Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves

OBJECTIVE: To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. ANIMALS: 25 calves. PROCEDURES: A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. RESULTS: At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.     

Differential alterations in ultrastructural morphology of chicken heterophils and lymphocytes induced by corticosterone and lipopolysaccharide

Birds are continuously confronted by a large number of stressors, including pathogens. Despite their variety, all stressors induce an elevation in plasma corticosterone concentration, and consequently increase heterophil to leukocyte (H/L) ratio. In order to evaluate and differentiate effects of endocrine (non-bacterial) and bacterial stress on the proportions and ultrastructural characteristics of chicken leukocytes, a series of experiments were conducted with seven-week old chickens exposed either to dietary corticosterone or to intravenous (i.v.)-injected lipopolysaccharide (LPS). Samples were taken for haematological, endocrine, and electron microscopy examination. Administration of corticosterone and LPS significantly elevated plasma corticosterone concentrations and increased H/L ratios. Electron microscopy observations indicated changes in heterophil size, shape, and granulation, and lymphocyte cytoplasmic characteristics. Immature heterophils were observed in the peripheral blood, suggesting that corticosterone and LPS both stimulate an earlier release of heterophils from bone marrow and enhance their influx into blood circulation. The LPS induced a degenerative morphology and the destruction of lymphocytes, whereas corticosterone appeared to stimulate their redistribution rather than destruction. The results indicate that exposure to corticosterone or LPS similarly increase H/L ratios, but differentially alter the ultrastructure of heterophils and lymphocytes. Elucidation of the mechanisms that cause such changes may play an important role in distinguishing between a nonimmune and immune stress challenge at the molecular level.     

Mycophenolic acid in patients with immune‐mediated inflammatory diseases: From humans to dogs

Mycophenolic acid (MPA), a noncompetitive, selective and reversible inhibitor of inosine 5′‐monophosphate dehydrogenase (IMPDH), is an immunosuppressive agent that has a long history in medicine. Mechanistically, the inhibition of IMPDH leads to the selective and eventual arrest of T‐ and B‐lymphocyte proliferation. Mycophenolate mofetil (MMF), the first MPA‐based product to receive marketing approval over two decades ago, was originally indicated for the prophylaxis of organ rejection in human transplant patients. Given its broad immunosuppressive properties and ability to selectively inhibit lymphocyte division and effector functions, the clinical utility of MPA was subsequently explored in a host of autoimmune diseases. Human clinical studies have shown MPA to be safe and effective and support its off‐label administration for immune‐mediated diseases such as lupus, myasthenia gravis and atopic dermatitis. MMF became generically available in the United States in 2008, and its clinical utility is increasingly being explored as a treatment option for dogs with immune‐mediated diseases. This review summarizes the available literature for MPA pharmacokinetics and pharmacodynamics, and the current status of MPA as a treatment for client‐owned dogs diagnosed with immune‐mediated diseases.     

Calf-level risk factors for neonatal diarrhea and shedding of Cryptosporidium parvum in Ontario dairy calves

This work was conducted to investigate calf-level factors that influence the risk of neonatal diarrhea and shedding of Cryptosporidium parvum oocysts in calves, on dairy farms in Ontario with histories of calf diarrhea or cryptosporidiosis. Fecal samples were collected weekly for 4 weeks from each of 1045 calves under 30 days of age on 11 dairy farms in south-western Ontario during the summer of 2003 and the winter of 2004. A questionnaire designed to gather information on calf-level management factors was administered on farm for each calf in the study. Samples were examined for C. parvum oocysts by microscopy, and a subset of specimens was also tested for enterotoxigenic Escherichia coli, Salmonella, bovine rotavirus and bovine coronavirus. The consistency of each sample was scored and recorded at the time of collection in order to assess the presence or absence of diarrhea. In addition, a blood sample was taken from each calf upon enrollment in the study, for assessment of maternal antibody transfer and for polymerase chain reaction testing for persistent bovine viral diarrhea virus infection. Using the GLLAMM function in Stata 9.0, multilevel regression techniques were employed to investigate associations between management practices and the risk of C. parvum shedding or diarrhea. C. parvum oocysts were detected in the feces of 78% of the 919 calves from which all four fecal samples had been collected. Furthermore, 73% of the 846 calves for which all four fecal consistency scores had been recorded were diarrheic at the time of collection of at least one sample. Significant predictors of the calf-level risk of C. parvum shedding included the use of calf diarrhea prophylaxis in pregnant cows, and the type of maternity facilities in which the calves were born. Factors associated with an increased risk of diarrhea were leaving the calf with the dam for more than an hour after birth, and the birth of a calf in the summer as opposed to winter. Calves shedding C. parvum oocysts had 5.3 (95% CI 4.4, 6.4) times the odds of diarrhea than non-shedding calves, controlling for other factors included in the final multivariable model. Furthermore, infected calves shedding more than 2.2 x 10(5) oocysts per gram of feces were more likely to scour than infected calves shedding lower numbers of oocysts (OR= 6.1, 95% CI 4.8, 7.8). The odds of diarrhea in calves shedding oocysts that had been allowed to remain with their dams for more than an hour were higher than the odds of diarrhea in shedding calves that had been separated from their dams within an hour after birth.     

Pathogenicity studies with the fungi Aphanomyces invadans, Achlya bisexualis, and Phialemonium dimorphosporum: induction of skin ulcers in striped mullet

Based on isolations from naturally infected fish in Florida, we investigated the role of the fungi Aphanomyces invadans, Achlya bisexualis, and Phialemonium dimorphosporum in the etiology of ulcerative mycosis (UM) in striped mullet Mugil cephalus. We injected healthy striped mullet subcutaneously with secondary zoospores of four oomycete isolates: two concentrations (50 and 115 zoospores/mL) of SJR (an endemic isolate of Aphanomyces invadans in American shad Alosa sapidissima from the St. Johns River); two concentrations each of CAL (25 and 65 zoospores/mL) and ACH (1,400 and 2,000 zoospores/mL; endemic isolates of Aphanomyces invadans and Achlyva bisexualis, respectively, in striped mullet from the Caloosahatchee River); and two concentrations of the ascomycete culture MTZ (2,500 and 3,500 zoospores/mL; endemic isolate of P. dimorphosporum from whirligig mullet M. gyrans in the Matanzas Inlet). All fish injected with either concentration of SJR developed granulomatous ulcers after 8 d and died within 21 d. Eighty percent (8/10) of fish injected with the high dose of CAL developed ulcers after 13 d and died within 28 d, but only 30% (3/10) of fish injected with the low dose of CAL developed ulcers. Four of the ulcerated fish died within 28 d, and the remaining fish were terminated after 32 d. Fish injected with zoospores of Aphanomyces invadans developed ulcers that were grossly and histologically similar to those observed in naturally infected striped mullet with UM from several estuaries or rivers in Florida. These hemorrhagic skin ulcers were characterized by myonecrosis and the presence of mycotic granulomas. None of the fish injected with ACH, MTZ, or sterile water developed ulcers. This study fulfilled Koch's postulates and demonstrated that ulcers could be experimentally induced in striped mullet after exposure via injection to secondary zoospores of an endemic Florida strain of Aphanomyces invadans.