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Seasonal variation of sensitivity of nasal mucosa in pollinosis.

The purpose of the present paper is to examine whether hypersensitivity of nasal mucosa observed in nasal allergy is cause or result of allergic reaction using the subjects with pollinosis in which the exposure period can be clearly distinguished. Subjects are 30 cases of Japanese cedar pollinosis and orchard grass pollinosis and 25 normal controls. Inferior turbinate of unilateral nasal cavity was stimulated by a piece of filter paper soaked with 0.02 ml of 0.1% and 0.5% histamine hydrochloride. Frequency of sneezing and amount of nasal secretion were measured quantatively and were compared among the subjects with pollinosis in season, off season, and normal controls. In subjects with pollinosis when stimulated with extrinsic histamine, frequency of sneezing and amount of nasal secretion were markedly enhanced in season, but during off season no apparent difference was observed compared with normal subjects. Relationship between frequency of sneezing and amount of nasal secretion indicated positive correlation (alpha less than 0.01). Positive correlation was also observed in amount of nasal secretion in ipsilateral and contralateral nasal cavity when unilateral nasal cavity was stimulated with histamine (alpha less than 0.01). Hyperrhinorrhea was closely related with hypersensitivity of nasal mucosa. The present study showed that hypersensitivity of nasal mucosa characteristic of nasal allergy is nonspecific and that it is largely a result of antigen antibody reaction, which in turn works in causing exaggeration of the allergic symptoms and allergic reaction through vicious cycle.

Antigens↗

The effect of cold water immersion on the nasal mucosa.

The response of the nasal mucosa to cold water immersion is not well known. We have attempted to document this response in normal individuals. Seventeen individuals with no history of nasal disease or allergy were studied. All subjects were asked to perform sustained cold water (15 degrees C) immersion of their hand and forearm on the side of the obstructed nostril for a period of 5 min. The nasal cross-sectional area was measured on both sides of the nose using an acoustic rhinometer. The individuals were then rested for at least 30 min and the test repeated with immersion of the opposite hand. There was a significant fall in nasal cross-sectional area on the side of immersion (median change = 0.32 cm2, P = 0.0003) with a significant rise in nasal cross-sectional area on the none test side (median change = 0.35 cm2, P = 0.0003). There were no significant differences between these results and those obtained by immersion on the opposite side. The results indicate that cold water immersion produces nasal obstruction and that both afferent and efferent arms of this reflex are side-specific.

Blood Pressure↗

Pharmacological characterization of postjunctional alpha-adrenoceptors in human nasal mucosa.

BACKGROUND: Functional alpha1- and alpha2-adrenoreceptor subtype pharmacology was characterized in an in vitro human nasal mucosa contractile bioassay. METHODS: Nasal mucosa was obtained from 49 donor patients and mucosal strips were placed in chambers filled with Krebs-Ringer solution and attached to isometric force transducers. RESULTS: Nonselective a-adrenoreceptor agonists epinephrine, norepinephrine, and oxymetazoline produced concentration-dependent contractions of isolated human nasal mucosa (pD2 = 5.2, 4.9, and 6.5, respectively). The alpha2-adrenoreceptor agonist BHT-920 (10 microM)-induced contractions were blocked by yohimbine (0.01-1 microM) and prazosin (0.01-1 microM) inhibited the contractile response to the alpha1-adrenoreceptor agonist phenylephrine (10 microM). Histological analysis showed that phenylephrine and BHT-920 differentially contracted the arteries and veins of human nasal mucosa, respectively. CONCLUSION: Our results indicate that functional alpha1- and alpha2-adrenoceptors are present and functional in human nasal mucosa. The alpha2-adrenoceptors display a predominant role in contracting the veins and the alpha1-adrenoceptors appear to preferentially constrict the human nasal arteries.

Adrenergic alpha-Agonists↗

The Vdelta1 T cell receptor repertoire in human nasal mucosa.

