bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGF and its related growth factors mediate sodium transport in mpkCCDc14 cells via ErbB2 (neu/HER‐2) receptor
Authors: Zheleznova Nadezhda N , Levchenko Vladislav , Pavlov Tengis S , Vandewalle Alain , Wilson Patricia D , Staruschenko Alexander 
Published: June 2021

Amiloride‐sensitive sodium entry, via the epithelial sodium channel (ENaC), is the rate‐limiting step for Na+ absorption. Epidermal growth factor (EGF) is involved in the regulation of Na+ transport and ENaC activity. However it is still controversial exactly how EGF regulates ENaC and Na+ absorption. The aim of the present study was to characterize the EGF regulation of Na+ transport in mpkCCDc14 cells. EGF dose dependently regulates basal transepithelial Na+ transport in two phases: an acute phase (< 4 hrs) and a chronic phase (> 8 hrs). Similar effects were observed with TGF‐α, HB‐EGF and amphiregulin. Inhibition of MEK1/2 by PD98059 or U0126 increased acute effects and disrupted chronic effects of EGF on Na+ reabsorption. Inhibition of PI3‐kinase with LY294002 abolished acute effect of EGF. As assessed by Western blotting, ErbB2 is the most predominant member of the ErbB family detected in mpkCCDc14 cells. Immunohistochemistry analysis revealed localization of ErbB2 in the CCD in rat kidneys. Both acute and long term effects of EGF were abolished when cells were treated with tyrphostin AG‐825, a selective inhibitor of the ErbB2 receptor. Thus, we conclude that EGF and its related growth factors are important for maintaining transepithelial Na+ transport and that EGF biphasically modulates sodium transport in mpkCCDc14 cells via the ErbB2 receptor.Supported by AHA and ASN.
Bronchial Epithelial Dysfunction In Asthma: Similarities To Metabolic Syndrome
Authors: Agrawal Anurag , Ahmad Tanvir , Mabalirajan Ulanganathan , Joseph Duraisamy Arul , Ghosh Balaram 
Published: June 2021

ObjectiveObesity and metabolic syndrome are epidemiologically associated with incident and prevalent asthma. To understand its mechanisms, we determined whether bronchial epithelial dysfunction in asthma is associated with metabolic stress.MethodsWe investigated the occurrence of oxidative stress, disordered arginine and nitric oxide metabolism, mitochondrial health and epithelial injury in lungs of mice with allergic airway inflammation. We further determined whether strategies known to be effective against similar dysfunction in metabolic syndrome, i.e. L‐arginine supplementation or statin therapy, are efficacious in the asthma model.ResultsIncreased levels of asymmetric dimethyl arginine (ADMA), an endogenous arginine analog that uncouples NOS, were found in asthmatic lungs. This was positively correlated with oxo‐nitrative stress, mitochondrial dysfunction, and epithelial injury. Treatment with either L‐arginine or simvastatin was able to restore normal ADMA and nitric oxide metabolism. This was associated with reduction of oxo‐nitrative stress, improved mitochondrial health, as well as attenuation of bronchial airway injury, remodeling, and hyperresponsiveness.ConclusionAsthmatic airways show patterns of metabolic stress similar to vascular dysfunction in metabolic syndrome, and respond to treatment with L‐arginine or simvastatin.
Acute and selective activation of pulmonary neuroepithelial bodies by mild hypo‐osmotic stimuli
Authors: Lembrechts Robrecht , Brouns Inge , Schnorbusch Kathy , Pintelon Isabel , Timmermans Jean‐Pierre , Adriaensen Dirk 
Published: June 2021

