Sodium fluoroacetate poisoning: A case report / Intoxicación por fluoroacetato de sodio, un reporte de caso

Abstract Introduction: Sodium fluoroacetate, known as compound 1080, was discovered in Germany during the Second World War. It is usually used as a rodenticide, it is an odorless and tasteless substance, with a lethal dose in humans of 2 mg / kg that is why it was withdrawn from the market in some countries, including Colombia; however, it is obtained illegally. This substance has biochemical and physiological effects at the cellular level that alter the transport of citrate at the mitochondrial level, generating accumulation of lactic acid and alteration of the glucose use. The clinical manifestations are nonspecific since there is no any cardinal symptom. Therefore, its diagnosis is made due to high clinical suspicion associated with establishment of exposure to the compound in view of the difficulty to obtain paraclinical confirmation in a timely manner. Methods: We present a case report of intentional ingestion of sodium fluoroacetate in an adolescent that is associated with an infection added to the bloodstream by methicillin- sensitive Staphylococcus aureus (MSSA). The patient developed multiple complications that lead to support in the Intensive Care Unit (ICU) with a satisfactory outcome. In view of the lack of a specific antidote, she was treated with ethanol in order to increase the level of acetate; thus, offering an alternative substrate to the Krebs cycle. It is suggested that the ethanol offers benefits in the acute treatment of these patients. Results: The patient with sodium fluoroacetate poisoning and kidney failure received renal replacement therapy with a favorable evolution and survival at discharge from the intensive care unit of a third-level hospital in the city of Pereira, Risaralda, Colombia. Conclusions: Sodium fluoroacetate poisoning is relatively rare and can cause acute kidney injury and multi-organ failure with a high rate of complications and death. A case of self-inflicted poisoning that received a timely manner continuous renal replacement therapy with a favorable outcome in terms of ICU survival was presented.

Resumen Introducción: El fluoroacetato de sodio ⎯conocido como compuesto 1080⎯, fue descubierto en Alemania durante la segunda guerra mundial, suele ser utilizado como raticida y se caracteriza por ser una sustancia inodora e insabora. En humanos, una dosis de 2 a mg/kg es letal; debido a su toxicidad fue retirado del mercado en algunos países, incluyendo Colombia, no obstante, se consigue de forma ilegal. Esta sustancia tiene efectos bioquímicos y fisiológicos a nivel celular que altera el transporte del citrato a nivel mitocondrial, generando acumulación de ácido láctico y alteración en la utilización de la glucosa. Las manifestaciones clínicas son inespecíficas y no existe un síntoma cardinal. Por ende, su diagnóstico se realiza por alta sospecha clínica, asociado al establecimiento de la exposición al compuesto, ya que la confirmación paraclínica es difícil de realizar oportunamente. Métodos: Se presenta un reporte de caso de ingestión intencional en un adolescente, asociado con infección agregada al torrente sanguíneo por Estafilococos Aureos Meticilino Sensible (EAMS). El paciente desarrolló múltiples complicaciones y requirió asistencia en Unidad de Cuidados Intensivos (UCI) con desenlace satisfactorio. Ya que no se cuenta con antídoto específico , se le dio tratamiento con etanol para aumentar el nivel de acetato, ofreciendo así un sustrato alterno al ciclo de Krebm. Se estima que el etanol puede ofrecer beneficios en el tratamiento agudo de estos pacientes. Resultados: Paciente con intoxicación por fluoroacetato de sodio e insuficiencia renal, recibe terapia de reemplazo renal con un evolución favorable y supervivencia al alta de la Unidad de Cuidados Intensivos de un hospital de tercer nivel en la ciudad de Pereira, Risaralda, Colombia. Conclusiones: La intoxicación por fluoroacetato de sodio es relativamente poco frecuente y puede causar injuria renal aguda y falla multiorgánica con alta tasa de complicaciones y muerte. Se presentó un caso de intoxicación autoinfligida que recibió terapia de reemplazo renal continua temprana con un desenlace favorable en términos de supervivencia en la UCI.

Herbaspirillum seropedicae as a degrading bacterium of monofluoroacetate: effects of its inoculation in goats by ingesting Amorimia septentrionalis and the concentrations of this compound in plants sprayed with the bacterium / Herbaspirillum seropedicae como bactéria degradadora de monofluoroacetato de sódio: efeitos de sua inoculação em caprinos ingerindo Amorimia septentrionalis e nas concentrações deste composto em plantas pulverizadas com a bactéria

Herbaspirillum seropedicae is a nitrogen-fixing bacterium capable of using toxic compounds as a source of carbon. Bacteria with this capacity can be used to make animals resistant to plant poisoning containing monofluoroacetate (MFA), such as Amorimia septentrionalis. The aim of this study was to evaluate if H. seropedicae is efficient in the degradation of MFA present in A. septentrionalis and if the inoculation of this bacterium in goats confers protection to A. septentrionalis intoxication. Two experiments were performed: in the first experiment 12 goats were divided into 2 groups. Goats in Group 1 were orally administered a solution containing the H. seropedicae bacterium for 10 days. From day 10 onwards, they received a daily dose of 5g/kg of A. septentrionalis with the bacteriauntil clinical signs of intoxication were observed. Group 2 goats received only the plant at the same dose, also until the observation of clinical signs of intoxication. The amount of MFA found in A. septentrionalis used in the experiment with goats was 1.6±0.058μg/mg. The total plant dose ingested by all goats in Group 1 was 80.83±12.81g/kg (129.33±20.50mg/kg MFA), which were significantly greater ​​(p<0.05) than those of Group 2 goats (39.16±19.08g/kg plant and 62.66±30.53mg/kg MFA). Group 1 goats took an average of 16.16±2.56 days to develop clinical signs of intoxication, significantly longer (p=0.0012) than Group 2 goats (7.83±3.81 days). Two Group 2 goats died on the same day that they developed clinical signs of intoxication. At necropsy of these two animals, no significant changes were observed. In the second experiment, samples of A. septentrionalis were sprayed with a solution containing H. seropedicae. Before and eight days after spraying, the samples were pressed and dried for quantitation of MFA. The amount of MFA present in samples of A. septentrionalis 8 days after spraying with H. seropedicae was significantly lower (p=0.017) than that found prior to spraying. It can be concluded that administration of H. seropedicae in goats is capable of causing greater resistance to A. septentrionalis intoxication, and spraying the plant with this bacterium significantly reduces the amount of MFA in the plant.(AU)

Herbaspirillum seropedicae é uma bactéria fixadora de nitrogênio, capaz de utilizar compostos tóxicos como fonte de carbono. Bactérias com essa capacidade podem ser utilizadas para tornar os animais resistentes à intoxicação por plantas que contém monofluoroacetato (MFA), como Amorimia septentrionalis. O objetivo do presente estudo é avaliar se H. seropedicae é eficiente na degradação do MFA presente em A. septentrionalis e se a inoculação dessa bactéria, em caprinos, confere proteção à intoxicação por A. septentrionalis. Foram realizados dois experimentos: no primeiro experimento foram utilizados 12 caprinos, divididos em dois grupos. Os caprinos do Grupo 1 receberam diariamente, oralmente, uma solução contendo a bactéria H. seropedicae durante 10 dias. A partir do décimo dia passaram a receber, diariamente, além da solução com a bactéria 5g/kg de A. septentrionalis até a observação de sinal clínico de intoxicação. Os caprinos do Grupo 2 receberam apenas a planta na mesma dose, também até que a observação de sinais clínicos de intoxicação. A quantidade de MFA encontrada em A. septentrionalis utilizada no experimento com caprinos foi de 1,6± 0,058µg/mg de planta em média. A dose total de planta ingerida por todos os caprinos do Grupo 1 foi de 80,83±12,81g/kg (129,33±20,50mg/kg de MFA), valores significativamente maiores (p<0,05) do que os dos caprinos do Grupo 2 (39,16±19,08g/kg de planta e 62,66± 30,53mg/Kg de MFA). Os caprinos do Grupo 1 demoraram em média 16,16 ±2,56 dias para desenvolver sinais clínicos da intoxicação, período significativamente maior (p=0,0012) que os caprinos do Grupo 2 (7,83±3,81dias). Dois caprinos do Grupo 2 morreram no mesmo dia que desenvolveram sinais clínicos da intoxicação. Na necropsia desses dois animais não foram observadas alterações significativas. No segundo experimento, amostras de A. septentrionalis foram pulverizadas com uma solução contendo a bactéria H. seropedicae. Antes e oito dias após a pulverização, as amostras foram prensadas e secas para posterior quantificação do MFA. A quantidade de MFA presente nas amostras de A. septentrionalis oito dias após a pulverização com H. seropedicae foi significativamente menor (p=0,017) do que a encontrada antes da pulverização. Pode-se concluir que a administração de H. seropedicae em caprinos é capaz de causar uma maior resistência à intoxicação por A. septentrionalis, e a pulverização da planta com esta bactéria reduz significativamente a quantidade de MFA na planta.(AU)

