bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of hindlimb suspension on the functional properties of slow and fast soleus fibers from three strains of mice
Authors: Stelzer Julian E. , Widrick Jeffrey J.
Published: March 2015

Cross-sectional area (CSA), peak Ca2+-activated force (Po), fiber specific force (Po/CSA), and unloaded shortening velocity ( Vo) were measured in slow-twitch [containing type I myosin heavy chain (MHC)] and fast-twitch (containing type II MHC) chemically skinned soleus muscle fiber segments obtained from three strains of weight-bearing and 7-day hindlimb-suspended (HS) mice. HS reduced soleus slow MHC content (from ∼50 to ∼33%) in CBA/J and ICR strains without affecting slow MHC content in C57BL/6 mice (∼20% of total MHC). Two-way ANOVA revealed HS-induced reductions in CSA, Po, and Po/CSA of slow and fast fibers from all strains. Fiber Vo was elevated post-HS, but not consistently across strains. No MHC × HS treatment interactions were observed for any variable for C57BL/6 and CBA/J mice, and the two significant interactions found for the ICR strain (CSA, Po) appeared related to inherent pre-HS differences in slow vs. fast fiber CSA. In the mouse HS models studied here, fiber atrophy and contractile dysfunction were partially dependent on animal strain and generally independent of fiber MHC isoform content.
Invited Review: Interplay between molecular chaperones and signaling pathways in survival of heat shock
Authors: Gabai Vladimir L. , Sherman Michael Y.
Published: March 2015

Heat shock of mammalian cells causes protein damage and activates a number of signaling pathways. Some of these pathways enhance the ability of cells to survive heat shock, e.g., induction of molecular chaperones [heat shock protein (HSP) HSP72 and HSP27], activation of the protein kinases extracellular signal-regulated kinase and Akt, and phosphorylation of HSP27. On the other hand, heat shock can activate a stress kinase, c-Jun NH2-terminal kinase, thus triggering both apoptotic and nonapoptotic cell death programs. Recent data indicate that kinases activated by heat shock can regulate synthesis and functioning of the molecular chaperones, and these chaperones modulate activity of the cell death and survival pathways. Therefore, the overall balance of the pathways and their interplay determine whether a cell exposed to heat shock will die or survive and become stress tolerant.
Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia
Authors: Bua Entela A. , McKiernan Susan H. , Wanagat Jonathan , McKenzie Debbie , Aiken Judd M.
Published: March 2015

The hypothesis that the accumulation of electron transport system (ETS) abnormalities and sarcopenia are linked was investigated. Vastus lateralis, soleus, and adductor longus muscles were studied in 5-, 18-, and 36-mo-old male Fischer 344 × Brown Norway F1 hybrid rats. A significant decrease in soleus and vastus lateralis muscle mass was observed with age. Adductor longus was resistant to muscle mass loss. Multiple serial sections were analyzed for the activities of cytochrome- c oxidase (COX) and succinate dehydrogenase (SDH). The number of fibers exhibiting a COX−/SDH++ phenotype increased with age in both vastus lateralis and soleus muscles. No ETS-abnormal fibers were identified in adductor longus at any age. Cross-sectional area of ETS-abnormal fibers decreased in the abnormal region (region displaying COX−/SDH++ phenotype), whereas control fibers did not. The vastus lateralis muscle, which undergoes a high degree of sarcopenia, exhibited more ETS abnormalities and associated fiber loss than the soleus and adductor longus muscles, which are more resistant to sarcopenia, suggesting a direct association between ETS abnormalities and fiber loss.
Fetal and adult cerebral artery KATPand KCachannel responses to long-term hypoxia
Authors: Long Wen , Zhang Lubo , Longo Lawrence D.
Published: March 2015

High-altitude long-term hypoxia (LTH) alters cerebral vascular contractile and relaxation responses in both fetus and adult. We tested the hypotheses that LTH-mediated vascular responses were secondary to altered K+channel function and that in the fetus these responses differ from those of the adult. In middle cerebral arteries (MCA) from both nonpregnant adult and fetal (∼140 days gestation) sheep, which were either acclimatized to high altitude (3,820 m) or sea-level controls, we measured norepinephrine (NE)-induced contractions and intracellular Ca2+concentration ([Ca2+]i) simultaneously, in the presence or absence of different K+channel openers or blockers. In adult MCA, LTH was associated with ∼20% decrease in NE-induced tension and [Ca2+]i, with a significant increase in Ca2+sensitivity. In contrast, in fetal MCA, LTH failed to affect significantly NE-induced contraction or [Ca2+]ibut significantly decreased the ATP-sensitive K+(KATP) channel and Ca2+-activated K+(KCa) channel-mediated relaxation. The significant effect of KATPand KCachannel activators on the relaxation responses and the fact that K+channels play a key role in myogenic tone support the hypotheses that K+channels play an important role in hypoxia-mediated responses. These results also support the hypothesis of significant developmental differences with maturation from fetus to adult.
Atrophy responses to muscle inactivity. II. Molecular markers of protein deficits
Authors: Haddad F. , Roy R. R. , Zhong H. , Edgerton V. R. , Baldwin K. M.
Published: March 2015

