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C-Fos-like immunoreactivity in the upper cervical spinal dorsal horn neurons following noxious chemical stimulation of the nasal mucosa in pentobarbital-anesthetized rats.

Noxious chemical stimulation of the rat nasal mucosa with mustard oil induces the expression of Fos-like immunoreactivity in trigeminal and other brain stem neurons which contribute to upper airway protective reflexes such as sneezing, coughing and apnea. To examine the role of nociceptive processing in the upper cervical spinal cord, we investigated the Fos-like immunoreactivity of the brainstem and upper cervical spinal cord following the injection of mustard oil (10 microl of 10%) into the nasal mucosa of pentobarbital anesthetized rats. Two hours after the application of mustard oil, numerous Fos-immunoreactive neurons were found in the mediolateral end of the C1 and dorsolateral division of the C2. The mean numbers of the Fos-immunoreactive neurons in the laminae I and II of the ipsilateral first and second spinal segments were significantly greater than in the control (vehicle treated) rats. There were no significant differences in the mean number of Fos-immunoreactive neurons in the contralateral C1 between the mustard oil and vehicle-treated rats. These results suggest that the C1-C2 dorsal horn neurons process the nociceptive information from nasal mucosa as well as other areas innervated by the trigeminal nerves, and that ethmoidal nerves may contribute to the exclusive conveyance of nociceptive information.

Adjuvants, Anesthesia↗

Expression of prostaglandin D synthase and the prostaglandin D2 receptors DP and CRTH2 in human nasal mucosa.

BACKGROUND: Prostaglandin D2 (PGD2) is released from mast cells during the allergic response. OBJECTIVE: Since PGD2 has been shown to induce nasal congestion in humans, we investigated the distribution of hematopoietic prostaglandin D synthase (PGDS) and the two PGD2 receptors, DP and CRTH2 in human nasal mucosa from healthy subjects and subjects suffering from polyposis, a severe form of chronic rhinosinusitis. METHODS: DP mRNA expression was detected by in situ hybridization while PGDS, CRTH2 and various leukocyte markers expression were revealed by immunohistochemistry. RESULTS: In the normal mucosa, PGDS was only detected in few resident mast cells while CRTH2 was undetectable. In contrast, DP receptor mRNA was detected in epithelial goblet cells, serous glands and in the vasculature. In the nasal mucosa of subjects suffering from polyposis: (1) PGDS was detected in mast cells and other large infiltrating inflammatory cells, (2) both DP mRNA and CRTH2 were detected in eosinophils and (3) CRTH2 was detected on a subset of infiltrating T cells. Although DP mRNA could not be detected in the T cells invading the nasal mucosa, it was found to be expressed in the T cells present in the lymph node and the thymus from normal individuals. CONCLUSION: This study indicates that cells capable of producing PGD2 are present in the nasal mucosa and that both PGD2 receptors, DP and CRTH2, might play a role in inflammatory disease of the upper airways.

Adult↗

Metabolism of dimethylamine in the nasal mucosa of the Fischer 344 rat.

The metabolism of dimethylamine (DMA) in the nasal mucosa of the male Fischer 344 rat was investigated in vitro and in vivo. Microsomes were prepared from liver, and from respiratory and olfactory nasal mucosa. All microsomal preparations metabolized DMA to formaldehyde (CH2O), though DMA was a poor substrate for the N-demethylation reaction when compared to benzphetamine. Phenobarbital-induced microsomes metabolized DMA at a rate less than that of control. The results indicated that DMA was a substrate for both cytochrome P-450 and FAD-containing monooxygenase, and that both enzyme activities were present in all microsomal preparations. Finally, unextractable radioactivity was observed in DNA, RNA, and protein isolated from respiratory and olfactory mucosa of rats exposed to either 10 or 175 ppm of [14C]DMA, suggesting metabolism of [14C]DMA to 14CH20 with subsequent incorporation of 14C into macromolecules. The results demonstrate that the respiratory and olfactory nasal mucosa have the capability to metabolize DMA to CH2O, and indicate that such metabolism occurs in vivo.

