Androgènes et obésité chez l'homme et la femme

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2008-200

Le travail du sexe : facteur de risque émergent de la séroconversion VIH chez les utilisateurs de drogue par injection du réseau SurvUDI

L’objectif de ce mémoire était de mieux comprendre l’apparition récente, dans les données de surveillance chez les utilisateurs de drogues injectables au Québec et à Ottawa, d’une association significative entre le travail du sexe et l’incidence du VIH. Les caractéristiques et comportements ont été comparés en fonction de l’activité sexuelle rapportée pour les six derniers mois, en séparant en trois catégories : les participants inactifs sexuellement, les participants actifs sexuellement rapportant des partenaires sexuels clients et les participants actifs sexuellement ne rapportant pas de partenaires clients. Les participants inactifs sexuellement avaient une incidence du VIH plus élevée, probablement en raison d’une dépendance plus lourde et d’une vulnérabilité plus importante. À l’autre extrémité du spectre d’activité sexuelle, le travail du sexe était associé indépendamment et significativement à l’incidence du VIH. D’autres études seront nécessaires pour comprendre si cette association est liée à la transmission sexuelle ou à d’autres facteurs de vulnérabilité.The objective of this thesis was to better understand the recent appearance of a significant association between sex work and HIV incidence in surveillance data among injection drug users (IDUs) in Quebec and Ottawa. The characteristics and behaviours were compared based on sexual activity reported for the last six months, separated into three categories: sexually inactive participants, sexually active participants reporting client sexual partners and sexually active participants not reporting client partners. Sexually inactive IDUs had a higher HIV incidence rate, likely due to more profound dependence leading to increased vulnerability. At the other end of the spectrum of sexual activity, sex work was independently associated with HIV incidence among IDUs. Further studies are needed to understand whether this association is related to sexual transmission or other vulnerability factors

The mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK) acts as a key regulator of keratinocyte terminal differentiation.

In the skin, epithelial cells undergo a terminal differentiation program leading to the formation of the stratum corneum. Although it is expected that the last phases of this process must be tightly regulated since it results in cell death, the signaling pathways involved in this induction remain ill defined. We now report that a single kinase, the mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK), acts in the epidermis to promote the terminal differentiation of human keratinocytes. In support of this notion, we showed that DLK expression was restricted to the granular layer in situ. In addition, cultured keratinocytes infected with a recombinant adenovirus expressing DLK exhibited morphological and biochemical changes, including a suprabasal localization, altered cell shape, compacted cytoplasm, DNA fragmentation, and the up-regulation of filaggrin, that are reminiscent of a terminally differentiated phenotype. Moreover the expression of wild-type DLK in keratinocytes stimulated transglutaminase activity and the consequent formation of the cornified cell envelope, while a kinase-inactive variant of DLK did not. Together these results identify DLK as a signaling molecule implicated in the regulation of keratinocyte terminal differentiation and cornification

Expression and activity of 20α-hydroxysteroid dehydrogenase (AKR1C1) in abdominal subcutaneous and omental adipose tissue in women

We have examined the expression and activity of 20a-hydroxysteroid dehydrogenase (20a-HSD) in abdominal adipose tissue in women. This recently-characterized enzyme from the aldoketoreductase 1C family (AKR1C1) is responsible for the conversion of progesterone into 20a-hydroxyprogesterone. Abdominal subcutaneous (SC) and omental (OM) adipose tissue biopsies were obtained from a sample of 32 women aged 47.7+-5.9 years (BMI: 27.6+-5.0 kg/m2 ) undergoing abdominal hysterectomies. Body composition and body fat distribution measurements were performed before the surgery by dual energy x-ray absorptiometry and computed tomography respectively. The expression of 20a-HSD was determined by real-time RT-PCR, and its activity was measured in whole tissue homogenates. Messenger RNA and activity of the enzyme were detected in both the SC and OM fat depots, the two measures being significantly higher in the SC compartment. Women characterized by a visceral adipose tissue area greater than or equal to 100 cm2 had an increased 20a-HSD conversion rate in their omental adipose tissue compared to women without visceral obesity (13.99+-2.07 vs. 7.92+-0.83 fmol/ug protein/24h, p<0.05). Accordingly, a positive correlation was found between omental adipose tissue 20a-HSD activity and computed tomography-measured visceral adipose tissue area (r=0.36, p<0.05). Significant positive correlations were also found between omental 20a-HSD activity and omental adipocyte diameter (r=0.49, p<0.05) and omental adipose tissue LPL activity (r=0.36, p=0.06). In conclusion, 20a-HSD activity and mRNA were detected in SC and OM adipose tissue in women, and omental 20a-hydroxylation of progesterone was highest in women with visceral obesity. Further studies are required to establish whether local conversion of progesterone may impact on the metabolism and function of adipocytes located within the abdominal cavity

