Biomedical subjects

Michael G Flynn

Publications and source records attributed to Michael G Flynn.

14 recordsLinked to original sources

PubMed2006

Carbohydrate consumption during cycling increases in vitro NK cell responses to IL-2 and IFN-gamma.

INTRODUCTION: Exercise has been shown to lower blood natural killer cell concentration and activity for up to 24-h after exercise; however, the mechanism underlying this effect is not clearly defined. We have speculated that an exercise-induced change in T-cell control of NK cells is at least partly responsible for the post-exercise suppression. As a follow-up to our previous research, the purpose of this study was to examine the T and NK cells responses during and following moderate/high-intensity endurance exercise. METHODS: Eight male subjects (20+/-1 y; VO(2peak)=67.22+/-2.79 mL.kg(-1).mL(-1)) were recruited to complete two 1-h (75-80% VO(2peak)) cycling trials in a random counterbalanced order: carbohydrate (CHO) and placebo (PLA). Venous blood samples were collected before (PRE), immediately (POST), 2-h (2H), and 4-h (4H) after exercise. NK (CD3(-)/56(+)) and activated NK (CD3(-)/56(+)/69(+)) number were measured using flow cytometry. NK cell activity (NKCA) was determined using both a (51)Cr release assay (NKCA-51) and activated NK cell number (NKCA-69). Whole blood samples were stimulated with IL-2, IFN-gamma, IL-4, IL-12, and no stimulation for 12-h and then analyzed for NK cell activity using a (51)Cr release assay (NKCA-51). RESULTS: Leukocyte counts and unstimulated NKCA were not different between CHO and PLA; however, exercise significantly increased NKCA (P<.05). Fold change in IL-2, IFN-gamma, and IL-2+IFN-gamma-stimulated NKCA were significantly greater in CHO compared to PLA (P<.05). No effect of drink was found for IL-4, IL-12, and IL-4+IL-12-stimulated NKCA. DISCUSSION: The fold change in IL-2-stimulated NKCA is consistant with our previous published work. The drink effect for Th1 (but not Th2) cytokines suggests they may play a more significant role in modulating NKCA following a strenuous bout of aerobic exercise when CHO is consumed.

Adult↗

PubMed2006

Energy restriction with different protein quantities and source: implications for innate immunity.

OBJECTIVE: Physical age, energy restriction (ER), and weight loss have been reported to suppress indices of innate immunity, which may increase the risk of illness. To evaluate these interactions, we recruited older, postmenopausal women (50 to 80 years) to fill one of the following 9-week ER (1250 kcal/d) groups: beef [n = 14; reported intakes 46% carbohydrate (CHO):24% protein (PRO):30% fat], chicken (n = 15; 51% CHO:25% PRO:24% fat), or CHO (n = 14; 59% CHO:17% PRO:24% fat), or a non-intervention control (n = 11). RESEARCH METHODS AND PROCEDURES: Fasting blood was collected before and after ER to determine leukocyte phenotype, neutrophil oxidative burst capacity, natural killer cell activity, stimulated interleukin-2 and interferon-gamma production, and blood zinc and iron concentrations. RESULTS: No significant effects of ER (8.6% weight loss) or PRO quantity and source were found for the majority of indices of innate immunity. Small but significant (p < 0.05) declines in interleukin-2 production were found in the chicken and CHO groups only; however, the clinical significance of this finding is not known. DISCUSSION: In the present study, 9 weeks of moderate ER did not suppress immunity in postmenopausal women. Also, contrary to our hypothesis, differential zinc and iron intakes did not significantly alter immunity.

Aged↗

PubMed2006

Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4.

