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Biomedical subjects

Dan Nemet

Publications and source records attributed to Dan Nemet.

At least 19 recordsLinked to original sources

Effect of rhIL-6 infusion on GH-->IGF-I axis mediators in humans.

Exercise leads to simultaneous increases in mediators signaling apparently antagonistic functional responses such as growth factors and inflammatory mediators. The aim of the present study was to demonstrate the physiological effect of IL-6 on circulating components of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis. Twelve men (ages 26 +/- 2 yr) were divided into two groups (n = 6 in each group), receiving either albumin or recombinant human (rh) IL-6 infusion. IL-6 was infused via an antecubital vein, and a contralateral antecubital vein was used for blood sampling. The IL-6 dose was chosen to reach plasma levels of IL-6 characteristic of intense exercise (5 microg/h, for 3 h, resulting in plasma levels of 100 pg/ml). Blood samples for GH, GH binding protein, IGF-I, and IGF binding protein (IGFBP)-1 and -3 were collected at baseline, 30 min, and 1, 2, 3, 4, 5, and 8 h after the beginning of the rhIL-6 infusion. IL-6 levels increased only in the rhIL-6-infused group (P < 0.0005) and returned to baseline after the infusion was stopped. IL-6 infusion led to a significant increase in GH, peaking 1 h after the beginning of infusion (P < 0.001). A decrease in total IGF-I levels was noted only in the rhIL-6-infused group (P < 0.027). An initial decrease in IGFBP-1 levels was noted in both groups during infusion (P < 0.03). Following the initial decrease, there was a significant increase in IGFBP-1 levels only in the IL-6-infused participants, peaking at 2 after the infusion cessation (P < 0.001). IL-6 infusion had no effect on GH binding protein, IGFBP-3, and acid-labile subunit levels. rhIL-6 levels similar to the levels found after strenuous exercise induced a typical exercise-associated GH-->IGF-I axis response (increase GH, decreased IGF-I, and elevated IGFBP-1). The results suggest that IL-6 plays a role in the GH-->IGF-I response to intense exercise.

Adult↗

Exercise, caloric restriction, and systemic oxidative stress.

BACKGROUND: In humans, the main sources of reactive oxygen species (ROS), the molecules causing oxidative stress, are mitochondrial superoxide ions and neutrophil-derived oxidative radicals. Circulating antioxidants contribute to the protection against oxidative stress. Although the formation of ROS and secretion of antioxidants are independently regulated by exercise and diet, little is known about their combined effect. We hypothesized that relatively brief, intense exercise training may reduce systemic oxidation via an intrinsic mechanism, independent of changes in circulating antioxidants and of neutrophil-derived enzymes (as may be caused by concomitant caloric restriction). METHODS: Nineteen volunteers exercised for 7 days, 3 hours/day at 75% of oxygen uptake. Caloric intake was either 110% of caloric expenditure (high calorie, n=10) or 75% of caloric expenditure (low calorie, n=9). Blood samples for F2-isoprostanes, catalase, myeloperoxidase (MPO), interleukin-x (IL-x), white blood cells (WBCs), and other metabolic variables were taken at baseline, at the end of training, and 1 week after completion of the study. RESULTS: Serum F2-isoprostanes (microg/mL), markers of lipid peroxidation, were similarly reduced after 7 days of exercise in the high-calorie (from 35+/-4 to 27+/-2) and low-calorie (from 35+/-3 to 24+/-2) groups. Similar reductions were observed in IL-x concentrations. Conversely, no change was observed in circulating concentrations of the antioxidant catalase. Whereas total WBCs and neutrophil counts were significantly reduced in the low-calorie group only, no difference in neutrophil-derived MPO was measured between groups. CONCLUSION: A significant reduction in systemic oxidation may occur relatively early during intense exercise training in healthy young men, independent of caloric intake. The potential contribution to these effects of circulating antioxidants and neutrophil-derived oxidative enzymes will require further investigation.

