bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of FcRn in Monoclonal Antibody Serum Uptake from the Intestine in Suckling Rat Pups
Authors: Cooper Philip R , Kliwinski Connie , Perkinson Robert , Mabus John , Giles‐Komar Jill , Hornby Pamela 
Published: June 2021

The neonatal Fc Receptor (FcRn) in intestinal epithelium is the primary mechanism for transfer of maternal immunoglobulin G (IgG) from suckled milk to serum, but the factors contributing to this rapid uptake are poorly understood. Therefore, the pharmacological characteristics of IgG monoclonal antibody (mAb) and its interactions with FcRn in the intestinal environment in rats were investigated.Binding affinities to rat FcRn at pH 6.0 and off‐rates of pre‐bound mAb wild type (WT) and variants at pH 7.4 were determined. In anesthetized rats, systemic levels of human (h)IgG were determined after regional intestinal delivery of hIgG variants. Quantification of full‐length mAb in serum, rat FcRn mRNA expression in regions of intestine, and mAb epithelial localization was measured.High serum levels of hIgG were detected 90 min after duodenal delivery in 2‐week, but not 4–8 week old rats. Serum levels of variants correlated with off‐rates, not FcRn affinity. Serum levels of WT mAb, administered to different regions of intestine, correlated with rFcRn mRNA regional expression.The suckling rat pup intestine is an ideal mechanistic model of FcRn‐IgG mediated transcytosis. While binding affinity to FcRn is important for obtaining serum levels, a variant with a faster off‐rate at pH 7.4 than WT resulted in greater serum levels.
A single bout of aerobic exercise prevents the transient endothelial dysfunction induced by mental stress in men with metabolic syndrome
Authors: Sales Allan Robson Kluser , Fernandes Igor A , Rocha Natalia G , Garcia Vinicius P , Costa Lucas S , Silva Bruno M , da Nóbrega Antonio C L 
Published: June 2021

Mental stress induces transient endothelial dysfunction and the association with metabolic syndrome (MetS) may increase the risk for the development of atherosclerosis. Given the beneficial impact of exercise on endothelium function, we hypothesized that a single session of aerobic exercise would prevent the endothelial dysfunction induced by mental stress in men with MetS. Thus, 14 men with MetS (36 ± 4 yrs) initially had their endothelial function assessed through the flow‐mediated dilation (FMD) of the brachial artery (Doppler ultrasound). Subjects were then submitted to a mental stress test (Stroop color), which was followed by either 40 min of leg cycling exercise (80% of the anaerobic threshold) or no exercise in two different sessions. FMD was performed again at 30 and 60 min after exercise (EX) or control (CT), with a mental stress stimulus in between. Mental stress reduced FMD at 30 and 60 min (baseline: 7.7 ± 1.0%; 30 min: 5.0 ± 0.9%; 60min: 3.8 ± 0.8%; p < 0.05) in the CT, whereas EX prevented the endothelial dysfunction caused by mental stress (baseline: 7.4 ± 0.9%; 30 min: 6.2 ± 1.0%; 60 min: 9.3 ± 1.1%; p >; 0.05). In a subgroup (n = 3) where mental stress was not performed, FMD increased at 60 min after the exercise, while no changes were observed in the CT. In conclusion, a single aerobic exercise session prevented the mental stress‐induced endothelial dysfunction in men with MetS.Supported by FAPERJ, FINEP and CNPq.
Pulmonary vascular reactivity with ageing
Authors: Pugh Keith , Balanos George 
Published: June 2021

