bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pulmonary vessel adventitia: role in the pathology of fat embolism (LB511)
Authors: Kesh Susamita , Molteni Agostino , Stevens Todd , Herndon Betty 
Published: June 2021

Background/rationale: Fat embolism (FE) a clinical presentation where fat droplets from site of injury are intravasated into the venous system and sequestered into the lungs is common following long bone fractures. Although considered subclinical, severe cases occur with mortality. Our animal models have shown progressive pulmonary fibrosis from FE with early respiratory distress. Vascular adventitial layer has recently been identified as a first responder to vascular stress or injury, characterized by chemokine/cytokine generation that activates functional vessel wall remodeling. Does FE progress through adventitial responses? Methods. With University clearance, FE was created in rats with 0.2 mL marrow‐like lipid I.V. (triolein) [n=18]or saline [n=18) followed at 6 weeks by a “second hit” on the lung by low dose LPS or saline (9 each dose/group). Lungs were studied at 48 hr following the LPS or saline, with emphasis on the pulmonary response to FE, exacerbated or not by LPS. BAL cells were counted, vessels stained (H&E, trichrome). Arterial layers were measured at 400x by researchers unaware of treatment groups.Results: PMN counts increased by 15% in the FE group over saline at 6 weeks. LPS produced a PMN BAL count threefold over saline. FE‐treated lungs at 6 weeks were inflamed with greater cellularity in the adventitial layer. When LPS was added to FE‐treated lungs the adventitia thickness difference vs saline showed p=0.11. Controls alone showed p=0.58.Summary: Arterial adventitial layer in lungs after FE is increased in thickness and cellularity; added LPS increases thickness. Percent PMN in BAL is significantly elevated by FE alone. Identification of the cells (and their secretions) that proliferate in the adventitia after FE remains an immediate goal.Grant Funding Source: Geldmacher Foundation Grant to GS
Physical training performance in the prevention of hepatic steatosis induced by a high fructose intake (LB519)
Authors: NAKAMOTO DEBORA , FARAH DANIELA , ANDRADE ROMARIO , NUNES JONAS , JUNIOR EDUARDO , FIORINO PATRICIA , FARAH VERA 
Published: June 2021

The aim of this study was examine the effects exercise training into prevent the hepatic steatosis induced by a high fructose intake in rats from weaning to adulthood.Weaned male Wistar Rats with 21 days old (50‐60g) were divided into (n=5 each): Sedentary control (SC); Trained control (TC); Sedentary fructose (SF) and Trained fructose (TF).Fructose‐drinking rats received D‐fructose during 8 weeks (100 g/l). The trained animals were assigned to a treadmill training protocol during 1 h/day, 5 days/week for 8 weeks. Measurements of triglyceride concentrations, white adipose tissue and piruvate tolerance test and glucose tolerance test were carried out to evaluate metabolic profile. At the end of the e experimental protocol, the animals were euthanized and a piece of the liver was collected for histological evaluation.Fructose induced dyslipidemia and glucose intolerance in SF and TF groups. Moreover, SF showed a decrease in the pyruvate tolerance test when compared to SC. Despite it was not observed significant changes in body weight between the groups, fructose induced an increase in adiposity mass. The liver weight was not different between the groups, however fructose induced an increase in % of liver fat cells in SF when compared to SC (8.3% ± 0.48 vs. 5.6% ± 0.61, p<0.001) and in TF compared to TC (3.5% ± 0.2 vs. 1.9% ± 0.30, p<0.0001). When we compared TC vs. SC the percentage was significantly higher in AS (5.6% ± 0.61 vs. 1.9% ± 0.30, p<0.0001). And the last analysis showed higher percentage in SF when compared with TF (8.2% ± 0.48 vs. 3.5% ± 0.23, p<0.0001) Findings indicate that a high fructose diet significantly increase the percentage of fat in the liver, which may lead to Hepatic Steatosis. This study suggests that physical exercise can be used as a non‐pharmacological treatment, since we found a decrease in the percentage of fat in the liver in trained animals.Grant Funding Source: Supported by MACKPESQUISA/PIBIC CNPQ
Mechanisms of cardioprotective effects of high concentration of magnesium on hypoxia/reoxygenation injury in chronic magnesium deficient rat heart are differ from normal rat heart (LB665)
Authors: Watanabe Makino , Nakamura Kyoko , Kato Megumi , Kakigi Ryo , Iesaki Takafumi , Okada Takao 
Published: June 2021

