Biomedical subjects

Dan M Cooper

Publications and source records attributed to Dan M Cooper.

30 records · Page 2Linked to original sources

PubMed2003

Airway diffusing capacity of nitric oxide and steroid therapy in asthma.

Exhaled nitric oxide (NO) concentration is a noninvasive index for monitoring lung inflammation in diseases such as asthma. The plateau concentration at constant flow is highly dependent on the exhalation flow rate and the use of corticosteroids and cannot distinguish airway and alveolar sources. In subjects with steroid-naive asthma (n = 8) or steroid-treated asthma (n = 12) and in healthy controls (n = 24), we measured flow-independent NO exchange parameters that partition exhaled NO into airway and alveolar regions and correlated these with symptoms and lung function. The mean (+/-SD) maximum airway flux (pl/s) and airway tissue concentration [parts/billion (ppb)] of NO were lower in steroid-treated asthmatic subjects compared with steroid-naive asthmatic subjects (1,195 +/- 836 pl/s and 143 +/- 66 ppb compared with 2,693 +/- 1,687 pl/s and 438 +/- 312 ppb, respectively). In contrast, the airway diffusing capacity for NO (pl.s-1.ppb-1) was elevated in both asthmatic groups compared with healthy controls, independent of steroid therapy (11.8 +/- 11.7, 8.71 +/- 5.74, and 3.13 +/- 1.57 pl.s-1.ppb-1 for steroid treated, steroid naive, and healthy controls, respectively). In addition, the airway diffusing capacity was inversely correlated with both forced expired volume in 1 s and forced vital capacity (%predicted), whereas the airway tissue concentration was positively correlated with forced vital capacity. Consistent with previously reported results from Silkoff et al. (Silkoff PE, Sylvester JT, Zamel N, and Permutt S, Am J Respir Crit Med 161: 1218-1228, 2000) that used an alternate technique, we conclude that the airway diffusing capacity for NO is elevated in asthma independent of steroid therapy and may reflect clinically relevant changes in airways.

Adolescent↗

PubMed2003

Negative energy balance plays a major role in the IGF-I response to exercise training.

Circulating IGF-I is correlated with fitness, but results of prospective exercise training studies have been inconsistent, showing both increases and decreases in IGF-I. We hypothesized that energy balance, often not accounted for, is a regulating variable such that training plus an energy intake deficit would cause a reduction in IGF-I, whereas training plus energy intake excess would lead to an increased IGF-I. To test this, 19 young, healthy men completed a 7-day strenuous exercise program in which they were randomly assigned to either a positive energy balance [overfed (OF), n = 10] or negative energy balance [underfed (UF), n = 9] group. IGF-I (free and total), insulin, and IGF-binding protein-1 were measured before, during, and 1 wk after the training. Weight decreased in the UF subjects and increased in the OF subjects. Free and total IGF-I decreased substantially in the UF group (P < 0.0005 for both), but, in the OF group, IGF-I remained unchanged. The UF group also demonstrated an increase in IGF-binding protein-1 (P < 0.027), whereas glucose levels decreased (P < 0.0005). In contrast, insulin was reduced in both the OF and UF exercise-training groups (P < 0.044). Finally, within 7 days of the cessation of the diet and training regimen, IGF-I and IGF-binding protein-1 in the UF group returned to preintervention levels. We conclude that energy balance during periods of exercise training influences circulating IGF-I and related growth mediators. Exercise-associated mechanisms may inhibit increases in IGF-I early in the course of a training protocol, even in overfed subjects.

Adolescent↗

PubMed2003

Catecholamine response to exercise in children with attention deficit hyperactivity disorder.

