| 1. |
- Andersson, Niklas, 1970, et al.
(författare)
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Investigation of central versus peripheral effects of estradiol in ovariectomized mice
- 2005
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Ingår i: J Endocrinol. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 187:2, s. 303-9
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Tidskriftsartikel (refereegranskat)abstract
- It is generally believed that estrogens exert their bone sparing effects directly on the cells within the bone compartment. The aim of the present study was to investigate if central mechanisms might be involved in the bone sparing effect of estrogens. The dose-response of central (i.c.v) 17beta-estradiol (E2) administration was compared with that of peripheral (s.c.) administration in ovariectomized (ovx) mice. The dose-response curves for central and peripheral E2 administration did not differ for any of the studied estrogen-responsive tissues, indicating that these effects were mainly peripheral. In addition, ovx mice were treated with E2 and/or the peripheral estrogen receptor antagonist ICI 182,780. ICI 182,780 attenuated most of the estrogenic response regarding uterus weight, retroperitoneal fat weight, cortical BMC and trabecular bone mineral content (P<0.05). These findings support the notion that the primary target tissue that mediates the effect of E2 on bone is peripheral and not central.
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| 2. |
- Andersson, Jan, et al.
(författare)
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Trafiksäkerhetspåverkan vid omkörning av 30-metersfordon
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Trafikverket överväger att tillåta längre och tyngre fordon på vägarna förutsatt att de inte påverkar trafiksäkerheten negativt. Syftet med studien var att undersöka säkerhetseffekten av fordonslängd, speciellt med avseende på olycksrisken vid omkörningar. Intervjuade förare av en 30-meters timmerbil hade inte upplevt de farhågor som förare av normallånga lastbilar uttryckt i samband med trånga rondeller och korsningar, men de nämner betydelsen av stödjande åkeri, arbetsmiljö och fordonsutrustning. En simulatorstudie studerade bilförares omkörningar av ett 30- och ett 18,75-metersfordon på en 2+1-väg i situationen då två körfält går ihop till ett. Tidluckan till ett återstående körfält var i genomsnitt 0,2 s (sign.) kortare efter omkörningar av 30-metersfordonet i situationer då bakänden var i samma relativa position som för 18,75-metersfordonet vid början av omkörningen. En fältstudie analyserade videoinspelade omkörningar av en 30- och en 24-meters timmerbil på en 2+1-väg och en tvåfältig väg. Ingen signifikant skillnad i tidluckor kunde påvisas mellan omkörningar av de två fordonen för någon av vägtyperna. Det senare resultatet ska dock tolkas med försiktighet på grund av ojämnt distribuerad data som insamlats under specifika förhållanden. Slutsatserna är att det finns en liten tendens till negativ säkerhetseffekt vid omkörningar av längre fordon, och att fler fältstudier är nödvändiga.
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| 3. |
- Andersson, Niklas, 1970, et al.
(författare)
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Repeated in vivo determinations of bone mineral density during parathyroid hormone treatment in ovariectomized mice.
- 2001
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Ingår i: The Journal of endocrinology. - 0022-0795 .- 1479-6805. ; 170:3, s. 529-37
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Tidskriftsartikel (refereegranskat)abstract
- The recent development of different genetically modified mice with potentially interesting bone phenotypes has increased the demand for effective non-invasive methods to evaluate effects on bone of mice during growth and development, and for drug evaluation. In the present study, the skeleton was analyzed by repeated in vivo scans using dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Ovariectomized (ovx) mice treated with parathyroid hormone (PTH) were used as an animal model to evaluate these two techniques at different times after the onset of treatment. Female mice (6 weeks of age) were allocated randomly to four groups: (1) sham-operated+vehicle; (2) ovx+vehicle; (3) sham-operated+PTH(1-84) 150 microg/kg per day; (4) ovx+PTH. Six weeks after ovariectomy the drug treatment began and was continued for 8 weeks. The total body bone mineral content (BMC) and total body areal bone mineral density (BMD) were measured by DXA. Ovariectomy reduced total body BMC and total body areal BMD by 6.2+/-1.7% and 2.6+/-0.9% respectively. No effect of PTH on total body BMC was seen during the treatment period. The trabecular volumetric BMD was measured by pQCT. Ovariectomy reduced the trabecular volumetric BMD by 52+/-6.7%. The pQCT technique detected a clear effect on trabecular volumetric BMD after 2 weeks of PTH treatment (ovx 94+/-29% and sham-operated 46+/-10% more than vehicle-treated). The cortical bone was measured in a mid-diaphyseal pQCT scan of the tibia. Ovariectomy reduced the cortical BMC by 9+/-2%. PTH treatment for 8 weeks increased cortical BMC in ovx mice. In conclusion, the pQCT technique is more sensitive than the DXA technique in the detection of bone loss after ovariectomy and increased bone mass after PTH treatment in mice. Notably, the pQCT, but not the DXA, technique detected a dramatic effect as early as after 2 weeks of PTH treatment. Dynamic pQCT measurements will be useful for monitoring skeletal changes during growth and development, and for drug evaluation in mice.
