| 1. |
- Edvinsson, Jacob Carl Alexander, et al.
(författare)
-
Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system
- 2020
-
Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 40:12, s. 1296-1309
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective: The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods: In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K+ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands. Results: Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC1 was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres. Conclusion: Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.
|
|
| 2. |
- Bergman, Maria, 1981-
(författare)
-
Constructing communities : The establishment and demographic development of sawmill communities in the Sundsvall district, 1850-1890
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation studies the establishment and demographic development of the sawmill communities that emerged in the Sundsvall district during the latter half of the 19th century. The intention is to highlight the importance of the sawmill communities and their resident populations by discussing community construction from a demographic perspective as well as socially and symbolically. Based on church registers, this is a longitudinal study that includes information from 31 individual sawmill communities. This study has shown that the establishment and demographic development of the sawmill communities was not an instant process that necessarily followed the construction of the sawmill industries. The prerequisites of the geographical locations and year of establishment influenced population development, but the speed and size of the settlements were individual to each mill site. More prosperous times for the industry during the 1870s resulted in that migration increased consequently leading to quickly populated communities and larger registered core populations in residence. Migration to the sawmill communities from within the parishes was infrequent and the geographical backgrounds revealed that an extremely small proportion of the populations had been born within the district, implying a migratory hesitation among locally born. The sawmill populations were male-dominated due to the large groups of temporary workers inhabiting the communities, although, adult males barely made up one-third of the registered populations. The largest demographic group was children aged 0-14 years. The strong presence of children and high proportions of married individuals suggests that the sawmill communities were family oriented communities, more so than non-sawmill areas. Long-time settled families had usually formed kinship networks with other residents. This dissertation concludes that while time was important for the development of the sawmill communities, so were the registered populations residing in these communities. Residency would have been key in claiming belonging to the sawmill communities and to be considered as a real sawmill worker. Residency, family and kin therefore contributed to the construction of community structures, geographically, socially and symbolically.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Bjärntoft, Sofie, et al.
(författare)
-
A participatory approach to identify key areas for sustainable work environment and health in employees with flexible work arrangements
- 2021
-
Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 13:24
-
Tidskriftsartikel (refereegranskat)abstract
- Flexible work arrangements are common worldwide, but knowledge on how to achieve a sustainable work environment is sparse. The aim of this study was to use a participatory approach to identify concrete suggestions and key areas for improvement that were considered relevant, effective, and feasible for promoting good work environment and health at organizational, work group and individual level (O-G-I), among office employees with flexible work arrangements. Eight focus group interviews (including 45 employees) were conducted in a large Swedish government agency in 2017. By using a Tree diagram approach, employees made a total of 279 suggestions for improvements, which were sorted into O-G-I levels and mapped into 18 key areas. We found that 13 key areas addressed organizational level (e.g., improving leadership, policy, job demands, and work efficiency), two key areas addressed group level (create common rules of availability and activity-based working), and three key areas addressed individual level (e.g., individuals’ responsibility to clearly communicate their availability). The participatory process was effective in obtaining concrete suggestions and key areas in need of improvement, which may provide an action plan that can guide organizations in developing interventions to promote good work environment and health in flexible work.
|
|
| 8. |
- Bömers, Jesper Peter, et al.
(författare)
-
The MEK Inhibitor Trametinib Improves Outcomes following Subarachnoid Haemorrhage in Female Rats
- 2022
-
Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 15:12
-
Tidskriftsartikel (refereegranskat)abstract
- Aneurysmal subarachnoid haemorrhage (SAH) is a haemorrhagic stroke that causes approximately 5% of all stroke incidents. We have been working on a treatment strategy that targets changes in cerebrovascular contractile receptors, by blocking the MEK/ERK1/2 signalling pathway. Recently, a positive effect of trametinib was found in male rats, but investigations of both sexes in pre-clinical studies are an important necessity. In the current study, a SAH was induced in female rats, by autologous blood-injection into the pre-chiasmatic cistern. This produces a dramatic, transient increase in intracranial pressure (ICP) and an acute and prolonged decrease in cerebral blood flow. Rats were then treated with either vehicle or three doses of 0.5 mg/kg trametinib (specific MEK/ERK1/2 inhibitor) intraperitoneally at 3, 9, and 24 h after the SAH. The outcome was assessed by a panel of tests, including intracranial pressure (ICP), sensorimotor tests, a neurological outcome score, and myography. We observed a significant difference in arterial contractility and a reduction in subacute increases in ICP when the rats were treated with trametinib. The sensory motor and neurological outcomes in trametinib-treated rats were significantly improved, suggesting that the improved outcome in females is similar to that of males treated with trametinib.
|
|
| 9. |
- Chorell, Erik, 1980-, et al.
