bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACUTE EFFECT OF ALDOSTERONE ON THE MEMBRANE POTENTIAL IN NEURONS OF THE NUCLEUS OF THE SOLITARY TRACT
Authors: Menegaz Danusa , Karlen‐Amante Marlusa , Fazan Frederico Sassoli , Varanda Wamberto Antonio , Menani José Vanderlei , Zoccal Daniel Breseghello , de Almeida Colombari Debora Simões , Colombari Eduardo 
Published: April 2020

IntroductionA population of neurons in the nucleus of the solitary tract (NTS) expresses both the mineralocorticoid receptor (MR) and the enzyme 11β‐hydroxysteroid dehydrogenase type 2 (HSD2), making these neurons responsive to aldosterone, not to glucocorticoids. HSD2 neurons in the NTS contribute to the development of sodium appetite which is stimulated by a combination of body sodium deficiency and low blood volume, a condition that activates the renin‐angiotensin‐aldosterone system. The effect of aldosterone in the NTS to induce sodium appetite may involve non‐genomic mechanisms, independent of nuclear MR, gene transcription and protein synthesis.ObjectiveIn the present study, we investigated the acute effect of aldosterone on the membrane potential of NTS neurons in brainstem slices of rats.MethodologyMale Holtzman rats (150 to 250 g) were decapitated and the brainstem rapidly removed and submerged in ice‐cold artificial cerebrospinal fluid (aCSF) with osmolality of 300–310 mosmol/KgH2O and pH 7.4. Brainstem coronal slices were obtained and then placed in the recording chamber, which was continuously perfused with oxygenated aCSF with or without aldosterone at room temperature. Whole‐cell patch‐clamp recordings of NTS neurons were done in current‐clamp mode to measure the membrane potential. Data are shown as mean ± SEM, and statistical significance was determined by unpaired Student's t‐test using the GraphPad Prism software. Experimental protocols were approved by the Ethics Committee for Animal Care and Use (CEUA 13/2018).ResultsAldosterone (1 □M) caused cell depolarization and increased firing frequency of action potentials (0.8 ± 0.2 Hz, *** p < 0.001), in silent NTS neurons. Only 30% of the recorded neurons (6 of 20 neurons) showed a reversible depolarization in response to aldosterone and repolarization upon washout.ConclusionThe present results suggest that aldosterone, acting via non‐genomic mechanisms, can depolarize and increase the firing frequency of action potentials in NTS neurons in vitro. These cells (possibly HSD2 neurons) might be those involved in the development of sodium appetite induced by aldosterone.Support or Funding InformationFunding: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Dynamic Arm and Leg Exercise on Muscle Sympathetic Nerve Activity and Vascular Conductance in the Inactive Leg
Authors: Millar Philip J , King Trevor J , Incognito Anthony V , Lee Jordan B , Shepherd Andrew D , Cacoilo Joseph A , Slysz Joshua T , Burr Jamie F , Doherty Connor J 
Published: April 2020

