RESUMO
CONTEXT: Pediatric studies have shown that aerobic exercise reduces metabolic risk, but dose-response information is not available. OBJECTIVES: To test the effect of different doses of aerobic training on insulin resistance, fatness, visceral fat, and fitness in overweight, sedentary children and to test moderation by sex and race. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled efficacy trial conducted from 2003 through 2007 in which 222 overweight or obese sedentary children (mean age, 9.4 years; 42% male; 58% black) were recruited from 15 public schools in the Augusta, Georgia, area. INTERVENTION: Children were randomly assigned to low-dose (20 min/d; n = 71) or high-dose (40 min/d; n = 73) aerobic training (5 d/wk; mean duration, 13 [SD, 1.6] weeks) or a control condition (usual physical activity; n = 78). MAIN OUTCOME MEASURES: The prespecified primary outcomes were postintervention type 2 diabetes risk assessed by insulin area under the curve (AUC) from an oral glucose tolerance test, aerobic fitness (peak oxygen consumption [VO2]), percent body fat via dual-energy x-ray absorptiometry, and visceral fat via magnetic resonance, analyzed by intention to treat. RESULTS: The study had 94% retention (n = 209). Most children (85%) were obese. At baseline, mean body mass index was 26 (SD, 4.4). Reductions in insulin AUC were larger in the high-dose group (adjusted mean difference, -3.56 [95% CI, -6.26 to -0.85] × 10(3) µU/mL; P = .01) and the low-dose group (adjusted mean difference, -2.96 [95% CI, -5.69 to -0.22] × 10(3) µU/mL; P = .03) than the control group. Dose-response trends were also observed for body fat (adjusted mean difference, -1.4% [95% CI, -2.2% to -0.7%]; P < .001 and -0.8% [95% CI, -1.6% to -0.07%]; P = .03) and visceral fat (adjusted mean difference, -3.9 cm3 [95% CI, -6.0 to -1.7 cm3]; P < .001 and -2.8 cm3 [95% CI, -4.9 to -0.6 cm3]; P = .01) in the high- and low-dose vs control groups, respectively. Effects in the high- and low-dose groups vs control were similar for fitness (adjusted mean difference in peak VO2, 2.4 [95% CI, 0.4-4.5] mL/kg/min; P = .02 and 2.4 [95% CI, 0.3-4.5] mL/kg/min; P = .03, respectively). High- vs low-dose group effects were similar for these outcomes. There was no moderation by sex or race. CONCLUSION: In this trial, after 13 weeks, 20 or 40 min/d of aerobic training improved fitness and demonstrated dose-response benefits for insulin resistance and general and visceral adiposity in sedentary overweight or obese children, regardless of sex or race. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00108901.
Assuntos
Adiposidade , Terapia por Exercício , Resistência à Insulina , Obesidade/terapia , Sobrepeso/terapia , Aptidão Física , Criança , Feminino , Humanos , Gordura Intra-Abdominal , Masculino , Comportamento Sedentário , Resultado do TratamentoRESUMO
Naturally derived chemical compounds are the foundation of much of our pharmacopeia, especially in antiproliferative and anti-infective drug classes. Here, we report that a naturally derived molecule called carmaphycin B is a potent inhibitor against both the asexual and sexual blood stages of malaria infection. Using a combination of in silico molecular docking and in vitro directed evolution in a well-characterized drug-sensitive yeast model, we determined that these compounds target the ß5 subunit of the proteasome. These studies were validated using in vitro inhibition assays with proteasomes isolated from Plasmodium falciparum. As carmaphycin B is toxic to mammalian cells, we synthesized a series of chemical analogs that reduce host cell toxicity while maintaining blood-stage and gametocytocidal antimalarial activity and proteasome inhibition. This study describes a promising new class of antimalarial compound based on the carmaphycin B scaffold, as well as several chemical structural features that serve to enhance antimalarial specificity.
Assuntos
Antimaláricos/farmacologia , Dipeptídeos/farmacologia , Oligopeptídeos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Inibidores de Proteassoma/farmacologia , Antimaláricos/síntese química , Artemisininas/farmacologia , Dipeptídeos/síntese química , Desenho de Fármacos , Ensaios Enzimáticos , Células Hep G2 , Humanos , Simulação de Acoplamento Molecular , Oligopeptídeos/síntese química , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/síntese química , Saccharomyces cerevisiae/efeitos dos fármacosRESUMO
The study tested the effect of aerobic exercise training on executive function in overweight children. Ninety-four sedentary, overweight but otherwise healthy children (mean age = 9.2 years, body mass index 85th percentile) were randomized to a low-dose (20 min/day exercise), high-dose (40 min/day exercise), or control condition. Exercise sessions met 5 days/week for 15 weeks. The Cognitive Assessment System (CAS), a standardized test of cognitive processes, was administered individually before and following intervention. Analysis of covariance on posttest scores revealed effects on executive function. Group differences emerged for the CAS Planning scale (p = .03). Planning scores for the high-dose group were significantly greater than those of the control group. Exercise may prove to be a simple, yet important, method of enhancing aspects of children's mental functioning that are central to cognitive and social development.
