bluuebunny/crossref_metadata_2025 huggingface dataset:
Pronounced effect of minor changes in body temperature on ischemia and reperfusion injury in rat liver
Authors: Heijnen Bob H. M. , van Veen Suzanne Q. , Straatsburg Irene H. , van Gulik Thomas M.
Published: December 2017

This study examined the effects of 1°C hypo- or hyperthermia on in vivo liver ischemia and reperfusion (I/R) injury in 15 fasted male Wistar rats. Rats were ventilated, and rectal temperature was maintained at 36, 37 (normothermic), or 38°C. In all rats, 70% liver ischemia was induced by clamping the afferent vessels to the median and left lateral lobes for 60 min, and reperfusion was allowed for 90 min. Changes in plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and α-glutathione S-transferase (α-GST) levels were measured, hemodynamics and bile secretion were monitored, and arterial blood-gas analysis was performed. All ventilated rats showed a normal pH, arterial Pco 2, and arterial Po 2. AST, ALT, and α-GST levels were significantly higher in the 38°C group when compared with the 36 and 37°C groups after ischemia. No differences in bile secretion were found between all groups. Histopathological alterations were in agreement with AST, ALT, and α-GST levels in plasma. We conclude that a decrease of only 1°C in body temperature significantly attenuates liver I/R injury, whereas an increase of 1°C significantly increases liver I/R injury.
Gravity effects on regional lung ventilation determined by functional EIT during parabolic flights
Authors: Frerichs Inéz , Dudykevych Taras , Hinz José , Bodenstein Marc , Hahn Günter , Hellige Gerhard
Published: December 2017

Gravity-dependent changes of regional lung function were studied during normogravity, hypergravity, and microgravity induced by parabolic flights. Seven healthy subjects were followed in the right lateral and supine postures during tidal breathing, forced vital capacity, and slow expiratory vital capacity maneuvers. Regional 1) lung ventilation, 2) lung volumes, and 3) lung emptying behavior were studied in a transverse thoracic plane by functional electrical impedance tomography (EIT). The results showed gravity-dependent changes of regional lung ventilation parameters. A significant effect of gravity on regional functional residual capacity with a rapid lung volume redistribution during the gravity transition phases was established. The most homogeneous functional residual capacity distribution was found at microgravity. During vital capacity and forced vital capacity in the right lateral posture, the decrease in lung volume on expiration was larger in the right lung region at all gravity phases. During tidal breathing, the differences in ventilation magnitudes between the right and left lung regions were not significant in either posture or gravity phase. A significant nonlinearity of lung emptying was determined at normogravity and hypergravity. The pattern of lung emptying was homogeneous during microgravity.
Dynamic ventilatory response to CO2in congestive heart failure patients with and without central sleep apnea
Authors: Topor Zbigniew L. , Johannson Linda , Kasprzyk Jerzy , Remmers John E.
Published: December 2017

Nonobstructive (i.e., central) sleep apnea is a major cause of sleep-disordered breathing in patients with stable congestive heart failure (CHF). Although central sleep apnea (CSA) is prevalent in this population, occurring in 40–50% of patients, its pathogenesis is poorly understood. Dynamic loop gain and delay of the chemoreflex response to CO2was measured during wakefulness in CHF patients with and without CSA by use of a pseudorandom binary CO2stimulus method. Use of a hyperoxic background minimized responses derived from peripheral chemoreceptors. The closed-loop and open-loop gain, estimated from the impulse response, was three times greater in patients with nocturnal CSA ( n = 9) than in non-CSA patients ( n = 9). Loop dynamics, estimated by the 95% response duration time, did not differ between the two groups of patients. We speculate that an increase in dynamic gain of the central chemoreflex response to CO2contributes to the genesis of CSA in patients with CHF.
Leukocyte counts and lymphocyte responsiveness associated with repeated bouts of strenuous endurance exercise
Authors: Ronsen Ola , Pedersen Bente Klarlund , Øritsland Tone Rasmussen , Bahr Roald , Kjeldsen-Kragh Jens
Published: December 2017

This study compared leukocyte counts and lymphocyte responsiveness during and after a second bout of high-intensity endurance exercise on the same day with the response to a similar but single bout of exercise. Nine athletes participated in three 24-h trials: 1) rest in bed (Rest); 2) one bout of exercise (One); and 3) two bouts of exercise (Two). All bouts consisted of 75 min at ∼75% of maximal O2uptake on a cycle ergometer. Lymphocytes in whole blood were stimulated with monoclonal antibodies against CD2 and assessed by flow cytometry for expression of the early activation molecule CD69. The second bout of exercise in the Two trial was associated with significantly increased concentrations of total leukocytes, neutrophils, lymphocytes, CD4+, CD8+, and CD56+cells and a significantly decreased percentage of CD56+cells expressing CD69 compared with a single bout. Additionally, there was a significantly decreased CD69 fluorescence in CD56+cells postexercise. These differences suggest a “carry-over” effect in the immune system from a first to a second bout of exercise on the same day.
Ambulatory estimates of maximal aerobic power from foot -ground contact times and heart rates in running humans
Authors: Weyand Peter G. , Kelly Maureen , Blackadar Thomas , Darley Jesse C. , Oliver Steven R. , Ohlenbusch Norbert E. , Joffe Sam W. , Hoyt Reed W.
Published: December 2017