Techniques for prevention and control of poisoning by sodium monofluoroacetate (MFA)-containing plants in ruminants / Técnicas para prevenção e controle da intoxicação em ruminantes por plantas que contém monofluoroacetato de sódio

Monofluoroacetate (MFA)-containing plants cause sudden death associated with exercise in ruminants, and are responsible for significant losses in Brazilian livestock, estimated at 500,000 bovine deaths annually. Most of the times, the control and treatment of this type of poisoning are not efficient, because disease evolution is superacute, usually causing the death of the animal. Due to the difficulty in controlling this intoxication, several studies have suggested alternatives to prevent it, mainly by making animals resistant to the MFA present in these plants or by avoiding their consumption. This literature review addresses the techniques used experimentally to control the poisoning of ruminants by plants containing MFA. The first studies carried out in Brazil demonstrated that goats and sheep that continuously receive non-toxic doses of plant containing MFA show greater resistance to poisoning than untreated animals, and that this resistance can be transmitted by ruminal fluid transfaunation, suggesting that poisoning occurs due to the presence of bacteria that hydrolyze MFA in the rumen. Based on this hypothesis, several MFA-hydrolyzing bacteria were isolated (Enterococcus faecalis, Bacillus sp., Paenibacillus sp., Burkholderia sp., Cupriavidus sp., Staphylococcus sp., Ancylobacter sp., Ralstonia sp., Stenotrophomonas sp., Pigmentiphaga kullae, and Ancylobacter dichloromethanicus). When some of these bacteria were administered intraruminally, they provided the animal with a different level of protection against poisoning. However, it was observed that protection is gradually lost when the bacterium administration is interrupted. Consequently, to obtain more efficient protection, these bacteria should be administered continuously, probably in the form of probiotics. In another assay, MFA was administered to sheep at non-toxic doses to test the hypothesis that this substance could induce the multiplication of bacteria that hydrolyze it in the rumen. There was no increase in resistance to poisoning after administration of MFA; however, no signs of poisoning were observed when animals received trifluoroacetate and no clinical signs were verified when they were challenged with toxic doses of MFA; in contrast, all control animals presented clinical signs. These results suggest that trifluoroacetate induces the proliferation of MFA-degrading bacteria, and can be used in intoxication prophylaxis. The conditioned food aversion technique, using lithium chloride, has been successfully used experimentally to prevent ruminants from ingesting plants that contain MFA. Another alternative tested was the spraying of Amorimia septentrionalis with the endophytic bacterium Herbaspirillum seropedicae, which degrades MFA, resulting in decreased concentration of this compound in the plants. In conclusion, several experimental techniques have been proved efficient in the control and prophylaxis of MFA-containing plant poisoning; however, none of these techniques are available commercially. Further experiments, mainly in the field, should be carried out to adapt some of these techniques to the conditions of extensive breeding in the numerous areas where MFA-containing plants occur.(AU)

As plantas que contém monofluoroacetato (MFA) causam morte súbita associada ao exercício em ruminantes, e são responsáveis por grandes perdas na pecuária brasileira, estimadas em 500.000 mortes de bovinos anualmente. O controle e tratamento desse tipo de intoxicação, na maioria das vezes, não apresenta eficiência, visto que a evolução da doença é superaguda, e geralmente ocasiona a morte do animal. Devido à dificuldade no controle dessa intoxicação, diversos estudos sugerem alternativas para preveni-la, principalmente tornando os animais resistentes ao MFA presente nessas plantas ou evitando seu consumo. O objetivo do presente trabalho é fazer uma revisão bibliográfica das técnicas utilizadas experimentalmente para controlar a intoxicação de ruminantes por plantas que contém MFA. Nos primeiros trabalhos realizados no Brasil, foi determinado que caprinos e ovinos que recebem continuadamente doses não tóxicas de planta que contém MFA apresentam maior resistência a intoxicação que animais não tratados e que essa resistência pode ser transmitida por transfaunação de fluído ruminal, sugerindo que a mesma ocorre devido a presença de bactérias que hidrolisam MFA no rúmen. Com base nessa hipótese foram isoladas diversas bactérias que hidrolisam MFA (Enterococcus faecalis, Bacillus sp., Paenibacillus sp., Burkholderia sp., Cupriavidus sp., Staphylococcus sp., Ancylobactersp., Ralstoniasp., Stenotrophomonas sp., Pigmentiphaga kullae e Ancylobacter dichloromethanicus). Quando algumas dessas bactérias foram administradas intraruminalmente conferiram diferentes graus de proteção contra a intoxicação. No entanto foi observado que a proteção se perde gradualmente quando se deixa de administrar a(s) bactéria(s). Em consequência, para obter uma proteção mais eficiente essas bactérias deveriam ser administradas continuadamente, provavelmente na forma de probiótico. Em outro ensaio administrou-se MFA a ovinos em doses não tóxicas para testar a hipótese de que esta substância poderia induzir a multiplicação de bactérias que hidrolisam o mesmo no rúmen. Não houve um aumento da resistência a intoxicação após a administração de MFA; no entanto quando foi administrado trifluoroacetato, os animais não desenvolveram nenhum sinal de intoxicação e quando desafiados com doses tóxicas de MFA não apresentaram sinais clínicos, pelo contrário todos os animais controles apresentaram sinais clínicos. Esses resultados sugerem que o trifluoroacetato induz a proliferação de bactérias que degradam MFA e pode ser utilizado para a profilaxia da intoxicação. A técnica da aversão alimentar condicionada, utilizando cloreto de lítio, tem sido empregada experimentalmente, com sucesso, para evitar que ruminantes ingiram plantas que contém MFA. Outra alternativa testada foi a pulverização de Amorimia septentrionalis com a bactéria endofítica Herbaspirullum seropedicae, que degrada MFA, resultando na diminuição da concentração deste composto na planta. Conclui-se que há diversas técnicas que experimentalmente tem demonstrado eficiência no controle e profilaxia das intoxicações por plantas que contém MFA; no entanto, nenhuma dessas técnicas está disponível comercialmente. Futuros experimentos, principalmente, a campo, deverão ser realizados para adaptar alguma(s) dessas técnicas as condições de criação extensiva nas numerosas áreas onde ocorrem plantas que contém MFA.(AU)

Neonatal mortality associated with sodium monofluoracetate in kids fed with colostrum from goats ingesting Amorimia septentrionalis / Mortalidade neonatal associada ao monofluoroacetato de sódio em cabritos alimentados com colostro de cabras ingerindo Amorimia septentrionalis

