Morphological Evaluation of Oxatomide – a New Anti-Allergic Drug in Guinea Pig Anaphylaxis

Abstract

The effects of oxatomide, a new anti-allergic drug, in protecting guinea pigs from acute anaphylactic shock have been evaluated by studying the morphologic changes in the lung with special focus on the topographical relationship between bronchiolar smooth muscle and peribronchiolar mast cells, during the anaphylactic reaction. After ovalbumin challenge of passively sensitized guinea pigs, the mast cells in the peribronchiolar area present the following characterstic alterations: general shape changes with the formation of multiple cytoplasmic pseudopods, a variable decrease in the number of granules, mitochondrial swelling and, most peculiarly, a consistent appearance of intranuclear microtubules. Cations, being localized with an oxalate-pyroantimonate precipitation technique, are displaced from the nuclei and the cytoplasm of mast cells that are presumed to be causally involved in the anaphylactic phenomenon. Guinea pigs, which have been orally treated with 2.5 mg/kg oxatomide before ovalbumin challenge show, together with a suppression of the anaphylactic symptoms, an almost total lack of the characterstic nuclear and mitochondrial changes in the peribronchiolar mast cells. These observations strongly suggest that at least part of the drug’s protecting effect can be attributed to its inhibiting action on mediator release from mast cells. The possible connection that might exist between mediator release, intracellular cation distribution and the appearance of intranuclear microtubules is discussed.

Changes in intra‐axonal calcium distribution following nerve crush

“…We have used a modification of the basic method described by Borgers et al (1977) in which oxalate is used to chelate calcium before precipitation with pyroantimonate. In any ultrastructural method of this type it is critical to demonstrate that the precipitates found reflect calcium specifically.…”

“…In order to delineate the role of calcium influx in the production of Wallerian degeneration in the distal axon, and to explore the possible role of alterations in calcium flux in the local regulation of the proximal axonal response to injury, we undertook this study of the ultrastructural localization of calcium in nerve following injury using an oxalate-pyroantimonate technique (Borgers et al, 1977). Oxalate is used to specifically chelate calcium during primary fixation while other cations are washed out, followed by fixation with pyroantimonate producing electron dense calcium pyroantirnonate precipitates.…”

Prevention of Halothane-Induced Malignant Hyperthermia in Stress-Susceptible Pigs With 5-Ht2 Antagonists

“…The muscle biopsy specimens of ketanserin treated pigs were further processed for ultrastructural localization of calcium using a combined oxalate-pyroantimonate method (Borgers et al, 1977).…”

Profilo clinico ed economico di oxatomide

“…Il primo meccanismo d'azione studiato consiste nell'antagonismo selettivo dei recettori H 1 -istaminergici [1], che inibisce le azioni dell'istamina, il principale mediatore preformato. L'attività antistaminica dell'oxatomide non si esplica solo a livello recettoriale: il farmaco, infatti, riduce anche il rilascio dell'istamina da parte di mastociti e basofili dopo stimolo, sia immunologo che non [2].…”