bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of ERK1/2 in uterine contractility and preterm labor in rats
Authors: Li Yunping , Je Hyun-Dong , Malek Sabah , Morgan Kathleen G.
Published: April 2004

The present study tested the hypothesis that ERK activation is an essential step in the onset of labor in a rat model of preterm labor. The administration of RU-486, an antiprogesterone agent, to rats induced preterm delivery 22.2 ± 0.24 h after treatment. Changes in basal signaling events were studied in myometrial tissue from CO2-euthanized rats. Rats treated with RU-486 displayed a dramatically increased in vitro uterine contractility compared with gestational stage-matched, sham-treated rats. In vitro contractility was not significantly different from that during spontaneous labor. During RU-486-induced preterm labor, as previously described for spontaneous labor, ERK phosphorylation levels increased, as did phosphorylation of caldesmon at Ser789, an ERK phosphorylation site. Also, a small but significant increase in 20-kDa myosin light chain phosphorylation was seen at a constant intracellular pCa of 7. When rats were chronically treated with an agent that prevents ERK activation, U-0126, the onset of RU-486-induced preterm labor was delayed in a statistically significant manner. Chronic in vivo treatment with U-0126 also significantly inhibited the RU-486-induced increase in in vitro contractility and ERK and caldesmon phosphorylation but did not alter the RU-486-induced increase in 20-kDa myosin light chain phosphorylation. These data indicate that ERK activation is a component of the multiple events leading to the development of labor in this rat model. We suggest that the ERK pathway could possibly be used to identify targets for the development of a novel class of tocolytic agents.
Spatial distribution of hypoxic pulmonary vasoconstriction in the supine pig
Authors: Hlastala Michael P. , Lamm Wayne J. E. , Karp Adam , Polissar Nayak L. , Starr Ian R. , Glenny Robb W.
Published: April 2004

Hypoxic pulmonary vasoconstriction (HPV) serves to maintain optimal gas exchange by decreasing perfusion to hypoxic regions. However, global hypoxia and nonuniform HPV may result in overperfusion of poorly constricted regions leading to local edema seen in high-altitude pulmonary edema. To quantify the spatial distribution of HPV and its response to regional Po2 (PrO2) among small lung regions, five pigs were anesthetized and mechanically ventilated in the supine posture. The animals were ventilated with an inspired O2 fraction (FiO2) of 0.50 and 0.21 and then (in random order) 0.15, 0.12, and 0.09. Regional blood flow (Q̇) and alveolar ventilation (V̇a) were measured by using intravenous infusion of 15 μm and inhalation of 1-μm fluorescent microspheres, respectively. PrO2 was calculated for each piece at each FiO2. Lung pieces differed in their Q̇ response to hypoxia in a manner related to their initial V̇a/Q̇ with FiO2 = 0.21. Reducing FiO2 < 0.15 decreased Q̇ to the initially high V̇a/Q̇ (higher PrO2) regions and forced Q̇ into the low V̇a/Q̇ (dorsal-caudal) regions. Resistance increased in most lung pieces as PrO2 decreased, reaching a maximum resistance when PrO2 is between 40 and 50 Torr. Local resistance decreased at Pro2 < 40 Torr. Pieces were statistically clustered with respect to their relative Q̇ response pattern to each FiO2. Some clusters were shown to be spatially organized. We conclude that HPV is spatially heterogeneous. The heterogeneity of Q̇ response may be related, in part, to the heterogeneity of baseline V̇a/Q̇.
Lower pulmonary diffusing capacity in the prone vs. supine posture
Authors: Peces-Barba G. , Rodríguez-Nieto M. J. , Verbanck S. , Paiva M. , González-Mangado N.
Published: April 2004

We evaluated the effect of prone positioning on gas-transfer characteristics in normal human subjects. Single-breath (SB) and rebreathing (RB) maneuvers were employed to assess carbon monoxide diffusing capacity (DlCO), its components related to capillary blood volume (Vc) and membrane diffusing capacity (Dm), pulmonary tissue volume (Vti), and cardiac output (Q̇c). Alveolar volume (Va) was significantly greater prone than supine, irrespective of the test maneuver used. Nevertheless, DlCO was consistently lower prone than supine, a difference that was enhanced when appropriately corrected for the higher Va prone. When adequately corrected for Va, diffusing capacity significantly decreased by 8% from supine to prone [SB: DlCO,corr supine vs. prone: 32.6 ± 2.3 (SE) vs. 30.0 ± 2 ml·min-1·mmHg-1 stpd; RB: DlCO,corr supine vs. prone: 30.2 ± 2.2 (SE) vs. 27.8 ± 2.0 ml·min-1·mmHg-1 stpd]. Both Vc and Dm showed a tendency to decrease from supine to prone, but neither reached significance. Finally, there were no significant differences in Vti or Q̇c between supine and prone. We interpret the lower diffusing capacity of the healthy lung in the prone posture based on the relatively larger space occupied by the heart in the dependent lung zones, leaving less space for zone 3 capillaries, and on the relatively lower position of the heart, leaving the zone 3 capillaries less engorged.
A novel method for measuring dynamic changes in cell volume
Authors: Davis Cristina E. , Rychak Joshua J. , Hosticka Bouvard , Davis Scott C. , John J. Edward , Tucker Amy L. , Norris Pamela M. , Moorman J. Randall
Published: April 2004