We examined the expression of several molecular markers of protein balance in response to skeletal muscle atrophy induced by spinal cord isolation (SI; i.e., a complete transection of the spinal cord at both a midthoracic and a high sacral level plus complete deafferentation between the two transection sites). This treatment nearly eliminates neuromuscular activity (activation and loading) of the hindlimb muscles while maintaining neuromuscular connectivity. SI was associated with a reduced transcriptional activity (via pre-mRNA analyses) of myosin heavy chain (MHC) and actin. In addition, there was an increased gene expression of enzyme systems impacting protein degradation (calpain-1; plus enzymes associated with polyubquitination processes) that could further contribute to the protein deficits in the SI muscles via degradative pathways. IGF-I receptor and binding protein-5 mRNA expression was induced throughout the 15-day period of SI, whereas IGF-I mRNA was induced at 8 and 15 days. These responses occurred in the absence of an upregulation of translational regulatory proteins (p70 S6 kinase; eukaryotic 4E binding protein 1) to compensate for the decreased protein translational capacity. These data collectively demonstrate that 1) the molecular changes accompanying SI-induced muscle atrophy are not necessarily the reverse of those occurring during muscle hypertrophy, and 2) the rapid and marked atrophy that defines this model of muscle inactivity is likely the result of multifactorial processes affecting transcription, translation, and protein degradation.
Tracking variations in airway caliber by using total respiratory vs. airway resistance in healthy and asthmatic subjects
Authors: Black L. D. , Dellacà R. , Jung K. , Atileh H. , Israel E. , Ingenito E. P. , Lutchen K. R.
Published: March 2015

An index of airway caliber can be tracked in near-real time by measuring airway resistance (Raw) as indicated by lung resistance at 8 Hz. These measurements require the placing of an esophageal balloon. The objective of this study was to establish whether total respiratory system resistance (Rrs) could be used rather than Raw to track airway caliber, thereby not requiring an esophageal balloon. Rrs includes the resistance of the chest wall (Rcw). We used a recursive least squares approach to track Raw and Rrs at 8 Hz in seven healthy and seven asthmatic subjects during tidal breathing and a deep inspiration (DI). In both subject groups, Rrs was significantly higher than Raw during tidal breathing at baseline and postchallenge. However, at total lung capacity, Raw and Rrs became equivalent. Measured with this approach, Rcw appears volume dependent, having a magnitude of 0.5–1.0 cmH2O · l-1 · s during tidal breathing and decreasing to zero at total lung capacity. When resistances are converted to an effective diameter, Rrs data overestimate the increase in diameter during a DI. Simulation studies suggest that the decrease in apparent Rcw during a DI is a consequence of airway opening flow underestimating chest wall flow at increased lung volume. We conclude that the volume dependence of Rcw can bias the presumed net change in airway caliber during tidal breathing and a DI but would not distort assessment of maximum airway dilation.
Noninvasive measurement of midexpiratory flow indicates bronchoconstriction in allergic rats
Authors: Glaab Thomas , Hoymann Heinz G. , Hohlfeld Jens M. , Korolewitz Regina , Hecht Matthias , Alarie Yves , Tschernig Thomas , Braun Armin , Krug Norbert , Fabel Helmut
Published: March 2015

This study was designed to evaluate the value and applicability of tidal breathing pattern analysis to assess bronchoconstriction in conscious rats. Using noninvasive, head-out body plethysmography and the decrease in tidal midexpiratory flow (EF50), we measured airway responsiveness (AR) to inhaled acetylcholine and allergen in conscious Brown-Norway rats, followed by invasive determination of pulmonary conductance (Gl) and EF50 in anesthetized rats. Dose-response studies to acetylcholine showed that noninvasively recorded EF50 closely reflected the dose-dependent decreases observed with the invasive monitoring of simultaneously measured Gl and EF50. After sensitization and intratracheal boost to ovalbumin or saline, rats were assessed for early and late AR to aerosolized ovalbumin. Ovalbumin aerosol challenge resulted in early and late AR in allergen-sensitized rats, whereas controls were unresponsive. The allergen-specific AR, as measured noninvasively by EF50, was similar in degree compared with invasively recorded EF50 and Gl and was associated with enhanced IgE and airway inflammation. We conclude that EF50 is a noninvasive and physiologically valid index of bronchoconstriction in a rat model of asthma.
Effect of age and endurance training on the capacity for epinephrine-stimulated gluconeogenesis in rat hepatocytes
Authors: Sumida Ken D. , Arimoto Steven M. , Catanzaro Michael J. , Frisch Frank
Published: March 2015

The effects of endurance training on hepatic glucose production (HGP) from lactate were examined in 24-h-fasted young (4 mo) and old (24 mo) male Fischer 344 rats by using the isolated-hepatocyte technique. The liver cells were incubated for 30 min with 5 mM lactate ([U-14C]lactate; 25,000 dpm/ml) and nine different concentrations of epinephrine (Epi). Basal HGP (with lactate only and no Epi) was significantly greater for young trained (T) (99.6 ± 6.2 nmol/mg protein) compared with young controls (C) (78.2 ± 6.0 nmol/mg protein). The basal HGP was also significantly greater for old T (97.3 ± 5.9 nmol/mg protein) compared with old C (72.2 ± 3.9 nmol/mg protein). After the incubation with the various concentrations of Epi, Hanes-Woolf plots were generated to determine kinetic constants ( Vmaxand EC50). Maximal Epi-stimulated hepatic glucose production ( Vmax) was significantly greater for young T (142.5 ± 6.5 nmol/mg protein) compared with young C (110.9 ± 4.8 nmol/mg protein). Similarly, the Vmaxwas significantly greater for old T (138.2 ± 5.0 nmol/mg protein) compared with old C (103.9 ± 2.5 nmol/mg protein). Finally, there was an increase in the EC50from the hepatocytes of old T (56.2 ± 6.2 nM) compared with young T (32.6 ± 4.9 nM). In like manner, there was an increase in the EC50from the hepatocytes of old C (59.7 ± 5.8 nM) compared with young C (33.1 ± 2.7 nM). The results suggest that training elevates HGP in the basal and maximally Epi-stimulated condition, but with age there is a decline in EC50that is independent of training status.
Validation of the DLW method in Japanese quail at different water fluxes using laser and IRMS
Authors: Van Trigt R. , Kerstel E. R. T. , Neubert R. E. M. , Meijer H. A. J. , McLean M. , Visser G. H.
Published: March 2015