Magnesium (Mg) deficiency has been reported to be associated with the development of cardiovascular diseases. We have reported that high concentration (12 mM) of extracellular Mg during hypoxia (high‐Mg) protected the heart from hypoxia/reoxygenation (H/R) injury, and its protective effect was induced not only by suppression of energy consumption, but also by opening of mitochondrial KATP channel in cardiomyocytes. The aim of this study was to determine whether high‐Mg could protect the H/R injury in chronic Mg‐deficient (Mg‐def) rat heart. Rats were fed an Mg‐def diet for 8 weeks, and the hearts were subjected to Langendorff perfusion with the protocol of 30 min hypoxia followed by 30 min reoxygenation. In Mg‐def group, the recovery of cardiac function (pressure‐rate product; PRP) from H/R injury was significantly impaired than that of control group. Recovery of PRP in Mg‐def group was restored to that of control group when extracellular Mg concentration was increased from 1.2 to 12 mM during hypoxia. A specific mitochondrial KATP channel blocker, 5‐hydroxy decanoic acid (5‐HD), did not inhibit the protective effect of high‐Mg in Mg‐def group. In isolated myocardial mitochondria from Mg‐def rat hearts, retention of Ca2+ to open the mitochondrial permeability transition pore (mPTP) was significantly lower than that of control group. These results suggest that the mechanisms of cardioprotective effects of high‐Mg do not depend on opening the mitochondrial KATP channel but on unknown other mechanisms, although the mitochondrial functions are impaired in Mg‐def rat hearts.Grant Funding Source: Supported by JSPS KAKENHI Grant Number 24614015
Continuous blood pressure assessment from a photoplethysmographic signal with Deep Belief Networks (LB674)
Authors: Ribas Vicent 
Published: June 2021

Continuous blood pressure assessment from a photoplethysmographic signal with Deep Belief Networks Vicent J. Ribas Ripoll PhD; Anna Wojdel PhD; Anna Sáez de Tejada Cuenca; Juan C. Ruiz‐Rodríguez, MD; Adolf Ruiz‐Sanmartín, MD; Miriam de Nadal MD, PhD; Enrique Romero PhD; Alfredo Vellido PhD A prospective study was conducted at a critical care department and post‐anesthesia care unit of a university teaching hospital in Barcelona, Spain. The study recruited 707 patients with invasive BP and finger PPG waves over a period of 26 months. Exclusion criteria were presence of major arrhythmia, immediate death condition and disturbances in the arterial or PPG curve morphology. For each patient we automatically recorded the systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and PPG curve for 30 minutes. The PPG signal was further processed to obtain a set of features that were used to construct a Deep Belief Network with Gaussian Restricted Boltzmann Machine (DBN‐RBM). The available dataset was split into three subsets (Training, Validation and Testing). The training and validation datasets included 85% of data and the testing dataset included 15% of the available data. The regression error was assessed through a Bland‐Altman analysis and the AAMI standard. The mean prediction error were ‐2.98+‐19.35 mmHg for SBP, ‐3.38+‐10.35 mmHg for MAP and 3.65+‐8.69 mmHg for DBP.The results obtained are promising for the assessment of MAP and DBP with DBN‐RBM. Further research and clinical validation are needed to bring this technology to standard medical practice.Grant Funding Source: Supported by Shockomics (FP7 framework)
Cell survival effects of an mTOR‐binding protein Tel2 in cardiomyocytes (LB682)
Authors: Yorichika Naaiko , Matsui Takashi 
Published: June 2021