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| 4. |
- Andersson, Ola, 1976-, et al.
(författare)
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Spectral shaping of DAC nonlinearity errors through modulation of expected errors
- 2001
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Ingår i: Circuits and Systems, 2001. ISCAS 2001. The 2001 IEEE International Symposium on. - : IEEE. - 0780366859 ; , s. 417-420
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Konferensbidrag (refereegranskat)abstract
- Traditionally, delta-sigma modulation has been used for shaping of quantization noise. We present a modified version of delta-sigma modulation which also takes into account unwanted nonlinearities by feeding back not only the quantization error, but also the expected physical error. Behavioral-level simulations of a 5th-order structure showing an improvement of up to 4 effective bits are included
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| 5. |
- Lindberg, Marie K, 1975, et al.
(författare)
-
Estrogen receptor specificity for the effects of estrogen in ovariectomized mice.
- 2002
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 174:2, s. 167-78
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogen exerts a variety of important physiological effects, which have been suggested to be mediated via the two known estrogen receptors (ERs), alpha and beta. Three-month-old ovariectomized mice, lacking one or both of the two estrogen receptors, were given estrogen subcutaneously (2.3 micro g/mouse per day) and the effects on different estrogen-responsive parameters, including skeletal effects, were studied. We found that estrogen increased the cortical bone dimensions in both wild-type (WT) and double ER knockout (DERKO) mice. DNA microarray analysis was performed to characterize this effect on cortical bone and it identified four genes that were regulated by estrogen in both WT and DERKO mice. The effect of estrogen on cortical bone in DERKO mice might either be due to remaining ERalpha activity or represent an ERalpha/ERbeta-independent effect. Other effects of estrogen, such as increased trabecular bone mineral density, thymic atrophy, fat reduction and increased uterine weight, were mainly ERalpha mediated.
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| 6. |
- Movérare-Skrtic, Sofia, et al.
(författare)
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Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice.
- 2006
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Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381 .- 1930-739X. ; 14:4, s. 662-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the role of androgen receptor (AR) activation for adipose tissue metabolism. Sex steroids are important regulators of adipose tissue metabolism in men. Androgens may regulate the adipose tissue metabolism in men either directly by stimulation of the AR or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors. Previous studies have shown that estrogen receptor alpha stimulation results in reduced fat mass in men. RESEARCH METHODS AND PROCEDURES: Orchidectomized mice were treated with the non-aromatizable androgen 5alpha-dihydrotestosterone (DHT), 17beta-estradiol, or vehicle. Vo(2), Vco(2), resting metabolic rate, locomotor activity, and food consumption were measured. Furthermore, changes in hepatic gene expression were analyzed. RESULTS: DHT treatment resulted in obesity, associated with reduced energy expenditure and fat oxidation. In contrast, DHT did not affect food consumption or locomotor activity. Furthermore, DHT treatment resulted in increased high-density lipoprotein-cholesterol and triglyceride levels associated with markedly decreased 7alpha-hydroxylase gene expression, indicating decreased bile acid production. DISCUSSION: We showed that AR activation results in obesity and altered lipid metabolism in orchidectomized mice. One may speculate that AR antagonists might be useful in the treatment of obesity in men.
