EXE Group Research Articles

Association between circulating endogenous androgens and insulin sensitivity changes with exercise training in midlife women

Aging induces a shift in circulating hormones in women, accompanied by weight gain during the late reproductive, menopausal transition, and postmenopausal years. Exercise has been shown to counter weight gain; however, it might increase circulating androgens. A 6-month aerobic and resistance training exercise regimen was implemented to examine interrelationships between circulating sex hormones, body composition, aerobic capacity, insulin sensitivity, and insulin resistance. Twenty-eight women, aged 42 to 52 years, completed the 6-month intervention study. They were randomly assigned to either a control (CON; n = 10) group-and maintained their sedentary lifestyle-or an exercise intervention (EXE; n = 18) group. The exercise intervention consisted of combined aerobic and resistance workouts scheduled 6 days/week for 60 minutes/day. Body weight, composition, VO2 peak, plasma insulin, glucose, lipid profile, estradiol, testosterone, progesterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate (DHEAS) were measured at baseline and on month 6. Insulin sensitivity was estimated using the insulin sensitivity index and the quantitative insulin sensitivity check index, whereas insulin resistance was estimated using the homeostatic model for insulin resistance. There was a trend toward increased DHEAS in both groups (P < 0.1), but not as a function of the intervention. Insulin sensitivity index increased in the EXE group compared with the CON group (P < 0.01). Multiple linear regression indicated that, at 6 months, DHEAS was a negative contributor to insulin sensitivity in the EXE group, but not in the CON group. In midlife women, an increase in circulating DHEAS, such as that previously reported during the menopausal transition, is associated with higher insulin resistance, but exercise can mitigate this risk by improving insulin sensitivity, thereby countering the effects of DHEAS.

Efectos del entrenamiento pliométrico sobre la resistencia cardiorrespiratoria de niños y adolescentes con síndrome de Down

AimTo ascertain the effects of 21 weeks of circuit training, including plyometric jumps, on cardiorespiratory fitness of youths with Down syndrome (DS). MethodsTwenty-seven children and adolescents aged 10 to 19 years with DS participated in this study and were divided in two groups: exercise (EXE, n=14) and control (CON, n=13). Work time, peak values of oxygen consumption, respiratory exchange ratio, heart rate and minute ventilation of the participants were measured in pre- and post-training moments with a graded exercise treadmill test. ResultsEXE group increased all their cardiorespiratory parameters compared to baseline after 21 weeks of training (all p<.05). Additionally, and despite having similar pre-training values, EXE group showed higher values than CON group in all cardiorespiratory parameters after training (all p<.05). ConclusionIt may be concluded that youths with DS can achieve improvements in several cardiorespiratory parameters when performing 21 weeks of training including plyometric exercises.

Effects of a circuit training including plyometric jumps on cardiorespiratory fitness of children and adolescents with Down syndrome

AimTo ascertain the effects of 21 weeks of circuit training, including plyometric jumps, on cardiorespiratory fitness of youths with Down's syndrome (DS). MethodsTwenty-seven children and adolescent aged 10 to 19 years with DS participated in this study and were divided in two groups: exercise (EXE, n=14) and control (CON, n=13). Work time, peak values of oxygen consumption, respiratory exchange ratio, heart rate and minute ventilation of the participants were measured pre- and post-training with a graded exercise treadmill test. ResultsEXE group increased all their cardiorespiratory parameters compared to baseline after 21 weeks of training (all P<.05). Additionally, and despite having similar pre-training values, the EXE group showed higher values than the CON group in all cardiorespiratory parameters after training (all P<.05). ConclusionIt may be concluded that youths with Down syndrome can achieve improvements in several cardiorespiratory parameters when performing 21 weeks of training including plyometric exercises.

Moderate intensity exercise is associated with decreased angiotensin-converting enzyme, increased β2-adrenergic receptor gene expression, and lower blood pressure in middle-aged men.

