Role of nuclear medicine during isolated limb perfusion

Aim:Isolated limb perfusion (ILP) is a technique consisting in administrating doses of chemotherapy up to 20 times higher than via systemic route in a limb affected by melanoma or sarcoma to maximise tumour reduction. ILP is performed in <50 centres worldwide and leads to partial or complete response, however without effect on overall survival. As an alternative to amputation, it improves patient quality of life. We report our >10-year single centre experience on the role of nuclear medicine in ILP. Material and method:From 2000 to 2012, we performed 77 ILP (45 women, 32 men; aged 62±16 years) for 49 melanoma (64%), 25 sarcoma (32%) and 3 others tumors (2 desmoid tumours and 1 aggressive fibromatosis) (3%). The affected limb vascularisation is isolated from the systemic circulation (SYS) using extracorporeal circulation, and chemotherapy (usually TNF and Melphalan) is administered. Peroperatively, limb isolation and eventual leakage from ILP to SYS are monitored by continuous measurement using a gamma-probe placed over the heart (150MBq of 99mTc-human serum albumin in ILP and 4MBq in SYS). The maximum acceptable leakage to the systemic circulation is 10% (maximum tolerated systemic TNF dose). Results:In total, 47 patients (61%) had positive leaks from the ILP to SYS of 4.1±14.5% (median 1% interquartile range 0.4% to 3.2%, range 0 to 100%) and 30 patients (39%) had negative leaks from the SYS to ILP of -0.9±1.2% (median -0.5%, interquartile range -0.8% to -0.2%, range -4.8% to -0.1%). In only 2 patients (2.6%), leaks >10% were observed leading to interrupting ILP. Conclusion:Nuclear Medicine has a crucial role for the safety and quality of ILP in monitoring leakage peroperatively and help deciding whether the procedure should be interrupted to minimize systemic toxicity.

Magnetism of isolated Mn12 single-molecule magnets detected by magnetic circular dichroism: Observation of spin tunneling with a magneto-optical technique

We report magnetic and magneto-optical measurements of two Mn12 single-molecule magnet derivatives isolated in organic glasses. Field-dependent magnetic circular dichroism (MCD) intensity curves (hysteresis cycles) are found to be essentially identical to superconducting quantum interference device magnetization results and provide experimental evidence for the potential of the optical technique for magnetic characterization. Optical observation of magnetic tunneling has been achieved by studying the decay of the MCD signal at weak applied magnetic field

Citrus asymmetric somatic hybrids produced via fusion of gamma-irradiated and iodoacetamide-treated protoplasts

The objective of this study was to produce citrus somatic asymmetric hybrids by fusing gamma-irradiated protoplasts with iodoacetamide-treated protoplasts. Protoplasts were isolated from embryogenic suspension cells of grapefruit (Citrus paradisi Macfad.) cultivars Ruby Red and Flame, sweet oranges (C. sinensis Osbeck) 'Itaboraí', 'Natal', Valencia', and 'Succari', from 'Satsuma' (C. unshiu Marcow.) and 'Changsha' mandarin (C. reticulata Blanco) and 'Murcott' tangor (C. reticulata x C. sinensis). Donor protoplasts were exposed to gamma rays and receptor protoplasts were treated with 3 mmol L-1 iodoacetamide (IOA), and then they were fused for asymmetric hybridization. Asymmetric embryos were germinated, and the resulting shoots were either grafted onto sour orange, rough lemon or 'Swingle' (C. paradisi x Poncirus trifoliata) x 'Sunki' mandarin rootstock seedlings, or rooted after dipping their bases in indol-butyric acid (IBA) solution. The products were later acclimatized to greenhouse conditions. Ploidy was analyzed by flow cytometry, and hybridity was confirmed by amplified fragment length polymorphism (AFLP) analysis of plantlet DNAsamples. The best treatment was the donor-recipient fusion combination of 80 Gy-irradiated 'Ruby Red' protoplasts with 20 min IOA-treated 'Succari' protoplasts. Tetraploid and aneuploid plants were produced. Rooting recalcitrance was solved by dipping shoots' stems in 3,000 mg L-1 IBA solution for 10 min.

