bluuebunny/crossref_metadata_2025 huggingface dataset:
Partial restoration of dietary fat induced metabolic adaptations to training by 7 days of carbohydrate diet
Authors: Helge Jørn W. , Watt Peter W. , Richter Erik A. , Rennie Michael J. , Kiens Bente
Published: March 2015

We tested the hypothesis that a shift to carbohydrate diet after prolonged adaptation to fat diet would lead to decreased glucose uptake and impaired muscle glycogen breakdown during exercise compared with ingestion of a carbohydrate diet all along. We studied 13 untrained men; 7 consumed a high-fat (Fat-CHO; 62% fat, 21% carbohydrate) and 6 a high-carbohydrate diet (CHO; 20% fat, 65% carbohydrate) for 7 wk, and thereafter both groups consumed the carbohydrate diet for an eighth week. Training was performed throughout. After 8 wk, during 60 min of exercise (71 ± 1% pretraining maximal oxygen uptake) average leg glucose uptake (1.00 ± 0.07 vs. 1.55 ± 0.21 mmol/min) was lower ( P < 0.05) in Fat-CHO than in CHO. The rate of muscle glycogen breakdown was similar (4.4 ± 0.5 vs. 4.2 ± 0.7 mmol · min−1· kg dry wt−1) despite a significantly higher preexercise glycogen concentration (872 ± 59 vs. 688 ± 43 mmol/kg dry wt) in Fat-CHO than in CHO. In conclusion, shift to carbohydrate diet after prolonged adaptation to fat diet and training causes increased resting muscle glycogen levels but impaired leg glucose uptake and similar muscle glycogen breakdown, despite higher resting levels, compared with when the carbohydrate diet is consumed throughout training.
Upper airway extraluminal tissue pressure fluctuations during breathing in rabbits
Authors: Kairaitis Kristina , Parikh Radha , Stavrinou Rosie , Garlick Sarah , Kirkness Jason P. , Wheatley John R. , Amis Terence C.
Published: March 2015

Transmural pressure at any level in the upper airway is dependent on the difference between intraluminal airway and extraluminal tissue pressure (ETP). We hypothesized that ETP would be influenced by topography, head and neck position, resistive loading, and stimulated breathing. Twenty-eight male, New Zealand White, anesthetized, spontaneously breathing rabbits breathed via a face mask with attached pneumotachograph to measure airflow and pressure transducer to monitor mask pressure. Tidal volume was measured via integration of the airflow signal. ETP was measured with a pressure transducer-tipped catheter inserted in the tissues of the lateral (ETPlat, n = 28) and anterior (ETPant, n = 21) pharyngeal wall. Head position was controlled at 30, 50, or 70°, and the effect of addition of an external resistor, brief occlusion, or stimulated breathing was examined. Mean ETPlat was ∼0.7 cmH2O greater than mean ETPant when adjusted for degree of head and neck flexion ( P < 0.05). Mean, maximum, and minimum ETP values increased significantly by 0.7-0.8 cmH2O/20° of head and neck flexion when adjusted for site of measurement ( P < 0.0001). The main effect of resistive loading and occlusion was an increase in the change in ETPlat (maximum - minimum ETPlat) and change in ETPant at all head and neck positions ( P < 0.05). Mean ETPlat and ETPant increased with increasing tidal volume at head and neck position of 30° (all P < 0.05). In conclusion, ETP was nonhomogeneously distributed around the upper airway and increased with both increasing head and neck flexion and increasing tidal volume. Brief airway occlusion increased the size of respiratory-related ETP fluctuations in upper airway ETP.
Declines in physiological functional capacity with age: a longitudinal study in peak swimming performance
Authors: Donato Anthony J. , Tench Kathleen , Glueck Deborah H. , Seals Douglas R. , Eskurza Iratxe , Tanaka Hirofumi
Published: March 2015

We followed up swimming performance times of 321 women and 319 men who participated in the US Masters Swimming Championships over a 12-yr period. All swimmers placed in the top 10 in their age group over 3 yr (mean = 5 yr). A random coefficients model for repeated measures was used to derive a line of best fit from a group of regression lines for each subject. Both 50- and 1,500-m swimming performance declined modestly until ∼70 yr of age, where a more rapid decline was observed in both men and women. Compared with 1,500-m swimming, the 50-m freestyle declined more modestly and slowly with age. The rate and magnitude of declines in swimming performance with age were greater in women than in men in 50-m freestyle; such sex-related differences were not observed in 1,500-m freestyle. Overall, the variability along a population regression line increased markedly with advancing age. The present longitudinal findings indicate that 1) swimming performance declines progressively until age 70, where the decrease becomes quadratic; 2) the rates of the decline in swimming performance with age are greater in a long-duration than in a short-duration event, suggesting a relatively smaller loss of anaerobic muscular power with age compared with cardiovascular endurance; 3) the age-related rates of decline are greater in women than in men only in a short-duration event; and 4) the variability of the age-related decline in performance increases markedly with advancing age.
Exercise effects on muscle β-adrenergic signaling for MAPK-dependent NKCC activity are rapid and persistent
Authors: Gosmanov Aidar R. , Nordtvedt Nicholas C. , Brown Richard , Thomason Donald B.
Published: March 2015