The purpose of the current study was to characterize the role of aerobic exercise in the gene expression of the angiotensin-converting enzyme (ACE) and the β2-adrenergic receptor (ADRB2) in untrained men. Twenty untrained middle-aged men were randomly assigned to exercise (Exe) and control (Con) groups. The Exe group performed aerobic exercises for eight weeks. ACE mRNA and ADRB2 mRNA were determined by PCR. The expression of ACE in week 4 and in the Exe group decreased significantly (p < .001). ADRB2 in the Exe group, in week 4 and in week 8, was markedly higher, and blood pressure was significantly lower than in the Con group (p < .001). In the Con group ADRB2 mRNA decreased. These results suggest that moderate intensity exercise promotes the leukocyte expression of gene markers that may affect blood pressure by improving cardiovascular fitness levels in middle-aged men.

Exercise training decreases myocardial collagen III and heart failure signs rate, and improves physical performance in spontaneously hypertensive rats (LB522)

The aim of this study was to evaluate the influence of physical exercise on physical performance, heart failure (HF) signs rate, and myocardial collagen I and III and lysyl oxidase protein expression in spontaneously hypertensive rats (SHR). Methods: Sixteen‐month‐old SHR were divided into two groups: sedentary (SED, n=8) and exercise (EXE, n=8). Physical training was performed 5 times per week for 16 weeks in a treadmill. Physical performance was assessed by exercise test on a treadmill with a gradual speed increase. At the moment of euthanasia, HF signs were evaluated: tachypnea in vivo, and ascyte, pleural effusion, atrial thrombi, right ventricular hypertrophy, and liver and lung congestion post mortem. Collagen I and III and lysyl oxidase protein expression were analyzed by Western blot. Statistics: The Student's t test and the Goodman test were used to compare the groups (p&lt;0.05). Results: The EXE group showed greater physical capacity and lower HF signs rate than SED group. Collagen III protein expression was lower in EXE group (1.00±0.58 vs. 0.73±0.43, p&lt;0.05). Collagen I and lysyl oxidase protein expression were not significantly different between groups. Conclusion: Physical exercise improves physical performance and reduces heart failure signs rate and myocardial collagen III expression in spontaneously hypertensive rats.Grant Funding Source: Supported by CAPES and CNPq

Exercise training can prevent cardiac hypertrophy induced by sympathetic hyperactivity with modulation of kallikrein-kinin pathway and angiogenesis.

Sympathetic hyperactivity induces adverse effects in myocardial. Recent studies have shown that exercise training induces cardioprotection against sympathetic overload; however, relevant mechanisms of this issue remain unclear. We analyzed whether exercise can prevent pathological hypertrophy induced by sympathetic hyperactivity with modulation of the kallikrein-kinin and angiogenesis pathways. Male Wistar rats were assigned to non-trained group that received vehicle; non-trained isoproterenol treated group (Iso, 0.3 mg kg−1 day−1); and trained group (Iso+Exe) which was subjected to sympathetic hyperactivity with isoproterenol. The Iso rats showed hypertrophy and myocardial dysfunction with reduced force development and relaxation of muscle. The isoproterenol induced severe fibrosis, apoptosis and reduced myocardial capillary. Interestingly, exercise blunted hypertrophy, myocardial dysfunction, fibrosis, apoptosis and capillary decreases. The sympathetic hyperactivity was associated with high abundance of ANF mRNA and β-MHC mRNA, which was significantly attenuated by exercise. The tissue kallikrein was augmented in the Iso+Exe group, and kinin B1 receptor mRNA was increased in the Iso group. Moreover, exercise induced an increase of kinin B2 receptor mRNA in myocardial. The myocardial content of eNOS, VEGF, VEGF receptor 2, pAkt and Bcl-2 were increased in the Iso+Exe group. Likewise, increased expression of pro-apoptotic Bad in the Iso rats was prevented by prior exercise. Our results represent the first demonstration that exercise can modulate kallikrein-kinin and angiogenesis pathways in the myocardial on sympathetic hyperactivity. These findings suggest that kallikrein-kinin and angiogenesis may have a key role in protecting the heart.

