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  • Koch, Bo L., et al. (författare)
  • Inhalation of substance P and thiorphan : acute toxicity and effects on respiration in conscious guinea pigs.
  • 1999
  • Ingår i: Journal of Applied Toxicology. - 0260-437X .- 1099-1263. ; 19:1, s. 19-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans.
  • Nilsson, S., et al. (författare)
  • A relationship between migraine and biliary tract disorders: findings in two Swedish samples of elderly twins
  • 2010
  • Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 1600-0404 .- 0001-6314. ; 122:4, s. 286-294
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives - To investigate whether there is a relationship between the clinical occurrence of migraine and biliary tract disorders (BTD) and to study whether there is a genetic influence on such an association. Materials and Methods - The near lifetime morbidity for migraine and BTD was examined in two Swedish twin-samples: OCTO-Twin (149 MZ and 202 DZ pairs; 234 men, 468 women; 80 years of age or older at inclusion), and the GENDER study (249 unlike-sex DZ-pairs; 70-80 years of age at inclusion). The diagnosis of BTD was established by perusal of medical records from the last twenty years. The diagnosis of migraine was based on iterated questionnaires and personal interviews. Results - The odds ratio (OR) of BTD among OCTO-Twin subjects suffering from migraine was 3.5 (1.9-6.7) in monozygotic pairs and 1.7 (1.0-2.9) in dizygotic pairs The corresponding figures among the GENDER unlike-sex DZ-pairs was 2.7 (1.6-4.5). Migraine was associated with female sex and waist circumference. Conclusions - There is a relationship between the occurrence of migraine and BTD, also when controlling for the fact that both disorders are more frequent in women. The association appears to be partly attributable to genetic influences.
  • Adner, Mikael, et al. (författare)
  • Contractile endothelin-B (ETB) receptors in human small bronchi
  • 1996
  • Ingår i: European Respiratory Journal. - : European Respiratory Society. - 1399-3003. ; 9:2, s. 351-355
  • Tidskriftsartikel (refereegranskat)abstract
    • Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.
  • Adner, Mikael, et al. (författare)
  • Regional variation in appearance of vascular contractile endothelin-B receptors following organ culture
  • 1998
  • Ingår i: Cardiovascular Research. - : Oxford University Press. - 1755-3245. ; 37:1, s. 254-262
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of this study was to investigate the appearance of contractile endothelin (ET)-B receptors following organ culture in different vascular regions. METHOD: The contractile responses of vascular smooth muscle induced by ET-1 and the selective ETB receptor agonist sarafotoxin 6c (S6c) were investigated in circular segments representing eight vascular regions in the rat (aorta, femoral artery, mesenteric artery, branch of the mesenteric artery, proximal and distal parts of the caudal artery, femoral and mesenteric veins). To allow the ETB receptor to be expressed, the segments were placed in organ culture for 1 to 5 days. Pharmacological characterisation of the ET receptors was performed in mesenteric arterial segments. All contractile responses were measured in percentage of K(+)-induced contraction. RESULTS: ET-1 induced strong concentration-dependent contractions of all fresh (not cultured) segments. S6c had negligible effects on all fresh vessels with the exception of the mesenteric vein, where a small contraction was seen. After 1 day of organ culture all tested segments, with the exception of aorta and the proximal part of the caudal artery, showed concentration-dependent contractile responses to S6c which were further augmented after 5 days of culture. The ET-1-induced responses were only slightly affected by organ culture. Contractions induced by S6c were more enhanced in small arteries and veins than in larger arteries. Furthermore, the S6c-induced response was more pronounced in the mesenteric region as compared to the hindlimb. In fresh mesenteric arterial segments FR139317 (ETA receptor antagonist) and bosentan (ETA/ETB receptor antagonist) but not IRL 2500 (ETB receptor antagonist) shifted the ET-1-induced concentration-response curve in parallel to the right. In contrast, after organ culture the S6c-induced concentration-response curves were shifted parallel to the right in the following potency order: IRL 2500 > bosentan > FR139317. CONCLUSION: During normal conditions, the ETA receptor is the dominating mediator of endothelin-induced contraction in eight different vascular regions. Furthermore, this study indicates that most of the vessels have the ability to develop contractile ETB receptors and that this plasticity differs in vascular regions.
  • Andersson, S E, et al. (författare)
  • Cutaneous vascular reactivity is reduced in aging and in heart failure: association with inflammation
  • 2003
  • Ingår i: Clinical Science. - : Portland Press. - 1470-8736. ; 105:6, s. 699-707
  • 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.
  • Andersson, Sven E, et al. (författare)
  • High NT-proBNP Is a Strong Predictor of Outcome in Elderly Heart Failure Patients.
