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Background: Bronchiolitis obliterans syndrome (BOS) is a common complication of lung transplantation (LT), associated with a tremendous mortality and morbidity. Recent innovative research has focused on bronchoalveolar lavage (BAL) analysis, assuming that neutrophilia might be a marker of chronic rejection. Patients and methods: To address this issue, we retrospectively analyzed 258 sequential BAL from 44 lung transplant recipients, having survived for more than 3 months after surgery. Results: At the end of the follow-up, 22, 7, 7 and 8 patients had BOS stage 0, 1, 2 and 3, respectively. The total cell count and neutrophilia increased with BOS severity (P<0.01). BOS occurring before and after the 12th month of LT were associated with early and more delayed increases of BAL neutrophils, respectively. Finally, the various kinetic profiles of neutrophil progression were identified, allowing for an earlier identification of BOS stages 2 and 3, by 3 and 6 months, respectively. Conversely, neutrophilia associated to BOS stage 1 remained low, and could not be distinguished from that of stage 0. Conclusions: These results support the possible role of neutrophils in BOS pathogenesis, and may be of interest for an earlier detection and management of chronic rejection. [ABSTRACT FROM AUTHOR]

Tetanus toxin (TeNT) is a heterodimeric protein antigen, whose light chain (L) is translocated in the cytosol of neuronal target cells specifically to cleave its substrates, vesicle-associated membrane protein-2 (VAMP-2, or synaptobrevin) or cellubrevin. We report that the L chain behaves as a nominal antigen recognized by specific T-cell clones upon either class I- or II-restricted presentation. Three types of responses are observed: (i) a TeNT- and L-specific CD8[sup +] T-cell response, that can be inhibited in a dose-dependent manner by the proteasome inhibitor clasto-Lactacystin β-lactone; (ii) a CD4[sup +] T-cell response specific for L but not TeNT, with recognition of a determinant processed in a chloroquine-sensitive and brefeldin A-resistant compartment; (iii) a CD4[sup +] T-cell response against both L and TeNT, with processing in a brefeldin A-sensitive compartment. The L chain processing was investigated in U937 cells by internalization and localization of L chain by separation of the cell content by differential centrifugation experiments. After incubation with TeNT or L chain in the presence of H chain, the L chain was predominantly distributed in the cytosolic fraction, whereas incubation with L alone led to localization in a lysosome/membrane fraction. The distribution of the TeNT L chain in both cytosolic and endocytic compartments of the antigen-presenting cell accounted for its processing by both class I and class II pathways. Furthermore, an epitope overlapping with the zinc-binding region was recognized by CD4[sup +] and CD8[sup +] T cells. [ABSTRACT FROM AUTHOR]

The article offers information on the effectiveness of tranexamic acid in sporadic idiopathic bradykinin angioedema (SIBAO). It informs that SIBAO is a rare entity sharing clinical similarities with hereditary angioedemas. It mentions that the patients with SIBAO are advised to take tranexamic acid (TA). It reports that tolerance of daily TA is better than danazol in case of SIBAO. It suggests that TA should be adviced to patients with SIBAO with ophtalmological and liver enzymes.

A letter to the editor is presented concerning a case of hereditary angio-oedema type III presenting with C1-inhibitor cleavage and a missence mutation in the F12 gene.

Calcium phosphates (CaP) such as biomimetic nanocrystalline apatite or amorphous calcium phosphate are hydrated bioactive compounds particularly suitable for bone repair applications due to their similarity with bone mineral. However, their consolidation in ceramic parts deserves special attention as they are thermodynamically metastable and can decompose into less bioactive phases upon heating. Adapted strategies are needed to obtain bulk bioceramics. Spark Plasma Sintering (SPS) has been shown to allow cold sintering of such compounds at temperatures like 150 °C while preserving the hydrated character and nanosized dimensions of the precursor powders. To this date, however, the role of the degree of carbonation of these precursors on the densification of CO 3 -bearing CaP compounds via SPS has not been explored despite the natural carbonation of bone. In this work, several carbonated CaP hydrated compounds were prepared and consolidated by SPS and the characteristics of the obtained ceramics was scrutinized with respect to the starting powders. Two carbonation routes were carried out: via volume carbonation during powder synthesis or via subsequent surface ion exchange. All samples tested led to apatitic compounds after SPS, including amorphous CaP. We show that the degree of carbonation negatively affects the densification rate and propose possible hypotheses explaining this behavior. Evolution in the nature of the carbonate sites (apatitic A-, B-types and labile surface carbonates) before and after SPS is also noticed and commented. The consolidation of such compounds is however proven possible, and gives rise to bone-like apatitic compounds with great potential as bioactive resorbable ceramics for bone regeneration. [ABSTRACT FROM AUTHOR]

