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Biomedical subjects

K Winther

Publications and source records attributed to K Winther.

At least 91 records · Page 5Linked to original sources
PubMed1987

Platelet alpha-adrenoceptor function and aging.

The effect of aging on platelet alpha-adrenoceptor binding of 3H-dihydro-alpha-ergocryptine (3H-DHE) and alpha-adrenoceptor response expressed as cAMP decrease, after the addition of noradrenaline 10 microM to intact platelets in vitro were examined and correlated with adrenaline induced platelet aggregation in a group of twelve young volunteers (mean age 21 years), and twelve old volunteers (mean age 88 years). The binding by platelets of 3H-DHE was considerably higher in the young than in the old group (mean 292.70 +/- 40.79 and 167.90 +/- 18.30 fmol/mg protein respectively, p less than 0.02). The affinity (Kd) was also influenced with values of 1.49 +/- 0.21 in the young and 3.32 +/- 0.45 nM in the old, p less than 0.01). Stimulation of platelets with noradrenaline caused a greater decrement of cAMP in the old than in the young group (mean 4.44 +/- 0.87 as compared with 0.32 +/- 0.75 pmol/10(9) platelets. Platelet sensitivity to adrenaline, when expressed as aggregation increased in the old group. These data suggest that the enhanced sensitivity to adrenaline as observed in old people is not the result of increased alpha-adrenoreceptor number of affinity, but related to changes in the platelet membrane possibly not related to the alpha-adrenoceptors.

Adolescent↗
PubMed1987

Aging and platelet beta-adrenoceptor function.

Ten young volunteers (mean age 20 years) and ten elderly volunteers (mean age 89 years), including equal numbers of healthy men and women, were tested regarding adrenaline-induced platelet aggregation in vitro, platelet cyclic AMP content before and after beta-adrenoceptor stimulation with isoprenaline, as well as binding by platelet membranes of 125I-hydroxybenzylpindolol. In the aged patients there was a highly significant decrease in the concentration of adrenaline needed to produce irreversible platelet aggregation, as compared with the young. Platelet basal cyclic AMP content did not differ but the response to isoprenaline stimulation, expressed as the percentage rise of cyclic AMP content above the unstimulated level, was significantly decreased in the old subjects. The beta-adrenoceptor number was unchanged but the affinity decreased significantly in the old group. The data suggest that the increased aggregation response to adrenaline in old people could be due in part to a diminished functional capacity of the platelet beta-adrenoceptor.

Adult↗
PubMed1987

Platelet involvement in salivary gland inflammation in patients with primary Sjögren's syndrome.

Seventeen consecutive patients under evaluation for Sjögren's syndrome (SS) had a lower lip salivary gland biopsy performed. Using a monoclonal mouse immunoglobulin against human platelet glycoprotein Ib in an indirect immunoperoxidase technique, it was found that platelets accumulate intravascularly in the inflamed salivary glandular areas. Platelets were demonstrated in the interstitial tissue of inflamed salivary glands from two patients. Saliva from 17 consecutive patients with previously well-established primary SS and 11 healthy controls, and blood from 11 of the patients and all controls were then examined for platelets and the platelet-specific release product beta-thromboglobulin (beta-TG). Platelets were not demonstrated in saliva from patients or controls. beta-TG was detected in saliva from five patients (11-150 ng/ml), but in none of the controls. There were no correlations between saliva beta-TG levels and saliva secretion rates or plasma beta-TG levels. We conclude that platelet release of beta-TG into saliva in patients with primary SS most likely is a result of immunoinflammatory reactions in salivary glands. Measurement of beta-TG in saliva may be of value in the estimation of disease activity.

Adult↗
PubMed1987

Lack of effect of 5-aminosalicylic acid on platelet aggregation and fibrinolytic activity in vivo and in vitro.

We have studied platelet aggregation and fibrinolytic activity in six patients with chronic inflammatory bowel disease treated with 5-aminosalicylic acid (mesalazine). There were no changes in these measurements during normal treatment, i.e. 1.5 g per day with a slow-release formulation, nor after an intravenous dose of 250 mg. Also in vitro tests were negative, in contrast to the inhibition seen with aspirin (acetylsalicylic acid). We conclude that treatment with mesalazine does not constitute a hazard to these patients in regard to prolonged bleeding time caused by an influence on platelet aggregation or fibrinolytic activity.

