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Biomedical subjects

I Mattiasson

Publications and source records attributed to I Mattiasson.

At least 55 records · Page 3Linked to original sources

Effects of platelets from men with risk factors for atherosclerosis on endothelial cell proliferation and prostacyclin production in vitro.

The hypothesis that variations in platelet size or composition might affect some endothelial cell (EC) functions was tested. Large and small platelets stimulated cell proliferation and prostacyclin production to the same extent at the same amount of protein. Endothelial cells exposed to platelet factors from healthy men at statistically high risk of cardiovascular disease (n = 30) manifested significantly less DNA synthesis than did EC exposed to platelet factors from men at statistically low risk (n = 30) (p = 0.007). There was no difference in prostacyclin production between the groups. Nor were there any difference in EC or smooth muscle cell (SMC) proliferation or in prostacyclin production between cells exposed to platelet factors from smokers and those exposed to platelet factors from non-smokers. In stepwise regression of the results for high risk groups, with thymidine incorporation as the dependent variable, including diastolic blood pressure, s-triglycerides and s-cholesterol, s-triglycerides were inversely correlated to thymidine incorporation. We suggest that the decreased endothelial cell DNA synthesis after exposure to platelet factors from high risk individuals may imply a decreased capability for damage repair in the vascular wall, and that the differences in platelet effects on EC proliferation may be due to differences in lipids, especially triglycerides.

Adult↗

The effect of psychosocial stress and risk factors for ischaemic heart disease on the plasma fibrinogen concentration.

OBJECTIVES: To assess the effect on the fibrinogen concentration of sleep disturbance and mental stress, taking into account the effect of 21 other variables related to the risk of cardiovascular disease. DESIGN: A cross-sectional study on men threatened by redundancy, and controls. SETTING: A health screening programme in Malmö, Sweden. SUBJECTS: Four hundred and eighty five workers in a shipbuilding yard, scheduled for closure, and 190 age-matched men. The subjects were randomly selected from a larger group of shipyard workers and controls invited to a health screening programme. Mean age was 51.6 years (range 38-62 years). MAIN OUTCOME MEASURES: Plasma fibrinogen concentration, serum cortisol concentration, body composition, blood pressure, heart rate, blood lipids, platelet number and size, white blood cell count, haemoglobin concentration, vital capacity, liver enzymes, blood glucose concentration fasting and after an oral glucose tolerance test. Questionnaire designed to evaluate muscle tension, sleep disturbance, anxiety, depression, job stress, alcohol and smoking habits and perceived health. RESULTS: In stepwise regression analysis fibrinogen concentration was found to be correlated to white blood cell count, muscle tension, heart rate, body mass index, age and serum cholesterol concentration in non-smokers, which together explained 14.9% of the variation in fibrinogen concentration. In smokers, platelet count, heart rate, serum triglyceride concentration, age and fasting glucose explained 22.5% of the variation in fibrinogen concentration. The fibrinogen concentration was inversely correlated to the psychological variables, but unrelated to the serum cortisol concentration or to factors connected with the job situation, and it was decreased in moderate alcohol consumers. CONCLUSIONS: Our interpretation of the findings is that an increase in the plasma fibrinogen concentration reflects the presence of a low-grade inflammatory process, and poor physical fitness.

Adult↗

Low blood pressure levels and signs of myocardial ischaemia: importance of left ventricular hypertrophy.

To clarify a possible relationship between the level of BP and signs of myocardial ischaemia, two groups of treated hypertensive patients with (n = 12) and without (n = 18) increased left ventricular mass defined by echocardiography were investigated with 24h ambulatory BP and ECG monitoring. It was found that hypertensive patients with increased left ventricular mass had the following. (1) Higher systolic BP, heart rate (HR) and SBP x HR product during the night indicating a higher ventricular work load than hypertensives without increased LVM in this period. (2) This increased left ventricular work load during the night was concomitant with a lower DBP consistent with a lower perfusion pressure of the left ventricular myocardium. (3) Significantly depressed ST segment levels throughout the 24 hours with a significant positive correlation between BP and the level of the ST segment indicating increased ischaemic metabolic changes within the myocardium the lower the BP. (4) A higher ratio between the systolic SBP x HR product and DBP during sleep than in hypertensives without increased left ventricular mass, further corroborating that low DBP during the night might cause ischaemia through an imbalance between left ventricular work load and coronary perfusion pressure. We conclude that low BPs in hypertensive patients with increased left ventricular mass seem to induce ischaemia of the left ventricle. These findings provide a possible mechanism for the increased risk of ischaemic heart disease in hypertensive patients with low achieved BP.

