Body Composition, Falls, and Freezing of Gait in Parkinson's Disease: Gender-Specific Effects.

BACKGROUND: Postural instability and gait difficulties (PIGD) are a significant cause of mobility loss and lower quality of life in Parkinson's disease (PD). When PD progresses, patients may experience falls and freezing of gait (FoG) resulting in fear of falling and increasing sedentariness. Sedentary behavior results in sarcopenia associated with other changes in body composition, especially in older patients becoming frail. Previous studies have shown gender-specific changes in body composition with aging as well as gender disparities in symptoms and progression of PD, yet the association between gender-specific body composition and PIGD symptoms such as FoG along with falls, remains unexplored. OBECTIVE: This study aimed to investigate the association between gender-specific changes in body composition, FoG and falls assessment. METHODS: 136 PD subjects underwent detailed clinical test batteries and had whole-body composition assessed using dual-energy X-ray absorptiometry (DXA). Multivariate logistic forward stepwise regression was performed to define body composition associations for FoG and falls. RESULTS: Multivariate regression analysis revealed that in males with PD, lower leg lean mass was significantly associated with the presence of FoG (OR, 0.429; 95% CI, 0.219-0.839; p=0.013) but not with falls. In females with PD, higher leg adipose mass was significantly associated with falls (OR, 4.780; 95% CI, 1.506-15.174; p=0.008) but not with FoG. CONCLUSION: These observations suggest gender specific associations between body composition and FoG vs. falls in PD. Future research should explore the impact of interventions on body composition in individuals with PD by paying specific attention to gender differences.

Endogenous secretory RAGE increases with improvements in body composition and is associated with markers of adipocyte health.

BACKGROUND AND AIMS: The receptor for advanced glycation end products (RAGE) is implicated in obesogenesis. Conversely, soluble RAGE (sRAGE) competitively inhibits RAGE. Our aim was to determine the effects of weight-loss via alternate day fasting (ADF) on sRAGE isoforms and evaluate potential relationships with body composition. METHODS AND RESULTS: 42 obese participants were randomized to control (CON) or ADF. For 24 weeks, the ADF group consumed 25% or 125% of their caloric requirements on alternating days while the CON group did not change their diet. Body fat was measured via DXA, visceral fat (VAT) via MRI and subcutaneous fat (SAT) was derived by subtracting VAT from total fat. sRAGE isoforms were measured via ELISAs. After 24 weeks, ADF -6.8 (-9.5, -3.5)kg (Median, IQR) lost more weight than CON -0.3 (-1.9, 1.0)kg (p < 0.05). The change in endogenous secretory RAGE (esRAGE) was different between ADF 15 (-30, 78)pg/mL and CON -21 (-72, 16)pg/mL after 24 weeks (p < 0.05). To examine the effect of changes in body composition, the cohort was stratified by median weight-, fat-, SAT-, and VAT-loss. The changes in all sRAGE isoforms were different between those above and below median weight-loss (p < 0.05) with sRAGE isoforms tending to decrease in individuals below the median. Changes in total sRAGE and esRAGE were different between individuals above compared to below median fat- and SAT-loss (p < 0.05). Those above median fat-loss increased esRAGE by 29 (-5, 66)pg/mL (p < 0.05). CONCLUSION: Improvements in body composition are related to increased sRAGE isoforms, implicating sRAGE as a potential target for the treatment of obesity. CLINICAL TRIAL REGISTRATION: NCT00960505.

Influence of acetaminophen and ibuprofen on in vivo patellar tendon adaptations to knee extensor resistance exercise in older adults.

