Made available in DSpace on 2016-04-28T20:16:31Z (GMT). No. of bitstreams: 1 2009 - Vivian de Assuncao Nogueira.pdf: 2112872 bytes, checksum: 276e22b789893e783e3b6baa392f3bf0 (MD5) Previous issue date: 2009-07-31 / Funda??o Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro / Sodium monofluoracetate (MF) was identified, by cromatography, in three of the 12 plants that cause "sudden death" in cattle in Brazil. Among these, Palicourea marcgravii is the most important due to its high toxicity (0.6g/kg), wide distribution, good palatability and cummulative effect. In 1959, D?bereiner & Tokarnia detected in the kidney of cattle poisoned by that plant, hydropic-vacuolar degeneration (HVD) of the distal convoluted uriniferous tubules, a lesion they considered typical for the poisoning. MF inhibits the citrate aconitase enzyme, resulting in blockage of the Krebs Cycle and the production of ATP. The objective of this study was to verify if the ingestion of MF causes the same lesions in the kidney of cattle poisoned by the plants which cause sudden death . This would prove that this substance is responsible for the deaths of animals which ingest these plants. Six cows received orally 0.5 and 1 mg/kg of MF (Sigma Aldrich Co) diluted in 50 mL of distilled water. Clinically the animals presented palpitation, replete jugular vein with positive pulse, abdominal breathing, slight balance loss with sometimes swaying gait, the animals laid down and placed the head on their flank. In the dramatic phase , all the animals fell into lateral decubitus, stretched out the legs, made peddling movements, presented opistotonus, nistagmus, and died. The dramatic phase lasted from 3 to 14 minutes. At postmortem examination, the heart auricles, jugulars and pulmonary veins were moderately ingurgitated. Slight to moderate edema of the subserosa was seen in places of fixation of the gall bladder to the liver, besides slight edema around the duodenum in contact with the pancreas. Histopathology revealed HVD of the epithelial cells of the distal convoluted uriniferous tubules associated with nuclear picnosis in all cows. Coagulation necrosis of individual or groups of hepatocytes and slight hepatic congestion secondary to the venous stasis were also observed. Hydropic-vacuolar degeneration has been observed in cases of poisoning by many substances, which cause acute tubular nephrosis, however not restricted to the distal renal tubules and without nuclear picnosis. This study demonstrates that this peculiar kind of HVD in the kidney can be caused by MF and, in analogy, the compound should be considered responsible for the death of cattle that ingest toxic plants which cause "sudden death" in Brazil. For the first time it has now been proved that MF causes HVD of the distal convoluted uriniferous tubules, what indicates that studies of possible degradation of MF by rumen bacteria could have economic importance, as there die annually at least 600.000 cattle by sudden death causing toxic plants. / Monofluoracetato de s?dio (MF) foi identificado, por cromatografia, em Palicourea marcgravii, Arrabidaea bilabiata e possivelmente em Mascagnia rigida, plantas do grupo das que causam morte s?bita em bovinos no Brasil. Em 1959, D?bereiner & Tokarnia detectaram no rim de bovinos intoxicados por P. marcgravii, uma les?o por eles considerada t?pica para intoxica??o, a degenera??o hidr?pico-vacuolar dos t?bulos urin?feros contorcidos distais (DHV). O modo de a??o do MF baseia-se na inibi??o da enzima citrato aconitase, do que redunda bloqueio do ciclo de Krebs e da produ??o de ATP. O objetivo deste trabalho foi verificar se a ingest?o de MF induz as mesmas les?es observadas no rim de bovinos intoxicados pelas plantas que causam morte s?bita , o que indicaria que essa subst?ncia ? respons?vel pelas mortes dos animais que ingeriram essas plantas. Foram realizados experimentos em que seis vacas receberam, por via oral, 0,5 e 1,0 mg/kg de MF dilu?dos em 50 mL de ?gua destilada. Clinicamente os animais apresentaram taquicardia, jugular repleta com pulso venoso positivo, respira??o abdominal, ligeira perda de equil?brio, por vezes cambaleavam, deitavam e apoiavam