Effectiveness of endoscopic sinus surgery and aspirin therapy in the management of aspirin-exacerbated respiratory disease.

Background: Aspirin therapy and/or type 2 (T2) biologics are used in the management of aspirin-exacerbated respiratory disease (AERD). Objective: To identify the number of patients with AERD who tolerated aspirin therapy, yet due to persistent symptoms, incorporated T2 biologic management. Methods: A retrospective review was performed between July 2016 and June 2019. Patients with AERD and who underwent endoscopic sinus surgery (ESS), aspirin desensitization (AD), and at least 6 months of aspirin therapy (ATAD) after AD, and who remained biologic-naive up through this timepoint were included in the study. Introduction of a T2 biologic while on ATAD was the primary outcome. The secondary outcome was a change in a validated patient-reported outcome measure for chronic rhinosinusitis score between the postoperative predesensitization timepoint, and the 6-month postdesensitization timepoint, presented as means and compared by using the Student's t-test. Results: A total of 103 patients met inclusion criteria. Two patients (1.9%) ultimately supplemented ATAD with a T2 biologic. The mean outcomes measure test score after 6 months of ATAD for patients who received biologics was 40.5 versus 15 in those who did not receive biologics (p = 0.02). The mean differences between the postoperative predesensitization test score and the 6-month postdesensitization test score for patients who went on to receive biologics was an increase of 13 versus a decrease of 10 for those patients who did not receive biologics (p = 0.12). Conclusion: ESS, coupled with AD and ATAD, was successful in the long-term management of the majority of the patients with AERD, which rarely required the incorporation of T2 biologics. Patient questionnaires, such as outcomes measure test score, may identify aspirin therapy failures and help guide the practitioner in deciding when to introduce T2 biologics into the patient's treatment regimen.

State-Dependent Biomechanical Behavior of Oropharyngeal Structures in Apneic and Control Subjects: A Proof-of-Concept Study.

Rationale: Apneic individuals have reduced airway caliber during sleep. The biomechanical changes in upper airway anatomy contributing to this airway narrowing are largely unknown. Objectives: We sought to investigate the state-dependent (wake vs. sleep) biomechanical behavior of the upper airway soft-tissue and craniofacial structures. Methods: Upper airway magnetic resonance imaging was performed in 15 sleep-deprived control subjects (apnea-hypopnea index, <5; 0.3 ± 0.5 events per hour) and 12 sleep-deprived apneic subjects (apnea-hypopnea index, ⩾5; 35.2 ± 18.1 events per hour) during wake and sleep and analyzed for airway measures and soft-tissue/mandibular movement. Results: In the retropalatal region, control subjects showed sleep-dependent reductions (P ⩽ 0.037) in average cross-sectional airway area (CSA), minimum CSA, and anteroposterior and lateral dimensions. Apneic subjects showed sleep-dependent reductions (P ⩽ 0.002) in average CSA, minimum CSA, and anteroposterior and lateral dimensions. In the retroglossal region, control subjects had no sleep-dependent airway reductions. However, apneic subjects had sleep-dependent reductions in minimal CSA (P = 0.001) and lateral dimensions (P = 0.014). Control subjects only showed sleep-dependent posterior movement of the anterior-inferior tongue octant (P = 0.039), whereas apneic subjects showed posterior movement of the soft palate (P = 0.006) and all tongue octants (P ⩽ 0.012). Sleep-dependent medial movement of the lateral walls was seen at the retropalatal minimum level (P = 0.013) in control subjects and at the retropalatal and retroglossal minimum levels (P ⩽ 0.017) in apneic subjects. There was posterior movement of the mandible in apneic subjects (P ⩽ 0.017). Conclusions: During sleep, control and apneic subjects showed reductions in retropalatal airway caliber, but only the apneic subjects showed retroglossal airway narrowing. Reductions in anteroposterior and lateral airway dimensions were primarily due to posterior soft palate, tongue and mandibular movement and to medial lateral wall movement. These data provide important initial insights into obstructive sleep apnea pathogenesis.

Postoperative mometasone irrigations improve quality of life in skull base tumor patients.

