Evaluation of sulfadimidine, amprolium and triquen to treat coccidiosis in wild pigeons

Abstract Coccidiosis remains one of the major problems in poultry all over the world. Very limited data on anticoccidial drugs in wild pigeons is available. The current study was aimed to understand the comparative efficacy of sulfadimidine, amprolium and triquen in wild pigeons of Dir district, Pakistan suffering from coccidiosis. The faecal matter of wild pigeons were purchased from the local market for coccidian infection. Results revealed that 88.8% (16/18) were found infected with Eimeria spp. Three positive groups were treated with sulfadimidine (0.2mg/L), amprolium (25mg/L) and triquen. Sulfadimidine was most effective (45%) followed by amprolium (44.6%) while triquen (24.0%) showed less effectiveness against coccidiosis in pigeons. Number of oocysts were 79, 81 and 80 before treatment and 60, 44 and 44 after treatment with sulfadimidine, amprolium and triquen respectively. This study showed that sulphadimidine, amprolium and triquen could not significantly reduce the coccidiosis in pigeons. Further studies are required to clear the mechanism of anti-coccidial drugs in wild pigeons.

Resumo A coccidiose continua sendo um dos maiores problemas em aves de todo o mundo. Dados muito limitados sobre drogas anticoccidiais em pombos selvagens estão disponíveis. O presente estudo teve como objetivo compreender a eficácia comparativa da sulfadimidina, amprólio e triquenho em pombos selvagens do distrito de Dir, no Paquistão, que sofrem de coccidiose. A matéria fecal dos pombos selvagens foi comprada no mercado local para infecção por coccídios. Os resultados revelaram que 88,8% (16/18) foram encontrados infectados com Eimeria spp. Três grupos positivos foram tratados com sulfadimidina (0,2mg / L), amprólio (25mg / L) e triquenho. A sulfadimidina foi mais eficaz (45%), seguida pelo amprólio (44,6%), enquanto o triquenho (24,0%) apresentou menor efetividade contra a coccidiose em pombos. O número de oocistos foram 79, 81 e 80 antes do tratamento e 60, 44 e 44 após o tratamento com sulfadimidina, amprólio e triquenho, respectivamente. Este estudo mostrou que sulphadimidine, amprolium e triquen não poderiam reduzir significativamente a coccidiose em pombos. Mais estudos são necessários para limpar o mecanismo de drogas anticoccidiais em pombos selvagens.

Evaluation of sulfadimidine, amprolium and triquen to treat coccidiosis in wild pigeons / Avaliação da sulfadimidina, amprólio e triquenho no tratamento da coccidiose em pombos selvagens de Lower Dir, Khyber Pakhtunkhwa, Paquistão

Coccidiosis remains one of the major problems in poultry all over the world. Very limited data on anticoccidial drugs in wild pigeons is available. The current study was aimed to understand the comparative efficacy of sulfadimidine, amprolium and triquen in wild pigeons of Dir district, Pakistan suffering from coccidiosis. The faecal matter of wild pigeons were purchased from the local market for coccidian infection. Results revealed that 88.8% (16/18) were found infected with Eimeria spp. Three positive groups were treated with sulfadimidine (0.2mg/L), amprolium (25mg/L) and triquen. Sulfadimidine was most effective (45%) followed by amprolium (44.6%) while triquen (24.0%) showed less effectiveness against coccidiosis in pigeons. Number of oocysts were 79, 81 and 80 before treatment and 60, 44 and 44 after treatment with sulfadimidine, amprolium and triquen respectively. This study showed that sulphadimidine, amprolium and triquen could not significantly reduce the coccidiosis in pigeons. Further studies are required to clear the mechanism of anti-coccidial drugs in wild pigeons.

A coccidiose continua sendo um dos maiores problemas em aves de todo o mundo. Dados muito limitados sobre drogas anticoccidiais em pombos selvagens estão disponíveis. O presente estudo teve como objetivo compreender a eficácia comparativa da sulfadimidina, amprólio e triquenho em pombos selvagens do distrito de Dir, no Paquistão, que sofrem de coccidiose. A matéria fecal dos pombos selvagens foi comprada no mercado local para infecção por coccídios. Os resultados revelaram que 88,8% (16/18) foram encontrados infectados com Eimeria spp. Três grupos positivos foram tratados com sulfadimidina (0,2mg / L), amprólio (25mg / L) e triquenho. A sulfadimidina foi mais eficaz (45%), seguida pelo amprólio (44,6%), enquanto o triquenho (24,0%) apresentou menor efetividade contra a coccidiose em pombos. O número de oocistos foram 79, 81 e 80 antes do tratamento e 60, 44 e 44 após o tratamento com sulfadimidina, amprólio e triquenho, respectivamente. Este estudo mostrou que sulphadimidine, amprolium e triquen não poderiam reduzir significativamente a coccidiose em pombos. Mais estudos são necessários para limpar o mecanismo de drogas anticoccidiais em pombos selvagens.

Evaluation of sulfadimidine, amprolium and triquen to treat coccidiosis in wild pigeons / Avaliação da sulfadimidina, amprólio e triquenho no tratamento da coccidiose em pombos selvagens de Lower Dir, Khyber Pakhtunkhwa, Paquistão

Coccidiosis remains one of the major problems in poultry all over the world. Very limited data on anticoccidial drugs in wild pigeons is available. The current study was aimed to understand the comparative efficacy of sulfadimidine, amprolium and triquen in wild pigeons of Dir district, Pakistan suffering from coccidiosis. The faecal matter of wild pigeons were purchased from the local market for coccidian infection. Results revealed that 88.8% (16/18) were found infected with Eimeria spp. Three positive groups were treated with sulfadimidine (0.2mg/L), amprolium (25mg/L) and triquen. Sulfadimidine was most effective (45%) followed by amprolium (44.6%) while triquen (24.0%) showed less effectiveness against coccidiosis in pigeons. Number of oocysts were 79, 81 and 80 before treatment and 60, 44 and 44 after treatment with sulfadimidine, amprolium and triquen respectively. This study showed that sulphadimidine, amprolium and triquen could not significantly reduce the coccidiosis in pigeons. Further studies are required to clear the mechanism of anti-coccidial drugs in wild pigeons.