Neuroepithelial bodies (NEBs) are morphologically well‐defined airway receptors composed of densely innervated groups of neuroendocrine cells. Besides other functions, NEBs have been proposed as transducers of mechanical changes in the airways. So far, however, physiological data are lacking. Hypo‐osmotic solutions cause cell swelling that will likely increase pressure in the tight junction sealed airway epithelium and more specifically in the NEB microenvironment. This study aimed at finding out whether NEBs are sensitive to hypo‐osmotic stimuli.Mouse lung vibratome slices were used for confocal live cell imaging of pulmonary NEBs. Short term (30s) perfusion with a hypo‐osmotic solution (230 mOsm) of lung slices loaded with the Ca2+ indicator Fluo‐4 showed a fast reversible Ca2+ rise in NEB cells, dependent on extracellular Ca2+, and a typical delayed activation of the shielding Clara‐like cells. All other airway epithelial cells, which in contrast to NEBs abundantly express hypo‐osmosensitive TRP channels, appeared to show a Ca2+ rise only at osmolarities lower than 200 mOsm, suggesting different signalling mechanisms.The first physiological evidence is provided for direct activation of NEBs by mild acute hypo‐osmotic stress that potentially mimics mechanical stimulation.Support: IWT fellowship SB/81162 (R.L); FWO grant G.0081.08 (D.A.); UA grants GOA BOF 2007 (D.A.) and KP BOF 2006 (I.B.)
ATP promotes Plasma Membrane Wound Repair by a P2Y2R dependent Mechanism
Authors: Belete Hewan A , Hubmayr Rolf D 
Published: June 2021

Cell wounding and repair are important drivers of the innate immune response of ventilator‐injured lungs. Cells repair plasma membrane (PM) wounds by several mechanisms including non‐secretory exocytosis and it is therefore not surprising that extra‐cellular ATP, a secretagogue, enhances PM repair. Neither the responsible purinergic receptor sub‐type nor the downstream signaling pathways have been identified.Expression of P2Y2R in A549 cells was validated by immunocytochemistry and immunoblot experiments using anti‐P2Y2R (Chemicon). Confluent A549 cells were incubated with the P2Y2 antagonist Suramin (400μM), ATP (50ìM) or ATP hydrolase Apyrase (20U/ml) and stretched by 30% at 8 cycles/min for 5 min. 2 min later, the cells were labeled with Propidium Iodide (PI; 4μl/ml), trypsinized and subjected to flow cytometry. PI + cells were considered wounded and necrotic. Pretreatment of A549 cells with Suramin showed a significantly higher fraction of PI + cells compared to controls (47 ± 9 % vs 22 ± 5%, p<0.05), while the addition of extracellular ATP appeared to promote PM wound repair (6± 1%, p<0.01). In contrast, pretreatment with apyrase did not significantly alter the number of necrotic cells (26 ± 6%)Our results suggest that ATP promotes PM wound repair by a P2Y2R dependent mechanism. The Apyrase data raises the possibility that ATP metabolites may also modulate PM repair.Support HL63178
Damage‐associated molecular pattern markers are triggered by pulmonary nanotube exposure
Authors: Herndon Betty L , Patel Aalok , Quinn Tim , Nalvarte‐Kostoryz Elisabet , Fibuch Eugene 
Published: June 2021

Nanoparticle exposure by accidental inhalation is increasing due to broad use in consumer and industrial products. We demonstrated a rapid eosinophilia following acute pulmonary exposure to long single wall carbon nanotubes (SWCNT). With the hypothesis that SWCNT are creating damage‐associated molecular patterns (DAMPs) in response to pulmonary exposure, 15 rats were intratracheally given either 50 μL surfactant containing 500 μg/mL SWCNT or surfactant. Sterility was determined by limulus lysate assay. Bronchoalveolar lavage (BAL), serum and tissue were harvested acutely (0.5 – 24 hr) or subchronically (1–4 wk). DAMP‐related proteins (high mobility box protein‐1 HMGB1 and heat shock protein‐70 HSP70), a receptor (RAGE), and TNFα were measured. BAL DAMP molecules and TNFα were elevated acutely vs subchronically (p=0.02) with HMGB1 and TNFα peaking at 30 min (34.7 and 36.7 pg/mL respectively, 4 times the surfactant controls). A robust lung tissue eosinophilia, 20 cells per field at 400x, was also seen at 30 min. RAGE receptors were widely upregulated in tissue as determined by immunostaining, strong at 24 hours. At 1–4 weeks granulomas were seen around particle clusters visible by light microscopy, and DAMP molecules and TNFα decreased in BAL to ~1/3 the acute titers. All markers increased again at 4 weeks, suggesting macrophage necrosis and secondary SWCNT release.Funding: St. Luke's Foundation, Kansas City
Transepithelial Ion Transport Properties of Human Native Small Airways
Authors: Shamsuddin A K M , Quinton Paul M 
Published: June 2021

