Aggregate or spheroid culture has emerged as a more biologically relevant method for screening pharmaceutical compounds and understanding exact mechanism of action. Here in, the aggregate approach applied to the freshwater toxins, microcystins, further unearths exact mechanism(s) of toxicity and provides a markedly improved in vitro predictor of toxicity. Microcystins result in acute intoxication by binding covalently to protein phosphatase 1/2A, resulting in hepatocellular necrosis, hemorrhaging and death. Hepatocellular uptake by organic anion transporting polypeptides (OATPs), in addition to other intracellular sequelae, is considered essential for toxicity. In aggregate HepG2, expression of OAT1B1 and OATP1B3 significantly increased relative to monolayer culture. Uptake of two fluorescently labeled substrates significantly increased in aggregates compared with monolayer, confirmed by inhibition of uptake with known competitive substrates. Increased reaction oxygen species (ROS) production occurred following a three-hour exposure of microcystin LR at concentrations from 100 nM to 100 μM, with reversal by ROS scavengers, in contrast with no response in monolayers. These results suggest monolayer culture inadequately predict intracellular effects of microcystins and support evidence that aggregate culture more closely approximates in vivo form and function. The approach results in more reliable prediction of microcystin toxicity in vitro.

Contamination of recreational waters with cyanobacterial toxins continues to increase and presents a risk to animals and humans. Although cases of acute hepato- and neurotoxicoses in dogs following cyanotoxin exposure exist, no reports of skin-related reactions in dogs exist. A 5-year-old female spayed 34 kg Bracco Italiano was initially presented for rapid onset of severe pruritus and urticaria. Marked excoriation and erythema were noted over the chest and neck, while urticaria was noted in the inguinal regions and ventral abdomen. Initial basic dermatology work-up excluded parasitic, fungal, and bacterial organisms. Due to the severity and progression of urticaria, the dog received IV dexamethasone and IM diphenhydramine. Improvement of the urticaria and the dog's clinical status was noted over the next 45 min. Assessment of the dog's environment revealed access to a lake on the property with visible algal bloom. Water from the lake was submitted for toxicology testing and revealed the presence of debromoaplysiatoxin. Access to the lake was discontinued and follow-up evaluation over the next few weeks revealed a complete resolution of the skin irritation. To the authors' knowledge, this is the first case report of debromoaplysiatoxin exposure in a dog after swimming in cyanobacteria-contaminated water. Veterinarians should recognize the potential harm that contaminated waters may cause in terms of dermal, hepatic, and neurological conditions. In addition, more prudent oversight of contaminated recreational waters is recommended for animals and humans to prevent adverse events and intoxications.

Harmful algal blooms expose humans and animals to microcystins (MCs) through contaminated drinking water. While hepatotoxicity following acute exposure to MCs is well documented, neurotoxicity after sub-lethal exposure is poorly understood. We developed a novel statistical approach using a generalized linear model and the quasibinomial family to analyze neurotoxic effects in adult Caenorhabditis elegans exposed to MC-LR or MC-LF for 24 h. Selective effects of toxin exposure on AWA versus AWC sensory neuron function were determined using a chemotaxis assay. With a non-monotonic response MCs altered AWA but not AWC function, and MC-LF was more potent than MC-LR. To probe a potential role for protein phosphatases (PPs) in MC neurotoxicity, we evaluated the chemotactic response in worms exposed to the PP1 inhibitor tautomycin or the PP2A inhibitor okadaic acid for 24 h. Okadaic acid impaired both AWA and AWC function, while tautomycin had no effect on function of either neuronal cell type at the concentrations tested. These findings suggest that MCs alter the AWA neuron at concentrations that do not cause AWC toxicity via mechanisms other than PP inhibition.