Cadmium-free quantum dots in aqueous solution: potential for fingermark detection, synthesis and an application to the detection of fingermarks in blood on non-porous surfaces

The use of quantum dots (QDs) in the area of fingermark detection is currently receiving a lot of attention in the forensic literature. Most of the research efforts have been devoted to cadmium telluride (CdTe) quantum dots often applied as powders to the surfaces of interests. Both the use of cadmium and the nano size of these particles raise important issues in terms of health and safety. This paper proposes to replace CdTe QDs by zinc sulphide QDs doped with copper (ZnS:Cu) to address these issues. Zinc sulphide-copper doped QDs were successfully synthesized, characterized in terms of size and optical properties and optimized to be applied for the detection of impressions left in blood, where CdTe QDs proved to be efficient. Effectiveness of detection was assessed in comparison with CdTe QDs and Acid Yellow 7 (AY7, an effective blood reagent), using two series of depletive blood fingermarks from four donors prepared on four non-porous substrates, i.e. glass, transparent polypropylene, black polyethylene and aluminium foil. The marks were cut in half and processed separately with both reagents, leading to two comparison series (ZnS:Cu vs. CdTe, and ZnS:Cu vs. AY7). ZnS:Cu proved to be better than AY7 and at least as efficient as CdTe on most substrates. Consequently, copper-doped ZnS QDs constitute a valid substitute for cadmium-based QDs to detect blood marks on non-porous substrates and offer a safer alternative for routine use.

Spatial visualization of DNA in solution.

An image analysis method is presented which allows for the reconstruction of the three-dimensional path of filamentous objects from two of their projections. Starting with stereo pairs, this method is used to trace the trajectory of DNA molecules embedded in vitreous ice and leads to a faithful representation of their three-dimensional shape in solution. This computer-aided reconstruction is superior to the subjective three-dimensional impression generated by observation of stereo pairs of micrographs because it enables one to look at the reconstructed molecules from any chosen direction and distance and allows quantitative analysis such as determination of distances, curvature, persistence length, and writhe of DNA molecules in solution.

3D culture of postnatal retinal stem cells using self assembling polymers

PURPOSE We have previously shown that retinal stem cells (RSCs) can be isolated from the radial glia population of the newborn mouse retina (Angénieux et al., 2006). These RSCs have a great capacity to renew and to generate a large number of neurons including cells differentiated towards the photoreceptor lineage (Mehri-Soussi et al., 2006). However, recent published results from our lab revealed that such cells have a poor integration and survival rate after grafting. The uncontrolled environment of a retina seems to prevent good integration and survival after grafting in vivo. To bypass this problem, we are evaluating the possibility of generating in vitro a hemi-retinal tissue before transplantation. METHODS RSC were expanded and cells passaged <10 were seeded in a solution containing poly-ethylene-glycol (PEG) polymer based hydrogels crosslinked with peptides that are chosen to be substrates for matrix metalloproteinases. Various doses of cross linkers peptides allowing connections between PEG polymers were tested. Different growth factors were studied to stimulate cell proliferation and differentiation. RESULTS Cells survived only in the presence of EGF and FGF-2 and generated colonies with a sphere shape. No cells migrated within the gel. To improve the migration and the repartition of the cells in the gels, the integrin ligand RGDSP was added into the gel. In the presence of FGF-2 and EGF, newly formed cell clusters appeared by cell proliferation within several days, but again no outspreading of cells was observed. No difference was even seen when the stiffness of the hydrogels or the concentration of the integrin ligand RGDSP were changed. However, our preliminary results show that RSCs still form spheres when laminin is entrapped in the gel, but they started to spread out having a neuronal morphology after around 2 weeks. The neuronal population was assessed by the presence of the neuronal marker b-tubulin-III. This differentiation was achieved after successive steps of stimulations including FGF-2 and EGF, and then only FGF-2. Glial cells were also present. Further characterizations are under process. CONCLUSIONS RSC can be grown in 3D. Preliminary results show that neuronal cell phenotype acquisition can be instructed by exogenous stimulations and factors linked to the gel. Further developments are necessary to form a homogenous tissue containing retinal cells.

Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation.

BACKGROUND: Red blood cell-derived microparticles (RMPs) are small phospholipid vesicles shed from RBCs in blood units, where they accumulate during storage. Because microparticles are bioactive, it could be suggested that RMPs are mediators of posttransfusion complications or, on the contrary, constitute a potential hemostatic agent. STUDY DESIGN AND METHODS: This study was performed to establish the impact on coagulation of RMPs isolated from blood units. Using calibrated automated thrombography, we investigated whether RMPs affect thrombin generation (TG) in plasma. RESULTS: We found that RMPs were not only able to increase TG in plasma in the presence of a low exogenous tissue factor (TF) concentration, but also to initiate TG in plasma in absence of exogenous TF. TG induced by RMPs in the absence of exogenous TF was neither affected by the presence of blocking anti-TF nor by the absence of Factor (F)VII. It was significantly reduced in plasma deficient in FVIII or F IX and abolished in FII-, FV-, FX-, or FXI-deficient plasma. TG was also totally abolished when anti-XI 01A6 was added in the sample. Finally, neither Western blotting, flow cytometry, nor immunogold labeling allowed the detection of traces of TF antigen. In addition, RMPs did not comprise polyphosphate, an important modulator of coagulation. CONCLUSIONS: Taken together, our data show that RMPs have FXI-dependent procoagulant properties and are able to initiate and propagate TG. The anionic surface of RMPs might be the site of FXI-mediated TG amplification and intrinsic tenase and prothrombinase complex assembly.