a cabe?a no flanco. Na fase dram?tica, todos os animais ca?am em dec?bito lateral, esticavam os membros, faziam movimentos de pedalagem, apresentavam opist?tono, nistagmo, mugidos e morriam. O per?odo da fase dram?tica durou entre 2 e 14 minutos. ? necropsia verificaram-se aur?culas, jugulares, ?zigos e pulmonares moderadamente ingurgitadas. Observaram-se ainda leve a moderado edema da subserosa nos locais de fixa??o da ves?cula biliar no f?gado, al?m de leve edema em torno do intestino delgado (duodeno) em contato com p?ncreas. O exame histopatol?gico revelou, em todos os animais, leve a acentuada DHV das c?lulas epiteliais dos t?bulos urin?feros contorcidos distais associada ? cariopicnose nuclear. Vacuoliza??o e necrose de coagula??o individual ou de grupos de hepat?citos e leve congest?o hep?tica secund?rios ? estase venosa tamb?m foram observados. DHV tem sido observada em casos de envenenamento por outras subst?ncias, por?m esta n?o est? restrita aos t?bulos distais e n?o se observa cariopicnose nuclear. Dessa forma, esse estudo demonstra que a DHV que ocorre no rim de bovinos ? caracter?stica do envenenamento por MF e, por analogia, essa subst?ncia pode ser considerada como um dos fatores importantes, sen?o o mais significativo, implicado no ?bito dos animais que ingerem plantas que causam morte s?bita no Brasil. Comprova-se, pela primeira vez, que o MF induz ? a causa da DHV dos t?bulos uriniferos contorcidos distais, o que indica que estudos que envolvam metaboliza??o de MF por bact?rias ruminais teriam grande aplicabilidade econ?mica, uma vez que pelo menos 600.000 bovinos morrem anualmente intoxicados por plantas do grupo das que causam morte s?bita no Brasil.

Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2016-09-19T11:49:34Z No. of bitstreams: 1 2011 - Michel Jos? Sales A. Helayel.pdf: 11350186 bytes, checksum: ab1a4bf6f150ee6e971e58207f995bff (MD5) / Made available in DSpace on 2016-09-19T11:49:34Z (GMT). No. of bitstreams: 1 2011 - Michel Jos? Sales A. Helayel.pdf: 11350186 bytes, checksum: ab1a4bf6f150ee6e971e58207f995bff (MD5) Previous issue date: 2011-03-16 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / This study aimed to evaluate the protective effect of acetamid in experimental poisoning by Pseudocalymma elegans in sheep, goats and rabbits, in order to prove indirectly that monofluoroacetate (MF) is responsible for the clinical signs and death of animals that ingested the plant. Experiments were performed to determine for sheep and goats the lethal dose of P. elegans collected in Rio Bonito, RJ, in different seasons, and to adjust the dose of acetamid to be administered. In the first experiment, four animals received 1.0g/kg of fresh P. elegans, and two others were pretreated with 2.0g/kg of acetamid. None of the animals showed clinical signs or died. Possibly, the plant could be less toxic, since it was collected at the end of the rainy season. In the second experiment, two sheep and two goats received 0.67 and 1.0g/kg of the dried plant, after pretreatment with 2.0 and 3.0g/kg of acetamid, respectively. All animals died, as the administered doses of P. elegans were very high. In the third experiment, two sheep and two goats received 0.333g/kg of dried P. elegans after previous administration of 2.0g/kg of acetamid; a week later, the protocol above was repeated, but without the antidote. In experiments with rabbits, doses of 0.5 and 1.0g/kg of dried P. elegans were given after administration of 3.0g/kg of acetamid; seven days later, the same protocol was repeated, except the administration of acetamide. This procedure, when acetamid was administered before, prevented the appearance of clinical signs and death of sheep, goats and rabbits. But the animals not treated with acetamid showed symptoms of poisoning and died. Clinically, the sheep and goats had tachycardia, engorged jugular vein, positive venous pulse, lateral recumbence, and muscle tremors. In the "dramatic phase?, the animals fell into lateral position, stretched the limbs, were paddling and died within minutes. The rabbits showed apathy, muscle tremors, vocalization and lateral decumbence minutes before death. At