Down-regulation of the Mixed-lineage Dual Leucine Zipper-bearing Kinase by Heat Shock Protein 70 and Its Co-chaperone CHIP

Dual leucine zipper-bearing kinase (DLK) is a mixed-lineage kinase family member that acts as an upstream activator of the c-Jun N-terminal kinases. As opposed to other components of this pathway, very little is currently known regarding the mechanisms by which DLK is regulated in mammalian cells. Here we identify the stress-inducible heat shock protein 70 (Hsp70) as a negative regulator of DLK expression and activity. Support for this notion derives from data showing that Hsp70 induces the proteasomal degradation of DLK when both proteins are co-expressed in COS-7 cells. Hsp70-mediated degradation occurs with expression of wild-type DLK, which functions as a constitutively activated protein in these cells but not kinase-defective DLK. Interestingly, the Hsp70 co-chaperone CHIP, an E3 ubiquitin ligase, seems to be indispensable for this process since Hsp70 failed to induce DLK degradation in COS-7 cells expressing a CHIP mutant unable to catalyze ubiquitination or in immortalized fibroblasts derived from CHIP knock-out mice. Consistent with these data, we have found that endogenous DLK becomes sensitive to CHIP-dependent proteasomal degradation when it is activated by okadaic acid and that down-regulation of Hsp70 levels with an Hsp70 antisense attenuates this sensitivity. Therefore, our studies suggest that Hsp70 contributes to the regulation of activated DLK by promoting its CHIP-dependent proteasomal degradation

Prevalence and temporal trends of crack injection among injection drug users in eastern central Canada

Background: Little is known about crack injection and its temporal trends in North America. This article describes the extent of crack injection and examines temporal trends among injection drug users (IDUs) recruited from 2003 to 2010 in the SurvUDI network. Methods: IDUs who injected recently (past 6 months) were recruited in harm reduction and health programs in eastern central Canada. Trend analyses were performed using generalized estimating equations. Some IDUs participated multiple times; first interview was retained for the descriptive analyses, while first interview per year was retained for the trend analyses. Results: Of the 4088 IDUs recruited, 15.2% (621) reported crack injection; large variations across sites were noted (range: 0.3%-39.5%). Trend analyses were limited to Ottawa (449 crack injectors) and Montréal (121). For Ottawa, a significant decline was observed, from 48.3% to 36.9%, with a prevalence ratio (PR) of 0.97 per year (95%CI: 0.94-0.99). For Montréal, a significant rise was observed, from 6.0% to 18.4%, with a PR of 1.29 per year (95%CI: 1.19-1.40). Conclusions: Strong variations in crack injection exist throughout the SurvUDI network, and reversed temporal trends have been observed in Ottawa and Montréal. These data will be useful to local harm reduction programs to evaluate the need to distribute items required by crack injectors and to develop prevention messages

Occurrence et tendance temporelle des absorbants UV et des antioxydants synthétiques chez le béluga (Delphinapterus leucas) de l'estuaire du Saint-Laurent, Québec, Canada