Aged↗

Insulin resistance and Na+/K(+)-ATPase in hypertensive women: a difference in mechanism depending on the level of glucose tolerance.

1. The peripheral glucose disposal rate (assessed with the euglycaemic-hyperinsulinaemic clamp technique), the serum sex hormone-binding globulin concentration and total and ouabain-sensitive 22Na-efflux rate constants in leucocytes were determined in 41 women with impaired glucose tolerance and in 40 women with normal glucose tolerance. The groups were matched for body mass index and diastolic blood pressure (range 55-112 mmHg). 2. Stepwise regression analysis showed that diastolic blood pressure in the group with impaired glucose tolerance was inversely correlated with the glucose disposal rate (model r2 = 21%) and was correlated with the plasma glucose concentration at 120 min after an oral glucose load (model r2 = 31%). In the group with normal glucose tolerance, however, neither of these two variables was correlated with blood pressure, although the ouabain-sensitive 22Na efflux rate constant was (model r2 = 11%). 3. Among insulin-resistant subjects, those with hypertension had significantly lower serum sex hormone-binding globulin concentrations than the normotensive subjects. 4. We conclude that insulin resistance is correlated with high blood pressure in women with glucose intolerance and increased androgenic activity. In women with normal insulin sensitivity, a low level of the Na+/K(+)-ATPase-mediated sodium efflux is associated with high blood pressure.

Blood Glucose↗

Sodium-lithium countertransport and platelet cytosolic free calcium concentration in relation to peripheral insulin sensitivity in postmenopausal women.

1. Peripheral glucose disposal (assessed by the euglycaemic-hyperinsulinaemic clamp technique), Na(+)-Li+ countertransport in erythrocytes and the cytosolic free Ca2+ concentration in platelets were determined in 41 women with impaired glucose tolerance and in 38 women with normal glucose tolerance. The groups were matched for body mass index (range 18-44 kg/m2) and diastolic blood pressure (range 58-109 mmHg). 2. Na(+)-Li+ countertransport was correlated significantly with body mass index, basal plasma insulin concentration and basal plasma glucose concentration, and was inversely correlated with peripheral glucose disposal rate. Stepwise regression analysis showed that Na(+)-Li+ countertransport was positively correlated with basal plasma insulin concentration (r2 = 8.7%). 3. Systolic blood pressure was correlated with fasting plasma insulin concentration (model r2 = 25%) and with Na(+)-Li+ countertransport (model r2 = 34%) in the group with impaired glucose tolerance. In the group with normal glucose tolerance there were no correlations between blood pressure and Na(+)-Li+ countertransport. 4. No correlation was found between platelet cytosolic free Ca2+ concentration and any of the variables measured. 5. It is concluded that Na(+)-Li+ countertransport is correlated with the degree of peripheral insulin sensitivity and with the plasma insulin concentration. Platelet cytosolic free Ca2+ concentration was not correlated with any of these variables, and there was no relationship between Na(+)-Li+ countertransport and the platelet cytosolic free Ca2+ concentration.

Antiporters↗

Tongue necrosis in temporal arteritis provoked by ergotamine.

A case of tongue necrosis in a patient with temporal arteritis who was taking ergotamine is described, and the role of ergotamine tartrate in provoking the tongue necrosis is considered. The literature on this unusual complication is critically reviewed, and the value of a carotid angiography in assessing the tongue ischaemia is exemplified.

Aged↗

Long-term effects on insulin sensitivity and sodium transport in glucose-intolerant hypertensive subjects when beta-blockade is replaced by captopril treatment.