Seeking to develop a simple ambulatory test of maximal aerobic power (V˙o2 max), we hypothesized that the ratio of inverse foot-ground contact time (1/ tc) to heart rate (HR) during steady-speed running would accurately predictV˙o2 max. Given the direct relationship between 1/ tcand mass-specific O2uptake during running, the ratio 1/ tc· HR should reflect mass-specific O2pulse and, in turn, aerobic power. We divided 36 volunteers into matched experimental and validation groups.V˙o2 maxwas determined by a treadmill test to volitional fatigue. Ambulatory monitors on the shoe and chest recorded foot-ground contact time ( tc) and steady-state HR, respectively, at a series of submaximal running speeds. In the experimental group, aerobic fitness index (1/ tc· HR) was nearly constant across running speed and correlated withV˙o2 max( r = 0.90). The regression equation derived from data from the experimental group predicted V˙o2 maxfrom the 1/ tc· HR values in the validation group within 8.3% and 4.7 ml O2· kg−1· min−1( r = 0.84) of measured values. We conclude that simultaneous measurements of foot-ground constant times and heart rates during level running at a freely chosen constant speed can provide accurate estimates of maximal aerobic power.
Comparison of a space shuttle flight (STS-78) and bed rest on human muscle function
Authors: Trappe Scott W. , Trappe Todd A. , Lee Gary A. , Widrick Jeffery J. , Costill David L. , Fitts Robert H.
Published: December 2017

The purpose of this investigation was to assess muscle fiber size, composition, and in vivo contractile characteristics of the calf muscle of four male crew members during a 17-day spaceflight (SF; Life and Microgravity Sciences Spacelab Shuttle Transport System-78 mission) and eight men during a 17-day bed rest (BR). The protocols and timelines of these two investigations were identical, therefore allowing for direct comparisons between SF and the BR. The subjects' age, height, and weight were 43 ± 2 yr, 183 ± 4 cm, and 86 ± 3 kg for SF and 43 ± 2 yr, 182 ± 3 cm, and 82 ± 4 kg for BR, respectively. Calf muscle strength was examined before SF and BR; on days 2, 8, and 12 during SF and BR; and on days 2 and 8 of recovery. Muscle biopsies were obtained before and within 3 h after SF (gastrocnemius and soleus) and BR (soleus) before reloading. Maximal isometric calf strength and the force-velocity characteristics were unchanged with SF or BR. Additionally, neither SF nor BR had any effect on fiber composition or fiber size of the calf muscles studied. In summary, no changes in calf muscle strength and morphology were observed after the 17-day SF and BR. Because muscle strength is lost during unloading, both during spaceflight and on the ground, these data suggest that the testing sequence employed during the SF and BR may have served as a resistance training countermeasure to attenuate whole muscle strength loss.
Myogenic satellite cells: physiology to molecular biology
Authors: Hawke Thomas J. , Garry Daniel J.
Published: December 2017

Adult skeletal muscle has a remarkable ability to regenerate following myotrauma. Because adult myofibers are terminally differentiated, the regeneration of skeletal muscle is largely dependent on a small population of resident cells termed satellite cells. Although this population of cells was identified 40 years ago, little is known regarding the molecular phenotype or regulation of the satellite cell. The use of cell culture techniques and transgenic animal models has improved our understanding of this unique cell population; however, the capacity and potential of these cells remain ill-defined. This review will highlight the origin and unique markers of the satellite cell population, the regulation by growth factors, and the response to physiological and pathological stimuli. We conclude by highlighting the potential therapeutic uses of satellite cells and identifying future research goals for the study of satellite cell biology.
Cardiac atrophy after bed rest and spaceflight
Authors: Perhonen Merja A. , Franco Fatima , Lane Lynda D. , Buckey Jay C. , Blomqvist C. Gunnar , Zerwekh Joseph E. , Peshock Ronald M. , Weatherall Paul T. , Levine Benjamin D.
Published: December 2017

Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 ( n = 5) and 12 ( n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 ± 2.2% ( P = 0.005) after 6 wk with an additional atrophy of 7.6 ± 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 ± 12.2 vs. 153.4 ± 12.1 g, P = 0.81). Mean wall thickness decreased (4 ± 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 ± 1.7% ( P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 ± 2.7% ( P = 0.06) and RV end-diastolic volume by 16 ± 7.9% ( P = 0.06). After spaceflight, LV mass decreased by 12 ± 6.9% ( P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity of cardiac muscle under different loading conditions.
An inexpensive meter to measure differences in electrical resistance in the rat vagina during the ovarian cycle
Authors: Ramos S. D. , Lee J. M. , Peuler J. D.
Published: December 2017

The inherent electrical resistance of the rat vaginal wall rises markedly near the beginning of estrus and then falls again to low levels for the remainder of the ovarian cycle. Accordingly, special instruments have been developed to measure such resistances (within seconds) on simply inserting a small probe fitted with a pair of recording electrodes into the vagina (i.e., the MK-10A impedance checker and the EC40 estrus cycle monitor). As described herein, these two instruments are far more convenient for monitoring individual cycles than more laborious methods in which vaginal smears are inspected for changes in numbers of cornified (C), nucleated (N), and leukocytic (L) cells. However, they are also expensive and their use has essentially remained uncited in the literature. Thus we sought to determine whether a simple, inexpensive electrical meter (with resistance-measuring capacity), as commonly used by professional electricians, would serve the same purpose. We chose a standard multifunctional meter (model 22-178, RadioShack) and attached leads to it fabricated from the internal wiring of a shielded audiocable (model 42-2387A, RadioShack), one male terminal of which was used as a vaginal probe. In rats from which vagina smears revealed cell numbers in the order of C > N > L (typical of early estrus) electrical resistances were high, 488 ± 130 kΩ (18 rats). In rats from which vagina smears revealed all other possible cell distributions, electrical resistances (combined) were much lower ( P < 0.05), 124 ± 23 kΩ (32 rats). Thus readily accessible, inexpensive electrical meters may be useful in assessing the status of estrus in female rats, either to improve reproductive efficiencies and/or for other purposes involving experiments in which such information is desirable.
Mechanical ventilation of isolated septic rat lungs: effects on surfactant and inflammatory cytokines
Authors: Nakamura Tomoo , Malloy Jaret , McCaig Lynda , Yao Li-Juan , Joseph Mariamma , Lewis Jim , Veldhuizen Ruud
Published: December 2017

