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Biomedical subjects

A Gustafson

Publications and source records attributed to A Gustafson.

At least 55 records · Page 3Linked to original sources

The influence of treatment with estrogens and estramustine phosphate on platelet aggregation and plasma lipoproteins in non-disseminated prostatic carcinoma.

The treatment of prostatic carcinoma with estrogens is associated with an increased risk of cardiovascular as well as thromboembolic complications. In the present study, patients harboring highly or moderately differentiated prostatic carcinoma without signs of metastases were treated with either polyestradiolphosphate + etinylestradiol, estramustine phosphate or given no treatment. Subsequently, these patients were investigated regarding factors (platelet aggregation, plasma and platelet phospholipid composition and lipoprotein patterns) that might contribute to increased thrombogenesis and cardiovascular risk. The results indicate the presence of increased in vitro platelet aggregation in patients treated with polyestradiolphosphate + etinylestradiol compared to those treated with estramustine phosphate or given no treatment. A possible relationship between the availability of arachidonic acid in platelet membrane phospholipids and in vitro platelet aggregation is suggested. On the other hand the alterations in plasma lipoproteins observed during treatment are generally considered positive from an atherogenic point of view and do not seem relevant to the elevated incidence of cardiovascular disease in these patients.

Aged↗

Effect of protein-reduced diet on plasma lipids, apolipoproteins and lipolytic activities in patients with chronic renal failure.

The effect of treatment with protein-reduced diet on plasma lipids, apolipoproteins and lipolytic activities was studied in 15 patients with chronic renal failure. Mean treatment time was 7.4 months. Before treatment serum triglycerides were elevated as were the levels of apolipoprotein C-I and especially C-III. Postheparin plasma lipolytic activities were reduced. The treatment was effective in reducing the serum urea levels but had no significant influence on either plasma lipids, apolipoprotein levels or lipolytic activities. The abnormalities of lipid transport in chronic renal failure thus seem to be more dependent on loss of renal function than the degree of uremic intoxication.

Adult↗

Effects of acetylsalicylic acid and dietary intervention on primary hemostasis.

There is evidence that pathological aggregation of platelets in atherosclerotic arteries is initiated by hemorrhage through fissures in atheromatous plaques. Bleeding time determination reflects in vivo the physiologic function of platelets in their aggregation in injured vessels and can be used as a relevant model for primary hemostasis in investigations with antithrombotic aims. Acetylsalicylic acid is known to cause prolongation of bleeding time by inhibiting prostaglandin biosynthesis. Recent experiments have shown that dietary supplementation with omega-3 polyunsaturated fatty acids results in prolongation of bleeding time and decreased platelet aggregability. This paper is mainly concerned with the effect of different doses of aspirin (3.5 mg/kg, 5 mg/kg, and 10 mg/kg), and fish diets rich in omega-3 polyunsaturated fatty acids, on bleeding time and platelet aggregation. The effects of aspirin separately, as well as aspirin administration during dietary intervention, will be described. Administration of all three dose levels of aspirin prolonged bleeding time significantly (p less than 0.001). The effect of aspirin on bleeding time was dose-dependent and an optimum interval was found. A fish diet, rich in omega-3 polyunsaturated fatty acids, causes bleeding time prolongation and decreased platelet aggregability similar to those caused by aspirin. Aspirin taken during this diet prolonged bleeding time by more than the sum of the increases in bleeding time caused by aspirin and the diet with omega-3 polyunsaturated fatty acids, separately, but the synergism was not significantly more than additive. These observations suggest that fish diets affect primary hemostasis by mechanisms different from those of aspirin. Dietary intervention may therefore enhance the antithrombotic effects of aspirin.

Animals↗

Plasma lipoproteins and lipolytic enzyme activities during endurance training in sedentary men: changes in high-density lipoprotein subfractions and composition.

