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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 3. |
- Gong, Y., et al.
(författare)
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Cytochrome P450 Oxidase 2C Inhibition Adds to-3 Long-Chain Polyunsaturated Fatty Acids Protection Against Retinal and Choroidal Neovascularization
- 2016
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Ingår i: Arteriosclerosis Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 36:9, s. 1919-1927
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Tidskriftsartikel (refereegranskat)abstract
- Objective Pathological ocular neovascularization is a major cause of blindness. Increased dietary intake of -3 long-chain polyunsaturated fatty acids (LCPUFA) reduces retinal neovascularization and choroidal neovascularization (CNV), but -3 LCPUFA metabolites of a major metabolizing pathway, cytochrome P450 oxidase (CYP) 2C, promote ocular pathological angiogenesis. We hypothesized that inhibition of CYP2C activity will add to the protective effects of -3 LCPUFA on neovascular eye diseases. Approach and Results The mouse models of oxygen-induced retinopathy and laser-induced CNV were used to investigate pathological angiogenesis in the retina and choroid, respectively. The plasma levels of -3 LCPUFA metabolites of CYP2C were determined by mass spectroscopy. Aortic ring and choroidal explant sprouting assays were used to investigate the effects of CYP2C inhibition and -3 LCPUFA-derived CYP2C metabolic products on angiogenesis ex vivo. We found that inhibition of CYP2C activity by montelukast added to the protective effects of -3 LCPUFA on retinal neovascularization and CNV by 30% and 20%, respectively. In CYP2C8-overexpressing mice fed a -3 LCPUFA diet, montelukast suppressed retinal neovascularization and CNV by 36% and 39% and reduced the plasma levels of CYP2C8 products. Soluble epoxide hydrolase inhibition, which blocks breakdown and inactivation of CYP2C -3 LCPUFA-derived active metabolites, increased oxygen-induced retinopathy and CNV in vivo. Exposure to selected -3 LCPUFA metabolites of CYP2C significantly reversed the suppression of both angiogenesis ex vivo and endothelial cell functions in vitro by the CYP2C inhibitor montelukast. Conclusions Inhibition of CYP2C activity adds to the protective effects of -3 LCPUFA on pathological retinal neovascularization and CNV.
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- Kinsman, John, et al.
(författare)
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A model for promoting physical activity among rural South African adolescent girls
- 2015
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Ingår i: Global Health Action. - : Co-Action Publishing. - 1654-9716 .- 1654-9880. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In South Africa, the expanding epidemic of non-communicable diseases is partly fuelled by high levels of physical inactivity and sedentary behaviour. Women especially are at high risk, and interventions promoting physical activity are urgently needed for girls in their adolescence, as this is the time when many girls adopt unhealthy lifestyles.OBJECTIVE: This qualitative study aimed to identify and describe facilitating factors and barriers that are associated with physical activity among adolescent girls in rural, north-eastern South Africa and, based on these, to develop a model for promoting leisure-time physical activity within this population.DESIGN: The study was conducted in and around three secondary schools. Six focus group discussions were conducted with adolescent girls from the schools, and seven qualitative interviews were held with sports teachers and youth leaders. The data were subjected to thematic analysis.RESULTS: Seven thematic areas were identified, each of which was associated with the girls' self-reported levels of physical activity. The thematic areas are 1) poverty, 2) body image ideals, 3) gender, 4) parents and home life, 5) demographic factors, 6) perceived health effects of physical activity, and 7) human and infrastructural resources. More barriers to physical activity were reported than facilitating factors.CONCLUSIONS: Analysis of the barriers found in the different themes indicated potential remedial actions that could be taken, and these were synthesised into a model for promoting physical activity among South African adolescent girls in resource-poor environments. The model presents a series of action points, seen both from the 'supply-side' perspective (such as the provision of resources and training for the individuals, schools, and organisations which facilitate the activities) and from the 'demand-side' perspective (such as the development of empowering messages about body image for teenage girls, and encouraging more parental involvement). The development of physical activity interventions that incorporate this supply- and demand-side model would represent an additional tool for ongoing efforts aimed at tackling the expanding non-communicable disease epidemic in South Africa, and in other resource-constrained settings undergoing rapid health transitions.
