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Biomedical subjects

R Brattsand

Publications and source records attributed to R Brattsand.

At least 73 records · Page 4Linked to original sources
PubMed1982

Effect of glucocorticoids on glycosaminoglycan metabolism in cultured human skin fibroblasts.

Human skin fibroblasts were exposed to 3 anti-inflammatory steroids in order to study their effects on the glycosaminoglycan metabolism. The potent glucocorticoids, fluocinolone acetonide and budesonide, even at low concentrations strongly reduced the accumulation of hyaluronic acid and sulfated glycosaminoglycans in the medium, at the cell surface, and in the cells. Hydrocortisone had considerably less effect. The 3 compartments were not influenced to the same extent and the least inhibition was noted in the cell surface pool. Dermatan sulfate was decreased to the same relative extent in all 3 compartments, while hyaluronic acid and heparan sulfate were specifically retained at the cell surface, explaining why this compartment was less affected than the others. Dermatan sulfate was studied in more detail regarding effects on its copolymeric structure. Glucocorticoid treatment changed the uronosyl composition of the polysaccharides so that a relative decrease of glucuronic acid residues and a relative increase of iduronic acid residues were noted. This change was most evident in dermatan sulfate of the medium and of the cell surface. Thus, glucocorticoid treatment not only reduces the quantity of various glycosaminoglycans but also changes the distribution, the relative proportion, and the structure of connective tissue proteoglycans. These effects probably contribute to the development of skin atrophy, which often is observed after long-term treatment with potent glucocorticoids.

Administration, Topical↗
PubMed1982

Protective effects of the glucocorticoid, budesonide, on lung anaphylaxis in actively sensitized guinea-pigs: inhibition of IgE-but not of IgG-mediated anaphylaxis.

1 The effect of glucocorticoid pretreatment on antigen-induced bronchoconstriction was studied in guinea-pigs actively sensitized to two different ovalbumin regiments (one producing IgE- and IgG-like antibodies and the other exclusively IgG-like antibodies). 2 Budesonide (50 mg/kg) and hydrocortisone (50 mg/kg) given as one intraperitoneal injection 15-20 h before and anaphylactic tests or as two consecutive intraperitoneal injections 5 and 6 days before, led to a decreased bronchial capacity. In this respect glucocorticoid pretreatment was effective only in guinea-pigs sensitized to produce both IgE-like and IgG-like antibodies. 3 Budesonide pretreatment also reduced the capacity of anaphylactically-challenged chopped lung tissue to release histamine in guinea-pigs sensitized to produce both IgE- and IgG-like antibodies. 4 Budesonide pretreatment did not change the levels of circulating IgG1a and IgE-like homocytotropic antibodies as measured by passive cutaneous anaphylaxis; nor did it affect histamine or methacholine-induced bronchoconstriction in vivo or the capacity of histamine or methacholine to contract the guinea-pig isolated trachea preparation of the isoprenaline-induced relaxation of this preparation. 5 The selective inhibitory effects of budesonide and hydrocortisone on IgE-mediated but not IgG-mediated anaphylaxis and the relevance to human atopic disease are discussed.

Anaphylaxis↗
PubMed1982

Development of new glucocorticosteroids with a very high ratio between topical and systemic activities.

The very potent topical anti-inflammatory glucocorticosteroids (GCS) most widely used are either 17 alpha-esters of halogenated 16-methyl-17 alpha-hydroxycorticosteroids (e.g. beclomethasone 17 alpha, 21-dipropionate = BDP) or 16 alpha, 17 alpha-acetals of halogenated 16 alpha, 17 alpha-dihydroxy corticosteroids (e.g. triamcinolone acetonide = TA). The purpose of the present investigation was to increase the ratio between the topical anti-inflammatory (TAIP) and the systemic potencies (SP) of GCS 16 alpha, 17 alpha-acetals, as such compounds are not biotransformed in the lung. Structure-activity investigations in rodents showed that fluoro substituents in positions 6 alpha or 9 alpha or both 6 alpha, 9 alpha 9 alpha increased SP more than TAIP. On the other hand, nonsymmetrical 16 alpha, 17 alpha-acetal substitution increased TAIP more than SP. The best TAIP:SP ratio was obtained with budesonide, which contains this new type of acetal substituent, but has no halogen atoms in the steroid nucleus. In the rat and the mouse budesonide has a 5--10 times better TAIP:SP ratio than 16 alpha, 17 alpha-acetonides, like TA, as well as 17 alpha-ester GCS, like BDP. The improved ratio for budesonide is probably due to a high intrinsic GCS activity at the site of application combined with an effective inactivation by biotransformation after systemic absorption. The importance of the inactivation in the liver was verified by experiments in which the biotransformation capacity of the liver was blocked by SKF-525 A.

Animals↗
PubMed1982

Topical and systemic glucocorticoid potencies of budesonide, beclomethasone dipropionate and prednisolone in man.

Topical anti-inflammatory ('intracutaneous vasoconstriction') and systemic glucocorticoid potencies (depression of plasma cortisol) were compared in human volunteers after administration of the glucocorticoids budesonide, beclomethasone dipropionate (BDP) and prednisolone. After topical application budesonide was about twice as potent as BDP and more than 1 000 times more potent than prednisolone and hydrocortisone in inducing 'vasoconstriction'. After oral administration, on the other hand, budesonide was one half to one third as potent as BDP in depressing plasma cortisol. After inhalation budesonide was only half as potent as BDP. When inhaled budesonide was compared to oral prednisolone budesonide 1 600 micrograms and prednisolone 5 mg were shown to have the same effect on plasma cortisol. The improved ratio between the topical and the systemic glucocorticoid effect of budesonide, makes the drug a promising alternative for aerosol treatment in asthma.

