The effects of exercise training in the cold on cerebral blood flow and cerebrovascular function in young healthy individuals.

Exercise elicits acute increases in cerebral blood flow velocity (CBFv) and provokes long-term beneficial effects on CBFv, thereby reducing cerebrovascular risk. Acute exposure to a cold stimulus also increases CBFv. We compared the impact of exercise training in cold and thermoneutral environments on CFBv, cerebrovascular function and peripheral endothelial function. Twenty-one (16 males, 22 ± 5 years) individuals were randomly allocated to either a cold (5 °C) or thermoneutral (15 °C) exercise intervention. Exercise consisted of 50-min cycling at 70% heart rate max, three times per week for eight weeks. Transcranial Doppler was used to determine pre and post intervention CBFv, dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity (CVRCO2). Conduit endothelial function, microvascular function and cardiorespiratory fitness were also assessed. Cardiorespiratory fitness improved (2.91 ml.min.kg-1, 95%CI 0.49, 5.3; P = 0.02), regardless of exercise setting. Neither intervention had an impact on CBFv, CVRCO2, FMD or microvascular function (P > 0.05). There was a significant interaction between time and condition for dCA normalised gain with evidence of a decrease by 0.192%cm.s-1.%mmHg-1 (95%CI -0.318, -0.065) following training in the cold and increase (0.129%cm.s-1.%mmHg-1, 95%CI 0.011, 0.248) following training in the thermoneutral environment (P = 0.001). This was also evident for dCA phase with evidence of an increase by 0.072 rad (95%CI -0.007, 0.152) following training in the cold and decrease by 0.065 (95%CI -0.144, 0.014) radians following training in the thermoneutral environment (P = 0.02). Both training interventions improved fitness but CBFv, CVRCO2 and peripheral endothelial function were unaltered. Exercise training in the cold improved dCA whereas thermoneutral negated dCA.

The effect of weight loss on the progression of meniscal extrusion and size in knee osteoarthritis: a post-hoc analysis of the Intensive Diet and Exercise for Arthritis (IDEA) trial.

OBJECTIVE: Weight loss has beneficial effects on clinical outcomes in knee osteoarthritis (OA), but the mechanism is still unclear. Since meniscus extrusion is associated with knee pain, this study assessed whether weight loss by diet and/or exercise is associated with less progression in meniscus extrusion measures over time. DESIGN: The Intensive Diet and Exercise for Arthritis trial (IDEA) was a prospective, single-blind, randomized-controlled trial including overweight and obese older adults with knee pain and radiographic OA. Participants were randomized to 18-month interventions: exercise only, diet only or diet + exercise. In a random subsample of 105 participants, MRIs were obtained at baseline and follow-up. The medial and lateral menisci were segmented and quantitative position and size measures were obtained, along with semiquantitative extrusion measures. Linear and log-binomial regression were used to examine the association between change in weight and change in meniscus measures. Between-group differences were analyzed using an analysis of covariance. RESULTS: Weight loss was associated with less progression over time of medial meniscus extrusion as measured by the maximum (ß: -24.59 µm, 95%CI: -41.86, -7.33) and mean (ß: -19.08 µm, 95%CI: -36.47, -1.70) extrusion distances. No relationships with weight loss were observed for lateral meniscus position, medial or lateral meniscus size or semiquantitative measures. Change in meniscus position and size did not differ significantly between groups. CONCLUSIONS: Weight loss was associated with beneficial modifications of medial meniscus extrusion over 18 months. This may be one of the mechanisms by which weight loss translates into a clinical benefit. CLINICAL TRIAL REGISTRATION: NCT00381290.

Inflammatory cytokines mediate the effects of diet and exercise on pain and function in knee osteoarthritis independent of BMI.

