Characterization of Oxidative Pathways in Chronic Rhinosinusitis and Sinonasal Polyposis

2006 ◽  
Vol 20 (3) ◽  
pp. 353-359 ◽  
Author(s):  
Martin J. Citardi ◽  
Wei Song ◽  
Pete S. Batra ◽  
Donald C. Lanza ◽  
Stanley L. Hazen
Keyword(s):  
Molecular Markers ◽  
Chronic Rhinosinusitis ◽  
Posttranslational Modifications ◽  
Protein Modification ◽  
Middle Turbinate ◽  
Control Group ◽  
Inflammatory Cell Infiltrate ◽  
Tissue Levels ◽  
Eosinophil Peroxidase ◽  
Sinonasal Polyposis

Background Eosinophils are a characteristic inflammatory cell infiltrate in both chronic rhinosinusitis (CRS) and sinonasal polyposis (SNP). The posttranslational modifications, 3-bromo-tyrosine (Br-Tyr) and 3-chloro-tyrosine (Cl-Tyr), serve as specific molecular markers for production of brominating and chlorinating oxidants, respectively, by the eosinophil peroxidase and myeloperoxidase systems of leukocytes. The aim of this study was to identify mechanisms of oxidative protein modifications in sinonasal mucosa of CRS and SNP patients by measuring Br-Tyr, Cl-Tyr, and alternative molecular markers of distinct oxidative pathways. Methods Levels of Br-Tyr; Cl-Tyr; di-Tyrosine (di-Tyr), a specific oxidative cross-link; ortho-tyrosine (o-Tyr) and meta-tyrosine (m-Tyr), markers for protein modification by hydroxyl radical-like oxidants; and nitro-tyrosine (NO2-Tyr), a stable product of nitric oxide (NO)–derived oxidants, were measured in anterior ethmoid mucosa tissue from CRS and SNP patients, as well as in middle turbinate mucosa from normal volunteers, using tandem mass spectrometry. Results Tissue levels of Br-Tyr were significantly higher in the CRS group compared with the control group (797 μmol/mol versus 515 μmol/mol tyrosine, p < 0.015), but no differences were detected for Cl-Tyr, di-Tyr, m-Tyr, o-Tyr, and NO2-Tyr. Tissue levels of both Br-Tyr and di-Tyr were significantly higher in the SNP group compared with the control group (879 μmol/mol versus 515 μmol/mol, p < 0.005; 5090 μmol/mol versus 1700 μmol/mol, p < 0.024, respectively), but no differences were detected for Cl-Tyr, m-Tyr, o-Tyr, and NO2-Tyr. Conclusion Br-Tyr, a molecular footprint predominantly formed by eosinophil peroxidase–catalyzed tissue damage, may serve as an objective index of CRS and SNP disease activity.

scholarly journals CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

2021 ◽  
Author(s):  
Wagner Vargas Souza Lino ◽  
André Luis Lacerda Bachi ◽  
José Arruda Mendes Neto ◽  
Gabriel Caetani ◽  
Jônatas Bussador do Amaral ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Nasal Polyposis ◽  
Transforming Growth Factor ◽  
Middle Turbinate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Histologic Analysis ◽  
Aspirin Intolerance ◽  
Tgf Β1

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

scholarly journals Revision endoscopic frontal sinus surgery for refractory chronic rhinosinusitis via modified agger nasi approach

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052199527
Author(s):  
Jun Dai ◽  
De Huai ◽  
Min Xu ◽  
Jingjing Cai ◽  
Haixu Wang
Keyword(s):  
Chronic Rhinosinusitis ◽  
Frontal Sinus ◽  
Middle Turbinate ◽  
Sinus Surgery ◽  
Control Group ◽  
Efficacy Rate ◽  
Clinical Effects ◽  
Observation Group ◽  
Frontal Sinus Surgery ◽  
Symptoms And Signs

Objective To examine the clinical effects of revision endoscopic frontal sinus surgery (RESS) through modified agger nasi (MAN)–middle turbinate resection on refractory chronic rhinosinusitis (CRS). Methods We reviewed 156 patients who were treated for refractory CRS from February 2012 to August 2014. These patients had been diagnosed with refractory CRS by computed tomography and endoscopy and had received several surgical and medical treatments in the past, but their condition had not been cured. They were divided into the observation group (RESS through MAN–middle turbinate resection, n = 78) and the control group (endoscopic sinus surgery, n = 78). Complete or partial control of the patient’s symptoms and signs suggested that the treatment was effective, and no improvement in the symptoms and signs indicated that the treatment was ineffective. Results The 6-month treatment efficacy rate was significantly higher in the observation group (91.03%) than in the control group (71.79%). The observation group had a significantly lower complication rate (7.69%) and recurrence rate (3.85%) than the control group (17.95% and 12.82%, respectively). Conclusion RESS through MAN–middle turbinate resection together with adequate perioperative preparation has a significant effect on the outcome of refractory CRS and is worthy of clinical promotion.