Nanocrystalline apatites constitute the mineral part of hard tissues, and can be reproduced synthetically. Nonetheless, the impact of synthesis/post-synthesis parameters is often disregarded. Based on actualized knowledge on their physico-chemical features, we investigated these aspects on a systematic experimental basis. The apatite maturation state has a direct effect on the surface and core of the nanocrystals. Drying and re-immersion aspects were also examined in view of applications as implantable biomaterials: an equilibration of the samples surface is proposed to avoid acidification phenomena after re-immersion of dried samples.

Abstract: Nanobiotechnologies have lately attracted much attention, both from therapeutic and diagnosis perspectives. In this view, the development of colloidal formulations of biocompatible nanoparticles capable of interacting with selected cells or tissues raises a particular interest, especially in link with cell-based pathologies such as cancer. In this context, the follow-up of colloidal stability and other physico-chemical features is of foremost relevance. In this contribution, we have focused our study on hybrid colloids based on biomimetic nanocrystalline apatites (analogous to those found in bone mineral) stabilized by adsorption of 2-aminoethylphosphate (AEP) molecules; these nanoparticles being intended to interact with cancer cells either for medical imaging (by conferring luminescence features to the apatite phase) or for therapeutic purposes. We show that various physico-chemical characteristics of the suspensions vary with time, including viscosity and mean particle size, suggesting a progressive structuration of the suspensions. Similar modifications were also noticed during the purification by dialysis. Finally, we report on preliminary experiments aimed at drying the colloids while retaining their capacity to recover their initial state after re-immersion in aqueous medium; so as to enable extended storage periods for the nanoparticles in their dry state while allowing their re-suspension at the time of use. On this matter, the addition of glucose prior to freeze-drying was found to be an effective way to avoid the formation of aggregates during drying. This contribution thus confers additional information relative to the stability of AEP-stabilized biomimetic apatite colloidal formulations, which proved in previous studies to be of particular relevance for nanomedicine. [Copyright &y& Elsevier]

Abstract: The enthalpy of formation from the elements of a well-characterized synthetic Pb-jarosite sample corresponding to the chemical formula (H3O)0.74Pb0.13Fe2.92(SO4)2(OH)5.76(H2O)0.24 was measured by high temperature oxide melt solution calorimetry. This value ( =−3695.9±9.7kJ/mol) is the first direct measurement of the heat of formation for a lead-containing jarosite. Comparison to the thermochemical properties of hydronium jarosite and plumbojarosite end-members strongly suggests the existence of a negative enthalpy of mixing possibly related to the nonrandom distribution of Pb2+ ions within the jarosite structure. Based on these considerations, the following thermodynamic data are proposed as the recommended values for the enthalpy of formation from the elements of the ideal stoichiometric plumbojarosite Pb0.5Fe3(SO4)2(OH)6: =−3118.1±4.6kJ/mol, =−3603.6±4.6kJ/mol and S°=376.6±4.5J/(molK). These data should prove helpful for the calculation of phase diagrams of the Pb–Fe–SO4–H2O system and for estimating the solubility product of pure plumbojarosite. For illustration, the evolution of the estimated solubility product of ideal plumbojarosite as a function of temperature in the range 5–45°C was computed (Log(K sp) ranging from −24.3 to −26.2). An Eh–pH diagram is also presented. [Copyright &y& Elsevier]

Abstract: Nanocrystalline apatites play an important role in biomineralisation and they are used as bioactive biominerals for orthopaedic applications. One of the most interesting characteristics of the nanocrystals, evidenced by spectroscopic methods, is the existence of a structured surface hydrated layer, well developed in freshly formed precipitates, which becomes progressively transformed into the more stable apatitic lattice upon ageing in aqueous media. The hydrated layer is very fragile and irreversibly altered upon drying. Several routes leading to different apatite compositions are found in biological systems. The loosely bound ions of the hydrated layer can be easily and reversibly substituted by other ions in fast aqueous ion exchange reactions. These ions can either be included in the growing stable apatite lattice during the ageing process or remain in the hydrated layer. The adsorption properties of nanocrystals appear to be strongly dependent on the composition of the hydrated layer and on ageing. The surface reactivity of the apatite nanocrystals can play a part in different biomaterials and could explain the setting reactions of biomimetic calcium phosphate cements and the possibility of obtaining adherent nanocrystalline coatings on different substrates. [Copyright &y& Elsevier]