Sleep apnoea (SA) and pulmonary hypertension are closely linked and SA is also a common condition in older people. It is possible that if ageing is associated with greater hypoxic pulmonary vasoconstriction (HPV) older SA patients could be at greater risk of developing pulmonary hypertension because of repeated intermittent hypoxia.6 young and 6 older participants (mean age ± S.D = 20.4 ± 0.5 and 56.5 ± 2.6 years, respectively) undertook two protocols. A hypoxia protocol consisted of 5 min isocapnic euoxia (PETO2 = 100 mmHg, PETCO2 = 1 mmHg >; normal) followed by 20 min isocapnic hypoxia (PETO2 = 50 mmHg, PETCO2 = 1 mmHg >; normal), followed by a further 5 min isocapnic euoxia. A control protocol consisted of 30 min isocapnic euoxia. During both protocols pulmonary artery pressure (PAP) and cardiac output were measured continuously using Doppler echocardiography.Baseline PAP was greater in older participants (21.6 ± 0.7 mmHg vs. 19.2 ± 1.1 mmHg, p <0.05). During hypoxia PAP rose more in older participants than in younger (13.3 ± 1.3 mmHg vs. 8.3 ± 1.0 mmHg, respectively, p<0.001). Cardiac output was similar between the two groups (p>;0.05). All data are mean ± SEM.Our results support the hypothesis that HPV is more pronounced in older people. A greater HPV response to intermittent hypoxia during the night could play a role in the development of pulmonary hypertension in older SA patients.
Transient receptor potential channels (TRPC) contribute to an enhanced endothelial cell proliferation and irreversible vascular remodeling associated with the development of pulmonary arterial hypertension (PAH)
Authors: Sundivakkam Premanand , Tang Haiyang , Fernandez Ruby , Drennan Abigail , Yuan Jason X.‐J. 
Published: June 2021

Disordered pulmonary arterial endothelial cell (PAEC) growth underlies the formation of angio‐proliferation and intimal lesions, obliterating the small pulmonary arteries (PAs), resulting in irreversible structural alterations, or pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) patients.ObjectiveTo demonstrate that transient receptor potential channel (TRPC6) contributes to PAEC proliferation and in the development of PAH.ResultsPAEC isolated from Idiopathic PAH (IPAH) patients showed an enhanced VEGF‐induced [Ca2+]cyt and proliferation. In parallel, TRPC6 (mRNA and protein) expression was markedly up regulated in IPAH compared to normal subjects. Interestingly, knockdown of TRPC6 in IPAH‐PAEC using siRNA significantly attenuated VEGF‐induced rise in [Ca2+]cyt and proliferation. Deletion of either TRPC6 (TRPC6−/−) or TRPC4 (TRPC4−/−) abolished thapsigargin‐induced store Ca2+ release‐activated Ca2+ entry (SOCE) in mice PAEC. In addition, TRPC6−/− mice showed significant abrogation of hypoxia‐induced changes in the right ventricular systolic pressure and right ventricular hypertrophy suggesting its role in vascular remodeling associated with PAH.ConclusionOur studies provide a comprehensive picture of TRPC6‐mediated Ca2+ entry mechanisms in contributing to an increased PAEC proliferation and vascular remodeling associated with PAH.
Loud sound induced hearing loss is prevented by methylene blue
Authors: Wilson Teresa M , Omelcheko Irina , Foster Sarah , Nuttall Alfred L 
Published: June 2021

RationaleMethylene blue (MB), a powerful synthetic redox compound that readily crosses the blood‐brain barrier, is currently in use as a treatment for methemoglobinemia and is being examined as a treatment for other human ailments including Alzheimer's disease. MB. In low doses, MB acts as an electron cycler in the mitochondrial electron transport chain facilitating oxidative respiration and greatly reducing superoxide production. Additionally, MB has been shown to directly inhibit the activity of both inducible and constitutive forms of nitric oxide synthetase (NOS).ObjectiveTo determine whether MB can protect against noise induced hearing loss.Methods and ResultsMale CBA/CaJ (8 weeks old) mice (n=5/group) were injected with MB (0.5 mg/kg IP) or water at 24 and 1 hr prior to exposure to the moderately damaging noise level of 110 dB SPL, 4–45 kHz for 3 hrs. At 1 and 2 weeks, Auditory Brain Stem Response and Distortion Product Otoacoustic Emission were measured. The effect of MB on NOS and NADPH oxidase activities was also measured. The results revealed that prior treatment with MB provided significant protection against noise induced hearing loss across all measured frequencies and greatly reduced reactive free radical production.ConclusionHere, we show that low dose MB can prevent hearing loss due to loud sound exposure.Supported by grants 5R01DC000105 (ALN) and P30DC005983.
Pulmonary functions in different phases of menstrual cycle
Authors: Saperova Elena , Dimitriev Dmitry 
Published: June 2021