BACKGROUND: Chronic inflammation has been implicated in the development of cardiovascular disease, diabetes mellitus, cachexia, and osteoporosis. Regular physical activity has been purported to possess "anti-inflammatory" properties which may limit chronic inflammation. Recently, we hypothesized that toll-like receptor 4 (TLR4) may play a role in activity-induced modulation of inflammation. Therefore, the purpose of this study was to determine the association between age, physical activity status, biomarkers of inflammation, and TLR4. METHODS: Male and female participants (n = 84) were recruited to fill one of the following groups: young (18-30 years), active; young, inactive; old (60-80 years), active; or old, inactive. To assess physical activity status, participants completed a Paffenbarger Physical Activity Questionnaire and a modified Balke submaximal treadmill test. After grouping and screening, participants were given a standard mixed diet to consume 24 hours prior to arriving at the laboratory. Participants were instructed to consume all food by 10 pm the night prior to blood sampling (8-hour fast). Following 30 minutes of seated rest in a quiet room, venous blood samples were collected. Lipopolysaccharide-stimulated inflammatory cytokine production and plasma high-sensitivity C-reactive protein (hsCRP) were determined by enzyme-linked immunosorbent assay, and TLR4 expression was determined by flow cytometry. RESULTS: Lipopolysaccharide-stimulated interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha production, TLR4 expression, and hsCRP were significantly lower in active compared to inactive participants (p <.05). Also, older participants had significantly higher hsCRP than young participants had (p <.05). CONCLUSIONS: The findings of the present study support previous reports which infer that acute exercise or a physically active lifestyle may possess anti-inflammatory properties. Also this study, along with previous work from our laboratory, suggests that TLR4 may play a role in regulating the link between inflammatory cytokine production and a physically active lifestyle.

Adult↗

PubMed2006

Toll-like receptor 4: link to the anti-inflammatory effects of exercise?

Evidence is emerging that exercise training has anti-inflammatory effects. Our early finding that blood cultures from trained subject had a reduced responsiveness to lipopolysaccharide led to a series of studies in which we measured toll-like receptor 4--the primary signaling receptor for lipopolysaccharide. The toll-like receptor 4 expression was consistently lower in physically active subjects compared with inactive subjects and reduced after training in previously inactive subjects.

Cytokines↗

PubMed2005

Influence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4.

The influence of an exercise training program and age on inflammatory cytokine production and CD14+cell-surface expression of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) was examined in 60 younger and older subjects. Subjects were assigned to: young physically active (YPA, n = 15; 25.2 +/- 5.0 years), young physically inactive (YPI, n = 14; 24.9 +/- 4.7 years), older physically active (OPA, n = 14; 71.2 +/- 4.4 years) or older physically inactive (OPI, n = 17; 71.0 +/- 4.3 years) groups. YPI and OPI completed 12 weeks (3 days/week) of endurance (20 min) and resistance exercise (eight exercises, two sets). YPA and OPA groups were instructed to continue their normal activity for 12 weeks. Blood was collected at rest, before and after the 12-week training and control period. A whole blood method was used to determine lipopolysaccharide-(LPS) and peptidoglycan-(PGN) stimulated IL-6, IL-1beta, and TNF-alpha production with supernatants analyzed using ELISA. CD14+ cell-surface expression of TLR2 and TLR4 were measured using flow cytometry. Training increased estimated VO(2max) by 10.4% and increased strength by an average of 38.1%. YPI and OPI had a post-training reduction in LPS-stimulated IL-6 production (P < .01), but LPS-stimulated IL-1beta and TNF-alpha and PGN-stimulated cytokines were not changed. CD14+ cell TLR4 was significantly reduced (P < .05) in YPI and OPI groups after training, but TLR2 was not significantly changed. An exercise training program reduced LPS-stimulated IL-6, concomitant with lower TLR4. These results provide further support for a training- or physical activity-induced lowering of TLR4 and inflammation.

Adolescent↗

PubMed2005

Chronic resistance exercise training improves natural killer cell activity in older women.

BACKGROUND: Regular exercise has been reported to slow the age-associated declines in natural killer cell activity (NKCA). To evaluate this response, we recruited older, postmenopausal women (65-85 years old) to fill one of two groups: training (10 weeks of resistance exercise; TR) or control. METHODS: Blood samples were collected from an arm vein in the TR group at rest (PRE), immediately following (POST), and 2 hours (2H) following an acute bout of resistance exercise both before (BEFORE) and after (AFTER) training. Leukocytes and NKCA were determined by flow cytometry and a whole blood (51)Cr release assay, respectively. RESULTS: Acute exercise increased total leukocyte (p < .05), CD8 (p < .05), CD4 (p < .05), and CD56 counts (p < .05), but there was no effect of training. NKCA was greater TR-AFTER-PRE (136%), -POST (80%), and -2H (127%) compared to similar values from TR-BEFORE (p < .05). CONCLUSION: Increased resting NKCA after chronic resistance training suggests that immunity has been improved.

