72 research outputs found
n-3 fatty acid ethyl ester administration to healthy subjects and to hypertriglyceridemic patients reduces tissue factor activity in adherent monocytes
n-3 Fatty acids are known to influence several functions of monocytes, including adhesion, cytokine synthesis, and superoxide generation. Monocytes express tissue factor, a membrane-bound glycoprotein, that acts as a catalyst in the coagulation cascade. In this study we evaluated the effects of administration of n-3 fatty acid ethyl esters to healthy volunteers and to hypertriglyceridemic patients on tissue factor activity (TF activity) in adherent monocytes. n-3 Fatty acids containing 75% eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (ratio of EPA to DHA, 1.34) were administered (3 g/d) to normal volunteers for 18 weeks. In addition, the effects of this treatment were evaluated in 30 hypertriglyceridemic patients for 24 weeks by using a double-blind, placebo-controlled study. TF activity in adherent monocytes was evaluated with a one-stage clotting assay. Plasma and monocyte fatty acid compositions were determined by gas-liquid chromatography. In healthy volunteers, n-3 fatty acids significantly reduced TF activity in adherent monocytes either in the unstimulated condition or after exposure to endotoxin. The inhibitory effect was observed after 12 weeks of treatment and was more pronounced after 18 weeks (> 70%, P < .001 versus baseline). Concomitantly, levels of EPA and DHA increased in plasma and monocyte lipids. Interestingly, after stopping treatment, monocyte TF activity remained inhibited for at least 14 weeks. Treatment with n-3 fatty acids for 24 weeks also resulted in a significant reduction of TF activity in adherent monocytes from hypertriglyceridemic patients (-31% and -40% in unstimulated and endotoxin-stimulated cells; P < .05 versus baseline).(ABSTRACT TRUNCATED AT 250 WORDS
Systematic Lab Knowledge Integration for Management of Lipid Excess in High-Risk Patients : Rationale and Design of the SKIM LEAN Project
SKIM LEAN aims at exploiting Electronic Health Records (EHRs) to integrate knowledge derived from routine laboratory tests with background analysis of clinical databases, for the identification and early referral to specialist care, where appropriate, of patients with hypercholesterolemia, who may be inadequately controlled according to their cardiovascular (CV) risk level. SKIM LEAN addresses gaps in care that may occur through the lack of coordination between primary and specialist care, incomplete adherence to clinical guidelines, or poor patient's compliance to the physician's prescriptions because of comorbidities or drug side effects. Key project objectives include: (1) improved health professionals' competence and patient empowerment through a two-tiered educational website for general practitioners (GPs) and patients, and (2) implementation of a hospital-community shared care pathway to increase the proportion of patients at high/very-high CV risk (Familial Hypercholesterolemia, previous CV events) who achieve target LDL cholesterol (LDL-C) levels. Thanks to a close collaboration between clinical and information technology partners, SKIM LEAN will fully exploit the value of big data deriving from EHRs, and filter such knowledge using clinically-derived algorithms to risk-stratify patients. Alerts for GPs will be generated with interpreted test results. GPs will be able to refer patients with uncontrolled LDL-C within the shared pathway to the lipid or secondary prevention outpatient clinics of NIG hospital. Metrics to verify the project achievements include web-site visits, the number of alerts generated, numbers of patients referred by GPs, the proportion of secondary prevention patients who achieve LDL-C 50% decrease from baseline
Assessment of a Waveguide-based Eye-Tracker
