C-fos and c-jun Proto-Oncogene Expression Is Decreased in Psoriasis: an In Situ Quantitative Analysis

Psoriasis is a common, sometimes sevcre, non-malignant skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes. Because proto-oncogenes are implicated in both cell proliferation and differentiation, their expression could be modified in skin diseases such as psoriasis. The c-fos and c-jun proto-oncogenes, whose products associate to form a heterodimeric transcription factor, are among the first genes to be expressed when certain cells are stimulated to either proliferate or differentiate. Recent studies in our laboratory have shown that the c-fos protooncogene is highly expressed in normal human adult skin. In the present study, we used in situ hybridization with RNA to compare the expression and localization of c-fos and c-jun transcripts in 15 lesional and non-lesional psoriatic skin samples. Two clinical variants of psoriasis were studied: the most severe and chronic form or plaque-type psoriasis (N = 10) and rapidly resolutive guttate-type psoriasis (N = 5). Quantitative analysis was performed using a semi-automatic image analyzer and the “Starwise grain” software program. Our control samples included 10 normal skins and eight specimens from other benign hyperproliferative non-psoriatic skin diseases, consisting of three with inflammation (seborrheic dermatitis and atopic dermatitis), and 5 without inflammation (seborrheic keratoses). Control genes we used for in situ hybridization and RNA integrity were keratin 14, which is expressed in the epidermis and was normally expressed in all tissue analyzed, and ribosomal RNA. Our data showed that c-fos and c-jun were expressed to an equivalent extent, both spatially and quantitatively, in all specimens tested. Expression was significantly decreased in plaque-type but not in guttate-type psoriasis. It was also decreased in the three other benign inflammatory cutaneous hyperproliferative disorders, but not in the five non-inflammatory cases. These results were surprising because hyperproliferation was here associated with a decrease in proto-oncogene expression, thus suggesting that c-fos and c-jun do not play a crucial role in the control of keratinocyte proliferation in vivo. However, their reduced expression in some abnormally differentiated skins indicates that both c-fos and c-jun proto-oncogenes may play a key role in keratinocyte differentiation. Their altered expression correlated with severity of the disease and the presence of an inflammatory infiltrate. These data offer a new insight into the role and regulation of these proto-oncogenes in vivo in humans

Merkel Cell Polyomavirus in Cutaneous Swabs

To assess the usefulness of using cutaneous swabs to detect Merkel cell polyomavirus (MCPyV) DNA, we analyzed swabs from persons with Merkel cell carcinoma (MCC), others with skin diseases, and healthy volunteers. MCPyV was detected in at least 1 sample from virtually all participants. Viral loads were higher in samples from patients with MCC

Eliminating HIV transmission through breast milk from women taking antiretroviral drugs

publishedVersio

Design and challenges of a large HIV prevention clinical study on mother-to-child transmission: ANRS 12397 PROMISE-EPI study in Zambia and Burkina Faso

Under embargo until: 2022-04-23Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6–8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants. The preventive intervention includes: a) Point of care testing for early infant HIV diagnosis and maternal viral load; b) infant, single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if mothers are virally unsuppressed. The primary outcome is HIV-transmission rate from EPI-2 to 12 months. The study targets to screen 37,000 mother/infant pairs in Zambia and Burkina Faso to identify 2000 mother/infant pairs for the clinical trial. The study design and challenges faced during study implementation are described, including the COVID-19 pandemic and the amended HIV guidelines in Zambia in 2020 (triple-drug PrEP in HIV exposed infants guided by quarterly maternal viral load). The changes in the Zambian guidelines raised several questions including the equipoise of PrEP options, the standard of care-triple-drug (control arm in Zambia) versus the study-single-drug (intervention arm).acceptedVersio

Facilitators and barriers to infant post-natal HIV prophylaxis, a qualitative sub-study of the PROMISE-EPI trial in Lusaka, Zambia

BackgroundInfant post-natal prophylaxis (PNP) is used to prevent HIV transmission through breastfeeding. The WHO edited recommendations but so far there is no consensus on the duration of prophylaxis and the type of drug used depends on national guidelines. In Zambia, the national recommendations include a three-drug prophylaxis, composed of a dispersible combined tablet of zidovudine (AZT) and lamivudine (3TC) and an oral suspension of nevirapine (NVP) for 12 weeks or until the mother’s viral load is <1,000 cp/mL. The PROMISE-EPI study, modified the PNP regimen to lamivudine only, initiated at 6 weeks and continued until 12 months to all HIV exposed uninfected infants of virally unsuppressed mothers. Our aim in this analysis was to identify barriers and facilitators to this extended PNP, the keystone toward an effective prevention.MethodsIndividual interviews and focus group discussion (FGD) were conducted with PROMISE-EPI participants who had received prophylaxis for their children from the national program up to 6 weeks and then lamivudine oral solution in PROMISE-EPI study. Health care providers and PROMISE-EPI staff were also interviewed. Sessions were recorded, transcribed verbatim and translated from local languages into English. An initial code-book was designed and then adapted on the basis of the emerging themes, to allow a descriptive thematic analysis.ResultsMore barriers to PNP adherence were identified with triple drug prophylaxis than with lamivudine. These barriers were related to the formulation and bitter taste of AZT/3TC tablets. The ready to use formulation and sweet taste of lamivudine syrup were appreciated by mothers. Extended PNP proposed in the PROMISE-EPI study was globally well accepted and strategies were found to increase adherence. Adherence to lamivudine appeared to be better than the mothers’ adherence to their own antiretroviral therapy.ConclusionAccompanying mothers living with HIV and giving them the choice of the PNP to prevent transmission via breastfeeding (type of PNP regimen and extended PNP in non-adherent mothers), may be one of the keys to reducing the burden of pediatric HIV acquisition in low and middle income countries

[Development of new skin substitutes based on bioresorbable polymer for treatment of severe skin defects]

International audienceOver the last years, increasing attention has been paid to skin engineering due to its predominant function in body integrity. Thus, many laboratories are attempting to develop a dermal-epidermal complex. The aim of this study was to evaluate the potential of poly(alpha-hydroxyacid)s in the development of biocompatible and bioresorbable dermal scaffold combining human fibroblasts and keratinocytes, in order to obviate the drawbacks of using natural polymers such as collagen, hyaluronic acid and fibrin. We first confirmed the interest of poly(d,l-lactic acid) (PLA(50)) during the reconstitution of epidermis and next, we investigated the potential of poly(d,l-lactic acid)-poly(ethylene glycol)-poly(d,l-lactic acid) (PLA(50)-PEG-PLA(50)) for either skin cytocompatibility or scaffold processing. Data showed that PLA(50)-PEG-PLA(50) is compatible with the culture of human skin cells (fibroblasts and keratinocytes) and the development of a porous scaffold; two requirements compulsory for being considered as an adequate skin substitute. In fine, this material could represent the first generation of new skin dressings, i.e. a new concept taking advantage of both implantable devices and current dressings

Etude des possibilités d'emploi de la drêche de brasserie dans l'alimentation des monogastriques. I. Expériences chez des rats et des poulets, concernant la qualité nutritive de la protéine de deux fractions de la drêche de brasserie

International audienc