Prostaglandin E2 Produced by the Lung Augments the Effector Phase of Allergic Inflammation

Elevated PGE2 is a hallmark of most inflammatory lesions. This lipid mediator can induce the cardinal signs of inflammation, and the beneficial actions of non-steroidal anti-inflammatory drugs are attributed to inhibition of cyclooxygenase COX-1 and COX-2, enzymes essential in the biosynthesis of PGE2 from arachidonic acid. However, both clinical studies and rodent models suggest that, in the asthmatic lung, PGE2 acts to restrain the immune response and limit physiological change secondary to inflammation. To directly address the role of PGE2 in the lung, we examined the development of disease in mice lacking microsomal prostaglandin E synthase 1 (mPGES1), which converts COX-1/COX-2 derived PGH2 to PGE2. We show that mPGES1 determines PGE2 levels in the naïve lung and is required for increases in PGE2 after ovalbumin (OVA) induced allergy. While loss of either COX-1 or COX-2 increases the disease severity, surprisingly mPGES1 −/− mice show reduced inflammation. However, an increase in serum IgE is still observed in the mPGES1 −/− mice, suggesting that loss of PGE2 does not impair induction of a TH2 response. Furthermore, mPGES1 −/− mice expressing a transgenic OVA-specific T cell receptor are also protected, indicating that PGE2 acts primarily after challenge with inhaled antigen. PGE2 produced by the lung plays the critical role in this response, as loss of lung mPGES1 is sufficient to protect against disease. Together this supports a model in which mPGES1-dependent PGE2 produced by populations of cells native to the lung contributes to the effector phase of some allergic responses

Photochemically Altered Air Pollution Mixtures and Contractile Parameters in Isolated Murine Hearts before and after Ischemia

Background: The cardiopulmonary effects of the individual criteria air pollutants have been well investigated, but little is known about the cardiopulmonary effects of inhaled multipollutant mixtures that more realistically represent environmental exposures

Comparison of intraosseous and intravenous iodinated contrast administration for CT imaging in Hispaniolan Amazon parrots (Amazona ventralis)

Establishing and maintaining intravenous access for contrast medium during CT imaging can be difficult in birds due to their small size and thin walled vessels. Intraosseous (IO) catheters are an alternative to intravenous catheters and are often used for fluid or medication administration in birds. To determine the feasibility of IO iodinated contrast enhancement for CT in birds, 10 adult Hispaniolan Amazon parrots (Amazona ventralis) weighing 260-325 g, were enrolled in a prospective randomized blinded crossover group study to evaluate the differences in contrast route administration. The parrots underwent pre- and postcontrast CT scans using both routes of contrast administration with a wash-out period of at least 1 week between the two methods. Scans were evaluated subjectively for diagnostic quality and objectively with Hounsfield units measured over three organs: the brain, right kidney, and liver. All scans were diagnostic, and there was no statistically significant measurable difference in contrast enhancement between the two methods in any of the three organs. Subjectively, IO catheters were technically more difficult to place, but once in place, they were easier to manipulate for the imaging procedure and provided no complications upon removal. Minimal adverse side effects were noted from the IO catheters. In this small study, IO iodinated contrast administration was comparable in enhancement characteristics to intravenous administration for CT imaging in Hispaniolan Amazon parrots

CONTRAST-ENHANCED COMPUTED TOMOGRAPHIC FINDINGS OF APPARENTLY CLINICALLY NORMAL CHEETAH () LIVERS

Hepatic veno-occlusive disease (VOD) is a significant cause of morbidity and mortality in captive cheetahs (), and the appearance of this disease in humans by computed tomography (CT) has been well described. Contrast-enhanced CT abdominal scans of cheetahs without evidence of hepatic disease ( = 5) were reviewed retrospectively to describe the normal appearance of cheetah livers as an aid to antemortem VOD diagnosis. Despite having no clinical signs, clinical pathology abnormalities, or hepatic biopsy histopathology supportive of VOD, all five cheetahs had at least one VOD consistent finding on CT. The results of this study suggest that given the progressive and potentially subclinical nature of VOD, CT could serve as a noninvasive screening tool and be used to monitor disease progression

Photochemically Altered Air Pollution Mixtures and Contractile Parameters in Isolated Murine Hearts before and after Ischemia

Background: The cardiopulmonary effects of the individual criteria air pollutants have been well investigated, but little is known about the cardiopulmonary effects of inhaled multipollutant mixtures that more realistically represent environmental exposures. Objectives: We assessed the cardiopulmonary effects of exposure to photochemically altered particle-free multipollutant mixtures. Methods: We exposed mice to filtered air (FA), multipollutant mixtures, or ozone (O(3)) for 4 hr in a photochemical reaction chamber. Eight hours after exposure, we assessed cardiac responses using a Langendorff preparation in a protocol consisting of 20 min of global ischemia followed by 2 hr of reperfusion. Cardiac function was assessed by measuring the index of left-ventricular developed pressure (LVDP) and contractility (dP/dt) before ischemia. On reperfusion after ischemia, recovery of postischemic LVDP and size of infarct were examined. We used bronchoalveolar lavage (BAL) cell counts to assess lung inflammation. Results: Exposure to the multipollutant mixtures decreased LVDP, baseline rate of left ventricular contraction (dP/dt(maximum)), and baseline rate of left ventricular relaxation (dP/dt(minimum)) compared with exposure to FA. Exposure to O(3) also decreased heart rate and dP/dt(minimum). Time to ischemic contracture was prolonged in the multipollutant-mixture group relative to that in the FA group. Mice in the multipollutant-mixture group had better recovery of postischemic LVDP and smaller infarct size. Exposure to multipollutant mixtures and to O(3) exposure increased numbers of macrophages in the BAL fluid. Conclusions: Exposure to photochemically altered urban air pollution appears to affect cardiac mechanics in isolated perfused hearts. Inhalation of acute multipollutant mixtures decreases LVDP and cardiac contractility in isolated non-ischemic murine hearts, prolongs ischemic contracture, increases postischemic recovery of LVDP, and reduces infarct size. Citation: McIntosh-Kastrinsky R, Diaz-Sanchez D, Sexton KG, Jania CM, Zavala J, Tilley SL, Jaspers I, Gilmour MI, Devlin RB, Cascio WE, Tong H. 2013. Photochemically altered air pollution mixtures and contractile parameters in isolated murine hearts before and after ischemia. Environ Health Perspect 121:1344–1348; http://dx.doi.org/10.1289/ehp.130660