Biomedical subjects

E Vinge

Publications and source records attributed to E Vinge.

At least 37 records · Page 2Linked to original sources

PubMed1993

Immunoreactive endogenous digoxin-like substances: plasma levels are dependent on the hypothalamic-pituitary-adrenal axis for release and on kidney function for elimination.

To identify factors that regulate the levels of immunoreactive digitalis-like substances (irEDLS) in body fluids, two studies were carried out. Plasma and urine levels of irEDLS were measured in uremic and normal subjects. Extracted material was fractionated (12 fractions) and assayed by digoxin radioimmunoassay. In four fractions, higher levels of irEDLS were found in uremic than in normal plasma. Urine from healthy subjects contained very high levels of irEDLS, but in urine collected from uremic patients irEDLS levels were similar to those in plasma. In another study, eight healthy subjects were given dexamethasone 1 mg orally and tetracosactide [an adrenocorticotropic hormone (ACTH) analogue] 0.25 mg i.v., on separate occasions. Dexamethasone suppressed the plasma and urine levels of cortisol and irEDLS. ACTH increased the levels of cortisol in plasma and urine, and of irEDLS in plasma. Taken together, these results support the hypothesis that irEDLS are of adrenal origin. However, decreased renal clearance, rather than increased production or release, may be the main cause of increased plasma levels of irEDLS in uremia.

Administration, Oral↗

PubMed1993

[Calcitonin as medication in pain?].

An antinociceptive effect of calcitonin has been reported in numerous studies on both animals and humans. In the present article, we review the controlled clinical studies in which calcitonin has been used to relieve skeletal pain (cancer metastases, osteoporotic fractures) as well as extraskeletal pain (phantom limb pain, neurogenic claudication, reflex sympathetic dystrophy, migraine). To date, a positive effect of calcitonin is well documented against placebo in short-term treatment of skeletal pain. However, for long-term treatment of skeletal pain, and for the treatment of extraskeletal pain, the present documentation is insufficient. No controlled trials against conventional analgesic treatment is published. Thus, further studies are required before the place of calcitonin in pain therapy can be established.

Bone Neoplasms↗

PubMed1992

Aggregation of human granulocytes by Staphylococcus aureus lipase.

The effects of purified extracellular lipase from Staphylococcus aureus on human granulocytes were studied in vitro with a turbidimetric technique. Within the concentration range 0.6-4.4 micrograms/ml, lipase caused monophasic aggregation accompanied by the release of lactoferrin; the corresponding concentrations of the solvent in which it was suspended, Triton X100, had no effect. Lipase-induced aggregation did not occur in the presence of autologous plasma.

Cell Aggregation↗

PubMed1992

Prediction of suicidal behavior from biologic tests.

Biochemical studies related with suicidal behavior have mainly dealt with monoaminergic and corticosteroidal measures. We used some of these measures in a study of 61 suicide attempters who, except for occasional doses of benzodiazepines, had been medication free for a mean of 16 days. The monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in lumbar cerebrospinal fluid (CSF). We found that violent suicide attempters (N = 18) had 5-hydroxyindoleacetic acid concentrations below the median of all patients, whereas the concentrations of 3-methoxy-4-hydroxyphenylglycol were mainly above the median. We found no significant differences between violent and nonviolent (N = 43) attempters concerning CSF homovanillic acid, 24-hour urinary norepinephrine-epinephrine and cortisol, activity of monoamine oxidase in platelets, or post-dexamethasone plasma cortisol. Four patients completed suicide, and 3 of them had CSF 5-hydroxyindoleacetic acid concentrations at or below the median. All completed suicides had CSF 3-methoxy-4-hydroxyphenylglycol concentrations above the median. Urinary measures and platelet monoamine oxidase activity of completed suicides were in the higher concentration ranges. Patients who repeated suicidal behavior after the index investigation had low 24-hour urinary cortisol levels more often than those who did not repeat. Because our subgroups of patients are small, we cannot draw any firm conclusions about the value of our CSF and urinary biochemical findings predicting suicidal behavior. However, our CSF findings in violent suicide attempters are similar to those observed in other studies.

