Borut Božič

• prof.
• Ljubljana University Medical Centre

The PHARMINE (“Pharmacy Education in Europe”) project studied pharmacy practice and education in the European Union (EU) member states. The work was carried out using an electronic survey sent to chosen pharmacy representatives. The surveys of the individual member states are now being published as reference documents. This paper presents the resul...

Autoantibodies against dsDNA are utilized for the diagnosis and prognosis of SLE as they are highly specific and correlate with disease activity/renal involvement. However, different detection methods are used in routine diagnostic laboratories. Farr radioimmunoassay (Farr-RIA) has been designated as the preferred method, since it provides very spe...

Background RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients. Aim To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC). Methods HCAEC were preincubated for 2 h wi...

This article presents the results of mapping the Slovenian pharmacy curriculum to evaluate the adequacy of the recently developed and validated European Pharmacy Competences Framework (EPCF). The mapping was carried out and evaluated progressively by seven members of the teaching staff at the University of Ljubljana’s Faculty of Pharmacy. Consensus...

Disaccharidases (DS) are brush border enzymes embedded in the microvillous membrane of small intestinal enterocytes. In untreated coeliac disease (CD), a general decrease of DS activities is seen. This manuscript reviews different aspects of DS activities in CD: their utility in the diagnosis and their application to in vitro toxicity testing. The...

About a third of patients with rheumatoid arthritis treated with adalimumab may develop anti-adalimumab antibodies. Anti-adalimumab antibodies are associated with reduced drug levels, loss of drug efficacy, clinical non-response and an increased risk of adverse effects. In case of suspected drug failure and in order to better define clinical effica...

This paper presents the results of the second European Delphi round on the ranking of competences for pharmacy practice and compares these data to those of the first round already published. A comparison of the numbers of respondents, distribution by age group, country of residence, etc., shows that whilst the student population of respondents chan...

The objective of the PHAR-QA (Quality assurance in European pharmacy education and training) project was to investigate how competence-based learning could be applied to a healthcare, sectoral profession such as pharmacy. This is the first study on evaluation of competences from the pharmacists’ perspective using an improved Delphi method with a la...

This paper looks at the way in which industrial pharmacists rank the fundamental competences for pharmacy practice. European industrial pharmacists (n = 135) ranked 68 competences for practice, arranged into 13 clusters of two types (personal and patient care). Results show that, compared to community pharmacists (n = 258), industrial pharmacists r...

This paper looks at the opinions of 241 European academics (who provide pharmacy education), and of 258 European community pharmacists (who apply it), on competences for pharmacy practice. A proposal for competences was generated by a panel of experts using Delphi methodology. Once finalized, the proposal was then submitted to a large, European-wid...

European students (n = 370), academics (n = 241) and community pharmacists (n = 258) ranked 13 clusters of 68 personal and patient care competences for pharmacy practice. The results show that ranking profiles for all three groups as a rule were similar. This was especially true of the comparison between students and community pharmacists concernin...

Antiphospholipid syndrome (APS

PHAR-QA, funded by the European Commission, is producing a framework of competences for pharmacy practice. The framework is in line with the EU directive on sectoral professions and takes into account the diversity of the pharmacy profession and the on-going changes in healthcare systems (with an increasingly important role for pharmacists), and in...

Do community pharmacists coming from different educational backgrounds rank the importance of competences for practice differently—or is the way in which they see their profession more influenced by practice than university education? A survey was carried out on 68 competences for pharmacy practice in seven countries with different pharmacy educati...

Objective. To determine the prevalence and clinical association of anti-phosphatidylserine/prothrombin antibodies (aPS/PT) in patients with a history of pregnancy complications relevant to antiphospholipid syndrome (APS). Materials and Methods. Two hundred and eleven patients with a history of (a) three or more consecutive miscarriages before 10th...

In patients with the antiphospholipid syndrome (APS), the presence of a group of pathogenic autoantibodies called antiphospholipid antibodies causes thrombosis and pregnancy complications. The most frequent antigenic target of antiphospholipid antibodies are phospholipid bound β2-glycoprotein 1 (β2GPI) and prothrombin. The international classificat...

