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Neutral endopeptidase activity and concentration of sensory neuropeptide in the human nasal mucosa.

Human nasal mucosa biopsy samples were studied by biochemical and histological methods to determine whether the concentration of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) as a marker of sensory nerves was dependent on the activity of neutral endopeptidase-like enzyme (NEP-LE). Mucosal samples from the middle turbinate were obtained from 32 patients undergoing functional endoscopic nasal surgery for non-allergic chronic rhinosinusitis. The degree of symptoms related to nasal obstruction, rhinorrhea and headaches was recorded. The number of inflammatory cells in each biopsy sample was evaluated by conventional histopathological examination. CGRP-LI was measured by radioimmunoassay. The activity of NEP-LE was evaluated in vitro using [3H] Leu5-enkephalin as substrate. A good correlation was observed between increased concentrations of CGRP, abundant inflammatory cells and the intensity of symptoms (R2 = 0.80). A low activity of NEP-LE was associated with a high concentration of both inflammatory cells and CGRP, suggesting that NEP-LE activity was reduced during inflammation. These observations further support the hypothesis that reduced degradation of sensory neuropeptides could be involved in the pathophysiological mechanisms of non-specific chronic rhinosinusitis.

Calcitonin Gene-Related Peptide↗

Postjunctional alpha 2-adrenoceptors in blood vessels of human nasal mucosa.

Human nasal mucosa has various types of blood vessels and is a good tissue for demonstrating receptors for many vasoactive substances, including alpha-adrenoceptors. In contrast to the large contractile response induced by alpha 1-agonists, our studies have shown that alpha 2-agonists produce a small maximal contraction. This alpha 2-induced response was easily blocked by alpha 1-antagonists, indicating that it is evoked, at least partially, by the stimulation of alpha 1-adrenoceptors. Noradrenaline (NA)-induced contractions could not be abolished by either alpha 1- or alpha 2-antagonists alone, but were almost completely blocked by the combination of both antagonists. This suggests the presence of postjunctional alpha 2-adrenoceptors. The low-maximal responsiveness to alpha 2-agonists and calcium independency of NA-induced contractions were distinct from our former results obtained on canine nasal specimens.

Adrenergic alpha-Agonists↗

[Diagnosis and pathogenetic aspects of the Kartagener syndrome based on nasal mucosa biopsies].

Nasal mucosa biopsies were taken from a child with Kartagener's syndrome. The biopsies were prepared for light and electron microscopic examination. Unfixed cryocut sections were stained with the magnesium-activated ATPase reaction. There was a partial loss of the dynein arms within the cilia. Many compound cilia were present and, sometimes, defects of the mitochondria of the lining epithelial cells as well as the glandular cells were observed. Histochemically the ATPase reaction was at first completely negative and sometime later it was greatly reduced within the lining and the glandular epithelial cells, especially in the apical border. Biopsies from children with cystic fibrosis and allergic rhinitis served as controls.

Biopsy↗

Controlled noxious chemical stimulation: responses of rat trigeminal brainstem neurones to CO2 pulses applied to the nasal mucosa.

The nasal mucosa of halothane-anesthetized rats was stimulated with defined CO2 pulses. Recordings were performed from single trigeminal brainstem neurons to characterize their responses to this controlled chemical irritation. All cells examined with this stimulus displayed graded discharges to increasing concentrations of CO2. Enhanced responses were obtained in a group of neurons when the duration of the interstimulus interval was increased. The application of chemical irritants, notably mustard oil or acetic acid induced vigorous ongoing discharges in all cells tested. The CO2 stimulation method described here thus provides an ideal model for the quantitative physiological and pharmacological examination of chemically induced nociception.

Acetates↗

[Effects of glucocorticoid on tissue remodeling of nasal mucosa of chronic rhinosinusitis with nasal polyposis after endoscopic surgery].

