bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmentation of Endothelium‐dependent Vasodilation during Mild Exercise Blunts Postjunctional α‐adrenergic Vasoconstriction
Authors: Kirby Brett S , Crecelius Anne R , Richards Jennifer C , Luckasen Gary J , Larson Dennis G , Dinenno Frank A 
Published: June 2021

Sympathetic stimulation of postjunctional α‐adrenergic receptors elicits vasoconstriction in resting skeletal muscle but is blunted in contracting muscle in an intensity dependent manner. We tested the hypothesis that augmentation of endothelium‐dependent vasodilation during low intensity exercise attenuates α‐adrenergic vasoconstriction similarly to higher intensity exercise. We measured forearm blood flow (Doppler ultrasound) and calculated vascular conductance (FVC) to local intra‐arterial infusion of phenylephrine (PE; α1‐agonist) during mild and moderate handgrip exercise, during control non‐exercise vasodilator conditions (acetylcholine, ACH; or sodium nitroprusside, SNP), and during combined mild exercise + ACH or SNP in a total of 18 young adults. Forearm vasoconstriction to PE was observed during ACH alone and mild exercise (ΔFVC = −38±4 and −31±4%), but was blunted during moderate intensity exercise and combined mild exercise + ACH (−12±2 and −3±6%). Forearm vasoconstriction to PE was observed during SNP alone and mild intensity exercise (−36±3 and −34±4%), and was also robust during combined mild exercise + SNP (−34±6%). Constriction was again blunted during moderate intensity exercise (−15±3%). These data suggest contracting skeletal muscle may blunt postjunctional α‐adrenergic vasoconstriction through an endothelium‐dependent vasodilatory pathway.Support NIH HL102720
Sustained ATP‐mediated vasodilation of cerebral arteries requires Ca2+ influx via TRPC3 channels to produce endothelial SKCa channel activation and hyperpolarization
Authors: Kochukov Mikhail Y , Abramowitz Joel , Birnbaumer Lutz , Marrelli Sean P 
Published: June 2021

Extracellular ATP acts through endothelial cell (EC) purinoceptors to produce vasodilation of cerebral arteries (CA). IKCa channels have been established in this mechanism; however, the role of SKCa channels is not clear. We hypothesize that sustained ATP‐mediated hyperpolarization and vasodilation requires Ca2+ influx via EC TRPC3 channels to produce activation of SKCa channels.MethodsVascular diameter was measured following luminal delivery of ATP in mouse pressurized superior cerebellar arteries (SCA). Changes in EC Ca2+ were measured by biosensor in SCA isolated from Cx40BAC‐GCaMP2 transgenic mice. Membrane currents and voltage were measured in freshly isolated EC from CA of WT and TRPC3 knock out (KO) mice using perforated patch whole cell recording in voltage or current clamp mode.ResultsApplication of a selective TRPC3 blocker (Pyr3) significantly attenuated the duration of endothelial Ca2+ increase and vasodilation to ATP in pressurized SCA and abbreviated ATP‐mediated hyperpolarization in freshly isolated ECs. Responses were replicated with arteries and EC isolated from TRPC3 KO mice. Selective SKCa channel inhibition (UCL1684) mirrored the abbreviated time course of EC hyperpolarization, suggesting a common pathway.ConclusionWe propose that Ca2+ influx via TRPC3 promotes SKCa activation to produce the sustained component of cerebral vasorelaxation to ATP. Supported by R01HL088435 to SPM
Network interactions within the intrinsic cardiac nervous system: Implications for reflex control of regional cardiac function
Authors: Beaumont Eric , Armour John Andrew , Salavatian Siamak , Vinet Alain , Jacquemet Vincent , Ardell Jeffrey L 
Published: June 2021

ObjectiveTo determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu vs respond to changes in central drive. Also to determine how IC network interactions, subsequent to induced neural imbalances, subserve the genesis of atrial fibrillation (AF).MethodsActivity from multiple IC neurons within the right atrial ganglionated plexus was recorded from anesthetized canines. Induced changes in IC neuronal activity were evaluated in response to: (1) cardiac touch; (2) electrical activation of the cervical vagus or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) focal left ventricular ischemia and (5) neurally induced atrial arrhythmias (AF).ResultsThe majority of IC neurons were local circuit in nature and in basal states displayed low level functional interconnectivity. The majority of IC neurons received indirect central inputs (vagus and stellate) and a lesser proportion transduced the cardiac milieu including responding to multimodal stressors applied to the great vessels and heart. In response to mediastinal nerve stimulation most IC neurons became excessive excited and their functional interconnectivity enhanced; such network behavior preceding and continuing throughout AF.ConclusionStochastic interactions among IC neuronal populations underlie control of regional cardiac function. (Supported by HL71830)
Cardiomyocyte specific overexpression of C3orf58 activates ER stress leading to impaired cardiac function
Authors: Zhang Zhiping , Mirotsou Maria , Payne Alan , Mu Hui , Zhang Lunan , Finch Elizabeth A , Pratt Richard E , Rosenberg Paul , Dzau Victor J 
Published: June 2021