The purpose of the present study was to evaluate the influence of the normal menstrual cycle on respiratory parameters.Material and methodsNineteen healthy regularly cycling woman (age 20–25 years) kept daily records of lung function parameters during the follicular phase (FP) and luteal phase (LP) over three menstrual cycles.ResultsTidal volume was significantly higher during the LP (0.583±0.017) compared to the FP (0.530±0.015; Mann‐Whitney test (U)=5181.00; p=0.008). Minute ventilation showed the same pattern, being significantly higher during the LP compared with the FP (11.47±0.42 vs 9.82±0.32; U=4801.00; p=0.0007). Peak expiratory flow was significantly higher in LP (6.70±0.08) than in the FP (6.43±0.09; U=5381.50; p=0.026). Breath rate also vas higher during the LP than that during the FP (19.58±0.39 vs 18.42±0.33; U=5342.00; p=0.043). Forced vital capacity, forced expiratory volume in one s, forced expired flow from 25–75% of FVC, forced expired flow at 25%, 50%, 75% of FVC and maximal voluntary ventilation were not different between the cycle phases. In conclusion, lung function changes were found during menstrual cycles in healthy women.ConclusionThe luteal increase in lung function parameters suggests a possible role for progesterone or other endogenous sex hormones in stimulating the respiratory drive, either centrally or through the peripheral chemoreceptors or by both.
Exercise pulmonary gas exchange differentiates type and severity of pulmonary hypertension in heart failure
Authors: Smetana Michael Robert , Taylor Bryan , Frantz Robert , O'Malley Kathy , Johnson Bruce 
Published: June 2021

BackgroundHeart failure (HF) is associated with impaired exercise pulmonary gas exchange (PGX) that is likely related to the development and severity of pulmonary hypertension (PH).PurposeTo determine whether PGX measures differentiate HF patients with reactive PH from patients with passive PH or no PH.Methods/ResultsPulmonary arterial pressure (PAP), pulmonary wedge pressure (PWP), transpulmonary pressure gradient (TPG) and PGX indices [end‐tidal CO2 (PETCO2), ventilatory efficiency (VE/VCO2), O2pulse, estimated pulmonary arterial capacitance (GXCAP)] were assessed simultaneously at rest and during cycle exercise in 38 HF patients undergoing right heart catheterization. Post hemodynamic evaluation, patients were classified as having no PH (n = 12), passive PH (n = 10) or reactive PH (n = 16). TPG increased during exercise in all groups but was greater at end exercise in the reactive PH vs. the passive PH and no PH patients (21±9 vs. 14±7 vs. 12±7 mmHg). At an equivalent VO2, PETCO2, O2pulse and GXCAP were higher and VE/VCO2 ratio lower in the no PH and, to a lesser extent, in the passive PH vs. the reactive PH subjects (Figure 1).ConclusionNoninvasive measures of PGX during exercise appear to differentiate HF patients with reactive PH from patients with passive PH or no PH and may be a useful adjunct to invasive catheterization in assessing PH type and severity. HL71478, AHA12POST12070084, Gilead Science
The influence of combined lower body negative pressure and mental stress on cerebral blood flow in men and women
Authors: Young Angelea H. , Strong Chelsea R. , Cooke William H. , Carter Jason R. , Durocher John J. 
Published: June 2021