Exercise, Energy Expenditure, and Body Composition in People With Spinal Cord Injury

The objective of this study was to verify the long-term effects of exercise on energy expenditure and body composition in individuals with spinal cord injury (SCI), as very little information is available on this population under free-living conditions. Free-living energy expenditure and body composition using doubly labeled water (DLW) was measured in 13 individuals with SCI, subdivided in 2 groups: (1) sedentary (SED; N = 7) and (2) regularly engaged in any exercise program, for at least 150 min·wk(-1) (EXE; N = 6). The total daily energy expenditure (TDEE) was significantly higher in the EXE group (33 ± 4.5 kcal·kg(-1)·day(-1)) if compared with SED group (27 ± 4.3 kcal·kg(-1)·day(-1)). The percentage of body fat was significantly higher in SED group than in EXE group (38 ± 6% and 28 ± 9%). Our findings revealed that, despite the severity of SCI, the actual ACSM's guidelines for weight management for healthy adults exercise could significantly increase TDEE and BMR and improve body composition in individuals who regularly perform exercise. However, the EXE group still showed a high percentage of body fat, suggesting that a more specific approach might be considered (ie, increased intensity or volume, or combining with a diet program).

Endurance training is feasible in severely disabled patients with progressive multiple sclerosis

This study tested whether upper-body endurance training (ET) is feasible and can be performed at sufficient intensity to induce cardiovascular adaptations in severely disabled patients with progressive multiple sclerosis (MS). Eleven progressive MS patients (6.5 ≤ EDSS ≤ 8.0) scheduled for a four-week inpatient rehabilitation program were randomized to a control group (CON, n = 5) that received standard individualized MS rehabilitation or an intervention group (EXE, n = 6) that in addition received 10 sessions of predominantly upper-body ET. One patient dropped out of the EXE group (drop-out rate: 1/6~17%) and no adverse events were recorded. The EXE group completed on average 9.3±0.8 sessions (~96.0±5%). During the ET sessions an average heart rate of 93.9±9.3beats*min–1 were sustained corresponding to 91.6±6.8% of the maximal pre-intervention heart rate. In the EXE group a trend toward a time*group interaction was seen for VO2peak (p = 0.06). ET is feasible in severely disabled patients with progressive MS and it can probably be performed at sufficient intensity to induce cardiovascular adaptations.

BOLERO-2: Efficacy and safety of first-line everolimus plus exemestane in advanced breast cancer.

152 Background: In the BOLERO-2 study, progression-free survival (PFS) was significantly longer with the combination of everolimus and exemestane (EVE + EXE) compared with placebo and exemestane (PBO + EXE; hazard ratio = 0.45; p &lt; .0001). Consistent efficacy results were observed in all subgroup analyses, such as in patients with visceral metastases and patients with disease recurrence during/after adjuvant therapy. This analysis of BOLERO-2 examines the efficacy of EVE + EXE in the subgroup of patients who received treatment immediately after recurrence during adjuvant therapy (i.e., as first-line therapy in the advanced setting). Methods: BOLERO-2 enrolled patients with hormone receptor–positive (HR+) advanced breast cancer with disease recurrence or progression after prior nonsteroidal aromatase inhibitors and compared EVE (10 mg/d) + EXE (25 mg/d) vs PBO + EXE. The primary end point was PFS by local investigator review. Results: A total of 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37) in the advanced setting. Of these patients, 74% of the EVE + EXE arm and 76% of the PBO + EXE arm had recurred after adjuvant endocrine therapy plus chemotherapy; 26% and 24%, respectively, had recurred after adjuvant endocrine therapy alone. Also, approximately 20% of patients entered the trial after recurring during or within 12 months of adjuvant therapy (21% EVE + EXE vs 16% PBO + EXE). The EVE + EXE group had significantly longer PFS compared with the PBO + EXE group (11.50 vs 4.07 months, respectively; hazard ratio = 0.39; 95% confidence interval, 0.25-0.62). Median PFS remained longer with EVE + EXE versus PBO + EXE, regardless of whether chemotherapy was included with the prior adjuvant hormonal therapy. Similar results were obtained from the analyses based on central review. The safety profile was consistent with the known profiles of each agent. Conclusions: EVE + EXE prolonged PFS in patients with HR+ advanced breast cancer who received treatment as first-line therapy. These results support the combination of EVE + EXE in patients with recurrence after adjuvant therapy. The recently initiated BOLERO-4 study is also evaluating the efficacy of EVE as a first-line therapy in patients with HR+ advanced breast cancer. Clinical trial information: NCT00863655.