This study investigated exercise adaptation of signaling mechanisms that control Na+-K+-2Cl− cotransporter (NKCC) activity in rat skeletal muscle. An acute bout of exercise increased total and NKCC-mediated 86Rb influx. Inhibition of extracellular signal-regulated kinase (ERK) activation abolished the exercise-induced NKCC upregulation. Treadmill training (20 m/min, 20% grade, 30 min/day, 5 days/wk) stimulated total 86Rb influx and increased NKCC activity in the soleus muscle after 2 wk and in the plantaris muscle after 4 wk. Exercise-induced NKCC activity was associated with a 1.4- to 2-fold increase in ERK phosphorylation. Isoproterenol, which activates ERK and NKCC in sedentary muscle, caused a remarkable inhibition of the exercise-induced NKCC activity. Furthermore, isoproterenol inhibition of exercise-induced NKCC activity was accompanied with decreased ERK phosphorylation in the plantaris muscle. Akt (protein kinase B) phosphorylation on both Thr308 and Ser473, which activates Akt and inhibits NKCC activity in sedentary muscle, was stimulated by acute and chronic exercise. This Akt activation was unaffected by isoproterenol. These results indicate an immediate and persistent exercise adaptation of the signal pathways that participate in the control of potassium transport.
Epinephrine inhibits insulin-stimulated muscle glucose transport
Authors: Hunt Desmond G. , Ivy John L.
Published: March 2015

We recently demonstrated that epinephrine could inhibit the activation by insulin of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase) in skeletal muscle (Hunt DG, Zhenping D, and Ivy JL. J Appl Physiol 92: 1285–1292, 2002). Activation of PI3-kinase is recognized as an essential step in the activation of muscle glucose transport by insulin. We therefore investigated the effect of epinephrine on insulin-stimulated glucose transport in both fast-twitch (epitrochlearis) and slow-twitch (soleus) muscle of the rat by using an isolated muscle preparation. Glucose transport was significantly increased in the epitrochlearis and soleus when incubated in 50 and 100 μU/ml insulin, respectively. Activation of glucose transport by 50 μU/ml insulin was inhibited by 24 nM epinephrine in both muscle types. This inhibition of glucose transport by epinephrine was accompanied by suppression of IRS-1-associated PI3-kinase activation. However, when muscles were incubated in 100 μU/ml insulin, 24 nM epinephrine was unable to inhibit IRS-1-associated PI3-kinase activation or glucose transport. Even when epinephrine concentration was increased to 500 nM, no attenuating effect was observed on glucose transport. Results of this study indicate that epinephrine is capable of inhibiting glucose transport activated by a moderate, but not a high, physiological insulin concentration. The inhibition of glucose transport by epinephrine appears to involve the inhibition of IRS-1-associated PI3-kinase activation.
Effect of pedal rate on primary and slow-component oxygen uptake responses during heavy-cycle exercise
Authors: Pringle Jamie S. M. , Doust Jonathan H. , Carter Helen , Tolfrey Keith , Jones Andrew M.
Published: March 2015

We hypothesized that a higher pedal rate (assumed to result in a greater proportional contribution of type II motor units) would be associated with an increased amplitude of the O2 uptake (V˙o 2) slow component during heavy-cycle exercise. Ten subjects (mean ± SD, age 26 ± 4 yr, body mass 71.5 ± 7.9 kg) completed a series of square-wave transitions to heavy exercise at pedal rates of 35, 75, and 115 rpm. The exercise power output was set at 50% of the difference between the pedal rate-specific ventilatory threshold and peakV˙o 2, and the baseline power output was adjusted to account for differences in the O2 cost of unloaded pedaling. The gain of the V˙o 2primary component was significantly higher at 35 rpm compared with 75 and 115 rpm (mean ± SE, 10.6 ± 0.3, 9.5 ± 0.2, and 8.9 ± 0.4 ml · min−1 · W−1, respectively; P < 0.05). The amplitude of theV˙o 2 slow component was significantly greater at 115 rpm (328 ± 29 ml/min) compared with 35 rpm (109 ± 30 ml/min) and 75 rpm (202 ± 38 ml/min) ( P < 0.05). There were no significant differences in the time constants or time delays associated with the primary and slow components across the pedal rates. The change in blood lactate concentration was significantly greater at 115 rpm (3.7 ± 0.2 mM) and 75 rpm (2.8 ± 0.3 mM) compared with 35 rpm (1.7 ± 0.4 mM) ( P < 0.05). These data indicate that pedal rate influences V˙o 2 kinetics during heavy exercise at the same relative intensity, presumably by altering motor unit recruitment patterns.
Selected Contribution: Genioglossus muscle activity at rest and in response to brief hypoxia in healthy men and women
Authors: Jordan A. S. , Catcheside P. G. , O'Donoghue F. J. , Saunders N. A. , McEvoy R. D.
Published: March 2015

10.1152/japplphysiol.00461.2001.—Obstructive sleep apnea (OSA) is more common in men than in women for reasons that are not clearly understood. An underlying difference between men and women in the respiratory-related neural control of upper airway dilator muscles has been suggested as a possible reason for the gender difference. We have compared three aspects of upper airway dilator muscle function in healthy men and women: 1) resting inspiratory genioglossus electromyogram (EMGgg) activity, 2) the respiratory EMGgg “afterdischarge” after a brief hypoxic stimulus, and 3) the relationship between the EMGgg and pharyngeal airway pressure. Inspired minute ventilation (V˙i), epiglottic pressure (Pepi), and EMGgg and diaphragm EMG (EMGdi) activity were measured in 24 subjects (12 men, 12 women in the luteal menstrual phase) and were compared between genders while lying supine awake. Every 7–8 min over 2 h, subjects were exposed to 45-s periods of isocapnic hypoxia (9% O2 in N2) that were abruptly terminated with one breath of 100% O2. The relationship between Pepi and EMGgg activity was also compared between genders. The results of 117 trials with satisfactory end-tidal Pco 2 control and no sighs or swallows are reported. There was no gender difference in the resting level of peak inspiratory EMGgg [3.7 ± 0.8 (women) vs. 3.2 ± 0.6% maximal activity (men)]. Repeated-measures ANOVA showed no gender or gender-by-time interaction effect between men and women inV˙i or EMGgg or EMGdi activity during or after the hypoxic stimulus. The relationship between Pepi and EMGgg was not different between men (slope −0.63 ± 0.20) and women (slope −0.69 ± 0.33). These results do not support the hypothesis that the higher prevalence of OSA in men is related to an underlying gender difference in respiratory neural control of upper airway dilator muscles.
Effect of morphine on sympathetic nerve activity in humans
Authors: Carter Jason R. , Sauder Charity L. , Ray Chester A.
Published: March 2015

