+ (NK) cells, and plasma norepinephrine immediately post exercise (p < or = 0.05). There was also a trend for decreased NK activity at 90 min (p = 0.075). No differences among treatment groups were found by 3 h post exercise. In MOD-INT, there were no differences from CON in any variable at any time. These data suggest that the typical NK response to intensive exercise in men, which consists of a brief increase followed by a more prolonged suppression, also occurs in women using oral contraceptives. However, it is important to use time-matched control measurements in determining this response.

Abstract: The effects of ingesting carbohydrate drinks on fatigue during intermittent, high-intensity cycling in men and women were determined. Physically active but untrained women (n = 7) and men (n = 9) completed one practice trial and two experimental sessions separated by 1 week. Sessions consisted of repeated 1-min cycling bouts on a bicycle ergometer at 120-130% VO2max separated by 3 min rest until fatigue. Carbohydrate (CHO) or placebo (P) beverages (4 ml.kg body weight-1) were ingested immediately before exercise (18% CHO) and every 20 min during exercise (6% CHO). Plasma glucose and insulin were higher, RPE for the legs was lower, and time to fatigue was longer in CHO than P. Men's and women's responses were not different for any variable measured. These data suggest a beneficial role of CHO drinks on performance of intermittent, high-intensity exercise in men and women.

Abstract: The effects of exercise on susceptibility to respiratory infection were determined by using a murine model of intranasal challenge with herpes simplex type 1 virus (HSV-1). Two doses of treadmill exercise were assessed: moderate short-term (30 min) exercise and prolonged strenuous exercise to voluntary fatigue (2.5-3.5 h). Morbidity and mortality among exercised and control mice were compared after intranasal challenge with HSV-1. We also assessed the ability of alveolar macrophages to restrict HSV-1 viral replication (intrinsic resistance) among exercise and control groups of mice at several time points postexercise. Exercise to fatigue followed by exposure to viral infection resulted in greater morbidity and mortality than either no exercise or short-term moderate exercise. In addition, antiviral resistance of macrophages obtained from the lungs of both exercised groups was suppressed, albeit for a longer duration in the fatigued group. These data are particularly important in that they identify an exercise-induced decrease in antiviral resistance of a specific component of the immune system within the lungs, in conjunction with increased susceptibility to respiratory infection in vivo. The specific mechanism of decreased antiviral resistance of alveolar macrophages and its role in respiratory infection after exercise remains to be determined.

Abstract: The causes of fatigue during muscular exercise include factors that reside in the brain (central mechanisms) as well as the muscles themselves (peripheral mechanisms). Central fatigue is largely unexplored, but there is increasing evidence that increased brain serotonin (5-HT) can lead to central (mental) fatigue, thereby causing a deterioration in sport and exercise performance. Although there are also strong theoretical grounds for a beneficial role of nutrition in delaying central fatigue, the data are much more tenuous. Dietary supplementation with branched-chain amino acids (BCAA) in low doses produces small and probably inconsequential effects on peripheral markers of brain 5-HT synthesis (plasma free tryptophan/BCAA), whereas larger doses are likely to be unpalatable, reduce the absorption of water in the gut, and may increase potentially toxic ammonia concentrations in the plasma. Alternatively, carbohydrate supplementation results in large reductions in plasma free tryptophan/BCAA and exercise time to fatigue is significantly longer, but it is difficult to distinguish between the effects of carbohydrate feedings on central fatigue mechanisms and the well-established beneficial effects of carbohydrate supplements on the contracting muscle. These data support the exciting possibility that relationships exist among nutrition, brain neurochemistry and sport performance. However, while the evidence is intriguing and makes good intuitive sense, our knowledge in this area is rudimentary at best.

Abstract: The mechanisms of central fatigue are largely unexplored, but the central fatigue hypothesis suggests that increased brain serotonin (5-HT) can cause a deterioration in sport and exercise performance. There is now convincing evidence that exercise-induced increases in the plasma free tryptophan (f-TRP)/branched-chain amino acids (BCCA) ratio are associated with increased brain 5-HT and the onset of fatigue during prolonged exercise. Furthermore, when drugs are administered to alter brain 5-HT, they have the predicted effects on exercise performance. The influence of nutritional manipulations of f-TRP/BCCA on performance is less well established. The effects of BCCA supplementation on exercise performance are mixed, and the published studies often suffer from methodological flaws. Alternatively, dramatic reductions in f-TRP/BCCA and enhanced performance accompany carbohydrate feedings during prolonged exercise. However, it is difficult to distinguish between the effects of carbohydrate feedings on mechanisms that reside in the brain versus the muscles themselves.