Aniline Compounds↗

Effects of topical chlorhexidine applied to the rabbit nasal mucosa.

OBJECTIVE: To search the effects of administration of various concentrations of a wide-spectrum antimicrobial agent, chlorhexidine, to the nasal mucosa. MATERIAL AND METHODS: About 0.20, 0.12, 0.06 and 0.03% concentrations of chlorhexidine gluconate were applied to the rabbit nasal mucosa as one puff twice a day throughout 5 days. Another group, treated with serum saline to the nose, behaved as the control group. On the fifth day following drug administration, specimens were taken from nasal mucosa of the rabbits and examined under light microscope. RESULTS: As a result of comparison between drug treated group and control group, with increasing drug concentrations progressively increased neutrophil infiltration in mucosa, ciliary loss in cells, and occasional metaplasia were observed. CONCLUSION: There is a linear, positive and strong association between concentrations of chlorhexidine and its irritative effects on rabbit nasal mucosa. While 0.20 and 0.12% concentrations of chlorhexidine cause excess irritation on the nasal cavity, 0.06 and 0.03% concentrations of chlorhexidine gluconate causes lower irritation and effects on the animals which have experimentally induced rhinosinusitis must be evaluated.

Aerosols↗

[Study on the sense neuropeptides of nasal mucosa in the allergic rhinitis animal model].

OBJECTIVE: To explore the roles of the sense neuropeptides in allergic rhinitis by observing their changes in the nasal mucosa after cutting the nasal autonomic nervous. METHOD: (1) Twelve rabbits were divided into two groups: group A (sensitized) and group B (control). Four rabbits were killed respectively in one and four weeks in group A after being sensitized . Two rabbits were killed respectively at the same time in group B. Their nasal mucosa were collected for detecting substance P (SP) and calcitonin gene-related peptide (CGRP) by immunohistochemistry. (2) Twenty-four rabbits were divided into two groups: group A (sphenopalatine nerve was cut), group B (sympathetic nerve was cut). Four rabbits were killed respectively in one, two, and four weeks in group A and B. Their nasal mucosa were collected for immunohistochemistry examination. RESULT: (1) SP and CGRP were apparently higher in allergic rabbits than non-allergic ones. (2) SP and CGRP decreased apparently in one and two weeks in group A and appeared no difference in four weeks. There were no apparently difference in group B among four weeks. CONCLUSION: SP and CGRP are correlative with the occurring and developing of all allergic rhinitis.

Animals↗

Response of nasal mucosa to histamine or methacholine challenge: use of a quantitative method to examine the modulatory effects of atropine and ipratropium bromide.

We have developed a new technique for the direct local administration of test solutions to the nasal mucosa and for quantification of nasal secretory responses. This technique, a variation on several published reports of filter paper use, allows simple and rapid determination of drug effects and facilitates the analysis of ipsilateral and contralateral responses to local challenge of the nasal mucosa. We have used this technique to investigate the secretory responses of the nasal mucosa to methacholine and histamine and to determine the effects of atropine and ipratropium bromide (Atrovent nasal spray) on these secretory responses.

Atropine↗

Low temperature decreased tension in isolated hypertrophic human nasal mucosa.

BACKGROUND: The purpose of this study was to evaluate the effect of low temperature on basal tension in isolated hypertrophic human nasal mucosa with or without alpha1-agonist stimulation. METHODS: A tissue bath for isolated nasal mucosa was used. Tension in strips of human turbinate mucosa that were untreated and treated with an alpha1-adrenoreceptor agonist, methoxamine (10 microM), was recorded continuously in a stepwise manner in temperatures that varied from 37 to 10 degrees C. RESULTS: The changes of tension in the human nasal mucosa were found to be temperature-dependent in both untreated and treated tissues, with tension decreasing to 48.6% at 10 degrees C in comparison with 100% at 37 degrees C in the untreated group, the presence of methoxamine (10 microM) had minimal effect. CONCLUSION: Low temperature induced a rapid and reproducible relaxation in isolated hypertrophic human nasal mucosa that was not affected by the presence of the alpha1-agonist methoxamine (10 microM).

