bluuebunny/crossref_metadata_2025_split huggingface dataset:
High cholesterol diet effects on ischemia–reperfusion injury of the heart
Authors: D’Annunzio Verónica , Donato Martín , Buchholz Bruno , Pérez Virginia , Miksztowicz Verónica , Berg Gabriela , Gelpi Ricardo J. 
Published: August 2012

Ischemic heart disease is the leading cause of morbi-mortality in developed countries. Both ischemia–reperfusion injury and mechanisms of cardioprotection have been studied for more than 50 years. It is known that the physiopathological mechanism of myocardial ischemia involves several factors that are closely related to its development, of which hypercholesterolemia is one of the main ones. Therefore, the objective of this review was to elucidate the effects of a high-cholesterol diet on normal ventricular function and ischemia–reperfusion injury associated phenomenon such as post-ischemic ventricular dysfunction (stunned myocardium). Although there exist many studies considering several aspects of this physiopathological entity, the majority were carried out on normal animals. Thus, experiments carried out on hypercholesterolemic models are controversial, in particular those evaluating different mechanisms of cardioprotection such as ischemic preconditioning and postconditioning, and cardioprotection granted by drugs such as statins, which apart from exerting a lipid-lowering effect, exert pleiotropic effects providing cardioprotection against ischemia–reperfusion injury. These controversial results concerning the mechanisms of cardioprotection vary according to quality, composition, and time of administration of the high-cholesterol diet, as well as the species used in each experiment. Thus, to compare the results it is necessary to take all of these variables into account, since they can change the obtained results.
The ability of phosphodiesterase-5 inhibitors sildenafil and ordonafil to reverse L-NAME induced cardiac hypertrophy in the rabbit: possible role of calcineurin and p38
Authors: Zeidan Asad , Siam Aiad , Al Kaabba Abdulaziz , Mohammad Mukhallad , Khatib Said 
Published: August 2012

Phosphodiesterase 5 inhibitors (PDE-5Is) can suppress and (or) reverse pressure overload induced myocardial hypertrophy. This study investigated the suppressive effect of 2 PDE-5Is (sildenafil and ordonafil) on N-nitro-l-arginine methyl ester (L-NAME)-induced cardiac hypertrophy in rabbit heart, and examined their possible mechanism of action. L-NAME increased left ventricular thickness to 6.1± 0.18 mm from 4.6 ± 0.13 mm (p < 0.05), which regressed after treatment with either sildenafil or ordonafil to 5.1 ± 0.1 mm and 4.8 ± 0.2 mm, respectively (p < 0.05). Phenylephrine increased neonatal rat ventricular myocyte cell surface area to 131% ± 3% of the control value, which was associated with significant increment in ERK1/2 to 143% ± 5% of the control value (p < 0.05). Ordonafil and sildenafil decreased cell surface area to 95% ± 3% and 90% ± 1% of the control value, respectively. Both drugs decreased ERK1/2 to 88% ± 4% of the control value. Calcineurin activity was significantly decreased after 1 h of treatment with 0.1 mg·L–1 ordonafil (1.15 ± 0.05, p < 0.05). For sildenafil (0.1 mg·L–1), calcineurin activity significantly decreased only after 24 h of incubation (22%). Also p38 activation was attenuated by ordonafil and sildenafil (0.1 mg·L–1). It is suggested that both drugs have the ability to reverse L-NAME-induced cardiac hypertrophy and suppress phenylphrine-induced myocyte hypertrophy, and that these effects may be mediated through the attenuation of calcineurin and its downstream signaling pathways (p38) in neonatal rat ventricular myocytes.
Up-regulation of myocardial connexin-43 in spontaneously hypertensive rats fed red palm oil is most likely implicated in its anti-arrhythmic effects
Authors: Bačová Barbara , Radošinská Jana , Viczenczová Csilla , Knezl Vladimír , Dosenko Victor , Beňova Tamara , Navarová Jana , Gonçalvesová Eva , van Rooyen Jacques , Weismann Peter , Slezák Jan , Tribulová Narcis 
Published: August 2012

