Anti-phospholipid antibodies in diabetes mellitus.

The presence of autoantibodies to phospholipids may be associated with various pathological disorders; diabetes could be one of them because of the changes occurring in lipid metabolism but there are only few reports examining this question, and they are not always leading to the same conclusions because of the differences in the procedures or in the phospholipids tested. We carried out a systematic comparative study of diabetic serum antibody binding to all phospholipids, anionic and zwitterionic, by a quantitative ELISA. The implication of the hydrophobic moiety of the lipids was also studied: the presence of autoantibodies to the fatty acyl chains was investigated. Our results show the presence of anti-phospholipid antibodies in diabetic sera, particularly anti-phosphatidylinositol and anti-phosphatidylcholine which have never been tested before, and appear to be associated with macroangiopathic complications. The antigenic epitopes are mainly the polar heads as no antibody binding to the hydrophobic moiety was observed. We discuss the relation of those antibodies to the angiopathic complications and to the direct effects of hyperglycemia on lipid antigenicity.     

Practical screening and early treatment of hepatocellular carcinoma. Results of a French survey

AIM: To describe French practices for screening hepatocellular carcinoma. METHODS: A standardized questionnaire was mailed to all French hospital hepato-gastroenterologists in June 1999. RESULTS: 411 out of 623 practitioners responded (66%). 394 (96%) routinely screen hepatocellular carcinoma, mainly with ultrasound (98%) and mainly at 6-month intervals (77%). Screening was performed in cirrhosis (100%) or extensive fibrosis (54%), independent of the etiology (21%) or the Child-Pugh score of the chronic liver disease (41%), but based on age and treatment feasibility. If of a small hypoechogenic nodule was detected in a young patient with compensated HCV-cirrhosis, 59% of practitioners performed a histological examination. In case of non biopsy-proven hepatocellular carcinoma, a second biopsy (49%), treatment (either percutaneous alcohol injection, resection or transplantation) (24%) or an ultrasonographic follow-up (23%) was proposed. In case of biopsy-proven hepatocellular carcinoma, resection (49%), transplantation (30%) or percutaneous alcohol injection (16%) was proposed. CONCLUSION: Almost all French specialists routinely screen cirrhotic patients for hepatocellular carcinoma, but use somewhat different modalities. In case of small HCC without contraindications to curative treatment, surgical resection is performed in half the patients.     

Cocaine use in Europe - a multi-centre study. Methodology and prevalence estimates

An increase in the use of cocaine and crack in several parts of Europe has raised the question whether this trend is similar to that of the USA in the 1980s. However, research in the field of cocaine use in Europe has been only sporadic. Therefore, a European multi-centre and multi-modal project was designed to study specific aspects of cocaine and crack use in Europe, in order to develop guidelines for public health strategies. Data on prevalence rates were analysed for the general population and for specific subgroups. Despite large differences between countries in the prevalence of cocaine use in the general population, most countries show an increase in the last few years. The highest rate with a lifetime prevalence of 5.2% was found for the United Kingdom, although with a plateau effect around the year 2000. With regard to specific subgroups, three groups seem to show a higher prevalence than the general population: (1) youth, especially in the party scene; (2) socially marginalized groups, such as homeless and prostitutes or those found in open drug scenes; (3) opiate-dependent patients in maintenance treatment who additionally use cocaine. Specific strategies need to be developed to address problematic cocaine use in these subgroups.     

Cryopyrinopathies: update on pathogenesis and treatment

Cryopyrinopathies are a group of rare autoinflammatory diseases that includes familial cold autoinflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurologic cutaneous articular syndrome (also termed neonatal-onset multisystemic inflammatory disease). These syndromes were initially considered to be distinct disease entities despite some clinical similarities; however, mutations of the same gene have since been found in all three cryopyrinopathies. These diseases, therefore, are not separate but represent a continuum of subphenotypes. The gene in question, CIAS1 (now renamed NLRP3) encodes NALP3 (also known as cryopyrin). NALP3 is an important mediator of inflammation and interleukin 1beta processing. New therapies based on biologic agents that specifically target interleukin 1beta are currently being developed. These new agents have provided very encouraging results for patients with these long-lasting inflammatory conditions--which used to be considered refractory to treatment. The development of therapeutic options for these cryopyrinopathies illustrates effective translation of basic science to clinical practice and the convergence of human genetics and targeted therapies.     

