Zinc, Copper, and Manganese Homeostasis and Potential Trace Metal Accumulation in Dairy Cows: Longitudinal Study from Late Lactation to Subsequent Mid-Lactation.

BACKGROUND: Trace metals are supplemented in cattle to prevent nutrient deficiencies. Levels supplemented to mitigate worst-case basal supply and availability scenarios can, however, result in trace metal intakes far above the nutritional requirements of dairy cows with high feed intakes. OBJECTIVES: We evaluated Zn, Mn, and Cu balance in dairy cows from late lactation through the subsequent mid-lactation, a period of 24 wk characterized by large changes in dry matter intake. METHODS: Twelve Holstein dairy cows were housed in a tie-stall from 10 wk before to 16 wk after parturition and fed 1 unique lactation diet when lactating and a dry cow diet otherwise. After 2 wk of adaptation to the facility and diet, Zn, Mn, and Cu balances were determined at weekly intervals, by calculating the difference between total intakes and complete fecal, urinary, and milk outputs, with the latter 3 fluxes quantified over a 48-h period. Repeated measure mixed models were used to evaluate the effects on trace mineral balances over time. RESULTS: The Mn and Cu balances of cows were not significantly different from 0 mg/d between 8 wk prepartum and calving (P ≥ 0.54), when dietary intake was the lowest of the period evaluated. However, when dietary intake was highest, between wk 6 and 16 postpartum, positive Mn and Cu balances were observed (80 and 20 mg/d, respectively, P ≤ 0.05). Cows were in positive Zn balance throughout the study except during the first 3 wk after calving during which the Zn balance was negative. CONCLUSIONS: Large adaptations occur in trace metal homeostasis in transition cows in response to changes in dietary intake. High dry matter intakes, associated with high milk production of dairy cows, combined with current Zn, Mn, and Cu supplementation practices may exceed regulatory homeostatic mechanisms resulting in potential body accumulation of Zn, Mn, and Cu.

Exploring the use of tablet PCs in veterinary medical education: opportunity or obstacle?

A tablet PC is a laptop computer with a touch screen and a digital pen or stylus that can be used for handwritten notes and drawings. The use of tablet PCs has been investigated in many disciplines such as engineering, mathematics, science, and education. The purpose of this article is to explore student and faculty attitudes toward and experiences with tablet PCs 6 years after the implementation of a tablet PC program in the College of Veterinary Medicine (CVM) at Kansas State University (K-State). This study reports that the use of tablet PCs has enhanced students' learning experiences through learner-interface interaction, learner-content interaction, learner-instructor interaction, and learner-learner interaction. This study also identifies digital distraction as the major negative experience with tablet PCs during class time. The tablet PC program provides CVM faculty the potential to pursue technology integration strategies that support expected learning outcomes and provides students the potential to develop self-monitoring and self-discipline skills that support learning with digital technologies.

Liver failure in a dog following suspected ingestion of blue-green algae (Microcystis spp.): a case report and review of the toxin.

A 2.5 yr old spayed female Weimaraner presented after ingestion of blue-green algae (Microcystis spp.). One day prior to presentation, the patient was swimming at a local lake known to be contaminated with high levels of blue-green algae that was responsible for deaths of several other dogs the same summer. The patient presented 24 hr after exposure with vomiting, inappetence, weakness, and lethargy. Blood work at the time of admission was consistent with acute hepatic failure, characteristic findings of intoxication by Microcystis spp. Diagnosis was suspected by analyzing a water sample from the location where the patient was swimming. Supportive care including fluids, fresh frozen plasma, whole blood, vitamin K, B complex vitamins, S-adenosyl methionine, and Silybum marianum were started. The patient was discharged on supportive medications, and follow-up blood work showed continued improvement. Ingestion is typically fatal for most patients. This is the first canine to be reported in the literature to survive treatment after known exposure.

Reference intervals for trace mineral and heavy metal concentrations in horse livers in the Netherlands.