Although accumulating evidence supports the crucial role of ER stress in cardiovascular diseases, essential information is still required for its role in the pathogenesis of these disorders. We previously reported the identification of C3orf58 (aka HASF) as a novel stem cell derived factor involved in cytoprotection. Transgenic mice with a high‐level of cardiac specific overexpression of HASF showed reduced fractional shortening as early as 4 weeks old. Neonatal cardiomyocytes isolated from these mice showed reduction in basal Ca2+ levels, abnormal calcium oscillation and a dramatic reduction in magnitude of store‐operated Ca2+ entry after stimulation. Adult transgenic cardiomyocytes exhibited reduced L type channel currents. Notable, all three pathways involved in ER stress, PERK, ATF6 and IRE1, were activated in the hearts of transgenic mice as early as 2 weeks old. Moreover, to demonstrate the specific effect of HASF on ER stress, fibroblasts isolated from HASF heterologous KO were treated with ER stress inducers thapsigargin and tunicamycin. The induction of ER stress sensor GPR78 was significantly lower in these treated fibroblasts. Based on our findings we propose that C3orf58 is a novel regulator of ER stress pathways whose overexpression is involved in cardiac pathology and disease.The study was supported by NHLBI/NIH grants RO1 HL35610, HL81744, HL72010, HL73219 and Foundation Leducq (to VJD).
Changes in renal sympathetic nerve activity during and after exposure to acute intermittent hypercapnia
Authors: Valic Zoran , Pecotic Renata , Dogas Zoran , Valic Maja 
Published: June 2021

Elevated levels of carbon dioxide (hypercapnia) and/or decreased level of oxygen (hypoxia) act through neural networks to influence ventilatory and cardiovascular function. Both hypercapnic and hypoxic stimuli can evoke increase in sympathetic nerve activity and it appears that hypoxia can evoke prolonged duration of this increase. The present study was performed to investigate the renal sympathetic nerve activity in urethane‐anesthetized, mechanically ventilated Sprague‐Dawley rats exposed to five hypercapnic stimuli each lasting 3 minutes. Blood pressure and renal sympathetic nerve activity were measured and recorded throughout the experiment. Analysis was performed in the period before and during hypercapnic exposures (15% of the CO2 in the air), as well as 15, 30 and 60 minutes after the last hypercapnic episode. Renal sympathetic nerve activity increased to 190.3±22.8% during hypercapnia when compared to baseline. At 15 minutes after the last hypercapnic exposure nerve activity remained elevated at 138.0±14.8%. At 30 and 60 minutes renal sympathetic nerve activity was 136.8±21.5% and 131.8±18.3%, respectively. Acute intermittent hypercapnia evoked increase in renal sympathetic nerve activity that lasted at least 60 minutes after cessation of stimulus.This study was supported by Croatian Science Foundation.
The effect of sleep restriction on the respiratory and vascular control
Authors: Pugh Keith , Taheri Shahrad , Balanos George 
Published: June 2021

Total sleep deprivation is known to disrupt respiratory and vascular control. However, partial sleep deprivation is far more common and its effects less known.Participants (mean age ± S.D = 23.4 ± 1.5 years) with normal habitual sleeping patterns undertook two protocols. A sleep restriction protocol consisted of a baseline night of 8 hours sleep, followed by 3 nights of 4 hours sleep. A control protocol consisted of the same initial night followed by 3 nights of 10 hours of sleep opportunity. Chemosensitivity and endothelial function measurements were performed each day.Central chemosensitivity increased by 51.6 ± 9.4 % after the second night of sleep restriction but returned to baseline after the third night. In the control protocol central chemosensitivity remained unchanged. Peripheral chemosensitivity did not differ between the two protocols. Endothelial function measured by flow‐mediated dilation was decreased by 46.7 ± 1.6 % after the second night of sleep restriction but recovered after the third night. No changes were observed in endothelial function during the control protocol.These results suggest that acute sleep restriction affects both respiratory and vascular control with a complex time course. It is plausible that partial sleep deprivation can be a precursor to conditions such as sleep apnoea and cardiovascular disease.
Nicotinic Acetylcholine Receptors expressed by Muscle Afferent Neurons
Authors: Baxter James Clifford , Elmslie Keith S 
Published: June 2021

