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Expression of guanylin and uroguanylin mRNA in human nasal mucosa and nasal polyps.

OBJECTIVES: Guanylin and uroguanylin are small, heat-stable peptides that were originally isolated from the small intestine and from urine, respectively. Functionally, it has been proposed that these peptides can regulate ion and water transport in various fluid-transporting epithelia. In the present study we evaluated the presence of mRNAs for human guanylin and uroguanylin in human inferior turbinate mucosa and nasal polyps. MATERIAL AND METHODS: The expression and localization of mRNAs for both peptides were investigated in inferior turbinate tissues and nasal polyps using reverse transcriptase polymerase chain reaction and in situ hybridization. RESULTS: mRNAs for both peptides were detected in human turbinate mucosa and nasal polyps. In situ hybridization revealed that they were localized in the epithelial layer and submucosal glands of inferior turbinate mucosa and in the epithelial layer of nasal polyps. However, their expression was noted at low levels in the superficial epithelium of nasal polyps, compared with that of inferior turbinate mucosa. CONCLUSIONS: These results indicate that guanylin and uroguanylin in the nasal mucosa may participate in normal physiological processes, but also suggest that altered expression of these genes in nasal polyps may cause impaired electrolyte and water transport across the epithelial cells.

Adult↗

Interleukin 5, IL6, IL12, IFN-gamma, RANTES and Fractalkine in human nasal polyps, turbinate mucosa and serum.

Polyps are considered to develop as an end result of an inflammatory process. Cytokines and chemokines in the respiratory mucosa may be a key to polyp pathophysiology. The main objective was to identify IL-5, IL-6, IL-12, RANTES, IFN-gamma and Fractalkine in humans on the protein level in nasal polyps and mucosa from the inferior turbinate (IT). Furthermore, the cytokines and chemokines RANTES and Fractalkine were analyzed in plasma. Tissue homogenates and plasma from 13 patients were analyzed by the ELISA technique. All the patients had longstanding nasal/paranasal polyposis. Fractalkine was detected in polyps and IT in two different patients. IL-5 was expressed in polyps and IT. IL-6 was expressed in all patients with a higher level in polyps than IT. IL-12 was present in plasma, polyps and IT, though at an increased level in polyps. RANTES was present at a higher level in plasma than in polyps and IT. IFN-gamma was detectable in polyps and IT. Fractalkine is detected in nasal polyps, which is a new observation. The overall results indicate a mixed T(H)1/T(H)2 cytokine profile in nasal polyps. RANTES and IL-12 are strongly present in plasma, suggesting an ongoing inflammatory "drive". IL-6 and IL-12 are up-regulated in polyps versus the IT. Up-regulation of IL-6 may be explained by increased fibroblast activity dependant on an ongoing local inflammation possibly initiated by an infection. IL-5, RANTES and IFN-gamma are equally represented in polyps and IT, indicating equilibrium between the nasal polyps and surrounding tissue, and that an up-regulation of cytokines in the polyp indicates a potential for polyp growth.

Adult↗

Increased epithelial cell proliferation in nasal polyps.

BACKGROUND AND PURPOSE: The mucociliary function of the sinonasal mucosa is an innate defense mechanism of the human nasal airway. Epithelial cell proliferation is required for cell renewal and repair of the sinonasal mucosa. In this study, the MIB-1 monoclonal antibody, which can detect the S-phase nuclear protein Ki-67, was used to evaluate the proliferation of the sinonasal mucosa in patients with various inflammatory conditions of the sinonasal mucosa. METHODS: Specimens from the inferior turbinates of patients with nasal allergy (n = 12), vasomotor rhinitis (n = 20), nasal polyps (n = 22), and control subjects undergoing rhinoplasty (n = 5) and mucosa of chronic sinusitis patients [inferior turbinates (n = 10), middle turbinates (n = 10), and maxillary sinus (n = 9)] were fixed in neutral formalin and embedded in paraffin. MIB-1 monoclonal antibody was used to detect proliferation of epithelial cells. RESULTS: Significantly increased epithelial cell proliferation was noted in nasal polyps compared to sinonasal mucosa. There was no difference among various sinonasal inflammatory conditions between patients and controls. CONCLUSIONS: Increased epithelial cell proliferation in nasal polyps may play an important role in covering the epithelial defects caused by the rupture of the epithelium and prolapse of connective tissue in nasal polyps.