Humoral factors of innate immunity in the saliva of patients with infectious inflammatory respiratory diseases

2018 ◽  
pp. 13-17
Author(s):  
Oleg Melnikov ◽  
Diana Zabolotnaya ◽  
Alexander Bredun ◽  
Bogdan Bil ◽  
Oksana Rylska ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Chronic Rhinosinusitis ◽  
Inflammatory Diseases ◽  
Activity Level ◽  
Chronic Tonsillitis ◽  
Control Group ◽  
Quantitative Composition ◽  
Upper Airways ◽  
Humoral Factors ◽  
Immune Modulators

Introduction: In recently ears factors of innate immunity both cellular and humoral have been paid considerable attention as they are a protective barrier of a fast response and that is why they are largely concentrated at the intersection of the digestive tract and airways. The data concerning the activity level of factors of innate immunity in the upper airways affected by nonspecific inflammatory processes is insufficient and sparse and therefore the purpose of this research was to study the content of humoral factors of innate immunity in the oropharyngeal secretion (ORS) of patients with chronic infectious inflammatory diseases of the upper airways in remission. Materials and Methods: There was an examination of 16 patients with chronic rhinosinusitis (CRS) of bacterial genesis (15-40 years old), 12 patients with rhinopharyngitis of post-viral genesis (8-16 years old), 12 people with scleroma from 30 tо 52 years of age (atrophic form), 10 patients with chronic tonsillitis in remission (from 10 to 33 years of age) and 11 patients of a control group (practically healthy donors from 12 tо 40 years of age). The content of MIP-1b, defensin-1β, lactoferrin, lysozyme, α-interferon was studied in the nonstimulated OPS. Statistics were carried out using Mann-Whitney U-test. Results: The greatest number of deviations in the decrease in the content of the examined nonspecific protective factors was found in cases of scleroma, chronic tonsillitis and chronic rhinosinusitis (p<0,05). The lack of protective humoral factors of innate immunity can be evidence of local immunodeficiency even in remission, which is a pathophysiological component of the maintenance of chronic inflammation. Conclusion: The decrease int he quantitative composition of factors of innate immunity in the oropharyngeal secretion of patients with chronic infectious inflammatory diseases of the airways is an objective ground not only for a replacement therapy, but also for the use of immune response modifiers from photo-immune modulators to “genuine immune modulators” controlling the state of the factors of both innate immunity and immunoglobulins, primarily of secretory type, the level and functionality of various groups of immunocompetent and accessory cells.

scholarly journals Arginase Isoform Expression in Chronic Rhinosinusitis

2019 ◽  
Vol 8 (11) ◽  
pp. 1809 ◽  
Author(s):  
Diana Vlad ◽  
Silviu Albu
Keyword(s):  
Nitric Oxide ◽  
Chronic Rhinosinusitis ◽  
Defense Mechanisms ◽  
Upper Airway ◽  
Control Group ◽  
Mrna Levels ◽  
Tissue Samples ◽  
Endoscopic View ◽  
Important Regulator ◽  
Arginase I

Nitric oxide (NO) has emerged as an important regulator of upper airway inflammation, mainly as part of the local naso-sinusal defense mechanisms. Increased arginase activity can reduce NO levels by decreasing the availability of its precursor, L-arginine. Chronic rhinosinusitis (CRS) has been associated with low levels of nasal nitric oxide (nNO). Thus, the present study investigates the activity of arginase I (ARG1) and II (ARG2) in CRS and its possible involvement in the pathogenesis of this disease. Under endoscopic view, tissue samples of pathologic (n = 36) and normal (n = 29) rhinosinusal mucosa were collected. Arginase I and II mRNA levels were measured using real-time PCR. Our results showed low arginase I activity in all samples. The levels of ARG2 were significantly higher in patients with chronic rhinosinusitis compared to the control group (fold regulation (FR) 2.22 ± 0.42 vs. 1.31 ± 0.21, p = 0.016). Increased ARG2 expression was found in patients with CRS without nasal polyposis (FR 3.14 ± 1.16 vs. 1.31 ± 0.21, p = 0.0175), in non-allergic CRS (FR 2.55 ± 0.52 vs. 1.31 ± 0.21, p = 0.005), and non-asthmatic CRS (FR 2.42 ± 0.57 vs. 1.31 ± 0.21, p = 0.028). These findings suggest that the upregulation of ARG2 may play a role in the pathology of a distinctive phenotype of CRS.

