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- Reker, D., et al.
(author)
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Sprifermin (rhFGF18) versus vehicle induces a biphasic process of extracellular matrix remodeling in human knee OA articular cartilage ex vivo
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Sprifermin, recombinant human fibroblast growth factor 18 (rhFGF18), induces cartilage regeneration in knees of patients with osteoarthritis (OA). We hypothesized that a temporal multiphasic process of extracellular matrix (ECM) degradation and formation underlie this effect. We aimed to characterize the temporal ECM remodeling of human knee OA articular cartilage in response to sprifermin treatment. Articular cartilage explants from patients with knee OA (npatients = 14) were cultured for 70 days, with permanent exposure to sprifermin (900, 450, 225 ng/mL), FGF18 (450 ng/mL), insulin-like growth factor-1 (100 ng/mL, positive control) or vehicle (nreplicates/treatment/patient = 2). Metabolic activity (AlamarBlue) and biomarkers of type IIB collagen (PIIBNP) formation (Pro-C2 enzyme-linked immunosorbent assay [ELISA]) and aggrecanase-mediated aggrecan neo-epitope NITEGE (AGNx1 ELISA) were quantified once a week. At end of culture (day 70), gene expression (quantitative reverse transcription polymerase chain reaction) and proteoglycan content (Safranin O/Fast green staining) were quantified. The cartilage had continuously increased metabolic activity, when treated with sprifermin/FGF18 compared to vehicle. During days 7–28 PIIBNP was decreased and NITEGE was increased, and during days 35–70 PIIBNP was increased. At end of culture, the cartilage had sustained proteoglycan content and relative expression of ACAN < COL2A1 < SOX9 < COL1A1, indicating that functional chondrocytes remained in the explants. Sprifermin induces a temporal biphasic cartilage remodeling in human knee OA articular cartilage explants, with early-phase increased aggrecanase activity and late-phase increased type II collagen formation.
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- Legouis, D., et al.
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Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality
- 2020
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In: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:8
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Journal article (peer-reviewed)abstract
- Acute kidney injury (AKI) is strongly associated with mortality, independently of its cause. The kidney contributes to up to 40% of systemic glucose production by gluconeogenesis during fasting and under stress conditions. Whether kidney gluconeogenesis is impaired during AKI and how this might influence systemic metabolism remain unknown. Here we show that glucose production and lactate clearance are impaired during human and experimental AKI by using renal arteriovenous catheterization in patients, lactate tolerance testing in mice and glucose isotope labelling in rats. Single-cell transcriptomics reveal that gluconeogenesis is impaired in proximal tubule cells during AKI. In a retrospective cohort of critically ill patients, we demonstrate that altered glucose metabolism during AKI is a major determinant of systemic glucose and lactate levels and is strongly associated with mortality. Thiamine supplementation increases lactate clearance without modifying renal function in mice with AKI, enhances glucose production by renal tubular cells ex vivo and is associated with reduced mortality and improvement of the metabolic pattern in a retrospective cohort of critically ill patients with AKI. This study highlights an unappreciated systemic role of renal glucose and lactate metabolism under stress conditions, delineates general mechanisms of AKI-associated mortality and introduces a potential intervention targeting metabolism for a highly prevalent clinical condition with limited therapeutic options.
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- Margot-Cattin, I, et al.
(author)
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Visiting Out-of-Home Places When Living With Dementia: A Cross-Sectional Observational Study: Visiter des lieux hors du domicile lorsque l'on vit avec une démence: étude transversale observationnelle
- 2021
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In: Canadian journal of occupational therapy. Revue canadienne d'ergotherapie. - : SAGE Publications. - 1911-9828. ; 88:2, s. 131-141
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Journal article (peer-reviewed)abstract
- Persons living with dementia face a reduction of their life space outside home and disengagement from participation, linked to places visited. Purpose. This study explored stability and change in perceived participation in places visited outside home and its relationship with occupational gaps among older adults. Method. Older adults living with ( n = 35) or without ( n = 35) dementia were interviewed using the Participation in ACTivities and Places OUTside Home (ACT-OUT) questionnaire and the Occupational Gaps Questionnaire (OGQ). Data analysis used descriptive and inferential statistics. Findings. The group of people living with dementia reported significantly fewer places ( p < .001) visited than the comparison group and having abandoned more places visited ( p < .001) than the comparison group. The number of occupational gaps was significantly different between groups ( p < .001). Implications. Participation outside home is not influenced in a uniform and straightforward way for persons living with dementia; the shrinking world effect appears differently in relation to types of places.
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