Recent studies including ours suggest that the mechanistic target of rapamycin (mTOR) is sufficient and necessary to prevent cardiomyocyte (CM) cell death against pathological stresses such as myocardial infarction. We also showed that the expression level of mTOR increases in patients and mice with heart failure. However, a mechanism of regulating mTOR expression in the heart remains unknown. Recent reports showed that telomere maintenance 2 (Tel2) interacts with mTOR and regulates its stability and abundance in other tissues. To assess the role of Tel2 in CMs, we examined whether Tel2 is sufficient to stabilize cardiac mTOR and prevent cell death against hypoxic stress. CM cell line HL‐1 cells were transiently overexpressed with Tel2 and then subjected to 24‐hour hypoxia. Cell survival was assessed by morphological changes and Cell Death Detection ELISA (Roche). The necessity of Tel2 was examined by the treatment of CMs with Tel2‐specific siRNA. Western blotting showed overexpression of Tel2 increased the expression level of mTOR by 60% (p<0.05, n=5), and the phosphorylation levels of both S6 (mTORC1 substrate) and Akt (mTORC2 substrate) (90%‐ and 60%‐increase, respectively; p<0.05, n=5). The CMs treated with siRNA targeting Tel2 showed significant decrease in the expression level of mTOR, and the phosphorylation levels of both S6 and Akt compared to controls (p<0.05, n=3). In the hypoxic culture, the round‐shape CMs, indicating cell injury, were less in Tel2‐overexpressed CMs. Cell Death ELISA showed that hypoxia increased apoptosis by 4‐fold compared to baseline controls, whereas Tel2 overexpression suppressed apoptosis by half compared to controls (p<0.05, n=3). These findings suggest that an mTOR‐binding protein Tel2 is sufficient and necessary to protect CMs against hypoxia at least in part by mTOR stabilization. A study of Tel2‐mediated mTOR activation would provide a novel target for a therapy of heart failure following myocardial infarction.Grant Funding Source: Supported by NIH R01 HL098423
Maternal diet and ovariectomy modify blood pressure response to Nω‐nitro‐L‐arginine methyl ester (LNAME) in the rat (LB684)
Authors: Clifford Bethan , Langley‐Evans Simon , Elmes Matthew 
Published: June 2021

It is well established that the developmental programming of hypertension occurs through dietary manipulations during pregnancy but the role of sex in developmental programming is not well understood. The study at hand aimed to further elucidate the mechanisms behind sexual dimorphism in blood pressure regulation using an established model of nutritional programming.Female Wistar rats were mated and allocated to a control (18% casein; C) or low protein (9% casein; LP) diet during gestation. At 10 weeks of age, female offspring were ovariectomised (OVX) or exposed to a sham surgery procedure. At 11 months of age all animals underwent aortic telemetry implantation. Blood pressure and heart rate were recorded for a 6 week period, including baseline recordings and treatment with the nitric oxide synthase inhibitor LNAME.LNAME induced a significant increase in blood pressure (~20mmHg, p< 0.001), in accordance with previous studies. A significant interaction was observed between surgery and diet groups (p<0.02) with differences between sham‐ and OVX females in the C and LP groups being reversed. OVX in C animals decreased systolic blood pressure by ~6mmHg compared to sham animals. In contrast OVX in LP animals, increased systolic blood pressure readings ~8mmHg higher than in sham animals.Gestational exposure to a LP diet results in altered blood pressure response to OVX surgery.Grant Funding Source: BBSRC
Apocynin and tempol restores cutaneous microvascular function in healthy, salt‐resistant adults on a high sodium diet (LB686)
Authors: Ramick Meghan , Brian Michael , Matthews Evan , Lennon‐Edwards Shannon , Farquhar William , Edwards David 
Published: June 2021

