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1.
Can Vet J ; 65(5): 496-503, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38694735

RESUMO

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).


Assuntos
Anticoagulantes , Doenças do Cão , Rodenticidas , Animais , Cães , Rodenticidas/intoxicação , Estudos Retrospectivos , Doenças do Cão/induzido quimicamente , Saskatchewan/epidemiologia , Masculino , Feminino , Anticoagulantes/intoxicação , Anticoagulantes/efeitos adversos , 4-Hidroxicumarinas/intoxicação
2.
Vet Radiol Ultrasound ; 63(1): 23-29, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34637582

RESUMO

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.


Assuntos
Exposição Ocupacional , Proteção Radiológica , Animais , Hospitais Veterinários , Hospitais de Ensino , Chumbo , Equipamento de Proteção Individual , Estudos Prospectivos , Doses de Radiação
3.
Can Vet J ; 63(2): 157-160, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35110773

RESUMO

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).


Assuntos
Rena , Animais , Cirrose Hepática/veterinária , Masculino , Territórios do Noroeste
4.
Can Vet J ; 61(1): 57-62, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892756

RESUMO

Trace mineral analyses of samples submitted to Prairie Diagnostic Services laboratory from Saskatchewan cattle between 2003 and 2012 were examined, with the objective of describing trends and reporting concentrations and deficiencies of minerals. Deficiencies were observed with copper, iron, manganese, magnesium, zinc, and cobalt. Deficiency was most commonly seen in copper, followed by iron, manganese, and magnesium accounting for 47.2%, 15.1%, 13.0%, and 10.8% of deficiencies, respectively. Deficiency in cobalt was least common followed by zinc accounting for 4.2% and 9.7% of deficiencies, respectively. The following minerals were also analyzed: barium, beryllium, bismuth, cadmium, chromium, antimony, tin, molybdenum, strontium, thallium, and vanadium. Submissions from 1434 animals were reviewed and a diagnosis of mineral deficiency was made for 509 animals with 92 of these having multiple deficiencies. There were significant differences in the number of deficient animals by year (P = 0.001), age group (P = 0.01), but not month (P = 0.109) or soil type (P = 0.172).


Concentrations et déficiences en minéraux dans des échantillons bovins soumis à un laboratoire de diagnostic en Saskatchewan entre 2003­2012 : une étude rétrospective. Les résultats d'analyse pour les oligo-éléments dans des échantillons provenant de bovins en Saskatchewan soumis au laboratoire de Prairie Diagnostic Services entre 2003 et 2012 furent examinés, avec comme objectif de décrire les tendances et rapporter les concentrations et déficiences en minéraux. Des déficiences furent observées pour le cuivre, le fer, le manganèse, le magnésium, le zinc, et le cobalt. Les déficiences étaient les plus fréquemment rencontrées avec le cuivre, suivi du fer, manganèse, et magnésium représentant 47,2 %, 15,1 %, 13,0 %, et 10,8 % des déficiences, respectivement. La déficience en cobalt était moins fréquente suivie par le zinc et représentant 4,2 % et 9,7 % des déficiences, respectivement. Les minéraux suivants furent également analysés : barium, béryllium, bismuth, cadmium, chromium, antimoine, étain, molybdène, strontium, thallium, et vanadium. Les soumissions provenant de 1434 animaux furent revues et un diagnostic de déficience en minéraux fut posé chez 509 animaux, avec 92 de ceux-ci ayant des déficiences multiples. Il y avait des différences significatives dans le nombre d'animaux déficients par année (P = 0,001), les groupes d'âge (P = 0,01), mais pas pour les mois (P = 0,109) ou le type de sol (P = 0,172).(Traduit par Dr Serge Messier).


