Morihiro Irifune

Effects of Capsaicin Desensitization on Nasal Allergy-like Symptoms and Histamine Release in the Nose Induced by Toluene Diisocyanate in Guinea Pigs

Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like symptoms of sneezing and watery rhinorrhea and decreased the histamine content of the nasal mucosa in guinea pigs. However, in the animals pretreated with capsaicin (capsaicin desensitization) before sensitization with TDI, nasal allergy-like symptoms were not induced. Capsaicin desensitization also inhibited histamine release in the nasal mucosa induced by TDI. These findings suggest that antidromic impulses of capsaicin-sensitive sensory nerves stimulated by TDI cause histamine release from mast cells in the nasal mucosa, resulting in nasal discharge and sneezing in guinea pigs. Thus neurogenic inflammation via an axon reflex in the nose may contribute to the pathogenesis of vasomotor rhinitis.

Laryngeal tuberculosis: a report of 15 cases.

Laryngeal tuberculosis is usually a complication of pulmonary tuberculosis. Recent studies have described a change in the clinical features of laryngeal tuberculosis. We present 15 cases of laryngeal tuberculosis treated at the Osaka Prefectural Habikino Hospital between 1993 and 2000. The results showed a mean age of 51 years, a male predominance by 2.75 to 1, and a 20% incidence (n = 3) of negative chest radiographic findings. The prominent presenting symptom was hoarseness (73.3%), and systemic symptoms were relatively rare. Seven patients showed ulcerative lesions, 5 showed granulomatous lesions, and the remaining 3 showed nonspecific inflammatory lesions in the larynx. Laryngeal lesions did not show any predilection for specific laryngeal sites in our series. In contrast to earlier studies, our study shows variations in clinical features of laryngeal tuberculosis. Physicians should consider tuberculosis in the differential diagnosis of laryngeal disease.

Histamine content, synthesis and degradation in nasal mucosa and lung of guinea‐pigs treated with toluene diisocyanate (TDI)

We have reported the presence of a histamine synthesizing enzyme, histidine decarboxylase (HDC), and histamine degrading enzymes, histamine N‐methyltransferase (HMT) and histaminase (diamine oxidase, DAO) in human nasal mucosa and the histamine content of the mucosa. In this study, we demonstrate the influences of the toluene diisocyanate (TDI) treatment on the histamine content and these enzyme activities in guinea‐pigs as an animal model of respiratory hypersensitivity. Application of TDI to the nasal vestibuli induced intense nasal allergy‐like and mild asthma‐like responses in TDI‐sensitized guinea pigs. Increases in the histamine content and HDC and HMT activities were observed in the nasal mueosa and lung of TDI‐sensitized guinea pigs. No apparent changes in the histaminase activities were observed in either the nasal mucosa or the lung. These data suggest that the turnover rate of histamine is increased in the nasal mucosa and the lung of guinea pigs with respiratory hypersensitivity.

Nasal mucosa sensitization with toluene diisocyanate (TDI) increases preprotachykinin A (PPTA) and preproCGRP mRNAs in guinea pig trigeminal ganglion neurons

Toluene diisocyanate (TDI) induces respiratory allergy in mammals. Using immunohistochemistry and in situ hybridization histochemistry, the present study examined effects of nasal mucosa sensitization by TDI on the immunoreactivity for substance P (SP) and calcitonin gene-related peptide (CGRP) and on the expression of their mRNAs in guinea pig trigeminal ganglion and their terminals. Single intranasal application of TDI (acute experiment) did not induce nasal allergy-like behaviours and failed to cause changes of SP and CGRP immunoreactivity and in the expression of preprotachykinin A (PPTA) mRNA and preproCGRP mRNA coding for SP and CGRP respectively in the trigeminal ganglion neurons. However, repeated application of TDI (chronic experiment) caused a dramatic increase of SP and CGRP immunoreactivity in peripheral neurites of sensory nerves in the nasal mucosa but a slight increase in the spinal trigeminal nucleus, a decrease of the same immunoreactivities in the cell bodies of the trigeminal ganglion neurons, and an increase of the expression of PPTA and preproCGRP mRNA in the same neurons. These findings suggest that chronic exposure of the nasal mucosa to TDI apparently causes enhancement of both the biosynthesis of SP and CGRP and their axonal transport in the trigeminal system.

Histamine content, synthesis and degradation in human nasal mucosa

Histamine content and enzyme activities of histamine metabolism, histidine decarboxy‐lase (HDC), histamine N‐methyltransferase (HMT) and histaminase (diamine oxidase, DAO) in human nasal mucosa were determined with a highly sensitive and specific fluorescent method which was combined with high performance liquid chromatography. Histamine content and HDC activity were determined in 10 specimens of nasal polyp, nine specimens of maxillary sinus and five specimens of inferior turbinate. HMT and histaminase activities were determined in 15 specimens of nasal polyp, nine specimens of maxillary sinus and five specimens of inferior turbinate obtained during surgical therapy. Histamine and activities of HDC, HMT and histaminase were detected in all specimens except the case of histaminase activity in one specimen of nasal polyp. The mean values of histamine content and activities of HDC, HMT and histaminase of human nasal mucosa were 137.3 nmol/g wet weight, 26.3 fmol/min/mg protein, 26.4 pmol/min/mg protein and 0.5 pmol/min/mg protein, respectively. Histamine content in the mucosal tissue of the maxillary sinuses was significantly higher than that of nasal polyps or inferior turbinates. There were no significant differences in HDC activities among three kinds of nasal mucosa. Activities of HMT and histaminase, including their kinetic constants (Km and Vmax values for histamine) indicated that HMT has a greater potential than histaminase for histamine degradation in the human nasal mucosa. The presence of these enzymes suggests that these activities constitute an important modulating factor in histamine mediated allergic and inflammatory reactions in human nasal mucosa.