There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at rest and during isometric handgrip (IHG). Eleven subjects performed 2 min of IHG (30% maximum) followed by 2 min of postexercise muscle ischemia (PEMI) before and after systemic infusion of morphine (0.075 mg/kg loading dose + 1 mg/h maintenance) or placebo (saline) in double-blinded experiments on separate days. Morphine increased resting muscle sympathetic nerve activity (MSNA; 17 ± 2 to 22 ± 2 bursts/min; P < 0.01) and increased mean arterial pressure (MAP; 87 ± 2 to 91 ± 2 mmHg; P < 0.02), but it decreased heart rate (HR; 61 ± 4 to 59 ± 3; P < 0.01). However, IHG elicited similar increases for MSNA, MAP, and HR between the control and morphine trial (drug × exercise interaction = not significant). Moreover, responses to PEMI were not different. Placebo had no effect on resting, IHG, and PEMI responses. We conclude that morphine modulates cardiovascular and sympathetic responses at rest but not during isometric exercise.
Branched-chain amino acid supplementation during bed rest: effect on recovery
Authors: Stein T. P. , Donaldson M. R. , Leskiw M. J. , Schluter M. D. , Baggett D. W. , Boden G.
Published: March 2015

Bed rest is associated with a loss of protein from the weight-bearing muscle. The objectives of this study are to determine whether increasing dietary branched-chain amino acids (BCAAs) during bed rest improves the anabolic response after bed rest. The study consisted of a 1-day ambulatory period, 14 days of bed rest, and a 4-day recovery period. During bed rest, dietary intake was supplemented with either 30 mmol/day each of glycine, serine, and alanine ( group 1) or with 30 mmol/day each of the three BCAAs ( group 2). Whole body protein synthesis was determined with U-15N-labeled amino acids, muscle, and selected plasma protein synthesis withl-[2H5]phenylalanine. Total glucose production and gluconeogenesis from alanine were determined with l-[U-13C3]alanine and [6,6-2H2]glucose. During bed rest, nitrogen (N) retention was greater with BCAA feeding (56 ± 6 vs. 26 ± 12 mg N · kg−1 · day−1, P < 0.05). There was no effect of BCAA supplementation on either whole body, muscle, or plasma protein synthesis or the rate of 3-MeH excretion. Muscle tissue free amino acid concentrations were increased during bed rest with BCAA (0.214 ± 0.066 vs. 0.088 ± 0.12 nmol/mg protein, P < 0.05). Total glucose production and gluconeogenesis from alanine were unchanged with bed rest but were significantly reduced ( P < 0.05) with the BCAA group in the recovery phase. In conclusion, the improved N retention during bed rest is due, at least in part, to accretion of amino acids in the tissue free amino acid pools. The amount accreted is not enough to impact protein kinetics in the recovery phase but does improve N retention by providing additional essential amino acids in the early recovery phase.
Effect of gravity and posture on lung mechanics
Authors: Bettinelli D. , Kays C. , Bailliart O. , Capderou A. , Techoueyres P. , Lachaud J. L. , Vaïda P. , Miserocchi G.
Published: March 2015

The volume-pressure relationship of the lung was studied in six subjects on changing the gravity vector during parabolic flights and body posture. Lung recoil pressure decreased by ∼2.7 cmH2O going from 1 to 0 vertical acceleration (Gz), whereas it increased by ∼3.5 cmH2O in 30° tilted head-up and supine postures. No substantial change was found going from 1 to 1.8 Gz. Matching the changes in volume-pressure relationships of the lung and chest wall (previous data), results in a decrease in functional respiratory capacity of ∼580 ml at 0 Gz relative to 1 Gz and of ∼1,200 ml going to supine posture. Microgravity causes a decrease in lung and chest wall recoil pressures as it removes most of the distortion of lung parenchyma and thorax induced by changing gravity field and/or posture. Hypergravity does not greatly affect respiratory mechanics, suggesting that mechanical distortion is close to maximum already at 1 Gz. The end-expiratory volume during quiet breathing corresponds to the mechanical functional residual capacity in each condition.
Albumin transcytosis from the pleural space
Authors: Agostoni Emilio , Bodega Francesca , Zocchi Luciano
Published: March 2015

Occurrence of transcytosis in pleural mesothelium was verified by measuring removal of labeled macromolecules from pleural liquid in experiments without and with nocodazole. To this end, we injected 0.3 ml of Ringer-albumin with 750 μg of albumin-Texas red or with 600 μg of dextran 70-Texas red in the right pleural space of anesthetized rabbits, and after 3 h we measured pleural liquid volume, labeled macromolecule concentration, and, hence, labeled macromolecule quantity in the liquid of this space. Labeled albumin left was 318 ± 28 μg in control and 419 ± 17 μg in nocodazole experiments (means ± SE); hence, whereas ventilation was similar its removal was greater ( P < 0.01) in control experiments. Labeled dextran left was 283 ± 10 μg in control and 381 ± 21 μg in nocodazole experiments; hence, whereas ventilation was similar its removal was greater ( P < 0.01) in control experiments. These findings indicate occurrence of transcytosis from the pleural space. Liquid removed by transcytosis was 0.05 ml/h. This amount times unlabeled albumin concentration under physiological conditions (10 mg/ml) times lumen-vesicle partition coefficient for albumin (0.78) provides fluid-phase albumin transcytosis: ∼203 μg · h−1 kg−2/3. Transcytosis might contribute a relevant part of protein and liquid removal from the pleural space.
Effect of hyperthyroidism on spontaneous physical activity and energy expenditure in rats
Authors: Levine James A. , Nygren Jonas , Short Kevin R. , Nair K. Sreekumaran
Published: March 2015