Objectives: The use of topical corticosteroids to manage postoperative sinonasal symptoms after endoscopic skull base surgery (ESBS) has not been well studied. We quantified long-term impact of postoperative steroid irrigations (SIs) on quality of life of patients after ESBS. Methods: Retrospective review of patients at the University of Pennsylvania undergoing ESBS from 2010 to 2019. Data on patient demographics and postoperative treatment with nasal saline irrigation twice daily with and without dissolved steroids (mometasone or budesonide) was collected. Preoperative, and 1-, 3-, 6-, 12-, 18-, and 24-month postoperative Sino-Nasal Outcome Test (SNOT-22) scores were assessed. Results: A total of 727 patients were assessed (53.4% males), with 479 patients in the no SI group and 248 patients in the SI group. Preoperative SNOT-22 scores did not differ significantly (P = 0.19). 1-, 3-, 6-, 12-, 18-, and 24-month post-op SNOT-22 scores did not significantly differ between groups. However, mometasone irrigations resulted in significantly lower postoperative 2-year SNOT-22 scores compared to budesonide (P < 0.01) and saline (P = 0.03). Conclusions: Though corticosteroid irrigations are routine in managing inflammatory sinus disease, their role in postoperative management after ESBS for tumors is unclear. Our findings suggest that mometasone irrigation may be effective at improving postoperative quality of life in patients after ESBS.

In-Hospital Costs for Open versus Endoscopic Endonasal Approach for Craniopharyngioma Resection.

OBJECTIVE: To determine the in-hospital cost implications of an expanded endoscopic endonasal approach (EEEA) for craniopharyngioma resection relative to the traditional open transcranial approach. METHODS: All craniopharyngioma surgeries performed at a single institution over a period from January 1st 2001 to October 31th 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate regression analysis was performed using R software. RESULTS: Thirty-six patients met study criteria, including 22 undergoing an open approach and 14 undergoing an EEEA. There was a significantly longer average length of stay among patients undergoing open resection (21.5 vs. 10.6 days, p = 0.024). The average total in-hospital cost of a patient undergoing an EEEA was $58979.3 compared to $89142.3 for an open approach (p = 0.127). On univariate regression analysis, the total in-hospital cost for a patient undergoing an open approach relative to an EEEA was $30163.0 (p = 0.127). The open approach was exclusively performed from study onset until April 2010 (16 patients). From April 2010 to August 2013, 6 open approaches and 5 EEEA were performed. The EEEA has been exclusively performed from August 2013 until the conclusion of our study period (9 patients). CONCLUSIONS: There has been a shift toward surgical resection of craniopharyngioma via an EEEA approach for amenable tumors. Our study demonstrates that the EEEA has become the preferred surgical approach at our institution, and shows that the EEEA is associated with shorter postoperative length of stay and lower total in-hospital cost. Laryngoscope, 133:83-87, 2023.

In-Hospital Cost Comparison for Open Versus Endoscopic Endonasal Approach for Meningioma Resection.

OBJECTIVE: To determine the in-hospital cost implications of an endoscopic expanded endonasal approach (EEEA) for meningioma resection relative to the open transcranial approach. METHODS: All anterior skull base meningioma surgeries performed over a period from January 1st, 2015 to October 31th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using R software. All cost data were converted into August 2021-equivalent dollar amounts using the United States Bureau of Labor Statistics consumer price index. RESULTS: Thirty-five patients met study criteria, including 27 patients undergoing an open transcranial approach and 8 undergoing an EEEA. Average length of stay for patients undergoing an open approach was 9.3 days compared to 5.6 within the EEEA group (P = .126). The average total in-hospital cost of patient undergoing an EEEA was $35417.1 compared to $46406.9 among patients undergoing an open transcranial approach (P = .168). On univariate analysis, the cost of an open transcranial approach relative to the EEEA was $10989.8 (P = .411). CONCLUSIONS: The open transcranial approach remained the dominant surgical approach to anterior skull base meningiomas over our study time period. However, despite limited patient numbers the EEEA was associated with decreased total in-hospital costs.

