bluuebunny/crossref_metadata_2025 huggingface dataset:
Pendrin localizes to the adrenal medulla and modulates catecholamine release
Authors: Lazo-Fernandez Yoskaly , Aguilera Greti , Pham Truyen D. , Park Annie Y. , Beierwaltes William H. , Sutliff Roy L. , Verlander Jill W. , Pacak Karel , Osunkoya Adeboye O. , Ellis Carla L. , Kim Young Hee , Shipley Gregory L. , Wynne Brandi M. , Hoover Robert S. , Sen Shurjo K. , Plotsky Paul M. , Wall Susan M.
Published: July 2015

Pendrin ( Slc26a4) is a Cl−/HCO3−exchanger expressed in renal intercalated cells and mediates renal Cl−absorption. With pendrin gene ablation, blood pressure and vascular volume fall, which increases plasma renin concentration. However, serum aldosterone does not significantly increase in pendrin-null mice, suggesting that pendrin regulates adrenal zona glomerulosa aldosterone production. Therefore, we examined pendrin expression in the adrenal gland using PCR, immunoblots, and immunohistochemistry. Pendrin protein was detected in adrenal lysates from wild-type but not pendrin-null mice. However, immunohistochemistry and qPCR of microdissected adrenal zones showed that pendrin was expressed in the adrenal medulla, rather than in cortex. Within the adrenal medulla, pendrin localizes to both epinephrine- and norepinephrine-producing chromaffin cells. Therefore, we examined plasma catecholamine concentration and blood pressure in wild-type and pendrin-null mice under basal conditions and then after 5 and 20 min of immobilization stress. Under basal conditions, blood pressure was lower in the mutant than in the wild-type mice, although epinephrine and norepinephrine concentrations were similar. Catecholamine concentration and blood pressure increased markedly in both groups with stress. With 20 min of immobilization stress, epinephrine and norepinephrine concentrations increased more in pendrin-null than in wild-type mice, although stress produced a similar increase in blood pressure in both groups. We conclude that pendrin is expressed in the adrenal medulla, where it blunts stress-induced catecholamine release.
Exercise-induced changes to in vitro T-lymphocyte mitogen responses using CFSE
Authors: Green Katherine J. , Rowbottom David G.
Published: July 2015

Carboxyfluorescein diacetate succinamidyl ester (CFSE) labeling of lymphocyte populations can provide unique insights into cell function at rest and with exercise, due to its ability to quantify cell division on an individual cell basis. This study aimed to characterize the effect of acute, intense exercise on T-lymphocyte function. Well-trained endurance runners completed 60 min of treadmill running at 95% of individual anaerobic threshold. Blood samples were collected before exercise; after 30 and 60 min of exercise; and after 30, 60, and 90 min of recovery. Isolated peripheral blood mononuclear cells were labeled with CFSE and cultured with or without mitogen (phytohemagglutinin). After culture, cell suspensions were labeled with CD3 (allophycocyanin) and CD8 (phycoerythrin), and expansion rates and cell death rates were calculated for each sample, as well as mitosis rates for each cell generation. Exercise was associated with a 60% decrease in cell expansion in both CD4 and CD8 cell types from before exercise to midexercise ( P < 0.05). The significant decrease in expansion rate in the midexercise samples for both cell types was mirrored by a 65% increase in cell death ( P < 0.05) in both cell types at that sample point. Exercise had no effect on the mitosis rate of either CD4 or CD8 cells in any cell generation ( generations 0–3). This study indicates that 1 h of intense exercise affects in vitro T-lymphocyte function. These data suggest, for the first time, that exercise decreases cell expansion rate via an increase in cell death of both CD4 and CD8 T lymphocytes, rather than a decrease in mitosis.
Venous cuff pressures from 30 mmHg to diastolic pressure are recommended to measure arterial inflow by plethysmography
Authors: Groothuis Jan T. , van Vliet Linda , Kooijman Miriam , Hopman Maria T. E.
Published: July 2015

Venous occlusion strain gauge plethysmography (VOP) is based on the assumption that the veins are occluded and arterial inflow is undisturbed by the venous cuff pressure. Literature is not clear concerning the pressure that should be used. The purpose of this study was to determine the optimal venous occlusion pressure at which the highest arterial inflow is achieved in the forearm, calf, and leg by using VOP. We hypothesized that, for each limb segment, an optimal (range of) venous cuff pressure can be determined. Arterial inflow in each limb segment was measured in nine healthy individuals by VOP by using pressures ranging from 10 mmHg up to diastolic blood pressure. Arterial inflows were similar at cuff pressures between 30 and 60 mmHg for the forearm, leg, and calf. Arterial inflow in the forearm was significantly lower at 10 mmHg compared with the other cuff pressures. In addition, arterial inflows at 20 mmHg tended to be lower in each limb segment than flow at higher cuff pressures. In conclusion, no single optimum venous cuff pressure, at which a highest arterial inflow is achieved, exists, but rather a range of optimum cuff pressures leading to a similar arterial inflow. Venous cuff pressures ranging from 30 mmHg up to diastolic blood pressure are recommended to measure arterial inflow by VOP.
Insulin does not mediate the attenuation of fatigue associated with glucose infusion in rat plantaris muscle
Authors: Karelis Antony D. , Péronnet François , Gardiner Phillip F.
Published: July 2015