(författare)
-
Design and synthesis of C-2 substituted Thiazolo and Dihydrothiazolo ring-fused 2-Pyridones : pilicides with increased antivirulence activity
- 2010
-
Ingår i: Journal of Medicinal Chemistry. - Washington, USA : American Chemical Society. - 0022-2623 .- 1520-4804. ; 53:15, s. 5690-5695
-
Tidskriftsartikel (refereegranskat)abstract
- Pilicides block pili formation by binding to pilus chaperones and blocking their function in the chaperone/usher pathway in E. coli. Various C-2 substituents were introduced on the pilicide scaffold by design and synthetic method developments. Experimental evaluation showed that proper substitution of this position affected the biological activity of the compound. Aryl substituents resulted in pilicides with significantly increased potencies as measured in pili-dependent biofilm and hemagglutination assays. The structural basis of the PapD chaperone-pilicide interactions was determined by X-ray crystallography.
|
|
| 10. |
- Chorell, Erik, et al.
(författare)
-
Design and Synthesis of Fluorescent Pilicides and Curlicides : Bioactive Tools to Study Bacterial Virulence Mechanisms
- 2012
-
Ingår i: Chemistry - A European Journal. - Berlin : Wiley-VCH Verlagsgesellschaft. - 0947-6539 .- 1521-3765. ; 18:15, s. 4522-4532
-
Tidskriftsartikel (refereegranskat)abstract
- Pilicides and curlicides are compounds that block the formation of the virulence factors pili and curli, respectively. To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized. This was achieved by using a strategy based on structure-activity knowledge, in which key pilicide and curlicide substituents on the ring-fused dihydrothiazolo 2-pyridone central fragment were replaced by fluorophores. Several of the resulting fluorescent compounds had improved activities as measured in pili- and curli-dependent biofilm assays. We created fluorescent pilicides and curlicides by introducing coumarin and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores at two positions on the peptidomimetic pilicide and curlicide central fragment. Fluorescence images of the uropathogenic Escherichia coli (UPEC) strain UTI89 grown in the presence of these compounds shows that the compounds are strongly associated with the bacteria with a heterogeneous distribution.
|
|
| 11. |
- Chorell, Erik, 1980-, et al.
(författare)
-
Design and synthesis of fluorescently labeled pilicides and curlicides: bioactive tools to study bacterial virulence mechanisms
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Pilicides and curlicides block formation of the E. coli virulence factors pili and curli. To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized. This was achieved using a strategy where key pilicide and curlicide substituents were replaced by fluorophores having similar physicochemical properties. The resulting fluorescent compounds had improved anti-virulence activities as measured in pili- and curli-dependent biofilm assays. We created fluorescent pilicides and curlicides by introducing both coumarin and 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores at two positions on the peptidomimetic pilicide and curlicide scaffold. Fluorescence images of the uropathogenic Escherichia coli (UPEC) strain UTI89 grown in the presence of these compounds shows that the compounds are strongly associated to the bacteria and seem to discriminate between different bacteria in a population.
|
|
| 12. |
- Chorell, Erik, 1980-, et al.
(författare)
-
Improved procedure for the enantioselective synthesis of dihydrooxazolo and dihydrothiazolo ring-fused 2-pyridones
- 2010
-
Ingår i: Tetrahedron Letters. - : Elsevier Ltd. - 0040-4039 .- 1359-8562. ; 51:18, s. 2461-2463
-
Tidskriftsartikel (refereegranskat)abstract
- Improved procedures to synthesize enantioselectively analogues of a peptidomimetic scaffold with high biological relevance have been developed. Experimental design led to a general method for the preparation of dihydrooxazolo ring-fused 2-pyridones in good yields and high enantiomeric purity. The knowledge gained from this was also used to improve the microwave-accelerated synthesis of dihydrothiazolo ring-fused 2-pyridones to give complete stereo retention and high yields.
|
|
| 13. |
- Chorell, Erik, et al.