Abstract: Ten young male adults (mean age 46.9 +/- 1.2 yrs) with 9.2 +/- 1.4 years of weight training experience and the ability to parallel squat at least 1.5 times their body mass were selected as subjects. The exercise session consisted of sets of 10 repetitions at 65% 1-RM of the parallel leg squat, with a cadence of one rep every 6 sec and 3 min rest between sets, to muscular failure. The average subject lifted a total of 9711 +/- 1576 kg during 98 +/- 14 reps for a total work output of 72.5 +/- 10.5 kJ before muscular failure occurred. Mean oxygen consumption during exercise was 1.58 +/- 0.06 l/min at 42.5 +/- 2.0% peak VO2. A strong leukocytosis, lymphocytosis, and lymphocytopenia, similar to what has been reported following high-intensity cardiorespiratory exercise, were measured following leg squat exercise. Con A-stimulated lymphocyte proliferation (unadjusted) rose 50% above preexercise levels (p = 0.07), but when these data were adjusted on a per T cell (CD3+) basis, no change from rest was observed. Natural killer cell cytotoxic activity (NKCA), when adjusted on a per NK cell (CD56+) basis, was decreased about 40% below preexercise levels for at least 2 h post-exercise. No significant increase in cortisol was seen after exercise, although norepinephrine and epinephrine increased moderately (465% and 133%, respectively), immediately following exercise. The data demonstrate that leg squat exercise to muscular failure results in a very similar immune response to that associated with intense endurance exercise, despite a lower mean oxygen consumption and only a moderate hormonal response.

Abstract: The effect of 2.5 h of treadmill running at 75.6 +/- 0.9% maximal O2 uptake (VO2max) on natural killer (NK) cell cytotoxic activity (NKCA) was investigated in 22 experienced marathon runners (VO2max 57.9 +/- 1.1 ml.kg-1.min-1, age 38.7 +/- 1.5 yr). Blood samples were taken before (0715) and immediately after exercise (1000), with three more samples taken during 6 h of recovery (1130, 1300, and 1600). Ten sedentary controls (VO2max 34.7 +/- 1.0 ml.kg-1.min-1, age 45.3 +/- 2.3 yr) sat in the laboratory during testing and had their blood sampled at the same time points. The pattern of change in NKCA over time was significantly different between groups [F(4,27) = 6.53; P = 0.001], with the runner's NKCA dropping 51-61% below preexercise levels throughout 6 h of recovery. Preincubation of blood mononuclear cells in vitro with indomethacin had no effect on the difference in pattern of change in NKCA between groups [F(4,17) = 8.59; P = 0.001] and did not attenuate the postexercise reduction in the runners. When NKCA was adjusted on a per-NK cell basis, group differences and the postexercise decline in NKCA were eliminated [F(4,80) = 0.65; P = 0.63]. Serum cortisol and plasma epinephrine in the runners were elevated relative to control subjects during recovery from exercise, but no significant correlation with changes in NK cells or NKCA was found. These data indicate that NKCA is decreased significantly during recovery from 2.5 h of running due to a numerical redistribution of NK cells.

Abstract: The effect of 2.5 h of treadmill running at 75.6 +/- 0.9% VO2max on circulating leukocyte and lymphocyte subpopulations, epinephrine and cortisol concentrations, and the Con A-induced lymphocyte proliferative response was investigated in 22 experienced marathon runners (VO2max 57.9 +/- 1.1 ml.kg-1.min-1, age 38.7 +/- 1.5 yrs). Blood samples were taken 15 min before (07.15h) and immediately after exercise (10.00h), with three more samples taken during 6h of recovery (11.30, 13.00, 16.00h). Ten sedentary controls (34.7 +/- 1.0 ml.kg-1.min-1, 45.3 +/- 2.3 yrs) sat in the laboratory during testing and had their blood sampled at the same time points. Serum cortisol was elevated relative to controls for more than 3 h post-exercise, and correlated significantly with the 3-h post-exercise, and correlated neutrophil/lymphocyte ratio (r = 0.68, p < 0.001). The concanavalin A- (Con A) induced lymphocyte proliferative response was decreased relative to controls for more than 3 h post-exercise, and except for the immediate post-exercise time point, tended to parallel the decrease in T cell (CD3+) concentrations.

Abstract: Epidemiological studies have found a relationship between increased physical activity and lower prevalence and mortality rates for various site-specific cancers. Animal studies are limited and often inconsistent, but also generally support this concept. However, the significance of this research will be questioned until the underlying physiological mechanisms are determined. It now seems likely that components of the innate immune system are involved. One such component includes cells of the monocyte-macrophage (Mo/M phi) lineage that have powerful inhibiting effects on tumor growth and can destroy cancer cells. Recent research suggests that exercise can alter the influx of Mo/M phi into tissues in response to an inflammatory challenge, promote the release of M phi-derived cytokines known to have antitumor properties, increase M phi antitumor cytotoxicity, and increase the number and functional activity of tumor-derived M phi. These effects are likely dependent on the dose of exercise and the functional state of the M phi at the time of the exercise stimulus. However, these responses have yet to be shown to inhibit experimental tumors in vivo. Future research must continue to develop appropriate animal models to study the mechanisms of exercise effects on the initiation, promotion and progression of cancer.