Millions of older individuals consume acetaminophen or ibuprofen daily and these same individuals are encouraged to participate in resistance training. Several in vitro studies suggest that cyclooxygenase-inhibiting drugs can alter tendon metabolism and may influence adaptations to resistance training. Thirty-six individuals were randomly assigned to a placebo (67 ± 2 yr old), acetaminophen (64 ± 1 yr old; 4,000 mg/day), or ibuprofen (64 ± 1 yr old; 1,200 mg/day) group in a double-blind manner and completed 12 wk of knee extensor resistance training. Before and after training in vivo patellar tendon properties were assessed with MRI [cross-sectional area (CSA) and signal intensity] and ultrasonography of patellar tendon deformation coupled with force measurements to obtain stiffness, modulus, stress, and strain. Mean patellar tendon CSA was unchanged (P > 0.05) with training in the placebo group, and this response was not influenced with ibuprofen consumption. Mean tendon CSA increased with training in the acetaminophen group (3%, P < 0.05), primarily due to increases in the mid (7%, P < 0.05) and distal (8%, P < 0.05) tendon regions. Correspondingly, tendon signal intensity increased with training in the acetaminophen group at the mid (13%, P < 0.05) and distal (15%, P = 0.07) regions. When normalized to pretraining force levels, patellar tendon deformation and strain decreased 11% (P < 0.05) and stiffness, modulus, and stress were unchanged (P > 0.05) with training in the placebo group. These responses were generally uninfluenced by ibuprofen consumption. In the acetaminophen group, tendon deformation and strain increased 20% (P < 0.05) and stiffness (-17%, P < 0.05) and modulus (-20%, P < 0.05) decreased with training. These data suggest that 3 mo of knee extensor resistance training in older adults induces modest changes in the mechanical properties of the patellar tendon. Over-the-counter doses of acetaminophen, but not ibuprofen, have a strong influence on tendon mechanical and material property adaptations to resistance training. These findings add to a growing body of evidence that acetaminophen has profound effects on peripheral tissues in humans.

Nonalcoholic fatty liver disease: biochemical and therapeutic considerations.

Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging chronic liver disease and is reported to affect up to 70-80% of overweight and obese individuals. NAFLD represents a spectrum of liver diseases that range from simple hepatic steatosis, to a more severe and treatment resistant stage that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy. The biochemical mechanisms that underlie NAFLD are unclear at this time, but there is evidence that insulin resistance is a major contributing factor. In addition, circulating concentrations of inflammatory cytokines (e.g., TNF-alpha, IL-6) as well as decreased antiinflammatory factors (e.g., adiponectin, IL-10) are not only implicated in the development of insulin resistance and type 2 diabetes, but are also related to NAFLD. Such inflammatory mechanisms are fundamental in the progression of NAFLD toward higher risk cirrhotic states. This review outlines the leading theories of pathogenesis of NAFLD and highlights the potential role of exercise in treating and preventing NAFLD. Regular exercise can reverse insulin resistance, suppress low-grade systemic inflammation, and attenuate inflammatory markers associated with NAFLD. Thus, exercise has the potential to become an effective treatment and prevention modality for NAFLD and NASH.

Influence of aging on the in vivo properties of human patellar tendon.

Tendons are important for optimal muscle force transfer to bone and play a key role in functional ability. Changes in tendon properties with aging could contribute to declines in physical function commonly associated with aging. We investigated the in vivo mechanical properties of the patellar tendon in 37 men and women [11 young (27 +/- 1 yr) and 26 old (65 +/- 1 yr)] using ultrasonography and magnetic resonance imaging (MRI). Patella displacement relative to the tibia was monitored with ultrasonography during ramped isometric contractions of the knee extensors, and MRI was used to determine tendon cross-sectional area (CSA) and signal intensity. At peak force, patellar tendon deformation, stress, and strain were 13 (P = 0.05), 19, and 12% less in old compared with young (P < 0.05). Additionally, deformation, stiffness, stress, CSA, and length were 18, 35, 41, 28, and 11% greater (P < 0.05), respectively, in men compared with women. After normalization of mechanical properties to a common force, no age differences were apparent; however, stress and strain were 26 and 22% higher, respectively, in women compared with men (P < 0.05). CSA and signal intensity decreased 12 and 24%, respectively, with aging (P < 0.05) in the midregion of the tendon. These data suggest that differences in patellar tendon in vivo mechanical properties with aging are more related to force output rather than an age effect. In contrast, the decrease in signal intensity indirectly suggests that the internal milieu of the tendon is altered with aging; however, the physiological and functional consequence of this finding requires further study.