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| 7. |
- Zhang, Renyun, et al.
(författare)
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Soap-film coating : High-speed deposition of multilayer nanofilms
- 2013
-
Ingår i: Scientific Reports. - Nature Publishing Group : Springer Science and Business Media LLC. - 2045-2322. ; 3, s. Art. no. 1477-
-
Tidskriftsartikel (refereegranskat)abstract
- The coating of thin films is applied in numerous fields and many methods are employed for the deposition of these films. Some coating techniques may deposit films at high speed; for example, ordinary printing paper is coated with micrometre-thick layers of clay at a speed of tens of meters per second. However, to coat nanometre thin films at high speed, vacuum techniques are typically required, which increases the complexity of the process. Here, we report a simple wet chemical method for the high-speed coating of films with thicknesses at the nanometre level. This soap-film coating technique is based on forcing a substrate through a soap film that contains nanomaterials. Molecules and nanomaterials can be deposited at a thickness ranging from less than a monolayer to several layers at speeds up to meters per second. We believe that the soap-film coating method is potentially important for industrial-scale nanotechnology.
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| 8. |
- Andersson, Niklas, 1975-, et al.
(författare)
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A strategy for implementing dynamic element matching in current-steering DACs
- 2000
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Ingår i: Mixed-Signal Design, 2000. SSMSD. 2000 Southwest Symposium on. - : IEEE. - 0780359755 ; , s. 51-56
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Interesting comparisons of dynamic element matching (DEM) techniques, have been presented during the last decade. However, not many chip implementations of these DEM techniques have been presented so far. A brief review of different DEM techniques are presented in this paper together with a strategy for implementing the partial randomization DEM, PRDEM, technique in a 3.3 V supply, 14 bit CMOS current-steering wideband digital-to-analog converter (DAC)
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| 9. |
- Andersson, Niklas, 1975-, et al.
(författare)
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Comparison of Different Dynamic Element Matching Techniques for Wideband CMOS DACs
- 1999
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Ingår i: Proceedings of the 17th Norchip Conference.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In the field of dynamic element matching, DEM, techniques, some ”new” important theoretical results have been presented during the last decade. However, no comparison between these different DEM techniques (FRDEM, PRDEM, NSDEM) used in wideband digital-to-analog converters, DACs, has been reported. A brief review of different DEM techniques and a comparison between their properties in terms of complexity, etc., are presented in this paper together with simulation results showing the impact of using different DEM techniques.
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| 10. |
- Andersson, Niklas, 1975-
(författare)
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Design of Integrated Building Blocks for the Digital/Analog Interface
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The integrated circuit has, since it was invented in the late 1950's, undergone a tremendous development and is today found in virtually all electric equipment. The small feature size and low production cost have made it possible to implement electronics in everyday objects ranging from computers and mobile phones to smart prize tags. Integrated circuits are typically used for data communication, signal processing and data storage. Data is usually stored in digital format but signal processing can be performed both in the digital and in the analog domain. For best performance, the right partition of signal processing between the analog and digital domain must be used. This is made possible by data converters converting data between the domains. A device converting an analog signal into a digital representation is called an analog-to-digital converter (ADC) and a device converting digital data into an analog representation is called a digital-to-analog converter (DAC). In this work we present research results on these data converters and the results are compiled in three different categories. The first contribution is an error correction technique for DACs called dynamic element matching, the second contribution is a power efficient time-to-digital converter architecture and the third is a design methodology for frequency synthesis using digital oscillators.The accuracy of a data converter, i.e., how accurate data is converted, is often limited by manufacturing errors. One type of error is the so-called matching error and in this work we investigate an error correction technique for DACs called dynamic element matching (DEM). If distortion is limiting the performance of a DAC, the DEM technique increases the accuracy of the DAC by transforming the matching error from being signal dependent, which results in distortion, to become signal independent noise. This noise can then be spectrally shaped or filtered out and hereby increasing the overall resolution of the system. The DEM technique is investigated theoretically and the theory is supported by measurement results from an implemented 14-bit DAC using DEM. From the investigation it is concluded that DEM increases the performance of the DAC when matching errors are dominating but has less effect at conversion speeds when dynamic errors dominate.The next contribution is a new time-to-digital converter (TDC) architecture. A TDC is effectively an ADC converting a time difference into a digital representation. The proposed architecture allows for smaller and more power efficient data conversion than previously reported and the implemented TDC prototype is smaller and more power efficient as compared to previously published TDCs in the same performance segment.The third contribution is a design methodology for frequency synthesis using digital oscillators. Digital oscillators generate a sinusoidal output using recursive algorithms. We show that the performance of digital oscillators, in terms of amplitude and frequency stability, to a large extent depends on the start conditions of the oscillators. Further we show that by selecting the proper start condition an oscillator can be forced to repeat the same output sequence over and over again, hence we have a locked oscillator. If the oscillator is locked there is no drift in amplitude or frequency which are common problems for recursive oscillators not using this approach. To find the optimal start conditions a search algorithm has been developed which has been thoroughly tested in simulations. The digital oscillator output is used for test signal generation for a DAC or used to generate tones with high spectral purity using DACs.
