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Expression of cytochrome p450 and other biotransformation genes in fetal and adult human nasal mucosa.

Despite recent progress in the identification and characterization of numerous nasal biotransformation enzymes in laboratory animals, the expression of biotransformation genes in human nasal mucosa remains difficult to study. Given the potential role of nasal biotransformation enzymes in the metabolism of airborne chemicals, including fragrance compounds and therapeutic agents, as well as the potential interspecies differences between laboratory animals and humans, it would be highly desirable to identify those biotransformation genes that are expressed in human nasal mucosa. In this study, a global gene expression analysis was performed to compare biotransformation enzymes expressed in human fetal and adult nasal mucosa to those expressed in liver. The identities of a list of biotransformation genes with apparently nasal mucosa-selective expression were subsequently confirmed by RNA-polymerase chain reaction (PCR) and DNA sequencing of the PCR products. Further quantitative RNA-PCR experiments indicated that, in the fetus, aldehyde dehydrogenase 6 (ALDH6), CYP1B1, CYP2F1, CYP4B1, and UDP glucuronosyltransferase 2A1 are expressed preferentially in the nasal mucosa and that ALDH7, flavin-containing monooxygenase 1, and glutathione S-transferase P1 are at least as abundant in the nasal mucosa as in the liver. The nasal mucosal expression of CYP2E1 was also detected. These findings provide a basis for further explorations of the metabolic capacity of the human nasal mucosa for xenobiotic compounds.

Adult↗

[Bioelectric properties of excised rabbit nasal mucosa].

The water flow across the respiratory epithelia is an important determinant of the efficiency of mucociliary clearance. Bulk water flow has been shown to be coupled to net ion flux. We studied ion transport across rabbit nasal mucosa by measuring bioelectric properties using Ussing chambers. Results were summarized as follows. (1) Compared with tracheal mucosa, nasal mucosa exhibited lower potential difference (p less than 0.01), lower short-circuit current (p less than 0.05), and higher conductance (p less than 0.01). (2) Ouabain 10(-4)M inhibited short-circuit current when added to the submucosal bath of Ussing chambers, and amiloride decreased short-circuit current to about 40% when added to the mucosal bath. (3) When the bubbling of the solution was changed from 95%O2, 5%CO2 to 100%N2, short-circuit current remarkably decreased. (4) A significant positive correlation existed between temperature ranging from 33 degrees C to 41 degrees C and short-circuit current (r = 0.46, p less than 0.02).

Amiloride↗

In vivo optical coherence tomography of the nasal mucosa.

BACKGROUND: Optical coherence tomography (OCT) is an emerging imaging modality that uses light to produce in vivo high-resolution cross-sectional images (7 microm) of tissues to depths of up to 3 mm. OCT is analogous to ultrasound, but relies on interferometry and low-coherence optical sources to produce images of tissue structure at the histological level. METHODS: In this study, OCT was used to image the mucosa overlying structures in the nasal cavity to obtain information regarding normative in vivo tissue microstructure. An OCT system using a Michaelson interferometer and a 1.3-microm broadband light source was incorporated into a fiber-optic imaging device that was inserted into the nasal cavity. Cross-sectional tomographic images of the anterior and posterior nasal septum, turbinates, and vestibule were acquired in 44 patients in either the office or the operating room during surgical endoscopy. RESULTS: OCT images of the nasal mucosa identified the distinct boundaries between the epithelium, lamina propria, and underlying bone/cartilaginous tissue. Within the lamina propria, features consistent with glands, ducts, and blood vessels were clearly identified. In patients who underwent decongestant therapy, before and after images showed distinct morphological changes in the mucosa. The thickness of the epithelium was tabulated, as well. CONCLUSION: This study establishes the potential of using OCT to produce high-resolution images of the nasal mucosa. As an in vivo tissue microstructural imaging modality, OCT may be valuable in studying the impact of allergic and infectious disease on the nasal mucosa and monitoring its response to pharmacologic therapy.

Adolescent↗

Extensive interstitial collagen deposition on the basement membrane zone in allergic nasal mucosa.

