PubMed · 9246148
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D Jack. 1997. Asthma guidelines.. https://pubmed.ncbi.nlm.nih.gov/9246148/
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Toluene is a commonly used solvent that has been shown to alter mixed-function oxidase (MFO) activity, in an organ- and isozyme-specific pattern, following intraperitoneal administration. The purpose of this study was to determine whether similar changes occurred following repeated, low-level inhalation exposure, and to investigate the role of toluene metabolites in these alterations. Exposure to 375 ppm toluene, 6 h/d for up to 5 d, resulted in significant inhibition of the activity of pulmonary arylhydrocarbon hydroxylase (AHH), cytochrome P-4502B1 (CYP2B1), and CYP4B1, but not CYP1A1. After exposure to lower toluene levels (125 ppm, 6 h/d, 3 d), the activities of lung AHH, CYP2B1, and CYP4B1 were also significantly decreased, but in a dose-related manner. MFO activity was not consistently altered in liver. Control pulmonary or liver microsomes were incubated with various concentrations (0.01-10 mM) of toluene or its metabolites and CYP2B1, CYP1A1, and/or CYP4B1 activities were subsequently determined. Benzaldehyde produced a significant dose-related inhibition in the activity of all three lung P-450s examined (IC50 10(-3) M). Toluene was found to be a more potent inhibitor of lung CYP2B1 and CYP1A1 (IC50, 10(-4) M) than benzaldehyde, but neither toluene nor benzyl alcohol was an effective inhibitor of lung CYP4B1. Toluene and its metabolites were weaker inhibitors of CYP1A1 than of CYP2B1. For CYP2B1 and CYP1A1, the order of inhibitory potency was toluene > benzaldehyde > benzyl alcohol and suggests that both the parent molecule and its metabolites may act in concert to inhibit catalytic activity of these cytochromes. The MFO inhibition seen after repeated low-level toluene inhalation exposure could result in altered metabolic profiles of other xenobiotics in an organ-specific fashion.
BACKGROUND: In children with croup, treatment with nebulized budesonide decreases symptoms, but it is uncertain how budesonide compares with dexamethasone, the conventional therapy for croup, and whether either reduces the rate of hospitalization. METHODS: We performed a double-blind, randomized trial involving 144 children with moderately severe croup. The children were treated with racepinephrine and a single dose of 4 mg of nebulized budesonide (48 children), 0.6 mg of intramuscular dexamethasone per kilogram of body weight (47 children), or placebo (49 children). The children were assessed before treatment and then hourly for five hours after treatment. Physicians who were unaware of the treatment assignments determined the children's need for further treatment and hospitalization. RESULTS: The characteristics of the groups were similar at base line, including the types of viruses identified, the types of croup, and the clinical severity of the illness. The overall rates of hospitalization were 71 percent in the placebo group (35 of 49 children), 38 percent in the budesonide group (18 of 48 children), and 23 percent in the dexamethasone group (11 of 47 children) (unadjusted P=0.001 for the comparison of budesonide with placebo, P<0.001 for the comparison of dexamethasone with placebo, and P=0.18 for the comparison of budesonide with dexamethasone). Children treated with budesonide or dexamethasone had a greater improvement in croup scores than those given placebo (P=0.03 and P<0.001, respectively), and those treated with dexamethasone had a greater improvement than those treated with budesonide (P=0.003). CONCLUSIONS: In children with moderately severe croup, treatment with intramuscular dexamethasone or nebulized budesonide resulted in more rapid clinical improvement than did the administration of placebo, with dexamethasone offering the greatest improvement. Treatment with either glucocorticoid resulted in fewer hospitalizations.
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