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| 11. |
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| 12. |
- Bergh, Niklas, 1979, et al.
(författare)
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A new biomechanical perfusion system for ex vivo study of small biological intact vessels
- 2005
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Ingår i: Ann Biomed Eng. - : Springer Science and Business Media LLC. - 0090-6964. ; 33:12, s. 1808-18
-
Tidskriftsartikel (refereegranskat)abstract
- The vascular endothelium transduces physical stimuli within the circulation into physiological responses, which influence vascular remodelling and tissue homeostasis. Therefore, a new computerized biomechanical ex vivo perfusion system was developed, in which small intact vessels can be perfused under well-defined biomechanical forces. The system enables monitoring and regulation of vessel lumen diameter, shear stress, mean pressure, variable pulsatile pressure and flow profile, and diastolic reversal flow. Vessel lumen measuring technique is based on detection of the amount of flourescein over a vessel segment. A combination of flow resistances, on/off switches, and capacitances creates a wide range of pulsatile pressures and flow profiles. Accuracy of the diameter measurement was evaluated. The diameters of umbilical arteries were measured and compared with direct ultrasonographic measurement of the vessel diameter. As part of the validation the pulsatile pressure waveform was altered, e.g., in terms of pulse pressure, frequency, diastolic shape, and diastolic reversal flow. In a series of simulation experiments, the hemodynamic homeostasis functions of the system were successfully challenged by generating a wide range of vascular diameters in artificial and intact human vessels. We conclude that the system presented may serve as a methodological and technical platform when performing advanced hemodynamic stimulation protocols.
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| 13. |
- Bruhn-Olszewska, Bozena, et al.
(författare)
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Loss of Y in leukocytes as a risk factor for critical COVID-19 in men.
- 2022
-
Ingår i: Genome medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription.Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs.Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93-143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e-11).We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.
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| 14. |
- Chagin, A S, et al.
(författare)
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Estrogen receptor-beta inhibits skeletal growth and has the capacity to mediate growth plate fusion in female mice.
- 2004
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431 .- 1523-4681. ; 19:1, s. 72-7
-
Tidskriftsartikel (refereegranskat)abstract
- To determine the long-term role of ER beta in the regulation of longitudinal bone growth, appendicular and axial skeletal growth was followed and compared in female ER beta-/-, ER alpha-/-, and ER alpha-/- beta-/- mice. Our results show that ER beta inhibits appendicular and axial skeletal growth and has the capacity to induce fusion of the growth plates. INTRODUCTION: Estrogen affects skeletal growth and promotes growth plate fusion in humans. In rodents, the growth plates do not fuse after sexual maturation, but prolonged treatment with supraphysiological levels of estradiol has the capacity to fuse the growth plates. It should be emphasized that the estrogen receptor (ER) alpha-/- and the ER alpha-/- beta-/-, but not the ER beta-/-, mouse models have clearly increased serum levels of estradiol. MATERIALS AND METHODS: The skeletal growth was monitored by X-ray and dynamic histomorphometry, and the growth plates were analyzed by quantitative histology, calcein double labeling, bromodeoxyuridine (BrdU) incorporation, and TUNEL assay in 4- and 18-month-old female ER beta-/-, ER alpha-/-, and ER alpha-/- beta-/- mice. RESULTS: Young adult (4-month-old) ER beta-/- mice demonstrated an increased axial- and appendicular-skeletal growth, supporting the notion that ER beta inhibits skeletal growth in young adult female mice. Interestingly, the growth plates were consistently fused in the appendicular skeleton of 18-month-old female ER alpha-/- mice. This fusion of growth plates, caused by a prolonged exposure to supraphysiological levels of estradiol in female ER alpha-/- mice, must be mediated through ER beta because old ER alpah-/- beta-/- mice displayed unchanged, unfused growth plates. CONCLUSIONS: Our results confirm that ER beta is a physiological inhibitor of appendicular- and axial-skeletal growth in young adult female mice. Furthermore, we made the novel observation that ER beta, after prolonged supraphysiological estradiol exposure, has the capacity to mediate growth plate fusion in old female mice.