Many cell types regulate their volume in response to extracellular tonicity changes through a complex series of adaptive mechanisms. Several methods that are presently used to measure cell volume changes include Coulter counters, fluorescent techniques, electronic impedance, and video microscopy. Although these methods are widely used and accepted, there are limitations associated with each technique. This paper describes a new method to measure changes in cell volume based on the principle that fluid flow within a rigid system is well determined. For this study, cos-7 cells were plated to line the inner lumen of a glass capillary and stimulated to swell or shrink by altering the osmolarity of the perfusing solution. The cell capillary was connected in series with a blank reference capillary, and differential pressure changes across each tube were monitored. The advantages of this method include 1) ability to continuously monitor changes in volume during rapid solution changes, 2) independence from cell morphology, 3) presence of physiological conditions with cell surface contacts and cell-cell interactions, 4) no phototoxic effects such as those associated with fluorescent methods, and 5) ability to report from large populations of cells. With this method, we could detect the previously demonstrated enhanced volume regulation of cells overexpressing the membrane phosphoprotein phospholemman, which has been implicated in osmolyte transport.
Hog barn dust extract augments lymphocyte adhesion to human airway epithelial cells
Authors: Mathisen T. , Von Essen S. G. , Wyatt T. A. , Romberger D. J.
Published: April 2004

The dust of hog confinement facilities induces airway inflammation. Mechanisms by which this dust modulates inflammation are not completely defined, although it is clear that exposure to dust can modulate both epithelial cell and inflammatory cell function. In this work, we demonstrate that airway epithelial cell (BEAS-2B) treatment with hog barn dust extract (HDE) results in augmentation of peripheral blood lymphocyte adhesion to epithelial cell cultures in vitro. The augmentation of lymphocyte adhesion to epithelial cells is dependent on the concentration of HDE and time of HDE exposure, with twofold increases observed by 3 h and maintained at 24 h. Similar results are seen with primary human bronchial epithelial cells in culture. Lymphocyte adhesion to epithelial cells is inhibited in a concentration-dependent fashion by the treatment of epithelial cells with antibody to intercellular adhesion molecule-1 (ICAM-1). In addition, HDE exposure of epithelial cells results in an approximate twofold increase in ICAM-1 expression as determined by flow cytometry analysis. Pretreatment of epithelial cells with a protein kinase C-α (PKC-α) inhibitor, Gö-6976, also inhibited subsequent lymphocyte adhesion to HDE-exposed epithelial cells. These data suggest that airway epithelial cell HDE exposure enhances subsequent lymphocyte adhesion to epithelial cells that is mediated in part by HDE modulation of ICAM-1 expression and PKC-α.
Aging, opioid-receptor agonists and antagonists, and the vestibulosympathetic reflex in humans
Authors: Ray Chester A. , Monahan Kevin D.
Published: April 2004

Animal studies indicate that opioids inhibit the firing rate of vestibular neurons, which are important in mediating the vestibulosympathetic reflex. Furthermore, this inhibition appears to be greater in more mature rats. In the present study, we tested the hypotheses that opioids inhibit the vestibulosympathetic reflex in humans and that endogenous opioids contribute to the age-related impairment of the vestibulosympathetic reflex. These hypotheses were tested by measuring muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate responses to otolith organ engagement during head-down rotation (HDR) in young (24 ± 2 yr old) and older (63 ± 2 yr) subjects before and after administration of either an opioid-receptor antagonist (16 mg naloxone in 9 young and 8 older subjects) or an opioid-receptor agonist (60 mg codeine in 7 young and 7 older subjects). Naloxone did not augment the reflex increase in MSNA during HDR in young (Δ7 ± 2 vs. Δ4 ± 2 bursts/min and Δ81 ± 23 vs. Δ60 ± 24% change in burst frequency and total MSNA before and after naloxone, respectively) or older subjects (Δ2 ± 2 vs. Δ1 ± 2 burst/min and Δ8 ± 7 vs. Δ8 ± 9% before and after naloxone). Similarly, codeine did not attenuate the increase in MSNA during HDR in young (Δ8 ± 1 vs. Δ7 ± 2 bursts/min and Δ53 ± 4 vs. Δ64 ± 16% before and after codeine) or older subjects (Δ6 ± 4 vs. Δ3 ± 3 bursts/min and Δ38 ± 21 vs. Δ33 ± 20%). Mean arterial blood pressure and heart rate responses to HDR were not altered by either naloxone or codeine. These data do not provide experimental support for the concept that opioids modulate the vestibulosympathetic reflex in humans. Moreover, endogenous opioids do not appear to contribute the age-associated impairment of the vestibulosympathetic reflex.
Rheology of airway smooth muscle cells is associated with cytoskeletal contractile stress
Authors: Stamenović Dimitrije , Suki Béla , Fabry Ben , Wang Ning , Fredberg Jeffrey J. , Buy Julie E.
Published: April 2004

Recently reported data from mechanical measurements of cultured airway smooth muscle cells show that stiffness of the cytoskeletal matrix is determined by the extent of static contractile stress borne by the cytoskeleton (Wang N, Tolić-Nørrelykke IM, Chen J, Mijailovich SM, Butler JP, Fredberg JJ, and Stamenović D. Am J Physiol Cell Physiol 282, C606-C616, 2002). On the other hand, rheological measurements on these cells show that cytoskeletal stiffness changes with frequency of imposed mechanical loading according to a power law (Fabry B, Maksym GN, Butler JP, Glogauer M, Navajas DF, and Fredberg JJ. Phys Rev Lett 87: 148102, 2001). In this study, we examine the possibility that these two empirical observations might be interrelated. We combine previously reported data for contractile stress of human airway smooth muscle cells with new data describing rheological properties of these cells and derive quantitative, mathematically tractable, and experimentally verifiable empirical relationships between contractile stress and indexes of cell rheology. These findings reveal an intriguing role of the contractile stress: although it maintains structural stability of the cell under applied mechanical loads, it may also regulate rheological properties of the cytoskeleton, which are essential for other cell functions.
Neuromuscular rehabilitation by treadmill running or electrical stimulation after peripheral nerve injury and repair
Authors: Marqueste Tanguy , Alliez Jean-Roch , Alluin Olivier , Jammes Yves , Decherchi Patrick
Published: April 2004