The purpose of this study was to test our hypothesis that red palm oil (RPO) intake may affect abnormalities of myocardial connexin-43 (Cx43) and protein kinase Cε (PKCε) signaling, and consequently the propensity of the spontaneously hypertensive rat heart (SHR) heart to arrhythmias. SHR and Wistar–Kyoto (WKY) rats fed a standard rat chow plus red palm oil (200 µL/day) for 5 weeks were compared with untreated rats. Cytosolic but not particulate PKCε expression as well as Cx43-mRNA, total Cx43 proteins, and its phoshorylated forms were increased, and disordered localization of Cx43 was attenuated in the left ventricle of RPO-fed SHR compared with untreated rats. These alterations were associated with suppression of early post-ischemic-reperfusion-related ventricular tachycardia and electrically inducible ventricular fibrillation. However, the treatment dose of RPO caused down-regulation of myocardial Cx43, but did not alter its cell membrane distribution or overall PKCε expression in WKY rats. It was, however, associated with poor arrhythmia protection, suggesting overdosing. Results indicate that SHR benefit from RPO intake, particularly because of its apparent anti-arrhythmic effects. This protection can be, in part, attributed to the preservation of cell-to-cell communication via up-regulation of myocardial Cx43, but not with PKCε activation.
The acutely occluded left main coronary artery culprit in cardiogenic shock and initial percutaneous coronary intervention: a substudy of the Manitoba “no option” left main PCI registry
Authors: Hussain Farrukh , Nguyen Thang , Elmayergi Nader , Ducas John , Minhas Kunal , Vo Minh , Kass Malek , Ravandi Amir , Parmar Gurpreet , Jassal Davinder S. , Tam James W. , Freed Darren , Menkis Alan H. , Philipp Roger K. 
Published: August 2012

We aim to describe the in-hospital outcomes of the first reported Canadian cohort of patients with cardiogenic shock and acute myocardial infarction (MI) due to acute and total occlusion of the left main coronary artery, treated with initial percutaneous coronary intervention (PCI). Acute left main thromboses with cardiogenic shock were identified (N = 8) from a retrospective consecutive cohort of high risk left main PCI (N = 56) performed at our institution from 2004–2009. The mean age was 62.3 ± 13.2 years, with 6 (75%) male patients. Successful PCI was performed in all patients, with thrombectomy utilized in 4 patients (50%), stenting in 7 patients (88%), and intra-aortic balloon pump augmentation in 7 patients (88%). Two patients (25%) required extracorporeal membrane oxygenation (ECMO) and 2 other patients required ventricular assist devices. Post-PCI coronary artery bypass grafting (CABG) was performed for 2 patients (25%). The mean SYNTAX score was 26.6 ± 10.5. The mean logistic EuroSCORE was 30.4 ± 12.6%. In-hospital mortality occurred in 3 patients (38%). Acute left main occlusion is a rare but devastating presentation of myocardial infarction, invariably with cardiogenic shock. Emergent PCI may be an effective method to acutely revascularize this subset of patients; however, aggressive post-PCI care including ECMO, CABG, and ventricular support may be required to improve patient survival.
Expression profiles of metamorphosis-related genes during natural transformations in tadpoles of wild Wood Frogs (Lithobates sylvaticus)
Authors: Navarro-Martín Laia , Lanctôt Chantal , Edge Christopher , Houlahan Jeff , Trudeau Vance L. 
Published: August 2012

Numerous studies using laboratory-reared tadpoles have shown the importance of thyroid hormones (TH), thyroid receptors (TR), and deiodinase (Dio) enzymes during anuran metamorphosis. Our study focuses on the analysis of thyroid-related genes in tadpoles of wild Wood Frogs ( Lithobates sylvaticus (LeConte, 1825); also known as Rana sylvatica (Cope, 1889)) during metamorphosis. Results showed that, in concordance with laboratory-reared studies, thyroid receptor beta (trb) gene expression profiles presented the most marked changes. At climax and compared with premetamorphic stages, brains, tails, and gonad–mesonephros complex (GMC) tissues increased trb expression levels 5-, 21-, and 41-fold, respectively (p < 0.05). In addition, gene expression levels of brain deiodinase type II and III showed opposite trends, where 3-fold decrease and 10-fold increase were, respectively, found. This finding supports the idea that thyroid hormone, as it has been demonstrated in laboratory-reared tadpoles, is also involved in natural metamorphosis in wild tadpoles. Interestingly, and contrary to our predictions, we observed that whole brain corticotropin-releasing factor (crf) and crf receptor 1 (crfr1) gene expression levels significantly decrease through metamorphosis in wild L. sylvaticus tadpoles. Further analyses are required to determine if a role of TH in the timing of anuran gonadal development exists, as well as the importance of cell-specific and tissue-specific expression of crf and crfr1 to metamorphosis.
Estimating the influence of the thermal environment on activity patterns of the desert woodrat (Neotoma lepida) using temperature chronologies
Authors: Murray Ian W. , Smith Felisa A. 
Published: August 2012