Thyroid hormone excess is associated with increased energy expenditure. The contributions of increases in spontaneous physical activity and nonexercise activity thermogenesis (NEAT) to this effect have not been defined. To address the hypothesis that hyperthyroidism is associated with increased spontaneous physical activity and NEAT, we rendered rats hyperthyroid by using continuous infusion of high-dose triiodothyronine for 14 days and measured the effects on physical activity and NEAT. On day 14, in the hyperthyroid group the mean ± SD triiodothyronine concentration was 755 ± 137 (range 574–919) ng/dl and in the control group 59 ± 0.5 (58–59) ng/dl. Over the 14-day treatment period, mean spontaneous physical activity increased in the hyperthyroid rats from 24 ± 7 to 36 ± 6 activity units (AU)/min; P < 0.001 but did not increase in the controls (23 ± 7 vs. 22 ± 4 AU/min). Also, over the 14-day period, daily NEAT increased in the hyperthyroid rats from 8.1 ± 2.8 to 19.7 ± 5.0 kcal/day ( P < 0.001) but did not increase in the controls (8.7 ± 3.5 cf 9.4 ± 1.7 kcal/day; not significant). In conclusion, hyperthyroidism is associated with increased spontaneous physical activity and NEAT.
Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance
Authors: Waters Wendy W. , Ziegler Michael G. , Meck Janice V.
Published: March 2015

About 20% of astronauts suffer postspaceflight presyncope. We studied pre- to postflight (5- to 16-day missions) cardiovascular responses to standing in 35 astronauts to determine differences between 1) men and women and 2) presyncopal and nonpresyncopal groups. The groups were presyncopal women, presyncopal men, and nonpresyncopal men based on their ability to stand for 10 min postflight. Preflight, women and presyncopal men had low vascular resistance, with the women having the lowest. Postflight, women experienced higher rates of presyncope (100 vs. 20%; P = 0.001) and greater losses of plasma volume (20 vs. 7%; P < 0.05) than men. Also, presyncopal subjects had lower standing mean arterial pressure (P ≤ 0.001) and vascular resistance ( P < 0.05), smaller increases in norepinephrine ( P ≤ 0.058) and greater increases in epinephrine ( P ≤ 0.058) than nonpresyncopal subjects. Presyncopal subjects had a strong dependence on plasma volume to maintain standing stroke volume. These findings suggest that postflight presyncope is greatest in women, and this can be ascribed to a combination of inherently low-resistance responses, a strong dependence on volume status, and relative hypoadrenergic responses. Conversely, high vascular resistance and postflight hyperadrenergic responses prevent presyncope.
Time course and dose response of relaxin-mediated renal vasodilation, hyperfiltration, and changes in plasma osmolality in conscious rats
Authors: Danielson Lee A. , Conrad Kirk P.
Published: March 2015

The pregnancy hormone relaxin elicits renal vasodilation, hyperfiltration, and osmoregulatory changes when chronically administered to conscious, nonpregnant rats. The objective in this study was to determine the dose response and time course of hormone action, as well as the time required for recovery on stopping its administration. The threshold dose of recombinant human relaxin (rhRLX) for renal vasodilation and reduction in plasma osmolality was 0.15 μg/h when given by subcutaneous osmotic minipump for 2 days (an infusion rate that achieved circulating levels of ∼6 ng/ml). The peak response was observed during the 0.4 μg/h infusion rate (serum rhRLX of ∼11 ng/ml), which was comparable to our previous work using a 4.0 μg/h (serum rhRLX of ∼20 ng/ml). In contrast, a dose of 40 μg/h was ineffective (serum rhRLX of ∼80 ng/ml). When 4.0 μg/h rhRLX was administered by osmotic minipump for shorter periods (≤24 h), renal circulatory and osmoregulatory changes were observed by ≤6 h. After removal of the osmotic minipump, these changes persisted for at least 12 h, but they were fully restored by 24 h. Even briefer administration of 4.0 μg/h rhRLX by intravenous infusion showed an onset of action in the kidney by 1-2 h. In contrast, the 40 μg/h dose of rhRLX elicited minimal effects, and comparable to our earlier report, 4.0 μg/h purified porcine relaxin was also relatively ineffective during short-term intravenous administration. In conclusion, the effect of relaxin on the renal circulation and osmoregulation is biphasic, insofar as high doses are relatively inactive, and the onset of action is more rapid than previously believed. These findings may be important to consider when evaluating relaxin in the treatment of renal disease.
Gender influence on vasoactive hormones at rest and during a 70° head-up tilt in healthy humans
Authors: Geelen Ghislaine , Laitinen Tomi , Hartikainen Juha , Länsimies Esko , Bergström Kim , Niskanen Leo
Published: March 2015

