Paula M. Imerman

Aflatoxicosis in nine dogs after exposure to contaminated commercial dog food

The purpose of this study was to characterize light and electron microscopic findings from 9 dogs that had consumed aflatoxin-contaminated commercial dog food from recalled batches. Four dogs died and 5 were euthanized after signs of liver failure. Analysis of feed and liver samples confirmed exposure to aflatoxin. Of the 9 dogs, 8 had classic signs of liver failure, and 1 had signs of liver failure. Enlarged, pale yellow livers were seen macroscopically at necropsy in the dogs with subacute hepatopathy, and cirrhosis was noted in the dog with chronic hepatopathy. Histopathologic findings included hepatic lipidosis, portal fibroplasia, and biliary hyperplasia, which supported a diagnosis of subacute toxic hepatopathy in the 8 symptomatic animals. Marked lobular atrophy, bridging portal fibrosis, and regenerative hepatocellular nodules characterized the dog with chronic hepatopathy. Electron microscopy revealed marked hepatocellular lipid vacuolation and early fibroplasia in the dogs with acute hepatopathy and marked fibrosis and regeneration in the dog with chronic hepatopathy. Analysis of feed for aflatoxin consistently revealed high levels of aflatoxin B1 (range of 223–579 ppb), and hepatic tissue contained elevated levels of aflatoxin B1metabolite M1 (0.6–4.4 ppb). Although dogs are not commonly affected by aflatoxicosis, they are highly susceptible and can present with classic signs of acute or chronic hepatopathy. Characteristic gross, histologic, and electron microscopic changes help pathologists determine a presumptive toxic insult. Detecting aflatoxins or their metabolites in feed or liver specimens can help confirm the diagnosis of aflatoxicosis.

Lead Contamination of Chicken Eggs and Tissues from a Small Farm Flock

Twenty mixed-breed adult laying hens from a small farm flock in Iowa were clinically normal but had been exposed to chips of lead-based paint in their environment. These chickens were brought to the Iowa State University Veterinary Diagnostic Laboratory, Ames, Iowa, where the concentration of lead in blood, eggs (yolk, albumen, and shell), and tissues (liver, kidney, muscle, and ovary) from 5 selected chickens was determined over a period of 9 days. Blood lead levels ranged from less than 50 to 760 ppb. Lead contamination of the yolks varied from less than 20 to 400 ppb, and shells were found to contain up to 450 ppb lead. Albumen contained no detectable amount. Lead content of the egg yolks strongly correlated with blood lead levels. Deposition of lead in the shells did not correlate well with blood lead levels. Mean tissue lead accumulation was highest in kidneys (1,360 ppb), with livers ranking second (500 ppb) and ovarian tissue third (320 ppb). Muscle contained the lowest level of lead (280 ppb). Lead contamination of egg yolks and edible chicken tissues represents a potential public health hazard, especially to children repeatedly consuming eggs from contaminated family-owned flocks.

Assessment of ruminal hydrogen sulfide or urine thiosulfate as diagnostic tools for sulfur induced polioencephalomalacia in cattle

To determine if ruminal hydrogen sulfide, urine thiosulfate, or blood sulfhemoglobin could be used as diagnostic indicators for sulfur-induced polioencephalomalacia, 16 steers (8 cannulated, 368 ± 12 kg; 8 unmodified, 388 ± 10 kg; mean ± standard error) were fed 1 of 2 dietary treatments. Diets consisted of a low sulfate (0.24% S; control) wheat midd–based pellet or the control pellet with sodium sulfate added to achieve a high-sulfate (0.68% S) pellet. As designed, intake did not differ (P = 0.80) between treatments. At 8 hr postfeeding, ruminal hydrogen sulfide was not affected by cannulation (P = 0.35) but was greater (P < 0.01) in high S (6,005 ± 475 mg/l) than control (1,639 ± 472 mg/l) steers. Time of day of sampling affected (P = 0.01) ruminal hydrogen sulfide, with peak concentrations occurring 4–12 hr after feeding. Urine was collected prefeeding (AM) and 7–9 hr postfeeding (PM). Urine thiosulfate concentrations of high S steers sampled in the PM were greater (P > 0.01) than in the AM. However, there was no difference due to time of sampling for control. In both the AM and PM, urine thiosulfate concentrations of high S were greater (P > 0.01) than control. Although hydrogen sulfide and thiosulfate were elevated by increased dietary S intake, a concentration at which polioencephalomalacia is likely to occur could not be determined. Sampling urine for thiosulfate or rumen gas for hydrogen sulfide of nonsymptomatic pen mates 4–8 hr after feeding may be useful to assess sulfur exposure and differentiate between causes of polioencephalomalacia.

