Ness D.,Elan Pharmaceuticals Inc. |
Ren Z.,Elan Pharmaceuticals Inc. |
Gardai S.,Elan Pharmaceuticals Inc. |
Sharpnack D.,Vet Inc. |
And 4 more authors.
PLoS ONE | Year: 2013
Genetic evidence links mutations in the LRRK2 gene with an increased risk of Parkinson's disease, for which no neuroprotective or neurorestorative therapies currently exist. While the role of LRRK2 in normal cellular function has yet to be fully described, evidence suggests involvement with immune and kidney functions. A comparative study of LRRK2-deficient and wild type rats investigated the influence that this gene has on the phenotype of these rats. Significant weight gain in the LRRK2 null rats was observed and was accompanied by significant increases in insulin and insulin-like growth factors. Additionally, LRRK2-deficient rats displayed kidney morphological and histopathological alterations in the renal tubule epithelial cells of all animals assessed. These perturbations in renal morphology were accompanied by significant decreases of lipocalin-2, in both the urine and plasma of knockout animals. Significant alterations in the cellular composition of the spleen between LRRK2 knockout and wild type animals were identified by immunophenotyping and were associated with subtle differences in response to dual infection with rat-adapted influenza virus (RAIV) and Streptococcus pneumoniae. Ontological pathway analysis of LRRK2 across metabolic and kidney processes and pathological categories suggested that the thioredoxin network may play a role in perturbing these organ systems. The phenotype of the LRRK2 null rat is suggestive of a complex biology influencing metabolism, immune function and kidney homeostasis. These data need to be extended to better understand the role of the kinase domain or other biological functions of the gene to better inform the development of pharmacological inhibitors. © 2013. Source
Pritt M.L.,Lilly Research Laboratories |
Hall D.G.,Lilly Research Laboratories |
Jordan W.H.,Vet Inc. |
Ballard D.W.,Lilly Research Laboratories |
And 3 more authors.
Toxicological Sciences | Year: 2014
Detection of compound-related neurodegeneration is currently limited to brain histopathology in veterinary species and functional measurements such as electroencephalography and observation of clinical signs in patients. The objective of these studies was to investigate whether concentrations of spectrin breakdown product 145 (SBDP-145) in cerebrospinal fluid (CSF) correlate with the severity of neurodegeneration in rats administered neurotoxic agents, as part of a longer term objective of developing in vivo biomarkers of neurotoxicity for use in non-clinical and clinical safety studies. Non-erythroid alpha-II spectrin is a cytoskeletal protein cleaved by the protease calpain when this enzyme is activated by dysregulation of calcium in injured cells. Calcium dysregulation is also associated with some toxicological responses in animals, and may be sufficient to activate neuronal calpain and produce SBDPs that can be released into CSF. Neurotoxicants (kainic acid, 2-chloropropionic acid, bromethalin, and pentylenetetrazole) known to affect different portions of the brain were administered to rats in dose-response and time-course studies in which neurodegeneration was measured by histopathology and SBDP-145 concentrations in CSF were measured by ELISA. We consistently observed >3-fold increases in SBDP-145 concentration in rats with minimal to slight neurodegenerative lesions, and 20 to 150-fold increases in animals with more severe lesions. In contrast, compounds that caused non-degenerative changes in central nervous system (CNS) did not increase SBDP-145 in CSF. These data support expanded use of SBDP-145 as a biomarker for monitoring compound-induced neurodegeneration in pre-clinical studies, and support the investigation of clinical applications of this biomarker to promote safe dosing of patients with compounds that have potential to cause neurodegeneration. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. Source
Jordan W.H.,Vet Inc.
Toxicologic pathology | Year: 2011
For many pathologists, neuropathology is intimidating. Practical approaches for nervous tissue histologic evaluations to meet both routine and advanced study designs can lead to rewarding neuropathology efforts. Cost-effective, high-quality histologic evaluations can occur if animals are exsanguinated quickly, brains removed carefully to maintain structural integrity and avoid dark neuron artifact, immersion-fixed quickly and thoroughly, and trimmed and processed to consistently survey multiple areas. While brightfield examination of H&E-stained sections is generally sufficient for survey evaluations, epifluorescent assessment of neuronal autofluorescence facilitates recognition of neurodegeneration in H&E-stained sections. Fluoro-Jade B or specialized immunohistochemical stains may be required to answer specific questions. Evaluations require that both technical staff and pathologists have a working knowledge of a few easily identified neuroanatomic landmarks and familiarity with use of a detailed brain atlas. At least four coronal sections should be routinely surveyed from young adult rats, with evaluation of comparable areas in other laboratory animal species. This number should be at least doubled if there is reason to suspect morphologic changes in the CNS. This article focuses on technical details of efficient specimen preparation for neuropathologic evaluations involving relatively large numbers of rodents, as well as a practical approach to basic neuroanatomic site identification. Source
Vet Inc. | Date: 2015-01-14
Veterinary preparations for reducing food pathogens in poultry; veterinary preparations for food safety, namely, compositions of probiotic microorganisms administered to poultry at feed withdrawal to reduce pathogens before processing for human consumption; veterinary preparations comprised of probiotic microorganisms including bacteria and/or bacteriophages for administration to poultry at feed withdrawal to reduce the presence of food safety pathogens in the gastrointestinal tract prior to the slaughter and processing of the poultry.
Vet Inc. | Date: 2016-07-13
All natural pet products, namely, paw butters, nose butters, shampoos and essential oil and aloe blends to be used as bug repellent.