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PubMedDate not supplied

Expression of cell cycle regulatory proteins and analysis of apoptosis in normal nasal mucosa and in nasal polyps.

BACKGROUND: The etiopathogenesis of nasal polyps still is to be clarified. Although hyperplasia is a typical feature of these pathological processes, little attention has been paid to specific aspects of cellular growth in polyps. We have evaluated the expression and localization of some of the regulatory proteins that direct the cell through the specific sequence of events culminating in mitosis or apoptosis in nasal polyps. METHODS: Twenty samples of nasal polyps and 20 samples of normal nasal mucosa have been analyzed for apoptotic index by detecting the DNA 3'OH ends deriving from DNA fragmentation. Moreover, they have been evaluated by immunohistochemical staining for expression of Ki-67, cyclins A and B1, p53, p21, p27, murine double minute clone 2, and Bcl-2. RESULTS: We have identified a greater proportion of proliferating cells in the lining epithelial cells of the polyps when compared with the normal mucosa as stained with anti-Ki-67 antibodies. An overexpression of p53, MDM2, and Bcl-2 and an increased apoptosis were observed in nasal polyps compared with the normal mucosa, whereas no variation of p27 expression was observed. The p21 and cyclins A and B1 were rarely expressed in both pathological and normal tissue. CONCLUSION: The p53-based control system of cell cycle progression appears to be altered in nasal polyps, potentially leading to an abrogation of the DNA damage checkpoint. Evaluation of the expression of the regulatory proteins that direct the cells throughout their cycle in nasal polyps may allow a better understanding of the biological behavior and clinical outcome of these benign pathological entities.

Adult↗

PubMed1996

Expression of nitric oxide synthase in the human nasal mucosa.

The nasal mucosa plays an important role in defense of the lung against harmful agents. It has been suggested that this is partly mediated by the production of nitric oxide (NO). We have investigated the localization of the messenger ribonucleic acids (MRNAs) for human endothelial NO synthase (Type III NOS) and inducible NO synthase (Type II NOS) and the immunoreactivities of these enzymes in human nasal mucosa by immunohistochemistry, in situ hybridization, and reduced nicotinamide adenine diphosphate (NADPH) diaphorase histochemistry. Inferior nasal turbinates were obtained from 27 patients at the time of surgery for local disease. Strong immunostaining for Type III NOS was localized to vascular endothelium, surface epithelium, and submucosal glands in all subjects. Moderate immunostaining for Type II NOS was seen in surface epithelium; glandular, inflammatory, and vascular endothelial cells; and smooth-muscle cells in the specimens from patients with chronic rhinitis only. In situ hybridization showed expression of the mRNA for Type III NOS in similar sites to those shown by immunohistochemistry, whereas the mRNA for Type II NOS was predominantly localized to inflammatory cells. The sites of NOS expression were further confirmed by NADPH histochemical staining. These findings demonstrate the cellular expression of NOS in the human nasal mucosa and suggest a possible role for Types II and III NO synthase in the regulation of blood flow, nasal secretion, and ciliary movement in health and disease.

Adult↗

PubMed2003

Expression of non-steroidal anti-inflammatory drug-activated gene-1 in human nasal mucosa and cultured nasal epithelial cells: a preliminary investigation.

OBJECTIVE: Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a recently discovered transforming growth factor-beta superfamily cytokine. The localization and functions of NAG-1 have not been thoroughly studied. The aims of this study were to investigate its expression and localization in human nasal mucosa and also the change in NAG-1 expression as a function of mucociliary and squamous differentiation. MATERIAL AND METHODS: Anterior and middle portions of human inferior turbinate were used and immunohistochemical studies were performed using NAG-1 antibody. Passage-2 normal human nasal epithelial (NHNE) cell culture was performed for 14 days using the air-liquid interface method and the cells were divided into retinoic acid (RA)-sufficient and -deficient groups. Each group of cells was stained with hematoxylin-eosin to study the degree of differentiation. Western blot analysis for NAG-1 expression was performed in each group after 0, 7 and 14 days. RESULTS: NAG-1 expression in mucociliated epithelium was noted in ciliated cells and serous acini, but was not found in goblet cells or mucous acini. In squamous epithelium, NAG-1 expression was weaker than that in mucociliated epithelium. In RA-sufficient culture, NHNE cells were differentiated into ciliated epithelium, but in RA-deficient culture, keratinizing squamous epithelium was noted. Western blot analysis showed that NAG-1 expression was significantly higher in RA-sufficient than -deficient culture (three-fold difference) and this expression was time-dependent. CONCLUSIONS: NAG-1 may be involved in differentiation and apoptotic processes of nasal epithelial cells. However, it is still unclear whether NAG-1 is an inducer or a byproduct of differentiation or apoptosis. The role of NAG-1 protein remains to be solved.