Environmental temperature influences the ecology and life history of animals. In habitats near the thermal range boundary, fluctuations in temperature may influence the ability of species to persist. Desert woodrats ( Neotoma lepida Thomas, 1893) occupy one of the hottest and most extreme environments in the western hemisphere, Death Valley, California, despite limited adaptations for water conservation or efficient heat dissipation. Moreover, N. lepida have a relatively low tolerance for high temperature. Thus, we hypothesized temperature might influence both the timing and the duration of activity. To test this idea, we attached iButton sensors to 56 animals over a 2-year period and recorded activity. Each sensor was set to record at 5 or 15 min intervals and stored approximately 2000 records before retrieval. We found a strong relationship between ambient temperature and onset and duration of activity, influenced by both body size and gender. Neotoma lepida did not emerge until air temperature fell below 42 °C. As daily high temperatures increased, both sexes had fewer nightly activity bouts of shorter duration. Our results suggest that activity of N. lepida is constrained during the climatically intense summer months. Animals face a trade-off between remaining in the thermal safety of the den vs. emerging to obtain resources.
Threonine 2609 Phosphorylation of the DNA-Dependent Protein Kinase Is a Critical Prerequisite for Epidermal Growth Factor Receptor–Mediated Radiation Resistance
Authors: Javvadi Prashanthi , Makino Haruhiko , Das Amit K. , Lin Yu-Fen , Chen David J. , Chen Benjamin P. , Nirodi Chaitanya S. 
Published: August 2012

AbstractThe EGF receptor (EGFR) contributes to tumor radioresistance, in part, through interactions with the catalytic subunit of DNA-dependent protein kinase (DNA-PKc), a key enzyme in the nonhomologous end joining DNA repair pathway. We previously showed that EGFR-DNA-PKcs interactions are significantly compromised in the context of activating mutations in EGFR in non–small cell lung carcinoma (NSCLC) and human bronchial epithelial cells. Here, we investigate the reciprocal relationship between phosphorylation status of DNA-PKcs and EGFR-mediated radiation response. The data reveal that both the kinase activity of DNA-PKcs and radiation-induced phosphorylation of DNA-PKcs by the ataxia telangiectasia–mutated (ATM) kinase are critical prerequisites for EGFR-mediated radioresponse. Alanine substitutions at seven key serine/threonine residues in DNA-PKcs or inhibition of DNA-PKcs by NU7441 completely abrogated EGFR-mediated radioresponse and blocked EGFR binding. ATM deficiency or ATM inhibition with KU55933 produced a similar effect. Importantly, alanine substitution at an ATM-dependent DNA-PKcs phosphorylation site, T2609, was sufficient to block binding or radioresponse of EGFR. However, mutation of a DNA-PKcs autophosphorylation site, S2056 had no such effect indicating that DNA-PKcs autophosphorylation is not necessary for EGFR-mediated radioresponse. Our data reveal that in both NSCLCs and human bronchial epithelial cells, activating mutations in EGFR specifically abolished the DNA-PKcs phosphorylation at T2609, but not S2056. Our study underscores the critical importance of a reciprocal relationship between DNA-PKcs phosphorylation and EGFR-mediated radiation response and elucidates mechanisms underlying mutant EGFR-associated radiosensitivity in NSCLCs. Mol Cancer Res; 10(10); 1359–68. ©2012 AACR.
Home-monitoring of oral anticoagulation vs. dabigatran
Authors: Zhou Qi , Guyatt Gordon , Alonso-Coello Pablo 
Published: August 2012