The purpose of this study was to determine if NADPH derived superoxide plays a role in attenuating cutaneous vasodilation in response to local heating in healthy, salt‐resistant adults on a high sodium diet. Nineteen healthy adults (33±3yrs) participated in a controlled feeding study. Subjects completed 7 days of a low sodium (LS) diet (20mmol sodium/day) and 7 days of a high sodium (HS) diet (300mmol sodium/day) in random order. On the final day of LS and HS diets cutaneous microvascular function was assessed using a standard heating protocol. RBC flux was measured via laser Doppler flowmetry coupled with interdermal microdialysis for the local delivery of 10µM tempol (scavenging superoxide) and 100 µM apocynin (inhibiting NADPH oxidase). Once a stable post‐heating plateau was achieved, 10mM L‐NAME was infused through all sites to determine NO contribution to vasodilation. The plateau phase of cutaneous vasodilation was attenuated in the HS condition compared to LS (91.0±1.8 vs 83.4±1.9; p<0.05) and was restored with the local infusion of both tempol and apocynin (p<0.05). The NO contribution to cutaneous vasodilation was also decreased on the HS diet compared to LS (62.7±4.2 vs 52.3±4.6; p<0.05). This was restored with the infusion of apocynin (p< 0.05) but was not improved by tempol (p=0.173). These finding suggest that NADPH derived superoxide plays a role in dietary sodium induced decreases in cutaneous vasodilation in response to local heating.Grant Funding Source: Supported by NIH Grant R01 HL104106‐01A1
TLR3‐induced expression patterns of human placental microRNAs (LB705)
Authors: Jamison Ashley , Jupiter Daniel , Chatterjee Piyali 
Published: June 2021

OBJECTIVE: Preeclampsia (PE) is a pregnancy‐specific hypertensive disorder that affects 5‐8% of women worldwide. The placenta is considered to be the main culprit as symptoms of PE typically reduce following delivery of the placenta. This study was designed to determine the effects of TLR3 activation on placental miRNA expression and whether these miRs are associated with PE in women.METHODS: Microarray for miRNAs was performed in human cytotrophoblasts (CTBs) treated with poly I:C for 24 hour and compared with vehicle‐treated CTBs. The expression of 10 miRNAs (5 upregulated and 5 downregulated) were confirmed by qRT‐PCR. Formalin fixed paraffin embedded placental tissues were obtained from patients with PE (n= 9‐11) and normal pregnant women (n = 6‐8) and the expression of these miRNAs were assessed by qPCR.RESULTS: Both human CTBs treated with poly I:C and placentas of PE women exhibited increased expression of miR‐155 and miR‐125a‐5p and decreased expression of miR‐575, miR‐149*, and miR‐145. Gene Ontology analysis of the target genes using miRTarBase revealed enrichment for specific biological process categories (chromatin binding and cell death: miR‐155; cell cycle and proliferation: miR‐145).CONCLUSIONS: Here we demonstrate that alterations in the expression of specific miRNAs induced by TLR3 activation in CTB were also observed in PE women. These data provide novel targets for further investigation into the pathophysiology of PE.Grant Funding Source: 13SDG14630018
Expression of collagen type 1a1 and 3a1 isoforms in aortic adventitial fibroblast cultured from ovariectomized and intact Long Evans rats (LB715)
Authors: Ringel Veronica , Boyd Denise , Novak Jacqueline , Ramirez Rolando , Underwood Adam 
Published: June 2021

