Towards a consensus view on understanding nanomaterials hazards and managing exposure

The aim of this article is to present an overview of salient issues of exposure, characterisation and hazard assessment of nanomaterials as they emerged from the consensus-building of experts undertaken within the four year European Commission coordination project NanoImpactNet. The approach adopted is to consolidate and condense the findings and problem-identification in such a way as to identify knowledge-gaps and generate a set of interim recommendations of use to industry, regulators, research bodies and funders. The categories of recommendation arising from the consensual view address: significant gaps in vital factual knowledge of exposure, characterisation and hazards; the development, dissemination and standardisation of appropriate laboratory protocols; address a wide range of technical issues in establishing an adequate risk assessment platform; the more efficient and coordinated gathering of basic data; greater inter-organisational cooperation; regulatory harmonization; the wider use of the life-cycle approaches; and the wider involvement of all stakeholders in the discussion and solution-finding efforts for nanosafety.

The Th2 lymphoproliferation developing in LatY136F mutant mice triggers polyclonal B cell activation and systemic autoimmunity.

Lat(Y136F) knock-in mice harbor a point mutation in Tyr(136) of the linker for activation of T cells and show accumulation of Th2 effector cells and IgG1 and IgE hypergammaglobulinemia. B cell activation is not a direct effect of the mutation on B cells since in the absence of T cells, mutant B cells do not show an activated phenotype. After adoptive transfer of linker for activation of T cell mutant T cells into wild-type, T cell-deficient recipients, recipient B cells become activated. We show in vivo and in vitro that the Lat(Y136F) mutation promotes T cell-dependent B cell activation leading to germinal center, memory, and plasma cell formation even in an MHC class II-independent manner. All the plasma and memory B cell populations found in physiological T cell-dependent B cell responses are found. Characterization of the abundant plasmablasts found in secondary lymphoid organs of Lat(Y136F) mice revealed the presence of a previously uncharacterized CD93-expressing subpopulation, whose presence was confirmed in wild-type mice after immunization. In Lat(Y136F) mice, B cell activation was polyclonal and not Ag-driven because the increase in serum IgG1 and IgE concentrations involved Abs and autoantibodies with different specificities equally. Although the noncomplement-fixing IgG1 and IgE are the only isotypes significantly increased in Lat(Y136F) serum, we observed early-onset systemic autoimmunity with nephritis showing IgE autoantibody deposits and severe proteinuria. These results show that Th2 cells developing in Lat(Y136F) mice can trigger polyclonal B cell activation and thereby lead to systemic autoimmune disease.

Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis.

Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels.

Complexitat i fenomen (socio)linguístic

Intermediate phenomena of reality present particular characteristics of systemic self-organization, multilevel interrelations, recursivity, emergence of new «objects» with properties different from those of the elements that form them, and evolutionary dynamics, that probably need the formulation of new theoretical concepts and different paradigm principles. The sciences or perspectives of complexity, or the «complex» thinking, try to respond adequately to this complexity of reality. This approach adopts a multidimensional, integrated and dynamic view of reality: the world is made up of overlapping levels of different elements which produce new properties or new organizations at higher levels. If we conceive what we call languages as simple and decontextualized objects, we can understand some of the more mechanical aspects but we will ignore their conditions of existence, functionality, maintenance, variation, change and extinction.

Insect eggs induce a systemic acquired resistance in Arabidopsis.

Although they constitute an inert stage of the insect's life, eggs trigger plant defences that lead to egg mortality or attraction of egg parasitoids. We recently found that salicylic acid (SA) accumulates in response to oviposition by the Large White butterfly Pieris brassicae, both in local and systemic leaves, and that plants activate a response that is similar to the recognition of pathogen-associated molecular patterns (PAMPs), which are involved in PAMP-triggered immunity (PTI). Here we discovered that natural oviposition by P. brassicae or treatment with egg extract inhibit growth of different Pseudomonas syringae strains in Arabidopsis through the activation of a systemic acquired resistance (SAR). This egg-induced SAR involves the metabolic SAR signal pipecolic acid, depends on ALD1 and FMO1, and is accompanied by a stronger induction of defence genes upon secondary infection. Although P. brassicae larvae showed a reduced performance when feeding on Pseudomonas syringae-infected plants, this effect was less pronounced when infected plants had been previously oviposited. Altogether, our results indicate that egg-induced SAR might have evolved as a strategy to prevent the detrimental effect of bacterial pathogens on feeding larvae.

A topological view of the replicon.

The replication of circular DNA faces topological obstacles that need to be overcome to allow the complete duplication and separation of newly replicated molecules. Small bacterial plasmids provide a perfect model system to study the interplay between DNA helicases, polymerases, topoisomerases and the overall architecture of partially replicated molecules. Recent studies have shown that partially replicated circular molecules have an amazing ability to form various types of structures (supercoils, precatenanes, knots and catenanes) that help to accommodate the dynamic interplay between duplex unwinding at the replication fork and DNA unlinking by topoisomerases.

Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience.

