Acute responses of regional vascular conductance to oral ingestion of fructose in healthy young humans

Background

Recently, it was reported in healthy young subjects that fructose containing drinks increased blood pressure acutely, without any apparent change in total vascular conductance (TVC). However, because it is well known that the splanchnic vasculature is dilated by oral fructose ingestion, it is assumed to be the concomitant vasoconstriction in other peripheral region(s) that is responsible for this finding. Thus, the purpose of this study was to determine the acute response of regional VC to oral fructose ingestion in young healthy humans.

Results

In 12 healthy young subjects, mean arterial blood pressure (MAP), heart rate, cardiac output, and blood flow (BF) in the superior mesenteric (SMA), brachial (BA), and popliteal (PA) arteries, in addition to forearm skin BF, were measured continuously for 2 h after ingestion of 400 ml fructose solution (containing 50 g fructose). Regional VC was calculated as BF/MAP. MAP increased for 120 min after fructose ingestion without any change in TVC. While VC in the SMA was elevated after ingestion, VC in BA and PA and forearm skin decreased.

Conclusions

While TVC was apparently unchanged during the 2 h after fructose ingestion, there were coincident changes in regional VCs in the peripheral circulation, but no net change in TVC.     

Tranilast Increases Vasodilator Response to Acetylcholine in Rat Mesenteric Resistance Arteries through Increased EDHF Participation

Background and Purpose

Tranilast, in addition to its capacity to inhibit mast cell degranulation, has other biological effects, including inhibition of reactive oxygen species, cytokines, leukotrienes and prostaglandin release. In the current study, we analyzed whether tranilast could alter endothelial function in rat mesenteric resistance arteries (MRA).

Experimental Approach

Acetylcholine-induced relaxation was analyzed in MRA (untreated and 1-hour tranilast treatment) from 6 month-old Wistar rats. To assess the possible participation of endothelial nitric oxide or prostanoids, acetylcholine-induced relaxation was analyzed in the presence of L-NAME or indomethacin. The participation of endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced response was analyzed by preincubation with TRAM-34 plus apamin or by precontraction with a high K⁺ solution. Nitric oxide (NO) and superoxide anion levels were measured, as well as vasomotor responses to NO donor DEA-NO and to large conductance calcium-activated potassium channel opener NS1619.

Key Results

Acetylcholine-induced relaxation was greater in tranilast-incubated MRA. Acetylcholine-induced vasodilation was decreased by L-NAME in a similar manner in both experimental groups. Indomethacin did not modify vasodilation. Preincubation with a high K⁺ solution or TRAM-34 plus apamin reduced the vasodilation to ACh more markedly in tranilast-incubated segments. NO and superoxide anion production, and vasodilator responses to DEA-NO or NS1619 remained unmodified in the presence of tranilast.

Conclusions and Implications

Tranilast increased the endothelium-dependent relaxation to acetylcholine in rat MRA. This effect is independent of the nitric oxide and cyclooxygenase pathways but involves EDHF, and is mediated by an increased role of small conductance calcium-activated K+ channels.     

Rotavirus Vaccination Coverage among Children Aged 2-59 Months: A Report from Guangzhou,China

Objective

We aimed to estimate the Lanzhou lamb rotavirus (LLR) vaccination coverage (VC) and timeliness among children aged 2 to 59 months in Guangzhou, China.

Methods

An electronic system-based VC survey was conducted using stratified cluster random sampling.

Results

We reported an overall Lanzhou lamb rotavirus vaccine coverage of 25.3% among children aged 2-59 months (2-8 months, 2.6%) in Guangzhou, China.

Conclusion

Great efforts should be taken to increase LLR VC in eligible children in Guangzhou, China.     

Possible influences of exercise-intensity-dependent increases in non-cortical hemodynamic variables on NIRS-based neuroimaging analysis during cognitive tasks: Technical note

[Purpose]

Functional near-infrared spectroscopy (fNIRS) provides functional imaging of cortical activations by measuring regional oxy- and deoxy-hemoglobin (Hb) changes in the forehead during a cognitive task. There are, however, potential problems regarding NIRS signal contamination by non-cortical hemodynamic (NCH) variables such as skin blood flow, middle cerebral artery blood flow, and heart rate (HR), which are further complicated during acute exercise. It is thus necessary to determine the appropriate post-exercise timing that allows for valid NIRS assessment during a task without any increase in NCH variables. Here, we monitored post-exercise changes in NCH parameters with different intensities of exercise.