The effects of mechanical ventilation (MV) on the surfactant system and cytokine secretion were studied in isolated septic rat lungs. At 23 h after sham surgery or induction of sepsis by cecal ligation and perforation (CLP), lungs were excised and randomized to one of three groups: 1) a nonventilated group, 2) a group subjected to 1 h of noninjurious MV (tidal volume = 10 ml/kg, positive end-expiratory pressure = 3 cmH2O), or 3) a group subjected to 1 h of injurious MV (tidal volume = 20 ml/kg, positive end-expiratory pressure = 0 cmH2O). Nonventilated sham and CLP lungs had similar compliance, normal lung morphology, surfactant, and cytokine concentrations. Injurious ventilation decreased compliance, altered surfactant, increased cytokines, and induced morphological changes compared with nonventilation in sham and CLP lungs. In these lungs, the surfactant system was similar in sham and CLP lungs; however, tumor necrosis factor-α and interleukin-6 levels were significantly higher in CLP lungs. We conclude that injurious ventilation altered surfactant independent of sepsis and that the CLP lungs were predisposed to the secretion of larger amounts of cytokines because of ventilation.
Mechanical output impedance of the lung determined from cardiogenic oscillations
Authors: Bijaoui Eve , Baconnier Pierre F. , Bates Jason H. T.
Published: December 2017

The beating heart naturally oscillates the lung because of the close juxtaposition between these organs producing cardiogenic oscillations in flow that can be measured at the mouth when the glottis is open. Correspondingly, if the mouth is occluded, the same phenomenon produces cardiogenic pressure oscillations that can be measured just distal to the site of occlusion. The Fourier-domain ratio of these oscillations in pressure and flow constitutes what we call cardiogenic respiratory impedance (Zc). We calculated Zc between about 1.5 and 10 Hz in relaxed normal subjects at functional residual capacity with open glottis. Zc was insensitive to heart rate changes induced by exercise and had an imaginary part close to zero at all frequencies investigated. Its real part was similar to or smaller than resistance determined by the forced oscillation technique. We speculate that Zc measures the flow resistance of the central and upper airways of the lung. Zc may be useful as a means of obtaining information about lung mechanics without the need for an external source of flow perturbations.
Regulation of vocal fold transepithelial water fluxes
Authors: Fisher Kimberly V. , Telser Alvin , Phillips Jonathan E. , Yeates Donovan B.
Published: December 2017

Vocal fold hydration is critical to phonation. We hypothesized that the vocal fold generates bidirectional water fluxes, which are regulated by activity of the Na+-K+- ATPase. Western blots and immunohistochemistry demonstrated the presence of the α-subunit Na+-K+-ATPase in the canine vocal fold ( n = 11). Luminal cells, basal and adjacent one to two layers of suprabasal cells within stratified squamous epithelium, were immunopositive, as well as basolateral membranes of submucosal seromucous glands underlying transitional epithelia. Canine ( n = 6) and ovine ( n = 14) vocal fold mucosae exhibited transepithelial potential differences of 8.1 ± 2.8 and 9.3 ± 1.3 mV (lumen negative), respectively. The potential difference and short-circuit current (ovine = 31 ± 4 μA/cm2; canine = 41 ± 10 μA/cm2) were substantially reduced by luminal administration of 75 μM acetylstrophanthidin ( P < 0.05). Ovine ( n = 7) transepithelial water fluxes decreased from 5.1 ± 0.3 to 4.3 ± 0.3 μl · min−1· cm−2from the basal to luminal chamber and from 5.2 ± 0.2 to 3.9 ± 0.3 μl · min−1· cm−2from the luminal to basal chamber by luminal acetylstrophanthidin ( P < 0.05). The presence of the Na+-K+-ATPase in the vocal fold epithelium and the electrolyte transport derived from its activity provide the intrinsic mechanisms to regulate cell volume as well as vocal fold hydration.
Pco 2 threshold for CNS oxygen toxicity in rats in the low range of hyperbaric Po 2
Authors: Arieli R. , Rashkovan G. , Moskovitz Y. , Ertracht O.
Published: December 2017