The objective of this study was to examine differences in catecholamine (CA) response to exercise between children who had received a diagnosis of attention-deficit/hyperactivity disorder (ADHD) and age- and gender-matched controls. On the basis of the notion of a CA dysfunction in ADHD, we reasoned that the normal robust increase in circulating CA seen in response to exercise would be blunted in children with ADHD. To test this, we recruited 10 treatment-naïve children with newly diagnosed ADHD and 8 age-matched controls (all male) and measured CA response to an exercise test in which the work was scaled to each subject's physical capability. After exercise, epinephrine and norepinephrine increased in both control and ADHD subjects (p = 0.006 and p = 0.002, respectively), but the responses were substantially blunted in the ADHD group (p = 0.018) even though the work performed did not differ from controls. Circulating dopamine increased significantly in the control subjects (p < 0.016), but no increase was noted in the subjects with ADHD. Finally, a significant attenuation in the lactate response to exercise was found in ADHD (between groups, p < 0.005). Our data suggest that CA excretion after exercise challenges in children with ADHD is deficient. This deficiency can be detected using a minimally invasive, nonpharmacologic challenge.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

Neuromotor noise limits motor performance, but not motor adaptation, in children.

Children do not typically appear to move with the same skill and dexterity as adults, although they can still improve their motor performance in specific tasks with practice. One possible explanation is that their motor performance is limited by an inherently higher level of movement variability, but that their motor adaptive ability is robust to this variability. To test this hypothesis, we examined motor adaptation of 43 children (ages 6-17) and 12 adults as they reached while holding the tip of a lightweight robot. The robot applied either a predictable, velocity-dependent field (the "mean field") or a similar field that incorporated stochastic variation (the "noise field"), thereby further enhancing the variability of the subjects' movements. We found that children exhibited greater initial trial-to-trial variability in their unperturbed movements but were still able to adapt comparably to adults in both the mean and noise fields. Furthermore, the youngest children (ages 6-8) were able to reduce their variability with practice to levels comparable to the remaining children groups although not as low as adults. These results indicate that children as young as age 6 possess adult-like neural systems for motor adaptation and internal model formation that allow them to adapt to novel dynamic environments as well as adults on average despite increased neuromotor or environmental noise. Performance after adaptation is still more variable than adults, however, indicating that movement inconsistency, not motor adaptation inability, ultimately limits motor performance by children and may thus account for their appearance of incoordination and more frequent motor accidents (e.g., spilling, tripping). The results of this study also suggest that movement variability in young children may arise from two sources--a relatively constant, intrinsic source related to fundamental physiological constraints of the developing motor system and a more rapidly modifiable source that is modulated depending on the current motor context.

Adaptation, Physiological↗

PubMed2003

Adipocytokines, body composition, and fitness in children.

Recent evidence suggests a role for adipose derived cytokines (adipocytokines) such as tumor necrosis factor-alpha (TNF-alpha), IL-6, and the recently discovered adiponectin in the mechanism of impaired glucose regulation and atherosclerosis in adults. However, the relationship between adipocytokines and body composition, fasting insulin, and fitness is virtually unknown children. Fasting blood sampling was performed in 30 healthy, predominately Hispanic- and Asian-American children (16 boys, mean age 12.7 +/- 0.1 y old) from a lower socioeconomic area in Los Angeles. Adiposity was measured by dual x-ray absorptiometry (DEXA); and peak oxygen uptake using cycle ergometry. Adiponectin (mean 10.8 +/- 0.8 micro g/mL) was inversely correlated with body mass index (BMI, as percentile by age) (r = -0.48, p = 0.011) and fat mass (r = -0.43, p = 0.03). In contrast, TNF-alpha and IL-6 were both positively correlated with BMI and fat mass. Adiponectin was inversely correlated with fasting insulin (r = -0.52, p = 0.006), but no correlations were found for insulin and either TNF-alpha or IL-6. Adiponectin was correlated with HDL (r = 0.448, p = 0.019). Paradoxically, peak oxygen consumption (an indicator of fitness) was negatively correlated with adiponectin levels (r = -0.471, p = 0.013) and positively correlated with TNF-alpha (r = 0.560, p = 0.002). In children, adipocytokines are correlated with fat mass, insulin sensitivity, and cardiovascular risk factors in a manner that is qualitatively similar to relationships recently observed in adults. In more obese children, the mass of fat tissue may attenuate potentially positive effects of fitness on circulating levels of adiponectin and TNF-alpha. The novel data on adiponectin suggest that deleterious dysregulation of adipocytokines associated with obesity may occur relatively early in life.