Sudden deaths after colostrum ingestion in kids and lambs born to mothers grazing in areas with Amorimia septentrionalis have been reported in the Brazilian northeastern semi-arid region, in Paraíba state. This study aimed to determine whether the sodium monofluoracetate (MF) contained in A. septentrionalis is eliminated in milk, causing the death of kids. After confirming gestation on the 25th day after mating, 26 goats were randomly distributed into three groups. In Group 1, eight goats received fresh leaves of A. septentrionalis in daily doses of 1g/kg body weight, administered at three different periods during gestation: from days 91 to 100, 116 to 125, and from day 140 until delivery day. In Group 2, consisting of 10 females, eight goats received 1g/kg body weight of A. septentrionalis dried and milled leaves, fed daily from the 140th day of gestation until delivery. The other two goats of this group did not ingest the plant during gestation and after delivery the colostrum supplied to their kids was replaced by colostrum of goats from that same group that had ingested the plant. Eight goats from Group 3 (control) did not ingest A. septentrionalis. Seven goats from Group 1 showed signs of poisoning from 2nd to 8th days of plant administration, in all periods, and recovered within 7 to 12 days. Another goat presented severe clinical signs and was submitted to euthanasia in extremis. Two goats aborted. Four kids, from two goats, received colostrum and, after 15 minutes, presented depression, breathing wheezing, lateral recumbence, bleating, and death. Two goats gave birth at night; the two kids were found dead and, at necropsy, it was verified that they were born alive. The last goat in this group gave birth to two kids which showed no signs of poisoning after colostrum ingestion. In Group 2, the eight goats that ingested dry leaves of the plant presented tachycardia and engorgement of the jugular veins; six aborted, and the kids of the other two goats died immediately after delivery without ingesting colostrum. The three kids of the two goats that did not ingest the plant during gestation did not show signs of poisoning after ingesting colostrum from the goats that had ingested the plant. In Group 3, all females kidded normally and the kids showed no signs of poisoning. Ten leaf samples of A. septentrionalis contained 0.00074% ±0.00018 MF. These results demonstrate that the MF of A. septentrionalis is eliminated in colostrum and may cause the death of kids. As in previous reports, the plant also caused abortion.(AU)

Mortes súbitas, após a ingestão do colostro, em cabritos e cordeiros nascidos de mães que pastejam em áreas com Amorimia septentrionalis são relatadas no semiárido da Paraíba. O objetivo deste trabalho foi determinar se o monofluoracetato de sódio (MF) contido em Amorimia septentrionalis é eliminado pelo leite, causando a morte dos cabritos. Após a confirmação da gestação no 25º dia após a cobertura, 26 cabras foram aleatoriamente distribuídas em três grupos. No Grupo 1, oito cabras receberam folhas frescas de A. septentrionalis em doses diárias de 1g/kg de peso vivo, administradas em três períodos diferentes durante a gestação: entre os dias 91 a 100, 116 a 125 e do 140º dia até o parto. No Grupo 2, composto por 10 fêmeas, oito cabras receberam 1g/kg de peso vivo de folhas secas e trituradas de A. septentrionalis, fornecida diariamente do 140º dia de gestação até o parto. As outras duas cabras desse grupo não ingeriram a planta durante a gestação e, ao parirem, o colostro fornecido aos seus cabritos foi substituído pelo colostro de cabras, desse mesmo grupo, que ingeriram a planta. Oito cabras do Grupo 3 (controle) não ingeriram A. septentrionalis. Sete cabras do Grupo 1 apresentaram sinais de intoxicação entre o 2º e 8º dia de administração da planta, em todos os períodos, e se recuperavam em 7 a 12 dias. Outra apresentou sinais clínicos graves e foi eutanasiada in extremis. Duas cabras abortaram. Quatro cabritos, oriundos de duas cabras, receberam colostro e, após 15 minutos, apresentaram depressão, respiração ofegante, decúbito lateral, berros e morte. Dois cabritos, nascidos de duas cabras que pariram durante a noite, foram encontrados mortos e os achados de necropsia permitem afirmar que nasceram vivos. A outra cabra desse grupo pariu dois cabritos que, mesmo mamando o colostro, não apresentaram sinais de intoxicação. No Grupo 2, as oito cabras que ingeriram a planta seca apresentaram taquicardia e ingurgitamento das veias jugulares; seis abortaram e os cabritos das outras duas morreram imediatamente após o parto, sem ingerir colostro. Os três filhotes das duas cabras que não ingeriram a planta durante a gestação não apresentaram sinais de intoxicação após ter ingerido colostro das cabras que tinham ingerido a planta. No Grupo 3, todas as fêmeas pariram normalmente e os filhotes não apresentaram sinais de intoxicação. Dez amostras de folhas de A. septentrionalis continham 0,00074% ± 0,00018 de MF. Estes resultados demonstram que o MF de A. septentrionalis, além de causar abortos, é eliminado pelo colostro podendo causar a morte dos cabritos.(AU)

Evaluation of resistance to natural poisoning by Amorimia septentrionalis in goats which had received sodium monofluoroacetate degrading bacteria / Avaliação da resistência à intoxicação natural por Amorimia septentrionalis em caprinos que receberam bactérias degradadoras de monofluoroacetato de sódio

Amorimia septentrionalis is an important sodium monofluoroacetate (MFA) containing plant that causes sudden death in ruminants in northeastern Brazil. MFA degrading bacteria are being used in the prevention against poisoning by this plant. The aim of this study was to evaluate if goats which had per os received MFA degrading bacteria remained resistant when exposed to natural poisoning by A. septentrionalis. Eighteen goats were randomly distributed into three groups: the goats of Group 1 previously received, during 40 days, a solution containing the bacteria Ralstonia sp. and Burkholderia sp., those goats in the Group 2 received the bacteria Paenibacillus sp. and Cupriavidus sp. and goats from Group 3 did not receive any bacteria. After the administration period, during 60 days, the animals of all groups were released to graze on a one hectare paddock, with significant amount of A. septentrionalis. They were observed daily for the spontaneous consumption of A. septentrionalis leaves and the occurrence of clinical signs of poisoning or sudden death. Goats from all groups consumed significant amounts of A. septentrionalis during the experimental period. Goats that did not receive MFA-degrading bacteria (Group 3) became sick and died from the 25th to the 27th day of the experiment, whereas the goats of the groups that received MFA-degrading bacteria showed only clinical sings when A. septentrionalis regrowth after the 55th day of the experiment. The days elapsed from field observation to death of Group 3 goats (25.5±0.9 days) were significantly lower (p<0.05) than Group 1 (58.6±1.3 days) and Group 2 (57.8±1.5 days). Thus, it can be concluded that administration of MFA degrading bacteria increases the resistance to natural poisoning by A. septentrionalis.(AU)

Amorimia septentrionalis que contém monofluoroacetato de sódio (MFA) é responsável pela ocorrência de mortes súbitas em ruminantes no nordeste do Brasil. Bactérias degradadoras desse composto estão sendo utilizadas na prevenção contra a intoxicação por essa planta. O objetivo deste estudo foi avaliar se caprinos que receberam, via oral, bactérias degradadoras de MFA permaneciam resistentes quando expostos a intoxicação natural por A. septentrionalis. Dezoito caprinos foram divididos em três grupos, os caprinos do Grupo 1 receberam anteriormente, durante 40 dias, uma solução contendo as bactérias Ralstonia sp. e Burkholderia sp., os do Grupo 2 receberam, também por 40 dias as bactérias Paenibacillus sp. e Cupriavidus sp. e os do Grupo 3 não receberam nenhuma bactéria. Após o período de administração, durante 60 dias, os animais de todos os grupos foram soltos para pastar em um piquete de um hectare, que apresentava uma quantidade significativa da planta. Diariamente eles foram observados quanto ao consumo espontâneo das folhas de A. septentrionalis e quanto à presença de sinais clínicos de intoxicação ou morte. Os caprinos de todos os grupos consumiram quantidades significantes da planta durante o período experimental. Os caprinos que não receberam as bactérias degradantes de MFA (Grupo 3) adoeceram e morreram entre o 25º e o 27º dia de experimento, enquanto que os que receberam as bactérias degradantes de MFA (Grupo 1 e 2) só apresentaram sinais clínicos no 55º dia de experimento, o que coincidiu com a rebrota da planta. Os dias transcorridos desde a observação a campo até a morte dos caprinos do Grupo 3 (25,5±0,9 dias) foram significativamente menores (p<0,05) que os do Grupo 1 (58,6±1,3 dias) e do Grupo 2 (57,8±1,5 dias). Com isso pode-se concluir que a administração de bactérias degradadoras de MFA aumenta à resistência a intoxicação natural por A. septentrionalis.(AU)