In Japanese quail ( Coturnix c. japonica; n = 9), the doubly labeled water (DLW) method (2H, 18O) for estimation of CO2 production (l/day) was validated. To evaluate its sensitivity to water efflux levels ( r H2 Oe ; g/day) and to assumptions of fractional evaporative water loss ( x; dimensionless), animals were repeatedly fed a dry pellet diet (average r H2 Oe of 34.8 g/day) or a wet mash diet (95.8 g/day). We simultaneously compared the novel infrared laser spectrometry (LS) with isotope ratio mass spectrometry. At low r H2 Oe , calculated CO2 production rate exhibited little sensitivity to assumptions concerning x, with the best fit being found at 0.51, and only little error was made employing an x value of 0.25. In contrast, at high r H2 Oe , sensitivities were much higher with the best fit at x = 0.32. Conclusions derived from isotope ratio mass spectrometry and LS were similar, proving the usefulness of LS. Within a threefold range of r H2 Oe , little error in the DLW method is made when assuming one single x value of 0.25 (recommended by Speakman JR, Doubly Labelled Water. Theory and Practice. London: Chapman & Hall, 1997), indicating its robustness in comparative studies.
Earliest cardiac toxicity induced by iron overload selectively inhibits electrical conduction
Authors: Schwartz Kenneth A. , Li Zy , Schwartz Dianne E. , Cooper Thomas G. , Braselton W. Emmett
Published: March 2015

Female guinea pigs were injected intraperitoneally with 0.083 g/kg iron dextran (Fe-D) to achieve progressively increasing levels of iron load; controls received dextran. Delayed and blocked cardiac conductivity at the Purkinje fiber-papillary muscle junction was initially observed with Fe-D loads of 0.33 g/kg. Serial magnetic resonance relaxation time measurements obtained from livers of live animals showed a decrease (8.1 ± 0.86 vs. 14.8 ± 1.03 ms in controls, P < 0.001) that was first observed in animals loaded with 0.25 g/kg Fe-D. Iron concentrations in hearts and livers were significantly increased ( P < 0.001). Left ventricular pressure measurements on 1.5 g/kg Fe-D animals failed to demonstrate a defect in contractility, but 27% (9/33) ( P < 0.050) of the animals died without warning signs. We conclude that 1) initial decreases in liver magnetic resonance-relaxation time occur in the same range of iron excess as the threshold of iron load that induces delay or blockade of cardiac conduction and 2) a high incidence of sudden death, presumably from cardiac arrhythmias, was observed with large doses of iron that did not decrease left ventricular contractility.
Differential responses of IGF-I molecular complexes to military operational field training
Authors: Nindl Bradley C. , Castellani John W. , Young Andrew J. , Patton John F. , Khosravi M. Javad , Diamandi Anastasia , Montain Scott J.
Published: March 2015

Insulin-like growth factor (IGF) I and IGF binding proteins (IGFBPs) modulate metabolic activity and tissue repair and are influenced by nutritional status. IGF-I circulates in free, ternary [IGF-I + IGFBP-3 + acid labile subunit (ALS)], and binary (IGF-I + IGFBP) molecular complexes, and the relative proportions regulate IGF-I extravascular shifting and bioavailability. This study examined the hypothesis that sustained physical activity and sleep deprivation superimposed on a short-term energy deficit would alter the IGFBP concentrations and alter the proportions of IGF-I circulating in ternary vs. binary molecular complexes. Components of the IGF-I system (total and free IGF-I; IGFBP-1, -3, and ALS; nonternary IGF-I and IGFBP-3), biomarkers of metabolic and nutritional status (transferrin, ferritin, prealbumin, glucose, free fatty acids, glycerol, β-hydroxybutyrate), and body composition were measured in 12 men (22 ± 3 yr, 87 ± 8 kg, 183 ± 7 cm, 20 ± 5% body fat) on days 1, 3, and 4 during a control and experimental (Exp) period. During Exp, subjects performed prolonged work (energy expenditure of ∼4,500 kcal/day) with caloric (1,600 kcal/day) and sleep (6.2 h total) restriction. IGF-I and IGFBP-3 were measured by immunoassay before and after immunoaffinity depletion of ALS-based complexes (i.e., ternary complex removal). Exp produced losses in body mass (-3.0%), lowered total IGF-I (-24%), free IGF-I (-42%), IGFBP-3 (-6%), nonternary IGF-I (-27%), and IGFBP-3 (-16%), and increased IGFBP-1 (256%). No Exp effects were observed for ALS. No changes were observed in the proportion of IGF-I circulating in free (∼1.2%), ternary (∼87.4%), or nonternary (∼11.4%) molecular complexes. During Exp, glucose concentrations were lower on day 3, but days 1 and 4 were statistically similar. In conclusion, during a short-term energy deficit in young, healthy men, 1) IGF-I system components differentially respond (both in direction and magnitude) to a given metabolic perturbation and 2) the relative proportion of IGF-I sequestered in ternary vs. nonternary molecular complexes appears to be well maintained.
Endothelial modulation of skeletal muscle blood flow andV˙o2during low- and high-intensity contractions
Authors: King-VanVlack Cheryl E. , Mewburn J. D. , Chapler C. K. , MacDonald P. H.
Published: March 2015

