RESUMO
Background: Hyperlipidemia is associated with chronic inflammation and thromboinflammation. This is an underlying cause of several cardiovascular diseases, including atherosclerosis. In diseased blood vessels, rampant thrombin generation results in the initiation of the coagulation cascade, activation of platelets, and endothelial cell dysfunction. Coagulation factor (F) XI represents a promising therapeutic target to reduce thromboinflammation, as it is uniquely positioned at an intersection between inflammation and thrombin generation. Objectives: This study aimed to investigate the role of FXI in promoting platelet and endothelial cell activation in a model of hyperlipidemia. Methods: Nonhuman primates (NHPs) were fed a standard chow diet (lean, n = 6) or a high-fat diet (obese, n = 8) to establish a model of hyperlipidemia. Obese NHPs were intravenously administered a FXI blocking antibody (2 mg/kg) and studied at baseline and at 1, 7, 14, 21, and 28 days after drug administration. Platelet activation and inflammatory markers were measured using fluorescence-activated cell sorting or enzyme-linked immunosorbent assay. Molecular imaging was used to quantify vascular cell adhesion molecule 1 (VCAM-1) expression at the carotid bifurcation. Results: Obese NHPs demonstrated increased sensitivity for platelet P-selectin expression and phosphatidylserine exposure in response to platelet GPVI or PAR agonists compared with lean NHPs. Obese NHPs exhibited elevated levels of C-reactive protein, cathepsin D, and myeloperoxidase compared with lean NHPs. Following pharmacological inhibition of FIX activation by FXIa, platelet priming for activation by GPVI or PAR agonists, C-reactive protein levels, and endothelial VCAM-1 levels were reduced in obese NHPs. Conclusion: FXI activation promotes the proinflammatory phenotype of hyperlipidemia by priming platelet activation and inciting endothelial cell dysfunction.
RESUMO
BACKGROUND: Adequate knowledge of malaria prevention and control can help in reducing the growing burden of malaria among vulnerable groups, particularly pregnant women and children aged under 5 years living in malaria endemic settings. Similar studies have been conducted but with less focus on these vulnerable groups. This study assessed knowledge of malaria prevention and control among the pregnant women and non-pregnant mothers of children aged under 5 years in Ibadan, Oyo State, South West Nigeria. METHODS: In this cross sectional study, data on socio-demographic, clinical and knowledge on malaria prevention was collected using interviewer administered questionnaires from consenting study participants attending Adeoyo maternity hospital between May and November 2016. Data was described using percentages and compared across the two maternal groups in the study population. Knowledge scoring from collected data was computed using the variables on causes, symptoms and prevention of malaria and thereafter dichotomised. Multivariate analyses were used to assess the interactive effect of socio demographic and clinical characteristics with malaria knowledge. Level of statistical significance was set at p < 0.05. RESULTS: Of the 1373 women in the study, 59.6% (818) were pregnant women while 40.4% (555) were mothers of children aged under 5 years. The respondents mean age was 29 years ± 5.2. A considerable proportion of both the pregnant women (n = 494, 60.4%) and the non-pregnant mothers of children aged under 5 years (n = 254, 45.8%) did not have correct knowledge on malaria prevention measures based on our assessment threshold (p < 0.001). Having a tertiary level education was associated with better knowledge on malaria (4.20 ± 1.18, F = 16.80, p < 0.001). Multivariate analyses showed that marital status, educational attainment, gravidity, and HIV status were significantly associated with knowledge of malaria prevention and control. CONCLUSION: The findings indicate that socio-demographic factors such as marital and educational status greatly influence knowledge on malaria prevention and control measures. Key health stakeholders and authorities need to implement strategies and direct resources to improve the knowledge of mothers on malaria prevention and control. This would stem the tides of malaria related deaths among pregnant women and children aged under 5 years.
