bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase
Authors: Zheng Donghai , MacLean Paul S. , Pohnert Steven C. , Knight John B. , Olson Ann Louise , Winder William W. , Dohm G. Lynis
Published: December 2017

Skeletal muscle GLUT-4 transcription in response to treatment with 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), a known activator of AMP-activated protein kinase (AMPK), was studied in rats and mice. The increase in GLUT-4 mRNA levels in response to a single subcutaneous injection of AICAR, peaked at 13 h in white and red quadriceps muscles but not in the soleus muscle. The mRNA level of chloramphenicol acyltransferase reporter gene which is driven by 1,154 or 895 bp of the human GLUT-4 proximal promoter was increased in AICAR-treated transgenic mice, demonstrating the transcriptional upregulation of the GLUT-4 gene by AICAR. However, this induction of transcription was not apparent with 730 bp of the promoter. In addition, nuclear extracts from AICAR-treated mice bound to the consensus sequence of myocyte enhancer factor-2 (from −473 to −464) to a greater extent than from saline-injected mice. Thus AMP-activated protein kinase activation by AICAR increases GLUT-4 transcription by a mechanism that requires response elements within 895 bp of human GLUT-4 proximal promoter and that may be cooperatively mediated by myocyte enhancer factor-2.
Nitric oxide synthase inhibition does not affect the exercise-induced arterial hypoxemia in Thoroughbred horses
Authors: Manohar Murli , Goetz Thomas E. , Hassan Aslam S.
Published: December 2017

Because sensitivity of equine pulmonary vasculature to endogenous as well as exogenous nitric oxide (NO) has been demonstrated, we examined whether endogenous NO production plays a role in exercise-induced arterial hypoxemia. We hypothesized that inhibition of NO synthase may alter the distribution of ventilation-perfusion mismatching, which may affect the exercise-induced arterial hypoxemia. Arterial blood-gas variables were examined in seven healthy, sound Thoroughbred horses at rest and during incremental exercise protocol leading to galloping at maximal heart rate without (control; placebo = saline) and with Nω-nitro-l-arginine methyl ester (l-NAME) administration (20 mg/kg iv). The experiments were carried out in random order, 7 days apart. At rest, l-NAME administration caused systemic hypertension, pulmonary hypertension, and bradycardia. During 120 s of galloping at maximal heart rate, significant arterial hypoxemia, desaturation of hemoglobin, hypercapnia, hyperthermia, and acidosis occurred in the control as well as in NO synthase inhibition experiments. However, statistically significant differences between the treatments were not found. In both treatments, exercise caused a significant rise in hemoglobin concentration, but the increment was significantly attenuated in the NO synthase inhibition experiments, and, therefore, arterial O2content (CaO2) increased to significantly lower values. These data suggest that, whereasl-NAME administration does not affect pulmonary gas exchange in exercising horses, it may affect splenic contraction, which via an attenuation of the rise in hemoglobin concentration and CaO2may limit performance at higher workloads.
Leukotriene B4 promotes reactive oxidant generation and leukocyte adherence during acute hypoxia
Authors: Steiner Dawn R. S. , Gonzalez Norberto C. , Wood John G.
Published: December 2017

Acute systemic hypoxia produces rapid leukocyte adherence in the rat mesenteric microcirculation, although the underlying mechanisms are not fully known. Hypoxia is known to increase reactive oxygen species (ROS) generation, which could result in formation of the lipid inflammatory mediator leukotriene B4 (LTB4). The goal of this study was to examine the role of LTB4 in hypoxia-induced microvascular alterations. Using intravital microscopy, we determined the effect of the LTB4 antagonist, LTB4-dimethyl amide (LTB4-DMA), on ROS generation and leukocyte adherence in mesenteric venules during hypoxia. Exogenous LTB4 increased ROS generation to 144 ± 8% compared with control values and also promoted leukocyte adherence. These responses to LTB4 were blocked by pretreating the mesentery with LTB4-DMA. Leukopenia did not significantly attenuate the LTB4-induced increase in ROS generation (142 ± 12.1%). LTB4-DMA substantially, though not completely, reduced hypoxia-induced ROS generation from 66 ± 18% to 11 ± 4% above control values. Hypoxia-induced leukocyte adherence was significantly attenuated by LTB4-DMA. Our results support a role for LTB4in the mechanism of hypoxia-induced ROS generation and leukocyte adherence in the rat mesenteric microcirculation.
Decreased neuronal excitability in hippocampal neurons of mice exposed to cyclic hypoxia
Authors: Gu Xiang Q. , Haddad Gabriel G.
Published: December 2017

To study the physiological effects of chronic intermittent hypoxia on neuronal excitability and function in mice, we exposed animals to cyclic hypoxia for 8 h daily (12 cycles/h) for ∼4 wk, starting at 2–3 days of age, and examined the properties of freshly dissociated hippocampal neurons in vitro. Compared with control (Con) hippocampal CA1 neurons, exposed (Cyc) neurons showed action potentials (AP) with a smaller amplitude and a longer duration and a more depolarized resting membrane potential. They also have a lower rate of spontaneous firing of AP and a higher rheobase. Furthermore, there was downregulation of the Na+ current density in Cyc compared with Con neurons (356.09 ± 54.03 pA/pF in Cyc neurons vs. 508.48 ± 67.30 pA/pF in Con, P < 0.04). Na+ channel characteristics, including activation, steady-state inactivation, and recovery from inactivation, were similar in both groups. The deactivation rate, however, was much larger in Cyc than in Con (at −100 mV, time constant for deactivation = 0.37 ± 0.04 ms in Cyc neurons and 0.18 ± 0.01 ms in Con neurons). We conclude that the decreased neuronal excitability in mice neurons treated with cyclic hypoxia is due, at least in part, to differences in passive properties (e.g., resting membrane potential) and in Na+ channel expression and/or regulation. We hypothesize that this decreased excitability is an adaptive response that attempts to decrease the energy expenditure that is used for adjusting disturbances in ionic homeostasis in low-O2conditions.
Selected Contribution: Roles of focal adhesion kinase and paxillin in the mechanosensitive regulation of myosin phosphorylation in smooth muscle
Authors: Tang Dale D. , Gunst Susan J.
Published: December 2017

