Local Administration of Carboplatin in Poloxamer 407 After an Ulnar Osteosarcoma Removal in a Dog.

An 8 yr old male castrated hound presented for a left distal ulnar osteosarcoma. Staging (computed tomography and nuclear scintigraphy) did not reveal any metastases. A limb-sparing ulnectomy with local adjunctive carboplatin in a poloxamer copolymer gel (poloxamer 407) was performed. The patient recovered without complications after surgery. No wound healing complications or adverse effects occurred after local use of carboplatin in poloxamer 407. The local recurrence-free interval was 296 days from surgery, and the survival time was 445 days from initial diagnosis. This is the first report in the veterinary literature of using poloxamer 407 as a carrier for local delivery of chemotherapeutic drugs in a clinical patient.

EVALUATION OF LOCALIZED INFLAMMATORY REACTIONS SECONDARY TO INTRAMUSCULAR INJECTIONS OF ENROFLOXACIN IN STRIPED BASS (MORONE SAXATILIS).

Enrofloxacin is a fluoroquinolone widely used in animals including fish. Intramuscular (IM) injection of enrofloxacin is a feasible and efficacious option for drug delivery. In many species IM injection has been associated with injection site reactions and increases in serum muscle enzymes. Injection site reactions have not been well characterized in fish. Three groups of striped bass (Morone saxatilis) received an IM injection of enrofloxacin 2.27% in the right epaxial musculature 24, 48, or 96 hr prior to evaluation. Mean dose was 7.69 mg/ kg (6.14-9.69 mg/kg). The 24- and 48-hr groups received an injection of equal-volume 0.9% saline in the left epaxial musculature. A corresponding noninjected tissue sample was designated in the left epaxial musculature from each fish of the 96-hr group. Fish were euthanized and injection sites and noninjection control sites were evaluated grossly and histologically. Grades 1-4 were assigned to samples, with grade 1 corresponding to normal tissue and grades 2, 3, and 4 corresponding to mild, moderate, and severe inflammation and/or necrosis respectively. Externally, all control and injection sites appeared visually unremarkable. On cut surface, epaxial muscle of the enrofloxacin-injected tissue appeared moderately to severely hemorrhagic compared to saline and noninjected tissue, which was normal or mildly hemorrhagic. Histologically, eight of eight noninjected tissues were grade 1. For saline-injected tissues, 14 of 16 tissues were grade 2 and 2 samples were grade 3 when 24- and 48-hr groups were combined. For enrofloxacin-injected tissues, 8 of the 8 24-hr samples were grade 3 and 16 of the 16 48- and 96-hr samples were grade 4. These data show that IM injection of enrofloxacin 2.27% is associated with severe hemorrhage, necrosis, and inflammation in striped bass, and may negatively affect animal welfare.

Pathology in Ecological Research With Implications for One Health: Session Summary.

This session explored the effects of pollutants on One Health at the ecosystem level that included microbes, insects, fish, and humans. The concept of One Health seeks to synergize medical, veterinary, and other health science disciplines to more effectively advance human and animal health. Presentations explored the interactions of pesticides, pathogens, phytochemicals, and xenobiotic biotransformation in bee colony losses critical for food security (bees have been recently listed under the 2017 US Food and Drug Administration (FDA) veterinary feed directive); the role of pathology in identifying the effects of pollutants on fish as sentinels for human health; the effects in rats of per- and polyfluoroalkyl substances (PFAS) that can persist in the environment and contaminate drinking water; harmful algal blooms and toxin production leading to animal and human disease; and the processing of environmental carcinogens by intestinal microbiota.

Endocrine Disruption and Reproductive Pathology.

During the past 20 years, investigations involving endocrine active substances (EAS) and reproductive toxicity have dominated the landscape of ecotoxicological research. This has occurred in concert with heightened awareness in the scientific community, general public, and governmental entities of the potential consequences of chemical perturbation in humans and wildlife. The exponential growth of experimentation in this field is fueled by our expanding knowledge into the complex nature of endocrine systems and the intricacy of their interactions with xenobiotic agents. Complicating factors include the ever-increasing number of novel receptors and alternate mechanistic pathways that have come to light, effects of chemical mixtures in the environment versus those of single EAS laboratory exposures, the challenge of differentiating endocrine disruption from direct cytotoxicity, and the potential for transgenerational effects. Although initially concerned with EAS effects chiefly in the thyroid glands and reproductive organs, it is now recognized that anthropomorphic substances may also adversely affect the nervous and immune systems via hormonal mechanisms and play substantial roles in metabolic diseases, such as type 2 diabetes and obesity.

Vitamin D deficiency serves as a precursor to stunted growth and central adiposity in zebrafish.

Emerging evidence demonstrates the importance of sufficient vitamin D (1α, 25-dihydroxyvitamin D3) levels during early life stage development with deficiencies associated with long-term effects into adulthood. While vitamin D has traditionally been associated with mineral ion homeostasis, accumulating evidence suggests non-calcemic roles for vitamin D including metabolic homeostasis. In this study, we examined the hypothesis that vitamin D deficiency (VDD) during early life stage development precedes metabolic disruption. Three dietary cohorts of zebrafish were placed on engineered diets including a standard laboratory control diet, a vitamin D null diet, and a vitamin D enriched diet. Zebrafish grown on a vitamin D null diet between 2-12 months post fertilization (mpf) exhibited diminished somatic growth and enhanced central adiposity associated with accumulation and enlargement of visceral and subcutaneous adipose depots indicative of both adipocyte hypertrophy and hyperplasia. VDD zebrafish exhibited elevated hepatic triglycerides, attenuated plasma free fatty acids and attenuated lipoprotein lipase activity consistent with hallmarks of dyslipidemia. VDD induced dysregulation of gene networks associated with growth hormone and insulin signaling, including induction of suppressor of cytokine signaling. These findings indicate that early developmental VDD impacts metabolic health by disrupting the balance between somatic growth and adipose accumulation.