Resistance exercise and cyclooxygenase (COX) expression in human skeletal muscle: implications for COX-inhibiting drugs and protein synthesis.

We have shown that ibuprofen and acetaminophen block cyclooxygenase (COX) synthesis of prostaglandin PGF(2alpha) and the muscle protein synthesis increase following resistance exercise. Confusingly, these two drugs are purported to work through different mechanisms, with acetaminophen apparently unable to block COX and ibuprofen able to nonspecifically block COX-1 and COX-2. A recently discovered intron-retaining COX, now known to have three variants, has been shown to be sensitive to both drugs. We measured the expression patterns and levels of the intron 1-retaining COX-1 variants (-1b1, -1b2, and -1b3), COX-1, and COX-2 at rest and following resistance exercise to help elucidate the COX through which PGF(2alpha), ibuprofen, and acetaminophen regulate muscle protein synthesis. Skeletal muscle biopsy samples were taken from 16 individuals (8M, 8F) before, 4, and 24 h after a bout of resistance exercise and analyzed using real-time RT-PCR. Relatively few individuals expressed the intron 1-retaining COX-1b variants (COX-1b1, -1b2, and -1b3) at any time point, and when expressed, these variants were in very low abundance. COX-1 was the most abundant COX mRNA before exercise and remained unchanged (P > 0.05) following exercise. COX-2 was not expressed before exercise, but increased significantly (P < 0.05) at 4 and 24 h after exercise. The inconsistent and low levels of expression of the intron 1-retaining COX-1 variants suggest that these variants are not likely responsible for the inhibition of PGF(2alpha) production and skeletal muscle protein synthesis after resistance exercise by ibuprofen and acetaminophen. Skeletal muscle-specific inhibition of COX-1 or COX-2 by these drugs should be considered.

The effect of strenuous aerobic exercise on skeletal muscle myofibrillar proteolysis in humans.

Relatively little is known about the dynamics of the skeletal muscle protein pool following aerobic exercise. Myofibrillar protein synthesis has recently been shown to be substantially elevated for 3 days after a strenuous 60 min bout of one-legged aerobic exercise, and this increase was surprisingly equal to or greater than what has been shown numerous times following resistance exercise over the same time course. Because net protein accretion is the sum of protein synthesis and degradation, we sought to directly measure skeletal muscle myofibrillar proteolysis in five healthy young males in response to an identical strenuous 60 min aerobic exercise bout and at the same time points (rest, 6, and 24 h post-exercise and 48 and 72 h post-exercise in a subset of subjects). We measured skeletal muscle myofibrillar proteolysis by monitoring the release of the natural tracer 3-methylhistidine (3MH) from the vastus lateralis muscle into the interstitial space via microdialysis. Skeletal muscle interstitial 3MH concentration was no different (P>0.05) from rest (5.16+/-0.38 nmol/mL) after 6 (5.37+/-0.55 nmol/mL), 24 (5.40+/-0.26 nmol/mL), 48 (5.50+/-0.74 nmol/mL), or 72 h (4.73+/-0.28 nmol/mL). These results suggest that proteolysis of the myofibrillar fraction of skeletal muscle is relatively refractory to an intense aerobic exercise stimulus for up to 3 days, despite the large increase in synthesis of this muscle fraction following the same exercise stimulus. The apparent net myofibrillar protein accretion in the hours and days after exercise may occur in order to offset the large elevation in mixed muscle proteolysis that has been shown during similar bouts of intense one-legged aerobic exercise.