Anticoagulant rodenticide toxicity in dogs: A retrospective study of 349 confirmed cases in Saskatchewan.

Objective: To evaluate the signalment and clinical, laboratory, treatment, and outcome features of dogs diagnosed with anticoagulant rodenticide (AR) intoxication in Saskatchewan. Animals: We studied 349 dogs. Procedure: Medical records from the Veterinary Medical Centre (Saskatoon, Saskatchewan) between 1999 and 2022 were reviewed. Cases were included if they met at least 1 of the following criteria: owner witnessed the dog ingesting an AR; AR was seen in the vomitus when emesis was induced; the dog had clinical signs of coagulopathy, with elevation of PT ± aPTT that normalized after vitamin K1 therapy, in the presence of appropriate clinical and paraclinical data and the absence of other causes of hypocoagulable state determined by the primary clinician. Results: Fifty-three percent of cases were seen between July and October. Most dogs (61%) came from an urban setting. Ninety-two percent of dogs ingested a 2nd-generation AR and the most frequent toxin was bromadiolone. Clinical signs were reported in 30% of AR intoxications and included lethargy (86%), dyspnea (55%), and evidence of external hemorrhage (44%). The most common site of hemorrhage was the pleural space, accounting for 43% of hemorrhage sites. Consumptive thrombocytopenia was reported in 24% of dogs with evidence of AR-induced hemorrhage, with moderate (platelet count < 60 K/µL) and marked (< 30 K/µL) thrombocytopenia in 7/12 and 2/12 dogs, respectively. Blood products were administered to 84% of dogs with AR-induced hemorrhage; the most common product administered was fresh frozen plasma (56% of cases). Among dogs with AR-induced hemorrhage, those that received blood products were more likely to survive to discharge (81%) compared to those that did not (19%) (P = 0.017). Eighty-six percent of dogs with AR-induced hemorrhage survived to discharge. Conclusion and clinical relevance: The pleural space was the most common site of hemorrhage. Moderate thrombocytopenia was a common finding. Eighty-six percent of dogs with AR-induced hemorrhage survived to discharge.

Toxicité des rodenticides anticoagulants chez les chiens : étude rétrospective de 349 cas confirmés en Saskatchewan. Objectif: Évaluer le signalement et les caractéristiques cliniques, de laboratoire, de traitement et de résultats des chiens diagnostiqués avec une intoxication par un rodenticide anticoagulant (AR) en Saskatchewan. Animaux: Nous avons étudié 349 chiens. Procédure: Les dossiers médicaux du Veterinary Medical Centre (Saskatoon, Saskatchewan) entre 1999 et 2022 ont été examinés. Les cas ont été inclus s'ils répondaient à au moins 1 des critères suivants : le propriétaire a vu le chien ingérer un AR; de l'AR a été observée dans les vomissures lorsque des vomissements ont été provoqués; le chien présentait des signes cliniques de coagulopathie, avec une élévation du PT ± aPTT qui s'est normalisée après un traitement par la vitamine K1, en présence de données cliniques et paracliniques appropriées et en l'absence d'autres causes d'état hypocoagulable déterminées par le clinicien initial. Résultats: Cinquante-trois pour cent des cas ont été observés entre juillet et octobre. La plupart des chiens (61 %) venaient d'un milieu urbain. Quatre-vingt-douze pour cent des chiens ont ingéré un AR de 2e génération et la toxine la plus fréquente était la bromadiolone. Des signes cliniques ont été rapportés dans 30 % des intoxications par AR et incluaient de la léthargie (86 %), de la dyspnée (55 %) et des signes d'hémorragie externe (44 %). Le site d'hémorragie le plus fréquent était l'espace pleural, représentant 43 % des sites d'hémorragie. Une thrombocytopénie de consommation a été rapportée chez 24 % des chiens présentant des signes d'hémorragie induite par l'AR, avec une thrombocytopénie modérée (nombre de plaquettes < 60 K/µL) et marquée (< 30 K/µL) chez 7 chiens sur 12 et 2 chiens sur 12, respectivement. Des produits sanguins ont été administrés à 84 % des chiens présentant une hémorragie induite par l'AR; le produit le plus fréquemment administré était le plasma frais congelé (56 % des cas). Parmi les chiens présentant une hémorragie induite par l'AR, ceux qui ont reçu des produits sanguins étaient plus susceptibles de survivre jusqu'à leur congé (81 %) que ceux qui n'en ont pas reçu (19 %) (P = 0,017). Quatre-vingt-six pour cent des chiens présentant une hémorragie induite par l'AR ont survécu jusqu'à leur sortie. Conclusion et pertinence clinique: L'espace pleural était le site d'hémorragie le plus fréquent. Une thrombocytopénie modérée était fréquente. Quatre-vingt-six pour cent des chiens présentant une hémorragie induite par l'AR ont survécu jusqu'à leur sortie.(Traduit par Dr Serge Messier).

Effect of continuous or intermittent feeding of ergot contaminated grain in a mash or pelleted form on the performance and health of feedlot beef steers.