Abstract 100: Delta Opioid Receptor Blockade Abolishes Exercise-Induced Cardioprotection Against Ischemia-Reperfusion Injury In Vivo

Introduction: Recent studies showed that exercise enhances myocardial tolerance to ischemia-reperfusion (I-R) injury via an opioid receptor-dependent mechanism. However, the specific subtype of opioid receptor involved in this response remains to be determined. Methods: Male Wistar rats were first divided into 2 groups: exercised and control. The exercised group underwent 4 consecutive days of treadmill training (60 min at 70% of maximal oxygen consumption). The exercised group was then divided into 4 subgroups: exercised (Exe; n = 10); exercised + kappa receptor antagonist (Exe + K; n=4); exercised + delta receptor antagonist (Exe + D; n=4); exercised + mu receptor antagonist (Exe + M; n=4). Control group was also divided into 2 groups: control (Ctr; n = 10) and control sham (Sham; n = 10). To induce I-R injury, anesthetized animals were submitted to a left thoracotomy and a 30 min interventricular coronary occlusion followed by 60 min of reperfusion. The hemodynamic parameters were recorded and infarct size was post-mortem determined by double staining using TTC/Evans blue and expressed as a percentage of the area at risk. Results: As shown in the figure, Sham group showed no infarct, Exe group showed a significant reduction in the infarcted area (27.6%) when compared to Ctr group (42.0%). The pretreatment with mu and kappa receptor antagonist did not alter the cardioprotective effect of exercise. However, the pretreatment with delta receptor antagonist prevented the exercise-induced cardioprotection. Conclusions: Endogenous opioid system is involved in cardioprotection conferred by acute exercise, and delta receptor subtype seems to play an important role in this response.

Abstract 099: Exercise-Induced Cardioprotection Against Ischemia-Reperfusion Injury Is Abolished by Opioid System Blockage Using an In Vitro Rat Model

Introduction: A single exercise session releases opioid peptides considered to be associated to cardioprotection. However, the link between exercise-induced cardioprotection and the opioid system remains unclear. Therefore, the study aims to investigate the involvement of opioid receptors in exercise-induced cardioprotection in rats submitted to myocardial injury by ischemia/reperfusion (I/R) in vitro . Methods: Male Wistar rats (250-300g) were randomly divided into 3 groups submitted to I/R: control (CTR; n=5), exercised (EX; n=5) and exercised treated by naloxone, a non-selective opioid receptor antagonist (EX+NAL; n=5). The exercised groups underwent 4 consecutive days of treadmill training (60 min at 70% of maximal oxygen consumption). After the last exercise session (24h), the hearts were removed and immediately installed on a modified Langendorff apparatus. A latex balloon was inserted in the left ventricle (LV) to monitor the LV developed pressure (%LVDP). All hearts underwent a period of 30 min of sustained global ischemia followed by 1 h of reperfusion. After reperfusion, LV was sliced and incubated 20 min in triphenyltetrazolium to measure infarct size. Results: Anova two-way showed that CTR group presented a larger infarct area when compared to EXE group (32.9±9.2% vs 11.3±4.0% respectively; p&lt;0.05). Naloxone treatment completely blocked the exercise-induced cardioprotection (28.1±8.0%). In respect to %LVDP, CTR and EXE+NAL showed significantly lower results compared to EXE group from 25 min of reperfusion. Conclusions: Our results indicate that opioid system is involved, at least in part, in cardioprotective effects of aerobic exercise in rats.

