| 11. |
- Ahmad, T, et al.
(författare)
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Skeletal changes in type-2 diabetic Goto-Kakizaki rats.
- 2003
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 178:1, s. 111-6
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Tidskriftsartikel (refereegranskat)abstract
- We characterized appendicular and axial bones in rats with type-2 diabetes in five female Goto-Kakizaki (GK) rats, a strain developed from the Wistar rat showing spontaneous type-2 diabetes, and five age- and sex-matched non-diabetic Wistar rats. The humerus, tibia, metatarsals and vertebral bodies were analysed by peripheral quantitative computerized tomography (pQCT). In diabetic rats, the height of the vertebral bodies and length of the humerus were decreased while the length of the metatarsals was increased. A decreased cross-sectional area was found in the vertebral end-plate region and the tibial metaphysis. Notably, the diaphysis in all long bones showed expansion of periosteal and endosteal circumference. In tibia this resulted in increased cortical thickness, whereas in humerus and metatarsal it was unchanged. Areal moment of inertia was increased in all diaphyses suggesting greater bending strength. The most conspicuous finding in diabetic rats pertained to trabecular osteopenia. Thus, trabecular bone mineral density was significantly reduced in all bones examined, by 33-53%. Our pQCT study of axial and appendicular bones suggests that the typical feature of diabetic osteopathy in the GK rat is loss of trabecular bone and expansion of the diaphysis. The loss of metaphyseal trabecular bone if also present in diabetic patients may prove to underlie the susceptibility to periarticular fracture and Charcot arthropathy. The findings suggest that the risk of fracture in diabetes varies according to the specific sub-regions of a bone. The approach described may prove to be useful in the early detection of osteopathy in diabetic patients who may be amenable to preventive treatment.
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| 12. |
- Ahrné, Karin, et al.
(författare)
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Rödlista över fjärilar Lepidoptera
- 2015
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Ingår i: Rödlistade arter i Sverige 2015. - Uppsala : ArtDatabanken SLU. - 9789187853104 ; , s. 98-112
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Almehed, Katarina, 1966, et al.
(författare)
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Prevalence and risk factors of osteoporosis in female SLE patients-extended report
- 2007
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Ingår i: Rheumatology (Oxford). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 46:7, s. 1185-90
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine the frequency of osteoporosis and possible risk factors of low bone mineral density (BMD) in women with systemic lupus erythematous (SLE) in western Sweden. In addition, to evaluate if adequate anti-osteoporotic treatment was provided. METHODS: BMD was measured at radius, lumbar spine and hip by dual X-ray absorptiometry (DXA). An 'expected' control BMD was calculated for each patient. Simple and multiple linear regression analyses were performed to determine associations between BMD and demographic and disease-related variables. RESULTS: One hundred and sixty-three women were included. Median age was 47 (20-82) yrs, 89 (55%) were post-menopausal and 85 (52%) were taking glucocorticosteroids. BMD was significantly reduced in all measured sites compared with expected BMD. Thirty-seven (23%), 18 (11%) and 6 (4%) of the patients were osteoporotic in at least one, two and three or more measured locations. Bisphosphonates were used by 23 (27%) of patients taking glucocorticosteroids and 13 (35%) with osteoporosis. High age and low weight or BMI were associated with low BMD in all measured sites. In total hip, high SLICC/American Collage of Rheumatology (ACR), ESR and 'combinations of DMARD' were additional markers of low BMD. High S-creatinine was associated with low BMD in lumbal spine whereas high S-creatinine and CRP were markers in radius. CONCLUSION: Women with SLE are at greater risk of osteoporosis compared with controls and few are treated adequately. Factors associated with low BMD in SLE are high age and low weight but also markers of inflammation, impaired kidney function and disease damage, however glucocorticosteroids were not associated.
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| 14. |
- Almehed, Katarina, 1966, et al.
(författare)
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Prevalence and risk factors of vertebral compression fractures in female SLE patients.