Eighteen healthy sedentary males took part in supervised bicycle training for 50 minutes three to five times a week. Twelve subjects (group A) trained for 6 weeks at heavy intensity, and six subjects (group B) trained for 12 weeks at moderate intensity. Maximal oxygen uptake increased by about 20% (P less than 0.01). Body weight and composition as well as diet remained unchanged. After 6 weeks plasma high-density lipoprotein (HDL) cholesterol concentrations had increased by 7% (P less than 0.05) in all subjects. The increase was most marked in group B at 14% (P less than 0.05) compared to 3% in group A (ns). Apolipoprotein AI (apo AI) increased by about 7% in both groups (P less than 0.01). After 12 weeks HDL cholesterol and apo AI levels had almost returned to initial values. Measurements of HDL components showed increases of 6% to 12% in free cholesterol, cholesteryl ester (P less than 0.05), and phospholipid (P less than 0.01); whereas, the minor triglyceride fraction decreased by 20% (P less than 0.01). Zonal ultracentrifugation in four subjects revealed a preferential rise of about 35% in the HDL2 subfraction, increasing the HDL2/HDL3 ratio by about 20%. In parallel, the composition of the lipoprotein classes changed. The protein moiety of all classes, except low-density lipoprotein (LDL), expanded at the expense of the core components cholesteryl ester and triglyceride. Hepatic lipase (HL) activity decreased by 6% (P less than 0.05), and lipoprotein lipase (LPL) activity in adipose tissue increased by about 50% (P less than 0.05) during the first 6 weeks of training, while LPL activity in postheparin plasma and skeletal muscle did not change. The transient rise in HDL cholesterol levels was correlated (P less than 0.05) to the elevation of adipose tissue LPL activity. The alterations in HDL concentration were also related to changes in body composition and diet, especially to an increase in fat intake.

Adult↗

Effects of acetylsalicylic acid on platelet aggregation before and during increase in dietary eicosapentaenoic acid.

The effect of acetylsalicylic acid (ASA) on platelet aggregation before and during a fish diet, already known to decrease the aggregability of platelets and to prolong the bleeding time, was studied in 10 healthy men. Two doses (3.5 and 10 mg/kg body weight) of ASA were given. Both doses equally decreased platelet aggregation to collagen and adenosine diphosphate (ADP). ASA, taken before the diet, diminished platelet aggregability to ADP by as much as did the diet alone. When ASA was administered during the diet, the effect on platelet aggregability to ADP was additive. Aggregation to collagen also decreased to the same extent as during the baseline period. The results, in conjunction with our earlier ones, indicate that the mechanism by which a fish diet delays primary haemostasis is different from the apparently similar effect of ASA. This raises the possibility of augmenting any antithrombotic effect of ASA by dietary means.

Adenosine Diphosphate↗

In-hospital exercise therapy in patients with severe angina pectoris.

The authors evaluated physiologic, psychologic and metabolic effects of a nine-week in-hospital training program on 14 men with severe disabling angina pectoris. The exercise program consisted of intensive interval training on an ergometer bicycle for two 30 min sessions daily. The physical performance increased by about 40% (p less than 0.001). Plasma insulin levels were reduced and glucose tolerance improved significantly. There was a decrease in plasma triglyceride and low-density lipoprotein (LDL) cholesterol levels, but no change in high-density lipoprotein (HDL) cholesterol, apolipoprotein AI and B concentrations. Plasma triglyceride (p less than 0.05) and LDL cholesterol (p less than 0.05) levels remained low three weeks after completion of the training period and the physical performance remained improved (p less than 0.01) even six months post-training. Four of the patients who had been disabled for at least five months were able to return to work. The authors suggest that comparatively short and intensive in-hospital rehabilitation of patients with coronary heart disease may be an attractive alternative to prolonged training on an outpatient basis, especially in patients with severe angina pectoris.

Angina Pectoris↗

Taurocholate is more potent than cholate in suppression of bile salt synthesis in the rat.

Synthesis of bile salts is regulated through negative feedback inhibition by bile salts returning to the liver. Individual bile salts have not been distinguished with regard to inhibitory potential. We assessed inhibition of bile salt synthesis by either cholate or its taurine conjugate in bile fistula rats. After allowing synthesis to maximize, baseline synthesis was determined by measuring bile salt output in four consecutive 6-hr periods. Next, sodium cholate (+[(14)C]cholate) or taurocholate (+[(14)C]taurocholate) was infused into the jugular vein for 36 hr and bile was collected in 6-hr aliquots. Hepatic flux of exogenous bile salt was determined by measuring output of radioactivity in bile divided by specific activity of the infusate. Synthesis was determined during the last four 6-hr periods of infusion by subtracting exogenous bile salt secretion from the total bile salt output. Thirteen studies using cholate and 13 using taurocholate were performed. Hepatic flux of infused bile salt varied from 1 to 12 micro mol/100 g per rat per hr. Percent suppression of synthesis varied directly with hepatic flux of exogenous bile salt for both cholate and taurocholate in a linear fashion (r = 0.66, P < 0.01 and r = 0.87, P < 0.0005, respectively). Slope of the taurocholate line was 7.82 (% suppression/ micro mol per 100 g per hr), while slope of the cholate line was 3.66 (P < 0.05), indicating that taurocholate was approximately twice as potent as cholate in suppression of synthesis. At fluxes of 10-12 micro mol/100 g per hr, taurocholate suppressed synthesis 84 +/- 8 (SEM) % while cholate suppressed synthesis only 42 +/- 12% (P < 0.02). The x-intercept of the taurocholate line was 0.65 ( micro mol/100 g per hr), while that of the cholate line was -1.01 (NS) suggesting that the threshold for initial suppression of synthesis did not differ for these two bile salts. We conclude that taurocholate is a more effective inhibitor of hepatic bile salt synthesis than cholate, and that intestinal deconjugation of bile salts may play a role in the regulation of synthesis.-Pries, J. M., A. Gustafson, D. Wiegand, and W. C. Duane. Taurocholate is more potent than cholate in suppression of bile salt synthesis in the rat.

