Clinical efficacy of a dry extract of five herbal drugs in acute viral rhinosinusitis.

OBJECTIVE: A herbal drug combination (Dry Extract BNO 1016) has been assessed for efficacy and tolerability in patients with acute viral rhinosinusitis. METHODOLOGY: In this randomised, controlled trial patients with symptom duration of up to 3 days, mild to moderate facial pain and a Major Symptom Score (MSS) between 8 and 12 were treated for 15 days with BNO 1016 or placebo (coated tablets administered orally). Primary efficacy endpoint was mean MSS at end of treatment. Secondary outcome measures included treatment response and changes in paranasal sinuses assessed by ultrasonography. RESULTS: Treatment resulted in clinically relevant, significant differences in mean MSS for BNO 1016 versus placebo. BNO 1016 provided symptom relief two days earlier than placebo. The number needed to treat for healing is 8. BNO 1016 was superior regarding responder rates at Day 10 and Day 14 and percentage of patients without signs of acute viral rhinosinusitis assessed by ultrasonography at end of treatment. BNO 1016 was well tolerated; no serious adverse events were reported. CONCLUSION: The herbal dry extract BNO 1016 is efficacious and well tolerated in patients with acute viral rhinosinusitis. TRIAL REGISTRATION: ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT01146860; EudraCT: 2009-016682-28).

Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis.

BACKGROUND: Chronic noninfectious, nonallergic rhinitis (NINAR) is a complex syndrome with a principally unknown pathophysiology. New technology has made it possible to examine differentially expressed genes and according to network theory, genes connected by their function that might have key roles in the disease. METHODS: Connectivity analysis was used to identify NINAR key genes. mRNA was extracted from nasal biopsies from 12 NINAR patients and 12 healthy volunteers. Microarrays were performed using Affymetrix chips with 54 613 genes. Data were analysed with the Ingenuity Pathway System for organization of genes into annotated biological functions and, thereafter, linking genes into networks due to their connectivity. The regulation of key genes was confirmed with reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In all, 43 genes were differentially expressed. The functional analysis showed that these genes were primarily involved in cellular movement, haematological system development and immune response. Merging these functions, 10 genes were found to be shared. Network analysis generated three networks and two of these 'shared genes' in key positions, c-fos and cell division cycle 42 (Cdc42). These genes were upregulated in both the array and the RT-PCR analysis. CONCLUSION: Ten genes were found to be of pathophysiological interest for NINAR and of these, c-fos and Cdc42 seemed to be of specific interest due to their ability to interact with other genes of interest within this context. Although the role of c-fos and Cdc42 in upper airway inflammation remains unknown, they might be used as potential disease markers.

Timing-dependent effects of restraint stress on eosinophilic airway inflammation in mice.

BACKGROUND: Chronic stress has been proposed to aggravate allergic inflammation, whereas acute stress may have functional beneficial effects. The aim of this study was to investigate the influence of timing of single short restraint stress (RST) in a model of eosinophilic airway inflammation. METHODS: The airways of ovalbumin (OVA)-sensitized mice were exposed to an intranasal OVA challenge. RST was applied in two different ways; either 2 h before (pre-stress) or after (post-stress) the OVA challenge, respectively, or as a combination of stress before and after (double-stress) the OVA challenge. One group of mice was also treated with metyrapone (ME) prior to a pre-stress challenge. The inflammatory cell response was evaluated in bronchoalveolar lavage fluid (BALF), lung and nasal tissue, as well as bone marrow. RESULT: RST applied prior to the OVA challenge (pre-stress) inhibited OVA-induced airway inflammation in BALF and lung tissue, and reduced nasal histopathology compared to unstressed mice. Given as post-stress or double-stress, RST did not affect the inflammation in BALF, lungs or nasal tissue. Pre-treatment with ME prevented the pre-challenge stress evoked decrease in inflammation in BALF and lungs. CONCLUSION: Effects of RST on eosinophilic airway inflammation appear to be strongly dependent on timing and, as could be judged from the ME inhibition pattern, also corticosterone dependent. Hypothalamic-pituitary-adrenal axis activation probably influences eosinophilic inflammation through specific sequences of compartmental activation and thereby timing effects are evident on cellular recruitment pattern during the allergic reaction.

