scholarly journals The Role of Mesenchymal Stem Cells in the Treatment of a Chronic Rhinosinusitis—An In Vivo Mouse Model

2021 ◽  
Vol 9 (6) ◽  
pp. 1182
Author(s):  
Veronica-Elena Trombitaș ◽  
Alina Anda Nagy ◽  
Cristian Berce ◽  
Emoke Pall ◽  
Flaviu Tăbăran ◽  
...  
Keyword(s):  
Mouse Model ◽  
Aspergillus Fumigatus ◽  
Chronic Rhinosinusitis ◽  
Squamous Metaplasia ◽  
Economic Life ◽  
Sinus Surgery ◽  
Control Group ◽  
Important Challenge ◽  
Two Stages

Objectives/Hypothesis: It is acknowledged that the treatment of chronic rhinosinusitis (CRS) represents an important challenge for rhinology and for social and economic life. At present, one of the most common treatments for CRS is represented by local corticosteroids followed by endoscopic sinus surgery (ESS). Starting from the example of the mesenchymal stem cell’s (MSC) capacity to migrate and to modulate a real response in the nasal mucosa of an allergic rhinitis mouse model, we try to obtain a response in a CRS mouse model, using MSC derived by adipose tissue. The aim of this study is to demonstrate that the MSC can be used in CRS treatment and could change its priorities. Methods: Seventy female mice (6 MSC donor mice) were randomized in two stages of study, 32 Aspergillus fumigatus (Af) exposure mice (20 for histological comparison to 1st control mice and 12 for MSC administration, to CRS/MCS model) and 32 control mice (20 for histological comparison to CRS model and 12 for MSC administration and histological control to MSC model); in the first stage, the Aspergillus fumigatus (Af) CRS mouse model was targeted, in this section were included 64 (n = 32) mice (treated and control group). In order to assess the inflammation level (histological analysis), the animals were euthanized; in the second stage MSCs (1 × 106/animal) were administered intravenously to a total of 24 (n = 24) mice (12 mice from the exposed group and 12 mice from the second control group). Results: After 12 weeks of Af intranasal instillation, the inflammation parameters evaluated indicated a severe diffuse chronic inflammation, associated with diffuse severe hyperplasia and mature diffuse squamous metaplasia. The MSCs’ injection via the ophthalmic vein induced important histopathological changes in the CRS experimental group, starting with the presence of MSCs in all samples and continuing with the important degenerative character of inflammation. Conclusions: MSC administration demonstrated a real improvement of CRS evolution on the CRS mouse model.

Distinct Patterns of Tissue Remodeling and Their Prognostic Role in Chronic Rhinosinusitis

ORL ◽  
2021 ◽  
pp. 1-7
Author(s):  
Ho Yun Lee ◽  
Jung-Soo Pyo ◽  
Su Jin Kim
Keyword(s):  
Chronic Rhinosinusitis ◽  
Structural Changes ◽  
Squamous Metaplasia ◽  
Tissue Remodeling ◽  
Sinus Surgery ◽  
Prognostic Role ◽  
High Power Field ◽  
Tissue Eosinophilia ◽  
Allergy Test ◽  
Stromal Edema

<b><i>Introduction:</i></b> Tissue remodeling refers to structural changes that occur in damaged tissue and is associated with disease severity in asthma. However, the characteristics of tissue remodeling and its prognostic role in chronic rhinosinusitis (CRS) remain unclear. In this report, we evaluated the clinical implications of tissue remodeling in CRS. <b><i>Methods:</i></b> We performed a retrospective cohort study of adult patients who underwent endoscopic sinus surgery for bilateral CRS. The histopathology of sinus mucosa was determined by evaluating the inflammatory cell count and tissue remodeling markers (squamous metaplasia, subepithelial gland proliferation, basement membrane [BM] thickening, stromal edema, and fibrosis). Eosinophilic CRS (ECRS) was defined as an eosinophil count &#x3e;15/high-power field in the biopsied tissue. Patient characteristics, allergy test grade, preoperative Lund-Mackay score (LMS), and pre- and postoperative Lund-Kennedy scores (LKSs) were analyzed. <b><i>Results:</i></b> Of the identified patients, 59.1% were classified as ECRS and the remaining 40.9% as non-ECRS. Regarding tissue remodeling markers, stromal edema was seen in 90.9%, BM thickening in 63.6%, and stromal fibrosis in 34.1% of patients. In cases with stromal edema and BM thickening, greater tissue eosinophilia was observed, while stromal fibrosis decreased tissue eosinophilia (<i>p</i> &#x3c; 0.05). Prognostically, subepithelial gland proliferation alone was an independent risk factor for poor postoperative endoscopic findings (odds ratio: 8.250, 95% confidence interval: 1.128–60.319, <i>p</i> = 0.038). <b><i>Conclusions:</i></b> Tissue eosinophilia was commonly associated with BM thickening and stromal edema. Subepithelial gland proliferation predicted a poor surgical prognosis in CRS. These findings imply that tissue remodeling provides additional information not only on the CRS endotype but also on the postsurgical prognosis.