A coccidiose continua sendo um dos maiores problemas em aves de todo o mundo. Dados muito limitados sobre drogas anticoccidiais em pombos selvagens estão disponíveis. O presente estudo teve como objetivo compreender a eficácia comparativa da sulfadimidina, amprólio e triquenho em pombos selvagens do distrito de Dir, no Paquistão, que sofrem de coccidiose. A matéria fecal dos pombos selvagens foi comprada no mercado local para infecção por coccídios. Os resultados revelaram que 88,8% (16/18) foram encontrados infectados com Eimeria spp. Três grupos positivos foram tratados com sulfadimidina (0,2mg / L), amprólio (25mg / L) e triquenho. A sulfadimidina foi mais eficaz (45%), seguida pelo amprólio (44,6%), enquanto o triquenho (24,0%) apresentou menor efetividade contra a coccidiose em pombos. O número de oocistos foram 79, 81 e 80 antes do tratamento e 60, 44 e 44 após o tratamento com sulfadimidina, amprólio e triquenho, respectivamente. Este estudo mostrou que sulphadimidine, amprolium e triquen não poderiam reduzir significativamente a coccidiose em pombos. Mais estudos são necessários para limpar o mecanismo de drogas anticoccidiais em pombos selvagens.

Evaluation of sulfadimidine, amprolium and triquen to treat coccidiosis in wild pigeons / Avaliação da sulfadimidina, amprólio e triquenho no tratamento da coccidiose em pombos selvagens de Lower Dir, Khyber Pakhtunkhwa, Paquistão

Coccidiosis remains one of the major problems in poultry all over the world. Very limited data on anticoccidial drugs in wild pigeons is available. The current study was aimed to understand the comparative efficacy of sulfadimidine, amprolium and triquen in wild pigeons of Dir district, Pakistan suffering from coccidiosis. The faecal matter of wild pigeons were purchased from the local market for coccidian infection. Results revealed that 88.8% (16/18) were found infected with Eimeria spp. Three positive groups were treated with sulfadimidine (0.2mg/L), amprolium (25mg/L) and triquen. Sulfadimidine was most effective (45%) followed by amprolium (44.6%) while triquen (24.0%) showed less effectiveness against coccidiosis in pigeons. Number of oocysts were 79, 81 and 80 before treatment and 60, 44 and 44 after treatment with sulfadimidine, amprolium and triquen respectively. This study showed that sulphadimidine, amprolium and triquen could not significantly reduce the coccidiosis in pigeons. Further studies are required to clear the mechanism of anti-coccidial drugs in wild pigeons.(AU)

A coccidiose continua sendo um dos maiores problemas em aves de todo o mundo. Dados muito limitados sobre drogas anticoccidiais em pombos selvagens estão disponíveis. O presente estudo teve como objetivo compreender a eficácia comparativa da sulfadimidina, amprólio e triquenho em pombos selvagens do distrito de Dir, no Paquistão, que sofrem de coccidiose. A matéria fecal dos pombos selvagens foi comprada no mercado local para infecção por coccídios. Os resultados revelaram que 88,8% (16/18) foram encontrados infectados com Eimeria spp. Três grupos positivos foram tratados com sulfadimidina (0,2mg / L), amprólio (25mg / L) e triquenho. A sulfadimidina foi mais eficaz (45%), seguida pelo amprólio (44,6%), enquanto o triquenho (24,0%) apresentou menor efetividade contra a coccidiose em pombos. O número de oocistos foram 79, 81 e 80 antes do tratamento e 60, 44 e 44 após o tratamento com sulfadimidina, amprólio e triquenho, respectivamente. Este estudo mostrou que sulphadimidine, amprolium e triquen não poderiam reduzir significativamente a coccidiose em pombos. Mais estudos são necessários para limpar o mecanismo de drogas anticoccidiais em pombos selvagens.(AU)

Mulberry extract as an ecofriendly anticoccidial agent: in vitro and in vivo application / Extrato de amoreira como agente anticoccidiano ecologicamente correto: aplicação in vitro e in vivo

Natural products are ecofriendly agents that can be used against parasitic diseases. Eimeria species cause eimeriosis in many birds and mammals and resistance to available medications used in the treatment of eimeriosis is emerging. We investigated the in vitro and in vivo activity of Morus nigra leaf extracts (MNLE) against sporulation of oocysts and infection of mice with Eimeria papillata. Phytochemical analysis of MNLE showed the presence of seven compounds and the in vitro effects of MNLE, amprolium, DettolTM, formalin, ethanol, and phenol were studied after incubation with oocysts before sporulation. Furthermore, infection of mice with E. papillata induced an oocyst output of approximately 12 × 105 oocysts/g of feces. MNLE significantly decreased oocyst output to approximately 86% and the total number of parasitic stages in the jejunum by approximately 87%. In addition, the reduction in the number of goblet cells in the jejuna of mice was increased after treatment. These findings suggest that mulberry exhibited powerful anticoccidial activity.(AU)

Os produtos naturais são agentes ecologicamente corretos que podem ser usados contra doenças parasitárias. As espécies de Eimeria causam eimeriose em muitas aves e mamíferos e a resistência aos medicamentos disponíveis usados no tratamento da eimeriose está emergindo. Foram investigadas as atividades in vitro e in vivo dos extratos de folhas de Morus nigra (MNLE) contra esporulação de oocistos e infecção de camundongos com Eimeria papillata. A análise fitoquímica do MNLE mostrou a presença de sete compostos e os efeitos in vitro do MNLE, amprolium, DettolTM, formalina, etanol e fenol foram estudados após incubação com oocistos antes da esporulação. Além disso, a infecção de camundongos com E. papillata induziu uma produção de oocistos de aproximadamente 12 × 105 oocistos / g de fezes. O MNLE reduziu significativamente a produção de oocistos para aproximadamente 86%, e o número total de estágios parasitários no jejuno em aproximadamente 87%. Além disso, a redução no número de células caliciformes no jejuno de camundongos aumentou após o tratamento. Esses achados sugerem que a amoreira exibia uma poderosa atividade anticoccidiana.(AU)