The gamma/delta T cells play important roles as the first line of defence in mucosal immunity. Vdelta1 bearing T cells comprise the major population of gamma/delta T cells in the human nasal mucosa. Recently, it was reported that certain receptors are predominant at given anatomical locations. The purpose of this study was to elucidate the gamma/delta T-cell receptor repertoire in human nasal mucosa. Nasal epithelia were scraped and peripheral blood were obtained from three healthy volunteers. We performed reverse-transcription polymerase chain reaction (RT-PCR) analysis and characterized the junctional sequences of Vdelta1 T-cell receptor (TCR) transcripts. Vgamma and Vdelta gene usage in intraepithelial lymphocytes (IELs) in right and left nasal mucosa were almost the same, but they were different from those in peripheral blood lymphocytes (PBLs). The VDJ sequence of nasal Vdelta1 T-cell receptor transcripts showed diversity and were different for each individual. Vdelta1 in the IELs were rearranged to Jdelta1 and Vdelta1 in the PBLs were rearranged not only to Jdelta1 but also to Jdelta3. Vdelta1 sequences in the IELs in the nasal mucosa showed no overlap with those in the PBLs. These results indicate that gamma/delta T cells in the nose are organ specific lymphocytes.

Adult↗

[Regulation of the swelling mechanism in the inferior turbinate of human nasal mucosa].

BACKGROUND: The swelling mechanism of human nasal mucosa is based on a complicated vascular system and regulated by a variety of classical and peptidergic transmitters as well as by endothelial transmitters. The aim of this study was to elucidate this mechanism taking into account the distribution of these substances and the morphology of the different vessels. METHODS: Tissue specimens of human inferior turbinates were evaluated by light and electron microscopy. We used frozen sections to localize enzymes of the transmitter synthesis by histochemical and immunocytochemical methods. The distribution of classical neurotransmitters, neuropeptides (calcitonin-gene-related-peptide, neuropeptide Y, substance P and vasoactive intestinal polypeptide), enzymes producing neuronal NO (neuronal nitric oxide synthase, nicotine-amid-adenine-dinucleotide-phosphate-diaphorase) as well as endothelial transmitters such as endothelin and endothelial nitric oxide were examined. For ultrastructal examination the specimens were fixed in glutaraldehyde und osmium tetroxide, embedded in araldide, cut and double contrasted. RESULTS: Most of the axons and immunoreactivity of transmitters were located in the arterial part of the human nasal vascular system. In venous vessels only a spare innervation was observed, whereas in the subendothelial muscular bolsters of the cushion veins a rich nerve supply could be detected. Near the fenestrated subendothelial and periglandular capillaries no axons were found. Nasal vasculature is supplied by a equilibrated aminergic and cholinergic innervation. Mainly arterial vessels showed reactions to antibodies directed against endothelial transmitters. CONCLUSION: Because of the dense innervation of arteries and subendothelial venous muscular bolsters we conclude that the swelling mechanism of human nasal mucosa is mainly regulated by these structures. A dual (endothelial and neuronal) control exists in arterioles whereas the control in the subendothelial muscular swellings of the cushion veins appears to be mainly neuronal. The swelling of the nasal mucosa is achieved by an simultaneous relaxation of all smooth muscle cells, which leads to dilatation of arteries as well as venous sinuses. The drainage of the vascular bed is reduced by the venous muscular bolsters protruding into the lumen of the venous sinuses. Vice versa, a contraction of all smooth muscle cells leads to a contraction of the arteries and, consecutively, to a reduction of blood supply. Simultaneously the muscular bolsters are torn out of the lumen of venous sinusoids allowing blood drainage to be increased: nasal concha decongests.

Airway Obstruction↗

Permeability of insulin entrapped in liposome through the nasal mucosa of rabbits.