Animals↗

Effects of thyrotrophin stimulation for two hours on mouse thyroid cyclic AMP levels in vivo and in vitro.

A thyrotrophin (TSH) stimulation in vivo in mice for 2 h, reflected by continuously increasing plasma triiodothyronine (T3) levels, was associated with an increase in the thyroid content of cyclic AMP (cAMP) during the first 25 min of stimulation; thereafter the level rapidly declined. A similar pattern of the cAMP response was found when mouse thyroid tissue was stimulated by TSH in vitro for 2 h. This is an in vivo demonstration of a type of cAMP response to prolonged hormonal stimulation that has been observed in several in vitro systems including thyroid tissue, generally referred to as hormone induced desensitization of adenyl cyclase. The present results indicate that the phenomenon is not confined to in vitro conditions but can be demonstrated also in vivo, and support the representativeness of in vitro experiments in this respect.

Animals↗

Lipid and carbohydrate metabolism studies in oophorectomized women: effects produced by the addition of norethisterone acetate to two estrogen preparations.

Norethisterone acetate (NET) was administered to 11 oophorectomized women, primed with either 17-C-alkylated ethinylestradiol (EE) or the non-alkylated estrogen, estradiol valerate (E2V), to evaluate the effects on lipid metabolism. Blood samples were drawn after a period without hormonal replacement therapy and after 6 weeks on each estrogen and estrogen-progestogen combination. Serum and lipoprotein lipids were followed and an oral glucose tolerance test was performed with blood glucose and plasma insulin determinations. NET reversed the increase in serum triglycerides induced by EE and, when added to either estrogen, increased low density lipoproteins and reversed the high density lipoprotein lipid increase induced by both estrogens. The NET + EE, but not the NET + E2V combination, imparied glucose tolerance.

Adult↗

Lipid metabolic studies in oophorectomised women: effects on serum lipids and lipoproteins of three synthetic progestogens.

Norethisterone acetate, medroxyprogesterone acetate and levonorgestrel were administered to oophorectomised women to evaluate the effects they have on lipid metabolism. Blood samples were drawn after a 3 wk period without hormone therapy and after 3 wk on each progestogen. Serum and lipoprotein lipids were followed and an oral glucose tolerance test with blood glucose and plasma insulin determinations were performed. The nortestosterone derivatives, norethisterone acetate and levonorgestrel, decreased high density lipoprotein cholesterol as well as alpha-lipoproteincholesterol, while the 17-hydroxyprogesterone derivative medroxyprogesterone acetate did not. Norethisterone acetate and medroxyprogesterone acetate impaired glucose tolerance. A difference between nortestosterone derivatives and 17-hydroxyprogesterone derivatives having an effect on high density lipoproteins is suggested.

Adult↗

Metabolic studies in gestational diabetic women during contraceptive treatment: effects on glucose tolerance and fatty acid composition of serum lipids.

Intravenous glucose tolerance tests (IVGTT) with simultaneous assessment of plasma insulin and analyses of the fatty acid composition of serum lecithin and cholesterol esters were performed in 11 women with previous gestational diabetes before and repeatedly during 6 months' administration of a low-dose progesterone (lynestrenol = LYN). 8 of these women were also followed in an identical manner during 6 months of nonhormonal contraception (intrauterine device = IUD) and additionally 6 of these women were followed also during the use of a combined oral contraceptive (OC) (ethinyl estradiol + lynestrenol - EE + LYN). LYN did not alter the IVGTT or plasma insulin but decreased the proportion of polyunsaturated fatty acids (PUFA) in serum lecithin (p less than 0.01) and cholesterol esters (p less than 0.01) where oleic acid was reciprocally increased (p less than 0.05). After 6 months' use of IUD, on the other hand, the k value of IVGTT increased by 45% (p less than 0.01) without significant changes in plasma insulin. In both lecithin and cholesterol ester PUFA increased (p less than 0.05) and cholesterol ester oleate decreased (p less than 0.01); i.e., virtually the reversal of the changes seen during LYN administration. The combined OC, EE + LYN, caused a decrease in the k value by 27% (p less than 0.05) which was apparent even when compared to the effects of LYN alone. EE + LYN also increased (p less than 0.05) lecithin palmitate and decreased stearate (p less than 0.05) and had a concomitant tendency to lower PUFA and increase oleic acid in both lecithin and cholesterol esters. These results indicate that LYN has little influence on the glucose tolerance in women predisposed to diabetes but may provide poorer conditions for dietary treatment of subclinical diabetes than do nonhormonal IUDs. The combined CO, EE + LYN, on the other hand, promptly diminishes glucose tolerance and may also have an unfavorable influence on liver metabolism.