Lower body negative pressure (LBNP) decreases mean middle cerebral blood velocity (MCAv) and mental stress (MS) typically increases MCAv, but the MCAv response to these combined autonomic stressors is unknown. We hypothesized that performing MS during LBNP would result in an additive MCAv interaction. Eighteen participants (9 men, 9 women) completed three randomized trials: 1) 3 min LBNP (−40 mmHg), 2) 3 min MS (serial subtraction), and 3) combined LBNP and MS. Mean arterial pressure (MAP), heart rate (HR) and MCAv were continuously measured. Baseline MAP (81±2 vs. 80±1 vs. 80±1 mmHg) and HR (65±2 vs. 64±2 vs. 65±2 beats/min) were similar preceding each trial. LBNP significantly (p<0.05) decreased MCAv (Δ−3±1 cm/s), but did not alter MAP or HR. MS significantly (p<0.05) increased MAP (Δ10±1 mmHg), HR (Δ17±2 beats/min) and MCAv (Δ3±1 cm/s; p=0.05). Combined LBNP and MS significantly (P<0.05) increased MAP (Δ7±3 mmHg) and HR (Δ18±4 beats/min) and significantly decreased MCAv (Δ−5±2 cm/s). Increases in MAP and HR were similar during the combination trial when compared to the calculated sum of the individual trials. However, the MCAv (Δ−5±2 vs. Δ0±2 cm/s) response was blunted during the combination trial vs. the sum of individual trials. In conclusion, our findings are contrary to our hypothesis and suggest there is not an additive MCAv interaction during combined cognitive and orthostatic stress.Supported by NASA.
Perinatal inflammation and oxidative stress induce fetal cardiac dysfunction
Authors: Velten Markus , Gorr Matthew W , Youtz Dane Y , Velten Christina , Rogers Lynette K , Wold Loren E 
Published: June 2021

BackgroundEpidemiological data suggest that maternal inflammation contributes to intrauterine growth restriction, preterm birth, and adult‐onset cardiovascular diseases.ObjectiveWe hypothesize that perinatal inflammation and oxidative stress may induce discernible alterations in cardiomyocyte contractility and calcium signaling, causing cardiac dysfunction in the absence of subsequent risk factors.MethodsPregnant C3H/HeN mice were LPS or saline injected on embryonic day 16. Offspring were placed in room air or 85% O2 for 14 days. In vivo echocardiography, in vitro cardiomyocyte function, protein, and RNA analyses were performed.Main ResultsLPS/O2 exposed mice exhibited a compromised LV function and decrease in myocyte peak shortening and time‐to‐90% peak shortening. β‐MHC protein levels were increased and calcium transient amplitude was greatest in LPS/O2 mice, a pattern observed in humans and animal models of heart failure. SERCA2a RNA and protein levels were increased and phospholamban mRNA levels were decreased in LPS/O2 mice, a pattern observed during fetal development. Phosphorylation of phospholamban was increased, along with Sorcin mRNA levels.ConclusionsMaternal inflammation and neonatal oxidative stress resulted in impaired cardiac contractility consistent with heart failure, with the fetal cardiac phenotype persistent during the postnatal stage.
Effects of Chronic Green Tea (GT) or Green Tea Extract (GTE) treatment in cardiovascular function in Hypertensive Rats.
Authors: Garcia Michelle Louvaes , Nishi Erika E , Lincevicius Gisele S , Veiga Glaucia R L , Pontes Roberto B , Campos Ruy R , Oyama Lila , Bergamaschi Cassia T 
Published: June 2021

To evaluate the effects of GT and purified GTE treatment in hypertension, male Wistar rats were treated orally for 2 weeks with L‐Name, 20 mg/Kg/day). By the end of the first week of treatment, the animals were divided in: L‐Name treated; L‐Name + GT (9,6g/L) and L‐Name + GTE (20 mg/Kg/day). The same treatment was performed in control normotensive animals. By the end of treatment period blood pressure (BP) and heart rate (HR) were directly measured. Baroreflex sensitivity was evaluated by changes in BP elicited by IV infusion of phenylephrine or sodium nitroprusside and reflex HR responses. Water/tea ingestion and urinary volume were also evaluated for 24h. L‐Name treated rats (188±11 mmHg) had a significant increase in BP compared to control group (103±5 mmHg) and treatment with GT (123±6 mmHg) or GTE (132±2 mmHg) promoted a significant reduction in this parameter. It was also observed an improvement in baroreflex sensitivity in treated rats. There was no statistically difference among groups in urinary or intake volume. Treatment with GT and GTE presented an important antihypertensive effect associated with improvement in baroreflex control, and independently of a diuretic effect.Supported by CAPES and Cnpq.
The relationship between peripheral endothelial function and cerebrovascular reactivity to CO2 in older adults
Authors: Brar Ikdip , Robertson Andrew , Hughson Richard L 
Published: June 2021