The pathogenicity of antibodies against β2-glycoprotein I (anti-β2GPI) depends on multiple factors such as subclass type, epitope binding and avidity. Due to their large heterogeneity, their impact on antiphospholipid syndrome (APS) onset is still not fully clarified. We studied the binding characteristics of IgG anti-β2GPI with known avidity from...

The goal of the PHAR-QA (quality assurance in European pharmacy education and training) project is the production of a European framework for a quality assurance system based on competences for pharmacy practice. The PHAR-QA framework will be European, consultative and will encompass the various aspects of pharmacy practice. In this review, we desc...

Abstract Studies concerning interactions between anti-β2-glycoprotein I antibodies (anti-β2GPI) and β2-glycoprotein I (β2GPI) suggest relevance of charge interactions and hydrogen bonds. However, paratope of diagnostically and clinically relevant anti-β2GPI and epitope characteristics of β2GPI, still remain unclear. The aim of our study was to dete...

With the changes in the Bologna process and the European directive on sectoral professions, the education and training of the pharmacists in the European Higher Education Area is moving towards a quality system based on competences. In this paper we analyze the existing quality assurance and accreditation systems in 10 countries and examine how far...

Patient biological material for isolation of β 2-glycoprotein I ( β 2GPI) and high avidity IgG anti- β 2-glycoprotein I antibodies (HAv anti- β 2GPI) dictates its full utilization. The aim of our study was to evaluate/improve procedures for isolation of unnicked β 2GPI and HAv a β 2GPI to gain unmodified proteins in higher yields/purity. Isolation...

The European Union directive on sectoral professions emphasizes the fact that pharmacists working in member states should possess the competences required for their professional practice; the directive does not, however, describe such competences in detail. The “Quality Assurance in European Pharmacy Education and Training—PHAR-QA” consortium, fund...

Antiprothrombin antibodies, measured with phosphatidylserine/prothrombin complex (aPS/PT) ELISA, have been reported to be associated with antiphospholipid syndrome (APS). They are currently being evaluated as a potential classification criterion for this autoimmune disease, characterized by thromboses and obstetric complications. Given the present...

To generate a catalog of citrullinated proteins that are present in the synovia of patients with rheumatoid arthritis (RA) and to elucidate their relevance for the anti–citrullinated protein antibody response in RA. Polypeptides isolated from the synovial fluid of patients with RA were identified by mass spectrometry. Three proteins (apolipoprotein...

Antibodies against β2-glycoprotein I (anti-β2GPI) are one of the hallmarks of the antiphospholipid syndrome (APS). However, they are heterogenic regarding their epitope specificity, pathogenic mechanisms and their avidity. In the current study we present some outstanding issues about avidity of anti-β2GPI antibodies. Our results confirmed that high...

Antiprothrombin antibodies can be measured by ELISA using either a prothrombin/phosphatidylserine complex (aPS/PT) or prothrombin alone (aPT) as antigen. We aimed to compare the clinical features of autoimmune patients with avidity of aPS/PT and determine the diagnostic efficiency of aPS/PT and aPT for assessing antiphospholipid syndrome (APS). aPS...

Introduction Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joints and the presence of autoantibodies directed against proteins containing the non-standard arginine-derived amino acid citrulline. The protein fibrinogen, which has an essential role in blood clotting, is one of the most prominent citrullinated...

The role of antiphospholipid antibodies (aPL) associated with cardiovascular diseases has been extensively studied in autoimmune patients, however it was largely unknown whether and how aPL associate with coronary artery disease (CAD), ishemic stroke (IS) and peripheral artery disease (PAD) in non-autoimmune patients. The current review attempts to...

β2-glycoprotein I (β2GPI) is a major autoantigen of autoimmune thrombophilia, known as the antiphospholipid syndrome. The exact mechanism underlying the β2GPI's involvement in the disease is not fully elucidated, as it is not its physiological role. We used random phage peptide library to identify sequences binding to β2GPI. Obtained K(L/V)WX(I/L/V...

