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Bonnelye E.,French Institute of Health and Medical Research | Reboul P.,Hospitalier Of Luniversite Of Montreal | Reboul P.,French National Center for Scientific Research | Duval N.,Pavillon des Charmilles | And 2 more authors.
Arthritis and Rheumatism | Year: 2011

Objective We reported previously that the orphan nuclear receptor, estrogen receptor-related receptor α (ERRα), is expressed in articular chondrocytes and is dysregulated in a mouse model of inflammatory arthritis. The aim of this study, therefore, was to determine whether ERRα is also dysregulated in patients with osteoarthritis (OA). Methods ERRα messenger RNA (mRNA) and protein were quantified in normal and OA cartilage samples and in OA chondrocytes in vitro, with and without short-term treatment with a variety of OA-associated factors and signaling pathway agonists and inhibitors. Results ERRα expression was lower in OA than in normal articular cartilage. Interleukin-1β (IL-1β) markedly up-regulated ERRα expression in OA chondrocytes in vitro, and agonist or inhibitor treatment indicated that the up-regulation was dependent on cyclooxygenase 2 (COX-2; NS398), prostaglandin E2, cAMP (8-bromo-cAMP), and protein kinase A (PKA; KT5720). Treatment with the ERRα inverse agonist XCT790 decreased the expression of SOX9 and the up-regulation of ERRα by IL-1β, suggesting autoregulation of ERRα in the IL-1β pathway. Matrix metalloproteinase 13 (MMP-13) expression was also decreased by treatment with XCT790 plus IL-1β versus IL-1β alone, and the down-regulation of MMP-13 mRNA and protein observed with XCT790 alone suggests that the up-regulation of MMP-13 by IL-1β is ERRα-dependent. Conclusion We report the first evidence that ERRα expression is regulated by IL-1β in COX-2-, cAMP-, and PKA-dependent pathways in OA chondrocytes. We confirmed that SOX9 is an ERRα target gene in human, as in rodent, chondrocytes and identified MMP-13 as a potential new target gene, which suggests that ERRα may both respond to the healing signal and contribute to extracellular degradation in OA cartilage. Copyright © 2011 by the American College of Rheumatology. Source

Pausova Z.,University of Nottingham | Pausova Z.,Hospitalier Of Luniversite Of Montreal | Abrahamowicz M.,Montreal Neurological Institute | Mahboubi A.,Montreal Neurological Institute | And 7 more authors.
Hypertension | Year: 2010

Intra-abdominal accumulation of fat is a hallmark of male body-fat distribution and a major risk factor for hypertension. Sympathoactivation may be one of the mechanisms linking intra-abdominal obesity to hypertension. The aim of the present study was to investigate whether a functional variation in the androgen-receptor gene (AR, a variable number of CAG repeats in exon 1) is associated with intra-abdominal adiposity, sympathetic modulation of vasomotor tone, and blood pressure in adolescent boys but not girls. We studied 223 boys and 259 girls (age 12 to 18 years) from a French-Canadian founder population. Intra-abdominal fat and subcutaneous-abdominal fat were quantified with an MRI. Blood pressure was recorded beat-to-beat during an hour-long protocol including physical and mental challenges, and these blood pressure time series were used to assess sympathetic modulation of vasomotor tone by power spectral analysis. The results showed that boys with a "low" versus " intermediate" or "high" CAG-repeat number in AR demonstrated higher intra-abdominal fat (by 28% and 48%, respectively) but not subcutaneous-abdominal fat. These intra-abdominal fat differences remained significant after adjusting for serum levels of sex hormones and subcutaneous-abdominal fat. Furthermore, boys with low versus intermediate or high CAG-repeat numbers also showed higher blood pressure, with the differences being most pronounced during mental stress (8.0 and 8.5 mm Hg, respectively) and higher sympathetic modulation of vasomotor tone. As expected, no such differences were seen among girls. In adolescent boys, low CAG-repeat numbers in AR may be a genetic risk factor for intra-abdominal obesity and hypertension; sympathoactivation may be an underlying link between the 2 conditions. Copyright © 2010 American Heart Association. All rights reserved. Source

Weghofer A.,Medical University of Vienna | Weghofer A.,The Center for Human Reproduction | Himaya E.,Hospitalier Of Luniversite Of Montreal | Kushnir V.A.,The Center for Human Reproduction | And 4 more authors.
Reproductive Biology and Endocrinology | Year: 2015