The permeability of liposome entrapping insulin through the nasal mucosa of rabbit has been studied and compared with the permeability of insulin solution with or without pretreatment by sodium glycocholate (GC). Insulin entrapped in liposome was not detected in the receiver cell using the diffusion cells with the nasal mucosa. On the other hand, permeability of insulin entrapped in liposome increased after the pretreatment of GC. The phospholipids which result from liposomes, were not observed in the receiver. Also, the GC remaining in the nasal mucosa was measured. Considering the mechanism of permeation of insulin entrapped in liposome through the nasal mucosa, the GC remaining in the nasal mucosa may cause the lysis of liposomes.

Administration, Intranasal↗

Benzalkonium chloride in nasal decongestive sprays has a long-lasting adverse effect on the nasal mucosa of healthy volunteers.

Twenty healthy volunteers participated in the present study on the long-term effects of a nasal decongestive spray composed of either a combination of oxymetazoline nasal spray and benzalkonium chloride or of oxymetazoline nasal spray alone. Three months before the present study the participants had undergone treatment with nasal decongestants for 4 weeks. Ten of the subjects had been treated with oxymetazoline nasal spray without benzalkonium chloride and 10 of them had been treated with oxymetazoline nasal spray with benzalkonium chloride. In a double-blind study the subjects who had been treated with oxymetazoline nasal spray and benzalkonium chloride were again treated with the same combination of substances as before, and the subjects who had been treated with oxymetazoline nasal spray alone were also treated again with oxymetazoline nasal spray alone, but on this occasion only for 10 days. Three variables were studied before and after the 10 days of treatment, i.e. nasal mucosa congestion, nasal reactivity and symptom scores. It was found that only the subjects who were treated with the combination of oxymetazoline nasal spray and benzalkonium chloride had increased nasal stuffiness, estimated by symptom scores and measurements of nasal mucosa swelling after 10 days of treatment. It is concluded that a nasal decongestant spray composed of a combination of vasoactive substance and benzalkonium chloride has a long-term adverse effect on the nasal mucosa.

Administration, Intranasal↗

[Study on expression and regulation of atrial natriuretic factor (ANF) gene in nasal mucosa].

Using 32P labelled rat ANF cDNA probe, the ANF gene transcripts in rat nasal mucosa and the effect of glucocorticoid and estrogen on the ANF gene transcripts was examined by Dot blot and Northern blot hybridization. Further more, the gene expression of ANF in nasal mucosa tissues of some patients with nasal diseases were also examined. The results showed that nasal mucosa contained ANF mRNA which could synthesize ANF. Both estrogen and glucocorticoid could enhance ANF gene expression in nasal mucosa with dose dependance. The gene expression of ANF in nasal polyps and inferior turbinate mucosa of patients with nasal polyps was more evident than that in other pathological conditions. The clinical significance of ANF in nasal mucosa was also discussed.

Adolescent↗

[Scanning electron microscopic observation of the nasal mucosa microvasculature].

The normal microvasculature of a rat nasal mucosa was investigated in microcorrosion casts viewed under a scanning electron microscope. The nasal mucosa microvasculature was composed of arterioles, venules, capillaries and cavernous sinuses. Both arterioles and venules ran parallel to the long axis of the nasal concha. The capillaries and cavernous sinuses were particularly abundant and interconnected by means of numerous short anastomoses to form a rich dense network. A characteristic feature of the nasal mucosa vasculature was that the capillaries possessed a fenestrated structure, the venules and arterioles were porous, and the surface of cavernous sinuses formed a three dimensional lace-work structure.

Animals↗

Comparison of norepinephrine responsiveness of mucosal veins in vivo with that of isolated mucosal tissue in vitro in guinea pig nasal mucosa.