Aged↗

PubMed2004

Effects of megestrol acetate on circulating interleukin-15 and interleukin-18 concentrations in healthy elderly men.

BACKGROUND: Interleukin-15 (IL-15) and interleukin-18 (IL-18) are potential regulators of body composition in humans. The authors previously reported that megestrol acetate ingestion causes a large accumulation of adipose tissue and reduces muscle mass. Therefore, the purpose of this investigation was to evaluate the effects of megestrol acetate ingestion on circulating IL-15 and IL-18 concentrations in healthy elderly men. METHODS: All participants received 800 mg of megestrol acetate per day during this 12-week study. Megestrol acetate was combined with testosterone injections (100 mg/week), placebo injections, resistance training, or resistance training and testosterone. Resting IL-15 and IL-18 concentrations were measured by enzyme-linked immunosorbent assay at week 0 (pre), week 6 (mid), and week 12 (post). RESULTS: The time effect for IL-15 was significant (p = .0008), with the mid and post values being significantly greater than the pre value. The change in IL-15 concentration was not significantly related to the change in muscle mass (r = -.31; p > .05), nor was it related to the change in fat mass (r =.17; p > .05). Differences among groups or over time were not significant for IL-18, nor were correlations between pre body weight and pre IL-18 (r = -.03), pre fat mass and pre IL-18 (r = .14), or the change in fat mass and the change in IL-18 (r = -.07). CONCLUSIONS: IL-15 was increased as a result of megestrol acetate ingestion; however, megestrol acetate did not affect circulating IL-18 concentrations, and the change in IL-18 did not correlate with any body composition variables.

Aged↗

PubMed2004

TLR4 is lower in resistance-trained older women and related to inflammatory cytokines.

INTRODUCTION/PURPOSE: Regular exercise may offset age-associated increases in inflammatory cytokines and reduce the risk of developing diseases with an inflammatory etiology by exerting "anti-inflammatory" effects. Toll-like receptor 4 (TLR4) signaling stimulates inflammatory cytokine production, and may explain the "anti-inflammatory" effect attributed to regular exercise. Therefore, the purpose of the present study was to compare the effect of acute (3 sets, 9 exercises, 10 repetitions at 80% of the 1-repetition maximum) and chronic resistance exercise on TLR4 and inflammatory cytokines. METHODS: Venous blood samples were collected from trained (TR, N = 10) and untrained (UT, N = 10) older (65-80 yr) postmenopausal women: before (PRE), immediately post (POST), and 2 h (2H), 6 h (6H), and 24 h (24H) after completion of exercise. Cell-surface expression of TLR4 (two-color immunofluorescent cytometry), LPS (25 microg x mL(-1))-stimulated cytokine production (ELISA), plasma cytokines (ELISA), and mRNA expression of TLR4 and cytokines (RT-PCR) were determined for each sample. RESULTS: TR had 124% less cell-surface TLR4 expression than UT (P < 0.05). A significant time effect was found for LPS-stimulated IL-6, IL-1beta, and TNF-alpha, where 6H was significantly greater than all other samples. No significant effects were found for plasma (IL-6 and TNF-alpha) or mRNA expression (IL-6, TNF-alpha, and IL-1beta) of inflammatory cytokines. When subjects were grouped according to cell-surface TLR4 expression (HI and LO), LPS-stimulated TNF-alpha (302%), IL-1beta (209%), and IL-6 (167%) production was greater for HI than LO (P < 0.05). CONCLUSION: Regularly exercising older women expressed less cell-surface TLR4 but did not have lower plasma levels or produce less LPS-stimulated inflammatory cytokines at rest or in response to a single bout of resistance exercise. TLR4 changes may explain the "anti-inflammatory" effect that has recently been attributed to chronic (2x wk for previous 24 months) resistance exercise training.

Adaptation, Physiological↗

PubMed2003

Carbohydrate intake during endurance exercise increases natural killer cell responsiveness to IL-2.