Effects of exercise during the menopausal transition on circulating inflammatory markers, including plasma zinc

The US Dietary Guidelines (DG) recommends 60 min of moderate to vigorous intensity activity most days of the week to help manage body weight and prevent gradual, unhealthy weight gain. Chronic exercise can improve markers of systemic low‐grade inflammation. Healthy, peri‐menopausal, sedentary women (42–52y, BMI 18–32) were assigned to a control (CON, n=10) or exercise (EXE, n=18) regimen for a 6 mo study. The EXE intervention was a combined aerobic and resistance workout 6 d/wk, 60 min/d. Body weight and composition were determined at mo 0, 3 &amp; 6. Fasting levels of insulin, pro‐inflammatory markers (IM: IL1‐ß, IL‐6, IL‐8, TNF‐α, hsCRP) and Zn were measured at mo 0, 1, 3 &amp; 6. Baseline IM were elevated in women with BMI&gt;;25.0 vs. BMI&lt;25.0. The EXE group had a significant decline in body weight at mo 6 (1.2 kg), with a significant decrease in fat mass (primarily android) and increase in lean body mass by mo 3. Controlling for baseline values, the EXE group had an improved insulin sensitivity index and decreased IL‐6 by mo 3. Positive correlations were observed between the changes in CRP &amp; BMI; IL‐8 &amp; IL1‐ß, TNF‐α and Zn; IL1‐ß &amp; Zn; and negative correlations with bone mineral density &amp; IL‐8 and TNF‐α. The decrease in IM in women with BMI&gt;;25.0 was more pronounced than in women with BMI&lt;25.0. Following the USDG for activity will result in health improvements in peri‐menopausal women as determined by body composition and IM. USDA, ARS, WHNRC

Abstract 19631: MicroRNAs Modulation in a Mice Model of Physiological Left Ventricular Hypertrophy

INTRODUCTION: Physiological left ventricular hypertrophy (LVH) has distinct phenotypic adaptations that might me modulated by microRNAs (miRs) which are fine-tune regulators of gene expression. We tested the hypothesis that physiological LVH has differential miRs expression in mice subjected to a voluntary exercise protocol. METHODS: Balb/c mice were kept in cages with exercising wheels (Exercise group - EXE; n=15 sacrificed on day 7 and n=17 sacrificed 35 days after training) or in cages without wheels (Sedentary group - SED; n=12 in each time point). LVH was evaluated by the left ventricular weight/body weight ratio (LVW/BW). MiRs were extracted with miRNeasy kit (Qiagen, USA). A microRNA microarray based on the miRBase version 16 (LC Sciences, Houston, Texas, EUA) was carried out using a pool of miRs extracted from the LV. After miR extraction, 50 pM of synthetic cel-miR-39 were spiked-in as a standard control. RT-qPCR was performed with microRNA Reverse Transcription Kit® and TaqMan Probes® (Applied Biosystems Inc., USA). RESULTS: After 7 days of training there was an increase of 7% in LVW/BW ratio on EXE compared to SED group (3.6±0.2 vs. 3.3±0.1, respectively; p=0.004) and this result was sustained at 35 days (12% increase; 3.7±0.2 vs. 3.3±0.1, respectively; p&lt;0.001). 7 DAYS analyses: expression of miR-26b and miR-143 was decreased in the EXE compared to the SED group (0.5-fold, p=0.017 and 0.7-fold, p=0.018, respectively). miR-150 showed an increased expression in the EXE group (3.0-fold, p=0.001). 35 DAYS analyses: expression of miR-27a was down-regulated (0.8-fold, p=0.03), while miR-150 was up-regulated (1.9-fold, p=0.016) in the EXE group. miRs previously described to be involved in cardiovascular diseases (miR-21, miR-195 and miR-499) were similar between groups. CONCLUSIONS: Our data suggest that physiological LVH was associated to significant modulation of miRs that might regulate affect metabolic adaptations (miR-26b:GSK3B) and apoptosis pathway activation (miR-150:FOXO4). Also miRs could have an effect on cellular growth and hypertrophy (miR-27a:IGF1 and miR-143:MTPN).

