bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of O‐linked β‐N‐acetylglucosamine in isoflurane induced cardiac protection
Authors: Tsutsumi Yasuo M. , Hirose Kayo , Katayama Erika , Tsutsumi Rie , Kinoshita Michiko , Tanaka Katsuya , Oshita Shuzo 
Published: June 2021

The administration of isoflurane, volatile anesthetics, before myocardial ischemia‐reperfusion exerts protective effects against myocardial infarction similar to that of ischemic preconditioning (IPC). Although the endogenous signaling mechanisms remains unknown, previous work suggests that the modification of proteins with O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) plays a critical role in IPC. We therefore examined the role of O‐GlcNAc in the cardiac protection induced by anesthetic preconditioning (APC).Mice were exposed to 30 min isoflurane or oxygen and allowed to recover for 15 min. After washout periods, mice then underwent 30 min ischemia, followed by 2 h of reperfusion. Some isoflurane‐treated mice were also given alloxan, an inhibitor of O‐GlcNAc‐transferase, 20 min prior to isoflurane exposure. The area at risk as a percent of left ventricular were similar among groups. Infarct size after reperfusion was reduced by isoflurane (29 ± 4% vs. 40 ± 4%, p<0.05) but not alloxane pretreated mice (42 ± 5%, n=4). Additionally, hearts excised from APC‐treated mice had a 1.5‐fold increase in O‐GlcNAc level (p<0.05, n=4) and pretreatment with alloxan reversed this effect of APC.These data demonstrate that cardiac protection produced by isoflurane are sensitive to O‐GlcNAc levels, suggesting O‐GlcNAc signaling may play a vital role in the isoflurane‐induced cardiac protection.
Accuracy and Reliability of Consumer Breath Alcohol Analyzers
Authors: Davis William , Andrews J C , Herb E , Lee J R , Latman N S , Bouma C L 
Published: June 2021

Between 1999 and 2007, there were approximately 13,000 fatalities/year in the United States as a result of alcohol‐impaired driving accidents. These accidents are preventable, and there are many personal breath alcohol concentration (BrAC) analyzers being utilized by consumers. The purpose of this study was to determine the accuracy and reliability of five consumer models of BrAC analyzers by comparing their results to blood alcohol concentration (BAC). Fifty‐seven subjects with ages ranging from 21–75 were tested with a %BAC range of 0.03 to 0.14.Results were:

Standard Line‐of‐ Equality
BACTrac S 50
BACTrac B 70
AlcoHAWK Pro
AlcoHAWK Slim
Alcomate Premium

y‐Intercept
0.00
0.006
0.061
0.026
0.026
0.001

Slope
1.00
1.23
0.52
1.20
1.05
0.77

Correlation Coefficient
1.00
0.52
0.29
0.76
0.75
0.81

Standard Error of Estimate
0.000
0.051
0.043
0.026
0.022
0.014

Mean Absolute Error
0.000
0.036
0.032
0.021
0.017
0.011

Reliability
0.000
0.012
0.019
0.008
0.005
0.007

None of the models of BrAC analyzers were sufficiently accurate to be useful in reliably warning drivers of their state of intoxication.This study was supported in part by Lifeloc Technologies, Inc.
Morphine‐induced motor stimulation and ataxia: differences among adolescent, late adolescent, and adult mice
Authors: Koek Wouter , France Charles P. 
Published: June 2021

