| 1. |
- Edvinsson, Lars, et al.
(författare)
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Neuropeptides in cerebrospinal fluid of patients with Alzheimer's disease and dementia with frontotemporal lobe degeneration
- 1993
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Ingår i: Dementia (Switzerland). - 1013-7424. ; 4:3-4, s. 71-167
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Tidskriftsartikel (refereegranskat)abstract
- The two major primary degenerative dementias, dementia of Alzheimer type (DAT) and frontal lobe degeneration of non-Alzheimer type (FLD) have several clinical features in common but also many symptoms that differ. In a clinical material of 80 patients with either of the two forms of dementia (DAT = 39, FLD = 41) we have studied the levels of neuropeptides in the cerebrospinal fluid (CSF) in order to find biochemical markers for CNS affection. The dementia forms were evaluated by careful clinical analysis, psychometric testing and measurement of regional cerebral blood flow. Approximately one third of the subjects died during the completion of the study and neuropathology was performed, confirming the diagnoses. We observed reductions in the CSF levels of antidiuretic hormone and somatostatin in both DAT and FLD. A strong tendency to reduction was noted for neuropeptide Y (NPY). There was a correlation with the duration of disease demonstrating a significant reduction in NPY levels in subjects with DAT. Most notably there was a strong reduction in the levels of delta sleep inducing peptide (DSIP) in DAT cases only. The levels of DSIP in FLD were the same as in controls. The reverse was found for corticotropin releasing factor (CRF) which had a significant reduction in FLD patients but not in those with DAT. The present study indicates a difference in the CSF levels of neuropeptides, observations that these may serve as biochemical markers which differentiate DAT and FLD.
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| 2. |
- Minthon, Lennart, et al.
(författare)
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Neuropeptide levels in Alzheimer's disease and dementia with frontotemporal degeneration
- 1990
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Ingår i: Journal of neural transmission. Supplementum. ; 30, s. 57-67
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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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| 3. |
- Minthon, Lennart, et al.
(författare)
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Tacrine treatment modifies cerebrospinal fluid neuropeptide levels in Alzheimer's disease
- 1994
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Ingår i: Dementia (Switzerland). - : S. Karger AG. - 1013-7424. ; 5:6, s. 295-301
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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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| 4. |
- Warkentin, Siegbert, et al.
(författare)
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Redistribution of blood flow in the cerebral cortex of normal subjects during head-up postural change
- 1992
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Ingår i: Clinical autonomic research : official journal of the Clinical Autonomic Research Society. ; 2:2, s. 119-24
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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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| 5. |
- Adner, Mikael, et al.
(författare)
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Human endothelin ETA receptor antisense oligodeoxynucleotides inhibit endothelin-1 evoked vasoconstriction
- 1994
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Ingår i: European Journal of Pharmacology. - 1879-0712. ; 261:3, s. 281-284
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Tidskriftsartikel (refereegranskat)abstract
- Antisense oligodeoxynucleotides to endothelin ETA receptor mRNA were used to characterize vascular smooth muscle receptors. The concentration-response curve showed a significant attenuation of endothelin-1-induced contraction in circular segments of the human superficial temporal artery. Endothelin ETB receptor antisense or mismatch oligodeoxynucleotides showed no alteration of the endothelin-1-induced contraction. Complementary experiments with the selective endothelin ETA receptor antagonist FR139317 demonstrated a shift of the concentration-response curve to the right in a competitive manner (pA2 = 6.93). The specific method of using the receptor antisense oligodeoxynucleotides approach revealed the presence of endothelin ETA receptors mediating contraction in the human superficial temporal artery.
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| 6. |
- Edvinsson, Lars, et al.