Small airways are the crucial target in the pathogenesis of cystic fibrosis and other airway diseases. Characterization of transepithelial ion transport properties of small airways have been limited by their relative inaccessibility, mainly in native human tissue. We used our recently introduced micro‐Ussing chamber (area=1 mm2) to obtain the first measurements of ion transport properties of human native small airways specimens (<2 mm i.d.). Spontaneous open circuit transepithelial potentials (Vt), conductance (Gt) and equivalent short circuit current were measured. In presence of Cl− gradient Vt hyperpolarized and Gt decreased significantly. In symmetric NaCl, activating Cl− conductance with cAMP mediators (Fsk/IBMX) and purinergic agonist (UTP) evoked distinctly opposite effects on Vt, depolarizing and hyperpolarizing, respectively. Luminal amiloride depolarized Vt and decreased Gt significantly. Results suggest that human small airway epithelia express very high constitutively active Cl− conductance that support both secretory as well as absorptive functions. Small airways may consist of separate populations of secretory and absorptive cells that recycle airway surface fluids locally to maintain appropriate airway hydration and hygiene.Supported by the Nancy Olmsted Trust, NIH (R01‐HL084042) and American Lung Association California.
Inspiratory neural network complexity of unusual gasping patterns in urethane‐anesthetized neonatal rats
Authors: Salay Lindsey D , Reid Inefta M , Solomon Irene C 
Published: June 2021

Gasping is an autoresuscitative mechanism in response to anoxia, and unusual gasp patterns (i.e., two or three closely spaced successive gasps termed ‘doublet’ and ‘triplet’ gasps) have been observed in infants with sudden infant death syndrome (SIDS) and non‐SIDS conditions during agonal respiration. Previously, we identified doublet and triplet gasps in spontaneously breathing urethane‐anesthetized P0‐P12 neonatal rats in response to an anoxic challenge, and characterized the timing features associated with these bursts. Here, we evaluated the complexity of the central inspiratory neural network underlying these unusual gasping patterns using approximate entropy (ApEn) analysis. For these analyses, the neonatal rats were divided into two groups based on the marked difference in the number of doublet gasps. In P0‐P6 rats (n=12), ApEn decreased from baseline (BL) when compared to singlet (from 0.318±0.008 to 0.279±0.003; P<0.01), but not doublet or triplet gasps. In contrast, in P7‐P12 rats (n=7), ApEn decreased from BL when compared to singlet (from 0.355±0.009 to 0.242±0.004; P<0.01), doublet (P<0.01), and triplet gasps (P<0.01). These data suggest that while the central inspiratory neural network underlying singlet gasps may be unaffected by developmental age, the network underlying unusual gasping patterns appears to be differentially influenced by maturation.Supported by HL63175, NS049310
Is there diurnal variation with the vestibulosympathetic reflex?
Authors: Cook Jonathan S , Chin‐Sang Stephanie A , Sauder Charity L , Ray Chester A 
Published: June 2021

