Voluntary acceptance and consumption of two oral ciclosporin formulations in dogs: two randomised,controlled studies

Background

Atopic dermatitis (AD) is the most common canine allergic skin disease and can significantly affect the quality of life of affected dogs. Treating canine AD with ciclosporin has been a subject of great interest in recent years. Many studies have provided substantial evidence of ciclosporin efficacy and safety in canine AD management, and for several years ciclosporin has been recognised as a major component of canine AD multimodal therapy. As a chronic condition, canine AD requires life-long medical management and treatment success relies in large part on product ease of administration. Two studies were conducted to assess the comparative voluntary acceptance and consumption of Cyclavance® (Virbac), a new oral liquid formulation of ciclosporin, and Atopica® (Novartis) either added to a small quantity of kibbles (study 1) or administered directly into the dog’s mouth (study 2).

Results

Over the course of the two studies 70 dogs assessed each of the ciclosporin formulations and 320 individual tests were performed for each tested product. Immediate prehension (in less than 2 seconds) occurred significantly more often with Cyclavance® (90.6% of the tests) than with Atopica® (14.4% of the tests) when products were mixed with 30 grams of dry food (p < 0.001). Moreover, Cyclavance® was significantly more often easily accepted than Atopica® (99.3% vs 27.1% of the tests, respectively) when products were administered directly into the dogs’ mouth (p < 0.0001). Cyclavance® was also more often totally consumed (98.3% of the tests) than Atopica® (2.2% of the tests) when mixed with a small amount of food (p < 0.001). However, both products were totally consumed once administered directly into the dogs’ mouth.

Conclusions

By facilitating cicloporin administration and consumption, Cyclavance® liquid formulation offers an interesting alternative to capsules that may improve dosing compliance and therefore the ability to benefit from the therapeutic effects in the long-term treatment of canine AD.     

Ostreid herpesvirus 1 detection and relationship with Crassostrea gigas spat mortality in France between 1998 and 2006

ABSTRACT: Since its molecular characterisation, Ostreid herpesvirus 1 (OsHV-1) has been regularly detected in Crassostrea gigas in France. Although its pathogenicity was demonstrated on larval stages, its involvement during mortality outbreaks at the juvenile stage was highly suspected but not evidenced. To investigate mortality outbreaks, the French National Network for Surveillance and Monitoring of Mollusc Health (REPAMO) carried out two surveys in juvenile C. gigas. The first survey lasted from 1998 to 2006 and was an epidemiological inquiry occurring when oyster farmers reported mortality outbreaks. The second survey, a longitudinal one, was set up in 1998 to complete the network observations on OsHV-1. Data analysis showed a specific pattern of mortality outbreaks associated with OsHV-1 detection. Ostreid herpesvirus 1 detection mainly appeared during the summer, suggesting the influence of the seawater temperature on its occurrence. It mostly presented a patchy distribution in the field in contrast to the nursery. Significant relationship between OsHV-1 detection and spat mortality was found, preferentially in sheltered and closed environments. The longitudinal survey confirmed most of the network observations. Although subsequent works particularly epidemiological surveys would be useful to confirm the causal link between the detection of OsHV-1 and the mortality outbreaks in juvenile C. gigas, the role of OsHV-1 in oyster mortality is progressing.     

Anticancer Alkaloid Lamellarins Inhibit Protein Kinases

Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dual-specificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors.     

Identification and Characterization of a New Type III Polyketide Synthase from a Marine Yeast,Naganishia uzbekistanensis

A putative Type III Polyketide synthase (PKSIII) encoding gene was identified from a marine yeast, Naganishia uzbekistanensis strain Mo29 (UBOCC-A-208024) (formerly named as Cryptococcus sp.) isolated from deep-sea hydrothermal vents. This gene is part of a distinct phylogenetic branch compared to all known terrestrial fungal sequences. This new gene encodes a C-terminus extension of 74 amino acids compared to other known PKSIII proteins like Neurospora crassa. Full-length and reduced versions of this PKSIII were successfully cloned and overexpressed in a bacterial host, Escherichia coli BL21 (DE3). Both proteins showed the same activity, suggesting that additional amino acid residues at the C-terminus are probably not required for biochemical functions. We demonstrated by LC-ESI-MS/MS that these two recombinant PKSIII proteins could only produce tri- and tetraketide pyrones and alkylresorcinols using only long fatty acid chain from C8 to C16 acyl-CoAs as starter units, in presence of malonyl-CoA. In addition, we showed that some of these molecules exhibit cytotoxic activities against several cancer cell lines.     

Lactoferrin against Staphylococcus aureus Mastitis. Lactoferrin alone or in combination with penicillin G on bovine polymorphonuclear function and mammary epithelial cells colonisation by Staphylococcus aureus

Antibiotics should combine good antibacterial activity and the capacity to work in association with the host defence system. In this study, we have investigated the effects of bovine lactoferrin alone or in combination with penicillin G on the phagocytic activity of bovine polymorphonuclear leukocytes against Staphylococcus aureus. We have shown that susceptibility of S. aureus to phagocytosis was decreased in the presence of penicillin in the medium. In a kinetic study, lactoferrin alone did not affect phagocytosis but, when used with penicillin, it reversed the negative effect of this antibiotic on phagocytosis. In addition, in an epithelial invasion assay, lactoferrin alone or in combination with penicillin reduced the invasion of mammary epithelial cells in culture by S. aureus. Lactating female CD-1 mice were infected by intra-mammary delivery of a virulent penicillin-susceptible S. aureus strain and were then randomly assigned to treatments according to a 2 x 2 factorial design. In this mouse mastitis model, 2 days of systemic treatments with lactoferrin and/or penicillin did not lead to a total clearance of infection by S. aureus, but bacterial number was significantly reduced by treatments with lactoferrin or penicillin. These data suggest that bovine lactoferrin, alone or in combination with penicillin G, enhances S. aureus susceptibility to immuno-defense mechanisms, which can be beneficial in the treatment of S. aureus infections.