Current approaches to the diagnosis and therapy of atherosclerosis cannot target to lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing inflammatory responses. The presence of these cells is positively associated with lesion progression, severity and destabilization. Hence, they are an important diagnostic and therapeutic target. The objective of this study was to noninvasively assess the distribution and accumulation of intimal macrophages using CD36-targeted nanovesicles. Soy phosphatidylcholine was used to synthesize liposome-like nanovesicles. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine was incorporated on their surface to target the CD36 receptor. All in vitro data demonstrate that these targeted nanovesicles had a high binding affinity for the oxLDL binding site of the CD36 receptor and participated in CD36-mediated recognition and uptake of nanovesicles by macrophages. Intravenous administration into LDL receptor null mice of targeted compared to non-targeted nanovesicles resulted in higher uptake in aortic lesions. The nanovesicles co-localized with macrophages and their CD36 receptors in aortic lesions. This molecular target approach may facilitate the in vivo noninvasive imaging of atherosclerotic lesions in terms of intimal macrophages accumulation and distribution and disclose lesion features related to inflammation and possibly vulnerability thereby facilitate early lesion detection and targeted delivery of therapeutic compounds to intimal macrophages.
Abstract. In February 2005, we conducted a cross-sectional study to determine the prevalence and the risk factors of giardiasis in 531 primary schoolchildren of a rural community, Chacheongsao province, Thailand. Using both sedimentation and flotation techniques to detect Giardia duodenalis, the prevalence of giardiasis was 6.2%. Assemblage A, subgenotype II and assemblage B, subgenotype IV were identified by PCR-RFLP of glutamate dehydrogenase gene. Our data might indicate that, in this population, only assemblage A, subgenotype II of G. duodenalis was transmitted via water. Using multivariate analysis, significant risk factors for giardiasis were children of age 5-9 years, households with Ն 3 children under the age of 12 years, low parental educational level, drinking bottled water, and living in close contact with dogs. Washing hands before meals had a protective effect. From these significant risk factors, multiple modes of transmission of G. duodenalis were suggested in this population.
IntroductionDabigatran, as compared with warfarin, was associated with lower rates of stroke and systemic embolism with similar rates of major hemorrhage. But it has a significantly higher risk of gastrointestinal bleeding (GIB). There are limited data on how to prevent GIB from dabigatran and what are the risk factors.MethodsWe performed a retrospective cohort study of patients with atrial fibrillation who have ever taken dabigatran for thromboprophylaxis from October 2010 to February 2013.ResultsA total of 247 patients were identified. There were 10 (4%) patients who developed GIB (6 (6.5%) in PPI/H2RA users vs 4 (2.6%) in non‐PPI/H2RA users; P = .184). History of GIB within 1 year prior to dabigatran initiation and HAS‐BLED score ≥3 are independent risk factors for GIB, with odds ratio of 25.14 (95% CI, 2.85‐221.47; P < .01) and 5.85 (95% CI, 1.31‐26.15; P = .021), respectively.ConclusionIn this real‐world cohort, PPI/H2RA use was not associated with reduced GIB events. HAS‐BLED score ≥3 and prior history of GIB within 1 year are independent risk factors for GIB among dabigatran users.
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