Embryonic death and abortion in goats caused by ingestion of Amorimia septentrionalis / Mortalidade embrionária e abortos em cabras causados pela ingestão de Amorimia septentrionalis

Amorimia spp. are sodium monofluoroacetate (MFA) containing plants causing sudden death in ruminants. In a previous study, Amorimia rigida caused abortion in one of the five pregnant sheep that received the plant suggesting that it may cause reproductive losses. This work aimed to study the embryotoxic and fetotoxic effects of Amorimia septentrionalis in goats in the Brazilian northeastern semi-arid region. The effects of A. septentrionalis on pregnancy were studied in 16 goats, divided into four groups according to their gestational period. In Groups 1, 2 and 3 the administration of A. septentrionalis at the daily dose of 5g of leaves per kg body weight was started on the 18th, 36th and 93th days of gestation, respectively. Goats from Group 4 did not ingest the plant. When the goats presented severe signs of poisoning the administration of the plant was suspended. Groups 1, 2 and 3 ingested the plant for 7.25±2.87, 9.25±2.21 and 12.50±0.57 days, respectively. All the goats recovered 7-12 days after the end of the administration of the plant. In Group 1, all the goats had embryonic death 6.25±3.59 days after the end of the ingestion of the plant. In Group 2, three goats aborted at 53, 54 and 78 days of gestation. Two goats from Group 3 gave birth normally and the other two aborted at 114 and 111 days of gestation. It is concluded that Amorimia septentrionalis is a sodium monofluoracetate-containing plant that causes embryonic deaths and abortions in goats that ingest non-lethal doses of the plant.(AU)

Amorimia spp. são plantas que contém monofluoroacetato de sódio (MFA), responsáveis por causar morte súbita em ruminantes. Em estudo prévio, Amorimia rigida causou aborto em uma de cinco ovelhas prenhas que receberam a planta, sugerindo que pode causar perdas reprodutivas. Este trabalho teve como objetivo estudar os efeitos embriotóxicos e fetotóxicos de Amorimia septentrionalis em caprinos na região semi-árida nordestina brasileira. Os efeitos de A. septentrionalis na prenhez foram estudados em 16 cabras, divididos em quatro grupos de acordo com seu período gestacional. Nos grupos 1, 2 e 3 a administração de A. septentrionalis foi diária, na dose de 5g de folhas por kg de peso corporal, iniciada nos dias 18, 36 e 93 da gestação, respectivamente. As cabras do grupo 4 não ingeriram a planta. Quando as cabras apresentavam sinais severos de intoxicação suspendia-se a administração da planta. Os grupos 1, 2 e 3 ingeriram a planta por 7,25±2,87, 9,25±2,21 e 12,50±0,57 dias, respectivamente. Todas as cabras se recuperaram 7-12 dias após o final da administração da planta. No grupo 1, todas as cabras apresentaram quadros de mortalidade embrionária 6,25±3,59 dias após o término da ingestão da planta. No grupo 2, três cabras abortaram aos 53, 54 e 78 dias de gestação. Duas cabras do Grupo 3 deram à luz normalmente e as outras duas abortaram aos 114 e 111 dias de gestação. Conclui-se que Amorimia septentrionalis é uma planta que contém monofluoroacetato de sódio e pode ocasionar mortes embrionárias e abortos em cabras que ingerem doses não letais da planta.(AU)

Intoxicação experimental por Niedenzuella stannea (Malpighiaceae) em ovinos / Experimental poisoning by Niedenzuella stannea (Malpighiaceae) in sheep

Niedenzuella stannea é uma planta que contém monofluoracetato de sódio e é incriminada como causa de morte súbita em bovinos na Região Sul do Estado de Mato Grosso. Este estudo descreve a toxidez e achados clínicos e patológicos da intoxicação experimental por N. stannea em ovinos. Foram utilizados no experimento, frutos, folhas maduras e folhas jovens de N. stannea coletadas em propriedades as margens de afluentes das bacias hidrográficas do Rio Araguaia onde havia histórico de morte súbita em bovinos. Folhas maduras em doses entre 10 e 40g/kg e frutos na dose de 10 g/kg não causaram alterações clínicas. Alterações clínicas foram observadas em ovinos que receberam a partir de 5g/kg de folhas jovens em dose única e a morte ocorreu nos que receberam a partir de 30g/kg. A toxicidade na dose de 30g/kg se manteve após a secagem da planta. Os principais sinais clínicos foram anorexia, apatia, dispneia, arritmia e taquicardia em evolução clínica que variou de 16 às 20h. Notou-se em uma fase terminal hiperaguda, com evolução de 13 a 20 min., relutância ao movimento, micção frequente, jugular ingurgitada, pulso venoso evidente, tremor muscular, decúbito esternal e decúbito lateral e morte. Na necropsia os principais achados foram ingurgitamento de grandes veias, das aurículas do coração e edema pulmonar. Microscopicamente a principal alteração ocorreu no rim e caracterizou-se por degeneração hidrópico-vacuolar no citoplasma de epitélio de túbulos contorcidos distais. Conclui-se que N. stannea na fase de brotação é tóxica para ovinos e que a intoxicação por esta planta deve ser incluída no diagnóstico diferencial das doenças com curso clínico hiperagudo ou morte súbita em ovinos em regiões onde a planta existe.(AU)

Niedenzuella stannea a sodium monofluoroacetate-containing plant cause sudden death in cattle in southern Mato Grosso State. This investigation describes the toxicity and clinical and pathological findings of experimental poisoning by N. stannea in sheep. Fruits, mature leaves and young leaves of the plant collected in properties near the margins of the Araguaia river basins with history of sudden death in cattle were used in the experiment. No clinical signs were observed in sheep ingesting doses between 10 and 40g/kg of mature leaves and 10g/kg of fruits. The animals had shown clinical signs when received young leaves of the plant orally in a single dose of 5, 10, 20g/kg, and death occurred in sheep receiving 30g/kg. The plant at the dose of 30g/kg of fresh leaves maintained its toxicity after being dried. The main clinical signs observed were anorexia, lethargy, dyspnea, tachycardia, and arrhythmia with a clinical course ranging 16-20 hours after the onset of clinical signs. In an hyperacute terminal phase the animals showed reluctance to move, frequent urination, engorged jugular, evident venous pulse, muscle tremor, sternal recumbence, lateral decubitus, and death. At necropsy engorgement of the atrium and large veins of the heart, and pulmonary edema were observed. Microscopically, the kidney had hydropic-vacuolar degeneration in the cytoplasm of the epithelial cells of the distal convoluted tubules. It is concluded that young leaves of N. stannea can cause intoxication in sheep and should be considered in the differential diagnosis of acute diseases or sudden death in sheep in regions where the plant exist.(AU)

Resistência à intoxicação por amorimia septentrionalis em caprinos, induzida pela inoculação ruminal das bactérias pigmentiphaga kullae e ancylobacter dichloromethanicus / Resistance to poisoning by amorimia septentrionalis in goats induced by ruminal inoculation of the bacteria pigmentiphaga kullae and ancylobacter dichloromethanicus