Given evidence for age‐related differences in the effects of drugs of abuse, surprisingly few preclinical studies have explored effects of opioids in adolescents (versus adults). The present study compared the motor stimulating and ataxic effects of morphine in adolescent and adult mice.Morphine (3.2–56 mg/kg, i.p.) increased locomotion along an inverted U‐shaped dose‐response curve in adolescent, late adolescent, and adult male C57BL/6J mice. In all age groups, the minimum effective dose to enhance locomotion was 10 mg/kg, and maximal stimulation was observed at 17.8 mg/kg. However, maximal stimulation was higher in adolescents than in adults. In contrast, adolescents showed less ataxia than adults when given morphine (5.6–100 mg/kg, i.p.).The finding that adolescent mice show larger locomotor‐stimulating effects of morphine than adults is consistent with previous findings in rats. This could be taken to indicate that adolescent animals are more sensitive to motor stimulating effects of morphine. Alternatively, larger locomotor effects of morphine could be due to less interference by its ataxic effects. Thus, it is possible that morphine‐induced motor stimulation appears larger in adolescents than in adults not because adolescents are more sensitive to the motor stimulating effects of morphine, but because they are less sensitive to its ataxic effects.Supported by DA23261 (WK), DA17918 (CF)
Effect of diacerein alone and combination with aceclofenac in adjuvant induced arthritis and in chronic inflammatory model in rats
Authors: Medhi Bikash , Prasad Byrav D.S. , Patyar Sazal , Prakash Ajay , Saikia Uma Nahar 
Published: June 2021

Present study was carried out evaluate the efficacy of diacerein alone and in combination with aceclofenac in different chronic inflammatory models in rats.48 male rats were divided into two groups of arthritis, and cotton wool granuloma. Each group had 4 subgroups Vehicle, Freund's adjuvant, Diacerein + Freund's adjuvant, Diacerein + Aceclofenac + Freund's adjuvant. And in cotton wool granuloma group Sham operated, Cotton wool pellet, Diacerein + Cotton wool pellet, Diacerein +Aceclofenac+ Cotton wool pellet. Animals were treated with diacerin alone and in combination irrespective to its groups. At the end of seventeen days in arthritis and seven days in cotton wool granuloma group, animals were sacrifice after assessment of inflammation. Blood sample were collected for TNF α and MPO estimation.The models of arthritis and CWG were effectively produced as evidenced by morphology and histology scores (p<0.001). Diacerein reduced the morphological, histological including cytokine and MPO activity (p<0.002), combination showed better effect on this parameters (p<0.001). In the arthritis group and cotton wool granuloma model TNF α and MPO levels in plasma were reduced following diacerein treatment (p<0.002) and combination showed better effect (p<0.001) in both the model.Diacerein is effective in above mentioned model however combination showed better efficacy in chronic inflammatory models.
Protection of NADH‐linked Fe‐S clusters in cardiac mitochondria by ranolazine
Authors: Gadicherla Ashish K. , Antholine William E. , Heisner James S. , Camara Amadou K.S. , Aldakkak Mohammed , Yang Meiying , Boelens Age D. , Stowe David F. 
Published: June 2021

Mitochondrial complex I (CI), composed of Fe‐S clusters numbered N1‐N5, is susceptible to damage by reactive oxygen species during cardiac ischemia reperfusion (IR). We used electron paramagnetic resonance (EPR) to assess how IR injury affects these Fe‐S clusters and if ranolazine (RAN), an antianginal drug, attenuates these effects. Guinea pig hearts were perfused with Krebs Ringer (KR) buffer and subjected to one of the following protocols: a) KR perfusion for 30 min, b) 30 min ischemia (I), c) 5 μM RAN for 1 min before ischemia (RAN+I), d) 30 min ischemia followed by 10 min reperfusion (IR) and e) 5 μM RAN for 1 min before 30 min ischemia and 10 min reperfusion (RAN+IR). Hearts were immediately ground in liquid N2 and the powder packed into EPR tubes. Changes in signal intensities at g=1.94, 1.86, and 1.89, assigned to N1b, N3, and N4, respectively, were recorded at 10°K (liquid He) at 9.6 GHz, 5 mW. Versus time control (100%), N1b signal decreased to 0% in the I hearts and was restored to 40%, 100%, and 70% in IR, RAN+I and RAN+IR hearts, respectively. N4 signal was 67% for I, 183% for RAN+I, 117% for IR, and 100% in RAN+IR hearts. N3 signal was 50% for both IR and RAN+IR hearts, and unaltered for I and RAN+I hearts (100%). These data suggest that RAN treatment before IR protects electron flux only through some Fe‐S centers. This finding may underlie a possible mechanism of RAN to attenuate electron flux in distinct Fe‐S clusters of CI.This work was supported in part by grants from NIH HL089514 and HL073246; VA 8204‐05P, and AHA 0855940G.
Reduction of Myocardial Reperfusion Injury by Mechanical Tissue Resuscitation (MTR) using a Bio‐absorbable Patch
Authors: Jordan James E , Mays Jennifer J. , Shelton Julie E , Thompson Edreca A , Bryant Allyson K , Morykwas Michael J , Argenta Louis C 
Published: June 2021

