Parentalité et vie familiale autour de la séropositivité

Ce Travail de Bachelor s’intéresse aux thématiques autour de la séropositivité et de la vie de famille. Je mobilise dans ce cadre des concepts comme la parentalité, le tabou, le stigmate ou la discrimination. La question de recherche autour de laquelle s’articule ce rapport est la suivante : Comment la séropositivité est-elle vécue au sein d’une famille dont l’un des parents, au moins, est séropositif ? J’ai cherché à déterminer, avec cette recherche, si et quand une intervention de professionnel-le-s dans le domaine du travail social peut être nécessaire en lien avec une des trois pistes d’action suivantes : le soutien à la parentalité et à la vie de famille, la complémentarité du réseau ainsi que la prévention et la réflexion autour de la discrimination. Pour permettre à mon travail de se moduler autour d’objectifs de recherche, j’ai posé trois hypothèses qui mentionnaient, en résumé, le fait que la séropositivité pouvait être un obstacle à la parentalité, qu’elle pouvait rendre la vie familiale plus difficile en ayant des impacts sur les personnes vivant dans ce contexte et que l’intervention d’un ou d’une TS pouvait être nécessaire dans une famille dont au moins l’un des parents était séropositif. Pour répondre à ces interrogations, j’ai décidé d’interviewer trois parents séropositifs et trois enfants dont, au moins, l’un des parents était atteint du VIH sous forme d’entretiens semi-directifs. En lien avec les trois hypothèses, il est ressorti tout d’abord des entretiens que bien que certains aient subi de la discrimination de la part de leur entourage ou du corps médical, dans toutes les familles interviewées, aucune d’entre elles n’a renoncé à avoir un enfant. Pour ce qui est de la difficulté que pouvait engendrer le VIH dans la parentalité et la vie de famille, les résultats montrent qu’effectivement cette infection peut avoir des conséquences négatives comme le ressenti d’un jugement discriminatoire ou la perte d’un proche dans le pire des cas. Cependant, dans d’autres situations, la séropositivité a aussi eu des impacts positifs et a permis de développer une certaine résilience. Enfin, il a été vu que les travailleurs et travailleuses sociales jouent déjà un rôle dans certains domaines en lien avec le VIH comme par exemple dans des hôpitaux ou dans des associations. Cependant, les personnes interviewées ont mentionné la nécessité de travailler au niveau de la prévention contre la discrimination et m’ont donné quelques pistes d’action en lien avec ce besoin, pistes que j’ai développées à la fin de ce travail de recherche. Concernant la structure de mon travail, elle a été faite selon l’ordre que j’ai suivi pour ma recherche. Ainsi à la suite de l’introduction, les premiers chapitres concernent le cadre théorique et les hypothèses de recherche. Puis j’aborde la méthodologie. Mes dernières parties sont l’analyse des données et l’interprétation des résultats pour finir par une partie conclusive

Ultraviolet B and A irradiation induces fibromodulin expression in human fibroblasts in vitro

Ultraviolet (UV) radiation affects the extracellular matrix (ECM) of the human skin. The small leucine-rich repeat protein fibromodulin interacts with type I and II collagen fibrils, thereby affecting ECM assembly. The aim of this study was to evaluate whether short wave UV (UVB) or long wave UV (UVA) irradiation influences fibromodulin expression. Exponentially growing human fibroblasts (IMR-90 cells) were exposed to increasing doses of UVB (2.5-60 mJ/cm(2)) or UVA (0.5-10 J/cm(2)). After UV irradiation fibromodulin, p21 and GADD45 levels were evaluated as well as cell viability, reactive oxygen species formation (ROS) and DNA damage. We found that fibromodulin expression: (i) increased after UVB and UVA irradiation; (ii) was 10-fold higher after UVA (10 J/cm(2)) versus 5-fold with UVB (10 mJ/cm(2)); (iii) correlated with reactive oxygen species formation, particularly after UVA; and (iv) was linked to the DNA damage binding protein (DDB1) translocation in the nucleus, particularly after UVB. These results further suggest that the UV-induced fibromodulin increase could counteract the UV-induced connective tissue damage, promoting the assembly of new collagen fibrils

