Neurotensin(8–13) analogs as dual NTS1 and NTS2 receptor ligands with enhanced effects on a mouse model of Parkinson's disease

: The modulatory interactions between neurotensin (NT) and the dopaminergic neurotransmitter system in the brain suggest that NT may be associated with the progression of Parkinson's disease (PD). NT exerts its neurophysiological effects by interactions with the human NT receptors type 1 (hNTS1) and 2 (hNTS2). Therefore, both receptor subtypes are promising targets for the development of novel NT-based analogs for the treatment of PD. In this study, we used a virtually guided molecular modeling approach to predict the activity of NT(8-13) analogs by investigating the docking models of ligands designed for binding to the human NTS1 and NTS2 receptors. The importance of the residues at positions 8 and/or 9 for hNTS1 and hNTS2 receptor binding affinity was experimentally confirmed by radioligand binding assays. Further in vitro ADME profiling and in vivo studies revealed that, compared to the parent peptide NT(8-13), compound 10 exhibited improved stability and BBB permeability combined with a significant enhancement of the motor function and memory in a mouse model of PD. The herein reported NTS1/NTS2 dual-specific NT(8-13) analogs represent an attractive tool for the development of therapeutic strategies against PD and potentially other CNS disorders

Risk factors for death from invasive pneumococcal disease, europe, 2010

We studied the possible association between patient age and sex, clinical presentation, Streptococcus pneumoniae serotype, antimicrobial resistance, and death in invasive pneumococcal disease cases reported by 17 European countries during 2010. The study sample comprised 2,921 patients, of whom 56.8% were men and 38.2% were >65 years of age. Meningitis occurred in 18.5% of cases. Death was reported in 264 (9.0%) cases. Older age, meningitis, and nonsusceptibility to penicillin were signifcantly asso ciated with death. Non-pneumococcal conjugate vaccine (PCV) serotypes among children 65 years of age, risk did not differ by serotype. These fndings highlight differences in case-fatality rates between sero types and age; thus, continued epidemiologic surveillance across all ages is crucial to monitor the long-term effects of PCVs

Il corpo tra metapsicologia e mentalizzazione. Linee di ricerca in psicoanalisi, dopo Freud

Gli autori ricostruiscono la questione del corpo negli scritti freudiani, segnalandone i molteplici aspetti teorici e clinici, e mettendone in luce la complessità concettuale attraverso le varie fasi di evoluzione della scoperta psicoanalitica, dalle origini, con l’isteria, alle manifestazioni silenziose della pulsione morte: vertici estremi del percorso di ricerca freudiano che, sul corpo, ha indicato elementi di riflessione articolati e privi di una sistematizzazione univoca e conclusa. Nella molteplicità delle direttrici teoriche diramatesi dagli spunti freudiani, la prevalenza concettuale della prospettiva “economica”, con i concetti di rappresentazione, affetto e narcisismo, caratterizza il contributo francofono contemporaneo sulla questione. Gli autori argomentano le posizioni di alcuni esponenti, in particolare Pierre Marty, André Green, Jean Laplanche e Christophe Dejours. Si precisa che il presente articolo può essere definito una rassegna essenzialmente storica e teorica di una delle possibili diramazioni della letteratura nel campo della psicosomatica psicoanalitica, che segue il filo della coordinata economica a partire dalla metapsicologia freudiana. Al fine di inserire il discorso nel campo del dibattito psicoanalitico attuale, gli autori rimandano, infine, a ulteriori vertici di lettura dello psicosoma

Determination of the trace element content in Bulgarian bottled potable waters by total reflection X-ray fluorescence analysis

The content of S, Cl, K, Ca, Mn, Fe, Ni, Cu, Zn, As, Br, Rb and Ba in several brands of Bulgarian bottled potable waters ("Savina" table, "Gorna Banya" mineral, "Bankya" mineral, "Kom" mineral, "Thorn Spring" mineral, "Hissar" mineral, "Devin" spring and mineral and "Mihalkovo" spring and mineral) was determined by total reflection X-ray fluorescence (TXRF) analysis using gallium as internal standard. The spring waters generally displayed lower mineralization (total dissolved solids, TDS content) than the mineral waters, even those originating from the same location. The content of S, Cl, K and Ca was at the mg L -1 level, while that of Mn, Fe, Ni, Cu, Zn, As, Br, Rb and Baat the lower µg L -1 level. The trace element content of the mineral waters did not considerably change (less than ±30 % difference) over a storage period of approx. 2.5 years after bottling

Silica-based organic-inorganic hybrid materials as potential adsorbents for Hg(II) ions

In the present study four functionalized mesoporous silica materials denoted as BIS-1, BIS-2, BIS-3 and BIS-4 have been synthesized through a simple co-condensation of bis-[3-(trimethoxyosilyl)propyl] amine (BTPA) and tetraethyl orthosilicate (TEOS). The influence of the BTPA amount on the structural and adsorption properties of the resultant materials was investigated. The novel hybrid materials have been characterized by FT-IR, BET, 13C CP MAS NMR and elemental analysis. The adsorption properties of mesoporous organic-inorganic materials containing amine functional groups, regarding Hg(II) ions were studied by the batch method. Experiments were carried out in acidic media. The material BIS-3 exhibits highest adsorption capacity for mercury ions. Kinetics of Hg (II) adsorption on BIS-3 was investigated. Equilibrium experimental data for BIS-3 were fitted to linear Langmuir and Freundlich models. All studied hybrid materials could be successfully used for effective removal of mercury ions from acidic aqueous solutions

Neonatal protection and preterm birth reduction following maternal group B streptococcus vaccination in a mouse model

Evaluate effects of maternal immunization in a mouse model of Group B Streptococcus (GBS) vaginal colonization using clinical isolates