Central nervous system (CNS) oxygen toxicity, as manifested by the first electrical discharge (FED) in the electroencephalogram, can occur as convulsions and loss of consciousness. CO2potentiates this risk by vasodilation and pH reduction. We suggest that CO2 can produce CNS oxygen toxicity at a Po 2 that does not on its own ultimately cause FED. We searched for the CO2 threshold that will result in the appearance of FED at a Po 2 between 507 and 253 kPa. Rats were exposed to a Po 2 and an inspired Pco 2 in 1-kPa steps to define the threshold for FED. The results confirmed our assumption that each rat has its own Pco 2 threshold, any Pco 2 above which will cause FED but below which no FED will occur. As Po 2 decreased from 507 to 456, 405, and 355 kPa, the percentage of rats that exhibited FED without the addition of CO2 (F0) dropped from 91 to 62, to 8 and 0%, respectively. The percentage of rats (F) having FED as a function of Pco 2 was sigmoid in shape and displaced toward high Pco 2 with the reduction in Po 2. The following formula is suggested to express risk as a function of Pco 2and Po 2 [Formula: see text] [Formula: see text] [Formula: see text]where P50 is the Pco 2 for the half response and N is power. A small increase in Pco 2 at a Po 2 that does not cause CNS oxygen toxicity may shift an entire population into the risk zone. Closed-circuit divers who are CO2 retainers or divers who have elevated inspired CO2 are at increased risk of CNS oxygen toxicity.
Influence of motoneuron firing synchronization on SEMG characteristics in dependence of electrode position
Authors: Kleine Bert U. , Stegeman Dick F. , Mund Daniela , Anders Christoph
Published: December 2017

The frequency content of the surface electromyography (SEMG) signal, expressed as median frequency (MF), is often assumed to reflect the decline of muscle fiber conduction velocity in fatigue. MF also decreases when motor unit firings synchronize, and we hypothesized that this effect can explain the electrode-dependent pattern in our previous recordings from the trapezius muscle. An existing motoneuron (MN) model describes the afterhyperpolarization following a spike as an exponential function on which membrane noise is superimposed. Splitting the noise into a common and an individual component extended the model to a MN pool with a tunable level of firing synchrony. An analytical volume conduction model was used to generate motor unit action potentials to simulate SEMG. A realistic level of synchrony decreased the MF of the simulated bipolar SEMG by ∼30% midway between endplate position and tendon but not above the endplate. This is in accordance with experimental data from the biceps brachii muscle. It was concluded that the pattern of decrease of MF during sustained contractions indeed reflects MN synchronization.
Swim-trained rats have greater bone mass, density, strength, and dynamics
Authors: Hart K. J. , Shaw J. M. , Vajda E. , Hegsted M. , Miller S. C.
Published: December 2017

Weight-bearing exercise is traditionally recommended for improving bone health in postmenopausal women. Effects of swim exercise were studied as an alternative to weight-bearing exercise in ovariectomized rats. Rats in a swim group (Sw, n = 8) swam for 12 wk, 5 days/wk for 60 min per session. A control group (Con, n = 9) engaged in no structured exercise. Femurs were analyzed for bone mineral density and for bone mineral content by dual energy X-ray absorptiometry, biomechanical properties by three-point bending (Instron), and bone structure and formation by histomorphometry. Food intake did not differ among groups. Final body weights were significantly lower in Sw compared with Con ( P< 0.05). Swimmers had significantly greater femoral shaft bone mineral density and content ( P < 0.05) compared with Con. Femurs of the Sw group had greater mechanical properties ( P< 0.05) compared with Con. Histomorphometric data were significantly better in the Sw group compared with Con after the 12-wk intervention ( P < 0.05). In conclusion, data from this study demonstrate some beneficial effects of swim exercise on bone structure, turnover, and strength.
Cellular adaptation to repeated eccentric exercise-induced muscle damage
Authors: Stupka N. , Tarnopolsky M. A. , Yardley N. J. , Phillips S. M.
Published: December 2017

Eccentrically biased exercise results in skeletal muscle damage and stimulates adaptations in muscle, whereby indexes of damage are attenuated when the exercise is repeated. We hypothesized that changes in ultrastructural damage, inflammatory cell infiltration, and markers of proteolysis in skeletal muscle would come about as a result of repeated eccentric exercise and that gender may affect this adaptive response. Untrained male ( n = 8) and female ( n = 8) subjects performed two bouts ( bout 1and bout 2), separated by 5.5 wk, of 36 repetitions of unilateral, eccentric leg press and 100 repetitions of unilateral, eccentric knee extension exercises (at 120% of their concentric single repetition maximum), the subjects' contralateral nonexercised leg served as a control (rest). Biopsies were taken from the vastus lateralis from each leg 24 h postexercise. After bout 2, the postexercise force deficit and the rise in serum creatine kinase (CK) activity were attenuated. Women had lower serum CK activity compared with men at all times ( P < 0.05), but there were no gender differences in the relative magnitude of the force deficit. Muscle Z-disk streaming, quantified by using light microscopy, was elevated vs. rest only after bout 1 ( P< 0.05), with no gender difference. Muscle neutrophil counts were significantly greater in women 24 h after bout 2 vs. rest and bout 1 ( P < 0.05) but were unchanged in men. Muscle macrophages were elevated in men and women after bout 1 and bout 2 ( P < 0.05). Muscle protein content of the regulatory calpain subunit remained unchanged whereas ubiquitin-conjugated protein content was increased after both bouts ( P < 0.05), with a greater increase after bout 2. We conclude that adaptations to eccentric exercise are associated with attenuated serum CK activity and, potentially, an increase in the activity of the ubiquitin proteosome proteolytic pathway.
Ozone causes lipid peroxidation but little antioxidant depletion in exercising and nonexercising hamsters
Authors: Long Nancy C. , Suh Jung , Morrow Jason D. , Schiestl Robert H. , Murthy G. G. Krishna , Brain Joseph D. , Frei Balz
Published: December 2017