Abstract: The effect of 45 min of high- (80% VO2max) versus moderate- (50% VO2max) intensity treadmill exercise on circulating leukocyte and lymphocyte subpopulations, catecholamine and cortisol concentrations, and the mitogen-stimulated lymphocyte proliferative response was investigated in 10 well-conditioned (mean VO2max 66.0 +/- 1.9 ml/kg/min), young males (mean age 22.1 +/- 1.3 yrs). Blood samples were taken before and immediately after exercise, with three more samples taken during 3.5 h of recovery. Treatment order on the treadmill (graded walking at 7.3 +/- 0.1 km/h, 6.5 +/- 0.6% grade, versus level running at 16.1 +/- 0.3 km/h) was counterbalanced, with subjects acting as their own controls and results analyzed using a 2 x 5 repeated measures ANOVA. The concanavalin A- (Con A) stimulated lymphocyte proliferative response was decreased at 1 h and 2 h post-exercise relative to baseline levels following both exercise-intensity conditions. However, when adjusted on a per-T cell (CD3+) basis to account for the change in number of T cells in the in vivo assay, only the high-intensity exercise condition was associated with a 1-h post-exercise decrease (21%, p = 0.05) in the proliferative response relative to baseline. Exercise at 80% versus 50% VO2max resulted in significantly greater increases in cortisol and epinephrine concentrations, providing a physiological rationale for the immediate-post-exercise lymphocytosis, 1- to 3.5-h lymphocytopenia, and the decrease in Con A-stimulated lymphocyte proliferative response (per CD3+ cell) that occurred in greater measure following high-intensity exercise.

Abstract: Recent evidence suggests that exercise affects macrophage functions and that amount of exercise may be important. We determined effects of moderate (MOD) and exhaustive treadmill running (EXH) on 1) ability of macrophages to become activated for antitumor cytotoxicity after injection of heat-inactivated Propionibacterium acnes in vivo, 2) macrophage responsiveness to activating agents lipopolysaccharide and interferon-gamma, and 3) role of glucocorticoids and various macrophage metabolic products in modulating cytotoxicity in exercised animals. Male C3H/HeN mice were randomly assigned to MOD (18 m/min, 5% grade, 30 min/day) or EXH (18-35 m/min, 5%, 2-4 h) on a motor-driven treadmill. Control animals were kept in simulated treadmill lanes located directly over the runners. In general, both MOD and EXH increased cytotoxicity (42 and 22%, respectively, across all experiments; P < 0.05). Enhanced cytotoxicity was not due to altered macrophage adherence, tumor necrosis factor-alpha, interleukin-1 beta, or reactive oxygen species. Reactive nitrogen species were responsible for enhanced toxicity in EXH only. Macrophage cytotoxicity was further increased by lipopolysaccharide and interferon-gamma to a similar maximal level that was the same in all groups. Plasma corticosterone was elevated two- and fourfold in MOD and EXH, respectively, but there was no correlation between plasma corticosterone and macrophage cytotoxicity when compared across all groups even though cells were sensitive to steroid-mediated suppression in vitro. However, consistent with a corticosterone effect, EXH reduced the number of peritoneal macrophages elicited during P. acnes inflammation and abolished the typical exercise-induced increase in cytotoxicity of activated macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: This study examined the effects of two doses of exercise on tumor incidence and progression, and the number and activity of intratumoral phagocytic cells (80% macrophages [M phi's]). Male mice were randomly assigned to control (CON), moderate (MOD) or exhaustive (EXH) treadmill running. Mice were inoculated subcutaneously with 2.5 x 10(5) mammary adenocarcinoma cells after 3 d of running (3 h after the last run at a point when enhancement in M phi cytotoxicity is observed). This tumor was chosen due to its susceptibility to M phi inhibition in vitro and in vivo. Mice continued daily running for 14 d. Food intakes were higher during the last 3 d in MOD and EXH, but body weights were no different. Flow cytometer analysis of tumor masses revealed that MOD had greater numbers of phagocytic cells (vs EXH) with slightly higher phagocytic activities (vs CON and EXH) (P < 0.05). However, no group differences in tumor appearance were seen except on day 7 when CON had less observable tumors than MOD and EXH (P < 0.05). Tumor size was also not different between groups at any point. These results indicate that moderate exercise can increase the phagocytic capacity of intratumoral phagocytic cells, but these changes had no apparent effect on tumor incidence or progression in this study.

