Evaluation of MMP-12 expression in chronic rhinosinusitis with nasal polyposis

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
S. Lygeros ◽  
G. Danielides ◽  
G.C. Kyriakopoulos ◽  
K. Grafanaki ◽  
F. Tsapardoni ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Gene Expression Regulation ◽  
Statistical Significance ◽  
Sinus Surgery ◽  
Mrna Levels ◽  
Tissue Samples ◽  
Potential Implication ◽  
Protein Levels ◽  
Healthy Mucosa ◽  
The Difference

Background: The purpose of this study was to evaluate the expression of MMP-12 in patients with chronic rhinosinusitis with polyps (CRSwNP). Methodology: Tissue samples from 37 patients with CRSwNP undergoing functional endoscopic sinus surgery and healthy mucosa specimens from 12 healthy controls were obtained intraoperatively. The mRNA and protein expression levels of MMP-12 were quantified by real-time polymerase chain reaction and Western blotting, respectively. Results: mRNA levels of MMP-12 were significantly elevated in the CRSwNP tissue samples compared to those in control ones. The protein levels of MMP-12 showed a trend of increasing but with no statistical significance. Conclusions: Elevation of MMP-12 in patients with CRSwNP suggests its potential implication in the pathogenesis of the disease. The difference in the expression profile observed between mRNA and protein levels could be due to post-translational gene expression regulation. Our findings provide evidence that MMP-12 along with other MMPs may serve as a biomarker and therapeutic target in the management of the disease.

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 Determination of CYP450 Expression Levels in the Human Small Intestine by Mass Spectrometry-Based Targeted Proteomics

2021 ◽  
Vol 22 (23) ◽  
pp. 12791
Author(s):  
Alexia Grangeon ◽  
Valérie Clermont ◽  
Azemi Barama ◽  
Fleur Gaudette ◽  
Jacques Turgeon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Small Intestine ◽  
Protein Expression ◽  
Mrna Levels ◽  
Targeted Proteomics ◽  
Tissue Samples ◽  
Human Organ ◽  
Expression Levels ◽  
Protein Levels ◽  
Human Small Intestine

The human small intestine can be involved in the first-pass metabolism of drugs. Under this condition, members of the CYP450 superfamily are expected to contribute to drug presystemic biotransformation. The aim of this study was to quantify protein expression levels of 16 major CYP450 isoforms in tissue obtained from nine human organ donors in seven subsections of the small intestine, i.e., duodenum (one section, N = 7 tissue samples), jejunum (three subsections (proximal, mid and distal), N = 9 tissue samples) and ileum (three subsections, (proximal, mid and distal), N = 9 tissue samples), using liquid chromatography tandem mass spectrometry (LC-MS/MS) based targeted proteomics. CYP450 absolute protein expression levels were compared to mRNA levels and enzyme activities by using established probe drugs. Proteins corresponding to seven of sixteen potential CYP450 isoforms were detected and quantified in various sections of the small intestine: CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, CYP3A5 and CYP4F2. Wide inter-subject variability was observed, especially for CYP2D6. CYP2C9 (p = 0.004) and CYP2C19 (p = 0.005) expression levels decreased along the small intestine. From the duodenum to the ileum, CYP2J2 (p = 0.001) increased, and a trend was observed for CYP3A5 (p = 0.13). CYP3A4 expression was higher in the jejunum than in the ileum (p = 0.03), while CYP4F2 expression was lower in the duodenum compared to the jejunum and the ileum (p = 0.005). CYP450 protein levels were better correlated with specific isoform activities than with mRNA levels. This study provides new data on absolute CYP450 quantification in human small intestine that could improve physiologically based pharmacokinetic models. These data could better inform drug absorption profiles while considering the regional expression of CYP450 isoforms.