Numerous studies have been devoted to the regeneration of the motor pathway toward a denervated muscle after nerve injury. However, the regeneration of sensory muscle endings after repair by self-anastomosis are little studied. In previous electrophysiological studies, our laboratory showed that the functional characteristics of tibialis anterior muscle afferents are differentially affected after injury and repair of the peroneal nerve with and without chronic electrostimulation. The present study focuses on the axonal regeneration of mechano- (fibers I and II) and metabosensitive (fibers III and IV) muscle afferents by evaluating the recovery of their response to different test agents after nerve injury and repair by self-anastomosis during 10 wk of treadmill running (LSR). Data were compared with control animals (C), animals with nerve lesion and suture (LS), and animals with lesion, suture, and chronic muscle rehabilitation by electrostimulation (LSE) with a biphasic current modulated in pulse duration and frequency, eliciting a pattern mimicking the activity delivered by the nerve to the muscle. Compared with the C group, results indicated that 1) muscle weight was smaller in LS and LSR groups, 2) the fatigue index was greater in the LS group and smaller in the LSE group, 3) metabosensibility remained altered in the LS and LSE groups, and 4) mechanosensitivity presented a large increase of the activation pattern in the LS and LSE groups. Our data indicated that chronic muscle electrostimulation partially favors the recovery of muscle properties (i.e., muscle weight and twitch response were close to the C group) and that rehabilitation by treadmill running also efficiently induced a better functional muscle afferent recovery (i.e., the discharge pattern was similar to the C group). The effectiveness of the chronic electromyostimulation and the treadmill exercise on afferent recovery is discussed with regard to parameters listed above.
Endurance exercise training inhibits activity of plasma GOT and liver caspase-3 of rats exposed to stress by induction of heat shock protein 70
Authors: Mikami Toshio , Sumida Satoshi , Ishibashi Yoshitomo , Ohta Shigeo
Published: April 2004

A single bout of exercise increases production of heat shock protein 70 (HSP70), which protects cells against various stresses. In this study, we investigated whether endurance exercise training enhances liver level of HSP70 and, if so, whether HSP70 contributes to hepatic protection against stress in vivo. Mice of an exercise-training group performed 60 min of treadmill running 5 days/wk for 4 wk. The resting level of liver HSP70 was 4.5 times higher in the trained than in sedentary mice. After 4 wk of exercise training, both groups of mice were exposed to the following stresses: 1) heat stress, 2) cold stress, 3) oxidative stress, 4) ethanol stress, and 5) exercise stress by compelling the mice to run on a treadmill until exhausted. After exposure to the stresses, the liver was immediately isolated. Elevation of liver HSP70 in the trained mice was evident, whereas no elevation was found in the sedentary mice. On exposure to heat, diethyldithiocarbamate and ethanol, activities of glutanic oxalacetic transaminase in plasma, and liver caspase-3, a key enzyme of apoptotic processing, were elevated in the sedentary mice but not in the trained mice. These results suggest that exercise training enhanced the resting level of liver HSP70 and hepatic protection against various stresses, at least partly attributing to the suppression of caspase-3 activity by the increase in HSP70.
Inhibition of medullary raphé serotonergic neurons has age-dependent effects on the CO2response in newborn piglets
Authors: Messier Michelle L. , Li Aihua , Nattie Eugene E.
Published: April 2004

Medullary raphé serotonergic neurons are chemosensitive in culture and are situated adjacent to blood vessels in the brain stem. Selective lesioning of serotonergic raphé neurons decreases the ventilatory response to systemic CO2in awake and sleeping adult rats. Abnormalities in the medullary serotonergic system, including the raphé, have been implicated in the sudden infant death syndrome ( 48 ). In this study, we ask whether serotonergic neurons in the medullary raphé and extra-raphé regions are involved in the CO2response in unanesthetized newborn piglets, 3-16 days old. Whole body plethysmography was used to examine the ventilatory response to 5% CO2before and during focal inhibition of serotonergic neurons by 8-hydroxy-2-di- n-propylaminotetralin (8-OH-DPAT), a 5-HT1Areceptor agonist. 8-OH-DPAT (10 or 30 mM in artificial cerebrospinal fluid) decreased the CO2response in wakefulness in an age-dependent manner, as revealed by a linear regression analysis that showed a significant negative correlation ( P < 0.001) between the percent change in the CO2response and piglet age. Younger piglets showed an exaggerated CO2response. Control dialysis with artificial cerebrospinal fluid had no significant effect on the CO2response. Additionally, 8-OH-DPAT increased blood pressure and decreased heart rate independent of age ( P < 0.05). Finally, sleep cycling was disrupted by 8-OH-DPAT, such that piglets were awake more and asleep less ( P < 0.05). Because of the fragmentary sleep data, it was not possible to examine the CO2response in sleep. Inhibition of serotonergic medullary raphé and extra-raphé neurons decreases ventilatory CO2sensitivity and alters cardiovascular variables and sleep cycling, which may contribute to the sudden infant death syndrome.
Exercise training attenuated the PKB and GSK-3 dephosphorylation in the myocardium of ZDF rats
Authors: Lajoie Claude , Calderone Angelino , Trudeau François , Lavoie Nathalie , Massicotte Guy , Gagnon Sylvain , Béliveau Louise
Published: April 2004