Reduced cerebrovascular reactivity to CO2 contributes to a higher risk of cerebrovascular events. Studies on healthy and hypertensive middle‐aged adults have suggested the involvement of nitric oxide in CO2 reactivity based on the relationship observed with peripheral reactive hyperemia. We tested the hypothesis that hyper‐and hypocapnic reactivity is correlated with peripheral vascular endothelial function assessed by flow‐mediated dilation (FMD) in healthy older adults.MethodsBlood pressure, heart rate, end‐tidal PCO2, middle cerebral artery blood flow velocity (CBFV), as well as brachial artery diameter and shear rate, were monitored in 31 individuals (18 women; 72 ± 5 yrs). CO2 reactivity was assessed by the relative change in CBFV during hypercapnia (5% CO2, 21% O2) and hypocapnia (mild hyperventilation). Peripheral vascular function was measured by the relative brachial artery dilation after 5 min of forearm ischemia.ResultsNon‐parametric analyses suggested a possible relationship between cerebral and peripheral vascular function, such that a trend was observed between cerebrovascular reactivity and FMD in the hypocapnic range (rs=0.284, p=0.1), but not the hypercapnic range (rs=−0.22, p>;0.1).ConclusionOur study suggests only a weak relationship between peripheral endothelial function and reactivity to hypocapnia in older adults free of cardiovascular disease. Funded by CIHR.
A novel method to detect in vivo oxidant production reveals microvascular endothelial dysfunction linked to NADPH oxidase in obese human skeletal muscle
Authors: La Favor Justin D , Anderson Ethan J , Hickner Robert C 
Published: June 2021

Excessive production of reactive oxygen species (ROS) contributes to the development of endothelial dysfunction and progression of vascular diseases that are observed in obesity. Three microdialysis probes were inserted into the vastus lateralis of young, sedentary lean (LN; n=7), overweight (OW; n=8) and obese (OB; n=7) individuals, allowing sampling of extracellular fluid. To measure extracellular ROS, probes were perfused with saline containing 5 mM ethanol, 100 μM Amplex Ultrared, 1 U/ml horseradish peroxidase, and 10 U/ml superoxide dismutase, with or without 300 μM apocynin (Apo; an NADPH oxidase inhibitor). Dialysate fluorescence was measured at the outlet. Endothelial function was assessed with addition of acetylcholine (ACh) to the perfusate, with local blood flow calculated from the ethanol outflow:inflow ratio. Extracellular ROS was elevated in OB 3.2‐fold over OW, and 5.6‐fold over LN (p < 0.05), which was prevented by Apo (p < 0.01). ACh‐stimulated blood flow was depressed 60% in OB vs. OW, and 68% vs. LN (p = 0.01). Apo augmented ACh‐stimulated blood flow only in OB (p = 0.02). Microvascular endothelial dysfunction was evident in OB, which was largely reversed by NADPH oxidase inhibition. It can be concluded that the substantial elevation in ROS in OB was predominantly driven by NADPH oxidase.Supported by a doctoral student grant from the American College of Sports Medicine.
Association between Cerebral tissue Structural Integrity and Dynamic Cerebral Autoregulation in Elderly Individuals
Authors: Purkayastha Sushmita , Fadar Otite , Mehregan Aujan , Lipsitz Lewis A , Sorond Farzaneh A 
Published: June 2021