Apoptosis↗

PubMed2004

[Neural control of the respiratory nasal mucosa].

Respiratory nasal mucosa fulfils the function of pretreating the inspired air. The periodic nasal cycle and pathologic functional disturbances of the endonasal tissue influence the nasal passages. The secretion of the seromucous glands and extravasation from the blood vessels are essential for mucocilliary transport. These physiological mechanisms are partially controlled by neural regulation. Besides classic neurotransmitter neuropeptides such as VIP, CGRP, SP and NPY, nitric oxide also shares this role. A network of sensory, sympathetic and parasympathetic nerve fibres protects the respiratory mucous membranes from external and internal irritation. In addition, blood vessels and glands are influenced by endothelial and humoral factors. For the different types of rhinitis, sensory neuropeptides and inflammatory mediators take part in the pathomechanisms and can lead to a so called neurogenic inflammation of the nasal mucosa.

Feedback↗

PubMed1998

Histological studies in primary neuritic leprosy: changes in the nasal mucosa.

The nasal mucosae of 39 cases of primary neuritic leprosy (PNL) registered at Karigiri were studied histologically to determine nasal mucosal involvement in PNL and its relevance to the pathogenesis of the disease. Specific changes of leprosy were seen in 20 (51%) biopsies, ranging from macrophage granulomas with acid fast bacilli, to epithelioid granulomas and nerve inflammation. The remaining biopsies revealed chronic inflammatory changes of the mucosa or mild non-specific nerve changes. These findings show that there are widespread effects of the disease even in PNL patients in whom the disease is believed to be confined to the peripheral nerves. The findings also show that early leprosy involvement can be found in the nasal mucosa even before lesions become apparent in the skin or other parts of the body. The nasal mucosa could be one of the sites for the primary lesion in leprosy. Clinical and histological examination of the nasal mucosa may be useful and important in the early diagnosis of leprosy and especially in contacts.

Biopsy, Needle↗

PubMed1992

Evaluation of the degradation of desamino1,D-arginine8-vasopressin by nasal mucosa.

The nasal route is a convenient and simple way to administer peptides to humans. Absorption of the drug, however, requires passage of the substance through the nasal mucosa. This is a possible site of enzymatic degradation of the peptide. It is shown that rabbit nasal mucosa homogenates rapidly degrade the synthetic anti-diuretic hormone analogue desamino1,D-arginine8-vasopressin in vitro. The metabolite formed has been identified as des-(amino,arginine8,glycineamide9)- vasopressin, which is stable under the prevalent in vitro incubation conditions. It is proposed that this process is catalyzed by intracellular post-proline cleavage enzyme. Reversed phase chromatography in combination with immunological detection has been used to study the possible presence of this metabolite in the circulation after intranasal administration to humans. The metabolite des-(amino,arginine8,glycineamide9)-vasopressin could not be detected in plasma following intranasal administration, possibly indicating a paracellular absorption of desamino1,D-arginine8-vasopressin or absence of this enzymatic activity in humans.

Administration, Intranasal↗

PubMed2005

Ultrastructural detection of nitric oxide in human nasal mucosa.

OBJECTIVE: Nasal vasculature and seromucous glands are exposed to complex mechanisms influenced by external as well as internal stimuli. In addition to classic and peptidergic neurotransmitters, nitric oxide (NO) was increasingly found to be important in the control of various physiologic functions. NO modulates nasal immunology, influences macrophage activity, and has antiviral and bacteriostatic properties. The aim of this study was to show the localization of nitric oxide synthases (NOS) I and III in the normal human nasal mucosa by using immunoelectron microscopical techniques. STUDY DESIGN: Specimens of noninflammed inferior turbinates from 35 patients who underwent nasal surgery were fixed in phosphate-buffered glutaraldehyde. After dehydration, incubation in unicryl and polymerization, ultrathin sections were cut. Primary antibodies against NOS I and III were applied and the immunocomplexes were visualized by an immunocytochemical staining-technique using gold-labeled antibodies. Immunostained structures were photodocumented using a transmission electron microscope. RESULTS: NOS-immunoreactive nerve fibers were mainly co-located in parasympathetic nerves in the adventitia of arterial vessels and in periglandular axons. Electron microscopy showed that NOS-positive axons were in close contact with acinus cells. A strong NOS III-immunoreactivity was found in endothelial cells of capillaries near the glands as well as in arterial vessels. Furthermore, immunoreaction products were deposited throughout the cytoplasm of fibroblasts. CONCLUSION: Nitric oxide in nerve fibers, seromucous glands, and endothelial cells of capillaries and arterial vessels suggest that NO takes part in the regulation of physiologic processes of the human nasal mucosa. NOS was co-localized in parasympathetic nerves and plays a role in the neurotransmission and neuromodulation of the vascular tone and glandular secretion. Arteries showed a distinctly developed nitrergic innervation and endothelial accumulation. The NO production in axons of the adventitia and in the endothelium of arteries demonstrated that these vessels are influenced by a dual NO system. NO could mainly act on these structures with vasodilatatory effects. Finally, NO would be able to influence the functions of perivascular fibroblasts.