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| 15. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density.
- 2006
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:12, s. 5029-37
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. OBJECTIVE: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)(n) microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. DESIGN AND STUDY SUBJECTS: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n congruent with 3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). MAIN OUTCOME MEASURES: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. RESULTS: In both cohorts, (TAAAA)(n) and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5alpha-androstane-3alpha,17beta-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. CONCLUSIONS: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.
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| 16. |
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| 17. |
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| 18. |
- Jalili, Armin, et al.
(författare)
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Calibration of sigma-delta analog-to-digital converters based on histogram test methods
- 2010
-
Ingår i: NORCHIP, 2010. - : IEEE. - 9781424489725 ; , s. 1-4
-
Konferensbidrag (refereegranskat)abstract
- In this paper we present a calibration technique for sigma-delta analog-to-digital converters (ΣΔADC) in which highspeed, low-resolution flash subADCs are used. The calibration technique as such is mainly targeting calibration of the flash subADC, but we also study how the correction depends on where in the ΣΔ modulator the calibration signals are applied. It is shown that the calibration technique can cope with errors that occur in the feedback digital-to-analog converter (DAC) and the input accumulator. Behavioral-level simulation results show an improvement of in effective number of bits (ENOB) from 6.6 to 11.3. Fairly large offset and gain errors have been introduced which illustrates a robust calibration technique.
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| 19. |
- Lindberg, Marie, 1975, et al.
(författare)
-
Liver-derived IGF-I is permissive for ovariectomy-induced trabecular bone loss
- 2006
-
Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 38:1, s. 85-92
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Estrogen deficiency results in trabecular bone loss, associated with T-cell proliferation in the bone marrow. Insulin-like growth factor I (IGF-I) is involved in the regulation of both bone metabolism and lymphopoiesis. A major part of serum IGF-I is derived from the liver. The aim of the present study was to investigate the role of liver-derived IGF-I for ovariectomy (ovx)-induced trabecular bone loss. MATERIALS AND METHODS: Mice with adult liver-specific IGF-I inactivation (LI-IGF-I-/-) and wild type mice (WT) were either ovx or sham operated. After 5 weeks, the skeletal phenotype was analyzed by pQCT and microCT. The bone marrow cellularity was analyzed using FACS technique, and mRNA levels were quantified using real-time PCR. RESULTS: Ovx resulted in a pronounced reduction in trabecular bone mineral density (-52%, P < 0.001), number (-45%, P < 0.01) and thickness (-13%, P < 0.01) in WT mice while these bone parameters were unaffected by ovx in LI-IGF-I-/- mice. Furthermore, ovx increased the number of T-cells in the bone marrow of the femur in WT but not in LI-IGF-I-/- mice. Interleukin 7 (IL-7) has been reported to stimulate the formation and function of osteoclasts by inducing the expression of receptor activator of NF-kappaB ligand (RANKL) on T-cells. IL-7 mRNA levels and the RANKL/osteoprotegerin ratio in bone were increased by ovx in WT but not in LI-IGF-I-/- mice. CONCLUSIONS: Liver-derived IGF-I is permissive for ovx-induced trabecular bone loss. Our studies indicate that IGF-I might exert this permissive action by modulation of the number of T-cells and the expression of IL-7, which in turn is of importance for the RANKL/OPG ratio and consequently osteoclastogenesis in the bone marrow.