Effects of temperature, incubation period and substrate on production of fusaproliferin by Fusarium subglutinans ITEM 2404.

The kinetics of the production of fusaproliferin by Fusarium subglutinans ITEM 2404 in maize and rice cultures was investigated at various incubation temperatures. The growth rate of F. subglutinans was highest at 20 degrees C and 25 degrees C in maize cultures and at 15 degrees C in rice cultures. Although the growth rate was higher in rice than in maize, the maximal production of fusaproliferin was obtained in maize cultures, with a maximum yield (4309 microg g(-1)) at 20 degrees C for 6 weeks. In rice cultures the optimal incubation regimen was at 15 degrees C for 6 weeks, with a fusaproliferin level of 1557 microg g(-1). The production of fusaproliferin at 25 degrees C and 30 degrees C in both substrates was very low, with maximal yield at 25 degrees C of 979 microg g(-1) after 2 weeks and 143 microg g(-1) after 3 weeks in maize and rice cultures, respectively.

Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms

Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a therapeutic approach that shows promise in the treatment of onchocerciasis and lymphatic filariasis. Here we demonstrate the use of a biodegradable polyanhydride nanoparticle-based platform for the co-delivery of the antibiotic doxycycline with the antiparasitic drug, ivermectin, to reduce microfilarial burden and rapidly kill adult worms. When doxycycline and ivermectin were co-delivered within polyanhydride nanoparticles, effective killing of adult female Brugia malayi filarial worms was achieved with approximately 4,000-fold reduction in the amount of drug used. Additionally the time to death of the macrofilaria was also significantly reduced (five-fold) when the anti-filarial drug cocktail was delivered within polyanhydride nanoparticles. We hypothesize that the mechanism behind this dramatically enhanced killing of the macrofilaria is the ability of the polyanhydride nanoparticles to behave as a Trojan horse and penetrate the cuticle, bypassing excretory pumps of B. malayi, and effectively deliver drug directly to both the worm and Wolbachia at high enough microenvironmental concentrations to cause death. These provocative findings may have significant consequences for the reduction in the amount of drug and the length of treatment required for filarial infections in terms of patient compliance and reduced cost of treatment.

Effects of nicotine on pulmonary surfactant proteins A and D in ovine lung epithelia.

Maternal smoking during pregnancy increases the incidence and severity of respiratory infections in neonates. Surfactant proteins A and D (SP‐A and SP‐D, respectively) are components of pulmonary innate immunity and have an important role in defense against inhaled pathogens. The purpose of this study was to determine if nicotine exposure during the third trimester of pregnancy alters the expression of SP‐A and SP‐D of fetal lung epithelia. Pregnant ewes were assigned to four groups; a nicotine‐exposed full‐term and pre‐term group, and control full‐term and pre‐term group. Lung tissue was collected for Western blot and IHC analysis of SP‐A level, Western blot analysis of SP‐D level and qPCR analysis of SP‐A and SP‐D mRNA expression. Exposure to nicotine significantly decreased SP‐A gene expression (P = 0.01) and SP‐A protein level in pre‐term lambs. This finding suggests that maternal nicotine exposure during the last trimester of pregnancy alters a key component of lung innate immunity in offspring. Pediatr Pulmonol. 2010; 45:255–262.

Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide–induced neurotoxicity and neurological sequelae

Hydrogen sulfide (H2S) is a highly neurotoxic gas. It is the second most common cause of gas‐induced deaths. Beyond mortality, surviving victims of acute exposure may suffer long‐term neurological sequelae. There is a need to develop countermeasures against H2S poisoning. However, no translational animal model of H2S‐induced neurological sequelae exists. Here, we describe a novel mouse model of H2S‐induced neurotoxicity for translational research. In paradigm I, C57/BL6 mice were exposed to 765 ppm H2S for 40 min on day 1, followed by 15‐min daily exposures for periods ranging from 1 to 6 days. In paradigm II, mice were exposed once to 1000 ppm H2S for 60 minutes. Mice were assessed for behavioral, neurochemical, biochemical, and histopathological changes. H2S intoxication caused seizures, dyspnea, respiratory depression, knockdowns, and death. H2S‐exposed mice showed significant impairment in locomotor and coordinated motor movement activity compared with controls. Histopathology revealed neurodegenerative lesions in the collicular, thalamic, and cortical brain regions. H2S significantly increased dopamine and serotonin concentration in several brain regions and caused time‐dependent decreases in GABA and glutamate concentrations. Furthermore, H2S significantly suppressed cytochrome c oxidase activity and caused significant loss in body weight. Overall, male mice were more sensitive than females. This novel translational mouse model of H2S‐induced neurotoxicity is reliable, reproducible, and recapitulates acute H2S poisoning in humans.

Sodium fluoride/copper naphthenate toxicosis in cattle.

Fourteen cattle on a Kansas pasture died from ingestion of a wood preservative compound containing sodium fluoride and copper naphthenate. Clinical signs included depression, anorexia, ataxia, diarrhea, and recumbency. Grossly visible lesions included perirenal edema, pale kidneys, and forestomach ulceration. All 3 cows that had postmortem evaluations had extensive renal cortical tubular necrosis. Tissue concentrations of fluoride were slightly elevated above expected background levels, while copper tissue concentrations were not elevated. The findings indicated that the sodium fluoride caused renal tubular necrosis leading to renal failure. Copper naphthenate may have contributed to abomasal ulceration; however, tissue copper concentrations indicated that copper from the formulation was not appreciably absorbed from the gastrointestinal tract.

Quality of veterinary pharmaceuticals and their use by pastoralists in the Far North Region of Cameroon

This study evaluates the quality of the veterinary drugs most frequently used in the Far North Region of Cameroon and describes how pastoralists use them to treat their cattle herds. High-performance liquid chromatography was used to identify and quantify the active ingredients in the drugs (penicillin G, levamisole, oxytetracycline, diminazene diaceturate, vitamin A, and vitamin E acetate) and gas chromatography mass spectrometry to determine if organic chemical contaminants were present. The results showed that 69% of surveyed pastoralists used veterinary medicines to treat common illnesses. In addition, the most commonly used medications (procaine penicillin G and oxytetracycline) were used in a manner inconsistent with the recommended dosage, frequency, duration, and withdrawal period by 98% of the pastoralists. However, contrary to previous studies, the quality of the medications used by pastoralists was generally good. The poor compliance with recommended treatment protocols was much more prevalent than use of poor quality medications and presents a potential for treatment failure, drug resistance of animal pathogens, and harmful drug residues in the human food supply, all of which have potentially negative consequences for animal and human health.

Mycotoxin and metallic element concentrations in peanut products sold in Ugandan markets

Abstract The increasing prevalence of cancer among Ugandans has aroused consumer concerns about food-borne carcinogens. This study sought to compare mycotoxin and metallic element concentrations in processed peanuts sold in selected markets in Kampala, Uganda to those traditionally prepared in homes. Market-processed peanut samples (n = 33) were purchased from four markets. Control samples (n = 5) were unground peanuts bought from markets but processed in homes by traditional methods. Aflatoxins B1, B2, G1, G2; Fumonisins; Deoxynivalenol, Nivalenol, Ochratoxin A, T2 toxin, Zearalenone, and Zearalenol were analyzed by LC/MS/MS while As, B, Ba, Cd, Cr, Cu, Hg, Mg, Ni, Pb and Zn were analyzed by ICP/MS. The data was statistically analyzed using Wilcoxon scores (rank sums) or the Kruskal-Wallis test. Aflatoxins were the predominant mycotoxins found in significant amounts. 55 and 34% of the samples had concentrations of total aflatoxins greater than 20 ppb (FDA acceptable limit). There were significantly higher concentrations of aflatoxins in market-processed than in home-processed samples. Metallic element concentrations were generally below FDA maximum acceptable concentrations. Roasting and duration of grinding had no significant effect on aflatoxin or metallic element concentrations. There is a need for food-borne toxicant monitoring of food sold in public markets in Uganda.