The dissertation describes the feasibility assessment of an holographic waveguide for eye tracking was demonstrated through lab experiments. Waveguides have been recognized as an attractive alternative to other image transmission component in AR and VR applications. In the development of this prototype, a custom-built holographic waveguide (HWG) with photopolymeric in- and out-couplers was employed to convey images of an illuminated eye model to a camera, that were subsequently processed using an off-line Matlab algorithm. A prosthetic ceramic eye model was used for this purpose. The custom-written procedure extracted the parameters relevant to the vector distance of the pupil center from the corneal reflection (CR). The relationship between the components of this vector distance and the relative rotation of the eye in the socket is known from literature to be linear over a wide range of rotations. The benchtop prototype confirmed the linear relationship between eye position and the vector components with a range of 60° degrees (horizontal) and 30° (vertical) with sub-pixel resolution. The system also showed good repeatability of the measure, as the standard deviation of repeated measured is very low (at most 1.2 pixels). This confirms the potential of HWGs for eye tracking applications. The final aim of this discovery would be a light-weight, see-through, wearable eye tracker that could be used both for commercial purposes but most importantly, to help improve current diagnostic techniques for oculomotor disorders (OD)
A new method for the non-invasive assessment of forearm arterial compliance in human subjects: impaired arterial compliance in hypercholesterolemia
A new plethysmographic method that allows the non-invasive assessment of forearm arterial compliance (FAC) was developed. A study was carried out in order to demonstrate its feasibility, reproducibility and capacity to detect changes induced by nitrates or by muscarinic stimuli. Moreover, it has been investigated whether the proposed method was sensitive enough to detect differences in FAC between normo- and hypercholesterolemic subjects. Simultaneous recordings of forearm pulse volume and blood pressure (BP) over the whole cardiac cycle are used to establish the pulse volume-BP relationship. Due to the not uniform structural composition of the arterial media this relationship is non-linear. Thus, compliance can be defined only in terms of a given BP. In order to compute the non-linear compliance and to account for the BP dependence, FAC was measured on-line by computing the ratio of dV/dP, and the area under the FAC/BP curve (FAC(AUC)) was determined in a standard range of blood pressures (70-130 mmHg). The method is highly reproducible; indeed, the FAC(AUC) values obtained from 16 subjects with two independent observations were highly significantly correlated (r=0.91; p<0.0001, C.V.=15.2%). The method is also highly sensitive to nitrate and muscarinic stimuli. The results show a reduced FAC(AUC) in hypercholesterolemics vs controls [2.28\ub10.8x10E-3 vs 4.12\ub11.06x10E-3 (ml/100ml forearm/mmHg)\u2022mmHg; p=0.0001]. In conclusion, this new plethysmographic method, allows the non-invasive assessment of the forearm arterial compliance and provides a potentially useful tool to detect and monitor in vivo, without stimulating arterial dilatation e.g. by acetylcholine infusion, the functional arterial changes in subjects with major risk factors for arterial disease as well as the effects of dietary/drug treatments
Clinical response to probucol in hypercholesterolemia: peculiar sensitivity of different subpopulations
The effectiveness of probucol therapy in group of 140 hypercholesterolemic patients who had been treated with probucol for at least six months, up to two years, was investigated in this study. The responses, in terms of individual percentage reduction of plasma LDL-C levels, have been evaluated trying to assess the sensitivity of specific subgroups of patients and their response to treatment. Clinical data and plasma lipid/lipoprotein levels were determined at baseline, at the sixth month and then at the end of 2 years. To identify and characterize subpopulation showing different sensitivity to the probucol treatment, the effectiveness of probucol therapy was related to the sex hormonal status and major lipid or non lipid parameters. Response to probucol was evaluated after stratification of patients by sex, tertiles of HDL-C levels (at baseline) and pre-/post-menopausal status in women. After six months plasma LDL-C levels was reduced of 7.0%. Stratifying patients into tertiles of HDL-C levels, the LDL-C response after six months of treatment was about 8.30% in the higher tertile group, vs a 6.5% of the lower. However in all patients who have been treated and followed for 2 years, the maximum LDL-C reduction was achieved at the end of the second year (11.6%