OBJECTIVE: Diet restriction and exercise form key treatments for osteoarthritis (OA) related symptoms in overweight and obese individuals. Although both interventions are known to influence systemic low-grade inflammation, which is related to pain levels and functional limitations, little is known about the potential changes in systemic inflammation as a working mechanism of diet restriction and exercise in knee OA. DESIGN: Data from the Arthritis, Diet, and Activity Promotion Trial (ADAPT) were used. Through causal mediation analyses, the proportion of the effect of a 18 months diet and exercise intervention explained by the 18 months change in interleukin (IL)-6, TNF-α, soluble IL-6 receptor, soluble IL-1 receptor, CRP, and BMI were assessed, using self-reported pain and function as outcomes. RESULTS: The change in inflammatory factors accounted for 15% of the total effect on pain and was totally independent of the change in BMI. The change in inflammatory factors accounted for 29% of the effect on function, with the change in BMI adding only 4% to the total mediated effect. CONCLUSIONS: The change in inflammatory factors after the diet and exercise intervention was a 'medium' size mediator of the effect on pain and a 'strong' mediator for the effect on function in overweight and obese individuals with knee OA. The change in BMI added minimally to the mediated effect on function. These results highlight the relevance of changes in systemic inflammation as drivers for clinically relevant effects after diet and exercise in overweight and obese individuals with knee OA.

Nutrient Intake During Diet-Induced Weight Loss and Exercise Interventions in a Randomized Trial in Older Overweight and Obese Adults.

OBJECTIVES: Dietary restriction in obese older adults undergoing weight loss may exacerbate nutrient deficiencies common in this group; the nutritional health of older adults is a factor in their quality of life, disability, and mortality. This study examined the effect of an 18-month weight loss program based in social cognitive theory incorporating partial meal replacements, on nutrient intake in older overweight and obese adults. DESIGN: The following analysis is from the Intensive Diet and Exercise for Arthritis (IDEA) trial, a single-blind, randomized controlled trial. Individuals were randomized into one of three 18-month interventions: exercise (E); intensive diet-induced weight loss (D); or intensive diet-induced weight loss plus exercise (D+E). SETTING: The study setting was at a university research facility. PARTICIPANTS: Overweight and obese older adults (n=388; BMI=33.7±3.8 kg/m2; 65.8±6.1 years) were recruited. INTERVENTIONS: The D and D+E interventions (group mean goal of ≥10% loss by 18-months) utilized partial meal replacements (2 meal replacement shakes/day for 6-months). Exercise training for E and D+E was 3 days/week, 60 minutes/day. MEASUREMENTS: Three day food records were collected at baseline, 6-months, and 18-months and analyzed for total energy and macro- and micronutrient intake. Comparisons of dietary intake among treatment groups were performed at 6 and 18 months using mixed linear models. RESULTS: Weight loss at 18-months was 11.3±8.3% (D), 10.3±6.8% (D+E), and 1.2±4.2% (E). Meal replacements were used by more than 60% (6-months) and 50% (18-months) of D and D+E participants, compared to ≤15% for E. Both D and D+E consumed less energy and fat, and more carbohydrates and selected micronutrients than E during follow-up. More than 50% of all participants consumed less than the recommended intake of particular vitamins and minerals. CONCLUSIONS: The diet intervention improved intakes of several nutrients. However, inadequate intake of several vitamins and minerals of concern for older adults suggests they need further guidance to assure adequate intake.

Repeated Warm Water Immersion Induces Similar Cerebrovascular Adaptations to 8 Weeks of Moderate-Intensity Exercise Training in Females.