S289 – Effect of Pterygopalatine Injection on EBL in Sinus Surgery

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P171-P171
Author(s):  
Michael Bublik ◽  
Jean A Eloy ◽  
Brian Tse ◽  
Ruiz Jose W ◽  
Roy R Casiano
Keyword(s):  
Statistical Significance ◽  
Demographic Data ◽  
Pterygopalatine Fossa ◽  
Sinus Surgery ◽  
Control Group ◽  
Simple Method ◽  
Injection Group ◽  
Greater Palatine Foramen ◽  
Estimated Blood Loss ◽  
The Difference

Objectives We compare estimated blood loss (EBL) during functional endoscopic sinus surgery between patients receiving transoral pterygopalatine fossa and transnasal infiltration (combined) to patients receiving only transnasal infiltration. Variables such as CT-stage, revision surgery, presence of polyps, and operative time are considered. Methods Injection with 1% lidocaine with 1:100,000 epinephrine was performed through the greater palatine foramen and transnasally in the “combined” study group (20 patients) and only transnasally in the control group (22 patients). Charts, operative reports, and CT scans were reviewed and demographic data as well as pertinent information were collected. Patients were followed up and all additional procedures and events were recorded. Results 12 females and 8 males, average age of 48, underwent combined injections; 16 males and 6 females (average age of 50) were in the control group. Using the Wilcoxon/ Kruskal-Wallis Tests (Rank Sums), mean EBL calculated for the combined injection group was 347ml and 493ml for the transnasal injection group (CI 0.95, p=0.093). Average ratio of EBL over OR time was 2.89 ml/min for the combined group and 4.11 ml/min for the control group. We also compare EBL between groups in patients with polyps, endoscopic and CT stage, and revision cases. No complications were reported. Conclusions Combined injection of the pterygopalatine fossa and nasal cavity appears to be a safe and relatively simple method to decrease EBL during sinus surgery, but initial data analysis shows that the difference did not reach statistical significance.

scholarly journals Is there an inflammatory stimulus to human term labour?

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256545
Author(s):  
Natasha Singh ◽  
Bronwen Herbert ◽  
Garvin Sooranna ◽  
Nishel M. Shah ◽  
Ananya Das ◽  
...  
Keyword(s):  
Statistical Significance ◽  
P Value ◽  
Mrna Levels ◽  
Inflammatory Stimulus ◽  
Rt Pcr ◽  
Protein Levels ◽  
Decidua Basalis ◽  
Early Labour ◽  
Transcription Factor Activation ◽  
Term Labour

Inflammation is thought to play a pivotal role in the onset of term and some forms of preterm labour. Although, we recently found that myometrial inflammation is a consequence rather than a cause of term labour, there are several other reproductive tissues, including amnion, choriodecidua parietalis and decidua basalis, where the inflammatory stimulus to labour may occur. To investigate this, we have obtained amnion, choriodecidual parietalis and decidua basalis samples from women at various stages of pregnancy and spontaneous labour. The inflammatory cytokine profile in each tissue was determine by Bio-Plex Pro® cytokine multiplex assays and quantitative RT-PCR. Active motif assay was used to study transcription activation in the choriodecidua parietalis. Quantitative RT-PCR was use to study the pro-labour genes (PGHS-2, PGDH, OTR and CX43) in all of the tissues at the onset of labour and oxytocin (OT) mRNA expression in the choriodecidual parietalis and decidua basalis. Statistical significance was ascribed to a P value <0.05. In the amnion and choriodecidua parietalis, the mRNA levels of various cytokines decreased from preterm no labour to term no labour samples, but the protein levels were unchanged. The choriodecidua parietalis showed increase in the protein levels of IL-1β and IL-6 in the term early labour samples. In the amnion and decidua basalis, the protein levels of several cytokines rose in term established labour. The multiples of the median derived from the 19-plex cytokine assay were greater in term early labour and term established labour samples from the choriodecidua parietalis, but only in term established labour for myometrium. These data suggest that the inflammatory stimulus to labour may begin in the choriodecidua parietalis, but the absence of any change in prolabour factor mRNA levels suggests that the cytokines may act on the myometrium where we observed changes in transcription factor activation and increases in prolabour gene expression in earlier studies.