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| 5. |
- Lundby, Carsten, et al.
(författare)
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Physiological, biochemical, anthropometric, and biomechanical influences on exercise economy in humans
- 2017
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Ingår i: Scandinavian Journal of Medicine & Science in Sports. - : Wiley. - 0905-7188. ; 27:12, s. 1627-1637
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Tidskriftsartikel (refereegranskat)abstract
- Interindividual variation in running and cycling exercise economy (EE) remains unexplained although studied for more than a century. This study is the first to comprehensively evaluate the importance of biochemical, structural, physiological, anthropometric, and biomechanical influences on running and cycling EE within a single study. In 22 healthy males (VO(2)max range 45.5-72.1mLmin-1kg-1), no factor related to skeletal muscle structure (% slow-twitch fiber content, number of capillaries per fiber), mitochondrial properties (volume density, oxidative capacity, or mitochondrial efficiency), or protein content (UCP3 and MFN2 expression) explained variation in cycling and running EE among subjects. In contrast, biomechanical variables related to vertical displacement correlated well with running EE, but were not significant when taking body weight into account. Thus, running EE and body weight were correlated (R-2=.94; P<.001), but was lower for cycling EE (R-2=.23; P<.023). To separate biomechanical determinants of running EE, we contrasted individual running and cycling EE considering that during cycle ergometer exercise, the biomechanical influence on EE would be small because of the fixed movement pattern. Differences in cycling and running exercise protocols, for example, related to biomechanics, play however only a secondary role in determining EE. There was no evidence for an impact of structural or functional skeletal muscle variables on EE. Body weight was the main determinant of EE explaining 94% of variance in running EE, although more than 50% of the variability of cycling EE remains unexplained.
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| 6. |
- Montero, D., et al.
(författare)
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Sexual dimorphism of substrate utilization: Differences in skeletal muscle mitochondrial volume density and function
- 2018
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670. ; 103:6, s. 851-859
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Tidskriftsartikel (refereegranskat)abstract
- Fat oxidation during exercise is greater in females than in males. We sought to determine whether sex differences in substrate metabolism are paralleled by distinct skeletal muscle mitochondrial volume density and oxidative capacity. Whole-body substrate (fat and carbohydrate) utilization during submaximal treadmill running was assessed, and skeletal muscle biopsies were taken to determine mitochondrial volume density and function in healthy young females (n=12) and males (n=12) matched by aerobic exercise capacity and exercise performance. Females presented a lower respiratory exchange ratio (0.87 +/- 0.04 versus 0.91 +/- 0.04, P=0.023) and whole-body carbohydrate oxidation (27.8 +/- 8.3 versus 35.8 +/- 6.5mgkg(-1)min(-1), P=0.027), whereas fat oxidation was higher (8.7 +/- 2.8 versus 5.9 +/- 2.6mgkg(-1)min(-1), P=0.034) during submaximal exercise compared with males. In skeletal muscle biopsies, females demonstrated augmented mitochondrial volume density (7.51 +/- 1.77 versus 5.90 +/- 1.72%, P=0.035) and oxidative capacity for fatty acid [36.6 +/- 12.8 versus 24.5 +/- 7.3pmol O(2)s(-1)(mg wet weight)(-1), P=0.009] and lactate [71.1 +/- 24.4 versus 53.2 +/- 14.6pmol O(2)s(-1)(mg wet weight)(-1), P=0.040]. No sex differences in respiratory exchange ratio, whole-body fat oxidation and skeletal muscle variables were detected when adjusted for anthropometric variables including body mass or leg mass, which were lower in females. In conclusion, female prioritization of fat over carbohydrate oxidation during exercise is underpinned by augmented body size-related mitochondrial volume density, fatty acid and lactate oxidative capacity in skeletal muscle fibres.
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