Adrenergic alpha-1 Receptor Agonists↗

Norepinephrine content in guinea-pig nasal mucosa response to histamine and methacholine provocation.

The effects of histamine and methacholine (cholinergic substance) on norepinephrine (NE) content in nasal mucosa of the guinea-pig has been investigated. Histamine application for seven consecutive days was found to reduce NE content on both sides of nasal mucosa with bilateral provocation and on the affected side with unilateral stimulation, whereas NE content increased on the unaffected side with unilateral application. Methacholine provocation enhanced NE content on both sides after the bilateral application to nasal mucosa and the affected side after the unilateral application, whereas there was no effect on the other side. Time course evaluation of NE content after unilateral histamine application demonstrated that NE content on the affected side was decreased 30 min after application, but was restored to a normal level by 120 min after application; there was no change on the other side. These results suggest that histamine promotes NE release in nasal mucosa although it possesses the inhibitory effect mediated by the parasympathetic nerve, suggesting that repeated histamine stimulation may deplete NE content and cause a functional disturbance of the sympathetic nerve predisposing patients to the non-specific nasal hypersensitivity observed in nasal allergy.

Animals↗

[Nasal mucosa remodeling in guinea pig model of allergic rhinitis].

OBJECTIVE: To explore the feature of nasal mucosa remodeling in experimental allergic rhinitis. METHODS: Twenty-four male Hartley guinea pigs (4 weeks, 250 -300 g) were randomly divided into four groups (control group and allergen exposure groups 1 - 3), each group had 6 guinea pigs. Allergen exposure animals were sensitized by intraperitoneal (ip) injection of ovalbumin (OVA). Sensitized guinea pigs were subjected to either brief or prolonged exposure to allergen. Both brief exposure group (allergen exposure groups) and prolonged exposure group (allergen exposure group 2 and 3) received a daily intranasal challenge with 5% OVA in 0.9% saline from Day 22 to Day 28, the prolonged exposure group (allergen exposure group 2 and 3) followed by twice weekly exposure to 5% OVA intranasal for an additional 8 and 12 weeks respectively. Control animals were given saline only. At 24 h after the last intranasal challenge, the guinea pigs were killed and the heads of the animals were removed and fixed in 10% neutral buffered formalin for 24 hours, then decalcified in 5% trichloroacetic acid for 10 days. The tissue blocks were embedded in paraffin. The paraffin sections 3 microm thick were stained with hematoxylin and eosin (HE), alcian blue (pH, 2. 6)-periodic acid-Schiff (AB-PAS), and Masson's Trichrome (MT). The infiltrating eosinophils in nasal mucosa were examined, AB-PAS-positive cells in the surface epithelium in nasal septal mucosa were counted. The percentage area of MT stained extracellular matrix in septal mucosa and conchae and damage of epithelium were determined by an image analyzer. RESULTS: The control group only presented a few eosinophils. Significant eosinophil infiltration was observed in the sensitized groups. Compared with control group (intact epithelium 87.7% +/- 11.1%), there was no significant epithelial damage in 1 week exposure group. Significant epithelial damage were observed in 8 and 12 weeks groups (intact epithelium 36.7% +/- 16.9%, 37.9% +/- 12.9%, respectively). An increase in AB-PAS-positive cells was observed in the mucosa of nasal septum in the prolonged allergen exposure groups, but not in the brief allergic inflammation group in comparison with the control. The brief OVA exposure group did not show increased collagen fibrils within the mucosa of nasal septum and conchae. In contrast, after prolonged OVA exposure an increase in matrix was observed. Furthermore, in both the nasal septum and conchae, significant increasing of ECM deposition was found in a further prolonged exposure for 12 weeks compared to 8 weeks. CONCLUSIONS: Epithelial damage, goblet cells hyperplasia and extracellular matrix deposition were observed as the features of remodeling in this guinea pig model of allergic rhinitis.