[Methods]

Fourteen healthy young participants cycled 30, 50 and 70% of their peak oxygen uptake (Vo_2peak) for 10 min per intensity, each on different days. Changes in skin blood flow velocity (SBFv), middle cerebral artery mean blood velocity (MCA V_mean) and HR were monitored before, during, and after the exercise.

[Results]

Post-exercise levels of both SBFv and HR in contrast to MCA V_mean remained high compared to basal levels and the times taken to return to baseline levels for both parameters were delayed (2-8 min after exercise), depending upon exercise intensity.

[Conclusion]

These results indicate that the delayed clearance of NCH variables of up to 8 min into the post-exercise phase may contaminate NIRS measurements, and could be a limitation of NIRS-based neuroimaging studies.     

Effects of different doses of leucine ingestion following eight weeks of resistance exercise on protein synthesis and hypertrophy of skeletal muscle in rats

[Purpose]

This study was designed to determine the appropriate Leucine intake volume to obtain the effects of restoring damaged muscle through the synthesis of muscle proteins to increase skeletal muscle and improve exercise performance, and to achieve enhanced muscle hypertrophy.

[Methods]

To clarify the effects of leucine on skeletal muscle hypertrophy of SD rats, following eight weeks of resistance exercise (climbing ladder), the mass of the FHL (Flexor hallucis longus) was measured after extraction, after which change in the activity of muscle signaling proteins (PKB/Akt, mTOR, p70S6K, 4EBP1) was analyzed.

[Results]

The expressions of PKB/Akt, mTOR and p70S6K were increased in L5 (Leucine 50% administration group) compared with the control group (CON) and exercise group (Ex, exercise training group); EL1 (exercise + 10% leucine administration group) and EL5 (exercise + 50% Leucine administration) also exhibited increased expressions of PKB/Akt, mTOR, and p70S6K, while no difference between EL1 and EL5 were observed. No significant differences in 4EBP1 were found among any of the groups. In addition, there were no differences in FHL mass, while relative mass (FHL/body mass) was increased in the exercise group (Ex, EL1, EL5) compared with the control group. No differences were observed among the exercise groups.

[Conclusion]

The present study demonstrated that the relative body mass was increased in the EX group compared with the CON group, while no significant differences in muscle mass could be found among the groups. Even though some signaling proteins were increased, or some differences existed among groups, there were no differences in muscle mass between the leucine administration and exercise training combined with leucine administration groups in the present study.     

Dynamic Cerebral Autoregulation Changes during Sub-Maximal Handgrip Maneuver

Purpose

We investigated the effect of handgrip (HG) maneuver on time-varying estimates of dynamic cerebral autoregulation (CA) using the autoregressive moving average technique.

Methods

Twelve healthy subjects were recruited to perform HG maneuver during 3 minutes with 30% of maximum contraction force. Cerebral blood flow velocity, end-tidal CO₂ pressure (PETCO₂), and noninvasive arterial blood pressure (ABP) were continuously recorded during baseline, HG and recovery. Critical closing pressure (CrCP), resistance area-product (RAP), and time-varying autoregulation index (ARI) were obtained.

Results

PETCO₂ did not show significant changes during HG maneuver. Whilst ABP increased continuously during the maneuver, to 27% above its baseline value, CBFV raised to a plateau approximately 15% above baseline. This was sustained by a parallel increase in RAP, suggestive of myogenic vasoconstriction, and a reduction in CrCP that could be associated with metabolic vasodilation. The time-varying ARI index dropped at the beginning and end of the maneuver (p<0.005), which could be related to corresponding alert reactions or to different time constants of the myogenic, metabolic and/or neurogenic mechanisms.

Conclusion

Changes in dynamic CA during HG suggest a complex interplay of regulatory mechanisms during static exercise that should be considered when assessing the determinants of cerebral blood flow and metabolism.     

