Liver-Specific Knockdown of IGF-1 Decreases Vascular Oxidative Stress Resistance by Impairing the Nrf2-Dependent Antioxidant Response: A Novel Model of Vascular Aging

Sammanfattning Syfte och frågeställningar. Studiens syfte var att ta reda på om det finns ett signifikant samband mellan 5-minuters pyramidtest (5MPT) och ett maximalt syreupptagningstest (VO2max) på löpband hos en gymnasieklass på samhällsvetenskapsprogrammet. Frågeställningarna var - Vilka är resultaten vid 5MPT och uppmätt VO2max med direkt syrgasmätning vid maxtest på löpband? - Hur stark är korrelationen mellan dessa två olika varianter av aeroba tester? - Föreligger en skillnad mellan första och andra testtillfället i power vid 5MPT och i så fall hur stor är denna skillnad? Då liknande studier har genomförts på mer vältränade grupper av gymnasielever och yngre vuxna är det nu intressant att se om testerna korrelerar signifikant även för denna grupp som inte alla har ett gemensamt specifikt intresse för fysisk aktivitet. Om en god korrelation erhålls är det möjligt att dra slutsatsen att 5-minuters pyramidtest (5MPT) kan användas för dessa gymnasielever i skolan och även på motsvarande grupper i andra hälsosammanhang för att mäta och följa den aeroba förmågan. Metod. I studien deltog 17 personer, varav 12 kvinnor och 5 män, i åldrarna 16-18 år. Deltagarna gick på Värmdö gymnasium på samhällsvetenskapsprogrammet. Sammanlagt två separata tester utfördes av 5MPT och ett maximalt syreupptagningstest på löpband med direkt syrgasmätning. Varje test utfördes med minst två dagars mellanrum och alla tester gjordes inom en månad. Vid 5MPT förflyttar sig individen så snabbt som möjligt över en pyramidformad trappramp, med högsta höjd 0,62 m och total sträcka 5,5 m. Antal vändor registrerades under 5 minuter, varefter en formel för utvecklad effekt beräknades. Vid maximalt test på löpband analyserades utandningsluften via en on-line-utrustning Oxycon Pro. Resultat. Ett signifikant samband (r=0,90) framkom mellan power (effekt) vid 5MPT och VO2max på löpband. Ingen signifikant skillnad framkom i power mellan det första och det andra testet av 5MPT, och skillnaden mellan dessa båda tester visades vara endast 0,44%. I arbetet presenteras ekvationen för att beräkna maximal syreupptagningsförmåga för denna grupp av individer baserat på resultaten för power i 5MPT. Slutsats. Således framkom en stark korrelation mellan de två olika varianterna av undersökta aeroba tester. Ingen inlärningseffekt sågs mellan ett första och ett andra testtillfälle av 5MPT. Förhoppningen är att det relativt enkla och billiga testet 5MPT kan användas för att undersöka och följa utveckling av aerob förmåga på denna grupp av individer.Abstract Aim. The purpose of the study was to find out if there is a significant connection between 5-minute pyramid test (5MPT) and a maximum oxygen uptake test (VO2max) on a treadmill in upper secondary students in the social sciences program. The questions were - What are the results at 5MPT and in a maximal treadmill test of VO2max with direct measurement of oxygen uptake. - How strong is the correlation between these two different variants of aerobic tests? - Is there a difference in power between the first and second test times of 5MPT and if so, how great is this difference? Since similar studies have been conducted in more well-trained groups in upper secondary school and in younger adults, it is now interesting to see whether the tests correlate significantly also for this group, not all of which have a common specific interest in physical activity. If a good correlation is obtained, it is possible to conclude that 5MPT can be used for students in upper secondary schools and also in corresponding groups of individuals in other health contexts to measure the aerobic ability. Method. In the study, 17 people, of which 12 women and 5 men, participated in the ages 16-18 years. The participants attended Värmdö Gymnasium at the Social Science Program. A total of two 5MPT separate tests were performed and a maximum oxygen uptake test on a treadmill. Each test was performed at least two days apart and all tests were done within a month. In the 5MPT, the individual moves as quickly as possible over a pyramidal stair ramp, with a maximum height of 0.62 m and a total distance of 5.50 m. The number of turns was recorded for 5 minutes, after which a formula for developed effect was calculated. At the maximal treadmill test, the exhalation air was analyzed via an on-line equipment Oxycon Pro. Results. A significant relationship (r = 0.90) was found between power (power) at 5MPT and VO2max on treadmill. No significant difference was found in power between the first and second tests of 5MPT, and the difference between these two tests was shown to be only 0.44%. In this essay, the equation is presented to calculate the maximum oxygen uptake for this group of individuals based on the results for power in 5MPT. Conclusion. It is clear that there was a strong correlation between the two different variants of aerobic tests. No learning effect was seen between a first and second test opportunity of 5MPT. The hope is that the relatively simple and inexpensive 5MPT test can be used to investigate and monitor the development of aerobic ability in this group of individuals

Vasoprotective Effects of Life Span-Extending Peripubertal GH Replacement in Lewis Dwarf Rats

In humans, growth hormone deficiency (GHD) and low circulating levels of insulin-like growth factor 1 (IGF-1) significantly increase the risk for cerebrovascular disease. Genetic growth hormone (GH)/IGF-1 deficiency in Lewis dwarf rats significantly increases the incidence of late-life strokes, similar to the effects of GHD in elderly humans. Peripubertal treatment of Lewis dwarf rats with GH delays the occurrence of late-life stroke, which results in a significant extension of life span. The present study was designed to characterize the vascular effects of life span-extending peripubertal GH replacement in Lewis dwarf rats. Here, we report, based on measurements of dihydroethidium fluorescence, tissue isoprostane, GSH, and ascorbate content, that peripubertal GH/IGF-1 deficiency in Lewis dwarf rats increases vascular oxidative stress, which is prevented by GH replacement. Peripubertal GHD did not alter superoxide dismutase or catalase activities in the aorta nor the expression of Cu-Zn-SOD, Mn-SOD, and catalase in the cerebral arteries of dwarf rats. In contrast, cerebrovascular expression of glutathione peroxidase 1 was significantly decreased in dwarf vessels, and this effect was reversed by GH treatment. Peripubertal GHD significantly decreases expression of the Nrf2 target genes NQO1 and GCLC in the cerebral arteries, whereas it does not affect expression and activity of endothelial nitric oxide synthase and vascular expression of IGF-1, IGF-binding proteins, and inflammatory markers (tumor necrosis factor alpha, interluekin-6, interluekin-1β, inducible nitric oxide synthase, intercellular adhesion molecule 1, and monocyte chemotactic protein-1). In conclusion, peripubertal GH/IGF-1 deficiency confers pro-oxidative cellular effects, which likely promote an adverse functional and structural phenotype in the vasculature, and results in accelerated vascular impairments later in life