Cardiac dysfunction is a severe secondary effect of Type 2 diabetes. Recruitment of the protein kinase B/glycogen synthase kinase-3 pathway represents an integral event in glucose homeostasis, albeit its regulation in the diabetic heart remains undefined. Thus the following study tested the hypothesis that the regulation of protein kinase B/glycogen synthase kinase-3 was altered in the myocardium of the Zucker diabetic fatty rat. Second, exercise has been shown to improve glucose homeostasis, and, in this regard, the effect of swimming training on the regulation of protein kinase B/glycogen synthase kinase-3 in the diabetic rat heart was examined. In the sedentary Zucker diabetic fatty rats, glucose levels were elevated, and cardiac glycogen content increased, compared with wild type. A 13-wk swimming regimen significantly reduced plasma glucose levels and cardiac glycogen content and partially normalized protein kinase B-serine473, protein kinase B-threonine308, and glycogen synthase kinase-3α phosphorylation in Zucker diabetic fatty rats. In conclusion, hyperglycemia and increased cardiac glycogen content in the Zucker diabetic fatty rats were associated with dysregulation of protein kinase B/glycogen synthase kinase-3 phosphorylation. These anomalies in the Zucker diabetic fatty rat were partially normalized with swimming. These data support the premise that exercise training may protect the heart against the deleterious consequences of diabetes.
Simultaneous control of hand displacements and rotations in orientation-matching experiments
Authors: Torres Elizabeth B. , Zipser David
Published: April 2004

In reach-to-grasp movements, the interaction between the hand changes in position and those in orientation is poorly understood. A theoretical approach previously proposed (Torres EB and Zipser D. J Neurophysiol 88: 1-13, 2002) assumes that motion strategies are resolved in space independently from the temporal dynamics of the motion and predicts the coarticulation of the hand transport and rotation along the path. The model implies that this simultaneous control is independent of variations in speed and initial posture and required matching orientation. This paper presents experimental data from human subjects that confirm the model's predictions in the context of realistic, unconstrained, orientation-matching motions. Speed independence is quantified in the similarity of the postural and endpoint position-orientation paths obtained under three different speeds. Significant differences in hand and joint kinematics are shown in response to changes in initial posture and target orientation. The robustness of coarticulation under all three experimental conditions supports the idea of an intermediate stage that resolves the geometry of the motion independent of its temporal dynamics.
Surfactant from diving aquatic mammals
Authors: Spragg Roger G. , Ponganis Paul J. , Marsh James J. , Rau Gunnar A. , Bernhard Wolfgang
Published: April 2004

Diving mammals that descend to depths of 50-70 m or greater fully collapse the gas exchanging portions of their lungs and then reexpand these areas with ascent. To investigate whether these animals may have evolved a uniquely developed surfactant system to facilitate repetitive alveolar collapse and expansion, we have analyzed surfactant in bronchoalveolar lavage fluid (BAL) obtained from nine pinnipeds and from pigs and humans. In contrast to BAL from terrestrial mammals, BAL from pinnipeds has a higher concentration of phospholipid and relatively more fluidic phosphatidylcholine molecular species, perhaps to facilitate rapid spreading during alveolar reexpansion. Normalized concentrations of hydrophobic surfactant proteins B and C were not significantly different among pinnipeds and terrestrial mammals by immunologic assay, but separation of proteins by gel electrophoresis indicated a greater content of surfactant protein B in elephant seal surfactant than in human surfactant. Remarkably, surfactant from the deepest diving pinnipeds produced moderately elevated in vitro minimum surface tension measurements, a finding not explained by the presence of protein or neutral lipid inhibitors. Further study of the composition and function of pinniped surfactants may contribute to the design of optimized therapeutic surfactants.
Intermittent normobaric hypoxia does not alter performance or erythropoietic markers in highly trained distance runners
Authors: Julian Colleen G. , Gore Christopher J. , Wilber Randall L. , Daniels Jack T. , Fredericson Michael , Stray-Gundersen James , Hahn Allan G. , Parisotto Robin , Levine Benjamin D.
Published: April 2004

This study was designed to test the hypothesis that intermittent normobaric hypoxia at rest is a sufficient stimulus to elicit changes in physiological measures associated with improved performance in highly trained distance runners. Fourteen national-class distance runners completed a 4-wk regimen (5:5-min hypoxia-to-normoxia ratio for 70 min, 5 times/wk) of intermittent normobaric hypoxia (Hyp) or placebo control (Norm) at rest. The experimental group was exposed to a graded decline in fraction of inspired O2: 0.12 ( week 1), 0.11 ( week 2), and 0.10 ( weeks 3 and 4). The placebo control group was exposed to the same temporal regimen but breathed fraction of inspired O2of 0.209 for the entire 4 wk. Subjects were matched for training history, gender, and baseline measures of maximal O2uptake and 3,000-m time-trial performance in a randomized, balanced, double-blind design. These parameters, along with submaximal treadmill performance (economy, heart rate, lactate, and ventilation), were measured in duplicate before, as well as 1 and 3 wk after, the intervention. Hematologic indexes, including serum concentrations of erythropoietin and soluble transferrin receptor and reticulocyte parameters (flow cytometry), were measured twice before the intervention, on days 1, 5, 10, and 19 of the intervention, and 10 and 25 days after the intervention. There were no significant differences in maximal O2uptake, 3,000-m time-trial performance, erythropoietin, soluble transferrin receptor, or reticulocyte parameters between groups at any time. Four weeks of a 5:5-min normobaric hypoxia exposure at rest for 70 min, 5 days/wk, is not a sufficient stimulus to elicit improved performance or change the normal level of erythropoiesis in highly trained runners.
Effects of five consecutive nocturnal hypoxic exposures on the cerebrovascular responses to acute hypoxia and hypercapnia in humans
Authors: Kolb Jon C. , Ainslie Philip N. , Ide Kojiro , Poulin Marc J.
Published: April 2004