To evaluate the influence of age and gender on the neuroendocrine control of blood pressure in normal subjects, a 13-min 70° head-up tilt (HUT) was applied after 3 h of recumbency to 109 healthy men and women aged 23–50 yr ( age group I) and 51–77 yr ( age group II). We found that age and gender had a significant influence on plasma norepinephrine (PNE) concentration at baseline and in the upright position. PNE was significantly higher in older men compared with the younger men and women of both age groups, suggesting a divergent age-related activation of the sympathetic nervous system between genders at baseline as well as during a sustained orthostatic challenge. There was no significant influence of age or gender on plasma epinephrine at baseline or during HUT. Plasma renin activity was significantly higher at baseline as well as in the upright position during HUT in elderly men than in women. Age or gender had no influence on plasma vasopressin (PAVP), and, regardless of age, nonhypotensive HUT induced an extremely modest increase in PAVP. The syncopal subjects displayed a hormonal pattern associating increased PNE and a surge in plasma epinephrine and PAVP minutes before syncope during HUT. The orthostatic intolerance appears not to be a feature of healthy aging per se. In healthy subjects, both age and gender modulate markedly the cardiovascular and neuroendocrine responses to an orthostatic challenge and must be taken into consideration, particularly when catecholamine responses are studied.
Transneuronal tracing of neural pathways influencing both diaphragm and genioglossal muscle activity in the ferret
Authors: Shintani T , Anker A. R. , Billig I , Card J. P. , Yates B. J.
Published: March 2015

In prior experiments that employed the transneuronal transport of isogenic recombinants of pseudorabies virus (PRV), we demonstrated that neurons located ventrally in the medial medullary reticular formation (MRF) of the ferret provide collateralized projections to both diaphragm and abdominal muscle motoneurons as well as to multiple abdominal muscle motoneuron pools. The goal of the present study was to determine whether single MRF neurons also furnish inputs to diaphragm motoneurons and those innervating an airway muscle with inspiratory-related activity: the tongue protruder genioglossus. For this purpose, PRV recombinants expressing unique reporters (β-galactosidase or enhanced green fluorescent protein) were injected into either the diaphragm or the genioglossal muscle. The virus injections produced transneuronal infection of overlapping populations of MRF neurons. A small proportion of these neurons (<15%) was infected by both PRV recombinants, which indicated that they provide collateralized inputs to genioglossal and diaphragm motoneurons. These findings show that, whereas some MRF neurons simultaneously influence the activity of upper airway and respiratory pump muscles, other cells in this brain stem region independently contribute to diaphragm and genioglossal muscle contraction regulation.
Invited Review: Pathogenesis of osteoporosis
Authors: Seeman Ego
Published: March 2015

Patients with fragility fractures may have abnormalities in bone structural and material properties such as larger or smaller bone size, fewer and thinner trabeculae, thinned and porous cortices, and tissue mineral content that is either too high or too low. Bone models and remodels throughout life; however, with advancing age, less bone is replaced than was resorbed within each remodeling site. Estrogen deficiency at menoause increases remodeling intensity: a greater proportion of bone is remodeled on its endosteal (inner) surface, and within each of the many sites even more bone is lost as more bone is resorbed while less is replaced, accelerating architectural decay. In men, there is no midlife increase in remodeling. Bone loss within each remodeling site proceeds by reduced bone formation, producing trabecular and cortical thinning. Hypogonadism in 20-30% of elderly men contributes to bone loss. In both sexes, calcium malabsorption and secondary hyperparathyroidism increase remodeling: more bone is removed from an ever-diminishing bone mass. As bone is removed from the endosteal envelope, concurrent bone formation on the periosteal (outer) bone surface during aging partly offsets bone loss and increases bone's cross-sectional area. Periosteal apposition is less in women than in men; therefore, women have more net bone loss because they gain less on the periosteal surface, not because they resorb more on the endosteal surface. More women than men experience fractures because their smaller skeleton incurs greater architectural damage and adapts less by periosteal apposition.
Effects of VDT tasks with a bright display at night on melatonin, core temperature, heart rate, and sleepiness
Authors: Higuchi Shigekazu , Motohashi Yutaka , Liu Yang , Ahara Mio , Kaneko Yoshihiro
Published: March 2015

The effects of performing video display terminal (VDT) tasks with a bright display (BD) at night on nocturnal salivary melatonin concentration, rectal temperature, heart rate, and sleepiness were examined. Seven healthy male adults performed exciting VDT tasks with a BD and a dark display (DD) and boring VDT tasks with a BD and a DD from 2300 to 0200. The light intensities of the BD and DD were 45 and 15 lx at each subject's eye level, respectively. The exciting VDT task with both BD and DD significantly suppressed the nocturnal decrease in rectal temperature and heart rate and the nocturnal increase in sleepiness. The BD significantly suppressed the nocturnal decrease in rectal temperature during both exciting and boring VDT tasks. The nocturnal salivary melatonin concentration was significantly suppressed by the combination of the exciting task and BD. The results suggest that performing an exciting VDT task with a BD suppresses the nocturnal changes in melatonin concentration and other physiological indicators of human biological clocks.
Raised plasma G-CSF and IL-6 after exercise may play a role in neutrophil mobilization into the circulation
Authors: Yamada Mutsuo , Suzuki Katsuhiko , Kudo Satoru , Totsuka Manabu , Nakaji Shigeyuki , Sugawara Kazuo
Published: March 2015