This study evaluated the effect of feeding ergot contaminated grain continuously or intermittently through backgrounding (BG) and finishing (FN) in a mash or pelleted supplement on the growth performance, health and welfare parameters, and carcass characteristics of feedlot beef steers. Sixty black Angus steers (300 ±â€…29.4 kg BW) were used in a complete randomized 238-d study. Steers were stratified by weight and randomly assigned to four different diets (15 steers/treatment) and individually housed. Treatments included: (1) control [CON; no added ergot alkaloids (EA)], (2) continuous ergot mash (CEM; fed continuously at 2 mg total EA/kg of DM), (3) intermittent ergot mash (IEM; fed at 2 mg total EA/kg of DM, during the first week of each 21-d period and CON for the remaining 2 wk, this feeding pattern was repeated in each period), and (4) intermittent ergot pellet (IEP; fed at 2 mg of total EA/kg of DM as a pellet during the first week of each 21-d period and CON for the remaining 2 wk as described for IEM). Steers were fed barley based BG diets containing 40% concentrate:60% silage (DM basis) for 84 d (four 21-d periods), transitioned over 28 d (no ergot fed) to an FN diet (90% concentrate:10% silage DM basis) and fed for 126 d (six 21-d periods) before slaughter. In the BG phase, steer DMI (P < 0.01, 7.45 vs. 8.05 kg/d) and ADG (P < 0.01) were reduced for all EA diets compared to CON. The CEM fed steers had lower ADG (P < 0.01, 0.735 vs. 0.980 kg) and shrunk final BW (P < 0.01, 350 vs. 366 kg) than CON. CEM had lower gain:feed (P < 0.07, 0.130 vs. 0.142) than CON. In the FN phase, steer DMI (P < 0.01, 9.95 vs. 11.05 kg/d) and ADG (P = 0.04) were also decreased for all EA fed steers compared to CON. Total shrunk BW gain (P = 0.03, 202.5 vs. 225.2 kg), final BW (P = 0.03, 617.9 vs. 662.2 kg), and carcass weight (P = 0.06) decreased for all EA fed steers compared to CON. The percentage of AAA carcasses decreased for all EA fed steers (P < 0.01, 46.7 vs. 93.3%) compared to CON. EA fed steers had increased rectal temperatures (P < 0.01, 39.8 vs. 39.4 °C) compared to CON. Pelleting ergot contaminated grain did not reduce the impact of ergot alkaloids on any of the measured parameters during BG or FN. Continuously or intermittently feeding ergot contaminated diets (2 mg total EA/kg of DM) significantly reduced intake, growth performance, and carcass weight, with minimal impact on blood parameters in feedlot steers. Pelleting was not an effective method of reducing ergot toxicity.

Produced by the fungus Claviceps purpurea, ergot alkaloids (EA) are toxic to beef cattle when consumed and can lead to reduction in feed intake and growth performance, vasoconstriction of the blood vessels, hyperthermia, damage to extremities (ears, tails, and hooves) and in severe cases, death. Grain is often cleaned to meet quality standards, and the resulting screenings are often utilized for feeding livestock and can have high concentrations of EA. The application of heat during pelleting of EA contaminated grain has been suggested to reduce its toxicity. Backgrounding and finishing beef cattle feeding experiments were conducted to assess the effect of continuously or intermittently feeding EA contaminated grain (2 mg/kg of diet DM) either as a pellet or as mash on growth performance, health, and animal welfare. Feeding EA grain continuously or intermittently either as a mash or pellet drastically reduced growth performance of steers, with no difference between treatments.

The C-8-S-isomers of ergot alkaloids - a review of biological and analytical aspects.

Ergot alkaloids are secondary metabolites that are produced by fungi and contaminate cereal crops and grasses. The ergot alkaloids produced by Claviceps purpurea are the most abundant worldwide. The metabolites exist in two configurations, the C-8-R-isomer (R-epimer) and the C-8-S-isomer (S-epimer). These two configurations can interconvert to one another. Ergot alkaloids cause toxic effects after consumption of ergot-contaminated food and feed at various concentrations. For bioactivity reasons, the C-8-R-isomers have been studied to a greater extent than the C-8-S-isomer since the C-8-S-isomers were considered biologically inactive. However, recent studies suggest the contrary. Analytical assessment of ergot alkaloids now includes the C-8-S-isomers and high concentrations of specific C-8-S-isomers have been identified. The inclusion of the C-8-S-isomer in regulatory standards is reviewed. This review has identified that further research into the C-8-S-isomers of ergot alkaloids is warranted. In addition, the inclusion of the C-8-S-isomers into regulatory recommendations worldwide for food and feed should be implemented. The objectives of this review are to provide an overview of historic and current studies that have assessed the C-8-S-isomers. Specifically, this review will compare the C-8-R-isomers to the C-8-S-isomers with an emphasis on the biological activity and analytical assessment.

The Impact of Storage Temperature and Time on Ergot Alkaloid Concentrations.

Ergot sclerotia produce toxic secondary metabolites, ergot alkaloids, that infect cereal crops and grasses. Ergot alkaloids have two isomeric configurations: the C-8-R-isomer (R-epimer), and the C-8-S-isomer (S-epimer). Ergot contaminated matrices, such as cereal grains or grasses, may be stored for extended periods at various temperatures before being analyzed, utilized, or consumed. This study assessed the concentration of six common ergot alkaloids in both configurations found in naturally contaminated wheat over time (one, two, and four months) at different temperatures (room temperature, +4 °C, and -20 °C) using ultra-high-performance liquid chromatography-tandem mass spectrometry. The data indicate that the total ergot concentration within a natural contaminated sample varies over time at room temperature, +4 °C, and -20 °C. The total ergot concentration increased until month two, and decreased at month four, independent of temperature (p < 0.05). The total R-epimer concentration appeared to be less stable over time than the total S-epimer concentration. The changes in the total R and total S-epimer concentrations may have been caused by changes in the ergocristine and ergocristinine concentrations, respectively. Time and temperature should be considered when storing potentially contaminated matrices in a laboratory or practical agriculture situations. Quantification of ergot contaminated matrices should occur prior to their use to ensure the most reliable estimates of the concentration of ergot.