We determined reference intervals (RIs) for concentrations of trace minerals and toxic elements based on liver samples from 122 apparently healthy horses at 2 slaughter facilities in the Netherlands. Samples were collected during the spring and fall of 2021, and the sex and age of the horses were registered upon sampling. Concentrations of arsenic, cadmium, chromium, cobalt, copper, iron, lead, manganese, molybdenum, nickel, selenium, vanadium, and zinc were measured in liver samples using inductively coupled plasma-mass spectrometry (ICP-MS) after nitric acid digestion. RIs were calculated using Reference Value Advisor software. The concentrations of most elements were not significantly different between sexes or in different seasons. Cadmium concentrations were higher than the European maximum residue limit of 2 mg/kg DW in 89% of livers. Positive significant correlations were observed between some elements (iron, molybdenum, lead, vanadium), and significant negative correlations between others (manganese, iron).

Evaluation of hair analysis for determination of trace mineral status and exposure to toxic heavy metals in horses in the Netherlands.

Analysis of hair to gain insight into the trace mineral status and exposure to toxic heavy metals of horses is attractive because hair is an easily accessible sample material. To investigate the potential value of hair analysis in horses for determination of trace mineral and heavy metal concentrations, we analyzed mane hair and liver samples from 62 horses presented for slaughter at a facility in the Netherlands that receives horses from all regions of the country. Hair samples were cleaned in warm water. After acid digestion of hair and liver specimens, we quantified, with inductively coupled plasma-mass spectrometry, arsenic, cadmium, chromium, cobalt, copper, iron, lead, manganese, molybdenum, nickel, selenium, vanadium, and zinc in the digests. Based on Pearson product moment correlations, we found no statistically significant correlations between concentrations of trace minerals in liver and hair, with the exception of a slight correlation for copper that was too weak to be of clinical relevance. Our results do not support the use of hair to determine trace mineral status and exposure to toxic heavy metals in the horse under field conditions.

A network model of successive partitioning-limited solute diffusion through the stratum corneum.

As the most exposed point of contact with the external environment, the skin is an important barrier to many chemical exposures, including medications, potentially toxic chemicals and cosmetics. Traditional dermal absorption models treat the stratum corneum lipids as a homogenous medium through which solutes diffuse according to Fick's first law of diffusion. This approach does not explain non-linear absorption and irregular distribution patterns within the stratum corneum lipids as observed in experimental data. A network model, based on successive partitioning-limited solute diffusion through the stratum corneum, where the lipid structure is represented by a large, sparse, and regular network where nodes have variable characteristics, offers an alternative, efficient, and flexible approach to dermal absorption modeling that simulates non-linear absorption data patterns. Four model versions are presented: two linear models, which have unlimited node capacities, and two non-linear models, which have limited node capacities. The non-linear model outputs produce absorption to dose relationships that can be best characterized quantitatively by using power equations, similar to the equations used to describe non-linear experimental data.

Tumor necrosis factor alpha increases P-glycoprotein expression in a BME-UV in vitro model of mammary epithelial cells.

P-glycoprotein is an efflux pump belonging to the ATP-binding cassette super-family that influences the bioavailability and disposition of many drugs. Mammary epithelial cells express various drug transporters including P-glycoprotein, albeit at low level during lactation. During inflammatory reactions, which can be associated with changes in epithelial barrier functions, pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) are elevated in milk and serum. In this study, the role of TNF-α in the regulation of P-glycoprotein was determined in cultured BME-UV cells, an immortalized bovine mammary epithelial cell line. The protein production of P-glycoprotein and mRNA expression of bABCB1, the gene encoding P-glycoprotein, were increased after 24 h of TNF-α exposure. The highest observed effects for TNF-α on the regulation of P-glycoprotein was after 72 h of exposure. Protein and mRNA expression also increased significantly after 120 h of TNF-α exposure, but was lower than the level observed in the cells exposed to TNF-α for 72 h. The apical to basolateral flux of digoxin, a P-glycoprotein substrate, was decreased in the TNF-α-exposed epithelium. This effect was reversed when verapamil or ketoconazole, compounds known to interact with P-glycoprotein, were added together with digoxin into the donor compartment. Probenecid, a compound known to interact with organic anion transporters, but not P-glycoprotein, did not increase the flux of digoxin. This model has important implications for understanding the barrier function of the mammary epithelium and provides insight into the role of P-glycoprotein in the accumulation and/or removal of xenobiotics from milk and/or plasma.