The effects of discontinuous hypoxia on cerebrovascular regulation in humans are unknown. We hypothesized that five nocturnal hypoxic exposures (8 h/day) at a simulated altitude of 4,300 m (inspired O2 fraction = ∼13.8%) would elicit cerebrovascular responses that are similar to those that have been reported during chronic altitude exposures. Twelve male subjects (26.6 ± 4.1 yr, mean ± SD) volunteered for this study. The technique of end-tidal forcing was used to examine cerebral blood flow (CBF) and regional cerebral O2 saturation (SrO2) responses to acute variations in O2 and CO2 twice before, immediately after, and 5 days after the overnight hypoxic exposures. Transcranial Doppler ultrasound was used to assess CBF, and near-infrared spectroscopy was used to assess SrO2. Throughout the nocturnal hypoxic exposures, end-tidal Pco2 decreased ( P < 0.001) whereas arterial O2 saturation increased ( P < 0.001) compared with overnight normoxic control measurements. Symptoms associated with altitude illness were significantly greater than control values on the first night ( P < 0.001) and second night ( P < 0.01) of nocturnal hypoxia. Immediately after the nocturnal hypoxic intervention, the sensitivity of CBF to acute variations in O2 and CO2 increased 116% ( P < 0.01) and 33% ( P < 0.05), respectively, compared with control values. SrO2 was highly correlated with arterial O2 saturation ( R2 = 0.94 ± 0.04). These results show that discontinuous hypoxia elicits increases in the sensitivity of CBF to acute variations in O2 and CO2, which are similar to those observed during chronic hypoxia.
Cooling vest worn during active warm-up improves 5-km run performance in the heat
Authors: Arngrïmsson Sigurbjörn Á. , Petitt Darby S. , Stueck Matthew G. , Jorgensen Dennis K. , Cureton Kirk J.
Published: April 2004

We investigated whether a cooling vest worn during an active warm-up enhances 5-km run time in the heat. Seventeen competitive runners (9 men, maximal oxygen uptake = 66.7 ± 5.9 ml·kg-1·min-1; 8 women, maximal oxygen uptake = 58.0 ± 3.2 ml·kg-1·min-1) completed two simulated 5-km runs on a treadmill after a 38-min active warm-up during which they wore either a T-shirt (C) or a vest filled with ice (V) in a hot, humid environment (32°C, 50% relative humidity). Wearing the cooling vest during warm-up significantly ( P < 0.05) blunted increases in body temperature, heart rate (HR), and perception of thermal discomfort during warm-up compared with control. At the start of the 5-km run, esophageal, rectal, mean skin, and mean body temperatures averaged 0.3, 0.2, 1.8, and 0.4°C lower; HR averaged 11 beats/min lower; and perception of thermal discomfort (5-point scale) averaged 0.6 point lower in V than C. Most of these differences were eliminated during the first 3.2 km of the run, and these variables were not different at the end. The 5-km run time was significantly lower ( P < 0.05) by 13 s in V than C, with a faster pace most evident during the last two-thirds of the run. We conclude that a cooling vest worn during active warm-up by track athletes enhances 5-km run performance in the heat. Reduced thermal and cardiovascular strain and perception of thermal discomfort in the early portion of the run appear to permit a faster pace later in the run.
Neuromuscular changes for hopping on a range of damped surfaces
Authors: Moritz Chet T. , Greene Spencer M. , Farley Claire T.
Published: April 2004

Humans hopping and running on elastic and damped surfaces maintain similar center-of-mass dynamics by adjusting stance leg mechanics. We tested the hypothesis that the leg transitions from acting like an energy-conserving spring on elastic surfaces to a power-producing actuator on damped surfaces during hopping due to changes in ankle mechanics. To test this hypothesis, we collected surface electromyography, video kinematics, and ground reaction force while eight male subjects (body mass: 76.2 ± 1.7 kg) hopped in place on a range of damped surfaces. On the most damped surface, most of the mechanical work done by the leg appeared at the ankle (52%), whereas 23 and 25% appeared at the knee and hip, respectively. Hoppers extended all three joints during takeoff further than they flexed during landing and thereby did more net positive work on more heavily damped surfaces. Also, all three joints reached peak flexion sooner after touchdown on more heavily damped surfaces. Consequently, peak moment occurred during joint extension rather than at peak flexion as on elastic surfaces. These strategies caused the positive work during extension to exceed the negative work during flexion to a greater extent on more heavily damped surfaces. At the muscle level, surface EMG increased by 50-440% in ankle and knee extensors as surface damping increased to compensate for greater surface energy dissipation. Our findings, and those of previous studies of hopping on elastic surfaces, show that the ankle joint is the key determinant of both springlike and actuator-like leg mechanics during hopping in place.
Effects on breathing in awake and sleeping goats of focal acidosis in the medullary raphe
Authors: Hodges M. R. , Klum L. , Leekley T. , Brozoski D. T. , Bastasic J. , Davis S. , Wenninger J. M. , Feroah T. R. , Pan L. G. , Forster H. V.
Published: April 2004