No Brasil, estima-se que as intoxicações por plantas tóxicas que contém monofluoroacetato de sódio (MFA) causam a morte de aproximadamente 500.000 bovinosao ano. A inoculação ruminal de bactérias que degradam MFA tem sido proposta como uma forma de prevenir a intoxicação. O presente trabalho teve como objetivo avaliar, em caprinos, a resistência ao MFA presente em Amorimia septentrionalis, induzida por inoculação ruminal das bactérias Pigmentiphaga kullae e Ancylobacter dichloromethanicus. Doze caprinos, que nunca tiveram contato prévio com plantas que contêm MFA, foram divididos em dois grupos, com seis animais cada. No grupo 1, 60 mL de uma mistura das duas bactérias foi inoculada, diariamente, durante 10 dias em cada caprino. No grupo 2, os caprinos não receberam as bactérias. A partir do 10º dia de inoculação, A. septentrionalis foi administrada, diariamente, na dose de 5g/kg de peso vivo, sendo interrompida em cada animal após a observação dos primeiros sinais clínicos da intoxicação. Os caprinos do grupo 1 apresentaram sinais clínicos 5,83±2,56 dias após a administração da planta o que diferiu significativamente (p=0,037) dos caprinos do grupo 2, que apresentaram sinais clínicos aos 2,67±0,52 dias. A quantidade de planta ingerida pelos caprinos inoculados (28,83±12,97g/kg) e os não inoculados (12,03±3,65g/kg) para desencadear os sinais clínicos foi, também, estatisticamente diferente entre os grupos (p=0,025). Conclui-se que a administração intraruminal de Pigmentiphaga kullae e Ancylobacter dichloromethanicus induz resistência à intoxicação por plantas que contêm MFA.

In Brazil is estimated that poisoning of livestock by sodium monofluoroacetate (MFA) containing plants causes the death of about 500.000 cattle per year. The ruminal inoculation of bacteria that degrade MFA has been proposed as a way to prevent the poisoning. This study aimed to evaluate in goats resistance to the MFA-containing plant Amorimia septentrionalis induced by ruminal inoculation of the bacteria Pigmentiphaga kullae and Ancylobacter dichloromethanicus. Twelve goats, without previous contact with MFA-containing plants, were divided into two groups of six animals each. In group 1, 60ml of a mixture of the two bacteria was inoculated every day for 10 days into each goat. In group 2, the goats did not receive the bacteria. At the 10th day of inoculation, A. septentrionalis began to be administered daily at a dose of 5g/kg body weight to both groups. The administration was interrupted in each goat after first clinical signs of poisoning were observed.. The goats of group 1 showed clinical signs 5.83±2.56 days after the administration of the plant, what differed significantly (p=0.037) from goats of group 2, that showed clinical signs 2.67±0 52 days after the beginning of ingestion. The amount of A. septentrionalis ingested by inoculated goats (28.83±12.97g/kg) to cause clinical sings was significantly greater (p=0.025) than the amount ingested by the non-inoculated (12.03±3.65) goats to cause clinical signs and was also statistically different between the groups. We concluded that the intraruminal administration of Pigmentiphaga kullae and Ancylobacter dichloromethanicus increases the resistance to poisoning by MFA-containing plants.

Administração repetida de doses não tóxicas de monofluoroacetato de sódio não protege contra a intoxicação por este composto em ovinos / Repeated administration of non-toxic doses of sodium monofluoroacetate does not protect against poisoning by this compound in sheep

Com o objetivo de avaliar se repetidas doses não tóxicas de monofluoroacetato de sódio (MFA) induzem resistência à intoxicação por essa substância, 18 ovinos foram distribuídos aleatoriamente em dois grupos experimentais de nove animais cada. Os ovinos do Grupo 1 ingeriram doses crescentes não letais de MFA por seis períodos: 0,05mg/kg por 5 dias; 0,08mg/kg por 4 dias; 0,08mg/kg por 4 dias; 0,1mg/kg por 3 dias; 0,1mg/kg por 3 dias e 0,25mg/kg por 3 dias. Entre o primeiro e o segundo período de administração e entre o segundo e o terceiro período os animais não receberam o MFA por 10 dias consecutivos; entre o terceiro e o quarto período e dentre os demais períodos de administração, os ovinos permaneceram 15 dias sem ingerir o MFA. Quinze dias após o último período de administração os ovinos foram desafiados com a dose única de 1mg/kg de MFA. O Grupo 2 não foi adaptado a ingestão de MFA, estes ovinos receberam dose única de 1mg/kg de MFA no mesmo período em que o G1 foi desafiado. No desafio sete ovinos do Grupo 1 apresentaram sinais clínicos da intoxicação e um ovino se recuperou. No Grupo 2 todos os animais manifestaram quadro clínico da intoxicação por MFA, no entanto, dois ovinos se recuperaram. Os coeficientes de mortalidade foram de 66,6 por cento para o Grupo 1 e de 77,7 por cento para o Grupo 2. Os resultados deste trabalho sugerem que a administração repetida de doses não tóxicas de MFA não protege contra a intoxicação aguda por este composto, portanto, outras alternativas para a profilaxia da intoxicação por plantas que contêm MFA deverão ser pesquisadas, principalmente a utilização intraruminal de bactérias que hidrolisam MFA.

With the objective to assess whether repeated non-toxic doses of sodium monofluoroacetate (MFA) induce resistance to poisoning by this compound, 18 sheep were randomly divided into two experimental groups of nine animals each. Sheep from Group 1 ingested non-lethal increasing doses of MFA for six periods: 0.05mg/kg for 5 days; 0.08mg/kg for 4 days; 0.08mg/kg for 4 days; 0.1mg/kg for 3 days; 0.1mg/kg for 3 days and 0.25mg/kg for 3 days. Between the first and second period of administration and between the second and third period the animals did not receive MFA for 10 consecutive days, between the third and fourth period and during the remaining periods of administration the sheep were left 15 days without ingesting MFA. Group 2 was not adapted to the ingestion of MFA and received a single dose of 1mg/kg of MFA at the same time that Group 1 was challenged. After challenge, seven sheep of Group 1 showed clinical signs of poisoning and one sheep recovered. In Group 2, all animals showed clinical signs of poisoning by MFA, however two sheep recovered. The mortality rate was 66.6 percent in Group 1 and 77.7 percent for Group 2. These results suggest that repeated administration of non-toxic doses of MFA does not protect against acute poisoning by this compound; therefore other alternatives of prophylaxis for poisoning by plants containing MFA should be searched, mainly the use of intraruminal bacteria that hydrolyze MFA.

Fibrose cardíaca associada à intoxicação por Amorimia septentrionalis em bovinos / Cardiac fibrosis associated to the poisoning by Amorimia septentrionalis in cattle

Amorimia septentrionalis contém monofluoracetato de sódio e quando consumida por ruminantes provoca morte súbita. Este estudo teve o objetivo de relatar a epidemiologia, os sinais clínicos e patológicos de surtos de morte súbita em bovinos provocadas por Amorimia septentrionalis nos Estados de Pernambuco e Paraíba. Para isso, realizaram-se visitas técnicas em diversas propriedades nas Microrregiões do Médio Capibaribe/PE e Itabaiana/PB. Oito bovinos foram necropsiados. Coletaram-se tecidos das cavidades abdominal e torácica, além do encéfalo e medula espinhal. As alterações clínicas consistiram em lentidão, decúbito esternal prolongado, relutância em se movimentar quando em estação, cansaço, taquipneia, taquicardia e pulso venoso positivo. Os bovinos que foram forçados a se movimentar apresentaram instabilidade, tremores musculares e queda repentina seguida de vocalizações, movimentos de pedalagem e morte súbita em cerca de 5 a 7 minutos. As principais alterações macroscópicas consistiram em edema pulmonar, coração com aspecto globular com áreas esbranquiçadas, petéquias e equimoses no epicárdio, miocárdio e músculos papilares. À microscopia observou-se aumento da eosinofilia do citoplasma dos cardiomiócitos, núcleos picnóticos, cariorrexia, cariólise, perda das estriações, edema intersticial, infiltrado inflamatório intersticial mononuclear e áreas multifocais de fibrose cardíaca. Nos rins, constatou-se degeneração hidrópico vacuolar e necrose das células epiteliais em túbulos contorcidos. Os sinais clínicos foram semelhantes aos sinais clínicos já descritos em bovinos por plantas que contém MFA. As lesões macro e microscópicas descritas no coração e rins são de grande valor diagnóstico. A. septentrionalis é a principal planta tóxica de interesse pecuário nas microrregiões do Médio Capibaribe e Itabaiana devido às perdas econômicas diretas e indiretas que provoca na pecuária dessas regiões.

