Report of the 3rd Havemeyer workshop on allergic diseases of the Horse, Hólar, Iceland, June 2007

Allergic diseases occur in most mammals, although some species such as humans, dogs and horses seem to be more prone to develop allergies than others. In horses, insect bite hypersensitivity (IBH), an allergic dermatitis caused by bites of midges, and recurrent airway obstruction (RAO), a hyperreactivity to stable born dust and allergens, are the two most prevalent allergic diseases. Allergic diseases involve the interaction of three major factors: (i) genetic constitution, (ii) exposure to allergens, and (iii) a dysregulation of the immune response determined by (i) and (ii). However, other environmental factors such as infectious diseases, contact with endotoxin and degree of infestation with endoparasites have been shown to influence the prevalence of allergic diseases in humans. How these factors may impact upon allergic disease in the horse is unknown at this time. The 3rd workshop on Allergic Diseases of the Horse, with major sponsorship from the Havemeyer Foundation, was held in Hólar, Iceland, in June 2007 and focussed on immunological and genetic aspects of IBH and RAO. This particular venue was chosen because of the prevalence of IBH in exported Icelandic horses. The incidence of IBH is significantly different between Icelandic horses born in Europe or North America and those born in Iceland and exported as adults. Although the genetic factors and allergens are the same, exported adult horses show a greater incidence of IBH. This suggests that environmental or epigenetic factors may contribute to this response. This report summarizes the present state of knowledge and summarizes important issues discussed at the workshop.     

Pharmacokinetics of morphine and its metabolites in freshwater rainbow trout (Oncorhynchus mykiss)

In this study, we injected morphine sulfate IP into rainbow trout and measured the concentration of morphine and all potential metabolites in plasma using LC-MS/MS at a series of times after the injection. The pharmacokinetics of morphine were similar to those previously reported for seawater-acclimated rainbow trout, i.e. they were about one order of magnitude slower than in similarly sized mammals. The only metabolite of morphine present in the plasma was morphine-3-β- d -glucuronide (M3G); morphine-6-β- d -glucuronide (M6G) was not detected. M3G gradually increased after the morphine injection, peaked about 2 days later, then gradually decreased. In mammals, M3G plasma levels exceed morphine levels extremely rapidly, i.e. in less than an hour, regardless of dose, route of administration, or species. In trout, it took 2 days for M3G levels to exceed morphine levels. This is the first study of the metabolites of morphine in any ectotherm. We conclude that trout can metabolize morphine, but at a rate much slower than in mammals.     

Dopamine Antagonist Affects Luteal Function But Not Cyclicity During the Autumn Transition

The autumn transition is characterized by a number of anomalies affecting the luteal phase of the estrous cycle, such as declining progesterone secretion from the corpus luteum and increased rate of failure of luteolysis. Prolactin also decreases. We theorized that these events may be linked, possibly through dopamine. We administered domperidone, a specific dopamine D2 receptor antagonist from September 12 to anestrus or January 15, either daily (n = 8), or once per day for the first 7 days of each month (n = 7). Controls (n = 7) received no treatment. Mean progesterone and prolactin concentrations were compared with summer cycles. Time to entry into anestrus and incidence of spontaneously prolonged luteal activity was compared between groups during the autumn transition. Prolactin declined from June through October equally in all groups. There was no difference between groups in time to anestrus. Progesterone decline was prevented (daily treatment) or delayed for a prolonged period (weekly group) in autumn. The incidence of spontaneously prolonged corpus luteum activity was reduced to summer levels in both domperidone groups compared with the control. We concluded that autumn prolactin decline was not driven through dopaminergic D2 receptor inhibition of pituitary lactotrophs. Sustained progesterone synthesis through the autumn may be the result of action of the D2 receptor antagonist with dopamine receptors on the corpus luteum. Autumnal luteolytic function appears to have a dopamine-influenced component. There does not appear to be a causative relationship between autumnal progesterone and prolactin secretion.     

Pathology methods for the evaluation of embryonic and perinatal developmental defects and lethality in genetically engineered mice

The normal embryonic development of organs and other tissues in mice and all species is preprogrammed by genes. Inactivation of a gene involved in any stage of normal embryonic development can have severe consequences leading to embryonic or postnatal developmental defects and lethality. Pathology methods are reviewed for evaluating normal and abnormal placenta and embryo, especially after E12.5. These methods include pathology protocols for necropsy and histopathology in addition to references that will provide additional knowledge for embryo assessment including histology atlases and advanced embryo imaging techniques.     