(författare)
-
Mapping pilicide anti-virulence effect in Escherichia coli, a comprehensive structure-activity study
- 2012
-
Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier. - 0968-0896 .- 1464-3391. ; 20:9, s. 3128-3142
-
Tidskriftsartikel (refereegranskat)abstract
- Pilicides prevent pili formation and thereby the development of bacterial biofilms in Escherichia coli. We have performed a comprehensive structure activity relationship (SAR) study of the dihydrothiazolo ring-fused 2-pyridone pilicide central fragment by varying all open positions. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to distinguish active from inactive compounds in which polarity proved to be the most important factor for discrimination. A quantitative SAR (QSAR) partial least squares (PLS) model was calculated on the active compounds for prediction of biofilm inhibition activity. In this model, compounds with high inhibitory activity were generally larger, more lipophilic, more flexible and had a lower HOMO. Overall, this resulted in both highly valuable SAR information and potent inhibitors of type 1 pili dependent biofilm formation. The most potent biofilm inhibitor had an EC(50) of 400nM.
|
|
| 14. |
- Christensen, Simon T., et al.
(författare)
-
Pre-clinical effects of highly potent MEK1/2 inhibitors on rat cerebral vasculature after organ culture and subarachnoid haemorrhage
- 2019
-
Ingår i: Clinical Science. - 0143-5221. ; 133:16, s. 1797-1811
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Aneurysmal subarachnoid haemorrhage (SAH) is a variant of haemorrhagic stroke with a striking 50% mortality rate. In addition to the initial insult, secondary delayed brain injury may occur days after the initial ischemic insult and is associated with vasospasms leading to delayed cerebral ischemia. We have previously shown that the MEK1/2 inhibitor U0126 improves neurological assessment after SAH in rats. Aim: The purpose of the present study was to analyse the impact of a broad selection of high potency MEK1/2 inhibitors in an organ culture model and use the IC50 values obtained from the organ culture to select highly potent inhibitors for pre-clinical in vivo studies. Results: Nine highly potent mitogen activated protein kinase kinase (MEK1/2) inhibitors were screened and the two most potent inhibitors from the organ culture screening, trametinib and PD0325901, were tested in an in vivo experimental rat SAH model with intrathecal injections. Subsequently, the successful inhibitor trametinib was administered intraperitoneally in a second in vivo study. In both regimens, trametinib treatment caused significant reductions in the endothelin-1 induced contractility after SAH, which is believed to be associated with endothelin B receptor up-regulation. Trametinib treated rats showed improved neurological scores, evaluated by the ability to traverse a rotating pole, after induced SAH. Conclusion: The PD0325901 treatment did not improve the neurological score after SAH, nor showed any beneficial therapeutic effect on the contractility, contrasting with the reduction in neurological deficits seen after trametinib treatment. These data show that trametinib might be a potential candidate for treatment of SAH.
|
|
| 15. |
- Edvinsson, Johanna, Doktorand, et al.
(författare)
-
A Work Time Control Tradeoff in Flexible Work: Competitive Pathways to Need for Recovery
- 2023
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Work time control may offer opportunities, but also implies risks for employee recovery, influenced by increased work-related ICT use and overtime work. However, this risk–opportunity tradeoff remains understudied. This study aimed to test two different models of associations between work time control, work-related ICT use, overtime work, and the need for recovery. These models were constructed based on data on office workers with flexible work arrangements. Cross-sectional data were obtained with questionnaires (n = 2582) from employees in a Swedish multi-site organization. Regression models treated the three determinants of the need for recovery either as independent, or as linked in a causal sequence. The test of independent determinants confirmed that more work time control was associated with less need for recovery, whereas more ICT use and overtime work were associated with a higher need for recovery. In a test of serial mediation, more work time control contributed to a greater need for recovery through more ICT use and then more overtime work. Work time control also had a competitive, indirect effect through a negative association with overtime work. Our results suggest that work time control is beneficial for employee recovery, but may for some be associated with more work-related ICT use after regular working hours, thus increasing recovery needs. Policies that support work time control can promote recovery, but employers must attend to the risk of excessive use of ICT outside of regular working hours.
|
|
| 16. |
- Edvinsson, Sofie, et al.
