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Biomedical subjects

B Fredholm

Publications and source records attributed to B Fredholm.

At least 37 records · Page 2Linked to original sources
PubMed1986

High doses of fluoride do not affect cyclic AMP levels in human and rat plasma or urine.

The effect of fluoride ingestion on plasma and urinary cyclic AMP levels was studied in healthy volunteers, children undergoing prophylactic fluoride treatment and in rats. In the first series of experiments fluoride ingestion led to a 20-fold increase in plasma fluoride concentration, which was unrelated to changes in plasma cyclic AMP. The only significant effect on plasma cyclic AMP occurred prior to fluoride, an effect attributed to stress. In the second series performed in children increases in urinary F- of up to 200-fold were associated with slight but nonsignificant changes in cyclic AMP excretion. In rat experiments the blood sampling procedure was associated with a rise in plasma cyclic AMP. When this was prevented by pretreatment with propranolol (3 mg/kg), the effect of fluoride (50 ppm in the drinking water) was tested. A fall in urine production was not associated with any change in cyclic AMP excretion or in nephrogenic cyclic AMP. It is concluded that if fluoride alters cyclic AMP in rats and man the effect is small and easily masked by other factors such as catecholamine release following stress.

Adult↗
PubMed1984

Actions and interactions of acetylsalicylic acid, salicylic acid and diflunisal on platelet aggregation.

Acetylsalicylic acid (ASA) is increasingly employed in the secondary prophylaxis of thromboembolic diseases, due to its capacity to inhibit platelet aggregation. The anti-aggregatory effect of ASA on platelets can be inhibited in vitro by a high concentration of salicylic acid (SA). SA is generated in vivo upon ASA administration, and the SA thus formed might impair the antiplatelet effect of ASA. To assess this possibility, the platelet response to ASA was tested in healthy volunteers before and after medication for 1 week with ASA 1 g t.i.d., with SA 1 g t.i.d., and with the SA derivative diflunisal 0.5 g b.i.d. Pre-medication test doses of 1 g ASA always inhibited platelet aggregation in vivo. Neither treatment with SA nor diflunisal, producing plasma steady-state concentrations of about 1.0 and 0.35 mmol/l, respectively, inhibited platelet aggregation. Nor did administration of SA, diflunisal or ASA itself impair the anti-aggregatory effect of a fresh test dose of ASA. ASA inhibited platelet aggregation in vitro at 0.03 mmol/l, whereas SA and diflunisal failed to impair platelet aggregation until concentrations exceeding 2.0 and 0.5 mmol/l, respectively, were reached. These findings make it unlikely that SA formed upon administration of ASA would impair the anti-aggregating capacity of ASA.

Adult↗
PubMed1983

Chronic antidepressant treatment and central 5-HT synapses.

The present studies have shown that chronic antidepressant treatment with desipramine, imipramine, zimelidine and alaproclate led to adaptive changes in both pre- and postsynaptic 5-hydroxytryptamine (5-HT) receptor mechanisms which appear to result in 5-HT sub- or supersensitivity development depending upon the 5-HT nerve terminal systems analyzed. The results underline the heterogeneity of the central 5-HT neurone systems in their responses to chronic antidepressant treatment. An involvement of 5-HT comodulators is postulated in the actions of antidepressants on central 5-HT synapses. Finally, the results point to the importance of 5-HT neurone systems as targets for the action for antidepressant drugs and they may mediate at least some of the therapeutic activity of antidepressant drugs.

Animals↗
PubMed1983

[Changes of the acid-base status, serum lactate concentration and purine metabolism in reconstructive arterial surgery].

Hypoxic damages are normally determined by acid-base status as well as lactate and pyruvate levels. Since several other illnesses lead also to raised levels of these parameter, they are not specific for tissue hypoxia. In animal experiments it was shown that purine metabolites, especially hypoxanthine, are a very exact indicator for hypoxia. To test its validity in clinical situations the changes in acid-base status, lactate, pyruvate and purine metabolism were measured in 17 patients undergoing reconstructive aortic surgery. Blood samples were taken just before and after declamping of the aorta systemically and from the femoral vein. After declamping especially the systemic hypoxanthine levels increased 3 fold, due to a 20 times higher hypoxanthine concentration in the femoralis vein. The concentration changes of hypoxanthine in percent correlated very good with the aorta clamping time (R = 0,85). The changes in acid-base status and lactate levels were erratic and showed no correlation with the duration of ischemic period. Systemic hypoxanthine concentrations are a more specific and reliable parameter for hypoxic damages.