Changes in immune regulation in response to examination stress in atopic and healthy individuals.

BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.

Development and characterization of an animal model of dental sinusitis.

CONCLUSION: The results of this study confirm that the present rabbit model of dental maxillary sinusitis (dMxS) is reproducible and simulates human dental sinusitis with respect to initiation, progression and inflammation. It is applicable to further studies of sinusitis of odontogenic origin. OBJECTIVES: To induce acute dMxS in rabbits by using their own oral microflora to create a periapical infection and to follow morphological, radiographic, bacteriological and histological changes to the sinus mucosa. MATERIAL AND METHODS: The experimental animals comprised 26 New Zealand White rabbits. Maxillary premolar root canals were identified bilaterally and the continuously growing germs of the roots were severed by diathermy. The animals were randomized into 2 groups: in Group 1 (n=20) the teeth were left open for the entire study period; in Group 2 (n=6) the root canals were sealed 1 week after the initial intervention. The animals in Group 1 were sacrificed at intervals ranging from 2 h to 9 months after intervention. All animals in Group 2 were sacrificed 6 months after intervention. After macroscopic and radiographic examination, post-mortem inspection of the paranasal sinus cavity and maxillary complex and microbiological sampling, the entire nasal sinus complex with the hard palate in situ was resected and processed for serial coronal sectioning. RESULTS: In Group 1, after 3 months, the radiographic changes ranged from widening of the periodontal space to bone reaction. At sacrifice, changes in the sinus mucosa ranged from signs of mucosal inflammation to purulent dMxS. Microbial growth, predominantly Gram-negative aerobes, increased over time. In Group 2, the findings were generally more pronounced. Anaerobic microorganisms were predominant. In both groups the findings were consistent with dMxS.

Current perspectives on the treatment of nasal polyposis: a Swedish opinion report.

This Swedish study group has examined the current knowledge of nasal polyposis with emphasis on different treatment modalities. Polyposis is a multifactorial disease that exists for decades in the majority of cases. Different types of treatment must be considered, focusing on the underlying disease. However, as we only know the specific origin of polyposis in a minority of cases, treatment is usually symptomatic. When making a thorough evaluation of different treatment strategies, it is obvious that there is a real need for more controlled treatment studies which would make the scientific ground more stable when it comes to suggesting medical, surgical or combined treatments.

Herpes simplex virus type 1 infection and glucocorticoid treatment regulate viral yield, glucocorticoid receptor and NF-kappaB levels.

The interplay between the endocrine and immune systems has come into focus in recent years with the insight that endocrine parameters may affect susceptibility to both auto-immune and infectious diseases. Our interest in immunoendocrine regulation led us to investigate the effects of glucocorticoids on Herpes simplex virus type 1 (HSV-1) infections. Glucocorticoids used to treat inflammatory conditions are not yet recommended for HSV-1 therapy, since they have been reported to prolong viral shedding both in vivo and in vitro. Here we report that glucocorticoids did not alter the viral yield in human gingival fibroblast (HGF) cell culture when glucocorticoid treatment and viral infection occured simultaneously, but the viral yield increased when cells were treated with the glucocorticoid dexamethasone (dex) prior to viral infection. We found that viral infection in our primary cell system increased NF-kappaB levels and DNA binding. In addition, the amount of glucocorticoid receptor (GR) increased following viral infection, and HSV-1 infection as such could induce glucocorticoid-driven transcription of a reporter gene in human embryo kidney (HEK) 293 cells stably transfected with GR. Dex treatment did not affect HSV-1-induced binding of p65 to an NF-kappaB element in an electrophoretic mobility shift assay, and acyclovir was still efficient as an anti-viral drug in the presence of dex. Further studies of the observed effects of HSV-1 infection and glucocorticoid treatment on GR and NF-kappaB regulation could give insights into the immunoendocrine mechanisms important for defence and therapy against viral infections.

Estrogen receptors alpha and beta in the inner ear of the 'Turner mouse' and an estrogen receptor beta knockout mouse.

