Distinct expression of SARS-CoV-2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS-CoV-2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS-CoV-2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP. METHODS: The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. RESULTS: ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN-γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN-γ up-regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co-expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected. CONCLUSION: These findings indicate that ACE2 expression, regulated by IFN-γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation.

Oxidative CaMKII as a potential target for inflammatory disease (Review).

CaMKII is a calcium­activated kinase, proved to be modulated by oxidation. Currently, the oxidative activation of CaMKII exists in several models of asthma, chronic rhinosinusitis with nasal polyps, cardiovascular disease, diabetes mellitus, acute ischemic stroke and cancer. Oxidized CaMKII (ox­CaMKII) may be important in several of these diseases. The present review examines the mechanism underlying the oxidative activation of CaMKII and summarizes the current findings associated with the function of ox­CaMKII in inflammatory diseases. Taken together, the findings of this review aim to improve current understanding of the function of ox­CaMKII and provide novel insights for future research.

[Study on the relationship between 11ß-hydroxysteroid dehydrogenase and glucocorticoid response in nasal polyps].

Objective: To investigate the expression of 11ß-hydroxysteroid dehydrogenase (11ß-HSD) in polyps of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and its correlation with glucocorticoid sensitivity. Methods: The prospective study method was applied. Forty-three adult CRSwNP patients from Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University between April 2016 and June 2017 were enrolled in this study. There were 19 males and 24 females with the age of (37.44±7.42) years old. The endoscopic scores by nasal Polyps Grading System before and after one-week prednisone treatment (0.5 mg/(kg·d)) were evaluated. The response of glucocorticoid by the total endoscopic scores was estimated. According to the patient's reduced nasal polyp endoscopic score, patients were devided into nasal polyps insensitive to glucocorticoids treatment group (insensitive group) and nasal polyp sensitive to glucocorticoids treatment group (sensitive group). The expression of 11ß-HSD1, 11ß-HSD2 in nasal polyps were measured by Real-time PCR (RT-PCR), Western Blot and immunohistochemisty. According to the clinical data, the Logistic regression models and receiver operation characteristics (ROC) curves were used to explore the predictor for glucocorticoid response in CRSwNP. Results: The expression of 11ß-HSD1 and 11ß-HSD1/11ß-HSD2 was higher in sensitive group than that of insensitive group, while the expression of 11ß-HSD2 was lower (rank average was 26.08 vs 16.33, 27.24 vs 14.72, 18.66 vs 26.64, Z value was -2.511, 0.323, -2.059, respectively, all P<0.05). The endoscopic scores in CRSwNP group declined whereas the expression of 11ß-HSD1/11ß-HSD2 increased (r=0.528, P=0.001), while the cutoff value of the ratio of 11ß-HSD1/11ß-HSD2 was 2.290 (sensitivity was 79.17%, specificity was 88.89%). Conclusions: There is a positive correlation between the response of glucocorticoid and the ratio of 11ß-HSD1/11ß-HSD2, which could be used as a marker in predicting the level of tissue response to glucocorticoid therapy in CRSwNP.

The ratio of 11ß-hydroxysteroid dehydrogenase 1/11ß-hydroxysteroid dehydrogenase 2 predicts glucocorticoid response in nasal polyps.

BACKGROUND: Glucocorticoids are the first-line medical treatment for chronic rhinosinusitis with nasal polyps (CRSwNP), whose local metabolism is catalyzed by 11ß-HSD1 and 11ß-HSD2. This study investigates the role of 11ß-HSD1 and 11ß-HSD2 on the glucocorticoid response of CRSwNP patients and the pathogenic mechanism of these polyps. METHODS: Forty-three adult CRSwNP patients were enrolled in this study. We evaluated the endoscopic scores by a nasal polyp grading system before and after treatment. We estimated the response to glucocorticoids by the total endoscopic scores. The logistic regression models and inflammatory characteristic curves were conducted to explore the prediction of the response to glucocorticoid in CRSwNP. The expression of 11ß-HSD1 and 11ß-HSD2 on human sinonasal epithelial cells (HSECS) was measured under the stimulation of toll-like receptor agonists and dexamethasone. RESULTS: The endoscopic scores in the CRSwNP group declined, the expression of 11ß-HSD1/11ß-HSD2 increased (r = 0.5276, P = 0.0011), and the cutoff value of the ratio of 11ß-HSD1/11ß-HSD2 was 0.4654 (sensitivity 79.17%, specificity 88.89%). Dexamethasone induced a decrease in the ratio of 11ß-HSD1/11ß-HSD2 (P = 0.049) by the stimulation of PGN-BS. CONCLUSION: We found a strong correlation between the response to glucocorticoids and the ratio of 11ß-HSD1/11ß-HSD2, which could be used as a marker in predicting the level of tissue response to glucocorticoid therapy in CRSwNP. In addition, PGN-BS could also be a therapeutic target, as it is the negative factor that will decrease the sensitivity of glucocorticoids by reducing the ratio of 11ß-HSD1/11ß-HSD2.

