| 1. |
- Bower, Rebekah L., et al.
(författare)
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Mapping the calcitonin receptor in human brain stem
- 2016
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Ingår i: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 310:9, s. 788-793
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Tidskriftsartikel (refereegranskat)abstract
- The calcitonin receptor (CTR) is relevant to three hormonal systems: amylin, calcitonin, and calcitonin gene-related peptide (CGRP). Receptors for amylin and calcitonin are targets for treating obesity, diabetes, and bone disorders. CGRP receptors represent a target for pain and migraine. Amylin receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract, the hypoglossal nucleus, the cuneate nucleus, spinal trigeminal nucleus, the gracile nucleus, and the inferior olivary nucleus. CTR staining was also observed in the area postrema, the lateral reticular nucleus, and the pyramidal tract. The extensive expression of CTR in the medulla suggests that CTR may be involved in a wider range of functions than currently appreciated.
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| 2. |
- Jacobsson, Jesper, 1984-, et al.
(författare)
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An open-access database and analysis tool for perovskite solar cells based on the FAIR data principles
- 2022
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Ingår i: Nature Energy. - : Springer Nature. - 2058-7546. ; 7:1, s. 107-115
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Tidskriftsartikel (refereegranskat)abstract
- Large datasets are now ubiquitous as technology enables higher-throughput experiments, but rarely can a research field truly benefit from the research data generated due to inconsistent formatting, undocumented storage or improper dissemination. Here we extract all the meaningful device data from peer-reviewed papers on metal-halide perovskite solar cells published so far and make them available in a database. We collect data from over 42,400 photovoltaic devices with up to 100 parameters per device. We then develop open-source and accessible procedures to analyse the data, providing examples of insights that can be gleaned from the analysis of a large dataset. The database, graphics and analysis tools are made available to the community and will continue to evolve as an open-source initiative. This approach of extensively capturing the progress of an entire field, including sorting, interactive exploration and graphical representation of the data, will be applicable to many fields in materials science, engineering and biosciences.
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| 3. |
- Lukács, M., et al.
(författare)
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KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion
- 2016
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Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion. Methods: Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were investigated using immunohistochemistry and Western blot. Findings: Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. Conclusions: This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti-inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates.
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| 4. |
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| 5. |
- Andersson, S E, et al.
(författare)
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Cutaneous vascular reactivity is reduced in aging and in heart failure: association with inflammation
- 2003
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Ingår i: Clinical Science. - 1470-8736. ; 105:6, s. 699-707
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we have investigated whether changes in vascular reactivity in congestive heart failure (CHF) patients can be detected in the cutaneous microvessels and whether these changes are due to endothelial dysfunction, are affected by increasing age and related to an ongoing inflammation. The responses to local warming and iontophoretically administered endothelium-dependent and -independent vasodilators were investigated in healthy young adults, healthy elderly adults and elderly adults with CHE The results were correlated with plasma concentrations of vascular risk factors and markers for endothelial dysfunction and inflammation. The vasorelaxant responses were reduced in the elderly groups and were attenuated further in the CHF group. This group also had increases in levels of several markers associated with inflammation, higher blood glucose and homocysteine levels, a lower low-density lipoprotein-cholesterol and a rise in the concentration of von Willebrand factor, indicating a prothrombotic endothelial function. The severity of the heart failure, measured as the plasma level of brain natriuretic peptide, correlated with the intensity of inflammation and to the changes in vascular risk factors and endothelial function. It is concluded that the reactivity of the cutaneous microvessels is reduced with age, and the presence of CHF causes a further impairment. There is endothelial dysfunction in CHF, but it is uncertain to what extent this contributes to the reduced vasodilatory capacity. The inflammatory response appears central for many of the manifestations of the CHF syndrome.
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| 6. |
- Ardo, Shane, et al.