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| 20. |
- Lorentzon, Mattias, 1970, et al.
(författare)
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Free testosterone is a positive, whereas free estradiol is a negative, predictor of cortical bone size in young Swedish men: the GOOD study.
- 2005
-
Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431 .- 1523-4681. ; 20:8, s. 1334-41
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we evaluated the predictive roles of sex steroids for skeletal parameters in young men (n = 1068) at the age of peak bone mass. Serum free estradiol was a negative predictor, whereas free testosterone and SHBG were positive predictors of cortical bone size. INTRODUCTION: Previous studies have shown that free estradiol in serum is an independent predictor of areal BMD (aBMD) in elderly men. The aim of this study was to determine whether sex steroids are predictors of volumetric BMD (vBMD) and/or size of the trabecular and cortical bone compartments in young men at the age of peak bone mass. MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men, 18.9 +/- 0.6 years of age. Serum levels of testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured, and free levels of testosterone and estradiol were calculated. The size of the cortical bone and the cortical and trabecular vBMDs were measured by pQCT. RESULTS: Regression models including age, height, weight, free estradiol, and free testosterone showed that free estradiol was an independent negative predictor of cortical cross-sectional area (tibia beta = -0.111, p < 0.001; radius beta = -0.125, p < 0.001), periosteal circumference, and endosteal circumference, whereas it was a positive independent predictor of cortical vBMD (tibia beta = 0.100, p < 0.003; radius beta = 0.115, p = 0.001) in both the tibia and radius. Free testosterone was an independent positive predictor of cortical cross-sectional area (tibia beta = 0.071, p = 0.013; radius beta = 0.064, p = 0.039), periosteal circumference, and endosteal circumference in both the tibia and radius. Neither cortical nor trabecular vBMD was associated with free testosterone. SHBG was an independent positive predictor of parameters reflecting the size of the cortical bone, including cross-sectional area (beta = 0.078, p = 0.009), periosteal circumference, and endosteal circumference. CONCLUSIONS: Free estradiol is a negative, whereas free testosterone is a positive, predictor of cortical bone size in young men at the age of peak bone mass. These findings support the notion that estrogens reduce, whereas androgens increase, cortical bone size, resulting in the well-known sexual dimorphism of cortical bone geometry.
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| 21. |
- Molinaro, Antonio, et al.
(författare)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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| 22. |
- Movérare, Sofia, et al.
(författare)
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Estren is a selective estrogen receptor modulator with transcriptional activity.
- 2003
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Ingår i: Molecular pharmacology. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0026-895X .- 1521-0111. ; 64:6, s. 1428-33
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Tidskriftsartikel (refereegranskat)abstract
- It was recently reported that the synthetic compound estren increases bone mass without affecting reproductive organs or classic transcription. The aim of the present study was to further characterize the in vivo and in vitro effects of estren. We demonstrate that estren is a selective estrogen receptor modulator (SERM) with a strong effect on thymus, a moderate effect on uterus and trabecular bone, but no major effect on fat or cortical bone in 11-month-old ovariectomized mice. The effect of estren on trabecular bone and uterus is mediated via estrogen receptors (ERs) because no effect is seen in ER double-inactivated mice. Furthermore, with the use of ERalpha- and ERbeta-expressing reporter cell lines, we demonstrate that estren displays an agonistic effect on transcriptional activity of an estrogen-responsive element-driven reporter gene with a degree of agonism similar to that of 17beta-estradiol for both ERalpha and ERbeta. Thus, estren has the capacity to exert genomic effects via both ERalpha and ERbeta. We conclude, in contrast to what was previously reported by others, that estren is a SERM with transcriptional activity.
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| 25. |
- Siponen, Rebecca, 1993-, et al.