Ozone (O3), a major component of urban air pollution, is a strong oxidizing agent that can cause lung injury and inflammation. In the present study, we investigated the effect of inhalation of O3on levels of F2-isoprostanes in bronchoalveolar lavage fluid (BALF) and on levels of antioxidants in the BALF and plasma of hamsters. Because antioxidants, including urate, ascorbate, GSH, and vitamin E, defend the lungs by reacting with oxidizing agents, we expected to find a decrease in antioxidant levels after O3exposure. Similarly, we expected an increase in the levels of F2-isoprostanes, which are lipid peroxidation products. Exposure to 1.0 or 3.0 parts/million (ppm) O3for 6 h resulted in an increase in BALF neutrophil numbers, an indicator of acute inflammation, as well as elevation of BALF F2-isoprostanes. The higher dose of O3caused an increase in the BALF level of urate and a decrease in the plasma level of ascorbate, but 1.0 ppm O3had no effect on BALF or plasma antioxidant levels. Exposure to 0.12 ppm O3had no effect on BALF neutrophils or F2-isoprostanes nor on BALF and plasma antioxidants. We also investigated the effect of O3exposure of hamsters during exercise on F2-isoprostane and antioxidant levels. We found that exposure to 1.0 ppm O3during 1 h of exercise on a laddermill increased BALF levels of F2-isoprostanes but had no effect on BALF neutrophils or on BALF and plasma antioxidants. These results indicate that O3induces inflammation and biomolecule oxidation in the lungs, whereas extracellular antioxidant levels are relatively unchanged.
Transport properties of alveolar epithelium measured by molecular hetastarch absorption in isolated rat lungs
Authors: Conhaim Robert L. , Watson Kal E. , Lai-Fook Stephen J. , Harms Bruce A.
Published: December 2017

To evaluate the transport properties of the alveolar epithelium, we instilled hetastarch (Het; 6%, 10 ml, 1 − 1 × 104kDa) into the trachea of isolated rat lungs and then measured the molecular distribution of Het that entered the lung perfusate from the air space over 6 h. Het transport was driven by either diffusion or an oncotic gradient. Perfusate Het had a unique, bimodal molecular weight distribution, consisting of a narrow low-molecular-weight peak at 10–15 kDa (range, 5–46 kDa) and a broad high-molecular-weight band (range 46–2,000 kDa; highest at 288 kDa). We modeled the low-molecular-weight transport as (passive) restricted diffusion or osmotic flow through a small-pore system and the high-molecular-weight transport as passive transport through a large-pore system. The equivalent small-pore radius was 5.0 nm, with a distribution of 150 pores per alveolus. The equivalent large-pore radius was 17.0 nm, with a distribution of one pore per seven alveoli. The small-pore fluid conductivity (2 × 10−5ml · h−1· cm−2· mmHg−1) was 10-fold larger than that of the large-pore conductivity.
Influence of ribose on adenine salvage after intense muscle contractions
Authors: Zarzeczny Ryszard , Brault Jeffrey J. , Abraham Kirk A. , Hancock Chad R. , Terjung Ronald L.
Published: December 2017

The influence of ribose supplementation on skeletal muscle adenine salvage rates during recovery from intense contractions and subsequent muscle performance was evaluated using an adult rat perfused hindquarter preparation. Three minutes of tetanic contractions (60 tetani/min) decreased ATP content in the calf muscles by ∼50% and produced an equimolar increase in IMP. Effective recovery of muscle ATP 1 h after contractions was due to reamination of IMP via the purine nucleotide cycle and was complete in the red gastrocnemius but incomplete in the white gastrocnemius muscle section. Adenine salvage rates in recovering muscle averaged 45 ± 4, 49 ± 5, and 30 ± 3 nmol · h−1· g−1for plantaris, red gastrocnemius, and white gastrocnemius muscle, respectively, which were not different from values in corresponding nonstimulated muscle sections. Adenine salvage rates increased five- to sevenfold by perfusion with ∼4 mM ribose (212 ± 17, 192 ± 9, and 215 ± 14 nmol · h−1· g−1in resting muscle sections, respectively). These high rates were sustained in recovering muscle, except for a small (∼20%) but significant ( P < 0.001) decrease in the white gastrocnemius muscle. Ribose supplementation did not affect subsequent muscle force production after 60 min of recovery. These data indicate that adenine salvage rates were essentially unaltered during recovery from intense contractions.
Exchange dynamics of nitric oxide in the human nose
Authors: Chambers Daniel C. , Carpenter Dominic A. , Ayres Jon G.
Published: December 2017

Nasal nitric oxide (NO) exchange dynamics are poorly understood but potentially are of importance, inasmuch as they may provide insight into the NO-related physiology of the bronchial tree. In healthy human volunteers, NO output was assessed by isolating the nasal cavity through elevation of the soft palate and application of tight-fitting nasal olives. Mean NO output was 334 nl/min and was a positive function of gas flow. With the use of a mathematical model and the introduction of nonzero concentrations of NO, the diffusing capacity for NO in the nose (DNO) and the mucosal NO concentration (Cw) were determined. DNO ranged from 0.52 to 2.98 × 10−3nl · s−1 · ppb−1 and Cw from 1,236 to 8,947 ppb. Cw declined with increasing gas flow, while DNO was constant. NO output declined with luminal hypoxia, particularly at oxygen tensions <10%. Measurement of nasal DNO and Cw is easy using this method, and the range of intersubject values of Cwraises the possibility of interindividual differences in NO-dependent nasal physiology.
Exposure to perflubron is associated with decreased Syk phosphorylation in human neutrophils
Authors: Fernandez Rosemarie , Sarma Vidya , Younkin Ellen , Hirschl Ronald B. , Ward Peter A. , Younger John G.
Published: December 2017