Exercise training has the potential to enhance cerebrovascular function. Warm water immersion has recently been shown to enhance vascular function including the cerebrovascular response to heating. We suggest that passive heating can be used alternatively to exercise. Our aim was to compare the effects of exercise with warm-water immersion training on cerebrovascular and thermoregulatory function. 18 females (25±5 y) performed 8 weeks of cycling (70% HRmax) or warm water immersion (42°C) for 30 min 3 times per week. Brachial artery flow-mediated dilation (FMD) and peak cardiorespiratory fitness (VO2peak) were measured prior to and following both interventions. A passive heat stress was employed to obtain temperature thresholds (Tb) and sensitivities for sweat rate (SR) and cutaneous vasodilation (CVC). Middle cerebral artery velocity (MCAv) was measured throughout. FMD and VO2peak improved following both interventions (p<0.05). MCAv and cerebrovascular conductance were higher at rest and during passive heating (p<0.001 and <0.001, respectively) following both interventions. SR occurred at a lower Tb following both interventions and SR sensitivity also increased, with a larger increase at the chest (p<0.001) following water immersion. CVC occurred at a lower Tb (p<0.001) following both interventions. Warm water immersion elicits similar cerebrovascular, conduit, and thermoregulatory adaptations compared to a period of moderate-intensity exercise training.

The Intensive Diet and Exercise for Arthritis (IDEA) trial: 18-month radiographic and MRI outcomes.

PURPOSE: Report the radiographic and magnetic resonance imaging (MRI) structural outcomes of an 18-month study of diet-induced weight loss, with or without exercise, compared to exercise alone in older, overweight and obese adults with symptomatic knee osteoarthritis (OA). METHODS: Prospective, single-blind, randomized controlled trial that enrolled 454 overweight and obese (body mass index, BMI = 27-41 kg m(-2)) older (age ≥ 55 yrs) adults with knee pain and radiographic evidence of femorotibial OA. Participants were randomized to one of three 18-month interventions: diet-induced weight loss only (D); diet-induced weight loss plus exercise (D + E); or exercise-only control (E). X-rays (N = 325) and MRIs (N = 105) were acquired at baseline and 18 months follow-up. X-ray and MRI (cartilage thickness and semi-quantitative (SQ)) results were analyzed to compare change between groups at 18-month follow-up using analysis of covariance (ANCOVA) adjusted for baseline values, baseline BMI, and gender. RESULTS: Mean baseline descriptive characteristics of the cohort included: age, 65.6 yrs; BMI 33.6 kg m(-2); 72% female; 81% white. There was no significant difference between groups in joint space width (JSW) loss; D -0.07 (SE 0.22) mm, D + E -0.27 (SE 0.22) mm and E -0.16 (SE 0.24) mm (P = 0.79). There was also no significant difference in MRI cartilage loss between groups; D -0.10(0.05) mm, D + E -0.13(0.04) mm and E -0.05(0.04) mm (P = 0.42). CONCLUSION: Despite the potent effects of weight loss in this study on symptoms as well as mechanistic outcomes (such as joint compressive force and markers of inflammation), there was no statistically significant difference between the three active interventions on the rate of structural progression either on X-ray or MRI over 18-months.

A coiled-coil mimetic intercepts BCR-ABL1 dimerization in native and kinase-mutant chronic myeloid leukemia.

Targeted therapy of chronic myeloid leukemia (CML) is currently based on small-molecule inhibitors that directly bind the tyrosine kinase domain of BCR-ABL1. This strategy has generally been successful, but is subject to drug resistance because of point mutations in the kinase domain. Kinase activity requires transactivation of BCR-ABL1 following an oligomerization event, which is mediated by the coiled-coil (CC) domain at the N terminus of the protein. Here, we describe a rationally engineered mutant version of the CC domain, called CC(mut3), which interferes with BCR-ABL1 oligomerization and promotes apoptosis in BCR-ABL1-expressing cells, regardless of kinase domain mutation status. CC(mut3) exhibits strong proapoptotic and antiproliferative activity in cell lines expressing native BCR-ABL1, single kinase domain mutant BCR-ABL1 (E255V and T315I) or compound-mutant BCR-ABL1 (E255V/T315I). Moreover, CC(mut3) inhibits colony formation by primary CML CD34(+) cells ex vivo, including a sample expressing the T315I mutant. These data suggest that targeting BCR-ABL1 with CC mutants may provide a novel alternative strategy for treating patients with resistance to current targeted therapies.

Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis.

OBJECTIVE: To describe associations between total and regional body fat mass loss and reduction of systemic levels of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) in obese, older adults with osteoarthritis (OA), undergoing intentional weight loss. DESIGN: Data come from a single-blind, 18-month, randomized controlled trial in adults (age: 65.6 ± 6.2; Body mass index (BMI): 33.6 ± 3.7) with knee OA. Participants were randomized to diet-induced weight loss plus exercise (D + E; n = 150), diet-induced weight loss-only (D; n = 149), or exercise-only (E; n = 151). Total body and region-specific (abdomen and thigh) fat mass were measured at baseline and 18 months. High-sensitivity CRP and IL-6 were measured at baseline, six and 18 months. Intervention effects were assessed using mixed models and associations between inflammation and adiposity were compared using logistic and mixed linear regression models. RESULTS: Intentional total body fat mass reduction was associated with significant reductions in log-adjusted CRP (ß = 0.06 (95% CI = 0.04, 0.08) mg/L) and IL-6 (ß = 0.02 (95% CI = 0.01, 0.04) pg/mL). Loss of abdominal fat volume was also associated with reduced inflammation, independent of total body fat mass; although models containing measures of total adiposity yielded the best fit. The odds of achieving clinically desirable levels of CRP (<3.0 mg/L) and IL-6 (<2.5 pg/mL) were 3.8 (95% CI = 1.6, 8.9) and 2.2 (95% CI = 1.1, 4.6), respectively, with 5% total weight and fat mass loss. CONCLUSIONS: Achievement of clinically desirable levels of CRP and IL-6 more than double with intentional 5% loss of total body weight and fat mass. Global, rather than regional, measures of adiposity are better predictors of change in inflammatory burden. CLINICAL TRIAL REGISTRATION NUMBER: NCT00381290.

Impact of Body Composition on Physical Performance Tasks in Older Obese Women Undergoing a Moderate Weight Loss Program.

BACKGROUND: Although obesity is a recognized risk factor for impaired physical function in older adults, there is still debate on whether older obese adults should undergo intentional weight loss due to concern of loss in lean body mass, including appendicular lean soft tissue mass. This may put them at risk for worsening muscle strength and mobility. OBJECTIVES: Therefore, the purpose of this study was to examine the effect of a weight loss intervention on body composition and physical function in obese older women. DESIGN: Women were randomized into either a weight stable (WS) (n=20) or an intensive weight loss (WL) (n=26) group. SETTING: The study setting was at a university research facility. PARTICIPANTS: Women (age, 67.8±1.3 yrs; BMI, 34.9 (0.7) kg/m2; mean±standard error of the mean) were recruited. INTERVENTION: The WL intervention was for 6 months and included moderate dietary energy restriction and aerobic and strength exercise training. MEASUREMENTS: Variables were obtained at baseline and 6-months and included body weight, dual energy x-ray absorptiometry (DXA), 6-minute walk distance, stair climb time, and concentric knee extension muscular strength. RESULTS: Estimated marginal means (SEM) for weight loss at 6-months was -8.5 (0.9)% for WL and +0.7 (1.0)% for WS. There was a significant loss of body fat mass, lean body mass, appendicular lean soft tissue mass, relative muscle mass, and skeletal muscle index for WL vs. WS at 6-months. However, improvements for WL vs. WS were seen in 6-minute walk distance and stair climb time, and trends for improved relative strength and leg muscle quality. Change in body fat mass was positively related to improved physical function and muscle strength and quality. CONCLUSION: These results further support the use of a sound intentional weight loss program incorporating moderate dietary energy restriction and exercise training in older obese women to improve physical function. Although lean soft tissue mass was lost, over the 6-month program there was no deleterious effect on muscle strength or muscle quality.

