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Biomedical subjects

M Aliaga

Publications and source records attributed to M Aliaga.

24 records · Page 2Linked to original sources

Pharmacological comparison of the immune and non-immune inflammations induced by picryl chloride and oxazolone in mice.

Picryl chloride applied to the ears of Swiss mice induced a clearcut primary irritation inflammation (maximal after 3 to 6 hr) and after contact sensitization performed 7 days before a delayed hypersensitivity reaction. Oxazolone produced only a weak primary irritation reaction. After contact sensitization in the same conditions as above, oxazolone induced an immune response that was already substantial 3 to 6 hr after the challenge and generally reached a maximum after 24 hr. We tried to alter these four types of inflammation (the primary irritation and delayed hypersensitivity to picryl chloride, and the 6-hr and 24-hr phases of hypersensitivity to oxazolone) by various types of compounds administered cutaneously or sytemically. Mepyramine, methysergide, cimetidine, disodium cromoglycate, phenylbutazone, and acetylsalicylic acid reduced to varying degrees after cutaneous application the primary irritation and the delayed hypersensitivity inflammation induced by picryl chloride. Methysergide was the only one of these drugs that on topical application clearly reduced the immune response to oxazolone (decrease in the 6-hr phase). After systemic administration, these same drugs had no effect on the four types of reaction. Both the corticosteroids tested (hydrocortisone acetate and desonide) reduced all the inflammations to various degrees and were always more active (particularly desonide) when applied topically than when administered systemically. On the other hand indomethacin, which inhibited all types of inflammation, was more active when administered systemically. Study of the kinetics and trials of pharmacological modulation of the various reactions induced by picryl chloride and oxazolone in Swiss mice provided evidence of differences in behavior between the two agents.

Adrenal Cortex Hormones↗

Pharmacological studies on zymosan inflammation in rats and mice. 1: Zymosan-induced paw oedema in rats and mice.

Injections of zymosan in mouse and rat paws provoke inflammatory reactions, the kinetics of which are different. In both models, inflammation occurs at an early stage but oedema is maximal at 30 min in rat paw and 6 h in mouse paw. In this study the two reactions have been studied up to 6 h. The reduction of oedema by anti-H1 compounds, as well as by disodium cromoglycate, proves the active role played by histamine in rat paw oedema. In mouse its role appears to be minor or non-existent. Serotonin seems to be clearly implicated in the early stages of the oedema in mouse, somewhat less in rat. In the two species, non-steroidal anti-inflammatory compounds only reduce the 4-6 h phase. BW755C and phenidone reduce the early and late phase of paw oedema in both species, with the exception of phenidone which is inactive on the 4-6 h phase in the mouse. We can hypothesize that in the two species some leukotrienes seem to be implicated principally in the early phases, while derivatives of cyclooxygenase play a more important role in the late phases. Theophylline reduces inflammation in the two models, hydrocortisone acetate, however, is only active on the late phases. These results indicate that there are important differences in the participation of the various mediators studied in the two models.

Animals↗

Pharmacological studies on zymosan inflammation in rats and mice. 2: Zymosan-induced pleurisy in rats.

Injection of zymosan in rat pleural cavity provokes an exudate which is already detectable at 15 min and which is maximum at 24 h. The leucocyte count (mostly neutrophils) increases at 2-4 h and is maximum at 48 h. In this paper the reaction has been studied up to 6 h. Evidence of histamine release, of mast cell degranulation and of reduction of the exudate by anti-H1 compounds, as well as by sodium cromoglycate, proves the active role played by histamine in the early stage of pleurisy. Serotonin (whose role was studied exclusively using antagonists) seems to have only a minor part in the early phase of the reaction. Some metabolites of arachidonic acid were determined in the pleural exudate at 1 h and 6 h. The concentration of leukotriene B4 was high at 1 h and decreased at 6 h. The thromboxane B2 level was already high at 1 h and was neatly augmented at 6 h while the amount of prostaglandin F1 alpha was high at both times. The non-steroidal anti-inflammatory substances studied all reduced the pleural exudate at 1 h but their activity then varied from each other at 6 h. Cyclooxygenase and lipoxygenase inhibitors (phenidone, BW755C) induced a reduction of the exudate at both times. Zymosan-induced pleurisy seemed thus to be an excellent model for the investigation of antiallergic and anti-inflammatory compounds active on histamine and cyclooxygenase and lipoxygenase pathways.

Animals↗

Action of tioxamast on various models of anaphylactic shock, hyperreactivity and bronchial inflammation in guinea-pigs.

Tioxamast, an anti-allergic compound inhibiting the release and synthesis of certain mediators of allergy and having no major antagonist effect towards such mediators, was experimented on various models of anaphylactic shock, hyperreactivity and bronchial inflammation in guinea-pigs. Tioxamast does not reduce passive pulmonary anaphylactic shocks induced in anaesthetized or conscious guinea-pigs by i.v. challenge of antigen. Likewise, the compound has no effect on systemic hyperreactivity towards i.v. histamine induced in anaesthetized guinea-pigs after a passive anaphylactic shock caused by i.v. challenge of antigen. On the other hand, tioxamast inhibits passive pulmonary anaphylactic shock induced in guinea-pigs by antigen aerosol in conscious guinea-pigs. Likewise, tioxamast decreases hyperreactivity to inhalation of histamine or carbamylcholine obtained after an active or passive anaphylactic shock by aerosol in conscious guinea-pigs. The oxamate derivative attenuates the increase in number of eosinophils and mononuclear cells obtained in the bronchoalveolar lavage fluid 24 hr after an active anaphylactic shock induced by aerosol. The anti-allergic activity of tioxamast on the various models carried out in guinea-pigs thus appears when these models are induced by a challenge of antigen or mediator by inhalation.

Aerosols↗

[Comparative antiallergic and anti-inflammatory action of F1865, mepyramine maleate, desonide and disodium cromoglycate after cutaneous administration].

The actions of F 1865 (ethyl 4' methoxy 4 phenyl thiazolyl 2 oxamate), an inhibitor of the release of histamine from mast cell, desonide, a corticosteroid, mepyramine maleate, an anti-H1 antihistaminic, and disodium cromoglycate were compared after cutaneous application in various experimental models of allergy and inflammation. F 1865 decreased IgE- and IgG-dependent passive cutaneous anaphylaxis in rats at doses having no effect on histamine- and serotonin-induced capillary permeability. Disodium cromoglycate showed the same activity spectrum, but its action was only found after intradermal application. The reduction of cutaneous anaphylaxis by desonide was found parallel to its inhibition of histamine effects, and to a lesser extent of serotonin effects. In the case of mepyramine, the antiallergic effect may be explained by its antihistaminic action. Desonide was highly active on cantharidin-induced non-immune inflammation and on non-immune and delayed hypersensitivity reactions induced by picryl chloride in mouse ear. Although far less active than the corticosteroid, F 1865, mepyramine and disodium cromoglycate did reduce the three types of reactions in mice. This evidenced a part played by histamine in such inflammations. Then it is likely that the inhibition of histamine release by F 1865 plays an important part in the effect of the compound observed in the various inflammations studied. However we cannot exclude actions against other mediators involved in these reactions.

Administration, Topical↗