The increase in intracellular Ca2+ and myosin light chain (MLC) phosphorylation in response to the contractile activation of tracheal smooth muscle is greater at longer muscle lengths (21). However, MLC phosphorylation can also be stimulated by Ca2+-insensitive signaling pathways (19). The cytoskeletal proteins paxillin and focal adhesion kinase (FAK) mediate a Ca2+-independent length-sensitive signaling pathway in tracheal smooth muscle (30). We used α-toxin-permeabilized tracheal smooth muscle strips to determine whether the length sensitivity of MLC phosphorylation can be regulated by a Ca2+-insensitive signaling pathway and whether the length sensitivity of active tension depends on the length sensitivity of myosin activation. Although active tension remained length sensitive, ACh-induced MLC phosphorylation was the same at optimal muscle length ( L o) and 0.5 L o when intracellular Ca2+ was maintained at pCa 7. MLC phosphorylation was also the same at L o and 0.5 L o in strips stimulated with 10 μM Ca2+. In contrast, the Ca2+-insensitive tyrosine phosphorylation of FAK and paxillin stimulated by ACh was higher at L o than at 0.5 L o. We conclude that the length-sensitivity of MLC phosphorylation depends on length-dependent changes in intracellular Ca2+ but that length-dependent changes in MLC phosphorylation are not the primary mechanism for the length sensitivity of active tension.
Effects of volatile anesthetics on stiffness of mammalian ventricular muscle
Authors: Bartunek Anna E. , Claes Victor A. , Housmans Philippe R.
Published: December 2017

To assess the effects of halothane, isoflurane, and sevoflurane on cross bridges in intact cardiac muscle, electrically stimulated (0.25 Hz, 25°C) right ventricular ferret papillary muscles ( n = 14) were subjected to sinusoidal load oscillations (37–182 Hz, 0.2–0.5 mN peak to peak) at the instantaneous self-resonant frequency of the muscle-lever system. At resonance, stiffness is proportional to m ∗ ω2 (where m is equivalent moving mass and ω is angular frequency). Dynamic stiffness was derived by relating total stiffness to values of passive stiffness at each length during shortening and lengthening. Shortening amplitude and dynamic stiffness were decreased by halothane > isoflurane ≥ sevoflurane. At equal peak shortening, dynamic stiffness was higher in halothane or isoflurane in high extracellular Ca2+ concentration than in control. Halothane and isoflurane increased passive stiffness. The decrease in dynamic stiffness and shortening results in part from direct effects of volatile anesthetics at the level of cross bridges. The increase in passive stiffness caused by halothane and isoflurane may reflect an effect on weakly bound cross bridges and/or an effect on passive elastic elements.
Effect of C-fiber-mediated, ozone-induced rapid shallow breathing on airway epithelial injury in rats
Authors: Schelegle E. S. , Alfaro M. F. , Putney L. , Stovall M. , Tyler N. , Hyde D. M.
Published: December 2017

We examined the relationship between C-fiber-mediated, ozone-induced rapid shallow breathing and airway epithelial cell injury at different airway sites within the lower respiratory tract of conscious Wistar rats ( n = 24). We combined an acute 8-h ozone inhalation with vagal perineural capsaicin treatment, a selective C-fiber conduction block, and 5-bromo-2′-deoxyuridine (BrdU) labeling as an index of epithelial injury. Vehicle-treated rats that inhaled ozone developed a rapid shallow breathing pattern during ozone inhalation, whereas the capsaicin-treated rats that inhaled ozone showed no changes in respiratory frequency. In vehicle-treated, ozone-exposed rats that developed rapid shallow breathing, a progressive increase in BrdU-labeling density (no. of BrdU-labeled cells/mm2airway) was observed starting at the bifurcation of the left main stem bronchi (central airway) and going down either a short or long airway path. In vehicle-treated, ozone-exposed rats, terminal bronchioles supplied by short and long airway paths had a similar degree of BrdU-labeling density that was significantly ( P < 0.05) greater than the BrdU-labeling density of the proximal airways that supply them. In contrast, the attenuation of rapid shallow breathing produced by capsaicin treatment resulted in a significantly reduced BrdU-labeling density in the terminal bronchioles supplied by short airway paths compared with the terminal bronchioles supplied by long airway paths. Our data indicate that ozone-induced rapid shallow breathing protects large conducting airways while producing a more even distribution of injury to terminal bronchioles.
Effects of neutrophil elastase inhibitor (ONO-5046) on lung injury after intestinal ischemia-reperfusion
Authors: Takayama Masanori , Ishibashi Masayoshi , Ishii Hisao , Kuraki Takashige , Nishida Tomiaki , Yoshida Minoru
Published: December 2017