Effects of Erythromycin on the Proliferation and Apoptosis of Cultured Nasal Polyp-Derived Cells and the Extracellular Signal-Regulated Kinase (ERK)/Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway.

BACKGROUND Erythromycin and its derivatives have been used to treat nasal polyposis and reduce inflammation, but the mechanism of action remains unclear. The extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase (MAPK) pathway proteins are expressed in nasal polyps. The aim of this study was to investigate the effects of erythromycin on cell proliferation, apoptosis, and the expression of p-MEK1 and p-ERK1 on cultured nasal polyp-derived cells. MATERIAL AND METHODS Nasal polyp-derived cells (n=32) and control cells from normal inferior turbinate tissue (n=32) were divided into four groups: the control group; the erythromycin-treated (100 µM) group; the selumetinib-treated (2 nM) group; and the erythromycin + selumetinib-treated group. Western blot was used to detect p-MEK1 and p-ERK1 proteins. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect mRNA expression of BCL-2 and BAX. Flow cytometry detected expression of Ki-67 and cell apoptosis. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL). Spectrophotometry assessed caspase-3 activity. RESULTS The expression of Ki-67 was significantly increased, and cell apoptosis was significantly reduced in untreated nasal polyp-derived cells compared with controls. Erythromycin treatment significantly decreased cell proliferation and the expression of p-MEK1 and p-ERK1, and increased apoptosis in nasal polyp-derived cells compared with control cells. Selumetinib treatment had a synergistic effect with erythromycin to reduce the expression of p-MEK1 and p-ERK1, reduce cell proliferation, and increase cell apoptosis. CONCLUSIONS In cultured cells derived from nasal polyps, erythromycin treatment reduced cell proliferation and increased apoptosis by inhibiting the activation of the ERK/MAPK signaling pathway.

Emerging Role of Proteases in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous upper airway disease with multiple etiologies. Clinically, CRSwNP can be classified into either eosinophilic or non-eosinophilic subtypes. The eosinophilic phenotype of CRSwNP is widely thought to be highly associated with recurrence of nasal polyps or surgical failure. Epithelial cells have a crucial role in the development of Th2-biased airway diseases. Recent studies have shown that a wide range of external stimuli such as allergens and microorganisms can elicit the release of epithelial-derived Th2-driving cytokines and chemokines. Protease activity is a feature common to these multiple environmental insults and there is growing evidence for the concept that an imbalance of proteases and protease inhibitors in the epithelial barrier leads to both the initiation and maintenance of chronic eosinophilic airway inflammation. In this review, we analyze recent work on the role of proteases in the development of the sinonasal mucosal type 2 immune response with an emphasis on the molecular pathways promoting adaptive Th2 cell immunity.

Hyaluronan synthases and hyaluronidases in nasal polyps.

Nasal polyps (NPs) are benign lesions of nasal and paranasal sinuses mucosa affecting 1-4 % of all adults. Nasal polyposis affects the quality of patient's life as it causes nasal obstruction, postnasal drainage, purulent nasal discharge, hyposmia or anosmia, chronic sinusitis, facial pain and snoring. Without treatment, the disease can alter the craniofacial skeleton in cases of extended growth of polyps. The development of NPs is caused by the hyperplasia of nasal or paranasal sinuses mucosa, and edema of extracellular matrix. This is usually the result of high concentration of high molecular mass hyaluronan (HA) which is either overproduced or accumulated from blood supply. The size of HA presents high diversity and, especially in pathologic conditions, chains of low molecular mass can be observed. In NPs, chains of about 200 kDa have been identified and considered to be responsible for the inflammation. The purpose of the present study was the investigation, in NPs and normal nasal mucosa (NM), of the expression of the wild-type and alternatively spliced forms of hyaluronidases, their immunolocalization, and the expression of HA synthases to examine the isoform(s) responsible for the increased amounts of HA in NPs. Hyaluronidases' presence was examined on mRNA (RT-PCR analysis) and protein (immunohistochemistry) levels. Hyaluronan synthases' presence was examined on mRNA levels. Hyaluronidases were localized in the cytoplasm of epithelial and inflammatory cells, as well as in the matrix. On mRNA level, it was found that hyal-1-wt was decreased in NPs compared to NM and hyal-1-v3, -v4 and -v5 were substantially increased. Moreover, HAS2 and HAS3 were the only hyaluronan synthases detected, the expression of which was almost similar in NPs and NM. Overall, the results of the present study support that hyaluronidases are the main enzymes responsible for the decreased size of hyaluronan observed in NPs; thus they behave as inflammatory agents. Therefore, they could be a potential target for the design of a more advanced treatment for nasal polyposis.

