| 1. |
- Edvinsson, Jacob C.A., et al.
(författare)
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C-fibers may modulate adjacent Aδ-fibers through axon-axon CGRP signaling at nodes of Ranvier in the trigeminal system
- 2019
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Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Monoclonal antibodies (mAbs) towards CGRP or the CGRP receptor show good prophylactic antimigraine efficacy. However, their site of action is still elusive. Due to lack of passage of mAbs across the blood-brain barrier the trigeminal system has been suggested a possible site of action because it lacks blood-brain barrier and hence is available to circulating molecules. The trigeminal ganglion (TG) harbors two types of neurons; half of which store CGRP and the rest that express CGRP receptor elements (CLR/RAMP1). METHODS: With specific immunohistochemistry methods, we demonstrated the localization of CGRP, CLR, RAMP1, and their locations related to expression of the paranodal marker contactin-associated protein 1 (CASPR). Furthermore, we studied functional CGRP release separately from the neuron soma and the part with only nerve fibers of the trigeminal ganglion, using an enzyme-linked immunosorbent assay. RESULTS: Antibodies towards CGRP and CLR/RAMP1 bind to two different populations of neurons in the TG and are found in the C- and the myelinated Aδ-fibers, respectively, within the dura mater and in trigeminal ganglion (TG). CASPR staining revealed paranodal areas of the different myelinated fibers inhabiting the TG and dura mater. Double immunostaining with CASPR and RAMP1 or the functional CGRP receptor antibody (AA58) revealed co-localization of the two peptides in the paranodal region which suggests the presence of the CGRP-receptor. Double immunostaining with CGRP and CASPR revealed that thin C-fibers have CGRP-positive boutons which often localize in close proximity to the nodal areas of the CGRP-receptor positive Aδ-fibers. These boutons are pearl-like synaptic structures, and we show CGRP release from fibers dissociated from their neuronal bodies. In addition, we found that adjacent to the CGRP receptor localization in the node of Ranvier there was PKA immunoreactivity (kinase stimulated by cAMP), providing structural possibility to modify conduction activity within the Aδ-fibers. CONCLUSION: We observed a close relationship between the CGRP containing C-fibers and the Aδ-fibers containing the CGRP-receptor elements, suggesting a point of axon-axon interaction for the released CGRP and a site of action for gepants and the novel mAbs to alleviate migraine.
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| 2. |
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| 3. |
- Edvinsson, Marie-Louise, et al.
(författare)
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Characterization of Relaxant Responses to Natriuretic Peptides in the Human Microcirculation In Vitro and In Vivo
- 2016
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Ingår i: Microcirculation. - : Wiley. - 1073-9688. ; 23:6, s. 438-446
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We characterized the vasodilatory effects of ANP, BNP, and CNP in human subcutaneous arterioles in vitro and the cutaneous microcirculation in vivo. Methods: The in vitro experiments were performed using wire myography and the responses were characterized by the use of inhibitors for nitric oxide (L-NAME), prostaglandin synthesis (indomethacin), or the endothelium-derived hyperpolarization factor. In vivo, the vasorelaxant effect of iontophoretically administrated BNP or CNP was measured with a noninvasive laser Doppler technique. Involvement of nitric oxide or prostaglandins was assessed by L-NAME or indomethacin given by iontophoresis. Results: In vitro all three peptides showed significant vasodilatation with the efficacy order: CNP > BNP = ANP. The BNP-induced vasodilatation, but not that of ANP or CNP, was significantly reduced by pretreatment with indomethacin or L-NAME. In vivo administration of BNP induced a marked vasodilatory response that was attenuated by local pretreatment of L-NAME. Indomethacin by itself resulted in increased cutaneous perfusion. Conclusions: NPs are potent vasodilators in the human subcutaneous circulation. The response to BNP differs from that of the other peptides as it seems dependent on cyclooxygenase products and nitric oxide.
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| 4. |
- Skovsted, Gry Freja, et al.