Animals↗

Deposition of ragweed pollen and extract on nasal mucosa of patients with allergic rhinitis: effect on nasal airflow resistance and nasal mucus velocity.

This study was undertaken to ascertain whether nasal mucus velocity (NMV) could be altered by short-term exposure to antigen. Asymptomatic patients with a history of allergic rhinitis who had a positive cutaneous reaction to ragweed extract were investigated. The plan was to achieve approximately a fourfold elevation of nasal airflow resistance (NAR) with antigen challenge and then obtain serial measurements of NAR and NMV. NMV was not significantly altered when the antigen was introduced by nasal inhalation of (1) ragweed pollen grains, (2) nebulized ragweed extract for 10 breaths, and (3) nebulized ragweed extract for 30 min on each of 3 successive days. When ragweed extract was introduced by direct instillation of the solution into the nose, NMV fell below baseline values at either 0.5 or 1.5 hr, or at both times after administration. Persistence of impairment of mucociliary transport at a time when nasal airway constrictor response had dissipated suggested that a chemical mediator might have been responsible for the alteration of clearance. The failure to demonstrate depression of mucus transport with the inhalation studies might have been due to insensitivity of the radiopaque Teflon disk method or to a qualitatively different allergic reaction to direct instillation of antigen solution.

Adult↗

Increased pressure in venous sinusoids during decongestion of rat nasal mucosa induced by adrenergic agonists.

The haemodynamic effects of sympathetic agonists causing decongestion of the nasal mucosa have been investigated in rats. Access to mucosa was obtained from the dorsal side through a small cavity drilled in the nasal bone. The pressures in the venous sinusoids and in the interstitial fluid of nasal mucosa were recorded by micropuncture technique. The local red cell flux (LDF) was monitored by laser Doppler flowmetry, and the blood volume in the mucosa was measured by radio-labelled erythrocytes and albumin. In control rats the tissue blood volume was 0.25 +/- 0.03 g (g wet wt)-1. The interstitial fluid pressure (IFP) was 2.4 +/- 0.6 mmHg and the average blood pressure in venous sinusoids (Ps) was 12.8 +/- 2.7 mmHg. After topical application of noradrenaline (NA) the local blood volume was reduced to 0.12 +/- 0.03 g g-1. Ps was increased to 18.0 +/- 4.0 mmHg, whereas IFP was maintained and LDF was reduced to 40.4% of control, indicating a greater rise in post than in presinusoid vascular resistance. Blocking of both alpha 1 and alpha 2-receptors by phentolamine caused a rise in mucosa blood volume and in LDF by 16 and 20% of control, respectively. Ps increased significantly to 15.2 +/- 3.3 mmHg. Specific stimulation or blocking of alpha 1-receptors by phenylephrine or prazosin induced similar or slightly smaller vascular responses than NA or phentolamine. The effects of the specific alpha 2-agonist (clonidine) or antagonist (yohimbine) on rat mucosa were small, indicating a domination of the alpha 1-receptors. Thus, application of NA caused a rise in blood pressure in the venous sinusoids of nasal mucosa. As LDF fell simultaneously, the reduced blood volume must be due to an increased tone in the muscular wall of venous sinusoids.

Adrenergic alpha-Agonists↗

Histochemical and lectinhistochemical studies on nasal mucosa of pigs with or without respiratory diseases.

Histochemical and lectinhistochemical examinations were carried out on nasal mucosa of pigs with or without respiratory diseases. As the results, both acid and neutral mucins coexisted in nasal mucosa of normal pigs while acid sialomucins were mainly observed in nasal mucosa of pigs infected with Bordetella bronchiseptica and/or Pasteurella multocida. Lectinhistochemistry revealed that the nasal epithelial cells of normal pigs were rich in N-acetylgalactosamine, fucose and N-acetyl-glucosamine residues which showed a tendency to disappear in porcine cytomegalovirus infection and to increase in atrophic rhinitis, respectively.