We examined the hypothesis that the short, intensive exercise-induced increase in circulating neutrophil counts is affected by the interaction between the endocrine and immune systems. Twelve male winter-sports athletes underwent a maximal exercise test on a treadmill. Blood samples were collected before, immediately after (Post), and 1 h (Post 1 h) and 2 h (Post 2 h) after the exercise. The neutrophil counts increased significantly at Post 1 h ( P < 0.05) and remained significantly high even at Post 2 h ( P < 0.05), showing a leftward shift. Plasma granulocyte colony-stimulating factor (G-CSF) increased at Post ( P < 0.05), and interleukin-6 (IL-6) increased at Post 1 h ( P < 0.05). Plasma G-CSF at Post significantly correlated with the numbers of both neutrophils and stab cells at Post 1 h ( P < 0.05). Plasma IL-6 at Post 1 h levels also correlated significantly with the number of neutrophils at Post 2 h ( P < 0.05). The increase in the levels of plasma G-CSF and IL-6 after intensive exercise may play a role in the mobilization of neutrophils into the circulatory system.
Exogenous NO administration and α-adrenergic vasoconstriction in human limbs
Authors: Rosenmeier Jaya B. , Fritzlar Sandy J. , Dinenno Frank A. , Joyner Michael J.
Published: March 2015

Nitric oxide (NO) is capable of blunting α-adrenergic vasoconstriction in contracting skeletal muscles of experimental animals (functional sympatholysis). We therefore tested the hypothesis that exogenous NO administration can blunt α-adrenergic vasoconstriction in resting human limbs by measuring forearm blood flow (FBF; Doppler ultrasound) and blood pressure in eight healthy males during brachial artery infusions of three α-adrenergic constrictors (tyramine, which evokes endogenous norepinephrine release; phenylephrine, an α1-agonist; and clonidine, an α2-agonist). To simulate exercise hyperemia, the vasoconstriction caused by the α-agonists was compared during adenosine-mediated (>50% NO independent) and sodium nitroprusside-mediated (SNP; NO donor) vasodilation of the forearm. Both adenosine and SNP increased FBF from ∼35–40 to ∼200–250 ml/min. All three α-adrenergic constrictor drugs caused marked reductions in FBF and calculated forearm vascular conductance ( P < 0.05). The relative reductions in forearm vascular conductance caused by the α-adrenergic constrictors during SNP infusion were similar (tyramine, –74 ± 3 vs. –65 ± 2%; clonidine, –44 ± 6 vs. –44 ± 6%; P > 0.05) or slightly greater (phenylephrine, –47 ± 6 vs. –33 ± 6%; P < 0.05) compared with the responses during adenosine. In conclusion, these results indicate that exogenous NO sufficient to raise blood flow to levels simulating those seen during exercise does not blunt α-adrenergic vasoconstriction in the resting human forearm.
Integration-differentiation and gating of carotid afferent traffic that shapes the respiratory pattern
Authors: Young Daniel L. , Eldridge Frederick L. , Poon Chi-Sang
Published: March 2015

The phase-dependent plasticity of carotid chemoafferent signaling was studied with electrical stimulation of a carotid sinus nerve during either inspiration or expiration in anesthetized, glomectomized, vagotomized, paralyzed, and ventilated rats. Stroboscopic and interferometric analyses of the resulting phase-contrast disturbances of the respiratory rhythm revealed that carotid chemoafferent traffic was dynamically filtered centrally by a parallel bank of leaky integrators and differentiators, each being logically gated to the inspiratory or expiratory phase in a stop-and-go manner as follows: 1) carotid short-term potentiation of inspiratory drive was mediated by dual integrators that both shortened inspiration and augmented phrenic motor output cooperatively in long and short timescales; 2) carotid short-term depression of respiratory frequency was mediated by a (possibly pontine) integrator that lengthened expiration with a relatively long memory; and 3) carotid “chemoreflex” shortening of expiration was mediated by an occult fast integrator, which, together with carotid short-term depression, formed a differentiator. These effects were modulated anteriorly by integrators in the nucleus tractus solitarius that were “auto-gated” to, or recruited by, the carotid sinus nerve input. Such phase-selective and activity-dependent time-frequency filtering of carotid chemoafferent feedback in parallel neurological-neurodynamic central pathways may profoundly affect respiratory stability during hypoxia and sleep and could contribute to the dynamic optimization of the respiratory pattern and maintenance of homeostasis in health and in disease states.
Effect of exercise intensity on the postexercise sweating threshold
Authors: Kenny Glen P. , Périard Julien , Journeay W. Shane , Sigal Ronald J. , Reardon Francis D.
Published: March 2015

The hypothesis that the magnitude of the postexercise onset threshold for sweating is increased by the intensity of exercise was tested in eight subjects. Esophageal temperature was monitored as an index of core temperature while sweat rate was measured by using a ventilated capsule placed on the upper back. Subjects remained seated resting for 15 min (no exercise) or performed 15 min of treadmill running at either 55, 70, or 85% of peak oxygen consumption (V̇o2 peak) followed by a 20-min seated recovery. Subjects then donned a liquid-conditioned suit used to regulate mean skin temperature. The suit was first perfused with 20°C water to control and stabilize skin and core temperature before whole body heating. Subsequently, the skin was heated (∼4.0°C/h) until sweating occurred. Exercise resulted in an increase in the onset threshold for sweating of 0.11 ± 0.02, 0.23 ± 0.01, and 0.33 ± 0.02°C above that measured for the no-exercise resting values ( P < 0.05) for the 55, 70, and 85% of V̇o2 peak exercise conditions, respectively. We did note that there was a greater postexercise hypotension as a function of exercise intensity as measured at the end of the 20-min exercise recovery. Thus it is plausible that the increase in postexercise threshold may be related to postexercise hypotension. It is concluded that the sweating response during upright recovery is significantly modified by exercise intensity and may likely be influenced by the nonthermal baroreceptor reflex adjustments postexercise.
Otoacoustic emissions at different click intensities: invariant and subject-dependent features
Authors: Zimatore Giovanna , Giuliani Alessandro , Hatzopoulos Stavros , Martini Alessandro , Colosimo Alfredo
Published: March 2015