Nanocrystalline titanium dioxide and magnesium oxide in vitro dermal absorption in human skin.

The dermal absorption potential of a nanocrystalline magnesium oxide (MgO) and titanium dioxide (TiO(2)) mixture in dermatomed human skin was assessed in vitro using Bronaugh-type flow-through diffusion cells. Nanocrystalline material was applied to the skin surface at a dose rate of 50 mg/cm(2) as a dry powder, as a water suspension, and as a water/surfactant (sodium lauryl sulfate) suspension, for 8 hours. Dermal absorption of nanocrystalline MgO and TiO(2) through human skin with intact, functional stratum corneum was not detectable under the conditions of this experiment.

Levels of trace elements and potential toxic elements in bovine livers: A trend analysis from 2007 to 2018.

Trace elements and potential toxic elements were analyzed in bovine livers submitted for autopsy in the Netherlands during the years 2007 to 2018. The age of each animal was recorded. In total, 1544 livers were analyzed for cadmium, cobalt, chromium, copper, iron, molybdenum, nickel, lead, selenium and zinc. Less than 2% of the liver samples were from veal calves. Young animals had significantly higher concentrations of iron and zinc in their livers compared to animals older than one year, while older animals had significantly higher levels of cadmium and molybdenum in their livers. Animals aged 1 to 2 years had the lowest copper and selenium levels. There was a tendency for lower chromium and nickel levels during the last years of the testing period, while copper showed an increase. Lead intoxication was only seen in the youngest group of cattle, while copper intoxication, defined as a liver copper of more than 1000 mg/kg dry matter, occurred in older animals, mainly in animals of 3 to 4 years old. This trend analysis of trace elements in bovine livers of cattle over time in recent years, and the relation of liver element concentrations with age of the animal, provides insight in the uptake and storage of these elements by cattle in The Netherlands. Possible reasons for observed trends and age-related patterns are discussed.

Nucleotides, micro- and macro-nutrients, limonoids, flavonoids, and hydroxycinnamates composition in the phloem sap of sweet orange.

Currently, the global citrus production is declining due to the spread of Huanglongbing (HLB). HLB, otherwise known as citrus greening, is caused by Candidatus Liberibacter asiaticus (CLas) and is transmitted by the Asian citrus psyllids (ACP), Diaphorina citri Kuwayama. ACP transmits CLas bacterium while feeding on the citrus phloem sap. Multiplication of CLas in the phloem of citrus indicates that the sap contains all the essential nutrients needed for CLas. In this study, we investigated the micro- and macro-nutrients, nucleotides, and others secondary metabolites of phloem sap from pineapple sweet orange. The micro- and macro-nutrients were analyzed using inductively coupled plasma-mass spectroscopy (ICP-MS) and inductively coupled plasma-optical emission spectroscopy (ICP-OES). Nucleotides and other secondary metabolites analysis was accomplished by reversed phase HPLC coupled with UV, fluorescence detection, or negative mode electrospray ionization mass spectrometry (ESI-MS). Calcium (89 mM) was the highest element followed by potassium (38.8 mM) and phosphorous (24 mM). Magnesium and sulfur were also abundant and their concentrations were 15 and 9 mM, respectively. The rest of the elements were found in low amounts (< 2mM). The concentrations of ATP, ADP, and AMP were 16, 31, and 3 µ mole/Kg fwt, respectively. GTP, GMP. NAD, FMN, FAD, and riboflavin were found at concentrations below (3 µ mole/Kg fwt). The phloem was rich in nomilin 124 mM and limonin 176 µ mole/Kg fwt. Hesperidin, vicenin-2, sinensetin, and nobiletin were the most predominant flavonoids. In addition, several hydroxycinnamates were detected. The results of this study will increase our knowledge about the nature and the chemical composition of citrus phloem sap.

Effect of vehicles and sodium lauryl sulphate on xenobiotic permeability and stratum corneum partitioning in porcine skin.