Adolescent↗

[Influence of rhinologic usual and unusual drugs on fibroblasts from nasal polyps in cell culture].

BACKGROUND: Nasal polyposis is treated by surgery and/or by medication but in parts without permanent remission. Fibroblasts and their proliferation are involved in the complex mechanism of polyp genesis. Therefore we have analysed the influence of 12 medications on fibroblasts from nasal polyps growing in vitro. METHOD: Nasal polyps, obtained during usual surgical procedure, are enzymatically digested and cultured in serum containing media. The growing cells are identified as fibroblasts using flow cytometry with a AS02-FITC antibody (Dianova). The analysis is achieved with 5 - 6 different fibroblast cultures in each medicament tested, mostly using concentrations of the active substance from 0.006 to 1.333 mg/ml. The fibroblasts are cultured 4 days in the presence of active substances or as controls. Finally the cells are trypsinated and counted. RESULTS: Mometason, Beclomethason, Fluticason, Verapamil and Timolol are the group with the strongest reduction of fibroblasts. Mometason shows a reduction to 6 % of controls at a concentration of 30 micro g/ml whereas the reduction at this concentration amounts to 30 - 60 % in the other members of this group. Mesazalin, Methylprednisolone and Pentoxifylline demonstrate the smallest influence; Prednisolon-21-hydrogen-succinate, Pilocarpin, Piroxicam and Diclofenac show an effect on a middle level. CONCLUSIONS: A strong reduction of fibroblasts from nasal polyps in vitro is possible with usual rhinological medicaments but also with unusual substances in this field.

Administration, Topical↗

Significance of nasal polyps in chronic rhinosinusitis: symptoms and surgical outcomes.

PURPOSE: To demonstrate the significance of nasal polyps on the symptoms of chronic rhinosinusitis (CRS) and their influence on surgical outcomes. METHODS: Retrospective analysis of prospectively collected data comparing two groups of patients diagnosed with CRS with and without nasal polyps that underwent surgical management with a minimum 1-year follow-up period. Subjective scoring was performed using the Sino-Nasal Outcome Test (SNOT-20) questionnaire. Computed tomography (CT) scans were compared using the Lund-Mackay scoring system. The two groups were analyzed for the need of revision surgery. RESULTS: Two hundred one patients underwent surgical management of CRS over a 3-year period. One hundred four were male, 97 were female, and the average age was 49 (range 18-80) years. Polyps were present in 78 patients with CRS, whereas 123 patients did not have polyps. The average CT score was 18 for the polyp group and 9.5 for the patients without polyps (P = .0000). Nonpolyp group SNOT-20 scores were 26.5 preoperatively with improvement to 5.1 at 6 months and 5.0 at 12 months postoperatively (85% improvement). Polyp group SNOT-20 preoperative scores averaged 32.2 with improvement to 9.2 at 6 months and 9.1 at 12 months postoperatively (81% improvement, P = .003). Nine patients required revision surgery (4.5%), eight (10%) who had polyps and one (0.8%) who did not (P = .002). CONCLUSION: The presence of nasal polyps has a significant negative impact on patients with CRS. Patients with nasal polyps have more severe symptoms with less improvement after operative intervention, higher CT scores at presentation, and a significantly higher need for revision surgery.

Adolescent↗

[The regulation of PKCalpha in eosinophil infiltration and proliferation in nasal polyps].

OBJECTIVE: To explore the regulation of protein kinase C (PKC) isoform--PKCalpha in eosinophil (EOS) proliferation and infiltration in nasal polyp tissues. METHOD: With the methods of in situ hybridization staining and immunohistochemistry MGG staining, to check out the relationship between PKC and bcl-2/BaxmRNA and associated protein, especially PKC isoform--PKCalpha, PKCbeta1 , PKCbeta2, and PKCgamma did not express at all. RESULT: There were PKC expression in the eosinophils of 26 cases from nasal polyps, and the expression of PKC and Bcl-2 mRNA/their protein in EOS of nasal polyps showed remarkably positive relation (r1 = 0.0875, r2 = 0.0823, P < 0.01), but in PKC isoforms, PKCalpha expression was the strongest, but PKCbeta1 and PKCbeta2 expressed thinner and PKCgamma did not express at all. CONCLUSION: The reason of eosinophil proliferation and infiltration in nasal polyps is that PKC signal transduction pathway was activated, and leaded to inhibition of eosinophil apoptosis, and eosinophil survival was delayed, and eosinophil proliferated and infiltrated, and in PKC family, PKCalpha is main.

