bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1
Authors: Ohga Eijiro , Tomita Tetsuji , Wada Hiroo , Yamamoto Hiroshi , Nagase Takahide , Ouchi Yasuyoshi
Published: March 2015

Obstructive sleep apnea syndrome (OSAS) is one of the most important risk factors of cardiovascular disorders. In the treatment of OSAS, nasal continuous positive airway pressure (nCPAP) has been widely used and found to be effective. In the present study, we hypothesized that the hypoxic stress caused by obstructive sleep apnea would increase circulating intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) in untreated OSAS patients compared with an age-matched control group. In addition, we hypothesized that nCPAP may decrease OSAS-induced hypoxic stress and mediators. To examine these hypotheses, we measured circulating ICAM-1 and IL-8 before and after nCPAP therapy in OSAS patients. We observed that nCPAP decreased apnea, desaturation, and the circulating ICAM-1 and IL-8 levels in OSAS patients. The circulating levels of ICAM-1, IL-8, and MCP-1 in untreated OSAS patients were significantly greater than those in the controls. These observations suggest that nCPAP therapy could reduce OSAS-induced hypoxia and generation of inflammatory mediators. Treatment of OSAS using nCPAP can be, therefore, a potential approach to decrease risk of the progression of OSAS-associated disorders.
Changes in lung permeability and lung mechanics accompany homeostatic instability in senescent mice
Authors: Tankersley Clarke G. , Shank Jessica A. , Flanders Susan E. , Soutiere Shawn E. , Rabold Richard , Mitzner Wayne , Wagner Elizabeth M.
Published: March 2015

Aging and lung disease are recognized factors that increase mortality risk in subjects exposed to ambient particulate matter (PM). In an effort to understand the mechanisms of enhanced susceptibility, the present study examined an inbred mouse model of senescence to 1) determine changes in lung permeability as animals approach the end-of-life and 2) characterize age-dependent changes in lung mechanics in presenescent and terminally senescent mice. The clearance of technetium-99m (99mTc)-diethylenetriamine pentaacetic acid (DTPA) was used to test the hypothesis that lung permeability increases with age and enhances uptake of soluble components of PM principally during the period several weeks before death in AKR/J mice. Quasistatic pressure-volume curves were conducted on robust and on terminally senescent AKR/J mice several weeks before death to assess the relative importance of lung mechanics. Abrupt body weight loss was used to signal imminent death because it accompanies indexes of physiological aging and terminal senescence. 99mTc-DTPA clearance from the lung 30 min after tracheal instillation was significantly ( P < 0.05) enhanced in senescent mice. Age-dependent changes in lung mechanics were indicative of significant ( P < 0.05) decrements in lung volume and compliance several weeks before death. Thus, during a period of homeostatic instability leading toward natural death, AKR/J mice showed enhanced permeability of soluble particles despite a decrease in lung volume and concomitant alveolar surface area. These results suggest that pulmonary epithelial-endothelial barrier dysfunction occurs in terminally senescent mice just before death. Furthermore, this senescent-dependent increase in lung permeability may be a contributing factor for increased PM susceptibility in the elderly and patients with lung disease.
Low-O2 affinity erythrocytes improve performance of ischemic myocardium
Authors: Berlin Gösta , Challoner Keith E. , Woodson Robert D.
Published: March 2015

O2 transport and O2 diffusion interact in providing O2 to tissue, but the extent to which diffusion may be critical in the heart is unclear. If O2 diffusion limits mitochondrial oxygenation, a change in blood O2 affinity at constant total O2 transport should alter cardiac O2consumption (V˙o 2) and function. To test this hypothesis, we perfused isolated isovolumically working rabbit hearts with erythrocytes at physiological blood-gas values and P50 (Po 2 required to half-saturate hemoglobin) values at pH of 7.4 of 17 ± 1 Torr (2,3-bisphosphoglycerate depletion) and 33 ± 5 Torr (inositol hexaphosphate incorporation). When perfused at 40 and 20% of normal coronary flow, mean V˙o 2 decreased from the control value by 37 and 46% ( P < 0.001), and function, expressed as cardiac work, decreased by 38 and 52%, respectively ( P < 0.001). Perfusion at higher P50 during low-flow ischemia improvedV˙o 2 by 20% ( P < 0.001) and function by 36% ( P < 0.02). There was also modest improvement at basal flow ( P < 0.02 and P < 0.002, respectively). The improvement inV˙o 2 and function due to the P50 increase demonstrates the importance of O2diffusion in this cardiac ischemia model.
Calibration of pneumotachographs using a calibrated syringe
Authors: Tang Yongquan , Turner Martin J. , Yem Johnny S. , Baker A. Barry
Published: March 2015

Pneumotachograph require frequent calibration. Constant-flow methods allow polynomial calibration curves to be derived but are time consuming. The iterative syringe stroke technique is moderately efficient but results in discontinuous conductance arrays. This study investigated the derivation of first-, second-, and third-order polynomial calibration curves from 6 to 50 strokes of a calibration syringe. We used multiple linear regression to derive first-, second-, and third-order polynomial coefficients from two sets of 6–50 syringe strokes. In part A, peak flows did not exceed the specified linear range of the pneumotachograph, whereas flows in part B peaked at 160% of the maximum linear range. Conductance arrays were derived from the same data sets by using a published algorithm. Volume errors of the calibration strokes and of separate sets of 70 validation strokes ( part A) and 140 validation strokes ( part B) were calculated by using the polynomials and conductance arrays. Second- and third-order polynomials derived from 10 calibration strokes achieved volume variability equal to or better than conductance arrays derived from 50 strokes. We found that evaluation of conductance arrays using the calibration syringe strokes yields falsely low volume variances. We conclude that accurate polynomial curves can be derived from as few as 10 syringe strokes, and the new polynomial calibration method is substantially more time efficient than previously published conductance methods.
Inhaled nitric oxide attenuates acute lung injury via inhibition of nuclear factor-κB and inflammation
Authors: Kang Jihee Lee , Park Wann , Pack In Soon , Lee Hui Su , Kim Mi Jung , Lim Chae-Man , Koh Younsuck
Published: March 2015