Assuntos
Níquel/análise , Oligoelementos , Animais , Bovinos , Cobre , Minerais , Estudos Retrospectivos , Saskatchewan , Zinco/análise
5.
Can Vet J ; 57(4): 421-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27041761

RESUMO

This study describes the epidemiology of acute lead poisoning in western Canadian cattle over the 16-year period of 1998 to 2013 and reports background bovine tissue lead concentrations. Case records from Prairie Diagnostic Services, Western College of Veterinary Medicine, identified 525 cases of acute lead toxicity over the investigational period. Poisonings were influenced by year (P < 0.0001) and month (P < 0.0001). Submissions were highest in 2009 (15.6%), 2001 (11.2%), and 2006 (9.9%). Most cases were observed during May, June, and July (62.3%). Cattle 6 months of age and younger were frequently poisoned (53.5%; P < 0.0001). Beef breeds were predominantly poisoned. Mean toxic lead concentrations (mg/kg wet weight) in the blood, liver, and kidney were 1.30 ± 1.70 (n = 301), 33.5 ± 80.5 (n = 172), and 56.3 ± 39.7 (n = 61). Mean normal lead concentrations in the blood, liver, and kidney were 0.036 ± 0.003 mg/kg (n= 1081), 0.16 ± 0.63 mg/kg (n = 382), and 0.41 ± 0.62 mg/kg (n = 64).


Empoisonnement aigu par le plomb chez les bovins de l'Ouest canadien ­ étude rétrospective de 16 ans de dossiers de cas de diagnostics. Cette étude décrit l'épidémiologie de l'empoisonnement aigu par le plomb chez les bovins de l'Ouest canadien pendant une période de 16 ans, de 1998 à 2013, et signale les concentrations sous-jacentes de plomb dans les tissus des bovins. Les dossiers de cas de Prairie Diagnostic Services, du Western College of Veterinary Medicine, ont identifié 525 cas de toxicité aiguë par le plomb pendant la période d'enquête. Les empoisonnements étaient influencés par l'année (P < 0,0001) et le mois (P < 0,0001). Les soumissions étaient les plus élevées en 2009 (15,6 %), en 2001 (11,2 %) et en 2006 (9,9 %). La plupart des cas ont été observés en mai, juin et juillet (62,3 %). Les bovins âgés de 6 mois et moins étaient les plus fréquemment empoisonnés (53,5 %; P < 0,0001). Les races de bovins de boucherie étaient principalement empoisonnées. Les concentrations moyennes toxiques de plomb (mg/kg poids frais) dans le sang, le foie et le rein étaient de 1,30 ± 1,70 (n = 301), 33,5 ± 80,5 (n = 172) et de 56,3 ± 39,7 (n = 61). Les concentrations moyennes normales de plomb dans le sang, le foie et les reins étaient de 0,036 ± 0,003 mg/kg (n = 1081), de 0,16 ± 0,63 mg/kg (n = 382) et de 0,41 ± 0,62 mg/kg (n = 64).(Traduit par Isabelle Vallières).


Assuntos
Doenças dos Bovinos/epidemiologia , Intoxicação por Chumbo/veterinária , Animais , Canadá/epidemiologia , Bovinos , Rim/química , Chumbo/sangue , Intoxicação por Chumbo/epidemiologia , Fígado/química , Carne Vermelha/análise , Estudos Retrospectivos
6.
Can Vet J ; 57(1): 53-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26740698

RESUMO

Veterinary toxicoses are frequently observed in western Canada. This study reports the frequency and characteristics of intoxications in animals reported between January 1, 1998 and December 31, 2013. Information was obtained from toxicological case records from the Prairie Diagnostic Services, Saskatoon, Saskatchewan. There were 1341 animal poisonings with 19 compounds over the investigational period. Lead poisoning was the most common toxicity (43.7%). Poisoning with acetylcholinesterase inhibitors and strychnine were also common events. Poisonings were most common in 2001, 2009, and 2012. Intoxications occurred most frequently during the months of May through July. Cattle were the most commonly poisoned species (n = 696), followed by dogs and eagles.