Autoimmune diseases affect approximately 3% of the population and are a significant cause of morbidity and mortality. Therefore, they are the focus of vivid research aimed at the delineation of pathology, more efficient diagnosis and therapy. Phage display is a simple methodology markedly useful in studying protein-protein interactions which are th...

Redox-reactive antibodies, mainly of the IgG class, gained a wide area of interest after their autoimmune reactivity was revealed following the application of chemical and physiological oxidants. In this study, we examined the susceptibility of IgMs to oxidation and evaluated their binding to the autoantigens important in some autoimmune diseases....

Objective. The objective of this study was to extend the findings of the preliminary study by measuring the avidity of IgG anti-β2-glycoprotein I antibodies (anti-β2-GPI) on a larger group of patients with primary or secondary antiphospholipid syndrome (APS) and anti-β2-GPI positive patients without APS in the frame of the European Forum on antipho...

Despite available treatment, there is still significant morbidity and mortality present among patients with the autoimmune thrombophilic condition termed 'antiphospholipid syndrome' (Espinosa, G. and Cervera, R. 2009. Morbidity and mortality in the antiphospholipid syndrome. Curr. Opin. Pulm. Med. 15:413.). High-avidity (HAv) anti-β(2)-glycoprotein...

Two approaches for detecting anti-prothrombin antibodies have been described. The first detects antibodies against prothrombin alone and the second, phos-phatidylserine-dependent antiprothrombin antibodies. The latter more often correlate with clinical manifestations of antiphospholipid syndrome and with lupus anticoagulant activity. In order to in...

The natural structuring of the immune system is responsible for the functional physiological state of the body. The development of natural autoantibodies involved in homeostasis relies on the ability to distinguish between exposed/masked and altered/non-altered self antigens. The objectives of this article were to address the relationships between...

Antiphospholipid syndrome (APS) is diagnosed by the simultaneous presence of vascular thrombosis and/or pregnancy morbidity and detection of antiphospholipid antibodies in plasma. We have shown that prolongation of clotting time by anti-beta2-glycoprotein I (beta2GPI) antibodies correlates better with thrombosis than a positive classic lupus antico...

Antibodies against β2-glycoprotein I are a subset of very heterogeneous family of antiphospholipid antibodies. It is well recognised that anti-β2-glycoprotein I antibodies are the main pathogenic players in the autoimmune disease known as antiphospholipid syndrome. Many mechanisms have been proposed through which these autoantibodies could cause mi...

Patients with recurrent pregnancy loss and a history of thrombotic events have often been noted to have autoantibodies directed at annexin A5. However, the relationship of these autoantibodies to immunopathology is still unknown, although it has been proposed that they have a direct effect on the function of annexin A5. Annexin A5 may be a signific...

The diagnosis of inflammatory bowel disease (IBD), particularly the differentiation between ulcerative colitis (UC) and Crohn's disease (CD), is difficult and delayed in many cases, despite invasive diagnostic tools. To determine the presence and evaluate the diagnostic accuracy of the potential serological diagnostic markers perinuclear antineutro...

A possible co-appearance of anticardiolipin (aCL), anti-β2-glycoprotein I (anti-β2-GPI), anti-prothrombin (aPT) and anti-annexin V (aANXV) antibodies of IgG, IgM and IgA class were studied in 58 patients with SLE alone and 32 patients APS in the view of rational laboratory diagnostics. The presence of anti-phospholipid antibodies (aPL) were defined...

Isolation buffer characteristics and storage conditions could partially transform natural antibodies. 50 IgG factions were isolated from seven healthy donors' sera using various protein G columns and buffers. PAGE revealed no major antibody cleavages; purity of IgGs eluted at pH 2.4-3.5 was close to homogeneity, independent of buffer composition. A...

Annexin A5 is a potent anticoagulant protein with a thrombomodulatory function. It is frequently mentioned with systemic inflammatory autoimmune disease, which share higher vulnerability to cardiovascular diseases. The protein has the ability to bind to membranes containing negatively charged phospholipids in a calcium-dependent manner. The potent...

The aim of this report was an overview of beta2-glycoprotein I (beta2-GPI)- and annexin A5 (AnxA5)-phospholipid interactions including candidate beta2-GPI receptors, and their relevance to the investigation of physiological/pathological processes. Both beta2-GPI and AnxA5 have thrombomodulatory functions in vivo and their antigenicity is particular...

The way proteins associate with the lipid bilayer defines not only their function, but in autoimmune diseases, such as antiphospholipid syndrome (APS), also represents the conformational change of an antigen necessary for the exposure of critical epitopes recognized by potential autoantibodies. These interactions between the antigen (bound to phosp...

Patients suffering from systemic lupus erythematosus (SLE) or Sjögren's syndrome (SS) often contain autoantibodies directed to the Ro(SS-A) complex. In this study the antigcnic determinants on two of the components of the Ro complex, i.e. the Ro60 and the Ro52 polypeptides, were investigated. Anti-Ro+ sera were selected by counter-immunoelectrophor...

Oxidation reactions can modify protein activity or specificity. Recently, a novel redox-reactive family of autoantibodies was described, which indicated involvement of altered antibodies (beside altered antigens) into autoimmune reactions. The aim of our study was to determine the binding capacity alterations of electro-oxidized blood donors' IgGs,...

The basic knowledge and clinical applications of the detection of affinity/avidity of autoantibodies are relatively scarce. Surprisingly, there have been very few recent studies concerning this topic. While theoretical thermodynamics of antigen-antibody interactions are well known, their practical use in detection or determination of autoantibodies...

Proteins, including immunoglobulins, can be modified by oxidation. Extensive oxidation of immunoglobulins leads to denaturation and loss of biological activity, while initial steps of oxidation may change their specificity due to chemical alteration of the paratope. Electro-oxidation of the IgG fraction from healthy persons progress to auto-immunor...

Anti-phospholipid antibodies have been recognized to play a role in vascular thrombosis and pregnancy morbidity. They were first thought to be directed to phospholipids, but it is now known that the majority of pathogenic antibodies recognizes epitopes on phospholipid-binding plasma proteins such as beta2-glycoprotein I (beta2GPI) or possibly also...

Cited By (since 1996):1, Export Date: 18 October 2014

The immune response may be changed due to altered proteins or modifications of immunoglobulins, including oxidative processes. The susceptibility to oxidative modifications depends greatly on amino-acid moiety composition due to chemical characteristics (instability) of their side-chains. Initial steps of oxidation may change the specificity and av...

This study was undertaken to evaluate the possible role of hepatitis B recombinant vaccine inducing the synthesis of IgG and IgM anti-cardiolipin antibodies (aCL), antibodies against beta(2)GPI (anti-beta(2)GPI), lupus anti-coagulant (LA), anti-nuclear antibodies and antibodies against extractable nuclear antigens (anti-ENA). The study population c...

Antiphospholipid syndrome (APS) has been defined as a clinical and laboratory entity. Laboratory criteria include the presence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA), collectively termed as antiphospholipid antibodies (aPL). However, there has been a rising interest in antibodies against so-called protein cofactors, par...

We aimed to evaluate avidity of anti-beta(2)-glycoprotein I antibodies (anti-beta(2)-GPIs) in patients with antiphospholipid syndrome (APS) at the time of acute thrombotic events or pregnancy loss as compared with clinical event-free periods. To do so, 69 sera samples from 16 patients (6 with primary APS and 10 with APS secondary to systemic lupus...

The terms affinity and avidity are often used indiscriminately, despite clearly differing. Since affinity refers to monovalent binding of antibodies to a monovalent epitope, the majority of data on the binding of anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) characterized their avidity rather than affinity. Anti-beta2-GPI were generally bel...