Background: Women with hyper-and hypothyroidism are at increased risk for infertility and adverse pregnancy outcomes. Whether in women considered euthyroid thyroid function (TSH values) and thyroid autoimmunity (thyroid antibodies) influence in vitro fertilization (IVF) cycle outcome has, however, remained controversial. Any such effect should be easily visible in women with low functional ovarian reserve (LFOR) and thus small oocyte and embryo numbers. Methods: We evaluated the relationship between TSH levels and embryo quality in euthyroid women with LFOR undergoing IVF. Mean age for the study population was 39.9 ± 4.6 years. Embryo quality was assessed in 431 embryos from 98 first IVF cycles according to TSH levels (with cut-off 2.5μIU/mL), and to presence versus absence of thyroid autoantibodies. Results: Mean Anti Mullerian hormone (AMH) was 0.8 ± 0.8 ng/mL and mean TSH was 1.8 ± 0.9 μIU/mL. Comparable embryo quality was observed in women with TSH ≤ and >2.5μIU/mL. TPO antibodies significantly affected embryo quality in women with low-normal TSH levels (P = 0.045). In women with high-normal TSH levels, increasing TSH had a negative impact on embryo quality (P = 0.027). A trend towards impaired embryo quality with TPO antibodies was also observed in these patients (p = 0.057). Conclusions: TPO antibodies affect embryo quality in euthyroid women with low-normal TSH ≤2.5 μIU/mL. In women with high-normal TSH levels, increasing TSH levels, and possibly TPO antibodies, appear to impair embryo quality. These results suggest that the negative impact of thyroid autoimmunity becomes apparent, once thyroid hormone function is optimized. © 2015 Weghofer et al.; licensee BioMed Central. Source

Ferguson R.,McGill University | Ramanakumar A.V.,McGill University | Richardson H.,Queens University | Tellier P.-P.,McGill University | And 4 more authors.
Human Immunology | Year: 2011

Human leukocyte antigen (HLA)-E and HLA-G molecules act as powerful modulators of innate and adaptive immune responses. The study examined whether HLA-E and/or HLA-G polymorphisms are associated with human papillomavirus (HPV) infection susceptibility and persistence in 636 female university students in Montreal. HLA-G*01:01:02 and HLA-G*01:01:08 alleles were associated with increased risk of HPV-16 (odds ratio (OR) = 2.10, 95% confidence interval (CI), 1.11-3.96) and any infections with HPV types from α species 1, 8, 10, and 13 (OR = 2.72, 95% CI, 1.11-6.68). HLA-G*01:01:02 and HLA-G*01:03 alleles were associated with persistent HPV-16 (OR = 2.07, 95% CI, 1.16-3.68) and persistent infections with HPV types from α species 2, 3, 4, and 15 (OR = 2.99, 95% CI, 1.12-8.00). HLA-E polymorphism was not associated with risk of acquisition or persistence of HPV infection. These results suggest that HLA-G molecules may play a role in mediating HPV infection risk. © 2011 American Society for Histocompatibility and Immunogenetics. Source

Vela C.,Hopital Maisonneuve Rosemont Recherche Ophtalmologie | Samson E.,Hopital Maisonneuve Rosemont Recherche Ophtalmologie | Zunzunegui M.V.,Hospitalier Of Luniversite Of Montreal | Haddad S.,Hospitalier Of Luniversite Of Montreal | And 3 more authors.
BMC Ophthalmology | Year: 2012

Background: The risk of visual impairment increases dramatically with age and therefore older adults should have their eyes examined at least every 1 to 2 years. Using a world-wide, population-based dataset, we sought to determine the frequency that older people had their eyes examined. We also examined factors associated with having a recent eye exam. Methods. The World Health Surveys were conducted in 70 countries throughout the world in 2002-2003 using a random, multi-stage, stratified, cluster sampling design. Participants 60 years and older from 52 countries (n = 35,839) were asked "When was the last time you had your eyes examined by a medical professional?". The income status of countries was estimated using gross national income per capita data from 2003 from the World Bank website. Prevalence estimates were adjusted to account for the complex sample design. Results: Overall, only 18% (95% CI 17, 19) of older adults had an eye exam in the last year. The rate of an eye exam in the last year in low, lower middle, upper middle, and high income countries was 10%, 24%, 22%, and 37% respectively. Factors associated with having an eye exam in the last year included older age, female gender, more education, urban residence, greater wealth, worse self-reported health, having diabetes, and wearing glasses or contact lenses (p < 0.05). Conclusions: Given that older adults often suffer from age-related but treatable conditions, they should be seen on a regular basis to prevent visual impairment and its disabling consequences. © 2012 Vela et al; licensee BioMed Central Ltd. Source

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