Adult↗

PubMed2003

[Ultrastructural localization of nitric oxide synthase (NOS I and III) in human nasal mucosa].

BACKGROUND: Nasal vasculature and seromucous glands are exposed to complex mechanisms influenced by external as well as internal stimuli. In addition to classic and peptidergic neurotransmitters, Nitric oxide (NO) was increasingly found to be important in the control of various physiological functions. NO regulates nasal immunology, influences macrophages activity and has antiviral and bacteriostatic properties. The aim of this study was to detect the localization of nitric oxide synthases (NOS) I and III in the normal human nasal mucosa with immunoelectron microscopical techniques. METHODS: Specimens of non-inflamed inferior turbinates from 35 patients who required nasal surgery were fixed in phosphate-buffered glutaraldehyde. After dehydration, incubation in unicryl and polymerization ultrathin sections were cut. Primary antibodies against NOS I and III were applied and the immunocomplexes were visualized by an immunocytochemical staining-technique using a gold-labeled antibody. Immunostained structures were photodocumented by using a transmission electron microscope. RESULTS: NOS-immunoreactive nerve fibers were mainly colocated in parasympathetic nerves in the adventitia of arterial vessels and in periglandular axons. Electron microscopy showed that NOS-positive axons were in close contact with acinus cells. A strong NOS III-immunoreactivity was found in endothelial cells of capillaries near the glands as well as in arterial vessels. Furthermore, immunoreaction products were deposited throughout the cytoplasm of fibroblasts. CONCLUSIONS: Nitric oxide in nerval fibers, seromucous glands and endothelial cells of capillaries and arterial vessels suggests that NO takes part in the regulation of physiological processes of the human nasal mucosa. NO was colocalized in parasympathetic nerves and plays a role in the neurotransmission and neuromodulation of the vascular tone and glandular secretion. Arteries showed a distinctly developed nitric innervation and endothelial accumulation. The NO production in axons of the adventitia and in the endothelium of arteries demonstrated that these vessels are influenced by a dual NO system. Mainly NO could act on these structures with vasodilatory effects. Finally NO would be able to influence the functions of perivascular fibroblasts.

Axons↗

PubMed1986

Metabolism of diethylnitrosamine by nasal mucosa and hepatic microsomes from hamster and rat: species specificity of nasal mucosa.

The oxidative metabolism of diethylnitrosamine (DEN) was investigated by acetaldehyde determination using microsomes from nasal mucosa and liver of Sprague-Dawley rats and nasal mucosa and liver of Syrian Golden hamsters, to establish the role of metabolic activation in the organo-targets for the carcinogenicity of the nitrosamine. The hepatic microsomal de-ethylation of DEN followed simple and biphasic Michaelis-Menten kinetics for rat liver and hamster liver, respectively. Both de-ethylations were inducible by phenobarbital (PB) and the DEN-de-ethylase activities and the Michaelis constants were determined. Microsomes from hamster liver showed a higher metabolic rate (Vmax) and a better affinity (Km) towards DEN with respect to microsomes from rat liver. In hamster, microsomes from nasal tissue biotransformed DEN at a rate and affinity quite similar to those of liver. In contrast, nasal mucosa of rat metabolized DEN poorly. The effect of metyrapone, a classical inhibitor of P-450 monooxygenases, on DEN de-ethylation was studied. It inhibited both hepatic and nasal DEN-de-ethylase activity, with greater affinity towards the latter. In addition metyrapone had a greater inhibitory effect on the hepatic P-450 isozymes induced in PB-treated animals. These results correlate well with the organotrophy of DEN carcinogenesis in the nasal region of hamster, but not of rat. They suggest that for the nose the metabolic activation of DEN in situ is necessary to elicit its carcinogenic effect.