Glucose infusion attenuates fatigue in rat plantaris muscle stimulated in situ, and this is associated with a better maintenance of electrical properties of the fiber membrane (Karelis AD, Péronnet F, and Gardiner PF. Exp Physiol 87: 585–592, 2002). The purpose of the present study was to test the hypothesis that elevated plasma insulin concentration due to glucose infusion (∼900 pmol/l), rather than high plasma glucose concentration (∼10–11 mmol/l), could be responsible for this phenomenon, because insulin has been shown to stimulate the Na+-K+pump. The plantaris muscle was indirectly stimulated (50 Hz, for 200 ms, 5 V, every 2.7 s) via the sciatic nerve to perform concentric contractions for 60 min, while insulin (8 mU · kg-1· min-1: plasma insulin ∼900 pmol/l) and glucose were infused to maintain plasma glucose concentration between 4 and 6 [6.2 ± 0.4 mg · kg-1· min-1: hyperinsulinemic-euglycemic (HE)] or 10 and 12 mmol/l [21.7 ± 1.1 mg · kg-1· min-1: hyperinsulinemic-hyperglycemic clamps (HH)] (6 rats/group). The reduction in submaximal dynamic force was significantly ( P < 0.05) less with HH (-53%) than with HE and saline only (-66 and -70%, respectively). M-wave characteristics were also better maintained in the HH than in HE and control groups. These results demonstrate that the increase in insulin concentration is not responsible for the increase in muscle performance observed after the elevation of circulating glucose.
Exercise delays the hypoxic thermal response in rats
Authors: Ray A. D. , Roberts A. J. , Lee S. D. , Farkas G. A. , Michlin C. , Rifkin D. I. , Ostrow P. T. , Krasney J. A.
Published: July 2015

Exercise exacerbates acute mountain sickness. In infants and small mammals, hypoxia elicits a decrease in body temperature (Tb) [hypoxic thermal response (HTR)], which may protect against hypoxic tissue damage. We postulated that exercise would counteract the HTR and promote hypoxic tissue damage. Tb was measured by telemetry in rats ( n = 28) exercising or sedentary in either normoxia or hypoxia (10% O2, 24 h) at 25°C ambient temperature (Ta). After 24 h of normoxia, rats walked at 10 m/min on a treadmill (30 min exercise, 30 min rest) for 6 h followed by 18 h of rest in either hypoxia or normoxia. Exercising normoxic rats increased Tb (°C) vs. baseline (39.68 ± 0.99 vs. 38.90 ± 0.95, mean ± SD, P < 0.05) and vs. sedentary normoxic rats (38.0 ± 0.09, P < 0.05). Sedentary hypoxic rats decreased Tb (36.15 ± 0.97 vs. 38.0 ± 0.36, P < 0.05) whereas Tb was maintained in the exercising hypoxic rats during the initial 6 h of exercise (37.61 ± 0.55 vs. 37.72 ± 1.25, not significant). After exercise, Tb in hypoxic rats reached a nadir similar to that in sedentary hypoxic rats (35.05 ± 1.69 vs. 35.03 ± 1.32, respectively). Tb reached its nadir significantly later in exercising hypoxic vs. sedentary hypoxic rats (10.51 ± 1.61 vs. 5.36 ± 1.83 h, respectively; P = 0.002). Significantly greater histopathological damage and water contents were observed in brain and lungs in the exercising hypoxic vs. sedentary hypoxic and normoxic rats. Thus exercise early in hypoxia delays but does not prevent the HTR. Counteracting the HTR early in hypoxia by exercise exacerbates brain and lung damage and edema in the absence of ischemia.
Glutamine supplementation further enhances exercise-induced plasma IL-6
Authors: Hiscock N. , Petersen E. W. , Krzywkowski K. , Boza J. , Halkjaer-Kristensen J. , Pedersen B. K.
Published: July 2015

Exercise stimulates the production and release of interleukin-6 (IL-6) from skeletal muscle. Glutamine is also synthesized in skeletal muscle and is involved in protein synthesis within this tissue. During exercise, plasma levels of glutamine decline, and this may affect the concentration of plasma IL-6 via a decrease in IL-6 synthesis and release from muscle. We hypothesized that glutamine supplementation would attenuate the exercise-induced decrease in plasma glutamine concentration and, thus, further enhance levels of plasma IL-6. Eight healthy men participated in a randomized, double-blind, crossover study in which they performed 2 h of cycle ergometry at 75% of peak O2 uptake. They received glutamine, glutamine-rich protein, or placebo supplementation at intervals during and 2 h after exercise. Exercise induced an 11-fold increase in plasma IL-6, which was further enhanced by glutamine (18-fold) and glutamine-rich protein (14-fold) supplementation, administered at doses that attenuated the exercise-induced decrease in plasma glutamine concentration.
Bradykinin stimulates respiratory drive by activating pulmonary sympathetic afferents in the rabbit
Authors: Soukhova G. , Wang Y. , Ahmed M. , Walker J. F. , Yu J.
Published: July 2015