The underlying mechanisms of lung endothelial injury after intestinal ischemia-reperfusion (I/R) injury are not fully known. Here we investigated the effects of posttreatment with a neutrophil elastase inhibitor (NEI; ONO-5046) on lung injury after intestinal I/R injury in a rat model. Intestinal I/R was produced by 90 min of ischemia followed by either 60 or 240 min of reperfusion. For all experimental groups, the endothelial permeability index increased, neutrophil H2O2production increased in the pulmonary vasculature blood, neutrophil counts increased in bronchoalveolar lavage fluid (BALF), and the cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-3 levels were increased in BALF after 240 min ( P < 0.01). In rats treated with NEI from 60 min after reperfusion, the lung endothelial permeability index was significantly reduced ( P < 0.05), whereas neutrophil H2O2production in pulmonary vasculature blood and neutrophil count in BALF were significantly suppressed by NEI ( P < 0.05 and P < 0.01, respectively). In addition, NEI significantly suppressed the increase of CINC-1 and CINC-3 levels in BALF ( P < 0.05). Our study clearly indicates that posttreatment with NEI reduces neutrophil activation in the pulmonary vessels and neutrophil accumulation in the lungs and suggests that ONO-5046, even when administered after the primary intestinal insult, can prevent the progression of lung injury associated with intestinal I/R.
TGF-β1 gene-race interactions for resting and exercise blood pressure in the HERITAGE Family Study
Authors: Rivera Miguel A. , Echegaray Marcos , Rankinen Tuomo , Pérusse Louis , Rice Treva , Gagnon Jacques , Leon Arthur S. , Skinner James S. , Wilmore Jack H. , Rao D. C. , Bouchard Claude
Published: December 2017

We examined the possible association between a transforming growth factor (TGF)-β1 gene polymorphism in codon 10 and blood pressure (BP) at rest, in acute response to exercise in the pretrained (sedentary) and trained states, as well as in its training response (Δ) to 20 wk of endurance exercise. Subjects were 257 black and 480 white, healthy sedentary normotensive subjects from the HERITAGE Family Study. The polymorphism was detected by polymerase chain reaction and digestion with the Msp A1 I endonuclease yielding a wild (leucine-10) and a mutant (proline-10) allele. Resting and exercise [50 W plus 60, 80, and 100% maximal oxygen consumption (V˙o 2 max)] BP were determined before and after training. Significant ( P < 0.05) race-genotype interactions were found for systolic (S) BP in both the sedentary and trained states. Among whites but not in blacks, the TGF-β1 genotypes were significantly ( P < 0.05) associated with sedentary-state SBP at rest, at 50 W, and at 60 and 100% V˙o 2 max as well as with trained-state SBP at rest and at 80 and 100%V˙o 2 max. The leucine-10 homozygotes had significantly ( P < 0.05) lower SBP than proline-10 homozygotes. ΔBP was not significantly associated with genotype. These results support the hypothesis of an association between the TGF-β1 marker in codon 10 and SBP at rest and in response to acute exercise in whites but not in blacks.
Invited Review: Cardiovascular protective effects of 17β-estradiol metabolites
Authors: Dubey Raghvendra K. , Jackson Edwin K.
Published: December 2017

17β-Estradiol (estradiol), the most abundant endogenous estrogen, affords cardiovascular protection. However, in a given cohort of postmenopausal women, estradiol replacement therapy provides cardiovascular protection in only a subset. The reasons for this variable action can only be understood once the mechanisms by which estradiol induces its cardiovascular protective effects are known. Because most biological effects of estradiol are mediated via estrogen receptors (ERs) and the heart and blood vessels contain both ER-α and ER-β, the prevailing view is that ERs mediate estradiol-induced cardiovascular protection. However, recent findings that estradiol protects against vascular injury in arteries of mice lacking either ER-α or ER-β seriously challenges this concept. Thus other non-ER mechanisms may be operative. Endogenous estradiol is enzymatically converted to several nonestrogenic metabolites, and some of these metabolites induce potent biological effects via ER-independent mechanisms. Therefore, it is conceivable that the cardiovascular protective effects of estradiol are mediated via its endogenous metabolites. On the basis of the evidence cited in this review, the cardiovascular protective effects of estradiol are both ER dependent and independent. The purpose of this article is to review the evidence regarding the cardiovascular protective effects of estradiol metabolites and to discuss the cellular, biochemical, and molecular mechanisms involved.
Selected Contribution: Estrogen receptor-α antisense decreases brain estrogen receptor levels and affects ventilation in male and female rats
Authors: Inamdar Shashita R. , Eyster Kathleen M. , Schlenker Evelyn H.
Published: December 2017

We hypothesized that administration of an antisense oligodeoxynucleotide (ODN) to estrogen receptor (ER)-α mRNA decreases the ER protein in the neonatal rat brain, alters the sex-specific ventilatory responses to aspartic acid in rats, and counteracts the effects of testosterone proportionate (TP) in females. One-day-old rat pups were injected intraventricularly with vehicle, antisense ER ODN, or scrambled ODN control. Additional groups of females received TP or vehicle and one of the three treatments. Brain ER protein levels were decreased by 65% at 6 h and 35% at 24 h after antisense ODN. Aspartic acid decreased ventilation in all groups of weanling males and females except ER ODN-treated females and TP-vehicle-treated females. Aspartic acid decreased ventilation in all groups of adult females except those given TP and in males. Weanling ER ODN-treated rats were shorter and weighed less than controls. Only adult ER ODN-treated males exhibited these traits. Thus neonatal ER affects aspartic acid modulation of breathing and body growth in a sex-specific and developmental manner.
Bone-loading response varies with strain magnitude and cycle number
Authors: Cullen D. M. , Smith R. T. , Akhter M. P.
Published: December 2017