Adult↗

[Adenylate cyclase activity in human nasal polyps under conditions of stimulation of serotonin biosynthesis (in vitro)].

Nasal polyp tissue possess adenylatecyclase activity. Under conditions of incubation of nasal polyps with the use of reserpine (an activator of serotonin synthesis in this tissue) there can be observed a statistically significant increase of adenylatecyclase activity. During the first minutes of the polyp incubation with reserpine the activity of the enzyme rose ten-fold. Participation of the adenylatecyclase system at the initial stages of morphological and biochemical differentiation, accompanying serotonin biosynthesis in human nose polyps was confirmed.

Adenylyl Cyclases↗

[Effects of dexamethasone on mucin gene expression in human nasal polyps].

OBJECTIVE: To clarify whether glucocorticoid influences mucin 8 gene expression in human nasal polyps. METHOD: Thirty patients were randomly divided into two groups. The first group were given dexamethasone intravenously before surgery. We make sure the second group of patients didn't receive any kind of glucocorticoid therapy during thirty days before surgery. MUC8 MRNA expression in nasal polyps of each group was detected by reverse transcription polymerase chain reaction (RT-PCR). RESULT: The MUC8 MRNA expression in the first group (0.71 +/- 0.34) was lower than that of the second group (1.12 +/- -0.26). CONCLUSION: DXM supress MUC8 MRNA expression in nasal polyps and this result provide another aspect for glucocorticoid's antiinflammatory mechanism.

Adolescent↗

A survey to determine the extent of previous symptoms and surgery on patients presenting with nasal polyps.

The aim of our study was to investigate the prevalence of surgery on the nose prior to first time diagnosis of nasal polyps. We interviewed 60 patients who presented to the ENT Department at the Royal South Hants Hospital Southampton and were diagnosed as suffering from nasal polyps for the first time. Patients who suffered from cystic fibrosis or known primary ciliary dyskinesia were excluded. The average length of time of nasal blockage as the main symptom prior to the diagnosis of nasal polyps was less than two years. Out of the 60 patients six (10 per cent) had had previous nasal surgery. Out of these six patients, only four patients had a previous procedure on the nose that could be considered to be related to the later diagnosis of nasal polyps. Only one patient had had radiological investigation of his sinuses in the past. We conclude that polypoid nasal disease is a de novo diagnosis with a relatively short history in the majority of patients and not preceded by a long history of ENT investigations nor surgery on the nose.

Adult↗

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↗

The effect of topical corticosteroid on basic fibroblast growth factor in nasal polyp tissue.

BACKGROUND: The etiology of nasal polyposis and pathophysiological mechanisms of polyp formation is still poorly understood. Experimental models have suggested that nasal polyp growth requires extracellular matrix formation and is associated with fibroblast proliferation. Intranasal corticosteroids appear to be useful in reducing nasal polypoid lesions and the likelihood of polyp recurrence after surgery. Basic fibroblast growth factor (bFGF) is a potent angiogenesis factor and is mitogenic for a wide range of cell types. We investigated the alteration of bFGF levels in nasal polyp tissue after administration of topical corticosteroid. METHODS: Nasal polyp tissues were obtained from 36 patients with diffuse nasal polyposis before and after topical nasal steroid treatment. As a topical nasal steroid mometasone furoate was given for 4 weeks in a dosage of 200 microg/day. The bFGF levels were measured by competitive enzyme immunoassay method. RESULTS: The mean levels of tissue bFGF, before and after topical nasal steroid treatment, were 1485 +/- 826 ng/mg protein (range, 416-3434 ng/mg) and 1340 +/- 749 ng/mg protein (range, 330-3288 ng/mg), respectively. The levels of bFGF in nasal polyps were significantly lower than those before treatment after administration of topical nasal steroid (p = 0.011). CONCLUSION: Administration of topical nasal steroid decreases bFGF levels of nasal polyp. It may be suggested that one of the effects in diminishing the size of nasal polyps is by decreasing the bFGF.