Production of steroid hormones is complex and dependent upon steroidogenic enzymes, cofactors, receptors, and transporters expressed within a tissue. Collectively, these factors create an environment for tissue-specific steroid hormone profiles and potentially tissue-specific responses to drug administration. Our objective was to assess steroid production, including sulfated steroid metabolites in the boar testis, prostate, and liver following inhibition of aromatase, the enzyme that converts androgen precursors to estrogens. Boars were treated with the aromatase inhibitor, letrozole from 11 to 16 weeks of age and littermate boars received the canola oil vehicle. Steroid profiles were evaluated in testes, prostate, and livers of 16, 20, and 40 week old boars using liquid chromatography/mass spectrometry. Testis, prostate, and liver had unique steroid profiles in vehicle-treated animals. Only C18 steroid hormones were altered by treatment with the aromatase inhibitor, letrozole; no significant differences were detected in any of the C19 or C21 steroids evaluated. Testis was the only tissue with significantly decreased free estrogens following treatment with the aromatase inhibitor; estrone and estradiol concentrations were lower (p < 0.05) in testes from 16, 20, and 40 week letrozole-treated boars. However, concentrations of the sulfated conjugates, estrone-sulfate and estradiol-sulfate, were significantly decreased (p<0.05) in 16 and 20 week boar testes, prostates, and livers from letrozole-treated boars. Hence, the distribution of estrogens between the free and conjugated forms was altered in a tissue-specific manner following inhibition of aromatase. The results suggest sulfated testicular estrogens are important estrogen precursors for the prostate, potentially enabling peripheral target tissues to synthesize free estrogens in the male pig.

Although the USA has made significant strides in reducing lead exposure, new and emerging sources are raising cause for public concern. Recent reports of finding lead in eggs from chickens raised in urban gardens has highlighted the need to consider the potential health risks of consuming eggs from backyard chickens. Following the detection of 0.33 μg/g lead in the edible portion of eggs submitted for lead analysis from a backyard chicken owner, further investigation was conducted to determine the source and extent of lead exposure in the flock. Several birds, almost two dozen eggs, and environmental samples were submitted to the California Animal Health and Food Safety Laboratory for further testing. Lead was detected in the blood, liver, kidney, and bone at varying concentrations in all birds but was not detected in the muscle tissue. All egg shells contained detectable amounts of lead, while only a little over half of the edible portion of the eggs contained lead. The detected concentrations in the edible portion approached or exceeded the recommended threshold of lead consumption per day that should not be exceeded by young children if a child consumed one average-sized egg. Peeling paint from a wooded structure adjacent to the flock's coop was the likely lead source containing 3,700 μg/g lead. Thus, removal of the chickens from the source and periodic testing of eggs for lead were recommended. This case illustrates the need for consumers and health care workers to be aware of potential sources for lead exposure such as backyard chickens.

Objective

To determine the profile of 14 polybrominated diphenyl ethers (PBDEs) and 23 polychlorinated biphenyls (PCBs) in serum of domestic canines and whether this was predictive of thyroid hormone status.

Samples

Serum samples were collected from 51 client-owned dogs visiting the University of California Davis William R. Pritchard Veterinary Medical Teaching Hospital during 2012 to 2016 for routine appointments. Fifteen dogs were diagnosed with hypothyroxinemia while 36 were euthyroid.

Procedures

Concentrations of PBDEs and PCBs in canine serum samples were measured by gas chromatography mass spectrometry. Logistic regression analysis was used to determine the association between the presence/absence of canine hypothyroxinemia and the serum concentration of individual PBDE or PCB congeners.

Results

The median concentrations of total PBDE and PCB congeners in the hypothyroxinemic group were 660 and 1,371 ng/g lipid, respectively, which were higher than concentrations detected in the control group. However, logistic regression analysis determined that current concentrations of PBDEs and PCBs in canines were not significantly associated with hypothyroxinemia. BDE 183 was the only congener showing near significance (p = 0.068).

Conclusions

PBDE and PCB congeners were detected in all canine samples confirming ongoing exposure to these pollutants. Because household dogs share the human environment, they may serve as biosentinels of human exposure to these contaminants.