Liquid ventilation with perflubron is associated with reduced neutrophil recruitment into the lung during acute injury. Perflubron also reduces chemotactic responses, the respiratory burst, and cytokine production in neutrophils and in alveolar macrophages in vitro. In the current studies, the effect of perflubron on neutrophil chemotaxis to formyl-Met-Leu-Phe (fMLP) and phagocytosis of opsonized sheep erythrocytes (EA) correlated with decreased phosphorylation of Syk, an important intracellular second messenger in pathways regulating neutrophil functional responses. Brief (5 min) exposure of neutrophils to perflubron resulted in a dose-dependent reduction in chemotaxis to fMLP and reduced phagocytosis of EA but no apparent morphological changes as seen by electron microscopy. Concurrently, there was a reduction in both total cytosolic tyrosine phosphorylation and Syk phosphorylation. Binding studies indicated that this effect was neither a result of impaired ligand-receptor affinity nor a change in the number of fMLP receptors available on the neutrophil surface. These results suggest that perflubron nonspecifically affects cellular activation as measured by tyrosine phosphorylation perhaps by interfering with transmembrane signal transduction.
Muscle fiber and tendon length changes in the human vastus lateralis during slow pedaling
Authors: Muraoka T. , Kawakami Y. , Tachi M. , Fukunaga T.
Published: December 2017

Muscle fascicle lengths of vastus lateralis (VL) muscle were measured in five healthy men during slow pedaling to investigate the interaction between muscle fibers and tendon. Subjects cycled at a pedaling rate of 40 rpm (98 W). During exercise, fascicle lengths changed from 91 ± 7 (SE) to 127 ± 5 mm. It was suggested that fascicles were on the descending limb of their force-length relationship. The average shortening velocity of fascicle was greater than that of muscle-tendon complex in the first half of the knee extension phase and was less in the second half. The maximum shortening velocity of fascicle in the knee extension phase was less than that of muscle-tendon complex by 22 ± 9%. These discrepancies in velocities were mainly caused by the elongation of the tendinous tissue. It was suggested that the elasticity of VL tendinous tissue enabled VL fascicles to develop force at closer length to their optimal length and kept the maximum shortening velocity of VL fascicles low during slow pedaling.
Skeletal muscle glycogen phosphorylaseakinetics: effects of adenine nucleotides and caffeine
Authors: Rush James W. E. , Spriet Lawrence L.
Published: December 2017

This study aimed to determine physiologically relevant kinetic and allosteric effects of Pi, AMP, ADP, and caffeine on isolated skeletal muscle glycogen phosphorylase a (Phos a). In the absence of effectors, Phos a had Vmax= 221 ± 2 U/mg and Km= 5.6 ± 0.3 mM Piat 30°C. AMP and ADP each increased Phos a Vmaxand decreased Kmin a dose-dependent manner. AMP was more effective than ADP (e.g., 1 μM AMP vs. ADP: Vmax= 354 ± 2 vs. 209 ± 8 U/mg, and Km= 2.3 ± 0.1 vs. 4.1 ± 0.3 mM). Both nucleotides were relatively more effective at lower Pilevels. Experiments simulating a range of contraction (exercise) conditions in which Pi, AMP, and ADP were used at appropriate physiological concentrations demonstrated that each agent singly and in combination influences Phos a activity. Caffeine (50–100 μM) inhibited Phos a( Km∼8–14 mM, ∼40–50% reduction in activity at 2–10 mM Pi). The present in vitro data support a possible contribution of substrate (Pi) and allosteric effects to Phos a regulation in many physiological states, independent of covalent modulation of the percentage of total Phos in the Phos a form and suggest that caffeine inhibition of Phos a activity may contribute to the glycogen-sparing effect of caffeine.
Bcl-2 mediates sex-specific differences in recovery of mice from LPS-induced signs of sickness independent of IL-6
Authors: Tesfaigzi Yohannes , Rudolph Karin , Fischer Mark J. , Conn Carole A.
Published: December 2017

Chronic pulmonary diseases are more common in boys than in girls. Therefore, we investigated the differences in signs of sickness in male and female mice that were exposed to lipopolysaccharide (LPS) by intranasal instillation. Because apoptosis is important in the resolution of inflammation, we tested the hypothesis that reduced levels of Bcl-2, a regulator of apoptosis, may play a role in gender-specific differences in response to inflammation. Bcl-2 wild-type (+/+) female mice recovered from an LPS-induced drop in body temperature and loss in body weight significantly faster than male (+/+) mice. Female heterozygous (+/−) mice showed reduced Bcl-2 levels and exhibited a slower recovery than female (+/+) mice that was similar to the recovery pattern in male (+/+) and (+/−) mice. Interleukin-6 (IL-6) activity levels in the bronchoalveolar lavage fluid were higher in male than in female mice but were not different between (+/+) and (+/−) mice. We conclude that Bcl-2 plays a role in mediating the faster recovery of female (+/+) mice from LPS-induced signs of sickness independent of IL-6. These studies indicate that apoptotic mechanisms may be involved in gender-specific differences in chronic pulmonary diseases.
Development of a novel, nonimmunogenic, soluble human TNF receptor type I (sTNFR-I) construct in the baboon
Authors: Rosenberg Jason J. , Martin Steven W. , Seely James E. , Kinstler Olaf , Gaines Gregory C. , Fukuzuka Kunitaro , Rose Jeff , Kohno Tadahiko , Boyle William J. , Nelson Angela , Kieft Gary L. , Marshall William S. , Feige Ulrich , Gasser Jill , St. Clair Judy , Frazier Janet , Abouhamze Amer , Moldawer Lyle L. , Edwards Carl K.
Published: December 2017