Mechanical loading stimulates bone formation and regulates bone size, shape, and strength. It is recognized that strain magnitude, strain rate, and frequency are variables that explain bone stimulation. Early loading studies have shown that a low number (36) of cycles/day (cyc) induced maximal bone formation when strains were high (2,000 με) (Rubin CT and Lanyon LE. J Bone Joint Surg Am 66: 397–402, 1984). This study examines whether cycle number directly affects the bone response to loading and whether cycle number for activation of formation varies with load magnitude at low frequency. The adult rat tibiae were loaded in four-point bending at 25 (−800 με) or 30 N (−1,000 με) for 0, 40, 120, or 400 cyc at 2 Hz for 3 wk. Differences in periosteal and endocortical formation were examined by histomorphometry. Loading did not stimulate bone formation at 40 cyc. Compared with control tibiae, tibiae loaded at −800 με showed 2.8-fold greater periosteal bone formation rate at 400 cyc but no differences in endocortical formation. Tibiae loaded at −1,000 με and 120 or 400 cyc had 8- to 10-fold greater periosteal formation rate, 2- to 3-fold greater formation surface, and 1-fold greater endocortical formation surface than control. As applied load or strain magnitude decreased, the number of cyc required for activation of formation increased. We conclude that, at constant frequency, the number of cyc required to activate formation is dependent on strain and that, as number of cyc increases, the bone response increases.
Chronic administration of therapeutic levels of clenbuterol acts as a repartitioning agent
Authors: Kearns Charles F. , McKeever Kenneth H. , Malinowski Karyn , Struck Maggie B. , Abe Takashi
Published: December 2017

The purpose of this study was to examine the effect of therapeutic levels of clenbuterol, with and without exercise training, on body composition. Twenty-three unfit Standardbred mares were divided into four experimental groups: clenbuterol (2.4 μg/kg body wt twice daily) plus exercise (ClenEx; 20 min at 50% maximal oxygen consumption 3days/wk; n = 6), clenbuterol only (Clen; n = 6), exercise only (Ex; n = 5), and control (Con; n = 6). Rump fat thickness was measured at 2-wk intervals by using B-mode ultrasound, and percent body fat (%fat) was calculated by using previously published methods. For Ex, body fat decreased ( P < 0.05) at week 4 (−9.3%), %fat at week 6 (−6.9%), and fat-free mass (FFM) increased ( P < 0.05) at week 8 (+3.2%). On the other hand, Clen had significant changes in %fat (−15.4%), fat mass (−14.7%), and FFM (+4.3%) at week 2. ClenEx had significant decreases in %fat (−17.6%) and fat mass (−19.5%) at week 2, which was similar to Clen; however, this group had a different FFM response, which significantly increased (+4.4%) at week 6. Con showed no changes ( P > 0.05) in any variable at any time. These results suggest that exercise training and clenbuterol have additive effects with respect to %fat and fat mass but antagonistic effects in terms of FFM. Furthermore, chronic clenbuterol administration causes significant repartitioning in the horse, even when administered in therapeutic doses.
Dynamic cerebral autoregulation is preserved in neurally mediated syncope
Authors: Schondorf Ronald , Stein Reuben , Roberts Richard , Benoit Julie , Cupples William
Published: December 2017

To test whether cerebral autoregulation is impaired in patients with neurally mediated syncope (NMS), we evaluated 15 normal subjects and 37 patients with recurrent NMS. Blood pressure (BP), heart rate, and cerebral blood velocity (CBV) (transcranial Doppler) were recorded at rest and during 80° head-up tilt (HUT). Static cerebral autoregulation as assessed from the change in cerebrovascular resistance during HUT was the same in NMS and controls. Properties of dynamic cerebral autoregulation were inferred from transfer gain, coherence, and phase of the relationship between BP and CBV estimated from filtered data segments (0.02–0.8 Hz). During the 3 min preceding syncope, dynamic cerebral autoregulation of subjects with NMS did not differ from that of controls nor did it change over the course of HUT in patients with NMS or in control subjects. Dynamic cerebral autoregulation was also unaffected by the degree of orthostatic intolerance as inferred from latency to onset of syncope. We conclude that cerebral autoregulation in patients with recurrent syncope does not differ from that of normal control subjects.
Inhibitory effects of voluntary wheel exercise on apoptosis in splenic lymphocyte subsets of C57BL/6 mice
Authors: Avula C. P. Reddy , Muthukumar A. R. , Zaman K. , McCarter R. , Fernandes G.
Published: December 2017

Two-month-old mice were placed in cages with (Ex) or without exercise running wheels with free access to the wheel 24 h/day for 10 mo. An equal amount of food for both groups was provided daily. Ex mice ran an average of 33.67 km/wk initially, and exercise decreased gradually with age. Ex mice had gained an average of 43.5% less body weight at the end of the experiment. Although serum lipid peroxides were not altered by exercise, superoxide dismutase and glutathione peroxidase activities in serum were significantly increased. Flow cytometric analysis of spleen cells revealed an increased percentage of CD8+T cells and a decreased percentage of CD19+B cells in Ex mice ( P< 0.05). Exercise decreased apoptosis in total splenocytes and CD4+cells incubated with medium alone or with H2O2, dexamethasone, tumor necrosis factor-α (TNF-α), or anti-CD3 monoclonal antibody ( P < 0.05) and CD8+cells with medium alone or with TNF-α ( P < 0.05). Even though exercise did not alter the intracellular cytokines (TNF-α and interleukin-2) or Fas ligand, it did significantly lower interferon-γ in CD4+and CD8+cells ( P < 0.05). In summary, voluntary wheel exercise appears to decrease H2O2-induced apoptosis in immune cells as well as decrease interferon-γ production.
Sex differences in the fatigability of arm muscles depends on absolute force during isometric contractions
Authors: Hunter Sandra K. , Enoka Roger M.
Published: December 2017