The effect of inhaled nitric oxide (NO) on inflammatory process in acute lung injury (ALI) is unclear. The aims of this study were to 1) examine whether inhaled NO affects the biochemical lung injury parameters and cellular inflammatory responses and 2) determine the effect of inhaled NO on the activation of nuclear factor-κB (NF-κB) in lipopolysaccharide (LPS)-induced ALI. Compared with saline controls, rabbits treated intravenously with LPS showed increases in total protein and lactate dehydrogenase in the bronchoalveolar lavage (BAL) fluid, indicating ALI. LPS-treated animals with NO inhalation (LPS-NO) showed significant decreases in these parameters. Neutrophil numbers in the BAL fluid, the activity of reactive oxygen species in BAL cells, and the levels of interleukin (IL)-1β and IL-8 in alveolar macrophages were increased in LPS-treated animals. In contrast, neutrophil numbers and these cellular activities were substantially decreased in LPS-NO animals, compared with LPS-treated animals. NF-κB activation in alveolar macrophages from LPS-treated animals was also markedly increased, whereas this activity was effectively blocked in LPS-NO animals. These results suggest that inhaled NO attenuates LPS-induced ALI and pulmonary inflammation. This attenuation may be associated with the inhibition of NF-κB activation.
Invited Review: Understanding airway pathophysiology with computed tomograpy
Authors: Brown Robert H. , Mitzner Wayne
Published: March 2015

Conventional pulmonary function tests are limited in the mechanistic insight that they can provide by the fact that they can only provide average measures of lung function. For example, a measurement of decreased expiratory flow assessed with conventional spirometry could result from narrowed large airways, narrowed small airways, closed airways, altered elasticity, or regional heterogeneities in parenchyma or airways. To examine specific mechanisms and pathology in the airways, a method is required that can actually look at specific individual airways. Over the past decade, several more direct methods of assessing specific mechanisms and structural alterations in normal airways and airway pathology in asthma have become available for such purposes. One such method is high-resolution computed tomography (HRCT), a method that allows the study of multiple individual airways during either contraction to closure or relaxation in real time, as well as changes in airway size with changes in lung volume. Although other imaging modalities have the potential to image airways in vivo, none presently has the convenience and the accessibility coupled with the resolution required to visualize the parenchymal airways in vivo. Although HRCT may never be widely utilized for routine measurements or screening, because of radiation exposure, cost issues, and a limited ability to follow changes over extended time periods, the method has distinct and unique advantages in quantifying the behavior of airways in vivo. In this mini-review, we focus on these capabilities of HRCT by briefly reviewing highlights of experimental results from several canine and human studies.
Discriminative power of phrenic twitch-induced dynamic response for diagnosis of sleep apnea during wakefulness
Authors: Verin Eric , Similowski Thomas , Teixeira Antonio , Sériès Frédéric
Published: March 2015

The diagnosis of the obstructive sleep apnea syndrome relies on polysomnography. Bilateral anterior magnetic phrenic stimulation (BAMPS) mimics the dissociation between upper airway (UA) muscles and diaphragm commands that leads to UA closure during sleep. We evaluated BAMPS as a mean to identify obstructive sleep apnea syndrome patients through the characterization of the UA dynamics in 28 consecutive awake patients (18 apneic and 10 nonapneic). Driving pressure (Pd) and instantaneous flow (V˙) were recorded in response to BAMPS to determine the point of flow limitation (V˙imax) and of minimal flow (V˙imin) and the flow-pressure relationship [V˙i = ( k 1× Pd) + ( k 2 × Pd2)]. V˙imax,V˙imin, UA resistance atV˙i min, and the coefficient of the flow-pressure relationship ( k 1) were correlated with apnea-hypopnea index (respectively, R = −0.735, P < 0.0001; R = −0.584, P = 0.001; R = 0.474, P= 0.01; and R = −0.567, P < 0.01). Body mass index was also correlated with apnea-hypopnea index ( R = 0.500, P < 0.01). Apneic patients had a lower V˙imax (V˙imax = 678 ± 386 vs. 1,247 ± 271 ml/s; P < 0.001), a lower V˙imin (V˙imin = 460 ± 313 vs. 822 ± 393 ml/s; P < 0.05) and a lower k 1 ( k 1 = 162 ± 67 vs. 272 ± 112 ml · cmH2O · s−1; P < 0.01) than nonapneic ones. Using a classification and regression tree approach, we found that aV˙imax of <803 ml/s ( n = 12) selected only apneic patients. When V˙imax of >803 ml/s ( n = 16), a k 1 of >266.7 ml · cmH2O · s−1identified only nonapneic patients ( n = 5). In 11 cases, V˙imax > 803 ml/s and k 1 < 266.7 ml · cmH2O · s−1. These included five nonapneic and six apneic patients. We conclude that UA dynamic properties studied with BAMPS during wakefulness significantly differ between nonapneic and apneic patients.
A multicompartment model of carboxyhemoglobin and carboxymyoglobin responses to inhalation of carbon monoxide
Authors: Bruce Eugene N. , Bruce Margaret C.
Published: March 2015