Adolescent↗

[Exercise and the male reproductive system].

In contrast to the effect of exercise training on the menstrual cycle in female athletes, the effect of physical activity on the male reproductive system is described far less extensively in the scientific literature. The male reproductive system consists of the hypothalamic-pituitary unit and the testes. The testes are responsible for the production of sperm and androgens, mainly testosterone. Androgens are responsible for the development of secondary male characteristics, muscle and bone growth, production of red blood cells, sex drive and other behavioral aspects. The effect of physical activity on the male reproductive axis depends on the intensity and duration of the activity, the fitness level of the individual, and his nutritional status. A single bout of short and intensive aerobic and anaerobic exercise usually increases serum testosterone level. Prolonged moderate to intense exercise (> 2 hours) leads to an initial increase followed by a decline to or below the baseline levels. Exercise training frequently results in a decrease of serum testosterone, and may rarely be associated with reduced libido, sperm production and fertility. In addition, the reduced testosterone levels may attenuate the exercise-associated muscle hypertrophy, reduce the repair of muscle damage, reduce post exercise muscle rehabilitation and may play an important role in the development of over-training syndrome. Other consequences include decreased bone density and a possible effect on mood and behavior. Surprisingly, even in the medically well-supervised elite athletes, changes in testosterone levels and their effects on performance and health are rarely evaluated.

Exercise↗

Reduced exercise-associated response of the GH-IGF-I axis and catecholamines in obese children and adolescents.

Obesity blunts catecholamine and growth hormone (GH) responses to exercise in adults, but the effect of obesity on these exercise-associated hormonal responses in children is unclear. Therefore, the aim of the present study was to asses the effect of childhood obesity on the counterregulatory hormonal response to acute exercise. Twenty-five obese children (Ob; body mass index > 95%), and 25 age, gender, and maturity-matched normal-weight controls (NW) participated in the study. Exercise consisted of ten 2-min bouts of constant-cycle ergometry above the anaerobic threshold, with 1-min rest intervals between each bout. Pre-, post-, and 120-min postexercise blood samples were collected for circulating components of the GH-IGF-I axis and catecholamines. There were no differences in peak exercise heart rate, serum lactate, and peak O2 uptake normalized to lean body mass between the groups. Obesity attenuated the GH response to exercise (8.9 +/- 1.1 vs. 3.4 +/- 0.7 ng/ml in NW and Ob participants, respectively; P < 0.02). No significant differences in the response to exercise were found for other components of the GH-IGF-I axis. Obesity attenuated the catecholamine response to exercise (epinephrine: 52.5 +/- 12.7 vs. 18.7 +/- 3.7 pg/ml, P < 0.02; norepinephrine: 479.5 +/- 109.9 vs. 218.0 +/- 26.0 pg/ml, P < 0.04; dopamine: 17.2 +/- 2.9 vs. 3.5 +/- 1.9 pg/ml, P < 0.006 in NW and Ob, respectively). Insulin levels were significantly higher in the obese children and dropped significantly after exercise in both groups. Despite the elevated insulin levels and the blunted counterregulatory response, none of the participants developed hypoglycemia. Childhood obesity was associated with attenuated GH and catecholamine response to acute exercise. These abnormalities were compensated for, so that exercise was not associated with hypoglycemia, despite increased insulin levels in obese children.

Adolescent↗

Constitutive pro- and anti-inflammatory cytokine and growth factor response to exercise in leukocytes.