Absorptiometry, Photon↗

PubMed2003

Effect of water polo practice on cytokines, growth mediators, and leukocytes in girls.

PURPOSE: The effects of exercise on growth and development are mediated through a complex interaction between the endocrine, immune, and nervous systems. Very little is known about how these systems respond to exercise in children or adolescents. Moreover, there are few studies that have examined growth factors, inflammatory cytokines, and leukocyte responses to "real-life" or field exercise solely in girls. Thus, the goal of the present study was to determine the acute exercise-induced alterations in the growth hormone --> insulin-like growth factor-I axis, inflammatory cytokines, and certain aspects of immune function in a group of adolescent girls after a typical water polo practice. METHODS: Ten, healthy, high-school female subjects, 14-16 yr old, performed a single, typical, 1.5-h water polo practice session. Blood was sampled before and after the session. RESULTS: The exercise resulted in an increase in HR (from 82 +/- 2 to 161 +/- 5 beats.min(-1) at 30 min, P < 1.4.10(-6) ), as well as in circulating lactate levels (375 +/- 66%, P < 0.0005). Significant increases where noted in circulating IL-6 (396 +/- 162%, P < 0.005) and IL-1ra (71 +/- 20%, P < 0.015). A substantial increase in the level of IGFBP-1 (1344 +/- 344%, P < 0.001) was also observed. Interestingly, TNF-alpha levels decreased after the exercise (-10.4 +/- 3.8%, P < 0.04) as did insulin (55 +/- 12%, P < 0.005). The exercise led to significant increases in granulocytes, monocytes, and lymphocytes. The exercise significantly influenced adhesion molecules (such as CD62L and CD54), which has not been previously studied in adolescent girls. CONCLUSIONS: These data demonstrate that an intense "real-life" exercise bout in adolescent females leads to profound increases in inflammatory cytokines and reductions in anabolic mediators with substantial alterations in white blood cell subpopulations and adhesion molecules. The role of these frequent, almost daily immune and cytokine changes on growth and development have yet to be determined.

Adolescent↗

PubMed2003

Impact of high-intensity exercise on nitric oxide exchange in healthy adults.

PURPOSE: After exercise, exhaled NO concentration has been reported to decrease, remain unchanged, or increase. A more mechanistic understanding of NO exchange dynamics after exercise is needed to understand the relationship between exercise and NO exchange. METHODS: We measured several flow-independent NO exchange parameters characteristic of airway and alveolar regions using a single breath maneuver and a two-compartment model (maximum flux of NO from the airways, J'(awNO), pL x s-1; diffusing capacity of NO in the airways, D(awNO), pL x s-1 x ppb-1; steady state alveolar concentration, C(alv,ss), ppb; mean airway tissue NO concentration, C(awNO), ppb), as well as serum IL-6 at baseline, 3, 30, and 120 min after a high-intensity exercise challenge in 10 healthy adults (21-37 yr old). RESULTS: D(awNO) (mean +/- SD) increased (37.1 +/- 44.4%), whereas J'(awNO) and C(awNO) decreased (-7.27 +/- 11.1%, -26.1 +/- 24.6%, respectively) 3 min postexercise. IL-6 increased steadily after exercise to 481% +/- 562% above baseline 120 min postexercise. CONCLUSION: High-intensity exercise acutely enhances the ability of NO to diffuse between the airway tissue and the gas phase, and exhaled NO might be used to probe both the metabolic and physical properties of the airways.

Adult↗

PubMed2002

Flow-independent nitric oxide exchange parameters in cystic fibrosis.