We recently identified a vagally mediated excitatory lung reflex by injecting hypertonic saline into the lung parenchyma (Yu J, Zhang JF, and Fletcher EC. J Appl Physiol 85: 1485–1492, 1998). This reflex increased amplitude and burst rate of phrenic (inspiratory) nerve activity and suppressed external oblique abdominal (expiratory) muscle activity. In the present study, we tested the hypothesis that bradykinin may activate extravagal pathways to stimulate breathing by assessing its reflex effects on respiratory drive. Bradykinin (1 μg/kg in 0.1 ml) was injected into the lung parenchyma of anesthetized, open-chest and artificially ventilated rabbits. In most cases, bradykinin increased phrenic amplitude, phrenic burst rate, and expiratory muscle activity. However, a variety of breathing patterns resulted, ranging from hyperpnea and tachypnea to rapid shallow breathing and apnea. Bradykinin acts like hypertonic saline in producing hyperpnea and tachypnea, yet the two agents clearly differ. Bradykinin produced a higher ratio of phrenic amplitude to inspiratory time and had longer latency than hypertonic saline. Although attenuated, bradykinin-induced respiratory responses persisted after vagotomy. We conclude that bradykinin activates multiple afferent pathways in the lung; portions of its respiratory reflexes are extravagal and arise from sympathetic afferents.
Local blood circulation among knee extensor synergists in relation to alternate muscle activity during low-level sustained contraction
Authors: Kouzaki Motoki , Shinohara Minoru , Masani Kei , Tachi Masanobu , Kanehisa Hiroaki , Fukunaga Tetsuo
Published: July 2015

The relation between local circulation and alternate muscle activity among knee extensor synergists was determined during low-level sustained knee extension at 2.5% of maximal voluntary contraction for 60 min in seven subjects. Blood volume of rectus femoris (RF) and vastus lateralis (VL) was assessed by using near-infrared spectroscopy. Surface electromyogram (EMG) was recorded from RF, VL, and vastus medialis (VM). Alternate muscle activity was observed between RF and either VL or VM. Cross-correlation analysis was used to investigate the relation between blood volume and integrated EMG (iEMG) sequences throughout the task. One negative peak in the cross-correlation function was seen between the iEMG and blood volume with time lag of 30–60 s, indicating that muscle activity increases (or decreases) with the decrease (or increase) in local circulation with the corresponding time lag. Two cases in the emergence of alternate muscle activities, i.e., an increase in the EMG of RF accompanied by a decline of EMG in VL ( case I) and vice versa ( case II) were further analyzed. The time lag between iEMG and blood volume was longer in case I than that in case II. These results were statistically significant in the RF but not in the VL. It is concluded that even during low-level sustained contraction, local circulation is modulated by the alternate muscle activity of knee extensor synergists, and a negative correlation between the muscle activity and blood volume sequences was found in only RF but not in VL.
Muscle oxygenation and pulmonary gas exchange kinetics during cycling exercise on-transitions in humans
Authors: Grassi Bruno , Pogliaghi Silvia , Rampichini Susanna , Quaresima Valentina , Ferrari Marco , Marconi Claudio , Cerretelli Paolo
Published: July 2015

Near-infrared spectroscopy (NIRS) was utilized to gain insights into the kinetics of oxidative metabolism during exercise transitions. Ten untrained young men were tested on a cycle ergometer during transitions from unloaded pedaling to 5 min of constant-load exercise below (VT) the ventilatory threshold. Vastus lateralis oxygenation was determined by NIRS, and pulmonary O2 uptake ( V̇o2) was determined breath-by-breath. Changes in deoxygenated hemoglobin + myoglobin concentration {Δ[deoxy(Hb + Mb)]} were taken as a muscle oxygenation index. At the transition, Δ[deoxy(Hb + Mb)] was unmodified [time delay (TD)] for 8.9 ± 0.5 s at VT (both significantly different from 0) and then increased, following a monoexponential function [time constant (τ) = 8.5 ± 0.9 s for VT]. For >VT a slow component of Δ[deoxy(Hb + Mb)] on-kinetics was observed in 9 of 10 subjects after 75.0 ± 14.0 s of exercise. A significant correlation was described between the mean response time (MRT = TD + τ) of the primary component of Δ[deoxy(Hb + Mb)] on-kinetics and the τ of the primary component of the pulmonary V̇o2 on-kinetics. The constant muscle oxygenation during the initial phase of the on-transition indicates a tight coupling between increases in O2 delivery and O2 utilization. The lack of a drop in muscle oxygenation at the transition suggests adequacy of O2 availability in relation to needs.
Measurement of nutritional status in simulated microgravity by bioelectrical impedance spectroscopy
Authors: Bartok Cynthia , Atkinson Richard L. , Schoeller Dale A.
Published: July 2015

The potential of bioelectrical impedance spectroscopy (BIS) for assessing nutritional status in spaceflight was tested in two head-down-tilt bed-rest studies. BIS-predicted extracellular water (ECW), intracellular water (ICW), and total body water (TBW) measured using knee-elbow electrode placement were compared with deuterium and bromide dilution (DIL) volumes in healthy, 19- to 45-yr-old subjects. BIS was accurate during 44 h of head-down tilt with mean differences (BIS - DIL) of 0–0.1 kg for ECW, 0.3–0.5 for ICW, and 0.4–0.6 kg for TBW ( n = 28). At 44 h, BIS followed the within-individual change in body water compartments with a relative prediction error (standard error of the estimate/baseline volume) of 2.0–3.6% of water space. In the second study, BIS did not detect an acute decrease (-1.41 ± 0.91 kg) in ICW secondary to 48 h of a protein-free, 800 kcal/day diet ( n = 18). BIS's insensitivity to ICW losses may be because they were predominantly (65%) localized to the trunk and/or because there was a general failure of BIS to measure ICW independently of ECW and TBW. BIS may have potential for measuring nutritional status during spaceflight, but its limitations in precision and insensitivity to acute ICW changes warrant further validation studies.
Control and quantitation of voluntary weight-lifting performance of rats
Authors: Wirth Oliver , Gregory Erik W. , Cutlip Robert G. , Miller G. Roger
Published: July 2015