Adult↗
PubMed1987

The effect of beta-blockade on platelet function and fibrinolytic activity.

Two groups of hypertensives and a group of migraine sufferers were tested during treatment with the nonselective beta-blocker propranolol and the beta 1-selective metoprolol. During treatment with propranolol, an increased platelet aggregability and a decrease in platelet content of cyclic AMP were seen when compared with metoprolol treatment. In addition, propranolol treatment increased the plasma level of adrenaline as well as the euglobulin clot lysis time.

Adrenergic beta-Antagonists↗
PubMed1986

Effect of metoprolol and propranolol on platelet aggregation and cAMP level in hypertensive patients.

Ten patients with uncomplicated moderate essential hypertension were recruited to evaluate the effect of the non-selective beta-blocker propranolol and the beta 1-selective beta-blocker metoprolol on platelet aggregation and cAMP formation. Five patients began treatment with propranolol 80 mg b.i.d. and 5 with metoprolol 100 mg b.i.d., and after 2 weeks the treatments were exchanged. ADP- and adrenaline-induced platelet aggregation and the basal level of platelet cAMP were measured at the end of each treatment period. Platelet aggregation was tested turbidometrically, using the threshold value for irreversible aggregation, and cAMP measurements were performed using a protein-binding assay. Both ADP and adrenaline threshold values were significantly lower after propranolol than after metoprolol. The basal cAMP level was lower during propranolol than metoprolol treatment. The results indicate that platelet aggregation and basal cAMP level are influenced by beta-blockers in proportion to their affinity to different beta-adrenoceptors. This may be of value in the beta-blocker treatment of patients at high thrombotic risk.

Adenosine Diphosphate↗
PubMed1986

Platelet function in patients with primary Sjögren's syndrome.

Platelet function tests were performed in 15 patients with primary Sjögren's syndrome (SS) and in 15 normal controls. Platelet counts were within the normal range in all except two patients in whom they were only slightly decreased. P-beta-thromboglobulin was increased in several patients compared to controls, although not significantly (p less than 0.1). Platelet aggregation was enhanced in patients when measured upon stimulation with epinephrine (p less than 0.05), ADP (p less than 0.01) and collagen (p less than 0.01). No correlation was found between enhanced platelet activity and sex, age, duration of disease, extraglandular manifestations, positive ANA test, elevated P-IgG or P-immune complexes. Enhanced platelet activity in patients with primary SS is a new observation. Future studies are needed to elucidate the pathogenetic background.

Adenosine Diphosphate↗
PubMed1986

The difference between non-selective and beta 1-selective beta-blockers in their effect on platelet function in migraine patients.

Platelet function has been postulated as playing a role in the pathogenesis of migraine. This study aimed to investigate to what extent beta 1-selective and non-selective beta-blockers interfere with the platelet function in migraine patients. Twelve patients with classical migraine were included. After a 2-week drug-free period, the patients were randomly allocated to either beta 1-selective metoprolol (50 mg b.i.d.) or non-selective propranolol (40 mg b.i.d.) treatment for one month. After a wash-out period, the patients were changed to the corresponding beta-blocker for one month. ADP-induced platelet aggregability, platelet cAMP, ATP and ADP levels, plasma cAMP and TxB2 concentration, as well as the serum production of TxB2 were measured before and after each treatment period. After propranolol treatment, the patients showed lower ADP threshold values for producing irreversible platelet aggregation and lower platelet and plasma cAMP levels as compared to metoprolol. Neither of the beta-blockers induced any change in the plasma concentration or serum production of TxB2. In conclusion, non-selective beta-blockade (propranolol) significantly increases the platelet aggregability compared to beta 1-selective blockade (metoprolol).

Adenosine Diphosphate↗
PubMed1986

Beta-adrenoceptor blockade, platelets, and rheologic factors.