Analysis of Histopathological Endotyping for Chronic Rhinosinusitis Phenotypes Based on Comorbid Asthma and Allergic Rhinitis

2019 ◽  
Vol 33 (5) ◽  
pp. 507-512 ◽  
Author(s):  
Jeffrey P. Radabaugh ◽  
Joseph K. Han ◽  
Rachel G. Moebus ◽  
Evan Somers ◽  
Kent Lam
Keyword(s):  
Allergic Rhinitis ◽  
Chronic Rhinosinusitis ◽  
Plasma Cells ◽  
Inverse Correlation ◽  
Cell Types ◽  
Sinus Surgery ◽  
Controlled Study ◽  
Histopathological Analysis ◽  
Tissue Samples ◽  
Direct Management

Background An emerging trend in clinical research has centered on improving the characteristics of chronic rhinosinusitis (CRS) according to phenotypes and endotypes. The objective of this study is to utilize histopathological markers to better characterize CRS phenotypes that are defined by the presence or absence of comorbid bronchial asthma (BA) and allergic rhinitis (AR). Methods A prospective case-controlled study of CRS patients was conducted. For the CRS cohort, mucosal biopsies were obtained during endoscopic sinus surgery, while samples of ethmoid mucosa were collected in control patients undergoing endoscopic skull base surgery. Histopathological analysis of tissue samples determined the relative frequency of inflammatory cell types, including eosinophils, lymphocytes, neutrophils, mast cells, and plasma cells. The presence and absence of comorbid BA and AR were used to further divide CRS, allowing for further subgroup analysis. Results Of 82 recruited patients, there were 67 CRS patients and 15 controls. Significantly increased eosinophil ratios were found in CRS patients with AR, BA, or both, when compared with controls ( P < .001). Conversely, CRS patients with neither comorbid diagnosis failed to demonstrate statistically significant elevations in eosinophil ratios ( P > .05). Lymphocyte ratios showed a significantly inverse correlation with trends demonstrated by eosinophil ratios in all patient subgroups ( P < .001). Neutrophil, mast cell, and plasma cell ratios did not show significant differences across the evaluated subgroups. Conclusions The clinical diagnosis of comorbid BA and AR may aid in better characterizing CRS endotypes without invasive testing and better direct management of the disease.

Identifying Intracellular Staphylococcus Aureus in Chronic Rhinosinusitis: A Direct Comparison of Techniques

2012 ◽  
Vol 26 (6) ◽  
pp. 444-449 ◽  
Author(s):  
Neil C.-W. Tan ◽  
Hai Bac Tran ◽  
Andrew Foreman ◽  
Camille Jardeleza ◽  
Sarah Vreugde ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Chronic Rhinosinusitis ◽  
Imaging Techniques ◽  
Simultaneous Detection ◽  
Sinus Surgery ◽  
Confocal Scanning Laser Microscopy ◽  
Tissue Samples ◽  
Complementary Techniques ◽  
Confocal Scanning Laser ◽  
A Prospective Study

Background The emerging concept of intracellular pathogens such as Staphylococcus aureus playing a role in chronic rhinosinusitis (CRS) has led to the development of numerous imaging techniques for their identification. Traditional methods of bacterial culture are not effective at localizing bacteria to the surface or within tissue samples. The aim of this study was to develop and validate a novel imaging technique using confocal scanning laser microscopy (CSLM) coupled with a fluorescence in situ hybridization (FISH) probe and nucleic acid counterstain (propidium iodide [PI]) that allows for simultaneous analysis of S. aureus intracellular status and surface biofilm within whole mucosal samples. Methods A prospective study was performed including 17 patients undergoing endoscopic sinus surgery for CRS. Tissue samples were analyzed with both CSLM-FISH/PI and immunohistochemistry (IHC) for intracellular S. aureus status. Results Using CSLM-FISH/PI intracellular S. aureus was identified in 9/17 (47%) patients and in 7/17 (39%) using IHC. Surface biofilm can be identified with CSLM-FISH/PI in the same piece of tissue; however, deeper imaging to the submucosa is impossible. IHC showed submucosal bacteria in three patients. Conclusion Both CSLM-FISH/PI and IHC are complementary techniques that can be used to identify intracellular S. aureus. CSLM-FISH/PI allows for the simultaneous detection of intracellular status and surface biofilm within the tissue analyzed. IHC has a role in the identification of intracellular and submucosal S. aureus within these tissues. Additional investigation is required to identify the true pathogenic nature of intracellular organisms as well as any relationship to surface biofilm status.