Leukocytosis following exercise is a well-described phenomenon of stress/inflammatory activation in healthy humans. We hypothesized that, despite this increase in circulating inflammatory cells, exercise would paradoxically induce expression of both pro- and anti-inflammatory cytokines and growth factors within these cells. To test this hypothesis, 11 healthy adult men, 18-30 yr old, performed a 30-min bout of heavy cycling exercise; blood sampling was at baseline, end-exercise, and 60 min into recovery. The percentage of leukocytes positive for intracellular cytokines and growth factors and mean fluorescence intensity was obtained by flow cytometry. Proinflammatory cytokines (IL-1alpha, IL-2, IFN-gamma, and TNF-alpha), a pleiotropic cytokine (IL-6), and anti-inflammatory cytokines and growth factors [IL-4, IL-10, growth hormone (GH), and IGF-I] were examined. Median fluorescence intensity was not affected by exercise; however, we found a number of significant changes (P < 0.05 by mixed linear model and modified t-test) in the numbers of circulating cells positive for particular mediators. The pattern of expression reflected both pro- and anti-inflammatory functions. In T-helper lymphocytes, TNF-alpha, but also IL-6, and IL-4 were significantly increased. In monocytes, both IFN-gamma and IL-4 increased. B-lymphocytes positive for GH and IGF-I increased significantly. GH-positive granulocytes also significantly increased. Collectively, these observations indicate that exercise primes an array of pro- and anti-inflammatory and growth factor expression within circulating leukocytes, perhaps preparing the organism to effectively respond to a variety of stressors imposed by exercise.

Adolescent↗

Effect of muscle fatigue on internal model formation and retention during reaching with the arm.

The motor system adapts to novel dynamic environments by forming internal models that predict the muscle forces needed to move skillfully. The goal of this study was to determine how muscle fatigue affects internal model formation during arm movement and whether an internal model acquired while fatigued could be recalled accurately after rest. Twelve subjects adapted to a viscous force field applied by a lightweight robot as they reached to a target. They then reached while being resisted by elastic bands until they could no longer touch the target. This protocol reduced the strength of the muscles used to resist the force field by approximately 20%. The bands were removed, and subjects adapted again to the viscous force field. Their adaptive ability, quantified by the amount and time constant of adaptation, was not significantly impaired following fatigue. The subjects then rested, recovering approximately 70% of their lost force-generation ability. When they reached in the force field again, their prediction of the force field strength was different than in a nonfatigued state. This alteration was consistent with the use of a higher level of effort than normally used to counteract the force field. These results suggest that recovery from fatigue can affect recall of an internal model, even when the fatigue did not substantially affect the motor system's ability to form the model. Recovery from fatigue apparently affects recall because the motor system represents internal models as a mapping between effort and movement and relies on practice to recalibrate this mapping.

Adaptation, Physiological↗

Breath ethanol and acetone as indicators of serum glucose levels: an initial report.

BACKGROUND: Many volatile organic compounds are present in exhaled breath and may represent by-products of endogenous biological processes. Ethanol is produced via alcoholic fermentation of glucose by gut bacteria and yeast, while acetone derives from oxidations of free fatty acids, influenced by glucose metabolism. We hypothesized that the integrated analysis of breath ethanol and acetone would provide a good approximation of the blood glucose profile during a glucose load. METHODS: We collected simultaneous exhaled breath gas, ambient air, and serum glucose and insulin samples from 10 healthy volunteers at baseline and during an oral glucose tolerance test (OGTT) (ingestion of 75 g of glucose followed by 120 min of sampling). Gas samples were analyzed by gas chromatography/mass spectrometry. RESULTS: Mean glucose values displayed a typical OGTT pattern (rapid increase, peak values at 30-60 min, and gradual return to near baseline by 120 min). Breath ethanol displayed a similar pattern early in the test, with peak values at 30 min; this was followed by a fast return to basal levels by 60 min. Breath acetone decreased progressively below basal levels, with lowest readings obtained at 120 min. A multiple regression analysis of glucose, ethanol, and acetone was used to estimate glucose profiles that correlated with measured glucose values with an average individual correlation coefficient of 0.70, and not lower than 0.41 in any subject. CONCLUSION: The integrated analysis of multiple exhaled gases may serve as a marker of blood glucose levels. Further studies are needed to assess the usefulness of this method in different populations.