OBJECTIVE: To evaluate the effects of glucocorticoid on tissue remodeling of nasal mucosa from patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) after endoscopic surgery. METHODS: Nasal mucosa obtained from 30 cases of CRSwNP during nasal endoscopic surgery were considered as preoperation group. These patients were equally divided into two groups after surgery, ie. glucocorticoid group and contrast group. Uncinate process mucosa samples from 6 patients during septoplasty were considered as normal control group. Epithelial damage and expressions of transforming growth factor-beta1 (TGF-beta1) and collagen III were studied by light microscopy and immunohistochemistry. RESULTS: In nasal mucosa samples of preoperation group, epithelial damage showed 90% (27/30) of stage 3 and 10% (3/30) of stage 2; TGF-beta1 positive cells and collagen III positive basement membrane with more than 20 microm were seen in 87% (26/30) and 97% (29/30) of samples, respectively. No significant difference was observed in morphology of nasal mucosa and expressions of TGF-beta1 and collagen III between glucocorticoid group and contrast group at 1th month after surgery. At 3th month after surgery, epithelial damage displayed 53% (8/15) of stage 3, 33% (5/15) of stage 2 and 14% (2/15) of stage 1 in contrast group; however, 93% (14/15) of stage 0 and 7% (1/15) of stage 1 in glucocorticoid group. The difference of epithelial damage between two groups was significant (Uc = 4.481, P < 0.05). The amount of TGF-beta1 positive cell was markedly higher in contrast group than in glucocorticoid group (t = 2.32, P < 0.05). The thickness of basement membrane was above 20 microm in 67% of contrast group (10 cases) and 27% of glucocorticoid group (4 cases); the difference between the two groups was significant (P < 0.05). CONCLUSIONS: Tissue remodeling is present in nasal mucosa of CRSwNP after endoscopic surgery. Early and appropriate administration of glucocorticoid plays an important role in inhibition of tissue remodeling and prevention of relapse. Postoperative follow-up should not be less than 3 month.

Administration, Intranasal↗

[Effect of over dose sex hormone on rabbit's nasal mucosa].

The nasal respiratory mucosa of thirty-eight rabbits were studied with histopathological method. Among those rabbits, sixteen were injected with estrogen, sixteen androgen, and the other eight as control. The nasal respiratory mucosa of all animals were observed under light microscope, seven of them were observed under transmission electron microscope. Animals injected with estrogen showed the following changes: the nasal respiratory mucosa became thick. The submucosa was spongy and edematous, the capillaries were dilated and congested. The tunical glands were hyperplastic and hyperactive. Numerous newly-produced collagen fibrils deposited in the lamina propria. After one or two months of drug administration, some thick-walled arterioles appeared. The effect of androgen on nasal mucosa of the animals was similar to that of estrogen in some respects, but the effect on the vessels was slight, no newly-produced collagen fibril deposition. Many epithelial cells and glandular cells were degenerated. The effect on nasal respiratory mucosa between male and female animals seemed to be different.

Animals↗

Sympathetic nerve disturbance and fine structure of adrenergic nerve terminals in nasal mucosa after experimentally-induced nasal hypersensitivity.

Electron microscopic observations were used to study the relation between the adrenergic nerve terminal and the effector cell in the nasal mucosa of toluene diisocyanate-sensitized and non-sensitized guinea pigs. Adrenergic nerve terminals were abundantly distributed in the adventitia of arterioles, however, no synapse formation was observed in smooth muscle cells of the mesothelium, i.e., effector cells. Adrenergic nerve terminals were observed separated from smooth muscle cells of the mesothelium of the arteriole by distances of 1000 A-3000 A. Neurotransmission by the sympathetic nerve in the nasal mucosa is assumed to be by diffusion of norepinephrine (NE) or by diffusive synaptic conduction. The mechanism of sympathetic hypofunction in the nasal mucosa in nasal hypersensitivity is assumed to be as follows: Released histamine directly stimulates H-1 receptors at the sympathetic nerve terminal, leading to the release of NE. Once released, NE is not readily reabsorbed, and is gradually depleted in the sympathetic nerve terminal, leading to hypofunction of the sympathetic nerve.

Adrenergic Fibers↗

Adrenergic and cholinergic receptors in human nasal mucosa in cases of nasal allergy.