BACKGROUND: The vascular responsiveness of nasal mucosa has been determined frequently by using isolated mucosal tissues although it is not clear whether the response of the whole tissue truly reflects the response of the vasculature (especially veins) in mucosa. In this study, the in vivo responsiveness of mucosal veins was compared with in vitro responsiveness of isolated mucosal tissue in guinea pig nasal septa. METHODS: The in vivo venous responsiveness to norepinephrine (NE) of guinea pig nasal septal mucosa was measured by changes in the diameters of mucosal veins, stereomicroscopically. The in vitro responsiveness to NE of isolated nasal septal mucosae from guinea pigs also was determined by standard organ-bath technique. RESULTS: Application of NE induced concentration-dependent contractile responses both in vivo and in vitro with the pD2 (negative logarithm for 50% effective concentration [M] of NE) values of 5.23 +/- 0.29 and 5.00 +/- 0.17, respectively. CONCLUSION: The equal potencies obtained by the in vivo and in vitro experiments suggest that an increase in tension of isolated nasal mucosal tissue might be caused by the contraction of mucosal veins. Both the in vivo and the in vitro methods used in this study might be useful for determining vasoreactivity of nasal mucosa in experimental animals.

Adrenergic alpha-Agonists↗

Uptake of ovalbumin-conjugated starch microparticles by pig respiratory nasal mucosa in vitro.

The uptake of ovalbumin-conjugated starch microparticles (OVA-MP) was studied after application to porcine respiratory nasal mucosa in vitro. Nasal mucosa from freshly slaughtered pigs was mounted in horizontal Ussing chambers, which permit monitoring of the viability of the tissue exposed to microparticles and ensure that the microparticles are deposited on the mucosa. The antigen-conjugated starch microparticles have previously been shown to produce strong mucosal, cellular and systemic immune responses to conjugated model antigens following oral administration. Intranasal administration of vaccines for mucosal immunisation is an interesting alternative to oral administration, since nasal delivery systems generally require lower doses of antigen and the site of application is better suited for protection against air-borne antigens. Most of a nasally administered dose is deposited on the surface of the respiratory area of the nasal mucosa. It is therefore important to examine whether the microparticles are taken up in this area and, if so, by which cell type. Confocal laser scanning microscopy and transmission electron microscopy (TEM) of the nasal tissue both showed intracellular OVA-MP in non-ciliated epithelial cells after 45 min' incubation. The morphology of the cells in the TEM preparations did not support the presence of either M cells (specialised antigen sampling cells) or adjacent lymphocytes. Anticytokeratin-18 (Ac18) was used as a potential M cell marker. However, there was no indication of Ac18 binding to M cells, but it did bind to mucus-producing cells in the respiratory nasal mucosa. In conclusion, OVA-MP were taken up intracellularly by non-ciliated epithelial cells in the nasal respiratory mucosa of pigs, in vitro.

Animals↗

[Measurement of blood flow in nasal mucosa].

OBJECTIVE: To determine the amount of blood flow in the human nasal mucosa and its change in patients with nasal polyps and allergic rhinitis. METHODS: Using the Ameflow-H2, the amount of blood flow in nasal mucosa was examined in 98 normal adults, 18 cases of nasal polyps and 14 cases of allergic rhinitis before and after application of the vaso constrictor. RESULT: Before the application of the vaso constrictor, blood flow of nasal mucosa of patients with nasal polyps and allergic rhinitis was lower than that of healthy people (P < 0.01). After using the vaso constrictor, the amount of blood flow was decreased in all cases with a significant decrease in patients with nasal polyps. CONCLUSION: Ameflow-H2 may be the best tool to measure nasal blood flow than other devices. The method is technically simple, less traumatic, and repeatable.

Adolescent↗

Involvement of cytochrome P450 2E1-like isoform in the activation of N-nitrosobis(2-oxopropyl)amine in the rat nasal mucosa.

Induction of tumours in the nasal olfactory region of MRC rats by N-nitrosobis(2-oxopropyl)amine (BOP) is inhibited by orchiectomy and restored by testosterone. These results suggest the involvement of a sex-specific enzyme in BOP bioactivation in rat nasal mucosa. The present study was undertaken to identify this enzyme. Enzyme-linked immunosorbent assay (ELISA) and the metabolism of known substrates (p-nitrophenol) pointed to a microsomal cytochrome P450 (P450) 2E1-like isoform as a candidate enzyme. A correlation was found between the enzyme activity in nasal mucosal microsomes and serum testosterone levels. Four times more activity was detected in the nasal mucosa than in the liver of male rats. Vanillin inhibited the activity of the nasal mucosal enzyme to a greater extent than that of the liver enzyme. The overall results suggest that a nasal mucosal P450 2E1-like isoform is involved in BOP metabolism.