Amorimia (Mascagnia) septentrionalis contains sodium monofluoracetate and when consumed by ruminants cause outbreaks of sudden death. This study aimed to describe the epidemiology, clinical and pathological signs of outbreaks of sudden deaths in cattle caused by A. septentrionalis in the states of Pernambuco and Paraíba. For this, technical visits where made on various properties in the regions of Médio Capibaribe/PE and Itabaiana/PB. Eight cattle were necropsied. Tissues were collected from abdominal and thoracic cavities, besides brain and spinal cord. The clinical changes consisted in apathy, prolonged sternal recumbency, reluctance to move, fatigue, tachypnea, tachycardia and positive venous pulse. The animals that were forced to move showed instability, muscular tremors and then a single fall followed by vocalizations, paddling and death in 5-7 minutes. Macroscopic changes consisted in pulmonary edema, globular heart with whitish areas, petechiae and ecchymosis in the epicardium, myocardium and papillary muscles. Microscopically there was an increase of eosinophilia of cytoplasm of cardiomyocytes, picnosis, cariorrexia, karyolysis, loss of striations and multifocal areas of cardiac fibrosis. In the kidney, there was hydropic vacuolar degeneration and necrosis of epithelial cells in convoluted tubules. The clinical signs presented by the cattle poisoned were similar to those previously described by plants containing MFA. The macroscopic and microscopic lesions described in the heart and kidneys are of great diagnostic value. A septentrionalis is the main toxic plant of livestock interests in the studied regions due to direct and indirect economic losses in livestock that causes.

Importância da intoxicação por Amorimia pubiflora (Malpighiaceae) em bovinos em Mato Grosso: reprodução experimental da intoxicação em ovinos e bovinos / The importance of poisoning by Amorimia pubiflora (Malpighiaceae) in cattle in Mato Grosso: experimental reproduction of the poisoning in sheep and cattle

No município de Colniza, Mato Grosso, a principal limitação para expansão pecuária é a ocorrência de "morte súbita" em bovinos, com registros de mortalidade próxima a 50% dos animais. Em visitas realizadas em áreas de ocorrência do problema, nos anos de 2004, 2011 e 2012, constatou-se que havia coincidência entre a ocorrência de "mortes súbitas" no rebanho e a presença de Amorimia pubiflora nas pastagens. As mortes ocorrem durante todo ano, porém acentuam-se no início do período das chuvas, quando há maior quantidade de brotação nas áreas de pastoreio. A intoxicação foi reproduzida em ovinos e bovinos através da administração de folhas jovens coletadas em dois períodos do ano, e, em ovinos, através de folhas maduras e dos frutos. Nos ovinos que morreram, as primeiras manifestações clínicas foram observadas entre 34min e 17h34min após a administração da planta e a evolução clínica foi de 3min a 15h20min, com uma fase final superaguda de 3 a 21min. As principais alterações clínicas encontradas foram taquicardia, evidenciação da jugular, tremores musculares, apatia e relutância à movimentação. Todos os sinais acentuavam-se após a movimentação. A fase final superaguda foi caracterizada por relutância para caminhar, cifose, tremores e contrações musculares generalizadas, principalmente de membros, cabeça e pescoço. Notou-se também taquipneia com respiração abdominal, decúbito esternal e rapidamente lateral ou quedas em decúbito lateral, opistótono, nistagmo e cianose de mucosa oral, seguidos de morte. As folhas jovens, independentemente do período da coleta, foram mais tóxicas; causaram a morte de ovinos a partir de 2g/kg e de um bovino que ingeriu 3g/kg. Já as folhas maduras revelaram-se tóxicas e causaram morte na dose de 20g/kg e os frutos ocasionaram a morte de um ovino que ingeriu 5g/kg. Concluímos que monofluoracetato de sódio (MFA), encontrado na concentração de 0,015% nas folhas em brotação de A. pubiflora, é o princípio tóxico responsável pela "morte súbita" causada por Amorimia pubiflora. Esse estudo mostra a importância de A. pubiflora para a região Centro-Oeste do Brasil, principalmente para a pecuária bovina do município de Colniza, MT. Essa planta é tóxica, também, para ovinos e o quadro clínico é similar ao descrito para bovinos.

In the county of Colniza, Mato Grosso, the main limitation for livestock production is the occurrence of "sudden death" in cattle, which affects in some farms up to 50% of the herd. In visits to some of the farms where the problem occurred, in 2004, 2011 and 2012, the presence of Amorimia pubiflora on the pastures was associated with the occurrence of "sudden deaths" in cattle. The deaths occurred throughout the year, however more frequently at beginning of the rainy season, when A. pubiflora sprouts in the grazing areas. The poisoning was experimentally reproduced in sheep and cattle by the administration of young leaves of the plant collected during two seasons, and in sheep by the administration of mature leaves and fruits. In the sheep that died, the first clinical signs were observed between 34min and 17h34min after the administration of the plant, and the clinical course varied from 3min to 15h20min, with a final peracute phase of 3 to 21 minutes. The main clinical signs were tachycardia, engorgement of the jugular veins, muscle trembling, apathy and reluctance to move, which were more evident when the animals were moved. The peracute final phase was characterized by generalized tremors and muscle contractions mainly of limbs, head and neck, respiratory distress and abdominal respiration, sternal and quick lateral recumbence or falling to the ground with peddling movements, opisthotonus, nystagmus, nystagmus and cyanosis of the oral mucosa, followed by death. The young leaves of A. pubiflora, independent of the collection period, were more toxic and caused death of sheep and cattle after ingestion of 2g/kg and 3g/kg respectively. Mature leaves caused death at the dose of 20g/kg, and the fruits at 5g/kg. The young leaves contained 0.015% of sodium monofluoracetate which is responsible for clinical signs of the "sudden death". These findings show the importance of Amorimia pubiflora for cattle raising in Midwestern Brazil. The plant is toxic also for sheep causing a clinical picture similar to that reported in cattle poisoned by monofluoracetate-containing plants.

Estudio comparativo de los efectos de hidrato de cloral y etanol en ratas expuestas a fluoracetato de sodio / Comparative study of the effects of cloral hydrate and ethanol in rats exposed to sodium fluoracetate

El fluoroacetato de sodio, es un raticida prohibido en algunos países y permitido en otros, que causa severas intoxicaciones humanas y animales. Actúa por inhibición del ciclo de Krebs e interfiere con la producción de energía, lo cual conduce a disfunción celular irreversible, especialmente en sistema nervioso central y corazón. El alcohol etílico, debido a su oxidación a acido acético y a su amplia disponibilidad, es uno de los fármacos usados en esta intoxicación, lo que podría causar controversias éticas y legales. La biotransformación del hidrato de cloral a tricloroetanol y a ácido tricloroacético, el efecto anticonvulsivante y su amplio uso en Pediatría, fueron las razones para su evaluación en la intoxicación por fluoroacetato. Se realizó un estudio experimental, para comparar los efectos de hidrato de cloral y alcohol en ratas intoxicadas con fluoroacetato de sodio. El análisis estadístico aplicado fue la prueba de chi cuadrado. Los resultados mostraron que el hidrato de cloral a dosis bajas, permite la sobrevivencia en 100% de los animales expuestos. Se confirmó igualmente la efectividad del alcohol etílico a dosis altas. Este resultado sugiere que el hidrato de cloral puede ser una opción tan útil como el etanol y que podría ser el fármaco de elección en aquellos pacientes que no puedan recibir monoacetin o etanol o porque haya mayor accesibilidad al hidrato de cloral.