The present paper describes an exercise model that produces a voluntary hindlimb weight-lifting response. Each rat was operantly conditioned to enter a vertical tube, insert its head into a weighted ring (either 70 g or 700 g), lift the ring until its nose interrupted an infrared detector, and then lower the ring. Load cells measured the external force generated, and displacement transducers measured the vertical displacement of the ring during each lifting and lowering movement. The apparatus and training procedures were computer automated. Peak force, velocity, work, and power were calculated for each movement. Rats in both groups easily acquired the task after 12–15 training sessions, on average, conducted 5 days/wk. Once rats were trained, the lifting patterns were quite stable during several more weeks of posttraining exercise; however, the lighter 70-g load gave rise to more variable performances across rats. Results demonstrate the utility of quantitating the biomechanics of volitional movements and suggest that the present model can establish and maintain controlled repetitive movements necessary for studies of adaptation and/or injury in muscles, tendon, and bone.
Increased susceptibility to Pseudomonas aeruginosa infection under hindlimb-unloading conditions
Authors: Aviles Hernan , Belay Tesfaye , Fountain Kimberly , Vance Monique , Sonnenfeld Gerald
Published: July 2015

It has been reported that spaceflight conditions alter the immune system and resistance to infection [Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 170: 262–268, 2002; Hankins WR and Ziegelschmid JF. In: Biomedical Results of Apollo. Washington, DC: NASA, 1975, p. 43–81 . (NASA Spec. Rep. SP-368)]. Ground-based models, including the hindlimb-unloading model, have become important tools for increasing understanding of how spaceflight conditions can influence physiology. The objective of the present study was to determine the effect of hindlimb unloading on the susceptibility of mice to Pseudomonas aeruginosa infection. Hindlimb-unloaded and control mice were subcutaneously infected with 1 LD50 of P. aeruginosa. Survival, bacterial organ load, and antibody and corticosterone levels were compared among the groups. Hindlimb unloading had detrimental effects for infected mice. Animals in the hindlimb-unloaded group, compared with controls, 1) showed significantly increased mortality and reduced time to death, 2) had increased levels of corticosterone, and 3) were much less able to clear bacteria from the organs. These results suggest that hindlimb unloading may induce the production of corticosterone, which may play a critical role in the modulation of the immune system leading to increased susceptibility to P. aeruginosa infection.
Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity
Authors: Zhang Li-Fan , Sun Biao , Cao Xin-Sheng , Liu Chun , Yu Zhi-Bin , Zhang Le-Ning , Cheng Jiu-Hua , Wu Yan-Hong , Wu Xing-Yu
Published: July 2015

This study was designed to compare the effectiveness of daily short-duration -G x gravity exposure in preventing adverse changes in skeletal and cardiac muscles and bone due to simulated microgravity. Tail suspension for 28 days was used to simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G for 1, 2, or 4 h/day or centrifugation (CEN) at 1.5 or 2.6 G for 1 h/day was used to provide -Gx gravitation as a countermeasure. The results indicate that the minimum gravity exposure requirements vary greatly in different systems. Cardiac muscle is most responsive to such treatment: 1 h/day of -G x gravitation by STD was sufficient to prevent adverse changes in myocardial contractility; bone is most resistant: 4 h/day of -G x gravitation only partially alleviated the adverse changes in physical and mechanical properties of the femur. The responsiveness of skeletal muscle is moderate: 4 h/day of -G x gravitation prevented mass reduction and histomorphometric changes in the soleus muscle during a 28-day simulation period. Increasing gravitational intensity to 2.6 G showed less benefit or no additional benefit in preventing adverse changes in muscle and bone. The present work suggests that system specificity in responsiveness to intermittent gravity exposure should be considered one of the prerequisites in proposing intermittent artificial gravity as a potential countermeasure.
Chronic intermittent hypoxia decreases the expression of Na/H exchangers and HCO3-dependent transporters in mouse CNS
Authors: Douglas R. M. , Xue J. , Chen J. Y. , Haddad C. G. , Alper S. L. , Haddad G. G.
Published: July 2015

Chronic intermittent hypoxia (CIH) is a component of several disease states, including obstructive sleep apnea, which results in neurocognitive and cardiovascular morbidity. Because chronic hypoxia can induce changes in metabolism and pH homeostasis, we hypothesized that CIH induces changes in the expression of acid-base transporters. Two- to three-day-old mice, exposed to alternating cycles of 2 min of hypoxia (6.0–7.5% O2) and 3 min of normoxia (21% O2) for 8 h/day for 28 days, demonstrated decreases in specific acid-base transport protein expression in most of the central nervous system (CNS). Sodium/hydrogen exchanger isoform 1 (NHE1) and sodium-bicarbonate cotransporter expression were decreased in all regions of the CNS but especially so in the cerebellum. NHE3, which is only expressed in the cerebellum, was also significantly decreased. Anion exchanger 3 protein was decreased in most brain regions, with the decrease being substantial in the hippocampus. These results indicate that CIH induces downregulation of the major acid-extruding transport proteins, NHE1 and sodium-bicarbonate cotransporter, in particular regions of the CNS. This downregulation in acid-extruding capacity may render neurons more prone to acidity and possibly to injury during CIH, especially in the cerebellum and hippocampus. Alternatively, it is possible that O2 consumption in these regions is decreased after CIH, with consequential downregulation in the expression of certain cellular proteins that may be less needed under such circumstances.
Temporal association of nitric oxide levels and airflow in asthma after whole lung allergen challenge
Authors: Khatri Sumita B. , Hammel Jeffrey , Kavuru Mani S. , Erzurum Serpil C. , Dweik Raed A.
Published: July 2015

