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

Erythromycin-Resistant Group A Streptococcal Isolates Recovered in Sofia, Bulgaria, from 1995 to 2001

The frequency of erythromycin resistance within group A streptococci in Sofia, Bulgaria, from 1995 to 2001 was 2.1% (26 isolates). Of this, 57.7% was macrolide-lincosamide-streptogramin (MLS) inducible, 7.7% was MLS constitutive, and 34.6% had the M phenotype. Eleven different emm sequence types were found among 25 erythromycin-resistant isolates tested. Nineteen of 26 erythromycin-resistant isolates were additionally resistant to tetracycline and/or chloramphenicol

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