Abstract: Pharmacological manipulation of brain serotonergic [5-hydroxytryptamine (5-HT)] activity affects run time to exhaustion in the rat. These effects may be mediated by neurochemical, hormonal, or substrate mechanisms. Groups of rats were decapitated during rest, after 1 h of treadmill running (20 m/min, 5% grade), and at exhaustion. Immediately before exercise rats were injected intraperitoneally with 1 mg/kg of quipazine dimaleate (QD; a 5-HT agonist), 1.5 mg/kg of LY 53857 (LY; a 5-HT antagonist), or the vehicle (V; 0.9% saline). LY increased and QD decreased time to exhaustion (approximately 28 and 32%, respectively; P < 0.05). At fatigue, QD animals had greater plasma glucose, liver glycogen, and muscle glycogen concentrations but lower plasma free fatty acid concentration than did V and LY animals (P < 0.05). In general, plasma corticosterone and catecholamine levels during exercise in QD and LY rats were similar to those in V rats. Brain 5-HT and 5-hydroxyindole-3-acetic acid concentrations were higher at 1 h of exercise than at rest (P < 0.05), and the latter increased even further at fatigue in the midbrain and striatum (P < 0.05). Brain dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were higher at 1 h of exercise (P < 0.05) but were similar to resting levels at fatigue. QD appeared to block the increase in DA and DOPAC at 1 h of exercise, and LY prevented the decrease in DA and DOPAC at fatigue (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: This study determined the effects of exercise on the ability of inflammatory macrophages to inhibit tumor cell growth in vitro (macrophage cytotoxicity). Thioglycollate injection (1 ml ip) was used as an inflammatory challenge and to partially activate macrophages for cytotoxicity. Inbred male C3H/HeN mice (n = 180) exercised moderately (MOD, 18 m/min, 30 min/day, 5% grade) or to exhaustion (EXH, 18-35 m/min, 2-4 h, 5% grade) on a motor-driven treadmill for 3 consecutive days after injection. Control (CON) mice were kept in stimulated treadmill lanes directly over the runners. Mice were killed immediately or 3 or 8 h postexercise. Macrophages from both MOD and EXH exercise groups manifested significantly (P < 0.05) enhanced (approximately 50%) cytotoxicity compared with those from CON group at all time points postexercise. This potentially beneficial exercise effect was not related to macrophage production of interleukin-1 beta, reactive nitrogen or oxygen intermediates, or number of macrophages in the assay but may have been manifested, in part, by tumor necrosis factor-alpha. Plasma corticosterone was significantly elevated immediately postexercise in MOD and EXH compared with CON mice; however, no evidence existed for an immuno-suppressive effect of corticosterone on macrophage cytotoxicity, perhaps because of insensitivity of inflammatory macrophages to glucocorticoid suppression seen in vitro. These data only partially support the "inverted U hypothesis," which states that moderate exercise may enhance, whereas very heavy exercise or a lack of exercise may attenuate, the immune response. Further study is needed to determine the physiological significance of these findings and the effects of exercise on macrophage subsets sensitive to glucocorticoid suppression (i.e., fully activated macrophages).

Abstract: Both reinforcing intracranial self-stimulation (ICSS) and physical exercise result in heightened cardiovascular and endocrine responses. This study compared the cardiovascular and endocrine responses to ICSS in rats after either chronic ICSS or treadmill running. Male rats (n = 35) were implanted with bipolar electrodes aimed at the ventral tegmental area of the brain, and those that performed vigorous lever pressing for ICSS (> 50 presses/min; n = 30) were counter balanced into three groups: chronic ICSS (PRESS), chronic run training (RUN), or sedentary controls (CONT). PRESS, RUN, and CONT rats performed ICSS, ran on a motorized treadmill, or sat quietly in cages for 30 min/day, 5 day/wk, for 12 wk, respectively. All animals then performed 30 min of lever pressing for ICSS and were immediately killed. Oxygen consumption, heart rate, blood pressure, rectal temperature, and plasma norepinephrine, epinephrine, and corticosterone increased (P < 0.05) for all groups during lever pressing. PRESS rats did not differ from CONT rats for any variable studied. However, heart rate was lower and oxygen consumption, norepinephrine, and corticosterone were higher in RUN than in CONT rats. Heart and ventricle weights were higher in PRESS and RUN than in CONT rats; body weights were not different. These data suggest that chronic treadmill running results in adaptations that influence cardiovascular and hormonal responses to ICSS.

Abstract: The purpose of this experiment was to examine the effects of administration of serotonergic (5-HT) agonist and antagonist drugs on run-time to exhaustion (RUN-EXH) in male and female rats. RUN-EXH was reduced (p < 0.05) in a dose related manner by increasing dosages of quipazine dimaleate (QD: general 5-HT agonist) (0-5 mg.kg-1 i.p.) administered immediately prior to exercise (treadmill running at 20 m.min-1 and 5% grade). Conversely, RUN-EXH was increased (p < 0.05) by the greatest dosage of LY 53,857 (LY: 5-HT1C and 5-HT2 antagonist) (1.5 mg.kg-1 i.p.). Drug effects were similar in male and female rats. The negative effects of QD administration on RUN-EXH were not attenuated by administration of the peripherally restricted antagonist, xylamidine tosylate (up to 200 ug.kg-1 i.p.). The results of this investigation indicated that fatigue during prolonged exercise can be influenced by direct pharmacological administration of a serotonergic agonist and antagonist and that the mechanisms underlying these effects are likely to be central (brain) in nature.