We have demonstrated for the first time alpha-1 adrenergic, beta-adrenergic, and muscarinic cholinergic receptors in human nasal mucosa obtained from patients with nasal allergy or sinusitis. Using the radioligand 3H-prazosin, 3H-dihydroalprenolol (3H-DHA) and 3H-quinaclidinyl benzilate (3H-QNB), we determined the receptor densities (Bmax) and affinities (KD) of alpha-1, beta, and muscarinic receptors. There was an increased number of muscarinic receptors and a decreased number of alpha-1, beta receptors in patients with nasal allergy but not in those with sinusitis. Binding affinities (KD) of alpha-1, beta, and muscarinic receptors were unchanged in all patients with nasal allergy and sinusitis. Disorders of the autonomic nerve receptors appear to play a definite role in pathology of nasal allergy.

Adult↗

Pharmacological characterization of alpha 2-adrenoceptor-mediated responses in pig nasal mucosa.

1. Pig nasal mucosal strips were incubated with alpha-adrenoceptor antagonists followed by alpha2-adrenoceptor agonist concentration-response curves. 2. Contractions elicited by the alpha2-adrenoceptor agonists BHT-920 (pD2 = 6.16 +/- 0.07), UK 14,304 (pD2 = 6.89 +/- 0.13) and PGE-6201204 (pD2 = 7.12 +/- 0.21) were blocked by the alpha2-adrenoceptor antagonist yohimbine (0.1 microm). In contrast, the alpha1-adrenoceptor antagonist prazosin (0.03 microm) had no effect on the BHT-920-, UK 14,304- and PGE-6201204-induced contractions, but blocked the contractile response to the alpha(1)-adrenoceptor agonist phenylephrine (pD2 = 5.38 +/- 0.04) and the mixed alpha1- and alpha2-adrenoceptor agonist oxymetazoline (pD(2) = 6.30 +/- 0.22). 3. The alpha2-adrenoceptor antagonist yohimbine (0.01-0.1 microm, pA2 = 8.04), alpha2B/C-adrenoceptor antagonist ARC 239 (10 microm, pK(b) = 6.33 +/- 0.21), alpha2A/C-adrenoceptor antagonist WB 4101 (0.3 microm, pK(b) = 8.01 +/- 0.24), alpha2A-adrenoceptor antagonists BRL44408 (0.1 microm, pK(b) = 6.82 +/- 0.34) and RX 821002 (0.1 microm, pKb = 8.31 +/- 0.35), alpha2C-adrenoceptor antagonists spiroxatrine (1 microm, pKb = 7.32 +/- 0.32), rauwolscine (0.1 microm, pKb = 8.16 +/- 0.14) and HV 723 (0.3 microm, pKb = 7.68 +/- 0.14) inhibited BHT-920-induced contractions in pig nasal mucosa. 4. The present antagonist potencies showed correlations with binding affinity estimates (pKi) obtained for these antagonists at the human recombinant alpha2A- and alpha2C-adrenoceptors (r = 0.78 and 0.83, respectively) and with binding affinity estimates (pKd) obtained in pig native alpha2A- and alpha2C-monoreceptor assays (r = 0.85 and 0.78, respectively). No correlation was observed for the alpha2B-subtype. 5. In conclusion, contractile responses to phenylephrine, BHT-920, UK 14,304, PGE-6201204 and oxymetazoline indicate that alpha1- and alpha2-adrenoceptors are present and mediate vasoconstriction in pig nasal mucosa. Furthermore, correlation analysis comparing antagonist potency in pig nasal mucosa with affinities for human recombinant alpha2-adrenoceptors and native pig alpha2-adrenoceptors suggest that alpha2A- and alpha2C-adrenoceptor subtypes constrict pig nasal mucosa vasculature.

Adrenergic alpha-2 Receptor Antagonists↗

Permeability of porcine nasal mucosa correlated with human nasal absorption.

The Ussing chamber diffusion system was used as a model to study the apparent permeability across porcine nasal mucosa of eight drugs and molecules with different physicochemical characteristics, namely insulin, lidocaine, nicotine, PEG 4000, propranolol, sumatriptan, melagatran and an amino diether. A weak correlation was found between the apparent permeability coefficients and the corresponding literature data on the fraction absorbed after nasal administration in humans. In the case of passively transported drugs, a closer correlation was found than for the substances where other mechanisms such as carrier-mediated transport or possible efflux were involved. Factors influencing the correlation between in vitro and in vivo data are discussed and the importance of electrophysiological control of the viability status of the excised mucosa is emphasised. Although caution has to be exercised in view of the limitations of the in vitro system, it seems to be a useful tool when evaluating different factors influencing permeability of nasal mucosa.