Aged↗

PubMed1991

Some substances with proposed digitalis-like effects evaluated on platelet functions sensitive for cardiac glycosides.

1. The effects of progesterone, corticosterone 21-acetate, chlormadinone acetate, dehydroepiandrosterone 3-sulfate and lysophosphatidylcholine were tested on 86Rb-uptake, 3H-5-HT-uptake, ADP-induced aggregation and 5-HT-induced shape change in human platelets. Ouabain and digoxin were used for reference. 2. Ouabain and digoxin 10(-5) M inhibited 86Rb-uptake by more than 85%, and chlormadinone acetate 10(-5) M by 20%. The other substances had no effects. 3. Ouabain and digoxin were potent inhibitors on 3H-5-HT-uptake, whereas chlormadinone acetate had no effect. 4. Ouabain and digoxin increased ADP-induced aggregation but chlormadinone acetate decreased it. 5-HT-induced shape change was decreased by ouabain and digoxin, and to a lesser extent by chlormadinone acetate and its vehicle (ethanol 1.0%).

Blood Platelets↗

PubMed1991

Interactions between isoprenaline, sodium nitroprusside, and isozyme-selective phosphodiesterase inhibitors on ADP-induced aggregation and cyclic nucleotide levels in human platelets.

The interactions between isoprenaline, sodium nitroprusside, and the isozyme-selective phosphodiesterase inhibitors OPC 3911 ("cAMP specific") and zaprinast ("cGMP specific") on platelet aggregation induced by adenosine diphosphate (ADP) and on levels of cAMP and cGMP were studied. Isoprenaline at 10(-6)M diminished aggregation by 28%, and this effect was enhanced by 10(-7)-10(-6)M OPC 3911. Neither 10(-6) M isoprenaline nor 10(-7)M OPC 3911 elevated cAMP, but in combination they caused a significant rise in cAMP (27% above the basal level), accompanying the synergistic functional inhibition, without affecting cGMP levels. Sodium nitroprusside at 10(-5) M diminished aggregation by 39%, elevated cGMP levels (81-110%), but also caused a statistically significant increase in cAMP (21-32%), and enhanced the effects of 10(-6)M isoprenaline on cAMP levels. Zaprinast at 10(-5) M caused a modest inhibition of aggregation by 20%, and a small increase in cGMP (20%), and it clearly enhanced the effects of 10(-5)M sodium nitroprusside on both cGMP and cAMP levels, but not on aggregation. The cAMP-increasing effect of sodium nitroprusside might be a consequence of a cGMP-mediated inhibition of the "low-Km cGMP-inhibited phosphodiesterase" that is also inhibited by OPC 3911. The effects of all of the drugs on ADP-induced aggregation seem to depend more on their effect on cAMP levels than on the levels on cGMP.

Cyclic AMP↗

PubMed1991

The efflux of 86Rb and [3H]5-HT from human platelets during continuous perfusion: effects of potassium-induced membrane depolarization and thrombin stimulation.

In order to study the ionic efflux or granule release from human platelets following pulse exposure to various stimuli, a method for continuous perfusion of platelets was developed. The method was applied to compare the effects of membrane depolarization and thrombin stimulation on the release of 86Rb and [3H]5-HT. Washed and preloaded human platelets were placed on a membrane filter in a temperature controlled polypropylene chamber, and subsequently perfused with buffer. After an initial washout period the efflux of 86Rb or [3H]5-HT reached steady, low levels. K+ induced concentration dependent increases in 86Rb efflux, corresponding to a depolarization of the membrane potential, whereas the efflux of [3H]5-HT was unaltered. Thrombin induced concentration dependent increases in the efflux of both 86Rb and [3H]5-HT. Pretreatment with K+ 12 or 30 mM did not alter the [3H]5-HT efflux induced by thrombin 0.1 U ml-1. Scanning electron micrographs of platelets on the filter showed that the unstimulated platelets had regular shape, whereas after addition of thrombin there was formation of pseudopods and minor aggregates. The effect of potassium-induced membrane depolarization on platelet aggregation was also studied. High concentration of K+ did not induce aggregation or shape change during 2 or 10 minutes of incubation. K+ had little or no effect on aggregation induced by ADP 2 microM or thrombin 0.4 U ml-1. The results from release experiments and aggregation tests argue against an immediate coupling between membrane potential and platelet reactivity.

