Established haematological, biochemical and acute phase protein reference intervals are necessary for the investigation of the systemic impact of mulesing and mulesing alternatives and for the investigation of systemic diseases affecting weaned, 9- to 16-week-old, female Merino lambs in general.
Cocaine use disorders are mediated by the cocaine blockade of the dopamine transporter in the central nervous system (CNS). On the basis of the concept that these effects could be obviated if cocaine were prevented from reaching its cognate receptors in the CNS, we have developed an anticocaine vaccine, dAd5GNE, based on a cocaine analog covalently linked to capsid proteins of an E1 -E3 -serotype 5 adenovirus. While the vaccine effectively blocks systemically administered cocaine from reaching the brain by mediating sequestration of the cocaine in the blood, the fact that cocaine also has significant peripheral effects raises concerns that vaccinationmediated redistribution could lead to adverse effects in the visceral organs. The distribution of systemically administered cocaine at a weight-adjusted typical human dose was evaluated along with cocaine metabolites in both dAd5GNE-vaccinated and control nonhuman primates. dAd5GNE sequestration of cocaine to the blood not only prevented cocaine access to the CNS, but also limited access of both the drug and its metabolites to other cocaine-sensitive organs. The levels of cocaine in the blood of vaccinated animals rapidly decreased, suggesting that while the antibody limits access of the drug and its active metabolites to the brain and sensitive organs of the periphery, it does not prolong drug levels in the blood compartment. Gross and histopathology of major organs found no vaccine-mediated untoward effects. These results build on our earlier measures of efficacy and demonstrate that the dAd5GNE vaccine-mediated redistribution of administered cocaine is not likely to impact the vaccine safety profile.
A 4-year-old, 6.5-kg, castrated male Boston Terrier was referred to the Cornell University Hospital for Animals for evaluation of seizures. Seizure activity was characterized by unconsciousness, tonic-clonic limb movements, and hypersalivation, with each seizure lasting approximately 1 minute. Three seizures had occurred during the 24 hours preceding presentation. Otherwise, the dog had been clinically healthy. No drugs were administered and toxin exposure was unlikely. Laboratory assessment completed by the referring veterinarian included CBC and serum biochemistry (sodium, potassium, chloride, total protein, albumin, globulin, BUN, creatinine, glucose, calcium, phosphorus, total bilirubin, and cholesterol concentrations; alkaline phosphatase [ALP], alanine aminotransferase [ALT], and amylase activities). Results disclosed eosinopenia (0.09 9 10 3 cells/lL; reference range 0.1-1.49 9 10 3 /lL) and mildly increased ALT activity (124 U/L; reference range, 10-100 U/L).On presentation, the dog was bright and alert with modest upper airway stridor attributable to brachycephalic conformation. Neurologic examination demonstrated decreased menace OD and equivocal cervical pain. h revealed multifocal, asymmetrical ill-defined intra-axial hyperintense areas in the cerebral cortex; these regions were slightly hyperintense to brain on T2-weighted images and fluid attenuated inversion recovery, but lacked contrast enhancement. A linear intra-axial lesion with the same signal intensity as cerebrospinal fluid (CSF) that did not contrast enhance was noted within spinal cord parenchyma at C1 and C2, consistent with mild syringohydromyelia.The CSF collected from the lumbosacral subarachnoid space was colorless and clear with normal nucleated cell count (3/lL; reference range, <5/lL) and total protein concentration (21 mg/dL; reference range, <45 mg/dL); cytologic examination disclosed 63% small lymphocytes and 37% macrophages. Collective findings were interpreted as changes secondary to the recent seizure activity and mild syringohydromyelia. The dog was prescribed the anticonvulsant zonisamide i (7.7 mg/kg PO q12h) for presumed idiopathic epilepsy.After 10 days of zonisamide administration, the dog was presented again for inappetence and vomiting. No seizure activity had occurred since instituting zonisamide. Results of CBC and serum biochemistry disclosed lymphopenia (0.5 9 10 3 /lL; reference range, 0.9-4.7 9 10 3 /lL), eosinopenia (0.0 9 10 3 /lL), mild thrombocytopenia (176 9 10 3 /lL; reference range, 186-545 9 10 3 /lL) with platelet clumps, few acanthocytes and keratocytes, marked increases in activities of ALT (16328 U/L) and aspartate aminotransferase (AST; 5908 U/L; reference range, 16-50 U/L), modest increases in activities of ALP (354 U/L; reference range, 12-122 U/L) and gamma-glutamyl transferase (GGT, 61 U/L; reference range, 0-10 U/L), and hyperbilirubinemia (2.3 mg/dL; reference range, 0-0.3 mg/ dL). Urine was concentrated (specific gravity 1.050) with bilirubinuria, 2+ proteinuria, pH 7.5, and sediment demonst...
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