Animals↗

Distribution of noradrenergic nerve fibers in canine nasal mucosa following selective neurectomies.

In this study, we have used noradrenergic histofluorescence and selective neurectomies of the vidian, ethmoid and caudal nasal nerves to evaluate the distribution of postganglionic sympathetic fibers in the canine nasal mucosa. In conjunction with the histochemical localization of the noradrenergic fibers in the nasal mucosa after vidian neurectomy, the norepinephrine content of the mucosa was also evaluated using high-performance liquid chromatography. Unilateral neurectomy of the superior cervical ganglion (SCG) resulted in the unilateral disappearance of all noradrenergic histofluorescence in the nasal mucosa, while no morphological changes in noradrenergic fibers could be identified after neurectomy of the cervical sympathetic trunk 1 cm below the SCG. Ethmoid neurectomy caused the disappearance of noradrenergic fibers of the upper third of the nasal mucosa, while vidian neurectomy resulted in a partial loss of noradrenergic fibers in the lower two-thirds of the nasal mucosa. The loss was chiefly in the area adjacent to venous sinusoids and was responsible for 50% of the norepinephrine content of this tissue. We concluded that all the postganglionic sympathetic fibers are from the ipsilateral SCG. Some of them travel via the ethmoid nerve and innervate the upper third of the nasal mucosa. The remaining fibers travel via the vidian nerve and perhaps the vessel walls of the supplying arteries and innervate the lower two-thirds of the nasal mucosa. The vidian nerve chiefly innervates the venous sinusoids of the lower two-thirds of the nasal mucosa.

Adrenergic Fibers↗

[Changes in the partial pressure of oxygen of the nasal mucosa caused by stellate ganglion block].

Stellate ganglion block (SGB) is clinically used for the treatments of various lesions diseases. SGB gives rise to nasal obstruction of transient duration. It is also suggested that derangement of the autonomic nervous system underlies nasal allergy. In order to study the hemodynamics of the nasal mucosa after SGB, two groups of the subjects, i.e. healthy volunteers and patients with nasal allergy, were included for evaluation of the partial pressure of oxygen of nasal mucosa (PtsO2) after SGB. Simultaneous evaluations were done to assess the nasal patency in the normal group and the temperature at the anterior tip of the inferior nasal turbinate in the nasal allergy group. The results thus obtained are summarized as follows: 1) In the normal group, SGB was resulted in a reduction in nasal patency on the blocked side and a significant increase in PtsO2 when compared with the non-blocked side. The PtsO2 remained higher than normal after although nasal patency was restored. 2) The PtsO2 at rest was lower in the nasal allergy group than in the normal group. 3) Changes in PtsO2 following SGB were similar in the two groups. 4) A parallelism was noted between changes in the temperature at the tip of inferior nasal turbinate and those in PtsO2 during SGB. These results suggest that SGB augments the arterial blood flow in the nasal mucosa. The compromised nasal mucosa of nasal allergy patients is in a state of hypoxia but showed virtually the similar improvement in circulation after SGB as noted in the nasal mucosa of normal subjects.

Adolescent↗

[The expression and significance of eotaxin gene in nasal mucosa and CCR3 in bone marrow in model of allergic rhinitis].