Economic Evaluation of Dupilumab Versus Endoscopic Sinus Surgery for the Treatment of Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND: Dupilumab is a novel monoclonal antibody that recently received US Food and Drug Administration approval for the treatment of chronic rhinosinusitis with nasal polyps. Endoscopic sinus surgery (ESS) has been the mainstay of treatment for patients refractory to initial medical therapy. Data comparing the cost-effectiveness of these treatments are scarce. The objective of this study is to compare the cost-effectiveness of dupilumab and ESS treatment for patients with chronic rhinosinusitis with nasal polyps refractory to medical therapy. METHODS: A cohort-style Markov decision tree economic evaluation with 10-year time horizon was performed. The two comparative treatment strategies were dupilumab therapy or ESS followed by postoperative maintenance therapy. Patients with response to treatment continued with either maintenance or dupilumab therapy; patients with no response underwent ESS. The primary outcome measure was incremental cost per quality-adjusted life-year calculated from Sino-Nasal Outcome Test (SNOT-22) scores. Sensitivity analyses were performed including discounting scenarios and a probabilistic sensitivity analysis. RESULTS: The dupilumab strategy cost $195,164 and produced 1.779 quality-adjusted life-years. The ESS strategy cost $20,549 and produced 1.526 quality-adjusted life-years. This implies an incremental cost of $691,691 for dupilumab for every 1-unit increase in quality-adjusted life-year compared with ESS. Probability sensitivity analysis indicated that ESS was more cost-effective than dupilumab in all iterations. CONCLUSIONS: While dupilumab and ESS may demonstrate similar clinical effectiveness, ESS remains the most cost-effective treatment option and should remain the standard of care for patients with chronic rhinosinusitis with nasal polyps refractory to medical therapy.

A Brief Educational Intervention to Increase ED Initiation of Buprenorphine for Opioid Use Disorder (OUD).

BACKGROUND: Despite the evidence in support of the use of buprenorphine in the treatment of OUD and increasing ability of emergency medicine (EM) clinicians to prescribe it, emergency department (ED)-initiated buprenorphine is uncommon. Many EM clinicians lack training on how to manage acute opioid withdrawal or initiate treatment with buprenorphine. We developed a brief buprenorphine training program and assessed the impact of the training on subsequent buprenorphine initiation and knowledge retention. METHODS: We conducted a pilot randomized control trial enrolling EM clinicians to receive either a 30-min didactic intervention about buprenorphine (standard arm) or the didactic plus weekly messaging and a monetary inducement to administer and report buprenorphine use (enhanced arm). All participants were incentivized to complete baseline, immediate post-didactic, and 90-day knowledge and attitude assessment surveys. Our objective was to achieve first time ED buprenorphine prescribing events in clinicians who had not previously prescribed buprenorphine in the ED and to improve EM-clinician knowledge and perceptions about ED-initiated buprenorphine. We also assessed whether the incentives and reminder messaging in the enhanced arm led to more clinicians administering buprenorphine than those in the standard arm following the training; we measured changes in knowledge of and attitudes toward ED-initiated buprenorphine. RESULTS: Of 104 EM clinicians enrolled, 51 were randomized to the standard arm and 53 to the enhanced arm. Clinical knowledge about buprenorphine improved for all clinicians immediately after the didactic intervention (difference 19.4%, 95% CI 14.4% to 24.5%). In the 90 days following the intervention, one-third (33%) of all participants reported administering buprenorphine for the first time. Clinicians administered buprenorphine more frequently in the enhanced arm compared to the standard arm (40% vs. 26.3%, p = 0.319), but the difference was not statistically significant. The post-session knowledge improvement was not sustained at 90 days in the enhanced (difference 9.6%, 95% CI - 0.37% to 19.5%) or in the standard arm (difference 3.7%, 95% CI - 5.8% to 13.2%). All the participants reported an increased ability to recognize patients with opioid withdrawal at 90 days (enhanced arm difference .55, 95% CI .01-1.09, standard arm difference .85 95% CI .34-1.37). CONCLUSIONS: A brief educational intervention targeting EM clinicians can be utilized to achieve first-time prescribing and improve knowledge around buprenorphine and opioid withdrawal. The use of weekly messaging and gain-framed incentivization conferred no additional benefit to the educational intervention alone. In order to further expand evidence-based ED treatment of OUD, focused initiatives that improve clinician competence with buprenorphine should be explored. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03821103.

Major complications of aspirin desensitization and maintenance therapy in aspirin-exacerbated respiratory disease.