To clarify whether tissue remodelling of the nasal mucosa is caused by allergic inflammation or not, we studied the amount and distribution of collagen in human nasal mucosa of 13 perennial allergic patients and 13 non-allergic subjects. The total amount of collagen and other proteins in nasal mucosa was determined by absorbency at 540 nm and 605 nm of a solution eluted from tissue sections stained with sirius red and fast green. Distribution of collagen type I, III and IV was observed by immunohistochemistry. The thickness of the basement membrane zone underlying epithelia was histologically estimated. Results were as follows: i) There was no significant difference in the total amount of collagen between allergic and non-allergic subjects. ii) Although there was no obvious change in localization of the three types of collagen, extensive immunoreactivity for types I and III collagen was observed at subepithelial basement membrane zone in allergic subjects. iii) The thickness of the basement membrane zone, which corresponds to regions positive for types I and III collagen antibodies, was statistically significantly greater in allergic subjects than in non-allergic ones. We thus concluded that tissue remodelling occurs in the allergic nasal mucosa, and that it is especially obvious in the basement membrane zone.

Adolescent↗

[Cytologic evaluation of nasal mucosa in healthy newborns].

Cytological evaluation of the nasal mucosa is one of the methods used in the diagnosis of upper respiratory diseases. Cytological examination of the nasal mucosa in very young children have sporadically been performed. In our study the evaluation was performed in 4 hospitals in 3 towns (Warsaw, Czestochowa, Bielsko-Biała) in Poland. Cytograms of 105 infants age 1-7 days of both sexes were evaluated. All the infants were born naturally, on time and were healthy, according to the opinion of physicians. The course of pregnancies and birth-giving were considered as normal. There were no history of allergic diseases in the families in each case. Cytograms of the nasal mucosa of 1-7 days old infants differ from these of adults and older children. Either columnar cells or neutrrophils are prevalent in cytograms of the healthy newborn children. Goblet cells do not occur. Cytological evaluation of nasal mucosa as non-invasive and easy to perform examination can be very useful in screening of the very young children from the group with a risk of respiratory system disorders including allergic diseases.

Adult↗

Capsaicin-, resiniferatoxin-, and lactic acid-evoked vascular effects in the pig nasal mucosa in vivo with reference to characterization of the vanilloid receptor.

Nasal cavity volume, mucosal and superficial skin blood flow as well as renal splenic vascular effects of capsaicin, resiniferatoxin and lactic acid were investigated, using a novel in vivo pig model. The present results show that locally intraarterially injected capsaicin, resiniferatoxin and lactic acid evoke similar vasodilatory responses, although with different duration, in the nasal mucosa and superficial skin as well as an increase in heart rate and mean arterial blood pressure. Nasal vascular responses evoked by capsaicin, resiniferatoxin and lactic acid were unaffected by the cyclooxygenase inhibitor diclofenac. Moreover, chlorisondamine did not alter the nasal vasodilatory responses evoked by capsaicin and lactic acid. However, chlorisondamine abolished sympathetic reflex-mediated vasoconstrictor effects of capsaicin in the spleen and kidney. Lactic acid-evoked vasodilation in the nasal mucosa and skin was inhibited by the 8-37 fragment of calcitonin gene-related peptide, a calcitonin gene-related peptide-receptor antagonist. Lactic acid-evoked vasoconstriction in the spleen and kidney was reduced but not abolished by chlorisondamine, suggesting that the effects of lactic acid are not exclusively reflex-mediated. Capsazepine did not inhibit the vasodilatation in the nasal mucosa evoked by capsaicin and lactic acid. [3H]Resiniferatoxin bound to pig nasal mucosa membranes with an affinity of 134 pM in a non-cooperative fashion; this binding behaviour contrasted to the apparent positive cooperativity (a Hill coefficient of 2.2) of specific resiniferatoxin binding to pig spinal cord preparations. Specific [3H]resiniferatoxin binding to nasal mucosa membranes was fully inhibited by capsaicin (Ki = 5 microM) and lactic acid (IC50 at pH 5.0) but not by capsazepine (up to 10 microM), in accord with the physiological findings. Capsazepine, by contrast, displaced [3H]resiniferatoxin from spinal vanilloid receptors with an affinity of 3 microM. These findings show the presence of vanilloid receptors in the pig nasal mucosa and suggest heterogeneity in the properties of vanilloid receptors in the pig. Furthermore, lactic acid evokes vascular effects similar to those of capsaicin and resiniferatoxin, possibly via interaction of protons and/or proton-generated substances at vanilloid receptors with a subsequent release of calcitonin gene-related peptide.

Animals↗

Influence of age on the production of interleukin-8-like chemokine (GRO/CINC-1) in rat nasal mucosa.