Effect of increasing concentration of ergot alkaloids in the diet of feedlot cattle: performance, welfare, and health parameters.

This study was designed to evaluate the effects of feeding increasing dietary concentrations of ergot alkaloids from cereal grains (EA; 0, 0.75, 1.5, 3.0 mg/kg of dietary DM) to feedlot cattle over backgrounding (BG) and finishing (FS) phases on health, welfare, and growth performance. Two hundred and forty commercial steers (280 ±â€…32 kg BW) were stratified by weight and randomly allocated to 16 pens (15 steers/pen), 4 of which were equipped with the GrowSafe system (1 pen/treatment) to measure individual feed intake. Each pen was randomly assigned to a treatment (n = 4/treatment). Treatments included 1) control (CTRL), no added EA; 2) CTRL + 0.75 mg/kg EA (EA075); 3) CTRL + 1.5 mg/kg EA (EA150); and 4) CTRL + 3.0 mg/kg EA (EA300). Steers were fed barley-based BG diets containing 40% concentrate: 60% silage (DM basis) for 84 d. Steers were then transitioned over 28 d to an FS diet (90% concentrate: 10% silage DM basis) and fed for 119 d before slaughter. The diet fed to EA300 steers was replaced with the CTRL diet after 190 d on feed (DOF), due to EA-induced hyperthermia starting at 165 DOF. In the BG phase, average meal length (P = 0.01) and size (P = 0.02), daily feeding duration (P = 0.03), final body weight (BW; P = 0.03), and total BW gain (P = 0.02) linearly decreased with increasing EA levels, while gain to feed (G:F) responded quadratically (P = 0.04), with EA150 having the poorest value. Increasing concentrations of EA in the diet linearly increased rectal temperature (P < 0.01) throughout the trial. Over the full FS phase, a quadratic response was observed for ADG (P = 0.05), final BW (P = 0.05), total BW gain (P = 0.02), and carcass weight (P = 0.05) with steers fed EA150 having the lowest performance, as EA300 steers were transferred to CTRL diet after 190 DOF. Dressing percentage (P = 0.02) also responded quadratically, with the lowest values observed for EA300. Thus, EA reduced ADG during BG and FS phases, although more prominently in FS, likely due to increased ambient temperatures and high-energy diet in FS triggering hyperthermia. When EA300 steers were transferred to the CTRL diet, compensatory gain promoted higher hot carcass weight (HCW) when compared with steers fed EA150. In conclusion, feeding feedlot steers diets with > 0.75 mg/kg EA caused reductions in performance and welfare concerns, although this breakpoint may be affected by duration of feeding, environmental temperatures, and EA profiles in the feed.

Ergot alkaloids (EA) are produced by a parasitic fungus (Claviceps purpurea) during the cereal grain growth cycle. Feeding cereal grain containing EA to beef cattle can cause constriction of blood vessels, hyperthermia, gangrene of extremities (ears, hoof, and tail), reduced feed intake and growth, and even death. Feed cleaning and processing technologies have been developed to remove EA from the human food chain, thus diverting contaminated feed for livestock use. We performed a beef cattle feedlot experiment to evaluate the impact of increasing levels of EA (0, 0.75, 1.50, 3.00 mg/kg of diet DM) on performance, health, and welfare. Steers fed 3.0 mg/kg of EA were transferred to the control diet (without EA) in the last half of finishing due to toxicity (hyperthermia). As EA levels increased, growth rate throughout the backgrounding and finishing phases decreased, while rectal temperatures increased and altered feeding behaviors occurred. Steers removed from 3 mg/kg EA diet exhibited compensatory gain, but their respiratory rate remained elevated 50 d after EA were last consumed.

Blood and Hand Surface Lead in Veterinary Workers Using Lead Shielding During Diagnostic Radiography.

OBJECTIVES: The objectives are to compare lead blood concentrations in veterinary workers using lead shielding with concentrations in a control population, to measure hand surface lead before and after use of shielding, and to compare hand surface lead with and without the use of disposable gloves worn under hand shielding. METHODS: Blood and hand wipe samples were analyzed for lead using inductively coupled plasma mass spectrometry. RESULTS: There was no difference in blood lead between exposed and control groups. After lead glove use, 69% (18/26) of hand surface lead samples from workers not using disposable gloves were greater than 500 µg, 42% (11/26) were greater than 1000 µg, and 12% (3/26) were greater than 2000 µg. CONCLUSIONS: If lead shielding use is unavoidable, disposable gloves should be worn, and skin should be decontaminated after use.

Investigation of the relationship between ergocristinine and vascular receptors.

Ergot alkaloids are secondary metabolites that exist in two configurations, the C-8-R-isomer (R-epimer), and the C-8-S-isomer (S-epimer). Toxic effects of ergot, such as vasoconstriction, have been primarily attributed to the R-epimer bioactivity, as compared to the S-epimer. Recent studies demonstrated potential bioactivity of S-epimers. Therefore, further cost-effective investigations of the S-epimers are needed. The present study investigated the S-epimer - vascular receptor binding relationship. An in silico molecular docking approach, utilizing AutoDock Vina and DockThor, was used to determine if the S-epimer (ergocristinine) binds to vascular receptors and to compare the binding affinity and interactions to the corresponding R-epimer (ergocristine) and a structural analogue (lysergic acid amide). The binding energy (kcal/mol) of ergocristinine was - 9.7 or - 11.0 to the serotonin (5-HT) 2 A receptor and - 8.7 or - 11.4 to the alpha 2 A adrenergic receptor, depending on the software used. A hydrogen bond was formed between ergocristinine and amino acid residues of the 5-HT 2 A and alpha 2 A adrenergic receptor binding sites, with bond lengths of 3.10 Å and 3.28 Å, respectively. Binding affinities and molecular interactions among the ligands to each receptor differed. Different affinities and interactions may relate to differences in the chemical structures. The binding affinities and strong molecular interactions of the S-epimer to vascular receptors may contribute to the observed physiological manifestations that occur after ergot alkaloid exposure. The results of the present study suggest further investigation on the receptor binding of the S-epimers of ergot alkaloids.

