Treatment with chondroitin sulfate to modulate inflammation and atherogenesis in obesity

Background and aims: Osteoarthritic patients treated with high doses of chondroitin sulfate (CS) have a lower incidence of coronary heart disease - but the mechanistic aspects of these beneficial effects of CS remain undefined. We examined how CS treatment affects the formation of atheroma via interaction with endothelial cells and monocytes. Methods: We characterized arterial atheromatous plaques by multiphoton microscopy and serum pro-inflammatory cytokines by immunoenzymatic techniques in obese mice receiving CS (1 g/kg/day, i.p.) or vehicle for 6 days. Effects of CS on signaling pathways, cytokine secretion and macrophage migration were evaluated in cultures of human coronary endothelial cells and in a monocyte cell line stimulated with TNF-α by Western blot, immunoenzymatic techniques and transwell migration assays. Results: Treatment of obese mice with CS reduced the extension of foam cell coverage in atheromatous plaques of arterial bifurcations by 62.5%, the serum concentration of IL1β by 70%, TNF-α by 82% and selected chemokines by 25-35%. Cultures of coronary endothelial cells and monocytes stimulated with TNF-α secreted less pro-inflammatory cytokines in the presence of CS (P < 0.01). CS reduced the activation of the TNF-α signaling pathway in endothelial cells (pErk 36% of reduction, and NFκB 33% of reduction), and the migration of activated monocytes to inflamed endothelial cells in transwells (81 ± 6 vs. 13 ± 2, P < 0.001). Conclusions: CS interferes with the pro-inflammatory activation of monocytes and endothelial cells driven by TNF-α thus reducing the propagation of inflammation and preventing the formation of atherosclerotic plaques

Treatment with chondroitin sulfate to modulate inflammation and atherogenesis in obesity

Background and aims: Osteoarthritic patients treated with high doses of chondroitin sulfate (CS) have a lower incidence of coronary heart disease - but the mechanistic aspects of these beneficial effects of CS remain undefined. We examined how CS treatment affects the formation of atheroma via interaction with endothelial cells and monocytes. Methods: We characterized arterial atheromatous plaques by multiphoton microscopy and serum pro-inflammatory cytokines by immunoenzymatic techniques in obese mice receiving CS (1 g/kg/day, i.p.) or vehicle for 6 days. Effects of CS on signaling pathways, cytokine secretion and macrophage migration were evaluated in cultures of human coronary endothelial cells and in a monocyte cell line stimulated with TNF-alpha by Western blot, immunoenzymatic techniques and transwell migration assays. Results: Treatment of obese mice with CS reduced the extension of foam cell coverage in atheromatous plaques of arterial bifurcations by 62.5%, the serum concentration of IL1 beta by 70%, TNF-alpha by 82% and selected chemokines by 25-35%. Cultures of coronary endothelial cells and monocytes stimulated with TNF-alpha secreted less pro-inflammatory cytokines in the presence of CS (P < 0.01). CS reduced the activation of the TNF-alpha signaling pathway in endothelial cells (pErk 36% of reduction, and NF kappa B 33% of reduction), and the migration of activated monocytes to inflamed endothelial cells in transwells (81 +/- 6 vs. 13 +/- 2, P < 0.001). Conclusions: CS interferes with the pro-inflammatory activation of monocytes and endothelial cells driven by TNF-alpha thus reducing the propagation of inflammation and preventing the formation of atherosclerotic plaques. (C) 2015 Elsevier Ireland Ltd. All rights reserved.BioibericaFundacio Empreses IQSSpanish Ministerium of EconomyFundacion Alfonso Martin EscuderoBeatriu de Pinos Program - AGAURNational Institutes of HealthMIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USARamon Llull Univ, Dept Bioengn, Inst Quim Sarria, Barcelona, SpainUniv Fed Sao Paulo, Escola Paulista Med, Dept Hlth Informat, Sao Paulo, BrazilBioiberica SA, Preclin R&D Area, Pharmasci Div, Barcelona, SpainHarvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USAUniv Fed Sao Paulo, Escola Paulista Med, Dept Hlth Informat, Sao Paulo, BrazilSpanish Ministerium of Economy: SAF2013-43302Beatriu de Pinos Program - AGAUR: 2013 BP_A 00051National Institutes of Health: R01 GM49039Web of Scienc

Implementing a pilot study of COVID-19 self-testing in high-risk populations and remote locations: results and lessons learnt

Abstract Background Rapid antigen-detection tests for SARS-CoV-2 self-testing represent a useful tool for pandemic control and expanding access to community-level case screening. COVID-19 self-tests have been extensively used in high-income countries since 2021; however, their introduction and programmatic implementation in low- and middle-income countries was delayed. We aimed to identify and continuously improve a weekly COVID-19 self-testing model among staff at healthcare facilities and schools. Methods This mixed-methods, observational prospective study was conducted in 5 healthcare centres and 24 schools in Georgia, between June and December 2022. The study comprised the integration of COVID-19 self-testing into the national mandatory testing programme for high-risk groups, with primary distribution of self-tests among staff performed weekly, plus secondary distribution to their household members. These use cases were selected because NCDC was seeking to strengthen their already strong weekly testing programme, by investigating self-testing to ease the burden of testing in the healthcare system. Online surveys and semi-structured interviews were used for data collection. Results In total, 2156 participants were enrolled (1963 female, 72%). At baseline and mid- and end-points, 88%, 97% and 99%, respectively, of participants agreed/strongly agreed they would self-test. Similarly, the majority were willing to report their self-testing results (88%, 98% and 96% at baseline and mid- and end-points, respectively). Weekly reporting of test results to the national COVID-19 database was high during all the implementation. There were 622 COVID-19 positive results reported, and linked to care, from 601 individuals (282 participants and 319 household members). Findings from qualitative interviews showed great satisfaction with self-testing for its convenience, ease of use, trust in the results, no need to travel for diagnostics, and increased perception of safety. Conclusions Our findings contribute to the evidence-base regarding self-testing strategies conducted via workplaces and secondary distribution to households. Willingness to perform a COVID-19 self-test increased after implementation. This pilot enhanced pandemic preparedness through expansion of the national self-testing reporting system, development of communications materials, changes in the national legal framework and coordination mechanisms, and improved perceptions around self-care in the community. The lessons learnt can inform operational aspects of the introduction and scale-up of self-care strategies