The purpose of this study was to evaluate the effect of high-intensity endurance exercise and carbohydrate consumption on in vitro responsiveness of natural killer (NK) to IL-2 (2.5 U/ml for 24 h). Thirteen male subjects (18-26 yr old; peak O2 consumption = 59.79 +/- 5.13 ml.kg-1.ml-1) were recruited to complete two 1-h (75-80% peak O2 consumption) cycling trials in a random counterbalanced order: carbohydrate (CHO) and placebo (Pla). Venous blood samples were collected before (Pre), immediately (Post), 2 h (2H), and 4 h (4H) after exercise. All resting samples were taken after 15 min of seated rest. NK (CD3-/56+), activated NK (CD3-/56+/69+), helper T cell (Th; CD3+/4+), and cytotoxic T cell (Tc; CD3+/8+) number were measured by using flow cytometry. NK cell activity (NKCA) was determined by using both a 51Cr release assay (NKCA-51) and activated NK cell number (NKCA-69). Immune system variables were not different between CHO and Pla, with the exception of NK cell responsiveness to IL-2, where Post (116.2%) and 4H (48.4%) was significantly greater in CHO (P < 0.05). NK, Th, and Tc were significantly higher Post (40.7, 102.7, and 82.0%, respectively) and lower at 2H (-51.9, -53.3, and -53.2%, respectively) than Pre (time effect). 4H was not different from Pre for NK, Th, and Tc. NKCA was significantly lower 2H (NKCA-51, NKCA-69) and 4H (NKCA-69) than Pre. CHO consumption during exercise did not prevent disruptions in unstimulated immune system function, but it did enhance NK responsiveness to IL-2.

Adolescent↗

PubMed2003

Toll-like receptor 4 and CD14 mRNA expression are lower in resistive exercise-trained elderly women.

The purpose of this study was to examine the influence of resistive exercise training and hormone status on mRNA expression of toll-like receptor 4 (TLR4), CD14, IL-1beta, IL-6, and TNF-alpha. Resistive exercise-trained women on "traditional" hormone replacements [hormone replacement therapy (HRT), n = 9], not taking hormones (NHR, n = 6), or taking medications known to influence bone (MIB, n = 7) were compared with untrained subjects not taking supplemental hormones (Con, n = 6). Blood was taken from trained subjects before, immediately after, and 2 h after resistive exercise (same time points for resting Con). TLR4 mRNA expression (RT-PCR) was not different among groups or across time but was significantly (P = 0.044) lower (1.9-fold) when trained groups were collapsed and compared with Con. There was also a significant group effect (P < 0.0001) for TLR4 mRNA when expressed per monocyte. CD14 expression was significantly (P = 0.006) lower (2.3-fold) for training groups collapsed and compared with Con. CD14 mRNA, expressed per monocyte, was significantly lower immediately after resistive exercise for NHR, HRT, and MIB compared with Con. There were few significant effects detected for IL-6, IL-1beta, and TNF-alpha mRNA, but there was a significant group effect (P < 0.0001) for TNF-alpha mRNA expressed per monocyte (Con > HRT, NHR, MIB). These findings suggest that there may be a resistive exercise training-induced reduction in TLR4/CD14 expression in older women. Further research is needed to determine whether lower TLR4/CD14 could explain the lower LPS-stimulated inflammatory cytokines observed in these women.

Aged↗

PubMed2003

Carbohydrate loading and supplementation in endurance-trained women runners.

The purpose of this study was to examine the effect of carbohydrate (CHO) augmentation on endurance performance and substrate utilization in aerobically trained women. Eight endurance-trained women completed a 24.2-km (15 mile) self-paced treadmill performance run under three conditions: CHO supplementation (S), CHO loading and supplementation (L+S), and placebo (P). Dietary CHO was approximately 75% of energy intake for L+S and approximately 50% for both S and P. A 6% CHO-electrolyte solution (S and L+S) or placebo (P) was ingested preexercise (6 ml/kg) and every 20 min during exercise (3 ml/kg). Blood glucose was significantly higher at 40, 60, and 100 min during L+S, and at 60, 80, and 100 min during S compared with P (P < 0.05). Blood lactate was significantly higher (P < 0.05) during L+S than S and P. Blood glycerol was significantly lower (P < 0.05) at 20, 80, and 100 min during L+S, and at 80 and 100 min during S than P. The proportion of CHO (%) utilized during exercise was significantly higher (P < 0.05) during L+S (71.3 +/- 3.8%) and S (67.3 +/- 4.3%) than P (59.2 +/- 4.6%). Performance times (P > 0.05) were 132.5 +/- 6.3 min (S), 134.4 +/- 6.3 min (L+S), and 136.6 +/- 7.9 min (P). In conclusion, it appears that when CHO availability in women is increased through CHO loading and/or CHO supplementation, there is a concomitant increase in CHO utilization. However, this may not necessarily result in significantly improved performance.

