Dexmedetomidine is an ␣ 2 -adrenoceptor agonist and anesthetic. The present study was designed to characterize the receptor subtypes and the downstream mechanisms of the vascular effects of dexmedetomidine in small (mesenteric artery) and large (aorta) arteries ex vivo. Isometric tension was measured in Sprague-Dawley rat mesenteric and aortic rings (with or without endothelium). To study relaxations, cumulative concentrations of dexmedetomidine, 5-bromo-N-(2-imidazolin-2-yl)-6-quinoxalinamine, (UK14304), or clonidine were added to rings contracted with 9,11-dideoxy-9␣,11␣-methanoepoxy prostaglandin F 2␣ (U46619) in the presence or absence of indomethacin; N L-657,743, (2S-trans)-1,3,4,5Ј,6,6Ј,7,12b-octahydro-1Ј,3Ј-dimethyl-spiro[2H-benzofuro[2,3-a]quinolizine-2,4Ј(1ЈH)-pyrimidin]-2Ј(3ЈH)-one hydrochloride hydrate (MK912); rauwolscine; prazosin; or pertussis toxin. To study contractions, dexmedetomidine was added to quiescent rings without endothelium or after incubation with L-NAME, rauwolscine, prazosin, indomethacin, or 3-[(6-amino-(4-chlorobenzensulfonyl)-2-methyl-5,6,7,8-tetrahydronaphth)-1-yl]propionic acid (S18886). Dexmedetomidine evoked relaxation at low concentrations (10 pM-30 nM) followed by contraction at higher concentrations (Ͼ30 nM) in the mesenteric artery. In the aorta, the relaxation was significantly smaller. The relaxation to dexmedetomidine depended on nitric oxide, endothelium, and G i protein, and it was mediated by ␣ 2A/D -adrenoceptors and possibly ␣ 2B -adrenoceptors. The contraction was mediated mainly by ␣ 2B -and ␣ 1 -adrenoceptors and involved the action of prostanoids. UK14304 and clonidine induced greater and smaller relaxations, respectively, than dexmedetomidine. In conclusion, depending on the concentration used and the presence of functional endothelium, dexmedetomidine may evoke both relaxation and contraction in isolated arteries. The vascular effects also vary depending on the blood vessel studied. Its vascular effect is different from that of clonidine and UK14304.
Purpose This paper aims to report a case study in flexible learning with multicomponent blended learning mode in an undergraduate chemistry course. Traditional chemistry courses usually include lectures, tutorials and laboratory sections. For a course “Advances in Organic Synthesis” at undergraduate level, it consists of advanced information in organic chemistry such as reaction mechanisms, asymmetric catalysis, retrosynthesis and applications in synthesis of natural products. This course is a difficult subject and requires deep understanding of contents. After learning this course, students should have comprehensive knowledge in advanced strategies of organic synthesis and have an ability to apply them to real cases. This “flexible learning with multicomponent blended learning mode” was implemented by the authors to enhance student engagement and self-motivation in their studies. Design/methodology/approach The authors hoped to enhance students’ engagement in “flexible learning” – a mixed concept with “blended learning” and “flipped classroom” – and called this approach as “multicomponent blended learning mode.” Blended learning combines face-to-face and e-learning components with interactive Web-based components and technical experimental videos were developed. The knowledge integrated in different components provides a natural environment to link the different synthetic methods together, which help students to get a better understanding of the complicated knowledge and strengthen their skills. For flipped classroom, students participated in the case studies of the organic synthesis and shared their findings to other classmates in oral presentations. Findings In this study, both course evaluation score and students’ academic performance in the “multicomponent blended learning mode” were increased significantly when comparing with traditional teaching methods in 2011. It was found that students’ engagement and their self-motivation in learning were enhanced. Originality/value The positive feedback from the students and the enhancement of their academic performance supported the value in this research. Besides, most universities in Hong Kong have suspended all face-to-face classes and conducted all teaching in online mode during COVID-19 outbreak. As the multicomponent blended learning mode of this course has already been conducted for eight cohorts, the authors are confident that this feature can minimize the sudden change in the learning habits for the students. As social factors and individual variations in students’ learning and study mode may affect the learning outcomes, these interactive multicomponent e-learning components in this special period make students excited when they can study and digest the knowledge according to their own pace.
The use of medication is effective in managing metabolic syndrome (MetS), but side effects have led to increased attention on using nutraceuticals and supplements. Astaxanthin shows positive effects in reducing the risk of MetS, but results from individual studies are inconclusive. This systematic review summarizes the latest evidence of astaxanthin in adults with risk factors of MetS. A systematic search of English and Chinese randomized controlled trials in 14 electronic databases from inception to 30 June 2021 was performed. Two reviewers independently screened the titles and abstracts, and conducted full-text review, quality appraisal, and extraction of data. Risk of bias was assessed by PEDro. A total of 7 studies met the inclusion criteria with 321 participants. Six studies were rated to have excellent methodological quality, while the remaining one was rated at good. Results show marginal effects of astaxanthin on reduction in total cholesterol and systolic blood pressure, and a significant attenuating effect on low-density lipoprotein cholesterol. Further robust evidence is needed to examine the effects of astaxanthin in adults at risk of MetS.
Background The α2-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations. l-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role of l-arginine in modulating the overall vascular response to dexmedetomidine. Methods Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; nitric oxide synthase inhibitor), prazosin (α1-adrenergic antagonist), rauwolscine (α2-adrenergic antagonist), l-arginine, (S)-(2-boronethyl)-l-cysteine hydrochloride (arginase inhibitor), NG-hydroxy-l-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed. Results Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated with l-NAME (Emax 50 ± 4%) or after endothelium-removal (Emax 74 ± 5%; N = 7 to 12). Exogenous l-arginine augmented the dexmedetomidine-induced contractions in the presence of l-NAME (Emax 75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-l-cysteine hydrochloride (Emax 16 ± 4%) and NG-hydroxy-l-arginine (Emax 18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect as l-arginine. Immunoassay measurements demonstrated an upregulation of arginase I by l-arginine treatment in the presence of l-NAME (N = 4). Conclusions These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of dexmedetomidine by l-arginine depends on arginase activity and the production of urea and ornithine.
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