PubMed · 10691582
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F Muñoz-López. Inhaled corticosteroids?. https://pubmed.ncbi.nlm.nih.gov/10691582/
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The sense of smell originates in a diverse array of receptor neurons, comprising up to 1000 different types. To understand how these parallel channels encode chemical stimuli, we recorded the responses of glomeruli in the olfactory bulbs of the anesthetized rat, by optical imaging of intrinsic signals. Odor stimulation produced two kinds of optical responses at the surface of the bulb: a broad diffuse component superposed by discrete small spots. Histology showed that the spots correspond to individual glomeruli, and that approximately 400 of them can be monitored in this way. Based on its wavelength-dependence, this optical signal appears to derive from changes in light scattering during neural activity. Pure odorants generally activated several glomeruli in a bilaterally symmetric pattern, whose extent varied greatly with concentration. A simple formalism for ligand binding accounts quantitatively for this concentration dependence and yields the effective affinity with which a glomerulus responds to an odorant. When tested with aliphatic molecules of increasing carbon chain length, many glomeruli were sharply tuned for one or two adjacent chain lengths. Glomeruli with similar tuning properties were located near each other, producing a systematic map of molecular chain length on the surface of the olfactory bulb. Given local inhibitory circuits within the olfactory bulb, this can account for the observed functional inhibition between related odors. We explore several parallels to the function and architecture of the visual system that help interpret the neural representation of odors.
BACKGROUND: Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. METHODS AND RESULTS: A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng. kg(-1). min(-1) for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48+/-0.38 to 0.27+/-0.16 (P:<0.001). Similarly, iloprost decreased the ratio from 0.49+/-0.38 to 0.26+/-0.11 (P:<0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6+/-11.9 to 34.7+/-21.4 nmol/L during iNO (P:<0.01), and plasma cAMP increased from 55.7+/-22.9 to 65.1+/-21.2 nmol/L during iloprost inhalation (P:<0.05). CONCLUSIONS: In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.
1,3-Butadiene (BD) is carcinogenic and mutagenic in B6C3F1 mice. BD inhalation induces an increased frequency of specific base substitution mutations in the bone marrow and spleen of B6C3F1 lacI transgenic mice. BD is bioactivated to at least three mutagenic metabolites: 1,2-epoxybutene (EB), 1,2-epoxy-3,4-butanediol (EBD), and 1,2,3,4-diepoxybutane (DEB), however, the contribution of these individual metabolites to the in vivo mutational spectrum of BD is uncertain. In the present study, lacI transgenic mice were exposed by inhalation (6h per day, 5 days per week for 2 weeks) to 0 or 29.9ppm of the BD metabolite, EB to assess its contribution to the in vivo mutational spectrum of BD. No increase in lacI mutant frequency was observed in the bone marrow or spleen of EB-exposed mice. The lack of mutagenicity in the bone marrow or spleen likely relate to insufficient levels of EB reaching these tissues. The lacI mutant frequency was increased 2.7-fold in the lungs of EB-exposed mice (mean+/-S.D., 9.9+/-3.0x10(-5)) compared to air control mice (3.6+/-0.7x10(-5)). DNA sequence analysis of 65 and 66 mutants from the lungs of air control and EB-exposed mice, respectively, revealed an increase in the frequency of two categories of base substitution mutation and deletions. Like mice exposed to BD, EB-exposed mice had an increased frequency of A:T-->T:A transversions. However, in contrast to the BD mutational spectra, G:C-->A:T transitions at 5'-CpG-3' sequences, occurred with increased frequency in the EB-exposed mice. The increased frequency of deletions as well as the induction of two tandem mutations and a tandem deletion in the lungs of EB-exposed mice are also inconsistent with previous mutational spectra from BD-exposed mice or EB-exposed cells in culture. We hypothesize that the direct in vivo mutagenicity and further in situ metabolism of EB in the lungs of EB-exposed mice played a prominent role in the generation of the current mutational spectrum.