Pharmacokinetics and immunogenicity of six different recombinant human soluble p55 tumor necrosis factor (TNF) receptor I (sTNFR-I) constructs were evaluated in juvenile baboons. The constructs included either an sTNFR-I IgG1 immunoadhesin (p55 sTNFR-I Fc) or five different sTNFR-I constructs covalently linked to polyethylene glycol. The constructs were administered intravenously three times, and pharmacokinetics and immunogenicity were examined over 63 days. All of the constructs were immunogenic, with the exception of a 2.6-domain monomeric sTNFR-I. To evaluate whether the nonimmunogenic 2.6-domain monomeric construct could protect baboons against TNF-α-induced mortality, baboons were pretreated with 1, 5, or 10 mg/kg body wt and were compared with baboons receiving either placebo or 1 mg/kg body wt of the dimeric 4.0-domain sTNFR-I construct ( n = 3 each) before lethal Escherichia colibacteremia. The monomeric construct protected baboons and neutralized TNF bioactivity, although greater quantities were required compared with the dimeric 4.0-domain sTNFR-I construct. We conclude that E. coli-recombinant-derived human sTNFR-I constructs can be generated with minimal immunogenicity on repeated administration and still protect against the consequences of exaggerated TNF-α production.
A theoretical model for oxygen transport in skeletal muscle under conditions of high oxygen demand
Authors: McGuire B. J. , Secomb T. W.
Published: December 2017

Oxygen transport from capillaries to exercising skeletal muscle is studied by use of a Krogh-type cylinder model. The goal is to predict oxygen consumption under conditions of high demand, on the basis of a consideration of transport processes occurring at the microvascular level. Effects of the decline in oxygen content of blood flowing along capillaries, intravascular resistance to oxygen diffusion, and myoglobin-facilitated diffusion are included. Parameter values are based on human skeletal muscle. The dependence of oxygen consumption on oxygen demand, perfusion, and capillary density are examined. When demand is moderate, the tissue is well oxygenated and consumption is slightly less than demand. When demand is high, capillary oxygen content declines rapidly with axial distance and radial oxygen transport is limited by diffusion resistance within the capillary and the tissue. Under these conditions, much of the tissue is hypoxic, consumption is substantially less than demand, and consumption is strongly dependent on capillary density. Predicted consumption rates are comparable with experimentally observed maximal rates of oxygen consumption.
No effects of oral ribose supplementation on repeated maximal exercise and de novo ATP resynthesis
Authors: Op 't Eijnde B. , Van Leemputte M. , Brouns F. , Van Der Vusse G. J. , Labarque V. , Ramaekers M. , Van Schuylenberg R. , Verbessem P. , Wijnen H. , Hespel P.
Published: December 2017

A double-blind randomized study was performed to evaluate the effect of oral ribose supplementation on repeated maximal exercise and ATP recovery after intermittent maximal muscle contractions. Muscle power output was measured during dynamic knee extensions with the right leg on an isokinetic dynamometer before (pretest) and after (posttest) a 6-day training period in conjunction with ribose (R, 4 doses/day at 4 g/dose, n = 10) or placebo (P, n = 9) intake. The exercise protocol consisted of two bouts ( A and B) of maximal contractions, separated by 15 s of rest. Bouts A and B consisted of 15 series of 12 contractions each, separated by a 60-min rest period. During the training period, the subjects performed the same exercise protocol twice per day, with 3–5 h of rest between exercise sessions. Blood samples were collected before and after bouts A and B and 24 h after bout B. Knee-extension power outputs were ∼10% higher in the posttest than in the pretest but were similar between P and R for all contraction series. The exercise increased blood lactate and plasma ammonia concentrations ( P < 0.05), with no significant differences between P and R at any time. After a 6-wk washout period, in a subgroup of subjects ( n = 8), needle-biopsy samples were taken from the vastus lateralis before, immediately after, and 24 h after an exercise bout similar to the pretest. ATP and total adenine nucleotide content were decreased by ∼25 and 20% immediately after and 24 h after exercise in P and R. Oral ribose supplementation with 4-g doses four times a day does not beneficially impact on postexercise muscle ATP recovery and maximal intermittent exercise performance.
Invited Review: Sex ratio and rheumatic disease
Authors: Lockshin Michael D.
Published: December 2017