The aim of this study was to comprehensively assess the effects of rhythmic handgrip (RHG), one‐leg cycling, and concurrent arm and leg exercise on muscle sympathetic nerve activity (MSNA) and vascular conductance responses in the inactive leg. Thirty‐five participants completed two study visits in a randomized order. During visit 1, hemodynamic (Finometer) and superficial femoral artery (SFA) blood flow (Doppler ultrasound) measurements were assessed at rest and during 3 min of RHG (1:1 duty cycle; 40% MVC), one‐leg cycling (17 ± 3% peak power output), and concurrent exercise at the same intensities. During visit 2, hemodynamic and MSNA (fibular nerve microneurography) measurements were acquired during the same exercise modes (MSNA; n=12). SFA blood flow and MSNA were both acquired in the inactive leg. Heart rate, blood pressure, cardiac output, and respiration rate increased during each exercise mode (all, P<0.0001), with the largest increases during concurrent exercise (all, P<0.006); no differences were detected between visit 1 and 2 (all, P>0.05). SFA mean blood flow increased during RHG (Δ24 ± 30 ml/min, P<0.0001) and concurrent exercise (Δ10 ± 38 ml/min, P=0.03) but not cycling (Δ2.3 ± 30 ml/min, P=0.9). SFA vascular conductance was unchanged during RHG (Δ0.02 ± 0.29 ml·min−1·mmHg−1, P=0.9) but reduced similarly during concurrent and cycling exercise (Δ−0.14 ± 0.33 ml·min−1·mmHg−1; Δ−0.14 ± 0.38 ml·min−1·mmHg−1, P<0.003). RHG increased MSNA burst frequency (Δ4 ± 8 burst/min, P=0.04) without altering burst amplitude (Δ7 ± 14 %, P=0.7) or total MSNA (Δ40 ± 40 %, P=0.07). In contrast, cycling and concurrent exercise had no effects on MSNA burst frequency (Δ−3 ± 6 burst/min and Δ4 ± 6 burst/min, P≥0.1) but increased burst amplitude (Δ34 ± 30 %; Δ31 ± 31 %, P≤0.001) and total MSNA (Δ59 ± 63 %; Δ94 ± 100 %, P≤0.007). In conclusion, during one‐leg cycling or concurrent exercise, reductions in inactive leg SFA vascular conductance occurred in parallel with increases in burst amplitude and total MSNA but not burst frequency. Exercise studies relying solely on measures of MSNA burst occurrence may not accurately reflect the corresponding changes in vascular conductance.Support or Funding InformationResearch was supported by a Natural Science and Engineering Research Council (NSERC) of Canada Discovery Grant (P.J.M; #06019), the Canada Foundation for Innovation (P.J.M.; #34379), and the Ontario Ministry of Research, Innovation, and Science (P.J.M. #34379).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Vanin‐1 as a novel biomarker for kidney injury for hydronephrosis
Authors: Hosohata Keiko 
Published: April 2020

Urinary tract obstruction and the subsequent development of hydronephrosis represent a common cause of kidney injury, resulting in chronic kidney disease. Neither currently used imaging techniques nor conventional laboratory parameters are sufficient to assess the onset of this condition. The purpose of the study was to assess whether vanin‐1 could be a novel renal biomarker in kidney injury due to hydronephrosis. Male Sprague‐Dawley rats were subjected to unilateral ureteric obstruction (UUO) or sham operation. For urinalysis, renal pelvic urine and voided urine were used for the UUO, and sham‐operated rats, respectively. Urinary vanin‐1 excretion was expressed as a vanin‐1/creatinine ratio. In addition to echographic images demonstrating time‐dependent accumulation of urine in the renal pelvis, histopathological renal tubular injuries became severe and renal fibrosis eventually developed. At day 7 after UUO, the vanin‐1 level in the renal pelvic urine was significantly higher than that in voided urine from the sham‐operated rats, and remained at the same level until day 14. Immunohistochemical staining of vanin‐1 in the renal cortices revealed that vanin‐1 expression was localized not only around the injured tubules, but also within a subset of injured tubules, but not in the area with interstitial fibrosis. Vanin‐1 mRNA and protein expression significantly decreased, whereas the expression of transforming growth factor (TGF)‐β1 and snail‐1, which plays a pivotal role in the pathogenesis of renal fibrosis via the epithelial‐to‐mesenchymal transition (EMT), increased. These results suggest that vanin‐1 in the renal pelvic urine is released from the renal tubular cells in UUO rats and reflects renal tubular injury at an early stage. Hydronephrosis always involves incomplete obstruction, and urinary vanin‐1 may serve as a candidate biomarker of renal tubular injury due to hydronephrosis.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Metabolism of Glycolate to Oxalate in Kidney Proximal Tubule Cells
Authors: Fargue Sonia 
Published: April 2020