Sodium fluoroacetate is a banned rodenticide in some countries and allowed in others, which causes severe human and animal poisonings. It acts for inhibition of Krebs's cycle and interferes with energy production leading to irreversible cellular dysfunction, specially in nervous central system and heart. Ethyl alcohol, because oxidation to acetic acid and to its wide availability, is one of the drugs used in this poisoning, which should can cause ethical and legal controversies. Biotransformation of chloral hydrate to trichloroethanol and trichloroacetic acid, the anticonvulsant effect and its widespread use in Pediatrics, were the reasons for its evaluation in fluoroacetate poisoning. An experimental study was conducted, to compare effects of chloral hydrate and ethanol in poisoned rats with sodium fluoroacetate. The statistical analysis applied was the chi square test. The results showed that chloral hydrate in low doses allows survival in 100 % of the exposed animals. It also confirms the effectiveness of ethyl alcohol at high doses. This result suggests that chIoral hydrate may be an option as useful as ethanol and could be the choice drug in those patients who could not receive monoacetin or ethanol or because there is greater accessibility to chloral hydrate.

A Case of Chemical Burn Caused by Trifluoroacetic Anhydride that Mimicked a Hydrofluoric Acid Burn

A 22-year-old woman was referred to our emergency department for the treatment of a chemical injury on her arm. She had accidentally spilled 99% trifluoroacetic anhydride (TFAA) over her left forearm during an organic chemistry experiment. She visited a primary care unit, and then she was referred to our hospital for inactivation of the released fluoride ions. Her skin lesions were different from those caused by hydrofluoric acid (HF) injury. The injured area showed painful whitish maculae and patchy areas with accentuated rim. No vesiculation and bulla formation was detected. We intradermally injected a 5% solution of calcium through a 24-gauge needle into the burned skin. After the injection, she complained of more severe pain. Although TFAA contains fluorine, it does not release free fluoride ions on contact with the skin, unlike HF. In fact, application of calcium gluconate for TFAA burns is not recommended. Rather, it should be avoided since it increases pain and local abscess formation.

A Successful Treatment of Patient with Fatal Complications after beta-fluoroethyl acetate Ingestion

The highly toxic sodium monofluoroacetate (SMFA) was banned as a rodenticide in this country in the 1980s. The fluoroacetate metabolite, fluorocitric acid blocks cellular metabolism by inhibiting the Klebs cycle, producing wide spread clinical effects including respiratory, neurologic, cardiologic, and fluid-electrolyte abnormalities. We report the survival case by continuous renal replacement therapy from fatal complications after beta-fluoroethyl acetate ingestion. 61-year old male was brought to our emergency center with chief complaint of beta-fluoroethyl acetate ingestion. Soon after 80 minutes of hospital admission, he developed the symptoms of mild metabolic acidosis, respiratory failure, coma, transient tachycardia, and refractory hypotension. On the second hospital day, we guessed that drug induced severe rhabdomyolysis and renal failure were in progress. At 28 hours after hospital admission, we started the continuous renal replacement therapy (CRRT) with the informed consent. Dramatically, at 24 hour after beginning the CRRT, the patient were completely recovered from coma, respiratory failure, and refractory shock, although severe rhabdomyolysis and renal failure still existed. Additionally, four times of hemodialysis were performed. On 25th hospital admission, he discharged with non oliguric renal failure state, arranging to return to out patient department.

Breeding of monofluoroacetate-resistant strains of Actinobacillus succinogenes and the mechanism based on metabolic flux analysis / 生物工程学报

Succinic acid has received a great deal of attention as an important green chemical stock for the manufacture of synthetic resins, biodegradable polymers and chemical intermediates. In this paper, the breeding mechanism of Actinobacillus succinogenes based on metabolic flux analysis was demonstrated to improve the yield of succinic acid by fermentation. After the NTG treatment, mutants from A. succinogenes CGMCC 1593 which were able to grow in medium containing concentrations of about 50-100 mmol/L of sodium monofluoroacetate were obtained. Among them, a mutant SF-9 was selected for producing more succinic acid and less acetic acid. When fermentations were conducted in a 5 L bioreactors, the final succinic acid concentration of SF-9 (34.8 g/L) increased 23.4%, and the mass ratio of succinic acid/acetic acid increased from 3.3 to 9 compared with those of the parent strain. Based on the metabolic flux analysis of A. succinogenes, PEP was found to be a key node which has an important effect on the production of succinic acid, and the flux ratio of by-productions (acetic, formic, lactic acid) was influenced by PYR node. Compared with the parent strain, the flux to succinic acid of mutant (A. succinogenes SF-9) was significantly increased, while the flux to by-productions had an obvious decline. Therefore, PEP and PYR are not rigid nodes in the metabolic regulation of A. succinogenes.

Evaluation of charcoal hemoperfusion in dogs with acute fluoroacetamide poisoning / 中华儿科杂志

<p><b>OBJECTIVE</b>In the past the mortality and sequelae rate of the patients with severe fluoroacetamide (FAM) poisoning treated only with traditional remedies was high. During the recent ten years the authors treated children with severe FAM poisoning with charcoal hemoperfusion (HP) and achieved better results. However evidence was not sufficient to show that reduced mortality and sequelae rates were obtained from HP without traditional treatment because of lack of prospective randomized, controlled clinical studies. Thus, a dog model for FAM poisoning was designed in order to study the therapeutic effect, high-efficiency time of HP, the time of tissue-poisoning to release after HP, and to investigate the toxicokinetics of the poison in the course of treatment and after HP.</p><p><b>METHOD</b>Fourteen dogs were given intraperitoneal FAM at a dose of 0.3 mg/kg body weight. HP was performed on 9 poisoned dogs for 30 - 120 minutes post intoxication. Each procedure lasted for 4 hours. Blood samples of the 9 poisoned dogs were collected before HP and 30, 60, 90, 120, 180, 240 minutes during HP and 2, 6, 24 hours after HP. Blood plasma was separated from blood samples and stored at -20 degrees C. The concentration of the poison was measured by gas chromatography (GC). The clinical symptoms of all the dogs were observed for one day.</p><p><b>RESULTS</b>The FAM concentration (ng/ml) of blood samples in poisoned dogs before HP, and 60, 120, 180, 240 minutes during HP were 230.11 +/- 52.48, 184.56 +/- 62.57, 141.00 +/- 44.83, 126.78 +/- 61.04, 113.11 +/- 54.65 respectively. The differences were significant (chi(2) = 31.978, P < 0.0005). The dispersion count between pre-HP and HP for 1 was 45.55, between 1 h and 2 h was 43.56, between 2 h and 3 h was 14.22 and between 3 h and 4 h was 13.67. The values of FAM had declined by 38.7%, 45.0% and 50.8% respectively at 2 h, 3 h, 4 h of HP compared with pre-HP. The rate of cleaning efficacy of FAM of every hour during HP were 19.79%, 23.6%, 10.09% and 10.78% respectively during HP 1, 2, 3, 4 h. The cleaning efficacy of HP was high within 2 hours during HP. The concentration of FAM slightly rose again 6 h after HP. The level of FAM had declined at 24 hour after HP when compared with pre-HP level. The reduction rate of FAM level for every hour during HP was higher than that after HP (12.71% vs 0.27% - 2.22%). The t(1/2) of FAM with and without HP were (4.50 +/- 1.20) h and (49.60 +/- 10.56) h. All the 5 poisoned dogs not treated with HP died. However 6 poisoned dogs treated with HP kept alive after HP. Three dogs had frequent seizures again 4h after HP. After HP the charcoal container was washed by 0.9% saline and FAM could not be detected in the douche.</p><p><b>CONCLUSIONS</b>Charcoal HP was an effective treatment for severe FAM poisoning. T(1/2) of the poison was shortened, and the poison clearing rate was accelerated by HP. The high-efficiency time of HP was 2 - 2.5 h. Activated charcoal can adsorb the poison vigorously, and return of blood to the body after HP by using 0.9% saline was feasible and safe.</p>

