Prise en charge des plaies, quoi de neuf? [Advances in wound care]

Wound care made great progress during last years related to several factors. The first is an awakening of the importance of wounds. The progress made in the comprehension of the physiopathology of wounds led to innovations in all stages of this complex process which is the wound healing. Autologus platelet concentrate producing growth factors are in use to stimulate the first phase of the healing. The second phase which is the phase of proliferation and secretion is currently better managed with new categories of bandages which are true local treatments. The nutrition became one of the pillars of wound treatments especially among old patients. The reconstructive surgery took great steps since the physiology and the vascular anatomy of the skin and soft tissues are better known. Finally the bio-engineering has entered the treatment of the wound there is more than 20 years ago and methods have improved and become more reliable

Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer.

While genetic mutation is a hallmark of cancer, many cancers also acquire epigenetic alterations during tumorigenesis including aberrant DNA hypermethylation of tumor suppressors, as well as changes in chromatin modifications as caused by genetic mutations of the chromatin-modifying machinery. However, the extent of epigenetic alterations in cancer cells has not been fully characterized. Here, we describe complete methylome maps at single nucleotide resolution of a low-passage breast cancer cell line and primary human mammary epithelial cells. We find widespread DNA hypomethylation in the cancer cell, primarily at partially methylated domains (PMDs) in normal breast cells. Unexpectedly, genes within these regions are largely silenced in cancer cells. The loss of DNA methylation in these regions is accompanied by formation of repressive chromatin, with a significant fraction displaying allelic DNA methylation where one allele is DNA methylated while the other allele is occupied by histone modifications H3K9me3 or H3K27me3. Our results show a mutually exclusive relationship between DNA methylation and H3K9me3 or H3K27me3. These results suggest that global DNA hypomethylation in breast cancer is tightly linked to the formation of repressive chromatin domains and gene silencing, thus identifying a potential epigenetic pathway for gene regulation in cancer cells.

Evaluation de la prise en charge des femmes de plus de 30 ans avec un diagnostic de L-SIL du col de l'utérus en vigueur depuis 2009 au CHUV

Introduction : Les lésions malpighiennes intraépithéliales de bas grade (LSIL) sont un diagnostic rencontré fréquemment lors des frottis de dépistage du cancer du col utérin. Leur prise en charge reste controversée. Au CHUV, avant 2009, un test HPV était effectué chez toutes les femmes avec un diagnostic de L-SIL et seules les patientes avec un test HPV positif pour les hauts risques (HR) étaient adressées en colposcopie. Actuellement, suivant les guidelines européennes de 2006, l'attitude est de faire une colposcopie à toutes les patientes avec un diagnostic initial de L-SIL, sans faire préalablement un test HPV. Cette démarche semble efficiente chez les jeunes patientes, mais pas chez les plus de 30 ans chez qui la prévalence de tests HPV HR positifs est inférieure. Plus de 40% des femmes de plus de 30 ans seraient référées inutilement en colposcopie car elles ne seraient pas infectées par un HPV HR et n'auraient pas de risque d'évolution de leur L-SIL vers une lésion de haut grade. Buts : Comparer les deux différentes prises en charge des femmes de plus de 30 ans présentant un diagnostic de L-SIL, soit celle qui était en vigueur au CHUV avant 2009 et la prise en charge actuelle. Etudier le rôle et l'utilité du test HPV et de la colposcopie dans le suivi de ces femmes. Méthode : Il s'agit d'une étude rétrospective, monocentrique. Nous avons étudié le dossier de toutes les femmes de plus de 30 ans ayant eu une cytologie avec un diagnostic initial de L-SIL du col de l'utérus au CHUV entre le 01.01.09 et le 31.12.10, soit 61 patientes. Résultats : Parmi les 61 femmes inclues dans notre étude 60 ont eu un test HPV effectué lors du diagnostic de L-SIL, dont seuls 29 (48,33%) étaient positifs pour les hauts risques. Comparé aux femmes avec test HPV négatif pour HR, les femmes positives pour HPV HR ont eu un taux inférieur d'évolution spontanément résolutive de leur lésion et un taux supérieur de conisation ou vaporisation du col. Cinq des femmes inclues dans l'étude ont eu une évolution de leurs lésions vers une pathologie plus avancée, dont 4 vers un CIN2 et 1 vers un CIN3. Ces cinq cas étaient positifs pour HPV HR. Conclusion : Les nouvelles guidelines en vigueur au CHUV concernant la prise en charge des femmes avec diagnostic de L-SIL n'étaient pas encore appliquées en 2010, en effet le test HPV a été effectué chez presque la totalité de ces patientes. Ces nouvelles guidelines ne semblent pas être applicables aux femmes de plus de 30 ans, chez qui la prévalence du HPV HR est inférieure, et qui risquent alors de subir des examens complémentaires invasifs, sans qu'il y ait de réel bénéfice sur le pronostic de leur pathologie.

On-line desorption of dried blood spots coupled to hydrophilic interaction/reversed-phase LC/MS/MS system for the simultaneous analysis of drugs and their polar metabolites.