Healing of brain lesions in sheep recovered from amprolium-induced polioencephalomalacia

ABSTRACT: To evaluate the outcome of acute lesions in the brains of sheep that completely clinically recover from acute polioencephalomalacia (PEM), ten sheep were used in this experiment. Eight of those sheep received varying doses of amprolium to induce PEM. Four sheep were treated intramuscularly with 40mg/kg/body weight with thiamine to allow recovery and four sheep were left untreated. Two control sheep did not receive either amprolium or thiamine and were kept along with the other eight sheep for the duration of the experiment. Except for the two drugs, the diet and water source were the same for the ten sheep. Two sheep receiving high daily doses of amprolium and one sheep receiving a lower dose had acute deaths and developed acute brain lesions consisting of neuronal laminar cortical necrosis (red neurons), edema, reactive astrocytes, swollen endothelial cells and gitter cells infiltration. Four sheep that recovered from lower doses of amprolium-induced PEM after being treated with thiamine and another one that recovered spontaneously were euthanatized six months after clinical recovery and had gross changes consisting of segmental absence of cortical tissue. Histologically these segmental cortex-deprived areas corresponded to quasi-empty spaces where only vessels and gitter cells existed. No changes were seen in the brains of the two control sheep.

RESUMO: Para avaliar a evolução das lesões agudas no cérebro de ovinos que se recuperam clinicamente de polioencefalomalacia aguda (PEM), dez ovinos foram usados neste experimento. Oito desses ovinos receberam doses variáveis de amprólio para induzir PEM. Quatro ovinos foram tratados intramuscularmente com 40mg/kg/peso corporal de tiamina para permitir a recuperação, e outros quatro ficaram sem tratamento. Dois ovinos controles não receberam amprólio nem tiamina e foram mantidos com os outros oito ovinos durante a duração do experimento. Exceto pelas duas drogas, a dieta e a fonte de água eram as mesmas para os dez ovinos. Dois ovinos que receberam doses diárias altas de amprólio, e um que recebeu doses menores, tiveram mortes agudas e desenvolveram lesões cerebrais constituídas por necrose neuronal laminar cortical (neurônios vermelhos), edema, tumefação de células endoteliais, astrócitos reativos, tumefação de células endoteliais e infiltração por células gitter. Quatro ovinos que se recuperam da PEM induzida por amprólio, após tratamento com tiamina, e outro que se recuperou espontaneamente, permaneceram clinicamente normais e foram submetidos a eutanásia seis meses após a recuperação clínica. Na necropsia, apresentavam alterações macroscópicas caracterizadas por ausência segmentar de tecido corticocerebral. Histologicamente, essas áreas privadas de tecido cortical consistiam de espaços praticamente vazios onde apenas vasos e células gitter eram vistos. Não foram encontradas alterações no encéfalo das duas ovelhas controle.

Healing of brain lesions in sheep recovered from amprolium-induced polioencephalomalacia / Cicatrização das lesões cerebrais em ovinos recuperados de polioencefalomalacia induzida por amprólio

To evaluate the outcome of acute lesions in the brains of sheep that completely clinically recover from acute polioencephalomalacia (PEM), ten sheep were used in this experiment. Eight of those sheep received varying doses of amprolium to induce PEM. Four sheep were treated intramuscularly with 40mg/kg/body weight with thiamine to allow recovery and four sheep were left untreated. Two control sheep did not receive either amprolium or thiamine and were kept along with the other eight sheep for the duration of the experiment. Except for the two drugs, the diet and water source were the same for the ten sheep. Two sheep receiving high daily doses of amprolium and one sheep receiving a lower dose had acute deaths and developed acute brain lesions consisting of neuronal laminar cortical necrosis (red neurons), edema, reactive astrocytes, swollen endothelial cells and gitter cells infiltration. Four sheep that recovered from lower doses of amprolium-induced PEM after being treated with thiamine and another one that recovered spontaneously were euthanatized six months after clinical recovery and had gross changes consisting of segmental absence of cortical tissue. Histologically these segmental cortex-deprived areas corresponded to quasi-empty spaces where only vessels and gitter cells existed. No changes were seen in the brains of the two control sheep.(AU)

Para avaliar a evolução das lesões agudas no cérebro de ovinos que se recuperam clinicamente de polioencefalomalacia aguda (PEM), dez ovinos foram usados neste experimento. Oito desses ovinos receberam doses variáveis de amprólio para induzir PEM. Quatro ovinos foram tratados intramuscularmente com 40mg/kg/peso corporal de tiamina para permitir a recuperação, e outros quatro ficaram sem tratamento. Dois ovinos controles não receberam amprólio nem tiamina e foram mantidos com os outros oito ovinos durante a duração do experimento. Exceto pelas duas drogas, a dieta e a fonte de água eram as mesmas para os dez ovinos. Dois ovinos que receberam doses diárias altas de amprólio, e um que recebeu doses menores, tiveram mortes agudas e desenvolveram lesões cerebrais constituídas por necrose neuronal laminar cortical (neurônios vermelhos), edema, tumefação de células endoteliais, astrócitos reativos, tumefação de células endoteliais e infiltração por células gitter. Quatro ovinos que se recuperam da PEM induzida por amprólio, após tratamento com tiamina, e outro que se recuperou espontaneamente, permaneceram clinicamente normais e foram submetidos a eutanásia seis meses após a recuperação clínica. Na necropsia, apresentavam alterações macroscópicas caracterizadas por ausência segmentar de tecido corticocerebral. Histologicamente, essas áreas privadas de tecido cortical consistiam de espaços praticamente vazios onde apenas vasos e células gitter eram vistos. Não foram encontradas alterações no encéfalo das duas ovelhas controle.(AU)

Healing of brain lesions in sheep recovered from amprolium-induced polioencephalomalacia / Cicatrização das lesões cerebrais em ovinos recuperados de polioencefalomalacia induzida por amprólio