- 2010
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Ingår i: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: INTRODUCTION: Our objective was to determine the frequency of and factors associated with prevalent vertebral compression fractures in female SLE patients attending rheumatologists in Western Sweden. METHODS: In this cross sectional study 150 women were included. They were examined with x-ray of thoracic and lumbar spine (Th4-L4). A reduction of at least 20% of any vertebral height, assessed by Genant's semiquantitative method, was defined as a fracture. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA). RESULTS: Median patient age was 47 years (20-82) and disease duration 11 years (1-41). Only 6 (4%) women had a history of clinical compressions whereas 43 (29%) had at least one radiological fracture each. The patients with at least one fracture at any site were characterized by higher age (p<0.001), being postmenopausal (p<0.01), higher Systemic Lupus International Collaborative Clinics Damage Index (p<0.05), lower BMD total hip and femoral neck (p<0.05), more peripheral fractures (p< 0.01), medication with bisphosphonates (p<0.05) and calcium and vitamin D3 (p<0.05). There were no significant differences regarding current or cumulative glucocorticosteroid dose between the groups. In logistic regression analyses high age remained as risk factor of at least one vertebral fracture at any site whereas low BMD in total hip was associated with vertebral fracture in lumbar spine. CONCLUSION: Radiological compression fractures are common but seldom diagnosed in SLE patients. High age and low BMD in total hip, but not in spine, was associated with vertebral fractures.
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| 15. |
- Amzaleg, Y., et al.
(författare)
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Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells
- 2018
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 183, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens attenuate bone turnover by inhibiting both osteoclasts and osteoblasts, in part through antagonizing Runx2. Apparently conflicting, stimulatory effects in osteoblast lineage cells, however, sway the balance between bone resorption and bone formation in favor of the latter. Consistent with this dualism, 17 beta-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner, and here we provide evidence for such locus specific regulation of Runx2 by E2 in vivo. We also demonstrate dual, negative and positive, regulation of Runx2-driven alkaline phosphatase (ALP) activity by increasing E2 concentrations in ST2 osteoblast progenitor cells. We further compared the effects of E2 to those of the Selective Estrogen Receptor Modulators (SERMs) raloxifene (ral) and lasofoxifene (las) and the phytoestrogen puerarin. We found that E2 at the physiological concentrations of 0.1-1 nM, as well as ral and las, but not puerarin, antagonize Runx2-driven ALP activity. At >= 10 nM, E2 and puerarin, but not ral or las, stimulate ALP relative to the activity measured at 0.1-1 nM. Contrasting the difference between E2 and SERMs in ST2 cells, they all shared a similar dose-response profile when inhibiting preosteoclast proliferation. That ral and las poorly mimic the locus-and concentration-dependent effects of E2 in mesenchymal progenitor cells may help explain their limited clinical efficacy.
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| 16. |
- Andersson, Annica, 1983, et al.
(författare)
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Roles of activating functions 1 and 2 of estrogen receptor α in lymphopoiesis.
- 2018
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Ingår i: The Journal of endocrinology. - 1479-6805. ; 236:2
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Tidskriftsartikel (refereegranskat)abstract
- Apart from the role of sex steroids in reproduction, sex steroids are also important regulators of the immune system. 17β-estradiol (E2) represses T and B cell development, but augments B cell function, possibly explaining the different nature of immune responses in men and women. Both E2 and selective estrogen receptors modulators (SERM) act via estrogen receptors (ER). Activating functions (AF)-1 and 2 of the ER bind to coregulators and thus influence target gene transcription and subsequent cellular response to ER activation. The importance of ERαAF-1 and AF-2 in the immunomodulatory effects of E2/SERM has previously not been reported. Thus, detailed studies of T and B lymphopoiesis were performed in ovariectomized E2-, lasofoxifene- or raloxifene-treated mice lacking either AF-1 or AF-2 domains of ERα, and their wild-type littermate controls. Immune cell phenotypes were analyzed with flow cytometry. All E2 and SERM-mediated inhibitory effects on thymus cellularity and thymic T cell development were clearly dependent on both ERαAFs. Interestingly, divergent roles of ERαAF-1 and ERαAF-2 in E2 and SERM-mediated modulation of bone marrow B lymphopoiesis were found. In contrast to E2, effects of lasofoxifene on early B cells did not require functional ERαAF-2, while ERαAF-1 was indispensable. Raloxifene reduced early B cells partly independent of both ERαAF-1 and ERαAF-2. Results from this study increase the understanding of the impact of ER modulation on the immune system, which can be useful in the clarification of the molecular actions of SERMs and in the development of new SERM.