Efeito do ultrassom pulsado e do ultrassom contínuo associado a exercícios em pacientes com osteoartrite de joelho: estudo piloto

A osteoartrite (OA) é uma doença crônica associada à morbidade significante. O objetivo deste estudo foi comparar o exercício isolado ao ultrassom pulsado (USP) e contínuo (USC) associados a exercício na redução da dor, melhora da amplitude de movimento (ADM), força muscular (FM), qualidade de vida (QV) e funcionalidade de pacientes com OA de joelhos. Trinta indivíduos, 50 a 75 anos, OA grau 2-4, foram randomizados: Grupo USC (USC + exercícios), Grupo USP (USP + exercícios) e Grupo EXE (exercícios). Os grupos foram avaliados antes e após o tratamento. A intervenção foi realizada três vezes por semana durante oito semanas: nas quatro primeiras foi aplicado USC ou USP e, nas demais foram realizados os exercícios. O Grupo EXE realizou exercícios durante oito semanas. Para análises intragrupos, utilizou-se o teste de Wilcoxon e, intergrupos, o teste de Kruskall-Walis. Na comparação intragrupos, o Grupo USC apresentou melhora significativa (p&lt;0,05) nas variáveis da Western Ontario and McMaster Universities Osteoarthritis (WOMAC) dor, função e escore total; o Grupo USP na dor repouso, ADM, FM e nas variáveis da WOMAC dor, função e escore total; já, o Grupo EXE na mobilidade e ADM. Na comparação intergrupos, o Grupo USC apresentou melhora significativa (p&lt;0,05) quando comparado aos demais grupos na dor repouso, ADM, escores função e total da WOMAC e o Grupo EXE na dor da WOMAC. A associação do USC a exercícios foi mais efetiva na melhora da dor, ADM, função e QV em pacientes com OA de joelho.

Hypothalamic mechanisms relating to improvement of thermal tolerance in heat‐and‐exercise‐acclimated mice

Repeated exposure to moderate heat improves heat tolerance and acclimation. Exercise induces the improvement more effectively than just being at rest. The underlying central mechanisms of those phenomena have remained unclear.Male mice were individually housed at 32°C (HE) or 25°C (NE). The mice in two groups had two‐different exercise conditions: with (EXE) and without (CON) access to running wheels. After eight weeks, the mice had a 2‐h exposure at 36°C.Core temperature and oxygen consumption were lower in HE groups than in NE groups. In the heat exposure of 36°C, core temperature was lower in EXE groups than in CON groups during the first 1 h of the exposure. Ki67‐immunoreactive cell, a marker of cell proliferation, was not observed in the hypothalamus in NE‐CON mice. However, the cells were found in medial preoptic nucleus and dorsomedial hypothalamus in NE‐EXE, HE‐CON, and HE‐EXE mice. cFos immunoreactive cell in the median and medial preoptic nucleus was greater in EXE groups than in CON groups.These results may indicate that daily exercise and long‐term exposure to mild heat, separately, are sufficient to improve heat tolerance and acclimation respectively, and their combined effect induces both improvements. Neurogenesis and neuronal reactivity in the hypothalamus may be responsible for these thermal adaptations.

Regular exercise prevents oxidative stress in the brain of hyperphenylalaninemic rats

Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase, leading to accumulation of phenylalanine and its metabolites. Clinical features of PKU patients include mental retardation, microcephaly, and seizures. Oxidative stress has been found in these patients, and is possibly related to neurophysiopatology of PKU. Regular exercise can leads to adaptation of antioxidant system, improving its capacity to detoxification reactive species. The aim of this study was to verify the effects of regular exercise on oxidative stress parameters in the brain of hyperphenylalaninemic rats. Animals were divided into sedentary (Sed) and exercise (Exe) groups, and subdivided into saline (SAL) and hyperphenylalaninemia (HPA). HPA groups were induced HPA through administration of alpha-methylphenylalanine and phenylalanine for 17 days, while SAL groups (n = 16-20) received saline. Exe groups conducted 2-week aerobic exercise for 20 min/day. At 18th day, animals were killed and the brain was homogenized to determine thiobarbituric acid reactives substances (TBA-RS) content, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. Soleus muscles were collected to determine glycogen content as a marker of oxidative adaptation. Exe groups showed enhanced glycogen content. HPA condition caused an increase in TBA-RS and SOD, and reduces CAT and GPx. Exercise was able to prevent all changes seen in the HPA group, reaching control values, except for SOD activity. No changes were found in the ExeSAL group compared to SedSAL. Hyperphenylalaninemic rats were more responsive to the benefits provided by regular exercise. Physical training may be an interesting strategy to restore the antioxidant system in HPA.