scholarly journals Expression of Transcript Variants of PTGS1 and PTGS2 Genes among Patients with Chronic Rhinosinusitis with Nasal Polyps

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 135
Author(s):  
Wioletta Pietruszewska ◽  
Wojciech Fendler ◽  
Marta Podwysocka ◽  
Adam J. Białas ◽  
Piotr Kuna ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Direct Sequencing ◽  
Adult Patients ◽  
Control Group ◽  
Reliable Test ◽  
Aggressive Disease ◽  
Transcript Variants

To date, there has been no reliable test to identify unfavorable course of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), especially in aspirin intolerant patients. The research aimed to analyze the expression of transcript variants of PTGS1 and PTGS2 genes in the pathobiology of the disease. The study was performed on 409 adult patients: 206 CRSwNP patients including 44 (21.36%) aspirin intolerant patients and 203 healthy volunteers in the control group. Transcript variants of the PTGS1 and PTGS2 genes named as follows: COX1.1 for NM_000962, COX1.2 for NM_080591, COX1.3 for NM_001271165.1, COX1.4 for NM_001271368.1, COX1.5 for NM_001271166.1, COX2.1 for NM_000963.3, COX2.2 for AY_151286 and COX2.3 for BQ_722004 were confirmed using direct sequencing and quantified using targeted qPCR. The coexistence of all examined transcript variants in the study and the control group and significant differences between both were found. In aspirin sensitive patients, the levels of COX1.2, COX1.3, COX1.4 and COX1.5 isoforms were higher compared to aspirin-tolerant patients. The severity of symptoms was bigger in patients with higher expressions of variants: COX1.1 (R with dCt = −0.134; p = 0.0490), COX1.3 (R = −0.1429; p = 0.0400) and COX1.5 (Rs = −0.1499; p = 0.032). The expression of COX1.1 (Rs = −0.098; p = 0.049) and COX1.5 (Rs = −0.141; p = 0.043) isoforms increased with polyposis advancement in endoscopy. With the CT extent of sinuses opacification, COX1.1 isoform also significantly increased (Rs = −0.163; p = 0.020). The isoforms COX1.3, COX1.4, COX1.5 and COX2.1 may promote milder CRSwNP course. On the contrary, the variants COX1.1, COX1.2 and COX2.2 may be involved in a more aggressive disease.

scholarly journals Characterization of Cytokines and Proliferation Marker Ki67 in Chronic Rhinosinusitis with Nasal Polyps: A Pilot Study

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 607
Author(s):  
Rudolfs Janis Viksne ◽  
Gunta Sumeraga ◽  
Mara Pilmane
Keyword(s):  
Connective Tissue ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Cellular Proliferation ◽  
Rank Correlation ◽  
Control Group ◽  
Relative Distribution ◽  
Proliferation Marker ◽  
Ki 67 ◽  
Stimulation Of

Background and Objectives: Chronic rhinosinusitis (CRS) is a condition that affects as much as 10.9% of the population and, along with presence of nasal polyps, is associated with significant morbidity and decreased quality of life. Studies on molecular pathways that have been activated in nasal polyp tissue are mainly based on cytokine concentration detection. Therefore, our aim is to investigate the complex appearance, relative distribution and interlinks of IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 and Ki 67 in chronic rhinosinusitis with nasal polyps (CRSwNP) affected human nasal mucosa. Materials and Methods: Samples of nasal polyps were obtained from 12 patients with previously diagnosed CRSwNP and no prior surgery. Control group consisted of samples from 17 otherwise healthy individuals with isolated nasal septum deviation. Tissues were stained for IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 and Ki67 immunohistochemically. Non-parametric statistic, Mann–Whitney U test and Spearman’s rank correlation coefficient were used. Results: All factors, except connective tissue cytokine IL-10 and proliferation marker Ki-67, had increased presence in connective tissue and decreased presence in epithelium of nasal polyps when compared to controls. Very strong and strong positive correlations between factors were observed. Conclusions: Decreased appearance of IL-1α, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 positive structures in the nasal epithelium with selective increase of IL-1α and IL-12 in nasal subepithelial connective tissue characterize the cytokine endotype with dysfunctional epithelial barrier and local stimulation of immune response in the connective tissue in case of chronic rhinosinusitis with polyps. Decrease of IL-6 in both—epithelium and connective tissue with strong correlation between it and IL-7 and IL-10 in connective tissue suggests significant stimulation of this regulatory cytokine and, possibly, the important role in pathogenesis of the development in nasal polyps. Correlations between Ki67 and cytokines indicate possible involvement of IL-4, IL-7 and IL-12 in regulation of cellular proliferation.