Long-term effects on insulin sensitivity and leucocyte sodium transport were studied in 42 glucose-intolerant hypertensives on beta-blockers, randomly assigned to continuous beta-blockade (beta group) or a switch to captopril treatment (mean daily dose 69.1 mg) (ACE group). In the ACE group, despite a tendency towards improvement, glucose uptake during the euglycaemic insulin clamp procedure did not change significantly from the baseline value of 4.0(0.5-12.9) mg/kg/min, values at 6 and 12 months being 4.8(1.3-14.7) and 4.4(1.5-9.8) mg/kg/min, respectively: the corresponding values for the beta group were 4.2(1.1-15.3), 3.6(1.2-8.9) and 4.0(1.5-12.0) mg/kg/min. The 22Na efflux rate constant, both baseline and follow-up values, was similar in both groups, and unrelated to insulin sensitivity. Owing to the surprisingly great variation in peripheral glucose uptake, the subgroup with values below the median for the population as a whole (4.9 mg/kg/min) was evaluated separately: those switched to captopril treatment manifested a 60% improvement in glucose disposal at 6 months and persisting at 12 months, the respective values being 2.1(0.5-4.8) (baseline), 3.5(1.3-6.3) and 3.4(1.5-6.1) mg/kg/min, (P = 0.012). The body mass index (BMI) was not significantly affected. Values for BMI, peripheral insulin and triglycerides were higher in the subgroup with glucose disposal below the median than in the subgroup with values above the median. Correlation between BMI and glucose uptake was highly significant (r = -0.75, P = 0.0001). The present findings suggest that captopril may be a better alternative than beta-blockers for treating the highly insulin-resistant, glucose-intolerant patients, predominantly to be found among the overweight.

Adrenergic beta-Antagonists↗

Threat of unemployment and cardiovascular risk factors: longitudinal study of quality of sleep and serum cholesterol concentrations in men threatened with redundancy.

OBJECTIVE: To assess whether the threat of unemployment affects risk factors for cardiovascular disease. DESIGN: Longitudinal study of a cohort of middle aged shipyard workers followed up for a mean of 6.2 (SD 1.9) years and a group of controls observed for the same period. The first investigation took place during a period of relative economic stability for the shipyard and the second during the phase of its closure. SETTING: An age cohort health screening programme in Malmö, Sweden. PARTICIPANTS: 715 Male shipyard workers and 261 age matched male controls. MAIN OUTCOME MEASURES: Changes in 19 variables related to the risk of cardiovascular disease, and psychological variables, alcohol consumption, smoking, and dietary habits as assessed by questionnaire. RESULTS: Serum cholesterol concentrations increased more (mean 0.25 (SD 0.68) mmol/l v 0.08 (0.66) mmol/l) and serum calcium concentrations decreased less (-0.06 (0.10) mmol/l v -0.08 (0.09) mmol/l) in the shipyard workers than in the controls. A correlation was found between scores for sleep disturbance and changes in serum cholesterol concentration. In the whole series there was a greater increase in serum cholesterol concentrations among men threatened with unemployment (437/976; 44.8%) than among those who were not. In stepwise regression analysis the change in serum cholesterol concentration was correlated with changes in haemoglobin concentration, body weight, and serum triglyceride and calcium concentrations. A positive correlation was found between change in cholesterol concentration and change in blood pressure, indicating that the overall risk profile had worsened among men with increased serum cholesterol concentrations. CONCLUSIONS: Risk of unemployment increases the serum cholesterol concentration in middle aged men, the increase being more pronounced in those with sleep disturbance. The increase in serum cholesterol is related to changes in other established risk factors for cardiovascular disease. These findings might partly explain the excessive mortality due to cardiovascular disease recorded among the unemployed and people with sleep disturbance.

Adult↗

[Serum creatinine content of questionable value in screening for renal disease].

In a health screening programme for men aged 28-48 years, a check of serum creatinine values was included as a renal function test. Of 21,362 men screened, 114 (0.53 per cent) had two values greater than or equal to 120 mumol/l, and were further investigated vis-à-vis possible kidney disease. Of the 114 cases, renal disease including essential hypertension was present in 63, though only 29 cases had not been diagnosed previously, and in only seven cases was there no albuminuria, hypertension or history of renal disease. These findings raise doubts as to the value of analysing s-creatinine when screening for renal disease.