We have developed a model that predicts the distribution of carbon monoxide (CO) in the body resulting from acute inhalation exposures to CO. The model includes a lung compartment, arterial and venous blood compartments, and muscle and nonmuscle soft tissues with both vascular and nonvascular subcompartments. In the model, CO is allowed to diffuse between the vascular and nonvascular subcompartments of the tissues and to combine with myoglobin in the nonvascular subcompartment of muscle tissue. The oxyhemoglobin dissociation curve is represented by a modified Hill equation whose parameters are functions of the carboxyhemoglobin (HbCO) level. Values for skeletal muscle mass and cardiac output are calculated from prediction formulas based on age, weight, and height of individual subjects. We demonstrate that the model fits data from CO rebreathing studies when diffusion of CO into the muscle compartment is considered. The model also fits responses of HbCO to single or multiple exposures to CO lasting for a few minutes each. In addition, the model reproduces reported differences between arterial and venous HbCO levels and replicates predictions from the Coburn-Forster-Kane equation for CO exposures of a 1- to 83-h duration. In contrast to approaches based on the Coburn-Forster-Kane equation, the present model predicts uptake and distribution of CO in both vascular and tissue compartments during inhalation of either constant or variable levels of CO.
Effects of exercise training on thermoregulatory responses and blood volume in older men
Authors: Okazaki Kazunobu , Kamijo Yoshi-Ichiro , Takeno Yoshiaki , Okumoto Tadashi , Masuki Shizue , Nose Hiroshi
Published: March 2015

We assessed the effects of aerobic and/or resistance training on thermoregulatory responses in older men and analyzed the results in relation to the changes in peak oxygen consumption rate (V˙o 2 peak) and blood volume (BV). Twenty-three older men [age, 64 ± 1 (SE) yr; V˙o 2 peak, 32.7 ± 1.1 ml · kg−1 · min−1] were divided into three training regimens for 18 wk: control (C; n = 7), aerobic training (AT; n = 8), and resistance training (RT; n = 8). Subjects in C were allowed to perform walking of ∼10,000 steps/day, 6–7 days/wk. Subjects in AT exercised on a cycle ergometer at 50–80%V˙o 2 peak for 60 min/day, 3 days/wk, in addition to the walking. Subjects in RT performed a resistance exercise, including knee extension and flexion at 60–80% of one repetition maximum, two to three sets of eight repetitions per day, 3 days/wk, in addition to the walking. After 18 wk of training,V˙o 2 peak increased by 5.2 ± 3.4% in C ( P > 0.07), 20.0 ± 2.5% in AT ( P < 0.0001), and 9.7 ± 5.1% in RT ( P < 0.003), but BV remained unchanged in all trials. In addition, the esophageal temperature (Tes) thresholds for forearm skin vasodilation and sweating, determined during 30-min exercise of 60% V˙o 2 peak at 30°C, decreased in AT ( P < 0.02) and RT ( P< 0.02) but not in C ( P > 0.2). In contrast, the slopes of forearm skin vascular conductance/Tes and sweat rate/Tes remained unchanged in all trials, but both increased in subjects with increased BV irrespective of trials with significant correlations between the changes in the slopes and BV ( P < 0.005 and P < 0.0005, respectively). Thus aerobic and/or resistance training in older men increased V˙o 2 peak and lowered Tes thresholds for forearm skin vasodilation and sweating but did not increase BV. Furthermore, the sensitivity of the increase in skin vasodilation and sweating at a given increase in Tes was more associated with BV than withV˙o 2 peak.
Long-term effects of diet on leptin, energy intake, and activity in a model of diet-induced obesity
Authors: Roberts Christian K. , Berger Joshua J. , Barnard R. James
Published: March 2015

This study investigated the effect of long-term high-fat sucrose (HFS) or low-fat complex-carbohydrate (LFCC) diet consumption on leptin, insulin, fat cell size, energy intake, and markers of activity to ascertain the role that leptin plays in long-term energy balance in a model of diet-induced obesity. Female Fischer 344 rats were fed either a HFS or LFCC diet ad libitum for a period of 20 mo. Measurements of leptin concentration, insulin concentration, and adipocyte size were performed at 2 wk, 2 mo, 6 mo, and 20 mo. Body weight and energy intake were measured weekly for calculation of feed efficiency. Body temperature and activity levels were assessed over a 5-day period after 12 mo of the dietary intervention. Plasma leptin and insulin concentrations were significantly elevated within 2 wk of HFS diet consumption and remained elevated throughout the course of the study. After 2 mo, the adipocytes of the HFS group were significantly larger and continued to increase in size throughout the course of the study. A significant correlation was noted between leptin and adipocyte cell size ( r = 0.96, P < 0.01). However, despite elevated leptin, energy intake was similar, and the HFS group weighed significantly more than the LFCC group, as a result of a higher feed efficiency. There were no significant differences in body temperature or activity levels between the groups. These results demonstrate that a HFS diet causes hyperleptinemia and hyperinsulinemia before adipocyte size is increased and suggests that leptin resistance may be present or, alternatively, that leptin does not to play a major role in the long-term regulation of energy intake or activity levels in this model.
Hormonal changes in satisfied and dissatisfied shift workers across a shift cycle
Authors: Axelsson John , Åkerstedt Torbjörn , Kecklund Göran , Lindqvist Anne , Attefors Reine
Published: March 2015

