Attenuation of negative effects of senescence in human skin using an extract from Sphingomonas hydrophobicum: development of new skin care solution.

OBJECTIVE: Intrinsic skin ageing is mainly caused by cellular senescence. p16 and p21 are two important tumour suppressor proteins that play essential roles during cell proliferation and ageing through regulating the expression of several genes. Moreover, physical changes between the ages of 55 and 60 years affect one's physical and disrupt self-esteem. The cosmetics industry has focused on bioactive substances derived from natural products such as plants, mushrooms and marine algae to counteract the deleterious effect on skin senescence. Besides these products, compounds produced by bacteria may decelerate individual senescence. METHODS: In order to evaluate the potential benefits of bacteria extract over skin ageing, we investigated whether a Sphingomonas hydrophobicum (SH) extract is able to protect our skin against senescence mechanisms. We used an ageing full-thickness skin equivalent model, which was treated or not with the bacteria extract in a systemic way for 42 days. p21 and p16 and senescence-associated galactosidase activity were used to detect cellular senescence with immunohistology. Using a psychobiological approach, we evaluated in vivo the effect of SH extract on self-esteem, isotropy and suppleness. RESULTS: Sphingomonas extract significantly suppressed senescence associated with ß-galactosidase activation. It also significantly inhibited the expression of cell cycle inhibitors (p21 and p16). At the same time, the bacteria extract has a significant positive impact on the issue by increasing the expression of versican and fibrillin-1. Significant improvements of self-esteem were reported after 56 days of SH extract application. These psychological benefits were accompanied by a significant improvement in skin suppleness and isotropy. CONCLUSION: Sphingomonas extract delays intrinsic skin ageing process by inhibiting cellular senescence, and has also the capability to restructure the skin. These beneficial physiological effects induced by SH extract have a positive influence on self-esteem. Because skin ageing causes emotional distress, SH extract can serve as an anti-ageing cosmeceutical agent and help to build a better psychological health, and help individuals to assume ageing.

OBJECTIF: Le vieillissement intrinsèque de la peau est principalement causé par la sénescence cellulaire. p16 et p21 sont deux importantes protéines suppressives de tumeurs qui jouent un rôle essentiel dans la prolifération et le vieillissement cellulaire en régulant l'expression de plusieurs gènes. De plus, les changements physiques survenant entre 55 et 60 ans affectent le physique et perturbent l'estime de soi. L'industrie cosmétique s'est concentrée sur les substances bioactives dérivées de produits naturels tels que les plantes, les champignons et les algues marines pour contrer les effets délétères sur la sénescence de la peau. En plus de ces produits, les composés produits par les bactéries peuvent ralentir la sénescence individuelle. MÉTHODES: Afin d'évaluer les bénéfices potentiels de l'extrait de bactérie sur le vieillissement cutané, nous avons étudié si un extrait de Sphingomonas hydrophobicum (SH) est capable de protéger notre peau des mécanismes de sénescence. Nous avons utilisé un modèle équivalent de peau vieillissante de pleine épaisseur, qui a été traitée ou non avec l'extrait de bactérie de façon systémique pendant 42 jours. p21 et p16, et l'activité galactosidase associée à la sénescence ont été utilisés pour détecter la sénescence cellulaire par immunohistologie. En utilisant une approche psychobiologique, nous avons évalué in vivo l'effet de l'extrait de SH sur l'estime de soi, l'isotropie et la souplesse. RÉSULTATS: L'extrait de Sphingomonas a considérablement supprimé la sénescence associée à l'activation de ß-galactosidase. Il a également inhibé de manière significative l'expression des inhibiteurs du cycle cellulaire (p21 et p16). En même temps, l'extrait de bactérie a un impact positif significatif sur le problème en augmentant l'expression du versican et de la fibrilline-1. Des améliorations significatives de l'estime de soi ont été rapportées après 56 jours d'application de l'extrait de SH. Ces bienfaits psychologiques s'accompagnaient d'une amélioration significative de la souplesse et de l'isotropie de la peau. CONCLUSION: L'extrait de Sphingomonas retarde le processus de vieillissement intrinsèque de la peau en inhibant la sénescence cellulaire et a également la capacité de restructurer la peau. Ces effets physiologiques bénéfiques induits par l'extrait de SH ont une influence positive sur l'estime de soi. Parce que le vieillissement de la peau provoque une détresse émotionnelle, l'extrait de SH peut servir d'agent cosméceutique anti-âge et aider à construire une meilleure santé psychologique, ainsi qu'aider les individus à assumer le vieillissement.

Uveal melanoma hepatic metastases mutation spectrum analysis using targeted next-generation sequencing of 400 cancer genes.

AIMS: Uveal melanoma (UM) is the most common malignant tumour of the eye. Diagnosis often occurs late in the course of disease, and prognosis is generally poor. Recently, recurrent somatic mutations were described, unravelling additional specific altered pathways in UM. Targeted next-generation sequencing (NGS) can now be applied to an accurate and fast identification of somatic mutations in cancer. The aim of the present study was to characterise the mutation pattern of five UM hepatic metastases with well-defined clinical and pathological features. METHODS: We analysed the UM mutation spectrum using targeted NGS on 409 cancer genes. RESULTS: Four previous reported genes were found to be recurrently mutated. All tumours presented mutually exclusive GNA11 or GNAQ missense mutations. BAP1 loss-of-function mutations were found in three UMs. SF3B1 missense mutations were found in the two UMs with no BAP1 mutations. We then searched for additional mutation targets. We identified the Arg505Cys mutation in the tumour suppressor FBXW7. The same mutation was previously described in different cancer types, and FBXW7 was recently reported to be mutated in UM exomes. CONCLUSIONS: Further studies are required to confirm FBXW7 implication in UM tumorigenesis. Elucidating the molecular mechanisms underlying UM tumorigenesis holds the promise for novel and effective targeted UM therapies.