Administration, Intranasal↗

Interleukin-4 C-590T polymorphism is associated with protection against nasal polyps in a Korean population.

BACKGROUND: Although many studies have implicated interleukin (IL)-4 promoter polymorphisms as potential determinants of disease susceptibility, there are no reports on the association between IL-4 promoter polymorphisms and nasal polyps. The aim of this study was to investigate the relationship between an IL-4 promoter polymorphism and nasal polyps. METHODS: The C-590T promoter polymorphism of the IL-4 gene was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 106 Korean chronic rhinosinusitis patients with or without nasal polyps and 70 healthy Korean subjects. RESULTS: The frequency of the T allele at position -590 of the IL-4 gene in a Korean population was 0.85, which was significantly higher than those of other ethnic groups, and the T/T allele at position -590 of IL-4 was associated with protection against nasal polyps if compared with the C/C allele (relative risk, 0.529; 95% confidence interval, 0.307-0.912; p = 0.028). CONCLUSION: T-590, which is dominant at position -590 of the IL-4 promoter, appears to be associated with a protective mechanism against nasal polyps in Korean populations.

Alleles↗

Asthma, aspirin intolerance and nasal polyps.

Asthma associated with aspirin intolerance (bronchospastic type) and nasal polyps is a special type of asthma with well established characteristics. Asthma and aspirin intolerance in these patients usually occurs at the same time in life followed by nasal polyps about 10 years later. Classically, it is a non allergic steroid-dependent asthma. Desensitization to aspirin is possible but does not improve asthma. Polypectomy does not aggravate or cause asthma. The pathogenic mechanism may involve arachidonic acid metabolism.

Adrenal Cortex Hormones↗

Systematic review of endoscopic sinus surgery for nasal polyps.

OBJECTIVES: To provide a systematic review of the clinical effectiveness of endoscopic sinus surgery (ESS) for the removal of nasal polyps. DATA SOURCES: Searches of electronic databases, websites and reference lists were made to identify relevant studies. REVIEW METHODS: An extensive search was performed to identify all articles where FESS is used for the excision of nasal polyps. Two reviewers independently screened articles for inclusion according to predefined criteria. Comparative studies were included if they were primary research, focused on FESS for the removal of nasal polyps, reported patient relevant outcomes and were published in English. In addition, case series studies were included if they met the above criteria and enrolled more than 50 patients with polyps. Data were then extracted by one reviewer and checked by a second. A structured form was used to assess the internal and external validity of included studies. Comparative data were reported where available. Excluded case series and case reports were grouped and described. A group of nine ear, nose and throat (ENT) experts were selected, then using the literature and their own experience, they generated a list of priority research questions. Existing economic evaluations were sought and described. RESULTS: Of the 33 studies included, the randomised controlled trials and controlled trials reported overall symptomatic improvement that ranged from 78 to 88% for FESS compared with 43 to 84% for similar techniques (including polypectomy, Caldwell-Luc and intranasal ethmoidectomy). Disease recurrence was 8% for FESS compared with 14% for Caldwell-Luc and polyp recurrence was 28% for endoscopic ethmoidectomy compared with 35% for polypectomy. Revision surgery was reported in one study only and was the same for FESS and Caldwell-Luc procedures. Percentage of overall complications was reported in only one comparative study and was 1.4% for FESS compared with 0.8% for conventional procedures. The case series studies reported overall symptomatic improvement for patients with nasal polyps ranging from 37 to 99% (median 89%). For the mixed patient groups (with and without polypoid disease) overall symptomatic improvement ranged from 40 to 98% (median 88%). Total complications in the case series studies ranged from 22.4 to 0.3% (median 6%). CONCLUSIONS: The majority of studies report that symptoms improve following FESS with relatively few complications; however, only a small proportion of evidence is comparative. Results from non-comparative studies do not inform the choices that need to be made by ENT surgeons and commissioners. Health economics data are also lacking and therefore cannot inform these decisions. FESS may offer some advantages in effectiveness over comparative techniques, but there is enormous variation in the range of results reported and there are severe methodological limitations. There is a clear need for quality-controlled trials in order to answer questions regarding the effectiveness of FESS. A number of priority research questions from a selection of ENT surgeons within the UK are identified and presented.