Effect of topically applied Saccharomyces boulardii on the healing of acute porcine wounds: a preliminary study.

BACKGROUND: Normal wound healing progresses through a series of interdependent physiological events: inflammation, angiogenesis, re-epithelialization, granulation tissue formation and extracellular matrix remodeling. Alterations in this process as well as the bacterial type and load on a wound may alter the wound healing rate. The purpose of this study was to evaluate the effect of topical Saccharomyces boulardii on the healing of acute cutaneous wounds, using a prospective, controlled, experimental study, with six purpose bred landrace pigs. RESULTS: All wounds healed without apparent complications. Comparison of the mean 3D and 2D wound surface area measurements showed no significant difference between treatment groups as wounds decreased similarly in size over the duration of the study. A significant reduction in wound surface area was identified sooner using 3D assessments (by day 9) compared to 2D assessments (by day 12) (P < 0.001). There was no significant effect of treatment group on the number of multiple isolates or the most common isolates obtained relative to control wounds. There was no histologically appreciable difference between the wounds of the different groups. CONCLUSIONS: Topical application of Saccharomyces boulardii does not hasten wound healing or change the wounds' microbiome under the conditions reported in this study.

Sources of endocrine-disrupting compounds in North Carolina waterways: a geographic information systems approach.

The presence of endocrine-disrupting compounds (EDCs), particularly estrogenic compounds, in the environment has drawn public attention across the globe, yet a clear understanding of the extent and distribution of estrogenic EDCs in surface waters and their relationship to potential sources is lacking. The objective of the present study was to identify and examine the potential input of estrogenic EDC sources in North Carolina water bodies using a geographic information system (GIS) mapping and analysis approach. Existing data from state and federal agencies were used to create point and nonpoint source maps depicting the cumulative contribution of potential sources of estrogenic EDCs to North Carolina surface waters. Water was collected from 33 sites (12 associated with potential point sources, 12 associated with potential nonpoint sources, and 9 reference), to validate the predictive results of the GIS analysis. Estrogenicity (measured as 17ß-estradiol equivalence) ranged from 0.06 ng/L to 56.9 ng/L. However, the majority of sites (88%) had water 17ß-estradiol concentrations below 1 ng/L. Sites associated with point and nonpoint sources had significantly higher 17ß-estradiol levels than reference sites. The results suggested that water 17ß-estradiol was reflective of GIS predictions, confirming the relevance of landscape-level influences on water quality and validating the GIS approach to characterize such relationships.

Long-term trends in liver neoplasms in brown bullhead in the Buffalo River, New York, USA.

The Buffalo River area of concern (AOC) was assigned an impaired status for the fish tumors and other deformities beneficial use impairment category by the New York State Department of Environmental Protection in 1989. This was initially based on an inadequately documented brown bullhead (Ameiurus nebulosus) feeding study using river sediment extracts. The presence of liver tumors was subsequently supported by reports of a 19 to 27% prevalence in wild brown bullhead between 1983 and 1988 and a 4.8% prevalence in 1998. However, neither fish size (or age) nor sample locations were given, and histopathological definitions were inconsistent in these previous studies. Therefore, in 2008, we re-evaluated the prevalence of hepatocellular and chloangiocellular tumors (as well as other gross indicators of fish health) in brown bullhead averaging 25 cm in length collected from three reaches of the Buffalo River and recorded our collection sites by global positioning system. Among the 37 fish of appropriate size collected, only three exhibited liver tumors (8%). The tumors were evenly distributed within the three reaches, and only hepatocellular tumors were found. There were no differences in the prevalence of hepatic foci of alteration, body weight, length, or hepatosomatic index among the three reaches, but the conditions factor was significantly lower in fish from reach 2. Natural attenuation of water and sediment quality are the most likely causes for the decrease in liver tumors. The prevalence of liver tumors between 1998 and 2008 in the Buffalo River is similar to that found in recovery-stage AOCs and some Great Lakes reference areas.

Characterization of toxic effects of sediment-associated organic pollutants using the lambda transgenic medaka.

A novel sediment-contact assay using embryos of the transgenic medaka was developed to fully characterize the toxic effects induced by exposure to a mixture of organic pollutants in sediments. Embryos of the lambda transgenic medaka were exposed for 10 days to a clean reference sediment spiked with either the solvent alone, benzo[a]pyrene (B[a]P), or three concentrations (0.3x, 1x, and 2x) of an organic extract (OE) of sediments from the Seine estuary. The 1 x OE-spiked sediment contained concentrations of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls similar to those in field-collected sediment. Exposure to this sediment, but not to the B[a]P-spiked sediment, significantly increased embryo-larval mortality and prevalence of spinal deformities. Mutant frequency at the cII mutation target gene in the liver of 10-week-old medaka was significantly increased following exposure to either B[a]P or the three doses of OE. The predominant OE-induced liver mutations were G:C to T:A transversions, consistent with PAHs being the major contributors to the mutation induction. Liver and gonadal tumors were observed in 35-week-old medaka exposed to either B[a]P (1/25) or to the 1 x OE (1/24). The benefits of medaka as a fish model for toxicological assessment and the benefits of the cII mutation assay for mutation detection combine to provide comprehensive assessment of a wide range of genotoxic and nongenotoxic effects of aquatic pollutants.