In the present study, we determined whether endothelin (ET)-1 contributed to the observed reduction in muscle blood flow (Q˙) during contractions with nitric oxide synthase (NOS) inhibition and whether muscle O2uptake (V˙o2) would be affected by the decrease in muscle Q˙ with NOS inhibition at different contraction intensities. Muscle Q˙,V˙o2, O2extraction ratio (OER), and tension development (TD) were studied in the in situ gastrocnemius muscle preparation in anesthetized dogs. A decrease in the V˙o2-to-TD ratio (V˙o2/TD) was used as an indicator of O2limitation. Three contraction protocols were used: 1) isometric twitch contractions at 2 twitches (tw)/s, 2) the same contractions at 4 tw/s, and 3) pretreatment with an ETA-receptor antagonist (BQ-123) before 2 tw/s contractions. The muscle was stimulated to contract, and measures were obtained at steady state (∼5–8 min). NOS inhibition ( Nω-nitro-l-arginine methyl ester) was then induced, and measures were repeated at 2, 5, 10, and 15 min. During 2 tw/s contractions, NOS inhibition reduced Q˙with and without ETA-receptor blockade. In both groups, OER increased in response to the fall in Q˙, with the result being no change in V˙o2/TD. NOS inhibition also decreased Q˙ during 4 tw/s contractions, but OER did not increase, resulting in a reduction inV˙o2/TD 5 and 15 min after Nω-nitro-l-arginine methyl ester. These data indicated that 1) a reciprocal increase in ET-1 during NOS inhibition does not influence active hyperemia in skeletal muscle, and 2) during 4 tw/s contractions, the ischemia with NOS inhibition was associated with either an O2limitation or an alteration in the efficiency of muscle contractions.
Diaphragm arterioles are less responsive to α1- adrenergic constriction than gastrocnemius arterioles
Authors: Aaker Aaron , Laughlin M. H.
Published: March 2015

The sympathetic nervous system has greater influence on vascular resistance in low-oxidative, fast-twitch skeletal muscle than in high-oxidative skeletal muscle (17). The purpose of this study was to test the hypothesis that arterioles isolated from low-oxidative, fast-twitch skeletal muscle [the white portion of gastrocnemius (WG)] possess greater responsiveness to adrenergic constriction than arterioles isolated from high-oxidative skeletal muscle [red portion of the gastrocnemius muscle (RG) and diaphragm (Dia)]. Second-order arterioles (2As) were isolated from WG, RG, and Dia of rats and reactivity examined in vitro. Results reveal that Dia 2As constrict less to norepinephrine (NE) (10−9to 10−4M) than 2As from RG and WG, which exhibited similar NE-induced constrictions. This difference was not endothelium dependent, because responses of denuded 2As were similar to those of intact arterioles. The blunted NE-induced constrictor response of Dia 2As appears to be the result of differences in α1-receptor effects because 1) arterioles from Dia also responded less to selective α1-receptor stimulation with phenylephrine than RG and WG arterioles; 2) arterioles from Dia, RG, and WG dilated similarly to isoproterenol (10−9to 10−4M) and did not respond to selective α2-receptor stimulation with UK-14304; and 3) endothelin-1 produced similar constriction in 2As from Dia, RG, and WG. We conclude that differences in oxidative capacity and/or fiber type composition of muscle tissue do not explain different NE responsiveness of Dia 2As compared with 2As from gastrocnemius muscle. Differences in α1-adrenergic constrictor responsiveness among arterioles in skeletal muscle may contribute to nonuniform muscle blood flow responses observed during exercise and serve to maintain blood flow to Dia during exercise-induced increases in sympathetic nerve activity.
CYP4A mRNA, protein, and product in rat lungs: novel localization in vascular endothelium
Authors: Zhu Daling , Zhang Chenyang , Medhora Meetha , Jacobs Elizabeth R.
Published: March 2015

The vasodilatory effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on lung arteries is opposite to the constrictor effect seen in cerebral and renal vessels. These observations raise questions about the cellular localization of 20-HETE-forming isoforms in pulmonary arteries and other tissues. Using in situ hybridization, we demonstrate for the first time CYP4A (a family of cytochrome P-450 enzymes catalyzing formation of 20-HETE from the substrate arachidonic acid) mRNA in pulmonary arterial endothelial and smooth muscle cells, bronchial smooth muscle and bronchial epithelial cells, type I epithelial cells, and macrophages in adult male rat lungs. Moreover, we detect CYP4A protein in rat pulmonary arteries and bronchi as well as cultured endothelial cells. Finally, we identify endogenously formed 20-HETE by using fluorescent HPLC techniques, as well as the capacity to convert arachidonic acid into 20-HETE in pulmonary arteries, bronchi, and endothelium. These data show that 20-HETE is an endogenous product of several pulmonary cell types and is localized to tissues that optimally position it to modulate physiological functions such as smooth muscle tone or electrolyte flux.
Prior exercise enhances passive absorption of intraduodenal glucose
Authors: Pencek R. Richard , Koyama Yoshiharu , Lacy D. Brooks , James Freyja D. , Fueger Patrick T. , Jabbour Kareem , Williams Phillip E. , Wasserman David H.
Published: March 2015