[The expression and clinical significance of hyaluronan synthase in nasal polyps].

OBJECTIVE: To study the expression of hyaluronan synthasel-3 (HAS1-3) in nasal polyps, and discuss their clinical significance. METHOD: The expression of HA, HAS1, HAS2 and HAS3 in nasal polyps group (25 cases) and inferior turbinate group (15 cases) was detected by immunohistochemistry and semi-quantitative RT-PCR. RESULT: Compared with the control, the expression of HA, HAS1 and HAS3 was higher in nasal polyps (P<0. 05), while there was no significant difference in HAS2 expression (P>0. 05). CONCLUSION: The increase of HASI and HAS3 expression may be the main cause of the excessive deposition of HA in nasal polyps, which may play an important role in the pathogenic process of nasal polyps, and become a potential target for therapy of nasal polyps.

Vitamin D decreases the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 in fibroblasts derived from Taiwanese patients with chronic rhinosinusitis with nasal polyposis.

Vitamin D and its derivatives have modulatory effects in immunological and inflammatory responses. Such properties suggest that they might have an impact on chronic inflammatory airway diseases, including nasal polyposis. The aim of this study was to understand the role of vitamin D in chronic rhinosinusitis with nasal polyps (CRSwNP) by investigating its effect on the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9 in nasal polyp-derived fibroblasts. Two primary fibroblast cultures were established from nasal polyp tissues obtained during surgery. The nasal polyp-derived fibroblasts were stimulated with tumor necrosis factor-α (TNF-α; 10 ng/mL) for 24 hours, followed by replacement with media alone or with vitamin D derivatives (calcitriol or tacalcitol; 10µM) and incubated for another 24 hours. After the treatments, the levels of MMP-2 and MMP-9 secreted were evaluated by both enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. ELISA results revealed that TNF-α could substantially stimulate the secretion of MMP-2 (p < 0.01) and MMP-9 (p < 0.001) in nasal polyp-derived fibroblasts. More importantly, such stimulatory effect was significantly suppressed by adding calcitriol (p ≤ 0.01 for MMP-2 and p < 0.001 for MMP-9) or tacalcitol (p < 0.005 for both MMP-2 and MMP-9). The ELISA results were also confirmed by Western blot analysis. The inhibitory effect of vitamin D derivatives on MMP-2 and MMP-9 secretion could potentiate their application in pharmacotherapy of Taiwanese CRSwNP patients.

Local and systemic proteolytic responses in chronic rhinosinusitis with nasal polyposis and asthma.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma coexist frequently and share similar features of inflammation and remodeling. Remodeling has become an important concept in the pathophysiology of asthma and CRSwNP. It happens early in the development of these diseases and is relatively resistant to treatments. The key enzymes responsible for remodeling are matrix metalloproteinases (MMPs). In this study we examined whether asthma and CRSwNP share similar MMP profiles. METHODS: Nasal secretion and serum specimens of controls (19 subjects) and patients with asthma (12), CRSwNP (39), or both (16) were collected between December 2007 and May 2009. Groups were divided into 2 subgroups according to atopy. MMP-7, MMP-9, MMP-13, tissue inhibitors of metalloproteinases (TIMPs), TIMP-1 and TIMP-2, myeloperoxidase (MPO), and human neutrophil elastase (HNE) were measured using enzyme-linked immunosorbent assay (ELISA), and MMP-8 was determined using immunofluorometric assay. High-sensitivity C-reactive protein (hs-CRP) was measured to estimate systemic involvement. RESULTS: Patients with asthma, CRSwNP, or both exhibited lower MMP-9, MMP-9/TIMP-1, MMP-9/TIMP-2, and MPO in nasal secretions (p < 0.05 in CRSwNP) and higher MMP-9, MMP-9/TIMP-1, MMP-9/TIMP-2, and HNE in serum (p < 0.05 in all groups) compared to controls, whereas no difference in MMP-7, MMP-13, TIMP-1, and TIMP-2 were detected. Atopy increased nasal MMP-9 and MPO expression. hs-CRP was higher in patients with CRSwNP and asthma compared to controls. CONCLUSION: Our findings suggest shared pathomechanisms behind asthma and CRSwNP. Contrasting local vs systemic results reflect a different ability of healthy mucosa to react to exogenous stimuli, possibly indicating a protective function of MMP-9 and possibly also MMP-8 in the airways.

