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Sökning: WFRF:(Edvinsson Lars)

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31.
  • Minthon, Lennart, et al. (författare)
  • Neuropeptide levels in Alzheimer's disease and dementia with frontotemporal degeneration
  • 1990
  • Ingår i: Journal of neural transmission. Supplementum. ; 30, s. 57-67
  • Tidskriftsartikel (refereegranskat)abstract
    • The CSF levels of somatostatin-LI (SLI), neuropeptide Y (NPY-LI) and Delta Sleep Inducing Peptide (DSIP-LI) have been measured in patients with dementia of Alzheimer type (DAT) and dementia with frontotemporal degeneration of non-Alzheimer type (FTD). The distribution pattern of cortical degeneration differs between these two types of dementia. DAT shows degeneration of mainly temporo-parietal and temporo-limbic structures, whereas FTD discloses its main degeneration in the frontotemporal regions (Brun, 1987). The somatostatin-LI was significantly reduced both in DAT and FTD. NPY-LI showed a significant reduction in DAT but not in FTD. A tendency to a reduction with duration of the disease was observed in DAT whereas the contrary was noted in FTD. The DSIP-LI levels were reduced in DAT and slightly increased in FTD. The study provides an evidence of neurochemical differences between the two primary degenerative dementias.
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32.
  • Minthon, Lennart, et al. (författare)
  • Somatostatin and neuropeptide Y in cerebrospinal fluid: correlations with severity of disease and clinical signs in Alzheimer's disease and frontotemporal dementia
  • 1997
  • Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 8:4, s. 232-239
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common types of progressive neurodegenerative disorder in our catchment area. The distribution of cortical degeneration in FTD is mainly the reverse of that in AD, while there are both differences and similarities in the clinical characteristics. Somatostatin and neuropeptide Y (NPY) are neuropeptides with a widespread distribution in the human cerebral cortex. Somatostatin is involved in the regulation of hormone release from the anterior pituitary and may act as a neurotransmitter-modulator. NPY is a potent anxiolytic neuropeptide. Somatostatin and NPY coexist in the cerebral cortex, basal ganglia and in amygdaloid complexes. The present study of AD (n = 34) and FTD (n = 22) analyses the cerebrospinal-fluid (CSF) levels of somatostatin-like immunoreactivity and NPY-like immunoreactivity and correlates their levels to 54 different clinical items, such as restlessness, anxiety, irritability and depression. The CSF levels of the two neuropeptides somatostatin and NPY were significantly correlated in FTD (p < 0.02), but not in AD. Several significant correlations to the clinical signs were found: in AD disorientation and dyspraxia, and in FTD agitation, irritability and restlessness. Somatostatin showed a significant negative correlation with severity of dementia in AD (p < 0.013).
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33.
  • Minthon, Lennart, et al. (författare)
  • Tacrine treatment modifies cerebrospinal fluid neuropeptide levels in Alzheimer's disease
  • 1994
  • Ingår i: Dementia (Switzerland). - : S. Karger AG. - 1013-7424. ; 5:6, s. 295-301
  • Tidskriftsartikel (refereegranskat)abstract
    • Biochemical and histochemical studies have demonstrated a widespread deficit in the activity of acetylcholinesterase (AChE) in the brains of patients with Alzheimer's disease (DAT). Multiple disturbances in several transmitter systems have been found. The most consistent neurochemical changes in DAT are reductions in the cholinergic system. The major pharmacological approach today in DAT is based on the cholinergic theory assuming that acetylcholine has a major cortical impact on cognitive processes. Tetrahydroaminoacridine (THA, tacrine) is a centrally active reversible acetylcholinesterase inhibitor. A large number of trials have been performed in patients with DAT. This article was to evaluate whether THA treatment induced neuropeptide alteration in DAT before and after 1 year on oral THA treatment.
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34.
  • Passant, Ulla, et al. (författare)
  • Orthostatic hypotension in organic dementia: relationship between blood pressure, cortical blood flow and symptoms
  • 1996
  • Ingår i: Clinical autonomic research : official journal of the Clinical Autonomic Research Society. ; 6:1, s. 29-36
  • Tidskriftsartikel (refereegranskat)abstract
    • Regional cerebral blood flow was measured in 35 patients with organic dementia (Alzheimer's disease, n = 13, vascular dementia, n = 17, frontotemporal dementia, n = 5) and orthostatic hypotension. Measurements were performed during supine rest and during head-up tilt (60 degrees). Despite marked blood pressure falls, few patients had symptoms of orthostatic hypotension. All three dementia groups had a decrease in regional cerebral blood flow in the frontal lobes during head-up tilt, but no change in mean hemispheric flow. All patients had a consistent drop in their systolic blood pressure upon head-up tilt, with a wide variation over time. The findings suggest that orthostatic hypotension needs to be considered, and actively sought for, in organic dementia as many patients may lack the typical symptoms of orthostatic hypotension, despite a marked fall in blood pressure.