BackgroundExcessive synthesis of oxalate is a hallmark of the inherited kidney stones disease primary hyperoxaluria. Evidence indicates that the liver is the main site of oxalate synthesis but that other tissues may also contribute up to 20%. Glycolate is one of the precursors of oxalate and both plasma and urine glycolate are elevated alongside oxalate in primary hyperoxaluria type 1, the most frequent and severe of PH types. New therapeutic strategies in PH1 further increase glycolate levels by inhibiting a liver‐specific enzyme, hydroxyacid oxidase 1 (HAO1), which catalyzes the oxidation of glycolate to glyoxylate, a precursor of oxalate. To examine whether kidneys contribute to oxalate synthesis, the metabolism of glycolate was studied in human and mouse kidney cell lines and tissue.MethodsTissue culture cells derived from human proximal tubule (HK2 cells) and mouse collecting duct (mIMCD cells) lineages were incubated with 13C2‐labeled glycolate (0 – 10mM) for up to 24 hours. Kidney tissue incubations with 13C2‐glycolate were performed on mouse kidneys and human surgical kidney remnants, by isolating and digesting cortical and medullary tissue fragments. The amount of 13C2‐labeled oxalate synthesized by the cells (and released in the media) was measured by ion chromatography coupled with mass spectrometry and normalized to total cell protein.ResultsMetabolism of glycolate to oxalate was observed in proximal tubule cells (HK2) in as little a time as 3 hours and with concentrations as low as 500 uM in contrast to cells isolated from the medulla and collecting duct (mIMCD). The synthesis of oxalate was also observed in human and mouse kidney cortical tissue but not medullary tissue. The involvement of the intermediate metabolite glyoxylate was suggested by the higher oxalate synthesis observed in the glyoxylate reductase knock‐out mouse model of PH type 2.ConclusionRenal cells, in particular proximal tubule cells, are equipped to metabolize glycolate to glyoxylate and oxalate. The time and dose dependence of glycolate to oxalate metabolism is compatible with an enzymatic pathway. The role of the candidate enzyme hydroxyacid oxidase 2, an isoenzyme of HAO1 and which is expressed in the proximal tubule, is currently being investigated.Support or Funding InformationNIH NIDDK K01DK114332This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Structural mechanism of vaccinia virus protein C6 mediated inactivation of transcription factors IRF3 and IRF7 via inhibition of TBK1 mediated scaffold protein‐protein interactions
Authors: Chakraborty Sayan , Xu Guozhou 
Published: April 2020

Interferons (IFNs) are signaling proteins with potent antiviral and immune stimulatory effects. IFN signaling is initiated after host cell pattern recognition receptors (PRRs) recognize pathogen‐associated molecular patterns (PAMPs) present in many viral proteins. This event in turn generates a complex signaling cascade involving numerous proteins, activation of various transcription factors (TF), such as IFN‐regulatory factors (IRF) 3 and 7. These TFs subsequently translocate to the nucleus to elevate the transcription of type I IFNs, cytokines, and chemokines. Viruses such as Vaccinia virus (VACV) have evolved many strategies to interfere with the IFNs or their mechanism of action. Specifically, VACV encodes a small 16kDa protein, C6, that inhibits the activation of IRF3/7 via binding with an upstream kinase, TBK1, and its adaptor proteins TANK, NAP1, and SINTBAD in order to interfere with the production of IFNβ. Binding with these adaptor proteins, C6 prevents TBK1/IKKɛ‐dependent activation of IRF3 and IRF7 allowing VACV to evade immune recognition. To elucidate the structural mechanism of how C6 mediated inhibition of these adaptor protein/TBK1 interactions can block the activation of IRF3 and IRF7, we have chosen C6 and TANK as canonical binding partners. We have identified the binding regions between C6 and TANK by utilizing co‐expression/co‐purification studies of C6 and TANK proteins, and co‐crystallization trials are ongoing. The immune evasive strategy exploited by VACV can be used to develop novel therapies, such as C6 mimetics to provide TBK1 inhibition. The development of therapeutics depends immensely on a detailed structural analysis of the interactions between C6 and adaptor proteins. Our structural studies of C6 and TBK1 adaptor proteins will provide useful insights in developing superior therapies against malignancies, infectious diseases, and autoimmune disorders.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impacts of a Balanced Omega 6:3 Diet on Fatty Acid Deposition in White and Brown Adipose Tissue and Circulating Plasma in the Hibernating Arctic Ground Squirrel
Authors: Rice Sarah , Mikes Monica , Drew Kelly , Bibus Doug 
Published: April 2020