Relationships between the extent of apnea-induced bradycardia and the vascular response in the arm and leg during dynamic two-legged knee extension exercise

Our aim was to test the hypothesis that apnea-induced hemodynamic responses during dynamic exercise in humans differ between those who show strong bradycardia and those who show only mild bradycardia. After apnea-induced changes in heart rate (HR) were evaluated during dynamic exercise, 23 healthy subjects were selected and divided into a large response group (L group; n = 11) and a small response group (S group; n = 12). While subjects performed a two-legged dynamic knee extension exercise at a work load that increased HR by 30 beats/min, apnea-induced changes in HR, cardiac output (CO), mean arterial pressure (MAP), arterial O(2) saturation (Sa(O(2))), forearm blood flow (FBF), and leg blood flow (LBF) were measured. During apnea, HR in the L group (54 ± 2 beats/min) was lower than in the S group (92 ± 3 beats/min, P < 0.05). CO, Sa(O(2)), FBF, LBF, forearm vascular conductance (FVC), leg vascular conductance (LVC), and total vascular conductance (TVC) were all reduced, and MAP was increased in both groups, although the changes in CO, TVC, LBF, LVC, and MAP were larger in the L group than in the S group (P < 0.05). Moreover, there were significant positive linear relationships between the reduction in HR and the reductions in TVC, LVC, and FVC. We conclude that individuals who show greater apnea-induced bradycardia during exercise also show greater vasoconstriction in both active and inactive muscle regions.     

The Effect of Laterality and Primary Tumor Site on Cancer-Specific Mortality in Breast Cancer: A SEER Population-Based Study

Background

Reduced overall survival has been observed in patients with left-sided versus right-sided breast cancer due to cardiac toxicity after radiotherapy. However, the effect of laterality and primary tumor site on breast cancer-specific mortality (BCSM) remains unclear.

Patients and Methods

We analyzed data from 305,443 women ages 20- to 79-years-old diagnosed with breast cancer between 1990 and 2009. The data were obtained from the population-based Surveillance, Epidemiology, and End Results (SEER) program of the U.S. National Cancer Institute. The survival outcomes with regard to laterality and primary tumor site were compared using univariate and multivariate (Cox proportional hazards regression model) methods.

Results

In the multivariate analysis, BCSM was affected by the primary tumor site (P<0.0001) but not laterality (P = 0.331). The combined effect was piecewise: using the left upper-outer quadrant as the reference, the BCSM hazard ratio (HR) was not significant in the right upper quadrant (P = 0.755) and the right central portion (P = 0.329). The BCSM HR was slightly increased in the left central portion as well as the left and right lower-outer quadrants (HRs from 1.136 to 1.145; P<0.0001). The BCSM HR was significantly increased in the upper-inner and lower-inner quadrants (HRs from 1.242 to 1.372; P<0.0001) on both sides. Laterality only impacted BCSM in patients with breast cancer located in the central portion (HR, 1.100; P = 0.013, using the right side as the reference).

Conclusion

Patients with tumors in the upper-outer quadrant of both sides and the right central portion have a better prognosis than patients with tumors at other locations. Laterality is not regarded as a prognostic factor in breast cancer.     

Exploratory analysis of a phase III trial of pirfenidone identifies a subpopulation of patients with idiopathic pulmonary fibrosis as benefiting from treatment

Background

A phase III trial in Japan showed that pirfenidone is effective for idiopathic pulmonary fibrosis (IPF). To find out which patients specifically benefit from pirfenidone, we analyzed in an exploratory manner the data from the phase III trial.

Methods

The patients in the phase III trial were stratified by baseline percentage predicted vital capacity (%VC), arterial oxygen partial pressure (PaO₂), and the lowest oxygen saturation by pulse oximetry (SpO₂) during the 6-minute steady-state exercise test (6MET). In the subpopulations, changes in VC and subjective symptoms (cough and dyspnea on the Fletcher, Hugh-Jones [F, H-J] Classification scale) were evaluated in patients treated with high-dose (1800 mg/day) pirfenidone, low-dose (1200 mg/day) pirfenidone, and placebo at week 52.

