Effect of platelet-activating factor on secretion of mucous glycoprotein from chinchilla middle ear epithelial cells in vitro

Platelet-activating factor (PAF) is a naturally occurring phospholipid that acts as a pleiotropic mediator and mediates cell-cell reactions under physiological and pathological conditions. Recently, it has been shown that PAF is a strong secretagogue of mucous glycoprotein in the airways, suggesting its role in mucous glycoprotein secretion and the pathogenesis of otitis media with effusion. In the current study, we examined the effect of PAF on mucous glycoprotein secretion in cultured chinchilla middle ear epithelial cells. PAF at 1 M significantly stimulated mucous glycoprotein secretion from cultured chinchilla middle ear epithelial cells. This action was concentration-dependent, with secretions reaching near maximum when the cells were incubated with PAF at 100 M. In a time-dependent study, PAF demonstrated an initial rapid stimulation of mucous glycoprotein secretion, followed by a gradual increase thereafter. A six-fold increase was seen in the first 2 h compared with controls. Cycloheximide, a protein synthesis inhibitor, demonstrated an inhibitory effect on PAF-stimulated mucous glycoprotein secretion in this study. These findings suggest that PAF plays an important role in the pathogenesis of otitis media with effusion by stimulating mucous glycoprotein secretion in vitro.Supported by NIH grant P0I-D000133 from the National Institute on Deafness and Other Communication Disorders.     

Glucosamine May Slow Osteoarthritis Progression

‘Best of the Literature’ presents summaries of sports medicine—related articles culled from more than 30 medical journals. Experts comment on what the new findings add to current medical thinking and on the implications for practice.     

Permeability of the normal round window membrane to Haemophilus influenzae type b endotoxin.

Sensorineural hearing loss associated with otitis media may be due to passage of ototoxic substances such as bacterial toxins and antibiotics, from the middle ear into the inner ear. The round window membrane is the most likely route for such transport. The aim of this study was to analyze the extent of endotoxin passage through the normal round window membrane. The round window membranes of 19 chinchillas were exposed in vivo to Gelfoam soaked in purified Haemophilus influenzae type b endotoxin at a concentration of 45,000 endotoxin units per ml (EU/ml) during 3 to 24 h. Endotoxin levels in the perilymph were measured with Limulus Amaebocyte Lysate or Quantitative Chromogenic Limulus Amaebocyte Lysate. Endotoxin was detected in half of the inner ears at concentrations close to the detection limit (approximately 4 EU/ml). The results suggest that the normal round window membrane efficiently protects the inner ear against the passage of bacterial endotoxins from the middle ear cavity. It is unlikely that endotoxin at concentrations found in the middle ear secretion during otitis media can traverse the round window membrane in sufficient amount to cause inner ear deterioration.     

Round window membrane permeability to human serum albumin in antigen-induced otitis media

The round window membrane (RWM) permeability to human serum albumin (HSA) was investigated in both normal chinchillas and chinchillas sensitized with HSA. The effect of a corticosteroid agent (triamcinolone) on the RWM permeability was also analyzed. It was found that HSA could not be detected in either the perilymph or the cerebrospinal fluid of normal chinchillas within 1 hour after instillation into the middle ear bulla. Perilymph levels of HSA peaked 24 hours after instillation. In antigen-induced otitis media, the HSA level in the perilymph at 12 hours after challenge was significantly higher than that in normal chinchillas (P less than .01), but it did not increase with the development of otitis media. A significant difference of HSA level in the perilymph of animals with and without steroid treatment was noted (P less than .025 at 24 hours and P less than .05 at 48 hours). It is concluded that little HSA passes through the normal RWM in a short time and that the RWM permeability to HSA increases in the early stage (about 12 hours) of antigen-induced otitis media. Corticosteroids can affect the RWM permeability to HSA by reducing the level of antigen-induced otitis media.     

Elimination kinetics of furosemide in perilymph and serum of the chinchilla. Neuropharmacologic correlates

This study was done to determine the comparative elimination kinetics of furosemide from chinchilla perilymph and serum, and to correlate perilymph concentration with changes in endocochlear potential. The elimination kinetics of furosemide (FU) were determined in sera and perilymph obtained from chinchillas injected with 100 mg/kg i.v. of FU. Concentrations of FU exhibited a linear decay pattern in serum and perilymph over the initial 60 minutes. The rate of decline of furosemide levels in perilymph was about four times slower than the rate of fall in serum. Chronic treatment (25 mg/kg i.p. every 12 hours) did not appear to influence the level of drug at 60 minutes after a dose of FU (100 mg/kg IV). Chinchillas were also studied following doses of FU ranging from 25--200 mg/kg i.v. to see the effect on endocochlear potential (EP). A positive correlation was found between FU dosage, the maximum millivolt reduction of EP and the time to initiation of recovery of EP. The perilymph concentration of furosemide when the EP began to recover was 5 microgram/ml (1.5 x 10(-5) M). Knowledge of furosemide kinetics may ultimately be applied to prevent ototoxicity in patients.     

Characterization of the duration from onset of asthma symptoms to asthma disease.

BACKGROUND: Little is known about factors associated with progression of childhood asthma from onset of symptoms to index date determined by medical records. OBJECTIVE: To determine the duration between the onset of asthma symptoms to index date of asthma (ie, time when one met the criteria for asthma) and associated factors. METHODS: Study participants came from a sample of 839 healthy children, aged 5 to 12 years, who had participated in a previous study. Comprehensive medical record reviews were conducted to determine first documentation of asthma symptoms and index date of asthma. Factors were evaluated for an association with the duration from onset of asthma symptoms to index date of asthma. RESULTS: Of the study sample, 222 children met the criteria for asthma and had an available onset date of asthma symptoms. The median ages at onset of asthma symptoms and the index date were 5.6 and 7.6 years, respectively. The median duration between onset of asthma symptoms and index date was 2.9 months, and the mean was 17.2 months. There was a tendency for patients with a pet at home (P = .047), exercise-induced symptoms (P = .04), younger age at symptom onset (P = .05), and more severe asthma (P = .05) to have a shorter duration from onset of symptoms to index date. CONCLUSIONS: The duration from onset of asthma symptoms to index date of asthma varies significantly depending on host and environmental factors. It does not necessarily correlate with commonly recognized risk factors for incidence or severity of asthma.