Chronic ergot exposure in adult bulls suppresses prolactin but minimally impacts results of typical breeding soundness exams.

Canadian standards allow ≤3000 µg ergot alkaloids/kg cattle feed. A concentration-response relationship was hypothesized between ergot in feed and reductions in plasma prolactin, sperm motility, sperm function, and increase in sperm abnormalities. The study consisted of pre-treatment (12 weeks), treatment (9 weeks), and post-treatment periods (10 weeks). Adult bulls were fed 1113 (n = 8; low ergot group) or 2227 (n = 6; high) µg/kg of dry matter intake. Endpoints were measured every two weeks. Ejaculates were analyzed for sperm concentration, total and progressive motility, plasma membrane and acrosome integrity, mitochondrial membrane potential and sperm abnormalities. Data were analyzed by repeated measures MIXED PROC in SAS. Average outside ambient temperature during the pre-treatment, treatment, and post-treatment periods was -13 (-31 to 1), 0.5 (-18 to 19), and 21 (13-28) °C. Plasma prolactin decreased markedly during treatment (-52.4%; Experimental period p < 0.01). Rectal temperature increased during the treatment and post-treatment periods (EP p < 0.01) but was within the normal physiological range. Bull weight increased during the study (EP p < 0.01). Scrotal circumference in low ergot group increased during treatment (+0.8 cm; Tx∗EP p = 0.05). Progressive motility in high ergot group decreased during treatment (-7%; Tx∗EP p = 0.05), however, semen volume and sperm concentrations were unaffected (p ≥ 0.11). Live sperm with high and medium MMP decreased during treatment (-1.4 and -3.7%; EP p < 0.01). Results suggest that feeding ≤2227 µg ergot alkaloids/kg has only minor effects on adult bull semen quality.

Effects of Heating, Pelleting, and Feed Matrix on Apparent Concentrations of Cereal Ergot Alkaloids in Relation to Growth Performance and Welfare Parameters of Backgrounding Beef Steers.

As the contamination of cereal grains with ergot has been increasing in Western Canada, studies were undertaken to evaluate the impacts of heating (60, 80, 120, or 190 °C) alone or in combination with pelleting on concentrations of ergot alkaloids. Fifteen samples of ergot-contaminated grain from Alberta and Saskatchewan were assayed for R and S epimers of six alkaloids (ergocryptine, ergocristine, ergocornine, ergometrine, ergosine, and ergotamine) using HPLC MS/MS. Five samples with distinct alkaloid profiles were then selected for heating and pelleting studies. Heating resulted in a linear increase (p < 0.05) of total R and total S epimers with increasing temperature, although some individual R epimers were stable (ergometrine, ergosine, ergotamine). Pelleting also increased (p < 0.05) concentrations of total R and total S epimers detected, although ergometrine concentration decreased (p < 0.05) after pelleting. A feeding study arranged in a 2 × 2 factorial structure used 48 backgrounding Angus-cross steers fed four different diets: (1) Control Mash (CM, no added ergot), (2) Control Pellet (CP), (3) Ergot Mash (EM), or (4) Ergot Pellet (EP). Pelleting heated the ergot to 90−100 °C under 4 bars pressure, but the ergot used in the feeding study was not otherwise heated. Alkaloid concentrations of EM and EP varied by up to 1.1 mg/kg depending on the feed matrix assayed. No differences among treatments were noted for growth performance, feed intake, feed conversion, concentrations of serum prolactin and haptoglobin, hair cortisol, or in temperatures of extremities measured by infrared thermography. The only negative impacts of ergot alkaloids were on blood parameters indicative of reduced immune function or chronic inflammation. Pelleting did not heighten the negative clinical outcomes of ergot, although alkaloid concentrations of pelleted feed increased depending on the matrix assayed. It was hypothesized that the heat and pressure associated with pelleting may enhance the recovery of alkaloids from pelleted feed.

Sustained vascular contractile response induced by an R- and S-epimer of the ergot alkaloid ergocristine and attenuation by a noncompetitive antagonist.

