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Résumé: La leishmaniose viscérale (LV) associée au syndrome d’hémophagocytose lympho-histiocytaire (HLH) chez l’enfant est une entité clinico-pathologique rare, de diagnostic difficile, mortelle en l’absence de traitement. Chez l’enfant, il faut l’évoquer devant un tableau clinique de fièvre prolongée avec splénomégalie. Nous rapportons deux observations d’HLH secondaire à une LV. Dans la première observation, il s’agissait d’un jeune nourrisson de 3 mois et demi hospitalisé pour une tricytopénie fébrile. Le diagnostic d’HLH avait été posé devant un tableau clinico-biologique complet incluant une hémophagocytose sur le myélogramme. La recherche d’une maladie génétique, métabolique ou d’une infection sous-jacente avait été négative. Une cause primitive d’HLH avait été d’emblée évoquée et un traitement immunosuppresseur (corticoïdes et ciclosporine) avait été instauré. Un myélogramme de contrôle à un mois d’évolution ayant retrouvé des leishmanies, l’évolution avait été rapidement favorable sous traitement par amphotéricine B liposomale. Dans la deuxième observation, il s’agissait d’un enfant de 10ans avec de multiples antécédents infectieux, hospitalisé pour une tricytopénie fébrile avec syndrome tumoral. Le diagnostic de LV avait été posé sur le myélogramme et un traitement par amphotéricine B liposomale avait été mis en route. Au 3e jour de traitement, une corticothérapie avait été instaurée devant l’apparition d’une HLH. Un déficit immunitaire héréditaire sous-jacent par défaut de l’axe interleukine-12 (IL-12) et interféron-γ (IFN- γ) avait été diagnostiqué devant l’évolution atypique de la LV sous traitement. [ABSTRACT FROM AUTHOR]

Abstract: Raman spectroscopy and mapping, coupled to molecular labelling, is used to analyse and monitor the first stage of carbon nanotube functionalization, i.e. their oxidation, which is usually performed to increase the number of surface carboxylic groups, allowing both a better dispersion in solution and the further attachment of biomolecules. Since the abundance of such surface groups is critical for the final application, it is important to develop a reliable but simple and fast method to investigate their presence on the tube walls. The presented data demonstrate the correlation between the presence and intensity of the Raman peak ascribed to the labelling molecule and the production of COOH groups on the nanotube walls. Between the analysed carbon nanotubes related spectral parameters, the G′ Raman peak position appears to be the most sensitive one to determine the degree of single walled carbon nanotube labelling, which directly depends on the number of COOH groups available for molecular attachment, i.e. on the efficiency of the oxidation treatment. [Copyright &y& Elsevier]

In this work, a new series of pentamethine indolenine cyanine dyes has been designed and synthesized with the aim to investigate a structure-activity relationship on their photodynamic activity. The heteroaromatic indolenine ring has been differently functionalized (no substituents, bromine, iodine and carboxylic acid) to determine the effect of the substitution on the ROS production, cytotoxicity, photodynamic activity and cellular uptake. A statistical multivariate design such as the Design of Experiments (DoE) has been applied to evaluate which factor greatly affects the cyanine photoactive behavior, maximizing the information content, precision and accuracy in the results, while keeping the number of experiments low. All the synthesized dyes present low cytotoxicity in dark, but only some of them are able to promote phototoxic effect, upon irradiation, in MCF-7 cell lines, confirming a structure-activity relationship. • Pentamethine cyanines with different substituents have been synthesized for PDT. • CY-C4 , Br-CY-C4 , and I-CY-C4 showed fast ROS production. • DoE was applied to investigate CYs photoactivity and the structure-activity relationship. • CY-C4 and Br-CY-C4 revealed the greatest photoactive potential against MCF-7 cells. • COOH-CY-C4 did not show phototoxicity and has not been internalized by MCF-7 cells. [ABSTRACT FROM AUTHOR]

Niemann Pick C 1 (NPC1) disease is an incurable, devastating lysosomal-lipid storage disorder characterized by hepatosplenomegaly, progressive neurological impairment and early death. Current treatments are very limited and the research of new therapeutic targets is thus mandatory. We recently showed that the stimulation of adenosine A 2A receptors (A 2A Rs) rescues the abnormal phenotype of fibroblasts from NPC1 patients suggesting that A 2A R agonists could represent a therapeutic option for this disease. However, since all NPC1 patients develop severe neurological symptoms which can be ascribed to the complex pathology occurring in both neurons and oligodendrocytes, in the present paper we tested the effects of the A 2A R agonist CGS21680 in human neuronal and oligodendroglial NPC1 cell lines (i.e. neuroblastoma SH-SY5Y and oligodendroglial MO3.13 transiently transfected with NPC1 small interfering RNA). The down-regulation of the NPC1 protein effectively resulted in intracellular cholesterol accumulation and altered mitochondrial membrane potential. Both effects were significantly attenuated by CGS21680 (500 nM). The protective effects of CGS were prevented by the selective A 2A R antagonist ZM241385 (500 nM). The involvement of calcium modulation was demonstrated by the ability of Bapta-AM (5–7 μM) in reverting the effect of CGS. The A 2A -dependent activity was prevented by the PKA-inhibitor KT5720, thus showing the involvement of the cAMP/PKA signaling. These findings provide a clear in vitro proof of concept that A 2A R agonists are promising potential drugs for NPC disease. [ABSTRACT FROM AUTHOR]

The growing interest for peptide therapeutics calls for new strategies to determine the physico-chemical properties responsible for the interactions of peptides with the environment. This study reports about the lipophilicity of two fragments of the amyloid β-peptide, Aβ 25–35 and Aβ 12–28 ⋅ Firstly, computational studies showed the limits of log D 7.4 oct in describing the lipophilicity of medium-sized peptides. Chromatographic lipophilicity indexes (expressed as log k ’, the logarithm of the retention factor) were then measured in three different systems to highlight the different skills of Aβ 25–35 and Aβ 12–28 in giving interactions with polar and apolar environments. CD studies were also performed to validate chromatographic experimental conditions. Results show that Aβ 12–28 has a larger skill in promoting hydrophobic and electrostatic interactions than Aβ 25–35 . This finding proposes a strategy to determine the lipophilicity of peptides for drug discovery purposes but also gives insights in unraveling the debate about the aminoacidic region of Aβ responsible for its neurotoxicity. [ABSTRACT FROM AUTHOR]

In the present study, the personal exposure to mancozeb and/or ethilenethiourea (ETU) in 13 Italian vineyard workers and in 13 subjects without occupational exposure to pesticides was investigated. With this aim, the level of ETU in urine and the dermal exposure to mancozeb were determined. Baseline urinary ETU results were lower than the analytical limit of detection for all controls (<0.5 μg/g creatinine) and for ten workers (median <0.5, range <0.5–3.4 μg/g creatinine). In workers, urinary ETU was significantly increased at the end of shift (2.5, <0.5–95.2 μg/g creatinine) compared with baseline levels. End-shift urinary ETU was higher in operators using open tractors (n=7) than in those using closed tractors (n=5) (16.2 vs. 2.4 μg/g creatinine), but the difference was not significant (P=0.073). End-shift urinary ETU was positively correlated with dermal exposure to mancozeb determined both over the clothes and on the skin (Spearman''s ρ=0.770 and 0.702, P=0.009 and 0.024, respectively). Wine consumption positively influenced the excretion of ETU. [Copyright &y& Elsevier]