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- Gustafsson, Susanne, et al.
(författare)
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Health-promoting interventions for persons aged 80 and older are successful in the short term-results from the randomized and three-armed elderly persons in the risk zone study
- 2012
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Ingår i: Journal of The American Geriatrics Society. - : John Wiley & Sons. - 0002-8614 .- 1532-5415. ; 60:3, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo examine the outcomes of the Elderly Persons in the Risk Zone study, which was designed to evaluate whether it is possible to delay deterioration if a health-promoting intervention is made when an older adult (≥80) is at risk of becoming frail and whether a multiprofessional group intervention is more effective in delaying deterioration than a single preventive home visit with regard to frailty, self-rated health, and activities of daily living (ADLs) at 3-month follow-up.DesignRandomized, three-armed, single-blind, controlled trial performed between November 2007 and May 2011.SettingTwo urban districts of Gothenburg, Sweden.ParticipantsFour hundred fifty-nine community-living adults aged 80 and older not dependent on the municipal home help service.InterventionA preventive home visit or four weekly multiprofessional senior group meetings with one follow-up home visit.MeasurementsChange in frailty, self-rated health, and ADLs between baseline and 3-month follow-up.ResultsBoth interventions delayed deterioration of self-rated health (odds ratio (OR) = 1.99, 95% confidence interval (CI) = 1.12-3.54). Senior meetings were the most beneficial intervention for postponing dependence in ADLs (OR = 1.95, 95% CI = 1.14-3.33). No effect on frailty could be demonstrated.ConclusionHealth-promoting interventions made when older adults are at risk of becoming frail can delay deterioration in self-rated health and ADLs in the short term. A multiprofessional group intervention such as the senior meetings described seems to have a greater effect on delaying deterioration in ADLs than a single preventive home visit. Further research is needed to examine the outcome in the long term and in different contexts.
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- Ahlin, Sofie, 1985, et al.
(författare)
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Adipose Tissue-Derived Human Serum Amyloid A Does Not Affect Atherosclerotic Lesion Area in hSAA(+/) (-/)ApoE(-/-) Mice
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Chronically elevated serum levels of serum amyloid A (SAA) are linked to increased risk of cardiovascular disease. However, whether SAA is directly involved in atherosclerosis development is still not known. The aim of this study was to investigate the effects of adipose tissue-derived human SAA on atherosclerosis in mice. hSAA1(+/-) transgenic mice (hSAA1 mice) with a specific expression of human SAA1 in adipose tissue were bred with ApoE-deficient mice. The hSAA1 mice and their wild type (wt) littermates were fed normal chow for 35 weeks. At the end of the experiment, the mice were euthanized and blood, gonadal adipose tissue and aortas were collected. Plasma levels of SAA, cholesterol and triglycerides were measured. Atherosclerotic lesion areas were analyzed in the aortic arch, the thoracic aorta and the abdominal aorta in en face preparations of aorta stained with Sudan IV. The human SAA protein was present in plasma from hSAA1 mice but undetectable in wt mice. Similar plasma levels of cholesterol and triglycerides were observed in hSAA1 mice and their wt controls. There were no differences in atherosclerotic lesion areas in any sections of the aorta in hSAA1 mice compared to wt mice. In conclusion, our data suggest that adipose tissue-derived human SAA does not influence atherosclerosis development in mice.
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- Fagman, Johan Bourghardt, 1980, et al.
(författare)
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Androgen receptor-dependent and independent atheroprotection by testosterone in male mice.
- 2010
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 151:11, s. 5428-37
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Tidskriftsartikel (refereegranskat)abstract
- The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P < 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P < 0.001) and ARKO mice (by 24%, P < 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P < 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P < 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.
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- Gustafsson, Susanne, et al.
(författare)
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Long-term outcome for ADL following the health-promoting RCT-Elderly persons in the risk zone
- 2013
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Ingår i: The Gerontologist. - : Oxford University Press. - 0016-9013 .- 1758-5341. ; 53:4, s. 654-663
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine independence in activities of daily living (ADL) at the 1- and 2-year followups of the health-promoting study Elderly Persons in the Risk Zone. Design and Method: A randomized, three-armed, single-blind, and controlled study. A representative sample of 459 independent and community-dwelling older adults, 80 years and older, were included. A preventive home visit was compared with four weekly multiprofessional senior group meetings including a follow-up home visit. Results: Analysis showed a significant difference in favor of the senior meetings in postponing dependence in ADL at the 1-year follow-up (odds ratio [OR] = 1.92, 95% confidence interval [CI] = 1.19-3.10) and also in reducing dependence in three (OR = 0.52, 95% CI = 0.31-0.86) and four or more ADL (OR = 0.40, 95% CI = 0.22-0.72) at the 2-year follow-up. A preventive home visit reduced dependence in two (OR = 0.40, 95% CI = 0.24-0.68) and three or more ADL (OR = 0.37, 95% CI = 0.17-0.80) after 1 year. Implications: A long-term evaluation of Elderly Persons in the Risk Zone showed that both senior meetings and a preventive home visit reduced the extent of dependence in ADL after 1 year. The senior meetings were superior to a preventive home visit since additional significant effects were seen after 2 years. To further enhance the long-term effects of the senior meetings and support the process of self-change in health behavior, it is suggested that booster sessions might be a good way of reinforcing the intervention.
