A5068655049- Cancer Research and Treatments
- Bladder and Urothelial Cancer Treatments
- Amino Acid Enzymes and Metabolism
- Veterinary Oncology Research
- Marine Toxins and Detection Methods
- Animal testing and alternatives
- Statistical Methods in Clinical Trials
- Cancer, Hypoxia, and Metabolism
- Nicotinic Acetylcholine Receptors Study
- Cardiac electrophysiology and arrhythmias
- Immunotoxicology and immune responses
- Neuroscience of respiration and sleep
- Immunotherapy and Immune Responses
- Ion channel regulation and function
- Sirtuins and Resveratrol in Medicine
- PARP inhibition in cancer therapy
- Melanoma and MAPK Pathways
- Biosimilars and Bioanalytical Methods
- T-cell and B-cell Immunology
- Health Systems, Economic Evaluations, Quality of Life
- Cell Adhesion Molecules Research
- Computational Drug Discovery Methods
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cardiovascular Conditions and Treatments
- Biomedical and Engineering Education
Marine Mammal Center
2002-2022
Pfizer (United States)
2022
Chicago Zoological Society
2022
Vancouver Aquarium
2022
Alaska SeaLife Center
2022
Sea Research Foundation
2022
Genentech
2012-2015
La Roche College
2010-2013
Amgen (United States)
2013
Roche (Switzerland)
2011-2012
Eighty‐one Californian sea lions ( Zalophus californianus ) with signs of domoic acid toxicity stranded along the coast California in 1998 when there were blooms acid‐producing alga Pseudonitzschia australis off‐shore. In 2000, a further 184 similar clinical signs, but strandings occurred both during detectable algal and after had subsided. The these 265 included seizures, ataxia, head weaving, decreased responsiveness to stimuli scratching behaviour. Affected animals high haematocrits,...
Harmful algal blooms are increasing worldwide, including those of Pseudo-nitzschia spp. producing domoic acid off the California coast. This neurotoxin was first shown to cause mortality marine mammals in 1998. A decade monitoring sea lion (Zalophus californianus) health since then has indicated that changes symptomatology and epidemiology toxicosis this species associated with increase toxigenic blooms. Two separate clinical syndromes now exist: acute as been previously documented, a second...
Animal models of human disease are commonly utilized to gain insight into the potential efficacy and mode action novel pharmaceuticals. However, conventional (healthy) rodent nonrodent generally in nonclinical safety testing. may be helpful understanding risks compounds or clinical development, with their greatest value being targeted hypothesis-driven studies help understand mechanism a particular toxicity. Limitations animal testing include lack historical control, heterogeneity...
Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein with intra- and extra-cellular functions as an enzyme, cytokine, growth factor, hormone. NAMPT of interest for oncology, because it catalyzes the rate-limiting step in salvage pathway to generate nicotinamide adenine dinucleotide (NAD), which considered universal energy- signal-carrying molecule involved cellular energy metabolism many homeostatic functions. This manuscript describes inhibitor-induced retinal toxicity...
Domoic acid is a glutaminergic neurotoxin produced by marine algae such as Pseudo-nitzschia australis. California sea lions (Zalophus californianus) ingest the toxin when foraging on planktivorous fish. Adult females comprise 60% of stranded animals admitted for rehabilitation due to acute domoic toxicosis and commonly suffer from reproductive failure, including abortions premature live births. has been shown cross placenta exposing fetus toxin. To determine whether was playing role in...
P38α is a protein kinase that regulates the expression of inflammatory cytokines, suggesting role in pathogenesis diseases such as rheumatoid arthritis (RA) or systemic lupus erythematosus. Here, we describe preclinical pharmacology pamapimod, novel p38 mitogen-activated inhibitor. Pamapimod inhibited p38α and p38β enzymatic activity, with IC<sub>50</sub> values 0.014 ± 0.002 0.48 0.04 μM, respectively. There was no activity against p38δ p38γ isoforms. When profiled across 350 kinases,...
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California sea lions have been a repeated subject of investigation for early life toxicity, which has documented to occur with increasing frequency from late February through mid-May in association organochlorine (PCB and DDT) poisoning infectious disease the 1970's domoic acid last decade. The mass mortality events result concentrated breeding grounds synchronization reproduction over 28 day post partum estrus cycle 11 month utero phase. This physiological is triggered by decreasing...