Adult↗

Platelet sodium and potassium ATPase [corrected] activity and noradrenaline efflux rate in relation to autonomic and peripheral nerve function in insulin-dependent diabetic patients.

Low sodium and potassium adenosine triphosphatase (ATPase) activity has been proposed as a mechanism behind diabetic neuropathy. In this study the platelet ATPase activity and platelet noradrenaline efflux rate were determined in 47 insulin-dependent diabetes mellitus (IDDM) patients and 20 controls. Ulnar motor conduction velocities, tested in a subgroup, were lower in patients than in controls (52.7 +/- 1.3 m s-1 vs. 61.3 +/- 1.4 m s-1; P less than 0.001). Platelet ATPase activity tended to be increased in the patients compared with the controls (29.9 +/- 1.0 x 10(-3) min-1 vs. 26.9 +/- 1.1 x 10(-3) min-1; NS). In ulnar nerve function tested subjects, ATPase activity was higher in patients than in controls (31.2 +/- 1.7 x 10(-3) min-3 vs. 25.9 +/- 1.3 x 10(-3) min-1; P less than 0.01). The platelet noradrenaline efflux rate tended to be higher in patients with lower brake indices, a sign of autonomic neuropathy, than in controls (29.0 +/- 3.0 x 10(-3) min-1 vs. 21.2 +/- 0.9 x 10(-3) min-1; P less than 0.05). The platelet ATPase activity was not decreased in IDDM patients, however, a connection between diabetic autonomic neuropathy and platelet transmittor leakage was indicated.

Adult↗

Effects of a competitive inhibitor (mevinolin) of 3-hydroxy-3-methylglutaryl coenzyme A reductase on human and bovine endothelial cells, fibroblasts and smooth muscle cells in vitro.

Mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, is a potent inhibitor of cholesterol synthesis. We have tested the effects of mevinolin on cell replication (3H-thymidine incorporation), prostacyclin production (6-keto-PGF1 alpha) and cell death (51Cr release) in cell cultures (human umbilical vein endothelial cells, bovine endothelial cells, human fibroblasts and bovine smooth muscle cells). Mevinolin concentrations ranging from 0.05 mumol/l (reported therapeutic concentration) to 20 mumol/l were used. In human endothelial cells the replication was reduced by 11% at a concentration of 2.0 mumol/l (P less than 0.01). In fibroblasts and smooth muscle cells the reduction was significant already at 0.1 mumol/l (10%, P less than 0.01). The prostacyclin production was reduced in endothelial cells at 1.0 mumol/l (19%, P less than 0.01) and in smooth muscle cells at 2.0 mumol/l (15%, P less than 0.05). At 20 mumol/l both cell replication and prostacyclin production was markedly reduced by about 40% in all cell types. No effects on 51Cr release or trypan blue staining was seen at any concentration. It is concluded that mevinolin has an effect on DNA synthesis and prostacyclin production on the tested cell types in vitro. These effects were, however, observed only at concentrations higher than those recommended for therapeutical use.

Animals↗

Verapamil and norverapamil in plasma and breast milk during breast feeding.

The concentrations of verapamil and norverapamil have been measured in milk and plasma samples from a 32 year-old woman treated with verapamil 80 mg tds while breast-feeding her child. The average steady-state concentrations of verapamil and noverapamil in milk were, respectively, 60% and 16% of the concentrations in plasma. The breast-fed child received less than 0.01% of the dose of verapamil given to the mother. No verapamil or norverapamil (less than 1 ng/ml) could be detected in the plasma from the child.

Adult↗

Platelet sodium kinetics, blood pressure and serum urate: aberrations in non-obese men at risk for type 2 diabetes mellitus.