Myocardial ischemia‐reperfusion injury (MI/R) follows a well defined sequence of early and late myocyte death. Most therapeutic strategies address only one facet of reperfusion injury. Mechanical resuscitation of injured tissue with sub‐atmospheric pressure reestablishes physiologic homeostasis and improves tissue survival. This study explores the use of absorbable material and a mechanical device to achieve resuscitation of myocardial tissue following MI/R.Anesthetized swine were subjected to 80 min of left coronary occlusion and 3 hours of reperfusion. Animals were assigned to either:1) control or 2) treatment with 50mmHg of MTR during reperfusion using a bio‐absorbable patch. Both groups had equivalent (p=0.07) areas at risk (16±1.0% and 13.7±0.6%, respectively). MTR applied directly on the injured myocardium for 180 minutes significantly (p<0.002) reduced infarct size compared to controls: 14.2±3.1% vs 30.2±2.6%. This reduction in infarct size (53%) is comparable to that observed previously when commercially available, non‐absorbable patch materials (55–65% reduction in infarct size) were used.MTR of injured myocardium using an absorbable patch for a defined period of time can reduce tissue death following MI/R. This study reproduces the reduction of infarct size previously observed while utilizing novel, bio‐absorbable materials. The use of degradable material for the application of MTR may allow for longer treatment and better outcomes in the clinical setting while at the same time eliminate the need for a second operation to remove the device. This treatment strategy offers a simple, effective, clinically relevant, non‐pharmacologic approach to reducing injury following MI/R.
Central TNF‐alpha enhances pressor hemodynamic response to acute stressor
Authors: Zera Tymoteusz , Ufnal Marcin , Szczepañska‐Sadowska Ewa 
Published: June 2021

Growing evidence points to the role of brain TNF‐alpha in the cardiovascular control. The aim of the present study was to determine whether TNF‐alpha acting in the brain is involved in regulation of the cardiovascular responses to acute stressor (AS) (air puff applied on the head of a rat). The experiments were carried out on freely moving Sprague‐Dawley rats pretreated for 28 days with saline or TNF‐alpha blocker etanercept delivered from osmotic minipump through cannula implanted into the lateral cerebral ventricle (LCV). Measurements of mean arterial pressure (MAP) and heart rate (HR) were performed during 60 min of LCV infusion of saline (5μl/hr) or TNF‐alpha (200ng/5μl/hr) followed by AS. Three groups of rats were analyzed: saline pretreatment + saline infusion, saline pretreatment + TNF‐alpha infusion, etanercept pretreatment + saline infusion. Baseline MAP and HR did not differ among groups. Infusion of TNF‐alpha resulted in increase of baseline MAP without changes in HR and enhanced pressor response to AS. Etanercept pretreatment resulted in lower MAP increases to AS than the saline pretreatment group. In conclusion present results show pressor action of centrally administered TNF‐alpha and its involvement in regulation of pressor response to acute stressor.The study was supported by a grant from the Polish Ministry of Education and Science nr 0085/B/P01/2008/35
New applications of automated electrophysiology: heat activation of TRPV1 and action potentials of cardiomyocytes
Authors: Haedo Rodolfo , Haythornthwaite Ali , Stoelzle Sonja , Haarmann Claudia , Farre Cecilia , Guinot David , Kreir Mohamed , Steindl Juergen , Beckler Matthias , George Michael , Brueggemann Andrea , Fertig Niels 
Published: June 2021

