In Silico Analysis of the Apolipoprotein E and the Amyloid β Peptide Interaction: Misfolding Induced by Frustration of the Salt Bridge Network

The relationship between Apolipoprotein E (ApoE) and the aggregation processes of the amyloid β (Aβ) peptide has been shown to be crucial for Alzheimer's disease (AD). The presence of the ApoE4 isoform is considered to be a contributing risk factor for AD. However, the detailed molecular properties of ApoE4 interacting with the Aβ peptide are unknown, although various mechanisms have been proposed to explain the physiological and pathological role of this relationship. Here, computer simulations have been used to investigate the process of Aβ interaction with the N-terminal domain of the human ApoE isoforms (ApoE2, ApoE3 and ApoE4). Molecular docking combined with molecular dynamics simulations have been undertaken to determine the Aβ peptide binding sites and the relative stability of binding to each of the ApoE isoforms. Our results show that from the several ApoE isoforms investigated, only ApoE4 presents a misfolded intermediate when bound to Aβ. Moreover, the initial α-helix used as the Aβ peptide model structure also becomes unstructured due to the interaction with ApoE4. These structural changes appear to be related to a rearrangement of the salt bridge network in ApoE4, for which we propose a model. It seems plausible that ApoE4 in its partially unfolded state is incapable of performing the clearance of Aβ, thereby promoting amyloid forming processes. Hence, the proposed model can be used to identify potential drug binding sites in the ApoE4-Aβ complex, where the interaction between the two molecules can be inhibited

Étude en phase i de l'alizapride chez des patients cancéreux traites au cisplatine

Alizapride in a new methoxy-2 benzamide derivative with antiemetic properties. The dose-effect relationship of this compound was studied in 24 cancer patients treated with cis-platin regimens. Alizapride was administered as 15 min intravenous infusions at doses of 1 to 5 mg/kg repeated every 2 hours for 3 administrations. No adverse reactions were noted at doses of 1 to 3 mg/kg. Serious orthostatic hypertension was observed at the highest dose level. Other side effects were essentially mild to moderate and consisted of somnolence and diarrhea. The study indicated that the dosage level of 4 mg/kg is suitable for clinical use. The antiemetic activity of alizapride in patients receiving cis-platin therapy remains to the firmly established in a randomized study. This trial suggested a better antiemetic effect of alizapride in naive patients as compared to those previously treated with anticancer chemotherapy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Infections à mycobactéries atypiques liées à des soins esthétiques en France, 2001-2010

International audienceAbstractNon-tuberculous mycobacteria (NTM) infections usually occur in immunocompromised patients but also in immunocompetent patients following invasive procedures, especially for esthetic purposes. Since 2001, 20 episodes (57 cases) of NTM infections, seven of which (43 cases) were related to esthetic care, have been reported to the regional infection control coordinating centers (RICCC), the local health authorities (LHA), and the national institute for public health surveillance. Four notifications (40 cases) were related to non-surgical procedures performed by general practitioners in private settings: mesotherapy, carboxytherapy, and sclerosis of microvaricosities. The three other notifications (three cases) concerned surgical procedures-lifting and mammary prosthesis. Practice evaluations performed by the RICCC and LHA for five notifications showed deficiency of standard hygiene precautions and tap water misuse for injection equipment cleaning, or skin disinfection. Microbiological investigations (national reference center for mycobacteria) demonstrated the similarity of patient and environmental strains: in one episode (16 cases after mesotherapy), M. chelonae isolated from tap water was similar to those isolated from 11 cases. Healthcare-associated NTM infections are rare but have a potentially severe outcome. These cases stress the need of healthcare-associated infection notifications in outpatient settings.Les infections à mycobactéries atypiques (MA) surviennent généralement chez des patients immunodéprimés, mais elles sont également observées chez des patients immunocompétents, secondairement à des soins invasifs, notamment à visée esthétique. Depuis 2001, 20 signalements (57 cas) d’infections à MA, dont sept (43 cas) étaient liés à des soins esthétiques, ont été reçus par les centres de coordination de la lutte contre les infections nosocomiales (CClin), les directions départementales des affaires sanitaires et sociales (Ddass) et l’institut de veille sanitaire. Des procédures non chirurgicales, réalisées en ville, étaient en cause dans quatre signalements (40 cas) : mésothérapie, carboxythérapie et scléroses de microvaricosités. Les trois autres signalements (trois cas) concernaient des actes chirurgicaux - lifting et pose de prothèse mammaire. Des évaluations de pratique, réalisées par les CClin et les Ddass pour cinq signalements, ont montré le non-respect des précautions standard et un usage inapproprié de l’eau du robinet pour le nettoyage des appareils d’injection ou la désinfection de la peau. Les investigations microbiologiques (centre national de référence) ont permis d’identifier et de comparer les souches des patients et de l’environnement : dans un signalement (16 cas après mésothérapie), la souche de M. chelonae isolée de l’eau du robinet était similaire à celles isolées chez 11 cas. Les infections à MA associées aux soins sont rares mais parfois graves. Ces cas montrent l’intérêt du signalement des infections associées aux soins et aux pratiques invasives en médecine libérale