A Comparative Analysis of the Photo-Protective Effects of Soy Isoflavones in Their Aglycone and Glucoside Forms

Isoflavones exist in nature predominantly as glucosides such as daidzin or genistin and are rarely found in their corresponding aglycone forms daidzein and genistein. The metabolism and absorption of isoflavones ingested with food is well documented, but little is known about their use as topical photo-protective agents. The aim of this study was to investigate in a comparative analysis the photo-protective effects of isoflavones in both their aglycone and glucoside forms. In human skin fibroblasts irradiated with 60 mJ/cm(2) ultraviolet B (UVB), we measured the expression levels of COX-2 and Gadd45, which are involved in inflammation and DNA repair, respectively. We also determined the cellular response to UVB-induced DNA damage using the comet assay. Our findings suggest that both the isoflavone glucosides at a specific concentration and combination with an aglycone mixture exerted an anti-inflammatory and photo-protective effect that prevented 41% and 71% of UVB-induced DNA damage, respectively. The advantages of using either isoflavone glucosides or an aglycone mixture in applications in the field of dermatology will depend on their properties and their different potential uses

Isoflavones in aglycone solution enhance ultraviolet B-induced DNA damage repair efficiency.

The isoflavones daidzein and genistein are natural compounds which have anti-inflammatory and photoprotective activities, and may be effective in the repair of ultraviolet (UV)-induced photodamage. In this study, an alcoholic solution of aglycone isoflavones with a genistein:daidzein ratio of 1:4 [Rottapharm (RPH)-aglycone] was examined for its effects on the repair of DNA damage induced by a single dose of UVB irradiation (20 mJ/cm2). For this purpose, human skin cells were first UVB-irradiated and then treated with RPH-aglycone. Comet assay analysis was used to estimate the UVB-induced DNA damage at different time points after treatment by measuring the tail moment parameter. We found that treatment with 10 μmol/L RPH-aglycone solution resulted in a significantly reduced tail moment at 1 h after treatment, and 34-35% enhancement of damage repair at 4 h after treatment. These results suggest that isoflavone aglycones are protective against UVB-induced DNA damage. © 2014 British Association of Dermatologists

622. Oncolytic Adenoviruses Loaded With Active Drugs as a Novel Drug Delivery System for Cancer Therapy

L-carnosine (β-Ala-His) is a naturally occurring histidine dipeptide, normally found in brain, kidney and in large amounts in muscle. L-carnosine has biological functions, including antioxidant activity, ability to chelate metal ions, as well as anti-inflammatory and anti-senescence properties. Recent studies have demonstrated that 50-100 mM of L-carnosine decreases cell proliferation in a colon cancer cell line HCT116, bearing a mutation in codon 13 of the RAS proto-oncogene. In addition, pre-treatment with L-carnosine decreases the intracellular concentration of Adenosine Triphosphate (ATP) and Reactive Oxygen Species (ROS) and inhibits the cell cycle progression in the G1 phase. The proto-oncogene KRAS is mutated in a wide array of human cancers and is important both in tumour progression and resistance to anticancer drugs. To overcome treatment limitations due to the high intracellular concentration required we have hypothesized that L-carnosine can be conjugated on the capsid of oncolytic viruses. Oncolytic viruses are viruses that are able to replicate specifically in and destroy tumor cells and this property is either inherent or genetically-engineered. The association of viruses with specific drugs, would increase the efficacy of the treatment of human neoplasia due to the synergistic action of virus and drug. First we have developed a strategy to conjugate peptides on viral capsid, based on electrostatic interaction. Then, using different cancer cell lines we found that oncolytic virus coated with L-carnosine with a tail of positively charged polylysine was able to enhance a positive anticancer synergistic effect. Finally, in order to investigate the molecular mechanisms underlying the effect of tumor reduction by oncolytic virus coated with modified L-carnosine, we have used three different approaches. First, we have examined, in samples with virus alone, or in combination with L-carnosine, the oncolytic replication by evaluating the E1A expression, second the apoptotic mechanism by expression of specific genes and at end the autophagy regulation via the amount of LC3-II. In conclusion, we have developed a model to use oncolytic adenovirus as a scaffold to deliver active drugs. Once validated the proposed model could be used as a novel drug delivery system for cancer therapy