Exhaled nitric oxide (NO) remains a promising noninvasive index for monitoring inflammatory lung diseases; however, the plateau concentration (C(NO,plat)) is nonspecific and requires a constant exhalation flow rate. We utilized a new technique that employs a variable flow rate to estimate key flow-independent parameters characteristic of NO exchange in a group (n = 9) of 10 to 14 yr-old healthy children and children with cystic fibrosis (CF): maximum flux of NO from the airways (J(NO,max'), pl s(-1)), diffusing capacity of NO in the airways (D(NO,air'), pl s(-1) ppb(-1)), steady-state alveolar concentration (C(alv,ss'), ppb), and mean tissue concentration of NO in the airways (C(tiss,air'), ppb). We determined the following mean (+/- SD) values in the healthy children and patients with CF for J(NO,max'), D(NO,air'), C(alv,ss'), and C(tiss,air'), respectively: 784 +/- 465 and 607 +/- 648 pl s(-1); 4.82 +/- 3.07 and 17.6 +/- 12.1 pl s(-1) ppb(-1); 4.63 +/- 3.59 and 1.96 +/- 1.18 ppb; and 198 +/- 131 and 38 +/- 25 ppb. D(NO,air) is elevated (p = 0.007), and both C(alv,ss) and C(tiss,air) are reduced (p = 0.05 and 0.002, respectively) in CF. In contrast, C(NO,plat) for healthy control subjects and patients with CF are not statistically different at both exhalation flow rates of 50 ml/s (17.5 +/- 11.5 and 11.5 +/- 8.97) and at 250 ml/s (7.11 +/- 5.36 and 4.28 +/- 3.43). We conclude that D(NO,air'), C(tiss,air'), and C(alv,ss) may be useful noninvasive markers of CF.

Adolescent↗

PubMed2002

Systemic vs. local cytokine and leukocyte responses to unilateral wrist flexion exercise.

We hypothesized that brief exercise of a small muscle group would lead to local rather than systemic alterations in cytokines, peripheral blood mononuclear cells, and mediators of angiogenesis. Fifteen men and eight women (age range 22-36 yr old) performed 10 min of unilateral wrist flexion exercise. Blood was sampled from venous catheters in the resting and exercising arm at baseline, at the end of exercise, and at 10, 30, 60, and 120 min after exercise. Lactate was significantly elevated in the exercising arm (+276 +/- 35%; P < 0.0005) with no change in the resting arm. In contrast, increases in both arms were observed for interleukin-6 (+139 +/- 51%; P < 0.0005), growth hormone (+1,104 +/- 284%; P < 0.003), natural killer cells (+81 +/- 9%; P < 0.0005), and lymphocytes expressing CD62L, CD11a, and CD54. There were no significant differences in these increases between the resting and exercising arm. Catecholamines increased in both arms [epinephrine peak increase, +226 +/- 36% (P < 0.001); norepinephrine peak increase, +90 +/- 15% (P < 0.01)]. Fibroblast growth factor-2 initially decreased with exercise in both arms, and this was followed by a rebound increase. Vascular endothelial growth factor demonstrated a small but significant increase in both arms (+124 +/- 31%; P < 0.05). Brief, low-intensity exercise leads to a systemic rather than local response of mediators that could be involved in inflammation, repair, or angiogenic adaptation to physical activity.

Adult↗

PubMed2002

The effect of endurance-type exercise training on growth mediators and inflammatory cytokines in pre-pubertal and early pubertal males.

