Airway obstruction and hyperreactivity are characteristics of human asthma and of "heaves," a naturally occurring respiratory disorder of horses and ponies. To document the role of cyclooxygenase products of arachidonic acid metabolism in the pathogenesis of heaves, we measured plasma and bronchoalveolar lavage (BAL) fluid concentrations of metabolites of thromboxane (TX)A2 and prostaglandins (PG) I2 and D2 in five affected ponies and their age- and gender-matched controls prior to and during acute airway obstruction precipitated by housing the ponies in a barn and exposing them to hay dust. Pulmonary resistance increased significantly and dynamic compliance and arterial oxygen tension decreased significantly in affected ponies that were placed in the barn. At this time, histamine aerosol challenge demonstrated the presence of airway hyperresponsiveness in the affected ponies. Plasma TXB2 was the only metabolite that increased significantly during the acute disease state. In a subsequent experiment, the ponies were treated with flunixin meglumine, a cyclooxygenase inhibitor, to determine if this would alter the onset or development of clinical disease. At a dose of 1.1 mg/kg intramuscularly, 3 times daily, flunixin meglumine inhibited TXB2 production but did not alter the degree of airway obstruction or airway hyperreactivity measured at pasture and in the barn. We conclude that cyclooxygenase products of arachidonic acid metabolism are altered but do not play a role in the airway obstruction and hyperreactivity observed in ponies with heaves.
Methyl esters of aliphatic acids have occupied an important position in the study of dielectric absorption in long-chain molecular crystals. They were the first to be studied over a wide frequency range1t2 over a range of temperature^.^ These studies showed that methyl esters have two absorptions, one a t microwave frequencies, the other in the radio frequency range. The former, which does not depend on the chain-length of the molecule and which is absent4 in compounds having the dipole close to the middle of the chain, appears to be due to motion of the end dipole of the molecule. It will not be considered further in the present communication.The lower frequency absorption is strongly dependent on the chain-length of the molecule. Similar dependence on chain-length is found for the corresponding absorption in ethyl estersG4 It is believed that the absorption is due to rotation of the whole molecule, occurring near an imperfection of the crystal lattice.5~6At present the crystal structures of only these two series of aliphatic esters (methyl esters' and ethyl esters8) are known in any detail, so that the two series are critical to discussion of mechanism. They have essentially the same side-by-side packing of chains, but differ in end packing.Unfortunately the activation energies for these series reported from this Laboratory are of low accuracy, illustrated by the discrepancy between our value for methyl stearate (11 kcal/mole) and a value (12.7 kcal/mole) determined recently by B r o a d h~r s t .~ The inaccuracy is due mainly to the use of a limited temperature range for the measurements.It appeared desirable to remeasure these activation energies before attempting deductions from the way in which they vary with chain-length. We have therefore
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