Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Otitis media with effusion (OME) is generally benign and self-limiting but is often recurrent and can change into a chronic type. We have previously reported that intratympanic inoculation of lipopolysaccharide (LPS) from Klebsiella pneumoniae can develop experimental OME in the guinea pig. However, OME induced by 10 micrograms/ml of LPS was of a self-limiting type. Our hypothesis was that a higher concentration of LPS might develop a chronic OME because LPS reduces the ciliary activity in the tubotympanum in a dose related manner. In our present study we inoculated 100 micrograms/ml of LPS from K. pneumoniae into the tympanic cavity of the guinea pig, in the hope of illuminating a possible mechanism predisposing to the chronicity of the disease. A longer-term OME was observed after tympanic inoculation of 100 micrograms/ml of LPS. Ciliary activity in the Eustachian tube was depressed for a longer term by this dose than by the previous one. In addition to mucociliary pathologies and general inflammatory changes similar to those induced by 10 micrograms/ml of LPS, intracytoplasmic ciliary cysts were observed after inoculation of 100 micrograms/ml of LPS, which appeared to show disturbed ciliogenesis and chronic mucociliary lesions. In conclusion, intratympanic inoculation of a higher concentration of LPS developed a longer-term OME in the guinea pig, which was supported by functional as well as morphological examinations.
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PMID:Experimental otitis media with effusion induced by lipopolysaccharide from Klebsiella pneumoniae. Mucociliary pathology of the eustachian tube. 184 60

Inner ear function was assessed by a frequency-specific (+/-100 Hz) auditory brainstem response (ABR) technique after a single instillation of a suspension of purified E. coli lipopolysaccharide in sterile water into the round window (RW) niche in rats. Instillation of endotoxin caused a transient concentration and tonotopically dependent dysfunction of the inner ear. The largest threshold impairment occurred in the high-frequency region anatomically located close to the RW. At 31.5 kHz the threshold impairment persisted throughout the study. Morphologic damage to the inner ear was not detected at the light microscopic level when using serial sections from decalcified specimens. Our study supports the clinical hypothesis that remnants of non-viable bacteria such as endotoxins, when trapped in the middle ear, can promote middle ear effusion and dysfunction of the inner ear.
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PMID:Inner ear disturbances following inoculation of endotoxin into the middle ear. 264 47

Lipopolysaccharide (10 micrograms/mL) derived from Klebsiella pneumoniae was injected into the middle ear of guinea pigs. The animals were killed painlessly on days 1, 3, and 7 after inoculation, and the mucosal samples from two sites within the tympanic cavity, close to the tympanic orifice and distal to the orifice, were examined for ciliary activity and epithelial morphology. At day 1 and day 3 serous effusion was observed and deterioration of ciliary activity and morphologic changes were observed. No effusion was recognized at day 7, when the ciliary activity in the distal mucosa was still diminished and that in the proximal mucosa had recovered to a normal level. Our data have shown that lipopolysaccharide extracted from K pneumoniae can produce otitis media with effusion in laboratory animals, and dysfunction of cilia due to lipopolysaccharide probably is responsible for the accumulation of middle ear effusion. The mucociliary system is indeed an important defense system and failure of such a system, especially in the mucosa close to the tympanic orifice, can cause the buildup of effusions.
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PMID:Mucociliary disease of the middle ear during experimental otitis media with effusion induced by bacterial endotoxin. 265 18

Otitis media with effusion was induced in guinea pigs by intratympanic instillation of lipid A, the lipid moiety of gram-negative bacterial lipopolysaccharide from Salmonella minnesota Re595. Lipid A was chosen as an inducer because of its similar composition among various bacterial species. Animals were killed from the first to 14th day after instillation of various concentrations (0.2, 2, 20, 200 micrograms/ml) of lipid A in 0.5% triethylamine. By 3 days after instillation, all experimental animals developed serous middle ear effusion. The histologic findings included hemorrhage, mucosal edema, capillary engorgement, and migration of infiltrative cells including macrophages, polymorphonuclear neutrophils, and lymphocytes. These findings were most prominent 3 days after instillation, and the recovery of the middle ear epithelium was observed within 14 days. Repeated instillation of lipid A (2 micrograms/ml) at an interval of 14 days reinforced the local response accompanied by serous middle ear effusion. These findings indicate that lipid A can induce the inflammatory changes with middle ear effusion and that lipid A plays an important role in the pathogenesis of otitis media with effusion.
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PMID:Experimental otitis media with effusion induced by intratympanic lipid A instillation. 357 74