Two distinct mechanisms regulate the levels of a cellular tumor antigen, p53

1983 ◽  
Vol 3 (12) ◽  
pp. 2143-2150
Author(s):  
N C Reich ◽  
M Oren ◽  
A J Levine
Keyword(s):  
Steady State ◽  
Cell Line ◽  
P53 Protein ◽  
Mrna Levels ◽  
3T3 Cells ◽  
Transformed Cell ◽  
Protein Levels ◽  
Steady State Levels ◽  
The Difference ◽  
P53 Mrna

The steady-state levels of p53 protein and p53 mRNA in transformed and nontransformed cells were examined to elucidate the mechanisms controlling expression of p53. mRNA levels were determined by Northern blot hybridization analysis, employing a p53-specific cDNA clone (M. Oren and A.J. Levine, Proc. Natl. Acad. Sci. U.S.A. 80:56-59, 1983), and protein levels were determined by the Western blotting technique. Analysis of p53 mRNA revealed a single polyadenylated mRNA species migrating at ca. 18S. Levels of p53 mRNA in simian virus 40-transformed cell line (SVT2) and in an homologous nontransformed cell line (3T3) were equivalent, although the steady-state levels of p53 protein were 25- to 100-fold higher in the SVT2 cells than in the 3T3 cells. A study with a non-virus-transformed cell system revealed a different result. Embryonal carcinoma cells (F9) were found to have nearly 20-fold higher levels of p53 mRNA in comparison with differentiated benign progeny cells. In this system the difference in p53 mRNA levels corresponded to the difference in p53 protein levels. Pulse-chase experiments were performed to study the half-life of p53 protein in these four types of cells. The turnover of p53 protein occurred with biphasic kinetics. In addition, it was found that protein synthesis inhibitors placed in the medium during the chase period prevented the turnover of p53 protein in transformed cells, but not in nontransformed (3T3) cells. These results provide evidence that the regulation of p53 expression in cells can occur at the level of p53 mRNA abundancy or p53 protein stability depending upon the experimental system under study, and that a regulated degradation process controls the turnover of p53 protein.

Mycoplasma pneumoniaeandChlamydophila pneumoniae: a comparative study in patients with nasal polyposis and healthy controls

2015 ◽  
Vol 129 (9) ◽  
pp. 865-869 ◽  
Author(s):  
D G Ioannidis ◽  
V A Lachanas ◽  
Z Florou ◽  
J G Bizakis ◽  
E Petinaki ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Real Time ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Inferior Turbinate ◽  
Sinus Surgery ◽  
Control Group ◽  
Chain Reaction ◽  
Tissue Samples ◽  
Polymerase Chain

AbstractIntroduction:The role played byMycoplasma pneumoniaeandChlamydophila pneumoniaein the pathogenesis of chronic rhinosinusitis with nasal polyps has been the object of ongoing debate. We used real-time polymerase chain reaction to investigate the prevalence of both microorganisms in the nasal tissue samples of patients and controls.Methods:We extracted DNA from nasal polyp samples obtained during functional endoscopic sinus surgery and the inferior turbinate samples of controls undergoing septoplasty. We used the highly sensitive real-time polymerase chain reaction to detect the presence ofM pneumoniaeandC pneumoniaeDNA.Results:Patients with chronic rhinosinusitis with nasal polyps consisted of 62 individuals (39 men; mean age 51 years); the control group consisted of 24 individuals (13 men; mean age 45 years). All samples from both groups were negative forM pneumoniaeandC pneumoniaeDNA.Conclusion:We have demonstrated that the likelihood ofM pneumoniaeandC pneumoniaeacting as an ongoing inflammatory stimulus in chronic rhinosinusitis with nasal polyps is slim.

scholarly journals Differential Expression of TFF1 and TFF3 in Patients Suffering from Chronic Rhinosinusitis with Nasal Polyposis