(författare)
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Myocardial ischemia-reperfusion enhances transcriptional expression of endothelin-1 and vasoconstrictor ETB receptors via the protein kinase MEK-ERK1/2 signaling pathway in rat
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Coronary artery remodelling and vasospasm is a complication of acute myocardial ischemia and reperfusion. The underlying mechanisms are complex, but the vasoconstrictor peptide endothelin-1 is suggested to have an important role. This study aimed to determine whether the expression of endothelin-1 and its receptors are regulated in the myocardium and in coronary arteries after experimental ischemia-reperfusion. Furthermore, we evaluated whether treatment with a specific MEK1/2 inhibitor, U0126, modified the expression and function of these proteins. Methods and findings: Sprague-Dawley rats were randomly divided into three groups: sham-operated, ischemiareperfusion with vehicle treatment and ischemia-reperfusion with U0126 treatment. Ischemia was induced by ligating the left anterior descending coronary artery for 30 minutes followed by reperfusion. U0126 was administered before ischemia and repeated 6 hours after start of reperfusion. The contractile properties of isolated coronary arteries to endothelin-1 and sarafotoxin 6c were evaluated using wire-myography. The gene expression of endothelin-1 and endothelin receptors were measured using qPCR. Distribution and localization of proteins (pERK1/2, prepro-endothelin-1, endothelin-1, and endothelin ETA and ETB receptors) were analysed by Western blot and immunohistochemistry. We found that pERK1/2 was significantly augmented in the ischemic area 3 hours after ischemia-reperfusion; this correlated with increased ETB receptor and ET-1 gene expressions in ischemic myocardium and in coronary arteries. ETB receptor-mediated vasoconstriction was observed to be increased in coronary arteries 24 hours after ischemia-reperfusion. Treatment with U0126 reduced pERK1/2, expression of ET-1 and ETB receptor, and ETB receptor-mediated vasoconstriction. Conclusions: These findings suggest that the MEK-ERK1/2 signaling pathway is important for regulating endothelin-1 and ETB receptors in myocardium and coronary arteries after ischemia-reperfusion in the ischemic region. Inhibition of the MEK-ERK1/2 pathway may provide a novel target for reducing ischemia-reperfusion damage in the heart.
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| 5. |
- Ahnland, Lars, 1974-
(författare)
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Financialization in Swedish Capitalism : Debt, inequality and crisis in Sweden, 1900-2013
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation adresses financialization – the increasing role of financial activities in the overall economy – in Sweden in 1900-2013. The focus is on the long run relationships between private debt, asset markets, inequality and financial crisis during this period. In line with established scholarship, the present study finds that changes in bank debt had a positive impact on the probability of financial crisis in Sweden. Functional income distribution between profits and wages was an underlying factor influencing the formation of bank debt levels through its impact on collateral in stock markets. Expenses related to the Swedish welfare state – the size of the public sector, government investment and housing construction – had a long run relationship with the wage share. The welfare state has been an effective counter-measure not just against a high profit share, but also against financialization. Moreover, the dissertation shows that the recent era of financialization in Swedish capitalism is not unique in kind. Rather, recent financialization is very similar to the macroeconomic situation during the early decades of the 20th Century. These findings are consistent with much of heterodox economic theory, in particular the Neo-Marxist approach.
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| 6. |
- Ahnstedt, Hilda, et al.
(författare)
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U0126 attenuates cerebral vasoconstriction and improves long-term neurologic outcome after stroke in female rats.
- 2015
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 35:3, s. 454-460
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Tidskriftsartikel (refereegranskat)abstract
- Sex differences are well known in cerebral ischemia and may impact the effect of stroke treatments. In male rats, the MEK1/2 inhibitor U0126 reduces ischemia-induced endothelin type B (ETB) receptor upregulation, infarct size and improves acute neurologic function after experimental stroke. However, responses to this treatment in females and long-term effects on outcome are not known. Initial experiments used in vitro organ culture of cerebral arteries, confirming ERK1/2 activation and increased ETB receptor-mediated vasoconstriction in female cerebral arteries. Transient middle cerebral artery occlusion (tMCAO, 120 minutes) was induced in female Wistar rats, with U0126 (30 mg/kg intraperitoneally) or vehicle administered at 0 and 24 hours of reperfusion, or with no treatment. Infarct volumes were determined and neurologic function was assessed by 6-point and 28-point neuroscores. ETB receptor-mediated contraction was studied with myograph and protein expression with immunohistochemistry. In vitro organ culture and tMCAO resulted in vascular ETB receptor upregulation and activation of ERK1/2 that was prevented by U0126. Although no effect on infarct size, U0126 improved the long-term neurologic function after experimental stroke in female rats. In conclusion, early prevention of the ERK1/2 activation and ETB receptor-mediated vasoconstriction in the cerebral vasculature after ischemic stroke in female rats improves the long-term neurologic outcome.Journal of Cerebral Blood Flow & Metabolism advance online publication, 10 December 2014; doi:10.1038/jcbfm.2014.217.
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| 7. |
- Bayrak Pehlivan, Ilknur, et al.
(författare)
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Bifunctional solar electrocatalytic water splitting using CIGS solar modules and WO3-based electrolyzers
- 2019
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Ingår i: EMRS Spring Meeting 2019.