Adult↗

PubMed2002

Effects of endurance training and resistance training on plasma lipoprotein profiles in elderly women.

It has been shown that high levels of high-density lipoprotein (HDL) cholesterol and low levels of low-density lipoprotein (LDL) cholesterol are associated with health maintenance in older women, but the few studies that have examined the relationship between exercise and plasma lipoprotein levels in this elderly population have been equivocal. In addition, there are no studies that examine the plasma lipoprotein response of two different types of exercise in a group of active but nonexercising women. Thus, the effects of exercise training on plasma lipoprotein levels in elderly women remain unclear. The purpose of this research was to examine the effects of endurance and resistance exercise on plasma lipoprotein levels in elderly women who were active but nonexercising prior to the study. A total of 45 healthy, active women, aged 70-87 years, were randomly assigned to either an aerobic training (AT, 76 +/- 5 years, n = 15), resistance training (RT, 73 +/- 3 years, n = 15), or control (C, 74 +/- 5 years, n = 15) group. The AT group walked 3 days a week at 70% heart rate reserve. The duration on day 1 was 20 minutes, and it was increased by 5 minutes each day until subjects were walking for 50 minutes (week 3). The exercise training session for the RT group consisted of one to three sets of eight repetitions of eight different exercises at an eight repetition maximum; the C group maintained normal activity. Weight and diet were unchanged across groups. The exercise interventions lasted 10 weeks. Blood samples were obtained from all subjects at week 0 and week 11. Training resulted in a significant decrease in 1-mile walk times and heart rate at completion of the walk for the AT group and a significant increase in eight repetition maximum of all RT exercises. Both AT and RT groups experienced increased HDL cholesterol and decreased triglycerides at week 11 compared with week 0. There were no positive changes in control lipoproteins. Both triglycerides and the total cholesterol to HDL ratio increased significantly while total cholesterol, HDL cholesterol, and LDL cholesterol remained unchanged. The RT group also had significantly lower LDL cholesterol and total cholesterol compared with controls at week 11. Both RT and endurance training resulted in favorable changes to plasma lipoprotein levels for elderly women in only 10 weeks. The fact that this occurred without concurrent changes in weight or diet is an indication that high-intensity exercise alone can be used to modify lipoproteins in populations of healthy elderly women.

Age Factors↗

PubMed2002

Fatigue during high-intensity intermittent exercise: application to bodybuilding.

Resistance exercise is an activity performed by individuals interested in competition, those who wish to improve muscle mass and strength for other sports, and for individuals interested in improving their strength and physical appearance. In this review we present information suggesting that phosphocreatine depletion, intramuscular acidosis and carbohydrate depletion are all potential causes of the fatigue during resistance exercise. In addition, recommendations are provided for nutritional interventions, which might delay muscle fatigue during this type of activity.

Acid-Base Equilibrium↗

PubMed2002

Reliability of an exercise protocol designed to evaluate resistance exercise performance.

The purpose of the present investigation was to evaluate the reliability a protocol used to assess short-term resistance exercise performance. Six men participated in this investigation after giving their consent. Subjects (N = 6) performed 6 sets of leg extensions at 80% of 10 repetition maximum (RM). Ten repetitions were performed during the first 3 sets; during the last 3 sets subjects exercised to fatigue. Ninety seconds of seated passive recovery separated each set. Subsequently, 2 experimental trials were conducted in which the exercise protocol was identical to the familiarization trial. There was a significant decline in performance from set 4 (13.5 +/- 0.9 reps) to set 5 (11.9 +/- 0.8 reps) and set 4 to set 6 (10.8 +/- 1.0 reps), suggesting that the protocol did induce fatigue. The intraclass correlations were 0.992, 0.992, and 0.993 for the fourth, fifth, and sixth sets, respectively. The average coefficients of variation for the fourth, fifth, and sixth sets were 6.7, 2.7, and 7.1%, respectively. These data suggest that the resistance training protocol used in this investigation is reliable and may be useful in evaluating interventions designed to improve fatigue resistance.

Adult↗