Historians in Flux: The Concept, Task and Challenge of ego-histoire

No abstrac

Historians in Flux: The Concept, Task and Challenge of ego-histoire

No abstrac

Developments in anaplastic large-cell lymphoma: targeting the anaplastic lymphoma kinase

Francesca Farina, Alessandra Stasia, Carlo Gambacorti-Passerini Department of Health Sciences, University of Milano Bicocca, Monza, Italy Abstract: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase protein implicated in a variety of hematological malignancies and solid tumors. ALK contributes to the development of cancers in different cell lineages through a variety of genetic mechanisms: gene fusions, activating point mutations, and possibly gene amplification. Recent developments led to significant therapeutic advances, including efficient diagnostic tests and ALK-targeting agents. This review addresses some therapeutic considerations with regard to the use of ALK inhibitors in ALK-positive lymphomas where, in spite of the advanced stage of the disease, long-lasting responses could be obtained in a substantial portion of heavily pretreated patients. Data and mechanisms for the development of resistance to ALK inhibitors will also be presented and discussed. Keywords: ALK, lymphoma, tyrosine kinase, targeted therapy, crizotini

Glutathione-loaded solid lipid microparticles as innovative delivery system for oral antioxidant therapy

The present study aimed to develop a novel formulation containing glutathione (GSH) as an oral antioxidant therapy for the treatment of oxidative stress-related intestinal diseases. To this purpose, solid lipid microparticles (SLMs) with Dynasan 114 and a mixture of Dynasan 114 and Dynasan 118 were produced by spray congealing technology. The obtained SLMs had main particle sizes ranging from 250 to 355 µm, suitable for oral administration. GSH was efficiently loaded into the SLMs at 5% or 20% w/w and the encapsulation process did not modify its chemico-physical properties, as demonstrated by FT-IR, DSC and HSM analysis. Moreover, in vitro release studies using biorelevant media showed that Dynasan 114-based SLMs could efficiently release GSH in various intestinal fluids, while 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay demonstrated the good radical scavenging activity of this formulation. Dynasan 114-based SLMs exhibited an excellent biocompatibility on intestinal HT-29 cells at concentrations up to 2000 µg/mL. SLMs containing GSH alone or together with another antioxidant agent (catalase) were effective in reducing intracellular reactive oxygen species (ROS) levels. Overall, this study indicated that spray congealed SLMs are a promising oral drug delivery system for the encapsulation of one or more biological antioxidant agents for local intestinal treatment

Decoupling segmental relaxation and ionic conductivity for lithium-ion polymer electrolytes

International audienceThe use of polymer electrolytes instead of liquid organic systems is considered key for enhancing the safety of lithium batteries and may, in addition, enable the transition to high-energy lithium metal anodes. An intrinsic limitation, however, is their rather low ionic conductivity at ambient temperature. Nonetheless, it has been suggested that this might be overcome by decoupling the ion transport and the segmental relaxation of the coordinating polymer. Here, we provide an overview of the different approaches to achieve such decoupling, including a brief recapitulation of the segmental-relaxation dependent ion conduction mechanism, exemplarily focusing on the archetype of polymer electrolytes – polyethylene oxide (PEO). In fact, while the understanding of the underlying mechanisms has greatly improved within recent years, it remains rather challenging to outperform PEO-based electrolyte systems. Nonetheless, it is not impossible, as highlighted by several examples mentioned herein, especially in consideration of the extremely rich polymer chemistry and with respect to the substantial progress already achieved in designing tailored molecules with well-defined nanostructures

Decoupling segmental relaxation and ionic conductivity for lithium-ion polymer electrolytes

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Application Of Safety And Security Principles To Flood Event Management In Highly Populated Urban Areas

This paper refers to non-structural actions which are to be carried out on the Arno river basin (Italy). In particular the town of Florence is considered where 56 catastrophic flood events have been recorded in the last 1000 years, the latter in 1966 with damages estimated at 10,000 billion euros. A huge system of structural works is presently being carried out planned to the 200-year return period event in the next ten years. To manage the present and future residual risk, specific safety plans have been provided at the scale of single buildings in order to give residents an effective instrument to prevent and protect them from the major flooding risk. This paper illustrates how safety and security principles can be applied to the management of a flood event at the scale of several thousands of square kilometres. A specific Security Plan and, if needed, a Recovery Plan is linked to each building which is potentially subject to flooding. Based on analytical hazard assessment and mapping, techniques to improve or increase the safety-level as well as appropriated information are described. These local scale plans are interfaced with civil protection and disaster management plans at the regional scale by suitable procedures. Keywords: risk assessment, flood event, security plan, recovery plan, signs, procedures, building. 1 Introduction A study for a plan in order to provide the residents of the area of the Arno River basin (and in future perspective all the residents) with one useful instrument t

Ground calcium carbonate as a low cost and biosafety excipient for solubility and dissolution improvement of praziquantel

Calcium carbonate is an abundant mineral with several advantages to be a successful carrier to improve oral bioavailability of poorly water-soluble drugs, such as praziquantel. Praziquantel is an antiparasitic drug classified in group II of the Biopharmaceutical Classification System hence characterized by high-permeability and low-solubility. Therefore, the dissolution rate is the limiting factor for the gastrointestinal absorption that contributes to the low bioavailability. Consequently, the therapeutic dose of the praziquantel must be high and big tablets and capsules are required, which are difficult to swallow, especially for pediatric and elderly patients. Mixtures of praziquantel and calcium carbonate using solid-solid physical mixtures and solid dispersions were prepared and characterized using several techniques (X-ray diffraction differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, laser diffraction, Fourier transform infrared and Raman spectroscopies). Solubility of these formulations evidenced that the solubility of praziquantel-calcium carbonate interaction product increased in physiological media. In vitro dissolution tests showed that the interaction product increased the dissolution rate of the drug in acidic medium. Theoretical models were studied to understand this experimental behavior. Cytotoxicity and cell cycle studies were performed, showing that praziquantel-calcium carbonate physical mixture and interaction product were biocompatible with the HTC116 cells, because it did not produce a decrease in cell viability or alterations in the cell cycle