Hibernators, such as arctic ground squirrels (AGS), fuel the majority of all their metabolic needs from fat deposits through the hibernation season (Dark 2005). Natural fatty acid profiles of free‐ranging AGS have omega 6:3 ratios close to 1:1, showing a far higher consumption of omega 3 fatty acids than captive animals, fed a standard Mazuri rodent chow (which have omega 6:3 ratios close to 8:1). Specific concentrations of omega 6 polyunsaturated fatty acids (PUFAs) enhance hibernation (Frank 2008) and absence of essential fatty acids reduce time in torpor (Florant 1993). To our knowledge, only three studies have investigated the impact of omega 3s on hibernation physiology (Giroud 2018, Frank 2004, and Hill and Florant 2000). In other species, high consumption of omega 3 fatty acids show dose‐dependent lowering of serum triglycerides with other health benefits (Balk 2006). How increased consumption of omega 3 fatty acids impact brown adipose tissue deposition and fatty acid profiles in tissue and serum related to storage and utilization in hibernating AGS is unknown.A group of wild juvenile AGS (female=12, male=12) were fed either a test diet, with an omega 6:3 ratio of 1.3:1, or a standard chow control diet, with an omega 6:3 ratio of 8:1, from mid‐July (after trapping and quarantine) till animals entered hibernation (August–September). Tissues were collected mid‐December at three specific physiological states of hibernation: early torpor, late torpor and arousal. Total lipid fatty acid profiles of plasma, brown adipose and white adipose tissue were quantified by GC analysis. Axillar brown adipose tissue was dissected and weighed.Preliminary results show a significant increase in axillar brown adipose tissue mass in the omega 6:3 balanced diet animals (p<0.038). Preliminary data also indicates increased percentages of circulating levels of polyunsaturated fatty acids in plasma of hibernating AGS compared to summer or fall animals (p<0.01). Full fatty acid analysis is pending.In conclusion, our preliminary results indicate a balanced diet of omega 6:3 (1:3:1) in hibernating Arctic Ground Squirrels may enhance brown adipose tissue deposition.Support or Funding InformationThis work was supported by NIH 20GM103395, UL1GM118991, TL4GM118992, or RL5GM118990. This work was performed in conformance with the FASEB Statement of Principles for animals used in research.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Kinetics of Reactive Oxygen Species and Total Antioxidant Capacity during Moderate Treadmill Running after 8 Weeks of Endurance Training
Authors: Yoon Aram , Hughley Timothy , Williams Richard H. 
Published: April 2020

The purpose of this study is to investigate the effect of aerobic exercise intensity on the kinetics of reactive oxygen species and total antioxidant capacity during the moderate intensity of treadmill running. Twelve healthy collegiate male students participated and were randomly divided into two groups. Each group of subjects trained at 80% and 50% HRmax respectively for 30 min per session, 3 times per week for 8 weeks. After 48 hours of the training session, treadmill running task was imposed on each group at 70% of VO2max for 90 minutes. Metabolic data were monitored using a gas analysis system. Blood samples were taken from the finger before exercise and after 30 minutes, 60 minutes, and 90 minutes of exercise for measuring the blood lactate, derivatives of Reactive Oxygen Metabolites (d‐ROM), and biological antioxidant potential (BAP). All data were analyzed by two‐way ANOVA of SPSS 18.0. The differences between pre and post training were significant in d‐ROM and BAP (p<.05). The changes of d‐ROM were significantly increased by aerobic training, and there were significant differences among exercise durations (p<.05). The changes of BAP were not significantly different between training intensity groups, and there were significant differences among exercise durations (p<.05). As shown above, the occurrence of d‐ROM and BAP were altered by training intensity and exercise duration. In other words, the occurrence of reactive oxygen by high intensive training was abundant and there were significant changes in 30 minutes of exercise based on exercise duration. On the other hand, there were significant changes in total antioxidant capacity in 60 minutes of exercise based on exercise duration. In conclusion, low‐intensity training and within 60 minutes of exercise might be suitable in the point of defending the cellular damage caused by exercise.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
ECG Assessment of Cardiac Function Before, During, and After a 1 km Swim
Authors: Wilson Ted , Bergen Silas R. , Johnson Bruce D. , Harrison Micheal F. 
Published: April 2020

