Photoactivated chemotherapy (PACT) : the potential of excited-state d-block metals in medicine

The fields of phototherapy and of inorganic chemotherapy both have long histories. Inorganic photoactivated chemotherapy (PACT) offers both temporal and spatial control over drug activation and has remarkable potential for the treatment of cancer. Following photoexcitation, a number of different decay pathways (both photophysical and photochemical) are available to a metal complex. These pathways can result in radiative energy release, loss of ligands or transfer of energy to another species, such as triplet oxygen. We discuss the features which need to be considered when developing a metal-based anticancer drug, and the common mechanisms by which the current complexes are believed to operate. We then provide a comprehensive overview of PACT developments for complexes of the different d-block metals for the treatment of cancer, detailing the more established areas concerning Ti, V, Cr, Mn, Re, Fe, Ru, Os, Co, Rh, Pt, and Cu and also highlighting areas where there is potential for greater exploration. Nanoparticles (Ag, Au) and quantum dots (Cd) are also discussed for their photothermal destructive potential. We also discuss the potential held in particular by mixed-metal systems and Ru complexes

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

Towards low cost, high sensitivity point of care diagnostics using VCO based ESR on a chip detectors

In this paper, we present a new architecture for VCO based ESR detection for a future use in portable, point ofcare ESR spectrometers. The proposed architecture is centered around an ASIC containing a VCO based ESR detector with two distinct tuning ports with largely different VCO gains to enable wide frequency sweeps and small signal frequency modulations while keeping the requirements on the digital to analog converter driving the ports manageable. Additionally, the proposed ASIC features a second VCO for an on chip frequency downconversion via mixing. To allow for a precise derivation of the operating frequency from an external reference as it is required for quantitative ESR experiments, the two on chip VCOs are embedded into an offset phase locked loop. The proposed architecture is verified with ESR experiments on commonly used ESR standard samples DPPH and BDPA . In these experiments, a spin sensitivity of 1.7 109 spins G amp; 8730; Hz has been achieved at B0 450 mT, which is comparable to the state of the art, using a permanent magnet and low cost signal processing on an FPGA. The presented proof of concept experiments clearly demonstrate the potential of the proposed VCO based ESR detection system for future point of care applications

Ru-labeled oligonucleotides for photoinduced reactions on targeted DNA guanines

A series of 17-mer oligonucleotides labeled with [Ru(tap)2(dip)]2+ (tap = 1,4,5,8-tetraazaphenanthrene; dip = 4,7-diphenylphenanthroline) at position 5 of an uracil residue in the middle of the sequence (e.g. see scheme) have been prepared and characterized. The luminescence of the chemically attached complex is quenched by hybridization with the complementary sequence, when it contains guanines in the vicinity of the Ru site. This electron-transfer quenching process generates a photoproduct on the illuminated duplex, that is responsible for an irreversible photocrosslinking of the two strands.FLWINinfo:eu-repo/semantics/publishe

Oligonucleotides-derivatized with luminescent and photoreactive Ru(II) complexes: models for photo-electron transfer and photocrosslinking

info:eu-repo/semantics/publishe

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

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