The in vivo physiologic role of beta2-glycoprotein I (beta2GPI) is presumed to be related to its interactions with negatively charged phospholipid membranes. Increased quantities of procoagulant microparticles derived by the vesiculation of blood cells have been detected in patients with antiphospholipid syndrome (APS) frequently associated with an...

To evaluate avidity of IgG anti-beta 2-glycoprotein I antibodies (anti-beta2-GPI) in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) in relation to thrombosis, and to demonstrate a possible affinity maturation of IgG anti-beta 2-GPI during the disease course. 64 sera from 32 patients (18 with primary or secondar...

We studied the influence of different binding conditions on the interaction between high- or low-avidity IgG anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) and beta2-GPI, which was either free in solution or bound to microtitre plates or nitrocellulose membranes. Sera from 30 patients with antiphospholipid syndrome and/or systemic lupus eryt...

Vesicle shape transformations caused by decreasing the difference between the equilibrium areas of membrane monolayers were studied on phospholipid vesicles with small volume to membrane area ratios. Slow transformations of the vesicle shape were induced by lowering of the concentration of lipid monomers in the solution outside the vesicle. The com...

beta2-Glycoprotein I (beta2GPI) is the major target molecule for so-called anticardiolipin antibodies. We evaluated the isolation procedure of beta2GPI from human plasma with special emphasis on the time of precipitation, composition of different isolated fractions and their antigenic properties. The isolation was initiated by perchloric acid preci...

The antiphospholipid antibodies are a large and heterogenous family of immunoglobulins which, despite their name, do not bind to phospholipids, but are directed to plasma proteins with affinity for anionic (phospholipid) surfaces. β2-glycoprotein I is the most common and investigated antigenic target. In this article, we discuss on molecular struct...

Annexin V (ANXV) is a protein with a high affinity for negatively charged phospholipids and shows in vitro a potent anticoagulant activity. It has been suggested that it has a significant role in the prevention of arteriovenous thromboses or fetal loss, or both.1 Increased levels of antibodies against ANXV (aANXV) have been reported in patients wit...

To examine histomorphological and immunohistological changes in an autopsy series of systemic lupus erythematosus (SLE) patients with or without anticardiolipin antibodies (aCL). Fourteen SLE patients who died at our department from 1988 to 1996 were included. The patients' medical files were reviewed for the clinical history and the presence of Ig...

To analyse the influence of HLA-DR, DQ and corresponding DQA1 and DQB1 promoter alleles (QAP and QBP) on the anti-Ro alone autoantibody response in systemic lupus erythematosus (SLE). Sixty-five unrelated anti-La antibody-negative SLE patients, 37 of them with and 28 without anti-Ro antibodies, were included. Anti-Ro antibodies were determined by b...

Antiphospholipid antibodies (aPL) are strongly associated with clinical manifestations of the antiphospholipid syndrome (APS) such as thromboembolic events and/or pregnancy loss. IgG anticardiolipin (aCL) at moderate/high titre and IgG anti-β2-glycoprotein I (aB2GPI) are closely related to clinical complications, IgM are commonly transient, present...

Antiphospholipid antibodies (aPL) are strongly associated with arterial and/or venous thrombosis and recurrent foetal loss. The only neurological manifestation satisfying the diagnostic criteria for the antiphospholipid syndrome (APS) is ischemic cerebrovascular insult (CVI). Because of previous contradicting reports on the association between aPL...

Anticardiolipin antibodies (aCL) have been frequently detected in juvenile idiopathic arthritis (JIA), but have not been associated with disease activity or clinical features of the antiphospholipid syndrome (APS). Our aim was to determine aCL and anti-beta2 glycoprotein I (anti-beta2GPI) antibody levels and lupus anticoagulant (LA) in serial sampl...

To determine the prevalence of myositis specific autoantibodies (MSAs) and several myositis associated autoantibodies (MAAs) in a large group of patients with myositis. A total of 417 patients with myositis from 11 European countries (198 patients with polymyositis (PM), 181 with dermatomyositis (DM), and 38 with inclusion body myositis (IBM)) were...