Proteinase-activated receptor-2: physiological and pathophysiological roles

Protease-activated receptor 2 (PAR2) is the second member of a new subfamily of G-protein coupled receptors: the protease-activated receptors (PARs). At present, four different PARs have been cloned and all of them share the same basic mechanism of activation. A serine protease cleaves the extended, extracellular N-terminus of the receptor at a specific site within the protein chain to expose an N-terminal tethered ligand domain, which binds to and activates the cleaved receptor. In this manner, trypsin and mast cell beta-tryptase activate PAR2. PARs are single use receptors because proteolytic activation is irreversible and the cleaved receptors are degraded in lysosomes. Thus, PARs play important roles in emergency situations, such as trauma and inflammation. Emerging evidence indicates that PAR2 is involved in the cardiovascular, pulmonary and gastrointestinal systems, where it controls inflammation and nociception. Work with selective agonists and knockout animals suggests a contribution of PAR2 to certain inflammatory diseases. Therefore, selective antagonists or agonists of these receptors may be useful therapeutic agents for the treatment of human diseases.     

Breastfeeding Practices in Relation to Country of Origin Among Women Living in Denmark: A Population-Based Study

The objective of this study was to describe breastfeeding practices and to compare the risk of suboptimal breastfeeding of women living in Denmark according to country of origin, and further to examine how socio-economic position and duration of stay in the country affected this risk. Information on breastfeeding of 42,420 infants born 2002–2009 and living in eighteen selected Danish municipalities was collected from the Danish Health Visitor’s Child Health Database. The data was linked with data on maternal socio-demographic information from Danish population-covering registries. Suboptimal breastfeeding was defined as <4 months of full breastfeeding as described by the Danish Health and Medicines Authority. We used logistic regression to model the crude associations between suboptimal breastfeeding and country of origin, and taking maternal age and parity, and a variety of parental socio-economic measures into account. Suboptimal breastfeeding was more frequent among non-Western migrant women than among women of Danish origin. Women who were descendants of Turkish and Pakistani immigrants had a higher risk of suboptimal breastfeeding as compared to the group of women who had migrated from the same countries, suggesting that acculturation did not favor breastfeeding. For all but the group of women who had migrated from Pakistan, adjustment for socio-demographic indicators (age, parity, education, attachment to labour market, and income) eliminated the increased risk of suboptimal breastfeeding. There was no evidence for differences in the breastfeeding support provided at hospital level according to migrant status. Suboptimal breastfeeding was more frequent among women who were non-Nordic migrants and descendants of migrants than among women with Danish origin.     

A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial

Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3–6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81–0.91] before the change to 0.32 (95 % CI 0.26–0.40; p < 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p < 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.     

A microdevice for parallelized pulmonary permeability studies

We describe a compartmentalized microdevice specifically designed to perform permeability studies across a model of lung barrier. Epithelial cell barriers were reproduced by culturing Calu-3 cells at the air-liquid interface (AIC) in 1 mm² microwells made from a perforated glass slide with an embedded porous membrane. We created a single basolateral reservoir for all microwells which eliminated the need to renew the growth medium during the culture growth phase. To perform drug permeability studies on confluent cell layers, the cell culture slide was aligned and joined to a collection platform consisting in 35 μL collection reservoirs connected at the top and bottom with microchannels. The integrity and functionality of the cell barriers were demonstrated by measurement of trans-epithelial electrical resistance (TEER), confocal imaging and permeability assays of ¹⁴C-sucrose. Micro-cell barriers were able to form confluent layers in 1 week, demonstrating a similar bioelectrical evolution as the Transwell systems used as controls. Tight junctions were observed throughout the cell-cell interfaces, and the low permeability coefficients of ¹⁴C-sucrose confirmed their functional presence, creating a primary barrier to the diffusion of solutes. This microdevice could facilitate the monitoring of biomolecule transport and the screening of formulations promoting their passage across the pulmonary barrier, in order to select candidates for pulmonary administration to patients.