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 Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Chronic Rhinosinusitis With Nasal Polyps: Etiopathogenesis and Recurrence

2020 ◽  
pp. 014556131989663
Author(s):  
Germano Guerra ◽  
Domenico Testa ◽  
Francesco Antonio Salzano ◽  
Domenico Tafuri ◽  
Eleonora Hay ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Matrix Metalloproteinases ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Polymerase Chain Reaction Analysis ◽  
Sinus Surgery ◽  
Control Group ◽  
Nonallergic Rhinitis ◽  
Tissue Inhibitors ◽  
Immunologic Diseases

Chronic rhinosinusitis with nasal polyps is a multifactorial disease of the nasal and paranasal sinus mucosa and it includes, as comorbidities, anatomic and morphologic alterations, allergic rhinitis, and immunologic diseases. We investigated matrix metalloproteinases (MMP-2, MMP-7, and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) concentration in different etiopathogenetical groups of patients with nasal polyposis (NP) in relation to recurrence after sinonasal surgery. The study group consisted of 45 patients with NP (those with allergic rhinitis, nonallergic rhinitis and asthma or nonallergic rhinitis, and obstruction of osteomeatal complex [OMC]) who underwent endonasal sinus surgery. We also collected 10 patients who underwent septoplasty as control. Immunohistochemistry of nasal mucosa fragments, Western blotting, and polymerase chain reaction analysis showed increased MMPs levels (MMP-9 more than MMP-2 and MMP-7) and decreased tissue inhibitors of MMPs levels (TIMP-1 less than TIMP-2), in patients with chronic rhinosinusitis with nasal polyps compared with control group, in particular in patients with nonallergic rhinitis and asthma compared to those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC. We observed a higher risk of recurrence in patients with nonallergic rhinitis and asthma than in those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC after 36 months from surgery. In this research, we evaluated pathogenesis of NP related to MMPs and their inhibitors concentrations in polypoid tissue.

scholarly journals The Development of Dry Eye Disease after Surgery-Indicated Chronic Rhinosinusitis: A Population-Based Cohort Study

2020 ◽  
Vol 17 (11) ◽  
pp. 3829
Author(s):  
Chia-Yi Lee ◽  
Kun-Lin Yang ◽  
Chi-Chin Sun ◽  
Jing-Yang Huang ◽  
Hung-Chih Chen ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Dry Eye ◽  
Dry Eye Disease ◽  
Sinus Surgery ◽  
Eye Disease ◽  
Cumulative Probability ◽  
Control Group ◽  
Study Group ◽  
Diagnostic Code ◽  
Research Database

We aim to evaluate the risk of dry eye disease (DED) occurrence in patients with surgery-indicated chronic rhinosinusitis (CRS) via the national health insurance research database in Taiwan. After exclusion, patients with a diagnostic code of CRS and had received functional endoscopic sinus surgery (FESS) were regarded as having surgery-indicated CRS and enrolled in the study group, then each patient in the study group was age- and gender-matched to four non-CRS patients that served as the control group. The outcome was considered as the development of DED and Cox proportional hazard regression was used for the statistical analysis, which involved multiple potential risk factors of DED. A total of 6076 patients with surgery-indicated CRS that received FESS and another 24,304 non-CRS individuals were enrolled after exclusion. There were 317 and 770 DED events in the study group and the control group during the 16-year follow-up interval, and the study group demonstrated a significantly higher adjusted hazard ratio (1490, 95% confidence intervals (CI): 1.303-1.702) of DED development compared to the control group in the multivariable analysis. In addition, the cumulative probability analysis illustrated a positive correlation of DED occurrence and the disease period of surgery-indicated CRS (p < 0.0001). In the subgroup analysis, both genders revealed a higher but not significant incidence of developing DED in the study group. In conclusion, the existence of surgery-indicated CRS will increase the risk of developing DED, which correlated to the disease interval.

