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Biomedical subjects

I Moodley

Publications and source records attributed to I Moodley.

26 records · Page 2Linked to original sources
PubMed1983

A comparison of the in vivo effects of ketotifen, clemastine, chlorpheniramine and sodium cromoglycate on histamine and allergen induced weals in human skin.

The effect of ketotifen was compared with that of clemastine and chlorpheniramine, known antihistamines, and sodium cromoglycate, a drug considered to have mast cell "stabilizing' properties on histamine and allergen wealing reactions in human skin, in random order, double-blind, placebo controlled studies. Ketotifen was significantly more potent in the inhibition of both histamine (P less than 0.001) and allergen (P less than 0.001) skin wealing reactions than either clemastine or chlorpheniramine. Sodium cromoglycate had no significant effect on either histamine or allergen skin wealing reactions in any of the concentrations tested. However ketotifen, like clemastine, had a significantly greater inhibitory effect on histamine than on allergen induced weals (P less than 0.001) and both drugs were shown to act as competitive antagonists of histamine. Ketotifen has been shown to be a potent anti-histamine but there is no evidence from these in vivo studies to suggest that it has any additional inhibitory activity on release of mediators from mast cells in human skin.

Allergens↗
PubMed1983

Plasma histamine in asthmatic and control subjects following exercise: influence of circulating basophils and different assay techniques.

Arterial plasma histamine concentrations were measured after exercise in 10 subjects with extrinsic atopic asthma, 10 who were non-atopic and non-asthmatic and seven who were atopic but non-asthmatic, by a single isotope radioenzymatic assay. Significantly higher plasma histamine concentrations were found in the asthmatic subjects before exercise than in the non-atopic controls (p less than 0.05). The mean histamine concentration rose after exercise in all groups but the increased levels were not significantly different from pre-exercise values. Similarly, mean circulating basophil counts increased in all groups after exercise, and a highly significant correlation was found between basophil counts and whole blood histamine concentrations (p less than 0.001). In vitro studies showed that there was a significant correlation between the number of basophils added to plasma samples and the concentrations of histamine subsequently detected. Although the mean concentrations of plasma histamine and whole blood histamine and number of basophils in the atopic control group were intermediate between those found in the atopic asthmatic and non-atopic controls, none of the differences was significant. Venous plasma histamine concentrations after exercise were measured in a further five subjects with extrinsic atopic asthma and five non-atopic, non-asthmatic subjects before and after exercise with the more sensitive and specific double isotope radioenzymatic assay. Concentrations of plasma histamine measured by this assay were about one tenth of those measured by the single isotope radioenzymatic assay. Although a small rise in mean plasma histamine concentration occurred in both groups after exercise there was no significant difference in these levels either between or within the groups. We find no evidence from these studies on measurement of peripheral blood histamine to support the hypothesis that mast cell mediator release is implicated in the pathogenesis of exercise induced asthma.

Adult↗
PubMed1982

Histamine release induced by dextran: the nature of the dextran receptor.

Dextrans of molecular weight 10(4) to 2 x 10(6) induced histamine release from rat peritoneal mast cells in the presence of calcium (1 mM) and phosphatidyl serine (10 micrograms/ml). Glucose and low molecular weight dextrans inhibited the histamine release induced by high molecular weight dextrans but the inhibition could not be explained in terms of a simple competitive model. Structure-activity relationships for the inhibition of dextran-induced histamine release by a number of saccharides demonstrated that substitution at the C-3, C-4, and C-6 positions of glucose were most important for activity. Inhibition of histamine release by glucose was specific for the dextran stimulus. Soluble IgE and IgG antibodies failed to interfere with histamine release induced by dextran. Phlorizin specifically inhibited the histamine release induced by dextran. Purification of mast cells on albumin or ficoll gradients produced a selective loss of response to dextran which was not due to the removal of non-mast cells but to some change in the mast cells themselves. The possible nature of the dextran receptor is discussed.

Animals↗
PubMed1982

Histamine, neutrophil chemotactic factor and circulating basophil levels following exercise in asthmatic and control subjects.