(författare)
-
An efficient procedure for the synthesis of formylacetic esters
- 2012
-
Ingår i: Tetrahedron Letters. - : Elsevier BV. - 0040-4039 .- 1359-8562. ; 53:50, s. 6819-6821
-
Tidskriftsartikel (refereegranskat)abstract
- An efficient synthesis of formylacetic esters via ozonolysis of trans-beta-hydromuconic esters followed by a solid-supported triphenylphosphine reduction has been developed. In addition, an extension toward formylacetic amides and a one-pot preparation of more stable intermediates which can be used for further transformations are also described.
|
|
| 17. |
- Grell, Anne-Sofie, et al.
(författare)
-
Cerebrovascular gene expression in spontaneously hypertensive rats
- 2017
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:9
-
Tidskriftsartikel (refereegranskat)abstract
- Hypertension is a hemodynamic disorder and one of the most important and well-established risk factors for vascular diseases such as stroke. Blood vessels exposed to chronic shear stress develop structural changes and remodeling of the vascular wall through many complex mechanisms. However, the molecular mechanisms involved are not fully understood. Hypertension-susceptible genes may provide a novel insight into potential molecular mechanisms of hypertension and secondary complications associated with hypertension. The aim of this exploratory study was to identify gene expression differences in the middle cerebral arteries between 12-week-old male spontaneously hypertensive rats and their normotensive Wistar-Kyoto rats using an Affymetrix whole-transcriptome expression profiling. Quantitative PCR and western blotting were used to verify genes of interest. 169 genes were differentially expressed in the middle cerebral arteries from hypertensive compared to normotensive rats. The gene expression of 72 genes was decreased and the gene expression of 97 genes was increased. The following genes with a fold difference ≥1.40 were verified by quantitative PCR; Postn, Olr1, Fas, Vldlr, Mmp2, Timp1, Serpine1, Mmp11, Cd34, Ptgs1 and Ptgs2. The gene expression of Postn, Olr1, Fas, Vldlr, Mmp2, Timp1 and Ser-pine1 and the protein expression of LOX1 (also known as OLR1) were significantly increased in the middle cerebral arteries from spontaneously hypertensive rats compared to Wistar-Kyoto rats. In conclusion, the identified genes in the middle cerebral arteries from spontaneously hypertensive rats could be possible mediators of the vascular changes and secondary complications associated with hypertension. This study supports the selection of key genes to investigate in the future research of hypertension-induced end-organ damage.
|
|
| 18. |
- Grell, Anne Sofie, et al.
(författare)
-
Cerebrovascular Gene Expression in Spontaneously Hypertensive Rats After Transient Middle Cerebral Artery Occlusion
- 2017
-
Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 367, s. 219-232
-
Tidskriftsartikel (refereegranskat)abstract
- Hypertension is a major risk factor for stroke, which is one of the leading global causes of death. In the search for new and effective therapeutic targets in stroke research, we need to understand the influence of hypertension in the vasculature following stroke. We used Affymetrix whole-transcriptome expression profiling as a tool to address gene expression differences between the occluded and non-occluded middle cerebral arteries (MCAs) from spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats after transient middle cerebral artery occlusion (tMCAO), to provide clues about the pathological mechanisms set in play after stroke. Verified by quantitative PCR, expression of Ccl2, Edn1, Tgfβ2, Olr1 and Serpine1 was significantly increased in the occluded compared to non-occluded MCAs from both SHRs and WKY rats. Additionally, expression of Mmp9, Icam1, Hif1α and Timp1 was increased in the occluded compared to non-occluded MCAs isolated from WKY rats. In comparison between occluded MCAs from SHRs versus occluded MCAs from WKY rats, expression of Ccl2, Olr1 and Serpine1 was significantly increased in SHR MCAs. However, the opposite was observed regarding expression of Edn1. Thus these data suggest that Ccl2, Edn1, Tgfβ2, Olr1 and Serpine1 may be possible mediators of the vascular changes in the occluded MCAs from both SHRs and WKY rats after tMCAO. The aforementioned genes possess biological functions that are consistent with early stroke injuries. In conclusion, these genes may be potential targets in future strategies for acute stroke treatments that can be used in patients with and without hypertension.
|
|
| 19. |
- Grell, Anne Sofie, et al.