2019 ◽  
Vol 20 (21) ◽  
pp. 5461 ◽  
Author(s):  
Martina Mihalj ◽  
Maro Bujak ◽  
Josip Butković ◽  
Željko Zubčić ◽  
Maja Tolušić Levak ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Target Gene ◽  
Nasal Polyposis ◽  
Sinus Surgery ◽  
Mrna Levels ◽  
Nasal Turbinate ◽  
Family Factor ◽  
Nasal Septoplasty ◽  
Type 2 Inflammation

Trefoil family factor (TFF) proteins contribute to antimicrobial defense and the maintenance of sinonasal epithelial barrier integrity. Dysregulation of TFF expression may be involved in the development of chronic inflammation and tissue remodeling characteristically found in chronic rhinosinusitis with nasal polyposis (CRSwNP). Expressions of TFF1 and TFF3 were determined in specimens of middle nasal turbinate (MNT-0), bulla ethmoidalis (BE), and nasal polyps (NP) from CRSwNP patients (n = 29) and inferior nasal turbinate from a group of control patients (underwent nasal septoplasty, n = 25). An additional MNT sample was collected 6 months after functional endoscopic sinus surgery (FESS, MNT-6). TFF1 mRNA levels were significantly reduced in all specimens by approximately three- to five-fold, while TFF3 was increased in MNT-0, as compared with controls. Six months after surgery their levels were reversed to control values. CRSwNP patients with S. epidermidis isolated from sinus swabs showed upregulation of TFF3 in MNT and NP as compared with patients with sterile swabs. Target gene regulation was not affected by the presence of type 2 inflammation in patients with confirmed allergy. Results of this study imply participation of TFFs genes in the development of CRSwNP.

scholarly journals Moulds and Staphylococcus aureus enterotoxins are relevant allergens to affect Type 2 inflammation and clinical outcomes in chronic rhinosinusitis patients

2020 ◽  
Vol 6 (4) ◽  
pp. 00265-2020
Author(s):  
Yoshihiro Kanemitsu ◽  
Kensuke Fukumitsu ◽  
Ryota Kurokawa ◽  
Norihisa Takeda ◽  
Yoshiyuki Ozawa ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Outcomes ◽  
Chronic Rhinosinusitis ◽  
Specific Ige ◽  
Sinus Surgery ◽  
Tissue Samples ◽  
Asthmatic Patients ◽  
Staphylococcus Aureus Enterotoxins ◽  
Type 2 Inflammation

BackgroundSensitisation to moulds and Staphylococcus aureus enterotoxins (SEs) is associated with the pathophysiology of both asthma and chronic rhinosinusitis (CRS). The purpose of this study was to clarify the contribution of sensitisation to these allergens to Type 2 inflammation in the blood, nose and the lower airways, and clinical outcomes in CRS patients.MethodsWe prospectively enrolled 56 CRS patients who underwent endoscopic sinus surgery (ESS) (20 with comorbid asthma) and 28 healthy controls between October 2015 and December 2017. CRS patients were followed up for 12 months after surgery. Type 2 inflammation-related biomarkers were analysed using blood, resected tissue samples and sputum. 10 allergens including Alternaria, Aspergillus and SEs were measured. Type 2 inflammation-related biomarkers and clinical outcomes were compared in the stratification with the presence or absence of allergen sensitisation.ResultsSensitisation rate to moulds and SEs in asthmatic patients was increased when changing the cut-off value of specific IgE titre from 0.35 UA·mL−1 to 0.10 UA·mL−1 (1.7- and 4.5-fold, respectively). Moulds and SEs affected the prevalence of asthma and eosinophilic CRS by interacting with each other. All Type 2 inflammation-related biomarkers except for eosinophils in sinus tissue were significantly higher in patients with mould or SE (mould/SE) sensitisation (≥0.10 UA·mL−1) (n=19) than in those without (n=37) and healthy subjects (all p<0.05). Meanwhile, mould/SE sensitisation did not affect longitudinal changes in clinical outcomes after ESS. Changes in serum mould/SE-IgE levels after ESS remained unclear.ConclusionMould/SE sensitisation (≥0.10 UA·mL−1) may affect the development of Type 2 inflammation and clinical outcomes in CRS patients.

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