Our aim was to determine the effects of focal acidification in the raphe obscurus (RO) and raphe pallidus (RP) on ventilation and other physiological variables in both the awake and sleep states in adult goats. Through chronically implanted microtubules, 1) a focal acidosis was created by microdialysis of mock cerebrospinal fluid (mCSF), equilibrated with various levels of CO2, and 2) medullary extracellular fluid (ECF) pH was measured by using a custom-made pH electrode. Focal acidosis in the RO or RP, by dialyzing either 25 or 80% CO2 (mCSF pH ∼ 6.8 or 6.3), increased ( P < 0.05) inspiratory flow by 8 and 12%, respectively, while the animals were awake during the day, but not at night while they were awake or in non-rapid eye movement sleep. While the animals were awake during the day, there were also increases in heart rate and blood pressure ( P < 0.05) but no significant change in metabolic rate or arterial Pco2. Dialysis with mCSF equilibrated with 25 or 80% CO2 reduced ECF pH by the same amount (25%) or three times more (80%) than when inspired CO2 was increased to 7%. During CO2 inhalation, the reduction in ECF pH was only 50% of the reduction in arterial pH. Finally, dialysis in vivo only decreased ECF pH by 19.1% of the change during dialysis in an in vitro system. We conclude that 1) the physiological responses to focal acidosis in the RO and RP are consistent with the existence of chemoreceptors in these nuclei, and 2) local pH buffering mechanisms act to minimize changes in brain pH during systemic induced acidosis and microdialysis focal acidosis and that these mechanisms could be as or more important to pH regulation than the small changes in inspiratory flow during a focal acidosis.
Sensorimotor integration at spinal level as a basis for muscle coordination during voluntary movement in humans
Authors: Nielsen Jens Bo
Published: April 2004

Spinal reflexes have traditionally been treated as separate from voluntary movements. However, animal experiments since the 1950s and human experiments since the 1970s have documented that sensory activities in afferents from muscles, skin, and joints are integrated with descending motor commands at the level of common spinal interneurons. Two different roles of this sensorimotor integration at the spinal level may be discerned. First, sensory feedback evoked by the active muscles may help to drive the motoneurons. Second, external stimuli, such as sudden perturbations of a limb, may give rise to “error signals,” which are integrated into the ongoing motor activity and form the basis of corrective responses. When interpreting experimental data, it is important to consider these two different roles. Application of external stimuli may provide little information about how the spinal cord integrates sensory feedback evoked as part of ongoing movements. The complexity of the spinal machinery that is activated by external stimuli also makes the interpretation of data obtained from experiments dealing with artificial external stimuli, such as electrical stimuli, difficult. Nevertheless, such experiments have provided and will continue to provide very valuable information about how the brain and spinal cord ensure coordination of muscle activity during voluntary movement. So far, spinal control mechanisms have only been investigated to a limited extent in relation to sports and occupational activities. Provided that researchers consider the methodological problems of the techniques and that they seek independent validation of the findings, this may be a very fruitful research field in the future.
Hyperthermia-induced vasoconstriction of the carotid artery, a possible causative factor of heatstroke
Authors: Mustafa Seham , Thulesius O. , Ismael H. N.
Published: April 2004

Clinical and experimental studies indicate that hyperthermia can cause heatstroke with cerebral ischemia and brain damage. However, no study has examined the direct effects of heating carotid artery smooth muscle and tested the hypothesis that hyperthermia induces arterial vasoconstriction and, thereby, decreases cerebral blood flow. We recorded isometric tension of rabbit carotid artery strips in organ baths during stepwise temperature elevation. The heating responses were tested at basal tone, in norepinephrine- and KCl-precontracted vessels, and after electrical field stimulation. Stepwise heating from 37°C to 47°C induced reproducible graded contraction proportional to temperature. The responses could be elicited at basal tone and in precontracted vessels. Heating decreased the contractile responses to norepinephrine and electrical field stimulation but increased contraction to KCl. These responses were not eliminated by pretreatment with the neuronal blocker tetrodotoxin. Our results demonstrate that heating carotid artery preparations above 37°C (normothermia) induced a reversible graded vasoconstriction proportional to temperature. In vivo this reaction may lead to a decrease in cerebral blood flow and cerebral ischemia with brain damage as in heatstroke. The heating-induced contraction is not mediated by a neurogenic process but is due to altered transcellular Ca2+ transport. Cooling, in particular of the neck area, therefore, should be used in the treatment of heatstroke.
Role of heat shock protein 27 in cytoskeletal remodeling of the airway smooth muscle cell
Authors: An Steven S. , Fabry Ben , Mellema Mathew , Bursac Predrag , Gerthoffer William T. , Kayyali Usamah S. , Gaestel Matthias , Shore Stephanie A. , Fredberg Jeffrey J.
Published: April 2004