Développement d'une solution orale pédiatrique de captopril

Introduction: Le captopril, inhibiteur de l'enzyme de conversion de l'angiotensine, est largement utilisé dans le traitement de l'hypertension artérielle et de l'insuffisance cardiaque chez l'adulte et l'enfant . De par son instabilité en milieu aqueux (oxydation en captopril disulfure), il n'est actuellement commercialisé que sous forme de comprimés. La prescription fréquente de doses faibles et variables en pédiatrie justifiait le développement d'une forme orale liquide, tant sur le plan pratique et économique, que sur celui de la sécurité d'administration. Cependant toutes les formulations orales liquides publiées présentent une stabilité courte, ne dépassant guère 1 mois. Objectif: Développer une forme orale liquide de captopril d'une stabilité d'au moins 6 mois. Méthode: Sur la base des données de la littérature, élaboration de 8 formulations liquides différentes de captopril 1 mg/ml (concentration permettant le prélèvement d'un volume adéquat pour une administration en pédiatrie). Mise au point d'une « stability indicating method » par HPLC par des tests de dégradation accélérée à la chaleur (100°C), en milieu acide, basique, en présence d'un agent oxydant et de la lumière. Sélection de la formulation la plus stable durant le premier mois. Etude de stabilité sur 2 ans de 3 lots (3 échantillons/lot) dans leur conditionnement final à température ambiante (TA), au frigo et à 40° ± 2°C. Contrôle microbiologique au début et à la fin de l'étude selon la méthode de la Ph. Eur. (Ed. 3). Résultats: La formule retenue est une solution aqueuse de captopril 1 mg/ml additionnée d'EDTA 1 mg/ml comme stabilisateur et conditionnée dans des flacons VERAL en verre brun de 60 ml. Après dégradation dans les conditions définies ci-dessus, le pic du captopril est nettement séparé sur les chromatogrammes de ceux des produits de dégradation. Après 2 ans, la concentration mesurée est de 104.6% (±0.32%) au frigo, 103.6% (±0.86%) à TA et 96.5 % (±0.02%) à 40°C. Aucune croissance n'a été observée sur la durée de l'étude. Discussion et conclusion: La solution de captopril 1 mg/ml mise au point est simple à préparer. En partant du principe actif pur et en présence d'EDTA comme complexant, les traces de métaux éventuellement présents n'induisent pas l'oxydation du captopril et par conséquent le recours à d'autres stabilisateurs n'est pas nécessaire. La méthode HPLC développée est une « stability indicating method ». Les résultats de l'étude ont montré que cette solution a une durée de validité de 2 ans au frigo et à TA. Compte tenu du fait que la préparation ne contient pas d'agent antimicrobien, une conservation au frigo (2 - 8°C) est toutefois recommandée. La formule proposée présente un réel avantage en pédiatrie tant sur le plan de la sécurité d'administration que sur celui de l'économie.

A Widely Used Machine Translation Service and its Migration to a Free/Open-Source Solution : the Case of Softcatalà

Softcatalà is a non-profit associationcreated more than 10 years ago to fightthe marginalisation of the Catalan languagein information and communicationtechnologies. It has led the localisationof many applications and thecreation of a website which allows itsusers to translate texts between Spanishand Catalan using an external closed-sourcetranslation engine. Recently,the closed-source translation back-endhas been replaced by a free/open-sourcesolution completely managed by Softcatalà: the Apertium machine translationplatform and the ScaleMT web serviceframework. Thanks to the opennessof the new solution, it is possibleto take advantage of the huge amount ofusers of the Softcatalà translation serviceto improve it, using a series ofmethods presented in this paper. In addition,a study of the translations requestedby the users has been carriedout, and it shows that the translationback-end change has not affected theusage patterns.

The continuous wavelet transform as a maximum entropy solution of the corresponding inverse problem

The continuous wavelet transform is obtained as a maximumentropy solution of the corresponding inverse problem. It is well knownthat although a signal can be reconstructed from its wavelet transform,the expansion is not unique due to the redundancy of continuous wavelets.Hence, the inverse problem has no unique solution. If we want to recognizeone solution as "optimal", then an appropriate decision criterion hasto be adopted. We show here that the continuous wavelet transform is an"optimal" solution in a maximum entropy sense.