Results

Significant efficacy of pirfenidone in reducing the decline in VC could be seen in a subpopulation having %VC ≥ 70% and SpO₂ < 90% at baseline. This favorable effect was accompanied by categorical change in VC and progression-free survival time. In the subpopulation, pirfenidone significantly suppressed cough and dyspnea.

Conclusions

IPF patients having %VC ≥ 70% and SpO₂ < 90% at baseline will most likely benefit from pirfenidone when evaluated using changes in VC (and %VC), and cough and dyspnea symptoms. This subpopulation could expect to benefit most from pirfenidone treatment.

Trial Registration

This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (Registration Number: JAPICCTI-050121).     

Does Increased Exercise or Physical Activity Alter Ad-Libitum Daily Energy Intake or Macronutrient Composition in Healthy Adults? A Systematic Review

Background

The magnitude of the negative energy balance induced by exercise may be reduced due to compensatory increases in energy intake.

Objective

To address the question: Does increased exercise or physical activity alter ad-libitum daily energy intake or macronutrient composition in healthy adults?

Data Sources

PubMed and Embase were searched (January 1990–January 2013) for studies that presented data on energy and/or macronutrient intake by level of exercise, physical activity or change in response to exercise. Ninety-nine articles (103 studies) were included.

Study Eligibility Criteria

Primary source articles published in English in peer-reviewed journals. Articles that presented data on energy and/or macronutrient intake by level of exercise or physical activity or changes in energy or macronutrient intake in response to acute exercise or exercise training in healthy (non-athlete) adults (mean age 18–64 years).

Study Appraisal and Synthesis Methods

Articles were grouped by study design: cross-sectional, acute/short term, non-randomized, and randomized trials. Considerable heterogeneity existed within study groups for several important study parameters, therefore a meta-analysis was considered inappropriate. Results were synthesized and presented by study design.

Results

No effect of physical activity, exercise or exercise training on energy intake was shown in 59% of cross-sectional studies (n = 17), 69% of acute (n = 40), 50% of short-term (n = 10), 92% of non-randomized (n = 12) and 75% of randomized trials (n = 24). Ninety-four percent of acute, 57% of short-term, 100% of non-randomized and 74% of randomized trials found no effect of exercise on macronutrient intake. Forty-six percent of cross-sectional trials found lower fat intake with increased physical activity.

Limitations

The literature is limited by the lack of adequately powered trials of sufficient duration, which have prescribed and measured exercise energy expenditure, or employed adequate assessment methods for energy and macronutrient intake.

Conclusions

We found no consistent evidence that increased physical activity or exercise effects energy or macronutrient intake.     

Hydrogen Sulfide in Paraventricular Nucleus Enhances Sympathetic Activity and Cardiac Sympathetic Afferent Reflex in Chronic Heart Failure Rats

Background

Intracerebroventricular infusion of NaHS, a hydrogen sulfide (H₂S) donor, increased mean arterial pressure (MAP). This study was designed to determine the roles of H₂S in the paraventricular nucleus (PVN) in modulating sympathetic activity and cardiac sympathetic afferent reflex (CSAR) in chronic heart failure (CHF).

Methodology/Principal Findings

CHF was induced by left descending coronary artery ligation in rats. Renal sympathetic nerve activity (RSNA) and MAP were recorded under anesthesia. CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin. PVN microinjection of low doses of a H₂S donor, GYY4137 (0.01 and 0.1 nmol), had no significant effects on RSNA, MAP and CSAR. High doses of GYY4137 (1, 2 and 4 nmol) increased baseline RSNA, MAP and heart rate (HR), and enhanced CSAR. The effects were greater in CHF rats than sham-operated rats. A cystathionine-β-synthase (CBS) inhibitor, hydroxylamine (HA) in PVN had no significant effect on the RSNA, MAP and CSAR. CBS activity and H₂S level in the PVN were decreased in CHF rats. No significant difference in CBS level in PVN was found between sham-operated rats and CHF rats. Stimulation of cardiac sympathetic afferents with capsaicin decreased CBS activity and H₂S level in the PVN in both sham-operated rats and CHF rats.

Conclusions

Exogenous H₂S in PVN increases RSNA, MAP and HR, and enhances CSAR. The effects are greater in CHF rats than those in sham-operated rats. Endogenous H₂S in PVN is not responsible for the sympathetic activation and enhanced CSAR in CHF rats.     