Abstract: The effect of 45 min of high- (80% VO2max) vs moderate- (50% VO2max) intensity treadmill exercise on natural killer cell cytotoxic activity (NKCA) was investigated in 10 well-conditioned (66.0 +/- 1.9 ml.kg-1.min-1), young males (22.1 +/- 1.3 yr). Blood samples were taken before and immediately after exercise, with three more samples taken during 3.5 h of recovery, and analyzed for proportion of NK cells (CD3-CD16+CD56+) and NKCA. Exercise at 80% vs 50% VO2max resulted in a greater immediate postexercise increase in proportion of NK cells, followed by a 1-h and 2-h decrease below preexercise levels for both intensity conditions. NKCA rose significantly above preexercise levels following high- but not moderate-intensity exercise. For both exercise intensity conditions, NKCA tended to drop below preexercise levels by 1 h postexercise, rising back to preexercise levels by 3.5 h postexercise. When NKCA was expressed on a per-NK cell basis, however, no change relative to preexercise levels occurred following moderate-intensity exercise, while a significant increase occurred after 2-h recovery from high-intensity exercise. These data demonstrate that both high- and moderate-intensity exercise are associated with significant shifts in circulating proportions of NK cells which significantly influence interpretation of NKCA data based on assays using separated mononuclear cells.

Abstract: The thermogenic effects of pre- and postprandial exercise was examined in six obese premenopausal females. Using open circuit calorimetry, energy expenditure was measured for 3 hours following five separate treatments: Resting Control, Exercise Only (25 min cycle at 60% VO2 max), Meal Only (902 kcal mixed meal), Exercise-Meal, and Meal-Exercise. Meal Only, Exercise-Meal, and Meal-Exercise were significantly higher than Rest Only and Exercise Only treatments. However, Meal-Exercise resulted in the greatest energy expenditure. These results suggest that in obese female subjects exercise following a meal will produce the greatest thermogenic response and could possibly influence weight maintenance or weight loss if implemented in food and exercise patterns of behavior.

Abstract: Brain serotonin (5-hydroxytryptamine, 5-HT) has been suggested to be involved in central fatigue during prolonged exercise. Changes in the ratio of plasma free tryptophan (free Trp) to branched-chain amino acids (BCAA) are associated with altered brain 5-HT synthesis. The purposes of this study were to describe systematically the effects of prolonged exercise on changes in plasma free Trp and BCAA and to examine the effects of carbohydrate (CHO) feedings on these same variables. Eight well-trained men [VO2max = 57.8 (SE 4.1) ml kg-1 min-1] cycled for up to 255 min at a power output corresponding to VO2 at lactate threshold (approximately 68% VO2max) on three occasions separated by at least 1 week. Subjects drank 5 ml kg-1 body wt-1 of either a water placebo, or a liquid beverage containing a moderate (6% CHO) or high (12% CHO) concentration of carbohydrate beginning at min 14 of exercise and every 30 min thereafter. Exercise time to fatigue was shorter in subjects receiving placebo [190 (SE 4) min] as compared to 6% CHO [235 (SE 10) min] and 12% CHO [234 (SE 9) min] (P < 0.05). Glucose and insulin decreased in the placebo group, and free Trp, free-Trp/BCAA, and free fatty acids increased approximately five- to sevenfold (P < 0.05). These changes were attenuated in a dose-related manner by the carbohydrate drinks.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: This study observed oxygen consumption (VO2), heart rate (HR), and rating of perceived exertion (RPE) during both maximal and submaximal exercise tests on a conventional Monark cycle ergometer and a new Velodyne ergometer. The Velodyne uses the subject's own bicycle attached to an electrically braked roller, which regulates power output. Trained male cyclists performed maximal exercise tests on both ergometers (N = 7) and two submaximal tests on each of three identical Velodynes and a Monark (N = 6). VO2, HR and RPE were measured during the submaximal and maximal tests. Data were analyzed via multiple repeated-measures ANOVA. No differences were found across cycles during the maximal or submaximal tests. The results indicate that the Monark and the Velodyne ergometers elicited similar physiologic and perceptual responses and that the Velodyne can be a viable alternative to the conventional Monark ergometer.