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Konferensbidrag (refereegranskat)abstract
- Using energy from the sun to produce a fuel and finally obtaining only water as an exhaust is a promising future technology for renewable energy and environmental sustainability. Solar driven water splitting is a method to produce hydrogen from solar energy. Coupling a solar cell with an electrolyzer is the approach with highest technological readiness. CuInxGa1-xSe2 (CIGS) is here a promising solar cell material for water splitting because it is possible to tune the band gap between 1.0 and 1.7 eV by changing the ratio between Ga and In, thus enabling maximum power point matching with an electrolyzer. Tungsten oxide is known as a photocatalytic material and mainly used for the oxygen evolution reaction in a water splitting process. However, WO3 films also show electrochromic activity together with hydrogen evolution. This result is interesting because it shows that WO3 films can be used as bifunctional materials for both hydrogen and oxygen evolution in water splitting, and provide additional functionalities to the system. In this study, WO3 films coated at different sputtering conditions on Ni foam and indium tin oxide substrates were investigated in the potential range of the hydrogen evolution reaction. The best overpotential of 164 mV vs. RHE at 10 mA/cm2 was obtained for WO3 films on Ni foam in 0.5 M H2SO4. The lowest potential needed for 10 mA/cm2 was measured 1.768 V for the electrolyzers consisting WO3 films on Ni foam as the cathode and non-coated Ni foam as the anode. Optimum solar-to-hydrogen (STH) efficiency of the CIGS solar cell modules and the electrolyzers was examined for different band gaps of the CIGS modules and sputtering conditions of WO3 films. Operation points of the combined system were calculated from the intersection of the voltage-current density curves for the CIGS modules and the electrolyzers. The results showed that the detailed sputtering conditions were not very critical to obtain high STH efficiency, indicating that the system could be robust and easily manufactured. The best-matched band gap of the CIGS was 1.19 eV and the highest STH efficiency of the CIGS driven WO3-based electrolyzers was 12.98 %.
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| 8. |
- Bayrak Pehlivan, Ilknur, et al.
(författare)
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Optimum Band Gap Energy of ((Ag),Cu)(InGa)Se2 Materials for Combination with NiMo–NiO Catalysts for Thermally Integrated Solar-Driven Water Splitting Applications
- 2019
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Ingår i: Energies. - : MDPI AG. - 1996-1073. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Solar-driven water splitting is considered one of the promising future routes to generate fuel in a sustainable way. A carbon-free solar fuel, molecular hydrogen, can here be produced along two different but intimately related routes, photoelectrochemical (PEC) water splitting or photovoltaic electrolysis (PV-electrolysis), where the latter builds on well-established solar cell and electrolysis materials with high efficiency. The PV-electrolysis approach is also possible to construct from an integrated PEC/PV-system avoiding dc-dc converters and enabling heat exchange between the PV and electrolyzer part, to a conventionally wired PV-electrolysis system. In either case, the operating voltage at a certain current needs to be matched with the catalyst system in the electrolysis part. Here, we investigate ((Ag),Cu)(In,Ga)Se-2 ((A)CIGS)-materials with varying Ga-content modules for combination with NiMo-NiO catalysts in alkaline water splitting. The use of (A)CIGS is attractive because of the low cost-to-performance ratio and the possibility to optimize the performance of the system by tuning the band gap of (A)CIGS in contrast to Si technology. The band gap tuning is possible by changing the Ga/(Ga + In) ratio. Optoelectronic properties of the (A)CIGS materials with Ga/(Ga + In) ratios between 0.23 and 0.47 and the voltage and power output from the resulting water splitting modules are reported. Electrolysis is quantified at temperatures between 25 and 60 degrees C, an interval obtainable by varying the thermal heat exchange form a 1-sun illuminated PV module and an electrolyte system. The band gaps of the (A)CIGS thin films were between 1.08 to 1.25 eV and the three-cell module power conversion efficiencies (PCE) ranged from 16.44% with 1.08 eV band gap and 19.04% with 1.17 eV band gap. The highest solar-to-hydrogen (STH) efficiency was 13.33% for the (A)CIGS-NiMo-NiO system with 17.97% module efficiency and electrolysis at 60 degrees C compared to a STH efficiency of 12.98% at 25 degrees C. The increase in STH efficiency with increasing temperature was more notable for lower band gaps as these are closer to the overpotential threshold for performing efficient solar-driven catalysis, while only a modest improvement can be obtained by utilizing thermal exchange for a band gap matched PV-catalysts system. The results show that usage of cost-effective and stable thin film PV materials and earth abundant catalysts can provide STH efficiencies beyond 13% even with PV modules with modest efficiency.
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| 9. |
- 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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| 10. |
- Blixt, Frank W., et al.
(författare)
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Distribution of CGRP and its receptor components CLR and RAMP1 in the rat retina
- 2017
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Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835. ; 161, s. 124-131
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Tidskriftsartikel (refereegranskat)abstract
- Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide with several functions including vasodilation, the perception of painful stimuli, and inflammation. The CGRP receptor consists of two main components; calcitonin-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). While there is a growing recognition that CGRP plays a key role in migraine, the function of CGRP in the retina has not been fully established. This study aims to investigate the distribution of CGRP and its two receptor components in the rat retina, visually by immunohistochemistry and quantitatively using flow cytometry. CGRP immunoreactivity was found in the Müller cells while CLR/RAMP1 was located in the nerve fiber layer. Furthermore, since almost all RAMP1 immunoreactive cells co-express CLR, we propose that RAMP1 expression in the retina reflects functional CGRP receptors.
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