Basal growth hormone concentration increased following a weight loss focused dietary intervention in older overweight and obese women.

OBJECTIVES: Growth and sex steroid hormones decrease with aging and obesity. The effect of dietary weight loss and exercise training lifestyle interventions was examined on hormones as well as determining their relationships with physical function in older obese and overweight adults. DESIGN: Individuals were randomized into one of four 18 month interventions: Healthy Lifestyle (HL), Exercise, Diet, and Exercise-Diet. SETTING: Clinical research setting with facility based exercise and nutrition education and behavior classrooms. PARTICIPANTS: Older (≥60 yrs) overweight and obese (BMI≥28 kg/m(2)) adults with knee osteoarthritis (n=309) were recruited for the study. INTERVENTION: Weight loss goal for Diet groups was ≥5%. Exercise groups trained (mostly walking and resistance training) 3 days/week for 60 min/session. MEASUREMENTS: Body weight, growth hormone (GH), corticosterone, sex-hormone binding globulin (SHBG), testosterone, and dehydroepiandrosterone (DHEA) were measured at baseline, 6, and 18 months. Physical function was determined through performance task (6-min walking distance) and self-reported questionnaires (Western Ontario McMaster University Osteoarthritis Index-WOMAC) at similar time points. RESULTS: Diet, Exercise, and Exercise-Diet groups lost 4.9%, 3.5%, and 6.2% of their weight at 18 months, respectively. There was a significant diet treatment effect on GH levels in women as higher concentrations of this hormone were apparent following dietary weight loss intervention (p=0.01). No other hormones were affected by either diet or exercise treatments in men or women. A significant inverse correlation between baseline 6-minute walking distance and SHBG (r=-0.33) was found in men. CONCLUSION: The increase in basal GH levels from the diet treatment in women suggests that this lifestyle behavior intervention may mitigate the age- and obesity-related decreases in growth hormone levels, to help preserve muscle mass, strength, and physical function in older adults.

Regional fat changes following weight reduction from laparoscopic Roux-en-Y gastric bypass surgery.

Fat accumulation in muscle (intermuscular, IM) and viscera plays a role in obesity comorbidities. This study examined the impact of Roux-en-Y gastric bypass (RYGB) surgery in morbid obesity on changes in regional fat and muscle depots, and these body composition markers were correlated with physical function. Women (n = 18) were assessed prior to (baseline) and 12 months following RYGB for regional body composition and physical function. Weight loss from baseline to 12 months was 33.7 (s.e.m. = 1.7)%; total body fat decreased from 86.8 (s.e.m. = 5.8) to 45.8 (s.e.m. = 3.9) kg during follow-up. Differential changes in regional body fat were apparent with a volume loss of 58.4% in visceral fat, 19.8% in abdomen IM fat and 50.7% in thigh IM fat. At baseline, abdomen IM fat volume was related to physical function. There was less loss of abdomen IM fat volume than other depots following surgery; furthermore its relationship with physical function is a novel finding.

Improved nutrient intake in older obese adults undergoing a structured diet and exercise intentional weight loss program.

