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Topical corticosteroid eye drops are commonly used for ocular sarcoidosis. That systemic absorption of corticosteroids by eye drops may influence the clinical course of sarcoidosis may be speculated because it has been reported that the serum concentration of corticosteroids after drop administration was dose-related. To evaluate the effects of corticosteroid eye drops on the clinical course of patients with stage I pulmonary sarcoidosis, we compared the serum levels of angiotensin converting enzyme (ACE) and bilateral hilar lymphadenopathy (BHL) on chest radiographs of group CS, which is consisted of patients who received topical therapy of betamethasone in the form of eye drops for anterior uveitis, and group CN, which is consisted of patients who did not receive any medications throughout the entire course of the disease. Although the serum ACE level was not significantly different between groups CS and CN at the time of the diagnosis of pulmonary sarcoidosis, the level of serum ACE in group CS was significantly higher than that in group CN 20 months after the topical corticosteroid treatment (24 IU/ml and 16 IU/ml, respectively). Further, the size of BHL on chest radiography in group CS was significantly larger than that in group CN 20 months after the topical treatment (82% and 37% of before control, respectively). These findings suggest the possibility that the topical corticosteroid therapy influenced the clinical course of pulmonary sarcoidosis, inducing some delay in the spontaneous remission in the long-term course.

TAMURA, G., SAKAI, K., TANIGUCHI, Y., IIJIMA, H., HONMA, M., KATSUMATA, U., MARUYAMA, N., AIZAWA, T. and TAKISHIMA, T. Neurokinin A-Induced Bronchial Hyperresponsiveness to Methacholine in Japanese Monkeys. Tohoku J. Exp. Med., 1989, 159 (1), 69-73-The present study was designed to investigate whether neurokinin A (NKA) and substance P (SP) increase bronchial responsiveness to methacholine (MCh). Before and 1, 2, 3 and 4 weeks after three Japanese monkeys had inhaled 10-8M NKA and 10-8M SP for 2min, bronchial responsiveness to inhaled MCh was evaluated. Pulmonary flow resistance (R1) and dynamic lung compliance (Cdyn) were used as pulmonary function tests. Dose-response curves of R1 to inhaled MCh were shifted to the left 1 to 4 weeks after NKA treatment, compared with that obtained before treatment. However, SP treatment did not change the R1 dose-response curve. Thus, bronchial responsiveness to MCh was increased by inhalation of 10-8M NKA in Japanese monkeys.

In order to elucidate the mechanism of the bronchial response of monkeys to constrictive stimuli, the effects of pretreatment with aerosolized lidocaine, atropine, and isoproterenol were studied. Treatment with aerosolized lidocaine and atropine not only extinguished the cough reflex, but also decreased bronchial susceptibility to aerosolized methacholine. Moreover, the pretreatment with lidocaine blocked the histamine challenge, but atropine did not. The aerosolized lidocaine decreased the bronchoconstriction induced with methacholine, but not with histamine. Pretreatment with over 1% of isoproterenol did not extinguish the cough reflex. However, this dose of isoproterenol did suppress an increase in Rrs due to the challenge of both methacholine and histamine. Isoproterenol also decreased the bronchoconstriction due to the previous challenge by both methacholine and histamine. The antagonistic effects of lidocaine, atropine, and isoproterenol on the broncho-constriction of monkeys are discussed in relation to the subepithelial receptor.

OHTSU, H., MUE, S., TAMURA, G., YAMAUCHI, K., ISHIHARA, T., SATO, K. and TAKISHIMA, T. Measurement of SRS-A Activities in Plasma of Asthmatic Patients. Tohoku J. exp. Med., 1985, 145 (2), 197-203-Ethanol extracts of arterial blood from 20 of 29 asthmatic patients during attacks produced sustained contractions of the guinea pig ileum. These contractions were inhibited by FPL 55712, a specific antagonist of slow reacting substance of anaphylaxis (SRS-A). SRS-A activity was significantly higher during attack than during remission. Reverse-phase high pressure liquid chromatography (HPLC) was performed on two extracts which had shown high SRS-A activity with bioassay. One extract showed double peaks, which had retention times identical to those of leukotriene (LT) C4 and LTD4. The other extract showed a single peak, which had a retention time identical to that of synthetic LTC4.

Bronchial responses to inhaled histamine significantly increased on the 2nd day and the 7th day after influenza virus vaccination in monkeys. Bronchial responses to inhaled methacholine also significantly increased on the 14th day and the 21st day after the vaccination.