To evaluate the outcome of acute lesions in the brains of sheep that completely clinically recover from acute polioencephalomalacia (PEM), ten sheep were used in this experiment. Eight of those sheep received varying doses of amprolium to induce PEM. Four sheep were treated intramuscularly with 40mg/kg/body weight with thiamine to allow recovery and four sheep were left untreated. Two control sheep did not receive either amprolium or thiamine and were kept along with the other eight sheep for the duration of the experiment. Except for the two drugs, the diet and water source were the same for the ten sheep. Two sheep receiving high daily doses of amprolium and one sheep receiving a lower dose had acute deaths and developed acute brain lesions consisting of neuronal laminar cortical necrosis (red neurons), edema, reactive astrocytes, swollen endothelial cells and gitter cells infiltration. Four sheep that recovered from lower doses of amprolium-induced PEM after being treated with thiamine and another one that recovered spontaneously were euthanatized six months after clinical recovery and had gross changes consisting of segmental absence of cortical tissue. Histologically these segmental cortex-deprived areas corresponded to quasi-empty spaces where only vessels and gitter cells existed. No changes were seen in the brains of the two control sheep.(AU)

Para avaliar a evolução das lesões agudas no cérebro de ovinos que se recuperam clinicamente de polioencefalomalacia aguda (PEM), dez ovinos foram usados neste experimento. Oito desses ovinos receberam doses variáveis de amprólio para induzir PEM. Quatro ovinos foram tratados intramuscularmente com 40mg/kg/peso corporal de tiamina para permitir a recuperação, e outros quatro ficaram sem tratamento. Dois ovinos controles não receberam amprólio nem tiamina e foram mantidos com os outros oito ovinos durante a duração do experimento. Exceto pelas duas drogas, a dieta e a fonte de água eram as mesmas para os dez ovinos. Dois ovinos que receberam doses diárias altas de amprólio, e um que recebeu doses menores, tiveram mortes agudas e desenvolveram lesões cerebrais constituídas por necrose neuronal laminar cortical (neurônios vermelhos), edema, tumefação de células endoteliais, astrócitos reativos, tumefação de células endoteliais e infiltração por células gitter. Quatro ovinos que se recuperam da PEM induzida por amprólio, após tratamento com tiamina, e outro que se recuperou espontaneamente, permaneceram clinicamente normais e foram submetidos a eutanásia seis meses após a recuperação clínica. Na necropsia, apresentavam alterações macroscópicas caracterizadas por ausência segmentar de tecido corticocerebral. Histologicamente, essas áreas privadas de tecido cortical consistiam de espaços praticamente vazios onde apenas vasos e células gitter eram vistos. Não foram encontradas alterações no encéfalo das duas ovelhas controle.(AU)

Amprolium-induced thiamine deficiency in mice: evaluation of a practical model by oral administration

Thiamine is an essential cofactor for several cellular functions. Your deficiency results in important neurological disorders, with mechanisms and lesions not fully understood. The purpose of this work was to evaluate a thiamine deficiency through the model of oral administration of amprolium in mice. The animals, treated for 20 or 80 days, received amprolium in drinking water at doses of 10, 20, and 30 mg/mL (deficient groups A, B, and C, respectively). Deficient groups A and B showed reduction in body weight gain and performance changes in the open field (decreased distance and rearing, and increased grooming) and rotarod (reduced latency to fall) behavioural tests, when treated for 80 days. However, no histological changes were observed in the central nervous system. Moreover, group B animals exposed to amprolium developed proteinuria, with moderate tubular nephrosis, at 80 days. At the highest dose (group C) there was no interest to drink water. The data suggest that the use of oral amprolium in mice may be an interesting and viable model, when using adequate exposure times and doses. The amprolium induces thiamine deficiency progressively and moderately, which may be potentially useful for disturbed pathogenesis studies.

Amprolium-induced thiamine deficiency in mice: evaluation of a practical model by oral administration

Thiamine is an essential cofactor for several cellular functions. Your deficiency results in important neurological disorders, with mechanisms and lesions not fully understood. The purpose of this work was to evaluate a thiamine deficiency through the model of oral administration of amprolium in mice. The animals, treated for 20 or 80 days, received amprolium in drinking water at doses of 10, 20, and 30 mg/mL (deficient groups A, B, and C, respectively). Deficient groups A and B showed reduction in body weight gain and performance changes in the open field (decreased distance and rearing, and increased grooming) and rotarod (reduced latency to fall) behavioural tests, when treated for 80 days. However, no histological changes were observed in the central nervous system. Moreover, group B animals exposed to amprolium developed proteinuria, with moderate tubular nephrosis, at 80 days. At the highest dose (group C) there was no interest to drink water. The data suggest that the use of oral amprolium in mice may be an interesting and viable model, when using adequate exposure times and doses. The amprolium induces thiamine deficiency progressively and moderately, which may be potentially useful for disturbed pathogenesis studies.(AU)

Polioencefalomalacia em ruminantes: aspectos etiológicos, clínicos e anatomopatológicos

Polioencefalomalacia é uma doença cosmopolita, multifatorial, que acomete bovinos,bubalinos, caprinos e ovinos. O termo polioencefalomalacia indica um diagnóstico morfológico deamolecimento por necrose (malacia) da substância cinzenta (pólio) do córtex cerebral. As causas de PEMsão variadas, no entanto possuem patogênese semelhante por promoverem alterações irreversíveis nometabolismo das células nervosas que invariavelmente evoluem para morte (necrose). As principaiscausas conhecidas são: deficiência de tiamina, intoxicação por enxofre, meningoencefalite porherpesvírus bovino tipo 5 (BoHV-5), intoxicação por sal associada a privação por água, intoxicação porchumbo, intoxicação por plantas que produzem tiaminases, amprólio e “Uva do Japão”.