RÉSUMÉ : Une exposition élevée aux contaminants a été identifiée comme un facteur de stress ayant un impact négatif sur la santé et le rétablissement de la population de bélugas (Delphinapterus leucas) en voie de disparition de l'estuaire du Saint-Laurent (ESL). Cependant, l'accumulation de nombreux groupes de contaminants préoccupants est encore inconnue chez le béluga de l'ESL. L'objectif de cette étude était d'étudier l'occurrence et les tendances temporelles (2000-2017) des antioxydants phénoliques synthétiques (ASP), des amines aromatiques secondaires (Ar-SA), des stabilisants UV benzotriazole (BZT-UV) et des filtres UV organiques (UVF). ) dans la graisse (n = 69) et le foie (n = 80) des carcasses de béluga de l'ESL récupérées dans l'ESL. Le SPA 2,6-di-tert-butyl-1,4-benzoquinone (BHTQ) était le contaminant le plus répandu dans la graisse (fréquence de détection : 86 % ; médiane : 71,1 ng/g poids humide (ww)) et le foie (50 % ; 12,2 ng/g poids humide) de bélugas de l'ESL. Dans le petit lard, 2-hydroxy-4-méthoxybenzophénone (BP3) (36 % ; 3,15 ng/g poids humide) et 2-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tétraméthylbutyle )phénol (UV329) (49 % ; 6,84 ng/g poids humide) étaient respectivement les UVF et les UV-BZT les plus fréquemment détectés. Les Ar-SA n'ont pas été détectés dans la plupart des échantillons de graisse et de foie. La graisse a accumulé des niveaux plus élevés de BHTQ et d'UV329 que le foie, alors que les niveaux de BP3 étaient plus élevés dans le foie. Les bélugas mâles de l'ESL ont accumulé de plus grandes concentrations d'UV329 dans la graisse que les femelles. Ces résultats indiquent que l'accumulation de BHTQ, d'UV329 et de BP3 chez les bélugas de l'ESL est spécifique au tissu et au sexe. Le BHTQ a montré une tendance à la baisse dans la graisse (2000-2017) des bélugas mâles de l'ESL, alors qu'aucune tendance significative de ce contaminant n'a été trouvée chez les femelles. UV329 n'a montré aucune tendance temporelle discernable. Cette étude a établi une base de référence pour la surveillance future des SPA, des Ar-SA, des BZT-UV et des UVF chez les bélugas et d'autres mammifères marins. -- Mot(s) clé(s) en français : Antioxydants phénoliques synthétiques, Amines aromatiques secondaires, Stabilisateurs UV de benzotriazole, Filtres UV organiques, Béluga, Estuaire du Saint-Laurent. -- ABSTRACT : Elevated contaminant exposure has been identified as a stressor that has negative impacts on the health and recovery of the endangered St. Lawrence Estuary (SLE) beluga (Delphinapterus leucas) population. However, the accumulation of many groups of contaminants of emerging concern is still unknown in the SLE beluga. The objective of this study was to investigate the occurrence and temporal trends (2000-2017) of synthetic phenolic antioxidants (SPAs), secondary aromatic amines (Ar-SAs), benzotriazole UV stabilizers (BZT-UVs), and organic UV filters (UVFs) in the blubber (n = 69) and liver (n = 80) of SLE beluga carcasses recovered in the SLE. The SPA 2,6-di-tert-butyl-1,4-benzoquinone (BHTQ) was the most prevalent contaminant in the blubber (detection frequency: 86%; median: 71.1 ng/g wet weight (ww)) and liver (50%; 12.2 ng/g ww) of SLE belugas. In the blubber, 2-hydroxy-4-methoxybenzophenone (BP3) (36%; 3.15 ng/g ww) and 2-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethyl butyl)phenol (UV329) (49%; 6.84 ng/g ww) were the most frequently detected UVFs and BZT-UVs, respectively. Ar-SAs were not detected in most of the blubber and liver samples. Blubber accumulated higher levels of BHTQ and UV329 than liver, whereas the levels of BP3 was greater in the liver. Male SLE belugas accumulated greater concentrations of UV329 in blubber compared to females. These results indicated that the accumulation of BHTQ, UV329 and BP3 in SLE belugas is tissue- and sex-specific. BHTQ showed a decreasing trend in the blubber (2000-2017) of male SLE belugas, whereas no significant trend of this contaminant was found in females. UV329 showed no discernible temporal trend. This study established a baseline for the future monitoring of SPAs, Ar-SAs, BZT-UVs and UVFs in belugas and other marine mammals. -- Mot(s) clé(s) en anglais : Synthetic phenolic antioxidants, Secondary aromatic amines, Benzotriazole UV stabilizers, Organic UV filters, Beluga, St. Lawrence Estuary

Evaluation de la qualité des zones de production conchylicole. Département : Loire-Atlantique. Edition 2016

Après un rappel des objectifs, du fonctionnement et de la méthode d’interprétation des résultats du réseau de contrôle microbiologique REMI et du réseau de surveillance chimique ROCCH, ce rapport décrit le programme annuel du département de Loire-Atlantique. Il présente l’ensemble des résultats obtenus en 2015, en particulier l’estimation de la qualité microbiologique et chimique des zones de production de coquillages classées. Les classements sanitaires arrêtés le 17 décembre 2015 sont concordants avec la qualité microbiologique estimée sur l’ensemble des zones, sauf pour « le traict de Pen Bé » groupe 2, « La Prée » groupe 3, le « Nord de la baie de Bourgneuf » groupe 3 et « Le Traict du Croisic » groupe 2. Le dispositif d’alerte a été déclenché à neuf reprises en 2015 : six faisaient suite à des épisodes de contamination détectée sur les zones de production. Une alerte renforcée (niveau 2) a été activée suite à la persistance de la contamination. La répartition des résultats acquis sur les trois dernières années ne permet pas cette année d’alléger la surveillance. La raréfaction et la difficulté d’accès à la ressource sur le gisement de palourde de « Saint Brévin » n’ont pas permis d’assurer un échantillonnage mensuel. De même l’absence d’exploitation et/ou d’échantillons de la part de la profession entraîne l’absence de résultat sur trois zones de production (Branly, Banc de Mindin et Estuaire Loire)

DEPARTEMENT DES SCIENCES DES ALIMENTS ET DE NUTRITION

à la Faculté des études supérieures de l&apos;Université Laval dans le cadre du programme de doctorat en nutrition pour l&apos;obtention du grade de Philosophiae doctor (Ph.D.