Vasoconstriction is a known effect associated with ergot alkaloid consumption. The vascular contractile responses are often sustained for an extended period after exposure. Ergot alkaloids exist in two molecular configurations, the C-8-(R)-isomer (R-epimer) and the C-8-(S)-isomer (S-epimer). The sustained vascular contractile response to the R-epimers has been studied previously, unlike the S-epimers which are thought to be biologically inactive. Additionally, antagonists have been utilized to attenuate the vascular contraction associated with the R-epimers of ergot alkaloids utilizing ex vivo techniques. This study utilized an arterial tissue bath to examine and compare the sustained vascular contractile response attributed to ergocristine (R) and ergocristinine (S) using dissected bovine metatarsal arteries. The contractile blocking effect of a noncompetitive alpha-adrenergic antagonist, phenoxybenzamine (POB), was also investigated in precontracted arteries. Arteries (n = 6/epimer) were exposed to a single dose of ergocristine or ergocristinine (1 × 10-6 M in buffer). Each of the epimer doses was followed by a POB (1 × 10-3 M) or methanol (control) treatment at 90 min and the response was observed for another 90 min. Both epimers produced a sustained contractile response over the 180-min incubation period in the control groups. The R-epimer caused a greater sustained contractile response from 60 to 180 min post epimer exposure, compared to the S-epimer (P < 0.05, generalized estimating equations, independent t-test). Phenoxybenzamine caused a decrease in the contractile response induced by ergocristine and ergocristinine from 105 to 180 min, compared to the control (P < 0.05, generalized estimating equations, paired t-test). Overall, these results demonstrate the presence of a sustained vascular contractile response attributed to the R- and S-epimer of an ergot alkaloid with differences in contractile response between the epimers, suggesting differences in receptor binding mechanisms. Furthermore, this study demonstrated that a noncompetitive antagonist could attenuate the sustained arterial contractile effects of both ergot configurations ex vivo. Additional investigation into S-epimers of ergot alkaloids is needed. This research contributes to the understanding of the ergot epimer-vascular receptor binding mechanisms, which may support the investigation of different approaches of minimizing ergot toxicity in livestock.

Ergot alkaloids cause blood vessels to contract when contaminated feed is consumed by animals. Vascular contraction often remains for a prolonged period and involves the binding of ergot to specific receptors in the blood vessels. This study assessed and compared the sustained contraction of cow arteries after exposure to two forms of an ergot alkaloid, namely, ergocristine and ergocristinine. The effects of a specific receptor blocker, phenoxybenzamine, on the vascular contraction induced by these forms were also examined. This study showed that both forms of ergot caused a sustained contraction of cow arteries but to different magnitudes. Differences in contraction could be related to differences in how each form of ergot binds to receptors. The receptor blocker decreased the sustained contractile response of both forms of ergot. Further understanding of how the different forms of ergot bind to receptors, and how to decrease the adverse effects, may help mitigate the toxic effects of ergotism.

Ammonization of the R- and S-Epimers of Ergot Alkaloids to Assess Detoxification Potential.

Detoxification of ergot-contaminated feed by ammonia would be a practical application, given that ammonia is routinely used in the agriculture industry. To assess the effects of ammonia on ergot alkaloids, natural ergot-contaminated wheat was ammoniated. The total concentration of ergot alkaloids (R- and S-epimers) decreased after exposure to ammonia (8-29%). Separately, the total R-epimers decreased in concentration (40-66%), whereas the total S-epimers increased (21-81%). Specific ergot alkaloids demonstrated degradation and/or epimerization after exposure to ammonia, potentially associated with structural differences, and influenced the total concentrations observed. Ammonization of ergot standards resulted in potential degradation products and epimerization, supporting the above results. The use of ultrahigh-performance liquid chromatography-tandem mass spectrometry provides an updated assessment of the detoxification potential of ammonia for ergot alkaloids and the quantification of the S-epimers. Ammonia alters the R- and S-epimers of ergot alkaloids, which may lead to a potential practical detoxification process of ergot-contaminated feed.

Effect of ergot alkaloids and a mycotoxin deactivating product on in vitro ruminal fermentation using the Rumen simulation technique (RUSITEC).

The rumen simulation technique (RUSITEC) was used to investigate the effect of ergot alkaloids (EA) and a mycotoxin deactivating product (Biomin AA; MDP) on nutrient digestion, ruminal fermentation parameters, total gas, methane, and microbial nitrogen production. Ruminal fermentation vessels received a feedlot finishing diet of 90:10 concentrate:barley silage (DM basis). Using a randomized complete block design, treatments were assigned (n = 4 vessels/treatment) within two RUSITEC apparatuses in a 2 × 2 factorial arrangement. Treatments included: (1) control (CON) diet (no EA and no MDP); (2) CON diet + 1 g/d MDP; (3) CON diet + 20 mg/kg EA; and (4) CON diet + 20 mg/kg EA + 1 g/d MDP. The study was conducted over 14 d with 7 d of adaptation and 7 d of sample collection. Data were analyzed in SAS using PROC MIXED including fixed effects of EA, MDP, and the EA×MDP interaction. Random effects included RUSITEC apparatus and cow rumen inoculum (n = 4). Ergot alkaloids decreased dry matter (DMD) (P = 0.01; 87.9 vs. 87.2%) and organic matter disappearance (OMD) (P = 0.02; 88.8 vs. 88.4%). Inclusion of MDP increased OMD (P = 0.01; 88.3 vs. 88.9%). Neutral detergent fiber disappearance (NDFD) was improved with MDP; however, an EA×MDP interaction was observed with MDP increasing (P < 0.001) NDFD more with EA diet compared to CON. Acetate proportion decreased (P = 0.01) and isovalerate increased (P = 0.03) with EA. Consequently, acetate:propionate was reduced (P = 0.03) with EA. Inclusion of MDP increased total volatile fatty acid (VFA) production (P < 0.001), and proportions of acetate (P = 0.03) and propionate (P = 0.03), and decreased valerate (P < 0.001), isovalerate (P = 0.04), and caproate (P = 0.002). Treatments did not affect (P ≥ 0.17) ammonia, total gas, or methane production (mg/d or mg/g of organic matter fermented). The inclusion of MDP reduced (P < 0.001) microbial nitrogen (MN) production in the effluent and increased (P = 0.01) feed particle-bound MN. Consequently, total MN decreased (P = 0.001) with MDP. In all treatments, the dominant microbial phyla were Firmicutes, Bacteroidota, and Proteobacteria, and the major microbial genus was Prevotella. Inclusion of MDP further increased the abundance of Bacteroidota (P = 0.04) as it increased both Prevotella (P = 0.04) and Prevotellaceae_UCG-003 (P = 0.001). In conclusion, EA reduced OMD and acetate production due to impaired rumen function, these responses were successfully reversed by the addition of MDP.