The ability of the nasal mucosa to produce various cytokines has been shown to correlate closely with the capacity to regulate an inflammatory condition in the nasal cavity. Immune senescence is characterized by a dysregulation of the immune system. This change is reflected by the altered production of cytokines during aging. We measured the in vivo production and gene expression of IL-8-like cytokines (GRO/CINC-1) in nasal lavages and mucosa from young (2- to 4-week-old and 11- to 15-week-old) and older (81-to 98-week-old) rats by using enzyme-linked immunosorbent assays and reverse transcription-polymerase chain reactions. Significant increases of GRO/CINC-1 levels were found in unstimulated nasal lavages of the older rats compared to that of the 2- to 4-week-old animals. GRO/CINC-1 showed time-dependent production with lipopolysaccharide (LPS) stimulation in nasal lavages. The GRO/CINC-1 production reached a plateau by 4 h with LPS in any group. However, the manner of the initial time course showed no significant differences among these three groups. At the time of peak production of GRO/CINC-1, messenger RNA for the GRO/CINC-1 was found to be induced in the nasal mucosa. These findings may be important for understanding the mechanisms of the altered immune response and inflammation in the nasal cavity associated with aging.

Aging↗

Effects of female hormones on the muscarinic and alpha 1-adrenergic receptors of the nasal mucosa. An experimental study in guinea pigs.

During pregnancy aggravation of nasal allergic symptoms is occasionally observed in subjects with nasal allergy. To evaluate the effect of female hormones on the muscarinic receptor and the alpha 1-adrenergic receptor of the nasal mucosa, receptor binding assay was performed using the nasal mucosa of pregnant guinea pigs and of male guinea pigs; the latter were treated either with estrogen or with progesterone. Pregnancy induced a significant decrease of the density of the alpha 1-adrenergic receptor of the nasal mucosa (p less than 0.05). Estrogen induced a significant increase of the density of the muscarinic receptor (p less than 0.05), while progesterone induced a significant decrease of the density of the alpha 1-adrenergic receptor of the nasal mucosa of guinea pigs. When similar changes of the receptor can be induced by female hormones in the nasal mucosa of the human subjects, this may facilitate secondary development of hyperreactive nasal symptoms in subjects who have been sensitized before without apparent nasal symptoms.

Animals↗

Keratin and involucrin in preneoplastic and neoplastic lesions. Distribution in the nasal mucosa of nickel workers.

Nasal mucosal biopsy specimens encompassing normal and pathological epithelia were obtained from nickel workers, a population with an increased incidence of carcinomas of the respiratory tract. The immunohistochemical detection of keratins was carried out using monoclonal antibodies AE1 and AE3. The antibody AE1 stained only the basal cells of normal mucociliary epithelium. Regular metaplasias showed an increased stain with AE3; all layers of the surface epithelium were stained. The dysplastic and neoplastic lesions exhibited an extraordinary increase in the staining patterns with AE3 and to a lesser extent with AE1. Involucrin, which was absent from the normal pseudostratified epithelium, appeared in all metaplastic-dysplastic lesions and in keratinized areas of carcinomas. The combined detection of keratins and involucrin proved useful in detecting the degree of maturity and differentiation of preneoplastic and neoplastic lesions of the nasal mucosa.

Antibodies, Monoclonal↗

[Autonomic innervation of the vessels of the nasal mucosa: current concepts].

The nasal cycle enables the conditioning of air breathed in. It depends on the vascular vegetative innervation. Whilst its central diencephalic origin is probable, its mechanics remain mysterious. The involvement at the loco-regional level of short circuits ensuring the anatomical links between the vegetative, sensitive and cellular systems of the nasal mucosa is the basis of a new approach to chronic rhinological pathologies and certain facial algias.

Autonomic Nervous System↗

[Histochemical study of human nasal mucosa].

The histochemical study of the fetal nasal mucosa collected from fetus of different months is reported. The concentration of succinic dehydrogenase and acid phosphatase in nasal epithelium kept pace with the fetal growth which explained a steady improving metabolism and secretory activity of the fetal nasal mucosa. On the other hand, activities of alkaline phosphatase in the mesenchymal cells, the fibroblasts and the glandular cells were getting weaker and weaker indicating the functional maturation of the fetal nasal mucosa. During the sixth month, mucins occur red in the glands, which showed the establishment of the secretory function in the nasal mucous glands.

Acid Phosphatase↗

Comparison of intranasal and transdermal estradiol on nasal mucosa in postmenopausal women.

