Hyperlipidemia is one of the important risk factors of cardiovascular and cerebrovascular diseases. Monitoring of adverse reactions of hypolipidemic drugs is very crucial for clinical administration. In this study, in...
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ISBN:
(纸本)9781538667774
Hyperlipidemia is one of the important risk factors of cardiovascular and cerebrovascular diseases. Monitoring of adverse reactions of hypolipidemic drugs is very crucial for clinical administration. In this study, in order to explore the occurrence characteristics of ADRs for hypolipidemic drugs, we manually annotated and normalized the ADRs of hypolipidemic drugs from Chinese adverse event reports. Totally 579 records are involved in the study. Also we constructed a new dictionary of ADRs and a classification standard of the Severity of ADR to standardize the description of adverse drug reactions. Finally, we got a dictionary of ADR which have 171 terms, of 129 are from WHO-ART and 42 are self-defined. A new classification criteria for the severity of ADRs were built and each record were annotated by the criteria. Our annotated corpus, ADR dictionary and the classification standard can provide data source and dictionary resource to support future machine-learning-based ADR mining to better explore ADRs of hypolipidemic drugs.
Aims: Arrhythmogenesis of chronic myocardial infarction (MI) is associated with the prolongation of action potential, reduction of inward rectifier potassium (I-K1, Kir) channels and hyper-activity of Calcium/calmodul...
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Aims: Arrhythmogenesis of chronic myocardial infarction (MI) is associated with the prolongation of action potential, reduction of inward rectifier potassium (I-K1, Kir) channels and hyper-activity of Calcium/calmodulin-dependent kinase II (CaMKII) in cardiomyocytes. Zacopride, a selective I-K1 agonist, was applied to clarify the cardioprotection of I-K1 agonism via a CaMKII signaling on arrhythmias post-MI. Methods: Male SD rats were implanted wireless transmitter in the abdominal cavity and subjected to left main coronary artery ligation or sham operation. The telemetric ECGs were monitored per day throughout 4 weeks. At the endpoint, isoproterenol (1.28 mg/kg, i.v.) was administered for provocation test. The expressions of Kir2.1 (dominant subunit of I-K1 in ventricle) and CaMKII were detected by Western-blotting. Key findings: In the telemetric rats post-MI, zacopride significantly reduced the episodes of atrioventricular conduction block (AVB), premature ventricular contraction (PVC), ventricular tachycardia (VT) and ventricular fibrillation (VF), without significant effect on superventricular premature contraction (SPVC). In provocation test, zacopride suppressed the onset of ventricular arrhythmias in conscious PMI or sham rats. The expression of Kir2.1 was significantly downregulated and p-CaMKII was upregulated post-MI, whereas both were restored by zacopride treatment. Significance: I-K1/Kir2.1 might be an attractive target for pharmacological controlling of lethal arrhythmias post MI.
The A1 subunit of cholera toxin (CTA1) retains the adjuvant function of CT, without its toxic side effects, making the molecule a promising mucosal adjuvant. However, the methods required to obtain a pure product are ...
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The A1 subunit of cholera toxin (CTA1) retains the adjuvant function of CT, without its toxic side effects, making the molecule a promising mucosal adjuvant. However, the methods required to obtain a pure product are both complicated and expensive, constricting its potential commercial applicability. Here, we fused the peptidoglycan binding domain (PA) to the C-terminus of CTA1, which enabled the fusion protein to be expressed by Bacillus subtilis, and secreted into the culture medium. CTA1 was then purified and displayed on GEM particles using a one step process, which resulted in the formation of CTA1-GEM complexes. Next, the CTA1-GEM complexes were used as an adjuvant to enhance the immune responses of mice to the influenza subunit vaccine. It was observed that the CTA1-GEM complexes enhanced specific systemic (IgG) and mucosal (IgA) immune responses against antigen, and induced cellular immune responses as well. The data presented here suggests that CTA1-GEM complexes can serve as a viable mucosal adjuvant. (C) 2017 Elsevier Inc. All rights reserved.
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