Characterization of calcitonin gene-related peptide receptors in human cerebral vessels. Vasomotor responses and cAMP accumulation.
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Biomedical subjects
Publications and source records attributed to A Mortensen.
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The present study compares the atherogenicity of a standard diet and diets with 10% olive oil or 10% margarine added, in rabbits maintained at a mean plasma cholesterol level of about 20 mM for 13 weeks. Each group consisted of 15 animals. The distribution of cholesterol in plasma between VLDL, IDL, LDL and HDL was similar in the 3 groups. The thoracic aortic cholesterol accumulation was 16.6 +/- 1.6, 11.4 +/- 1.0 (P < 0.05) and 12.6 +/- 1.7 (P > 0.05) nmol/mg wet weight for the group receiving standard diet, diet with 10% olive oil added and diet with 10% margarine added, respectively. There was no significant difference between groups in the occurrence of the atherosclerotic changes in the proximal and distal parts of coronary arteries, abdominal aorta and renal arteries. The occurrence of atherosclerotic changes in the pulmonary arteries was equal in the groups receiving standard diet and diet with 10% margarine added while it was significantly lower (P < 0.05) in the group receiving diet with 10% olive oil added. The atherosclerotic changes at the aortic orifice of coronary arteries were quanticated morphometrically and were most severe in the group on the standard diet. The results indicate a comparable atherogenic effect of 10% olive oil or margarine addition to standard diet on development of atherosclerosis in rabbits maintained at a similar plasma cholesterol level. The study also suggests that supplementation of olive oil or margarine to standard rabbit diet leads to lower cholesterol accumulation in the thoracic aorta compared with standard diet, an effect not modulated by changes in plasma cholesterol concentrations.
The action of sumatriptan, putatively a selective 5-HT1D or 5-HT1-like receptor agonist which is effective in the treatment of migraine, has been studied on fresh human dural (middle meningeal) arteries. In low concentrations (10(-8)-10(-7) M) it was found to be a significantly stronger vasoconstrictor of dural arteries compared to cerebral and temporal arteries. However, its potency was less than that of 5-HT. The sumatriptan-induced vasoconstriction was antagonized by methiothepin (10(-9)-10(-8) M), but not by ketanserin (10(-7) M). The observations suggest that the sumatriptan-induced contraction of the dural artery is mediated via activation of 5-HT1D or 5-HT1-like receptors, whereas it does not appear to activate the 5-HT2 receptors.
Two hydraulic fluids, Fyrquel EHC (trixylenyl phosphate) and Reofos 65 (trialkyl/aryl phosphate mixture), were examined for effects of organophosphorus-induced delayed neurotoxicity (OPIDN) in hens using the OECD Test Guideline (1984). Furthermore, the influence of atropine and the concentration of tri-o-tolyl phosphate (TOTP) in the oil vehicle on the development of OPIDN were investigated. For Fyrquel EHC a neurotoxic effect was demonstrated with single oral doses of 5, 10 and 15 g/kg. Reofos 65 caused no clinical neurotoxic effect after single oral doses of 5, 10 and 15 g/kg. Redosing at day 22 with Reofos 65 did not result in clinical delayed neurotoxicity, but minor histopathological changes were found in the spinal cord and peripheral nerves. Atropine 10 mg/kg im delayed the onset of OPIDN caused by TOTP 1 g/kg po without affecting the final neurotoxic effect. Dilution of TOTP in large amounts of soybean oil vehicle reduced its neurotoxic effect. In conclusion, the neurotoxic potential of the hydraulic fluids was very low. The effect of atropine and the concentration of the test compound in oil vehicle should be taken into consideration when designing experiments on OPIDN.
Human cerebral vessels were found to contain calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) which in the reversed phase HPLC co-eluted with authentic human alpha-CGRP. The level was significantly lower in arteries removed from patients who had died from a subarachnoid haemorrhage (SAH) as compared to patients who died of a coronary infarction. On a molar basis human alpha-CGRP was more potent than human beta-CGRP to dilate human brain vessels and to dilate vasoconstriction elicited by whole blood. It is suggested that the trigemino-cerebrovascular system storing CGRP-LI may be involved in the pathophysiology of SAH in man.