The purpose of this study was to assess whether a prior bout of exercise enhances passive gut glucose absorption. Mongrel dogs had sampling catheters, infusion catheters, and a portal vein flow probe implanted 17 days before an experiment. Protocols consisted of either 150 min of exercise ( n = 8) or rest ( n = 7) followed by basal (-30 to 0 min) and a primed (150 mg/kg) intraduodenal glucose infusion [8.0 mg · kg-1· min-1, time ( t) = 0-90 min] periods. 3- O-[3H]methylglucose (absorbed actively, facilitatively, and passively) and l-[14C]glucose (absorbed passively) were injected into the duodenum at t = 20 and 80 min. Phloridzin, an inhibitor of the active sodium glucose cotransporter-1 (SGLT-1), was infused (0.1 mg · kg-1· min-1) into the duodenum from t = 60-90 min with a peripheral venous isoglycemic clamp. Duodenal, arterial, and portal vein samples were taken every 10 min during the glucose infusion, as well as every minute after each tracer bolus injection. Net gut glucose output in exercised dogs increased compared with that in the sedentary group (5.34 ± 0.47 and 4.02 ± 0.53 mg · kg-1· min-1). Passive gut glucose absorption increased ∼100% after exercise (0.93 ± 0.06 and 0.45 ± 0.07 mg · kg-1· min-1). Transport-mediated glucose absorption increased by ∼20%, but the change was not significant. The infusion of phloridzin eliminated the appearance of both glucose tracers in sedentary and exercised dogs, suggesting that passive transport required SGLT-1-mediated glucose uptake. This study shows 1) that prior exercise enhances passive absorption of intraduodenal glucose into the portal vein and 2) that basal and the added passive gut glucose absorption after exercise is dependent on initial transport of glucose via SGLT-1.
Selected Contribution: Ambient temperature for experiments in rats: a new method for determining the zone of thermal neutrality
Authors: Romanovsky Andrej A. , Ivanov Andrei I. , Shimansky Yury P.
Published: March 2015

There is a misbelief that the same animal has the same thermoneutral zone (TNZ) in different experimental setups. In reality, TNZ strongly depends on the physical environment and varies widely across setups. Current methods for determining TNZ require elaborate equipment and can be applied only to a limited set of experimental conditions. A new, broadly applicable approach that rapidly determines whether given conditions are neutral for a given animal is needed. Consistent with the definition of TNZ [the range of ambient temperature (Ta) at which body core temperature (Tc) regulation is achieved only by control of sensible heat loss], we propose three criteria of thermoneutrality: 1) the presence of high-magnitude fluctuations in skin temperature (Tsk) of body parts serving as specialized heat exchangers with the environment (e.g., rat tail), 2) the closeness of Tsk to the median of its operational range, and 3) a strong negative correlation between Tskand Tc. Thermocouple thermometry and liquid crystal thermography were performed in five rat strains at 13 Ta. Under the conditions tested (no bedding or filter tops, no group thermoregulation), the Ta range of 29.5–30.5°C satisfied all three TNZ criteria in Wistar, BDIX, Long-Evans, and Zucker lean rats; Zucker fatty rats had a slightly lower TNZ (28.0–29.0°C). Skin thermometry or thermography is a definition-based, simple, and inexpensive technique to determine whether experimental or housing conditions are neutral, subneutral, or supraneutral for a given animal.
Strength training counteracts motor performance losses during bed rest
Authors: Shinohara Minoru , Yoshitake Yasuhide , Kouzaki Motoki , Fukuoka Hideoki , Fukunaga Tetsuo
Published: March 2015

The purpose of the study was to determine the effect of bed rest with or without strength training on torque fluctuations and activation strategy of the muscles. Twelve young men participated in a 20-day bed rest study. Subjects were divided into a non-training group (BRCon) and a strength-training group (BRTr). The training comprised dynamic calf-raise and leg-press exercises. Before and after bed rest, subjects performed maximal contractions and steady submaximal isometric contractions of the ankle extensor muscles and of the knee extensor muscles (2.5-10% of maximal torque). Maximal torque decreased for both the ankle extensors (9%, P < 0.05) and knee extensors (16%, P < 0.05) in BRCon but not in BRTr. For the ankle extensors, the coefficient of variation (CV) for torque increased in both groups ( P < 0.05), with a greater amount ( P < 0.05) in BRCon (88%) compared with BRTr (41%). For the knee extensors, an increase in the CV for torque was observed only in BRCon (22%). The increase in the CV for torque in BRCon accompanied the greater changes in electromyogram amplitude of medial gastrocnemius (122%) and vastus lateralis (59%) compared with BRTr ( P < 0.05). The results indicate that fluctuations in torque during submaximal contractions of the extensor muscles in the leg increase after bed rest and that strength training counteracted the decline in performance. The response varied across muscle groups. Alterations in muscle activation may lead to an increase in fluctuations in motor output after bed rest.
Energy cost of walking and running at extreme uphill and downhill slopes
Authors: Minetti Alberto E. , Moia Christian , Roi Giulio S. , Susta Davide , Ferretti Guido
Published: March 2015

The costs of walking (Cw) and running (Cr) were measured on 10 runners on a treadmill inclined between −0.45 to +0.45 at different speeds. The minimum Cw was 1.64 ± 0.50 J · kg−1· m−1at a 1.0 ± 0.3 m/s speed on the level. It increased on positive slopes, attained 17.33 ± 1.11 J · kg−1· m−1at +0.45, and was reduced to 0.81 ± 0.37 J · kg−1· m−1at −0.10. At steeper slopes, it increased to reach 3.46 ± 0.95 J · kg−1· m−1at −0.45. Cr was 3.40 ± 0.24 J · kg−1· m−1on the level, independent of speed. It increased on positive slopes, attained 18.93 ± 1.74 J · kg−1· m−1at +0.45, and was reduced to 1.73 ± 0.36 J · kg−1· m−1at −0.20. At steeper slopes, it increased to reach 3.92 ± 0.81 J · kg−1· m−1at −0.45. The mechanical efficiencies of walking and running above +0.15 and below −0.15 attained those of concentric and eccentric muscular contraction, respectively. The optimum gradients for mountain paths approximated 0.20–0.30 for both gaits. Downhill, Cr was some 40% lower than reported in the literature for sedentary subjects. The estimated maximum running speeds on positive gradients corresponded to those adopted in uphill races; on negative gradients they were well above those attained in downhill competitions.
Differential metabolic fate of the carbon skeleton and amino-N of [13C]alanine and [15N]alanine ingested during prolonged exercise
Authors: Korach-André M. , Burelle Y. , Péronnet F. , Massicotte D. , Lavoie C. , Hillaire-Marcel C.
Published: March 2015