Shedding and serological patterns of dairy cows following abortions associated with Coxiella burnetii DNA detection

To describe both shedding and serological patterns following abortions detected as being associated with Coxiella burnetii (Cb), 24 cows experiencing an abortion due to Cb were followed over a one month period. Samples taken on the day of abortion (D0) were followed 3-fold by weekly samplings from day 14 (D14) to D28 after the abortion. Milk and vaginal mucus were collected at each weekly sampling and tested using real-time PCR while blood samples were collected 2-fold on D21 and D28 and tested using ELISA. We found a very short duration of C. burnetii shedding in vaginal mucus after abortion, highlighting the need to collect samples as rapidly as possible following an abortion to avoid false negative results. In contrast with previous results, concomitancy of vaginal and mucus shedding was frequent, especially for cows shedding a high bacterial load on DO leading to the hypothesis that the clinical onset of the infection influences the modalities of Cb shedding. Lastly, serological results indicating a lack of sensitivity to detect Cb shedder cows (especially for cows for which Ct values were high) suggest that ELISA is not a useful tool to diagnose abortions at the individual level.     

Prognostic studies of canine and feline mammary tumours: the need for standardized procedures

For several years, veterinary oncologists have been struggling with the prognosis of mammary tumours in dogs and cats. Translation of tumour characteristics into prognostic information is an invaluable tool for the use of the most appropriate therapies, as well as for planning innovative therapeutic trials. Moreover, canine and feline spontaneous mammary gland tumours are good models for the study of human breast cancer. Collecting and interpreting information regarding the prognosis of canine and feline mammary tumours is difficult due to the fact that different methods have been applied to study various components and characteristics. This review identifies some of the challenges of prognostic studies of spontaneous canine and feline mammary tumours and suggests standardized procedures to overcome these challenges and facilitate reproducibility and assessment of results.     

Phenotypic and genetic evaluation of elbow dysplasia in Dutch Labrador Retrievers, Golden Retrievers, and Bernese Mountain dogs

Canine elbow dysplasia encompasses four developmental diseases: ununited anconeal process, osteochondrosis of the medial part of the humeral condyle, fragmented medial coronoid process (FCP), and incongruity of the elbow joint. Four radiographic views per joint were used to evaluate 2693 Labrador Retrievers (LRs), 1213 Golden Retrievers (GRs), and 974 Bernese Mountain Dogs (BMDs) for the presence of elbow dysplasia between 2002 and 2009 in the Netherlands. The views were also graded for signs of osteoarthritis and sclerosis. FCP was diagnosed most frequently in LRs, GRs and BMDs, with an incidence of 6%, 5%, and 15%, and a heritability of 0.17, 0.24, and 0.06, respectively. Heritabilities were estimated using a sire model and all available ancestors. Sclerosis at the base of the medial coronoid process was the radiographic sign most strongly correlated with FCP (r=0.95, 0.92, and 0.95 in LRs, GRs and BMDs, respectively). The sex of the dog was significantly correlated with the presence of osteoarthritis in LRs, but not in GRs and BMDs. Male LRs were 1.7-fold more frequently, but not more severely, affected by osteoarthritis than female dogs. Age at radiographic examination was significantly associated with osteoarthritis in all three breeds. The heritability estimates in Retrievers were high enough to warrant including FCP findings in the breeding policy, but until the biomechanical and genetic background of elbow dysplasia are better understood, correct phenotyping with a sensitive technique is essential.     

Pyrethroid tolerance in the chewing louse Bovicola (Werneckiella) ocellatus

Equine pediculosis is a significant health and welfare issue, particularly in elderly and chronically debilitated animals. Currently infestation is controlled predominantly using topically applied pyrethroid insecticides, allowing limited scope for the rotation of drugs and increasing the risk of selection for resistance. Here the insecticidal efficacies of two pyrethroid-based products against the louse Bovicola (Werneckiella) ocellatus collected from donkeys were examined in vitro. The products were cypermethrin (Deosect?, Pfizer Ltd., 5% (w/v) cypermethrin, cutaneous spray) and permethrin (Switch?, VetPlus Ltd., 4% (w/v) permethrin, pour-on). The pyrethroid efficacy was contrasted with that of the organophosphate diazinon, since the louse populations examined were unlikely to have had prior exposure to this compound. The efficacy of diluted pure permethrin, the excipient, butyl dioxitol and the synergist piperonyl butoxide in the presence of the pyrethroids, were also considered. At the concentrations recommended for animal application, neither 4% (w/v) permethrin, nor 0.1% (w/v) cypermethrin had any significant effect on the mortality of B. ocellatus and neither induced significantly more mortality than an acetone-only control. In contrast, 0.04% diazinon caused 70% mortality within 4h and 100% mortality after 24h exposure. The addition of a potential pyrethroid synergist, piperonyl butoxide, in combination with cypermethrin and permethrin, resulted in no significant increase in mortality. It is concluded that the population of lice tested display a high level of pyrethroid tolerance which is likely to reflect the development of resistance. Twenty-four hours after routine treatment of 10 donkeys with a pour-on permethrin product (Switch?, VetPlus Ltd., 4% (w/v) permethrin, pour-on) hair tufts taken from their flanks were not significantly insecticidal compared with hair from the midline application site, implying a low level of insecticide distribution. Such a distribution pattern is likely to create an insecticide concentration gradient over the body and further facilitate selection for resistance.