76 research outputs found
The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction
Modulation of renin-angiotensin system (RAS) by angiotensin-(1–7) (Ang-(1–7)) is an attractive approach to combat the detrimental consequences of myocardial infarction (MI). However Ang-(1–7) has limited clinical potential due to its unfavorable pharmacokinetic profile. We investigated effects of a stabilized, thioether-bridged analogue of Ang-(1–7) called cyclic Ang-(1–7) in rat model of myocardial infarction. Rats underwent coronary ligation or sham surgery. Two weeks thereafter infusion with 0.24 or 2.4 μg/kg/h cAng-(1–7) or saline was started for 8 weeks. Thereafter, cardiac morphometric and hemodynamic variables as wells as aortic endothelial function were measured.
The average infarct size was 13.8% and was not changed by cAng-(1–7) treatment. MI increased heart weight and myocyte size, which was restored by cAng-(1–7) to sham levels. In addition, cAng-(1–7) lowered left ventricular end-diastolic pressure and improved endothelial function. The results suggest that cAng-(1–7) is a promising new agent in treatment of myocardial infarction and warrant further research
Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data
<p>Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.</p>
<p>Methods: The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.</p>
<p>Results: The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.</p>
<p>Conclusion: This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.</p>
Teacher Use of Loss-Focused, Utility Value Messages, Prior to High-Stakes Examinations, and Their Appraisal by Students
This study set out to assess a new instrument designed to measure the perceived frequency that teachers use fear appeals (communicated value messages that focus on avoiding failure) prior to a high-stakes examination and their appraisal as a challenge or a threat. Data were collected from two samples of students preparing for their high-stakes school exit examinations. Exploratory and confirmatory factor analyses supported a three-factor structure of message frequency, challenge, and threat appraisal. Challenge appraisal positively correlated with value, academic self-efficacy, and engagement. Threat appraisal negatively correlated with academic self-efficacy and engagement. Message frequency was unrelated to value, academic self-efficacy, and engagement. The critical factor in determining relations with antecedents and outcomes is not the message frequency but how it is appraised
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Process account of curiosity and interest: a reward-learning perspective
Previous studies suggested roles for curiosity and interest in knowledge acquisition and
exploration, but there has been a long-standing debate about how to define these concepts
and whether they are related or different. In this paper, we address the definition issue by
arguing that there is inherent difficulty in defining curiosity and interest, because both curiosity
and interest are naïve concepts, which are not supposed to have a priori scientific definitions.
We present a reward-learning framework of autonomous knowledge acquisition and use this
framework to illustrate the importance of process account as an alternative to advance our
understanding of curiosity and interest without being troubled by their definitions. The
framework centers on the role of rewarding experience associated with knowledge acquisition
and learning and posits that the acquisition of new knowledge strengthens the value of further
information. Critically, we argue that curiosity and interest are the concepts that they subjectively construe through this knowledge-acquisition process. Finally, we discuss the implications of the reward-learning framework for education and empirical research in educational
psychology
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