(författare)
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Neuropeptide Y in sympathetic co-transmission: recent advances in the search for neuropeptide Y antagonists
- 1994
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Ingår i: Pharmacology and Toxicology. - 1600-0773. ; 74:4-5, s. 193-201
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Tidskriftsartikel (refereegranskat)abstract
- Since the discovery of neuropeptide Y which is co-stored and co-operate with noradrenaline (NA) in sympathetic nerve fibers, several scientific groups have searched for structures with neuropeptide Y antagonistic properties. Research has mainly focused on various peptide fragments which originate from or are related to the neuropeptide Y sequence. Some non-peptide antagonists have been proposed but they are mostly of low potency and non-selective. Our recent observations that alpha-trinositol (D-myo-inositol 1.2.6-trisphosphate) is an inhibitor of neuropeptide Y effects will hopefully lead to the development of useful non-peptide neuropeptide Y inhibitors. As a novel approach the highly selective approach of down-regulating neuropeptide Y receptors with antisense oligodeoxynucleotides is also discussed. Neuropeptide Y antagonistic agents would help us to understand the physiological role of neuropeptide Y and may serve as useful medication in circulation disorders.
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| 7. |
- Edvinsson, Lars, et al.
(författare)
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Sensory nerve terminal activity in severe hypertension as reflected by circulating calcitonin gene-related peptide (CGRP) and substance P
- 1992
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 1:4, s. 223-229
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Tidskriftsartikel (refereegranskat)abstract
- In patients with severe hypertension and in age and sex matched controls the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P-LI were measured. Samples were taken before medication, after 2-4 weeks and 2-12 months of pharmacological treatment to normotension. In the control group CGRP-LI levels were significantly higher for females than for males. No such relation was seen for substance P-LI. There were no correlations between CGRP-LI, substance P-LI or blood pressure. In the untreated acute hypertensive group there was a significant correlation between circulating levels of CGRP-LI and both diastolic and systolic blood pressure. No such relationship was seen for substance P-LI. The plasma levels of substance P-LI were significantly elevated (2.8 +/- 4.0) compared to controls (1.3 +/- 1.3, pmol/l, mean +/- S.D., p < 0.01). The levels of CGRP-LI did not differ from the control group. After 2-4 weeks of treatment the blood pressure decreased significantly and the plasma levels of substance P-LI were normalized while the CGRP-LI still did not differ from that of controls. After 2-12 months of treatment the blood pressure was still normalized, and the plasma levels of CGRP-LI and substance P-LI were not different from the control group. In the present study there was a positive correlation in hypertensives between the circulating CGRP-LI levels and diastolic and systolic blood pressure and elevated levels of substance P-LI. This would implicate the existence of a dynamic control through which the sensory system may register and damp the pressure response.
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| 8. |
- Edvinsson, Sören, 1953-
(författare)
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Den osunda staden : sociala skillnader i dödlighet i 1800-talets Sundsvall
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study deals with the topic of social class and mortality. In particular, the analyses are concentrated on the question of how social differences developed in an era which was characterised by industrialisation, urbanisation and sanitary improvements. This work also discusses how the problems of social class and health were dealt with in the nineteenth Century. The development of medicai care and public health are especially studied. The development of mortality in different social classes is analysed on micro level in the town of Sundsvall during the 19th century, for which the parish registers for the period 1803-1894 have been transferred on to data. This town became the centre of an expansive saw mill area from the middle of the Century.In contrast to the view of contemporary witnesses, inequality seems to have been fairly small in some age groups, but the pattems diverged between them. Mortality among adults was largely dependent on cultural variables such as life style and attitudes, and social differences played a minor role. Men had much higher mortality than women. The development does not seem to have been primarily affected by industrialisation, urbanisation or sanitary improvements. For children 1-14 years old, on the other hand, conditions created by industrialisation and urbanisation seem to have been of the utmost importance. Child mortality increased from 1860, affecting first of all working class children. Overcrowding increased the spread of infectious diseases. Sanitary improvements may have had an effect on the mortality level from around 1880, but more definitely in the 1890's. The same is also the case regarding infant mortality. They may have had some impact on the initial decline in infant mortality, but the connection appears to be stronger in the 1890's. The social inequality in infant mortality was insignificant until late 19th centuiy, but increased at that time. Among infants, feeding practises were also of importance.
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| 9. |
- Ekelund, Ulf, et al.