Variabilidade clínica na determinação da dose tóxica oral em intoxicação experimental por fluoroacetato de sódio em gatos / Clinical variability in the determination of oral toxic dosis in the experimental intoxication with sodium fluoroacetate in cats

O fluoroacetato de sódio (FAS) ou composto 1080 é um potente rodenticida utilizado no controle de roedores e predadores manúferos. Sua utilização está proibida por lei em diversos países devido à sua alta toxicidade, mas no Brasil há evidências do uso ilegal e sem critérios causando intoxicações, principalmente em crianças e animais domésticos. O FAS age por meio do seu metabólito tóxico, o fluorocitrato, no bloqueio do ciclo de Krebs com consequente diminuição da produção de energia do organismo, provocando principalmente manifestações clínicas neurológicas e cardíacas. No presente estudo compararam quatro doses orais tóxicas do fluoroacetato de sódio, descritas em gatos, na literatura, observando-se o aparecimento dos sinais clínicos predominantes da intoxicação, as diferenças entre as doses quanto a variabilidade clínica em relação ao período de latência para o aparecimento dos sinais clínicos e sua respectiva intensidade. A dose oral tóxica que melhor caracterizou o quadro clínico da intoxicação por FAS em gatos, sem causar a letalidade aguda, foi de 0,4Smg/kg. As diferenças entre as manifestações clínicas foram dose-dependentes e em ordem crescente de intensidade, caracterizando-se como sinais leves (dose 1: 0,3mg/kg), leves a moderados (dose 2: 0,4mg/kg), moderados a graves (dose 3: 0,45mg/ kg) e graves (dose 4: 0,5mg/kg). Houve também variabilidade clínica individual entre animais intoxicados com a mesma dosagem do tóxico.

The sodium monofluoroacetate (FAC) or compound 1080 is a potent rodenticide used for a rodents and vertebrate pest control. lt was prohibited in many countties because of its high toxicity, but in Brazil exist evidences of ilegal use causing the intoxication in children and domestic animals. The fluoroacetate metabolite, fluorocitric acid, blocks body energy production by inhibit the Krebs cycle, resulting in neurological and cardiacs signs. ln the present study, four group of oral toxic dosis of the FAC were compared in cats. The best oral toxic dose for clinical signs presentation, without cause acute lethality, was 0,45mg/kg. The clinical variability was dosis dependent and its intensity , in crescent order, was: light signs (dose 1: 0,3mg/kg), light to moderate (dose 2: 0,4mg/kg), moderate to severe (dose 3: 0,45mg/ kg) and severe (dose 4: 0,5mg/kg). There was individual clinical variability between animals that received the same oral toxic dose.

Effect of fluoroacetamide on cardiomyocytes of rat and the antidotal effect of acetamide / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the effect of fluoroacetamide on cardiomyocytes of rat and the antidotal effect of acetamide.</p><p><b>METHODS</b>4 groups of SD rats were treated with various dosages of fluoroacetamid(p.o.) and 2 groups of them were treated with acetamide(i.p.). The changes of cardiomyocytes and serum AST, LDH, CK, CK-MB and HBDH were measured at different intervals after poisoning.</p><p><b>RESULTS</b>In the group treated with fluoroacetamid 8 mg/kg. bw, serum AST[(589.58 +/- 821.72) U/L], CK[(916.78 +/- 343.55) U/L], HBDH[(504.47 +/- 148.88) U/L] raised obviously compared with control[(187.70 +/- 46.87), (755.65 +/- 498.90), (347.25 +/- 228.40) U/L respectively] (P < 0.01), and the pathological findings such as degeneration, liquefactive necrosis and filtration of inflammatory cells in cardiac muscles were observed 24 hours later, while all the male dead within 3 days. In the group treated with fluoroacetamid 4 mg/kg. bw, serum LDH and HBDH rose significantly compared with control(P < 0.01) 5 day later. On the day of 10, myocardial enzymes restored in all experiment groups with some interstitial fibroblastic proliferation. The pathological changes were reduced in the group treated with acetamide synchronously (100 mg/kg. bw).</p><p><b>CONCLUSION</b>Acute intoxication of fluoroacetamide could damage cardiomyocytes while acetamide could reduce the injury of them, but the injury was reversible. The levels of serum myocardial enzymes could be a usable index for early diagnosis.</p>

Acute fluoroacetamide poisoning with main damage to the heart / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the heart damage in 10 patients with acute fluoroacetamide poisoning.</p><p><b>METHODS</b>Monitoring serum activities of myocardial enzymes [creatine kinase (CK), asparate aminotransferase (AST), lactate dehydrogenase(LDH) and hydroxybutyrate dehydrogenase(HBDH)] and recording ECG on these 10 patients were performed during the period of their hospitalization. In the mean while, 24 hour dynamic ECG were also recorded and analysed using GP7000L Holter.</p><p><b>RESULTS</b>(1) Urinary fluorine ion concentrations were increased in 9 patients before therapy and in all these 10 patients during therapeutic period. (2) The activities of serum CK in 2 patients and that of serum HBDH in one patient were increased before therapy. However, the serum activities of one or more than one myocardial enzymes were increased in all these 10 patients during therapeutic period. (3) Four patients had abnormal change of ECG before therapy and 5 patients during therapeutic period. (4) 24 hour dynamic ECG records showed that there were heart electrical alternans in 9 patients. One patient had wandering pacemaker and 6 patients had arythmia.</p><p><b>CONCLUSION</b>Fluoroacetamide may cause obvious heart damage, and also heart electrical alternation.</p>

Chemical and biological demonstration of the presence of monofluoroacetate in the leaves of Palicourea marcgravii St. Hil

Cattle losses in Brazil have been attributed to Palicourea marcgravii St. Hil., a toxic plant for cattle. The crude extract from the leaves of P. marcgravii was successively fractionated using solvents with different polarities to determine whether monofluoroacetic acid and/or some other substance present in the leaves may be responsible for the acute symptoms caused by the plant. Authentic sodium monofluoroacetate (SMFA) was used fopr comparison. The only P. marcgravii fraction which induced seizures and death in intoxicated rats was water soluble. The signs and symptoms induced in the animals by the crude extract and water-soluble fraction were the same as induced by SMFA and included tonic seizures and other actions on the CNS. The dose-lelthality and dose-latency to the 1st seizure curves constructed for the water soluble fraction of the leaf extract (30-100 mg/Kg) and SMFA (0.6-3.0 mg/Kg) were parallel. Five animals per dose were used. The potency ratio of SMFA in relation to the water-soluble fraction of the leaf extract was 53.8 (dose-lethality curve) and 64.1 (dose latency to the 1st seizure curve). The water-soluble fraction contained a substance with hRf = 20 which the same as that of authentic SMFA. The 19F NMR spectra of authentic SMFA and the P. marcgravii water-soluble fraction were identical. These data demosntrate the presence of SMF in the water-soluble fraction of P. marcgravii leaves and show that monofluoroacetate is the active principle repsonsible for the signs and symptoms of acute intoxications