Caractérisation de 1341 cas confirmés de toxicoses vétérinaires dans l'Ouest canadien : une étude rétrospective de 16 ans. Les toxicoses vétérinaires sont fréquemment observées dans l'Ouest canadien. Cette étude présente un rapport de la fréquence et des caractéristiques des intoxications chez les animaux signalées entre le 1er janvier 1998 et le 31 décembre 2013. Des renseignements ont été obtenus dans les dossiers de cas toxicologiques de Prairie Diagnostic Services, à Saskatoon, en Saskatchewan. Il y a eu 1341 empoisonnements d'animaux causés par 19 composés pendant la période d'enquête. L'empoisonnement au plomb était la toxicité la plus fréquente (43,7 %). L'empoisonnement aux inhibiteurs d'acétylcholinestérase et à la strychnine était aussi fréquemment observé. Les empoisonnements ont été les plus fréquents en 2001, en 2009 et en 2012. Les intoxications se sont le plus fréquemment produites durant les mois de mai à juillet. Les bovins de boucherie représentaient l'espèce la plus fréquemment empoisonnée (n = 696), suivie des chiens et des pygarques.(Traduit par Isabelle Vallières).


Assuntos
Intoxicação por Chumbo/veterinária , Praguicidas/intoxicação , Intoxicação/veterinária , Oligoelementos/intoxicação , Animais , Animais Domésticos , Animais Selvagens , Canadá/epidemiologia , Intoxicação por Chumbo/epidemiologia , Plantas Tóxicas , Intoxicação/epidemiologia , Estudos Retrospectivos
7.
Can Vet J ; 56(6): 587-90, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26028680

RESUMO

This study describes observations related to 93 cases of strychnine poisoning in dogs over a 16-year period in Saskatchewan, Alberta, and Manitoba. Epidemiological information describing age, gender, breed, and size of the dogs, geographical distribution of poisonings, and strychnine concentrations in tissue matrices were tabulated. The mortality in dogs poisoned with strychnine was 60.2%. Strychnine poisoning cases varied by year (P = 0.0012) and by season (P = 0.0005). The highest number of confirmed cases occurred in years 2000 and 2001. Poisonings occurred most frequently during the spring. There were no statistical differences related to age or gender, but older, male dogs appeared to be more commonly affected. Large dog breeds were most commonly affected. Strychnine was detected in multiple tissue matrices, including stomach contents, liver, urine, vomitus, and gastric washings. The study indicates that strychnine poisoning in the dog remains a common toxicosis in western Canada.


Étude rétrospective des empoisonnements canins à la strychnine de 1998 à 2013 dans l'Ouest canadien. Cette étude décrit les observations se rapportant à 93 cas d'empoisonnement à la strychnine chez des chiens pendant une période de 16 ans en Saskatchewan, en Alberta et au Manitoba. Des renseignements épidémiologiques décrivant l'âge, le sexe, la race et la taille des chiens, la répartition géographique des empoisonnements et les concentrations de strychnine dans les matrices des tissus ont été compilés. La mortalité des chiens empoisonnés à la strychnine était de 60,2 %. Les cas d'empoisonnement à la strychnine variaient selon l'année (P = 0,0012) et selon la saison (P = 0,0005). Le nombre le plus élevé de cas confirmés s'est produit en 2000 et en 2001. Les empoisonnements se produisaient le plus fréquemment au printemps. Il n'y avait pas de différences statistiques reliées à l'âge ou au sexe, mais les chiens mâles âgés semblaient être le plus fréquemment touchés. Les chiens de grande race étaient le plus souvent affectés. La strychnine a été détectée dans des plusieurs matrices de tissus, notamment le contenu de l'estomac, le foie, l'urine, les vomissures et les lavages gastriques. L'étude indique que l'empoisonnement à la strychnine chez le chien demeure une toxicose commune dans l'Ouest canadien.(Traduit par Isabelle Vallières).


Assuntos
Doenças do Cão/induzido quimicamente , Estricnina/intoxicação , Alberta/epidemiologia , Animais , Doenças do Cão/mortalidade , Cães , Feminino , Masculino , Manitoba/epidemiologia , Estudos Retrospectivos , Saskatchewan/epidemiologia , Fatores de Tempo
8.
Mycotoxin Res ; 40(1): 1-17, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37953416

RESUMO

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.


Assuntos
Claviceps , Alcaloides de Claviceps , Compostos Heterocíclicos de 4 ou mais Anéis
9.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38442241

RESUMO

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.