Between June 1 and 30, 2011, a partnership between the U.S. Fish and Wildlife Service, The Nature Conservancy, and Island Conservation successfully implemented a project to remove introduced black rats from Palmyra Atoll National Wildlife Refuge. Prior to the rat eradication, we assessed several environmental risk factors associated with the application of an anticoagulant rodenticide to Palmyra’s emergent land area. Here, we present the findings from a study of toxicant migration from bait pellets into topsoil. Topsoil from plots characterized as “sandy” or “humus” was collected after exposure to bait pellets containing 50 ppm of diphacinone or 25 ppm of brodifacoum. Brodifacoum and diphacinone were detected in samples of both sandy and organic topsoil while control samples collected outside of the study plots tested negative for both toxicants. With both toxicants, residue concentrations decreased with time and neither toxicant was detected in most of the 28, 36, and 50-day samples; trace amounts (=0.2 ppm for brodifacoum and =2 ppm for diphacinone) of the toxicants were detected in a few samples from these groupings. We did not find a significant difference in toxicant concentrations between the two types of topsoil. The results from this study suggest that following a broadcast of rodenticide across Palmyra’s emergent land area, small amounts of brodifacoum or diphacinone would migrate to, and remain in, Palmyra’s topsoil for a short period of time.

We determined 12 polybrominated diphenyl ethers (PBDEs) and 19 polychlorinated biphenyls (PCBs) congeners in eight different brands of commercial whole milk (WM) and fat free milk (FFM) produced and distributed in California. Congeners were extracted using a modified quick, easy, cheap, effective, rugged and safe (QuEChERS) method, purified by gel permeation chromatography, and quantified using gas chromatography-triple quadruple mass spectrometry. PBDEs and PCBs were detected in all FFM and WM samples. The most prevalent PBDE congeners in WM were BDE-47 (geometric mean: 18.0 pg/mL, 0.51 ng/g lipid), BDE-99 (geometric mean: 9.9 pg/mL, 0.28 ng/g lipid), and BDE-49 (geometric mean: 6.0 pg/mL, 0.17 ng/g lipid). The dominant PCB congeners in WM were PCB-101(geometric mean: 23.6 pg/mL, 0.67 ng/g lipid), PCB-118 (geometric mean: 25.2 pg/mL, 0.72 ng/g lipid), and PCB-138 (geometric mean: 25.3 pg/mL, 0.72 ng/g lipid). The sum of all 19 PCB congeners in FFM and WM were several orders of magnitude below the U.S. FDA tolerance. The sum of PBDEs in milk samples suggest close proximity to industrial emissions, and confirm previous findings of elevated PBDE levels in California compared to other regions in the United States.

Background

Hyperthyroidism is the most common endocrine disorder observed in domestic felines; however, its etiology is largely unknown. Two classes of persistent organic pollutants, polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are known to interfere with thyroid hormone (TH) signaling and regulation; thus, it is postulated that they contribute to the etiopathogenesis of feline hyperthyroidism and pose a risk to humans and other species. In this case-control study, the concentrations of 13 PBDE and 11 PCB congeners were measured by gas chromatography mass spectrometry in serum or plasma samples from 20 hyperthyroid and 31 control cats in order to investigate the association between concentration of PBDE and PCB congeners and feline hyperthyroidism. Logistic regression analysis was used to determine whether elevated concentrations of individual congeners were associated with a higher risk of feline hyperthyroidism.

Results

Hyperthyroid cats had higher concentrations of four PBDE congeners (BDE17, BDE100, BDE47, and BDE49) and five PCB congeners (PCB131, PCB153, PCB174, PCB180, and PCB196), compared to control cats. In addition, the sum of both PBDE and PCB congener concentrations were elevated in the hyperthyroid group compared to control cats; however, only the increased PCB concentrations were statistically significant. The sum total PBDE concentrations in our feline samples were approximately 50 times greater than concentrations previously reported in human populations from a geographically similar area, whereas sum total PCB concentrations were comparable to those previously reported in humans.

Conclusions

These observational findings support the hypothesis that PBDEs and PCBs may contribute to the etiopathogenesis of hyperthyroidism in felines. As domestic house cats are often exposed to higher concentrations of PBDEs than humans, they may serve as sentinels for the risk of TH disruption that these pollutants pose to humans and other species.

Horses, goats, sheep, and cattle can sicken or die if they eat from a poisonous plant. The best strategy is just to keep these plants out of reach. Here are photos, ID info, and poisoning symptoms for more than 30 hazardous ornamental and range plants.