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We examined the effects of estrogen on tumor necrosis factor alpha (TNF-alpha)-induced expression of intracellular adhesion molecule (ICAM-1) and vascular adhesion molecule (VCAM-1) in cultured human bronchial smooth muscle cells (BSMC). Experiments were performed in triplicate in T-75 tissue culture flasks containing normal human BSMC. Four experiments were carried out: untreated BSMC cells (control); TNF-alpha 1000 U/ml stimulation of BSMC; forskolin 5 microM before TNF-alpha stimulation of BSMC; and estradiol 30 microM before TNF-alpha stimulation of BSMC. Cyclic adenosine monophosphate was measured by a commercially available radioimmunoassay kit. Cell expression of ICAM-1 and VCAM-1 was quantified by flow cytometry Incubation of cells with TNF-alpha 1000 U/ml for 24 hours elicited a 27-fold increase in basal expression of ICAM-1 and a 2-fold increase in VCAM-1 (p>0.05). Incubation of BSMC with forskolin 5 microM, for 1 hour before TNF-alpha, decreased TNF-alpha-induced expression of ICAM-1 by 62% and VCAM-1 slightly by 17%. The BSMC incubated with estradiol 30 microM, 1 hour before TNF-alpha, decreased TNF-alpha-induced expression of ICAM-1 by 21%; VCAM-1 remained unchanged (p>0.05). We found a trend toward inhibition of TNF-alpha-stimulated ICAM-1 expression in cultured BSMC with pretreatment with estradiol. However, due to large variability within the cell culture model, statistical significance was not reached.

We attempted to determine the effects of cyclosporine on beta-adrenergic receptors in bovine pulmonary artery smooth muscle cells. Bovine pulmonary artery smooth muscle cells were exposed to cyclosporine at a concentration of 100 ng/ml in culture media for 5 days, and control bovine pulmonary artery smooth muscle cells were exposed to only culture media for the same 5-day period. Beta-adrenergic receptors were measured as total binding capacity (Bmax) by nonlinear least squares fit of the specific binding curve. In a separate experiment beta1- versus beta2-adrenergic receptor subtypes were identified by computer modeling (LIGAND) of 17-19 point CGP20712A-125ICYP competition curves. Cyclosporine significantly (p=0.02) decreased bovine pulmonary artery smooth muscle beta-adrenergic receptor density by 54%+/-7%. The Bmax for control versus treated cells was 38.9+/-18 versus 17.7+/-12 fmol/mg protein, respectively. Subtype determination of beta-receptors revealed 70% or more beta2- and 30% or less beta1-adrenergic receptors. Cyclosporine caused a 54% reduction in overall beta-adrenergic receptor density in bovine pulmonary artery smooth muscle cells. The reduction in Bmax is suspected not to be a result of selective down-regulation of beta1-adrenergic receptors alone. We believe that cyclosporine may also contribute to a decrease in beta2-adrenergic receptors.

Study Objective: To evaluate the metabolic and cardiopulmonary effects of nebulized albuterol in patients suffering moderate to severe exacerbations of asthma or chronic obstructive pulmonary disease., Design: Open-label, prospective study., Setting: The emergency department of a university medical center., Patients: Ten patients with moderate to severe exacerbation of asthma., Interventions: Each patient received nebulized albuterol 2.5 mg for approximately 10 minutes., Measurements and Main Results: Serum potassium, heart rate and rhythm, blood pressure, and pulmonary function were measured before treatment and every 15 minutes for 2 hours after treatment. Serum potassium concentrations decreased significantly (p < 0.05) within 75 minutes after initiation of treatment, from a baseline value of 4.5 +/- 0.6 mEq/L (range 3.5-5.5 mEq/L) to 3.7 +/- 0.5 mEq/L (range 2.8-4.4 mEq/L) at the end of the collection period (120 minutes). Forced expiratory volume in 1 second significantly increased over time in patients with asthma (p < 0.05). No statistically significant changes in blood pressure, heart rate, or corrected QT intervals occurred. Pre-emergency department use of a beta 2-agonist by metered-dose inhaler was not associated with a decreased serum potassium on admission., Conclusions: Nebulized beta 2-agonists are generally efficacious and safe in patients with acute bronchospasms. However, close monitoring of serum electrolytes, heart rate, and rhythm in patients at risk (elderly, those with pre-existing cardiac disease) is advised before these individuals receive repeat doses by continuous aerosol administration.

Omeprazole is a substituted benzimidazole that has gained widespread use in the treatment of acidic and peptic ulcer disease. Adverse events with the drug are rare and involve mainly the gastrointestinal and central nervous systems. Skin inflammation, urticaria, pruritus, alopecia, and dry skin have been reported in 0.5-1.5% of patients. To date, no published report has linked angioedema with omeprazole. We report a case of a 34-year-old woman with cellulitis, ulcerative erosive esophagitis, and gastric and duodenal ulcers who developed several hypersensitivity reactions characterized by shortness of breath, wheezing, cough, mild angioedema, and total body urticaria and pruritus. These symptoms correlated with the addition of omeprazole to her regimen and the timing of its administration. A previous case report prompted a rechallenge with enteric-coated omeprazole granules removed from the capsule shell. Recurrence of the adverse events suggested an allergy to the drug itself and not the capsule. Angioedema can be a life-threatening allergic reaction requiring immediate treatment. Rechallenge using omeprazole with or without the capsule shell should be done only in a hospital setting where prompt action can be taken in the event of an emergency.