Pharmacokinetics of masitinib in cats

Masitinib is the first veterinary drug recently approved in Europe to treat mast cell tumours in dogs (Hahn et al. JVIM, Masivet). This inhibitor is selective and highly efficient in blocking c-Kit, PDGFR, and Lyn tyrosine kinase activities. It showed good efficacy and acceptable toxicity in several animal studies such as mice, rats, rabbits and dogs (Dubreuil P, et al. submitted, and Hahn et al. (J Vet Intern Med 22(6):8, 2008)). C-kit is a tyrosine kinase receptor that plays a critical role in the biology of mast cells including differentiation, survival, migration and cytokine/mediator release. Mast cells are involved in a number of allergy-and immune-related diseases in cats such as asthma (Reinero Carol et al. Vet Immunol Immunopathol 121(3–4):9, 2008), inflammatory bowel disease, (Janeczko et al. Vet Mic 128(1–2):15, 2008), and feline mast cell tumours (Rassnick et al. J Am Vet Med Assoc 232(8):1200–1205, 2008). Therefore, there might be a strong rationale to use masitinib in these indications. Here, we report the results of a preliminary pharmacokinetic study of masitinib in cats which showed a good bioavailability of ~60% in both sexes. We propose that an oral dose of 10–15 mg/kg masitinib is appropriate to achieve adequate plasma concentrations.     

Comparison of viraemia- and clinical-based estimates of within- and between-pen transmission of classical swine fever virus from three transmission experiments

Analyses of recent classical swine fever (CSF) epidemics in the European Union have shown that silent circulation of CSF virus (CSFV) occurs before the first outbreak is detected and this may lead to a large epidemic. However, severity of CSF disease signs may be linked with efficacy of disease transmission, the most severely affected animals having a higher infectivity than the less affected ones. The purpose of this study was to combine disease transmission quantification methods with CSF clinical signs quantification tools to investigate whether clinical signs, considered as infectivity markers, may allow us to calculate reliable estimates for disease transmission parameters. Data from three transmission experiments were used, varying according to the viral strain (Eystrup or Paderborn) and to the contact structure between experimentally inoculated and contact animals (direct or indirect contact). Within- and between-pen basic reproduction ratios (R0) were compared using viraemia data or clinical data. Between-pen R0 estimates were close and not significantly >1, with either strain or computation mode (using viraemia or clinical data). Conversely, within-pen R0s (Paderborn strain) computed using clinical data appeared higher than the estimates obtained using viraemia data. A models comparison (Bayes information criterion) showed a better fit of the clinical-based models, for both strains. This suggests that, in affected herds, the most severely affected animals could play a prominent role in CSFV transmission.     

Babesia and its hosts: adaptation to long-lasting interactions as a way to achieve efficient transmission

Babesia, the causal agent of babesiosis, are tick-borne apicomplexan protozoa. True babesiae (Babesia genus sensu stricto) are biologically characterized by direct development in erythrocytes and by transovarial transmission in the tick. A large number of true Babesia species have been described in various vertebrate and tick hosts. This review presents the genus then discusses specific adaptations of Babesia spp. to their hosts to achieve efficient transmission. The main adaptations lead to long-lasting interactions which result in the induction of two reservoirs: in the vertebrate host during low long-term parasitemia and throughout the life cycle of the tick host as a result of transovarial and transstadial transmission. The molecular bases of these adaptations in vertebrate hosts are partially known but few of the tick-host interaction mechanisms have been elucidated.     