Exhaled nitric oxide (NO) levels are high in asthmatic subjects and increase with exacerbations. We hypothesized that higher levels of NO observed during asthma exacerbations are due to increased synthesis of NO. Exhaled NO and peak flows were measured in 11 asthmatic and 9 healthy control subjects before and after experimental asthmatic response induced by whole lung allergen challenge. Baseline peak flows of asthmatics were significantly lower than controls and decreased significantly immediately after challenge ( P = 0.004). NO was measured by collecting exhaled breaths without breath hold (NO0) and after a 15-s breath hold (NO15). The rate of NO accumulation over time [parts/billion per second (ppb/s)] was calculated by ΔNO/Δ t = (NO15 - NO0)/15, where Δ denotes a change and t is time. The NO accumulation rates in asthmatic and control subjects were similar at baseline; however, NO accumulation at 24 h increased threefold from baseline in asthmatic compared with control subjects (asthmatic subjects, 0.6 ± 0.2 ppb/s; control subjects, 0.2 ± 0.1 ppb/s; P = 0.01). Our study suggests that increased NO during an asthma exacerbation is due to increased synthesis, perhaps by increased expression of NO synthases.
Histamine alters E-cadherin cell adhesion to increase human airway epithelial permeability
Authors: Zabner Joseph , Winter Michael , Excoffon Katherine J. D. Ashbourne , Stoltz David , Ries Dana , Shasby Sandra , Shasby Michael
Published: July 2015

During the immediate response to an inhaled allergen, there is an increase in the paracellular permeability of the airway epithelium.1Histamine is an important agonist released during the immediate response to inhaled allergen. We hypothesized that histamine would increase human airway epithelial paracellular permeability and that it would do this by interrupting E-cadherin-based cell adhesion. Histamine, applied to the basolateral surface, increased the paracellular permeability of cultured human airway epithelia, and this effect of histamine was blocked by the histamine receptor antagonist promethazine. ECV304 cells express a histamine receptor, N-cadherin, and elements of the tight junction, including claudins, but they do not express E-cadherin. Histamine increased the paracellular permeability of ECV304 cells transfected with a vector and expressing E-cadherin but not ECV304 cells expressing lac-Z in the same vector. L cells do not express the histamine receptor, cadherins, or claudins. Histamine decreased adhesion of L cells expressing the human histamine receptor and E-cadherin to an E-cadherin-Fc fusion protein. Histamine did not alter the adhesion to the E-cadherin fusion protein of L cells expressing either the histamine receptor or E-cadherin alone. When applied to the apical surface, adenovirus poorly infects airway epithelial cells because its receptor, CAR, is restricted to the basolateral surface of the cells. When histamine was applied to the basolateral surface of airway epithelial cells, infection of the cells by adenovirus increased by approximately one log. This effect of histamine was also blocked by promethazine. Histamine increases airway paracellular permeability and increases susceptibility of airway epithelial cells to infection by adenovirus by interrupting E-cadherin adhesion.
Effect of surface tension of mucosal lining liquid on upper airway mechanics in anesthetized humans
Authors: Kirkness Jason P. , Eastwood Peter R. , Szollosi Irene , Platt Peter R. , Wheatley John R. , Amis Terence C. , Hillman David R.
Published: July 2015

Upper airway (UA) patency may be influenced by surface tension (γ) operating within the (UAL). We examined the role of γ of UAL in the maintenance of UA patency in eight isoflurane-anesthetized supine human subjects breathing via a nasal mask connected to a pneumotachograph attached to a pressure delivery system. We evaluated 1) mask pressure at which the UA closed (Pcrit), 2) UA resistance upstream from the site of UA collapse (RUS), and 3) mask pressure at which the UA reopened (Po). A multiple pressure-transducer catheter was used to identify the site of airway closure (velopharyngeal in all subjects). UAL samples (0.2 μl) were collected, and the γ of UAL was determined by using the “pull-off force” technique. Studies were performed before and after the intrapharyngeal instillation of 5 ml of exogenous surfactant (Exosurf, Glaxo Smith Kline). The γ of UAL decreased from 61.9 ± 4.1 (control) to 50.3 ± 5.0 mN/m (surfactant; P < 0.02). Changes in Po, RUS, and Po - Pcrit (change = control - surfactant) were positively correlated with changes in γ ( r2> 0.6; P < 0.02) but not with changes in Pcrit ( r2= 0.4; P > 0.9). In addition, mean peak inspiratory airflow (no flow limitation) significantly increased ( P < 0.04) from 0.31 ± 0.06 (control) to 0.36 ± 0.06 l/s (surfactant). These findings suggest that γ of UAL exerts a force on the UA wall that hinders airway opening. Instillation of exogenous surfactant into the UA lowers the γ of UAL, thus increasing UA patency and augmenting reopening of the collapsed airway.
Actions of a hydrogen sulfide donor (NaHS) on transient sodium, persistent sodium, and voltage-gated calcium currents in neurons of the subfornical organ
Authors: Kuksis Markus , Ferguson Alastair V.
Published: July 2015