Acid-Base Equilibrium↗
PubMed1982

Labetalol, a combined alpha- and beta-blocker, in hypertension of pregnancy.

Labetalol was given to women with hypertension of pregnancy in their last trimester to study its acute effect on circulation and metabolism. Seven women were given 50 mg labetalol i v. There was a significant decrease of blood pressure from a mean of 143/101 +/- 4/2 (SEM) to 127/88 +/- 5/2 mm Hg. Maternal heart rate fell significantly from 77 +/- 5 to 68 +/- 3 beats per min. These changes persisted during a three-hour observation period. The hypotensive response was accompanied by a significant increase in plasma noradrenaline from 1.54 +/- 0.16 to 2.37 +/- 0.41 nmol/l, suggesting sympathetic activation. Plasma cyclic AMP, which is increased by beta 2-adrenoceptor stimulation, was significantly elevated after labetalol. This supports the hypothesis of partial beta-agonist activity of labetalol. Lipid metabolism, as judged from measurements of plasma FFA, glycerol and 3-hydroxybuturic acid, showed little change. The acute effect of labetalol on uteroplacental blood flow was determined in eight women with pregnancy hypertension using a gammacamera on line with a computer. 0.5 mCi indium-113m was given i v before and 30 min after labetalol was administered i v in a dose of 1 mg per kg body weight. After the injections of indium-113m, serial scintigrams were recorded during 10 s periods for 240 s. By computerized summation of the scintigrams, an image was obtained in which the placenta could be outlined for time-activity analysis of the isotope accumulation curve. From this curve a uteroplacental blood flow index could be calculated. Labetalol induced a significant drop of mean arterial blood pressure from 114 +/- mm Hg to 100 +/- 3 mm Hg after 30 min in this group of women. However, the uteroplacental blood flow index did not change. As we have earlier shown with this technique that uteroplacental blood flow can be severely impaired in hypertension of pregnancy, the finding of substained uteroplacental blood flow simultaneously with a decrease in blood pressure should be of clinical importance. Taken together with other studies of clinical effects, these results indicate that labetalol is useful in the treatment of hypertension of pregnancy.

Adult↗
PubMed1982

Metabolic and circulatory effects of intravenous and oral salbutamol in late pregnancy in diabetic and non-diabetic women.

The present study investigated the cardiovascular and metabolic "side-effects" of the beta 2-adrenoceptor stimulating drug salbutamol in the third trimester of pregnancy in diabetic and non-diabetic women. Salbutamol was administered either orally or as an intravenous infusion. Blood samples were collected for analyses of plasma cyclic AMP, insulin, C-peptide, and carbohydrate and lipid metabolites. Fetal heart rate, maternal heart rate, and blood pressure were registered simultaneously. After both intravenous and oral salbutamol, there was a statistically significant decrease in diastolic blood pressure, increase in maternal heart rate, plasma levels of cyclic AMP, insulin, and carbohydrate and lipid metabolites showing stimulation of glycogenolysis, lipolysis, and insulin secretion. The increase in fetal heart rate was slight. In diabetic women, the glycogenolytic and lipolytic effects of salbutamol were significantly more pronounced than in non-diabetics. The acute maternal circulatory and metabolic effects after salbutamol are probably too slight to have any clinical significance in healthy women. However, in diabetics, due to their impaired insulin function, a serious metabolic deterioration after salbutamol might occur.

Administration, Oral↗
PubMed1981

Evidence against a role of cyclic nucleotides in the regulation of anaphylactic histamine release in isolated rat mast cells.

The effect of different phosphodiesterase (PDE) inhibitors on the antigen or 48/80 induced histamine release from isolated Hooded Lister rat mast cells was tested. The unselective PDE inhibitors theophylline (2.5 mM) and IBMX (0.2 mM) and the selective cyclic GMP PDE inhibitor M & B 22948 (0.1 mM) inhibited the antigen induced histamine release by 50% while 48/80 induced release was inhibited by about 25%. The cyclic AMP selective PDE inhibitors ICI 63197 (0.5 mM) or Ro 20-1724 (0.2 mM) had no effect on 48/80 induced histamine release but tended to enhance antigen induced release. There was no correlation between the measured levels of cyclic AMP and the effect on histamine release by the investigated PDE inhibitors. Cyclic AMP or cyclic GMP up to 10(-3) M did not affect the anaphylactic histamine release. Dibutyryl-cAMP and dibutyryl-cGMP (10(-4) M) both inhibited the release about 20% but this effect could be explained by the effect of butyric acid as sodium butyrate (2 X 10(-4) M) also inhibited the release by 20%. The presence results suggest that cyclic nucleotides are not important regulators of histamine release from isolated mast cells.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Cellular localization of peptides in neural structures.