Assessments of electrocardiographic (ECG) responses during swimming activities are impossible without mobile waterproof recording units and rarely completed. This preliminary study characterized changes in the ventricular diastolic, PR‐, QT‐, and RR‐intervals that occurred during a 1 km indoor swim in 78°F water with a waterproof Actiwave ECG recording system (CamNtech Inc., Boerne, TX) and the .epf data files were analyzed with software from ADInstruments Inc. (Colorado Springs CO). Values within times expressed as mean ± SE with significance evaluated using ANOVA and repeated measures. Competitive club swimmers (3 male, 1 female) with an age, height, and weight of 51 ± 3 years, 175 ± 4 cm, and 83 ± 8 kg, with a BMI of 27 ± 2 completed the 1 km swim (44 laps × 75 foot laps) using a standard crawl in 17.9 ± 1.3 minutes using 10.5 ± 0.50 arm cycles/second. A continuous ECG with waveform was obtained and measurements were performed 120 and 30 seconds before swim, during the swim (at end of lap‐1, ‐22 and ‐43), and at 30 and 300 seconds post‐completion. Heart rate (from RR‐interval) −120, and −30 seconds prior to the swim, at end of swim lap 1, 22 and 43, and during recovery 30 and 300 seconds post swim was 68 ± 5, 73 ± 6, 107 ± 3, 142 ± 4, 147 ± 5, 132 ± 8 and 89 ± 3 beats/minute (P<0.0001). Respective QT‐intervals were 392 ± 14, 374 ± 13, 307 ± 38, 259 ± 15, 254 ± 2, 255 ± 14, and 338 ± 6 msec (n = 2 at lap‐1, and n = 3 at lap‐22) (P<0.0001). Respective ventricular diastole time was 509 ± 61, 468 ± 61, 253 ± 45, 166 ± 10, 166 ± 7, 204 ± 25 and 339 ± 26 msec (P<0.0001). Respective PR‐Intervals were 130 ± 12, 127 ± 12, 111 ± 18, 111 ± 2, 105 ± 14, 107 ± 15 and 125 ± 18 msec (P<0.094). Heart rate increased and duration of ventricular diastole decreased between lap 1 and 22, and was relatively stable between lap 22 and the end of lap 43. This study determined that with appropriate waterproof equipment a continuous ECG record can be collected from swimming athletes and used to provide an accurate assessment swim‐associated changes in cardiac function.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intrathecal Morphine versus Intrathecal Hydromorphone for Analgesia after Cesarean Delivery
Authors: Sharpe Emily E. , Molitor Rochelle J. , Arendt Katherine W. , Torbenson Vanessa E. , Olsen David A. , Johnson Rebecca L. , Schroeder Darrell R. , Jacob Adam K. , Niesen Adam D. , Sviggum Hans P. 
Published: April 2020

Abstract

Background
Intrathecal opioids are routinely administered during spinal anesthesia for postcesarean analgesia. The effectiveness of intrathecal morphine for postcesarean analgesia is well established, and the use of intrathecal hydromorphone is growing. No prospective studies have compared the effectiveness of equipotent doses of intrathecal morphine versus intrathecal hydromorphone as part of a multimodal analgesic regimen for postcesarean analgesia. The authors hypothesized that intrathecal morphine would result in superior analgesia compared with intrathecal hydromorphone 24 h after delivery.

Methods
In this single-center, double-blinded, randomized trial, 138 parturients undergoing scheduled cesarean delivery were randomized to receive 150 µg of intrathecal morphine or 75 µg of intrathecal hydromorphone as part of a primary spinal anesthetic and multimodal analgesic regimen; 134 parturients were included in the analysis. The primary outcome was the numerical rating scale score for pain with movement 24 h after delivery. Static and dynamic pain scores, nausea, pruritus, degree of sedation, and patient satisfaction were assessed every 6 h for 36 h postpartum. Total opioid consumption was recorded.

Results
There was no significant difference in pain scores with movement at 24 h (intrathecal hydromorphone median [25th, 75th] 4 [3, 5] and intrathecal morphine 3 [2, 4.5]) or at any time point (estimated difference, 0.5; 95% CI, 0 to 1; P = 0.139). Opioid received in the first 24 h did not differ between groups (median [25th, 75th] oral morphine milligram equivalents for intrathecal hydromorphone 30 [7.5, 45.06] vs. intrathecal morphine 22.5 [14.0, 37.5], P = 0.769). From Kaplan–Meier analysis, the median time to first opioid request was 5.4 h for hydromorphone and 12.1 h for morphine (log-rank test P = 0.200).

Conclusions
Although the hypothesis was that intrathecal morphine would provide superior analgesia to intrathecal hydromorphone, the results did not confirm this. At the doses studied, both intrathecal morphine and intrathecal hydromorphone provide effective postcesarean analgesia when combined with a multimodal analgesia regimen.

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