Absorption↗

T cell dominated inflammatory reactions in the bronchioles of asymptomatic asthmatics are also present in the nasal mucosa.

Endobronchial and nasal mucosa biopsies were obtained from 5 patients with clinically-stable, diagnosed asthma (ATS criteria). A comparison was made of the presence and distribution of immunocompetent lymphocytes and macrophages within each sample. The distribution of immunocompetent cells within the nasal biopsies of the asthmatic patients reflected a very similar inflammatory infiltrate to that seen in the bronchial biopsies. Significantly raised numbers of T lymphocytes, CD45RO + lymphocytes, RFD1 + macrophage-like cells and RFD7 + macrophages were seen in both the nasal mucosa and the bronchial biopsies. Increases in HLA-DR expression were also seen in the nasal mucosa biopsies from asthmatics although the increases over normal did not reach statistical significance. It is concluded that inflammation present in the nasal mucosa of asymptomatic asthmatics exhibits cellular characteristics also seen in endobronchial biopsies. This observation offers the possibility that mucosal biopsy may be an alternative and less invasive approach for studying the cells involved in the bronchial inflammatory reaction that possibly predisposes asthmatics to bronchial hyper-responsiveness.

Adolescent↗

The origin of vasoactive intestinal polypeptide (VIP) nerves in the feline nasal mucosa.

The feline nasal mucosa is richly supplied with vasoactive intestinal polypeptide (VIP) immunoreactive nerve fibres. The nerves occur in the subepithelial connective tissue, around small blood vessels and around the acini of seromucous glands. The ptergopalatine ganglion contains numerous VIP immunoreactive nerve cell bodies among non-reactive ones. Extirpation of the ganglion results in an almost complete disappearance of VIP-containing nerves in the nasal mucosa, while sectioning of the preganglionic nerve (Vidian nerve) does not affect the number of nasal VIP nerves. Hence the bulk of VIP nerve fibers in the nasal mucosa derive from cell bodies located in the pterygopalatine ganglion.

Animals↗

Regeneration of nasal mucosa following mechanical injury.

Nasal mucosa is a subject of surgical operation for patients with nasal disorders. However, our knowledge about the regeneration of nasal mucosa after such a mechanical injury is still limited. In this study we investigated the recovery or regenerative process of nasal mucosa in rabbits after mechanical injury on the basis of ultrastructural as well as functional observations. Complete recovery of nasal mucosa was obtained in 5 days if the basal cells and basement membrane were intact. When the total layer of nasal mucosa was injured mechanically, regenerative stratified epithelium covered the defect in 1 week, new ciliated cells appeared in 3 weeks, and complete regeneration was observed at 6 weeks. At 3 weeks when the first appearance of cilia was observed, the beating activity of the cilia was in the normal range. In conclusion, we observed a great regeneration ability following mechanical injury in the nasal mucosa. The process of regeneration in the nasal mucosa after mechanical injury appears to depend on whether the basal cells and basement membrane are intact or not.

Animals↗

Study of eosinophil activation in nasal mucosa in patients with perennial nasal allergy: effects of CO2 laser surgery.

Carbon dioxide (CO2) laser surgery has been shown to be clinically effective in the treatment of nasal allergy. To investigate the mechanisms of eosinophil infiltration and activation underlying the therapeutic effects of CO2 laser surgery, we examined changes in the cytological profile of nasal mucosa after surgery. Twenty-two patients with perennial nasal allergy against house-dust mites underwent two or three rounds of laser surgery at 1-month intervals on an outpatient basis. The following parameters were evaluated at each visit: (i) improvement of clinical symptoms (nasal obstruction, rhinorrhea, and sneezing), (ii) percentage of infiltrating eosinophils in nasal mucosa, and (iii) the degree of EG2+ cells and intracellular adhesion molecule 1 (ICAM-1) expression by immunocytochemistry. All clinical symptoms significantly decreased after surgery. Significant reductions in eosinophil infiltration (p < 0.01) and the percentage of EG2+ cells (p < .005) were observed also. However, the degree of ICAM-1 expression in epithelial cells was not changed. These results suggest that CO2 laser surgery partially reduced the allergic reactions, leading to improvement of clinical symptoms.

Adolescent↗