Ergot formed from a parasitic fungus (Claviceps purpurea) affects various types of grains (rye, wheat, or oats) and may contain several toxic ergot alkaloids (EA). Individual EA may impact the rumen microorganisms, and cattle feed intake, digestibility, health, and overall performance. A common method to alleviate toxicity in mycotoxin-contaminated feed is through the addition of mycotoxin binders (MDP); however, their efficacy against EA is unknown. To better understand the effect of EA in cattle, we performed an in vitro experiment to examine the impact of EA on the ruminal microbial populations and fermentation of a finishing feedlot diet using an artificial rumen (RUSITEC). Additionally, an MDP was added to test if it could reduce the detrimental effects of EA on rumen fermentation. MDP increased total volatile fatty acids (VFA) and reduced total microbial protein synthesis. Furthermore, EA reduced microbial diversity and the acetate:propionate ratio. Although EA reduced organic matter digestibility and acetate production, these negative effects were reversed by the addition of the MDP.

Prolonged absorption and susceptibility to enterohepatic circulation after oral administration of ergot alkaloids in ewes.

The objective of this study was to evaluate the pharmacokinetics profile of ergot alkaloids when administered to sheep orally. Although ergot alkaloids frequently contaminate animal feed, current understanding of their pharmacokinetics in animals cannot adequately predict toxicity. Blood samples were collected from ewes at 0.5, 1, 3, 5, and 12 h after oral exposure to 4 ergot alkaloids: ergocornine, ergocristine, ergocryptine, and ergosine, followed by serum analysis of these alkaloids using high performance liquid chromatography and tandem mass spectrometry. The alkaloids showed extended absorption time, in addition to clear signs of enterohepatic circulation. This pharmacokinetic profile suggests potential enhanced toxicity in animals with disorders related to secretion of bile acid. It may also explain the high susceptibility of sheep to ergot poisoning compared to other species. An extended sampling protocol (> 12 h) is necessary, however, to identify the pharmacokinetic properties of ergot alkaloids in ewes. In conclusion, ewes exposed to ergot alkaloids showed a prolonged absorption phase and enterohepatic circulation, which is in contrast with human ergot pharmacokinetics.

L'objectif de cette étude était d'évaluer le profil pharmacocinétique des alcaloïdes de l'ergot lorsqu'ils sont administrés à des moutons par voie orale. Bien que les alcaloïdes de l'ergot contaminent fréquemment les aliments pour animaux, la compréhension actuelle de leur pharmacocinétique chez les animaux ne permet pas de prédire de manière adéquate la toxicité. Des échantillons de sang ont été prélevés chez les brebis à 0,5, 1, 3, 5 et 12 h après exposition orale à quatre alcaloïdes de l'ergot : ergocornine, ergocristine, ergocryptine et ergosine, suivi d'une analyse sérique de ces alcaloïdes par chromatographie liquide à haute performance et spectrométrie de masse en tandem. Les alcaloïdes ont montré un temps d'absorption prolongé, en plus de signes évidents de circulation entérohépatique. Ce profil pharmacocinétique suggère une toxicité potentiellement accrue chez les animaux présentant des troubles liés à la sécrétion d'acide biliaire. Cela peut également expliquer la forte sensibilité des moutons à l'empoisonnement par l'ergot par rapport aux autres espèces. Un protocole de prélèvement étendu (> 12 h) est cependant nécessaire pour identifier les propriétés pharmacocinétiques des alcaloïdes de l'ergot chez les brebis. En conclusion, les brebis exposées aux alcaloïdes ont montré une phase d'absorption prolongée et une circulation entérohépatique, ce qui contraste avec la pharmacocinétique de l'ergot chez l'humain.(Traduit par Docteur Serge Messier).

Hepatic fibrosis and mineralization in a free-ranging barren-ground caribou (Rangifer tarandus groenlandicus) from the Northwest Territories.

Due to concerns about the appearance of portions of liver from a harvested adult, male barren-ground caribou (Rangifer tarandus groenlandicus), samples were submitted for diagnostic investigation. The gross and histologic findings were consistent with severe hepatic fibrosis and mineralization. Concentrations of vitamin E in the liver were also deficient. Disease investigations in wildlife of detectable abnormalities such as this provide important information for understanding the role of disease as populations change, as well as for safety of human food sources.

Fibrose hépatique et minéralisation chez un caribou de la toundra ( Rangifer tarandus groenlandicus ) en liberté provenant des Territoires du Nord-Ouest. En raison de préoccupations concernant l'apparence de portions de foie provenant d'un caribou de la toundra mâle adulte (Rangifer tarandus groenlandicus), des échantillons ont été soumis à des fins d'enquête diagnostique. Les résultats macroscopiques et histologiques étaient compatibles avec une fibrose hépatique sévère et une minéralisation. Les concentrations de vitamine E dans le foie étaient également déficientes. Les enquêtes sur les maladies de la faune sauvage portant sur des anomalies détectables telles que celle-ci fournissent des informations importantes pour comprendre le rôle des maladies à mesure que les populations changent, ainsi que pour la sécurité des sources de nourriture humaine.(Traduit par Dr Serge Messier).

Workers should take steps to mitigate surface lead exposure when using lead-containing personal protective equipment.