Using a rat model, the authors investigated the role of nitric oxide (NO) in endotoxin-induced middle ear effusion (MEE). After the eustachian tube was obstructed, the middle ear was transtympanically injected with 35 microL of either 1 mg/mL lipopolysaccharide (LPS) or LPS and 1 mmol/L N-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase. Over the next 6 hours, the fluid within the middle ear was collected every 2 hours, and the quantity of albumin in the fluid, an index of vascular leakage, was determined using enzyme-linked immunosorbent assay. L-NAME significantly reduced LPS-induced vascular extravasation into the middle ear. Inoculation of the ear with L-arginine, the substrate for NO synthase, reversed the effects of L-NAME. These results indicate that NO is a mediator of LPS-induced MEE. Therefore, inhibition of NO synthase may represent a novel approach to the treatment of otitis media with effusion.
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PMID:Nitric oxide: a mediator of endotoxin-induced middle ear effusions. 869 94

The clinical efficacy of erythromycin (EM) therapy has been demonstrated in otitis media with effusion (OME). However, the mechanism of action of this drug is not clear. In this study, to elucidate the possible mechanism of action of EM, we examined the effect of the drug on the expression of neutrophil adhesion molecules such as L-selectin and Mac-1. Furthermore, we examined production of leukotrienes B4, C4 (LTB4, C4) and prostaglandin E2 (PGE2) in rat OME induced by injection of a lipopolysaccharide. EM down-regulated L-selectin expression, and inhibited up regulation of Mac-1 expression on peripheral blood neutrophils. Also it inhibited the accumulation of inflammatory cells such as neutrophils and macrophages in middle ear effusion (MEE). Furthermore, EM suppressed the exudation of plasma protein and the production of LTB4, C4 and PGE2, in OME. These results suggest that EM may exert the antiinflammatory effect on MEE through suppression of leukocyte accumulation the middle ear by affecting the expression of adhesion molecules on leukocytes and inhibiting the production of arachidonic acid metabolitis.
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PMID:[Evaluation of the effect of erythromycin on otitis media with effusion in experimental rat models]. 883 Dec 36

In a rat model, we investigated the role of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in endotoxin-induced middle ear effusions (MEEs). After the eustachian tube was obstructed, the middle ear was transtympanically injected with 35 microL of either 1) 1 mg/ mL lipopolysaccharide (LPS); 2) LPS and 100 micrograms TNF binding protein (TNFbp); 3) LPS and 1 microgram IL-1 receptor antagonist (IL-1ra); or 4) LPS, TNFbp, and IL-1ra. Every 2 hours, the fluid within the middle ear was collected, and the quantity of albumin in the fluid, an index of vascular leakage, was determined by enzyme-linked immunosorbent assay. After 6 hours, the middle ear was fixed for histologic analysis. The TNFbp significantly attenuated vascular extravasation into the middle ear. The IL-1ra did not significantly alter effusion development. These results indicate that TNF, but not IL-1, is a mediator of LPS-induced MEE. Therefore, TNFbp may represent a novel approach to the treatment of otitis media with effusion.
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PMID:Role of tumor necrosis factor and interleukin-1 in endotoxin-induced middle ear effusions. 927 Apr 24