(författare)
-
Contractile Responses in Spontaneously Hypertensive Rats after Transient Middle Cerebral Artery Occlusion
- 2018
-
Ingår i: Pharmacology. - : S. Karger AG. - 0031-7012 .- 1423-0313. ; 101, s. 120-132
-
Tidskriftsartikel (refereegranskat)abstract
- Stroke is one of the leading causes of mortality and morbidity worldwide, and few therapeutic treatments have shown beneficial effect clinically. One reason for this could be the lack of risk factors incorporated into the preclinical stroke research. We have previously demonstrated phenotypic receptor changes to be one of the injurious mechanisms occurring after stroke but mostly in healthy rats. The aim of this study was to investigate if hypertension has an effect on vasoconstrictive receptor responses to endothelin 1, sarafotoxin 6c and angiotensin II after stroke by inducing transient middle cerebral artery occlusion in spontaneously hypertensive rats and Wistar-Kyoto rats using the wire-myograph. We demonstrated an increased contractile response to endothelin 1 and extracellular potassium as well as an increased carbachol-induced dilator response in the middle cerebral arteries from hypertensive rats after stroke. This study demonstrates the importance of including risk factors in experimental stroke research.
|
|
| 20. |
- Grell, Anne-Sofie, et al.
(författare)
-
Regulatory mechanism of endothelin receptor B in the cerebral arteries after focal cerebral ischemia.
- 2014
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
-
Tidskriftsartikel (refereegranskat)abstract
- Increased expression of endothelin receptor type B (ETBR), a vasoactive receptor, has recently been implied in the reduced cerebral blood flow and exacerbated neuronal damage after ischemia-reperfusion (I/R). The study explores the regulatory mechanisms of ETBR to identify drug targets to restore normal cerebral artery contractile function as part of successful neuroprotective therapy.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Jahncke, Helena, 1982-, et al.
(författare)
-
Symposium: Återhämtning och ledarskap i flexibla arbeten: resultat från ett forskningsprojekt på Trafikverket
- 2018
-
Ingår i: FALF KONFERENS 2018 Arbetet – problem eller potential för en hållbar livsmiljö? 10-12 juni 2018 Gävle. - Gävle : Gävle University Press. - 9789188145284 ; , s. 78-
-
Konferensbidrag (refereegranskat)abstract
- IntroduktionDen stressrelaterade ohälsan ökar i samhället i stort och det är möjligt att bristande återhämtning kan vara bidragande. Det finns dock ännu inte några tydliga svar på hur ett gynnsamt mönster av arbete och återhämtning bör se ut. Frågan om balansen mellan krav i arbetet och möjligheter till återhämtning är särskilt aktuell i yrken där digital teknik möjliggör flexibelt arbete, dvs. ett arbete där de anställda till stor del själva kan styra över sin arbetstid, sitt arbetsställe och/eller sitt arbetssätt. Möjligheten att arbeta flexibelt kan innebära både för- och nackdelar för såväl individen som organisationen och medföra nya utmaningar för chefer när det gäller hur de ska leda sina medarbetare på ett hälsofrämjande sätt. Samtidigt kan flexibiliteten underlätta för medarbetare att få ihop livspusslet och att anpassa arbetsinsatsen utifrån arbetstoppar, vilket kan gynna organisationens produktivitet. Risken är dock att den stressrelaterade ohälsan ökar om balansen mellan arbete och återhämtning rubbas genom t.ex. övertidsarbete och ständig tillgänglighet till arbetet på ogynnsamma tider.Det här symposiet presenterar resultat från ett forskningsprojekt som undersökt flexibelt arbete på Trafikverket. I ett första steg genomfördes en kartläggning av arbetsvillkor, återhämtning och hälsa med hjälp av en webbaserad enkät till 4926 anställda. Resultaten från kartläggningen har sedan legat till grund för fokusgruppsdiskussioner med chefer och medarbetare, där åtgärdsförslag har tagits fram i syfte att förstärka fördelarna och reducera riskerna med flexibelt arbete. Även åtgärdsförslagen från fokusgrupperna kommer att presenteras vid symposiet.
|
|
| 31. |
- Le, Thi Lisa, et al.