Veterinary workers use lead shielding for protection against harm from ionizing radiation during diagnostic imaging. Surface lead on shielding has been reported as a potential exposure hazard. The purpose of this prospective, analytical, descriptive study was to measure surface lead on lead-containing shielding in the field service and small animal radiology areas of a veterinary teaching hospital, and to examine potential risk factors for surface lead. Surface lead on a convenience sample of 54 lead shielding items was measured in a commercial laboratory using inductively coupled plasma mass spectrometry. The median and range of surface lead for aprons, thyroid collars, and gloves were 3.6 µg/dm2 (range, 1.3-22.4 µg/dm2 ), 23.1 µg/dm2 (range, 2.6-116 µg/dm2 ), and 134 µg/dm2 (range, 1.5-155 µg/dm2 ), respectively. In the final multivariable analysis, the mean surface lead on thyroid collars and gloves was higher than on aprons (relative differences 4.8, 95% confidence interval [CI] 2.2, 10.5, P < 0.001; and 9.5, 95% CI 4.4, 20.6, P < 0.001, respectively). The mean surface lead on shielding in the worst condition was higher than on shielding in the intermediate and best conditions (P < 0.001). Lead shielding provides effective protection against the harmful effects of ionizing radiation, and shielding should always be worn during radiation exposure. Based on our findings and the common use of lead shielding in veterinary workplaces, we recommend that employers inform workers of this hazard and provide training on steps to mitigate exposure, including the use of disposable gloves when wearing lead shielding and handwashing after use.

Sustained low-dose ergot alkaloids minimally affect post-thaw sperm characteristics in mature and yearling Angus bulls.

Our objectives were to determine if feeding mature and yearling Angus bulls ergot alkaloids (from Claviceps purpurea) within the Canadian permissible limit (∼3 mg/kg) affect post-thaw sperm quality. In Experiment 1, mature Angus bulls were group-fed ergot alkaloids (∼1 and ∼2 mg/kg of daily dry matter intake, DMI; n = 8 and n = 6 bulls, respectively) for 61 d; semen was collected and cryopreserved bi-weekly, from 12 wk pre-exposure to 10 wk post-exposure. In Experiment 2, yearling Angus bulls (12-13 mo) were individually fed placebo or ergot alkaloids (3.4 mg/kg of DMI; n = 7 bulls/group) daily for 9 wk, with semen collected and cryopreserved once weekly, from 5 wk before to 9 wk after exposure. All frozen semen was assessed 0 and 2 h post-thaw. In Experiment 1, post-thaw total and progressive sperm motilities decreased (P ≤ 0.05) from pre-exposure to exposure period, then returned to pre-exposure level. Likewise, during exposure, VAP and VSL decreased (P ≤ 0.01) at 0 h compared to pre-exposure and subsequently returned. Live sperm with intact acrosomes at 2 h post-thaw was affected by ergot (P = 0.01). Medium mitochondrial membrane potential increased (P ≤ 0.01) during exposure compared to pre-exposure and subsequently decreased. In Experiment 2, total and progressive sperm motilities at 0 and 2 h increased (P ≤ 0.01) throughout the study. During post-exposure, VCL, VAP and VSL at 0 h increased (P ≤ 0.01) whereas VSL at 2 h increased (P ≤ 0.01) from pre-exposure to exposure to post-exposure. Live sperm with intact acrosomes increased (P ≤ 0.01) at both 0 and 2 h during post-exposure. Medium mitochondrial membrane potential increased (P ≤ 0.01) from pre-exposure to exposure, followed by a slight decrease post-exposure. Mature Angus bulls partially supported our hypothesis, with only transient effects of ergot on sperm motilities and velocities. Post-thaw sperm characteristics in yearling bulls underwent expected age-related improvements, with any effects of ergot alkaloids potentially masked by sexual maturation. Overall, results partially supported our hypotheses that ergot has no detectable adverse effect on post-thaw sperm characteristics in mature and yearling bulls.

Vasoactive Effects of Acute Ergot Exposure in Sheep.

Ergotism is a common and increasing problem in Saskatchewan's livestock. Chronic exposure to low concentrations of ergot alkaloids is known to cause severe arterial vasoconstriction and gangrene through the activation of adrenergic and serotonergic receptors on vascular smooth muscles. The acute vascular effects of a single oral dose with high-level exposure to ergot alkaloids remain unknown and are examined in this study. This study had two main objectives; the first was to evaluate the role of α1-adrenergic receptors in mediating the acute vasocontractile response after single-dose exposure in sheep. The second was to examine whether terazosin (TE) could abolish the vascular contractile effects of ergot alkaloids. Twelve adult female sheep were randomly placed into control and exposure groups (n = 6/group). Ergot sclerotia were collected and finely ground. The concentrations of six ergot alkaloids (ergocornine, ergocristine, ergocryptine, ergometrine, ergosine, and ergotamine) were determined using HPLC/MS at Prairie Diagnostic Services Inc., (Saskatoon, SK, Canada). Each ewe within the treatment group received a single oral treatment of ground ergot sclerotia at a dose of 600 µg/kg BW (total ergot) while each ewe in the control group received water. Animals were euthanized 12 h after the treatment, and the pedal artery (dorsal metatarsal III artery) from the left hind limb from each animal was carefully dissected and mounted in an isolated tissue bath. The vascular contractile response to phenylephrine (PE) (α1-adrenergic agonist) was compared between the two groups before and after TE (α1-adrenergic antagonist) treatment. Acute exposure to ergot alkaloids resulted in a 38% increase in vascular sensitivity to PE compared to control (Ctl EC50 = 1.74 × 10-6 M; Exp EC50 = 1.079 × 10-6 M, p = 0.046). TE treatment resulted in a significant dose-dependent increase in EC50 in both exposure and control groups (p < 0.05 for all treatments). Surprisingly, TE effect was significantly more pronounced in the ergot exposed group compared to the control group at two of the three concentrations of TE (TE 30 nM, p = 0.36; TE 100 nM, p < 0.001; TE 300 nM, p < 0.001). Similar to chronic exposure, acute exposure to ergot alkaloids results in increased vascular sensitivity to PE. TE is a more potent dose-dependent antagonist for the PE contractile response in sheep exposed to ergot compared to the control group. This study may indicate that the dry gangrene seen in sheep, and likely other species, might be related to the activation of α1-adrenergic receptor. This effect may be reversed using TE, especially at early stages of the disease before cell death occurs. This study may also indicate that acute-single dose exposure scenario may be useful in the study of vascular effects of ergot alkaloids.