659 oncolytic adenovirus loaded with bioactive modified peptide as a novel approach to treat cancer

Cancer is still a leading cause of death worldwide. Although many kinds of treatment have been developed during the past decades, there is still a lack of effective therapy for advanced cancer. Currently treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase patient life expectancy. Therefore new treatment strategies against cancer are in high demand. Efficient anticancer agent and its targeted delivery into the tumor mass is a key prerequisite for the successful cancer therapy. Oncolytic virotherapy is emerging as a potential approach to treat cancer, using viruses, which are specifically engineered to selectively infect, replicate in and kill cancer cells without causing damage to normal cells. Their combination with chemotherapeutic agents have shown promising results due to the synergistic effect of viruses and drugs; therefore the combinatorial therapy is considered a beneficial approach for cancer treatment. Taken into account these considerations we optimized a strategy to conjugate peptides on the viral capsid, based on electrostatic interaction and used this strategy to deliver an active anti-tumor dipeptide. We used L-carnosine, a naturally occurring histidine dipeptide with anti-proliferative activity. A modified L-carnosine, positively charged was absorbed onto the viral capsid of an oncolytic adenovirus to generate a virus-carnosine complex. The complex showed enhanced anti tumor efficacy in vitro and in vivo and higher infectious titer compared to a naked oncolytic adenovirus in colorectal and lung cancer cells. The in vivo efficacy of the complex was analyzed in lung and colon cancer xenograft models, displaying a significant reduction in tumor growth and synergistic effect between virus and dipeptide. Moreover, we studied the molecular mechanisms underlying the effects of complex on tumor growth reduction. Complex can induce apoptosis in both cells lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in further studies also for specific delivery of other active drugs

Oncolytic adenovirus loaded with L-carnosine as novel strategy to enhance the antitumor activity

Oncolytic viruses are able to specifically replicate, infect, and kill only cancer cells. Their combination with chemotherapeutic drugs has shown promising results due to the synergistic action of virus and drugs; the combinatorial therapy is considered a potential clinically relevant approach for cancer. In this study, we optimized a strategy to absorb peptides on the viral capsid, based on electrostatic interaction, and used this strategy to deliver an active antitumor drug. We used L-carnosine, a naturally occurring histidine dipeptide with a significant antiproliferative activity. An ad hoc modified, positively charged L-carnosine was combined with the capsid of an oncolytic adenovirus to generate an electrostatic virus-carnosine complex. This complex showed enhanced antitumor efficacy in vitro and in vivo in different tumor models. In HCT-116 colorectal and A549 lung cancer cell lines, the complex showed higher transduction ratio and infectious titer compared with an uncoated oncolytic adenovirus. The in vivo efficacy of the complex was tested in lung and colon cancer xenograft models, showing a significant reduction in tumor growth. Importantly, we investigated the molecular mechanisms underlying the effects of complex on tumor growth reduction. We found that complex induces apoptosis in both cell lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in future studies also for delivery of other bioactive drugs. Mol Cancer Ther; 15(4); 651-60. ©2016 AACR

Multi-messenger searches via IceCube’s high-energy neutrinos and gravitational-wave detections of LIGO/Virgo

We summarize initial results for high-energy neutrino counterpart searches coinciding with gravitational-wave events in LIGO/Virgo\u27s GWTC-2 catalog using IceCube\u27s neutrino triggers. We did not find any statistically significant high-energy neutrino counterpart and derived upper limits on the time-integrated neutrino emission on Earth as well as the isotropic equivalent energy emitted in high-energy neutrinos for each event