Women are capable of longer endurance times compared with men for contractions performed at low to moderate intensities. The purpose of the study was 1) to determine the relation between the absolute target force and endurance time for a submaximal isometric contraction and 2) to compare the pressor response and muscle activation patterns of men [26.3 ± 1.1 (SE) yr] and women (27.5 ± 2.3 yr) during a fatiguing contraction performed with the elbow flexor muscles. Maximal voluntary contraction (MVC) force was greater for men (393 ± 23 vs. 177 ± 7 N), which meant that the average target force (20% of MVC) was greater for men (79.7 ± 6.5 vs. 36.7 ± 2.0 N). The endurance time for the fatiguing contractions was 118% longer for women (1,806 ± 239 vs. 829 ± 94 s). The average of the rectified electromyogram (%MVC) for the elbow flexor muscles at exhaustion was similar for men (31 ± 2%) and women (30 ± 2%). In contrast, the heart rate and mean arterial pressure (MAP) were less at exhaustion for women (94 ± 6 vs. 111 ± 7 beats/min and 121 ± 5 vs. 150 ± 6 mmHg, respectively). The target force and change in MAP during the fatiguing contraction were exponentially related to endurance time ( r 2 = 0.68 and r 2 = 0.64, respectively), whereas the change in MAP was linearly related to target force ( r 2 = 0.51). The difference in fatigability of men and women when performing a submaximal contraction was related to the absolute contraction intensity and was limited by mechanisms that were distal to the activation of muscle.
Comparison of transfusion with DCLHb or pRBCs for treatment of intraoperative anemia in sheep
Authors: Vane Luiz A. , Funston J. Sean , Kirschner Robert , Harper Don , Deyo Donald J. , Traber Daniel L. , Traber Lillian L. , Kramer George C.
Published: December 2017

Isoflurane-anesthetized sheep were transfused with packed red blood cells (pRBCs) or diaspirin cross-linked hemoglobin (DCLHb) for treatment of intraoperative hemorrhage. A rapid 15-min hemorrhage with lactated Ringer (LR) infusion maintained filling pressure at baseline and reduced blood hemoglobin (Hb) to ∼5 g/dl. Sheep received 2 g/kg Hb, DCLHb ( n = 6), or pRBCs ( n = 7); control group received LR alone ( n = 6). After 2 h, anesthesia was discontinued; sheep were monitored in the animal intensive care unit for 48 h. DCLHb expanded blood volume more, but increased total blood Hb less, than pRBCs. Lower Hb and increased methemoglobin resulted in lower arterial oxygen content compared with the pRBCs. DCLHb caused pulmonary hypertension (from 13 to 30 mmHg) and elevated filling pressure (from 6 to 15 mmHg). Cardiac outputs (CO) were similar for all groups during anesthesia; however, during recovery CO increased only in the LR and packed pRBCs groups. DCLHb may limit the reflex ability to increase CO after volume expansion. Hemodynamic effects of DCLHb may be exaggerated when infused after large-volume LR.
Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects
Authors: Franceschini Maria Angela , Boas David A. , Zourabian Anna , Diamond Solomon G. , Nadgir Shalini , Lin David W. , Moore John B. , Fantini Sergio
Published: December 2017

We present a noninvasive method to measure the venous oxygen saturation (SvO2) in tissues using near-infrared spectroscopy (NIRS). This method is based on the respiration-induced oscillations of the near-infrared absorption in tissues, and we call it spiroximetry (the prefix spiro means respiration). We have tested this method in three piglets (hind leg) and in eight human subjects (vastus medialis and vastus lateralis muscles). In the piglet study, we compared our NIRS measurements of the SvO2(SvO2-NIRSresp) with the SvO2of blood samples. SvO2-NIRSrespand SvO2of blood samples agreed well over the whole range of SvO2considered (20–95%). The two measurements showed an average difference of 1.0% and a standard deviation of the difference of 5.8%. In the human study, we found a good agreement between SvO2-NIRSrespand the SvO2values measured with the NIRS venous occlusion method. Finally, in a preliminary test involving muscle exercise, SvO2-NIRSrespshowed an expected postexercise decrease from the initial baseline value and a subsequent recovery to baseline.
Invited Review: How sleep deprivation affects gene expression in the brain: a review of recent findings
Authors: Cirelli Chiara
Published: December 2017

The identification of the molecular correlates of sleep and wakefulness is essential to understand the restorative processes occurring during sleep, the cellular mechanisms underlying sleep regulation, and the functional consequences of sleep loss. To determine what molecular changes occur in the brain during the sleep-waking cycle and after sleep deprivation, our laboratory is performing a systematic screening of brain gene expression in rats that have been either sleeping or spontaneously awake for a few hours and in rats that have been sleep deprived for different periods of time ranging from a few hours to several days. So far, ∼10,000 transcripts expressed in the cerebral cortex have been screened. The expression of the vast majority of these genes does not change either across behavioral states or after sleep deprivation, even when forced wakefulness is prolonged for several days. A few hours of wakefulness, either spontaneous or forced by sleep deprivation, increase the expression of the same small groups of genes: immediate-early genes/transcription factors, genes related to energy metabolism, growth factors/adhesion molecules, chaperones/heat shock proteins, vesicle- and synapse-related genes, neurotransmitter/hormone receptors, neurotransmitter transporters, and enzymes. Sleep, on the other hand, induces the expression of a few unknown transcripts whose characterization is in progress. Thus, although the characterization of the molecular correlates of behavioral states is not yet complete, it is already apparent that the transition from sleep to waking can affect basic cellular functions such as RNA and protein synthesis, neural plasticity, neurotransmission, and metabolism. The pattern of changes in gene expression after long periods of sleep deprivation is unique and does not resemble that of short-term sleep deprivation or spontaneous wakefulness. A notable exception is represented, however, by the enzyme arylsulfotransferase, whose induction appears to be proportional to the duration of previous wakefulness. Arylsulfotransferase in rodents plays a major role in the catabolism of catecholamines, suggesting that an important role for sleep may be that of interrupting the continuous activity, during wakefulness, of brain catecholaminergic systems.
Tidal exhaled nitric oxide in healthy, unsedated newborn infants with prenatal tobacco exposure
Authors: Hall Graham L. , Reinmann Benjamin , Wildhaber Johannes H. , Frey Urs
Published: December 2017