Heavy Metal Lability in Porewater of Highway Detention Pond Sediments in South-Eastern France in Relation to Submerged Vegetation

Highway detention ponds can fill with sediments from runoff water loaded with traffic-related materials. Sediment disposal is problematic and various protocols are currently studied, including phytoremediation. Here we present a preliminary study on four highway detention ponds in southern France to identify key sediment characteristics. Our objectives were to characterize metal content and physicochemical properties of the sediments and to evaluate the role of charophytes, which grow spontaneously in ponds, on metal lability. Vegetated and non-vegetated areas were compared. The lability of Mn, Cu, Zn, and Pb complexes was greater in the presence of charophytes. No variation in grain size composition was observed between non-vegetated and vegetated areas. These results may be useful to implement a phytoremediation strategy using those spontaneous charophytes. Our results suggest that local factors may impact sediment characteristics: for instance, strong gusts of wind, typical of southern France climate, may blow particles (some of them not related to traffic) in and out of detention ponds.     

Comparative effects of fumonisins on sphingolipid metabolism and toxicity in ducks and turkeys

Fumonisins (FBs) are mycotoxins that are found worldwide in maize and maize products. Their main toxic effects have been well characterized in poultry, but differences between species have been demonstrated. Ducks appeared very sensitive to toxicity, whereas turkeys are more resistant. At the same time, alterations of sphingolipid metabolism, with an increase of the concentration of the free sphinganine (Sa) in serum and liver, have been demonstrated in the two species, but the link between the toxicity of FBs and Sa accumulation remains difficult to interpret. The aim of the present work was to compare the effects of FBs (10 mg FB1 + FB2/kg body weight) on sphingolipid metabolism in ducks and turkeys. Growth, feed consumption, and serum biochemistry were also investigated to evaluate toxicity. The main results showed that FBs increased Sa concentrations in liver and serum in ducks and turkeys, but these accumulations were not directly correlated with toxicity. Sa accumulation was higher in the livers of turkeys than in ducks, whereas Sa levels were higher in the sera of ducks than in turkeys. Hepatic toxicity was more pronounced in ducks than in turkeys and accompanied a decrease of body weight and an increase of serum biochemistry in ducks but not in turkeys. So, although FBs increase Sa concentration in the livers of both species, this effect is not directly proportional to toxicity. The mechanisms of FB toxicity and/or the mechanisms of protection of ducks and turkeys to the Sa accumulation within the liver remain to be established.     

Synthesis of pyrethroic acids from natural products and from isomeric compounds: Strategy and practice

Pyrethroic acids are essential constituents of the pyrethroids, which are now some of the most powerful commercially available insecticides. A number of syntheses of pyrethroic acids have been published since the elucidation of the structure of chrysanthemic acid, one of the naturally occurring acids present as esters in Chrysanthemum cinerarefolium Vis. This paper reports some results of the stereoselective synthesis of the most biologically active enantiomers of pyrethroic acids obtained over the last five years in our laboratory. Two different approaches, which have been patented by two leading European companies in the agrochemical field, have been carried out simultaneously. The first uses the cheap chiral natural products mannitol and tartaric acid as starting materials and allows the rapid construction of the cyclopropane framework. The second takes advantage of the isomeric relationship between dimethyl dimedone, a readily available, non-chiral compound and chrysanthemic acid. Enantioselective isomerisation of dimethyl dimedone to (1R)-cis- and (1R)-trans-chrysanthemic acid has been achieved successfully using a lipase. These two approaches to the synthesis of chrysanthemic acid are compared with related approaches in the literature, which use other natural products or isomers of chrysanthemic acid as starting materials.     

Genetic immunisation of cattle against bovine herpesvirus 1: glycoprotein gD confers higher protection than glycoprotein gC or tegument protein VP8