Adult↗

Lipid metabolic studies in oophorectomized women: effects of synthetic progestogens on individual serum phospholipids and serum lecithin fatty acid composition.

Norethisterone acetate (NET), levonorgestrel (NORG) and medroxyprogesterone acetate (MPA) were administered to oophorectomized women to evaluate the effects on individual serum phospholipids as well as serum lecithin and cholesterol ester fatty acid composition. Blood samples were drawn after a 3-week period without hormonal replacement therapy and after 3 weeks on each progestogen. NORG reduced cepahlin and lecithin with a concomitant increase in lysolecithin. This shift in individual phospholipids has previously been induced by exogenous androgens. The 17C-alkylated synthetic progestogens NET and NORG but not the non-alkylated MPA caused a redistribution among the 1-position fatty acids of serum lecithin with an increase in palmitic concomitant with a decrease in stearic acid. These findings indicate differences between 19-nortestosterone derivatives and 17-hydroxyprogesterone derivatives in effect on individual serum phospholipids and in influence on liver lecithin synthesis as judged from serum lecithin fatty acid composition.

Adult↗

Factors influencing the release of cyclic AMP from mouse thyroid tissue stimulated by TSH in vitro.

The accumulation of cyclic AMP (cAMP) in mouse thyroid tissue in response to TSH in the presence of 1 mM theophylline was accompanied by a release of the nucleotide from the tissue into the incubation medium. This cAMP release was almost rectilinearly related to the time of exposure to TSH, and rectilinearly related to the log concentration of TSH in the range 0.1-5 mU/ml. The cAMP release proved to be independent of the pre-incubation time up to 4 h, and took place also in the absence of methylxanthines when the cAMP level was low. The total cAMP accumulation in response to TSH was augmented by different inhibitors of protein synthesis but the fraction of the nucleotide that was retained intracellularly was increased only by puromycin. Dipyridamole had an effect similar to that of puromycin. Depolarization or treatment with ouabain did not change the distribution of cAMP between tissue and medium. It is concluded that the release of cAMP from thyroid tissue stimulated by TSH may take place under physiological conditions, that it seems to be regulated by the actual concentration of TSH, and that it may be of significance for the regulation of the intracellular cAMP level.

Animals↗

Metabolic studies in women with previous gestational diabetes during contraceptive treatment: effects on serum lipids and high density lipoproteins.

Triglycerides, cholesterol and phospholipids in serum and high density lipoproteins (HDL) were assessed in 11 women with previous gestational diabetes before and repeatedly during 6 months of low dose progestogen (lynoestrenol = LYN) contraceptive administration. Eight of these women also were followed in an identical manner during non-hormonal contraception (IUD) and 6 of them during combined oral contraceptive administration (EE + LYN). During the use of IUD or LYN administration neither serum nor HDL lipids changed. The combined OC, EE + LYN, increased serum triglycerides progressively: 73% (P less than 0.01) after 6 months concomitant with a 100%-increment of HDL triglycerides (P less than 0.01) HDL-cholesterol and -phospholipids were not consistently changed. The EE + LYN induced alterations differed from the effects of LYN alone (P less than 0.01). During the use of IUD or LYN administration neither serum nor HDL lipids changed. The combined OC, EE + LYN, increased serum triglycerides progressively: 73% (P less than 0.01) after 6 months concomitant with a 100%-increment of HDL triglycerides (P less than 0.01). HDL-cholesterol and -phospholipids were not consistently changed. The EE + LYN induced alterations differed from the effects of LYN alone (P less than 0.01). These results suggest that low dose progestogens, such as LYN, could be considered as contraceptive alternatives in women with gestational diabetes. However, combined OC should be avoided in these patients. The present findings differ from those obtained in insulin-dependent diabetics and suggest that a diabetic prediposition enhances the effects of synthetic oestrogens and/or diminishes some of the effects of progestogens on lipid metabolism.