(författare)
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Pathways to electrochemical solar-hydrogen technologies
- 2018
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Ingår i: Energy & Environmental Science. - : Royal Society of Chemistry. - 1754-5692 .- 1754-5706. ; 11:10, s. 2768-2783
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Forskningsöversikt (refereegranskat)abstract
- Solar-powered electrochemical production of hydrogen through water electrolysis is an active and important research endeavor. However, technologies and roadmaps for implementation of this process do not exist. In this perspective paper, we describe potential pathways for solar-hydrogen technologies into the marketplace in the form of photoelectrochemical or photovoltaic-driven electrolysis devices and systems. We detail technical approaches for device and system architectures, economic drivers, societal perceptions, political impacts, technological challenges, and research opportunities. Implementation scenarios are broken down into short-term and long-term markets, and a specific technology roadmap is defined. In the short term, the only plausible economical option will be photovoltaic-driven electrolysis systems for niche applications. In the long term, electrochemical solar-hydrogen technologies could be deployed more broadly in energy markets but will require advances in the technology, significant cost reductions, and/ or policy changes. Ultimately, a transition to a society that significantly relies on solar-hydrogen technologies will benefit from continued creativity and influence from the scientific community.
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| 7. |
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| 8. |
- Edvinsson, M-L, et al.
(författare)
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Comparison of CGRP and NO responses in the human peripheral microcirculation of migraine and control subjects.
- 2008
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 28:5, s. 563-566
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Tidskriftsartikel (refereegranskat)abstract
- Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are two molecules shown to have a role in migraine pathophysiology. Our objective was to test the hypothesis that migraine subjects are particularly sensitive to these signal molecules. The cutaneous microvascular responses to endothelial and non-endothelial dependent dilators were tested using laser Doppler flowmetry in combination with iontophoresis. The blood flow responses to iontophoretic administration of the endothelium-dependent vasodilator acetylcholine (ACh), or to the endothelium-independent dilators sodium nitroprusside (SNP) and CGRP, and to local warming (44 degrees C) were compared in this controlled trial. The design was that of two arms: patients diagnosed with migraine without aura (n = 9) for >10 years were compared with nine healthy subjects matched for age and gender (seven female and two male, age range 30-60 years). Iontophoretic administration resulted in local vasodilation. ACh induced a relaxation of 1225 +/- 245% (relative to baseline) in controls and 1468 +/- 368% (P > 0.05) in migraine. The responses to SNP were 873 +/- 193% in controls and 1080 +/- 102% (P > 0.05) in migraine subjects. The responses to CGRP were 565 +/- 89% in controls and 746 +/- 675% (P > 0.05) in migraine patients. The responses to local heating which induced maximum dilation did not differ between the groups (1976 +/- 314% for controls and 1432 +/- 226% in migraine; P > 0.05. We conclude that there is no change in the microvascular responsiveness of the subcutaneous microvasculature in migraine.
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| 9. |
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| 10. |
- Lukács, M., et al.
(författare)
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Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis : attenuated by KYNA derivate (SZR72)
- 2017
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Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund’s Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72. Methods: Activation in the trigeminal nucleus caudalis (TNC) and the trigeminal tract (Sp5) was achieved by application of CFA onto the dural parietal surface. SZR72 was given intraperitoneally (i.p.), one dose prior CFA deposition and repeatedly daily for 7 days. Immunohistochemical studies were performed for mapping glutamate, c-fos, PACAP, substance P, IL-6, IL-1β and TNFα in the TNC/Sp5 and other regions of the brainstem and at the C1-C2 regions of the spinal cord. Results: We found that CFA increased c-fos and glutamate immunoreactivity in TNC and C1-C2 neurons. This effect was mitigated by SZR72. PACAP positive fibers were detected in the fasciculus cuneatus and gracilis. Substance P, TNFα, IL-6 and IL-1β immunopositivity were detected in fibers of Sp5 and neither of these molecules showed any change in immunoreactivity following CFA administration. Conclusion: This is the first study demonstrating that dural application of CFA increases the expression of c-fos and glutamate in TNC neurons. Treatment with the KYNA analogue prevented this expression.
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| 11. |
- Pavliuk, Mariia V., et al.