Perfusion Index Derived from a Pulse Oximeter Can Detect Changes in Peripheral Microcirculation during Uretero-Renal-Scopy Stone Manipulation (URS-SM)

Background

The objective of this study was to test the effect of removal of a ureteral obstruction (renal calculus) from anesthetized patients on the perfusion index (PI), as measured by a pulse oximeter, and on the estimated glomerular filtration rate (eGFR).

Patients and Methods

This prospective study enrolled 113 patients with unilateral ureteral obstructions (kidney stones) who were scheduled for ureteroscopy (URS) laser lithotripsy. One urologist graded patient hydronephrosis before surgery. A pulse oximeter was affixed to each patient''s index finger ipsilateral to the intravenous catheter, and a non-invasive blood pressure cuff was placed on the contralateral side. Ipsilateral double J stents and Foley catheters were inserted and left indwelling for 24 h. PI and mean arterial pressure (MAP) were determined at baseline, 5 min after anesthesia, and 10 min after surgery; eGFR was determined at admission, 1 day after surgery, and 14 days after surgery.

Results

Patients with different grades of hydronephrosis had similar age, eGFR, PI, mean arterial pressure (MAP), and heart rate (HR). PI increased significantly in each hydronephrosis group after ureteral stone disintegration. None of the groups had significant post-URS changes in eGFR, although eGFR increased in the grade I hydronephrosis group after 14 days. The percent change of PI correlates significantly with the percent change of MAP, but not with that of eGFR.

Conclusion

Our results demonstrate that release of a ureteral obstruction leads to a concurrent increase of PI during anesthesia. Measurement of PI may be a valuable tool to monitor the successful release of ureteral obstructions and changes of microcirculation during surgery. There were also increases in eGFR after 14 days, but not immediately after surgery.     

Aerobic exercise training reduces cannabis craving and use in non-treatment seeking cannabis-dependent adults

Background

Cannabis dependence is a significant public health problem. Because there are no approved medications for this condition, treatment must rely on behavioral approaches empirically complemented by such lifestyle change as exercise.

Aims

To examine the effects of moderate aerobic exercise on cannabis craving and use in cannabis dependent adults under normal living conditions.

Design

Participants attended 10 supervised 30-min treadmill exercise sessions standardized using heart rate (HR) monitoring (60–70% HR reserve) over 2 weeks. Exercise sessions were conducted by exercise physiologists under medical oversight.

Participants

Sedentary or minimally active non-treatment seeking cannabis-dependent adults (n = 12, age 25±3 years, 8 females) met criteria for primary cannabis dependence using the Substance Abuse module of the Structured Clinical Interview for DSM-IV (SCID).

Measurements

Self-reported drug use was assessed for 1-week before, during, and 2-weeks after the study. Participants viewed visual cannabis cues before and after exercise in conjunction with assessment of subjective cannabis craving using the Marijuana Craving Questionnaire (MCQ-SF).

Findings

Daily cannabis use within the run-in period was 5.9 joints per day (SD = 3.1, range 1.8–10.9). Average cannabis use levels within the exercise (2.8 joints, SD = 1.6, range 0.9–5.4) and follow-up (4.1 joints, SD = 2.5, range 1.1–9.5) periods were lower than during the run-in period (both P<.005). Average MCQ factor scores for the pre- and post-exercise craving assessments were reduced for compulsivity (P  = .006), emotionality (P  = .002), expectancy (P  = .002), and purposefulness (P  = .002).

Conclusions

The findings of this pilot study warrant larger, adequately powered controlled trials to test the efficacy of prescribed moderate aerobic exercise as a component of cannabis dependence treatment. The neurobiological mechanisms that account for these beneficial effects on cannabis use may lead to understanding of the physical and emotional underpinnings of cannabis dependence and recovery from this disorder.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00838448","term_id":"NCT00838448"}}NCT00838448]     

Right atrial pressure affects the interaction between lung mechanics and right ventricular function in spontaneously breathing COPD patients

Introduction

It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia. Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firmly established in spontaneously breathing patients at rest or during exercise, nor has it been determined whether these cardiopulmonary interactions are influenced by right atrial pressure.