By means of the immunohistochemical technique of Coons and collaborators, numerous peptide-containing neurons have been observed in the brain, spinal cord and periphery. These neurons may contain peptides such as substance P, vasoactive intestinal polypeptide (VIP), enkephalin or somatostatin. Some systems are very extensive. For example, immunoreactive substance P has been observed in more than 30 cell groups in the central nervous system, in primary sensory neurons, in sensory neurons in the vagus nerve and in taste buds, and in intestinal neurons. Thus, one and the same peptide can be utilized at many different levels in the nervous system. Several examples are now known where a regulatory peptide occurs together with a classical transmitter, such as a catecholamine, in the same neuron, which suggests the possibility that a neuron can release more than one transmitter substance. Of particular interest is the occurrence of VIP in presumed cholinergic neurons innervating exocrine glands in the cat, and the coexistence of a cholecystokinin (CCK)-like peptide in dopamine neurons projecting mainly to limbic areas. In the former system VIP seems to be responsible mainly for vasodilation, whereas acetylcholine mainly causes secretion. Furthermore, combined infusion of both substances in very low doses results in a marked potentiation of the secretory and vasodilatory responses. Thus, we have an example where two putative transmitters, released from the same nerve endings, seem to cooperate to activate a physiological response (secretion). With regard to the central CCK/dopamine neurons the type of interaction between the two coexisting transmitter candidates is at present unclear. It is suggested that elucidation of different types of coexistence phenomena may advance our understanding of chemical transmission at synapses under normal and pathological conditions, and may lead to new approaches to the treatment of some nervous disorders.

Adrenocorticotropic Hormone↗
PubMed1980

Central monoamine synapses as sites of action for ergot drugs.

The acute and subacute effects of ergot drugs on central monoaminergic mechanisms were studied in the rat. The most significant findings are: 1. After acute treatment, lergotrile and bromocriptine were found to block apomorphine-induced locomotion and rearing, suggesting that these two ergot drugs can block postsynaptic DA receptors within the nucleus accumbens. 2. Several ergot drugs were shown to have high affinity for some 3H-ADTN binding sites. Earlier studies indicate that 3H-ADTN appears to label postsynaptic dopamine receptors located on nerve cells in the striatum. These ergot-sensitive 3H-ADTN binding sites appear not to be linked to the adenylate cyclase system. In addition, bromocriptine, unlike CM 29-712, was found to have a high affinity for 3H-spiperone binding sites in the striatum. 3. Bromocriptine and CM 29-712 increased norepinephrine turnover in periventricular and paraventricular hypothalamic areas, suggesting a blockade of norepinephrine receptors. CM 29-712 also increased DA turnover in the medial palisade zone of the median eminence. 4. Some ergot drugs also had affinity for 5-HT receptor binding sites, possibly reflecting a 5-HT agonistic action in some areas, as shown in behavioral studies. 5. Apomorphine and bromocriptine displaced in vivo 3H-spiperone binding in the hypothalamus, septal area, and substantia nigra, but not in the striatum. 6. Subacute treatment with bromocriptin and CM 29-712 were found to produce two types of changes in behavior: The apomorphine-induced locomotion was enhanced while the chewing and licking activity (stereotypies) was reduced. These behavioral changes may be associated with an increased affinity in the 3H-ADTN binding sites in the striatum. This treatment also produced persistent increases of DA turnover in the tuberculum olfactorium but not in striatum.

5-Hydroxytryptophan↗
PubMed1978

Mammary tumour inhibition and subacute toxicity in rats of prednimustine and of its molecular components chlorambucil and prednisolone.

Prednimustine, a chlorambucil ester of pregnisolone, retarded growth of DMBA-induced mammary tumours in rats and reduced the number of tumours. A combination of chlorambucil and prednisolone (C + P) in the same proportion as in prednimustine, had similar effects, 8 and 26 mg per kg of the C + P combination being equipotnet to 16 and 64 mg per kg of prednimustine, respectively. The mortality figures suggested that prednimustine was considerably less toxic than equipotent doses of C + P. This toxicity difference was confirmed in a parallel investigation of the subacute toxicity in rats of prednimustine and C + P. This study showed that the mortality, reduction of lymphocytes and platelets, and bone marrow depression was much lower after pregnimustine than after equimolar amounts of the C + P combination. The results suggest that the low toxicity of prednimustine makes this drug a better cytostatic agent than the C + P combination treatment.

