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- Key, T. J., et al.
(författare)
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Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies
- 2015
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X. ; 99, s. 49-55
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study.
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| 2. |
- Kiss, Anita, et al.
(författare)
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Synthesis of novel 17-triazolyl-androst-5-en-3-ol epimers via Cu(I)-catalyzed azide-alkyne cycloaddition and their inhibitory effect on 17 alpha-hydroxylase/ C-17,C-20-lyase
- 2018
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X .- 1878-5867. ; 135, s. 79-91
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Tidskriftsartikel (refereegranskat)abstract
- The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of 17 alpha- and 17 beta-azidoandrost-5-en-3 beta-ol epimers (3b and 5b) with different terminal alkynes afforded novel 1,4-substituted triazolyl derivatives (8a-k and 9a-k). For the preparation of 5'-iodo-l',2',3'-triazoles (8m-n and 9m-n), an improved method was developed, directly from steroidal azides and terminal alkynes, in reaction mediated by Cul and IC1 as iodinating agents. Acetolysis and subsequent hydrolysis of 8n and 9n yielded 5'-hydroxy-l',2',3'-triazoles 8o and 9o. The inhibitory effect of 8a-o, 9a-o, 3, and 5 on rat testicular C-17,C-20-lyase was investigated by means of an in vitro radioincubation technique. The results revealed that the C-17 epimers of steroidal triazoles influence the C-17,C-20-lyase effect. Inhibitors were found only in the 17 alpha-triazolyl series (8a-o), whereas in the C-17 azide pair the 17 beta compound (5b) was more potent.
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| 3. |
- Larik, Fayaz Ali, et al.
(författare)
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Synthetic approaches towards the multi target drug spironolactone and its potent analogues/derivatives
- 2017
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X .- 1878-5867. ; 118, s. 76-92
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Forskningsöversikt (refereegranskat)abstract
- Spironolactone is a well-known multi-target drug and is specifically used for the treatment of high blood pressure and heart failure. It is also used for the treatment of edema, cirrhosis of the liver, malignant, pediatric, nephrosis and primary hyperaldosteronism. Spironolactone in association with thiazide diuretics treats hypertension and in association with furosemide treats bronchopulmonary dyspepsia. The therapeutic mechanism of action of spironolactone involves binding to intracellular mineralocorticoids receptors (MRs) in kidney epithelial cells, thereby inhibiting the binding of aldosterone. Since its first synthesis in 1957 there are several synthetic approaches have been reported throughout the years, Synthetic community has devoted efforts to improve the synthesis of spironolactone and to synthesize its analogues and derivatives. This review aims to provide comprehensive insight for the synthetic endeavors devoted towards the synthesis of a versatile drug spironolactone and its analogues/derivatives.
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| 6. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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The association between urinary cortisol excretion and cardiovascular risk factors, bone status and quality of life in the population
- 2015
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X. ; 101, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Patients with glucocorticoid excess have increased cardiovascular risk, decreased bone mineral density and impaired quality of life (QoL). The aim of this study was to evaluate the association between urinary cortisol excretion and cardiovascular risk factors, bone status and QoL in the population. We hypothesized that higher cortisol excretion was associated with adverse cardiovascular risk profile, worse skeletal health and QoL. Design, patients and methods: This was a cross-sectional study including a population sample (n = 348), aged 38-77 years. The mean age in women was 64.0 +/- 8.5 years (n = 276) and 60.3 +/- 10.2 years in men (n = 72). The metabolic syndrome, body composition measured with bioimpedance, calcaneal quantitative ultrasound, fractures and QoL evaluated with the Nottingham Health Profile, Psychological General Well-Being (PGWB) and the Short Form 36 (SF-36) were studied. Urinary free cortisol (UFC) was measured using radioimmunoassay. Results: UFC was higher in men (230 +/- 120 nmol/L) compared to women (153 +/- 71; P < 0.001) and decreased with increasing age (P < 0.001). In a regression analysis, after adjustment for gender, age and body mass index, higher UFC was associated with higher fat-free mass (P < 0.01), favourable calcaneal bone measurements (P < 0.05), better general health measured with PGWB (P < 0.01) and SF-36 (P = 0.001) and tended to be negatively associated with the metabolic syndrome (P = 0.07). Conclusion: In contrast to our hypothesis, UFC in the upper physiological range was associated with a favourable cardiovascular risk profile, bone measures and QoL.
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| 7. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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Urinary free cortisol and androgens in the population—Hormone interactions and the relationship with body composition and bone status
- 2016
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Ingår i: Steroids. - : Elsevier BV. - 0039-128X. ; 115, s. 154-159
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Tidskriftsartikel (refereegranskat)abstract
- Objective Abnormal secretion of thyroid hormones, growth hormone, cortisol and androgens influences body composition. We hypothesised that higher cortisol excretion, in combination with higher androgen and IGF-I concentrations, had a synergistic, favourable effect on body mass and bone. Design, patients and methods This was a cross-sectional study on a population sample of 290 women and 93men. The mean age was 65.4±7.2yearsinwomen and 59.7±10.0yearsinmen. Body composition was assessed with bioimpedance, and skeletal health with calcaneal quantitative ultrasound and fracture rate. The influence of urinary free cortisol (UFC), serum DHEAs (women), testosterone (men), free T4andIGF-I on the outcome was studied with regression analyses adjusted for age and body mass index. Results In women, higher concentrations of UFC, DHEAs, IGF-I and lower free T4, were associated with higher fat-free mass. Only a higher UFC concentration was associated with favourable calcaneal measurements. In men, higher testosterone was associated with higher fat-free mass and lower fat mass. Higher IGF-I concentration, but not UFC, was independently associated with higher fat-free mass in men. Interaction analyses did not reveal any additive effects of hormones on body composition or bone in either sex. In both men and women, only age was associated with osteoporotic fractures. Conclusion Serum concentrations of androgens together with IGF-I were positively associated with body composition in both sexes. Urinary cortisol was positively associated with fat-free mass and bone status in women only. Increasing age, but not hormones, was the major determinant of osteoporotic fractures in this population sample. © 2016 Elsevier Inc.
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