Effects of Endurance Exercise Training and Zoledronic Acid Treatment on Biomaterial Properties of Femora in Ovariectomized Rats

PURPOSE: To determine the effects of endurance exercise training (EXE) and zoledronic acid treatment (ZOL) on bone material properties in ovariectomized rats. METHODS: Sixty female Wistar rats (35 weeks old) were assigned to one sham operated group (SHAM) and four ovariectomized groups with different treatment, which were the OVX, EXE, ZOL; EXE+ZOL groups (n=12 for each). A single injection of zoledronic acid (20 μg/kg body weight) was done on the ZOL and EXE+ZOL groups. And for the EXE and EXE+ZOL groups, animals were subjected to treadmill running training by a protocol of 16m/min, 60min/day and 5 days/week for 10 weeks. Methods of biomechanical properties analysis were included in the current study. Statistical analysis was preceded using one-way ANOVA. Fisher's LSD method was adopted for post hoc comparisons when statistical significance (p<0.05) was shown. RESULTS: Treatment with zoledronic acid resulted in significant increase in femoral fracture load of the EXE+ZOL and ZOL groups as compared to that of the EXE and SHAM groups (53.1±2.2 and 52.4±1.3 vs. 47.2±2.3 and 46.9±1.1 N, p<0.05). Additionally, femoral fracture load of the EXE+ZOL group was significantly higher than that of the OVX group (53.1±2.2 vs. 48.3±1.5 N, p<0.05). Femoral bending stiffness in the EXE+ZOL group was significantly higher than the ZOL, OVX and SHAM groups (154.1±7.9 vs. 133.5±7, 121.9±6.8 and 114.8±4.7 N/mm, p<0.05). And, bending stiffness of the EXE group (139.1±10.2 N/mm) was significantly higher than that of the SHAM group (p<0.05). Conversely, in tissue-level properties, the treadmill running training resulted in significant increase in Young's modulus in the EXE group as compared to the ZOL, SHAM and OVX groups (1.57±0.23 vs. 1.10±0.07, 1.03±0.07 and 1.01±0.08 GPa, p<0.05). In addition, there was a significant difference between the EXE+ZOL and OVX groups (1.33±0.09 vs. 1.01±0.08 GPa, p<0.05). CONCLUSIONS: According to the results of bone biomechanical test, exercise and zoledronic acid treatment protected ovariectomized induced bone degradation through different way. No synergistic or antagonistic effects were shown between exercise training and zoledronic acid treatment.

Abstract 3670: A randomized, placebo-controlled, phase II, presurgical biomarker trial of celecoxib or exemestane in postmenopausal breast cancer patients