Abstract: The purpose of this investigation was to examine the effects of oral iron supplementation on endurance performance in initially iron-depleted, nonanemic female distance runners. Eighteen iron-depleted (serum ferritin less than 20 ng.ml-1, hemoglobin greater than or equal to 12 g.dl-1) women (22-39 yr) performed a VO2max test and an endurance run to exhaustion. Subjects were pair-matched on the basis of endurance time and then randomly assigned to an iron supplement or a placebo group. Following supplementation, the iron group had a significantly higher (P = 0.03) mean serum ferritin concentration (23.4 vs 15.7 ng.ml-1) and lower (P = 0.04) mean total iron-binding capacity than the placebo group. Both groups increased their time to exhaustion (25.5% and 22.2% for the iron and placebo groups, respectively) but were not significantly different (P = 0.72) from each other. There were also no differences (P greater than 0.05) between the groups with respect to lactate concentrations and physiological measures taken during the two exercise tests. The results of this study suggest that 8 wk of oral iron supplementation improves iron status in iron-depleted female distance runners, but does not enhance endurance capacity.

Abstract: The purpose of this study was to determine the effects of a single period of swim exercise to exhaustion on the cellular distribution of hexokinase in rat skeletal muscle. The gastrocnemius muscle from male rats exercised (n = 16) to exhaustion or allowed to remain inactive (n = 14) was analyzed for hexokinase activity (HK) in the whole muscle homogenate and the mitochondrial-rich fraction. Although exercise produced a slight, non-significant, increase in HK activity in the whole muscle homogenate (p less than 0.09), HK activity in the mitochondrial-rich fraction was significantly increased in the exercised muscle (p less than 0.02). This shift in the cellular distribution of HK is towards the more active mitochondrial bound form and indicates an enhanced regulation of HK activity during physical exercise.

Abstract: Ten healthy males (mean age 22.3 +/- 0.8 yr) pedaled with maximal effort for 30 s against a workload adjusted prior to the start of the test to 0.98 N.kg body mass-1. Blood samples were collected before, and 3 min and 1 h following exercise. Peak and average power mean values were 1020 +/- 51 and 738 +/- 34 W, respectively. Total leukocytes increased 40% in response to the exercise bout, but were 16% below pretest levels after 1 h of recovery (F = 123, P < 0.001). Neutrophils and lymphocytes represented approximately 60% and 30% of the leukocytosis, respectively. Lymphocytes increased 30% following exercise, but were 36% below pretest levels after 1 h recovery (F = 56.4, P < 0.001). The post-test lymphocytosis can be explained primarily from the 176% increase in natural killer cells (NK) and 28% increase in cytotoxic/suppressor T cells, while the 1-h recovery lymphopenia occurred because of a sharp decrease in total T cells and a moderate decrease in NK cells. No significant changes in lymphocyte proliferative response or serum immunoglobulin levels were found when appropriate adjustments for changes in plasma volume or lymphocyte subset changes were made. Plasma epinephrine increased 300% in response to the exercise bout, and best explains the measured changes in circulating levels of lymphocyte subsets. These results demonstrate that changes in circulating levels of leukocyte and lymphocyte subsets, especially NK cells, occur rapidly in response to 30 s of brief, heavy exertion.

Abstract: This study examined the effects of glucose ingestion on differentiated and undifferentiated ratings of perceived exertion (RPE) during prolonged cycling exercise. On two occasions, seven trained males cycled for 180 min on a Monark cycle ergometer at 70% peak VO2 (VO2peak). Subjects consumed an 8% glucose/electrolyte drink (G) or a flavored water placebo (P) every 15 min throughout exercise. Measurement of RPE, ventilation (VE), oxygen uptake (VO2), respiration rate (RR), respiratory exchange ratio (RER), heart rate (HR), and venous blood sample collection preceded ingestion of the drink. Subjects were homogenous with respect to height, weight, and VO2peak. RPE for the legs and overall body were significantly attenuated (P less than 0.05) during the last 45 min of exercise. Plasma glucose and insulin were higher (P less than 0.05) in G than in P at virtually all time points. CHO oxidation and work rate were maintained throughout exercise in G but not during the last 30 min of exercise in P (P less than 0.05). Percent changes in plasma volume, plasma lactate, HR, VE, RR, and RPE for the chest were not different between conditions (P greater than 0.05). The data suggest that ingestion of carbohydrate beverages during endurance cycling can maintain plasma glucose and CHO oxidation during the latter stages of prolonged exercise. As a result, it appears that a relationship exists between attenuation of ratings of perceived exertion (especially in the legs), blood glucose, and CHO oxidation late in prolonged exercise. The mechanism for this probably involves the increased availability of blood-borne glucose to serve as substrate for brain and/or muscle energy metabolism during a time when endogenous stores of carbohydrate are low.