Otitis media with effusion (OME) is characterized by the presence of fluid in the middle ear without signs or symptoms of acute infection and by persistent changes in the middle ear mucosa. These are mainly induced by gram-negative bacterial infection and dysfunction of the eustachian tube (ET). Gram-negative bacteria (GNB) contain lipopolysaccharide (LPS) in their outer membrane that is responsible for inflammatory reactions in the middle ear. In this study we investigated the therapeutic effect of a recombinant LPS-binding protein, bactericidal/permeability-increasing protein (rBPI21), on the repair of mucosal damage in rats with experimentally induced OME. OME was induced by obstruction of the eustachian tube in combination with LPS injection. Twelve weeks after OME induction, secretory cells in the tympanic orifice of the middle ear were increased from an average of 14 +/- 2 to 31 +/- 5, ciliated cells were decreased from 24 +/- 4 to 6 +/- 4, and the number of macrophages in the subepithelial layer increased from 13 +/- 4 to 27 +/- 3. A single dose of rBPI21 was administered directly into the middle ear cavity 2 weeks after the induction of OME. Histologic examination of the middle ear mucosa at 4 and 12 weeks after OME induction showed that mucosal changes were restored by rBPI21 treatment. These results demonstrate that the middle ear mucosa recovers from inflammatory changes associated with OME after treatment with rBPI21. This suggests that rBPI21 may be useful in the treatment of OME and of mucosal infections of the respiratory tract.
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PMID:Efficacy of bactericidal/permeability-increasing protein in experimental otitis media with effusion in rats: a new therapy for mucosal infections. 1128 26

Tumor necrosis factor (TNF)-alpha is important in the pathogenesis of otitis media with effusion (OME). The purpose of this study was to determine the effect of TNF-alpha antagonist on the outcome of lipopolysaccharide (LPS)-induced OME in rats. Otitis media was induced by injecting Pseudomonas aeruginosa LPS transtympanically. Another (combination) group was pretreated with TNF-alpha antagonist, soluble TNF receptor type I (sTNF RI), before transtympanic injection of LPS. Saline and phosphate-buffered saline solutions were used as controls. Twelve hours after the transtympanic injection, otoscopic examination and aspiration of middle ear effusion (MEE) were done. The temporal bones in each group were examined histopathologically, and the vascular permeability of the middle ear mucosa was measured by the Evans blue vital dye technique. In the LPS and combination groups, MEE developed in 90% and 0% of ears, respectively. The combination group showed less inflammation, less mucosal thickening, and significantly decreased vascular permeability as compared to the LPS group. Transtympanic administration of sTNF RI appears to suppress the development of LPS-induced OME. This study suggests that TNF-alpha antagonist, along with antibiotics, may have an adjunctive role in the future treatment of MEE.
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PMID:Effect of inhibitor of tumor necrosis factor-alpha on experimental otitis media with effusion. 1164 23

The relationship between acute otitis media and otitis media with effusion (OME) is uncertain and the aetiology of OME is multifactorial. Otitis media with effusion may be an inflammatory condition; both bacteria and viral infections could play a part in this inflammation. The four bacteria Streptococcus pneumoniae, Haemophilus influenza, Staphylococcus aureus and Branhamella catarrhalis cause 60% of the infections whereas S. pneumoniae accounts for up to 35%. IgA provides the dominant surface response to polysaccharide and lipopolysaccharide antigens, of which IgA2 is the main subclass. Once the mucosa has been breached, most protection is provided by IgG. IgG2 acts mainly against bacterial capsular antigens. This study looked at two groups of 50 children with and without OME who were aged between 3 and 10 years. The aims were to determine if, firstly, the levels of the serum immunoglobulins were different in the two groups, secondly whether these children made the appropriate antibody response to the capsular antigen to S. pneumoniae (PCP), and finally if there was a delay in the maturity of the IgA response. The total IgG, IgA and all subclass levels were measured using radial immunodiffusion. Levels of functional IgA and IgG were measured using ELISAs (25 patients in each group). The results were analysed with non-parametric tests. The immunoglobulin levels were within the normal levels for both groups. There were very good correlations between the IgG total anti-PCP and the IgG2 anti-PCP (R > 0.9, p = 0.001). There was a good correlation between the levels of both IgG total and IgG2 anti-PCP against IgA total anti-PCP in both groups (R > 0.85, p > 0.01). This confirms a normal antibody response between both groups of patients. The ages of the controls and patients (50 samples) were correlated with increasing titres of circulating functional antibodies (P = 0.001). This is highly suggestive of a normal age-related response. In conclusion, the findings were contradictory to our original hypothesis that there is a subtle difference in surface protection between children with and without OME. We believe that a previous history of recurrent acute otitis media is unrelated to the development of OME after 3 years of age.
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PMID:Serum IgA and IgG functional antibodies and their subclasses to Streptococcus pneumoniae capsular antigen found in two aged-matched cohorts of children with and without otitis media with effusion. 1287 Dec 48


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