Although the literature claims that shift work is harmful, it overlooks the fact that that many shift workers are satisfied and stay healthy. There is little knowledge of the biological mechanisms mediating the differences in susceptibility. The present study compared satisfied and dissatisfied shift workers with respect to major anabolic and catabolic hormones. Forty-two male shift workers, with an extremely rapidly rotating shift schedule, were divided into two groups according to their ratings of satisfaction with their work hours. Morning blood samples were taken during the first and last morning shift in the shift cycle. Serum was analyzed with respect to testosterone, cortisol, and prolactin. Dissatisfied shift workers had lower morning testosterone than satisfied ones, but they did not significantly differ with respect to cortisol or prolactin. Low testosterone levels were, in addition, associated with a greater sleep need, disturbed sleep/wakefulness, and an increased need for recovery after the work period, the latter being the best predictor of testosterone levels. The only change across the shift cycle concerned a significant decrease of morning cortisol at the end of the shift cycle. High morning cortisol was related to having a morning personality and fewer sleep problems before the morning shift. Dissatisfaction with the shift system seems related to lower testosterone levels, which in turn are related to disturbed sleep/wakefulness and increased need for sleep and recovery. Furthermore, morning cortisol was reduced across a shift cycle. It is suggested that reduced testosterone levels may be part of a mechanism of shift work maladjustment.
Selected Contribution: Modulation of insulin resistance and hypertension by voluntary exercise training in the TG(mREN2)27 rat
Authors: Kinnick Tyson R. , Youngblood Erik B. , O'Keefe Matthew P. , Saengsirisuwan Vitoon , Teachey Mary K. , Henriksen Erik J.
Published: March 2015

Hypertension is often accompanied by insulin resistance of skeletal muscle glucose transport. The male heterozygous TG(mREN2)27 rat, which harbors a mouse transgene for renin, displays local elevations in the renin-angiotensin system and exhibits markedly elevated systolic blood pressure (SBP). The present study was undertaken to characterize insulin-stimulated skeletal muscle glucose transport in male heterozygous TG(mREN2)27 rats and to evaluate the effect of voluntary exercise training on SBP and skeletal muscle glucose transport. Compared with normotensive Sprague-Dawley rats, TG(mREN2)27 rats displayed a 53% elevation ( P < 0.05) in SBP, a twofold increase in plasma free fatty acid levels, and an exaggerated insulin response during an oral glucose tolerance test. Moreover, insulin-mediated glucose transport (2-deoxyglucose uptake) in isolated epitrochlearis and soleus muscles of TG(mREN2)27 animals was 33 and 43% less, respectively, than in Sprague-Dawley controls. TG(mREN2)27 rats ran voluntarily for 6 wk and achieved daily running distances of 6–7 km over the final 3 wk. Training caused a 36% increase in peak aerobic capacity and a 16% reduction in resting SBP. Fasting plasma insulin (21%) and free fatty acid (34%) levels were reduced in the trained TG(mREN2)27 rats. Whole body glucose tolerance was improved in the trained TG(mREN2)27 rats and was associated with increases of 39 and 50% in insulin-mediated glucose transport in epitrochlearis and soleus muscles, respectively. Whole muscle GLUT-4 protein was increased in the soleus (23%), but not in the epitrochlearis, of trained TG(mREN2)27 rats. These data indicate that the male heterozygous TG(mREN2)27 rat is a model of both hypertension and insulin resistance. Importantly, both of these defects can be beneficially modified by voluntary exercise training.
Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia
Authors: Lauretani Fulvio , Russo Cosimo Roberto , Bandinelli Stefania , Bartali Benedetta , Cavazzini Chiara , Di Iorio Angelo , Corsi Anna Maria , Rantanen Taina , Guralnik Jack M. , Ferrucci Luigi
Published: March 2015

Sarcopenia, the reduction of muscle mass and strength that occurs with aging, is widely considered one of the major causes of disability in older persons. Surprisingly, criteria that may help a clinician to identify persons with impaired muscle function are still lacking. Using data from a large representative sample of the general population, we examined how muscle function and calf muscle area change with aging and affect mobility in men and women free of neurological conditions. We tested several putative indicators of sarcopenia, including knee extension isometric torque, handgrip, lower extremity muscle power, and calf muscle area. For each indicator, sarcopenia was considered to be present when the measure was >2 SDs below the mean. For all four measures, the prevalence of sarcopenia increased with age, both in men and women. The age-associated gradient in prevalence was maximum for muscle power and minimum for calf-muscle area. However, lower extremity muscle power was no better than knee-extension torque or handgrip in the early identification of poor mobility, defined either as walking speed <0.8 m/s or inability to walk at least 1 km without difficulty and without developing symptoms. Optimal cutoff values that can be used in the clinical practice to identify older persons with poor mobility were developed. The findings of the study lay the basis for a cost-effective, clinical marker of sarcopenia based on a measure of isometric handgrip strength. Our findings should be verified in a longitudinal study.
Effect of different protocols of caffeine intake on metabolism and endurance performance
Authors: Cox Gregory R. , Desbrow Ben , Montgomery Paul G. , Anderson Megan E. , Bruce Clinton R. , Macrides Theodore A. , Martin David T. , Moquin Angela , Roberts Alan , Hawley John A. , Burke Louise M.
Published: March 2015

