| 1. |
- Colldén, Hannah, et al.
(författare)
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Comprehensive Sex Steroid Profiling in Multiple Tissues Reveals Novel Insights in Sex Steroid Distribution in Male Mice
- 2022
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 163:3
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive atlas of sex steroid distribution in multiple tissues is currently lacking, and how circulating and tissue sex steroid levels correlate remains unknown. Here, we adapted and validated a gas chromatography tandem mass spectrometry method for simultaneous measurement of testosterone (T), dihydrotestosterone (DHT), androstenedione, progesterone (Prog), estradiol, and estrone in mouse tissues. We then mapped the sex steroid pattern in 10 different endocrine, reproductive, and major body compartment tissues and serum of gonadal intact and orchiectomized (ORX) male mice. In gonadal intact males, high levels of DHT were observed in reproductive tissues, but also in white adipose tissue (WAT). A major part of the total body reservoir of androgens (T and DHT) and Prog was found in WAT. Serum levels of androgens and Prog were strongly correlated with corresponding levels in the brain while only modestly correlated with corresponding levels in WAT. After orchiectomy, the levels of the active androgens T and DHT decreased markedly while Prog levels in male reproductive tissues increased slightly. In ORX mice, Prog was by far the most abundant sex steroid, and, again, WAT constituted the major reservoir of Prog in the body. In conclusion, we present a comprehensive atlas of tissue and serum concentrations of sex hormones in male mice, revealing novel insights in sex steroid distribution. Brain sex steroid levels are well reflected by serum levels and WAT constitutes a large reservoir of sex steroids in male mice. In addition, Prog is the most abundant sex hormone in ORX mice.
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| 2. |
- Colldén, Hannah, et al.
(författare)
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Dehydroepiandrosterone Supplementation Results in Varying Tissue-specific Levels of Dihydrotestosterone in Male Mice
- 2022
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 163:12
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Tidskriftsartikel (refereegranskat)abstract
- Dehydroepiandrosterone (DHEA), an adrenal androgen precursor, can be metabolized in target tissues into active sex steroids. It has been proposed that DHEA supplementation might result in restoration of physiological local sex steroid levels, but knowledge on the effect of DHEA treatment on local sex steroid levels in multiple tissues is lacking. To determine the effects of DHEA on tissue-specific levels of sex steroids, we treated orchiectomized (ORX) male mice with DHEA for 3 weeks and compared them with vehicle-treated ORX mice and gonadal intact mice. Intra-tissue levels of sex steroids were analyzed in reproductive organs (seminal vesicles, prostate, m. levator ani), major body compartments (white adipose tissue, skeletal muscle, and brain), adrenals, liver, and serum using a sensitive and validated gas chromatography-mass spectrometry method. DHEA treatment restored levels of both testosterone (T) and dihydrotestosterone (DHT) to approximately physiological levels in male reproductive organs. In contrast, this treatment did not increase DHT levels in skeletal muscle or brain. In the liver, DHEA treatment substantially increased levels of T (at least 4-fold) and DHT (+536%, P < 0.01) compared with vehicle-treated ORX mice. In conclusion, we provide a comprehensive map of the effect of DHEA treatment on intra-tissue sex steroid levels in ORX mice with a restoration of physiological levels of androgens in male reproductive organs while DHT levels were not restored in the skeletal muscle or brain. This, and the unexpected supraphysiological androgen levels in the liver, may be a cause for concern considering the uncontrolled use of DHEA.
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| 3. |
- Narangifard, Ali, et al.
(författare)
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Molecular Reorganization during the Formation of the Human Skin Barrier Studied In Situ
- 2021
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 141:5, s. 1243-1253
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Tidskriftsartikel (refereegranskat)abstract
- In vertebrates, skin upholds homeostasis by preventing body water loss. The skin's permeability barrier is located intercellularly in the stratum corneum and consists of stacked lipid lamellae composed of ceramides, cholesterol, and free fatty acids. We have combined cryo-electron microscopy with molecular dynamics modeling and electron microscopy simulation in our analysis of the lamellae's formation, a maturation process beginning in stratum granulosum and ending in stratum corneum. Previously, we have revealed the lipid lamellae's initial- and end-stage molecular organizations. In this study, we reveal two cryo-electron microscopy patterns representing intermediate stages in the lamellae's maturation process: a single-band pattern with 2.0-2.5 nm periodicity and a two-band pattern with 5.5-6.0 nm periodicity, which may be derived from lamellar lipid structures with 4.0-5.0 nm and 5.5-6.0 nm periodicity, respectively. On the basis of the analysis of the data now available on the four maturation stages identified, we can present a tentative molecular model for the complete skin barrier formation process.