Dermal contact with potentially toxic agricultural and industrial chemicals is a common hazard encountered in occupational, accidental spill and environmental contamination scenarios. Different solvents and chemical mixtures may influence dermal absorption. The effects of sodium lauryl sulphate (SLS) on the stratum corneum partitioning and permeability in porcine skin of 10 agricultural and industrial chemicals in water, ethanol and propylene glycol were investigated. The chemicals were phenol, p-nitrophenol, pentachlorophenol, methyl parathion, ethyl parathion, chlorpyrifos, fenthion, simazine, atrazine and propazine. SLS decreased partitioning into stratum corneum from water for lipophilic compounds, decreased partitioning from propylene glycol and did not alter partitioning from ethanol. SLS effects on permeability were less consistent, but generally decreased permeability from water, increased permeability from ethanol and had an inconsistent effect on permeability from propylene glycol. It was concluded that, for the compounds tested, partitioning into the stratum corneum was determined by the relative solubility of the solute in the donor solvent and the stratum corneum lipids. Permeability, however, reflected the result of successive, complex processes and was not predictable from stratum corneum partitioning alone. Addition of SLS to solvents altered partitioning and absorption characteristics across a range of compounds, which indicates that partition coefficients or skin permeability from neat chemical exposure should be used with caution in risk assessment procedures for chemical mixtures.

Multivariate meta-analysis of pharmacokinetic studies of ampicillin trihydrate in cattle.

OBJECTIVE: To investigate the feasibility of using multivariate cluster analysis to meta-analyze pharmacokinetic data obtained from studies of pharmacokinetics of ampicillin trihydrate in cattle and identify factors that could account for variability in pharmacokinetic parameters among studies. SAMPLE POPULATION: Data from original studies of the pharmacokinetics of ampicillin trihydrate in cattle in the database of the Food Animal Residue Avoidance Databank. PROCEDURE: Mean plasma or serum ampicillin concentration versus time data and potential factors that may have affected the pharmacokinetics of ampicillin trihydrate were obtained from each study. Noncompartmental pharmacokinetic analyses were performed, and values of pharmacokinetic parameters were clustered by use of multivariate cluster analysis. Practical importance of the clusters was evaluated by comparing the frequency of factors that may have affected the pharmacokinetics of ampicillin trihydrate among clusters. RESULTS: A single cluster with lower mean values for clearance and volume of distribution of ampicillin trihydrate administered PO, compared with other clusters, was identified. This cluster included studies that used preruminant calves in which feeding was withheld overnight and calves to which probenecid had been administered concurrently. CONCLUSIONS AND CLINICAL RELEVANCE: Meta-analysis was successful in detecting a potential subpopulation of cattle for which factors that explained differences in pharmacokinetic parameters could be identified. Accurate estimates of pharmacokinetic parameters are important for the calculation of dosages and extended withdrawal intervals after extralabel drug administration.

Harmful algal bloom characterization at ultra-high spatial and temporal resolution using small unmanned aircraft systems.

Harmful algal blooms (HABs) degrade water quality and produce toxins. The spatial distribution of HAbs may change rapidly due to variations wind, water currents, and population dynamics. Risk assessments, based on traditional sampling methods, are hampered by the sparseness of water sample data points, and delays between sampling and the availability of results. There is a need for local risk assessment and risk management at the spatial and temporal resolution relevant to local human and animal interactions at specific sites and times. Small, unmanned aircraft systems can gather color-infrared reflectance data at appropriate spatial and temporal resolutions, with full control over data collection timing, and short intervals between data gathering and result availability. Data can be interpreted qualitatively, or by generating a blue normalized difference vegetation index (BNDVI) that is correlated with cyanobacterial biomass densities at the water surface, as estimated using a buoyant packed cell volume (BPCV). Correlations between BNDVI and BPCV follow a logarithmic model, with r(2)-values under field conditions from 0.77 to 0.87. These methods provide valuable information that is complimentary to risk assessment data derived from traditional risk assessment methods, and could help to improve risk management at the local level.

Human illnesses and animal deaths associated with freshwater harmful algal blooms-Kansas.