BackgroundThe Exercise Pressor Reflex (EPR) is activated during exercise to increase cardiovascular function. Acetylcholine (ACh) triggers muscle contraction and could be a potent signal of muscle activity during exercise. We show that nicotinic ACh receptors (nAChR) are expressed by muscle afferents.MethodsIdentified muscle afferent neurons were isolated from male Sprague‐Dawley rats. ACh‐induced currents were measured using the patch clamp technique. All neurons had diameters < 40 μm and expressed Nav1.8 channels. The role of α7 nAChR was tested using α‐Conotoxin IMI.ResultsACh‐induced current was measured in 48% (22/45) of muscle afferents. Of the ACh responsive neurons, 9 responded to capsaicin and 9 responded to ATP. 63% (7/11) of ACh responses were blocked by α‐Conotoxin IMI (α7). We are also testing blockers of other nAChRs.ConclusionnAChRs are expressed by muscle afferent neurons and α7 nAChR mediate the majority of these responses. It will be interesting to test α7 blockers in vivo to determine the role of nAChRs in the EPR. nAChRs could be pharmacological targets for suppressing the EPR in patients with peripheral vascular disease.
Oral administration of high doses of pseudoephedrine (PSE) hydrochloride accelerates the onset of CNS oxygen toxicity (CNS‐OT) seizures in rats exposed to hyperbaric oxygen (HBO) at 5 atmospheres absolute (ATA)
Authors: Pilla Raffaele , Held Heather E. , Landon Carol , Dean Jay B. 
Published: June 2021

Commonly, PSE salts are utilized by scuba divers as nasal decongestants. Anecdotal reports from Divers Alert Network (DAN) suggest that taking PSE prior to a deep dive while breathing pure O2 (i.e., Nitrox or using a rebreather) increases the risk for CNS‐OT. We hypothesized that high doses of PSE reduce latency to seizure (LS) in male and female Sprague‐Dawley rats breathing a lethal dose of HBO (5ATA).63 male and 63 female rats were implanted with radio‐transmitters for recording EEG, body temperature (BT) and activity. After ≥7 days, and 2hr before “diving”, rats were orally administered either saline solution (control) or PSE hydrochloride at the doses of (mg PSE/Kg): 0, 40, 80, 100, 120, 160 & 320 (LD50for PSE in rats is 640 mg/Kg). Rats were exposed to pure O2 at 5ATA until the onset seizures and LS was measured.We observed a significant decrease in LS at doses of 80 and 320 mg/Kg in females, whereas in males data displayed a more regular dose‐dependent decrease, notably at dosages of 100–320 mg/Kg. No consistent variation was observed at other doses. In addition, BT consistently dropped after the administration of each PSE dose, highlighting direct correlations among PSE dose, BT and LS (females).High doses of PSE are potentially harmful breathing pure O2 at 5 ATA of depth. Doses taken by commercial, technical and military divers breathing oxygen‐enriched gas mixes should not exceed the recommended guidelines. (DAN)
Small intestine microscopic changes induced by HIV‐1 Nef expression in brain
Authors: Loucil Raisa , Chompre Gladys , Cruz Myrella L. , Hernandez Siomara , Isidro Raymond A. , Isidro Angel A. , Appleyard Caroline B. , Noel Richard J. 
Published: June 2021