The decarboxylation/oxidation and the deamination of13C- and [15N]alanine ingested (1 g/kg or 73.7 ± 2 g) during prolonged exercise at low workload (180 min at 53 ± 2% maximal O2uptake) was measured in six healthy male subjects fromV˙13co2at the mouth and [15N]urea excretion in urine and sweat. Over the exercise period, 50.6 ± 3.5 g of exogenous alanine were oxidized (68.7 ± 4.5% of the load), providing 10.0 ± 0.6% of the energy yield vs. 4.8 ± 0.4, 47.6 ± 4.3, and 37.4 ± 4.7% for endogenous proteins, glucose, and lipids, respectively. Alanine could have been oxidized after conversion into glucose in the liver and/or directly in peripheral tissues. In contrast, only 13.0 ± 3.2 mmol of [15N]urea were excreted in urine and sweat (10.6 ± 0.4 and 2.4 ± 0.5 mmol, respectively), corresponding to the deamination of 2.3 ± 0.3 g of exogenous alanine (3.1 ± 0.4% of the load). These results confirm that the metabolic fate of the carbon skeleton and the amino-N moiety of exogenous alanine ingested during prolonged exercise at low workload are markedly different. The large positive nitrogen balance (8.5 ± 0.3 g) suggests that in this situation protein synthesis could be increased when a large amount of a single amino acid is ingested.
Retinal venous oxygen saturation and cardiac output during controlled hemorrhage and resuscitation
Authors: Denninghoff Kurt R. , Smith Matthew H. , Lompado Art , Hillman Lloyd W.
Published: March 2015

The objective was to test calibration of an eye oximeter (EOX) in a vitiligo swine eye and correlate retinal venous oxygen saturation (SrvO2), mixed venous oxygen saturation (SvO2), and cardiac output (CO) during robust changes in blood volume. Ten anesthetized adult Sinclair swine with retinal vitiligo were placed on stepwise decreasing amounts of oxygen. At each oxygen level, femoral artery oxygen saturation (SaO2) and retinal artery oxygen saturation (SraO2) were obtained. After equilibration on 100% O2, subjects were bled at 1.4 ml · kg−1· min−1for 20 min. Subsequently, anticoagulated shed blood was reinfused at the same rate. During graded hypoxia, exsanguination, and reinfusion, SraO2and SrvO2were measured by using the EOX, and CO and SvO2were measured by using a pulmonary artery catheter. During graded hypoxia, SraO2correlated with SaO2( r = 0.92). SrvO2correlated with SvO2( r = 0.89) during exsanguination and reinfusion. SvO2and SrvO2correlated with CO during blood removal and resuscitation ( r = 0.92). Use of vitiligo retinas improved the calibration of EOX measurements. In this robust hemorrhage model, SrvO2correlates with CO and SvO2across the range of exsanguination and resuscitation.
Immunomodulatory effects of dehydroepiandrosterone in proestrus female mice after trauma-hemorrhage
Authors: Knöferl Markus W. , Angele Martin K. , Catania Robert A. , Diodato Michael D. , Bland Kirby I. , Chaudry Irshad H.
Published: March 2015

Studies indicate that administration of the adrenal steroid dehydroepiandrosterone (DHEA) after trauma-hemorrhage in male mice improved cellular immune functions and reduced mortality rates from subsequent sepsis. There is evidence, however, that DHEA is converted to estrogens in males and that estrogens are immunoprotective after trauma-hemorrhage (TH). In contrast, DHEA in females can be converted to testosterone that has deleterious effects on immune functions. The aim of our study, therefore, was to determine whether administration of DHEA in proestrus females after TH would deteriorate immune responses. Proestrus female C3H/HeN mice (age 7–8 wk) were subjected to laparotomy (i.e., soft tissue trauma induced) and hemorrhagic shock (35 ± 5 mmHg for 90 min) or sham operation. The mice then received DHEA (100 μ/25 g body wt) or vehicle subcutaneously followed by fluid resuscitation (4× the shed blood volume). Plasma IL-6, splenocyte proliferation, splenocyte IL-2, IL-3, IFN-γ, IL-10 release, and splenic Mφ IL-1β, IL-6, IL-10, and IL-12 release were determined 24 h after TH. Plasma IL-6 levels were significantly increased in vehicle-treated females, and DHEA administration markedly attenuated this response. In vehicle-treated females, splenocyte proliferation, IL-2, IL-3, and IFN-γ release, and splenic Mφ IL-1β, IL-6, and IL-12 release were maintained or slightly enhanced after TH. In DHEA-treated females, however, these immune functional parameters were either unaltered compared with vehicle-treated animals or even further enhanced, but surprisingly were not depressed. Moreover, DHEA reduced splenocyte and splenic Mφ anti-inflammatory cytokine (i.e., IL-10) production after TH compared with vehicle-treated females. Because DHEA further enhances the immune responsiveness in proestrus females after TH, this hormone might be a useful adjunct even in females for further enhancing immune responses and decreasing the mortality rate after trauma and severe blood loss.
Invited Review: Active fluid clearance from the distal air spaces of the lung
Authors: Matthay Michael A. , Clerici Christine , Saumon Georges
Published: March 2015