postmortem examination, the sheep and goats had engorged jugular veins and atria, dilated Vena cava cranialis and caudalis, as well as pulmonary edema, hepatic congestion and edema of the gallbladder subserosa. In rabbits, the main macroscopic alterations were dilated atria, engorged Vena cava cranialis and caudalis, and congested liver and diaphragm vessels. Histopathology revealed, in two sheep and one goat, vacuolar-hydropic degeneration of the distal convoluted kidney tubules, together with caryopicnosis. In the rabbits, the liver showed severe congestion with numerous shock corpuscles. The experimental results show indirectly that MF is to be held responsible for death of the animals that ingested P. elegans; since "acetate donor" compounds, such as acetamid, are capable to reduce the competitive inhibition of MF for the same active site (Coenzyme A) which prevents the formation of fluorocitrate, its active metabolite, formed in the body through the socalled "lethal synthesis". / O presente trabalho teve como objetivo avaliar o efeito protetor da acetamida nas intoxica??es experimentais por Pseudocalymma elegans (Bignoniaceae) em ovinos, caprinos e coelhos, com a finalidade de comprovar indiretamente que o monofluoroacetato ? respons?vel pela sintomatologia e morte dos animais que ingerem essa planta. Foram realizados experimentos para determinar a dose letal da planta coletada em Rio Bonito, RJ, em diferentes ?pocas do ano para ovinos e caprinos e ajustar a dose de acetamida a ser administrada. No primeiro experimento, dois ovinos e dois caprinos receberam 1,0 g/kg de P. elegans fresca e um animal de cada esp?cie foi tratado previamente com 2,0 g/kg de acetamida. Nenhum animal apresentou altera??es cl?nicas ou morreu. Ao que tudo indica a planta poderia estar menos t?xica, j? que foi coletada no fim da esta??o das ?guas. No segundo experimento, dois ovinos e dois caprinos receberam 0,67 e 1,0 g/kg da planta dessecada, ap?s tratamento pr?vio, com 2,0 e 3,0 g/kg de acetamida, respectivamente. Todos os animais morreram, pois administramos doses muito altas de P. elegans. No terceiro experimento, dois ovinos e dois caprinos receberam, 0,333 g/kg de P. elegans dessecada, ap?s administra??o pr?via de 2,0 g/kg de acetamida. Uma semana depois, o protocolo acima foi repetido, por?m sem o ant?doto. Nos experimentos com coelhos, foram administradas doses de 0,5 e 1,0 g/kg de P. elegans dessecada ap?s a administra??o de 3,0 g/kg de acetamida. Sete dias depois, o mesmo protocolo foi repetido, com exce??o da administra??o de acetamida. Esta, quando administrada previamente, evitou o aparecimento dos sinais cl?nicos e a morte dos ovinos, caprinos e coelhos, j? os animais n?o tratados com acetamida apresentaram sintomatologia e morreram. Clinicamente, os ovinos e caprinos manifestaram taquicardia, jugulares ingurgitadas, pulso venoso positivo, dec?bito esternal e tremores musculares. Na ?fase dram?tica?, os animais ca?am em dec?bito lateral, esticavam os membros, faziam movimentos de pedalagem e morriam em poucos minutos. Nos coelhos observaram-se apatia, tremores musculares, dec?bito lateral e vocaliza??o minutos antes da morte. A avalia??o macrosc?pica revelou, nos ovinos e caprinos, jugulares ingurgitadas, aur?culas, veia cava caudal e cranial dilatadas, al?m de edema pulmonar, congest?o hep?tica e edema na subserosa da ves?cula biliar. Nos coelhos as principais altera??es observadas foram aur?culas dilatadas, veia cava caudal e cranial ingurgitadas, f?gado e vasos do diafragma congestos. O exame histopatol?gico revelou, em dois ovinos e um caprino, degenera??o hidr?pico-vacuolar dos t?bulos urin?feros contornados distais associada ? cariopicnose. Nos coelhos havia congest?o hep?tica acentuada com numerosos corp?sculos de choque. Nossos resultados comprovam, de forma indireta, que o MF ? respons?vel pela morte dos animais que ingerem essa planta, uma vez que compostos ?doadores de acetato? como a acetamida, s?o capazes de reduzir a inibi??o competitiva do MF pelo mesmo s?tio ativo (Coenzima A), o que impede a forma??o do fluorocitrato, seu metab?lito ativo, formado no organismo por meio da denominada ?s?ntese letal?.