Neuronal NOS localises to human airway cilia.

BACKGROUND: Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. METHODS AND RESULTS: Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker ß-tubulin in the proximal part of the ciliary axoneme. CONCLUSIONS: We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function.

Expression of MMP-9/TIMP-2 in nasal polyps and its functional implications.

Nasal polyps (NP) involve tissue repair and structural remodel, both of which require the extracellular matrix. Matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) are known regulators for tissue reconstruction. This study therefore aimed to analyze the expressional profile of MMP-9 and TIMP-2 in NP patients, with further investigation of their roles in pathogenesis. A total of 60 NP tissue samples (including 15 type I, 21 type II and 24 type III) were collected from surgeries in our hospital, in addition to 6 normal ethmoid sinus mucosa samples. The mRNA and protein expression levels of MMP-9/TIMP-2 were quantified by real-time PCR and Western blotting, respectively. Serum levels were also checked by enzyme-linked immunosorbent assay (ELISA). Both mRNA and protein levels of MMP-9 in NP tissues or serum were significantly elevated compared to those in control ones (P<0.05) while the TIMP-2 expression was suppressed (P<0.05). In patients with more advanced stage, MMP-9 expression was further elevated, with lowered TIMP-2 levels (P<0.05 in both cases). Pathogenesis and progression of NP is closely related with elevated MMP-9 and suppressed TIMP-2 expression, suggesting the role of those factors as indexes for evaluating NP stage. Our results also provide evidences for further studies of pathogenesis and drug targets of NP.

Relationships of indoleamine 2,3-dioxygenase activity and cofactors with asthma and nasal polyps.

BACKGROUND: Asthma and chronic rhinosinusitis with nasal polyps (CRSwNPs) are coexisting diseases that are multifactorial. The rural environment seems to protect from atopy, but its relation with nonatopic airway inflammations has been less investigated. Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in the catabolism of the essential amino acid tryptophan (Trp) to kynurenine (Kyn). Low IDO activity has been previously observed in atopy and asthma. The objective was to investigate the relationships of IDO activity, eosinophils, and cofactors during asthma and/or CRSwNPs. METHODS: A Finnish population-based cohort of adult asthmatic patients (n = 245) and nonasthmatic patients (n = 405) was used. The presence of asthma and atopy were based on patient history and standardized diagnostic tests. The presence of acetyl salicylic acid intolerance, doctor-diagnosed NPs, and countryside environment during childhood were based on a questionnaire report. Serum IDO activity was evaluated by assessing the Kyn/Trp ratio by liquid chromatography. RESULTS: Low IDO activity was associated significantly with atopy, CRSwNPs, and an urban background. IDO activity did not correlate with pulmonary function. As expected, CRSwNPs was more frequent among asthmatic patients. A rural background has a protective effect from atopy and atopic asthma but it did not affect the prevalence of CRSwNPs or nonatopic asthma. CONCLUSION: Low IDO activity might result from the urban environment and influence the development of the atopic phenotype. On the other hand, low IDO activity, found in CRSwNPs, does not seem to be related to the urban background and thus may result from other, still unknown, factors.

The activity of N-acetyl-ß-d-hexosaminidase A and B and ß-glucuronidase in nasal polyps and hypertrophic nasal concha.