(författare)
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A population-based study of unintentional injury and premature death among non-imprisoned and imprisoned youth offenders
- 2023
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Ingår i: Journal of criminal justice. - : Elsevier. - 0047-2352 .- 1873-6203. ; 84
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Tidskriftsartikel (refereegranskat)abstract
- Background: Youth offenders have a high risk of being injured or dying prematurely. However, few studies have considered the role of imprisonment and potential childhood risk factors for these high rates.Aim: To examine the risk of unintentional injury and premature death in non-imprisoned and imprisoned youth offenders, and to examine the role of parental criminal convictions and psychiatric disorders and own childhood psychiatric disorders.Methods: All individuals (N = 1,839,711) born in Sweden between 1978 and 1996 were identified using Swedish population-based registers. The exposure was criminal conviction between ages 15-20 years of age.Results: Imprisoned youth offenders had the highest risk for unintentional injury (HR = 2.29 [2.19-2.40]) and premature death (HR = 10.76 [9.52-12.16]), followed by nonimprisoned youth offenders, compared to non -convicted youth. All childhood risk factors increased the risk for these outcomes among non-imprisoned youth offenders. Among imprisoned youth offenders, parental criminal convictions and parental psychiatric disorders increased the risk for unintentional injury, and parental psychiatric disorders and own childhood psychiatric disorders increased the risk for premature death.Conclusions: Our study shows there are robust modifiable childhood risk factors for injury and mortality among youth offenders. However, the importance of them to assess risk may differ between non-imprisoned and imprisoned youth offenders.
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| 26. |
- Sjögren, Klara, 1970, et al.
(författare)
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Elevated Aromatase Expression in Osteoblasts Leads to Increased Bone Mass without Systemic Adverse Effects.
- 2009
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Ingår i: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 24:7, s. 1263-70
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The stimulatory effects of testosterone (T) on bone can either be via a direct activation of the androgen receptor (AR) or mediated via aromatization of T to estradiol (E2), followed by activation of estrogen receptors (ERs) in bone. Aromatase expression in osteoblasts and reproductive tissues is dependent on different promoters, which are differentially regulated. To investigate the effect of elevated local aromatization of T to E2 in bone, we developed a transgenic mouse model (Coll-1alpha1-Arom) that over-expresses the human aromatase gene under the control of the osteoblast specific rat type I alpha I procollagen promoter. The Coll-1alpha1-Arom mice expressed human aromatase mRNA specifically in bone and had unaffected serum E2 and T levels. Male Coll-1alpha1-Arom mice had clearly increased total body bone mineral density (BMD), trabecular BMD, cortical BMD and cortical thickness associated with elevated osteoprotegerin mRNA levels and reduced number of osteoclasts (p<0.01). Treatment of ovariectomized mice with T increased cortical and trabecular thickness in the Coll-1alpha1-Arom mice (p<0.001) but not in the wild type mice. In conclusion, elevated aromatase expression specifically in osteoblasts results in stimulatory estrogenic effects in bone without increasing serum E2 levels. As osteoblast specific aromatase expression results in an increased ER to AR activation ratio in bone, we propose that activation of ERs results in a more pronounced increase in bone mass than what is seen after activation of the AR. Development of osteoblast specific inducers of aromatase expression might identify substances with stimulatory effects on bone without systemic adverse effects.
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| 27. |
- Strandberg, Louise, 1981, et al.
(författare)
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Mice chronically fed high-fat diet have increased mortality and disturbed immune response in sepsis.
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are few effective therapies for sepsis, increased basic knowledge about factors predisposing is needed. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study was to study the effect of Western diet on mortality induced by intravenous S. aureus inoculation and the immune functions before and after bacterial inoculation. Here we show that C57Bl/6 mice on high-fat diet (HFD) for 8 weeks, like genetically obese Ob/Ob mice on low-fat diet (LFD), have increased mortality during S. aureus-induced sepsis compared with LFD-fed C57Bl/6 controls. Bacterial load in the kidneys 5-7 days after inoculation was increased 10-fold in HFD-fed compared with LFD-fed mice. At that time, HFD-fed mice had increased serum levels and fat mRNA expression of the immune suppressing cytokines interleukin-1 receptor antagonist (IL-1Ra) and IL-10 compared with LFD-fed mice. In addition, HFD-fed mice had increased serum levels of the pro-inflammatory IL-1beta. Also, HFD-fed mice with and without infection had increased levels of macrophages in fat. The proportion and function of phagocytosing granulocytes, and the production of reactive oxygen species (ROS) by peritoneal lavage cells were decreased in HFD-fed compared with LFD-fed mice. CONCLUSIONS: Our findings imply that chronic HFD disturb several innate immune functions in mice, and impairs the ability to clear S. aureus and survive sepsis.