OBJECTIVE: To study the expression and significance of Eotaxin gene in nasal mucosa and CCR3 in bone marrow in model of allergic rhinitis. METHOD: Twenty SD rats were randomly divided into allergic rhinitis (AR) group and normal control group. Ovalbumin (OVA) sensitized and challenged rats were used as the model of allergic rhinitis. The leucocytes in the smears of bone marrow and peripheral blood were counted, and the expression of CCR3 in bone marrow was detected by immunohistochemistry. The pathologic samples of nasal mucosa were stained with HE. The expression of Eotaxin mRNA in nasal mucosa was detected by in situ hybridization (ISH), and the expression of Eotaxin in nasal mucosa was detected by immunohistochemistry. RESULT: The ratio of eosinophils to white cells in bone marrow smears of AR group was significantly higher than that of normal control group (P < 0.01). The ratio of eosinophils to white cells in peripheral bloods mears of AR group was significantly higher than that of normal control group (P < 0.01). Eotaxin positive cell and the expression of Eotaxin mRNA in nasal mucosa of AR group were significantly higher than that of normal control group (P < 0.01). The expression of Eotaxin mRNA significantly positively correlated with the expression of Eotaxin (r = 0.804, P < 0.01). The number of Eotaxin positive cells in nasal mucosa was significantly positively correlated with the number of eosinophils in nasal mucosa of AR group (r = 0.795, P < 0.01). The ratio of CCR3 positive cells to white cells in bone marrow smears of AR group was significantly higher than that of normal control group (P < 0.01). The ratio of CCR3 positive cells to white cells was significantly positively correlated with the ratio of eosinophils to white cells in bone marrow smears of AR group (r = 0.736, P < 0.05). CONCLUSION: The expression of Eotaxin and Eotaxin mRNA in nasal mucosa increased, and the expression of CCR3 in bone marrow increased in the model of allergic rhinitis. It supplies a cooperation between CCR3 and Eotaxin to allow rapid mobilization of a pool of bone marrow eosinophils followed by recruitment to the nasal mucosa.

Animals↗

[The difference between response of nasal mucosa to specific antigen and non-specific stimulation].

To examine the difference between response of nasal mucosa to specific antigen and that to non-specific stimulus in the same patient, specific nasal provocation was performed using the house dust antigen disk while nasal respiratory resistance was continuously measured by Rhinograph. On the other hand, non-specific nasal provocation was performed with inhalation of methacholine while nasal respiratory resistance was continuously measured with Astograph. Thereafter the resulting response curves were analyzed. Subjects were 12 males and 9 females, who had nasal obstruction, watery rhinorrhoea and sneeze, and were proved to have allergic rhinitis by house dust. To analyze specific response curve, primary nasal respiratory resistance (Rrs.N), reacting time (Ta) and slope signifying increase of nasal respiratory resistance (delta Rrs.N) were used as parameters. To analyze non-specific response curve, primary nasal respiratory resistance (Rrs.N.cont), minimum dose of methacholine that caused an increase of nasal respiratory resistance (Dmin.N) and slope signifying increase of nasal respiratory resistance (Sd.N) were used as parameters. Ta and Dmin.N reflect sensitivity of nasal mucosa. Their values become smaller, it means sensitivity of nasal mucosa becomes higher. Delta Rrs.N and Sd.N reflect reactivity of nasal mucosa. Their values become larger, it means reactivity of nasal mucosa becomes larger.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Vascular effects of slow reacting substance (SRS) in the cat nasal mucosa and the appearance of a SRS-like principle in cat nasal secretion on nerve stimulation.

Stimulation of parasympathetic secreto-vasomotor nerve fibres in cat nasal mucosa produced nasal secretions with biological activity similar to cat paw SRS. The biologically active principle was purified by ethanol extraction, Amberlite XAD-2 and anion exchange chromatography. It had elution characteristics common with cat paw SRS but different to those of prostaglandin F2 alpha. The biological activity on the guinea pig ileum was antagonized by FPL 55712. In the cat intraarterial administration of cat paw SRS resulted in a dose-dependent but modest increase in nasal blood flow whereas local blood content was not affected. Provided SRS has similar effects on human nasal blood flow the importance for SRS as a mediator for nasal congestion in allergic rhinitis or parasympathetically induced vasomotor rhinitis seems less likely.

Angiotensin II↗