UNLABELLED: Nasal polyps and hypertrophic lower nasal conchae are common disorders of nasal cavity. The majority of etiopathogenetic theories indicate inflammatory background of polyps and hypertrophic concha. N-acetyl-ß-D-hexosaminidase and ß-glucuronidase are lysosomal exoglycosidases revealing accelerated activity in inflammatory processes. AIM: The aim of the study was to evaluate the catabolism of glycoconjugates in nasal polyps and hypertrophic nasal concha basing on the activity of N-acetyl-ß-D-hexosaminidase (HEX) and ß-glucuronidase (GLU). MATERIAL AND METHODS: Material consisted of nasal polyps taken from 40 patients during polypectomy in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and hypertrophic lower nasal conchae taken from 20 patients during mucotomy. The activity of HEX, HEX A, HEX B and GLU in supernatant of homogenates of nasal polyps and hypertrophic lower nasal concha tissues has been estimated using colorimetric method. RESULTS: Statistically significant decrease has been observed in concentration of the activity (per 1mg of tissue) of HEX (p<0.05), HEX B (p<0.001) and specific activity (per 1mg of protein) of HEX B (p<0.001) in nasal polyps tissue in comparison to hypertrophic lower nasal conchae tissue. CONCLUSIONS: Decrease in the activity and specific activity concentration of the majority of examined lysosomal exoglycosidases (increasing in inflammations) in comparison to hypertrophic lower nasal conchae suggests electrolytes disorders and questions the inflammatory background of nasal polyps.

Nasal polyp chitinolytic activity associated with smoking or allergy.

BACKGROUND: Cells of the innate immune system that are implicated in allergy and immunity bind to chitin during tissue infiltration in a process negatively regulated by vertebrate chitinases. Both acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) exert chitinolytic activity. The levels of activities of these enzymes in nasal polyps (NPs) of subjects who smoke or who suffer from allergies are unknown. In the present work, we measured the activities of AMCase and ChT in NPs of smokers and allergic subjects. METHODS: We report a prospective cohort study in a tertiary care facility. AMCase and ChT activities of NPs were measured in buffers of several pH values using the fluorogenic substrate 4-methylumbelliferyl-ß-d-N,N',N″-triacetyl-chitotriose. RESULTS: The activities of AMCase and ChT in NPs did not differ significantly among smokers, nonsmokers, and ex-smokers. AMCase and ChT activities were significantly higher in NPs of allergic subjects than in NPs of those who did not suffer from allergy. CONCLUSION: Increased levels of chitinolytic activities in NPs were associated with the allergic rhinitis. We suggest that control of such rhinitis may help to prevent the development and growth of NPs.

Inducible nitric oxide synthase (iNOS) in sinonasal polyp pathogenesis.

OBJECTIVES: We investigated the role of inducible nitric oxide synthase (iNOS) in the pathogenesis of sinonasal polyps. METHODS: Adult patients (21 men, 3 women) with nasal polyposis underwent functional endoscopic sinus surgery. Nine adults without polyps (6 men) who underwent septoplasty and/or rhinoplasty served as controls. Polyp specimens came from three regions: the maxillary sinus (10), ethmoid sinus (14), and nasal cavity (10). Control group samples (9) came from the inferior turbinate. Specimens were evaluated in eight mucosal layers for count and distribution of inflammatory cells and iNOS expression. An iNOS positivity index (PI) was determined for the epithelium (E), subepithelial layer of the lamina propria (SE), and deep paraglandular layer of the mucosa (D). RESULTS: Polymorphonuclear cell (PMNC) % values of the ethmoid and maxillary sinus and overall ethmoid sinus PI were significantly higher in the polyp group. Patients with longer polyp duration, D-perivascular (D-pv), and a higher Brinkmann index had decreased ethmoid sinus D PIs. However, in older patients and patients with longer polyp duration, perivascular PIs increased in maxillary sinus SE and D, respectively. Furthermore, as PMNC % and iNOS-PMNC PI increased, SE_glandular and epithelial_apical iNOS values decreased. In the ethmoid and maxillary sinuses, iNOS_D_. endothelial values increased but decreased in the nasal cavity. CONCLUSIONS: iNOS may play a role in sinonasal polyp pathogenesis, especially in mucosal SE and D layers. Increased vascular permeability, stromal edema, inflammatory cell migration into the stroma of the mucosa, and increased mucosal gland secretion may result in polyp formation.

Respiratory epithelial adenomatoid hamartoma: a poorly recognized entity with mast cell recruitment and frequently associated with nasal polyposis.