Hydrogen sulfide (H2S) is an endogenously found gasotransmitter that has been implicated in a variety of beneficial physiological functions. This study was performed to investigate the cellular mechanisms underlying actions of H2S previously observed in subfornical organ (SFO), where H2S acts to regulate blood pressure through a depolarization of the membrane and an overall increase in the excitability of SFO neurons. We used whole cell patch-clamp electrophysiology in the voltage-clamp configuration to analyze the effect of 1 mM NaHS, an H2S donor, on voltage-gated potassium, sodium, and calcium currents. We observed no effect of NaHS on potassium currents; however, both voltage-gated sodium currents (persistent and transient) and the N-type calcium current had a depolarized activation curve and an enhanced peak-induced current in response to a series of voltage-step and ramp protocols run in the control and NaHS conditions. These effects were not responsible for the previously observed depolarization of the membrane potential, as depolarizing effects of H2S were still observed following block of these conductances with tetrodotoxin (5 μM) and ω-conotoxin-GVIA (100 nM). Our studies are the first to investigate the effect of H2S on a variety of voltage-gated conductances in a single brain area, and although they do not explain mechanisms underlying the depolarizing actions of H2S on SFO neurons, they provide evidence of potential mechanisms through which this gasotransmitter influences the excitability of neurons in this important brain area as a consequence of the modulation of multiple ion channels.
PBMC transcriptomic responses to primary and secondary vaccination differ due to divergent lean growth and antibody titers in a pig model
Authors: Adler Marcel , Murani Eduard , Ponsuksili Siriluck , Wimmers Klaus
Published: July 2015

The genetic relationship between immune responsiveness and performance is not well understood, but a major topic of the evolution of resource allocation and of relevance in human medicine and livestock breeding, for instance. This study aims to show differences of transcript abundance changes during the time intervals before and after two tetanus toxoid (TT) vaccinations in domestic pigs differing in lean growth (LG) and anti-TT-antibody titers (AB) parameters of performance and immunocompetence. During response to the first vaccination all animals had a general decrease in transcript abundances related to various functional pathways as measured by comparative Affymetrix microarray hybridization and Ingenuity Pathway analyses. Low-AB phenotypes had predominantly decreased immune response transcripts. Combined phenotypes high-AB/high-LG had decreased transcripts related to growth factor signaling pathways. However, during the interval after the booster vaccination, high-LG and high-AB animals responded exclusively with increased immune transcripts, such as B-cell receptor signaling and cellular immune response pathways. In addition, high-LG and low-AB animals had predominantly increased transcripts of several cellular immune response pathways. Conversely, low-LG and high-AB animals had few elevated immune transcripts and decreased transcripts related to only two nonimmune-specific pathways. In response to booster vaccination high-LG phenotypes revealed enriched transcripts related to several different immune response pathways, regardless of AB phenotype. Different from the expected impact of AB titers, divergent AB phenotypes did not reflect considerable differences between immune transcripts. However, highly significant differences observed among divergent LG phenotypes suggest the compatibility of high performance and high vaccine responses.
Lung Epithelial Fluid Transport and the Resolution of Pulmonary Edema
Authors: Matthay Michael A. , Folkesson Hans G. , Clerici Christine
Published: July 2015

The discovery of mechanisms that regulate salt and water transport by the alveolar and distal airway epithelium of the lung has generated new insights into the regulation of lung fluid balance under both normal and pathological conditions. There is convincing evidence that active sodium and chloride transporters are expressed in the distal lung epithelium and are responsible for the ability of the lung to remove alveolar fluid at the time of birth as well as in the mature lung when pathological conditions lead to the development of pulmonary edema. Currently, the best described molecular transporters are the epithelial sodium channel, the cystic fibrosis transmembrane conductance regulator, Na+-K+-ATPase, and several aquaporin water channels. Both catecholamine-dependent and -independent mechanisms can upregulate isosmolar fluid transport across the distal lung epithelium. Experimental and clinical studies have made it possible to examine the role of these transporters in the resolution of pulmonary edema.
Modification of Brain Aging and Neurodegenerative Disorders by Genes, Diet, and Behavior
Authors: Mattson Mark P. , Chan Sic L. , Duan Wenzhen
Published: July 2015

Multiple molecular, cellular, structural, and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively, or they may succumb to neurodegenerative cascades that result in disorders such as Alzheimer's and Parkinson's diseases. Multiple mechanisms are employed to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands and promote recovery of function after injury. The mechanisms include production of neurotrophic factors and cytokines, expression of various cell survival-promoting proteins (e.g., protein chaperones, antioxidant enzymes, Bcl-2 and inhibitor of apoptosis proteins), preservation of genomic integrity by telomerase and DNA repair proteins, and mobilization of neural stem cells to replace damaged neurons and glia. The aging process challenges such neuroprotective and neurorestorative mechanisms. Genetic and environmental factors superimposed upon the aging process can determine whether brain aging is successful or unsuccessful. Mutations in genes that cause inherited forms of Alzheimer's disease (amyloid precursor protein and presenilins), Parkinson's disease (α-synuclein and Parkin), and trinucleotide repeat disorders (huntingtin, androgen receptor, ataxin, and others) overwhelm endogenous neuroprotective mechanisms; other genes, such as those encoding apolipoprotein E4, have more subtle effects on brain aging. On the other hand, neuroprotective mechanisms can be bolstered by dietary (caloric restriction and folate and antioxidant supplementation) and behavioral (intellectual and physical activities) modifications. At the cellular and molecular levels, successful brain aging can be facilitated by activating a hormesis response in which neurons increase production of neurotrophic factors and stress proteins. Neural stem cells that reside in the adult brain are also responsive to environmental demands and appear capable of replacing lost or dysfunctional neurons and glial cells, perhaps even in the aging brain. The recent application of modern methods of molecular and cellular biology to the problem of brain aging is revealing a remarkable capacity within brain cells for adaptation to aging and resistance to disease.
Cyclic Nucleotide-Gated Ion Channels
Authors: Kaupp U. Benjamin , Seifert Reinhard
Published: July 2015