Adenosine Diphosphate↗

PubMed1990

Low dose acetylsalicylic acid and thromboxane release at the site of plug formation in vivo in elderly patients with cardiovascular disease.

Thromboxane B2 (TXB2) levels in bleeding time blood and in serum were measured in 13 elderly patients with cardiovascular disease, seven of whom were receiving continuous treatment with low dose acetylsalicylic acid (ASA, 125 mg every second day--250 mg daily) for prevention of stroke. Blood sampling was performed openly, but assays of TXB2 were performed by a blinded investigator. In patients treated with ASA, median serum TXB2-levels were 4% and TXB2-levels in bleeding-time blood were less than 16% of the corresponding levels in patients without ASA (P less than 0.01). The results show that in elderly atherosclerotic patients very low doses of ASA substantially suppress TXB2 formation, not only in serum but also at the site of local haemostasis. The extent of suppression is comparable to that previously reported from young healthy subjects.

Aged↗

PubMed1990

Effects of isozyme-selective phosphodiesterase inhibitors on rat aorta and human platelets: smooth muscle tone, platelet aggregation and cAMP levels.

The inhibitors of the cGMP-inhibited, low-Km cAMP phosphodiesterase--milrinone and OPC 3911--and an inhibitor of a non-cGMP-inhibited low-Km cAMP phosphodiesterase--rolipram--were used to evaluate the functional importance of the two cAMP phosphodiesterase activities in vascular smooth muscle and in platelets. Vinpocetine, an inhibitor of a calcium-calmodulin-dependent phosphodiesterase was also studied. OPC 3911 and milrinone relaxed the contracted rat aorta, inhibited ADP-induced platelet aggregation and also enhanced isoprenaline-induced relaxation as well as the antiaggregatory effects of adenosine. In platelets, OPC 3911 and milrinone increased cAMP levels, but in the rat aorta the increase was significant only for milrinone (OPC 3911 P = 0.062). In both tissues OPC 3911 and milrinone enhanced the increase in cAMP caused by activators of adenylate cyclase (isoprenaline/adenosine). Rolipram had no effects on aggregation or cAMP levels in platelets and no overadditive effects in combination with adenosine. Rolipram had little effect on relaxation and cAMP levels, did not alter isoprenaline-induced relaxation of guanfacin-contracted rat aorta, but showed synergistic effects with isoprenaline in raising cAMP levels. In PGF2 alpha-contracted aorta rolipram enhanced relaxation caused by isoprenaline. Vinpocetine had a relaxant effect without affecting cAMP levels, but had no effect on platelets. These results support the concept that the cGMP-inhibited phosphodiesterase is an important modulator of vascular smooth muscle tone and platelet function. The role of the non-cGMP-inhibited phosphodiesterase in these tissues is less obvious.

Animals↗

PubMed1990

Effects of desmopressin acetate on platelet aggregation, von Willebrand factor, and blood loss after cardiac surgery with extracorporeal circulation.