Competitive athletes completed two studies of 2-h steady-state (SS) cycling at 70% peak O2uptake followed by 7 kJ/kg time trial (TT) with carbohydrate (CHO) intake before (2 g/kg) and during (6% CHO drink) exercise. In Study A, 12 subjects received either 6 mg/kg caffeine 1 h preexercise (Precaf), 6 × 1 mg/kg caffeine every 20 min throughout SS (Durcaf), 2 × 5 ml/kg Coca-Cola between 100 and 120 min SS and during TT (Coke), or placebo. Improvements in TT were as follows: Precaf, 3.4% (0.2–6.5%, 95% confidence interval); Durcaf, 3.1% (−0.1–6.5%); and Coke, 3.1% (−0.2–6.2%). In Study B, eight subjects received 3 × 5 ml/kg of different cola drinks during the last 40 min of SS and TT: decaffeinated, 6% CHO (control); caffeinated, 6% CHO; decaffeinated, 11% CHO; and caffeinated, 11% CHO (Coke). Coke enhanced TT by 3.3% (0.8–5.9%), with all trials showing 2.2% TT enhancement (0.5–3.8%; P < 0.05) due to caffeine. Overall, 1) 6 mg/kg caffeine enhanced TT performance independent of timing of intake and 2) replacing sports drink with Coca-Cola during the latter stages of exercise was equally effective in enhancing endurance performance, primarily due to low intake of caffeine (∼1.5 mg/kg).
Major gene effects on exercise ventilatory threshold: the HERITAGE Family Study
Authors: Feitosa Mary F. , Gaskill Steven E. , Rice Treva , Rankinen Tuomo , Bouchard Claude , Rao D. C. , Wilmore Jack H. , Skinner James S. , Leon Arthur S.
Published: March 2015

This study investigates whether there are major gene effects on oxygen uptake at the ventilatory threshold (V˙o2VT) and theV˙o2VTmaximal oxygen uptake (VT%V˙o2 max), at baseline and in response to 20 wk of exercise training by using data on 336 whites and 160 blacks. Segregation analysis was performed on the residuals ofV˙o2VTand VT%V˙o2 max. In whites, there was strong evidence of a major gene, with 3 and 2% of the sample in the upper distribution, that accounted for 52 and 43% of the variance in baseline V˙o2VTand VT%V˙o2 max, respectively. There were no genotype-specific covariate effects (sex, age, weight, fat mass, and fat-free mass). The segregation results were inconclusive for the training response in whites, and for the baseline and training response in blacks, probably due to insufficient power because of reduced sample sizes or smaller gene effect or both. The strength of the genetic evidence for V˙o2VTand VT%V˙o2 maxsuggests that these traits should be further investigated for potential relations with specific candidate genes, if they can be identified, and explored through a genome-wide scan.
A finite element model of cell deformation during magnetic bead twisting
Authors: Mijailovich Srboljub M. , Kojic Milos , Zivkovic Miroslav , Fabry Ben , Fredberg Jeffrey J.
Published: March 2015

Magnetic twisting cytometry probes mechanical properties of an adherent cell by applying a torque to a magnetic bead that is tightly bound to the cell surface. Here we have used a three-dimensional finite element model of cell deformation to compute the relationships between the applied torque and resulting bead rotation and lateral bead translation. From the analysis, we computed two coefficients that allow the cell elastic modulus to be estimated from measurements of either bead rotation or lateral bead translation, respectively, if the degree of bead embedding and the cell height are known. Although computed strains in proximity of the bead can be large, the relationships between applied torque and bead rotation or translation remain virtually linear up to bead rotations of 15°, above which geometrical nonlinearities become significant. This appreciable linear range stands in contrast to the intrinsically nonlinear force-displacement relationship that is observed when cells are indented during atomic force microscopy. Finally, these computations support the idea that adhesive forces are sufficient to keep the bead firmly attached to the cell surface throughout the range of working torques.
Vastus lateralis fatigue alters recruitment of musculus quadriceps femoris in humans
Authors: Akima Hiroshi , Foley Jeanne M. , Prior Barry M. , Dudley Gary A. , Meyer Ronald A.
Published: March 2015

This study tested the hypothesis that fatigue of a single member of musculus quadriceps femoris (QF) would alter use of the other three muscles during knee extension exercise (KEE). Six men performed KEE with the left QF at a load equal to 50% of the 4 × 10 repetitions maximum. Subsequently, electromyostimulation (EMS), intended to stimulate and fatigue the left m. vastus lateralis (VL), was applied for 30 min. Immediately after EMS, subjects repeated the KEE. Transverse relaxation time (T2)-weighted magnetic resonance images were taken before and after each bout of KEE and at 3 and 30 min of EMS to assess use and stimulation, respectively, of the QF. T2 of each of the QF muscles was increased 8–13% after the first KEE. During EMS, T2 increased ( P < 0.05) even more in VL (10%), whereas it decreased ( P < 0.05) to pre-KEE levels in m. vastus medials (VM) and m. rectus femoris (RF). The VL and, to some extent, the m. vastus intermedius were stimulated, whereas the VM and RF were not, thereby recovering from the first bout of KEE. Isometric torque, initially 30% of maximal voluntary, was reduced to 13% at 3 min and 7% at 30 min. T2 was greater ( P < 0.05) after the second than the first bout of KEE, especially the increase for the VM and RF. These results suggest that subjects were able to perform the second bout with little contribution of the VL by greater use of the other QF muscles. The simplest explanation is increased central command to the QF such that the intended act could be accomplished despite acute fatigue of one of its synergists.
Exercise and insulin signaling: a historical perspective
Authors: Tomás Eva , Zorzano Antonio , Ruderman Neil B.
Published: March 2015

Over the past 30 years, a considerable body of evidence has revealed that a prior bout of exercise can increase the ability of insulin to stimulate glucose transport and glycogen synthesis in skeletal muscle. Apart from its clinical implications, this work has led to a considerable effort to determine at a molecular level how exercise causes this effect and, in particular, whether it does so by enhancing specific events in the insulin-signaling cascade. The objective of this review is to discuss from a historical perspective how our current thinking in this area has evolved and the people responsible for it. Areas to be discussed include the effect or lack of effect of prior exercise on the insulin-signaling pathway, effects of exercise on the regulation by insulin of the GLUT-4 glucose transporter in muscle, and the emerging role of AMP-activated protein kinase as a mediator of exercise-induced signaling events. In addition, we will discuss briefly some of the avenues that research in this area is likely to follow.
Phospholipids modulate the biophysical properties and vasoactivity of PACAP-(1—38)
Authors: Tsueshita Takaya , Gandhi Salil , Önyüksel Hayat , Rubinstein Israel
Published: March 2015