Baiting with sodium monofluoroacetate (1080) to protect lambs (Ovis aries) from red foxes (Vulpes vulpes L.) has become more frequent in NSW and other parts of Australia during the last 10 years despite the lack of reported evidence evaluating the effects of fox baiting on lamb survival. NSW Agriculture has developed fox control recommendations aimed at minimising impact, but these guidelines have not been tested experimentally. Defining the extent of a pest problem and the effectiveness of pest control are key components of a strategic approach to vertebrate pest management as it is the damage of pests that justifies their control. This thesis describes an experimental evaluation of the recommended practice of fox control in NSW. The effects of three levels of fox control were tested in the experiment; no treatment, baiting once a year before lambing (the recommended practice) and baiting three times a year (thought to be the maximum farmers would instigate). Each treatment had two replicates. No previous manipulative experiment using synchronous controls and matched replicates has been undertaken to test the effects. The study quantifies the level of fox predation on healthy lambs and the level of predation on lambs that had other causes including illness and mismothering contributing to this fox predation. It also examines the response of the fox population, lamb predation and lambing outcomes to different levels of fox control. The cost effectiveness of fox control is examined in relation to lamb predation and an investigation of the optimum level of fox control is begun. The experiment also provides the first chance to consider the examination of multiple response variables and the scale of field ecology experiments required to recognise a significant response and avoid a Type II error due to between replicate variability even with tightly controlled site selection criteria to standardise experimental sites, and with the synchrony of experimental control and treatment surveys. The study occurred on five sheep properties near Boorowa (34°28'S, 148°32'E) and Murringo (34°18'S, 148°3 1'E) in south-eastern Australia. The terrain was undulating to hilly with a maximum elevation of 660 m above sea level. The main agricultural enterprises in the district are Merino wool, fat lamb and beef cattle production and winter cereal cropping. The native vegetation of Eucalyptus woodland has been mostly cleared, though remnant patches occur. Most of the area is now sown with pasture of Phalaris tuberosa, Lolium spp. and clover Trifolium spp.. The experimental properties grazed self-replacing Merino flocks, primarily for wool production, so lamb survival was vital to the economic operation of the farm. Over 50 selection criteria including lamb survival rates, ewe fertility and bloodline, sheep management practices, climate and habitat features that affect lamb survival, past fox control practices and prey species were used to select sites Sites were representative of most sheep farming properties in the region, but were also extremely similar in factors that affected fox abundance and ewe and lamb survival, thus minimising variation between replicate sites. The manufactured meat baits used to poison foxes contained 3 mg of sodium monofluoroacetate (compound 1080). A replacement baiting program was carried out in 1995 and 1996. Fox control programs were carried out over the experimental units and adjacent buffer zones covering approximately two fox territories, approximately 6km2, around the lambing paddock under study. The recommended fox control practices described by NSW Agriculture also included neighbouring farmers taking part in an extended group baiting program. In all the area baited at varying intensities totalled 3400 km2. Synchronised lambing with neighbours was a further recommended practice to reduce fox predation and was carried out on these sites. Lambing occurred during a six to eight week period in late winter on all sites, a practice known as 'spring lambing', and on many surrounding properties so a surplus of lambs was available to foxes over a relatively short time. The benefits of fox control were measured directly as enhanced lamb survival derived from differences in lamb marking rates between ultrasounded flocks of approximately 1000 ewes and the predation of lambs was measured from over 2000 lamb carcases post-mortemed in 1994, 1995 and 1996. A mean of 138 lambs were expected at ultrasounding from 100 ewes and 113 lambs per 100 ewes were alive at lamb marking. There was no significant (P>0.05) effect of fox control on lambing performance (the number of lambs per 100 ewes that lambed) Fox predation was inferred as the cause of lamb death in a minimum of 0.8% and a maximum of 5.3% of lamb carcases during 1995 and 1996. There was a significant (P<0 05) effect of fox control on the minimum possible percentage of lamb carcases classified as healthy lambs killed by foxes, with the percentage declining from 1.50% (no fox control), to 0.90% (fox control once per year) to 0.25% (fox control three times per year). There was also a significant (P<0.005) effect of fox control on the maximum possible percentage of lamb carcases classified as healthy lambs killed by foxes with the percentage declining from 10.25% (no fox control), to 6.50% (fox control once per year) to 3.75% (fox control three times per year). The observed results were used to estimate the number of treatment replicates needed to be confident of detecting an effect of predator control on lamb marking performance. The estimated numbers were very high if small effects were to be detected. No significant correlation between the fox density and the minimum and maximum possible number of lambs carcases classified as killed by foxes was found. Bait uptake was monitored as were the costs of fox control.