Endoscopy↗

[RANTES expression in nasal polyps fibroblasts; spontaneously and after stimulation with lipopolisaccharides (LPS) and phytohemagglutinin (PHA)].

INTRODUCTION: According to the results of research carried out by a number of authors, one of the main mechanisms of the generation of polyps is local inflammatory processes accompanied by immune system disorders. It has recently been shown that a number of differentiation factors and inflammatory mediators may be involved in the growth of nasal polyps. RANTES is a eosinophil chemoattractant factor likely could play an important role in a chronic inflammatory response in the nasal tissue that subsequently leads to the development of nasal polyps. OBJECTIVE: The objective of this study was detection of the chemokine RANTES in nasal polyps fibroblasts and researching influence of stimulation with lipopolisaccharides and phytohemagglutinin for RANTES expression in cultured nasal fibroblasts in vitro. METHODS: Nasal polyps were obtained from 17 subjects (9 atopic and 8 nonatopic) during polypectomy. RANTES was measured by immunofluorescence method. RESULTS: Intensive granular luminescence was observed in all cytoplasm of cells with the exception of nucleus. Immunoreactive RANTES was found to be present in 70% of cells. We not find increase percentage of positive RANTES fibroblasts after stimulation with lipopolisaccharides and phytohemagglutinin. RANTES expression was similar in the both: atopic and nonatopic polyps. CONCLUSIONS: This study demonstrates that cultured fibroblasts derived from both atopic and nonatopic patients release RANTES spontaneously and after stimulation with lipopolisaccharides and phytohemagglutinin. This observation and the finding that RANTES is present in nasal polyps fibroblasts suggest that this chemokine may be an important mediator of eosinophil in both atopic and nonatopic nasal polyposis. More research needs to expand on chemotactic factors such as RANTES and their interplay with other local cytokines.

Adult↗

Haemorrhagic nasal polyps of the horse.

A series of 10 haemorrhagic polyps of the equine nasal cavity is described. The lesions show haematoma formation, abundant haemosiderin in macrophages and giant cells, and organising fibrous tissue. In one case, angiomatoid lesions were observed in the mucous membrane of the paranasal sinuses and it is suggested that some haemorrhagic nasal polyps may originate from pre-existing haemangiomatous areas in the respiratory mucosa.

Animals↗

Goblet cell density in nasal polyps.

The goblet cell density was determined in 29 nasal polyps from 22 patients by use of the periodic acid Schiff-alcian blue whole-mount method. The distribution of goblet cells was found to be extremely irregular, ranging from areas completely devoid of goblet cells to areas with a relatively high density. The median density varied from 280 cells/mm2 to 10,000 cells/mm2. The total median density for all 15 polyps located anteriorly in the nose was 3,450 cells/mm2, compared with 6,050 cells/mm2 for 14 posteriorly located polyps. The density was highest in pseudostratified, cylindric epithelium, although great variations occurred among the different areas with this type of epithelium. The goblet cell density may be influenced by several factors, such as the airflow, type and thickness of the epithelium, and whether the genesis of the nasal polyps is infectious or allergic, in addition to polyp growth, size, and age.

Basement Membrane↗

[Good results of endoscopic paranasal sinus surgery for chronic or recurrent sinusitis and for nasal polyps].

Endoscopic sinus surgery is being applied increasingly for chronic or recurrent sinusitis and nasal polyps. We investigated the results, which we classified as subjective results (i.e. the opinion of the patient) and objective results (i.e. the result as seen with nasal endoscopy). The subjective result was 'good' in 85% of 92 patients with chronic or recurrent sinusitis, the objective result in 77% of the treated sides, with a median follow-up of 46 months. In 90 patients with nasal polyps the percentages were 90% and 65% respectively, with a follow-up of 24 months. In 63% of 30 patients with chronic obstructive lung disease and nasal polyps the pulmonary function increased postoperatively (FEV1). In 4.2% of 1235 operated sides in 593 patients local complications were seen. These were mainly minor complications. Only in 0.3% serious complications as a orbital hematoma or a CSF leak were seen. Endoscopic sinus surgery has good results and little morbidity.

Adult↗