scholarly journals Association between obesity and chronic rhinosinusitis with nasal polyps: a national population-based study

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e047230
Author(s):  
Jae-Sung Nam ◽  
Yun Ho Roh ◽  
Wasan Almazouq Fahad ◽  
Hae-Eun Noh ◽  
Jong-Gyun Ha ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Chronic Rhinosinusitis ◽  
Logistic Regression Analysis ◽  
Central Obesity ◽  
Nasal Polyps ◽  
Control Group ◽  
Cross Sectional ◽  
Cross Sectional Analysis ◽  
Sectional Analysis

ObjectivesWe performed a cross-sectional analysis of data from the nationwide Korea National Health and Nutrition Examination Survey to evaluate the association between obesity and chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyp (CRSsNP).DesignRetrospective cross-sectional analysis of health survey data.SettingVoluntary survey of representative South Korean populations.ParticipantsIn total, 32 384 individuals aged 19 years or older with available data on CRS and obesity were included.Primary and secondary outcome measuresDiagnosis of CRSwNP or CRSsNP was performed by trained otolaryngologists through sinus endoscopy and surveys of medical history. General and central obesity was diagnosed using body mass index (BMI) and waist circumference (WC), respectively.MethodsA multivariate logistic regression analysis was used to clarify the association between CRSwNP or CRSsNP and obesity according to BMI and WC. Non-obese individuals were recruited as controls.ResultsThe prevalence of CRSwNP was higher in the general (OR, 1.438; 95% CI, 1.170 to 1.768; p<0.001) and central (OR, 1.251; 95% CI, 1.031 to 1.520; p=0.033) obesity groups than in the control group. Prevalence of CRSsNP was not correlated with obesity. In a logistic regression analysis, olfactory dysfunction (OR, 1.329; 95% CI, 1.137 to 1.553; p<0.001) and purulent discharge (OR, 1.383; 95% CI, 1.193 to 1.603; p<0.001) showed a higher incidence in the central obesity group than in the control group.ConclusionsWe demonstrated an association between CRSwNP and general and central obesity. Further investigations on the mechanism underlying this correlation are necessary for an improved understanding of the pathogenesis of CRSwNP.

scholarly journals JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1059
Author(s):  
Yu-Tsai Lin ◽  
Wei-Chih Chen ◽  
Ming-Hsien Tsai ◽  
Jing-Ying Chen ◽  
Chih-Yen Chien ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Disease Severity ◽  
Nasal Polyps ◽  
Inflammatory Diseases ◽  
Janus Kinase ◽  
Sinus Surgery ◽  
Control Group ◽  
Jak2 Inhibitor ◽  
Ifn Γ ◽  
Snot 22

Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.

scholarly journals Embryo-induced transcriptome changes in bovine endometrium reveal species-specific and common molecular markers of uterine receptivity

Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 319-331 ◽  
Author(s):  
Stefan Bauersachs ◽  
Susanne E Ulbrich ◽  
Karin Gross ◽  
Susanne E M Schmidt ◽  
Heinrich H D Meyer ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Molecular Mechanisms ◽  
Cdna Array ◽  
Early Embryo ◽  
Cdna Libraries ◽  
Control Group ◽  
Regulation Of Transcription ◽  
Uterine Receptivity ◽  
Subtracted Cdna Libraries ◽  
Species Specific

The endometrium plays a central role among the reproductive tissues in the context of early embryo–maternal communication and pregnancy. This study investigated transcriptome profiles of endometrium samples from day 18 pregnant vs non-pregnant heifers to get insight into the molecular mechanisms involved in conditioning the endometrium for embryo attachment and implantation. Using a combination of subtracted cDNA libraries and cDNA array hybridisation, 109 mRNAs with at least twofold higher abundance in endometrium of pregnant animals and 70 mRNAs with higher levels in the control group were identified. Among the mRNAs with higher abundance in pregnant animals, at least 41 are already described as induced by interferons. In addition, transcript levels of many new candidate genes involved in the regulation of transcription, cell adhesion, modulation of the maternal immune system and endometrial remodelling were found to be increased. The different expression level was confirmed with real-time PCR for nine genes. Localisation of mRNA expression in the endometrium was shown byin situhybridisation forAGRN,LGALS3BP,LGALS9,USP18,PARP12andBST2. A comparison with similar studies in humans, mice, and revealed species-specific and common molecular markers of uterine receptivity.

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