Freshwater harmful algal bloom (FHAB) toxins can cause morbidity and mortality in both humans and animals, and the incidence of FHABs in the United States and Kansas has increased. In 2010, the Kansas Department of Health and Environment (KDHE) developed a FHAB policy and response plan. We describe the epidemiology of FHAB-associated morbidity and mortality in humans and animals in Kansas. Healthcare providers and veterinarians voluntarily reported FHAB-associated cases to KDHE. An investigation was initiated for each report to determine the source of exposure and to initiate public health mitigation actions. There were 38 water bodies with a confirmed FHAB in 2011. There were 34 reports of human and animal FHAB-associated health events in 2011, which included five dog deaths and hospitalization of two human case patients. Five confirmed human illnesses, two dog illnesses and five dog deaths were associated with one lake. Four human and seven dog cases were exposed to the lake after a public health alert was issued. Public health officials and FHAB partners must ensure continued awareness of the risks to the public, educate healthcare providers and veterinarians on FHAB-related health events and encourage timely reporting to public health authorities.

Dog and cat exposures to hazardous substances reported to the Kansas State Veterinary Diagnostic Laboratory: 2009-2012.

Pet dogs and cats in the USA are commonly exposed to potentially hazardous substances found in domestic environments. Requests for assistance and advice received by the Kansas State Veterinary Diagnostic Laboratory regarding exposures in dogs and cats to substances perceived by their caretakers to be potentially harmful included 1,616 phone calls, over a 3-year period covering 2009-2012. Enquiries occurred more often during summer. Dogs were involved in 84.7 % of calls and cats in 15.3 %. Oral exposures were reported in 95.5 % of calls, dermal exposures in 3.7 % of calls, inhalation exposures in 0.6 % of calls, and parenteral exposures in 0.2 % of calls. Therapeutic drugs were the most frequently reported substances, accounting for 35.4 % of calls, followed by household chemicals (15.5 %); foods (14.8 %); pesticides (13.9 %); plants (12 %), industrial chemicals and fertilizers (3.6 %); cosmetics and personal care products (2.8 %); and animal, insect, and microorganism toxins (2.1 %). Although requests for information or assistance are not a measure of poisoning incidence, it can provide insight regarding relative exposure rates, help to identify changing exposure trends and emerging exposures, and reflect the public concern regarding actual or apparent harmful exposures in pets.

Spatial variation of epoxyscillirosidine concentrations in Moraea pallida (yellow tulp) in South Africa.

Moraea pallida (yellow tulp) poisoning is economically the most important intoxication of livestock in South Africa. Poisoning varies according to locality, climatic conditions and growth stage of the plant. The primary objective of this study was to determine the concentration of the toxic principle, epoxyscillirosidine, in yellow tulp leaves and to ascertain the variability of epoxyscillirosidine concentrations within and between different locations. A secondary objective was to utilise Geographic Information Systems in an attempt to explain the variability in toxicity. Flowering yellow tulp plants were collected at 26 sampling points across 20 districts of South Africa. The leaves of five plants per sampling point were extracted and submitted for liquid chromatography/mass spectrometry analysis. A large variation in mean epoxyscillirosidine concentrations, ranging from 3.32 µg/g - 238.27 µg/g, occurred between different geographical regions. The epoxyscillirosidine concentrations also varied tremendously between individual plants (n = 5) collected at the same sampling point, with up to a 24 times difference between the lowest and highest concentration detected. No generalised correlation between epoxyscillirosidine concentrations and soil elemental concentrations could be established. However, samples obtained from the north-eastern part of the sampling region tended to have higher epoxyscillirosidine concentrations compared to samples obtained from the south-western part of the sampling region. Higher toxin concentrations in the north-east were associated with statistically significant higher soil concentrations of iron, bismuth, bromide, cadmium, chromium, rubidium, tellurium, thallium, titanium and zinc, whilst soil concentrations of strontium and soil pH, were significantly lower. This study corroborated the contention that epoxyscillirosidine concentration in yellow tulp fluctuates and may explain the variability in toxicity.

Investigation of a Microcystis aeruginosa cyanobacterial freshwater harmful algal bloom associated with acute microcystin toxicosis in a dog.

