Both paraoxonase-1 genotype and activity do not predict the risk of future coronary artery disease; the EPIC-Norfolk Prospective Population Study.

Background: Paraoxonase-1 (PON1) is an antioxidant enzyme, that resides on high-density lipoprotein (HDL). PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL.

C-reactive protein elicits white blood cell activation in humans.

Objective: Consistent epidemiologic evidence suggests that acute infections increase the risk for acute cardiovascular events. We tested in humans whether activation of peripheral leukocytes in reaction to the administration of recombinant human C-reactive protein (rhCRP) may provide a mechanism for infectious diseases to promote atherosclerotic disease.

Methods And Results: By using quantitative real-time polymerase chain reaction analysis, whole-blood expression profiles were analyzed for 95 inflammatory markers before and after infusion of 1.

Effects of short-term and long-term danazol treatment on lipoproteins, coagulation, and progression of atherosclerosis: two clinical trials in healthy volunteers and patients with hereditary angioedema.

Background: Danazol is a synthetic androgen derivative frequently used as prophylaxis in patients with hereditary angioedema (HAE) due to complement-1 esterase inhibitor deficiency. However, danazol has been reported to decrease high-density lipoprotein cholesterol (HDL-C) levels and to adversely affect coagulation parameters, which are considered to be proatherothrombotic.

Objective: The short- and long-term effects of danazol were evaluated on proatherogenic intermediate end points in healthy volunteers and patients with HAE.

Induction of IRAK-M is associated with lipopolysaccharide tolerance in a human endotoxemia model.

Recent in vitro and murine in vivo studies have identified several potential LPS tolerance factors. In this study, we describe the expression kinetics of these LPS tolerance factors in standardized human endotoxemia models using i.v.

A single bolus infusion of C-reactive protein increases gluconeogenesis and plasma glucose concentration in humans.

Recently, we reported that C-reactive protein (CRP) elicits inflammatory and procoagulant responses in humans. In addition, CRP has been associated with the development of type 2 diabetes mellitus. To further explore interactions between CRP and glucose handling, we evaluated the effects of CRP infusion on glucose metabolism in humans.

Apolipoprotein A-II is inversely associated with risk of future coronary artery disease.

Background: Although the vasculoprotective effects of apolipoprotein A-I (apoA-I), the major protein associated with high-density lipoprotein, have been universally accepted, apoA-II has been suggested to have poor antiatherogenic or even proatherogenic properties. To study this suggestion more closely, we evaluated how serum levels of apoA-II and apoA-I relate to the risk of future coronary artery disease (CAD) in a large, prospective study.

Methods And Results: We performed a nested case-control study in the prospective EPIC-Norfolk (European Prospective Investigation into Cancer and Nutrition-Norfolk) cohort.

High-density lipoprotein attenuates inflammation and coagulation response on endotoxin challenge in humans.

Objective: Low high-density lipoprotein (HDL) cholesterol is a strong independent cardiovascular risk factor, which has been attributed to its role in reverse cholesterol transport. Whereas HDL also has potent antiinflammatory effects, the relevance of this property remains to be established in humans. In the present study, we evaluated whether there is a relation between HDL and sensitivity toward a low-dose endotoxin challenge.

Effects of CRP infusion on endothelial function and coagulation in normocholesterolemic and hypercholesterolemic subjects.

C-reactive protein (CRP) has been suggested to exert direct adverse effects on the vasculature in experimental setups, including endothelial dysfunction and proinflammatory changes. Here, we assessed the consequences of 1.25 mg/kg highly purified recombinant human CRP, administered as an intravenous bolus, in six patients with familial hypercholesterolemia (FH) and six normocholesterolemic subjects.

Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials.

Objectives: The aim of this research was to estimate the efficacy and safety of current high-density lipoprotein cholesterol (HDL-C)-increasing drugs.

Background: Epidemiologic evidence has shown that HDL-C is inversely related to coronary heart disease (CHD) risk. However, the evidence for reducing CHD risk by raising HDL-C is thin, predominantly due to the paucity of effective and safe HDL-increasing drugs.

Loss of heterozygosity and immunohistochemistry of adenocarcinomas of the esophagus and gastric cardia.

Purpose: Adenocarcinomas of the distal esophagus and gastric cardia are two tumors that have many features in common. They have similar prognoses, treatment modalities, and patterns of dissemination. The etiology is different, with gastroesophageal reflux disease playing a major role for esophageal adenocarcinoma, in contrast to adenocarcinoma of the gastric cardia.