Tidal fractional exhaled nitric oxide (Fe NO) changes were investigated in healthy, unsedated infants with or without prenatal tobacco exposure. Tidal flow (V˙), Fe NO, and CO2were measured in 20 healthy, unsedated infants [age: 25–58 days, length: 56.5 ± 2.5 (SE) cm]. NO output (V˙no) was calculated (V˙no = Fe NO × V˙). Two approaches were used to investigate within-breath changes of Fe NOand V˙no. First, we identified phases II and III from the expiratory capnogram. Second, we divided expiration into time-based quartiles. Tidal Fe NO (range: 14.5 ± 1.6 to 17.6 ± 2.1 parts/billion: quartile 4 and phase II, respectively) was not different between portions and exhibited significant negative V˙ dependence. V˙no was significantly dependent on the expiratory portion, with quartile 4 being significantly lower than the remaining expiratory portions. Infants exposed to prenatal cigarette smoke ( n = 7) exhibited significantly lower Fe NO and V˙no compared with nonexposed ( n = 13) infants. We conclude that tidal Fe NO is V˙ dependent and thatV˙no may be a more suitable outcome parameter in variable V˙ conditions. Prenatal tobacco exposure resulted in a decreased Fe NO and V˙no in infants.
Fatty Acids as Useful Serological Markers for Crohn’s Disease
Authors: Ito Zensho , Uchiyama Kan , Odahara Shunichi , Takami Shinichiro , Saito Keisuke , Kobayashi Hiroko , Koido Shigeo , Kubota Takahiro , Ohkusa Toshifumi , Saruta Masayuki
Published: December 2017

Background: We have previously reported that patients with Crohn’s disease (CD) have a very specific erythrocyte membrane phospholipid fatty acid profile. The findings of this study suggest that the activities of enzymes involved in the metabolism of linoleic acid (LA), that is, delta-6 desaturase, are higher in CD patients than in healthy individuals. Methods: We evaluated the utilities of various fatty acid compositions of the plasma (p-) as new serological markers for CD compared to those of erythrocyte membranes (e-). Results: Fifty CD patients and 50 healthy individuals were enrolled. In both plasma and erythrocyte membranes, the weight percentages of palmitic acid (PA) were significantly higher, while those of LA were significantly lower in CD patients than in controls. Fatty acids with high sensitivity and specificity were p-PA (0.86 and 0.74) and e-PA (0.80 and 0.74). With PA and LA as a CD fatty acid index (CDFAi), that is, CDFAi = (PA/LA), the sensitivity and specificity of plasma CDFAi (p-CDFAi) and e-CDFAi were 0.80 and 0.80; and 0.82 and 0.88 respectively. Conclusion: In CD patients, various fatty acids were specifically altered in both plasma and erythrocytes, and p-PA and p-CDFAi are potentially useful as new serological markers for CD.
Mechanism of Action of the Anti-Influenza Virus Active Kampo (Traditional Japanese Herbal) Medicine, Hochuekkito
Authors: Dan Katsuaki , Takanashi Keita , Akiyoshi Hiroko , Munakata Kaori , Hasegawa Hideki , Ogawa Kaoru , Watanabe Kenji
Published: December 2017

When the Kampo medicine, Hochuekkito (Hochu), was administered to normal mice for 2 weeks, influenza virus titer was reduced. The mechanism of action of Hochu was examined using the plaque assay method. It was suggested that Hochu may either obstruct the first stage of the infection process (adsorption and entry) or may directly target viral particles. Using the plaque assay method, these 2 modes of action could not be differentiated. Virus RNA in the infected cell was verified by quantitative real-time polymerase chain reaction. An equal inhibition effect was obtained when Hochu was preprocessed for normal cells and when they were made to act simultaneously with virus adsorption. The viral load at the cell surface following UV irradiation was higher in the Hochu-administered group as compared with that of the control. Moreover, the affinity of Hochu for the influenza virus was hundred times higher than its affinity for the host cell. The effect of entry obstruction by Hochu was observed via image analysis, where the amount of virus nucleocapsid protein (NP) invading the cell was visualized with FITC-labeled NP antibody. Hochu does not seem to have an effect on nucleic acid synthesis, viral release from infected cells, and on the subsequent second round of infection. In conclusion, Hochu binds to viral particles and forms complexes that can obstruct the entry of influenza virus into cells.
Maternal and Cord Blood Adiponectin Concentrations in Small for Gestational Age: A Meta-Analysis
Authors: Goto Eita
Published: December 2017

Background: Adiponectin, which may have a growth-promoting effect through its insulin-sensitizing action, is thought to play a key role in fetal growth. This study was performed to determine whether maternal and/or cord blood adiponectin concentrations differ between small for gestational age (SGA) and healthy controls. Methods: Databases were searched to identify good quality English language studies providing the number of SGA and healthy controls, and the means and standard deviations of maternal or cord blood adiponectin concentration in both groups. A meta-analysis was performed to summarize the standardized mean differences (SMDs) in maternal and cord blood adiponectin concentrations between SGA and healthy controls. Results: There was no statistically significant difference in maternal blood adiponectin concentration between SGA and healthy controls (n = 8, p = 0.951). However, cord blood adiponectin concentration was significantly lower in SGA than in healthy controls (n = 6, p = 0.028), and the effect was large (i.e., SMD >0.7). Conclusions: Maternal blood adiponectin concentration is not low in SGA compared with healthy controls. However, SGA shows lower cord blood adiponectin concentration than healthy controls.
O edifício sede da Pavan Engenharia e Indústria projetado por Vilanova Artigas em São Paulo
Authors: Florio Wilson , Tagliari Ana
Published: December 2017