Adult↗

Oral contraception in diabetic women. A cross-over study on serum and high density lipoprotein (HDL) lipids and diabetes control during progestogen and combined estrogen/progestogen contraception.

Twenty-three young women with insulin-dependent diabetes were randomly allocated to contraceptive treatment with either a progestogen only (Lynestrenol 0.5 mg) (LYN) or a combined oral contraceptive (OC) (ethinyl estradiol 50 micrograms + lynestrenol 2.5 micrograms) (EE + LYN). After six months treatment the medication was withdrawn for at least two months, after which the patients were placed on the other preparation. Diabetes control and serum and high density lipoprotein (HDL) lipids were assessed before and after 1, 3 and 6 months of treatment. Low-dose LYN administration did not alter the insulin requirement, blood glucose or body weight while the combined EE + LYN treatment increased the insulin requirement (p less than 0.01) without altering blood glucose or body weight. Low-dose LYN reduced serum triglycerides (p less than 0.001), serum cholesterol (p less than 0.001) and serum phospholipids (p less than 0.01) without affecting HDL lipids, while EE + LYN gave an inconsistent increase in serum triglycerides (p less than 0.01) but no change in HDL lipids. These findings confirm our earlier results and we conclude that EE + LYN influences diabetes control slightly more (although still not seriously) than the low-dose LYN. It is suggested that insulin-dependent diabetics (in contrast to non-diabetics) are more sensitive to the influence of 19-norprogestogens than to alkylated estrogens, with respect to lipid metabolism.

Adolescent↗

Alterations in plasma proteins and lipoproteins in acute myocardial infarction: effects on activation of lipoprotein lipase.

Plasma lipoprotein concentrations were followed in 21 men with acute myocardial infarction. HDL and LDL cholesterol concentrations showed similar time-courses with average maximal decreases of about 20%, 10-14 days after onset of symptoms. The decrease in HDL levels (measured as HDL cholesterol and apolipoprotein AI) was significantly correlated to the inflammatory response, as reflected by plasma orosomucoid concentrations, and to the extent of myocardial injury, as mirrored by serum activities of lactate dehydrogenase. In samples drawn 10 days after myocardial infarction we found marked changes in the ability of the patients' sera to enhance the activity of purified lipoprotein lipase. The maximal activating ability (at saturating serum concentrations) increased by about 30%; however, at suboptimal serum concentrations, the activating ability of the patients' sera declined (50% higher serum concentrations were required to reach half maximal reaction rate). The altered activation characteristics were correlated to the changes in HDL concentrations. By affecting the activity of lipoprotein lipase and thereby the rate of intravascular lipoprotein metabolism, this phenomenon may contribute to the lipoprotein alterations seen after myocardial infarction.

Adult↗

Effects of 11-week increases in dietary eicosapentaenoic acid on bleeding time, lipids, and platelet aggregation.

The effect of a diet rich in eicosapentaenoic acid (EPA) on platelet phospholipid fatty acid composition, platelet aggregation, and bleeding time was studied in 10 healthy men, whose usual diet was partly replaced by fish for 11 weeks. This diet provided 2-3 g EPA per day. Two doses (3.5 and 10 mg/kg body-weight) of acetylsalicylic acid (ASA) were given before and during the diet. The fish diet prolonged bleeding time (by 42%) and decreased platelet aggregability. The changes in platelet phospholipid fatty acid composition consisted of increases in the omega-3 series (C20:5 and C22:6) and decreases in the omega-6 series (C18:2 and C20:3). The reduction in platelet aggregation induced by collagen and ADP did not parallel the changes in platelet membrane phospholipids and bleeding times. Diminished platelet aggregation induced by collagen lasted only 3 weeks (while subject was still on the diet), whereas the decreased sensitivity to ADP persisted for at least 11 weeks after the volunteers had resumed their normal diet. ASA taken before the diet prolonged bleeding time by as much as did the diet itself. ASA taken during the diet prolonged bleeding time by more than the sum of the increases in bleeding time caused by ASA and by the EPA diet separately, but the synergism was not significantly more than additive. The findings suggest that a diet rich in omega-3 polyunsaturated fatty acids reduces tha interaction between platelets and the vessel wall by mechanisms which are more complex than just a reduction in susceptibility of platelets to the naturally occurring agents collagen and ADP, or an imbalance between proaggregatory and anti-aggregatory prostaglandin derivatives.

Adult↗