Domoic acid, produced by marine algae, can cause acute and chronic neurologic sequela in California sea lions (Zalophus californianus) from toxicity or sublethal exposure. Eight lions, representing cases, both sexes, all age classes, were selected to demonstrate a concurrent degenerative cardiomyopathy. Critical aspects of characterizing the cardiomyopathy lesion distribution morphology development heart dissection tissue-trimming protocol delineation cardiac conducting system...
Novel skeletal muscle (SKM) injury biomarkers that have recently been identified may outperform or add value to the conventional SKM aspartate transaminase (AST) and creatine kinase (CK). The relative performance of these novel including troponin I (sTnI), myosin light chain 3 (Myl3), CK M Isoform (Ckm), fatty acid binding protein (Fabp3) was assessed in 34 rat studies both toxicants compounds with toxicities tissues other than SKM. sTnI, Myl3, Ckm, Fabp3 all outperformed AST and/or added...
Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies the U.S. Food Drug Administration (FDA), formed Vascular Injury Working Group (VIWG) develop qualify translatable DIVI. VIWG focused its research on acute DIVI because early detection for clinical safety monitoring is desirable. developed...
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Abstract OBJECTIVE To describe the prevalence, clinical findings, lesions, and risk factors associated with chlamydial infections in free-ranging raptors presented to a university veterinary medical teaching hospital. METHODS Medical records retrospectively searched for admitted from January 1993 through April 2022 were tested Chlamydia spp using quantitative PCR (qPCR), immunohistochemistry, culture, sequencing. Findings collected analyzed. Multivariable logistic regression analyzed...
A6-year-old male castrated Greyhound was presented to the William R. Pritchard Veterinary Medical Teaching Hospital, University of California, Davis, with a 4-week history apparent spinal pain and paraparesis. There no improvement despite treatment consisting oral carprofen (unknown dose) for 10 days followed by tapering course prednisone 6 before referral (1.2–0.2 mg/kg/d). Abnormalities on physical examination included 5% dehydration, large flaccid bladder that easily expressed, moderate...
During routine safety evaluation of RO2910, a non-nucleoside reverse transcriptase inhibitor for HIV infection, histopathology findings concurrent with robust hepatocellular induction occurred in multiple organs, including unique, albeit related, finding the pituitary gland. For fourteen days, male and female rats were administered, by oral gavage vehicle, 100, 300, or 1000 mg/kg/day RO2910. Treated groups had elevated serum thyroid-stimulating hormone decreased total thyroxine, hypertrophy...
Pulmonary arteriopathy (PA) is the pathologic hallmark in human medicine of diffuse constrictive (medial and intimal remodeling) or multifocal complex (plexiform dilatative lesions) arterial lesions, both, that lead to irreversible obliteration lumen. Clinically, PA leads pulmonary hypertension (PAH), which idiopathic (IPAH) one 5 subsets, ultimately, right-sided heart failure (RHF). Clinical findings from 6 dogs with diagnosis IPAH were reviewed. These various pure (5/6, 83%) mixed (1/6,...
A set of best practices for the conduct histopathology evaluation in nonclinical safety studies was endorsed by Society Toxicologic Pathology (STP) 2004. These indicate that study pathologist should have knowledge treatment group and access to all available study-related data animal from which tissue obtained. new review biomarker qualification has been STP is summarized this document. are generally similar those studies, specifically be "unblinded" or data. Although must performed without...
Nicotinamide adenine dinucleotide (NAD) is an essential co-factor in glycolysis and a key molecule involved maintaining cellular energy metabolism. phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step of important salvage pathway which nicotinamide recycled into NAD. NAMPT up-regulated many types cancer inhibitors (NAMPTi) have potential therapeutic benefit by impairing tumor Clinical trials with NAMPTi APO-866 GMX-1778, however, failed to reach projected efficacious exposures...
Abstract BRAF-targeted therapies including vemurafenib (Zelboraf) induce dramatic cancer remission; however, drug resistance commonly emerges. The purpose was to characterize a naturally occurring canine model harboring complex features of human cancer, complement experimental models improve therapy. A phase I/II clinical trial performed in pet dogs with invasive urothelial carcinoma (InvUC) the homologue BRAFV600E. safety, MTD, pharmacokinetics, and antitumor activity were determined....