Durante os anos de 2012 e 2014, foi realizada a pesquisa “Análise de projetos não construídos de Vilanova Artigas”, com o apoio do CNPq, na qual foram analisados doze projetos não construídos de Vilanova Artigas disponíveis no acervo digital da Biblioteca da Faculdade de Arquitetura e Urbanismo da Universidade de São Paulo, a partir de simulações e animações computacionais, no objetivo de se investigar esses espaços por meio dos passeios virtuais, além de relacioná-los com exemplares de sua obra construída, agregando esse conhecimento ao tema. Este texto apresenta parte dessa pesquisa com a análise do projeto do edifício sede da Pavan Engenharia Ltda., concebido em 1972, que seria construído na cidade de São Paulo. O objetivo deste texto é apresentar os resultados da pesquisa realizada, especificamente sobre esse projeto selecionado, realçando o material inédito, os procedimentos de pesquisa, a metodologia de investigação dos projetos, a análise realizada, os resultados obtidos, a discussão e a relação com a obra do arquiteto. Pudemos constatar a importância das novas tecnologias para o auxílio no processo de análise e representação de projetos não construídos. Sobre os resultados atingidos, é possível concluir que a pesquisa contribui para o enriquecimento do debate em torno da arquitetura de Vilanova Artigas, agregando material original a partir de fontes primárias, que permitem a interpretação e investigação da obra desse grande arquiteto.
Ocupar, mediar e ressignificar a imagem da cidade
Authors: Prata Didiana
Published: December 2017

A inauguração da ciclovia Av. Paulista e o fechamento das pistas de veículos, aos domingos, para uso exclusivo do pedestre transformaram a avenida ícone da cidade em mais um espaço ressignificado pelo seu uso temporário. A partir desse exemplo de acontecimento coletivo, relacionaremos a experiência do pedestre ou ciclista e a produção de imagens da paisagem urbana feita com dispositivos móveis, as câmeras de celular. O enfoque principal será verificar como se dá a apreensão estética das coisas urbanas, por meio da produção, mediação e veiculação de imagens nas redes sociais – especificamente no Instagram – e em que medida a superprodução de imagens, motivadas a partir de um evento, e a estetização do cotidiano possibilitam a produção de novas poéticas e novos vínculos com a cidade.
Formas modernas em jardins pitorescos: correlações entre as casas de Bratke e a (sub)urbanização do bairro Paineiras do Morumbi
Authors: Dall'Alba Anderson
Published: December 2017

O artigo examina o projeto de urbanização idealizado por Oswaldo Bratke para o bairro Paineiras do Morumbi, em São Paulo, ao final dos anos 1940, e os projetos das residências Morumbi (1951) e Oscar Americano (1952), construídas concomitantemente à formação do bairro em terrenos pertencentes à gleba delineada. Sabe-se que o modelo dos bairros-jardins implantados em algumas regiões da cidade a partir da década de 1910, que era inspirado na paisagem pitoresca da cidade-jardim teorizada por Howard, foi uma referência para o padrão urbano proposto por Bratke. Por outro lado, as residências Morumbi e Oscar Americano, exemplares da arquitetura idealizada para o local, são reconhecidas como obras importantes da arquitetura moderna brasileira: a primeira integrou os catálogos de Hitchcock (1955) e Mindlin (1956), enquanto a última foi destacada em periódicos relevantes do período, tais como as revistas Acrópole (1957) e Habitat (1957). Apesar dessas publicações destacarem a sintonia entre a arquitetura das residências e o contexto de inserção, nenhuma delas examina o projeto urbano, tampouco menciona a participação decisiva e ativa de Bratke – que atuava enquanto arquiteto-empresário – no empreendimento imobiliário. Ao analisar sequencialmente os projetos do bairro e das casas, este artigo demonstra, inicialmente, certos princípios de concepção comuns, que buscavam uma relação coerente entre arquitetura e paisagem. Na escala urbana, porém, verifica-se que Bratke não previu intervir sobre o bairro com estratégias sofisticadas de paisagismo, tendo acompanhado estratégias de desenho urbano já difundidas no contexto paulista, que buscavam, essencialmente, converter a paisagem em instrumento de capitalização. De forma similar, argumenta-se que tal atitude parece ter se refletido até mesmo no apelo visual evidente nas duas casas, que incorporavam a paisagem imediata evidenciando, desde a própria arquitetura, o modo de vida tradicional de famílias de elite a que ainda dariam suporte. Partindo dos estudos já realizados acerca da trajetória de Bratke, o trabalho pretende contribuir para uma melhor compreensão desses projetos, concepções relevantes enquanto produção do arquiteto e, até agora, tratadas separadamente pela historiografia.
Legendagem e transferência intercultural: investigação e prática docente
Authors: Lerma Sanchis María Dolores
Published: December 2017

Neste artigo, apresentamos uma investigação sobre a tradução de referentes culturais para legendagem entre as línguas e culturas espanhola e portuguesa. O objetivo é identificar as técnicas de tradução preferidas e detectar tendências de tradução no corpus analisado. Paralelamente, refletimos sobre a aplicação didática de pesquisas deste género em unidades curriculares de ensino e aprendizagem da tradução para legendagem. Neste contexto, os estudantes devem atingir um bom domínio da competência cultural ou extralinguística.
Contribuições da semântica argumentativa para o delineamento da expressão da anterioridade em espanhol
Authors: Araujo Leandro Silveira de
Published: December 2017