.The prevalence of cardiovascular disease is lower in premenopausal women when compared to equally aged men. Decreased arterial compliance may contribute to the increased risk. This reduced vascular compliance can be attributed to increases in adventitial collagen deposition in the postmenopausal state. The goal of this project was to determine if collagen type 1a1 and 3a1 are expressed differently in aortic fibroblasts cultured from an animal model of post‐menopausal physiology; surgically ovariectomized Long Evans rats and control animals with ovaries intact and subjected to a sham surgery. Fibroblasts were established in T‐25 flasks from 0.5‐1.5 mm sections of thoracic aorta isolated from three ovariectomized and control animals. Fibroblasts were grown for seven days in Dulbecco’s Modified Eagles Medium (DMEM) containing 15% FBS and then passed and cultured for 48 hours in DMEM containing 10% FBS. Immunodetection of the proteins desmin and vimentin was used to verify fibroblast identity. Prior to RNA extraction all cells were incubated for 72 hours in DMEM clear. After cDNA synthesis, the relative expression (∆∆CT) of collagens 1a1 and 3a1 was determined using real‐time PCR and 18S as an endogenous control. From these runs it was determined that collagen 1a1 and 3a1 expression is 1.6 and 1.4 fold higher respectively in fibroblasts isolated from ovariectomized rats when compared to the control. This indicates that lack of ovarian hormones can lead to increased adventitial collagen expression, which may reduce arterial compliance. Studies focusing on the influence of hormones, such as relaxin, on collagen expression are underway.Grant Funding Source: Supported by NIH 1R15HL09343
Sympathetic neural recruitment during severe chemoreflex stimulation (LB732)
Authors: Badrov Mark , Usselman Charlotte , Shoemaker J. Kevin 
Published: June 2021

Sympathetic neural recruitment during severe chemoreflex stimulation Mark B. Badrov1, Charlotte W. Usselman1, J. Kevin Shoemaker1,2: 1School of Kinesiology, 2Department of Physiology and Pharmacology, Western University, London, Ontario, Canada This study tested the hypothesis that severe chemoreflex stress stimulates the recruitment of sub‐populations of previously silent, larger amplitude sympathetic action potentials. Muscle sympathetic nerve activity was measured via microneurography in 7 healthy males (27 ± 2 yrs, 180 ± 4 cm, 82 ± 13 kg; mean ± SD) at baseline and during a maximal end‐inspiratory apnea, which was preceded by a rebreathing protocol designed to elicit progressive hypoxia and hypercapnia, thereby maximizing the severity of sympathoexcitation evoked during the subsequent apnea (End‐apnea: PO2 = 58 ± 4 Torr; PCO2 = 55 ± 5 Torr). Compared to baseline, burst frequency (19 ± 6 to 43 ± 10 bursts/min; P < 0.01), burst incidence (37 ± 12 to 73 ± 11 bursts/100 heartbeats; P < 0.01), and mean normalized burst amplitude (30 ± 6 to 56 ± 6 AU; P < 0.001) were increased during apnea. For sympathetic action potential analyses, action potential frequency (211 ± 205 to 617 ± 354 spikes/min; P < 0.01), action potential incidence (408 ± 400 to 1068 ± 598 spikes/100 heartbeats; P < 0.001), and mean action potential content per burst (10 ± 6 to 15 ± 9 spikes/burst; P < 0.05) were increased during apnea compared to baseline. Furthermore, the total number of distinct amplitude‐based ‘clusters’ of action potentials increased from 15 ± 5 at baseline to 19 ± 8 during apnea (P < 0.05). This was concomitant with an increase in the number of distinct ‘clusters’ per sympathetic burst (5 ± 2 to 6 ± 3 clusters/burst; P < 0.01) during apnea. In conclusion, a neural recruitment strategy exists whereby previously silent sub‐populations of larger amplitude action potentials are recruited as sympathetic activity is elevated during periods of severe chemoreflex stress.Grant Funding Source: Supported by NSERC and CIHR
Improved efficacy of metformin therapy when combined with caloric restriction in the treatment of type 2 diabetes and NAFLD in OLETF rats (LB743)
Authors: Linden* Melissa , Lopez* Kristi , Fletcher Justin , Meers Grace , Siddique Sameer , Morris E. , Crissey Jacqueline , Kearney Monica , Laughlin M. , Sowers James , Thyfault John , Ibdah Jamal , Rector R. 
Published: June 2021