Polioencephalomalacia is a cosmopolitan, multifactorial disease that affects cattle,buffaloes, goats and sheep. Polioencephalomalacia is a morphological diagnosis that means necrosis(malacia) in the cerebral cortex causing the softening of the gray matter (polio). Although the etiologicalagents are multiples, they have similar pathogenesis causing irreversible lesions in the metabolism ofnerve cells, leading to the cellular death. Among the main etiological agents are thiamine deficiency,sulfur intoxication, bovine herpesvirus type 5 (BHV-5) meningoencephalitis, salt intoxication associatedwith water deprivation, lead intoxication, intoxication by plants that produce thiaminases, amprolium andJapanese.

CICATRIZAÇÃO DAS LESÕES CEREBRAIS EM OVINOS RECUPERADOS DE POLIOENCEFALOMALACIA INDUZIDA POR AMPRÓLIO

Para avaliar a evolução das lesões agudas no cérebro de ovinos que se recuperam clinicamente de polioencefalomalacia aguda (PEM), dez ovinos foram usados neste experimento. Oito desses ovinos receberam doses variáveis de amprólio para induzir PEM. Quatro ovinos foram tratados intramuscularmente com 40mg/kg/peso corporal de tiamina para permitir a recuperação, e outros quatro ficaram sem tratamento. Dois ovinos controles não receberam amprólio nem tiamina e foram mantidos com os outros oito ovinos durante a duração do experimento. Exceto pelas duas drogas, a dieta e a fonte de água eram as mesmas para os dez ovinos. Dois ovinos que receberam doses diárias altas de amprólio, e um que recebeu doses menores, tiveram mortes agudas e desenvolveram lesões cerebrais constituídas por necrose neuronal laminar cortical (neurônios vermelhos), edema, tumefação de células endoteliais, astrócitos reativos, tumefação de células endoteliais e infiltração por células gitter. Quatro ovinos que se recuperam da PEM induzida por amprólio, após tratamento com tiamina, e um outro que se recuperou espontaneamente, permaneceram clinicamente normais e foram submetidos a eutanásia seis meses após a recuperação clínica. Na necropsia, apresentavam alterações macroscópicas caracterizadas por ausência segmentar de tecido corticocerebral. Histologicamente, essas áreas privadas de tecido cortical consistiam de espaços praticamente vazios onde apenas vasos e células gitter eram vistos. Não foram encontradas alterações no encéfalo das duas ovelhas controle.

To evaluate the outcome of acute lesions in the brains of sheep that completely clinically recover from acute polioence phalomalacia (PEM), ten sheep were used in this experiment. Eight of those sheep received varying doses of amprolium to induce PEM. Four sheep were treated intramuscularly with 40mg/ kg/body weight with thiamine to allow recovery and four sheep were left untreated. Two control sheep did not receive either amprolium or thiamine and were kept along with the other eight sheep for the duration of the experiment. Except for the two drugs, the diet and water source were the sarne for the ten sheep. Two sheep receivi ng high daily doses of amproli um and one sheep receivi ng a lower dose had acute deaths and developed acute brain lesions consisting of neuronal laminar cortical necrosis (red neurons), edema, reactive astrocytes, swollen endoth elial cells and gitter cells infiltration. Four sheep that recove red from lower doses of amprolium-induced PEM after being treated with thiamine and another one that recovered spontaneously were euthanatized six months after clinica!recovery and had gross changes consisting of segmenta! absence of cortical tissue. Histologically these segmenta) cortex-deprived areas corresponded to quasi-empty spaces where only vessels and gitter cells existed. No changes were seen in the brains of the two control sheep.

Modelo Experimental de Deficiência de Tiamina Induzida por Amprólio em Camundongos

As doenças neurológicas são bastante variadas e de grande impacto econômico na pecuária. Os distúrbios do sistema nervoso central (SNC) podem ser causados por vários agentes etiológicos, como agentes biológicos e por distúrbios metabólicos. Neste caso, destaca-se a polioencefalomalácia (PEM) desencadeada por deficiência de tiamina (vitamina B1). A PEM tem sido descrita em várias regiões do Brasil, envolvendo bovinos, ovinos e caprinos. Entretanto, a deficiência de tiamina é importante também para carnívoros (paralisia de Chastek) e humanos (doença de Wernicke e síndrome de Wernicke-Korsakoff). As regiões do SNC envolvidas na PEM são variadas e contraditórias, mas são afetadas desde áreas corticais até regiões profundas como mesencéfalo e tálamo. Nestes locais, tipicamente há degeneração e necrose neuronal, com envolvimento adjacente de alterações astrocitárias e inflamatórias. Pouco ainda se conhece sobre os mecanismos moleculares e celulares da degeneração e morte dos neurônios, entretanto, considera-se que o processo relacionado à deficiência de tiamina se inicia por defeitos metabólicos na mitocôndria com consequente estabelecimento de estresse oxidativo. No presente trabalho objetivou-se determinar diferentes parâmetros relacionados à deficiência de tiamina no sistema nervoso central em um modelo in vivo com intuito de avaliar a ocorrência de morte celular e os mecanismos moleculares envolvidos, associação de alterações comportamentais nos animais-modelo e o delineamento de estratégias neuroprotetoras eficientes, caracterizando as áreas do SNC envolvidas na degeneração induzida por deficiência de tiamina. O modelo de deficiência dietética em associação com injeções do antagonista de tiamina, amprólio, foi utilizado no presente estudo. Os animais foram tratados por 15 ou 20 dias, divididos em 6 grupos de tratamento: controle (Cont), amprólio (Amp), amprólio e Trolox® (Amp+Tr), amprólio e DMSO (Amp+Dmso), Trolox® (Tr) e DMSO (Dmso). Os camundongos submetidos ao modelo de deficiência de tiamina (grupo Amp) exibiram redução significativa no ganho de peso corporal, após 15 e 20 dias de tratamento. À análise histopatológica, foi observado no grupo Amp esteatose hepática centrolobular em 15 dias e difusa quando tratados por 20 dias, além de proteinúria moderada. Trolox e DMSO atenuaram acentuadamente a esteatose (grupos Amp+Tr e Amp+Dmso). Não foram observadas alterações histológicas no SNC em 15 ou em 20 dias de tratamento. Entretanto, a viabilidade celular do córtex cerebral reduziu significativamente no grupo Amp após 20 dias de tratamento; efeito que foi revertido nos grupos Amp+Tr e Amp+Dmso. Além disso, os animais deficientes (Amp) apresentaram alterações comportamentais como redução nas atividades de ambulação e exploratória e na coordenação motora e, de modo interessante, Trolox e DMSO atenuaram estes efeitos. Estes dados sugerem que no modelo de deficiência de tiamina com amprólio os animais desenvolvem alterações neurológicas e metabólicas, associadas ao estresse oxidativo e, possivelmente, inflamação. Além disso, o modelo se mostra viável para estudo da deficiência da vitamina com estabelecimento de um processo progressivo gradual, sem ser acentuadamente agressivo, como no clássico modelo da piritiamina.