LIPOPROTEIN STRUCTURE IN MALE-SUBJECTS DURING IN-VIVO LIPOLYSIS - EFFECT OF AN ANTI-LIPOLYTIC TREATMENT WITH ACIPIMOX
Plasma free fatty acid (FFA) levels were raised in healthy volunteers by the administration of a fatty meal and epinephrine infusion (0.15 mg/kg per min), to test the hypothesis that enhanced lipolysis might lead to changes in lipoprotein distribution and to the formation of lipoprotein complexes, also impairing the interconversion of high density lipoproteins (HDL). The study was carried out in double-blind conditions in volunteers pre-treated with either placebo or with acipimox, a nicotinic acid analogue with a long- lasting activity. Lipolysis was effectively induced; the treatment with acipimox prevented the rise of free fatty acids (FFA), and it also blunted the triglyceride (TG) increase occurring during the test. Whereas the mean low density lipoprotein (LDL) particle size did not change, the HDL particle distribution showed a progressive shift to smaller particles, both after placebo and after acipimox, the changes in size being maximal 3-7 h after the meal. Evaluation of HDL interconversion in plasma samples incubated at 37\ub0C for 6 h showed the expected accumulation of HDL(2a) particles, with a parallel decrease of HDL(3a); however, this conversion was not affected by the presence of elevated FFA levels and no difference was noted in subjects taking either placebo or acipimox. These clinical data fail to confirm the hypothesis that enhanced lipolysis may lead to dramatic changes in plasma lipoprotein distribution and/or in aggregation or fusion of lipoprotein particles, as reported from in vitro experiments. This study, however, successfully achieved a useful model of exaggerated lipolysis and confirmed the important activity of a low dose nicotinic acid analogue in inhibiting lipolysis
Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses
Elevations of plasma cholesterol and/or triglycerides, and the prevalence of small, dense LDL particles remarkably increase coronary risk in patients with familial combined hyperlipidemia (FCHL). A total of 14 FCHL patients were studied, to investigate the ability of Omacor, a drug containing the n-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA and DHA), to favorably correct plasma lipid/lipoprotein levels and LDL particle distribution. The patients received four capsules daily of Omacor (providing 3.4 g EPA+DHA per day) or placebo for 8 weeks in a randomized, double-blind, cross-over study. Omacor significantly lowered plasma triglycerides and VLDL-cholesterol levels, by 27 and 18%, respectively. Total cholesterol did not change but LDL-cholesterol and apolipoprotein B (apoB) concentrations increased by 21 and 6%. As expected, LDL particles were small (diameter=24.9\ub10.3 nm) and apoB-rich (LDL-cholesterol/apoB ratio=1.27\ub10.26) in the selected subjects. After Omacor treatment LDL became enriched in cholesterol (LDL-cholesterol/apoB ratio=1.40\ub10.17), mainly cholesteryl esters, indicating accumulation in plasma of more buoyant and core enriched LDL particles. Indeed, the separation of LDL subclasses by rate zonal ultracentrifugation showed an increase of the plasma concentration of IDL and of the more buoyant, fast floating LDL-1 and LDL-2 subclasses after Omacor, with a parallel decrease in the concentration of the denser, slow floating LDL-3 subclass. However, the average LDL size did not change after Omacor (25.0\ub10.3 nm). The resistance of the small LDL pattern to drug-induced modifications implies that a maximal lipid-lowering effect must be achieved to reduce coronary risk in FCHL patients. Copyright (C) 2000 Elsevier Science Ireland Ltd
Effect of plasma cholesterol reduction by pravastatin on the functional properties of forearm arteries in hypercholesterolemic patients
Since functional properties in the vasculature of hypercholesterolemic subjects are impaired, a six-month pravastatin treatment (20 mg/die) was tested in an open design, on the impaired unstimulated forearm arterial compliance (Un-FAC(AUC)) of 14 asymptomatic type IIa familial hypercholesterolemic patients. In order to evaluate whether FAC(AUC) changes might be related to the extent of cholesterol reduction achieved, this evaluation was carried out in five severely hypercholesterolemic patients, undergoing LDL-apheresis
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