Gastrointestinal (GI) pathology is a recurrent problem during HIV infection and progression. HIV enteropathy may be associated with a specific cause; however some HIV‐positive individuals present idiopathic enteropathy that appears to involve inflammatory processes. The presence of increased plasma LPS due to GI inflammation in patients with HIV associated dementia suggests a brain‐gut connection. We found that HIV‐1 Nef expression by astrocytes in rat hippocampus produces spatial memory deficits, but did not address possible GI effects.AimDetermine if microscopic changes in the GI tract result from expression of Nef in the rat hippocampus.MethodsAstrocytes transfected to express Nef or GFP (control) were infused into the right hippocampi of Sprague Dawley rats (30‐day‐old). After 2 days of recovery, the rats were euthanized to harvest the ileum. Paraffin embedded tissues were stained for H&E.ResultsHistological analysis showed thinning of the intestinal wall and increased size and number of goblet cells in the Nef group. The lamina propria of the Nef‐treated rats was wider and shorter and Peyer's patches in the ileum showed massive reactive follicular lymphoid hyperplasia.ConclusionThese studies suggest that HIV‐1 Nef expression in the rat hippocampus induces inflammation as well as microscopic changes in the small intestine. G12RR003050, G12MD007579 & R25GM082406.
Role of H+/K+‐ATPase and Na+/Ca2+ exchangers in pancreatic ductal adenocarcinoma cells
Authors: Giannuzzo Andrea , Wang Jing , Hoffman Else Kay , Pedersen Stine Helene , Novak Ivana 
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC) has one of the worst cancer prognoses and a new initiative is to map the ion transportome to provide new therapeutic targets. Some of the hallmarks of cancer are increased glycolysis, altered H+ and Ca2+ homeostasis that may promote survival, motility and invasiveness. Pancreatic ducts express several unusual H+ and Ca2+ transporters and P2X receptors involved in secretion HCO3−‐rich and Ca2+‐poor pancreatic secretion. Our aim is to elucidate roles of gastric and non‐gastric H+/K+‐ATPase subunits (ATP4A, ‐B, ATP12A) and Na+/Ca2+ exchangers (NCX1, ‐2, ‐3) in regulation of H+ and Ca2+ transport and their contribution to PDAC progression. Using qPCR we investigated expression of transporters in several pancreatic cell lines: normal human duct cells HPDE; and PDAC cells Capan‐1, AsPC‐1, BxPC‐3, MIAPaCa‐2 and Panc‐1. The results show that NCX1 was down‐regulated in, e.g. BxPC‐3, while NCX2 and ‐3 were up‐regulated in some PDAC lines, e.g. AsPC‐1. ATP4A, ‐B, and ATP12A were up‐regulated in some PDAC, e.g. BxPC‐3 and Capan‐1. BxPC‐3 proliferation was attenuated by proton pump inhibitors. In conclusion, our study shows mRNA changes in H+ pumps and Ca2+ transporters in PDAC, and future studies will clarify the functions of these transporters in PDAC progression, as well as their regulation by P2X receptors/ion channels.Funded by FP7 Marie Curie Initial Training Network “IonTraC”
Saline loading does not change renal medullary blood flow in essential hypertension
Authors: Assersen Kasper Bostlund , Gam Jens Christian , Damkjær Mads , Valentin Sara , Olsen Michael Hecht , Diederichsen Axel , Høilund‐Carlsen Poul Flemming , Bie Peter 
Published: June 2021

In essential hypertension (EH), the natriuresis during saline loading is exaggerated. It was hypothesized that this phenomenon is associated with an increase in renal medullary blood flow. Patients (n=6) with mild, monosymptomatic EH were investigated after an 18‐d drug washout period including 4 d on standardized diet. Regional, renal blood flows were determined before and after saline loading (0.72 mmol/kg/h for 4 h) by Positron Emission Tomography and Computer Tomography (PET/CT) using H215O tracer (Am J Physiol Regul Integr Comp Physiol 299:R1449, 2010). Renal medullary blood flows (ml/(g tissue)/min) were 2.0 ±0.4 and 1.7 ±0.3* before and after saline loading, respectively. During saline loading BP (mmHg) changed from 147.6/86.1 ±6.5/3.1 to 157.1*/92.1† ±4.4/3.3. Renal sodium excretion (μmol/min) increased from 39.2 ±7.0 to 145.6 ±38.5†. It is concluded that the increase in renal sodium excretion during saline loading is not associated with an increase in renal medullary blood flow. *(P = ns) †(P < 0.05)Funded by The Danish Heart Foundation and The University of Southern Denmark.
Assessing the cultural beliefs of medical students: impact on the cadaveric dissection experience in the gross anatomy laboratory
Authors: Khalil Ramy , Krum Janette , Jurjus Abdo R. , Slaby Frank , Jurjus Rosalyn A. 
Published: June 2021

