Portuguese Authorship in Published Clinical Trials: Differences in Industry and Investigator Initiated Trials.

Introduction: The aim of this study was to investigate the Portuguese authorship in publications resulting from trials initiated by the industry or investigators and run in Portugal.

Material And Methods: Clinical trials with Portuguese institutions as sponsor or recruiting centers, and registered in four clinical trial registries, in the last 14 years, were assessed. Publications of completed trials, from both the initiative of the industry and investigatorswere screened and compared.

Investigator Initiated Clinical Trials (IICTs): A Systematic Search in Registries to Compare the Czech Republic and Portugal in Terms of Funding Policies and Scientific Outcomes.

Objectives: Clinical trials provide one of the highest levels of evidence to support medical practice. Investigator initiated clinical trials (IICTs) answer relevant questions in clinical practice that may not be addressed by industry. For the first time, two European Countries are compared in terms of IICTs, respective funders and publications, envisaging to inspire others to use similar indicators to assess clinical research outcomes.

The role of high-density lipoprotein in the regulation of the immune response: implications for atherosclerosis and autoimmunity.

Inflammation and immune dysfunction have been increasingly recognized as crucial mechanisms in atherogenesis. Modifications in cell lipid metabolism, plasma dyslipidaemia and particularly low high-density lipoprotein (HDL) levels occur both in atherosclerosis and in autoimmune rheumatic diseases (which are strongly associated with an increased risk of atherosclerosis), suggesting the presence of a crucial link. HDL, the plasma lipoprotein responsible for reverse cholesterol transport, is known for its several protective effects in the context of atherosclerosis.

The 2-hydroxy-nevirapine metabolite as a candidate for boosting apolipoprotein A1 and for modulating anti-HDL antibodies.

The antiretroviral nevirapine (NVP) is associated to a reduction of atherosclerotic lesions and increases in high-density lipoprotein (HDL)-cholesterol. Despite being a hepatotoxic drug, which forbids its re-purposing to other therapeutic areas, not all NVP metabolites have the same potential to induce toxicity. Our aim was to investigate the effects of NVP and its metabolites in an exploratory study, towards the identification of a candidate to boost HDL.

Antibodies towards high-density lipoprotein components in patients with psoriasis.

Psoriasis is a chronic inflammatory immune disorder associated with an increased risk of atherosclerosis. This increased risk is not fully understood. High-density lipoproteins (HDL) play an important role in the prevention of atherosclerosis and any factors that may hamper HDL function such as anti-HDL antibodies (aHDL) might be associated with an increased cardiovascular risk.

ELISA methods comparison for the detection of auto-antibodies against apolipoprotein A1.

Background: Autoantibodies against apolipoprotein A1 (anti-apoA1 IgG) have emerged as an independent biomarker for cardiovascular disease and mortality. Across studies, different ELISA methods have been used to measure the level of circulating anti-apoA1 IgG which could lead to substantial result differences between assays.

Objectives: To make a comparative study of available anti-apoA1 IgG detection methods and to determine whether the choice of matrix sample (serum vs plasma) could influence the results.

Antibodies against HDL Components in Ischaemic Stroke and Coronary Artery Disease.

Quantitative and qualitative defects of high-density lipoprotein (HDL) are important in atherogenesis. In this study, we investigated whether antibodies against HDL components had additional value to conventional cardiovascular risk factors for the diagnosis of ischaemic stroke (IS) and coronary artery disease (CAD). Cross-sectional study was conducted on 53 patients with IS, 51 with CAD and 55 healthy controls, and in vitro studies to validate findings of the clinical study.

Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.

Aims: Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I).

Methods: Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl (men) or ≤50 mg dl (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over.

Nitric oxide metabolites, nitrative stress, and paraoxonase activity in hepatopulmonary syndrome.

Aim: To investigate possible abnormalities of vasoactive compounds, nitrative stress, and antioxidant activity of paraoxonase (PONa) in human hepatopulmonary syndrome (HPS), we determined endothelin-1 (ET), nitric oxide (NOx) metabolites, PONa alongside crude plasma nitrotyrosine (NT) as surrogate marker of nitrative stress.

Material And Methods: Liver cirrhosis (LC) patients with HPS (n = 12) were matched by age, sex, and Child-Pugh score to LC patients without HPS (n = 15) and to healthy controls (CTR) (n = 15); plasma NO2(-) (nitrite) (vascular metabolite), NO3(-) (nitrate) (inflammatory metabolite), and PONa were determined by a colorimetric assay, ET, and NT by immunoassays.

Results: HPS patients showed higher level of ET (p = 0.

Aspirin insensitive thromboxane generation is associated with oxidative stress in type 2 diabetes mellitus.

Introduction: Aspirin (ASA) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) leading to decreased thromboxane-mediated platelet activation. The effect of ASA ingestion on platelet activation, thromboxane generation, oxidative stress and anti-oxidant biomarkers was studied in type 2 diabetes mellitus (DM).