Abstract: Most animal running models have traditionally used aversive motivators to induce exercise tasks. This study demonstrates treadmill running motivated by reinforcement of intracranial self-stimulation (ICSS), providing an alternative model with which to study physiological responses to exercise. Twenty-nine male Sprague-Dawley rats were stereotaxically implanted with bipolar electrodes aimed at the ventral tegmental area of the brain. After 7 days of operant lever-press training for ICSS, rats that pressed at least 50 presses/min were randomly divided into three conditions: exercise-reinforcing brain stimulation (Ex-St), exercise-aversive shock (Ex-Sh), and sedentary controls (C). Ex-St and Ex-Sh ran for 30 min at 25 m/min at 5% grade for 2 wk with ICSS and electric shock as the motivator, respectively, while C did not run. At the end of 2 wk, Ex-St and Ex-Sh performed an endurance run. Results show that Ex-St ran longer than Ex-Sh [63 +/- 10 vs. 42 +/- 10 (SD) min; P less than 0.05]. HR was higher in Ex-St than in C (P less than 0.05). Rectal temperature increased similarly in both exercise groups. This model provides a highly effective method to motivate treadmill running in rats and as such can be used to characterize physiological responses to exercise without the potentially confounding influence of stress associated with an aversive shock motivator.

Abstract: The effects of ingesting a low dose of CHO on plasma glucose, glucoregulatory hormone responses, and performance during prolonged cycling were investigated. Nine male subjects cycled for 165 min at approximately 67% peak VO2 followed by a two-stage performance ride to exhaustion on two occasions in the laboratory. Every 20 min during exercise, subjects consumed either a flavored water placebo (P) or a dilute carbohydrate beverage (C). Blood samples were collected immediately before, every 20 min throughout, and immediately after exercise. Plasma was analyzed for glucose, lactate, free fatty acids (FFA), and various glucoregulatory hormones. VO2, RER, heart rate, perceived exertion, and exercise performance were also measured. Lactate, FFA, epinephrine, norepinephrine, ACTH, cortisol, and glucagon increased with exercise whereas glucose and insulin decreased (p < or = .05). Except for a small difference in glucose at 158 min of exercise and at exhaustion, no significant differences were found between drinks for any of the variables studied (P > or = .05). Ingestion of 13 g carbohydrate per hour is not sufficient to maintain plasma glucose, attenuate the glucoregulatory hormone response, and improve performance during prolonged moderate intensity cycling.

Abstract: Plasma D2O-accumulation profiles (qualitative indices of fluid-absorption rates) were determined in eight subjects after ingestion of 275 mL of five D2O-labeled beverages: a water placebo (W), 6% maltodextrin (6% M), and three solutions containing a 6%, 8%, and 10% glucose-fructose mix (6% GF, 8% GF, and 10% GF). Except for W all beverages contained 20 mmol sodium/L and 3 mmol potassium/L. No differences in plasma D2O accumulation were found. Plasma glucose increased at 20 and 30 min after ingestion of the carbohydrate drinks and returned to baseline (6% GF and 6% M) or below (8% GF and 10% GF) by 60 min. Insulin responded similarly and, except for a slightly lower value at 30 min for 6% GF, no differences were detected. It appears that fluids in drinks containing less than or equal to 8-10% carbohydrate (simple sugars or maltodextrins) are made available for dilution in body fluids at similar rates and should be similar in replenishing body fluids lost in sweat during exercise.

Abstract: This study compared the effects of glucose feeding and water on endurance performance, glycogen utilization, and endocrine responses to exhaustive running in rats. Forty-eight trained rats ran at approximately 70% peak O2 consumption (VO2) while receiving, via gavage, 1 ml of an 18% glucose solution or water every 30 min. Glucose- (GF) and water-fed rats (WF) were pair matched and killed at rest, at 25 or 50% of their previously determined run time to exhaustion, or at exhaustion. Run times to exhaustion were 4.6 +/- 1.0 and 3.0 +/- 0.9 h in GF and WF rats, respectively. In WF rats, plasma glucose declined continuously from a resting value of 7.4 +/- 0.5 to 1.8 +/- 0.5 mM at exhaustion and was lower than in GF rats at all exercise time points. In GF rats, glucose was maintained at 7.4 +/- 0.5 mM for 3 h before dropping to 3.9 +/- 0.6 mM at exhaustion. In both groups, liver and muscle glycogen decreased dramatically during the 1st h and changed only slightly thereafter. During the 3rd h, glycogen levels were maintained in GF rats but continued to decrease in WF rats (P less than 0.05). Insulin decreased during exercise and was not significantly different between groups. Glucagon, epinephrine, norepinephrine, and corticosterone increased to a greater extent in WF than in GF rats during the first 3 h of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: The thermogenic effects of pre- and postprandial exercise was examined in seven lean active females. Energy expenditure was measured for 3 h via open circuit indirect calorimetry after four separate treatments: Exercise Only (25 min treadmill run at 60% VO2 max), Meal Only (910 kcal mixed meal), Exercise-Meal and Meal-Exercise. The thermogenic response to the Exercise-Meal treatment was similar to the Meal Only treatment. However, the Meal-Exercise treatment resulted in a greater energy expenditure than the Meal Only and Exercise-Meal treatments. The Exercise Only treatment showed the lowest thermogenic response. These data suggest that exercise following a meal would be more beneficial than exercise before a meal in increasing and maintaining an elevated energy expenditure.

