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.

Adults with Down syndrome (DS) are at risk for developing Alzheimer disease (AD). While plasma Aβ is known to be elevated in DS, its relationship to cognitive functioning is unknown. To assess this relationship, samples from two groups of subjects were used. In the first group, nondemented adults with DS were compared to: 1) a group of young and old individuals without DS and 2) to a group of patients with AD. Compared to these controls, there were significantly higher levels of plasma Aβ in nondemented adults with DS while AD patients showed lower levels of plasma Aβ. A larger second group included demented and nondemented adults with DS, in order to test the hypothesis that plasma Aβ may vary as a function of dementia and ApoE genotype. Plasma Aβ levels alone did not dissociate DS adults with and without dementia. However, in demented adults with DS, ApoE4 was associated with higher Aβ40 but not Aβ42. After controlling for level of intellectual disability (mild, moderate, profound) and the presence or absence of dementia, there was an improved prediction of neuropsychological scores by plasma Aβ. In summary, plasma Aβ can help predict cognitive function in adults with DS independently of the presence or absence of dementia.

Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months-69 years) and in 26 controls (5 months-100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alphasecretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Aβ) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Aβ degradation and clearance.

Children with ADHD have significantly higher rates of incontinence, constipation, urgency, infrequent voiding, nocturnal enuresis and dysuria than those without ADHD. Further study is needed to discern the cause of this difference and develop appropriate treatment strategies.

A long-term intervention (2.69 years) with an antioxidant diet, behavioral enrichment, or the combined treatment preserved and improved cognitive function in aged canines. While each intervention alone provided cognitive benefits, the combination treatment was additive. We evaluate the hypothesis that antioxidants, enrichment, or the combination intervention reduces age-related beta-amyloid (Aβ) neuropathology, as one mechanism mediating observed functional improvements. Measures assessed were Aβ neuropathology in plaques, biochemically extractable Aβ40 and Aβ42 species, soluble oligomeric forms of Aβ, and various proteins in the beta-amyloid precursor protein (APP) processing pathway. The strongest and most consistent effects on Aβ pathology were observed in animals receiving the combined antioxidant and enrichment treatment. Specifically, Aβ plaque load was significantly decreased in several brain regions, soluble Aβ42 was decreased selectively in the frontal cortex, and a trend for lower Aβ oligomer levels was found in the parietal cortex. Reductions in Aβ may be related to shifted APP processing towards the non-amyloidogenic pathway, as alpha-secretase enzymatic activity was increased, in the absence of changes in beta-secretase activity. While enrichment alone had no significant effects on Aβ, reduced Aβ load and plaque maturation occurred in animals receiving antioxidants as a component of treatment. AB measures did not correlate with cognitive performance on any of the 6 tasks assessed, suggesting that modulation of AB alone may be a relatively minor mechanism mediating cognitive benefits of the interventions. Overall, the data indicate that multi-domain treatments may be a valuable intervention strategy to reduce neuropathology and improve cognitive function in humans.

No abstract

Exercise can stimulate catabolic inflammatory cytokines even in healthy children. For patients with cystic fibrosis (CF), this may be problematic because CF is characterized by increased inflammation and suppressed growth. We examined fitness and the response to brief exercise of interleukin-6 (IL-6), tumor necrosis factor-␣ (TNF-␣ ), insulinlike growth factor-I (IGF-I), and IGF binding protein-1 (IGFBP-1) in 14 subjects with CF (10.5 Ϯ 0.8 yr of age), 9 of whom were treated with ibuprofen, and 14 healthy control subjects (11.6 Ϯ 0.5 yr of age, NS). Subjects performed brief intermittent, constant work rate protocol (scaled to each individual's exercise capacity) with blood and urine sampling. Peak O 2 was correlated with IGF-I (r ϭ 0.68, p Ͻ 0.01) in control subjects but not in subjects with CF. In subjects with CF, baseline IL-6 was 79% greater (p Ͻ 0.05) and IGF-I was 47% lower than in control subjects (p Ͻ 0.05). Post hoc analysis revealed a progressive increase in the IL-6 response to exercise, with the lowest increase observed in control subjects (11.8 Ϯ 4.6 pg/L/kJ), higher increases in patients with CF treated with ibuprofen (23.4 Ϯ 7.7 pg/L/kJ), and highest in subjects with CF not receiving ibuprofen (29.2 Ϯ 7.5 pg/L/kJ). Qualitatively similar results were observed for TNF-␣ . Exercise also significantly increased IGFBP-1 in both control subjects and subjects with CF. Brief exercise can increase even chronically elevated inflammatory mediators in CF, and this response may be attenuated by ibuprofen.

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.