We previously observed that exogenous melatonin (3 mg) attenuates the vestibulosympathetic reflex (VSR) in humans (Cook and Ray, Clin Auton Res 19:303, 2009). Because melatonin exhibits a circadian rhythm in humans by increasing at night, it was hypothesized that the VSR would be attenuated at night compared to day. Melatonin typically increases 8–10 times over daytime concentrations during the late evening hours. To test this hypothesis, arterial blood pressure, heart rate, calf blood flow and muscle sympathetic nerve activity (MSNA) were measured in 9 healthy subjects (28 ± 1 yr; 5 male, 4 female) at rest and during head‐down rotation (HDR). Each subject was tested around noon and 10–12 hr later that evening (day: 11:34 ± 13 min, night: 22:10 ± 5 min). Subjects were instructed not to sleep between the two testing sessions. During the day, HDR elicited an increase of Δ 3 ± 1 bursts/min (P < 0.05) from baseline with a significant decrease in calf blood flow (Δ 26 ± 7%; P < 0.05). HDR did not elicit changes in heart rate and arterial blood pressure. Contrary to our hypothesis, MSNA and cardiovascular responses to HDR were not significantly altered at night compared to day (Δ 3 ± 1 bursts/min, Δ 25 ± 6%, for MSNA and calf blood flow, respectively). These findings indicate that there is no diurnal variation in the VSR in humans. Moreover, endogenous increases in melatonin do not appear to modulate the VSR.NIH HL077670, NASA Space Fellowship
An alternative method to the traditional NASA hindlimb suspension model in mice
Authors: Ferreira J Andries , Crissey Jacqueline M , Brown Marybeth 
Published: June 2021

Animal models are used to induce atrophy and to evaluate interventions. The Morey‐Holton hindlimb unloading (HU) method is widely accepted.PURPOSEEvaluate an alternative to the Morey‐Holton HU technique in mice.METHODSForty adult female mice were HU for 14 days with (n=24) or without (n=16) recovery. Ambulatory controls (n=49) were used for comparison. A thin stainless steel wire was passed through the intervertebral disc spaces between the 5th and 7th sacral vertebrae and shaped into a ring from which the mice were suspended. The vertebral location was selected to appropriately balance the animal's body weight but not interfere with defecation. Success of this novel hindlimb unloading technique was assessed by percent body weight lost during suspension, soleus atrophy and adrenal mass.RESULTSBody mass of the mice prior to HU (24.8 ± 3.8g) was not significantly different immediately after HU (23.8 ± 2.8g), or after 3 days recovery (24.7 ± 2.5g. Soleus mass declined (−35.6%) with HU (p<0.001. Adrenal gland weights did not significantlyCONCLUSIONThe new method allows for ease of tail examination during suspension; decreases the likelihood of cyanotic, inflamed, and/or necrotic tails frequently observed with tail‐taping; and of mice chewing the traction tape (and becoming unsuspended). This tail‐ring method also ensures rapid recovery following HU. Support HD058834, MU Life Sciences Fellowship.
Effect of High Intensity Interval Training (HIIT) on Substrate Utilization
Authors: Roberson Daniel W , Astorino Todd A , Allen Ryan P , Trost Emily , Jurancich Matthew 
Published: June 2021

High‐intensity interval training (HIIT) provides a powerful stimulus that elicits similar physiological changes, such as increased VO2max and fat utilization, as traditional endurance training. However, the majority of studies employing this training regimen have used sedentary subjects, so it is unknown if it is still effective in active individuals.PURPOSEThe primary aim of the study was to examine the effect of HIIT on substrate utilization in recreationally active men and women.METHODSTen men and women (mean age and physical activity equal to 25.7 ± 5.18 yr and 7.0 ± 2.8 h/wk, respectively) completed HIIT consisting of 6 d of training (4 – 6 Wingate tests per day) over 3 wk. They regularly participated in cardiovascular exercise, resistance training, and/or sports, yet none were athletes. VO2max was measured pre‐ and post‐HIIT on the cycle ergometer. Via indirect calorimetry, substrate utilization was evaluated pre‐ and post‐training during 30 min of cycle ergometry, consisting of three 10 min bouts at 50, 60, and 70 % maximal workload (Wmax). Respiratory Exchange Ratio (RER) was used to assess substrate utilization, with gas exchange data averaged every five minutes. Subjects came to the laboratory after a minimum 3 h fast. Data were analyzed using a two‐way ANOVA with repeated measures.RESULTSVO2max was increased by 6 % with HIIT. There was a significant effect (p < 0.05) of HIIT on substrate utilization across time. For example, at 25 minutes of exercise, RER post‐training was equal to 0.96 ± .04 versus 0.99 ± .05 at baseline, indicating a 10 % increase in fat utilization.CONCLUSIONData from this preliminary study reveal that HIIT significantly alters (p < 0.05) RER, in the form of increased fat utilization, in active men and women.
Cortisol response to an acute bout of static stretching
Authors: Fuller Scott Eric , Stewart Laura K 
Published: June 2021