The purpose of this study was to elucidate the interactions between pituitary adenylate cyclase-activating peptide (PACAP)-(1—38) and phospholipids in vitro and to determine whether these phenomena modulate, in part, the vasorelaxant effects of the peptide in the intact peripheral microcirculation. We found that the critical micellar concentration of PACAP-(1—38) was 0.4–0.9 μM. PACAP-(1—38) significantly increased the surface tension of a dipalmitoylphosphatidylcholine monolayer and underwent conformational transition from predominantly random coil in saline to α-helix in the presence of distearoyl-phosphatidylethanolamine-polyethylene glycol (molecular mass of 2,000 Da) sterically stabilized phospholipid micelles (SSM) ( P < 0.05). Using intravital microscopy, we found that aqueous PACAP-(1—38) evoked significant concentration-dependent vasodilation in the intact hamster cheek pouch that was significantly potentiated when PACAP-(1—38) was associated with SSM ( P < 0.05). The vasorelaxant effects of aqueous PACAP-(1—38) were mediated predominantly by PACAP type 1 (PAC1) receptors, whereas those of PACAP-(1—38) in SSM predominantly by PACAP/vasoactive intestinal peptide type 1 and 2 (VPAC1/VPAC2) receptors. Collectively, these data indicate that PACAP-(1—38) self-associates and interacts avidly with phospholipids in vitro and that these phenomena amplify peptide vasoactivity in the intact peripheral microcirculation.
Terminology for contractions of muscles during shortening, while isometric, and during lengthening
Authors: Faulkner John A.
Published: March 2015

Communication among scientists must be clear and concise to avoid ambiguity and misinterpretations. The selection of words must be based on accepted definitions. The fields of biomechanics, muscle physiology, and exercise science have had a particularly difficult time with terminology, arising from the complexity of muscle contractions and by the use of inappropriate terminology by scientists. The dictionary definition of the verb “contract,” specifically for the case of muscle, is “to undergo an increase in tension, or force, and become shorter.” Under all circumstances, an activated muscle generates force, but an activated muscle generating force does not invariably shorten! During the 1920s and 1930s, investigators recognized that the interaction between the force generated by the muscle and the load on the muscle results in either shortening, no length change (isometric), or lengthening of the muscle. The recognition that muscles perform three different types of “contractions” required that contraction be redefined as “to undergo activation and generate force.” Modifiers of contraction are then needed to clarify the lack of movement or the directionality of movement. Despite the contradiction, for 75 years the lack of movement has been termed an “isometric contraction.” The directionality of the movement is then best described by the adjectives “shortening” and “lengthening.” The definitions of “concentric” as “having the same center” and of “eccentric” as “not having the same center” are consistent with hypertrophy, or remodeling of the heart muscle, but are inappropriate to describe the contractions of skeletal muscles.
Selected Contribution: Neurochemical phenotypes of MRF neurons influencing diaphragm and rectus abdominis activity
Authors: Billig I. , Card J. P. , Yates B. J.
Published: March 2015

In prior studies that used transneuronal transport of isogenic recombinants of pseudorabies virus, we established that medial medullary reticular formation (MRF) neurons sent collateralized projections to both diaphragm and abdominal muscle motoneurons. Furthermore, inactivation of MRF neurons in cats and ferrets increased the excitability of diaphragm and abdominal motoneurons, suggesting that MRF neurons controlling respiratory activity are inhibitory. To test this hypothesis, the present study determined the neurochemical phenotypes of MRF premotor respiratory neurons in the ferret by using immunohistochemical procedures. Dual-labeling immunohistochemistry combining pseudorabies virus injections into respiratory muscles with the detection of glutamic acid decarboxylase-like immunoreactive and glutamate-like immunoreactive cells showed that both GABAergic and glutamatergic MRF neurons project to respiratory motoneurons, although the latter are more common. These data suggest that the role of the MRF in respiratory regulation is multifaceted, as this region provides both inhibitory and excitatory influences on motoneuron activity.
Effects of high-cholesterol diet and parallel exercise training on the vascular function of rabbit aortas: a time course study
Authors: Yang Ai-Lun , Jen Chauying J. , Chen Hsiun-ing
Published: March 2015

It is plausible to assume that exercise training, when applied early enough, can completely correct atherosclerotic defects. Using rabbit aortic specimens, we examined the effects of chronic exercise and high-cholesterol diet feeding on vascular function for different time periods. Male New Zealand White rabbits were divided into four groups: the normal diet groups with or without exercise training and the high-cholesterol diet groups with or without exercise training. Animals in high-cholesterol diet groups were fed 2% cholesterol rabbit chow for 2, 4, or 6 wk. Those in exercise training groups ran on a treadmill at 0.88 km/h for up to 40 min/day, 5 days/wk for the same period of time as the diet feeding. Thoracic aortas were isolated for functional and immunohistochemical analyses. We found that 1) although high-cholesterol diet feeding (≥2 wk) elevated serum cholesterol levels and impaired acetylcholine-evoked vasorelaxation, only the latter effect was reversed by exercise training; 2) the effects of diet and exercise on acetylcholine-evoked vasorelaxation were mainly due to altered release of nitric oxide and endothelium-derived hyperpolarizing factor; and 3) diet feeding for 4 or 6 wk caused significant lipid deposition and expression of P-selectin, VCAM-1, monocyte chemoattractant protein-1, and inducible nitric oxide synthase, which were largely reduced by exercise training. In conclusion, parallel exercise training almost completely reverses the early-stage endothelial dysfunction caused by high-cholesterol diet feeding.
Invited Review: Theories of aging
Authors: Weinert Brian T. , Timiras Poala S.
Published: March 2015