It is well established that cadaver dissection offers a beneficial learning experience to medical students in gross anatomy courses. Although researchers have sought to identify different learning styles in the dissection lab among students of various nationalities, no study has addressed the specific question of how a student's cultural identity or beliefs play a role in the emotional aspect of cadaver dissection.The purpose of this study is to examine the emotional impact of cadaver dissection across cultures and whether this impact affects the learners or learning experience. This is a quantitative/qualitative study targeting first year medical students of various cultural backgrounds partaking in cadaveric dissection. Students will be recruited via e‐mail and will complete an online survey.Based on preliminary oral responses, a relationship between students’ cultural identities and unique experiences in the gross anatomy laboratory was reported.This study will help medical educators understand the student learning experience of cadaveric dissection as it relates to cultural identity and will facilitate the preparation of students for the dissecting room experience.Grant Funding Source: N/A
Effects of classroom structure on retention and implementation of knowledge in students
Authors: Banda Anisha Manika , Steed Kevin , Schmalz Naomi , Ojukwu Kene , Diaz Molly , Padilla Jessica , Wisco Jonathan J. 
Published: June 2021

Typical classroom instruction consisting of a block period style of education often incurs problems with retention and implementation of information by students. In the outreach program Anatomy Academy, students receive holistic health instruction regarding the human body. In this study two sessions of Anatomy Academy were conducted, each executed on different time tables. The first group of students attended a week long session, spending five hours each day at the program. The second group of students was taught the same curriculum for one hour each week for six weeks. While both groups were constructed with the same student‐teacher ratio, students in the second group who were on the block schedule were unable to connect with mentors on the same level as students in the first group. The increased willingness and ability of students in Group One to incorporate mentors’ advice into healthier lifestyle choices can be attributed to 1) the trust developed in the student‐teacher relationship over multiple hours of interaction; and 2) an excitement and incentive for retaining information. The integrative approach of AA speaks to the success of immersion‐style teaching in classroom settings in encouraging students to retain and actualize information beyond just the day of instruction.Grant Funding Source: AAA
Evaluation of a novel online systemic human anatomy course
Authors: Attardi Stefanie Marie , Rogers Kem A 
Published: June 2021

An online section of an existing undergraduate systemic human anatomy course with a laboratory component is in its inaugural year. Lectures for face‐to‐face (F2F) students are broadcast in live and archived format to online students using virtual classroom software (Blackboard Collaborate). Laboratory demonstrations are delivered online by a teaching assistant who can manipulate 3D anatomical models in the virtual classroom for the students to see. Students may independently study the 3D models on their own computers. A mixed methods approach is being undertaken to determine the effectiveness of the online delivery format. Means for each measure of student performance (4 tests, 24 laboratory quizzes) are under comparison between the sections. Incoming grade point averages will be compared to final Anatomy grades to determine if previous academic performance impacts performance in the F2F or online formats. Preliminary data suggest that student academic performance in the course is not impacted by the online delivery format. Student perceptions of the learning experiences in the online and F2F environments will be revealed. Student interviews will be conducted following a cross over that exposes them to both delivery formats. Themes will be established from interview data and used to generate data‐driven (grounded) theory about the strengths and weaknesses of the online format.Grant Funding Source: Departmental Funding
The development of a web‐based interactive tool to complement anatomy and radiology teaching and learning
Authors: Krebs Claudia , Oyedele Olusegun , Fejtek Monika , Tolhurst Stefano 
Published: June 2021

The ability to understand and interpret radiological images is a required competency in North American medical graduates. Prerequisite to this is a good knowledge of human anatomy. A radiology workshop, introduced as part of the Fundamentals of Body Design (FoBD) Year 1 UBC MD undergraduate program (MDUP), revealed our students’ need for a user‐friendly radiology resource to assist independent study of the material presented during the workshop. This study aimed to deliver such a resource to complement the teaching and learning of anatomy and radiology in the MDUP. Digital archives of normal X‐rays and CT scans, sourced from one of UBC's MDUP sites were accessed and compiled according to learning objectives of the FoBD radiology curriculum. Pixen® graphics open source software was used to highlight key anatomical structures, based on FoBD objectives. Multiple colour images thus created for each radiological film were saved as distinct graphics layers, built into interactive html web pages using JavaScript® and Cascading Style Sheets®, and uploaded to www.clinicalanatomy.ca. UBC students currently accessing these images are able to study radiological anatomy interactively by repeatedly highlighting/unmarking structures of interest with the click of a mouse. Landmarks indistinct or vaguely apparent to the untrained eye are rendered more easily discernible, thus enriching the student's learning experience.Grant Funding Source: Source of funding: UBC Faculty of Medicine Undergraduate Program