Abstract Background Treatment of breast cancer (BC) before surgery provides a window of opportunity to screen the activity and mechanism of action of selected agents. Exemestane (Exe) is an irreversible inactivator of aromatase, the enzyme converting androgens in estrogens. Celecoxib (Cel) is a selective inhibitor of cyclooxygenase-2 (Cox-2), the enzyme involved in the production of prostaglandins that play a key role in tumor proliferation. We conducted a double-blind, placebo-controlled, randomized trial to evaluate the activity and efficacy of Cel and Exe given for 6 weeks before surgery. The main endpoint biomarker was Ki-67 labeling index (LI), a well known marker of tumor proliferation. Secondary endpoints were the modulation of biomarkers associated to BC and cardiovascular disease. Methods Postmenopausal women with histologically-confirmed ER positive BC; stage T1-2, N0-1, M0 were randomly assigned to either Exe 25 mg/d (n=50), or Cel 800 mg/d (n=50) or placebo (n=25) for 6 weeks before surgery. Fasting blood samples were withdrawn at baseline and the day before surgery. Baseline median age was 62, 65, 63 years, and median BMI was 26.56, 24.89, 26.67 in the Exe, Cel and placebo group, respectively. Changes in biomarkers were analyzed through an ANCOVA model adjusting for baseline values. Results Compared to baseline, Exe showed a 10% statistically significant reduction in KI-67% LI (95%CI; -12.52, -7.75) and a 26% reduction in progesterone receptor (PgR) expression (95% CI; -32.67, -18.62) while in the Cel group, we observed a 5% decrease in PgR expression (95%CI: -12.08; 1.84). No change was observed in ER expression. In the placebo arm Ki-67% LI, ER and PgR expression did not change significantly. Compared to baseline, Exe significantly increased testosterone levels by 0.25 ng/mL (95%CI; 0.21, 0.28), while no modulation was observed in the other two arms: Least square means of changes in testosterone were -0.005 (95%CI:-0.05, 0.04) in the placebo arm and -0.001 (95%CI:-0.03, 0.03) in the Cel arm (P for differences between treatment arms&amp;lt;0.0001), respectively. As regards high-sensitivity C-reactive protein levels, no change was observed in any arm. Exe induced a statistically significant -10.87 (95%CI:-17.32, -4.41) decrease in total cholesterol and -6.61(95%CI: -9.63,-3.59) in HDL cholesterol. Triglycerides levels were unchanged. Conversely, Cel induced a borderline statistically significant reduction of antithrombin III levels (P among active treatments =.08) while no difference was observed for fibrinogen levels. Conclusions Our study confirms the anti-proliferative effects of Exe on BC, together with a favourable effect on lipid profile. Further investigations, including the modulation of markers of bone metabolism and the activity of Cox-2 will be conducted to better elucidate the mechanism of action of both drugs in BC prevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3670. doi:10.1158/1538-7445.AM2011-3670

Exercise Is Medicine. Effect Of One Year Combined Exercise And Mediterranean Diet On Metabolic Syndrome Subjects

PURPOSE: to verify the effectiveness of an annual program of endurance and resistance supervised training of physical activity and Mediterranean diet compared to the conventional counselling in nutrition physical activity in improving the glycemic control, the aerobic fitness and reduce the cardiovascular risk in patients with metabolic syndrome. METHODS: 40 subjects, randomized into 2 groups EXE and CON, mean age 58-66 years, BMI 30-34 kg/m2, underwent assessment of VO2 Max, 1 RM tests (of the upper arms and lower limbs), emato-chemical analysis and medical evaluation. The baseline parameters of the two groups were: HbA1c (%) 7.98 (SD 1.6), CRP (mg / l) 3.4 (SD 2.3), VO2max (ml / kg / min) 26.3 (SD 6). The patients in the EXE group were followed with a program of mixed physical activity (aerobic and strength) for 2 times / week, sessions of 70 minutes, for one year. The group EXE was reassessed every 3 months to calibrate the workout. RESULTS: In the EXE group parameters of HbA1 (from 7.98 to 6.85%, p <0.0001), hs-CRP (from 3.36 to 2.22 mg / l, p <0.0001) and VO2max (from 26.3 to 32.5 ml / kg / min, p <0.01) have changed significantly, while in the CON group there was no significant modification. CONCLUSIONS: The results show that only a long term physical exercise program, prescribed on an individual assessment, associated with the nutritional and pharmacological treatment improves the cardio-metabolic risk profile in patients with metabolic syndrome.

Personality, social support and affective states during simulated microgravity in healthy women

This study investigated the time-course of stress and recovery states and their relations to social support and personality traits in healthy women during a long-term head-down tilt bed rest. Personality, social support and affective states were assessed in 16 women exposed to simulated microgravity for a 60-day duration involving three stages: a 20-day baseline control period (BDC), a 60-day head-down tilt bed rest (HDT) and a 20-day post-HDT ambulatory recovery period (R+). Participants were divided into two groups: an exercise (Exe, n = 8) and a control group (Ctl, n = 8). All the participants experienced significantly more stress during the HDT period. But exercise did not improve the impaired effects of simulated microgravity. The Exe group perceived more stress and less recovery than the Ctl group during the HDT period. Among the five major personality factors, only Neuroticism was related to both social and affective variables. Neuroticism was positively associated with stress and negatively associated with recovery and social support (S-SSQ). Practical implications in psychological countermeasures for better dealing with the key human factor in spaceflights are discussed.