Respiratory epithelial adenomatoid hamartoma (REAH) is regarded as a rare tumor of the nasal cavity. The mechanisms driving the development of REAH are unknown, and its nature as a benign tumor, hamartoma, or reactive inflammatory process is still open to discussion. A total of 150 consecutive patients operated on for nasal polyposis (NP) were extensively checked for the diagnosis of REAH. The profile of REAH occurring in association with NP was compared with solitary REAH in a series of 19 cases. The possible role of tryptase-producing mast cells (MC) and of metalloproteinases MMP2 and MMP9 in REAH development was investigated by immunohistochemistry. REAH lesions were identified in 35% of patients who had surgery for NP (53/150). The distribution of the lesions suggested that REAH originated in the olfactory cleft. Solitary REAH occurred about 20 times less frequently than those observed in an NP context but shared the same microscopic characteristics. Tryptase-producing MCs were recruited at high density in REAH (135/10 hpf), compared with inflammatory polyps (45/10 hpf; P<0.00005) and hypertrophied turbinates (51/10 hpf; P<0.0005). REAH also showed constant MMP9 expression and to a lesser degree MMP2 expression in epithelial cells. If solitary REAH is a relatively rare lesion, we demonstrated that an exhaustive sampling allows the detection of a high proportion of NP-associated REAH, sharing the same clinical and histologic characteristics with solitary REAH. Tryptase-producing MCs, possibly in association with MMP expression, may play a central role in REAH formation.

[Influence of complex deacon-tetra (N1,3-triazole,кN2) copper (II) on the barrier and antioxidant pro people with nasal polyps]. / Wplyw kompleksu diaka-tetra (N1,3-triazol,кN2) miedz (II) na bariere pro- i antyoksydacyjna osób z polipami nosa.

INTRODUCTION: The aim of this study was synthesized properties 1,2,4-triazole complex ion Cu (II) to determine their potential antioxidant properties, further indication of activity of antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (Cu-Zn SOD) in patients with nasal polyps and the control group. MATERIAL AND METHODS: The study was conducted in a group of 30 patients with nasal polyps aged 48±13.50 (test 1 - group with a compound, test 2 - no relation), and 30 in the control group aged 48±17.90 (control 3 - group with a compound, control 4 - no relation). Blood samples were collected from the antecubital vein into tubes with anticoagulant (heparin sodium). The activity of catalase, superoxide dismutase and glutathione peroxidase were determined in erythrocytes of patients with nasal polyps and the control group (those without inflammatory conditions. RESULTS: We found that patients with nasal polyps show a decrease in the activity of antioxidant enzymes compared to control: CAT (control 3 - 13.78±6.71 BU/gHb; test 1 - 8.52±7.96 BU/gHb), SOD (control 3 - 1377,614.93±93.44 U/gHb/100ml; test 1 - 867,270.59±49 U/gHb/100ml) and GPX (control 3 - 101.62±8.23 U/gHb; test 1 - 72.97±14.34 U/gHb). Simultaneously, we observed that increasing the activity of antioxidant enzymes compared in the groups control 4 to test 2 (in groups which do not given coordination compound Cu (II): CAT (control 4 - 13.38±7.60 BU/gHb; test 2 - 10.12±3.62 BU/gHb) SOD (control 4 - 1138.88±490.10 U/gHb/100ml; test 2 - 1283.85±439.87 U/gHb/100ml) and GPX (control 4 - 65.18±20.94 U/gHb; test 2 - 90.27±19.42 U/gHb). CONCLUSIONS: The study shows that the complex deacon-tetra (N1,3-triazole,кN2) copper (II) affects the activity of antioxidant enzymes CAT, SOD and GPX.

Lysosomal exoglycosidases in nasal polyps.

INTRODUCTION: Nasal polyps are smooth outgrowths assuming a shape of grapes, formed from the nasal mucosa, limiting air flow by projecting into a lumen of a nasal cavity. Up to now the surgical resection is the best method of their treatment, but etiology and pathogenesis of the nasal polyps is not yet fully established. AIM OF THE STUDY: The aim of the study was the assessment of the selected lysosomal exoglycosidases activity in the nasal polyps. In this study the activity of ß-galactosidase, α-mannosidase and α-fucosidase was determined in the tissue of the nasal polyps obtained from 40 patients (10F, 30M) and control tissues derived from mucosa of lower nasal conchas obtained during mucotomy from 20 patients (10F, 10M). RESULTS: We observed significant lower values of GAL, FUC and tendency to decrease of MAN and GLU concentration in nasal polyps (P) in comparison to control healthy nasal mucosa (C). In nasal polyp tissue (P) no differences of GAL, MAN and FUC specific activity in comparison to control mucosa (C) were found. CONCLUSIONS: Our research supports bioelectrical theory of the nasal polyps pathogenesis and directs attention at research on glycoconjugates and glycosidases of the nasal mucosa extracellular matrix.