SummaryOral anticoagulation with vitamin k antagonists (VKAs) requires regular testing and dose adjustment. Home-monitoring (self-testing or self-management) is more effective than usual management. Dabigatran, does not require dose-adjustment and appears to be more effective at reducing the risk of stroke with similar risks of bleeding in patients with atrial fibrillation (AF). Dabigatran, however, has not been compared to the home-monitoring. It was the objective to evaluate the efficacy of dabigatran compared with home-monitoring of oral anticoagulation with VKAs. Randomised controlled trials (RCTs) comparing usual management of oral anticoagulation with home-monitoring, dabigatran with usual management, and RCTs comparing dabigatran with home-monitoring and including patient-important outcomes (thromboembolic events, death and major bleeding) were eligible. For our direct comparison we calculated pooled relative risks (RRs) using the Mantzel-Haenzel random effect model. For the indirect comparison we estimated lnRRs and back transformed to RR. We evaluated the quality of the evidence with the GRADE system. Dabigatran, compared with warfarin, was associated with lower rates of stroke or thromboembolism and systemic embolism but similar rates of major haemorrhage and death. Dabigatran 150 mg also increased non-significantly the rate of myocardial infarction. The quality of the evidence was high. Our indirect comparison of home-monitoring of oral anticoagulation versus dabigatran showed no convincing differences in the risk of thromboembolism, death or major bleeding. The estimates for self-management vs. dabigatran showed stronger but still non-significant trends. The quality of the evidence was low. In conclusion, the indirect comparison of home monitoring of oral anticoagulation with dabigatran suggests that the treatments have similar impact on thrombosis, bleeding and death. However, the confidence in the estimate of effect is low to very low. Our analyses contrast with the available comparison of dabigatran with conventional warfarin monitoring.
Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss
Authors: Bertinato Juliano , Bueno Carolina , da Silva Kelma , de Carvalho Mário , Francisco Rossana , Zugaib Marcelo , Cerda Alvaro , Morelli Vânia , Guerra-Shinohara Elvira M. 
Published: August 2012

SummaryRecurrent pregnancy loss (RPL) is a multifactorial condition. The effect of antithrombin (SERPINC1), protein C (PROC), thrombomodulin (THBD) and tissue factor pathway inhibitor (TFPI) single nucleotide polymorphisms (SNPs) on the risk of RPL is thus far unknown. Our objective was to determine the association of SNPs in the above mentioned genes with RPL. We included 117 non-pregnant women with three or more consecutive losses prior to 20 weeks of pregnancy without a previous history of carrying a fetus to viability, and 264 healthy fertile non-pregnant women who had at least two term deliveries and no known pregnancy losses. The PROC (rs1799809 and rs1799808), SERPINC1 (rs2227589), THBD (rs1042579) and TFPI (rs10931292, rs8176592 and rs10153820) SNPs were analysed by Real Time PCR. Genotype frequencies for PROC 2418A>G, PROC 2405C>T, THBD 1418C>T, TFPI (T-33C and TFPI C-399T) SNPs were similar in cases and controls. The carriers of SERPINC1 786A allele (GA + AA genotypes) had an increased risk for RPL (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.05 – 3.00, p= 0.034) while women carrying the TFPI –287C allele (TC + CC genotypes) had a protection effect on having RPL (OR: 0.46, 95% CI: 0.26 – 0.83, p= 0.009). The TCC haplotype for TFPI T-33C/ TFPI T-287C/ TFPI C-399T SNPs was less frequent in cases (5.7%) than in controls (11.6%) (OR: 0.45, 95% CI: 0.23 – 0.90, p= 0.025). In conclusion, our data indicate that SERPINC1 786G>A variant increases the risk for RPL, while TFPI T-287C variant is protective; however, further studies are required to confirm our findings.
Extracardiac Neural Remodeling in Humans With Cardiomyopathy
Authors: Ajijola Olujimi A. , Wisco Jonathan J. , Lambert H. Wayne , Mahajan Aman , Stark Elena , Fishbein Michael C. , Shivkumar Kalyanam 
Published: August 2012

Background—
Intramyocardial nerve sprouting after myocardial infarction is associated with ventricular arrhythmias. Whether human stellate ganglia remodel in association with cardiac pathology is unknown. The purpose of this study was to determine whether cardiac pathology is associated with remodeling of the stellate ganglia in humans.