Animals↗
PubMed1975

Enzymes regulating glycogen metabolism in swine subcutaneous adipose tissue. I. Phosphorylase and phosphorylase phosphatase.

Glycogen phosphorylase from swine adipose tissue was purified nearly 700-fold using ethanol precipitation, DEAE-cellulose adsorption, AMP-agarose affinity chromatography, and agarose gel filtration. The purified enzyme migrated as one major and several minor components during polyacrylamide gel electrophoresis. Activity was associated with the major component and at least one of the minor components. The molecular weight of the disaggregated, reduced, and alkylated enzyme, estimated by polyacrylamide gel electrophoresis performed in the presence of sodium dodecyl sulfate, was 90,000. Stability of the purified enzyme was considerably increased in the presence of AMP. The isoelectric pH of the enzyme in crude homogenates was 6.3. The sedimentation coefficient of the purified enzyme (7.9 S) and that in crude homogenates (7.3 S) was determined by sucrose density gradient sedimentation. Optimal pH for activity was between pH 6.5 and 7.1. Apparent Km values for glycogen and inorganic phosphate were 0.9 mg/ml and 6.6 mM, respectively. The Ka for AMP was 0.21 mM. Enzyme activity was increased by K2SO4, KF, KCl, and MgCl2 and decreased by NaCl, Na2SO4, D-glucose, and ATP. Inhibition by glucose was noncompetitive with the activator AMP; inhibition by ATP was partially competitive with AMP. The purified enzyme was activated by incubation with skeletal muscle phosphorylase kinase. Enzyme in crude homogenates was activated by the addition of MgCl2 and ATP; activation was not blocked by addition of protein kinase inhibitor, suggesting that phosphorylase kinase in homogenates of swine adipose tissue is present largely in an activated form. Deactivation of phosphorylase a by phosphorylase phosphatase was studied using enzyme purified approximately 200-fold from swine adipose tissue by ethanol precipitation, DEAE-cellulose chromatography, and gel filtration. The Km of the adipose tissue phosphatase for skeletal muscle phosphorylase a was 6 muM. The purified swine adipose tissue phosphorylase, labeled with 32-P, was inactivated and dephosphorylated by the adipose tissue phosphatase. Dephosphorylation of both skeletal muscle and adipose tissue substrates was inhibited by AMP and glucose reversed this inhibition. Several lines of evidence suggest that AMP inhibition was due to an action on the substrate rather than on the enzyme. We have previously reported that the system for phosphorylase activation in rat fat cells differs in some important characteristics from that in skeletal muscle. However, both swine fat phosphorylase and phosphorylase phosphatase have major properties very similar to those described for the enzymes from skeletal muscle.

Adenosine Monophosphate↗
PubMed1975

Enzymes regulating glycogen metabolism in swine subcutaneous adipose tissue. II. Glycogen synthase.

Glycogen synthase from swine adipose tissue was purified to apparent homogeneity using ethanol precipitation, DEAE chromatography, and affinity chromatography utilizing glucosamine 6-phosphate as the ligand. The purified enzyme migrated as a single protein component during electrophoresis on polyacrylamide gels at pH 7.3 although some protein failed to enter the running gel. Enzyme incubated with sodium dodecyl sulfate (SDS) migrated as one component (mol wt similar to 90,000) on SDS-polyacrylamide gel electrophoresis. The enzyme was relatively unstable at all stages of the purification procedure, but stability was increased in the presence of glucose 6-phosphate, UDPG, or glycerol. The isoelectric point of the purified enzyme and of enzyme activity in crude homogenates was pH 4.8. The sedimentation coefficient of the enzyme in crude homogenates was 8.5 S. The pH-activity profile showed an optimum at pH 7.8 in the absence of glucose 6-phosphate but no definable optimum between pH 7.0 and 9.2 in its presence. The Km of glycogen synthase I for UDPG was 250 muM in the absence and 37 muM in the presence of glucose 6-phosphate; the K-a for glucose 6-phosphate was 18 mu-M. The K-m of glycogen synthase D for UDPG was 130 mu-M in the presence of glucose 6-phosphate; the Ka for glucose 6-phosphate was 1 mM. The anions sulfate and phosphate activated the enzyme when assays were performed in the absence of glucose 6-phosphate. Fluoride produced activation of enzyme assayed either in the presence or in the absence of glucose 6-phosphate.

Adipose Tissue↗