The effects of desmopressin acetate (DDAVP) on platelet aggregation and the von Willebrand factor antigen (vWF:Ag) were studied in 19 patients undergoing cardiac surgery with extracorporeal circulation. The patients represented one of five blocks in a randomized double-blind placebo-controlled parallel group trial on the effects of DDAVP on postoperative bleeding after uncomplicated coronary artery bypass operations. After termination of extra-corporeal circulation, DDAVP (0.3 microgram/kg body wt) or its vehicle was infused into a peripheral vein throughout 15 minutes. The increase in factor VIII coagulant activity after infusion did not differ between the groups but there was a significantly larger increase in vWF:Ag levels in DDAVP-treated patients. The aggregatory response to adenosine-diphosphate (ADP) and ristocetin showed a normal pattern and was not significantly different between the two groups. As compared with placebo, DDAVP did not decrease the bleeding time or the postoperative blood loss. We conclude that DDAVP causes an increase in vWF:Ag levels but does not alter platelet aggregation, bleeding time, or blood loss in uncomplicated coronary artery bypass patients.

Coronary Artery Bypass↗

PubMed1990

Beta-adrenoceptor blockers and calcium antagonists in the prophylaxis and treatment of migraine.

Based on published reports of controlled double-blind studies, the efficacy of beta-receptor blockers and calcium antagonists in the prophylactic treatment of migraine is reviewed. Taking into consideration problems in trial design and evaluation of the effects of treatment, and the amount of documentation, it may be concluded that propranolol, metoprolol, timolol, nadolol and atenolol have been shown to reduce the frequency of migraine attacks in patients with common as well as classical migraine. The effect on duration and intensity of migraine attacks is less clear. Treatment effect is generally seen within 4 weeks, but seems to increase with time. Nonselective beta-receptor blockers as well as drugs selective for beta1-receptors may be effective, and their efficacy is comparable to that of other active antimigraine drugs. Available studies do not exclude the fact that beta-receptor blockers with partial agonist activity (intrinsic sympathomimetic activity) have an effect, but suggest that their efficacy is inferior to that of blockers lacking this property. Among the calcium antagonists tested for prophylactic effect in migraine, the effects of verapamil, nifedipine and diltiazem seem promising, but available documentation does not allow any definitive statements of efficacy to be made, particularly not for nifedipine and diltiazem. The ability of flunarizine to reduce the frequency of migraine attacks in patients with common and classical migraine is well documented; its effect on attack duration and intensity is less well established. The response rate is similar to that for beta-receptor blockers, and to that, for example, for pizotifen (pizotyline). Nimodipine also appears to reduce the frequency of migraine attacks, but the efficacy of this drug, compared with other alternatives, remains to be definitely established.

Adrenergic beta-Antagonists↗

PubMed1989

Pharmacokinetics of triethylamine and triethylamine-N-oxide in man.

The pharmacokinetics of the industrially important compound triethylamine (TEA) and its metabolite triethylamine-N-oxide (TEAO) were studied in four volunteers after oral and intravenous administration. TEA was efficiently absorbed from the gastrointestinal (GI) tract, rapidly distributed, and in part metabolized into TEAO. There was no significant first pass metabolism. TEAO was also well absorbed from the GI tract. Within the GI tract, TEAO was reduced into TEA (19%) and dealkylated into diethylamine (DEA; 10%). The apparent volumes of distribution during the elimination phase were 192 liters for TEA and 103 liters for TEAO. Gastric intubation showed that there was a close association between levels of TEA in plasma and gastric juice, the latter levels being 30 times higher. The TEA and TEAO in plasma had half-lives of about 3 and 4 hr, respectively. Exhalation of TEA was minimal. More than 90% of the dose was recovered in the urine as TEA and TEAO. The urinary clearances of TEA and TEAO indicated that in addition to glomerular filtration, tubular secretion takes place. For TEAO at high levels, the secretion appears to be saturable. The present data, in combination with those of earlier studies, indicate that the sum of TEA and TEAO in urine may be used for biological monitoring of exposure to TEA.

Administration, Oral↗

PubMed1988

Thromboxane A2 and prostacyclin release in bleeding time blood during primary haemostasis in healthy individuals.