BACKGROUND: Treatment of aspirin-exacerbated respiratory disease (AERD) includes endoscopic sinus surgery (ESS) and aspirin desensitization (AD) with aspirin therapy after desensitization (ATAD). The objective of this study was to determine the rate of major complications associated with aspirin use that resulted in the discontinuation of aspirin therapy. METHODS: This study was a retrospective chart review of patients with AERD who underwent ESS, AD, and ATAD at a single AERD tertiary center between July 2016 and February 2019. Complications associated with aspirin that resulted in the discontinuation of aspirin therapy were analyzed via analysis of variance and logistic regression. RESULTS: In total, 109 AERD patients underwent ESS with subsequent AD. Ten patients (9.2%) discontinued therapy after AD, before starting ATAD. Eight patients (7.3%) discontinued therapy after starting ATAD. There were 91 patients (83.5%) with no complications throughout ATAD. Reasons for discontinuation included gastritis, upper gastrointestinal (GI) bleed, anaphylaxis, persistent sinonasal symptoms, recurrent epistaxis, asthma exacerbation, and a nummular rash. There was no significant correlation between complication rate and (1) aspirin doses (analysis of variance [ANOVA] F: 0.69; p = 0.51), (2) gender (odds ratio [OR] 0.56; 95% confidence interval [CI], 0.19 to 1.65; p = 0.30), (3) age (OR 1.04; 95% CI, 0.96 to 1.09; p = 0.06), or (4) race/ethnicity (OR 1.12; 95% CI, 0.88 to 1.44; p = 0.36). CONCLUSION: AD with ATAD was associated with only a 0.92% incidence of a clinically significant GI bleed, and only a 0.92% incidence of anaphylaxis. A remaining 16 patients (14.7%) discontinued aspirin therapy due to minor clinical sequelae. These findings demonstrate that the majority of AERD patients tolerate AD with ATAD without any major complications.

The impact of endoscopic sinus surgery and aspirin desensitization on psychological burden in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is an aggressive inflammatory disorder of the upper and lower respiratory tract. Corticosteroids, leukotriene modifiers, endoscopic sinus surgery (ESS), aspirin (ASA) desensitization, and biological immunomodulators are currently used to treat the disorder. OBJECTIVE: The objective of this study was to determine the psychosocial impact of ESS and ASA desensitization on AERD patients. METHODS: All AERD patients who underwent complete ESS were divided into two cohorts based on ASA desensitization status. The psychosocial metrics of the SNOT-22 were collected and analyzed at the following time points: pre-operative, 1-month, 3-month, 6-month, and 12-month after ESS. RESULTS: One hundred and eighty-four AERD patients underwent ESS from November 2009 to November 2018. From this group, 130 patients underwent ASA desensitization (AD cohort) and 54 patients remained non-desensitized (ND cohort). AD patients showed a significantly greater reduction in total SNOT-22 scores over the study period compared to ND patients (p = 0.0446). Analysis of SNOT-22 psychosocial metrics showed a significantly greater improvement in patient productivity in the AD cohort when compared to the ND cohort (p = 0.0214). Further, a sub-group analysis accounting for subject attrition showed a significantly greater improvement in both productivity and concentration in AD patients when compared to the ND cohort (productivity: p = 0.0068; concentration: p = 0.0428). CONCLUSIONS: ESS followed by ASA desensitization decreases the overall psychosocial burden in AERD patients with a significant improvement in perceived productivity and concentration. This has significant implications given the psychosocial impact of chronic diseases.

Coronary Sinus Rupture Repair: Patency Is Important.

We report a case of coronary sinus (CS) injury with a retrograde cardioplegia catheter and repair that compromised CS patency. This resulted in acute global cardiac dysfunction shortly after weaning from bypass, which reversed after patch repair with confirmed CS patency. The case report shows that acute CS occlusion may not be tolerated in some humans.

Effect of Betel (Areca) Nut Chewing on Fractional Exhaled Nitric Oxide: A Pilot Study.

Betel (areca) nuts are extensively chewed in many countries. This has been associated with respiratory symptoms. We aimed to determine whether betel nut chewing is associated with acute changes in fractional exhaled nitric oxide, a non-invasive marker of airway inflammation. Betel nut chewing resulted in an immediate significant decline in fractional exhaled nitric oxide levels that persisted for up to 180 minutes. This effect has to be taken into account in epidemiological studies, reference ranges, and patient preparation.

Inhibition of adipogenesis by ghrelin.