OBJECTIVE: To compare nasal symptomatology and function and local concentrations of estradiol (E2), estradiol receptor (ERalpha), vasoactive intestinal peptide (VIP), substance P (SP) and neuropeptide Y (NPY) in nasal biopsies of 20 postmenopausal women complaining of paradoxical nasal stuffiness before and after treatment with intranasal or transdermal E2. DESIGN: Twenty healthy postmenopausal women willing to start hormone therapy (HT) were allocated to one of two groups, using a computer-generated randomization list. Ten postmenopausal women were treated with transdermal 17beta-estradiol 50 microg daily plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group A). Ten postmenopausal women were treated with intranasal 17beta-estradiol 300 microg/day (one spray delivery of 150 microg per nostril) plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group B). Fourteen fertile women undergoing nasal mucosa biopsy during plastic surgery were used as controls for the immunohistochemical evaluation (Group C). All women in groups A and B underwent evaluation of nasal stuffiness score, mucociliary transport time, rhinoscopy, and active anterior rhinomanometry at the beginning of the study and after, VIP, SP, and 6 months of HT. Nasal biopsies and evaluation of local concentrations of E2, ERalpha NPY were performed in groups A and B before and after 6 months of HT and in group C. RESULTS: Both intranasal and transdermal HT improve nasal symptomatology and nasal mucosa appearance and reduce mean mucociliary transport time. The effectiveness of intranasally administered therapy at improving nasal function is significantly better than transdermal therapy. In comparison with premenopausal controls, untreated postmenopausal women of group A and B showed significantly decreased immunopositivity for E2, ERalpha, and SP. HT induced a significant increase in E2, ERalpha, VIP, and SP and a decrease in NPY immunopositivity. Intranasal therapy was associated with a significantly higher immunopositivity for VIP and SP. CONCLUSIONS: HT improves nasal function and symptomatology in postmenopausal women with paradoxical nasal stuffiness, modulating nasal mucosa function through an action on cholinergic, adrenergic, and sensory peptides. Intranasally administered HT is more effective at improving nasal function than transdermal HT.

Estradiol↗

Electron microscopic study of the normal and allergic nasal mucosa.

Electron microscopic studies of the human nasal mucosa have complemented earlier histological and histochemical studies. In this paper, the fine structural details observed in different tissue components are described and discussed in relation to the function of the nasal mucosa under normal and pathological conditions. The physiological changes in the anterior part of the inferior turbinate which occur under the influence of air currents differ clearly from the electron microscopic picture of respiratory mucosa with typical ciliated epithelium. The fine structure of the allergic nasal mucosa differs according to the stage of the allergic reaction; the characteristic changes are described both after different time intervals following intranasal allergic testing with positive reaction as well as in patients with seasonal or perennial nasal allergy of longer duration.

Humans↗

Phenotypic expression of proteoglycan in mast cells of the human nasal mucosa.

The phenotypic expression of the proteoglycan of human mast cells in the nasal mucosa and normal skin was analysed using histochemical techniques. Nasal mucosa was obtained from normal subjects, from patients with seasonal allergic rhinitis before and during the pollen season and from patients with nasal polyps. In the latter groups, specimens were taken from both polyp tissue and adjacent nasal mucosa. Formaldehyde treatment blocked the cationic dye binding in 75-84% of the mast cells located in the nasal mucosa, as compared to the optimum fixation with IFAA (iso-osmotic formaldehyde-acetic acid). A significantly lower degree of blocking of dye binding was obtained in the human skin where 45% of the mast cells were susceptible to formaldehyde treatment (P less than 0.01). The mast cells of the polyp tissue also showed a relatively low degree of blocking (54%), which was significantly lower than the blocking of mast cells of the nasal mucosa taken from the same individuals (P less than 0.05). Staining of serial tissue sections in Alcian Blue containing graded concentrations of MgCl2 was used to determine the critical electrolyte concentration (CEC) of the dye binding, defined as the salt concentration at which the staining of 50% of the mast cells is extinguished. The CEC of the skin mast cells was 0.64M MgCl2 which is significantly higher than that of the mast cells of the nasal mucosa of normal subjects [0.49M (P less than 0.05)], allergic subjects [0.52M (P less than 0.01)], patients with polyp disease [0.52M (P less than 0.01)] and the polyp tissue proper [0.57M (P less than 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Determination of differentially expressed proteins and it's significance among chronic sinusitis, nasal polyps and normal nasal mucosa].

