A prospective study of clopidogrel therapy in dogs with primary immune-mediated hemolytic anemia

Background: A major cause of death in dogs with primary immune‐mediated hemolytic anemia (pIMHA) is thrombotic disease. Ultralow‐dose aspirin (ULDA) is commonly used to prevent thrombosis in dogs with pIMHA; however, the efficacy of antiplatelet agents in dogs with pIMHA is unknown. Hypothesis: The use of clopidogrel (CL), alone or in combination with ULDA, would improve survival to discharge and at 90 days without important adverse effects compared with ULDA alone in dogs with pIMHA treated with standard immunosuppressive therapy. Animals: Twenty‐four client‐owned dogs with pIMHA. Methods: Prospective, positive‐controlled, unmasked clinical trial with dogs randomized in 3 treatment groups to receive PO ULDA or CL or both. Results: There was no identifiable adverse reaction, evidence of hemorrhage, or increase in transfusion requirements associated with CL therapy, either alone or combined with ULDA, compared with ULDA alone. There was no significant difference between treatment groups with respect to survival to discharge and at 90 days. Conclusions and Clinical Importance: This study suggests that CL therapy, alone or in combination with ULDA, was safe and had similar short‐term survival compared with ULDA alone in a small group of dogs with pIMHA able to tolerate oral medications and treated with standard immunosuppressive treatment.     

Virulence factors analysis of native isolates of Xanthomonas albilineans and Xanthomonas sacchari from Tucumán,Argentina, reveals differences in pathogenic strategies

Xanthomonas albilineans (Xa) and X. sacchari (Xs) are both sugarcane pathogens. Xa is the causal agent of leaf scald disease, but there is limited information about the pathogenicity of Xs. The aim of this work was to study virulence factors of native strains of Xa (Xa32, Xa33, and XaM6) and Xs (Xs14 and Xs15) previously isolated from sugarcane with leaf scald symptoms, to gain insight into the biology of each microorganism. We analysed epiphytic survival, sensitivity to oxidative stress, extracellular degradative enzymes, cell motilities, exopolysaccharide (EPS) characteristics, cell adhesion, biofilm development, and control of stomatal regulation of the five strains. We observed that each species presented similar phenotypes for every factor analysed. Xa strains appeared to be more sensitive to oxidative stress and presented lower epiphytic survival than Xs. All strains presented endoglucanase activity; however, we could only detect protease and amylase activities in Xs strains. Swimming and sliding were higher in Xs, but twitching was variable among species. We also observed that only Xs strains produced a xanthan-like EPS, presented a strong cell adhesion, and structured biofilm. We detected some intraspecific variations showing that higher amounts of EPS produced by Xs14 correlated with its higher sliding motility and its homogenous and more adhesive biofilm. In addition, EPSs of Xs14 and Xs15 presented differences in strand height and acetyl percentage. Finally, we found that strains of both species were able to interfere with stomatal aperture mechanism. All these differences could influence the colonization strategies and/or disease progression in each species.     

Pool of resistance mechanisms to glyphosate in Digitaria insularis

Digitaria insularis biotypes resistant to glyphosate have been detected in Brazil. Studies were carried out in controlled conditions to determine the role of absorption, translocation, metabolism, and gene mutation as mechanisms of glyphosate resistance in D. insularis. The susceptible biotype absorbed at least 12% more (14)C-glyphosate up to 48 h after treatment (HAT) than resistant biotypes. High differential (14)C-glyphosate translocation was observed at 12 HAT, so that >70% of the absorbed herbicide remained in the treated leaf in resistant biotypes, whereas 42% remained in the susceptible biotype at 96 HAT. Glyphosate was degraded to aminomethylphosphonic acid (AMPA), glyoxylate, and sarcosine by >90% in resistant biotypes, whereas a small amount of herbicide (up to 11%) was degraded by the susceptible biotype up to 168 HAT. Two amino acid changes were found at positions 182 and 310 in EPSPS, consisting of a proline to threonine and a tyrosine to cysteine substitution, respectively, in resistant biotypes. Therefore, absorption, translocation, metabolism, and gene mutation play an important role in the D. insularis glyphosate resistance.     

Pharmacokinetics of ketorolac tromethamine in horses after intravenous,intramuscular, and oral single‐dose administration

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine‐sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5‐mg/kg dose of KT via each route of administration. Plasma was collected up to 48 h postadministration and analyzed for KT concentration using HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at steady‐state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o. dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The drug was rapidly absorbed after i.m. and p.o. administration, and mean bioavailability was 71% and 57% for i.m. and p.o. administration, respectively. Adverse effects were not observed after i.v., i.m., and p.o. administration. More studies are needed to evaluate the analgesic and anti‐inflammatory properties of KT in horses.     

Mutations of phosphatase and tensin homolog deleted from chromosome 10 in canine hemangiosarcoma

We examined the presence of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) abnormalities that could contribute to the origin or progression of naturally occurring canine endothelial tumors (hemangiosarcoma). Our results document somatic point mutations or deletions encompassing the PTEN C-terminal domain in canine hemangiosarcoma that might provide cells a survival advantage within their microenvironment. This represents the first characterization of a naturally occurring, highly metastatic tumor with biologically significant mutations of PTEN in the C-terminal domain.     

Abscisic acid in needles of Pinus cembra in relation to ozone exposure

Ozone pollution was analyzed in arolla pine (Pinus cembra L.) forests growing over two mountain ranges located in southern France by using specific ozone-sensitive tobacco plants as bio-indicators and a physico-chemical analyzer. Concentrations of abscisic acid (ABA) were determined in needles of healthy and declining trees in a massif with a declining forest and in a massif with a healthier forest. In addition, ABA was quantified in needles of trees exposed to either charcoal-filtered air or unfiltered air supplemented with ozone in open-top chambers located at the Col du Donon. The concentration of ABA in needles of injured trees increased when the trees were exposed to ozone either under field conditions or in open-top chambers; however, the difference in ABA concentration between control and ozone-exposed needles was less in the open-top chambers, where ozone was the sole variable, than in the field. The results are discussed in the context of the effects of ozone on plant water relations and hormone-mediated cell defense.