Methods

Twenty-one patients with COPD underwent simultaneous measurements of intrathoracic, right atrial and pulmonary artery pressures during spontaneous breathing at rest and during exercise. Intrathoracic pressure and right atrial pressure were used to calculate right atrial filling pressure. Dynamic changes in pulmonary artery pulse pressure during expiration were examined to evaluate changes in right ventricular output.

Results

Pulmonary artery pulse pressure decreased up to 40% during expiration reflecting a decrease in stroke volume. The decline in pulse pressure was most prominent in patients with a low right atrial filling pressure. During exercise, a similar decline in pulmonary artery pressure was observed. This could be explained by similar increases in intrathoracic pressure and right atrial pressure during exercise, resulting in an unchanged right atrial filling pressure.

Conclusions

We show that in spontaneously breathing COPD patients the pulmonary artery pulse pressure decreases during expiration and that the magnitude of the decline in pulmonary artery pulse pressure is not just a function of intrathoracic pressure, but also depends on right atrial pressure.     

Risk of severe knee and hip osteoarthritis in relation to level of physical exercise: a prospective cohort study of long-distance skiers in Sweden

Background

To complete long-distance ski races, regular physical exercise is required. This includes not only cross-country skiing but also endurance exercise during the snow-free seasons. The aim of this study was to determine whether the level of physical exercise is associated with future risk of severe osteoarthritis independent of previous diseases and injuries.

Methodology/Principal Findings

We used a cohort that consisted of 48 574 men and 5 409 women who participated in the 90 km ski race Vasaloppet at least once between 1989 and 1998. Number of performed races and finishing time were used as estimates of exercise level. By matching to the National Patient Register we identified participants with severe osteoarthritis, defined as arthroplasty of knee or hip due to osteoarthritis. With an average follow-up of 10 years, we identified 528 men and 42 women with incident osteoarthritis. The crude rate was 1.1/1000 person-years for men and 0.8/1000 person-years for women. Compared with racing once, participation in ≥5 races was associated with a 70% higher rate of osteoarthritis (multivariable-adjusted hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.33 to 2.22). The association was dose-dependent with an adjusted HR of 1.09, 95% CI 1.05 to 1.13 for each completed race. A faster finishing time, in comparison with a slow finishing time, was also associated with an increased rate (adjusted HR 1.51, 95% CI 1.14 to 2.01). Contrasting those with 5 or more ski races and a fast finish time to those who only participated once with a slow finish time, the adjusted HR of osteoarthritis was 2.73, 95% CI 1.78 to 4.18.

Conclusions/Significance

Participants with multiple and fast races have an increased risk of subsequent arthroplasty of knee and hip due to osteoarthritis, suggesting that intensive exercise may increase the risk.     

Resistance exercise training increase activation of AKT-eNOS and Ref-1 expression by FOXO-1 activation in aorta of F344 rats

Purpose

This study investigated the effects of resistance exercise on the Akt-eNOS, the activation of antioxidant protein and FOXO1 in the aorta of F344 rats.

Methods

Male 7 week-old F344 rats were randomly divided into 2 groups: a climbing group (n = 6) and a sedentary group (n = 6). H&E staining and western blotting were used to analyze the rat aortas and target proteins.

Results

Resistance exercise training did not significantly affect aortic structure. Phosphorylation of AKT and eNOS and expression of MnSOD and Ref-1 were significantly increased while FOXO1 phosphorylation was significantly decreased in the resistance exercise group compared with the sedentary group.

Conclusion

We demonstrate that resistance exercise activates the Akt-eNOS and Ref-1 protein without changes to aortic thickness via FOXO-1 activation in the aorta of F344 rats.     

Participation in Sports Organizations and the Prevention of Functional Disability in Older Japanese: The AGES Cohort Study

Background

We sought to examine prospectively the difference in the association between incident functional disability and exercise with or without sports organization participation.

Methods

The study was based on the Aichi Gerontological Evaluation Study (AGES) Cohort Study data. In October 2003, self-reported questionnaires were mailed to 29,374 non-disabled Japanese individuals aged 65 years or older. Of these, 13,310 individuals were introduced to the Study, and they were followed for 4 years. Analysis was carried out on 11,581 subjects who provided all necessary information for the analysis.