Adult↗
PubMed1979

Local anesthetics: importance of mode of application, concentration and adrenaline for the appearance of nerve lesions. An experimental study of axonal degeneration and barrier damage after intrafascicular injection or topical application of bupivacaine (Marcain).

Local anesthetics are designed for application in or close to nerve tissue. In spite of their wide clinical use, surprisingly few investigations deal with the neural toxicity of modern local anesthetics. In this experimental study, the effects were investigated of intrafascicular or topical application of the long-acting local anesthetic bupivacaine on the rabbit sciatic nerve. Axonal degeneration was histologically evaluated and a fluorescence-microscopic technique used to detect lesions in the blood-nerve barrier. Topical application of bupivacaine in clinically recommended concentrations around the nerve caused no detectable nerve injury, while intrafascicular injections caused considerable axonal degeneration and damaged the blood nerve barrier. Axonal degeneration was the same after injection of physiologic saline solution and bupivacaine 0.5%, but it increased with increasing bupivacaine concentration and especially with the addition of adrenaline. On the other hand, the acute effects of intrafascicular injection, as visualized in the barrier experiments, changed little with the addition of adrenaline, indicating that it is the injection trauma itself which is deleterious. It is concluded that intraneural injections should be avoided and that plain bupivacaine solutions should be routinely used.

Administration, Topical↗
PubMed1979

Synthesis and anti-inflammatory properties of budesonide, a new non-halogenated glucocorticoid with high local activity.

As part of a study of the local anti-inflammatory activity of corticosteroid 16 alpha, 17 alpha-acetals it was found that on acetalization of 16 alpha-hydroxyprednisolone with n-butyraldehyde the two possible epimers were formed in the ratio of 1: 1. The reaction product was resolved by column chromatography on Sephadex LH-20. The isolated epimers were studied by NMR and mass spectrometry. The epimeric mixture of this new non-halogenated corticoid, 16 alpha, 17 alpha-(22R,S)-propylmethylenedioxypregna-1,4-diene-11 beta,21-diol-3,20-dione (budesonide), was shown to have a local antiinflammatory potency comparable to that of fluocinolone acetonide in cotton pellet tests in rats. In contrast, its systemic glucocorticoid activity was found to be 4--7 times lower than that of fluocinolone acetonide, however.

Animals↗
PubMed1979

Enzymatic hydrolysis of pentaerythritoltetranicotinate and meso-inositolhexanicotinate in blood and tissues.

The esters between nicotinic acid and pentaerythritol (niceritrol, Perycit) or meso-inositol (MIHN) were hydrolyzed by enzymes present in plasma and tissues of man, rat and dog. Human plasma and rat tissues hydrolyzed niceritrol at a higher rate than did MIHN. The reversed relation was found with dog tissue. The ability of niceritrol and MIHN to raise the level of free nicotinic acid of plasma was studied on man, dog and rat and related with their hydrolysis in vitro and the different solubility of the esters. There was a relationship between these properties of the esters and their ability to increase the plasma level of nicotinic acid.

Animals↗
PubMed1977

Studies on the mechanism of flush induced by nicotinic acid.

Flush is a common side effect of nicotinic acid therapy in patients. The effect is present as long as the level of nicotinic acid increases in the plasma. The mechanism of flush after nicotinic acid has been studied in the ears of guinea-pigs in vivo. The threshold dose of nicotinic acid (1-3 mg/kg) to raise the skin temperature of the ears and to increase the cyclic AMP level of this tissue was similar. Indomethacin and acetylsalicylic acid which inhibit the synthesis of prostaglandins markedly reduce the duration and intensity of the flush. In isolated slices from guinea-pig ears, nicotinic acid increased the level of cyclic AMP; this effect was inhibited by indomethacin. The stimulating action of prostaglandin E1 on the cyclic AMP level of the ear slices was not inhibited by indomethacin. Since administration to man of both cyclic AMP and prostaglandin E1 produces flush it is suggested that nicotinic acid may induce flush by the formation of some prostaglandin which then increases the formation of cyclic AMP.

Animals↗
PubMed1977

Endothelial structure in rabbits with moderate hypercholesterolaemia. A scanning electron microscopic study.

The aortic surface of rabbits given a supplement of 0.1--0.3 per cent cholesterol to the diet was studied by scanning electron microscopy. In regions where increased haemodynamic strain was anticipated, similar structural changes were observed in normal and hypercholesterolaemic rabbits. However, changes indicating cell injury were more wide-spread in cholesterolfed animals. This suggests that hypercholesterolaemia may increase cell susceptibility to injury. In the same regions, the development of intimal thickenings was observed in cholesterol-fed rabbits. The central parts of such thickenings had been reendothlialized, whereas a region with cell injury surrounded each lesion. In regions with low haemodynamic strain, a loss of fine-structural details was observed in hypercholesterolaemic rabbits. It is suggested that these changes may be related to the deteriorated functional properties of the intact endothelium in such rabbits. In view of these data it is suggested that the interrelationship between hypercholesterolaemia and atherosclerotic arterial disease may partly be due to a deleterious effect of hypercholesterolaemia on the functional and structural integrity of the arterial endothelium.

Animals↗