Bovine herpesvirus 1 (BoHV-1) has frequently been used as a model for testing parameters affecting DNA immunisation in large animals like cattle. However, the selection of target antigens has been poorly studied, and most of the experiments have been conducted in mice. In the present study, we demonstrated in cattle that a DNA vaccine encoding BoHV-1 glycoprotein gD induces higher neutralising antibody titres than vaccines encoding BoHV-1 gC. Additionally, we show that a DNA vaccine encoding a secreted form of gD induces a higher immune response than a vaccine encoding full-length gD. However, the enhanced immunogenicity associated with the secretion of gD could not be extended to the glycoprotein gC. The current study also describes for the first time the development and the evaluation of a DNA vaccine encoding the major tegument protein VP8. This construct, which is the first BoHV-1 plasmid vaccine candidate that is not directed against a surface glycoprotein, induced a high BoHV-1 specific cellular immunity but no humoral immune response. The calves vaccinated with the constructs encoding full-length and truncated gD showed a non-significant tenfold reduction of virus excretion after challenge. Those calves also excreted virus for significantly (p < 0.05) shorter periods (1.5 days) than the non-vaccinated controls. The other constructs encoding gC and VP8 antigens induced no virological protection as compared to controls. Altogether the DNA vaccines induced weaker immunity and protection than conventional marker vaccines tested previously, confirming the difficulty to develop efficient DNA vaccines in large species.     

Effectiveness of steam pasteurization in controlling microbiological hazards of cull cow carcasses in a commercial plant

The purpose of the study, carried out in a beef processing plant, was to evaluate the effectiveness of a new prototype for steam pasteurization treatment in controlling microbiological hazards. Samples were taken by swabbing randomly selected sites before and after pasteurization and again after chilling to obtain total aerobic counts (TAC), total coliform counts (TCC), and generic Escherichia coli counts (ECC) on Petrifilm plates and to determine the prevalence of Salmonella spp., Listeria monocytogenes, and E. coli O157:H7 using standard enrichment techniques. Escherichia coli and L. monocytogenes strains were tested for various factors associated with their virulence by using colony hybridization and polymerase chain reaction (PCR), respectively. Antimicrobial susceptibility was determined for each isolate that was potentially pathogenic to humans by using the disk-diffusion method. Mean values for TAC, TCC, and ECC were 2.18, 0.16, and 0.06 log10 CFU/cm2, respectively, before pasteurization; 1.17, 0.03, and 0.01 log10 CFU/cm2 after pasteurization; and 0.89, 0.02, and 0.01 log10 CFU/cm2 after chilling. Prevalence of L. monocytogenes, Salmonella spp., and E. coli O157:H7 on carcasses was 0.8%, 0.0%, and 0.0%, respectively, before pasteurization; 2.6%, 0.0%, and 0.0% after pasteurization; and 3.1%, 0.1%, and 0.0% after chilling. The prevalence of E. coli containing > or = 1 virulence gene was 14.7%. More specifically, 11.88% of the isolates obtained before pasteurization, 22.2% obtained after pasteurization, and 31.2% obtained after chilling had virulence genes. All L. monocytogenes isolates tested positive for the presence of 3 major virulence factors (hlyA, inlB, and plcB). Antibiograms showed that certain isolates were susceptible to all antibiotics, some showed an intermediate sensitivity, and others were multiresistant. Overall, these results suggest that steam pasteurization is an effective means of improving safety quality of beef carcasses. However, pasteurization may indirectly contribute to the growth of some pathogenic microorganisms, such as L. monocytogenes.     

Sheep as a new experimental host for Babesia divergens

Babesia divergens was cultivated in sheep erythrocytes in RPMI 1640 supplemented with 10% Fetal Calf Serum (FCS) or sheep serum. In vitro cultures in sheep red blood cells were initiated with human erythrocytes infected in vitro with B. divergens Rouen 1987 or with gerbil blood infected with several isolates from bovine origin. After the first subcultures on sheep erythrocytes, a ten-fold multiplication of the parasites was obtained within 48 h. Erythrocytes from three splenectomized sheep were infected in vitro with B. divergens; when parasitaemia reached 10%, the animals were inoculated with homologous parasitized erythrocytes. All sheep expressed hyperthermia with a peak between the 6th and the 9th day post-infection (p-i) and a transitory parasitaemia 10 days p-i. In vitro primary cultures were performed on two of these sheep, demonstrating the parasite persistence at very low parasitaemia in the infected animals. Splenectomized sheep can be used as a new model for B. divergens chronic infection.