It is generally believed that prostacyclin (PGI2) generation is greatly stimulated when blood vessels are injured, even by minor trauma, such as venepuncture. The Simplate technique for measuring skin bleeding time was adapted to quantify by radioimmunoassay PGI2 and thromboxane A2 (TXA2) in the emerging blood, as the stable degradation products 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2), both of which were measured in venous plasma as well as in serum (clotted at 37 degrees C for 1 h). During bleeding, when platelets aggregate to occlude the injured vessels, the median TXB2 level in the emerging bleeding time blood was 1.7 ng/ml. The median TXB2 level in plasma was less than 1 ng/ml and in serum 275 ng/ml. The levels of immunoreactive 6-keto-PGF1 alpha were always below determination limit in bleeding time blood (0.2 ng/ml) and in plasma (0.1 ng/ml), whereas in serum the levels ranged between 0.26 and 0.47 ng/ml. The fact that enhanced PGI2 production in primary haemostasis in skin incisions could not be demonstrated calls for further investigations of possible PGI2 production with more sensitive assays or in injured large vessels.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Progesterone, some progesterone derivatives and urinary digoxin-like substances from pregnant women in radioimmuno- and 86Rb-uptake assays of digoxin.

Progesterone and some derivatives were tested in a radioimmunoassay (RIA) of digoxin and in a bioassay measuring the 86Rb-uptake into red blood cells as an index of Na+, K+-ATPase activity. The digitalis-like activity of the hormones was compared with that found in chromatographic fractions of material extracted from the urines of pregnant women at term. Progesterone at concentrations greater than 10(-6) M cross-reacted in the RIA, and at 10(-3) M it decreased 86Rb-uptake by 18%. The anaesthetic progesterone derivates 5 alpha-pregnane-3 alpha-ol-20-one and 5 alpha-pregnane-3,20-dione crossreacted to a lesser degree in the RIA and lacked effect in the bioassay. Similar results were obtained with pregnandiol-glucuronide, the major urinary metabolite of progesterone. In contrast, several fractions of the urinary material had significant effects in both assays. It is concluded that the digitalis-like activity of progesterone is not coupled to properties associated with its anaesthetic effects. Furthermore, although progesterone may account for a part of the endogenous digoxin-like substances in serum of neonates and pregnant women, neither progesterone proper nor pregnandiol-glucuronide explains the great amount of digoxin-like substances found in the urines.

Anesthetics↗

PubMed1988

Effects of ouabain on 86Rb-uptake, 3H-5-HT-uptake and aggregation by 5-HT and ADP in human platelets.

In the search of sensitive models for actions of digitalis-like substances on intact cells or tissues, the effects of ouabain on human platelets were investigated. In a concentration-dependent manner ouabain 10(-8)-10(-4) M inhibited Na+-K+-ATPase activity measured as uptake of 86Rubidium (86Rb), with about 90% inhibition of the total uptake at ouabain greater than or equal to 10(-6) M. An almost identical concentration-effect curve was found for platelet uptake of 3H-serotonin (3H-5-HT). The platelet shape change reaction to exogenous 5-HT (1 X 10(-6) M) was suppressed by ouabain (10(-8)-10(-4) M) in a concentration-dependent manner, but with no clear maximum effect within the range tested. Aggregation induced by adenosine-di-phosphate (ADP 2 X 10(-6) M) was enhanced by ouabain 10(-8)-10(-6) M. At the highest concentration tested the rate of aggregation was increased by 31% and the change in light transmission by 54%. At low concentrations (less than 10(-9) M) of ouabain, there was a tendency towards increased aggregation as well as increased uptake of 86Rb, which may be a parallel to observations of positive inotropic effects of low concentration of glycosides, which do not inhibit Na+-K+-ATPase. The results show that human platelets can be used as a model tissue for studying effects of cardiac glycosides. This suggests that it may be useful for further investigations of the biological effects of agents with a similar effect profile, e.g. endogenous digitalis-like substances.