Active ion transport drives iso-osmolar alveolar fluid clearance, a hypothesis originally suggested by in vivo studies in sheep 20 yr ago. Over the last two decades, remarkable progress has been made in establishing a critical role for active sodium transport as a primary mechanism that drives fluid clearance from the distal air spaces of the lung. The rate of fluid transport can be increased in most species, including the human lung, by cAMP stimulation. Catecholamine-independent mechanisms, including hormones, growth factors, and cytokines, can also upregulate epithelial fluid clearance in the lung. The new insights into the role of the distal lung epithelium in actively regulating lung fluid balance has important implications for the resolution of clinical pulmonary edema.
Comparison of rat and mouse pulmonary tissue mechanical properties and histology
Authors: Faffe Débora S. , Rocco Patricia R. M. , Negri Elnara M. , Zin Walter A.
Published: March 2015

The present study compares the dynamic mechanical properties and the contents of collagen and elastic fibers (oxytalan + elaunin + fully developed elastic fibers) of mice and rat lung strips. Resistance, elastance (E), and hysteresivity (η) were obtained during sinusoidal oscillations. The relative amounts of blood vessel, bronchial, and alveolar walls, as well as the mean alveolar diameter were determined. In both species, resistance had a negative and E a positive dependence on frequency, whereas η remained unchanged. Mice showed higher E and lower η than rats. Although collagen and elastic fiber contents were similar in both groups, mice had more oxytalan and less elaunin and fully developed elastic fibers than rats. Rats showed less alveolar and more blood vessel walls and higher mean alveolar diameter than mice. In conclusion, mice and rats present distinct tissue mechanical properties, which are accompanied by specific extracellular fiber composition.
Age is independently related to muscle metabolic capacity in premenopausal women
Authors: Hunter Gary R. , Newcomer Bradley R. , Weinsier Roland L. , Karapondo Daniel L. , Larson-Meyer D. Enette , Joanisse Denis R. , Bamman Marcas M.
Published: March 2015

The purpose of this study was to determine whether muscle metabolic capacity was inversely related to age after adjusting for physical activity in sedentary premenopausal women. Eighty-three women (ages 23–47 yr) had their free-living, activity-related energy expenditure evaluated with doubly labeled water procedures, and room calorimeter determined sleeping energy expenditure. Maximum O2 uptake and strength were evaluated in all subjects, whereas 31P-magnetic resonance spectroscopy determined metabolic economy during maximal exercise, and muscle biopsy maximal enzyme activity was evaluated in subsets of the sample (48 and 18 subjects, respectively). Age was significantly related to whole body treadmill endurance time ( r = −0.32), plantar flexion strength ( r = −0.29), maximum O2 uptake ( r = −0.27),31P-magnetic resonance spectroscopy ADP recovery rate ( r = −0.44), and anaerobic glycolytic capacity ( r = −0.37), and muscle biopsy citrate synthase activity ( r = −0.48), glyceraldehyde-3-phosphate dehydrogenase ( r = −0.54), phosphofructokinase ( r = −0.62), and phosphorylase ( r = −0.58) activity even after adjusting for activity-related energy expenditure. These data suggest that, in sedentary premenopausal women, both oxidative and glycolytic muscle capacity decrease with age even when physical activity is taken into account.
Sympathetic restraint of muscle blood flow at the onset of dynamic exercise
Authors: Hamann Jason J. , Buckwalter John B. , Valic Zoran , Clifford Philip S.
Published: March 2015

Little attention has focused on sympathetic influences on skeletal muscle blood flow at the onset of exercise. We hypothesized that 1) the sympathetic nervous system constrains muscle blood flow and 2) the decline from peak blood flow is mediated by increasing sympathetic vasoconstrictor tone. Mongrel dogs ( n = 7) ran on a treadmill after intra-arterial infusion of saline (control) or combined α1- and α2-adrenergic blockade (prazosin and rauwolscine). Immediate and rapid increases in hindlimb blood flow occurred at commencement of exercise with peak iliac blood flows averaging 933 ± 79 and 1,227 ± 90 ml/min during control and blockade conditions, respectively. At 1 min of exercise, hindlimb blood flow had decreased to 629 ± 54 and 1,057 ± 89 ml/min. In the absence of sympathetic vasoconstrictor tone, there was an enhanced peak blood flow at the onset of exercise. In addition, α-blockade attenuated the overshoot of hindlimb blood flow compared with the control condition. These data suggest that an immediate and sustained increase in sympathetic outflow restrains hindlimb blood flow at the onset of exercise and is responsible, at least in part, for an overshoot of blood flow to exercising skeletal muscle.
Contributions from rostral medullary nuclei to coordination of swallowing and breathing in awake goats
Authors: Feroah Thom R. , Forster H. V. , Fuentes Carla G. , Wenninger Julie , Martino Paul , Hodges M. , Pan L. , Rice Tom
Published: March 2015

The purpose of this study was to determine whether neurons in the facial (FN), gigantocellularis reticularis (RGN), and vestibular (VN) nuclei contribute to the regulation of breathing, swallowing, and the coordination of these two functions. Microtubules were chronically implanted bilaterally in goats. Two weeks later during wakefulness, 100-nl unilateral injections were made of mock cerebral spinal fluid or an excitatory amino acid receptor agonist or antagonists. When the agonist, N-methyl-d-aspartic acid, was injected into any nuclei, breathing and swallowing increased transiently (15–30%; P < 0.05), whereas only injections of the antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo-(f)quinoxaline into VN increased swallowing (20%; P < 0.05). The phase of breathing in which the swallows occurred was not altered by any injections. However, more importantly, injections of the agonist and the antagonists significantly altered ( P < 0.05) by 5–50% the respiratory phase-dependent timing and tidal volume effect of swallows on breathing relative to mock cerebral spinal fluid injections. In addition, these effects were not uniform for all three nuclei. We conclude that the FN, RGN, and VN are part of a neural circuit in the rostral medulla that regulates and/or modulates breathing, swallowing, and their coordination in the awake state.
Break point of serum creatine kinase release after endurance exercise
Authors: Totsuka Manabu , Nakaji Shigeyuki , Suzuki Katsuhiko , Sugawara Kazuo , Sato Koki
Published: March 2015