Weight loss is recommended for nonalcoholic fatty liver disease (NAFLD) patients while metformin may lower liver enzymes in type 2 diabetics. Yet, the efficacy of the combination of treatments on NAFLD is unclear. We sought to assess the effects of metformin, caloric restriction, and the combination on NAFLD in diabetic Otsuka Long‐Evans Tokushima Fatty (OLETF) rats. OLETF rats were (age 20 weeks; n=6‐8/group) fed ad libitum (AL), given metformin (300 mg/kg/d; Met), caloric restricted (70% of AL fed; CR), or CR+Met for 12 weeks. Met lowered body weight and adiposity compared with AL, but was less effective than CR and CR+Met (p<0.05). All therapies improved fasting insulin, glucose, and/or HbA1c, but only CR+Met improved post‐challenge glucose tolerance. Met, CR, and CR+Met reduced hepatic triglycerides by 40%, 70%, and 60% (p<0.05 Met vs. CR/CR+Met groups), respectively compared to AL rats; however, CR+Met further attenuated serum alanine aminotransferase levels. Only CR altered hepatic de novo lipogenesis proteins fatty acid synthase (FAS), acetyl‐CoA carboxylase (ACC), and stearoyl‐CoA desaturase‐1 (SCD‐1) and hepatic mitochondrial activity (palmitate oxidation and β‐hydroxy‐acyl‐CoA dehydrogenase (β‐HAD) activity). ACC and SCD‐1 protein content were further reduced with CR+Met. The combination of caloric restriction + metformin further benefited glycemic control, liver injury, and markers of hepatic de novo lipogenesis compared with either therapy alone in the diabetic OLETF rat. *co‐first authorship.Grant Funding Source: Supported by: NIH HL‐36088, DK‐088940, HL73101‐07, HL107910‐03, and T32 AR‐048523 and VA Merit System 0018 and CDA2‐1299.
Vitamin D Status and its Correlation with Blood Pressure Among Saudi Postmenopausal Women: A Cross‐Sectional Study (LB755)
Authors: Al Marhoumi Lujain , Al Kadi Hanan 
Published: June 2021

The aim of the present study was to assess the correlation between vitamin D status and blood pressure (BP) in a group of Saudi postmenopausal women.METHODS: This cross‐sectional study was conducted in the “Center of Excellence for Osteoporosis Research” (CEOR), King Abdulaziz University (KAU), Jeddah, Saudi Arabia, from March‐May 2013. The study population included 31 Saudi women (52‐70 years old), randomly selected from “Primary Health Care Centers” in Jeddah, Saudi Arabia. Blood pressure was measured by a standardized method using an automated BP monitor (BPTru). Anthropometric measurements were obtained and fasting blood samples were collected. Serum 25‐hydroxyvitamin D [25(OH) D] and parathyroid hormone (PTH) were measured by sandwich chemiluminescence immunoassay method.RESULTS: Vitamin D deficiency was highly prevalent among the study group with 68% of the women having levels <50 nmol/L and 39% having levels <25 nmol/L. In all women combined, 25(OH) D level was inversely associated with both systolic (r=‐0.39; P=0.028) and diastolic (r=‐0.39; P=0.030) BP. Blood pressure was higher in the group with severe vitamin D deficiency (<25 nmol/L), but this did not reach statistical significance. Linear regression analysis showed that 25(OH) D was independently and inversely associated with diastolic BP.CONCLUSION: In Saudi postmenopausal women, vitamin D deficiency is highly prevalent and 25(OH) D level was independently and inversely associated with diastolic BP. Correction of vitamin D deficiency in this high risk group is needed and may improve BP control in hypertensive postmenopausal women. Interventional studies to evaluate if attainment of optimal vitamin D status may prevent hypertension are necessary.Grant Funding Source: Supported by the Center of Excellence for Osteoporosis Research, King Abdulaziz University, Jeddah, Saudi Arabia