Estrogen receptors have earlier been shown in the normal mouse, rat and human inner ear. If estrogens are important in normal hearing and development of presbyacusis in the normal population is not known. However it is known that patients with Turner syndrome, where a lack of estrogens is one of the main characteristics, commonly develop an early presbyacusis. A 'Turner mouse' has been developed, as a model for the ear problems in Turner syndrome, and it shows otitis media and a premature aging of the hearing. Estrogen receptors exist in an alpha and a beta form. In this study inner ear tissue, from the Turner mouse and an estrogen receptor beta knockout mouse (betaERKO), was investigated regarding estrogen receptor alpha and beta using immunohistochemistry. Results show that the Turner mouse has the same pattern of inner ear labeling, both concerning the estrogen receptor alpha and beta, as that of a normal CBA/Ca mouse, with positive staining in the organ of Corti and spiral ganglion. The betaERKO mice show close to normal inner ear morphology and positive estrogen receptor alpha immunostaining at the same locations as the CBA/Ca mouse.

Central and peripheral glucocorticoid receptor function in abdominal obesity.

Abdominal obesity seems to be associated with a moderately deranged feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis where central glucocorticoid receptors (GR) are involved. Therefore, functions of central and peripheral GR were compared in this study. Furthermore, since trinucleotide repeats in early exons of steroid hormone receptor genes influence transcription, and therefore may influence receptor density, this was also studied. Ten middle-aged men, 5 with abdominal obesity and 5 controls, were studied. The suppression of dexamethasone (dex) on serum cortisol was used in dose-response tests to assess the function of central GR. Abdominal adipose tissue biopsies were incubated and exposed to cortisol in different concentrations, and the function of the peripheral GR assayed as induction of lipoprotein lipase (LPL) activity. Aberrant expansion of exonic trinucleotide repeats in the first coding exon of the GR gene was studied by sequencing of genomic DNA. Results showed that men with abdominal obesity showed less inhibition of serum cortisol by dex, particularly at lower concentrations, while in the controls cortisol secretion was inhibited in an apparent dose-response manner. LPL activity in adipose tissue was lower in abdominal obese men than in controls. However, the sensitivity to cortisol was not different between the groups. There was no evidence for expansion of trinucleotide repeats. These results suggest that the central GR and the peripheral GR in adipose tissue exhibit functional differences in abdominal obesity.

Sensitivity of a new grading system for studying nasal polyps with the potential to detect early changes in polyp size after treatment with a topical corticosteroid (budesonide).

We have previously compared different scoring systems for endoscopic staging of nasal polyps. Of the five methods evaluated, we found that two were better than the others with regard to reproducibility and agreement between physicians. One method was lateral imaging, developed by the authors, and the other was a scoring system developed by Lildholdt et al. The main objective of the present study was to compare the sensitivity of these two methods. Another aim was to study the effect on nasal polyposis of topical nasal corticosteroids over a 2-week period. Patients with bilateral nasal polyposis (n = 100) were randomized to a 2-week treatment with a topical corticosteroid (budesonide aqueous nasal spray: 128 microg b.i.d.) or placebo in a double-blind manner. Nasal symptoms were scored before treatment and after 3, 7 and 14 days of treatment, and the patients underwent nasal endoscopy at clinical visits. Patients treated with active substance had an improvement in their symptoms, an effect already detectable after 3 days of treatment, compared with those who received placebo. In addition, a statistically significant decrease in polyp size could be registered after 14 days using lateral imaging but not with the other scoring system. In conclusion, lateral imaging was more sensitive and could detect effects earlier than the other scoring system and can be recommended for the endoscopic staging of nasal polyps in clinical studies.

Na,K-ATPase expression in the mouse cochlea is not dependent on the mineralocorticoid receptor.

This study was performed in order to test the hypothesis that the mineralocorticoid hormone stimulates the expression of Na,K-ATPase in the cochlea of the mouse. Immunohistochemistry was used to investigate the distribution of the mineralocorticoid receptor (MR) in the cochlea of the C57Bl/J6 mouse at different ages between gestational day 19 and postnatal day 30, and the occurrence and distribution of Na,K-ATPase in the inner ear of a mouse with a null mutation of the MR. Adult patterns of staining for MR were found as early as on gestational day 19 in the cochlea, with small changes thereafter. MR was detected in the same structures in the cochlea as Na,K-ATPase in earlier studies, where the amount of Na,K-ATPase increased after postnatal day 4. Thus there is latency between the increase of MR and the increase of Na,K-ATPase. In the cochlea of the MR deficient mouse, antibody labelling of Na,K-ATPase showed no significant difference as compared to the control wild type mouse. The hypothesis that mineralocorticoid hormone alone via MR stimulates the formation of Na,K-ATPase in the inner ear could not be confirmed by this study, and other regulating mechanisms must be considered.