Alterations in platelet function and other hemorheologic factors have been reported to occur in patients with migraine. The prophylactic treatment of migraine with beta blockers is at present well established, and non-selective as well as beta 1-selective beta blockers exert an effect. The aim of this presentation is to summarize how beta blockers, depending on their receptor selectivity, modulate platelet function and hemorheologic factors. We conclude that non-selective beta blockade increases factors, such as platelet aggregability, and decreases fibrinolytic activity compared with beta 1-selective blockade with metoprolol. These differences do not reflect on their migraine prophylactic effect and indicate that alterations in platelet function are not a primary cause of migraine: rather, they are epiphenomena.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Platelets in blood and salivary glands of patients with primary Sjögren's syndrome.

Circulating platelets from 15 patients with primary Sjögren's syndrome (primary SS) and from 15 normal controls were enumerated and their aggregability determined. Blood platelet concentrations were within the normal range, except for two patients in whom they were slightly decreased. Platelet aggregation was enhanced in patients, when measured upon stimulation with epinephrine (p less than 0.05), ADP (p less than 0.01) and collagen (p less than 0.01). Plasma and saliva from 17 patients with primary SS and from 11 normal controls were examined for the platelet-specific release product beta-thromboglobulin (beta-TG). P-beta-TG was increased in the patients, although not significantly (p greater than 0.05). In saliva beta-TG was detected in 5 patients (11-150 ng/ml), but not in any of the controls. There was no correlation between levels of beta-TG in plasma and saliva. Lower lip minor salivary glands from 17 patients under evaluation for SS were examined for platelet accumulation. Indirect immuno-peroxidase staining with the monoclonal mouse anti-human platelet glycoprotein Ib antibody, showed platelet accumulation intravascularly in the inflamed areas. The combined results are in accordance with the hypothesis that platelet activation occurs in the salivary glands of patients with primary SS.

Humans↗
PubMed1985

Platelet function in surgical stress.

Ten patients for elective cholecystectomy were studied pre-, per-and postoperatively. All had neurolept anesthesia. Plasma concentrations of beta-TG, TXB2 and 5-HT and intraplatelet 5-HT were measured. Aggregation to ADP was recorded. Serum cortisol concentration was used as index of the stress response, showing peroperative increase and postoperative decrease. Closely related to this we observed a significant increase in P--beta-TG and P-TXB2 with postoperative normalization in 6 patients without complications. P--5-HT had a peak peroperatively and remained elevated postoperatively. A negative correlation between P--5-HT and decreasing intraplatelet 5-HT postoperatively was observed. High postoperative levels of P--5-HT seem to be related to low arterial PO2 and pulmonary dysfunction. In 3 patients with complications a second increase in P--beta-TG, P-TXB2 and partly in P--5-HT was found. Platelets were temporarily refractory to ADP immediately following surgery and showed increased aggregability postoperatively. We conclude that platelets are activated in surgical stress.

Adenosine Diphosphate↗
PubMed1985

Characterization of human platelet beta-adrenoceptors.

The widespread use of beta-adrenoceptor antagonists against hypertension, angina pectoris and migraine or as a preventive treatment after myocardial infarction has encouraged us to investigate the effects of these drugs on platelet function. The aim of this study was to examine whether beta-blocking drugs interfere with platelet beta- adrenoceptors and whether this dependency is related to their selectivity for beta-adrenoceptor subtypes. Beta-adrenoceptor stimulation of human platelets with isoprenaline increased cyclic AMP (cAMP), which is known to inhibit platelet aggregation. Furthermore, our studies showed that cAMP formation in vitro was stimulated by non-selective and beta 2-selective agonists, but not by the predominant beta 1-agonist prenalterol. Isoprenaline- stimulated cAMP formation was blocked by the non- selective beta-adrenoceptor antagonists propranolol, timolol, and alprenolol, while the beta 1-selective antagonists atenolol and metoprolol had no influence on an isoprenaline-induced cAMP formation. Receptor binding studies using (3H)-dihydroalprenolol revealed an IC50 value for propranolol of 85 nM, while metoprolol only displaced the bound (3H)-dihydroalprenolol at far higher concentrations (IC50, 20 microM). We conclude that the human platelet beta-adrenoceptors are mainly of the beta 2- subtype and that beta-adrenoceptor antagonists, especially the non-selective antagonists interfere with platelet function assessed as platelet cAMP formation.