Acetone↗

Short- and long-term beneficial effects of a combined dietary-behavioral-physical activity intervention for the treatment of childhood obesity.

BACKGROUND: Obesity has become the most common pediatric chronic disease in the modern era. Early prevention and treatment of childhood and adolescent obesity is mandated. Surprisingly, however, only a minor fraction of obese children participate in weight reduction interventions, and the longer-term effects of these weight-reduction interventions among children have not been elucidated. OBJECTIVE: To examine prospectively the short- and long-term effects of a 3-month, combined dietary-behavioral-physical activity intervention on anthropometric measures, body composition, dietary and leisure-time habits, fitness, and lipid profiles among obese children. METHODS: In this randomized prospective study, 24 obese subjects completed the 3-month intervention and were compared with 22 obese, age- and gender-matched, control subjects. RESULTS: At 3 months, there were significant differences in changes in body weight (-2.8 +/- 2.3 kg vs 1.2 +/- 2.2 kg), BMI (-1.7 +/- 1.1 kg/m2 vs -0.2 +/- 1.0 kg/m2), body fat percentage (from skinfold tests; -3.3 +/- 2.6% vs 1.4 +/- 4.7%), serum total cholesterol level (-24.6 +/- 15.1 mg/dL vs 0.8 +/- 18.7 mg/dL), low-density lipoprotein cholesterol level (-23.3 +/- 15.2 mg/dL vs -3.7 +/- 17.3 mg/dL), and fitness (215 +/- 107 seconds vs 50 +/- 116 seconds) in the intervention group versus the control group. After a 1-year follow-up period, there were significant differences between the intervention group (n = 20) and the control group (n = 20) in body weight (0.6 +/- 6.0 kg vs 5.3 +/- 2.7 kg), BMI (-1.7 +/- 2.3 kg/m2 vs 0.6 +/- 0.9 kg/m2), and body fat percentage. There was a significant increase in leisure-time physical activity among the intervention participants, compared with a decrease among the control subjects. CONCLUSIONS: Our data demonstrate the short- and longer-term beneficial effects of a combined dietary-behavioral-physical activity intervention among obese children. These results highlight the importance of multidisciplinary programs for the treatment of childhood obesity and emphasize their encouraging long-term effects.

Adolescent↗

Proteins and amino acid supplementation in sports: are they truly necessary?

Although dietary protein supplementation is commonly used by both athletes and people engaged in recreational sports, the data supporting its wide use are still limited. Some evidence supports the use of creatine and possibly HMB as ergogenic aids in specific situations [8], however this is also based on limited data. The use of supplements for the healthy, non-competitive adult engaged in recreational sports is usually not warranted.

Amino Acids↗

Osteopenia of prematurity - the role of exercise in prevention and treatment.

Premature infants have an increased risk of osteopenia due to limited bone mass accretion in utero and a greater need for bone nutrients. Currently, the diagnosis of osteopenia is based on clinical and radiological signs and measurements of biochemical markers. Recent studies suggest that measurements of circulating bone turnover markers, and bone strength assessment using quantitative ultrasound measurements of bone speed of sound (SOS) may help in the evaluation of bone metabolism in preterm infants. So far, most of the preventive efforts of osteopenia of prematurity focused on nutritional changes. Recent studies indicate that the passive range of motion exercise of the extremities results in a significantly greater increase of body weight, increased bone mineralization, increased bone formation markers and leptin levels, and attenuation of the natural post-natal decline in bone SOS. These results suggest that exercise may play an important role in the prevention and treatment of osteopenia of prematurity.

Bone Diseases, Metabolic↗

Effects of exercise on gene expression in human peripheral blood mononuclear cells.