Primary systemic amyloidosis (AL amyloidosis) continues to have a very poor prognosis. Most therapeutic strategies remain unsatisfactory. Conventional chemotherapy is known to offer at best only moderate efficacy. Several studies have yielded higher complete response rates after high-dose chemotherapy and autologous stem cell transplantation (ASCT) in addition to improving outcomes in a subgroup of patients. However, the superiority of an intensive approach in AL amyloidosis has not been confirmed in a randomised trial. The precise role of ASCT remains unclear. We report our experience in 16 patients diagnosed with AL amyloidosis and treated in a multidisciplinary approach with high-dose melphalan and ASCT. Median age was 59 (39-71) years. The kidneys were predominantly affected in 75% of cases; two or more organs were affected in 38%. Median time from diagnosis to transplantation was 2 (1-4) months. Three patients (19%) developed acute renal failure and required transient dialysis. Transplant-related mortality was 6% after 100 days. Haematological complete response (CR) was obtained in nine (56%) and organ response in six (38%) patients. Nine out of 12 patients (75%) with kidney involvement exhibited a sustained clinical benefit at 12 months. Half of all the patients (n = 8) were alive after a median follow-up of 33 months, including two in continuous CR. This suggests that high-dose chemotherapy and ASCT are still valid treatment options in AL amyloidosis and that a significant number of patients with renal involvement might benefit from this approach.

Allergologie: 2. Mastocytose systémique--nouvelles stratégies thérapeutiques [Systemic mastocytosis--new therapeutic strategies].

Systemic mastocytosis is characterized by an excessive proliferation of mast cells and their accumulation in different organs. Avoidance of trigger factors leading to anaphylaxis is a general measure valid for all forms of mastocytosis. A premedication is necessary in case of surgery, anesthesia or administration of radiocontrast agents. Symptomatic treatment comprises antihistamines, anti-leukotrienes, proton pump inhibitors and topical corticosteroids. Indolent mastocytosis with refractory symptoms, the rare cases of aggressive mastocytosis with organ dysfunction and the even rarer mast cell leukemia require cytoreductive therapy. First-line agents are interferon alpha 2b and imatinib, a tyrosine kinase inhibitor. To date there is no curative treatment.

Barnbyn Skå (Skå, la vila dels infants) 1947-1972: L’experiència terapèutica de Gustav Jonsson amb infants «irrecuperables»

The article presents the trajectory of the Swedish psychiatrist Gustav Jonsson (1907-1994) who, in the 1940s, revolutionised the therapeutic and educational treatment of children and young people, considered irreclaimable from the social point of view, who were committed to educational institutions. It analyses the social development of the Welfare State in Sweden, the legal framework of child protection, as well as the context of Swedish residential care centres for children and young people in the first half of the 20th century in order to go further into the psychological and educational work conducted with the Barnbyn Skå group. Jonsson redirected the analysis of violent behaviours that were manifest in these children and young people which made them intractable from the educational point of view and established elements of psychoanalytical understanding, based on a systemic approach in which the family context became essential in order to understand the children’s difficulties. Barnbyn Skå was the centre which, under the guidance of Jonsson, developed this new therapeutic and pedagogic approach. The educational work carried out there exceeded the traditional model in terms of control and surveillance. The methods were considered radical from within pedagogy and caused great controversy which led the centre to continuous investigations on behalf of the Social Services of Stockholm between 1960 and 1970. For several decades Barnbyn Skå has been considered a pioneering experience in the field of Scandinavian child psychiatry.

Induction of systemic resistance in tomato by the autochthonous phylloplane resident Bacillus cereus

The objective of this work was to verify if the induced resistance mechanism is responsible for the capacity of a phylloplane resident bacteria (Bacillus cereus), isolated from healthy tomato plants, to control several diseases of this crop. A strain of Pseudomonas syringae pv. tomato was used as the challenging pathogen. The absence of direct antibiosis of the antagonist against the pathogen, the significant increase in peroxidases activity in tomato plants exposed to the antagonist and then inoculated with the challenging pathogen, as well as the character of the protection, are evidences wich suggest that biocontrol efficiency presented by the antagonist in previous works might be due to induced systemic resistance (ISR).

Infections pulmonaires : le point de vue du radiologue [Pulmonary infections: the radiologist's point of view]

La place de l'imagerie est essentielle au cours des infections pulmonaires. La TDM doit être effectuée en cas de forte suspicion clinique de pneumonie avec aspect radiographique normal, équivoque ou non spécifique, ce qui concerne particulièrement les sujets immunodéprimés. Elle permet de détecter les anomalies associées ou une affection sous-jacente, d'orienter un lavage broncho-alvéolaire ou de guider une biopsie pulmonaire percutanée ou transbronchique. Les expressions d'un germe peuvent varier selon le degré d'immunodépression. Il en est ainsi pour la tuberculose au cours du sida. Les germes impliqués varient selon le type d'immunodépression, certaines infections pouvant engager rapidement le pronostic vital. Le spectre radiologique de l'aspergillose pulmonaire, complexe, doit être connu, ce diagnostic devant être proposé dans des conditions particulières.