(författare)
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Hydrogen evolution with nanoengineered ZnO interfaces decorated using a beetroot extract and a hydrogenase mimic
- 2017
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Ingår i: Sustainable Energy & Fuels. - : Royal Society of Chemistry. - 2398-4902. ; 1, s. 69-73
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we report a nano-hybrid photo-system based on abundant elements for H2 production with visible light. The photo-system's proficiency relates to the novel ZnO nanocrystals employed. The ZnO carboxylate oligoethylene glycol shell enhances charge separation and accumulates reactive electrons for the photocatalytic process.
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| 12. |
- Walker, Christopher S, et al.
(författare)
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A second trigeminal CGRP receptor: function and expression of the AMY1 receptor.
- 2015
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 2:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- The trigeminovascular system plays a central role in migraine, a condition in need of new treatments. The neuropeptide, calcitonin gene-related peptide (CGRP), is proposed as causative in migraine and is the subject of intensive drug discovery efforts. This study explores the expression and functionality of two CGRP receptor candidates in the sensory trigeminal system.
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| 13. |
- Bayrak Pehlivan, Ilknur, et al.
(författare)
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Scalable and thermally-integrated solar water-splitting modules using Ag-doped Cu(In,Ga)Se2 and NiFe layered double hydroxide nanocatalysts
- 2022
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 10:22, s. 12079-12091
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Tidskriftsartikel (refereegranskat)abstract
- Photovoltaic (PV) electrolysis is an important and powerful technology for environmentally-friendly fuel production based on solar energy. By directly coupling solar cell materials to electrochemical systems to perform water electrolysis, solar energy can be converted into hydrogen fuel utilizing locally-generated heat and avoid losses from DC-DC convertors and power grid transmission. Although there have been significant contributions to the photoelectrochemical and PV-electrolysis field using isolated laboratory cells, the capacity to upscale and retain high levels of efficiency in larger modules remains a critical issue for widespread use and application. In this study, we develop thermally-integrated, solar-driven water-splitting device modules using AgCu(In,Ga)Se2 (ACIGS) and an alkaline electrolyzer system with NiFe-layered double hydroxide (LDH) nanocatalysts with devices of 82-100 cm2 area. The Ga-content in the ACIGS solar cells is tuned to achieve an optimal voltage for the catalyst system, and the average efficiencies and durability of the PV-electrolyzer were tested in up to seven-day indoor and 21 day outdoor operations. We achieved a solar-to-hydrogen (STH) module efficiency of 13.4% from gas volume measurements for the system with a six-cell CIGS-electrolyzer module with an active area of 82.3 cm2 and a 17.27% PV module efficiency under 100 mW cm−2 illumination, and thus 77% electricity-to-hydrogen efficiency at one full sun. Outdoor tests under mid-Europeen winter conditions exhibited an STH efficiency between 10 and 11% after the initial activation at the installation site in Jülich, Germany, in December 2020, despite challenging outdoor-test weather conditions, including sub-zero temperatures.
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| 14. |
- Bayrak Pehlivan, Ilknur, et al.
(författare)
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The climatic response of thermally integrated photovoltaic-electrolysis water splitting using Si and CIGS combined with acidic and alkaline electrolysis
- 2020
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Ingår i: Sustainable Energy & Fuels. - : ROYAL SOC CHEMISTRY. - 2398-4902. ; 4:12, s. 6011-6022
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Tidskriftsartikel (refereegranskat)abstract
- The Horizon 2020 project PECSYS aims to build a large area demonstrator for hydrogen production from solar energy via integrated photovoltaic (PV) and electrolysis systems of different types. In this study, Si- and CIGS-based photovoltaics are developed together with three different electrolyzer systems for use in the corresponding integrated devices. The systems are experimentally evaluated and a general model is developed to investigate the hydrogen yield under real climatic conditions for various thin film and silicon PV technologies and electrolyser combinations. PV characteristics using a Si heterojunction (SHJ), thin film CuInxGa1-xSe2, crystalline Si with passivated emitter rear totally diffused and thin film Si are used together with temperature dependent catalyst load curves from both acidic and alkaline approaches. Electrolysis data were collected from (i) a Pt-IrO2-based acidic electrolysis system, and (ii) NiMoW-NiO-based and (iii) Pt-Ni foam-based alkaline electrolysis systems. The calculations were performed for mid-European climate data from Julich, Germany, which will be the installation site. The best systems show an electricity-to-hydrogen conversion efficiency of 74% and over 12% solar-to-hydrogen (STH) efficiencies using both acidic and alkaline approaches and are validated with a smaller lab scale prototype. The results show that the lower power delivered by all the PV technologies under low irradiation is balanced by the lower demand for overpotentials for all the electrolysis approaches at these currents, with more or less retained STH efficiency over the full year if the catalyst area is the same as the PV area for the alkaline approach. The total yield of hydrogen, however, follows the irradiance, where a yearly hydrogen production of over 35 kg can be achieved for a 10 m(2) integrated PV-electrolysis system for several of the PV and electrolyser combinations that also allow a significant (100-fold) reduction in necessary electrolyser area for the acidic approach. Measuring the catalyst systems under intermittent and ramping conditions with different temperatures, a 5% lowering of the yearly hydrogen yield is extracted for some of the catalyst systems while the Pt-Ni foam-based alkaline system showed unaffected or even slightly increased yearly yield under the same conditions.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Bigal, Marcelo E, et al.