Microcystin poisoning was diagnosed in a dog exposed to a Microcystis aeruginosa-dominated, freshwater, harmful algal bloom at Milford Lake, Kansas, which occurred during the summer of 2011. Lake water microcystin concentrations were determined at intervals during the summer, using competitive enzyme-linked immunosorbent assays, and indicated extremely high, localized microcystin concentrations of up to 126,000 ng/ml. Multiple extraction and analysis techniques were used in the determination of free and total microcystins in vomitus and liver samples from the poisoned dog. Vomitus and liver contained microcystins, as determined by enzyme-linked immunosorbent assays, and the presence of microcystin-LR was confirmed in vomitus and liver samples using liquid chromatography coupled with tandem mass spectrometry. Major toxic effects in a dog presented for treatment on the day following exposure included fulminant liver failure and coagulopathy. The patient deteriorated rapidly despite aggressive treatment and was euthanized. Postmortem lesions included diffuse, acute, massive hepatic necrosis and hemorrhage, as well as acute necrosis of the renal tubular epithelium. A diagnosis of microcystin poisoning was based on the demonstration of M. aeruginosa and microcystin-LR in the lake water, as well as in vomitus produced early in the course of the poisoning; the presence of microcystin-LR in liver tissue; and a typical clinical course including gastroenteritis and fulminant liver failure.

Adverse health effects in Canada geese (Branta canadensis) associated with waste from zinc and lead mines in the Tri-State Mining District (Kansas, Oklahoma, and Missouri, USA).

Lead and zinc poisoning have been recorded in a variety of bird species, including migrating waterfowl such as Canada Geese (Branta canadensis), at sites contaminated with mine waste from lead and zinc mines in the Tri-State Mining District, Kansas, Oklahoma, and Missouri, USA. The adverse health impacts from mine waste on these birds may, however, be more extensive than is apparent from incidental reports of clinical disease. To characterize health impacts from mine waste on Canada Geese that do not have observable signs of poisoning, four to eight apparently healthy birds per site were collected from four contaminated sites and an uncontaminated reference site, and examined for physical and physiologic evidence of metals poisoning. Tissue concentrations of silver, aluminum, arsenic, barium, cadmium, cobalt, chromium, copper, iron, magnesium, manganese, molybdenum, nickel, lead, selenium, thallium, vanadium, and zinc were determined by inductively coupled plasma mass spectroscopy. Adverse health effects due to lead were characterized by assessing blood δ-aminolevulinic acid dehydratase (ALAD) enzyme activity. Adverse effects associated with zinc poisoning were determined from histologic examination of pancreas tissues. Elevated tissue lead concentrations and inhibited blood ALAD enzyme activities were consistently found in birds at all contaminated sites. Histopathologic signs of zinc poisoning, including fibrosis and vacuolization, were associated with elevated pancreatic zinc concentrations at one of the study sites. Adverse health effects associated with other analyzed elements, or tissue concentrations indicating potentially toxic exposure levels to these elements, were not observed.

Dibucaine toxicosis in a dog.

INTRODUCTION: Dibucaine is a potent, long-lasting local anesthetic (LA). Topical dibucaine ointments are marketed directly to consumers in the USA without prescription. Dibucaine ointment is intended to treat discomfort associated with sunburn, eczema, minor rashes, minor scratches, insect bites, and poison ivy and is used alone or in combination with other active ingredients to treat pain associated with hemorrhoids or other anorectal disorders. Oral dibucaine toxicosis has been reported in children and includes gastrointestinal upset and neurologic and cardiovascular dysfunction. CASE REPORT: An 18-month-old, female, Parson Russell terrier ingested approximately 23 g of 1% dibucaine ointment (approximately 38 mg/kg dibucaine) recommended to the owner for the treatment of hemorrhoids. Onset and resolution of clinical signs were relatively rapid, 5 min and 60 min, respectively. Clinical signs included vomiting, ptyalism, whole-body muscle fasciculations, disorientation, and severe ataxia. DISCUSSION: Oral dibucaine toxicosis in dogs is similar to oral dibucaine toxicosis in children. Dibucaine ointment poses a real and potentially serious toxicological risk to pets and thus should be stored in a safe location.