Animals↗

Lysozyme producers in nasal mucosa. An immunocytochemical study.

The question of whether or not goblet cells in the nasal mucosa are lysozyme producers has yet to be examined. In the present study, lysozyme was localized by the protein A-gold technique in human nasal mucosa with special attention to goblet cells. Both light and electron microscopic immunostaining revealed lysozyme in the secretory granules of the goblet cells, although far less than the amount present in the serous cells of the nasal glands. We concluded that the nasal glands were the main producer and goblet cells the subsidiary producer of lysozyme in nasal mucosa.

Adult↗

[Distribution of calcitonin gene-related peptidergic terminals in rat nasal mucosa].

The distribution of calcitonin gene-related peptidergic (CGRP) terminals in rat nasal mucosa was observed with immunocytochemistry technique (ABC method). The results showed that CGRP-ergic terminals had extensive localizations along the walls of arterioles and venules, around the acini of glands and between the epithelial cells, with the walls of arterioles having highiest densities of such terminals. The typical morphology of CGRP-ergic terminals was one of multistage branched fibers in the form of rosary varicosities. CGRP immunoreactive neurons were also present in trigeminal ganglion (TG). Based on our observations, it is suggested that CGRP-ergic terminals in rat nasal mucosa are the peripheral fibers originating from the ganglion cells in TG. These fibers may be involved in the perception of local mucosal stimuli and propagation of neural impulses to the central terminals and will then release CGRP in the brain stem. There is also possibility that CGRP may be peripherally released in nasal mucosa and exerts influences on mucosal functions.

Animals↗

Effects of benzalkonium chloride on innate immunity physiology of the human nasal mucosa in vivo.

OBJECTIVE: Benzalkonium chloride (BC) is a preservative commonly used in nasal decongestant sprays. It has been suggested that BC may be harmful to the nasal mucosa. The present study, involving healthy volunteers, examines effects of BC on nasal mucosal end-organ functions. METHODS: Isotonic saline and BC (0.1 mg/mL) were administered acutely to the nasal mucosa using a nasal pool device. Nasal symptoms were determined. Nasal lavage fluid levels of alpha2-macroglobulin and fucose were measured as indices of plasma exudation and glandular secretion, respectively. In addition, BC (0.1 mg/mL) was given as single actuations of 100 microL per nasal cavity three times daily for 10 days. The ability of histamine (0.4 mg/mL) to evoke nasal symptoms and plasma exudation responses was determined before and after the repeated BC administration series. RESULTS: BC produced immediate nasal smart or pain (P < .05), but tolerance to this response developed by repeated administrations. BC increased nasal mucosal output of fucose (P < .05), whereas nasal lavage fluid levels of alpha2-macroglobulin were unaffected. Histamine produced significant symptoms and mucosal exudation of alpha2-macroglobulin (P values < .01), equally before and after the 10 days of BC exposure. CONCLUSIONS: BC in dosages commonly used as preservative in nasal decongestant sprays produced short-term glandular secretion and nasal smart or pain. However, 10 days' frequent exposure to BC was not associated with untoward symptomatic effects, nor was a sensitive mucosal variable such as histamine-induced exudative responsiveness affected by this repeated exposure 1 BC.

Administration, Topical↗

Extensive variations in nasal mucosa in infants with and without recurrent acute otitis media. A scanning electron-microscopic study.