(författare)
-
CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles
- 2020
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 875
-
Tidskriftsartikel (refereegranskat)abstract
- CGRP is a potent dilator of arteries and despite rich perivascular CGRP immunoreactivity in both arteries and veins the role of CGRP in veins remains unknown. The aim of the current study was to compare perivascular CGRP immunoreactivity and expression of CGRP receptor mRNA and CGRP receptor immunoreactivity in rat mesenteric arteries and veins. Furthermore, potential vasomotor effects of CGRP were explored in veins. Immunohistochemical studies reproduced rich perivascular CGRP innervation in arteries and in veins. Further, the presence of mRNA encoding the CGRP receptor subunits, CLR and RAMP1, were demonstrated in both arteries and veins using qPCR. Before comparing the vasoactive effects of CGRP in arteries and veins, we aimed to identify an experimental setting where vasomotor responses could be detected. Therefore, a length-tension study was performed in artery and vein segments. Whereas the arteries showed the characteristic monophasic curve with an IC/IC100 value of 0.9, surprisingly the veins showed a biphasic response with two corresponding IC/IC100 values of 0.7 and 0.9, respectively. There was no significant difference between fresh and cultured vasculature segments. To investigate whether a potential tension-dependent CGRP-induced dilation of veins caused the decline between the two IC/IC100 peaks, a second study was performed, with the CGRP receptor antagonist, BIBN4096BS (olcegepant) and the sensory nerve secretagogue, capsaicin. No significant vascular role of endogenous perivascular CGRP in mesenteric veins could be concluded, and a potential role of the rich perivascular CGRP and CGRP receptor abundancy in veins remains unknown.
|
|
| 32. |
|
|
| 33. |
- Pemberton, Nils, et al.
(författare)
-
Synthesis and evaluation of dihydroimidazolo and dihydrooxazolo ring-fused 2-pyridones - Targeting pilus biogenesis in uropathogenic bacteria
- 2008
-
Ingår i: Tetrahedron. - : Elsevier. - 0040-4020 .- 1464-5416. ; 64:40, s. 9368-9376
-
Tidskriftsartikel (refereegranskat)abstract
- Dihydrothiazolo ring-fused 2-pyridones have previously been shown to inhibit pilus assembly in uropathogenic Escherichia coli. Methods have now been developed to synthesize both dihydroimidazolo and dihydrooxazolo ring-fused 2-pyridones. To obtain the nitrogen analogs, Cbz-protected imidazolines were reacted with an acyl-Meldrum's acid derivative under acidic conditions. To prepare the oxygen analogs, a one-pot procedure was developed that allowed synthesis of dihydrooxazolo ring-fused 2-pyridones starting from acylated serine derivatives. After hydrolysis to their corresponding carboxylic acids and lithium carboxylates, biological evaluation revealed that the sulfur could be replaced by an oxygen atom and still maintains the ability to inhibit pilus assembly in uropathogenic E. coli. However, introducing a secondary amine instead of oxygen resulted in a substantial decrease in biological activity.
|
|
| 34. |
- Samraj, Ajoy K, et al.
(författare)
-
Role of unphosphorylated transcription factor STAT3 in late cerebral ischemia after subarachnoid hemorrhage.
- 2014
-
Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 34:5, s. 759-763
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular mechanisms behind increased cerebral vasospasm and local inflammation in late cerebral ischemia after subarachnoid hemorrhage (SAH) are poorly elucidated. Using system biology tools and experimental SAH models, we have identified signal transducer and activator of transcription 3 (STAT3) transcription factor as a possible major regulatory molecule. On the basis of the presence of transcription factor binding sequence in the promoters of differentially regulated genes (significant enrichment PE: 6 × 10(5)) and the consistent expression of STAT3 (mRNA, P=0.0159 and Protein, P=0.0467), we hypothesize that unphosphorylated STAT3 may directly DNA bind and probably affect the genes that are involved in inflammation and late cerebral ischemia to influence the pathologic progression of SAH.Journal of Cerebral Blood Flow & Metabolism advance online publication, 12 February 2014; doi:10.1038/jcbfm.2014.15.
|
|
| 35. |
- Skovsted, Gry Freja, et al.
(författare)
-
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
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:3
-
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.
|
|