Several factors (the lengthening of the average and, to a lesser extent, of the maximum human life span; the increase in percentage of elderly in the population and in the proportion of the national expenditure utilized by the elderly) have stimulated and continue to expand the study of aging. Recently, the view of aging as an extremely complex multifactorial process has replaced the earlier search for a distinct cause such as a single gene or the decline of a key body system. This minireview keeps in mind the multiplicity of mechanisms regulating aging; examines them at the molecular, cellular, and systemic levels; and explores the possibility of interactions at these three levels. The heterogeneity of the aging phenotype among individuals of the same species and differences in longevity among species underline the contribution of both genetic and environmental factors in shaping the life span. Thus, the presence of several trajectories of the life span, from incidence of disease and disability to absence of pathology and persistence of function, suggest that it is possible to experimentally (e.g., by calorie restriction) prolong functional plasticity and life span. In this minireview, several theories are identified only briefly; a few (evolutionary, gene regulation, cellular senescence, free radical, and neuro-endocrineimmuno theories) are discussed in more detail, at molecular, cellular, and systemic levels.
Role of l-glutamate in systemic AVP-induced hypothermia
Authors: Paro Flavia M. , Almeida Maria C. , Carnio Evelin C. , Branco Luiz G. S.
Published: March 2015

It has been reported that systemic injection of arginine vasopressin (AVP) induces a drop in body core temperature (Tc), but little is known about the mechanisms involved. Because glutamate is an important excitatory neurotransmitter involved in a number of thermoregulatory actions, in the present study, we tested the hypothesis that glutamate plays a role in systemic AVP-induced hypothermia. Wistar rats were pretreated intracerebroventricularly (icv) with kynurenic acid, an antagonist ofl-glutamate ionotropic receptors, α-methyl-(4-carboxyphenyl)glycine (MCPG), an antagonist ofl-glutamate metabotropic receptors, or saline 15 min before intravenous injection of AVP (2 μg/kg) or saline. Tc, brown adipose tissue (BAT) temperature, blood pressure, heart rate, and tail skin temperature were measured continuously. Administration of saline icv followed by intravenous AVP caused a significant drop in Tc brought about by a reduction in BAT thermogenesis and an increase in heat loss through the tail. MCPG treatment (icv) did not affect the fall in Tc induced by AVP. Treatment with kynurenic acid (icv) abolished AVP-induced hypothermia but did not affect the AVP-evoked rise in blood pressure or drop in heart rate and BAT temperature. Heat loss through the tail was significantly reduced in animals injected with AVP and pretrated with kynurenic acid. These data indicate that ionotropic receptors of l-glutamate in the central nervous system participate in peripheral AVP-induced hypothermia by affecting heat loss through the tail.
Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA
Authors: Floyd Thomas F. , Clark James M. , Gelfand Robert , Detre John A. , Ratcliffe Sarah , Guvakov Dimitri , Lambertsen Christian J. , Eckenhoff Roderic G.
Published: March 2015

Breathing 100% O2 at 1 atmosphere absolute (ATA) is known to be associated with a decrease in cerebral blood flow (CBF). It is also accompanied by a fall in arterial Pco2 leading to uncertainty as to whether the cerebral vasoconstriction is totally or only in part caused by arterial hypocapnia. We tested the hypothesis that the increase in arterial Po2 while O2 was breathed at 1.0 ATA decreases CBF independently of a concurrent fall in arterial Pco2. CBF was measured in seven healthy men aged 21–62 yr by using noninvasive continuous arterial spin-labeled-perfusion MRI. The tracer in this technique, magnetically labeled protons in blood, has a half-life of seconds, allowing repetitive measurements over short time frames without contamination. CBF and arterial blood gases were measured while breathing air, 100% O2, and 4 and 6% CO2 in air and O2 backgrounds. Arterial Po2 increased from 91.7 ± 6.8 Torr in air to 576.7 ± 18.9 Torr in O2. Arterial Pco2 fell from 43.3 ± 1.8 Torr in air to 40.2 ± 3.3 Torr in O2. CBF-arterial Pco2 response curves for the air and hyperoxic runs were nearly parallel and separated by a distance representing a 28.7–32.6% decrement in CBF. Regression analysis confirmed the independent cerebral vasoconstrictive effect of increased arterial Po2. The present results also demonstrate that the magnitude of this effect at 1.0 ATA is greater than previously measured.
VEGF enhances functional improvement of postinfarcted hearts by transplantation of ESC-differentiated cells
Authors: Yang Yinke , Min Jiang-Yong , Rana Jamal S. , Ke Qingen , Cai Jingbo , Chen Yu , Morgan James P. , Xiao Yong-Fu
Published: March 2015