Animals↗

PubMed1991

Interaction of cocaine with nasal mucosa.

Canine nasal mucosa was studied in vitro to examine (1) the production of vasoconstriction by cocaine and, (2) the epithelial permeability of cocaine. Cocaine, by itself, failed to induce any contraction of the nasal blood vessels but did enhance contractions resulting from electrical stimulation or addition of norepinephrine. Results indicate that cocaine produces vasoconstriction by blocking the reuptake of endogenous norepinephrine rather than any direct action on vascular smooth muscle. Cocaine was found to be three times more permeable than sucrose, which has a similar molecular weight. The transepithelial permeability of cocaine was independent of direction and did not display competition. Results indicate that cocaine permeates by simple diffusion and that the relatively high permeability is due to a greater lipid solubility. Cocaine was found to accumulate in the nasal mucosa. A significant portion of the accumulation is associated with specific sites that are characteristic of catecholamine uptake sites.

Animals↗

PubMed1997

Distribution and origin of nitric oxide synthase-containing nerve fibers in human nasal mucosa.

Human nasal mucosa was investigated by nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. NADPH-diaphorase-positive fibers were distributed around blood vessels and seromucous glands, but none was seen in the respiratory epithelium. The pterygopalatine ganglion was then studied to determine the origin of these fibers, and many neurons were found to be labeled. These labeled neurons (86.2%) consisted of small (14.7%), medium-sized (18.4%) and large cells (53.1%). These results suggest that nitrinergic nerve fibers may originate from the pterygopalatine ganglion and that nitric oxide may play some role in the nervous control of the human nasal mucosa.

Humans↗

PubMed1989

Lymphocytes and nonlymphoid cells in the nasal mucosa of patients with nasal polyps and of healthy subjects.

Immunohistochemical stainings were performed on biopsy specimens of the middle and inferior turbinates of the nasal mucosa of 14 patients with nasal polyps and 16 healthy subjects. Significantly more CD8+ (T suppressor/cytotoxic) cells than CD4+ (T helper/inducer) cells were found in the lamina propria of the middle and inferior turbinates of patients with nasal polyps and in the inferior turbinate of healthy subjects. The middle and inferior turbinates of healthy subjects contained significantly more CD4+ cells than the middle and inferior turbinates of patients with nasal polyps. CD19+ B cells were hardly detected in the patients and healthy subjects. More HLA-DR+ cells were found in the middle than in the inferior turbinate, especially in the patients. Varying but small numbers of eosinophils, neutrophils, mast cells, and plasma cells were found in patients and healthy subjects. The possible role of CD4+, CD8+, and HLA-DR+ cells in the nasal mucosa is discussed with regard to the pathogenesis of nasal polyps.

Adolescent↗

PubMedDate not supplied

Histamine H1 receptors and affinity analyses in human nasal mucosa in cases of nasal allergy.

An increased number (density) or sensitivity (affinity) of histamine H1 receptors could cause an increase of allergic symptoms. Using the specific H1 receptor blocker 3H-mepyramine, we have demonstrated for the first time an H1 receptor number (Bmax) and a binding affinity (Kd) in guinea pig and human nasal mucosa. H1 antihistamines inhibited that 3H-mepyramine binding sites represent H1 receptors in nasal mucosa. Bmax and Kd values were not significantly different among the nonallergic sinusitis, vasomotor rhinitis, or the nasal allergy group, suggesting that H1 receptors do not change quantitatively and qualitatively in allergic nasal mucosa. There was no significant correlation between H1 receptor number and clinical data (IgE, peripheral eosinophils, RAST). These data suggest that H1 receptor number and affinity are not main etiological and pathophysiological factors in nasal allergy.

Adolescent↗

PubMed1994

Human papillomavirus and normal nasal mucosa: detection of human papillomavirus DNA in normal nasal mucosa biopsies by polymerase chain reaction and in situ hybridization.

To determine a possible etiological role of human papillomavirus (HPV) in sinonasal papillomas and squamous cell carcinomas, it is necessary to investigate normal nasal mucosa of healthy persons for the presence of HPV. The material in the present study consists of 21 biopsies taken from the inferior concha of 21 otherwise healthy persons who underwent surgery for nose fractures or nasoseptal deviations. In addition, five inferior conchae were obtained from persons who had died of non-neoplastic diseases. HPV was not detected in any of these specimens, either by polymerase chain reaction or by in situ hybridization. Histologic evaluation showed that squamous metaplasia was a common finding in the biopsies. The presence of HPV in sinonasal papillomas and carcinomas may indicate that HPV is an etiological factor in these lesions.