PurposeThis study aimed to determine whether a single bout of static stretching affected salivary cortisol levels.MethodsUniversity students (n=22) were recruited to participate in the study. Participants were randomly assigned to a control group (n=9), or a stretching group (n=13). The stretching group underwent a series of five partner‐assisted stretches of the major muscle groups of the lower limb. Controls were subjected to a mock stretch in which the lower limb was moved by an investigator to a joint angle short of the point of discomfort. Before and immediately after stretching, saliva samples were collected by free expectoration for a duration of five minutes into a centrifuge tube. Saliva samples were then frozen at −80° C for later analysis by direct ELISA with a commercially available kit (ALPCO Diagnostics).ResultsStatistical analysis by 2‐way ANOVA with repeated measures revealed that the differences in pre‐ versus post‐stretch cortisol levels between the two groups were not significant (F = .01357, p = .9086). There was also no significant difference in mean salivary cortisol concentrations between the two groups in the pre‐ versus post‐stretch conditions (F= .19892, p = .6609).ConclusionThe data in the present study indicates that an acute bout of stretching does not induce significant changes in salivary cortisol concentrations.
Impaired hypoxic exercise vasodilation in older adults
Authors: Evans Trent Douglas , Blain Gregory , Limberg Jacqueline , Kiefer Adam , Sebranek Josh , Proctor Lester , Schrage William 
Published: June 2021

Research suggests exercise blood flow may be impaired in older adults. We hypothesized that forearm blood flow would be impaired during exercise in older subjects (64±3 years, n=10) compared to young controls (27±2 years, n=18), and that any impairment would be exaggerated under hypoxic conditions.We measured forearm blood flow (FBF, Doppler Ultrasound), blood pressure (BP, Finapress), and Hb saturation (pulse oximeter) while subjects performed dynamic forearm exercise (8 kg, 20 contractions/min) for 4 minutes in normoxic (~98% SaO2) and hypoxic (80% SaO2) conditions.BP was greater in older subjects than young controls (p<0.05), therefore FBF measures were normalized for perfusion pressure (FVC=FBF/BP). FVC was similar between groups at rest and steady‐state exercise in normoxia and hypoxia (p>0.05). FVC did not increase in either group from normoxia to hypoxia at rest (p>0.05). During hypoxic exercise, young subjects increased FVC from normoxic levels (p<0.05); older subjects did not (p>0.05).These preliminary results suggest that forearm exercise vasodilation is preserved in older adults under normoxic conditions, but impairments may exist when responding to hypoxia during exercise.Support: AFAR A08235, AHA 0815622G, APS UGSRF, NIH HL091397
Skeletal muscle metaboreflex overactivity is partially corrected by decreasing superoxide within the nucleus tractus solitarius of hypertensive rats
Authors: Murphy Megan N , Mizuno Masaki , Smith Scott A 
Published: June 2021