Assuntos
Ração Animal , Alcaloides de Claviceps , Bovinos , Animais , Ração Animal/análise , Dieta/veterinária , Suplementos Nutricionais , Silagem/análise , Grão Comestível
10.
Toxicol Rep ; 10: 604-611, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213815

RESUMO

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.

11.
Theriogenology ; 197: 71-83, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36476505

RESUMO

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.


Assuntos
Alcaloides de Claviceps , Análise do Sêmen , Masculino , Animais , Bovinos , Análise do Sêmen/veterinária , Sêmen/fisiologia , Prolactina , Motilidade dos Espermatozoides , Canadá , Espermatozoides/fisiologia , Alcaloides de Claviceps/farmacologia , Alcaloides de Claviceps/metabolismo
12.
J Occup Environ Med ; 65(9): 794-797, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37311074

RESUMO

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.


Assuntos
Chumbo , Pele , Humanos , Equipamentos de Proteção , Mãos , Radiografia , Luvas Protetoras
13.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37638650

RESUMO

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.


Assuntos
Alcaloides de Claviceps , Ocitócicos , Bovinos , Animais , Dieta/veterinária , Ingestão de Alimentos , Grão Comestível , Refeições
14.
Toxins (Basel) ; 15(8)2023 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-37624254

RESUMO

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.


Assuntos
Alcaloides de Claviceps , Temperatura , Agricultura , Cromatografia Líquida de Alta Pressão , Produtos Agrícolas , Grão Comestível , Poaceae
15.
Can J Vet Res ; 86(2): 108-112, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35388236

RESUMO

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).


Assuntos
Alcaloides de Claviceps , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/veterinária , Circulação Êntero-Hepática , Alcaloides de Claviceps/análise , Alcaloides de Claviceps/toxicidade , Feminino , Ovinos , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas em Tandem/veterinária
16.
J Anim Sci ; 100(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35775420

RESUMO

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.


Assuntos
Alcaloides de Claviceps , Metanol , Animais , Bovinos , Ergolinas , Alcaloides de Claviceps/química , Fenoxibenzamina
17.
J Agric Food Chem ; 70(29): 8931-8941, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35830571

RESUMO

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.


Assuntos
Claviceps , Alcaloides de Claviceps , Amônia , Cromatografia Líquida de Alta Pressão/métodos , Alcaloides de Claviceps/análise , Contaminação de Alimentos/análise , Compostos Heterocíclicos de 4 ou mais Anéis , Triticum/química
18.
J Anim Sci ; 100(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35748808

RESUMO

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.


Assuntos
Alcaloides de Claviceps , Micotoxinas , Amônia/metabolismo , Ração Animal/análise , Animais , Caproatos/metabolismo , Caproatos/farmacologia , Bovinos , Detergentes/metabolismo , Detergentes/farmacologia , Dieta/veterinária , Fibras na Dieta/metabolismo , Digestão , Alcaloides de Claviceps/farmacologia , Ácidos Graxos Voláteis/metabolismo , Feminino , Fermentação , Metano/metabolismo , Nitrogênio/metabolismo , Propionatos/farmacologia , Rúmen/metabolismo , Valeratos/farmacologia
19.
Toxins (Basel) ; 14(9)2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-36136518

RESUMO

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.


Assuntos
Claviceps , Alcaloides de Claviceps , Alberta , Ração Animal/análise , Animais , Bovinos , Claviceps/química , Grão Comestível/química , Ergonovina/análise , Alcaloides de Claviceps/análise , Ergotamina/análise , Ergotaminas/análise , Haptoglobinas/análise , Calefação , Hidrocortisona , Prolactina , Espectrometria de Massas em Tandem/métodos
20.
Can Vet J ; 52(1): 70-3, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21461211

RESUMO

Chronic selenium (Se) toxicosis was found in a herd of white-tailed deer showing signs of anorexia, weight loss, and lameness. Concentration of Se in the liver ranged from 2.7 to 8.97 mg/kg wet weight. Myocardial necrosis, mineralization, and fibroplasia were seen histologically. This is the first report of this toxicosis in white-tailed deer.


Assuntos
Cervos , Fígado/química , Selênio/intoxicação , Animais , Evolução Fatal , Fígado/metabolismo , Fígado/patologia , Masculino
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