Quantitative Analysis of Vasodilatory Action of Quercetin on Intramural Coronary Resistance Arteries of the Rat In Vitro

Background: Dietary quercetin improves cardiovascular health, relaxes some vascular smooth muscle and has been demonstrated to serve as a substrate for the cyclooxygenase enzyme. Aims: 1. To test quantitatively a potential direct vasodilatory effect on intramural coronary resistance artery segments, in different concentrations. 2. To scale vasorelaxation at different intraluminal pressure loads on such vessels of different size. 3. To test the potential role of prostanoids in vasodilatation induced by quercetin. Methods: Coronary arterioles (70-240 mu m) were prepared from 24 rats and pressurized in PSS, using a pressure microangiometer. Results: The spontaneous tone that developed at 50 mmHg was relaxed by quercetin in the 10(-9) moles/lit concentration (p<0.05), while 10(-5) moles/lit caused full relaxation. Significant relaxation was observed at all pressure levels (10-100 mmHg) at 10(-7) moles/lit concentration of quercetin. The cyclooxygenase blocker indomethacin (10(-5) moles/lit) induced no relaxation but contraction when physiological concentrations of quercetin were present in the tissue bath (p<0.02 with Anova), this contraction being more prominent in smaller vessels and in the higher pressure range (p<0.05, Pearson correlation). A further 2-8% contraction could be elicited by the NO blocker L-NAME (10(-4) moles/lit). Conclusion: These results demonstrate that circulating levels of quercetin (10(-7) moles/lit) exhibit a substantial coronary vasodilatory effect. The extent of it is commeasurable with that of several other physiological mechanisms of coronary blood flow control. At least part of this relaxation is the result of an altered balance toward the production of endogenous vasodilatory prostanoids in the coronary arteriole wall

European postgraduate curriculum in geriatric medicine developed using an international modified Delphi technique

the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed considerably since then and it has therefore become necessary to update these recommendations.under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators.the final recommendations include four different domains: General Considerations on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), Knowledge in patient care (36 sub-items), Additional Skills and Attitude required for a Geriatrician (9 sub-items) and a domain on Assessment of postgraduate education: which items are important for the transnational comparison process (1 item).the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states

Enhancing recombinant protein solubility with ubiquitin-like small archeal modifying protein fusion partners

A variety of protein expression tags with different biochemical properties has been used to enhance the yield and solubility of recombinant proteins. Ubiquitin, SUMO (small ubiquitin-like modifier) and prokaryotic ubiquitin like MoaD (molybdopterin synthase, small subunit) fusion tags are getting more popular because of their small size. In this paper we report on the use of ubiquitin-like small archaeal modifier proteins (SAMPs) as fusion tags since they proved to increase expression yield, stability and solubility in our experiments. Equally important, they did not co-purify with proteins of the expression host and there was information that their specific JAB1/MPN/Mov34 metalloenzyme (JAMM) protease can recognize the C-terminal VSGG sequence when SAMPs fused, either branched or linearly to target proteins, and cleave it specifically. SAMPs and JAMM proteases from Haloferax volcanii, Thermoplasma acidophilum, Methanococcoides burtonii and Nitrosopumilus maritimus were selected, cloned, expressed heterologously in Escherichia coli and tested as fusion tags and cleaving proteases, respectively. Investigated SAMPs enhanced protein expression and solubility on a wide scale. T. acidophilum SAMPs Ta0895 and Ta01019 were the best performing tags and their effect was comparable to the widely used maltose binding protein (MBP) and N utilization substance protein A (NusA) tags. Moreover, H. volcanii SAMP Hvo_2619 contribution was mediocre, whereas M. burtonii Mbur_1415 could not be expressed. Out of four investigated JAMM proteases, only Hvo_2505 could cleave fusion tags. Interestingly, it was found active not only on its own partner substrate Hvo_2619, but it also cleaved off Ta0895. (C) 2015 Elsevier B.V. All rights reserved

Biomechanics and vasoreactivity of female intramural coronaries in angiotensin II induced hypertension

Hypertension causes small vessel remodeling, vasomotor alterations. We investigated diameter, tone and mechanics of intramural small coronaries of female rats that received chronic angiotensin treatment to induce hypertension.Angiotensin II infusion (AII, 100 ng/bwkg/min, sc.) was used to establish hypertension in 10 female rats. Other 10 rats served as controls. Following 4 weeks of treatment, side branches of the left anterior descendant coronary (diameter∼200 μm) were isolated, cannulated and pressure-diameter curves were registered between 2–90 mmHg. Changes in vessel diameter were measured in Krebs solution, in the presence of thromboxane A2 receptor agonist (U46619, 10-6M), bradykinin (BK, 10-6M), and finally at complete relaxation (in Ca2+-free solution).Chronic AII treatment raised the mean arterial pressure (130±5 mmHg vs. 96±2 mmHg, average ±SEM) significantly. Wall thickness of the AII group was significantly greater (40.2±4.2 μm vs. 31.4±2.7 μm at 50 mmHg in Ca2+-free solution), but cross-section of the vessel wall did not differ. Tangentional wall stress and elastic modulus decreased significantly in hypertensive animals. Constrictions in the presence of U46619 were greater in the AII group (24.4± 5.6% vs. 14.5±3.3% at 50 mmHg).In hypertension, intramural small coronaries showed inward eutrophic remodeling, as a morphological adaptation following AII treatment enhanced thromboxane A2 — induced tone

European postgraduate curriculum in geriatric medicine developed using an international modified Delphi technique

Background the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed considerably since then and it has therefore become necessary to update these recommendations. Methods under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators. Results the final recommendations include four different domains: 'General Considerations' on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), 'Knowledge in patient care' (36 sub-items), 'Additional Skills and Attitude required for a Geriatrician' (9 sub-items) and a domain on 'Assessment of postgraduate education: which items are important for the transnational comparison process' (1 item). Conclusion the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states. © The Author(s) (2019). Published by Oxford University Press on behalf of the British Geriatrics Society