Adult↗
PubMed1985

Inhibition of human platelet aggregation by dihydropyrano- and dihydrofuranocoumarins, a new class of cAMP-phosphodiesterase inhibitors.

Certain esters of dihydropyranocoumarin and dihydrofuranocoumarin alcohols have previously been shown to inhibit the cAMP-phosphodiesterase from bovine heart. We now report that these naturally occurring coumarins inhibit the high affinity (Km = 1.1 microM) cAMP-phosphodiesterase from human platelets with activities that closely correlate with those obtained using phosphodiesterase from bovine heart tissue. Additionally the coumarins inhibit the aggregation of human platelets induced with ADP, adrenaline and collagen with activities comparable to those of dipyridamole. A lack of significant correlation between these metabolic and functional activities indicates that there exist, besides cAMP-phosphodiesterase inhibition, additional mechanisms of action for the platelet aggregation inhibitory effect of dihydropyrano- and dihydrofuranocoumarins.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Lack of evidence for human lymphokines with thrombocyte aggregating activity. An in vitro study.

The ability of human lymphocytes to produce soluble mediator(s) with thrombocyte aggregating activity (TAA) was investigated in an in vitro technique. Isolated human mononuclear cells were stimulated with phytohaemagglutinin or purified protein derivative of tuberculin. The supernatants were investigated for lymphokine activity in a leucocyte migration inhibitory factor assay. Supernatants were then tested for their ability to aggregate human thrombocytes, and in contrast to the results of previous studies, we were not able to demonstrate any TAA. Most likely, lymphokines with TAA are not involved in the thrombotic processes seen in human cell-mediated immune inflammatory reactions.

Adenosine Diphosphate↗
PubMed1984

Characterization of the beta-adrenergic receptor on the human platelet: a beta 2-subtype.

The human platelet beta-adrenergic receptor was characterized by using the ability of different drugs to stimulate the adenylate cyclase activity and the effects of various beta-antagonists to block the isoprenaline-stimulated adenylate cyclase activity. Isoprenaline was found 10 times more potent than adrenaline and 1000 times more potent than noradrenaline in stimulating the adenylate cyclase activity in these cells. Isoprenaline-stimulated activity was blocked by the non-selective beta-antagonists propranolol and alprenolol and by the beta 2-selective antagonist IPS 339 and prenalterol. Metoprolol, a beta 1-selective blocker, was without effect on the isoprenaline-stimulated adenylate cyclase activity. We conclude from our findings that the beta-adrenergic receptor type on the human platelet is mainly of the beta 2-subtype.

Adenylyl Cyclases↗
PubMed1981

An artificial betacell: assessment of the glucose analyser, infusion system and optimization of constants for the algorithms.

The glucose analyser and insulin infusion modules of the Biostator were tested. The infusion system was reliable since more than 99% of the computed volume of insulin solution was delivered by the infusion pump at infusion rates above 1/100 of maximum, and no insulin was adsorbed onto infusion bags or tubing. Blood glucose results from the Biostator were compared with routine laboratory methods during long-term feedback control. Both slope (0.73) and scatter (r=0.87) around the regression line were unsatisfactory when the recommended calibration procedure was used. Tests in fasting non-diabetic subjects showed a significant correlation between the variation in Biostator glucose read-out and the plasma protein concentration in the detector outflow. In diabetics the ratio between Biostator glucose read-out and laboratory glucose determinations declined significantly with time. These observations led to the introduction of a standardization procedure based on externally determined blood glucose concentrations. During long-term feedback experiments in diabetics this procedure resulted in a significant increase in slope (0.84) but no improvement in scatter around the regression line. Repeated OGTTs revealed a set of constants for the algorithms, which enabled normal glucose tolerance to be achieved with smaller amounts of insulin.

Adolescent↗