Abstract: This study compared the effects of ingesting 6% (MC) and 12% (HC) glucose/electrolyte beverages, and a flavored water placebo (P) on markers of fluid absorption, palatability, and physiological function during prolonged intermittent cycling in the heat. On three occasions, 15 trained male cyclists performed two 60 min cycling bouts at 65% VO2max (E1 and E2). A brief exhaustive performance ride (approximately 3 min) was completed after E1 and E2, and after 20 min recovery (P1, P2, P3). Every 20 min, subjects consumed 275 mL of P, MC or HC. The first drink contained 20 mL of D2O, a tracer of fluid entry into blood plasma. Plasma D2O accumulation was slower for HC than for P and MC (P less than 0.001). HC caused more nausea (P less than 0.01) and fullness (P less than 0.05) than MC or P, and subjects said they would be less likely to consume HC during training or competition (P less than 0.10). Sweat rates, HR, Tre, Tsk, VO2, and PV were similar for all drinks. Performance of P1, P2, P3 were not different among drinks. However, four cyclists failed to maintain the prescribed work rate during E2 for HC but only one failed for MC and P. These data suggest that the slow absorption of a 12% glucose/electrolyte beverage during prolonged intermittent exercise in the heat may increase the risk of gastrointestinal distress and thereby limit performance.

Abstract: On three occasions cyclists completed, as fast as possible, two exercise tasks (T1 and T2) separated by 30 min rest. T1 and T2 were equivalent to the work performed during 2 h cycling at 75% VO2max and 30 min at 75% VO2max, respectively. Every 20 min subjects drank 275 mL of a 6% (MC) or 2.5% (LC) carbohydrate-electrolyte beverage or a water placebo (P). The initial drink during both T1 and the rest period contained 20 g D2O as a marker for entry of ingested fluid into blood. No differences in drink effects were found for heart rate, sweat rate, change in plasma volume, rectal temperature, or D2O accumulation in blood. Blood glucose and respiratory exchange ratios were higher and T2 was performed faster with MC than with P. Ingestion of MC can help maintain blood glucose and enhance performance of prolonged cycling exercise without compromising fluid replenishment.

Abstract:

Abstract: Adult male rats were subjected to an acute bout of swimming exercise for 50 min during the early morning or late afternoon. Compared to nonexercised controls, all exercised groups showed an initial approximately 2-hr period of increased feeding (period I hyperphagia). A 50-min period of sham swimming (wading in water) was followed by period I hyperphagia but not period II hypophagia. Opioid modulation of period I hyperphagia was indicated by the ability of naltrexone to antagonize, in a dose-dependent manner, the postexercise hyperphagia. Furthermore, plasma concentrations of immunoreactive B-endorphin (Ir-B-ep) were increased during period I following exercise. Opioid modulation of the period II hypophagia was equivocal. Plasma Ir-B-ep was not altered in period II, and naltrexone did not modify period II hypophagia. The ability of 2-deoxy-D-glucose to induce feeding was slightly depressed (p less than 0.05) during period II after exercise, and the ability of exogenous insulin to induce feeding was not changed. These differential feeding responses to 2-deoxy-D-glucose (opioid-mediated) and insulin (relatively opioid-independent) suggest that an opioid deficiency may exist during period II and contribute to the hypophagia.

Abstract: Patterns of normal and stimulated food intake (FI) as well as its possible endogenous opioid (EO) modulation were investigated in male rats given regular swimming exercise (trained; TR) and compared with nonexercised sedentary (SED) controls. Rats in the TR group had lower body weights as well as reduced 24 hr FI due to lower nocturnal FI. TR rats also ate less food in response to injections of 2-deoxy-D-glucose (2-DG) but not insulin (INS) when injections were given during the first 4-5 weeks of training. However, this difference between TR and SED rats in the 2-DG induced feeding was not demonstrable after 10 or more weeks of training. Plasma concentrations of immunoreactive B-endorphin (IR-B-ep) were elevated, as expected, in TR rats (10-12 weeks) during nocturnal sampling whereas the nocturnal increase of IR-B-ep was absent in SED controls. However, these SED rats did increase daytime IR-B-ep in response to 2-DG and acute exercise, albeit somewhat less in magnitude when compared to TR rats. Injection of naltrexone (NTX) decreased feeding in TR rats (10-12 weeks) but not in contemporary SED controls. In summary, exercise training modified feeding behavior, and at 4 weeks of training, TR rats ate less in response to opioid-related feeding stimulus of 2-DG, but responded similarly to insulin (relatively opioid independent) treatment. At later stages of training this difference between TR and SED rats disappeared. Moreover, SED rats had atypical profiles of IR-B-ep and reduced hypophagic responses to NTX suggesting that TR rats might have greater EO modulation of feeding at this stage.