Characterization of two novel mutations in the glucocorticoid receptor gene in patients with primary cortisol resistance.

OBJECTIVE: Primary glucocorticoid resistance is characterized by decreased sensitivity to cortisol signalling. We have performed genetic analysis of the glucocorticoid receptor (GR) gene in 12 unrelated patients with primary cortisol resistance as defined by a pathological dexamethasone suppression test. METHODS: Exon specific polymerase chain reaction amplification of the GR gene and sequencing of each exon was carried out. The two mutations were characterized in vitro in terms of glucocorticoid driven reporter gene activity in a transient transfection assay and in a ligand binding assay. Molecular modelling of the R477H mutant was performed based on the X-ray structure of the GR-DNA binding domain. RESULTS: Two novel mutations in the GR gene were found: R477H in the DNA-binding domain which is the first reported mutation in that region of the human GR gene and G679S in the ligand binding domain. The R477H mutation showed no transactivating capacity, whereas the G679S mutation had reduced transactivation capacity compared to the wild-type (wt) GR. When tested for ligand binding capacity, the G679S mutation had 50% binding affinity compared to the wt GR. The effect of the point mutation R477H was deduced by a comparison between the wt structure and the model of the mutant. The wt GR has direct and water mediated contact with the phosphate groups of the glucocorticoid responsive element (GRE) whereas, in the model, the mutation R477H has no contact with the GRE. The G679S mutation is located on the surface of the ligand binding domain, at a distance from the steroid-binding site. A previously reported polymorphism, AAT to AAC at amino acid position 766, was found in four of the patients. CONCLUSIONS: In two of 12 patients with clinical glucocorticoid resistance, mutant forms of GR could be found. The glucocorticoid resistance in vivo in these two patients corresponds to impaired function of the two mutated GR forms in two in vitro assays. The relevance of the conservative polymorphism for the glucocorticoid insensitivity noted in these patients remains to be clarified.

Glucocorticoid receptor mRNA in patients with ulcerative colitis: a study of responders and nonresponders to glucocorticosteroid therapy.

BACKGROUND AND AIMS: Up to 30% of patients with severe-to-moderate attacks of ulcerative colitis (UC) respond poorly to glucocorticosteroid (GCS) treatment. The reason for this unresponsiveness is unknown. AIM: Our aim was to evaluate possible differences in glucocorticoid receptor (GR) density in peripheral leukocytes and effects of low-dose GCS treatment on GR density and on the hypothalamic-pituitary-adrenal axis in UC patients who had received high-dose GCS treatment due to a moderate or severe attack. Eleven UC patients in remission who were responders (Rs) to previous GCS treatment were compared with 10 patients who failed GCS therapy and had a colectomy (nonresponders. NRs). Ten healthy individuals served as controls. METHODS: Quantitation of GR mRNA by a solution hybridization assay in peripheral leukocytes and a low-dose adrenocorticotropin hormone stimulation test was performed before and after low-dose dexamethasone (DEX) treatment for 14 days. The glucocorticoid-responsive gene for metallothionein IIa (MTIIa) was also analyzed by a solution hybridization assay in peripheral leukocytes. RESULTS: Overall, basal GR mRNA levels were higher in patients than in controls (p < 0.0001). There were no significant differences between NRs and Rs. None of the groups down-regulated their GR mRNA levels in response to DEX treatment. Basal and stimulated cortisol levels decreased significantly only among NRs after DEX (p = 0.012 and 0.0093). MTIIa levels were lower in NRs as compared with Rs, both in mononuclear (p = 0.0059) and in polynuclear leukocytes (p = 0.030). CONCLUSION: Patients with UC in remission exhibit higher levels of GR mRNA in peripheral leukocytes. We speculate that this may be secondary to an underlying up-regulation of proinflammatory factors also present in patients in clinical remission. Differences in GR mRNA levels per se thus may not be important for the ability of patients with UC to respond to GCS treatment. The hypothalamic pituitary adrenal axis was suppressed by low-dose DEX treatment only in NRs, possibly indicating that steroid-resistance is not a generalized phenomenon. Lower levels of MTIIa in NRs may indicate a diminished efficiency of GR regulation in steroid-refractory patients.