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35.
  • Rehnström, Mimmi, et al. (författare)
  • Ovariectomy Reduces Vasocontractile Responses of Rat Middle Cerebral Arteries After Focal Cerebral Ischemia
  • 2022
  • Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 79:1, s. 122-128
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT: Effects of sex hormones on stroke outcome are not fully understood. A deleterious consequence of cerebral ischemia is upregulation of vasoconstrictor receptors in cerebral arteries that exacerbate stroke injury. Here, we tested the hypothesis that female sex hormones alter vasocontractile responses after experimental stroke in vivo or after organ culture in vitro, a model of vasocontractile receptor upregulation. Female rats with intact ovaries and ovariectomized (OVX) females treated with 17β-estradiol, progesterone, or placebo were subjected to transient, unilateral middle cerebral artery occlusion followed by reperfusion (I/R). The maximum contractile response, measured my wire myography, in response to the endothelin B receptor agonist sarafotoxin 6c was increased in female arteries after I/R, but the maximum response was significantly lower in arteries from OVX females. Maximum contraction mediated by the serotonin agonist 5-carboxamidotryptamine was diminished after I/R, with arteries from OVX females showing a greater decrease in maximum contractile response. Contraction elicited by angiotensin II was similar in all arteries. Neither estrogen nor progesterone treatment of OVX females affected I/R-induced changes in endothelin B- and 5-carboxamidotryptamine-induced vasocontraction. These findings suggest that sex hormones do not directly influence vasocontractile alterations that occur after ischemic stroke; however, loss of ovarian function does impact this process.
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36.
  • Saetrum Opgaard, Ole, et al. (författare)
  • Endocardial expression and functional characterization of endothelin-1
  • 2001
  • Ingår i: Molecular and Cellular Biochemistry. - 0300-8177. ; 224:1-2, s. 151-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Endothelin-1 (ET-1), a 21 amino acid peptide exerts a wide range of biological activities including vasoconstriction, mitogenesis and inotropic effects on the heart. In this study, we examined whether endocardial endothelial cells express ET-1 and evaluated its functional properties. Using immunofluorescence localization method, we demonstrated cytoplasmic staining of ET-1 in the human endocardial endothelial cells from the right atrium and left ventricle. Employing reverse transcriptase polymerase chain reaction (RT-PCR) expression of ET-1 mRNA and its receptors ET(A) and ET(B) mRNAs were found in human myocardial as well as in endocardial endothelial cells. Biological activity of endocardial endothelial cells derived ET-1 was established as the conditioned media obtained from cultured porcine endocardial endothelial cells induced a slowly developing, strong and long-lasting contraction of circular rat aortic segments, with similar characteristics to that obtained with exogenous ET-1. Furthermore, the selective endothelin-A receptor antagonist, FR 139317, blocked the conditioned media induced contractions. Our results suggest that endocardial endothelial cells express and release biologically active ET-1 which could play a pivotal role in the regulation of myocardial contractility as well as a circulatory peptide may further act in other peripheral target organs.
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37.
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38.
  • 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.
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39.
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40.
  • Warkentin, Siegbert, et al. (författare)
  • Redistribution of blood flow in the cerebral cortex of normal subjects during head-up postural change
  • 1992
  • Ingår i: Clinical autonomic research : official journal of the Clinical Autonomic Research Society. ; 2:2, s. 119-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Regional cerebral blood flow was measured in 21 normotensive subjects during supine rest and during head-up tilt to 70 degrees. The results showed significant and consistent regional cerebral blood flow changes in the frontal areas with lower relative flow distribution values (percentage of mean flow) during head-up tilt than during supine rest. The lower frontal flow distribution values during tilt were not related to habituation, to repeated measurements, or to the estimated level of arterial CO2 which was derived from expired end-tidal CO2 levels. None of the subjects had orthostatic hypotension and there was no significant difference in mean hemispheric blood flow between lying down and standing up. There was no significant gender difference in regional cerebral blood flow, although female subjects tended to have higher mean hemispheric flow than males in both postures. It remains to be established whether the flow decreases in the frontal cortex are caused by cerebral functional factors or by haemodynamic mechanisms.
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