Este trabalho apresenta algumas contribuições da semântica argumentativa ao estudo do funcionamento do perfecto simple (PPS) e compuesto (PPC) na língua espanhola. Com esse propósito, discutimos como essa disciplina concebe a argumentação e a insere no próprio sistema linguístico. Em seguida, encontramos no conceito de Operador Argumentativo forte evidência de que os elementos a língua abrigam um valor que indica a direção argumentativa que se pode construir em um enunciado. A partir desse quadro teórico demonstramos como, em algumas situações, o PPS e o PPC conduzem a diferentes posicionamentos argumentativos, funcionando, portanto, como Operadores Argumentativos. Em complemento, avaliamos a aplicabilidade das propostas de Benveniste (2005) e Weinreich (1968) para o estudo da temporalidade verbal sob a perspectiva da intencionalidade comunicativa, isso para sustentar a hipótese de que o uso de uma ou outra forma pode ser definido por questões argumentativas.
Horacio Quiroga no Brasil: os “efeitos da língua”
Authors: Alves-Bezerra Wilson
Published: December 2017

Este artigo analisa a única visita que o escritor uruguaio Horacio Quiroga (1878-1937) fez ao Brasil, em 1922. Considerando a importância daquele ano para a literatura brasileira – pois é nele que acontece a Semana de Arte Moderna –, reconstrói-se o contexto e os diálogos literários que o escritor estabelece no Brasil: seu principal interlocutor é Monteiro Lobato (1882-1948), o então diretor da Revista do Brasil e responsável pela introdução da obra de Quiroga no país. Recuperam-se e analisam-se as cartas inéditas trocadas entre os dois escritores e, para além dos diálogos e do credo literário de Quiroga e Lobato, busca-se avaliar a tensão entre a estética vanguardista e a realista que estava em jogo no debate intelectual de então.
A prática educativa docente sobre o Projeto Político Pedagógico: um relato de experiência junto à pós-graduação em enfermagem
Authors: Rodríguez Anna Maria Meyer Maciel , Cassemiro Larissa Karoline Dias da Silva , Dorneles Letícia Lopes , Peppe Mariana Vitor , Gonçalves Marlene Fagundes Carvalho , Fortuna Cinira Magali , Clapis Maria José
Published: December 2017

O objetivo deste estudo foi relatar a experiência de pós-graduandas na elaboração e aplicação de uma prática educativa sobre o Projeto Político Pedagógico (PPP), adequado ao ensino de graduação, utilizando metodologias ativas de ensino-aprendizagem. A atividade foi apresentada para pós-graduandos no contexto de uma disciplina de pós-graduação, sob orientação das docentes responsáveis. A aula ocorreu em 2015, teve a duração de três horas, contou com a participação de 35 pós-graduandos e teve como proposta desenvolver nos alunos condições de conceituar o PPP; entender sua importância, seus princípios e estrutura; compreender os processos que envolvem a sua elaboração e desenvolver pensamentos críticos e reflexivos sobre os desafios de sua implementação nas instituições de ensino. A aula foi desenvolvida em três etapas. Na primeira, disponibilizou-se aos alunos um texto com uma situação-problema fictícia que tratava da elaboração de um PPP para resolver dificuldades de uma instituição de ensino. Na segunda, adaptou-se a metodologia da Aprendizagem Baseada em Problemas (ABP) ao objetivo proposto, buscando os conhecimentos prévios dos alunos acerca do PPP. E na terceira, utilizaramse tarjas de cartolina que continham as etapas de construção de um PPP, para que os alunos as discutissem e as dispusessem em sequência correta. A atividade foi avaliada como satisfatória. Para as pós-graduandas, a experiência de planejar e aplicar metodologias ativas no contexto de ensino-aprendizagem possibilitou: compreender a relevância de um PPP, construir coletivamente sua concepção e desenvolver a formação docente.
Uso dos Mapas Conceituais na dinâmica da sala de aula: relato de experiência na disciplina Sociedade, Meio Ambiente e Cidadania (EACH-USP)
Authors: Dias Sylmara Lopes Francelino Gonçalves , Scótolo Denise , Aguirra Isadora , Silva Gabriel Trettel , Lima Bruno Avellar Alves de
Published: December 2017

Este relato versa sobre a experiência da utilização dos mapas conceituais como ferramenta de participação ativa dos alunos no processo de aprendizagem durante a disciplina Sociedade, Meio Ambiente e Cidadania no ciclo básico da Escola de Artes, Ciências e Humanidades da Universidade de São Paulo. O campo de conhecimento articulado nessa disciplina exige métodos de ensino-aprendizagem que incentivem a aquisição e a articulação de conhecimentos de forma interdisciplinar e complexa, o que foi propiciado pelo uso dos mapas conceituais. As atividades com os mapas foram realizadas ao longo da disciplina em três etapas: anteriormente à aula, construíam-se mapas conceituais individualmente, com base nos conceitos da leitura indicada, e coletivamente pelo grupo responsável pela elaboração do seminário temático; durante a aula, a partir das provocações despertadas pelo seminário, os alunos eram convidados a discutir e reelaborar seus mapas em grupos; após a aula, os mapas coletivos eram alocados no ambiente virtual de apoio à graduação (e-disciplina), permitindo o registro e o compartilhamento do conhecimento gerado. O uso dos mapas conceituais resultou em protagonismo dos alunos na construção ativa do conhecimento, em compreensão aprofundada e sistêmica da bibliografia, em maior interesse e engajamento com os conteúdos estudados e em boa avaliação da técnica de ensino-aprendizagem utilizada por parte dos alunos.