OBJECTIVES: Physicians are often reluctant to advise older obese patients to lose weight for fear of compromised nutrition and excessive loss of muscle mass and strength, all of which may lead to a loss of independence and accelerate disability. Therefore, the purpose of this study was to examine nutrient intake in older obese adults undergoing a weight loss intervention. SETTING: The study setting was at a university research facility. PARTICIPANTS: A total of 71 participants (age, 69.5 (SD = 5.8) yrs; 62% female; BMI, 34.6 (4.4) kg/m2) were recruited. DESIGN: Individuals were randomized into either a weight stable (WS) control group or an intensive weight loss (WL) group. INTERVENTION: The WL intervention was for 6 months and utilized partial meal replacements (PMR) and a facility-based 3 d/wk, 60 min/session exercise training program encompassing both aerobic and strength exercises. Weight loss goal for WL was 10% from baseline at 6-months. MEASUREMENTS: Variables were obtained at baseline and 6-months and included 3 day dietary records along with daily step counts for 7 days. Total energy, macronutrients (g and % of energy), micronutrients (vitamins and minerals), as well as use of PMR were assessed from the diet records. Body mass and body fat (g and % of body mass) were determined at the 2 time points. RESULTS: Estimated marginal means (SEM) for weight loss at 6-months was -8.8 (0.7)% for WL and -0.1 (0.7)% for WS. Daily energy intake at 6-months was lower for WL (1396 (64) kcals) compared to WS (1817 (71) kcals). Additionally, those in the WL group (compared to WS) had lower intakes of total fat (27.5 (1.2)%, WL vs. 36.1 (4.6)%, WS) and saturated fatty acids (8.5 (0.4)% vs. 10.8 (0.5)%), and had higher levels of carbohydrates (57.6 (1.5)% vs. 49.0 (1.7)%), protein (18.4 (0.5% vs. 16.2 (0.6)%), and dietary fiber (21.0 (0.9) g vs. 17.4 (1.0) g) at 6-months. Even with reduced total calorie intake, key micronutrients (calcium, iron, vitamin D, vitamin E, vitamin C) were higher for WL vs. WS at 6-months. Total daily step counts were higher for WL vs. WS at 6-months. CONCLUSION: A nutrition intervention to promote weight loss in older obese adults was achieved using PMR as a primary strategy. Diet quality was improved for WL vs. WS in using the nutrient fortified product, even with a reduction in total energy intake.

Effects of dietary protein on the composition of weight loss in post-menopausal women.

OBJECTIVES: To determine whether a hypocaloric diet higher in protein can prevent the loss of lean mass that is commonly associated with weight loss. DESIGN: An intervention study comparing a hypocaloric diet moderately high in protein to one lower in protein. SETTING: Study measurements were taken at the Wake Forest University General Clinical Research Center (GCRC) and Geriatric Research Center (GRC). PARTICIPANTS: Twenty-four post-menopausal, obese women (mean age = 58 +/- 6.6 yrs; mean BMI = 33.0 +/- 3.6 kg/m2). INTERVENTION: Two 20-week hypocaloric diets (both reduced by 2800 kcal/wk) were compared: one maintaining dietary protein intake at 30% of total energy intake (1.2-1.5 g/kg/d; HI PROT), and the other maintaining dietary protein intake at 15% of total energy (0.5-0.7 g/kg/d; LO PROT). The GCRC metabolic kitchen provided lunch and dinner meals which the women picked up 3 days per week and ate outside of the clinic. MEASUREMENTS: Body composition, including total body mass, total lean mass, total fat mass, and appendicular lean mass, assessed by dual energy x-ray absorptiometry, was measured before and after the diet interventions. RESULTS: The HI PROT group lost 8.4 +/- 4.5 kg and the LO PROT group lost 11.4 +/- 3.8 kg of body weight (p = 0.11). The mean percentage of total mass lost as lean mass was 17.3% +/- 27.8% and 37.5% +/- 14.6%, respectively (p = 0.03). CONCLUSION: Maintaining adequate protein intake may reduce lean mass losses associated with voluntary weight loss in older women.

Major scientific advances with dairy foods in nutrition and health.