Exercise leads to increases in circulating levels of peripheral blood mononuclear cells (PBMCs) and to a simultaneous, seemingly paradoxical increase in both pro- and anti-inflammatory mediators. Whether this is paralleled by changes in gene expression within the circulating population of PBMCs is not fully understood. Fifteen healthy men (18-30 yr old) performed 30 min of constant work rate cycle ergometry (approximately 80% peak O2 uptake). Blood samples were obtained preexercise (Pre), end-exercise (End-Ex), and 60 min into recovery (Recovery), and gene expression was measured using microarray analysis (Affymetrix GeneChips). Significant differential gene expression was defined with a posterior probability of differential expression of 0.99 and a Bayesian P value of 0.005. Significant changes were observed from Pre to End-Ex in 311 genes, from End-Ex to Recovery in 552 genes, and from Pre to Recovery in 293 genes. Pre to End-Ex upregulation of PBMC genes related to stress and inflammation [e.g., heat shock protein 70 (3.70-fold) and dual-specificity phosphatase-1 (4.45-fold)] was followed by a return of these genes to baseline by Recovery. The gene for interleukin-1 receptor antagonist (an anti-inflammatory mediator) increased between End-Ex and Recovery (1.52-fold). Chemokine genes associated with inflammatory diseases [macrophage inflammatory protein-1alpha (1.84-fold) and -1beta (2.88-fold), and regulation-on-activation, normal T cell expressed and secreted (1.34-fold)] were upregulated but returned to baseline by Recovery. Exercise also upregulated growth and repair genes such as epiregulin (3.50-fold), platelet-derived growth factor (1.55-fold), and hypoxia-inducible factor-I (2.40-fold). A single bout of heavy exercise substantially alters PBMC gene expression characterized in many cases by a brisk activation and deactivation of genes associated with stress, inflammation, and tissue repair.

Adolescent↗

Exercise, stress, and inflammation in the growing child: from the bench to the playground.

PURPOSE OF REVIEW: It is becoming increasingly clear that physical activity in children plays a critical role in growth and development, therapy for certain chronic diseases and disabilities, and in the pediatric origins of a variety of bone, metabolic, and cardiovascular diseases. New mechanistic insights have created the opportunity for a phase shift in understanding of the links between exercise and health in the context of the growing child. RECENT FINDINGS: Exercise even in healthy children profoundly alters stress, immune, and inflammatory mediators including peripheral blood mononuclear cells and circulating pro- and anti-inflammatory cytokines (like interleukin-6). Moreover, exercise even in healthy adults stimulates the production of reactive oxygen species (ROS) and mediators that attenuate them. Oxidative stress, in turn, alters growth and stress mediators. Both ROS and stress/inflammatory factors interact with powerful growth mediators like growth hormone and insulinlike growth factor-I. These findings suggest specific ways in which the balance between pro- and anti-inflammatory, catabolic, and anabolic factors associated with exercise can influence health and growth in children. SUMMARY: To address the current epidemic of physical inactivity and obesity in children and to optimize the therapeutic effects of exercise in children with disease and disability will require real changes in environments (eg, schools and playgrounds); innovative approaches to rehabilitation of children with chronic disease and disability; and enlightened training of child health professionals. Identifying novel exercise mechanisms involving stress, inflammation, and growth factors will help guide these efforts.

Age Factors↗

Cytokines and growth factors during and after a wrestling season in adolescent boys.

PURPOSE: Brief periods of aerobic exercise training lead to reductions, rather then the expected increases in circulating IGF-I. We hypothesized that intense exercise training in adolescents initially leads to simultaneous increases in proinflammatory cytokines and decreases in activity of the GH/IGF-I axis; and that as exercise training proceeds, levels of proinflammatory cytokines become reduced, and a rebound in IGF-I ensues leading to the higher IGF-I levels. METHOD: To test this, we evaluated the GH/IGF-I axis and levels of inflammatory cytokines (IL-6, TNF-alpha, IL-1beta, IL-1ra), body composition, and fitness in 13 healthy adolescent boys (mean age 15.9 +/- 0.3 yr) over the course of a high-school wrestling season. Subjects were tested preseason, midseason (6 wk), peak season (12-14 wk), and 4 wk postseason. RESULTS: No significant weight loss was noted throughout the season. During the wrestling season (mid and peak) both total (P < 0.046) and free (P < 0.002) IGF-I levels decreased, whereas proinflammatory cytokines (IL-1ra, P < 0.005; IGFBP-1, P < 0.013; and IGFBP-2, P < 0.025) increased. GHBP (P < 0.018) levels also decreased during the season. In the postseason, there were significant increases in GHBP, and free and total IGF-I, whereas proinflammatory cytokines decreased. CONCLUSIONS: An initial catabolic-type hormonal response occurs with intense exercise training in adolescents. This is followed by a rebound in circulating growth factors when the period of heavy training ceases.