Results

Analysis was carried out on incident functional disability by 4 groups of different combinations of performance of exercise and participation in a sports organization Active Participant (AP), Exercise Alone (EA), Passive Participant (PP) and Sedentary (S). Compared to the AP group, the EA group had a hazard ratio (HR) of 1.29 (1.02–1.64) for incident functional disability. No significant difference was seen with the PP group, with an HR of 1.16 (0.76–1.77). When a measure of social networks was added to the covariates, the HR of the EA group dropped to 1.27 (1.00–1.61), and significant differences disappeared. In contrast, it showed hardly any change when social support was added.

Conclusion

The results suggested that, even with a regular exercise habit, incident functional disability may be better prevented when a person participates in a sports organization than when he/she does not. In addition, participation in a sports organization correlates positively with social networks, which may lead to a small decrease in incident functional disability.     

Adults with Down syndrome have reduced cardiac response after light exercise testing

Objective

Physical fitness is reduced in adults with Down syndrome (DS). The present study was conducted to elucidate the exercise response in adults with DS.

Design

Case controlled before-after trial.

Setting

Residential centre for people with intellectual disabilities.

Participants

96 Adults with DS, 25 non-DS adults with an intellectual disability, 33 controls.

Interventions

Echocardiography to exclude heart defects and to measure cardiac index (CI) in the supine position, supine position with raised legs, and following ten knee bends.

Main outcome measure

Exercise testing

Results

At rest, mean CI was not significantly different between persons with DS and controls (2.3 vs. 2.4 l/min/m², p = 0.3). However, mean CI after exercise was significantly lower in DS (2.9 vs. 3.7 l/min/m², p < 0.001) and mean CI increase from rest to exercise was more than 50% lower in DS. On the contrary, CI after exercise was similar among controls and non-DS adults with an intellectual disability. Significantly lower stroke volumes in DS were found with insufficient heart rate response.

Conclusions

CI at rest was similar in adults with DS and controls; however persons with DS have a diminished cardiac response to exercise. Stroke volumes were significantly lower in DS during exercise and a compensated heightened heart rate was absent.     

Skeletal muscle-specific expression of PGC-1α-b, an exercise-responsive isoform, increases exercise capacity and peak oxygen uptake

Background

Maximal oxygen uptake (VO_2max) predicts mortality and is associated with endurance performance. Trained subjects have a high VO_2max due to a high cardiac output and high metabolic capacity of skeletal muscles. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a nuclear receptor coactivator, promotes mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training increases PGC-1α in skeletal muscle, PGC-1α-mediated changes may contribute to the improvement of exercise capacity and VO_2max. There are three isoforms of PGC-1α mRNA. PGC-1α-b protein, whose amino terminus is different from PGC-1α-a protein, is a predominant PGC-1α isoform in response to exercise. We investigated whether alterations of skeletal muscle metabolism by overexpression of PGC-1α-b in skeletal muscle, but not heart, would increase VO_2max and exercise capacity.

Methodology/Principal Findings

Transgenic mice showed overexpression of PGC-1α-b protein in skeletal muscle but not in heart. Overexpression of PGC-1α-b promoted mitochondrial biogenesis 4-fold, increased the expression of fatty acid transporters, enhanced angiogenesis in skeletal muscle 1.4 to 2.7-fold, and promoted exercise capacity (expressed by maximum speed) by 35% and peak oxygen uptake by 20%. Across a broad range of either the absolute exercise intensity, or the same relative exercise intensities, lipid oxidation was always higher in the transgenic mice than wild-type littermates, suggesting that lipid is the predominant fuel source for exercise in the transgenic mice. However, muscle glycogen usage during exercise was absent in the transgenic mice.

Conclusions/Significance

Increased mitochondrial biogenesis, capillaries, and fatty acid transporters in skeletal muscles may contribute to improved exercise capacity via an increase in fatty acid utilization. Increases in PGC-1α-b protein or function might be a useful strategy for sedentary subjects to perform exercise efficiently, which would lead to prevention of life-style related diseases and increased lifespan.