Despite considerable advances in medicine, the incidence of heart failure remains high in patients after myocardial infarction (MI). This study investigated the effects of engrafted early-differentiated cells (EDCs) from mouse embryonic stem cells, with or without transfection of vascular endothelial growth factor (VEGF) cDNA (phVEGF165), on cardiac function in postinfarcted mice. EDCs were transfected with green fluorescent protein (GFP) cDNA and transplanted into infarcted myocardium. Compared with the MI mice receiving cell-free medium, cardiac function was significantly improved in the MI mice 6 wk after transplantation of EDCs. Moreover, improvement of heart function was significantly greater in the mice implanted with EDCs overexpressing VEGF (EDCs-VEGF) than with EDCs alone. Frozen sections of infarcted myocardium with EDCs or EDCs-VEGF transplantation showed GFP-positive tissue. The area with positive immunostaining for cardiac troponin I and α-myosin heavy chain was larger in injured myocardium with EDCs or EDCs-VEGF transplantation than with medium injection. Transplantation of EDCs or EDCs-VEGF significantly increased the number of blood vessels in the MI area. However, the density of capillaries was significantly higher in the EDCs-VEGF animals than in the EDC mice. Double staining for GFP and connexin-43 was positive in injured myocardium with EDC transplantation. Our data demonstrate that engrafted EDCs or EDCs-VEGF regenerated cardiac tissue and significantly improved cardiac function in postinfarcted hearts. The novel EDCs-VEGF synergistic approach may have an important impact on future cell therapy for patients experiencing MI or heart failure.
Effects of chronic heart failure on skeletal muscle capillary hemodynamics at rest and during contractions
Authors: Richardson Troy E. , Kindig Casey A. , Musch Timothy I. , Poole David C.
Published: March 2015

Chronic heart failure (CHF) reduces muscle blood flow at rest and during exercise and impairs muscle function. Using intravital microscopy techniques, we tested the hypothesis that the speed and amplitude of the capillary red blood cell (RBC) velocity ( VRBC) and flux (FRBC) response to contractions would be reduced in CHF compared with control (C) spinotrapezius muscle. The proportion of capillaries supporting continuous RBC flow was less ( P < 0.05) in CHF (0.66 ± 0.04) compared with C (0.84 ± 0.01) muscle at rest and was not significantly altered with contractions. At rest, VRBC (C, 270 ± 62; CHF, 179 ± 14 μm/s) and FRBC (C, 22.4 ± 5.5 vs. CHF, 15.2 ± 1.2 RBCs/s) were reduced (both P < 0.05) in CHF vs. C muscle. Contractions significantly (both P < 0.05) elevated VRBC (C, 428 ± 47 vs. CHF, 222 ± 15 μm/s) and FRBC (C, 44.3 ± 5.5 vs. CHF, 24.0 ± 1.2 RBCs/s) in C and CHF muscle; however, both remained significantly lower in CHF than C. The time to 50% of the final response was slowed (both P < 0.05) in CHF compared with C for both VRBC (C, 8 ± 4; CHF, 56 ± 11 s) and FRBC (C, 11 ± 3; CHF, 65 ± 11 s). Capillary hematocrit increased with contractions in C and CHF muscle but was not different ( P > 0.05) between CHF and C. Thus CHF impairs diffusive and conductive O2 delivery across the rest-to-contractions transition in rat skeletal muscle, which may help explain the slowed O2 uptake on-kinetics manifested in CHF patients at exercise onset.
Invited Review: Aging and energy balance
Authors: Wilson Margaret-Mary G. , Morley John E.
Published: March 2015

Humans over 70 yr of age often lose weight. This appears to be due to a physiological anorexia of aging as well as a loss of lean mass (sarcopenia) and, to a lesser extent, fat mass. The causes of the physiological anorexia of aging include changes in taste and smell and a decrease in adaptive relaxation of the fundus of the stomach, which leads to more rapid antral filling and early satiation. In addition, basal and stimulated levels of the satiating hormone, cholecystokinin, are increased. In men, the decline in testosterone leads to an increase in leptin and a loss of lean mass. Although resting metabolic rate declines with aging, this is mainly due to the decline in lean body mass. Energy metabolism is also decreased due to a decline in Na+-K+-ATPase activity, decreased muscle protein turnover, and possibly changes in mitochondrial membrane protein permeability. Physical energy expenditure declines with aging. Meal-induced thermogenesis shows a delay to peak, possibly due to a delay in gastric emptying. Inadequate data are available on the effect of aging in humans on other energy-producing mechanisms such as adaptive thermogenesis. These physiological changes place older men and women at major risk of developing pathological weight loss when they develop disease states, especially those associated with cytokine elaboration.
Decline in insulin action with age in endurance-trained humans
Authors: Clevenger Christopher M. , Parker Jones Pamela , Tanaka Hirofumi , Seals Douglas R. , DeSouza Christopher A.
Published: March 2015

We tested the hypothesis that regular endurance exercise prevents the age-related decline in insulin action typically observed in healthy, sedentary adults. An index of whole body insulin sensitivity (ISI), obtained from minimal model analysis of insulin and glucose concentrations during a frequently sampled intravenous glucose tolerance test, was determined in 126 healthy adults: 25 young [27 ± 1 (SE) yr; 13 men/12 women] and 43 older (59 ± 1 yr; 20/13) sedentary and 25 young (29 ± 1 yr; 12/13) and 33 older (60 ± 1 yr; 20/13) endurance trained. ISI values were lower in the older vs. young adults in both sedentary (−53%; 3.9 ± 0.3 vs. 7.0 ± 0.7 ×10−4 · min−1 · μU−1 · ml−1; P < 0.01) and endurance-trained (−36%; 7.9 ± 0.6 vs. 12.4 ± 1.0 ×10−4min−1 · μU−1 · ml−1; P < 0.01) groups, but the value was 72–102% higher in the trained subjects at either age ( P < 0.01). In subgroup analysis of sedentary and endurance-trained adults with similar body fat levels ( n = 62), the age-related reduction in ISI persisted only in the endurance-trained subjects (12.9 ± 1.9 vs. 8.7 ± 1.2 ×10−4 · min−1 · μU−1 · ml−1; P < 0.01). The results of the present study suggest that habitual endurance exercise does not prevent the age-associated decline insulin action. Moreover, the age-related reduction in ISI in endurance-trained adults appears to be independent of adiposity.