scholarly journals Taurine Attenuates Carcinogenicity in Ulcerative Colitis-Colorectal Cancer Mouse Model

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Guifeng Wang ◽  
Ning Ma ◽  
Feng He ◽  
Shosuke Kawanishi ◽  
Hatasu Kobayashi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Drinking Water ◽  
Mouse Model ◽  
Histopathological Examination ◽  
Tumor Formation ◽  
Water Model ◽  
Control Group ◽  
Ki 67

Taurine (2-aminoethane-sulfonic acid) is a type of amino acids and has numerous physiological and therapeutic functions, including anti-inflammation. However, there are few studies on the anticancer action of taurine. Our previous studies have demonstrated that taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells in vitro. In this study, we have investigated whether taurine has an anticancer effect, using azoxymethane (AOM)/sulfate sodium (DSS)- induced mouse model for colon carcinogenesis. All mice, except those in control group, received a single intraperitoneal injection of AOM and DSS in the drinking water for 7 days twice, with 1-week interval. After the first DSS treatment, mice were given distilled water (model group) or taurine in the drinking water (taurine group) ad libitum. No tumor was observed in the control group. Taurine significantly suppressed AOM+DSS-induced tumor formation. Histopathological examination revealed AOM/DSS treatment induced colon cancer in all mice (8/8, 100%), and taurine significantly inhibited the progression of colon cancer (4/9, 44.4%). Taurine significantly attenuated cell proliferation in cancer tissues detected by Ki-67 staining. Taurine significantly increased the levels of an apoptosis marker cleaved caspase-9 and tumor suppressor protein PTEN. This is the first study that demonstrated that taurine significantly reduced carcinogenicity in vivo using AOM/DSS-induced colon cancer mouse model.

Preoperative Management of Chronic Rhinosinusitis Prior to Office Balloon Sinus Dilation: A 2011–2014 MarketScan® Analysis

2019 ◽  
Vol 33 (4) ◽  
pp. 347-353 ◽  
Author(s):  
David W. Jang ◽  
Cecily Abraham ◽  
Derek D. Cyr ◽  
Kristine Schulz ◽  
Ralph Abi Hachem ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Practice Patterns ◽  
Sinus Surgery ◽  
Ct Scans ◽  
Administrative Database ◽  
Control Group ◽  
Topical Steroids ◽  
Preoperative Period ◽  
Office Visits ◽  
Preoperative Management

Background In-office balloon sinus dilation (BSD) has recently gained popularity as a surgical treatment option for chronic rhinosinusitis (CRS). However, utilization, indications, and practice patterns surrounding in-office BSD remain unclear. Objective The purpose of this study was to use a large national administrative database to assess preoperative management of CRS prior to in-office BSD. Methods Patients undergoing standalone in-office BSD from 2011 to 2014 were identified on MarketScan and compared to a control group undergoing functional endoscopic sinus surgery (FESS). Visits to the otolaryngologist, number of computed tomography (CT) scans, number of antibiotic and steroid prescriptions, and duration of time from first visit to procedure were compared. Results When compared to the FESS group, the in-office BSD group overall had fewer office visits (2.0 vs 2.2), CT scans (1.0 vs 1.1), prescriptions for antibiotics (2.0 vs 2.2), prescriptions for systemic steroids (1.5 vs 1.8), and topical steroids (1.4 vs 1.5) in the preoperative period. They also had a shorter mean duration of time between first visit and CT scan (17.5 vs 21.4 days) as well as between first visit and procedure (55.0 vs 67.8 days). All of these findings were statistically significant. Conclusion In-office BSD for CRS was overall associated with less intense management in the preoperative period when compared to FESS. Such differences may reflect ongoing shifts in practice patterns and need to be further investigated.