Adenosine Diphosphate↗

PubMed1988

Effects of some calcium antagonists on aggregation by adrenalin and serotonin and on alpha-adrenoceptor radioligand binding in human platelets.

The inhibitory effects of verapamil, nifedipine and diltiazem, representatives of different classes of calcium antagonists, were studied on aggregation of human platelets induced by adrenalin and serotonin (5-HT). For references, the alpha-adrenoceptor-antagonists phentolamine (alpha 1 and alpha 2) and rauwolscine (alpha 2), and the 5-HT 2-receptor-antagonist ketanserin were included. Verapamil in the concentration range 10(-6) 10(-4) M inhibited both adrenalin- and serotonin-induced aggregation in a concentration-dependent manner, whereas nifedipine and diltiazem had little or no effect. Phentolamine and rauwolscine were clearly weaker than verapamil as antagonists of serotonin, and ketanserin lacked effect on adrenalin-induced aggregation. Binding studies with [3H]dihydro-alpha-ergocryptine and [3H]rauwolscine on human platelet membranes showed equal numbers of binding sites, suggesting that only alpha 2-adrenoceptors were present. In the same concentration range as inhibition of aggregation was obtained, verapamil inhibited binding of either radioligand. Nifedipine, diltiazem and 5-HT were all poor inhibitors of radioligand binding. The results suggest that verapamil at high concentrations not only has alpha-adrenoceptor antagonistic properties but also exerts 5-HT-receptor blocking effects. This was not found with the other calcium channel blockers examined (nifedipine, diltiazem).

Adrenergic alpha-Antagonists↗

PubMed1988

Thromboxane B2 levels in serum during continuous administration of nimodipine to patients with aneurysmal subarachnoid hemorrhage.

Twenty-four patients with subarachnoid hemorrhage due to rupture of a supratentorial aneurysm underwent surgery within 72 hours after subarachnoid hemorrhage. Immediately after clipping of the aneurysm the patients were treated with intravenous nimodipine for at least 7 days and then received the drug orally for another week. Nine patients had a documented or probable intake of aspirin or other nonsteroid anti-inflammatory drug during the days preceding admission. In all patients there was a gradual increase in serum thromboxane B2 concentration from low to normal levels during the treatment period, the increase being most pronounced in patients with prior nonsteroid anti-inflammatory drug intake. Thromboxane B2 concentrations were similar to those of four control patients not receiving nimodipine. In three patients who developed delayed ischemic dysfunction despite "therapeutic" nimodipine plasma concentrations, the thromboxane B2 levels were low or normal. Our present results do not support the idea that nimodipine exerts an effect on platelet function in patients with aneurysmal subarachnoid hemorrhage.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1988

Evaluation of cross-reactivity of urinary digoxin-like substance in different radioimmunoassays.

For the accuracy of routine monitoring of digoxin and digitoxin it seems important to get information on the cross-reactivity of endogenous digitalis-like substances (EDLS). To obtain EDLS, urine was passed on Sep-Pak columns and eluted in fractions by increasing concentrations of acetonitrile. Dilution series of two fractions were subjected to radioimmunoassay (RIA) with respect to digoxin- and digitoxin-like activity, using commercial kits from New England Nuclear, Farmos Diagnostica, and Diagnostic Products Corporation. Cross-reactivity and the degree of parallelism between dilution curves and standard curves varied markedly between the procedures. Recovery studies showed that the presence of EDLS, even at concentrations below the limit of determination of the respective assay, can influence the recovery of digoxin and digitoxin. When higher concentrations of EDLS were present, the combined effects of EDLS and drugs were not always additive. This again stresses the need for any RIA to be carefully characterized to minimize important sources of errors. Required prerequisites are detailed and highly specific information on specificity and the influence of endogenous interfering substances is given. To warrant reliable measurements of digoxin, it is important to identify the cross-reactive material known as EDLS.

Adult↗