Material And Methods: Baseline and post-ASA samples (100/325 mg x 7 days) were obtained from 75 DM patients and 86 healthy controls for urinary 11-dehydro-thromboxane B2 (11 dhTxB2), 8-iso-prostaglandin-F2α (8-isoPGF2α) and serum sP-Selectin, nitrite (NO(2)(-)), nitrate (NO(3)(-)) and paraoxonase 1 (PON1) activity.

Carotid body function in aged rats: responses to hypoxia, ischemia, dopamine, and adenosine.

The carotid body (CB) is the main arterial chemoreceptor with a low threshold to hypoxia. CB activity is augmented by A(2)-adenosine receptors stimulation and attenuated by D(2)-dopamine receptors. The effect of aging on ventilatory responses mediated by the CB to hypoxia, ischemia, and to adenosine and dopamine administration is almost unknown.

Clinical relevance of nitric oxide metabolites and nitrative stress in thrombotic primary antiphospholipid syndrome.

Objective: To assess the role of nitrite (NO(2)(-)), nitrate (NO(3)(-)), and nitrative stress in thrombotic primary antiphospholipid syndrome (PAPS).

Methods: We investigated 46 patients with PAPS: 21 asymptomatic but persistent carriers of antiphospholipid antibodies (PCaPL), 38 patients with inherited thrombophilia (IT), 33 patients with systemic lupus erythematosus (SLE), and 29 healthy controls (CTR). IgG anticardiolipin (aCL), IgG anti-beta(2)-glycoprotein I (anti-ß(2)-GPI), IgG anti-high density lipoprotein (aHDL), IgG anti-apolipoprotein A-I (aApoA-I), crude nitrotyrosine (NT) (an indicator of nitrative stress), and high sensitivity C-reactive protein (CRP) were measured by immunoassays.

Acute hypoxia modifies cAMP levels induced by inhibitors of phosphodiesterase-4 in rat carotid bodies, carotid arteries and superior cervical ganglia.

Background And Purpose: Phosphodiesterase (PDE) inhibitors are useful to treat hypoxia-related diseases and are used in experiments studying the effects of oxygen on 3'-5'-cyclic adenosine monophosphate (cAMP) production. We studied the effects of acute hypoxia on cAMP accumulation induced by PDE inhibitors in oxygen-specific chemosensors, the carotid bodies (CBs) and in non-chemosensitive CB-related structures: carotid arteries (CAs) and superior cervical ganglia (SCG).

Experimental Approach: Concentration-response curves for the effects of a non-specific PDE inhibitor [isobutylmethylxanthine (IBMX) ], PDE4 selective inhibitors (rolipram, Ro 20-1724) and a PDE2 selective inhibitor (erythro-9-(2-hydroxy-3-nonyl)adenine) on cAMP levels were obtained in normoxic (20% O(2)/5% CO(2)) or hypoxic (5% O(2)/5% CO(2)) conditions.

High-density lipoprotein inversely relates to its specific autoantibody favoring oxidation in thrombotic primary antiphospholipid syndrome.

Abnormalities of the lipid profile partly explain the atherogenic tendency of systemic lupus erythematosus but the picture is unclear in thrombotic primary antiphospholipid syndrome (PAPS). Herein we compare the lipid profile, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (CHO), apolipoprotein A (ApoA-I), apolipoprotein B (ApoB), triglycerides (TRY)), anti-lipoprotein antibodies, beta-2-glycoprotein I complexed to oxidized low-density lipoprotein (oxLDL-ss(2)GPI) and C-reactive protein (CRP) from thrombotic PAPS (n = 34), thrombotic patients with inherited thrombophilia (IT; n = 36), subjects persistently positive for antiphospholipid antibodies (aPL, n = 18) with no underlying autoimmune or non-autoimmune disorders and healthy controls (n = 28) and determined the reciprocal effects of anti-lipoprotein antibodies, the lipid profile, oxLDL-ss(2)GPI and CRP. Average concentrations of HDL (p < 0.

Effect of efavirenz on high-density lipoprotein antioxidant properties in HIV-infected patients.

What Is Already Known About This Subject: * In previous work, we showed a long-term and concentration-dependent beneficial effect of the non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) on high-density lipoproteins (HDL) in human immunodeficiency virus (HIV)-infected patients. * Furthermore, it has been suggested that instead of the current practice of only measuring HDL-chelesterol values, the evaluation of HDL function, namely its antioxidant properties, might be an improved tool for identifying subjects at increased risk for cardiovascular events. * Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is responsible for HDL antioxidant function.

C-reactive protein in systemic lupus erythematosus.

C-reactive protein (CRP) is an acute phase protein that plays a major role in the regulation of the inflammatory response. It activates the classical complement pathway in a controlled fashion, enhancing the capacity for defence against bacterial infections. It promotes the regulation of MPhi activity through FcgammaR, and is associated with the clearance of apo cells and nuclear antigen, thus becoming a protective molecule against pathogenic autoimmune responses in general, and systemic lupus erythematosus in particular.

Humoral mechanisms of atherogenesis.

