Biotin sulfone tagged oligomannosides as immunogens for eliciting antibodies against specific mannan epitopes

Biotinylated tri and tetrasaccharide: α Man (1→3) α Man (1→2) α Man; α Man (1→3) α Man (1→2) α Man (1→2) α Man were prepared using methyl tertbutyl phenyl thioglycosides glycosyl donors (MBP) and biotin sulfone strategy. Three key mannosyl thioglycosidic donors have been prepared: one for 1→2 linkage and two for the 1→3 linkage (protected with a 4,6-O-benzylidene or a 4,6-di-O-benzyl). The benzyliden protected one was not found reactive enough, and the benzylated donor was preferred. These biotinylated oligomanosides were evaluated as antigen in Crohn disease diagnosis and used coupled to streptavidin as hapten for eliciting polyclonal antibodies in mice

Systemic chemokine levels, coronary heart disease, and ischemic stroke events: The PRIME Study

OBJECTIVES: To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-γ-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study. METHODS: After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression. RESULTS: None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05–2.74), IP-10 (HR = 1.53; 95% CI 1.06–2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02–2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68–1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004). CONCLUSIONS: In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors

Effects of insulin-like growth factor 1 in preventing acute coronary syndromes: The PRIME study

ObjectiveInsulin-like growth factor-1 (IGF-1) has been associated with cardiovascular risk factors and atherosclerosis. The aim of the present study was to evaluate the prognostic value of IGF-1 concentrations with respect to occurrence of well-defined coronary syndromes.MethodsThe PRIME study is a prospective cohort having included 10,600 subjects from Northern Ireland and France. Detailed information on cardiovascular risk factors, socioeconomic and behavioural variables were collected and a cardiologic examination was performed. At 5-year follow-up, 317 incident cases of coronary events were recorded according to strict protocols. They were matched to 634 age- and centre-paired controls from the same cohort, free of coronary disease. Baseline IGF-1 concentrations were measured, together with variables of lipid and glucose metabolism and markers of vascular and systemic inflammation.ResultsBaseline IGF-1 concentration was lower in subjects developing an acute coronary syndrome than in unaffected controls. IGF-1 levels correlated negatively with age, waist circumference, tobacco consumption and markers of inflammation. Subjects in the highest quartile of IGF-1 distribution had a 55% reduction in the relative risk of developing myocardial infarction and a 45% decrease for all-combined acute coronary syndromes. A similar trend, although non-significant, was noted for angina pectoris. Multiple adjustments on classical risk factors and inflammation markers did not affect IGF-1 results. Elevated levels of both IGF-1 and apo A-I conferred a significantly greater risk reduction than either one alone. However, interaction between the two markers was not significant.ConclusionLike HDL markers, high levels of IGF-1 confer protection against coronary artery disease.<br/