(författare)
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Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study.
- 2015
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Ingår i: Lancet Neurology. - 1474-4465. ; 14:11, s. 1091-1100
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Tidskriftsartikel (refereegranskat)abstract
- Benefits of calcitonin-gene related peptide (CGRP) inhibition have not been established in chronic migraine. Here we assess the safety, tolerability, and efficacy of two doses of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of chronic migraine.
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| 20. |
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| 21. |
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| 22. |
- Borgström, Emilie W., et al.
(författare)
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Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors
- 2023
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Ingår i: Journal of Clinical Immunology. - : Springer. - 0271-9142 .- 1573-2592. ; 43, s. 136-150
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Tidskriftsartikel (refereegranskat)abstract
- Purpose; The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors.Methods: Mass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans.Results: Overall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-gamma and CXCL10 were downregulated.Conclusions: The clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.
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| 23. |
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| 24. |
- Bränn, Emma, et al.
(författare)
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Inflammatory markers in women with postpartum depressive symptoms
- 2020
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 98:7, s. 1309-1321
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Tidskriftsartikel (refereegranskat)abstract
- Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.
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| 25. |
- Christensen, S. T., et al.
(författare)
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Synergistic effects of a cremophor EL drug delivery system and its U0126 cargo in an ex vivo model
- 2019
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Ingår i: Drug delivery. - : Informa UK Limited. - 1071-7544 .- 1521-0464. ; 26:1, s. 680-688
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Tidskriftsartikel (refereegranskat)abstract
- Neuroprotection has proven clinically unsuccessful in subarachnoid hemorrhage. We believe that this is because the major component in the early damage pathway, the vascular wall, has not been given the necessary focus. U0126 is a potent inhibitor of vascular phenotypical changes, exemplified by functional endothelin B (ETB) receptor upregulation. The current study aimed to determine the optimal dose of U0126 ex vivo and test the toxicology of this dose in vivo. To find the optimal dose and test a suitable in vivo delivery system, we applied an ex vivo model of blood flow cessation and investigated functional ETB receptor upregulation (using a specific agonist) as the primary endpoint. The secondary endpoint was depolarization-induced contractility assessed by 60 mM K+ stimuli. Furthermore, an in vivo toxicology study was performed on the optimal selected doses. U0126 (10 µM) had a strong effect on the prevention of functional ETB receptor contractility, combined with minimal effect on the depolarization-induced contractility. When cremophor EL was chosen for drug delivery, it had an inhibitory and additive effect (combined with U0126) on the ETB receptor contractility. Hence, 10 µM U0126 in 0.5% cremophor EL seems to be a dose that will be close to the maximal inhibition observed ex vivo on basilar arteries, without exhibiting side effects in the toxicology studies. U0126 and cremophor EL are well tolerated at doses that have effect on ETB receptor upregulation. Cremophor EL has an additional positive effect, preventing functional ETB receptor upregulation, making it suitable as a drug delivery system.
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