Neurological diseases are quite varied and have a great economic impact on livestock. Central nervous system (CNS) disorders may be caused by various etiologic agents, such as biological agents and by metabolic disorders. In this case, we highlight the polioencephalomalacia (PEM) triggered by thiamine deficiency (vitamin B1). PEM has been described in several regions of Brazil, involving cattle, sheep and goats. However, thiamine deficiency is important also for carnivores (Chastek's palsy) and humans (Wernicke disease and Wernicke-Korsakoff syndrome). The CNS regions involved in PEM are varied and contradictory, but are affected from cortical areas to deep regions such as the midbrain and thalamus. At these sites, there is typically neuronal degeneration and necrosis, with adjacent involvement of astrocytic and inflammatory changes. Little is known about the molecular and cellular mechanisms of degeneration and death of neurons. However, it is considered that the process related to thiamine deficiency is initiated by metabolic defects in the mitochondria with consequent establishment of oxidative stress. In the present work, we aimed to determine different parameters related to thiamine deficiency in the CNS in an in vivo model to evaluate the occurrence of cell death and the molecular mechanisms involved, association of behavioral changes and the design of efficient neuroprotective strategies, characterizing the CNS areas involved in thiamine deficiency-induced degeneration. The model of dietary deficiency in combination with injections of the thiamine antagonist, amprolium, was used in the present study. The animals were treated for 15 or 20 days and divided into 6 treatment groups: control (cont), amprolium (Amp), amprolium and Trolox® (Amp+Tr), amprolium and DMSO (Amp+Dmso), Trolox® (Tr) and DMSO (Dmso). Mice subjected to the thiamine deficiency model (Amp) exhibited a significant reduction in body weight gain after 15 and 20 days of treatment. The histopathological analysis revealed in the Amp group, centrolobular hepatic steatosis at 15-day and diffuse hepatic steatosis when treated for 20 days, in addition to moderate proteinuria. Trolox® and DMSO markedly attenuated steatosis (Amp+Tr and Amp+Dmso groups). No histological changes were observed in the CNS within 15 or 20 days of treatment. However, the cellular viability of the cerebral cortex significantly reduced in the Amp group after 20 days of treatment; which effect was reversed in the Amp+Tr and Amp+Dmso groups. In addition, deficient animals (Amp) presented behavioral changes such as reduction in ambulation and exploratory activities and in motor coordination and, interestingly, Trolox® and DMSO attenuated these effects. These data suggest that in the model of thiamine deficiency with amprolium the animals develop neurological and metabolic alterations, associated with oxidative stress and possibly inflammation. In addition, the model proves feasible for the study of vitamin deficiency with the establishment of a gradual progressive process, without being markedly aggressive, as in the classic model of pyrithiamine.

Anticoccidial activity of hydrochloric acid (HCl) against Eimeria tenella in broiler chickens

The present study was planned to evaluate the anticoccidial activity of the different concentrations of the HCl against Eimeria tenella infection in broiler chickens in comparison with the amprolium anticoccidial. For this purpose, a total of 198 chicks were placed 11 per pen with three pens per treatment. The different concentrations of HCl (1000ppm, 2000ppm and 3000ppm) and amproilum (at the dose rate of 125ppm) were given to the experimental groups in drinking water from 10 to 19th days of age. One group was kept as infected non medicated control and one as non infected non medicated control. At the 12th day of age, all the groups were inoculated orally with 75,000 sporulated oocysts except non infected non medicated control. Anticoccidial activity was evaluated on the basis of performance (weight gain, feed conversion ratio) and pathogenic (oocyst score, lesion score and mortality percentage) parameters. Among HCl medicated groups, the maximum anticoccidial effect was seen in the group medicated with 1000ppm HCl followed by 2000ppm and 3000ppm HCl medicated groups. Amprolium and 1000ppm HCl were almost equivalent in suppressing the negative performance and pathogenic effects associated with coccidiosis (Eimeria tenella) challenge. In summary, the lower doses of HCl have the potential to be used as alternative to chemotherapeutic drugs for Eimeria tenella control. It is therefore suggested that further studies should be carried out to determine the possible minimum safe levels of HCl with least toxic effects to be used as anticoccidial.(AU)

Anticoccidial effects of acetic acid on performance and pathogenic parameters in broiler chickens challenged with Eimeria tenella

The objective of the present study was to evaluate the anticoccidial effect of the different concentrations of the acetic acid in the broiler chickens in comparison with the amprolium anticoccidial. A total of 198 chicks were placed 11 per pen with three pens per treatment. The different concentrations (1 percent, 2 percent and 3 percent) of acetic acid and amproilum (at the dose rate of 125ppm) were given to the experimental groups in drinking water from 10-19th days of age. One group was kept as infected non medicated control and one as non infected non medicated control. All the groups were inoculated orally with 75,000 sporulated oocysts at the 12th day of age except non infected non medicated control. Anticoccidial effect was evaluated on the basis of performance (weight gain, feed conversion ratio) and pathogenic (oocyst score, lesion score and mortality percentage) parameters. Among acetic acid medicated groups, the maximum anticoccidial effect was seen in the group medicated with 3 percent acetic acid followed by 2 percent and 1 percent acetic acid medicated groups. Amprolium and 3 percent acetic acid were almost equivalent in suppressing the negative performance and pathogenic effects associated with coccidiosis (Eimeria tenella) challenge. In summary, acetic acid has the potential to be used as alternative to chemotherapeutic drugs for Eimeria tenella control. Concentration-dependent anticoccidial effect of acetic acid suggests that further studies should be carried out to determine the possible maximum safe levels of acetic acid with least toxic effects to be used as anticoccidial.(AU)

