Hironari Shimizu

Effects of Suplatast Tosilate(IPD) on Allergic Sinusitis.

Chronic paranasal sinusitis encompasses a variety of pathologies, and eosinophil infiltration of nasal polyps is characteristic of chronic sinusitis in which allergy is a strong etiologic factor (allergic paranasal sinusitis). Suplatast tosilate is an anti-allergy agent that suppresses production of IgE antibody and inhibits tissue infiltration by eosinophils. In the present study we assessed the efficacy of suplatast tosilate immunohistochemically in surgical specimens of nasal polyps before and after drug therapy to evaluate its efficacy in allergic sinusitis.The subjects were 8 patients with allergic sinusitis associated with nasal polyps. These patients were treated with suplatast tosilate for about three months. Nasal polyps were collected before and after treatment, and 5-μm frozen serial sections were prepared and stained with HE and by immunochemical methods. The number of eosinophils and eosinophil activation were assessed by using EG2 antibody, which recognizes secretory type eosinophilic cationic protein (ECP) alone, as the primary antibody, to investigate eosinophil activation.Infiltration by numerous eosinophils, predominantly in the superficial layer of the lamina propria, was observed in the nasal polyps of allergic rhinitis patients. Significant decreases in the number of eosinophils and the number of EG2-positive cells were observed in the nasal polyps after treatment with suplatast tosilate, and a significant decrease was also observed in the ratio of the number of EG2-positive cells to the number of eosinophils. Thus, suplatast tosilate was shown to have eosinophil tissue infiltration suppressing activity in human nasal polyps, and to also possess inhibitory activity against eosinophil degranulation. Based on these findings, suplatast tosilate suppresses allergic inflammation, which is predominantly manifested by eosinophil infiltration, and was found to be effective in the treatment of allergic paranasal sinusitis.

Wirkung von Stickstoffdioxid auf das Riechepithel

An 8 Wochen alien Wistar-Ratten (n = 35) wurde der Effekt von Stickstoffdioxid (NO2) – einer Hauptkomponente der Luftverschmutzung – auf das Riechepithel untersucht. Die Tiere wurden uber 14 Tage 10 ppm NO2 ausgesetzt (Nationalinstitut fur Umweltstudien, Tsukuba, Japan). Das Riechvermogen der Tiere wurde anschliessend mittels Verhaltensolfaktometrie getestet. Nach der Totung wurden die Riechschleimhaute morphologisch und immunhistochemisch auf das mikrotubulusassoziierte Protein 5 (MAP 5) untersucht. MAP5 wird normalerweise in den neurinalen Zellkorpern und entlang ihrer Neuriten nachgewiesen und als Fruhzeichen eines aktiven axonalen Wachstums gedeutet. Histomorphologisch wurden Veranderungen der olfaktorischen Zilien und eine Erhohung der Anzahl der Bowman-Drusen unmittelbar nach der NO2-Exposition beobachtet. Alle Veranderungen im Riechepithel bildeten sich innerhalb von 14 Tagen nach der Exposition zuruck, jedoch hatten die exponierten Ratten Riechstorungen bis zum 30. Tag. In den Kontrolltieren konnte MAP5 diffus in den Neuriten der Riechzellen nachgewiesen werden, wahrend sich bei den exponierten Ratten MAP5 in signifikant starkerer Konzentration bis zu 30 Tage nach der Exposition fand. Der Nachweis der Aktivitat von MAP5 korrelierte mit der durch Verhaltensolfaktometrie festgestellten Geruchsstorung. Die morphologischen Veranderungen, die sich schnell zuruckbildeten, besassen nur geringe Aussagekraft hinsichtlich der Riechfahigkeit.

Nitrogen Dioxide Exposure's Effect on Olfactory Epithelium.

To investigate the effects of nitrogen dioxide (NO2), which is a major component of air pollution, on the olfactory epithelium, we exposed 38 8-week-old Wistar rats to 10 ppm NO2 for 14 days in an inhalation chamber at the National Institute for Environmental Studies. We performed histological examinations, including immunohistochemistry (microtubule-associated protein 5, MAP5), and behavioral olfactometry to examine the effect of NO2 on the olfactory epithelium. MAP5 is present in the cell bodies of neurons and all along their dendrites and is believed to be involved in the early stage of active axonal outgrowth.Irregular olfactory vesicles and olfactory cilia and increased numbers of Bowmans glands were observed immediately after NO2 exposure. Although the morphology of the olfactory epithelium was almost normal 14 days after exposure, behavioral olfactometry was still abnormal up to 30 days after the exposure. MAP5 was distributed diffusely in the dendrites of the olfactory epithelium in the control rats. In contract, MAP5 was dense in the upper regions of the olfactory epithelium from immediately until 30 days after the exposure. Thus, there was a discrepancy between the morphological changes and the behavioral olfactometry results, while immunoreactive test results with MAP5 were in accord with the behavioral olfactometry results. Our findings indicate that functional olfactory disturbances are not always in accord with morphological changes of the olfactory epithelium.