Human illnesses affect men and women differently. In some cases (diseases of sex organs, diseases resulting from X or Y chromosome mutations), reasons for sex discrepancy are obvious, but in other cases no reason is apparent. Explanations for sex discrepancy of illness occur at different biological levels: molecular (e.g., imprinting, X-inactivation), cellular (sex-specific receptor activity), organ (endocrine influences), whole organism (size, age), and environmental-behavioral, including intrauterine influences. Autoimmunity represents a prototypical class of illness that has high female-to-male (F/M) ratios. Although the F/M ratios in autoimmune diseases are usually attributed to the influence of estrogenic hormones, evidence demonstrates that the attributed ratios are imprecise and that definitions and classifications of autoimmune diseases vary, rendering at least part of the counting imprecise. In addition, many studies on sex discrepancy of human disease fail to distinguish between disease incidence and disease severity. In April 2001, the Institute of Medicine of the National Academy of Sciences published Exploring the Biological Contributions to Human Health: Does Sex Matter? (Wizemann T and Pardue M-L, editors). This minireview summarizes the section of that report that concerns autoimmune and infectious disease. Some thyroid, rheumatic, and hepatic autoimmune diseases have high F/M ratios, whereas others have low. Those that have high ratios occur primarily in young adulthood. Gonadal hormones, if they play a role, likely do so through a threshold or permissive mechanism. Examples of sex differences that could be caused by environmental exposure, X inactivation, imprinting, X or Y chromosome genetic modulators, and intrauterine influences are presented as alternate, theoretical, and largely unexplored explanations for sex differences of incidence. The epidemiology of autoimmune diseases (young, female) suggests that an explanation for sex discrepancy of these illnesses lies in differential exposure, vulnerable periods, or thresholds. Biologists have an opportunity to inform medical scientists about sex differences that explain different attack rates in specific diseases, and physicians offer biologists experiments of nature to test theories of sex.
From Belfast to Mayo and beyond: the use and future of plethysmography to study blood flow in human limbs
Authors: Joyner Michael J. , Dietz Niki M. , Shepherd John T.
Published: December 2017

Venous occlusion plethysmography is a simple but elegant technique that has contributed to almost every major area of vascular biology in humans. The general principles of plethysmography were appreciated by the late 1800s, and the application of these principles to measure limb blood flow occurred in the early 1900s. Plethysmography has been instrumental in studying the role of the autonomic nervous system in regulating limb blood flow in humans and important in studying the vasodilator responses to exercise, reactive hyperemia, body heating, and mental stress. It has also been the technique of choice to study how human blood vessels respond to a variety of exogenously administered vasodilators and vasoconstrictors, especially those that act on various autonomic and adrenergic receptors. In recent years, plethysmography has been exploited to study the role of the vascular endothelium in health and disease. Venous occlusion plethysmography is likely to continue to play an important role as investigators seek to understand the physiological significance of newly identified vasoactive factors and how genetic polymorphisms affect the cardiovascular system in humans.
Extravascular lung water in the exercising horse
Authors: Wilkins P. A. , Gleed R. D. , Krivitski N. M. , Dobson A.
Published: December 2017

Seven standardbred horses were exercised on a treadmill at speeds (∼12 m/s) producing maximal heart rate, hypoxemia, and a mean pulmonary arterial pressure of ∼75 mmHg. Extravascular lung water was measured by using transients in temperature and electrical impedance of the blood caused by a bolus injection of cold saline solution. Lung water was ∼3 ml/kg body wt when standing but did not increase significantly with exertion. We conclude that any increase in fluid extravasation from the pulmonary hypertension accumulates in the lung at a level that is less than that detectable by this method. At maximal exertion, the volume of blood measured between the jugular vein and the carotid artery increased by ∼8 ml/kg, and the actively circulating component of the systemic blood volume increased by ∼17 ml/kg with respect to corresponding values obtained when walking before exertion. These volume increases, reflecting recruitment and dilatation of capillaries, increase the area for respiratory gas exchange and offset the reduced transit times that would otherwise be imposed by the approximately eightfold increase in cardiac output at maximal exertion.
Gender influences coronary L-type Ca2+current and adaptation to exercise training in miniature swine
Authors: Bowles D. K.
Published: December 2017

Endurance exercise training increases smooth muscle L-type Ca2+current density in both resistance and proximal coronary arteries of female miniature swine. The purpose of the present study was to determine 1) whether gender differences exist in coronary smooth muscle (CSM) L-type Ca2+current density and 2) whether endurance training in males would demonstrate a similar adaptive response as females. Proximal, conduit (∼1.0 mm), and resistance [∼200 μm (internal diameter)] coronary arteries were obtained from sedentary and treadmill-trained swine of both sexes. CSM were isolated by enzymatic digestion (collagenase plus elastase), and voltage-gated Ca2+-channel current ( ICa) was determined by using whole cell voltage clamp during superfusion with 75 mM tetraethylammonium chloride and 10 mM BaCl2. Current-voltage relationships were obtained at test potentials from −60 to 70 mV from a holding potential of −80 mV, and ICawas normalized to cell capacitance (pA/pF). Endurance treadmill training resulted in similar increases in heart weight-to-body weight ratio, endurance time, and skeletal muscle citrate synthase activity in male and female swine. ICadensity was significantly greater in males compared with females in both conduit (−7.57 ± 0.58 vs. −4.14 ± 0.47 pA/pF) and resistance arteries (−11.25 ± 0.74 vs. −6.49 ± 0.87 pA/pF, respectively). In addition, voltage-dependent activation of ICain resistance arteries was shifted to more negative membrane potentials in males. Exercise training significantly increased ICadensity in both conduit and resistance arteries in females (−7.01 ± 0.47 and −9.73 ± 1.13 pA/pF, respectively) but had no effect in males (−8.61 ± 0.50 and −12.04 ± 1.07 pA/pF, respectively). Thus gender plays a significant role in determining both the magnitude and voltage dependence of ICain CSM and the adaptive response of ICato endurance training.