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| 4. |
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| 5. |
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| 6. |
- Skröder, H., et al.
(författare)
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Occupational exposure to whole body vibrations and birth outcomes – A nationwide cohort study of Swedish women
- 2021
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 751
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Tidskriftsartikel (refereegranskat)abstract
- Background: More women in reproductive ages are entering occupations where exposure to whole body vibrations (WBV) is common (e.g. in transportation and construction). Previous studies based on self-assessed exposure suggest increased risks of adverse birth outcomes, but it is unclear at what exposure levels and if the current exposure guidelines are appropriate during pregnancy. Objectives: To investigate whether occupational WBV-exposure increases the risk of preterm birth, low birth weight, and/or small-for-gestational age, in a large, nationwide, prospective, cohort study. Design: The Fetal Air Pollution Exposure cohort (FAIR) was formed by merging data from multiple, national registers, and the present study includes singletons born 1994–2014 to working women in Sweden (n = 1,091,080 births). WBV-exposure was assessed quantitatively using a job-exposure matrix based on measurements, and calculated odds ratios were adjusted for potential confounders such as smoking and BMI, and other occupational exposures like noise, combustion particles, and physically and psychologically strenuous work. Data on absence from work (full-/part time, sick leave, parental leave, etc.) was also used. Results: Exposure to WBV during pregnancy, among women with low absence from work (n = 476,419), was associated with an increased risk of preterm birth, below the occupational exposure limit (1.15 m/s2). Compared to unexposed mothers, the OR was 1.38 (95% CI: 1.05, 1.83) for exposure ≥0.5 m/s2, corresponding to an increase from 47/1000 cases to 65/1000 cases. No increased risk was found for small-for-gestational age. Conclusions: Exposure to WBV was associated with an increased risk of preterm birth. The results suggest that the current permissible exposure and action levels for WBV-exposure do not adequately protect pregnant women with continuous exposure.
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| 7. |
- Westin, Maria, et al.
(författare)
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A screening instrument for side dominance in competitive adolescent alpine skiers
- 2022
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Ingår i: Frontiers in Sports and Active Living. - : Frontiers Media S.A.. - 2624-9367. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has shown that high school ski students injure their left anterior cruciate ligament (ACL) more often than their right ACL, and that a prevention program focusing on equal load to the right and left ski turns prevents ACL injuries. Whether the injuries were in the dominant or non-dominant side of ski students was not determined but may be important knowledge to ski coaches for future design of ski-specific training programs. There is no gold standard on how to investigate the dominant side of alpine skiers. Therefore, the aim of this study was to develop a screening instrument consisting of five questions for identifying side dominance and to evaluate side dominance in competitive adolescent alpine skiers. First, 121 competitive adolescent alpine skiers answered the questions on side dominance using a test-retest design. The questions were: which hand/arm (left/right) or foot/leg (left/right) one uses as the first choice when writing, throwing, kicking a ball, jumping over a fence and stair-climbing. A question about safer/better ski turn to the left or to the right was also added. Second, 274 skiers answered the questions at one occasion. A very good agreement was shown in writing and throwing and kicking a ball, and a fair agreement was shown in jumping over a fence and stair climbing. A total of 243 skiers reported right-sided dominance, and seven skiers reported left-sided dominance. One hundred and nineteen of the 121 skiers who took part in the test-retest design answered the question safer/better ski turn, and of those 70 (59%) reported that they had a safer/better ski turn to one side than to the other side. However, the side was not consistent between the two test occasions, and the question did not correlate with side dominance. A combination of the three questions "What hand/arm do you use as first choice when writing?" "What hand/arm do you use as first choice when throwing?" and "What foot/leg do you use as first choice when kicking a ball?", may be used to decide side dominance in adolescent alpine skiers. Most adolescent alpine skiers reported right-sided dominance.
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