Cyclic nucleotide-gated (CNG) channels are nonselective cation channels first identified in retinal photoreceptors and olfactory sensory neurons (OSNs). They are opened by the direct binding of cyclic nucleotides, cAMP and cGMP. Although their activity shows very little voltage dependence, CNG channels belong to the superfamily of voltage-gated ion channels. Like their cousins the voltage-gated K+channels, CNG channels form heterotetrameric complexes consisting of two or three different types of subunits. Six different genes encoding CNG channels, four A subunits (A1 to A4) and two B subunits (B1 and B3), give rise to three different channels in rod and cone photoreceptors and in OSNs. Important functional features of these channels, i.e., ligand sensitivity and selectivity, ion permeation, and gating, are determined by the subunit composition of the respective channel complex. The function of CNG channels has been firmly established in retinal photoreceptors and in OSNs. Studies on their presence in other sensory and nonsensory cells have produced mixed results, and their purported roles in neuronal pathfinding or synaptic plasticity are not as well understood as their role in sensory neurons. Similarly, the function of invertebrate homologs found in Caenorhabditis elegans, Drosophila,and Limulus is largely unknown, except for two subunits of C. elegans that play a role in chemosensation. CNG channels are nonselective cation channels that do not discriminate well between alkali ions and even pass divalent cations, in particular Ca2+. Ca2+entry through CNG channels is important for both excitation and adaptation of sensory cells. CNG channel activity is modulated by Ca2+/calmodulin and by phosphorylation. Other factors may also be involved in channel regulation. Mutations in CNG channel genes give rise to retinal degeneration and color blindness. In particular, mutations in the A and B subunits of the CNG channel expressed in human cones cause various forms of complete and incomplete achromatopsia.
P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function
Authors: Roman Richard J.
Published: July 2015

Recent studies have indicated that arachidonic acid is primarily metabolized by cytochrome P-450 (CYP) enzymes in the brain, lung, kidney, and peripheral vasculature to 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) and that these compounds play critical roles in the regulation of renal, pulmonary, and cardiac function and vascular tone. EETs are endothelium-derived vasodilators that hyperpolarize vascular smooth muscle (VSM) cells by activating K+channels. 20-HETE is a vasoconstrictor produced in VSM cells that reduces the open-state probability of Ca2+-activated K+channels. Inhibitors of the formation of 20-HETE block the myogenic response of renal, cerebral, and skeletal muscle arterioles in vitro and autoregulation of renal and cerebral blood flow in vivo. They also block tubuloglomerular feedback responses in vivo and the vasoconstrictor response to elevations in tissue Po2both in vivo and in vitro. The formation of 20-HETE in VSM is stimulated by angiotensin II and endothelin and is inhibited by nitric oxide (NO) and carbon monoxide (CO). Blockade of the formation of 20-HETE attenuates the vascular responses to angiotensin II, endothelin, norepinephrine, NO, and CO. In the kidney, EETs and 20-HETE are produced in the proximal tubule and the thick ascending loop of Henle. They regulate Na+transport in these nephron segments. 20-HETE also contributes to the mitogenic effects of a variety of growth factors in VSM, renal epithelial, and mesangial cells. The production of EETs and 20-HETE is altered in experimental and genetic models of hypertension, diabetes, uremia, toxemia of pregnancy, and hepatorenal syndrome. Given the importance of this pathway in the control of cardiovascular function, it is likely that CYP metabolites of arachidonic acid contribute to the changes in renal function and vascular tone associated with some of these conditions and that drugs that modify the formation and/or actions of EETs and 20-HETE may have therapeutic benefits.
Genetic Variation, Heritability, and Diversity Analysis of Upland Rice (Oryza sativaL.) Genotypes Based on Quantitative Traits
Authors: Tuhina-Khatun Mst. , Hanafi Mohamed M. , Rafii Yusop Mohd , Wong M. Y. , Salleh Faezah M. , Ferdous Jannatul
Published: July 2015

Upland rice is important for sustainable crop production to meet future food demands. The expansion in area of irrigated rice faces limitations due to water scarcity resulting from climate change. Therefore, this research aimed to identify potential genotypes and suitable traits of upland rice germplasm for breeding programmes. Forty-three genotypes were evaluated in a randomised complete block design with three replications. All genotypes exhibited a wide and significant variation for 22 traits. The highest phenotypic and genotypic coefficient of variation was recorded for the number of filled grains/panicle and yields/plant (g). The highest heritability was found for photosynthetic rate, transpiration rate, stomatal conductance, intercellular CO2, and number of filled grains/panicle and yields/plant (g). Cluster analysis based on 22 traits grouped the 43 rice genotypes into five clusters. Cluster II was the largest and consisted of 20 genotypes mostly originating from the Philippines. The first four principle components of 22 traits accounted for about 72% of the total variation and indicated a wide variation among the genotypes. The selected best trait of the number of filled grains/panicle and yields/plant (g), which showed high heritability and high genetic advance, could be used as a selection criterion for hybridisation programmes in the future.
Synthesis, Crystallization, and Dielectric Behaviour of Lead Bismuth Titanate Borosilicate Glasses with Addition of 1% La2O3
Authors: Gautam C. R. , Madheshiya Abhishek , Dwivedi R. K.
Published: July 2015