Effects of topical budesonide treatment on glucocorticoid receptor mRNA down-regulation and cytokine patterns in nasal polyps.

UNLABELLED: The effects of a topically applied corticosteroid, budesonide, on the expression of glucocorticoid receptor (GR) mRNA and regulation of pro-inflammatory cytokine patterns in patients with nasal polyps were evaluated. All patients were eligible for surgical polypectomy, and a majority of them had been treated with nasal steroids. Patients were given 400 microg b.i.d. (group A, n = 11), 200 microg b.i.d. (group B, n = 10), or no treatment (group C, n = 15) during two months before polypectomy. Morning serum cortisol was analyzed on the day of surgery. Surgically removed polyps were taken for analysis of GR mRNA expression by solution hybridization. Remaining tissue was cryostat-sectioned, whereafter quantification of the cytokines interleukin 1beta, interleukin 2, interleukin 4, interleukin 5, interleukin 6, interleukin 10, tumor necrosis factor alpha, and interferon gamma was made by immunohistochemistry and digitized image analysis. No significant differences among the three groups were found for any of the parameters investigated. CONCLUSION: nasal polyps do not respond with down-regulation of GR mRNA or cytokines following topical corticosteroid treatment. The proposed corticosteroid resistance may be inherent, or induced by a change of local tissue bioavailability.

Treatment with dexamethasone arrests the development of myringosclerosis after myringotomy.

HYPOTHESIS: To attempt to inhibit the development of myringosclerosis by intraperitoneal injection of dexamethasone. BACKGROUND: The authors' earlier report showed that the development of myringosclerosis after myringotomy was associated with an inflammatory reaction. The present study was performed to secure evidence for this hypothesis. METHODS: Three groups of bilaterally myringotomized rats were treated at 12-hour intervals with intraperitoneal injection of dexamethasone, RU486 (a glucocorticoid receptor antagonist), and saline, respectively. At 6, 12, 24, and 48 hours after the myringotomy, 2 animals were anesthetized on each occasion and examined otomicroscopically. The animals were then killed, and the tympanic membranes were excised and prepared for light microscopic studies. RESULTS: Dexamethasone treatment retarded and diminished the development of sclerotic lesions markedly. Moreover, no inflammatory signs were seen in the flaccida specimens. When the RU486-treated animals were compared with the animals in the control group, there were no evident differences concerning the development of myringosclerosis or the extent of the inflammatory reaction. CONCLUSION: These findings confirm the earlier hypothesis that an inflammatory reaction in collagen tissue is involved in the mechanism that causes the development of myringosclerosis.

Association of bronchopneumonia with sinusitis due to Bordetella bronchiseptica in an experimental rabbit model.

An animal model for rhinogenic sinusitis was developed in rabbits naturally colonized with Bordetella bronchiseptica. It was found that ostial occlusion predisposes the sinus to invasion with this opportunistic bacterium and subsequent sinusitis as a result of reduced local host defense. In addition to the inflammatory lesions in the sinus, bronchitis and pneumonia were found in 84% of the experimental rabbits, suggesting that ostial dysfunction can also contribute to infectious disease of the lower respiratory tract. In such a model it is possible to study the significance of asymptomatic carriage of potential pathogens after ostial occlusion.

Evaluation of methods for endoscopic staging of nasal polyposis.