Polioencefalomalacia experimental induzida por amprólio em bovinos / Experimentally amprolium-induced polio-encephalomalacia in cattle

Para estabelecer um modelo experimental para o estudo da etiologia, patologia e patogênese da polioencefalomalacia (PEM) em bovinos, a condição foi induzida em quatro novilhos pela administração oral de amprólio nas doses diárias de 500 e 350mg/kg de peso vivo, respectivamente por 22 e 26-28 dias. Todos os bovinos morreram espontaneamente ou foram eutanasiados in extremis após um curso clínico de 4-7 dias. Três bovinos que receberam 1.000mg/kg de amprólio e dois que receberam 500mg/kg morreram espontaneamente com quadro clínico agudo a subagudo sem desenvolverem sinais e lesões de PEM. Nos novilhos que PEM foi reproduzida, os sinais neurológicos incluíram marcada apatia, incoordenação, posição de cavalete, quedas ocasionais, hiperexcitabilidade, tremores musculares, cegueira, bruxismo, estrabismo, nistagmo, midríase, opistótono, decúbito lateral e movimentos de pedalagem. Os principais achados de necropsia eram restritos ao encéfalo e consistiam de tumefação, achatamento, amolecimento e amarelamento das circunvoluções cerebrais. Histologicamente, havia necrose neuronal segmentar e laminar (neurônios vermelhos) associada a edema, tumefação endotelial, separação das lâminas de neurônios do córtex telencefálico ou entre as substâncias cinzenta e branca e infiltração moderada a acentuada de macrófagos espumosos. Essas alterações eram mais acentuadas nos lobos telencefálicos frontal, parietal e occipital. Adicionalmente, lesões similares e moderadas foram detectadas no mesencéfalo e hipocampo. A necrose neuronal e o edema afetaram uniformemente as camadas de neurônios da substância cinzenta dos lobos telencefálicos frontal, parietal e occipital. Esse modelo experimental de PEM com administração oral de amprólio parece ser útil para o estudo da doença em bovinos, conforme observado anteriormente em ovinos.(AU)

In order to establish an experimental model for the study of the etiology, pathology, and pathogenesis of polioencephalomalacia (PEM) in cattle, the condition was induced into four steers by oral administration of amprolium at daily doses of 500 and 350mg per kg of body weight respectively for 22 and 26-28 days. All steers died spontaneously or were euthanized in extremis after being sick for 4-7 days. Three steers that received the drug at 1,000mg/kg and two that received 500mg/kg died spontaneously with acute or subacute clinical signs and without lesions and signs of PEM. In those steers in which PEM was reproduced, the neurological signs included marked apathy, incoordination, sawhorse stance, occasional falls, hyperexcitability, muscle tremors, blindness, grinding of teeth, strabismus, nystagmus, mydriasis, opisthotonus, and lateral recumbency with paddling movements. Main gross lesions were restricted to the brain and included swelling, flattening, softening and yellow discoloration of the cerebral circumvolutions. Histologically, there was segmental laminar neuronal necrosis (red neurons) associated with edema, swelling of endothelial cells, cleavage of laminar neuronal layers or between gray and white matter and moderate to severe infiltration by foamy macrophages (gitter cells). These changes were more marked in the frontal, parietal and occipital telencephalic lobes. Additionally, similar and moderate lesions were detected in the midbrain and hippocampus. Neuronal necrosis and edema affected uniformly the neurons layers of the grey matter of the frontal, parietal and occipital lobes. This experimental model of PEM with oral administration of amprolium may be useful for the study in cattle, as previously observed in sheep.(AU)

Polioencefalomalacia experimental induzida por amprólio em ovinos / Experimentally amprolium-induced polioencephalomalacia in sheep

Para estabelecer um modelo experimental para o estudo da etiologia, patologia e patogênese da polioencefalomalacia em ruminantes, a condição foi induzida em cinco ovinos pela administração oral de amprólio nas doses diárias de 500 e 1.000mg/kg de peso animal, respectivamente por 28-59 dias e 13-39 dias. Todos os ovinos morreram ou foram eutanasiados in extremis após um curso clínico de 3-7 dias. Os sinais clínicos incluíam depressão, incoordenação, midríase, bruxismo, cegueira e decúbito com opistótono e movimentos de pedalagem. Salivação excessiva e posição de cavalete foi observada em um ovino e mioclonias em um outro. Os principais achados de necropsia restringiam-se ao sistema nervoso central e incluíam tumefação do encéfalo com achatamento dos giros telencefálicos e hemorragias nos lobos parietal e occipital do telencéfalo; as hemorragias ocorriam também nas áreas submeníngeas da medula espinhal e do mesencéfalo. Histologicamente, havia necrose segmentar laminar de neurônios (neurônios vermelhos) associada a edema, tumefação de células endoteliais, hemorragias e infiltração por macrófagos espumosos (células gitter). Essas alterações eram mais marcadas nos lobos frontal, parietal e occipital do telencéfalo e havia uma demarcação abrupta entre as lesões e o neurópilo normal adjacente. Adicionalmente, lesões semelhantes, mas menos acentuadas, eram observadas no mesencéfalo, tálamo e hipocampo. Levando em consideração a reproducibilidade regular dos aspectos da polioencefalomalacia em ovinos pela administração de amprólio, esse modelo pode ser útil para o estudo da doença.(AU)