Ghrelin, a novel gastric hormone, regulates food intake and energy metabolism via central mechanisms. The peripheral effect of ghrelin on adiposity is poorly understood. We established a stable 3T3-L1 cell line expressing ghrelin to study the direct effect of ghrelin on adipogenesis. Cells overexpressing ghrelin demonstrate significantly attenuated differentiation of preadipocytes into adipocytes. Expression of peroxisome proliferator-activator receptor-gamma is significantly inhibited as demonstrated by decrease of peroxisome proliferator-activator receptor-gamma mRNA and protein. Both ghrelin overexpression and exogenous ghrelin stimulate cell proliferation. Phosphorylation of mitogen-activated protein kinase is increased after treatment of cells with ghrelin. Ghrelin binding activity is demonstrated in both native and ghrelin-overexpressing 3T3-L1 cells by radiolabeled ghrelin, although reverse transcription-polymerase chain reaction with the primer sequence of the previously identified ghrelin receptor subtypes detected no signal. Our results demonstrate that ghrelin inhibits adipogenesis by stimulation of cell proliferation via the mediation of a ghrelin receptor, likely a novel unidentified subtype.

Amplification and overexpression of the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2 (DYRK2) gene in esophageal and lung adenocarcinomas.

Genomic amplification can lead to the activation of cellular proto-oncogenes during tumorigenesis, and is observed in most, if not all, human malignancies, including adenocarcinomas of lung and esophagus. Using a two-dimensional restriction landmark genomic scanning technique, we identified five NotI/HinfI fragments with increased genomic dosage in an adenocarcinoma of the gastroesophageal junction. Four of these amplified fragments were matched within three contigs of chromosome 12 using the bioinformatics tool, Virtual Genome Scan. All three of the contigs map to the 12q13-q14 region, and the regional amplification in the tumor was verified using comparative genomic hybridization analysis. The 12q14 amplicon was characterized using sequence tagged site-amplification mapping with DNA from paired normal-tumor tissues of 75 gastroesophageal and 37 lung adenocarcinomas. The amplicon spans a region of >12 Mb between genes DGKA and BLOV1. The core-amplified domain was determined to be <0.5 Mb between marker WI-12457 and gene IFNG. However, MDM2, a well-documented oncogene of the region, is outside the core-domain. Eleven genes and expressed sequence tags within the amplicon were selected for quantitative reverse transcription-PCR, and DYRK2, a member of the dual-specificity kinase family, was overexpressed in all of the tumors showing gene amplification. Among the sequence tagged site/expressed sequence tag/gene markers tested, DYRK2 demonstrated the highest DNA copy number and the highest level of mRNA overexpression in the tumors. Moreover, DYRK2 mRNA overexpression (>2.5-fold of normal mean) was found in 18.6% of additional 86 lung adenocarcinomas in an assay using oligonucleotide microarrays. DYRK2 mRNA overexpression occurs more frequently than gene amplification in both esophageal and lung adenocarcinomas. This is the first report of amplification and overexpression of DYRK2 in any tumor type.

Stimulation of neurogenesis in rat nucleus of the solitary tract by ghrelin.

Ghrelin, a gastric hormone, regulates growth hormone secretion and energy homeostasis. The present study shows that ghrelin promotes neural proliferation in vivo and in vitro in the rat nucleus of the solitary tract (NTS). Systemic administration of ghrelin significantly increased 5-bromo-2'-deoxyuridine (BrdU) incorporation in the NTS in adult rats with cervical vagotomy. Cultured NTS neurons contain immature precursor cells as shown by expression of Hu protein. Exposure of cultured NTS neurons to ghrelin significantly increased the percentage of BrdU incorporation into cells in both dose- and time-dependent manners. Co-localization of Hu immunoreactivity with BrdU labeling was demonstrated by double fluorescent staining, suggesting that cells labeled with BrdU are neuronal cells. Ghrelin receptor mRNA was detected in tissues from the NTS. The mitotic effect of ghrelin was abolished by treatment of cultured NTS neurons with ghrelin receptor antagonists: D-Lys-3-GHRP-6 and [D-Arg1, D-Phe-5, D-Trp-7, 9, Leu-11] substance P. Diltiazem, a L-type calcium channel blocker, significantly attenuated ghrelin-mediated increments in BrdU incorporation. Ghrelin acts directly on NTS neurons to stimulate neurogenesis.

Sleep deprivation enhances peripheral serotonin secretion to regulate the large follicle steroidogenesis of rats.