scholarly journals PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2241-2246 ◽  
Author(s):  
Michael P. Reilly ◽  
Uma Sinha ◽  
Pierrette André ◽  
Scott M. Taylor ◽  
Yvonne Pak ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Immune Complex ◽  
Transgenic Mouse Model ◽  
Control Group ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Syk Inhibitor ◽  
Induced Aggregation

AbstractHeparin-induced thrombocytopenia (HIT) is a major cause of morbidity and mortality resulting from the associated thrombosis. Extensive studies using our transgenic mouse model of HIT have shown that antibodies reactive with heparin-platelet factor 4 complexes lead to FcγRIIA-mediated platelet activation in vitro as well as thrombocytopenia and thrombosis in vivo. We tested PRT-060318 (PRT318), a novel selective inhibitor of the tyrosine kinase Syk, as an approach to HIT treatment. PRT318 completely inhibited HIT immune complex-induced aggregation of both human and transgenic HIT mouse platelets. Transgenic HIT model mice were treated with KKO, a mouse monoclonal HIT-like antibody, and heparin. The experimental group received orally dosed PRT318, whereas the control group received vehicle. Nadir platelet counts of PRT318-treated mice were significantly higher than those of control mice. When examined with a novel thrombosis visualization technique, mice treated with PRT318 had significantly reduced thrombosis. The Syk inhibitor PRT318 thus prevented both HIT immune complex-induced thrombocytopenia and thrombosis in vivo, demonstrating its activity in HIT.

Squamous Metaplasia and Chronic Rhinosinusitis: A Clinicopathological Study

2008 ◽  
Vol 22 (6) ◽  
pp. 602-605 ◽  
Author(s):  
Robert G. Mynatt ◽  
Jennifer Do ◽  
Christine Janney ◽  
Raj Sindwani
Keyword(s):  
Chronic Rhinosinusitis ◽  
Clinical Features ◽  
Chronic Sinusitis ◽  
Squamous Metaplasia ◽  
Sinus Surgery ◽  
Preoperative Ct ◽  
Student’S T ◽  
Pathology Reports ◽  
Clinical Records ◽  
Student’S T Test

Background The significance of squamous metaplasia (SM) in chronic rhinosinusitis (CRS) is unknown. The objectives of this study were to determine the prevalence of SM in histopathological specimens from patients with CRS and to correlate these histological findings with clinical features. Methods We reviewed the clinical records and pathological slides from 87 consecutive patients who underwent endoscopic sinus surgery for CRS. Demographic and clinical data, preoperative Chronic Sinusitis Survey (CSS) scores, and sinus CT stage were evaluated. Pathological slides were graded by a pathologist to characterize the degree of inflammation and SM, when present. CRS patients with and without SM were compared using student's t-test and χ2 test. Results Evaluation of the pathology slides revealed that 18.4% of specimens had SM present, whereas only 2.2% of pathology reports noted this. Histological grading of chronic inflammation showed significantly greater severity in specimens with SM (n = 16) when compared with the cohort without SM (n = 75; 100.0% versus 77.5%, respectively; p = 0.016). There was no difference in preoperative CT stage or the presence of hyperostosis on imaging, CSS scores, duration of CRS symptoms, or other clinical features between those with SM and those without SM (p > 0.05). Immunodeficiency was the only comorbidity more prevalent in the metaplastic group (12.5% versus 0%, respectively; p = 0.003). Conclusion SM is present in ∼18% of routine CRS specimens. It has a positive correlation with the severity of inflammation noted histologically in CRS but does not correlate with disease severity or chronicity, clinically.

scholarly journals Evaluation of recombinant Brachyspira pilosicoli oligopeptide-binding proteins as vaccine candidates in a mouse model of intestinal spirochaetosis

2010 ◽  
Vol 59 (3) ◽  
pp. 353-359 ◽  
Author(s):  
Abdolreza Movahedi ◽  
David J. Hampson
Keyword(s):  
Mouse Model ◽  
Binding Proteins ◽  
Control Group ◽  
Cumulative Number ◽  
Igg Antibody ◽  
Brachyspira Pilosicoli ◽  
Distribution Study ◽  
Different Strains