Assuntos
Cognição/fisiologia , Exercício Físico/fisiologia , Sobrepeso , Criança , Georgia , Humanos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To determine whether regular aerobic exercise improves symptoms of sleep-disordered breathing in overweight children, as has been shown in adults. RESEARCH METHODS AND PROCEDURES: Healthy but overweight (BMI > or =85th percentile) 7- to 11-year-old children were recruited from public schools for a randomized controlled trial of exercise effects on diabetes risk. One hundred children (53% black, 41% male) were randomly assigned to a control group (n = 27), a low-dose exercise group (n = 36), or a high-dose exercise group (n = 37). Exercise groups underwent a 13 +/- 1.5 week after-school program that provided 20 or 40 minutes per day of aerobic exercise (average heart rate = 164 beats per minute). Group changes were compared on BMI z-score and four Pediatric Sleep Questionnaire scales: Snoring, Sleepiness, Behavior, and a summary scale, Sleep-Related Breathing Disorders. Analyses were adjusted for age. RESULTS: Both the high-dose and low-dose exercise groups improved more than the control group on the Snoring scale. The high-dose exercise group improved more than the low-dose exercise and control groups on the summary scale. No group differences were found for changes on Sleepiness, Behavior, or BMI z-score. At baseline, 25% screened positive for sleep-disordered breathing; half improved to a negative screen after intervention. DISCUSSION: Regular vigorous exercise can improve snoring, a symptom of sleep-disordered breathing, in overweight children. Aerobic exercise programs may be valuable for prevention and treatment of sleep-disordered breathing in overweight children.
Assuntos
Exercício Físico , Obesidade/complicações , Ronco/epidemiologia , Ronco/terapia , Índice de Massa Corporal , Criança , Transtornos do Comportamento Infantil/epidemiologia , Transtornos do Comportamento Infantil/etiologia , Transtornos do Comportamento Infantil/terapia , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Obesidade/terapia , Prevalência , Fatores de Risco , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/etiologia , Síndromes da Apneia do Sono/terapia , Ronco/etiologia , Resultado do TratamentoRESUMO
The purpose of this study was to determine the effects of yoga training and a single bout of yoga on the intensity of delayed onset muscle soreness (DOMS). 24 yoga-trained (YT; n = 12) and non-yoga-trained (CON; n = 12), matched women volunteers were administered a DOMS-inducing bench-stepping exercise. Muscle soreness was assessed at baseline, 24, 48, 72, 96, and 120 hours after bench-stepping using a Visual Analog Scale (VAS). Groups were also compared on body awareness (BA), flexibility using the sit-and-reach test (SR), and perceived exertion (RPE). Statistical significance was accepted at p = 0.05. A 2 x 2 mixed factorial ANOVA with repeated measures at 24 and 48 hours revealed a significant (p < 0.05) group main effect with VAS scores greater for CON than YT. Paired t-tests revealed that in YT, VAS scores were higher before yoga class than after yoga class at 24 hours (21.4 [+/- 6.9] mm vs. 11.1 [+/- 4.1] mm; p = 0.02). The SR was greater in YT than in CON (65.0 [+/- 7.9] cm vs. 33.3 [+/- 7.0] cm; p < 0.01); however, no differences were found between yoga and control in BA (94.0 [+/- 4.4] units vs. 83.8 [+/- 3.7] units; p = 0.21) or in RPE at 5-minute intervals (2.9 [+/- 0.3], 5.3 [+/- 0.8], 5.8 [+/- 0.9], and 5.2 [+/- 0.8] vs. 2.5 [+/- 0.3], 4.0 [+/- 0.5], 4.2 [+/- 0.3], and 4.9 [+/- 0.4]. Yoga training and a single bout of yoga appear to attenuate peak muscle soreness in women following a bout of eccentric exercise. These findings have significant implications for coaches, athletes, and the exercising public who may want to implement yoga training as a preseason regimen or supplemental activity to lessen the symptoms associated with muscle soreness.