Adolescent↗

PubMed1959

[Intravital microscopic studies on the nasal mucosa; absorption of foreign substances in the nasal mucosa (resorption)].

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Humans↗

PubMed1998

Increased nitric oxide in nasal lavage fluid and nitrotyrosine formation in nasal mucosa--indices for severe perennial nasal allergy.

BACKGROUND: The nose contributes the large amount of nitric oxide (NO) to exhaled air. NO is a mediator of vasodilation and yields peroxynitrite (ONOO-) by reacting with superoxide (O2-). ONOO attacks tyrosine residues to form nitrotyrosine. OBJECTIVE: The aim of this study was to examine the pathophysiological role of NO in nasal mucosa in patients with perennial nasal allergy. METHODS: We measured nitrite and nitrate (NO2-/NO3-) and 3',5'-guanosine monophosphate (cyclic GMP) in nasal lavage fluid, and also measured haemoglobin concentration in nasal mucosa as an indicator of blood volume in the patients and healthy volunteers. The deleterious role of NO was also investigated by measuring nitrotyrosine in nasal mucosa. RESULTS: The NO2-/NO3- concentration in the nasal lavage fluid was 39.5+/-2.8 microM in healthy volunteers (n=40), 42.4+/-3.0 microM in patients with mild allergy (mild group, n=32), and 88.7+/-6.6 microM in patients with severe allergy (severe group, n=61). In the patients whose symptoms were improved with treatment, NO2-/NO3- levels decreased to 45.7+/-10.4 microM. The concentration of cyclic GMP in nasal lavage fluid was higher in the severe group than in the healthy volunteers. The mucosal haemoglobin index was 88+/-4 in the healthy volunteers, 67+/-4 in the mild group, and 53+/-2 in the severe group. The formation of nitrotyrosine was expressed 0.58+/-10% to total tyrosine in the severe group (n=11), but was not found in non-allergy patients (n=9). CONCLUSIONS: The production of NO was increased in patients with perennial nasal allergy, but the blood flow in the nasal mucosa of patients was reduced. Nitrotyrosine formation suggests that there is a process of ONOO(-)-induced damage in mucosa of patients with the perennial nasal allergy and this damage may limit the dilatation of blood vessels, despite the presence of excessive NO.

Adult↗

PubMed1995

Spontaneous variations in congestion of the nasal mucosa.

BACKGROUND: Nasal patency shows spontaneous variations but is also influenced by exercise and allergic conditions. These variations have not been described in detail with regard to allergy. OBJECTIVES: The purpose of this study was to examine whether these variations are different in nonallergic subjects and in subjects with nasal allergy to pollen out of the pollen season. METHODS: We examined 12 of each type of subject in the winter on two days for seven hours in a climatic chamber with constant temperature and relative humidity, one day for examination of spontaneous variations and one day for examination of exercise response. Every 15 minutes the volume of the nasal cavities, minimum cross-sectional areas, and areas at fixed distances from the nostril were measured by acoustic rhinometry. Symptoms were scored by a questionnaire. RESULTS: There were more pronounced spontaneous variations expressed as the coefficient of variation of nasal volume in allergic than in nonallergic subjects (14% against 9%, P = .004). A nasal cycle was observed in four of the nonallergic subjects and three of the allergic subjects. In the postexercise period, the spontaneous variations in the nonallergic subjects were increased but decreased in the allergic subjects. Exercise increased nasal patency more in the allergic subjects but only significantly for the cross-sectional area at 3.3 cm (105% compared with 43% in the nonallergic subjects, P = .05). In contrast, pharmacologic decongestion in the allergic subjects showed a tendency to be more pronounced for the nasal cavity volume (55% increase versus 42%, P = .08). There was no difference between the groups in nasal symptom scores. CONCLUSION: Allergic subjects out of the pollen season have more congested and more sensitive nasal mucosa than nonallergic subjects.

Adolescent↗

PubMed1988

Autonomic innervation of the nasal mucosa.

The nasal passages play a crucial role in the protection and functioning of the lower airways. Consequently the nerve supply of the nasal mucosa is extensive, which is related to an immediate and adequate reaction upon a variety of external and internal stimuli. A brief review of the present knowledge on nasal autonomic innervation and pharmacology will be given. There is special attention to more advanced methods, such as radioligand receptor binding techniques, which might augment our insight in the significance of the nervous system in nasal (patho)physiology. Furthermore data on the secretory activity of the nasal glands in the rat and its neural regulation will be accentuated.

Animals↗