The anaerobic intestinal spirochaete Brachyspira pilosicoli colonizes the large intestine of humans, and various species of animals and birds, in which it may induce a mild colitis and diarrhoea. The aim of the current study was to evaluate the use of putative oligopeptide-binding proteins of B. pilosicoli as vaccine components. A partial genome sequence of B. pilosicoli porcine strain 95/1000 was subjected to bioinformatics analysis, and six genes predicted to encode oligopeptide-binding proteins were selected. Following a PCR-based distribution study of the genes across different strains of the spirochaete, they were amplified from B. pilosicoli human strain WesB and cloned in Escherichia coli. The recombinant histidine-tagged proteins were purified and subjected to in vitro and in vivo immunogenicity analysis. Recombinant products (P-1 and P-3) from two genes that were immunogenic and recognized by sera from pigs that had recovered from B. pilosicoli infections were tested in a mouse model of intestinal spirochaetosis. For each recombinant protein, groups of 12 C3H/HeJ mice were vaccinated subcutaneously with 100 μg protein emulsified in Freund's incomplete adjuvant, twice with a 2 week interval. Two weeks later the vaccinated and non-vaccinated control animals were challenged orally with B. pilosicoli strain WesB. Both proteins induced systemic and local colonic IgG antibody responses, and, following experimental infection, the cumulative number of colonization days was significantly (P<0.001) less in both groups of vaccinated mice compared to the control mice. There were significantly (P=0.012) fewer mice colonized in the group vaccinated with P-1 than in the non-vaccinated control group. The results suggest that oligopeptide-binding proteins may have potential for use as components of vaccines for B. pilosicoli.

scholarly journals Relationship of vitamin D3 deficiency and chronic rhinosinusitis with nasal and sinus polyposis in patients referring to the Department of Ear, Nose, and Throat Diseases Department of Vali-asr Hospital in Brigand, Iran

2021 ◽  
pp. 99-104
Keyword(s):  
Vitamin D ◽  
Chronic Rhinosinusitis ◽  
Vitamin D3 ◽  
Sinus Surgery ◽  
Control Group ◽  
Case Group ◽  
Significant Difference ◽  
Relationship Of ◽  
Vitamin D3 Deficiency ◽  
Nose And Throat

Introduction: Chronic rhinosinusitis may require referral to an ear, nose, and throat specialist for possible endoscopic sinus surgery if medical management fails. Vitamin D is one of the essential vitamins for the body that is effective in inflammatory processes. Therefore, it seems necessary to confirm the association between the deficiency of this vitamin and the occurrence of chronic rhinosinusitis with nasal polyposis. This study aimed to determine the relationship of vitamin D3 deficiency and chronic rhinosinusitis with nasal and sinus polyposis in patients referring to the Otorhinolaryngology Department of Valiasr Hospital, Birjand, Iran, in 2017. Methods: A case-control study was performed on individuals, including a group of patients with rhinosinusitis and a control group (n=20 each), referring to the Department of Ear, Nose, and Throat Diseases Department of Vali-asr Hospital. Among patients diagnosed with chronic rhinosinusitis, the cases that had polyps on endoscopic examination were included in the study. After completing the consent form, venous blood samples (10cc) were collected from the patients in fasting conditions. The electrochemical luminescence method was used for measuring the level of serum vitamin D. A questionnaire containing demographic information and clinical findings was completed by reviewing the patients' records. Data analysis was performed in SPSS software (Version. 22)using Chi-square and Mann-Whitney U-tests. Results: The mean and median scores of vitamin D level were obtained at14.13±12.99 and 10.25 in the case group, and 18.72±9.29 and 18.77 in the control group, respectively. The level of vitamin D was significantly higher in the control group than in the chronic group (P=0.04). In the case group, 16 (80%) patients lacked vitamin D and 3 patients had an insufficient level of vitamin D. In the control group, 13 (65%) patients lacked vitamin D and 4 cases had an insufficient level of vitamin D. There was no significant difference in vitamin D levels between the two groups (P=0.61). No significant difference was observed between the two clinical symptoms. Conclusion: It was revealed that the lack of vitamin D was likely to be an effective factor in the rhinosinusitis disease; therefore, proceedings need to be taken to cure the deficiency of this vitamin.

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