Adolescent↗

Parental obesity and higher pre-intervention BMI reduce the likelihood of a multidisciplinary childhood obesity program to succeed--a clinical observation.

OBJECTIVE: To assess the effects and identify factors associated with success of a combined, structured multidisciplinary weight management program in obese children and adolescents. METHODS: Seventy-seven obese children (age 6-16 years) participated in a 12-month combined dietary-behavioral-exercise intervention. Thirty-seven (age and maturity comparable) obese children who did not participate in the structured program served as controls. Body weight, BMI, and BMI percentiles were measured at baseline, after 6 months, and at the end of the intervention. RESULTS: The combined intervention was associated with a significant decrease in BMI (from 25.9+/-0.4 to 24.5+/-0.4 kg/m2, p <0.0005) and BMI percentile (from 97.3+/-0.2% to 92.6+/-0.9%, p <0.0005). In contrast, obese children who did not participate in the structured program gained weight (from 51.4+/-3.6 to 57.7+/-3.7 kg, p <0.0005), increased their BMI (from 25.2+/-1.0 to 26.6+/-0.9 kg/m2, p <0.0005), and had a non-significant increase in BMI percentiles (from 94.9+/-0.8% to 95.4+/-0.9%, NS). Children with higher BMI percentiles and parental overweight tended to respond less favorably to the combined multidisciplinary program (p <0.01). CONCLUSIONS: A prolonged (12 mo), combined, structured multidisciplinary intervention for childhood obesity resulted in a significant decrease in BMI and BMI percentiles. Higher pre-intervention BMI percentiles and parental obesity were associated with less favorable responses to the combined intervention.

Adolescent↗

Bone speed of sound in infants of mothers with gestational diabetes mellitus.

OBJECTIVE: Bone strength in infants of mothers with gestational diabetes mellitus (IGDM) was reported to be either decreased or unaltered. However, no report using quantitative ultrasound measurement of speed of sound (QUS-SOS) for bone strength assessment has been published. The aim of the present study was to assess bone strength by QUS-SOS measurements in IGDM in comparison to healthy matched full-term infants. DESIGN: Nineteen IGDM and 18 healthy controls participated in the study. Postnatal tibial bone SOS was measured by Sunlight Omnisense. RESULTS: Mean birth weight (BW) of IGDM (3,587.6+/-148.6 g) was higher compared to the control infants (3,311.1+/-74.5 g), but this difference was not statistically significant. Mean bone SOS was significantly lower in IGDM (2,976.7+/-27.2 m/sec) compared to the control infants (3,093.3+/-23.6 m/sec; p <0.003). There was a significant negative correlation between bone SOS and BW in all the study participants (r = -0.32, p <0.025). No significant difference in BW and bone SOS was noted between infants with postnatal hypoglycemia and normoglycemia. There was no correlation between maternal HbA1c during pregnancy and neonatal bone SOS. CONCLUSIONS: Bone strength was significantly decreased in IGDM compared to healthy controls. Neonates with higher BW had lower bone SOS. Since mechanical strain is a potent stimulation for bone formation and strength, it is suggested that the reduced bone strength in IGDM may also be the result of reduced intrauterine fetal mobility due to maternal gestational diabetes mellitus.

Blood Glucose↗

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↗