Remodeling of the airway smooth muscle (ASM) cell has been proposed to play an important role in airway hyperresponsiveness. Using a functional assay, we have assessed remodeling of the cultured rat ASM cell and the role of heat shock protein (HSP) 27 in that process. To probe remodeling dynamics, we measured spontaneous motions of an individual Arg-Gly-Asp-coated microbead that was anchored to the cytoskeleton. We reasoned that the bead could not move unless the microstructure to which it is attached rearranged; if so, then its mean square displacement (MSD) would report ongoing internal reorganizations over time. Each bead displayed a random, superdiffusive motion; MSD increased with time as ∼ t1.7, whereas an exponent of unity would be expected for a simple passive diffusion. Increasing concentrations of cytochalasin-D or latrunculin-A caused marked increases in the MSD, whereas colchicine did not. Treatments with PDGF or IL-1β, but not transforming growth factor-β, caused decreases in the MSD, the extent of which rank-ordered with the relative potency of these agents in eliciting the phosphorylation of HSP27. The chemical stressors anisomycin and arsenite each increased the levels of HSP27 phosphorylation and, at the same time, decreased bead motions. In particular, arsenite prevented and even reversed the effects of cytochalasin-D on bead motions. Finally, ASM cells overexpressing phospho-mimicking human HSP27, but not wild-type or phosphorylation-deficient HSP27, exhibited decreases in bead motions that were comparable to the arsenite response. Taken together, these results show that phosphorylated HSP27 favors reduced bead motions that are probably due to stabilization of the actin cytoskeleton.
Physiological and inflammatory response to instillation of an oxidized surfactant in a rat model of surfactant deficiency
Authors: Bailey Timothy C. , Da Silva Keith A. , Lewis James F. , Rodriguez-Capote Karina , Possmayer Fred , Veldhuizen Ruud A. W.
Published: April 2004

Pulmonary surfactant is a mixture of phospholipids (∼90%) and surfactant-associated proteins (SPs) (∼10%) that stabilize the lung by reducing the surface tension. One proposed mechanism by which surfactant is altered during acute lung injury is via direct oxidative damage to surfactant. In vitro studies have revealed that the surface activity of oxidized surfactant was impaired and that this effect could be overcome by adding SP-A. On the basis of this information, we hypothesized that animals receiving oxidized surfactant preparations would exhibit an inferior physiological and inflammatory response and that the addition of SP-A to the oxidized preparations would ameliorate this response. To test this hypothesis, mechanically ventilated, surfactant-deficient rats were administered either bovine lipid extract surfactant (BLES) or in vitro oxidized BLES of three doses: 10 mg/kg, 50 mg/kg, or 10 mg/kg + SP-A. When instilled with 10 mg/kg normal surfactant, the rats had a significantly superior arterial Po2responses compared with the rats receiving oxidized surfactant. Interestingly, increasing the dose five times mitigated this physiological effect, and the addition of SP-A to the surfactant preparation had little impact on improving oxygenation. There were no differences in alveolar surfactant pools and the indexes of pulmonary inflammation between the 10 mg/kg dose groups, nor was there any differences observed between either of the groups supplemented with SP-A. However, there was significantly more surfactant and more inflammatory cytokines in the 50 mg/kg oxidized BLES group compared with the 50 mg/kg BLES group. We conclude that instillation of an in vitro oxidized surfactant causes an inferior physiological response in a surfactant-deficient rat.
Rest insertion combined with high-frequency loading enhances osteogenesis
Authors: LaMothe Jeremy M. , Zernicke Ronald F.
Published: April 2004

Mechanical loading can significantly affect skeletal adaptation. High-frequency loading can be a potent osteogenic stimulus. Additionally, insertion of rest periods between consecutive loading bouts can be a potent osteogenic stimulus. Thus we investigated whether the insertion of rest-periods between short-term high-frequency loading bouts would augment adaptation in the mature murine skeleton. Right tibiae of skeletally mature (16 wk) female C57BL/6 mice were loaded in cantilever bending at peak of 800 μϵ, 30 Hz, 5 days/wk for 3 wk. Left tibiae were the contralateral control condition. Mice were randomly assigned into one of two groups: continuous high-frequency (CT) stimulation for 100 s ( n = 9), or 1-s pulses of high-frequency stimuli followed by 10 s of rest (RI) for 100 s ( n = 9). Calcein labels were administered on days 1 and 21; label incorporation was used to histomorphometrically assess periosteal and endosteal indexes of adaptation. Periosteal surface referent bone formation rate (pBFR/BS) was significantly enhanced in CT (>88%) and RI (>126%) loaded tibiae, relative to control tibiae. Furthermore, RI tibiae had significantly greater pBFR/BS, relative to CT tibiae (>72%). The endosteal surface was not as sensitive to mechanical loading as the periosteal surface. Thus short-term high-frequency loading significantly elevated pBFR/BS, relative to control tibiae. Furthermore, despite the 10-fold reduction in cycle number, the insertion of rest periods between bouts of high-frequency stimuli significantly augmented pBFR/BS, relative to tibiae loaded continually. Optimization of osteogenesis in response to mechanical loading may underpin the development of nonpharmacological regiments designed to increase bone strength in individuals with compromised bone structures.
Characterizing airway and alveolar nitric oxide exchange during tidal breathing using a three-compartment model
Authors: Condorelli Peter , Shin Hye-Won , George Steven C.
Published: April 2004

