| 1. |
- Sethi, Sunjay, et al.
(författare)
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Comparative Analyses of the 12 Most Abundant PCB Congeners Detected in Human Maternal Serum for Activity at the Thyroid Hormone Receptor and Ryanodine Receptor
- 2019
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 53:7, s. 3948-3958
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Tidskriftsartikel (refereegranskat)abstract
- Polychlorinated biphenyls (PCBs) pose significant risk to the developing human brain; however, mechanisms of PCB developmental neurotoxicity (DNT) remain controversial. Two widely posited mechanisms are tested here using PCBs identified in pregnant women in the MARBLES cohort who are at increased risk for having a child with a neurodevelopmental disorder (NDD). As determined by gas chromatography-triple quadruple mass spectrometry, the mean PCB level in maternal serum was 2.22 ng/mL. The 12 most abundant PCBs were tested singly and as a mixture mimicking the congener profile in maternal serum for activity at the thyroid hormone receptor (THR) and ryanodine receptor (RyR). Neither the mixture nor the individual congeners (2 fM to 2 μM) exhibited agonistic or antagonistic activity in a THR reporter cell line. However, as determined by equilibrium binding of [3H]ryanodine to RyR1-enriched microsomes, the mixture and the individual congeners (50 nM to 50 μM) increased RyR activity by 2.4-19.2-fold. 4-Hydroxy (OH) and 4-sulfate metabolites of PCBs 11 and 52 had no TH activity; but 4-OH PCB 52 had higher potency than the parent congener toward RyR. These data support evidence implicating RyRs as targets in environmentally triggered NDDs and suggest that PCB effects on the THR are not a predominant mechanism driving PCB DNT. These findings provide scientific rationale regarding a point of departure for quantitative risk assessment of PCB DNT, and identify in vitro assays for screening other environmental pollutants for DNT potential.
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| 2. |
- von Koch, Sacharias, et al.
(författare)
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Intracoronary Imaging of Proximal Coronary Artery Lesions – A Nationwide Lesion-Level Analysis From SCAAR
- 2023
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Ingår i: Journal of the Society for Cardiovascular Angiography & Interventions. - : Elsevier. - 2772-9303. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Current evidence suggests that use of intracoronary imaging during percutaneous coronary intervention (PCI) of the left main coronary artery (LMCA) reduces mortality. However, there is a scarcity of data on the overall role of intracoronary imaging, particularly in other non-LMCA proximal coronary artery lesions. We aimed to investigate the association of use of intracoronary imaging on outcome in proximal lesions treated with PCI.Methods: The Swedish Coronary Angiography and Angioplasty Registry was used to identify all proximal coronary artery lesions treated with stent implantation between June 11, 2013, and January 16, 2021. Proximal coronary artery lesions (LMCA, proximal left anterior descending artery, left circumflex artery, and right coronary artery) assessed by intracoronary imaging before and/or after stent implantation were matched to control lesions treated based on angiography alone using propensity score matching. The primary end point was target lesion revascularization with PCI, and secondary end points included all-cause mortality and definite stent thrombosis within 3 years.Results: Among the 3623 matched pairs, intracoronary imaging was associated with significantly lower risk of target lesion revascularization, 3.7% vs 4.7%; hazard ratio (HR), 0.77; 95% CI, 0.61-0.97; P = .025, and all-cause mortality, 9.1% vs 12.8%; HR, 0.70; 95% CI, 0.61-0.81; P < .001, with no difference in definite stent thrombosis.Conclusions: The use of intracoronary imaging in proximal coronary artery lesions is associated with lower rates of repeat revascularization and better survival. The results appear to be primarily driven by improved outcome of LMCA lesions. These results reinforce the role of intracoronary imaging in assessing and treating proximal coronary lesions.
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