A study of click-evoked otoacoustic emissions (CEOAEs) elicited at stimulation intensities from 35 to >80 dB was carried out by recurrence quantification analysis on signals from both normal and hearing-impaired subjects. In normal subjects, a clear scaling of determinism with increasing stimulation intensity was observed in the click intensity range from 41 to 59 dB. Outside that range and, in particular, above its upper end, subject-dependent features appeared in the form of different maximal levels of determinism. A comparative analysis of responses from hearing-impaired subjects with conductive hearing losses and sensorineural hearing losses suggested that the principal contributor to this behavior is the middle ear and allowed us to discriminate the two pathologies solely on the basis of CEOAEs. These observations are consistent with a simple phenomenological model of the auditory periphery in which different functional modules are sequentially recruited at increasing stimulus intensities, with a consequent rise in CEOAE coherence.
Human neuromuscular fatigue is associated with altered Na+-K+-ATPase activity following isometric exercise
Authors: Fowles J. R. , Green H. J. , Tupling R. , O'Brien S. , Roy B. D.
Published: March 2015

The purpose of this study was to investigate the hypothesis that reductions in Na+-K+- ATPase activity are associated with neuromuscular fatigue following isometric exercise. In control (Con) and exercised (Ex) legs, force and electromyogram were measured in 14 volunteers [age, 23.4 ± 0.7 (SE) yr] before and immediately after (PST0), 1 h after (PST1), and 4 h after (PST4) isometric, single-leg extension exercise at ∼60% of maximal voluntary contraction for 30 min using a 0.5 duty cycle (5-s contraction, 5-s rest). Tissue was obtained from vastus lateralis muscle before exercise in Con and after exercise in both the Con (PST0) and Ex legs (PST0, PST1, PST4), for the measurements of Na+-K+-ATPase activity, as determined by the 3- O-methylfluorescein phosphatase (3- O-MFPase) assay. Voluntary (maximal voluntary contraction) and elicited (10, 20, 50, 100 Hz) force was reduced 30–55% ( P < 0.05) at PST0 and did not recover by PST4. Muscle action potential (M-wave) amplitude and area (measured in the vastus medialis) and 3- O-MFPase activity at PST0-Ex were less than that at PST0-Con ( P < 0.05) by 37, 25, and 38%, respectively. M-wave area at PST1-Ex was also less than that at PST1-Con ( P < 0.05). Changes in 3- O-MFPase activity correlated to changes in M-wave area across all time points ( r = 0.38, P < 0.05, n= 45). These results demonstrate that Na+-K+- ATPase activity is reduced by sustained isometric exercise in humans from that in a matched Con leg and that this reduction in Na+-K+-ATPase activity is associated with loss of excitability as indicated by M-wave alterations.
Rapid blunting of sympathetic vasoconstriction in the human forearm at the onset of exercise
Authors: Tschakovsky M. E. , Hughson R. L.
Published: March 2015

The purpose of this study was to test the hypothesis that sympathetic vasoconstriction is rapidly blunted at the onset of forearm exercise. Nine healthy subjects performed 5 min of moderate dynamic forearm handgrip exercise during −60 mmHg lower body negative pressure (LBNP) vs. without (control). Beat-by-beat forearm blood flow (Doppler ultrasound), arterial blood pressure (finger photoplethysmograph), and heart rate were collected. LBNP elevated resting heart rate by ∼45%. Mean arterial blood pressure was not significantly changed ( P = 0.196), but diastolic blood pressure was elevated by ∼10% and pulse pressure was reduced by ∼20%. At rest, there was a 30% reduction in forearm vascular conductance (FVC) during LBNP ( P = 0.004). The initial rapid increase in FVC with exercise onset reached a plateau between 10 and 20 s of 126.6 ± 4.1 ml · min−1 · 100 mmHg−1 in control vs. only 101.6 ± 4.1 ml · min−1 · 100 mmHg−1 in LBNP (main effect of condition, P = 0.003). This difference was quickly abolished during the second, slower phase of adaptation in forearm vascular tone to steady state. These data are consistent with a rapid onset of functional sympatholysis, in which local substances released with the onset of muscle contractions impair sympathetic neural vasoconstrictor effectiveness.
Physiological, metabolic, and performance implications of a prolonged hill walk: influence of energy intake
Authors: Ainslie Philip N. , Campbell Iain T. , Frayn Keith N. , Humphreys Sandy M. , MacLaren Donald P. M. , Reilly Thomas
Published: March 2015

We aimed to examine the effects of different energy intakes on a range of responses that are relevant to the safety of hill walkers. In a balanced design, 16 men completed a strenuous self-paced mountainous hill walk over 21 km, under either a low-energy (2.6 MJ; 616 kcal) intake (LEI) or high-energy (12.7 MJ; 3,019 kcal) intake (HEI) condition. During the hill walk, rectal temperatures were measured continuously, and blood samples for the analysis of metabolites and hormones were drawn before breakfast and immediately after the walk. Subjects also completed a battery of performance tests that included muscular strength, reaction times, flexibility, balance, and kinesthetic differentiation tests. During the LEI, mean blood glucose concentrations leveled off at the low-middle range of normoglycemia, whereas, on the HEI, they were significantly elevated compared with the LEI. The maintained blood glucose concentrations, during the LEI, were probably mediated via the marked fat mobilization, reflected by a two- to fivefold increase in nonesterified fatty acids, 3-hydroxybutyrate, and glycerol concentrations. The LEI group showed significantly slower one- and two-finger reaction time, had an impaired ability to balance, and were compromised in their ability to maintain body temperature, when compared with the HEI group. The modestly impaired performance (particularly with respect to balance) and thermoregulation during the LEI condition may increase susceptibly to both fatigue and injury during the pursuit of recreational activity outdoors.
Skeletal muscle ouabain binding sites are reduced in rats with chronic heart failure
Authors: Musch Timothy I. , Wolfram Swen , Hageman K. Sue , Pickar Joel G.
Published: March 2015