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| 17. |
- Andersson, Annica, 1983, et al.
(författare)
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Selective oestrogen receptor modulators lasofoxifene and bazedoxifene inhibit joint inflammation and osteoporosis in ovariectomised mice with collagen-induced arthritis.
- 2016
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 55:3, s. 553-563
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Tidskriftsartikel (refereegranskat)abstract
- RA predominantly affects post-menopausal women and is strongly associated with development of generalised osteoporosis. To find treatments that target both joint manifestations and osteoporosis in RA is desirable. The third generation of selective oestrogen receptor modulators (SERMs) [lasofoxifene (LAS) and bazedoxifene (BZA)] are new treatment options for post-menopausal osteoporosis. The aim of this study was to investigate the effects of LAS and BZA on arthritic disease and inflammation-associated bone loss using CIA in mice.
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| 18. |
- Andersson, Annica, 1983, et al.
(författare)
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Suppression of Experimental Arthritis and Associated Bone Loss by a Tissue-Selective Estrogen Complex.
- 2016
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 157:3, s. 1013-20
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Tidskriftsartikel (refereegranskat)abstract
- In addition to the systemic inflammation present in rheumatoid arthritis (RA), decreased estradiol levels in postmenopausal RA patients further accelerate bone loss in these patients. The tissue-selective estrogen complex (TSEC), an estrogen combined with a selective estrogen receptor modulator, is a new hormone replacement therapy option. The first approved TSEC, containing conjugated estrogens and bazedoxifene (BZA), reduces menopausal symptoms and prevents osteoporosis with an improved safety profile compared with conventional hormone replacement therapy. Previous studies have shown that estrogens strongly inhibit experimental arthritis whereas BZA is mildly suppressive. In this study the antiarthritic potential of combined BZA and estradiol is explored for the first time. Female ovariectomized DBA/1 mice were subjected to collagen-induced arthritis, an experimental postmenopausal RA model, and treated with BZA, 17β-estradiol (E2), combined BZA and E2 (BZA/E2), or vehicle. BZA/E2 suppressed arthritis severity and frequency, synovitis, and joint destruction, equally efficient as E2 alone. Unwanted estrogenic proliferative effects on the endometrium were blocked by the addition of BZA, determined by collecting uterine weights. Bone mineral density was measured by peripheral quantitative computed tomography, and all treatments protected collagen-induced arthritis mice from both trabecular and cortical bone loss. Moreover, BZA/E2, but not E2 alone, inhibited preosteoclast formation and reduced serum anticollagen type II antibodies. In conclusion, a TSEC, herein combined BZA/E2, suppresses experimental arthritis and prevents associated bone loss as efficiently as E2 alone but with minimal uterine effects, highlighting the need for clinical trials that evaluate the addition of a TSEC to conventional postmenopausal RA treatment.
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| 19. |
- Andersson, Niklas, 1970, et al.
(författare)
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A gene expression fingerprint of mouse stomach ECL cells.
- 2005
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 332:2, s. 404-10
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Tidskriftsartikel (refereegranskat)abstract
- Many of the endocrine cells in the stomach are poorly characterized with respect to physiological significance. In some cases, the anticipated hormone has not yet been identified. Global gene expression analysis of mouse stomach was performed in an attempt to identify the ECL-cell peptide/protein. Specific functional activation (omeprazole-induced hypergastrinaemia) was used as a tool to generate a gene expression fingerprint of the ECL cells. The proposed fingerprint includes 14 genes, among them six are known to be expressed by ECL cells (=positive controls), and some novel ones, which are likely to be ECL-cell-related. The known ECL-cell-related genes are those encoding histidine decarboxylase, chromogranin A and B, vesicular monoamine transporter 2, synaptophysin, and the cholecystokinin-B receptor. In addition, the fingerprint included five genes, which might be involved in the process of secretion and three ESTs with unknown function. Interestingly, parathyroid hormone-like hormone (Pthlh) was identified as a candidate ECL-cell peptide hormone.
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| 20. |
- Andersson, Niklas, 1970, et al.
(författare)
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A variant near the interleukin-6 gene is associated with fat mass in Caucasian men
- 2010
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 34:6, s. 1011-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. DESIGN AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies. MAIN OUTCOME: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. RESULTS: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. CONCLUSIONS: The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.
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