The rate constants for the ouabain- and frusemide-sensitive 22Na+ efflux, the number of [3H]ouabain binding sites and the effect of plasma on [3H]ouabain binding were determined in platelets, as were blood pressure (BP) and serum urate concentrations, in 35 normoglycaemic men with family histories of type 2 diabetes (hereditary group), in 18 subjects with impaired glucose tolerance (IGT) and in 28 normoglycaemic controls. All subjects were non-obese males of comparable age. Earlier findings of increased BP both in normoglycaemic subjects with family histories of type 2 diabetes and in IGT subjects were confirmed. The mean serum urate concentration was significantly higher in the hereditary group than in controls, and intermediate in IGT subjects. The ouabain-sensitive 22Na+ efflux rate constant was significantly decreased in IGT subjects without any concomitant change in the number of [3H]ouabain binding sites. No differences in any of the rate constants for 22Na+ efflux, or in the number of [3H]ouabain binding sites, were noted between the hereditary group and controls. The ability of deproteinized plasma samples to interfere with [3H]ouabain binding to test platelets from one healthy individual was similar in all three groups. The present findings are not consistent with the hypothesis that the BP increase in normoglycaemic subjects with family histories of type 2 diabetes is linked to a disturbance in sodium transport. Our data suggest a decreased Na+/K+-ATPase activity in IGT, which may be of pathophysiological significance in relation to hypertension.

Binding Sites↗

[3H]noradrenaline efflux from platelets and synaptosomes of ethanol-treated rats.

Platelets have the ability to take up, store and release biogenic amines and have therefore been used as models for neurons in studies of neuropsychiatric disorders and hypertension. We have studied the spontaneous efflux of [3H]noradrenaline from platelets and synaptosomes of rats chronically treated with ethanol. Male control rats had a more rapid [3H]noradrenaline efflux both from synaptosomes and platelets than female control rats. Ethanol treatment increased efflux in female rats, again both in platelets and synaptosomes. These results suggest that a parallelism exists in noradrenaline release between synaptosomes and platelets, both basal and in situations which stimulate the release.

Animals↗

Sodium and noradrenaline effluxes from platelets in male relatives to hypertensive individuals.

The efflux rate constants for noradrenaline efflux and 22Na-efflux from platelets, the number of ouabain binding sites on platelets and the influence of plasma on ouabain binding to platelets were determined in 35 normotensive men belonging to families with a high incidence of essential hypertension and 31 men from families, where no hypertension was registered in the close relatives. The earlier finding of a higher efflux rate constant for noradrenaline in relatives was confirmed. There was a significant negative correlation between the total 22Na-efflux rate constant and the noradrenaline rate constant in relatives as well as between the number of ouabain binding sites and the noradrenaline rate constant. No such correlations were registered in the controls. The ouabain resistant 22Na-efflux rate constant was lower in relatives, but the ouabain sensitive 22Na-efflux rate constant did not differ between the groups, nor did the total number of ouabain binding sites on platelets. Number of ouabain-binding sites measured at a low concentration of (3H)-ouabain in the presence of deproteinized plasma samples was the same in both groups, contradicting the presence of an endogenous ouabain-like plasma factor in the relatives.

Adult↗

Distribution of the methyl acceptor proteins within platelet granules.

Fractionation of platelet alpha-granules and dense bodies demonstrated that methyl acceptor proteins (MAP) were present in the alpha-granule fractions, but seemed to be low or absent in the dense body fraction. MAP activity in four intragranular proteins (albumin, fibrinogen, beta-thromboglobulin and platelet derived growth factor) was low or absent and could not explain the difference in methyl acceptor proteins distribution between alpha-granules and dense bodies.

Adenosine Triphosphate↗

The relation between protein carboxyl methylating and demethylating enzyme activities and noradrenaline efflux in platelets.

To test the hypothesis that the raised noradrenaline efflux rate constant in platelets observed in hypertensive individuals and some normotensive relatives to hypertensives could be ascribed to disturbances in the protein carboxyl methylation, protein carboxyl methylase activity and noradrenaline efflux rate constant were measured in platelets from 33 young healthy males. Sixteen had inheritance of hypertension. Protein methyl esterase activity and the noradrenaline efflux rate constant were measured in 43 men, 22 of whom had inheritance of hypertension. No correlation was found between unstimulated noradrenaline efflux from platelets and enzyme activity.

Adult↗