Author's personal copy Peroxisome proliferator-activated receptora (PPARa) agonists down-regulate a2-macroglobulin expression by a PPARa-dependent mechanism

Rat Mouse a b s t r a c t Fibrates are peroxisome proliferator-activated receptor alpha (PPARa) ligands used to normalize lipid and glucose parameters and exert anti-inflammatory effects. The acute-phase response (APR) is an important inflammatory process. One of the most important acute-phase proteins in rats is a2-macroglobulin (A2Mg). Whereas normal adult rats present low serum levels, pregnant rats display high amounts. Therefore, we used pregnant rats to detect the effect of fenofibrate on hepatic A2Mg expression by RT-PCR and Northern blot. Virgin rats were used as controls. The expression of other APR genes, a known fibrate-responder gene, gamma-chain fibrinogen (g-Fib), and one gene from the same family as A2Mg, complement component 3 (C3), were also measured in liver. In order to determine whether the fibrateeffects were mediated by PPARa, wild-type mice and PPARa-null mice were also used and treated with WY-14,643 (WY) or di-2-ethylhexyl phthalate (DEHP). Fenofibrate depressed A2Mg expression in virgin rats, but expression was decreased more sharply in pregnant rats. Expression of C3 and g-Fib was diminished after treatment only in pregnant rats. On the other hand, WY, but not DEHP, reduced A2Mg and g-Fib expression in the livers of wild-type mice, without any effect in PPARa-null mice. WY or DEHP did not affect C3 expression. Therefore, A2Mg expression is modified by PPARa agonists not only in pregnant rats under augmented APR protein synthesis, but also in virgin rats and mice under basal conditions. Interestingly, our results also identify A2Mg as a novel PPARa agonist-regulated gene

Effect of heartworm disease and heartworm-associated respiratory disease (HARD) on the right ventricle of cats

Abstract Background Dirofilaria immitis infection occurs in dogs and cats, both of which species are clinically affected by mature adult infections. Cats are uniquely affected by immature-adult infections with an inflammatory pulmonary disease called Heartworm-Associated Respiratory Disease (HARD). D. immitis infection causes pulmonary parenchymal and vascular pathology in the dog and cat. Dogs develop pulmonary hypertension and cor pulmonale, whereas the development of pulmonary hypertension is rare in the cat. D. immitis infection in the dog causes alteration of the right ventricular (RV) extracellular matrix, including a decrease in myocardial collagen. In this study, the RV myocardial changes of cats infected with adult and immature-adult D. immitis were assessed. Methods The cardiopulmonary systems of six groups of SPF cats (n = 9-10 per group) were examined 8 or 18 months after infection with L3 D. immitis. Two groups were untreated and allowed to develop adult HW; two groups were treated with ivermectin starting 3 months post infection, thus allowing HARD but no mature adult heartworms; and two groups were treated with selamectin beginning 1 month post infection, preventing development of L5 or adult heartworms. A group of specific pathogen free (SPF) normal cats was utilized as a negative control (n = 12). Lung pathologic lesions were objectively assessed, and both RV and left ventricular (LV) weights were obtained to calculate an RV/LV ratio. Intramural RV myocardial collagen content was quantitatively assessed. Results RV/LV weight ratios were not different between groups. Negative control cats had significantly greater RV collagen content than all other affected groups (P = 0.032). Analysis of the RV/LV ratios and collagen content revealed no significant relationship (r = 0.03, P = 0.723, respectively). Collagen content had a modest, but significant, negative correlation, however, with both pulmonary vascular pathology (r = −0.25, P = 0.032) as well as the total pulmonary parenchymal and vascular pathology (r = −0.26, P = 0.025). Conclusions Cats infected with mature and immature D. immitis did not develop RV hypertrophy but did demonstrate loss of RV myocardial collagen content. The collagen loss was present at 8 and 18 months after infection in all infected cats. This loss of RV myocardial collagen was correlated with the severity of pulmonary parenchymal and vascular pathology

Experimental inoculation of house flies Musca domestica with Corynebacterium pseudotuberculosis biovar equi

Corynebacterium pseudotuberculosis (Actinomycetales Corynebacteriaceae) infection in horses causes three different disease syndromes: external abscesses, infection of internal organs and ulcerative lymphangitis. The exact mechanism of infection in horses remains undetermined, but transmission by insect vectors is suspected. The present study first determined the optimal culture media for inoculation of house flies (Musca domestica L.) (Diptera Muscidae), with C. pseudotuberculosis biovar equi and the time required for fly inoculation. A second experiment determined the duration of bacterial survival on flies. Exposure of house flies to 3 different preparations of blood agar supplemented with dextrose and colonized with C. pseudotuberculosis determined that a 10 minute exposure to the bacteria was enough to inoculate the flies. C. pseudotuberculosis could be recovered for up to 24 hours after house flies were exposed for 30 minutes to a blood agar plate colonized with the bacteria and moistened with 10% dextrose. These findings support the hypothesis that the house fly is a potential vector of pigeon fever and aid in establishing a protocol for a future experimental model to demonstrate the role of house flies as mechanical vectors in C. Pseudotuberculosis infection