Neurogenic Inflammation in Nasal Allergy: Histochemical and Pharmacological Studies in Guinea Pigs: A review

The role of neuropeptides in nasal allergy was examined in guinea pigs by histochemical and pharmacological study. Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like behaviors: sneezing and watery rhinorrhea, and decreased histamine content in the nasal mucosa in guinea pigs sensitized with TDI. The immunoreactivity of substance P (SP) and calcitonin gene-related peptide (CGRP) in the nerve terminals in the nasal mucosa was increased after intranasal application of TDI. We also observed a decrease in the immunoreactivity of SP and CGRP, and an increase in their mRNA expression in the trigeminal ganglion neurons. These findings indicate that exposure to TDI enhanced the biosynthesis of both SP and CGRP in the trigeminal ganglion neurons and their axonal transportation to the terminals in the nasal mucosa. In animals pretreated with capsaicin before sensitization, TDI did not induce nasal allergy-like behaviors and histamine release in the nasal mucosa. Since capsaicin depletes SP and CGRP in the sensory nerves, this finding indicates neuropeptide-mediated histamine release in the nasal mucosa. All these findings suggest that, on exposure to TDI, the antidromic release of SP and CGRP in the nasal mucosa triggers the release of histamine, resulting in the development of symptoms of nasal allergy.

Arachidonic Acid Metabolites in Human Nasal Polyps

Arachidonic acid metabolites (AAMs) are known to be involved in inflammation. It is suggested that AAMs play an important role in the pathogenesis of nasal polyp. We have measured the levels of prostaglandin E2, 6-keto prostaglandin F1 alpha, thromboxane B2, leukotriene B4 and a mixture of leukotriene C4, D4 and E4 in both nasal polyp and maxillary sinus mucosa by radioimmunoassay. Our results showed that arachidonic acid metabolism in nasal polyps from allergic patients was more active than that from non-allergic patients. The arachidonic acid metabolism in nasal polyp was more active than in maxillary sinus mucosa among allergic patients. On the other hand, arachidonic acid metabolism in maxillary sinus mucosa was more active than that in nasal polyps among non-allergic patients. On the basis of these results, we hypothesized the causal mechanisms of nasal polyps as follows: The nasal polyp in allergic patients is caused by primary inflammation of the nasal mucosa, and sinusitis occurs secondarily. In non-allergic patients, the primary side of inflammation is located in the maxillary sinus mucosa, leading to the secondary formation of nasal polyp.

Tuberculous Otitis Media: Clinical Aspects of 12 Cases

The clinical features of tuberculous otitis media (TOM) have changed. This study was performed to evaluate changing trends in the clinical manifestations of TOM. We reviewed a series of 12 cases of TOM (13 ears) recently treated at Osaka Prefectural Habikino Hospital. The results showed a mean age of 41 years and a male predominance of 1.4 to 1. Central or total perforations of the tympanic membrane were observed in most cases, but none of the patients had multiple perforations. Nine patients (75%) had active pulmonary tuberculosis. Normal lung status or inactive pulmonary tuberculosis was significantly more frequent in the older age group. Diagnosis of primary TOM required more time than that of secondary TOM. Most cases of primary TOM had high infectiousness of the primary lesion. We summarize the clinical features of patients who should be evaluated for TOM.

Nasal mucociliary clearance in patients with upper and lower respiratory diseases.

The nasal mucociliary clearance was measured in 71 subjects with nasal allergy (NA) (56 subjects without sinusitis and 15 with sinusitis), 12 subjects with bronchial asthma (BA) (7 without, 5 with) and 7 subjects with aspirin-induced asthma (AIA) using a saccharin test. The results were compared with those obtained in a control group of 15 healthy subjects. The saccharin time (ST) values for both NA and BA subjects without sinusitis (16.9 +/- 9.9 and 20.1 +/- 9.4 min, respectively) did not differ from that of the healthy subjects (16.3 +/- 5.3 min). However, ST values in NA and BA subjects with sinusitis (37.6 +/- 22.9 and 57.0 +/- 6.7 min, respectively) were significantly higher than those of healthy subjects (p < 0.01). The ST value of AIA subjects (13.0 +/- 5.4 min) showed no significant difference compared with that of the control group. These results suggest that allergic reactions do not influence the nasal mucociliary clearance and that the property of mucus complicated with sinusitis is important. Also, sinusitis observed in AIA may be somewhat different from ordinary sinusitis complicated with NA and BA.

Topical treatment of nasal polyps with a beclomethasone dipropionate powder preparation

The clinical efficacy of a topical preparation consisting of beclomethasone dipropionate (BDP) powder and a mucous membrane adhesive agent (hydroxypropylcellulose, HPC) for nasal polyps was examined. For 1 week, in 31 patients with bilateral nasal polyposis, the clinical efficacy of the topical BDP-HPC powder treatment was examined. The effect of this treatment on the histology of the nasal polyps was also investigated. The controls were six patients with bilateral nasal polyposis, who underwent identical surgery without prior use of the topical steroid therapy. Polyp shrinkage and improvement of some nasal symptoms (rhinorrhea, ease of noseblowing, and nasal blockage) were observed with the topical treatment. Significant clinical improvement (P < 0.05) was seen in the group treated with topical BDP HPC powder compared with the untreated control group. Histological examination of the excised nasal polyps in both groups demonstrated no clear differences attributable to BDP HPC powder. The topical treatment of nasal polyps with BDP HPC powder is a useful conservative therapy.