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| 28. |
- Sudow, Mattias, 1980, et al.
(författare)
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SiC varactors for dynamic load modulation of high power amplifiers
- 2008
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Ingår i: IEEE Electron Device Letters. - 0741-3106 .- 1558-0563. ; 29:7, s. 728-730
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Tidskriftsartikel (refereegranskat)abstract
- SiC Schottky diode varactors with a high breakdown voltage, a high tuning ratio, and a low series resistance have been designed and fabricated. These characteristics are particularly necessary for the dynamic load modulation of high power amplifiers (PAs), which is an attractive alternative to other efficiency enhancement techniques. For a SiC Schottky diode varactor with a 50-µm radius fabricated by using a graded doping profile, a breakdown voltage of 40 V, a tuning range of 5.6, and a series resistance of 0.9 O were achieved. The results show the great potential of this type of varactors for the use in the dynamic load modulation of high power amplifiers. © 2008 IEEE.
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| 29. |
- Windahl, Sara H, 1971, et al.
(författare)
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Reduced bone mass and muscle strength in male 5α-reductase type 1 inactivated mice.
- 2011
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5α-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5α-reductase (type 1 and type 2), encoded by separate genes (Srd5a1 and Srd5a2). 5α-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5α-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5α-reductase type 1 for bone mass using Srd5a1⁻/⁻ mice. Four-month-old male Srd5a1⁻/⁻ mice had reduced trabecular bone mineral density (-36%, p<0.05) and cortical bone mineral content (-15%, p<0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male Srd5a1⁻/⁻ mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p<0.05) in orchidectomized WT mice but not in orchidectomized Srd5a1⁻/⁻ mice. Male Srd5a1⁻/⁻ mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p<0.05). Female Srd5a1⁻/⁻ mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5α-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5α-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female Srd5a1⁻/⁻ mice, is an indirect effect mediated by elevated circulating androgen levels.
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| 30. |
- Windahl, Sara H, 1971, et al.
(författare)
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The role of the G protein-coupled receptor GPR30 in the effects of estrogen in ovariectomized mice.
- 2009
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 296:3
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Tidskriftsartikel (refereegranskat)abstract
- In vitro studies suggest that the membrane G protein-coupled receptor GPR30 is a functional estrogen receptor (ER). The aim of the present study was to determine the possible in vivo role of GPR30 as a functional ER primarily for the regulation of skeletal parameters, including bone mass and longitudinal bone growth, but also for some other well-known estrogen-regulated parameters, including uterine weight, thymus weight, and fat mass. Three-month-old ovariectomized (OVX) GPR30-deficient mice (GPR30(-/-)) and wild-type (WT) mice were treated with either vehicle or increasing doses of estradiol (E(2); 0, 30, 70, 160, or 830 ng.mouse(-1).day(-1)). Body composition [bone mineral density (BMD), fat mass, and lean mass] was analyzed by dual-energy-X ray absorptiometry, while the cortical and trabecular bone compartments were analyzed by peripheral quantitative computerized tomography. Quantitative histological analyses were performed in the distal femur growth plate. Bone marrow cellularity and distribution were analyzed using a fluorescence-activated cell sorter. The estrogenic responses on most of the investigated parameters, including increase in bone mass (total body BMD, spine BMD, trabecular BMD, and cortical bone thickness), increase in uterine weight, thymic atrophy, fat mass reduction, and increase in bone marrow cellularity, were similar for all of the investigated E(2) doses in WT and GPR30(-/-) mice. On the other hand, E(2) treatment reduced longitudinal bone growth, reflected by decreased femur length and distal femur growth plate height, in the WT mice but not in the GPR30(-/-) mice compared with vehicle-treated mice. These in vivo findings demonstrate that GPR30 is not required for normal estrogenic responses on several major well-known estrogen-regulated parameters. In contrast, GPR30 is required for a normal estrogenic response in the growth plate.
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