In order to establish an experimental model for the study of the etiology, pathology, and pathogenesis of polioencephalomalacia in ruminants, the condition was induced in five sheep by oral administration of amprolium at daily doses of 500 and 1,000mg per kg of body weight respectively for 28-59 days and for 13-39 days. All sheep died or were euthanized in extremis after illness of 3-7 days. Clinical signs included depression, incoordination, midriasis, grinding of the teeth, blindness, and laying down with opisthotonus and paddling movements. Drooling and a sawhorse stance were observed in one sheep and myoclonus in another one. Main gross lesions were restricted to the central nervous system and included swelling of the brain with flattening of telencephalic gyri, and hemorrhages in the parietal and occipital lobes of the telencephalon, in the submeningeal areas of the spinal cord and in the mesencephalon. Histologically, there was segmental laminar neuronal necrosis (red neurons) associated with edema, swelling of endothelial cells, hemorrhages and infiltration by foamy macrophages (gitter cells). These changes were more marked in the frontal, parietal and occipital telecephalic lobes and there was sharp demarcation between the lesions and the adjacent normal neuropile. Additionally, similar, but less marked lesions were seen in the mesencephalon, thalamus and hippocampus. Considering the consistent reproducible aspects of polioencephalomalacia in sheep using amprolium, this may be an useful model for the study of the disease.(AU)

Reactivation of latent bovine herpesvirus type 5 in cattle with polioencephalomalacia induced by ammonium sulphate / Reativação de herpesvírus bovino tipo 5 latente em bovinos com polioencefalomalacia induzida por sulfato de amônia

In the state Mato Grosso do Sul, Brazil, outbreaks of meningoencephalitis by BoHV-5 and polioencephalomalacia (PEM) display similar epidemiological features, suggesting that meningoencephalitis may be associated with reactivation of a latent BoHV-5 infection, during the development of PEM. To test this hypothesis, four 7-8 months old steers negative for BoHV-5 antibodies were inoculated intranasally with BoHV-5 and received amprolium from day 35 to day 105 after inoculation. Because PEM was not produced during this period, ammonium sulphate was given from day 114 to day 180 after inoculation. Two uninfected control steers received amprolium and ammonium sulphate for the same periods. All inoculated cattle developed antibodies against BoHV-5 after inoculation and the virus was isolated from nasal swabs, indicating that they were infected. Two inoculated steers had clinical signs of PEM after 118 and 146 days after virus inoculation. One was euthanized after a clinical manifestation period of seven days and had severe lesions of PEM and meningoencephalitis. BoHV-5 was isolated from the central nervous system of this animal. The other animal recovered but continued to manifest chronic signs of PEM and was euthanatized. On histological examination, the cerebral cortex, caudate nucleus and thalamus had multifocal areas of malacia and mild meningoencephalitis of the cortex. BoHV-5 was not isolated from the brain. One uninfected control steer had signs of neurological disease on day 158 and had lesions of PEM without meningoencephalitis at necropsy. The simultaneous production of PEM and diffuse meningoencephalitis, with isolation of BoHV-5, in one steer treated with ammonium sulphate, 118 days after BoHV-5 inoculation, suggests that latent BoHV-5 was reactivated in this animal submitted to experimental induction of PEM.(AU)

No Mato Grosso do Sul surtos de meningoencefalite por herpesvírus bovino-5 (BoHV-5) e polioencefalomalacia (PEM) apresentam características epidemiológicas semelhantes, o que sugere que a meningoencefalite pode estar associada com a reativação de uma infecção latente por BoHV-5 em animais com PEM. Para testar esta hipótese, 4 garrotes de 7-8 meses de idade, sem anticorpos séricos para BoHV-5 foram inoculados intranasal com BoHV-5 e receberam amprólio desde o dia 35 até o dia 105 após inoculação. Como não foi reproduzida PEM durante este período, os animais receberam sulfato de amônia desde o dia 114 até o dia 180 após inoculação. Dois bovinos controles, não inoculados, receberam amprólio e sulfato de amônia durante os mesmos períodos. Todos os bovinos inoculados apresentaram anti-corpos contra BoHV-5 após a inoculação e o vírus foi isolado de suabes nasais, indicando que foram infectados. Dois bovinos inoculados tiveram sinais clínicos de PEM após 118 e 146 dias da inoculação de vírus. Um que foi eutanasiado após um curso clínico de 7 dias apresentou lesões severas de PEM e meningoencefalite. BoHV-5 foi isolado do sistema nervoso central. O outro se recuperou, mas continuou a apresentar sinais crônicos de PEM. No exame histológico o córtex cerebral, núcleo caudato e tálamo apresentavam áreas multifocais de malacia e no córtex havia moderada meningoencefalite. BoHV-5 não foi isolado do encéfalo. Um garrote controle, não inoculado, apresentou sinais nervosos aos 158 dias após inoculação e na necropsia apresentava lesões de PEM, mas sem meningoencefalite. A reprodução simultânea de PEM e encefalite difusa em um animal tratado com sulfato de amônia, 118 dias após a inoculação de BoHV-5 e o re-isolamento do vírus do animal infectado sugere que a infecção latente por BoHV-5 foi reativada no animal submetido a indução experimental de PEM.(AU)

Amprolium-induced thiamine deficiency in mice: evaluation of a practical model by oral administration

Thiamine is an essential cofactor for several cellular functions. Your deficiency results in important neurological disorders, with mechanisms and lesions not fully understood. The purpose of this work was to evaluate a thiamine deficiency through the model of oral administration of amprolium in mice. The animals, treated for 20 or 80 days, received amprolium in drinking water at doses of 10, 20, and 30 mg/mL (deficient groups A, B, and C, respectively). Deficient groups A and B showed reduction in body weight gain and performance changes in the open field (decreased distance and rearing, and increased grooming) and rotarod (reduced latency to fall) behavioural tests, when treated for 80 days. However, no histological changes were observed in the central nervous system. Moreover, group B animals exposed to amprolium developed proteinuria, with moderate tubular nephrosis, at 80 days. At the highest dose (group C) there was no interest to drink water. The data suggest that the use of oral amprolium in mice may be an interesting and viable model, when using adequate exposure times and doses. The amprolium induces thiamine deficiency progressively and moderately, which may be potentially useful for disturbed pathogenesis studies.