Lead bismuth titanate borosilicate glasses were prepared in the glass system 65[(PbxBi1-x)·TiO3]-34[2SiO2·B2O3]-1La2O3(0.0≤x≤1.0) doped with one mole percent ofLa2O3via conventional melt quench method. The amorphous nature of glass samples in this glass system is confirmed by using X-ray diffraction (XRD) study. Differential thermal analysis (DTA) has been employed to determine the glass transition temperature,Tg, as well as crystallization temperature,Tc. DTA measurements were recorded in temperature range from 30 to 1200°C. The prepared glasses were crystallized by regulated controlled heat treatment process on the basis of their DTA results. These samples are carried out for XRD measurements in the 2θrange from 20 to 80° to study the crystallization behaviour and phase formation of the glass ceramic samples. The scanning electron microscopy (SEM) of these glass ceramic samples has been carried out to explore the morphology through nucleation and growth of the crystallites in the glassy matrix. The values of dielectric constant as well as dielectric loss were increased with increasing the temperature within the frequency range from 20 Hz to 100 Hz. The addition of 1 mol% ofLa2O3to the lead bismuth titanate glasses enhances the crystallization and acts as donor dopant for this glass system.
Clinical Outcome after Colonic Resection in Women with Endometriosis
Authors: Klugsberger Bettina , Shamiyeh Andreas , Oppelt Peter , Jabkowski Christina , Schimetta Wolfgang , Haas Dietmar
Published: July 2015

Background. In severe forms of endometriosis, the colon or rectum may be involved. This study evaluated the functional results and long-term outcome after laparoscopic colonic resection for endometriosis.Patients and Methods.Questionnaire survey with 24 women who had experienced typical symptoms, including pelvic pain, infertility, and endometriotic lesions in the bowel and undergone laparoscopic surgery, including low anterior resection, from 2009 to 2012, was conducted.Results.Information about the postoperative outcome was obtained from 22 women and was analyzed statistically. Twenty-one had undergone low anterior resection; one patient required a primary Hartmann procedure due to a rectovaginal fistula. The conversion rate was 4.5%. Major complications occurred in one patient, including an anastomotic leakage, and a Hartmann procedure was carried out subsequently in this patient. The symptoms of pain during defecation, pelvic pain, dyspareunia, dysmenorrhea, and hematochezia showed clear improvement one year after the operation and at the time of the questionnaire.Conclusion. Laparoscopic low anterior resection for deeply infiltrative endometriosis is technically demanding but feasible and safe, and it improves the clinical symptoms of endometriosis in the bowel.
Periodic Switched Control of Dual-Rate Sampled-Data Systems
Authors: Zhang Dawei , Bai Wei , Jia Xinchun
Published: July 2015

This paper is concerned with the periodic switched control of a linear dual-rate sampled-data system. The state variables of the continuous-time plant are sampled by two types of sensors. The ratio of two sampling rates is assumed to be a rational number. Depending on whether the sampled-data of state variables at two sampling rates is available simultaneously or separately, a periodic switched controller is constructed. Applying an input delay approach, the closed-loop system is modeled as a switched system with subsystems having different input delays. Some delay-dependent criteria for theH∞performance of the switched system and the existence of the switched controller are derived by employing a Lyapunov-Krasovskii functional that includes information about two sampling periods. The dual-rate sampled-data control of a vehicle dynamic system is given to show that the proposed method is effective and it can achieve a betterH∞control performance than the single-rate design method.
First Reported Case of Methicillin-ResistantStaphylococcus aureusVertebral Osteomyelitis with Multiple Spinal and Paraspinal Abscesses Associated with Acupuncture
Authors: Singh Lubana Sandeep , Alfishawy Mostafa , Singh Navdeep , Brennessel Debra J.
Published: July 2015

Acupuncture is one of the oldest medical procedures in the world and originated in China about 2,000 years ago. Acupuncture is a form of complementary medicine and has gained popularity worldwide in the last few decades. It is mainly used for the treatment of chronic pain. Acupuncture is usually considered a safe procedure but has been reported to cause serious complications including death. It has been associated with transmission of many viruses and bacteria. Two cases of Methicillin-ResistantStaphylococcus aureushave been reported recently following acupuncture therapy. We are reporting a case of a 57-year-old Korean female who developed vertebral osteomyelitis and intraspinal and paraspinal abscesses as a complication of acupuncture. Blood cultures, skin lesion culture, and body fluid culture yielded Methicillin-ResistantStaphylococcus aureus(MRSA). Good anatomical and medical knowledge, good hygiene standards, and proper acupuncture techniques should be followed to prevent the complications. Acupuncturists should consistently review the infection control guidelines to acupuncture. This case should raise awareness of such condition and hazards of presumably benign procedures such as acupuncture.
Effects of Curved Wavefronts on Conductor-Backed Reflection-Only Free-Space Material Characterization Techniques
Authors: Fenner Raenita A. , Rothwell Edward J.
Published: July 2015

A true plane wave is often not physically realizable in a laboratory environment. Therefore, wavefront curvature introduces a form of systematic error into Free-space material characterization methods. Free-space material characterization is important to the determination of the electric permittivity and magnetic permeability of conductor-backed and in situ materials. This paper performs an error analysis of the impact on wavefront curvature on a Free-space method called the two-thickness method. This paper compares the extracted electric and magnetic permeability computed with a plane wave versus a line source for a low-loss dielectric and magnetic radar absorbing material. These steps are conducted for TE and TM plane waves and electric and magnetic line sources.