A large body of scientific evidence collected in recent decades demonstrates that an adequate intake of calcium and other nutrients from dairy foods reduces the risk of osteoporosis by increasing bone acquisition during growth, slowing age-related bone loss, and reducing osteoporotic fractures. These results have culminated in the new (2005) Dietary Guidelines for Americans that now recommend 3 servings of milk products per day to reduce the risk of low bone mass and contribute important amounts of many nutrients that may have additional health attributes beyond bone health. A number of animal, observational, and clinical studies have shown that dairy food consumption can help reduce the risk of hypertension. Clinical trials indicate that the consumption of recommended levels of dairy products, as part of a healthy diet, can contribute to lower blood pressure in individuals with normal and elevated blood pressure. Emerging data also indicate that specific peptides associated with casein and whey proteins can significantly lower blood pressure. In addition, a growing body of evidence has provided support for a beneficial effect of dairy foods on body weight and fat loss. Clinical studies have demonstrated that during caloric restriction, body weight and body fat loss occurs when adequate calcium is provided by supplements and that this effect is further augmented by an equivalent amount of calcium supplied from dairy foods. Several studies support a role for calcium, vitamin D, and dairy foods against colon cancer. Additionally, conjugated linoleic acid, a fatty acid found naturally in dairy fat, confers a wide range of anticarcinogenic benefits in experimental animal models and is especially consistent for protection against breast cancer.

Vapor-transport equilibrated near-stoichiometric lithium tantalate for frequency-conversion applications.

Near-stoichiometric lithium tantalate (SLT) crystals were produced from congruent lithium tantalate by a vapor-transport equilibration process. Because of the resultant increase in photoconductivity and reduction in photogalvanism, the crystals showed no observable photorefractive damage at 514.5 nm up to the highest intensity used, 2 MW/cm2. The crystals also exhibited low green-induced infrared absorption, a Curie temperature of 693 degrees C, and a coercive field of 80 V/mm. The SLT samples were periodically poled with an 8-microm-period grating, permitting first-order quasi-phase-matched second-harmonic generation of 532-nm radiation at 43 degrees C. A 17-mm-long sample generated 1.6 W of continuous-wave output power at 532 nm for 50 h. With 150-ns pulses at a 100-kHz repetition rate in the same sample, 5-W average-power, 532-nm radiation was generated for 1000 h. No damage to the crystal and no aging effects were observed during these experiments.

Is serum leptin related to physical function and is it modifiable through weight loss and exercise in older adults with knee osteoarthritis?

OBJECTIVE: To determine the effect of weight loss and exercise interventions on serum leptin and to investigate the relationship of physical function and osteoarthritis (OA) severity with serum leptin in older overweight and obese adults with knee OA. In addition, the study examined if serum leptin predicts weight loss. DESIGN: Longitudinal, controlled clinical trial of weight loss and exercise interventions. SUBJECTS: Community dwelling, older, overweight and obese adults (n=316; >60 years of age; body mass index >/=28.0 kg m(-2)) with symptomatic knee OA and self-reported difficulty in performing selected physical activities were recruited. INTERVENTIONS: Participants were randomized into one of four groups for the 18-month study duration: Healthy Lifestyle Controls, Dietary Weight Loss (Diet), Exercise Training (Exercise), and a combination of Dietary Weight Loss and Exercise Training (Diet+Exercise). The weight loss goal for the two Diet groups was 5% from baseline at 18 months. Participants in the Exercise groups were trained for 3 days week(-1), 60 min day(-1). MEASUREMENTS: Body weight, body mass index, serum leptin, physical function, and OA severity were measured at baseline, 6 months, and 18 months. RESULTS: Diet and Diet+Exercise groups lost 5.3 and 6.1% of their weight, respectively, at 18 months with the Exercise group losing 2.9%. There was a significant main effect of weight loss on serum leptin with a decrease in serum leptin averaged across the 6- and 18-month time points for the Diet and Diet+Exercise groups compared to the other two groups (beta=0.245; P<0.01). No main effect for exercise training was observed. Serum leptin was related to self-reported physical function. In all participants, a mixed model analysis demonstrated that lower levels of baseline serum leptin predict larger weight loss (beta=-2.779; P=0.048). CONCLUSION: Decreases in serum leptin may be one mechanism by which weight loss improves physical function and symptoms in OA patients.

