Clinical application of computed tomography for the diagnosis of feline hepatic lipidosis

The usefulness of computed tomography (CT) for the diagnosis of feline hepatic lipidosis (FHL) was evaluated. Liver CT number was 54.7+/-5.6 HU (mean+/-SD) in 26 healthy cats. We fast 6 healthy cats for 72 hr to induced FHL experimentally and the cats were assessed by CT and serum biochemical analysis. Liver CT number of the six cats was 53.8+/-3.0 HU before fasting, 46.8+/-2.4 HU after fasting, and 50.2+/-3.6 HU two weeks after restarted feeding. The decreased CT number was associated with the elevation of serum non-esterified fatty acid (NEFA) and beta-hydroxybutyrate levels. These results indicate that measurement of CT number of the liver is an effective procedure for the diagnosis of FHL.     

Thirteen-week Intravenous Toxicity Study of a Novel Humanized Anti-Human Death Receptor 5 Monoclonal Antibody, CS-1008, in Cynomolgus Monkeys

CS-1008, a humanized monoclonal antibody that is agonistic to human death receptor 5, was intravenously administered to cynomolgus monkeys twice a week for 13 weeks at 3 different dose levels (5, 15 and 42 mg/kg) in order to evaluate its potential toxicity. A control group received phosphate buffered saline containing 0.01% polysorbate 80. Each of the 4 groups consisted of 3 male and 3 female cynomolgus monkeys. No animal in any group died during the dosing period. No toxic changes in clinical signs, food consumption, body weight, electrocardiography, ophthalmology, urinalysis, hematology, blood chemistry, gross pathology, organ weights or histopathology were noted in any group during the dosing period. In the toxicokinetic analysis, the values for the maximum concentration of CS-1008 in plasma and the area under the curve generally increased with increasing dose. No clear differences in the toxicokinetic parameters or profiles were observed between the sexes. Development of anti-CS-1008 antibodies was not detected in any sample. The no-observed adverse-effect level (NOAEL) of CS-1008 in cynomolgus monkeys under the conditions of this study was concluded to be 42 mg/kg in both sexes, when administered intravenously twice a week for 13 weeks. This study supports the development of CS-1008 as a therapeutic biopharmaceutical.     

A case of hyperplastic dermatosis of the West Highland White Terrier controlled by recombinant canine interferon-gamma therapy

A 3.5-year-old, male West Highland White Terrier was diagnosed as having hyperplastic dermatosis by clinical and histopathological findings. Controlling of Malassezia overgrowth by antifungal drugs provided a temporal improvement of the skin lesions, but the disease was deteriorated within the next 2 months despite the negative demonstration of the yeasts. Induction of recombinant canine interferon-gamma (rCaIFN-gamma) therapy resulted in almost complete cure of the skin lesions within 2 months after the initiation of the therapy. No adverse effects were detected during the therapy. Our results suggested that the rCaIFN-gamma therapy is potential to be a novel therapeutic option for controlling the breed-specific hyperplastic skin disease.     

Cyclosporine A inhibits the mRNA expressions of IL-2, IL-4 and IFN-gamma, but not TNF-alpha, in canine mononuclear cells

The effects of the calcineurin inhibitors cyclosporine A (CsA) and FK506 on the mRNA expressions of various cytokines were evaluated in dogs to determine whether the effects of CsA and FK506 in dogs were similar to those in humans. The mRNA expression levels of the cytokines IL-2, IL-4, IFN-gamma and TNF-alpha were measured in PHA-stimulated canine PBMC using real-time RT-PCR after incubation with CsA or FK506 for 5 hr. Both reagents inhibited IL-2, IL-4 and IFN-gamma mRNA expressions in a dose-dependent manner. However, CsA hardly inhibited the mRNA expression of TNF-alpha. These findings are important for assessing the indications of CsA treatment in dogs.     

FC‐51 Comparison of intradermal test and antigen‐specific IgE test in 22 cases of feline allergic dermatitis

The usefulness of the intradermal test (IDT) and the serological allergy test (SAT) for detecting antigen‐specific IgE in allergic cats has not yet been established. In this study, we compared the results of IDT with those of SAT and evaluated the clinical usefulness of the two tests for detecting possible allergens in allergic cats. IDT and SAT using eight antigens were performed on 22 cats with intense pruritus after excluding ectoparasites and performing diet elimination tests. Approximately 50% of the cats reacted to at least one allergen by either IDT or SAT, and 36.4% of the cats reacted on both IDT and SAT. In contrast, seven healthy cats did not show any reactions on IDT or SAT. The most commonly detected allergen in both tests was house dust mites (IDT, 36.4%; SAT, 40.9%). Five cats reacted to one allergen and the others reacted to more than one allergen with IDT. Three cats reacted to one allergen with SAT. The following percentage agreement between the results of the two tests was calculated: house dust mites (86.4%), cat fleas (63.6%), grass mix (86.4%), common mugwort (81.8%), cat epithelia (90.9%), ragweed (86.4%), Japanese cedar (90.9%), and plantain (81.8%). The overall mean percentage agreement was 83.5%. In summary, the present study showed good agreement between IDT and SAT for cats, and SAT may be more sensitive than IDT, but less specific for detecting sensitized allergens. Funding: Self‐funded.     

Molecular cloning of interleukin-12 receptor beta2 chain and its expression in dogs

This study cloned canine interleukin-12 receptor beta2 (IL-12Rbeta2). Its nucleotide sequences were determined. Canine IL-12Rbeta2 showed 85.4% homology at the nucleotide level and 76.8% homology at the amino acid level with human IL-12Rbeta2. Its structural motifs were well conserved. We also cloned cDNA with a 91-bp deletion including the transmembrane region, which produced a frame shift and an early stop codon. Examination of the expression of deleted canine IL-12Rbeta2 mRNA revealed that both deleted and intact mRNAs were expressed at a constant ratio in all the dogs. Results suggested that expression of the deleted mRNA was constitutive and produced by alternative splicing.     

Regulation of muscular glutamate metabolism by high‐protein diet in broiler chicks

The major taste active component, glutamate (Glu), improves the taste of meat. In this study, we investigated the effect of a short‐term high‐protein (HCP) diet on the intramuscular free Glu content to improve the taste of meat. Furthermore, we elucidated how the muscle free Glu content was controlled by the HCP diet. Chicks (14 days old) were fed the control diet or HCP diet for 10 days. Plasma and muscle free amino acid concentrations, and activity and messenger RNA (mRNA) expression of muscle enzymes related to Glu metabolism were determined. Muscle free Glu content was increased (P < 0.01) by 51%. Activity and mRNA expression of glutaminase (GA), which is one of the major Glu‐related enzymes, were significantly decreased (P < 0.05) in the HCP group because of feedback inhibition. The mRNA expression of lysine α‐ketoglutarate reductase (LKR), which is the enzyme involved in lysine (Lys) degradation and Glu production, was significantly increased (P < 0.001) in the HCP group. These results suggest that short‐term dietary HCP feeding is an effective treatment for improving the taste of meat. Furthermore, our results suggest that the free Glu content in muscle is regulated by GA and LKR.