Methods and Results—

Left stellate ganglia were collected from patients undergoing sympathetic denervation for intractable ventricular arrhythmias and from cadavers, along with intact hearts. Clinical data on patients and cadaveric subjects were reviewed. We classified ganglia from normal, scarred, and nonischemic cardiomyopathic hearts without scar as NL (n=3), SCAR (n=24), and NICM (n=7), respectively. Within left stellate ganglia, neuronal size, density, fibrosis, synaptic density, and nerve sprouting were determined. Nerve density and sprouting were also quantified in cadaveric hearts. Mean neuronal size in normal, scarred, and nonischemic cardiomyopathic hearts without scar groups were 320±4 μm
2
, 372±10 μm
2
, and 435±10 μm
2
(
P
=0.002), respectively. No significant differences in neuronal density and fibrosis were present between the groups. Synaptic density in ganglia from SCAR and NICM groups were 57.8±11.2 μm
2
/mm
2
(
P
=0.084) and 44.5±7.9 μm
2
/mm
2
(
P
=0.039), respectively, compared with the normal group, 17.8±7 μm
2
/mm
2
(overall
P
=0.162). There were no significant differences in left stellate ganglia nerve sprouting or myocardial nerve density between the groups.

Conclusions—
Neuronal hypertrophy within left stellate ganglia is associated with chronic cardiomyopathy in humans. Ganglionic and myocardial nerve sprouting and nerve density were not significantly different. These changes may be related to increased cardiac sympathetic signaling and ventricular arrhythmias. Further studies are needed to determine the electrophysiological consequences of extracardiac neuronal remodeling in humans.
The Indian Ocean: The Region of Highest Skill Worldwide in Decadal Climate Prediction*
Authors: Guemas Virginie , Corti Susanna , García-Serrano J. , Doblas-Reyes F. J. , Balmaseda Magdalena , Magnusson Linus 
Published: August 2012

Abstract
The Indian Ocean stands out as the region where the state-of-the-art decadal climate predictions of sea surface temperature (SST) perform the best worldwide for forecast times ranging from the second to the ninth year, according to correlation and root-mean-square error (RMSE) scores. This paper investigates the reasons for this high skill by assessing the contributions from the initial conditions, greenhouse gases, solar activity, and volcanic aerosols. The comparison between the SST correlation skill in uninitialized historical simulations and hindcasts initialized from estimates of the observed climate state shows that the high Indian Ocean skill is largely explained by the varying radiative forcings, the latter finding being supported by a set of additional sensitivity experiments. The long-term warming trend is the primary contributor to the high skill, though not the only one. Volcanic aerosols bring additional skill in this region as shown by the comparison between initialized hindcasts taking into account or not the effect of volcanic stratospheric aerosols and by the drop in skill when filtering out their effect in hindcasts that take them into account. Indeed, the Indian Ocean is shown to be the region where the ratio of the internally generated over the externally forced variability is the lowest, where the amplitude of the internal variability has been estimated by removing the effect of long-term warming trend and volcanic aerosols by a multiple least squares linear regression on observed SSTs.
Interdecadal Relationship between the Mean State and El Niño Types*
Authors: Chung Pei-Hsuan , Li Tim 
Published: August 2012

Abstract
The interdecadal change of the mean state and two types of El Niño was investigated based on the analysis of observational data from 1980 to 2010. It was found that easterly trades and sea surface temperature (SST) gradients across the equatorial Pacific undergo a regime change in 1998/99, with enhanced trades and a significant cooling (warming) over tropical eastern (western) Pacific in the later period. Accompanying this mean state change is more frequent occurrence of central Pacific (CP) El Niño during 1999–2010. The diagnosis of air–sea feedback strength showed that atmospheric precipitation and wind responses to CP El Niño are greater than those to the eastern Pacific (EP) El Niño for given a unit SST anomaly (SSTA) forcing. The oceanic response to the same wind forcing, however, is greater in the EP El Niño than in the CP El Niño. A mixed layer heat budget analysis reveals that zonal advection (thermocline change induced vertical advection) primarily contributes to the CP (EP) El Niño growth.
The role of the mean SST zonal gradient in El Niño selection was investigated through idealized numerical experiments. With the increase of the background zonal SST gradient, the anomalous wind and convection response to a specified EP or CP SSTA shift to the west. Such a difference results in a bifurcation of maximum SSTA tendency, as shown from a simple ocean model. The numerical results support the notion that a shift to the La Niño–like interdecadal mean state is responsible for more frequent occurrence of CP-type El Niño.