(författare)
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Effects of selective ETB-receptor stimulation on arterial, venous and capillary functions in cat skeletal muscle
- 1994
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Ingår i: British Journal of Pharmacology. - 1476-5381. ; 112:3, s. 887-894
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Tidskriftsartikel (refereegranskat)abstract
- 1. This paper describes, in quantitative terms, the in vivo effects of two selective ETB-receptor agonists (IRL 1620 and BQ 3020) on vascular resistance (tone) in the following consecutive sections of the vascular bed of sympathectomized cat skeletal muscle: large-bore arterial resistance vessels (> 25 microns), small arterioles (< 25 microns) and the veins. The effects on capillary pressure transcapillary fluid exchange were also recorded. 2. Both IRL 1620 and BQ 3020, infused i.a. to the muscle preparation, evoked an initial transient dilator response followed by a moderate dose-dependent constrictor response, both being preferentially confined to the small arterioles. The dilator response was associated with a transient increase, and the constrictor response with a sustained decrease, in capillary pressure, the latter causing net transcapillary fluid absorption. The capillary filtration coefficient decreased during the constrictor response, indicating constriction of terminal arterioles/precapillary sphincters. 3. The vascular responses to the ETB-receptor agonists were unaffected by blockade of endothelium-derived nitric oxide (NG-nitro-L-arginine methyl ester) and by selective ETA-receptor blockade (FR139317). However, blockade of prostacyclin production with indomethacin decreased the amplitude of the dilator response, and decreased the time required to reach a steady-state vasoconstrictor response to the ETB-receptor agonists. 4. The effect of ETB-receptor stimulation on vascular tone was also evaluated in vitro on the cat femoral artery and vein. IRL 1620 had no effect on the femoral artery but caused a weak dose-dependent relaxation in the femoral vein. This large vein relaxation response seemed to be mediated by endothelium-derived nitric oxide and not by prostacyclin.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 10. |
- Ekelund, Ulf, et al.
(författare)
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In-vivo effects of endothelin-1 and ETA receptor blockade on arterial, venous and capillary functions in skeletal muscle
- 1993
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 148:3, s. 273-283
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Tidskriftsartikel (refereegranskat)abstract
- Results from in vitro studies have indicated that endothelin-1 is a main candidate for endothelium-derived contracting factors. The aim of this in vivo study was to describe in quantitative terms the effects of endothelin-1 (ET-1), and of ETA receptor blockade, on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 microns), small arterioles (< 25 microns) and the veins, as well as on capillary pressure and fluid exchange in cat gastrocnemius muscle. Endothelin-1 (100-1600 ng kg-1 min-1, i.a.) elicited, after an initial transient dilation, a strong dose-dependent constrictor response in all three consecutive vascular sections, yet with a preferential action on the small arterioles and the veins. The vasoconstriction developed very slowly over about 1 h and was also long-lasting after cessation of the infusion. Our main quantitative analysis refers to effects elicited by 20 min long i.a. infusions of ET-1 at a dose of 400 ng kg-1 min-1. At the end of this period, the peptide caused, on average, a three-fold increase in total regional vascular resistance, in turn explained by a 70% increase in large-bore arterial resistance, a 280% increase in arteriolar resistance and a 220% increase in venous resistance. The latter effect was also manifested as a pronounced capacitance response, and as a decrease in the pre- to post-capillary resistance ratio leading regularly to a rise in capillary pressure, net transcapillary fluid filtration and oedema formation which is unusual for a vasoconstrictor. The new specific competitive ETA receptor antagonist FR 139317 was found to be fully effective in vivo, insofar as it abolished the constrictor response to endothelin-1. ETA receptor blockade, or administration of phosphoramidon, an inhibitor of ET-1 production, did not influence the level of basal vascular tone, indicating no significant endogenous release of ET-1 under resting conditions. This contrasts to the established pronounced endogenous release of endothelium-derived nitric oxide. Finally, vascular myogenic regulation was found not to be mediated by ET-1. The results, taken together, suggest a possible role of ET-1 in long-term, rather than short-term, regulation of vascular tone in vivo, perhaps especially during pathophysiological conditions.
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