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- Lee, Po-Shun, et al.
(författare)
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mTORC1-S6K activation by endotoxin contributes to cytokine up-regulation and early lethality in animals.
- 2010
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- mTORC1 (mammalian target of rapamycin complex 1) activation has been demonstrated in response to endotoxin challenge, but the mechanism and significance are unclear. We investigated the effect of mTORC1 suppression in an animal model of endotoxemia and in a cellular model of endotoxin signaling.Mice were treated with the mTORC1 inhibitor rapamycin or vehicle prior to lethal endotoxin challenge. Mortality and cytokine levels were assessed. Cultured macrophage-like cells were challenged with endotoxin with or without inhibitors of various pathways known to be upstream of mTORC1. Activated pathways, including downstream S6K pathway, were assessed by immunoblots. We found that mTORC1-S6K suppression by rapamycin delayed mortality of mice challenged with lethal endotoxin, and was associated with dampened circulating levels of VEGF, IL-1β, IFN-γ and IL-5. Furthermore, in vitro cellular studies demonstrated that LPS (lipopolysaccharide) activation of mTORC1-S6K still occurs in the presence of PI3K-Akt inhibition alone, but can be suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways.We conclude that cellular activation of mTORC1-S6K contributes to cytokine up-regulation and mortality in response to endotoxin, and may occur via multiple pathways.
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- Stubelius, Alexandra, 1983, et al.
(författare)
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Sexual dimorphisms in the immune system of catechol-O-methyltransferase knockout mice
- 2012
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985. ; 217:8, s. 751-760
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Tidskriftsartikel (refereegranskat)abstract
- The enzyme catechol-O-methyltransferase (COMT) is part of the metabolic pathway of 17 beta-estradiol, converting 2-hydroxyestradiol to 2-methoxyestradiol. We recently showed that administration of the COMT product 2-methoxyestradiol has anti-inflammatory and anti-osteoporotic effects. We have now investigated whether COMT affects the immune system, by immunologically phenotyping COMT deficient (COMT-/-) mice. Immunoglobulin production, T lymphocyte proliferation, NK cell cytotoxicity and oxygen radical production were assessed. In male COMT-/--mice, the total number of T-, and B-lymphocytes from spleen increased but the T-cell proliferative response decreased. The NK cell population shifted toward less mature cells, leaving cytotoxic capacity unaffected. In COMT-/--females, a higher frequency of neutrophils was found but the oxygen radical production was unaltered. In conclusion, only minor changes of the immune system were seen in COMT deficient mice, and the changes were usually seen in males. This study provides clues into how COMT activity, and hence gender differences, affects the immune system. (c) 2012 Elsevier GmbH. All rights reserved.
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- Wilhelmson, Anna S K, et al.
(författare)
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Catechol-O-methyltransferase is dispensable for vascular protection by estradiol in mouse models of atherosclerosis and neointima formation.
- 2011
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 152:12, s. 4683-90
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Tidskriftsartikel (refereegranskat)abstract
- Estradiol is converted to the biologically active metabolite 2-methoxyestradiol via the activity of the enzyme catechol-O-methyltransferase (COMT). Exogenous administration of both estradiol and 2-methoxyestradiol reduces experimental atherosclerosis and neointima formation, and COMT-dependent formation of 2-methoxyestradiol likely mediates the antimitogenic effect of estradiol on smooth muscle cells in vitro. This study evaluated whether 2-methoxyestradiol mediates the vasculoprotective actions of estradiol in vivo. Wild-type (WT) and COMT knockout (COMTKO) mice on an apolipoprotein E-deficient background were gonadectomized and treated with estradiol or placebo. Exogenous estradiol reduced atherosclerotic lesion formation in both females (WT, -78%; COMTKO, -82%) and males (WT, -48%; COMTKO, -53%) and was equally effective in both genotypes. We further evaluated how exogenous estradiol affected neointima formation after ligation of the carotid artery in ovariectomized female mice; estradiol reduced intimal hyperplasia to a similar extent in both WT (-80%) and COMTKO (-77%) mice. In ovarian-intact female COMTKO mice, atherosclerosis was decreased (-25%) compared with WT controls. In conclusion, the COMT enzyme is dispensable for vascular protection by exogenous estradiol in experimental atherosclerosis and neointima formation in vivo. Instead, COMT deficiency in virgin female mice with intact endogenous production of estradiol results in relative protection against atherosclerosis.
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