ObjectiveCerebral white matter hyperintensity (WMH) is prevalent in the elderly population and is associated with hypoperfusion and ischemia presumably due to altered cerebral autoregulation (CA). Our study sought to examine the association between cerebral white matter structural integrity and dynamic CA in elderly individuals.MethodsFifty‐three subjects (75±7 years, Mean ± SD) were enrolled in the study and WMH was assessed using magnetic resonance imaging and microstructural integrity of the white matter (WM) was estimated from fractional anisotropy (FA) and mean diffusivity (MD) using diffusion tensor imaging. Arterial blood pressure and middle cerebral artery blood velocity (MCAV) was obtained using finger plethysmography and Transcranial Doppler ultrasound while subjects were seated upright for 5 minutes. Transfer function analysis was used to evaluate dynamic CA.ResultsHigher phase (better CA) in the low‐frequency range (0.03–0.15Hz) was associated with smaller WMH volume (P = 0.02), higher FA (better microstructural integrity) in normal WM (P <0.001) and WMH (P= 0.001) and lower MD (better microstructural integrity) in normal WM (P= 0.006) and WMH (P= 0.012).ConclusionOur results suggest that higher WMH burden and loss of cerebral microstructure integrity are associated with impaired dynamic CA in elderly individuals.Research supported by NIH T32 grant (5 T32 AG 23480–7).
Identification of candidate susceptibility genes in a murine model of respiratory syncytial virus (RSV)‐induced bronchiolitis
Authors: Verhein Kirsten C , High Monica , Marzec Jacqui , McCaw Zachary , Wiltshire Tim , Chen Yu , Burkholder Adam , Klimczak Les , Fargo David , Kleeberger Steven R 
Published: June 2021

RSV is the most common cause of serious lower respiratory illnesses in infants and children. While genetic association studies have been reported for candidate susceptibility genes for RSV disease, no biomarkers exist for predicting severe versus mild disease. Here we use a combined genetics and genomics approach to understand the genetic basis of RSV disease susceptibility. We screened 32 inbred mouse strains for response to RSV by measuring disease phenotypes, including bronchoalveolar lavage inflammatory cells. Quantitative trait loci (QTL) were found for all disease phenotypes using SNPster (Novartis), and expression QTLs were identified with the FastMap haplotype algorithm. To identify transcripts differentially expressed at baseline that predict response to RSV, baseline mouse lung gene transcript expression for 24 strains of mice (Novartis) was correlated to phenotype data from the RSV strain screen using linear regression. These studies identified a battery of baseline gene transcripts significantly correlated with RSV disease severity. Disease and gene correlations in the final model were validated using cross validation. Together, these approaches have identified genetic markers of susceptibility to RSV disease to predict severe responders and potentially provide more effective therapeutic targets.Supported by the NIEHS Intramural Program.
Acceptability of pumping breastmilk among working mothers in Vietnam, a rapidly industrializing country
Authors: Henry Megan E. , Christian Parul , Kim Sunny S. , Pham Van , Nguyen Nam , Nguyen Phuong , Menon Purnima , Rawat Rahul 
Published: June 2021

Previous research identified returning to work as a major barrier to exclusive breastfeeding (EBF) in Vietnam. Pumping breastmilk (BM) is a potential solution to this constraint. In the context of a process evaluation (PE) of the Alive & Thrive program to promote EBF, an analysis of in‐depth interviews with 22 rural Vietnamese mothers identified cultural facilitators and barriers to pumping BM. Facilitators included an awareness of the benefits of BM, a culture of predominant breastfeeding, and support from grandparents. Hand‐expressing BM was also common, but mainly for discarding some foremilk after activities such as washing dishes or returning from the market, which exposed the mother to ngoai (outside) influences and “cold” milk, causing infant stomach illness. Scientific knowledge about bacterial contamination reinforced negative perceptions of BM stored at room temperature. Mothers expressed concern that cooling and reheating BM stored in a refrigerator degraded it. Most mothers responded unfavorably to pumping, emphasizing the importance of milk directly from the breast, and formula feeding as the best alternative. An understanding of traditional practices and current pressures helps to identify challenges to pumping as a solution to continued breastfeeding in this context.Grant Funding Source: Alive & Thrive, funded by the Bill & Melinda Gates Foundation and managed by FHI360