Biopsy specimens of the nasal mucosa from the inferior turbinate of infants aged 2 to 26 months were examined by scanning electron microscopy. The specimens were obtained from 23 clinically healthy infants and compared with those from 43 infants with recurrent acute otitis media (RAOM). Potentially pathogenic bacteria were isolated from 61% of the control subjects and 90% of those with RAOM. Infants with RAOM had about as extensive alterations as the healthy ones. A single healthy child and one with RAOM had what was interpreted as a normal nasal mucosa; all others showed reduced frequencies of ciliated cells, deformation of cilia, extensive loss of normal mucosal epithelium, and metaplasia in their nasal epithelial lining. Severely damaged area could be seen close to more normal ones. Nasal mucosa in clinically healthy infants rarely had a normal appearance, probably due to frequent infections and the fairly long time needed for the repair process. We proposed that the high frequency of damaged, incompletely healed nasal mucosa may constitute an important factor with regard to the susceptibility to further infections.

Biopsy↗

A preliminary report on the effects of paclitaxel-impregnated stents on sheep nasal mucosa.

INTRODUCTION: Traditional frontal sinus stents serve only as mechanical devices. It has been proposed that stents also may serve as drug-delivery systems for the topical application of drugs that minimize postoperative scarring. Paclitaxel (Taxol), which has recognized antiscarring effects, may be incorporated via a polymeric formulation into standard rubber stents. The impact of topically applied paclitaxel on the morphology of the nasal mucosa is unknown. METHODS: An adult sheep model was used for this study. A modified rubber T-tube stent (incorporating paclitaxel at varying dosages) was secured to each side of the septum in four animals (eight sides). An unmodified T-tube was placed on each side of one animal, a T-tube with the drug carrier (but no paclitaxel) was placed on each side of the second animal, and T-tubes with varying paclitaxel were placed on each side of the final two animals. After 4 weeks, animals were killed and the nasal mucosa was harvested. The nasal mucosa was sectioned and stained with hematoxylin and eosin. A pathologist then assessed the nasal mucosa for vascular congestion, glandular atrophy, chronic inflammation, mucosal metaplasia, and mucosal ulceration. RESULTS: No consistent histopathological differences were noted in the specimens. All specimens showed varying degrees of vascular congestion, glandular atrophy, chronic inflammation, and mucosal metaplasia; the paclitaxel-impregnated stents were not consistently associated with more severe mucosal injury. Finally, mucosal ulceration was noted to be very rare in all specimens. CONCLUSION: This preliminary report describes the impact of paclitaxel-impregnated stents on sheep nasal mucosa, which tolerated these stents very well. Because paclitaxel minimizes scarring reactions at very low concentrations, paclitaxel-impregnated stents may prove useful in clinical situations in which frontal sinus stenting is deemed necessary. Additional investigations with animal models, as well as clinical trials, may be warranted.

Animals↗

[Study of the enzyme peptidyl peptidase IV in nasal mucosa].

INTRODUCTION: The endothelial serine protease dipeptidyl peptidase IV (DPP IV) cleaves the tyrosin-prolin dipeptide of several inflammatory mediators and neuropeptides, including neuropeptide Y (NPY), yielding the endogenous Y2-receptor agonist NPY (3-36) which modulates sensory and parasympathetic nerve activity. The aims of the study were to investigate the localisation of DPP IV in human nasal mucosa and to measure in vitro activity of DPP IV in nasal mucosa biopsies from patients suffering from chronic rhinosinusitis. PATIENTS AND METHODS: Using immunohistochemistry we have studied the localisation of DPP IV in human nasal biopsies. The activity of DPP IV was measured in vitro in nasal mucosa samples obtained from 45 patients suffering from chronic rhinosinusitis and compared with the density of inflammatory cell infiltration. RESULTS: Positive immunoreactivity for DPP IV was observed in the human nasal mucosa. Low activity of DPP IV was associated with high density of inflammatory cells in the mucosa of patients suffering from chronic rhinosinusitis. The regressive correlation was statistically significant (p < 0.001). CONCLUSION: Low level DPP IV activity is associated with inflammation of the nasal mucosa. This enzyme may be involved in the pathophysiological mechanism of nasal hyperreactivity and chronic rhinosinusitis.

Adolescent↗