The concept that atherosclerosis is an autoimmune disease is no longer controversial. Attention has been paid to cellular immune response, but current research is now focused on the humoral component of this complex disease. Heat shock proteins, oxidized low-density lipoproteins, beta2-glycoprotein 1, cardiolipins, and, more recently, high-density lipoproteins have been considered to be autoantigens that play a part in atherogenesis.

Vascular abnormalities, paraoxonase activity, and dysfunctional HDL in primary antiphospholipid syndrome.

Context: Accelerated atherosclerosis has been described in antiphospholipid syndrome, but the vascular abnormalities and the underlying mechanisms remain unclear.

Objectives: To compare vascular structure and function in patients with positive antiphospholipid antibodies (aPL) with controls and to assess their relationship with paraoxonase activity.

Design, Setting, And Participants: A cross-sectional study of 77 women with positive antiphospholipid antibodies from a lupus outpatient clinic in London, England (90% of the eligible population) and 77 controls matched on frequency basis for age and cardiovascular risk factors between June 2006 and April 2009.

Anti-atherogenic and anti-inflammatory properties of high-density lipoprotein are affected by specific antibodies in systemic lupus erythematosus.

Objective: To determine whether antibodies against high-density lipoprotein (aHDL) and apolipoprotein A-I (aApo A-I) interfere with the anti-atherogenic functions of high-density lipoprotein (HDL) and relate to disease activity and damage in SLE.

Methods: Seventy-seven SLE patients were compared with an age- and sex-frequency matched control group. Immunoglobulin G (IgG) aHDL, IgG aApoA-I, soluble vascular cell and intracellular cell adhesion molecules (VCAM-1 and ICAM-1, respectively) were measured by ELISA, paraoxonase (PON) activity by spectrophotometry, nitric oxide (NOx) metabolites by the Griess reaction, and total anti-oxidant capacity (TAC) by chemiluminescence.

Primary antiphospholipid syndrome: a low-grade auto-inflammatory disease?

Objective: To test the inflammation and immune activation hypothesis in primary thrombotic APS (PAPS) and to identify clinical and laboratory factors related to inflammation and immune activation.

Methods: PAPS (n = 41) patients were compared with patients with inherited thrombophilia (IT, n = 44) and controls (CTR, n = 39). IgG aCL, IgG anti-beta2-glycoprotein I (beta(2)GPI), high-sensitivity CRP (hs-CRP), serum amyloid A (SAA), CRP bound to oxidized low-density lipoprotein-beta(2)GPI complex (CRP-oxLDL-beta(2)GPI) (as inflammatory markers) neopterin (NPT), soluble CD14 (sCD14) (as immune activation markers) were measured by ELISA.

An antagonistic interaction between A2B adenosine and D2 dopamine receptors modulates the function of rat carotid body chemoreceptor cells.

We have previously demonstrated that adenosine controls the release of catecholamines (CA) from carotid body (CB) acting on A2B receptors. Here, we have tested the hypothesis that the control is exerted via an interaction between adenosine A2B and dopamine D2 receptors present in chemoreceptor cells. Experiments were performed in vitro in CB from 3 months rats.

Subclinical atherosclerosis in primary antiphospholipid syndrome.

To test the atherosclerosis hypothesis in primary antiphospholipid syndrome (PAPS) we measured intima media thickness (IMT) of carotid arteries and other cardiovascular risk factors in 44 patients with PAPS (mean age 35 +/- 12 years), in 25 patients with inherited thrombophilia (mean age 40 +/- 10 years), and in 34 normal controls (mean age 38 +/- 11 years). The frequency of smoking, hypertension, and dyslipidemia was similar across groups. IMT was almost similar across groups at age groups below 40 years but IMT was greater in PAPS than controls at the common carotid (P = 0.

Antibodies toward high-density lipoprotein components inhibit paraoxonase activity in patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have an increased incidence of vascular disease, and oxidative stress is recognized as an important feature in this condition, despite the underlying mechanisms not being fully understood. In these patients, an interaction between lipoproteins and the immune system has been suggested, but most studies have only looked at antibodies against oxidized low-density lipoproteins. This study was undertaken to determine the presence of antibodies directed against high-density lipoproteins (HDL) and to identify a possible association between these antibodies and paraoxonase (PON), an antioxidant enzyme present in HDL.

Antibodies against beta2-glycoprotein I complexed with an oxidised lipoprotein relate to intima thickening of carotid arteries in primary antiphospholipid syndrome.

To explore whether antibodies against beta2-glycoprotein I (beta2GPI) complexed to 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and to oxidised low-density lipoproteins (oxLDL) relate to paraoxonase activity (PONa) and/or intima media thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS). As many as 29 thrombotic patients with PAPS, 10 subjects with idiopathic antiphospholipid antibodies (aPL) without thrombosis, 17 thrombotic patients with inherited thrombophilia and 23 healthy controls were investigated. The following were measured in all participants: beta2GPI-oxLDL complexes, IgG anti-beta2GPI-oxLig-1, IgG anti-beta2GPI-oxLDL antibodies (ELISA), PONa, (para-nitrophenol method), IMT of common carotid (CC) artery, carotid bifurcation (B), internal carotid (IC) by high resolution sonography.