Studies suggest the skeletal muscle metaboreflex (SMM) is overactive in hypertension and contributes to the exaggerated mean arterial pressure (MAP) response to exercise in this disease. The mechanisms responsible for abnormal SMM activity remain undetermined. Afferent information generated by the SMM is processed within the nucleus tractus solitarius (NTS) of the brainstem. In normotensive Wistar‐Kyoto (WKY) rats, the production of nitric oxide (NO) within the NTS buffers SMM activity. However, in spontaneously hypertensive rats (SHR), the production of the NO scavenger superoxide is elevated in the NTS. Increased production of superoxide may reduce the amount of NO available to buffer SMM activity. Therefore, we hypothesized that decreasing superoxide in the NTS reduces SMM overactivity in hypertension. In decerebrate WKY and SHR, the SMM was activated by injecting capsaicin (0.3 μg/100 μL) in the arterial supply of hindlimb skeletal muscle before and after the dialysis of tempol (30μM; a superoxide oxide dismutase mimetic) in the NTS. In SHR, tempol significantly reduced the MAP response to SMM activation from 68±2 mmHg (before dialysis) to 46±4 mmHg (after dialysis). Tempol had little effect on the SMM‐mediated MAP response in WKY. The data suggest that reducing superoxide within the NTS can partially correct the exaggerated MAP response to activation of the SMM in hypertension.Supported by NIH HL‐088422
Oxytocin (OXT)‐immunoreactive axons closely appose tyrosine hydroxylase (TH)‐immunoreactive neurons in the rat nucleus of the solitary tract (NTS) and dorsal vagal motor (DMV) neurons that supply the gastrointestinal tract
Authors: Llewellyn‐Smith Ida J. , Travagli R. Alberto , Browning Kirsteen N 
Published: June 2021

It has long been known that catecholaminergic NTS neurons provide synaptic input to vagal preganglionic neurons of the DMV. Cholinergic and catecholaminergic DMV neurons, in turn, supply the motor innervation to the gastrointestinal tract, from the lower esophagus to the transverse colon Axons of paraventricular hypothalamic neurons release OXT that modulates DMV neurons via both pre‐ and postsynaptic sites of action. The aim of the present study was to investigate whether OXT inputs directly target DMV or NTS neurons. We used double (TH+OXT) and triple (TH+OXT+ChAT) immunoperoxidase labelling to determine whether OXT axons closely apposed catecholaminergic NTS and/or DMV neurons. We also assessed OXT input to DMV neurons retrogradely labelled with cholera toxin B subunit from the corpus or ileum. OXT axons were most numerous in the caudal DMV and in the lateral aspects of the rostral DMV, but were sparsely distributed in the NTS. Close appositions by OXT axons occurred on TH‐positive NTS neurons and DMV neurons, as well as on DMV neurons projecting to either the ileum or corpus. These results suggest a prominent role of OXT in controlling different subpopulations of neurons in the dorsal vagal complex circuitry that controls gut function.Support: NH&MRC of Australia and NIH grant DK55530
Effect of pyridostigmine on the sympathovagal balance and cardiac morphometry in heart failure
Authors: Lataro Renata M , Silva Carlos Alberto A , Prado Cibele M , Rossi Marcos A , Fazan Rubens , Salgado Helio C 
Published: June 2021

Sympathovagal balance and cardiac morphometry were evaluated in heart failure (HF) rats, 4 weeks after treatment with the reversible acetylcholinesterase inhibitor pyridostigmine (PYR). HF was produced by left coronary artery ligation under anesthesia. Conscious animals were equipped with catheters in the femoral artery and vein. Methyl atropine and propranolol were used to evaluate the sympathovagal balance and the intrinsic heart rate (IHR). In HF rats PYR reduced heart rate (Control: 335±5; HF: 388±11; HF+PYR: 347±4 bpm), increased vagal tone (Control: 92±13; HF: 40±8; HF+PYR: 107±9 bpm), reduced sympathetic tone (Control: 19±4; HF: 47±9; HF+PYR: 23±5 bpm) and did not change IHR (Control: 377±5; HF: 392±6; HF+PYR: 394±8 bpm) or cardiac/body weight ratio (Control: 2.9±0.1; HF: 3.5±0.1; HF+PYR: 3.6±0.1 mg/g). However, PYR reduced the diameter of the myocytes from the left ventricle (Control: 13.2±0.2; HF: 19.9±0.6; HF+PYR: 17.0±0.5 ìm). In conclusion, it was demonstrated that pyridostigmine increased cardiac vagal tone and reduced the sympathetic tone without changing the IHR of HF rats. In addition, PYR reduced the diameter of the myocytes from the left ventricle.Support: FAPESP, CNPq and CAPES.