Significant increase in the maximum post-exercise values of plasma histamine (PH), whole blood histamine (WBH) and neutrophil chemotactic factor (NCF) occurred in arterial blood within the first hour after exercise in asthmatic patients. However, similar changes in PH and WBH also occurred in the control group. Significant increases in circulating basophil counts following exercise were found in both groups, which closely mirrored the changes in PH and NCF, and there was a highly significant correlation between rises in WBH and basophil counts (P less than 0.001). When plasma histamine as assayed in venous blood using a more sensitive and specific double isotope radio enzymatic assay no significant alteration in plasma histamine levels was detected in either the asthmatic or the control group. We conclude that there is no evidence from these studies to support the suggestion that mast cell mediator release is involved in the pathogenesis of exercise-induced asthma, and that any observed changes in levels of PH and NCF after exercise may be related to changes in levels of circulating basophils.

Adult↗
PubMed1982

The mechanism of ketotifen-induced histamine release from human peripheral leucocytes.

Ketotifen-induced histamine release from human leucocytes is independent of extracellular calcium and does not require metabolic energy. Furthermore, histamine release is accompanied by a loss of cellular cytoplasmic contents. This suggests that the mechanism of ketotifen-induced histamine release at high concentrations is non-specific and is similar to that of clemastine, a typical H1 antagonist.

Calcium↗
PubMed1981

IgG receptors on the mast cells.

Antisera to the IgG subclasses, 1, 2a, 2b, and 2c, induced histamine release from mast cells obtained from the peritoneal washings of Lister hooded rats. The maximum responses obtained with anti-IgG1 and anti-IgG2a were as great as that for anti-IgE (more than 60% histamine release). Cells from unresponsive Wistar rats which did not secrete appreciable amounts of histamine in response to any of the antisera, produced on active sensitization with ovalbumin a small but significant response on challenge with anti-IgG1 and anti-IgG2b as well as with anti-IgE. Passive sensitization with rat myeloma serum of mast cells from the unresponsive rats produced a large response on challenge with anti-IgE but no release to the anti-IgG group 2 subclasses. IgE myeloma serum (1:1000) neutralized the histamine-releasing activity on anti-IgE serum (87% inhibition) and the antisera to all subclasses of IgG. When the IgE in the myeloma serum was inactivated by heating, the response to the IgG antisera remained completely inhibited except for anti-IgG2a where some reversal was observed. When purified myeloma IgE (30 microgram/ml) was used in place of whole serum, marked inhibition (86%) of the response to anti-IgE was obtained leaving the responses to the IgE subclasses unaffected (except for IgG2a, which was 65% inhibited).

Animals↗
PubMedDate not supplied

Anti-inflammatory properties of tixocortol 17-butyrate,21-propionate (JO 1222), a novel, locally acting corticosteroid.

Tixocortol 17-butyrate,21-propionate (JO 1222) is a novel, locally acting, C-21 thioester-linked corticosteroid with significant activity in a number of models of inflammation. In models of acute inflammation, JO 1222 had an ED30 of 3 micrograms in carrageenan-induced oedema, an ED50 of 5 ng in croton oil-induced inflammation, and 4 micrograms and 2 micrograms/pleural cavity in carrageenin-induced pleurisy in the rat and mouse respectively. In a model of subchronic inflammation JO 1222 had an ED50 of 39 micrograms/pellet (cotton pellet-induced granuloma) and an ED50 of 13 ng in oxazolone-induced hypersensitivity. The overall relative potency was found to be beclomethasone DP greater than betamethasone DP = JO 1222 greater than hydrocortisone 17-butyrate,21-propionate greater than hydrocortisone acetate. In contrast to any of the other corticosteroids, including beclomethasone DP, JO 1222 did not have any marked systemic effects in any of the above models following oral or local administration. Furthermore, in contrast to other locally acting corticosteroids such as beclomethasone DP, JO 1222 had little or no effect on the thymus or body weight. These findings suggest that JO 1222 is a novel, potent, locally acting corticosteroid with little or no systemic effects and thus has therapeutical potential in diseases such as asthma, arthritis, ulcerative colitis and rhinitis.

Adrenal Cortex Hormones↗