Automated patch clamp devices, with their increased throughput and high data quality, are finding their place in the market of automated electrophysiological measurements.Unique features coupled with ease of use and higher throughput, make some of these planar patch clamp devices ideal tools for ion channel screening and safety testing. E.g., the ability of temperature control and rapid application of heated solution is an advantage in compound discovery, targeting TRPV ion channels. Discrimination of antagonising the ligand‐activated vs. the heat‐activated response of TRP channels could be important in the discovery of novel compounds with reduced side‐effects. Data will be shown of TRPV1 currents activated by heated solution and block of these responses by ruthenium red.Another novel feature of the planar patch clamp device used is its ability to conduct parallel current‐clamp recordings. This in combination with the temperature control allows unique experiments of action potential recordings from stem‐cell derived cardiomyocytes, a system becoming increasingly important in drug safety testing. Current recordings from hERG, NaV, CaV and KV channels as well as action potential recordings and modulation of the latter by hERG active compounds, all done at 35¢a C will be shown.
Quantification of inflammatory and Toll‐like receptor gene expression in insulin resistant horses
Authors: Stokes Ashley Michelle , Carlisle Katherine , Madara Elise , McGeachy Matthew , Lavie Nicholas , Keowen Michael , Garza Frank , Andrews Frank 
Published: June 2021

The objectives of this study were to quantify the expression of several inflammatory‐related genes from the Toll‐like receptor signaling pathway found in leukocyte samples taken from insulin resistant horses in comparison to normal horses. Genes of interest are Toll‐like receptors 2 and 4, (TLR2, 4), Cluster of Differentiation Factor 14 (CD‐14), Interleukin‐8 (IL‐8), Phosphoinositide 3‐kinase (PI3K), and nuclear factor NFKBIA inhibitor IkBa. Alterations should reflect chronic low‐grade inflammation resulting from insulin resistance as found in other species.Objectives were to identify horses with insulin resistance and quantify expression of these genes in insulin resistant horses in comparison to normal horses.Insulin resistance was determined in 21 horses using an IV glucose‐insulin tolerance test.Total leukocyte RNA was extracted from a single baseline jugular venous sample from normal (n=13) and insulin resistant (n=8) adult horses. TaqMan RT‐PCR was used to examine the samples and quantify the genes of interest.Significance was determined after calculating ΔΔCT values with a P‐value considered significant < 0.05.There was significant down‐regulation of inflammatory inhibitors (IkBa, PI3K) and up‐regulation of indicators of TLR involvement and inflammation (TLR‐4, IL‐8) indicating the possibility of the existence of chronic inflammation in insulin resistant horses.
Inhibition of Phosphodiesterases Prevents Mitochondrial Permeability Transition Pore Opening by Inactivating GSK‐3β via PKA and PKG in Cardiac Cells
Authors: Chanoit Guillaume , Lee SungRyul , McIntosh Rachel , Zvara David A. , Xu Zhelong 
Published: June 2021