OBJECTIVE: To investigate the differentially expressed proteins among chronic sinusitis, nasal polyps and normal nasal mucosa by means of proteomic technology, and select the candidate biomarkers of chronic sinusitis and nasal polyps. METHODS: Proteins extracted from chronic sinusitis, nasal polyps and normal nasal mucosa were separated and the differentially expressed proteins were identified by series of proteomic tools, including immobilized pH4-7 gradient two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis, modified coomassie brilliant blue staining, images scanning by the Image Scanner apparatus, PDQuest analysis software, peptide mass fingerprinting based on matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) by in-gel digestion extract, and Mascot searching in NCBInr and SWISS-PROT databases. RESULTS: The 2-DE patterns with high resolution and reproducibility were obtained. The protein spots separated and visualized in chronic sinusitis, nasal polyps and normal nasal mucosa gel were 1020 +/- 40, 1112 +/- 10 and 1008 +/- 25, respectively. And the match rates were (93 +/- 2)%, (95 +/- 1)% [see text] (90 +/- 3)% respectively. Thirteen differentially expressed spots were found from chronic sinusitis, nasal polyps and normal nasal mucosa gel. We selected and recommend Keratin 8 and APOA1 proteins as candidate biomarkers of nasal polyps, and PLUNC protein, PACAP protein, NKEF-B and SOD as candidate biomarkers of chronic sinusitis. CONCLUSIONS: The differentially expressed proteins among chronic sinusitis, nasal polyps and normal nasal mucosa can be efficiently and relatively reliably identified via the techniques of proteomics. These techniques will play a very important role in the researches for new objective indicators possibly employed in the future classifying, staging and prognosis.

Adolescent↗

Stimulation and resection of Vidian nerve in patients with chronic hypertrophic non-allergic rhinitis: effect on histamine content in nasal mucosa.

Parasympathetic innervation of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.). The present study investigated the effect of Vidian nerve stimulation and resection on the histamine contents and on the morphological pattern in mucosal samples of patients with C.H.N.A.R. Vidian nerve stimulation determines a significant decrease in histamine content in the samples examined; microscopical observations showed significant variations in the glandular, stromal and vascular components. The changes indicate an enhanced secretory activity, intensive vasodilatation and active degranulation of mast cells, which were significantly decreased in number in the samples obtained after 90 sec of stimulation. The neurectomy of the Vidian nerve resolves quite completely the clinical symptomatology and in parallel decreases the mucosal histamine contents, which are increased in patients with C.H.N.A.R. before the operation in comparison with the normal controls.

Chronic Disease↗

Differential activity of nitric oxide synthase in human nasal mucosa and polyps.

Nitric oxide (NO) plays an important regulatory role in airway function and seems to be implicated in the pathophysiology of several airway diseases. To better understand the involvement of NO in the upper airways, we examined the presence of nitric oxide synthase (NOS) activity in human nasal mucosa and nasal polyp tissues. Nasal mucosa was obtained from seven patients undergoing septoplasty, and nasal polyps came from nine patients following polypectomy. NOS activity was quantified in tissue homogenates using the citrulline release assay and localized in tissue sections using reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. The results showed that nasal polyps (n = 9) contained higher levels of total NOS activity (mean +/- SD 5.94 +/- 5.71, range 1.29-18.0 pmol.min-1.mg protein) than nasal mucosa tissues (n = 7) (0.28 +/- 0.22, range 0.01-0.57 pmol.min-1.mg protein). In addition, nasal polyps mainly contained inducible NOS activity (4.67 +/- 4.57, range 1.23-15.5 pmol.min-1.mg protein) whereas in nasal mucosa all NOS activity detected was in constitutive form. In both cases, NOS activity was localized in the epithelial cells. Since NO synthase is induced in inflamed upper airways, we conclude that NO may be an important inflammatory mediator in the respiratory system and that the epithelium may be a source of NO production in the human upper airways.

Adult↗

[Nitric oxide synthase activity in nasal mucosa].

Nitric oxide (NO) plays an important regulatory role in airway function and seems to be implicated in the pathophysiology of several airway diseases. We studied the presence of NO synthase activity in human nasal mucosa and nasal polyp tissues obtained from patients undergoing septoplasty or polypectomy, respectively. NO synthase activity was quantified in tissue homogenates using citrulline release assay and was located in tissue sections using NADPH-diaphorase histochemistry. The results indicated that nasal polyps contain higher levels of total NO synthase activity than nasal mucosa tissue. In addition, nasal polyps contained mainly inducible NO synthase activity whereas all NO synthase activity detected in the nasal mucosa was in constitutive form. In both cases, NO synthase activity was localized in epithelial cells. In view of these results, we conclude that NO may be an important inflammatory mediator in the respiratory system and that the epithelium may be a source of NO production.

Adult↗