(R)-N-[4,4-Bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid (NO 328) has previously been shown to be a potent anticonvulsant in both mice and rats. Here, we report that NO 328 is a potent inhibitor of gamma-[3H]aminobutyric acid [( 3H]GABA) uptake in a rat forebrain synaptosomal preparation (IC50 = 67 nM) and in primary cultures of neurons and astrocytes. Inhibition of [3H]GABA uptake by NO 328 is apparently of a mixed type when NO 328 is preincubated before [3H]GABA uptake; the inhibition is apparently competitive without preincubation. NO 328 itself is not a substrate for the GABA uptake carrier, but NO 328 is a selective inhibitor of [3H]GABA uptake. Binding to benzodiazepine receptors, histamine H1 receptors, and 5-hydroxytryptamine1A receptors was inhibited by NO 328 at 5-30 microM, whereas several other receptors and uptake sites were unaffected. [3H]NO 328 showed saturable and reversible binding to rat brain membranes in the presence of NaCl. The specific binding of [3H]NO 328 was inhibited by known inhibitors of [3H]GABA uptake; GABA and the cyclic amino acid GABA uptake inhibitors were, however, less potent than expected. This indicates that the binding site is not identical to, but rather overlapping with, the GABA recognition site of the uptake carrier. The affinity constant for binding of [3H]NO 328 is 18 nM, and the Bmax is 669 pmol/g of original rat forebrain tissue. The regional distribution of NaCl-dependent [3H]NO 328 binding followed that of synaptosomal [3H]GABA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Two cases of fibrous dysplasia of the skull are reported. Both patients were young women with acromegaly and were treated with radiotherapy. Progressive pareses of cranial nerves, pain, and a malignant course of the disease were characteristic in both patients, and the diagnosis of osteogenous sarcoma proved in one of them by histological examination. The clinical picture of fibrous dysplasia of the skull and the role of radiotherapy with the risk of development of malignancy is discussed.
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This study was designed to establish whether SK&F 93574 releases histamine in dogs. Three female beagle dogs each received single infusions (on separate days) of each of SK&F 93574 (2.5 mg kg-1), polyvinylpyrrolidone (PVP, 20 mg kg-1) and sterile saline. The treatments were given at 14 day intervals by rapid intravenous infusion at 0.5 mL kg-1 min-1 for 2 minutes. Dogs showed clinical signs of histamine release such as vasodilation, licking lips, head drooping and increased gut movement after treatment with the known histamine releaser PVP or the test compound SK&F 93574. These signs were of similar severity and duration for the two compounds. No such changes were observed when the dogs received vehicle alone. Treatment with PVP or SK&F 93574 also resulted in markedly elevated plasma histamine concentrations (greater than 10-fold increase over control). It is concluded that intravenous administration of SK&F 93574 to dogs is associated with histamine release.
The dimension of flow in uterine artery (ua) and ovarian artery (oa) was measured. It was conducted in the isolated porcine (100-130 kg/per head) reproductive organs perfused with their own blood or Krebs-Henseleit fluid when the pressure was kept on the constant level 100 m Hg. Phenoxybenzamine (Ph), phentolamine (R), propranolol (P), pronetalol (Pr) were used and also after them adrenaline (A), noradrenaline (NA) or isoprenaline (I) were administrated. Changes in blood flow (bf) through the organs connected with inhibition or stimulation of adrenergic receptors during estrous cycle were analysed. It was stated that R increased bf, but not significantly. Ph increased significantly bf in the reproductive organs and blocked decreasing bf influence of A and NA in ua and oa areas. Both A and I administrated after Ph and R caused the increase in bf in the both investigated vessel areas. Beta-adrenolytic agents P and Pr decreased bf and also blocked increasing bf action of I. When we used A or NA after P or Pr administration, there was observed significant limitation of bf in the reproductive organs. Reactions evoked by alpha- and beta-adrenergic stimulation were different during estrous cycle. The highest activity of alpha receptor--which dominates the vessels of porcine reproductive organs--was found in the luteal phase of cycle where the activity of beta receptor was the lowest. The activity of alpha receptor decreased and increased activity of beta receptor in the pre and postovulatory phase of cycle compared to the state observed in the luteal phase. Beta receptor did not play any significant role in the regulation of bf in the porcine reproductive organs. Data from references discussed in this work and our results suggest that regulation of sensitivity of vessels in the porcine reproductive organs was not connected with quantitative representation of adrenergic receptors. Changes of vessel sensitivity were connected with changes of alpha-adrenergic receptor activity.
Food intake (FI), feeding activity (FA), and body mass (BM) were recorded continuously throughout a 13-mo period in Svalbard rock ptarmigan kept under natural conditions of light and ambient temperature at Svalbard (79 degrees N). FI was persistently high from March until August, including the period when daylight is continuous, whereas it was low from November until January, when it is permanently dark. From August until November, BM doubled, while FI dropped to one-third. BM fell rapidly from mid-November until April despite a doubling of FI from February until March. From August until mid-November and from February until mid-April FA occurred mainly during the light period of the day. From late November until February and from mid-April until August intermittent FA occurred continuously. It is suggested that the seasonal changes in BM are not determined by FI alone but depend heavily on seasonal changes in locomotor activity as reflected in FA.