Endoscopy is needed for reliable evaluation of the treatment of nasal polyposis. In this study, we compared the reproducibility of various score systems for staging nasal polyposis and the inter-individual variations between investigators. The mass of the polyps was assessed by five methods, three new techniques (numbers 1, 2 and 3) and two established ones (numbers 4 and 5). These were: 1, lateral imaging projecting the extension of the polyps by drawing on a schematic picture of the lateral wall of each nasal cavity; 2, assessment of polyp obstruction estimating the proportion of the total nasal cavity volume occupied by polyps; 3, nasal airway patency--determining the relationship between the patient's patent airway lumen and an imaginary maximal nasal airway lumen; 4, a score system with four steps ad modum Lildholdt et al.--determining their relationship to fixed anatomical landmarks; and 5, a score system with three steps ad modum Lund and Mackay--determining their relationship to the middle meatus. High correlations were found between the first and the second assessments by a given investigator with all five methods used to score nasal polyposis. High correlations were also shown between the various methods. When three investigators examined a given patient, there were no significant differences between the investigators using score systems 1, 3 and 4. However, with score systems 2 and 5, there was insufficient agreement between the investigators. The patient's symptom of nasal blockage was not a good indicator of the size of the polyps, especially as regards small polyps. Two of the best methods tested (1 and 4) were selected for further clinical studies regarding evaluation of the sensitivity of score systems to detect changes in polyp size during treatment.

Labeling of the glucocorticoid receptor and Na,K-ATPase in a rat otitis media model.

HYPOTHESIS: Glucocorticoid hormones exert an influence on the inflammatory response of the middle ear during acute otitis media. Rats with experimentally induced purulent otitis media were given either glucocorticoid hormones in excess or a glucocorticoid hormone blocker that deprived the animals of the hormone. BACKGROUND: Acute otitis media is a common inflammatory disease among children. Streptococcus pneumoniae is the most usual causative agent. The standard treatment today is phenoxymethylpenicillin. The role of glucocorticoid hormones in inflammatory reactions in the middle ear has been widely debated. METHODS: In an otitis media model, a suspension of pneumococci was inoculated into the bulla of the rat, after the animals were pretreated with either a dose of corticosteroid hormones or the glucocorticoid receptor blocking agent RU 486. Rats with induction of otitis media only, but no pretreatment, were used as control subjects, as were the left control-operated ears of all rats. The inflammatory response in the inner ear and in the middle ear was evaluated. The presence of glucocorticoid receptors and the enzyme Na,K-ATPase was investigated with immunohistochemistry. RESULTS: The inflammatory response in the animals with untreated otitis media and in the group with otitis media in rats pretreated with the receptor blocker was much more extensive than in the group of animals pretreated with corticosteroids. In the corticosteroid-treated group, the tympanic membrane and the mucous membrane of the middle ear were less edematous, but the middle ear cavity contained more pus. Only a few lymphocytes were found in the inner ears of these rats. When the inner ear was labeled with antibodies against glucocorticoid receptors, there seemed to be no difference between the labeling patterns in the three groups. This was also the case for antibody labeling against Na,K-ATPase. CONCLUSION: The present results indicate that the reaction in the middle ear mucous membrane is more pronounced in rats that had been pretreated with the hormone receptor blocking drug. An increase of corticosteroid hormone levels during the inflammatory process seem to diminish the reaction in the tympanic membrane and the middle ear mucosa. Neither the hormone receptor blocking drug nor the steroid hormones change the content of glucocorticoid receptors and Na,K-ATPase in the inner ear in the otitis media rat model.

The relationship of nasal polyps, infection, and inflammation.

The role of infection as cause or effect in nasal polyps is debated. In experimentally induced sinusitis in rabbits, polyps are frequent. The initial polyp formation sequence involves multiple epithelial disruptions with proliferating granulation tissue. Regenerating epithelial branches spread into the underlying connective tissue, where intraepithelial microcavities give rise to a polyp body from the adjacent mucosa. Clinical as well as experimental studies indicate that nasal polyp formation and growth are activated and perpetuated by an integrated process of mucosal epithelium, matrix, and inflammatory cells, which in turn may be initiated by both infectious and noninfectious inflammation. The complexity of the pathophysiologic events in nasal polyposis is reinforced by the finding that epithelial desquamation, combined with infection or inflammation, will initiate polyp formation. Systemic glucocorticosteroids inhibit polyp formation as well as growth of pathogenic bacteria in the sinuses of rabbits with experimental infection. Therapeutic use of corticosteroids in polyp disease, combined with antibiotics or surgery, should be modified in relation to long-term progression, intensity variations, and predisposing conditions.