Evaluation of metallothionein and Ki-67 expression in chronic cholangiohepatitis in cats.

Chronic cholangiohepatitis (CCH) is a common pathological condition in cats with a guarded prognosis and unknown etiology. Recently, in human medicine, there has been increased interest in enhancing liver defense mechanisms as an effective treatment strategy to control liver diseases that have a poor prognosis. Metallothionein (MT) is a ubiquitous protein, which has been widely researched for its role in liver defense through heavy metal detoxification, neutralization of reactive oxygen species, and liver regeneration. In this study, immunohistochemistry was used to evaluate the role of MT in CCH and hepatocellular regeneration in 34 cats histologically diagnosed with this condition by assessing the correlation between hepatocellular MT and Ki-67 (marker for cellular proliferation) expression with histological parameters of CCH, such as inflammation, fibrosis, and bile duct proliferation. Statistical analysis was performed using the Spearman-rank correlation test. A significant positive correlation was observed between inflammation and the number of MT-positive hepatocytes (r = 0.36, P = 0.03) and MT labelling intensity (r = 0.37, P = 0.03). In 16 of 34 cases (47%) MT labelling intensity was noted to be pronounced towards the centrilobular zone and very weak or absent towards the portal zone. The results suggest that MT is induced in the liver during chronic inflammatory conditions, which could be speculated as a host defensive mechanism to protect the liver from inflammation-mediated liver injury. Therapeutic interventions utilizing MT, therefore, may have a positive effect on cats with chronic cholangiohepatitis.

La cholangiohépatite chronique (CCH) est une affection pathologique courante chez les chats avec un pronostic réservé et une étiologie inconnue. Récemment, en médecine humaine, il y a eu un intérêt accru pour l'amélioration des mécanismes de défense hépatique en tant que stratégie de traitement efficace pour contrôler les maladies du foie qui ont un mauvais pronostic. La métallothionéine (MT) est une protéine omniprésente, qui a été largement étudiée pour son rôle dans la défense du foie par la détoxification des métaux lourds, la neutralisation des espèces réactives de l'oxygène et la régénération du foie. Dans cette étude, l'immunohistochimie a été utilisée pour évaluer le rôle de la MT dans la CCH et la régénération hépatocellulaire chez 34 chats diagnostiqués histologiquement avec cette condition en évaluant la corrélation entre l'expression hépatocellulaire de la MT et du Ki-67 (marqueur de la prolifération cellulaire) avec les paramètres histologiques de la CCH, comme l'inflammation, la fibrose et la prolifération des voies biliaires. L'analyse statistique a été réalisée à l'aide du test de corrélation de rang de Spearman. Une corrélation positive significative a été observée entre l'inflammation et le nombre d'hépatocytes MT-positifs (r = 0,36, P = 0,03) et l'intensité de marquage MT (r = 0,37, P = 0,03). Dans 16 des 34 cas (47 %), l'intensité du marquage MT était prononcée vers la zone centrolobulaire et très faible ou absente vers la zone porte. Les résultats suggèrent que la MT est induite dans le foie pendant les états inflammatoires chroniques, ce qui pourrait être supposé comme un mécanisme de défense de l'hôte pour protéger le foie contre les lésions hépatiques induites par l'inflammation. Les interventions thérapeutiques utilisant la MT peuvent donc avoir un effet positif sur les chats atteints de cholangiohépatite chronique.(Traduit par Docteur Serge Messier).

Validation of a New Sensitive Method for the Detection and Quantification of R and S-Epimers of Ergot Alkaloids in Canadian Spring Wheat Utilizing Deuterated Lysergic Acid Diethylamide as an Internal Standard.

Ergot sclerotia effect cereal crops intended for consumption. Ergot alkaloids within ergot sclerotia are assessed to ensure contamination is below safety standards established for human and animal health. Ergot alkaloids exist in two configurations, the R and S-epimers. It is important to quantify both configurations. The objective of this study was to validate a new ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for quantification of six R and six S-epimers of ergot alkaloids in hard red spring wheat utilizing deuterated lysergic acid diethylamide (LSD-D3) as an internal standard. Validation parameters such as linearity, limit of detection (LOD), limit of quantification (LOQ), matrix effects, recovery and precision were investigated. For the 12 epimers analyzed, low LOD and LOQ values were observed, allowing for the sensitive detection of ergot epimers. Matrix effects ranged between 101-113% in a representative wheat matrix. Recovery was 68.3-119.1% with an inter-day precision of <24% relative standard deviation (RSD). The validation parameters conform with previous studies and exhibit differences between the R and S-epimers which has been rarely documented. This new sensitive method allows for the use of a new internal standard and can be incorporated and applied to research or diagnostic laboratories.