Mass spectrometry-compatible ICH (International Conference on Harmonization) impurity analysis with a high-pH mobile phase advantages and pitfalls.

Recent advances in bonding chemistry and novel silica synthesis have significantly extended the pH range of silica-based HPLC columns. This extended range now enables the analysis of water-soluble basic drugs at high pH without ion-pairing reagents, thus offering an alternative approach to assay or impurity analyses. This paper describes the many advantages and potential pitfalls of using high-pH mobile phases in the development of MS-friendly LC gradient impurity analytical methods for water-soluble basic drugs under International Conference on Harmonization (ICH) guidelines. Operating at high-pH provides excellent peak shapes and retention, and accentuates selectivity differences of structurally similar impurities and degradants. However, several problems unique to the use of high-pH mobile phases, such as column lifetime, robustness of pH adjustments, peak fronting, and on-column dimerization, were encountered. Each of these problems is discussed with its respective remedy.

The importance of meeting calcium needs with foods.

Calcium can be obtained from foods naturally rich in calcium such as dairy foods, from calcium-fortified foods and beverages, from supplements or from a combination of these. Recognition of calcium's many health benefits, along with Americans' low calcium intake, has led to interest in how best to meet calcium needs. Foods are the preferred source of calcium. Milk and other dairy foods are the major source of calcium in the U.S. In addition, these foods provide substantial amounts of other essential nutrients. Consequently, intake of dairy foods improves the overall nutritional quality of the diet. Other foods such as some green leafy vegetables, legumes and cereals provide calcium, but generally in lower amounts per serving than do dairy foods. Also, some components such as phytates in cereals and oxalates in spinach reduce the bioavailability of calcium. Calcium-fortified foods and calcium supplements are an option for individuals who cannot meet their calcium needs from foods naturally containing this mineral. However, their intake cannot correct poor dietary patterns of food selection which underlie Americans' low calcium intake. Considering the adverse health and economic effects of low calcium intakes, strategies are needed to optimize calcium intake. A first step is to recognize factors influencing dietary calcium consumption. Substituting soft drinks for milk and eating away from home are among the barriers to adequate calcium intake. The American public needs to understand why consuming foods containing calcium is the best way to meet calcium needs and learn how to accomplish this objective.

Differential effects of maximal- and moderate-intensity runs on plasma leptin in healthy trained subjects.

This study investigated the effect of different exercise bouts on plasma leptin response. Trained men (n = 9) performed a short duration, maximal intensity (MAX) bout and a 60-min endurance run at approximately 70% of maximal oxygen consumption (END). Blood was collected before, immediately after, 24 h after (24 h Post), and 48 h after exercise (48 h Post) for measurement of plasma leptin, insulin, and glucose. VO(2)max and percent body fat were 57.8 +/- 2.1 mL x kg(-1) x min(-1) and 10.8 +/- 1.5% (mean +/- SEM), respectively. Energy expenditure was 197.5 +/- 11.8 and 882.7 +/- 14.4 kcal for MAX and END, respectively. Plasma leptin levels did not differ between time points for the MAX run. Leptin was significantly lower 48 h Post (2.2 +/- 0.3 ng/mL) versus before, immediately after, and 24 h Post exercise (3.1 +/- 0.3, 3.0 +/- 0.3, and 2.5 +/- 0.4 ng/mL, respectively) for END. Leptin tended to be lower at 24 h Post than before or immediately after exercise (P = 0.10). Plasma insulin was lower 24 h Post- versus preexercise for the END, but was not correlated to changes in leptin levels. Plasma glucose levels did not change significantly during the endurance test. We found a delayed decrease in leptin at 48 h after an extended exercise session (900 kcal). Furthermore, this effect did not appear to be related to changes in insulin or glucose levels. Findings from this study address the effects of exercise on leptin, aiding in the evaluation of the impact of exercise and energy expenditure on plasma leptin concentrations in the prevention and treatment of obesity.