Recent studies demonstrate an unexpected reduction in circulating levels of IGF-I after 5 wk of endurance-type exercise training in adolescent boys and girls and prepubertal girls. We hypothesized that the reduction in IGF-I would be accompanied by a training-associated stimulation of proinflammatory cytokines IL-1beta, IL-6, or tumor necrosis factor-alpha (TNF-alpha), each of which can inhibit the GH-->IGF-I axis. Healthy boys (age range 9-11 y old, mean Tanner 1.7) volunteered for the study and were randomized to control (n = 14) and training groups (n = 12) for 5 wk. After the intervention, significant increase in fitness was observed in the training group but not control group. Although IGF-I was correlated at baseline to peak oxygen consumption in all subjects, there was a significant decrease in IGF-I and IGF binding protein-3 in the training subjects (-12.8 +/- 7.3% and -17.5 +/- 7%, respectively, p < 0.05). In contrast, IGF binding protein-2, known to inhibit anabolic effects of IGF-I, increased in the training subjects (27.8 +/- 11%, p < 0.02) as did IL-1beta and TNF-alpha (51.5 +/- 30.22%, p < 0.02, and 44.5 +/- 23.2%, p < 0.02, respectively). Finally, we also found that GHBP was inversely correlated with fitness, suggesting altered GH function in more-sedentary boys. Thus, these data support the hypothesis that a sustained increase in physical activity can stimulate proinflammatory cytokines, which may contribute to suppression of the GH-->IGF-I axis. Physical activity can influence growth and development through its influence on anabolic and catabolic mediators.

Body Constitution↗

PubMed2002

Exercise, diet, and childhood obesity: the GH-IGF-I connection.

The recent "obesity epidemic" among children and adolescents is a major public health concern. The mechanisms responsible for the increased incidence of childhood obesity are not yet well understood. The absence of a clear mechanism makes treating the obese child or adolescent a difficult task, and standardized therapeutic approaches simply do not yet exist. Metabolic derangements associated with obesity may contribute to the difficulty in treatment. Observed abnormalities in the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis in obese adults and the impact of exercise on the GH-IGF-I system are of particular relevance to the growing obese child. In this review, we focus on the interacting mechanisms of diet and exercise through specific hormonal mediators and their contribution to the current obesity epidemic. An improved understanding of these mechanisms may be helpful in creating effective treatment programs for children with obesity.

Adipose Tissue↗

PubMed2002

Effect of intense exercise on inflammatory cytokines and growth mediators in adolescent boys.

OBJECTIVE: Exercise can enhance growth and development in children, but recent investigations have revealed an intriguing paradox. Namely, the early (4-5 weeks) response to training programs in children lead to a catabolic, growth hormone (GH)-resistant state rather than the expected anabolic activation of the GH-->insulin-like growth factor-I (IGF-I) axis. This paradox led us to hypothesize that single bouts of exercise in children could stimulate proinflammatory cytokines known to inhibit directly anabolic activity of the GH-->IGF-1 axis (interleukin [IL]-6, IL-1beta, and tumor necrosis factor-alpha [TNF-alpha]). METHODS: Eleven healthy high school-age boys, age 14 to 18.5 years, performed a single, typical, 1.5-hour wrestling practice session. Blood was sampled before and after the session. RESULTS: We found significant decreases in anabolic mediators: total IGF-I (-11.2 +/- 2.3%), bound IGF-I (-11.2 +/- 2.4%), and insulin (-42 +/- 10%. However, there was no change in unbound IGF-I. Remarkable increases were found in proinflammatory cytokines IL-6 (795 +/- 156%), TNF-alpha (30 +/- 12%), and IL-1beta (286 +/- 129%) and in IGF-binding protein-1 (835 +/- 234%), which itself is stimulated by inflammatory cytokines and is known to inhibit IGF-I. Evidence for compensatory mechanisms to counter the antianabolic inflammatory response to acute exercise were also noted: IL-1ra increased (80 +/- 20%) and IGF-binding protein-3 proteolysis (which can maintain unbound, biologically active IGF-I despite losses in total IGF-I) increased significantly (101 +/- 39%) as well. CONCLUSIONS: These data demonstrate that an intense exercise bout in male adolescents leads to reductions in anabolic mediators and profound increases in inflammatory cytokines. This might explain the development of what seems to be a paradoxical catabolic state in the initial phases of exercise training programs.

Adolescent↗