OBJECTIVE: Sleep deprivation (SD) leads to the disturbance of the estrous cycle. Serotonin, the levels of which increase with SD, has been shown to inhibit luteinizing hormone production and the receptor has been found in the follicles. In this study, the serotonin effect on preovulatory follicular steroidogenesis is investigated and the underlying mechanisms are elucidated. MATERIALS AND METHODS: Female rats were subjected to SD for a time span of 1-4 days using the dish-over-water-method with a Rechtschaffen apparatus. Serum estradiol and serotonin concentrations were assessed; thereafter, they were evaluated with the effect of serotonin on the estradiol production and steroidogenic acute regulatory (StAR) protein expression in a serum-free culture system. Preovulatory follicles were dissected mechanically from the ovaries of 21-day-old rats, which induced follicle growth, and cultured for 24 hours with or without recombinant human follicle-stimulating hormone (FSH) in the presence or absence of serotonin. RESULTS: SD, led to a significant decrease in serum estradiol concentrations, while serotonin concentrations were significantly elevated (all p < 0.05). Follicles were cultured with a constant dose of FSH (50 mIU/mL) and increasing doses of serotonin, estradiol production was reduced by 20%. The inhibitory effect of serotonin was concentration dependent. The addition of serotonin (0.1 µg/mL) decreased FSH-induced estradiol production and attenuated FSH-stimulated follicular StAR protein expression. The inhibitory effects of serotonin could be reduced by the serotonin receptor antagonist ketanserin. CONCLUSION: These findings suggest that decreased serum estradiol concentrations in SD rats may be the result of serotonin-related inhibition of estradiol production and decreased large follicle expression of StAR protein.

Stimulation of rat pancreatic exocrine secretion by urocortin and corticotropin releasing factor.

Neural and hormonal mechanisms control pancreatic secretion. The effects of the corticotropin releasing factor (CRF) related neuropeptide urocortin (UCN) on pancreatic exocrine secretion were examined. In anesthetized male rats, pancreatic secretion volume and total protein were assayed. UCN increased pancreatic secretory volume and protein secretion and potentiated cholecytokinin-stimulated protein secretion. Astressin, a non-specific CRF receptor antagonist, inhibited UCN-stimulated protein output while CRF(2) receptor antagonist, antisauvagine-30, was without effect. Atropine, but not subdiaphragmatic vagotomy, inhibited UCN-mediated secretion. In acinar cells, UCN did not stimulate release of amylase nor intracellular cAMP. UCN is a pancreatic exocrine secreatagogue with effects mediated through cholinergic intrapancreatic neurons.

Activation of c-fos expression in the rat inferior olivary nucleus by ghrelin.

Ghrelin, a novel 28-amino-acid hormone secreted by gastric oxyntic glands, stimulates food intake and induces adiposity. We examined whether ghrelin activates the inferior olivary nucleus. Systemic administration of ghrelin (37 nmol/kg) induced the expression of c-fos immunoreactivity in inferior olive neurons (n=6 rats). The number of neurons containing c-fos staining was significantly increased in the ghrelin-treated rats (65+/-14 vs.11+/-6 positive neurons, n=5). No significant difference in c-fos-positive neurons was observed between left (32+/-5) and right (33+/-6) inferior olivary nuclei. The number of c-fos-positive neurons in rats with bilateral vagotomy was not significantly different from those with intact vagal nerves. The present study demonstrates that ghrelin induces c-fos expression in inferior olivary nucleus via a central mechanism.

Interleukin-1beta and interleukin-6 stimulate matrix metalloproteinase-9 secretion in cultured myenteric glia.

Western blotting of culture media of myenteric glia stained positive for GFAP revealed increased secretion of matrix metalloproteinase-9 (MMP-9) in interleukin-1beta (IL-1beta) stimulated cells (10 ng/mL) versus control (142 +/- 19 versus 42 +/- 19, P < 0.05). Interleukin-6 (IL-6) stimulated cells also showed increased expression of MMP-9 (10 ng/mL) versus control (69 +/- 14 versus 4 +/- 2, P < 0.01). Control and cytokine-stimulated cells secreted MMP-2 constituitively. Gelatin zymography demonstrated that products were biologically active. Cytoplasmic staining for MMP-9 was detected in IL-1beta and IL-6-stimulated cells but was negligible in controls. Cultured myenteric glia are responsive to IL-1beta and IL-6 stimulation by secreting MMPs into the extracellular environment.