We investigated whether there is a break point of creatine kinase (CK) release after daily endurance exercise and whether CK response depends on individual physical characteristics. Fifteen healthy young men performed 90 min of bicycle exercise for 3 consecutive days. Body composition, properties of the quadriceps femoris muscle (QFM), and aerobic and anaerobic capacities were estimated before the test. Blood samples were obtained 22 times during the experimental period. Endurance exercise significantly elevated serum CK from 3 h after the first exercise session ( P < 0.05) and gradually increased thereafter. Subjects were classified into two groups according to their peak CK values: high responders (HR; >500 IU/l of CK) and low responders (LR; <300 IU/l of CK). Peak CK values during the experimental period correlated ( P < 0.01) with workload/cross-sectional area of the QFM ( r = 0.658), workload/volume of the QFM ( r = 0.648), and knee extensor strength/body mass ( r = −0.634); however, the HR and LR groups were separated in each variable. Thus the break point of CK release after endurance exercise under these conditions is 300–500 IU/l, two or three times higher than in the resting condition, and is associated with properties of the QFM.
Cholinergic Control of Heart Rate by Nitric Oxide is Site Specific
Authors: Herring Neil , Danson Edward J. F. , Paterson David J.
Published: March 2015

Parasympathetic control of heart rate involves the exocytotic release of acetylcholine and muscarinic receptor regulation of pacemaking currents. Endogenous nitric oxide can potentially regulate all of these processes; however, recent work suggests that the main functional role of nitric oxide lies in the modulation of acetylcholine release.
Ubiquitin-Dependent Proteolysis in Neurons
Authors: Klimaschewski Lars
Published: March 2015

Various studies identified the ubiquitin-proteasome system as the prime suspect in causing neurodegenerative diseases. The present review summarizes our current knowledge about the expression, regulation, and functions of this major protein degradation pathway in the brain, with particular reference to the pathogenesis of associated neurological diseases.
“The Force Be with You”: ATP in Gut Mechanosensory Transduction
Authors: Cooke Helen J. , Wunderlich Jacqueline , Christofi Fievos L.
Published: March 2015

Nucleotides such as ATP and UTP are everywhere. They play a key role in transducing mechanosensory signals via P2Y receptors in the large intestine or colon, leading to secretion of the sensory mediator 5-HT, and act as autocrine, paracrine, or neurocrine mediators in neural reflexes regulating chloride secretion.
Self Glycosphingolipids: New Antigens Recognized by Autoreactive T Lymphocytes
Authors: De Libero Gennaro , Mori Lucia
Published: March 2015

T cells may recognize glycolipids and lipids of bacterial and self origin associated with the CD1 antigen-presenting molecules. Understanding the mechanisms governing CD1-self glycolipid interaction will provide information on the molecular rules of glycolipid presentation and suggest new approaches to immunotherapy.
Fish or Chips?
Authors: Heller Axel R. , Theilen Hermann J. , Koch Thea
Published: March 2015

Cell membranes are not simply barriers separating intracellular from extracellular space. Rather, they represent a dynamic high-turnover system that adapts to current demands. During inflammation, prostaglandins and leukotrienes are formed from membrane-derived phospholipids. Encouraging improvements in critically ill patients were observed after nutritional replacement of long-chain omega-6 fatty acids with long-chain omega-3-fatty acids, contained in fish oil.
Cell Adhesion Molecules: Key Players in Memory Consolidation?
Authors: Welzl Hans , Stork Oliver
Published: March 2015

Experimental evidence implies that L1 and neural cell adhesion molecule (NCAM) are involved in long-term memory formation. Changes in their expression and glycosylation appear to modify the synaptic strength underlying memory consolidation. Interference with L1 and NCAM function in a variety of learning tasks in different species severely attenuates memory consolidation, indicating their involvement in an evolutionary conserved mechanism of neural plasticity.
Hypoxia, Hormones, and Red Blood Cell Function in Chick Embryos
Authors: Dragon Stefanie , Baumann Rosemarie
Published: March 2015

The red blood cell function of avian embryos is regulated by cAMP. Adenosine A2Aand β-adrenergic receptor activation during hypoxic conditions cause changes in the hemoglobin oxygen affinity and CO2transport. Furthermore, experimental evidence suggests a general involvement of cAMP in terminal differentiation of avian erythroblasts.
Nonredundant Gap Junction Functions
Authors: White Thomas W.
Published: March 2015

The need for molecular heterogeneity of gap junction channel proteins in vivo has been enigmatic. Recently, functional replacement of one channel gene with another in mice and flies has revealed that cellular health depends not simply on gap junction communication but also requires the correct type of intercellular channel subunit.
Matching the Heart to Heat-Induced Circulatory Load: Heat-Acclimatory Responses
Authors: Horowitz Michal
Published: March 2015

Heat acclimation enhances cardiac efficiency by increasing stroke volume and decreasing heart rate. These adaptations involve biochemical changes in the contractile apparatus, switched on by altered expression of genes coding contractile and calcium-regulatory proteins and partially mediated by persistent low thyroxine. Heat acclimation also produces cross-tolerance to oxygen deprivation, thus reinforcing cardiac adaptation to oxygen demand/supply mismatching via energy-sparing pathways.