Both protein kinase A (PKA) and protein kinase G (PKG) can inactivate glycogen synthase kinase 3β (GSK‐3β), and inactivation of GSK‐3â may lead to cardioprotection through suppression of the mitochondrial permeability transition pore (mPTP) opening. The aim of this study was to test if inhibition of phosphodiesterases (PDEs) can moderate the pore opening via GSK‐3β. IBMX (1‐methyl‐3‐isobutylxanthine), a non‐selective inhibitor of PDEs, prevented H2O2‐induced mPTP opening in cardiac cells. IBMX was not able to inhibit the pore opening in cells transfected with the constitutively active GSK‐3β mutant, suggesting that IBMX prevents the pore opening by inactivating GSK‐3β. IBMX reduced reperfusion injury in a GSK‐3β –dependent manner. In support, IBMX significantly increased GSK‐3β phosphorylation at Ser9, an effect that was reversed by both the PKA inhibitor H89 and the PKG inhibitor KT5823, implying that IBMX inactivates GSK‐3β via PKA and PKG. IBMX also activated both PKA and PKG. IBMX failed to prevent the pore opening in cells treated with H89 or PKA siRNA, suggesting a role of PKA in the action of IBMX. Similarly, KT5823 and PKG siRNA also reversed the protective effect of IBMX. In conclusion, inhibition of PDEs prevents the mPTP opening by inactivating GSK‐3β through both PKA and PKG. Inhibition of PDEs may serve a useful approach to attenuate reperfusion injury.This study was supported by NIHR01HL08336.
Ranolazine delays Ca2+‐induced mitochondrial permeability transition pore opening and membrane potential depolarization in guinea pig heart mitochondria
Authors: Aldakkak Mohammed , Camara Amadou K.S. , Heisner James S. , Gadicherla Ashish K. , Boelens Age D. , Yang Meiying , Dash Ranjan K. , Stowe David F. 
Published: June 2021

Ranolazine (RAN) is an antianginal drug that may block a late Na+ current in cardiac cells during ischemia. We showed previously that RAN improved cardiac function and reduced ROS emission during ischemia and reperfusion (IR). Here we tested if these effects of RAN are associated with delay in opening of the mitochondrial (m) permeability transition pore (PTP) and membrane potential (ΔΨm) depolarization induced by incrementally adding buffer CaCl2 to mitochondrial suspension. Guinea pig hearts were perfused with RAN (5 μM) for 1 min followed by 30 min ischemia and 120 min reperfusion to assess m[Ca2] and infarct size (IS) in intact hearts, or reperfused for only 10 min to isolate mitochondria. ΔΨm and matrix Ca2+ uptake were measured using fluorescence spectrophotometry with rhodamine 123 and indo‐1. We found that m[Ca2+] increased less during early ischemia in RAN (296±25 nM) vs control hearts (436±34 nM), and m[Ca2+] was less in RAN treated (280±39 nM) vs control hearts (429±45 nM) during early reperfusion. RAN reduced IS (24±3%) vs control (37±3%). More buffer CaCl2 (20–25%) was required to open PTP and to induce full ΔΨm depolarization in RAN vs control hearts. Reduced ROS emission during ischemia may delay cytosolic Na+, Ca2+ loading, and consequently mCa2+ loading. The delay in PTP opening by Ca2+ in RAN treated hearts could result from improved mitochondrial bioenergetics with increased capacity to extrude Ca2+.This work was supported in part by the American Heart Association [0355608Z, 0855940G to D.F. Stowe]; the National Institutes of Health [K01 HL73246 to A.K.S. Camara, R01 HL089514 to D.F. Stowe]
Cyclin D1 is a bona fide target gene of NFATc1 and is sufficient in the mediation of injury‐induced vascular wall remodeling
Authors: Wang Dong , Karpurapu Manjula , Van Quyen Dong , Kundumani‐Sridharan Venkatesh , Pulusani Srinidhi , Rao Gadiparthi N 
Published: June 2021