Intrinsic skeletal muscle abnormalities decrease muscular endurance in chronic heart failure (CHF). In CHF patients, the number of skeletal muscle Na+-K+pumps that have a high affinity for ouabain (i.e., the concentration of [3H]ouabain binding sites) is reduced, and this reduction is correlated with peak oxygen uptake. The present investigation determined whether the concentration of skeletal muscle [3H]ouabain binding sites found during CHF is related to 1) severity of the disease state, 2) muscle fiber type composition, and/or 3) endurance capacity. Four muscles were chosen that represented slow-twitch oxidative (SO), fast-twitch oxidative glycolytic (FOG), fast-twitch glycolytic (FG), and mixed fiber types. Measurements were obtained 8–10 wk postsurgery in 23 myocardial infarcted (MI) and 18 sham-operated control (sham) rats. Eighteen rats had moderate left ventricular (LV) dysfunction [LV end-diastolic pressure (LVEDP) < 20 mmHg], and five had severe LV dysfunction (LVEDP > 20 mmHg). Rats with severe LV dysfunction had significant pulmonary congestion and were likely in a chronic state of compensated congestive failure as indicated by an approximately twofold increase in both lung and right ventricle weight. Run time to fatigue and maximal oxygen uptake (V˙o2 max) were significantly reduced (↓39 and ↓28%, respectively) in the rats with severe LV dysfunction and correlated with the magnitude of LV dysfunction as indicated by LVEDP (run time: r = 0.60, n = 21, P < 0.01 and V˙o2 max: r = 0.93, n = 13, P < 0.01). In addition, run time to fatigue was significantly correlated withV˙o2 max( r = 0.87, n = 15, P < 0.01). The concentration of [3H]ouabain binding sites (Bmax) was significantly reduced (21–28%) in the three muscles comprised primarily of oxidative fibers [soleus: 259 ± 14 vs. 188 ± 17; plantaris: 295 ± 17 vs. 229 ± 18; red portion of gastrocnemius: 326 ± 17 vs. 260 ± 14 pmol/g wet tissue wt]. In addition, Bmaxwas significantly correlated withV˙o2 max(soleus: r = 0.54, n = 15, P < 0.05; plantaris: r = 0.59, n = 15, P < 0.05; red portion of gastrocnemius: r = 0.65, n = 15, P < 0.01). These results suggest that downregulation of Na+-K+pumps that possess a high affinity for ouabain in oxidative skeletal muscle may play an important role in the exercise intolerance that attends severe LV dysfunction in CHF.
Mechanical ventilation of isolated rat lungs changes the structure and biophysical properties of surfactant
Authors: Veldhuizen Ruud A. W. , Welk Blayne , Harbottle Rob , Hearn Stephen , Nag Kaushik , Petersen Nils , Possmayer Fred
Published: March 2015

Mechanical ventilation is an essential but potentially harmful therapeutic intervention for patients with acute lung injury. The objective of this study was to investigate the effects of mechanical ventilation on large-aggregate surfactant (LA) structure and function. Isolated rat lungs were randomized to either a nonventilated control group, a relatively noninjuriously ventilated group [1 h, 10 ml/kg tidal volume, 3 cmH2O positive end-expiratory pressure (PEEP)], or an injuriously ventilated group (1 h, 20 ml/kg tidal volume, 0 cmH2O PEEP). Injurious ventilation resulted in significantly decreased lung compliance compared with the other two groups. LA structure, as determined by electron microscopy, revealed that LA from the injurious group had significantly lower amounts of organized lipid-protein structures compared with LA obtained from the other groups. Analysis of the biophysical properties by using a captive bubble surfactometer demonstrated that adsorption and surface tension reduction were significantly impaired with LA from the injuriously ventilated lungs. We conclude that the injurious mechanical ventilation impairs LA function and that this impairment is associated with significant morphological alterations.
Wheel-running exercise alters rat diaphragm action potentials and their regulation by K+ channels
Authors: van Lunteren Erik , Moyer Michelle
Published: March 2015

Endurance exercise modifies regulatory systems that control skeletal muscle Na+ and K+ fluxes, in particular Na+-K+-ATPase-mediated transport of these ions. Na+ and K+ ion channels also play important roles in the regulation of ionic movements, specifically mediating Na+ influx and K+ efflux that occur during contractions resulting from action potential depolarization and repolarization. Whether exercise alters skeletal muscle electrophysiological properties controlled by these ion channels is unclear. The present study tested the hypothesis that endurance exercise modifies diaphragm action potential properties. Exercised rats spent 8 wk with free access to running wheels, and they were compared with sedentary rats living in conventional rodent housing. Diaphragm muscle was subsequently removed under anesthesia and studied in vitro. Resting membrane potential was not affected by endurance exercise. Muscle from exercised rats had a slower rate of action potential repolarization than that of sedentary animals ( P = 0.0098), whereas rate of depolarization was similar in the two groups. The K+ channel blocker 3,4-diaminopyridine slowed action potential repolarization and increased action potential area of both exercised and sedentary muscle. However, these effects were significantly smaller in diaphragm from exercised than sedentary rats. These data indicate that voluntary running slows diaphragm action potential repolarization, most likely by modulating K+ channel number or function.