The flow in uterine artery (ua) and ovarian artery (oa) was measured in isolated reproductive organs of sows perfounded with own blood of the animal or with Krebs-Henseleit fluid at the constant pressure of 100 mm Hg applying the haemotachometric method. Controlling parallel to the flow, the condition of tension in smooth muscle of the organ, the sensitivity of vessels of ua and oa areas to: norepinephrine (NA), phenylephrine (F), epinephrine (A) and isoprenaline (I) on the 1-2, 13-14 and 16-18 days of oestrous cycle was investigated. It was found that the blood flow in the vessels under investigation diminishes after intraarterial application of alpha-adrenomimetic NA and F and after ambi-receptor acting A, while it increases after beta-adrenomimetic I. It was also shown, that the vessels of the area oa are many times less sensitive to the applied agents than the vessels of the ua area. During the oestrous cycle significant changes in sensitivity of both areas to adrenomimetic agents take place. The highest sensitivity to NA, A and F simultaneous with the lowest sensitivity to I were noted in the ua area on 13-14 days. On the 16-18 and 1-2 days of the cycle the diminished sensitivity to NA, A and F and increased to I comparing with the 13-14 day was found. Also, the vessels of the oa area show the lowest sensitivity to NA, A and F and the highest to I on the 1-2 day of the cycle. It is the highest to NA and F on the 13-14 day and is accompanied by the lowest sensitivity to I. The sensitivity on 13-14 day is similar to that on 16-18 day. The sensitivity of oa area to A increases from the lowest on 1-2 days to the highest on 16-18 day of the cycle.
Urine entering the caeca of birds contains significant amounts of uric acid. The discovery of great numbers of bacteria utilizing uric acid in the caeca has encouraged the discussion about nitrogen recycling in birds. In this work caecal decomposition of uric acid in wild and captive willow ptarmigan has been investigated using radioactively labelled uric acid injected directly into one of the caeca. The appearance of radioactive CO2 in the expired air was taken as an indication of uric acid breakdown. The decomposition occurred at a rate corresponding to a half-life of 26 min (11-36 min). The results are in accordance with the previously reported observations of huge numbers of uric acid utilizing bacteria in the caeca of a variety of birds, and also with the nitrogen recycling theory. However, no conclusion concerning the nitrogen recycling can be drawn.
The willow ptarmigan has two large caeca housing dense populations of microorganisms. Urine, containing uric acid, is transported from the cloaca into the caeca when these are filled. Here the uric acid is rapidly broken down, suggesting that the caeca take part in a recycling of excretory nitrogen. In this work it is shown that ammonia produced by the uric acid decomposition is incorporated into new amino acids in a glutamic dehydrogenase catalyzed reaction. We have, however, not been able to detect any absorption of amino acids from the caeca, indicating that nitrogen recycling via the amino acid route does not occur.
A fluorometric method for the determination of naproxen in serum, albumin solutions and protein free buffer solutions is described. The detection limit is about 10 ng/ml. Furosemide, thiopental and salicylic acid did not show any disturbing fluorescence while phenprocoumon did. The in vitro binding of naproxen in albumin solutions and serum was studied by equilibrium dialysis. A small but significant increase was found in the percentual binding in albumin solutions as compared to serum. The percentual binding was not affected by changes in the pH from 5--8. By fitting the binding data to a model assuming two classes of binding sites, association constants and binding capacities were determined. A very high affinity and a high capacity were found. The association constant for the first class of binding sites was higher for human serum albumin than for serum (8.5 versus 5.3 . 10(6) M-1). The difference in the protein binding to the first class of binding sites in human serum albumin and serum can be explained by the existence of a competitive inhibitor in serum.
Out of a total of 150 patients attending an out-patient clinic for anticoagulant therapy, 12 had disorders which normally would indicate a prolonged use of an antirheumatic drug. To 6 of these patients, naproxen (1/4 g twice daily) was given while anticoagulant treatment with phenprocoumon was continued in an unchanged dosage schedule (average dose 2.1 mg/day). On the average, the prothrombin complex activity (PP%) was reduced to a stable level 10--20% below that obtained during a 2-month period before the naproxen treatment was started. No bleeding episodes or other effects were observed. Thus the simultaneous administration of naproxen caused no problems for the maintenance of a stable anticoagulant therapy.
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