Platelet‐derived growth factor BB (PDGF‐BB) induced cyclin D1 expression in a time‐ and NFAT‐dependent manner in human aortic smooth muscle cells (HASMCs) and blockade of NFATs prevented HASMC DNA synthesis and their cell cycle progression from G1 to S phase. Selective inhibition of NFATc1 by its siRNA also blocked HASMC proliferation and migration. Characterization of cyclin D1 promoter revealed the presence of several NFAT binding sites and the site at −1333 was found to be sufficient in mediating PDGF‐BB‐induced cyclin D1 promoter‐reporter gene activity. In addition to its role in cell cycle progression, cyclin D1 mediated HASMC migration in NFATc1‐dependent manner. Balloon injury‐induced cyclin D1‐CDK4 activity requires NFAT activation and adenovirus‐mediated transduction of cyclin D1 was found to be sufficient to overcome the blockade effect of NFATs by VIVIT on balloon injury‐induced vascular wall remodeling events, including SMC migration from medial to luminal region, their proliferation in the intimal region and neointima formation. Together, these results provide another mechanistic evidence for the role of NFATs, particularly NFATc1 in the regulation of HASMC proliferation and migration as well as vascular wall remodeling. NFATc1 could be a potential therapeutic target against the re‐narrowing of artery after angioplasty.This work was supported by a grant from NIH (HL069908).
BAY 41‐2272 reduces vascular smooth muscle cell growth via PK‐G & PK‐A signals
Authors: Brown Trisha A , Mendelev Natalia N. , Fox Jonathan C. , Joshi Chintamani N. , Tulis David A. 
Published: June 2021

In the cardiovascular system, abnormal growth of vascular smooth muscle (VSM) is intimately involved in both primary disease and during complications following therapeutic intervention. In turn, approaches aimed at modifying the cell signaling pathways responsible for VSM growth are scientifically significant. The objective of the current study is to investigate novel routes for cyclic nucleotide‐based control of VSM growth. We hypothesize that BAY 41‐2272 (BAY), a recently characterized soluble guanylate cyclase (sGC) stimulator and inducer of cyclic guanosine monophosphate (cGMP) synthesis, has capacity to reduce VSM cell proliferation and migration and that these occur through protein kinase‐G (PK‐G) and protein kinase‐A (PK‐A) pathways. In rat thoracic aorta primary VSM cells (passage ≤ 6), BAY reduces proliferation and inhibits migration using a modified Boyden chemotaxis assay and an in vitro scrape wounding injury model. Cyclic nucleotide assays and Western blot analyses reveal that BAY induces both the cGMP and cAMP signaling pathways, and inhibitor studies suggest that BAY operates through both PK‐G and PK‐A. These novel findings show that BAY is capable of reducing VSM growth through stimulation of parallel cGMP and cAMP systems and suggest that BAY may prove therapeutic for the treatment of cardiovascular diseases.Research Support: NHLBI NIH Award Numbers R01HL081720 and R01HL081720‐03S1.
An ethyl acetate extract from a subaleurone layer of Japanese rice inhibits angiotensin ll–induced signal transduction and hypertrophy in vascular smooth muscle cells
Authors: Takaguri Akira , Utsnomiya Hirotoshi , Kono Ryohei , Akazawa Shin‐ichi , Eguchi Satoru 
Published: June 2021

ObjectiveRice has been consumed well in many countries. However, whether rice contains an ingredient useful to prevent cardiovascular diseases remains unknown. We have shown that angiotensin II (AngII) induces hypertrophy and migration of vascular smooth muscle cells (VSMCs) through activation of epidermal growth factor receptor (EGFR) and Rho/Rho‐kinase. A subaleurone layer of rice is rich in oligosaccharide and dietary fibers. In this study, we examined the effects of ethyl acetate extract from a subaleurone layer on AngII‐induced signal transduction and hypertrophy in VSMCs.Methods and ResultsVSMCs were prepared from the aorta of 12‐week‐old male Sprague Dawley rats. Phosphorylation and expression of the signaling proteins were evaluated by immuoblotting. Pretreatment of the ethyl acetate extract (100 μg/ml) inhibited AngII (100 nM)‐induced EGFR transactivation and phosphorylation of a ROCK substrate, myosin phosphatase target subunit‐1. Also, AngII‐induced c‐fos expression was inhibited by the ethyl acetate extract. Thus, AngII‐induced hypertrophy was significantly inhibited by the ethyl acetate extract.ConclusionThese data suggest that an ethyl acetate extract from a subaleurone layer might have a protective effect toward cardiovascular diseases by interfering with signal transduction induced by enhanced rennin‐angiotensin system