An oyster-associated hepatitis A outbreak in France in 2007.

Following the notification of nine hepatitis A cases clustered in the Cotes d Armor district in northwestern France, epidemiological, environmental and microbiological investigations were set up in order to identify the source and vehicle of contamination and implement control measures. In total, 111 cases were identified in the outbreak, all of whom lived or had stayed as tourists in the Cotes d Armor district. Of the cases, 87% had eaten raw shellfish, and 81% specifically oysters. Traceback investigations carried out on raw shellfish consumed by the cases showed that the raw shellfish originated from a single shellfish farm. The shellfish were probably contaminated either in the submersible tanks or in a depuration land-based tank where they were stored. The source of contamination was not identified but shellfish could have been tainted by sewage overflows or by wastewater releases from a polluted storm sewer close to the shellfish farm or from on-site sanitation facilities. To prevent future hepatitis A outbreaks due to shellfish consumption from this area, hazards specific to each farm should be analysed. Timely information on sewage overflows should also be part of communities efforts regarding sewage collection and treatment.

[The course of postpartum period after mandatory ambulatory labor]. / Barselsperiodens forløb efter tvungen ambulant fødsel.

Mandatory early discharge for all normal multiparae was introduced as a trial arrangement in the County of Ringkøbing from 1.1.1990. A total of 113 early discharged women and 90 patients who remained in hospital participated in a questionnaire investigation comprising 41 questions about problems and need for support during the first postpartum period and about satisfaction with the postpartum period. A total of 64% of all the multiparae were early discharged and were discharged 4.2 hours after the delivery. On the whole, the women were satisfied with the postpartum period and only few problems in infants or mothers occurred. The early discharged group, however, as compared with the control group, stated that they had received less satisfactory support concerning breast-feeding (p less than 0.005) and that, in general, they had received less support from friends (p less than 0.01) and hospital staff (p = 0.04). The group of early discharged felt that they had received less satisfactory information (p less than 0.005) and, on the whole, they were less satisfied with the postpartum period (p less than 0.005). In addition, the group who were early discharged had 67% more telephone conversations with and 127% more visits from the midwife, health nurse or practitioner.

Electrophysiological evidence for a role of the anterolateral quadrant of the spinal cord in the transmission of noxious messages to the thalamic ventrobasal complex in the rat.

Responses to noxious mechanical and thermal stimulation applied to the hindpaws were recorded extracellularly from the same neurons of the ventrobasal complex of the rat thalamus (VB) before and after lesions of various areas of the cervical cord in order to determine the pathways carrying the afferent messages. It was demonstrated that lesions of the dorsal and dorsolateral portions of the cord failed to eliminate the VB neuronal responses to noxious stimulation. By contrast, lesion of one anterolateral quadrant eliminated the responses to a noxious stimulation applied to the hindpaw contralateral to the lesion. This occurred whether the lesion was ipsilateral or contralateral to the recording site. From the present study and the data in the literature, it is concluded that the fibers of the spino-thalamic tract which are completely crossed in the spinal cord, travel in the anterolateral quadrant and project directly onto the VB, are involved in the transmission of noxious messages from the cord to the VB neurons. This conclusion indicates that the VB neuronal responses to noxious stimulation of the hindpaw ipsilateral to the recording site depend on the spinothalamic projection to the opposite ventrobasal complex. This therefore suggests that some noxious messages which reach a particular VB neuron are conveyed via the opposite VB and the existence of a thalamo-cortico-thalamic loop is discussed.

Electrophysiological properties of lemniscal afferents in rat after kainic acid lesions in the ventrobasal thalamus.

Kainic acid (KA) has been largely used as a neurotoxin, and its axon-sparing effect being repeatedly emphasized, on the basis of anatomical and biochemical data. The present study examines this 'axon-sparing' effect from an electrophysiological point of view and demonstrates that lemniscal fibers retain the capacity to convey somesthetic information 5-60 days after an injection of KA in the ventrobasal complex of the thalamus depriving these afferent fibers of their target cells.

[Changes in cortical evoked potentials in relation to cutaneous sensory thresholds. Application to a study of analgesic electrostimulation]. / Variations des potentiels évoqués corticaux en fonction des seuils sensitifs cutanés. Application à l'étude d'une électrostimulation analgésiante.

The potentials (EPs) evoked by cutaneous electric shock of increasing intensity and the corresponding sensitivity thresholds were studied in 25 healthy volunteers: analgesic electrical stimulation (AES) was performed on only 10 of these. The stimuli (0.5 msec; 0-140 V) applied in a random way with a needle electrode implanted in the horny layer of the tip of the middle finger can produce 4 sensations: initial awareness, pressure sensation, diffusion and pain. The EP recorded on the somatosensory areas had the typical somatosensory (SEP) morphology only at the pressure stage. At the pain thresholds, the response was a well-demarcated 'nociceptive' EP (NEP), with main components at P100, N140, P240. After 45 min of AES, the increase of the sensitivity thresholds was peculiarly pronounced for that of pain, homolaterally (80%) and contralaterally (45%) to the AES. With respect to the EPs, the NEP and especially its late waves showed a noteworthy reduction in amplitude, more significant on the homolateral side (66%) than on the contralateral one (50%), whilst the SEP was only slight modified. The evolution of the thresholds and of the EPs was followed for 45 min after cessation of AES and revealed a significant residual effect of comparable values for the two parameters.