Exhaled nitric oxide (NO) may be a useful marker of lung inflammation, but the concentration is highly dependent on exhalation flow rate due to a significant airway source. Current methods for partitioning pulmonary NO gas exchange into airway and alveolar regions utilize multiple exhalation flow rates or a single-breath maneuver with a preexpiratory breath hold, which is cumbersome for children and individuals with compromised lung function. Analysis of tidal breathing data has the potential to overcome these limitations, while still identifying region-specific parameters. In six healthy adults, we utilized a three-compartment model (two airway compartments and one alveolar compartment) to identify two potential flow-independent parameters that represent the average volumetric airway flux (pl/s) and the time-averaged alveolar concentration (parts/billion). Significant background noise and distortion of the signal from the sampling system were compensated for by using a Gaussian wavelet filter and a series of convolution integrals. Mean values for average volumetric airway flux and time-averaged alveolar concentration were 2,500 ± 2,700 pl/s and 3.2 ± 3.4 parts/billion, respectively, and were strongly correlated with analogous parameters determined from vital capacity breathing maneuvers. Analysis of multiple tidal breaths significantly reduced the standard error of the parameter estimates relative to the single-breath technique. Our initial assessment demonstrates the potential of utilizing tidal breathing for noninvasive characterization of pulmonary NO exchange dynamics.
Skeletal muscle hypertrophy in response to isometric, lengthening, and shortening training bouts of equivalent duration
Authors: Adams Gregory R. , Cheng Daniel C. , Haddad Fadia , Baldwin Kenneth M.
Published: April 2004

Movements generated by muscle contraction generally include periods of muscle shortening and lengthening as well as force development in the absence of external length changes (isometric). However, in the specific case of resistance exercise training, exercises are often intentionally designed to emphasize one of these modes. The purpose of the present study was to objectively evaluate the relative effectiveness of each training mode for inducing compensatory hypertrophy. With the use of a rat model with electrically stimulated (sciatic nerve) contractions, groups of rats completed 10 training sessions in 20 days. Within each training session, the duration of the stimulation was equal across the three modes. Although this protocol provided equivalent durations of duty cycle, the torque integral for the individual contractions varied markedly with training mode such that lengthening > isometric > shortening. The results indicate that the hypertrophy response did not track the torque integral with mass increases of isometric by 14%, shortening by 12%, and lengthening by 11%. All three modes of training resulted in similar increases in total muscle DNA and RNA. Isometric and shortening but not lengthening mode training resulted in increased muscle insulin-like growth factor I mRNA levels. These results indicate that relatively pure movement mode exercises result in similar levels of compensatory hypertrophy that do not necessarily track with the total amount of force generated during each contraction.
Longer static flexion duration elicits a neuromuscular disorder in the lumbar spine
Authors: LaBry Rebecca , Sbriccoli Paola , Zhou Bing-He , Solomonow Moshe
Published: April 2004

The objective of this study was to assess the impact of two sequential long, static, anterior lumbar flexions on the development of a neuromuscular disorder and to compare it with previously obtained data from a series of short static flexion periods of the same cumulative time (Sbriccoli P, Solomonow M, Zhou BH, Baratta RV, Lu Y, Zhu MP, and Burger EL, Muscle Nerve 29: 300-308, 2004). Static flexions with loads of 20, 40, and 60 N were applied to the lumbar spine over two 30-min periods with a 10-min rest in between. The reflex EMG activity from the multifidus muscles and supraspinous ligament displacement (creep) was recorded during the flexion periods. Creep and EMG were also monitored over 7 h of rest following the work-rest-work cycle. It was found that the creep that developed in the first 30-min flexion period did not recover completely during the following 10 min of rest, giving rise to a large cumulative creep at the end of the work-rest-work session. Spasms were frequently seen within the EMG during the static flexion. Initial and delayed hyperexcitabilities were observed in all of the preparations at any of the three loads explored during the 7-h rest period. ANOVA revealed a significant effect of time ( P < 0.0001) on the postloading data. Larger loads elicited larger magnitudes of the initial and delayed hyperexcitabilities, yet were not statistically different. It was concluded that the 3:1 work-to-rest duration ratio resulted in a neuromuscular disorder, regardless of the load magnitude. The conclusions are reinforced in view of the results from a previous study using 60 min of flexion overall but at 1:1 work-to-rest ratio in which only the highest load elicited a delayed hyperexcitability (Sbriccoli et al., Muscle Nerve 29: 300-308, 2004). An optimal dose-to-duration ratio needs to be established to limit, attenuate, or prevent the adverse effects of static load on the lumbar spine while considering the loading duration as a major risk factor.
Developmental changes in the expression of GABAAreceptor subunits α1, α2, and α3 in the rat pre-Bötzinger complex
Authors: Liu Qiuli , Wong-Riley Margaret T. T.
Published: April 2004

Previously, we reported that the pre-Bötzinger complex (PBC) exhibited a dramatic reduction in cytochrome oxidase activity at postnatal day (P) 12. This coincided in time with decreases in glutamate and NMDA receptor subunit 1 and increases in GABA, GABAB, glycine receptor, and glutamate receptor GluR2. To test our hypothesis that various α-subunits of GABAAreceptors also undergo changes in their expression during postnatal development, as they do in other brain regions, we undertook an in-depth immunohistochemical study of GABAAreceptor subunits α1, α2, and α3 in the PBC of P0 to P21 rats. We found that 1) GABAAα3-subunit was expressed at relatively high levels at P0, which then declined with age; 2) GABAAα1-subunit was expressed at relatively low levels at P0 but increased with age; 3) the developmental trends of subunits α1 and α3 intersected at P12; and 4) GABAAα2-subunit expression was moderate to light at P0 and remained quite constant during development, being lowest at P21. These findings suggest that the apparent switch in relative expressions of subunits α3 and α1 during development and the intersection of slopes around P12 may be associated with possible changes in GABAAreceptor subtypes that would mediate different functional properties of GABA transmission, such as primarily a less efficient inhibitory transmission before P12 and a more mature inhibitory effect at P12 and thereafter, as suggested by the kinetics of distinct postsynaptic potentials. This mechanism may contribute partially to the dramatic reduction in cytochrome oxidase activity within the PBC at P12, as shown previously.