An assay for the simultaneous analysis of pharmaceutical compounds and their metabolites from micro-whole blood samples (i.e. 5 microL) was developed using an on-line dried blood spot (on-line DBS) device coupled with hydrophilic interaction/reversed-phase (HILIC/RP) LC/MS/MS. Filter paper is directly integrated to the LC device using a homemade inox desorption cell. Without any sample pretreatment, analytes are desorbed from the paper towards an automated system of valves linking a zwitterionic-HILIC column to an RP C18 column. In the same run, the polar fraction is separated by the zwitterionic-HILIC column while the non-polar fraction is eluted on the RP C18. Both fractions are detected by IT-MS operating in full scan mode for the survey scan and in product ion mode for the dependant scan using an ESI source. The procedure was evaluated by the simultaneous qualitative analysis of four probes and their relative phase I and II metabolites spiked in whole blood. In addition, the method was successfully applied to the in vivo monitoring of buprenorphine metabolism after the administration of an intraperitoneal injection of 30 mg/kg on adult female Wistar rat.

Purpura de Henoch-Schönlein: une prise en charge entre pédiatre et néphrologue pédiatre [Henoch-Schönlein Purpura a dual follow up between pediatrician and pediatric nephrologist].

Henoch-Schönlein purpura is a well known paediatric disease characterized by the classic triad: purpura, arthritis and abdominal pain. Short term prognosis is excellent and is mostly dependant on abdominal complications. Long term morbidity depends essentially on the severity of renal involvement which occurs in 35% of cases. Microhematuria and light proteinuria are the only signs in 80% of cases. The remaining 20% presents with nephrotic or nephritic syndrome and acute renal insufficiency. Among patients with Henoch-Schönlein nephritis the risk of developing renal insufficiency varies between 11-30% of cases. Currently, the follow up guidelines are multiple and the optimal treatment of nephritis is controversial; this is what this article proposes to discuss.

Profiling of steroid metabolites after transdermal and oral administration of testosterone by ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

The screening of testosterone (T) misuse for doping control is based on the urinary steroid profile, including T, its precursors and metabolites. Modifications of individual levels and ratio between those metabolites are indicators of T misuse. In the context of screening analysis, the most discriminant criterion known to date is based on the T glucuronide (TG) to epitestosterone glucuronide (EG) ratio (TG/EG). Following the World Anti-Doping Agency (WADA) recommendations, there is suspicion of T misuse when the ratio reaches 4 or beyond. While this marker remains very sensitive and specific, it suffers from large inter-individual variability, with important influence of enzyme polymorphisms. Moreover, use of low dose or topical administration forms makes the screening of endogenous steroids difficult while the detection window no longer suits the doping habit. As reference limits are estimated on the basis of population studies, which encompass inter-individual and inter-ethnic variability, new strategies including individual threshold monitoring and alternative biomarkers were proposed to detect T misuse. The purpose of this study was to evaluate the potential of ultra-high pressure liquid chromatography (UHPLC) coupled with a new generation high resolution quadrupole time-of-flight mass spectrometer (QTOF-MS) to investigate the steroid metabolism after transdermal and oral T administration. An approach was developed to quantify 12 targeted urinary steroids as direct glucuro- and sulfo-conjugated metabolites, allowing the conservation of the phase II metabolism information, reflecting genetic and environmental influences. The UHPLC-QTOF-MS(E) platform was applied to clinical study samples from 19 healthy male volunteers, having different genotypes for the UGT2B17 enzyme responsible for the glucuroconjugation of T. Based on reference population ranges, none of the traditional markers of T misuse could detect doping after topical administration of T, while the detection window was short after oral TU ingestion. The detection ability of the 12 targeted steroids was thus evaluated by using individual thresholds following both transdermal and oral administration. Other relevant biomarkers and minor metabolites were studied for complementary information to the steroid profile, including sulfoconjugated analytes and hydroxy forms of glucuroconjugated metabolites. While sulfoconjugated steroids may provide helpful screening information for individuals with homozygotous UGT2B17 deletion, hydroxy-glucuroconjugated analytes could enhance the detection window of oral T undecanoate (TU) doping.

Amplitude envelope synchronization in coupled chaotic oscillators.

A peculiar type of synchronization has been found when two Van der PolDuffing oscillators, evolving in different chaotic attractors, are coupled. As the coupling increases, the frequencies of the two oscillators remain different, while a synchronized modulation of the amplitudes of a signal of each system develops, and a null Lyapunov exponent of the uncoupled systems becomes negative and gradually larger in absolute value. This phenomenon is characterized by an appropriate correlation function between the returns of the signals, and interpreted in terms of the mutual excitation of new frequencies in the oscillators power spectra. This form of synchronization also occurs in other systems, but it shows up mixed with or screened by other forms of synchronization, as illustrated in this paper by means of the examples of the dynamic behavior observed for three other different models of chaotic oscillators.

Generalized synchronization in directionally coupled systems with identical individual dynamics

A simple chaotic flow is presented, which when driven by an identical copy of itself, for certain initial conditions, is able to display generalized synchronization instead of identical synchronization. Being that the drive and the response are observed in exactly the same coordinate system, generalized synchronization is demonstrated by means of the auxiliary system approach and by the conditional Lyapunov spectrum. This is interpreted in terms of changes in the structure of the system stationary points, caused by the coupling, which modify its global behavior.