Luminescence quenching of Ru-labeled oligonucleotides by targeted complementary strands.

The yield of hole injection into guanines of different oligonucleotide duplexes by a photooxidizing tethered Ru(II) complex is examined by measuring the luminescence quenching of the excited complex. This yield is investigated as a function of the anchoring site of the complex (on a thymine nucleobase in the middle of the sequence or on the 5' terminal phosphate) and the number and position of the guanine bases as compared with the site of attachment of the Ru(II) compound. In contrast to other studies, the tethered complex, [Ru(tap)(2)(dip)](2+), is a non-intercalating compound and has been shown previously to produce an irreversible photocrosslinking between the two strands as the ultimate step of hole injection. The study of luminescence quenching of the anchored complex by emission intensity and lifetime measurements for the different duplexes indicates that a direct contact between the complex and the guanine nucleobase is needed for the electron transfer to take place. Moreover, for none of the sequences a clear contribution of a static quenching is evidenced independently of the two types of attachment of the [Ru(tap)(2)(dip)](2+) complex to the oligonucleotide. A comparison of the fastest hole-injection process by electron transfer to the excited anchored [Ru(tap)(2)(dip)](2+), with the rate of the photo-electron transfer between the same complex free in solution and guanosine-5'-monophosphate, indicates that the hole injection by the anchored complex is slower by a factor of 10 at least. A bad overlap between donor and acceptor orbitals is probably the cause of this slow rate, which could be attributed to some steric hindrance induced by the complex linker

Triazacyclohexane (tach) complexes of high-valent rhenium: syntheses of [(R(3)tach)ReO(3)](+) (R = -CH(3), -CH(2)C(6)H(5)) and its substitution reactions

N-Alkylated derivatives of 1,3,5-triazacyclohexane (tach) are versatile, facially coordinating ligands. We present the syntheses and full characterization of two new complexes of the (R(3)tach)ReO3](+) type. In these complexes, the tach ligand is readily substituted by bi- and tridentate ligands; hence, they can be considered as sources of the ReO3](+) motif for Re-VII complexes

Site-Selective DNA Photocleavage Involving Unusual Photoinitiated Tautomerization of Chiral Tridentate Vanadyl(V) Complexes Derived from N-Salicylidene α-Amino Acids

[[abstract]]The titled vanadyl(V) complexes serve as efficient reagents for cleaving supercoiled plasmid DNA by photoinitiation. Complex 3d, derived from 2-hydroxy-1-naphthaldehyde and l-phenylalanine, exhibits a unique wedge feature, inducing a site-selective photocleavage at the C22-T23 of the bulge backbone for a HIV-27 DNA system at 0.1−5 μM. Transient absorption experiments for 3d indicate the involvement of LMCT with concomitant tautomerization, leading to an o-quinone-methide V-bound hydroxyl species responsible for the cleavage profiles.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SC

Synthesis and electrochemical and photophysical properties of calixarene-based ruthenium(II) complexes as potential multivalent photoreagents.

The grafting of photoreactive and photooxidizing Ru(II)(TAP) (TAP = 1,4,5,8-tetraazaphenanthrene) complexes on calix[4 or 6]arene molecular platforms is reported. Thus, either [Ru(TAP)2(phen)](2+) (phen = 1,10-phenanthroline) or [Ru(TAP)2(pytz)](2+) [pytz = 2-(1,2,3-triazol-4-yl)pyridine] complexes are anchored to the calixarenes. The data in electrochemistry, combined with those in emission under steady state and pulsed illumination and the determination of the associated photophysical rate constants, indicate the presence of intramolecular luminescence quenching by the phenol moieties of calixarene. From transient absorption studies under pulsed laser irradiation, it is concluded that the quenching originates from a par proton-coupled electron transfer (PCET) process. Such an intramolecular quenching is absent when the phenol groups of the calixarene platform are derivatized by azido arms.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe