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- Bousquet, J, et al.
(författare)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Tidskriftsartikel (refereegranskat)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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- Baklanov, D. V., et al.
(författare)
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Comparison of transendocardial and retrograde coronary venous intramyocardial catheter delivery systems in healthy and infarcted pigs
- 2006
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Ingår i: Catheterization and cardiovascular interventions. - : Wiley-Blackwell. - 1522-1946 .- 1522-726X. ; 68:3, s. 416-423
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Tidskriftsartikel (refereegranskat)abstract
- We compared two routes for myocardial delivery of therapeutics, transendocardial (TE) delivery with an intramyocardial injection catheter, and retrograde coronary venous (RCV) delivery with a balloon occlusion catheter in the interventricular vein. Methods: TE and RCV injection of 15 mu m, neutron-activatable microspheres was compared in healthy pigs (Group I, n = 3), pigs with a 1-week-old myocardial infarction (MI; group II, n = 5), and pigs with a 2-weeks-old MI (group III, n = 4). The MI was induced by a 1-hr balloon occlusion in the LAD. Both methods were compared in the same animal using different microspheres. The RCV catheter allowed for continuous measurement of distal pressure and 2.5 x 10(6) microspheres were injected in 10 ml at 300 mmHg above balloon occlusion pressure. The TE injections were targeted to the infarct zone and 2.5 x 10(6) microspheres were distributed over 10 injections of 200 mu l. Results: The retention of microspheres decreased with increase in MI age, but was comparable between devices within the groups. RCV delivery resulted in (14.3 +/- 0.9)% microsphere retention in Group I, (10.3 +/- 0.2)% in Group II, and (6.4 +/- 0.1)% in group III (P less than 0.05 versus group I). Microsphere retention after TE was (15.1 +/- 0.7)% in group I, (18.9 +/- 0.6)% in group II, (4.1 +/- 0.1)% in Group III (P less than 0.05 versus groups I and II). The RCV catheter delivered primarily to midventricular, antero-septal segments, whereas TE targeted apical areas predominantly. Conclusions: Delivery efficacy was comparable between devices in each group however RCV targeted midventricular areas whereas TE targeted apical areas.
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- Mandinov, L., et al.
(författare)
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Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries
- 2006
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 291:6, s. H2692-H2697
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Tidskriftsartikel (refereegranskat)abstract
- Stress-induced release of IL-1 alpha and fibroblast growth factor-1 is dependent on intracellular copper and is a major driver of neointimal hyperplasia. Therefore, we assessed the effect of tetrathiomolybdate (TTM), a clinically proven copper chelator, on in-stent restenosis. Nine pigs were treated with TTM (5 mg/kg po) twice daily for 2 wk before stent implantation and for 4 wk thereafter, and nine pigs served as controls. In-stent restenosis was assessed by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), and histomorphometry. Serum ceruloplasmin activity was used as a surrogate marker of copper bioavailability. In TTM-treated animals, ceruloplasmin dropped 70 +/- 10% below baseline levels. Baseline characteristics were comparable in TTM-treated and control animals. At 4-wk follow-up, all parameters relevant to in-stent restenosis were significantly reduced in TTM-treated animals: minimal lumen diameter by QCA was 2.03 +/- 0.57 and 1.47 +/- 0.45 mm in TTM-treated and control animals, respectively (P less than 0.05), percent stenosis diameter was 39% less in TTM-treated animals (27.1 +/- 16.6% vs. 44.5 +/- 16.1%, P less than 0.05), minimal lumen area by IVUS was 60% larger in TTM-treated animals (4.27 +/- 1.56 vs. 2.67 +/- 1.19 mm(2), P less than 0.05), and neointimal volume by histomorphometry was 37% less in TTM-treated animals (34.9 +/- 11.5 vs. 55.2 +/- 19.6 mm(3), P less than 0.05). We conclude that systemic copper chelation with a clinically approved chelator significantly inhibits in-stent restenosis.
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- Baklanov, Dmitri V., et al.
(författare)
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Live 3D echo guidance of catheter-based endomyocardial injection
- 2005
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Ingår i: Catheterization and cardiovascular interventions. - : Wiley-Blackwell. - 1522-1946 .- 1522-726X. ; 65:3, s. 340-345
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Tidskriftsartikel (refereegranskat)abstract
- Local delivery of therapeutic agents into the myocardium is limited by suboptimal imaging. We evaluated the feasibility and accuracy of live 313 echo to guide left ventricular endomyocardial injection. An intramyocardial injection catheter was positioned in the left ventricle in five healthy Yorkshire pigs using fluoroscopy. All other catheter manipulations were performed with live biplane and 3D echo guidance. In each animal, a total of 12 endomyocardial injections (volume, 50-100 mu l) of echo contrast mixed with blue tissue dye were performed. Four injections, 10 mm apart, were directed to three myocardial target zones: the anterior septum at the mitral valve level (zone 1); the posterolateral wall between the heads of the papillary muscles (zone 2); and the apex (zone 3). The injections were aimed to form a transverse line in zones 1 and 2 and an inverted triangular pyramid in zone 3. The animals were sacrificed, the hearts were inspected and the left ventricular endocardium was examined to create a map of injection marks. Success, defined as a visible injection of tissue dye, was 95%, and accuracy, defined as an injection into the target zone, was 83%. There was no significant difference in accuracy between the zones. Live 3D echo can successfully guide endomyocardial injections by accurately targeting specific myocardial zones, verifying catheter apposition and, when combined with echo contrast, providing real-time visualization of injectate deposition. (c) 2005 Wiley-Liss, Inc.
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