  • 2008
  • Ingår i: American Journal of Geriatric Cardiology. - : John Wiley and Sons. - 1751-715X. ; 17:1, s. 13-20
  • Tidskriftsartikel (refereegranskat)abstract
    • All patients older than 65 years (184 men; mean age, 78+/-0.8 years/181 women; mean age, 82+/-0.6 years) seeking medical attention at the Lund University Hospital Emergency Clinic during a 2-year period who had an N-terminal prohormone brain natriuretic peptide (NT-proBNP) value >2000 pg/mL were followed up for survival. Mortality in the entire population was 21% after 3 months, 35% after 1 year, and 40% after 2 years. Multivariate analysis indicated that the NT-proBNP level and the New York Heart Association (NYHA) functional class were stronger predictors of mortality than were echocardiographic estimation of left ventricular ejection fraction or chest radiography. Patients who survived the first year were younger, had higher systolic blood pressure, had lower plasma creatinine, had lower inflammatory activity, and were treated with lower doses of furosemide. The results indicate that in this population, NT-proBNP level together with assessment of NYHA class gives the best prognostic information of 1-year mortality. (Am J Geriatr Cardiol. 2008;17:13-20).
  • Andersson, Sven, et al. (författare)
  • Reduction of Homocysteine in Elderly with Heart Failure Improved Vascular Function and Blood Pressure Control but did Not Affect Inflammatory Activity.
  • 2005
  • Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley-Blackwell. - 1742-7843. ; 97:5, s. 306-310
  • Tidskriftsartikel (refereegranskat)abstract
    • We have previously shown that hyperhomocysteinaemia is common in elderly heart failure patients, and is associated with endothelial dysfunction, impaired vasodilatory capacity and a low-grade inflammation. In the present study we examined if supplementation with B6, B12 and folate could normalize the hyperhomocysteinaemia and if so, in turn, would improve the associated parameters. This was an open study without placebo control on heart failure patients with plasma homocysteine > 15 microM. Measurements of cutaneous vascular reactivity, blood pressure, inflammatory activity and endothelial function were performed before and after intervention with intra-individual comparisons. The treatment reduced homocysteine to near normal values and enhanced the hyperaemic response to acetylcholine related to the response to heat. The mean arterial blood pressure and pulse rate was reduced. There was no effect on inflammatory activity, plasma levels of von Willebrand factor, subjective health quality or the hyperaemic responses to sodium nitroprusside or local warming. Hyperhomocysteinaemia in heart failure patients is multifactorial in origin. Folate deficiency, inflammatory activity and reduced renal function could be contributing. It is suggested that supplementation with B-vitamins can improve the vasodilatory capacity and reduce the blood pressure but additional studies are required to confirm this.
  • Belin, Andrea Carmine, et al. (författare)
  • Calcitonin gene-related peptide (CGRP) and cluster headache
  • 2020
  • Ingår i: Brain Sciences. - : Multidisciplinary Digital Publishing Institute (MDPI). - 2076-3425. ; 10:1
  • Forskningsöversikt (refereegranskat)abstract
    • Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP receptor complex have recently taken center stage as therapeutic targets for primary headaches, such as migraine. Multiple CGRP and CGRP receptor monoclonal antibodies, as well as small molecule antagonists (gepants) are on their way constituting a new frontier of migraine and possibly CH medication. During a CH attack, there is an activation of the trigeminal-autonomic reflex with the release of CGRP, and inversely if CGRP is administered to a CH patient in an active disease phase, it triggers an attack. Increased levels of CGRP have been found in ipsilateral jugular vein blood during the active phase of CH. This process is hypothesized to have a key role in the intense pain perception and in the associated distinctive vasodilation. So far, clinical tests of CGRP antibodies have been inconclusive in CH patients. This review summarizes the current state of knowledge on the role of CGRP in CH pathology, and as a target for future treatments.
  • Bengtsson, Christine, et al. (författare)
  • Effect of Medication on Microvascular Vasodilatation in Patients with Systemic Lupus Erythematosus
  • 2010
  • Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley-Blackwell. - 1742-7843. ; 107:6, s. 919-924
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the microvascular responses in the skin, to local heat, iontophoretically administered acetylcholine and to sodium nitroprusside in relation to cardiovascular damage in patients with systemic lupus erythematosus (SLE) and matched controls. We also wanted to examine if the ongoing medication in SLE patients influenced this vascular response. We investigated 30 women with SLE and compared them with 20 age and sex-matched controls. The cutaneous blood flow response to local heat (+44 degrees C), iontophoretically administered endothelium-dependent (acetylcholine), as well as independent (sodium nitroprusside) vasodilatation, was measured by laser Doppler flowmetry. Clinical data and medication were retrieved from the clinical database and patient records. The cutaneous microvascular reactivity did not differ between SLE patients and a group of matched controls nor did it correlate with cardiovascular damage [assessed by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)]. However, patients on antimalarial drugs (hydroxychloroquine n = 8 and chloroquine diphosphate n = 3) responded more strongly to sodium nitroprusside (endothelium-independent vasodilatation) compared with those without antimalarial drugs (p < 0.01). The response to acetylcholine was higher among patients on warfarin compared with those without (p < 0.05), whereas glucocorticoid use (>= 5 mg daily) was associated with reduced response to acetylcholine (p < 0.05). Smokers in general tended to have a lower response to acetylcholine (p = 0.064). Smoking SLE patients versus non-smoking SLE patients had a significantly lower response to acetylcholine (p = 0.01). Medication with antimalarial drugs-enhanced endothelium-independent vasodilatation, while glucocorticoid use was associated with reduction and warfarin-treatment with enhancement of endothelium-dependent vasodilatation. Therefore, despite there is no difference in microvascular endothelium-dependent vasodilatation, other factors such as medication and smoking may affect vasodilatation in SLE patients.
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