A ocorrência de monofluoroacetato de sódio (MFA-Na) em plantas foi registrada, pela primeira vez, em Dichapetalum cymosum. Posteriormente, esta substância tóxica foi encontrada em outras espécies de plantas, como Palicourea marcgravii, causadora de morte súbita. Amorimia rigida, que é bastante conhecida e frequente no Nordeste do Brasil, está entre as plantas tóxicas, que também causam morte súbita em bovinos, com quadro clínico semelhante ao decorrente da ingestão de plantas que contém fluoroacetato de sódio e ao apresentado por animais intoxicados experimentalmente com este tóxico. À A. rigida são imputadas significativas perdas econômicas, motivo pelo qual o objetivo do presente estudo foi identificar a substância tóxica nela presente e também estabelecer bioindicadores de efeito, quando da intoxicação por esta planta. No estudo por cromatografia em camada delgada de celulose - tendo como fase móvel solução de etanol/hidróxido de amônio/piridina/água (95:3:1:1, v/v/v/v) e como agente derivatizante o azul do Nilo - do extrato aquoso obtido da planta seca e moída, foi detectada a presença de MFA-Na. O fracionamento do extrato hidroalcoólico de A. rigida em coluna XAD-2 forneceu 4 frações: H2O 100% (F1), H2O:MeOH 80/20 (F2), H2O:MeOH 40/60 (F3) e MeOH 100% (F4) das quais, como indicado pelo monitoramento por CCDC, apenas a fração F1 continha o MFA-Na. Essa fração foi submetida à cromatografia em camada delgada preparativa, para isolamento do princípio ativo o qual, em estudo por espectrometria de infravermelho e em comparação com padrão de MFA-Na, comprovou a presença de mistura de mono, di e trifluoroacetato nas folhas desta planta. No estudo bioquímico, animais intoxicados com o padrão de MFA-Na e com o extrato de A. rigida apresentaram alterações nos níveis séricos de cálcio e citrato, sendo estas moléculas consideradas bioindicadoras de efeito a exposição ao MFA-Na. / The first occurrence of sodium monofluoroacetate in plants was reported in Dichapetalum cymosum. Further, this toxic substance was found in other plant species, as Palicourea marcgravii, which causes \"sudden death\". Amorimia rigida, which is well known and frequent in northeastern Brazil, it is among the poisonous plants that have identical lethal effects in cattle to that caused by the ingestion of plants containing sodium fluoroacetate. These intoxication signs are the same that ones presented by experimentally poisoned animals with this toxic. Significant economic losses can be imputed to A. rigida, therefore our aim was to identify its toxic compound and also to establish its biomarkers of effect. The study by cellulose thin layer chromatography using as mobile phase solution of ethanol /ammonium hydroxide/pyridine/water (95:3:1:1, v/v/v/v) and Nile blue as the derivatizing agent - of the aqueous extract of milled dried plant showed the presence of MFA-Na. The fractionation of the hydroalcoholic extract of A. rigida by XAD-2 column chromatography gave four fractions: 100% H2O (F1), H2O: MeOH 80/20 (F2) H2O: MeOH 40/60 (F3) and 100% MeOH (F4); only F1 fraction contained MFA-Na, according to CCDC monitoring. This fraction was subjected to preparative thin layer chromatography, in order to isolate the toxic principle which, in a study by infrared spectroscopy and by comparison with standard MFA-Na, confirmed being a mixture of mono-, di and trifluoroacetate. In the biochemical study, animals intoxicated by MFA-Na and by A. rigida extract showed serum calcium/citrate imbalances; such alterations may be considered biomarkers of MFA-Na exposure effect.

A ocorrência de monofluoroacetato de sódio (MFA-Na) em plantas foi registrada, pela primeira vez, em Dichapetalum cymosum. Posteriormente, esta substância tóxica foi encontrada em outras espécies de plantas, como Palicourea marcgravii, causadora de morte súbita. Amorimia rigida, que é bastante conhecida e frequente no Nordeste do Brasil, está entre as plantas tóxicas, que também causam morte súbita em bovinos, com quadro clínico semelhante ao decorrente da ingestão de plantas que contém fluoroacetato de sódio e ao apresentado por animais intoxicados experimentalmente com este tóxico. À A. rigida são imputadas significativas perdas econômicas, motivo pelo qual o objetivo do presente estudo foi identificar a substância tóxica nela presente e também estabelecer bioindicadores de efeito, quando da intoxicação por esta planta. No estudo por cromatografia em camada delgada de celulose - tendo como fase móvel solução de etanol/hidróxido de amônio/piridina/água (95:3:1:1, v/v/v/v) e como agente derivatizante o azul do Nilo - do extrato aquoso obtido da planta seca e moída, foi detectada a presença de MFA-Na. O fracionamento do extrato hidroalcoólico de A. rigida em coluna XAD-2 forneceu 4 frações: H2O 100% (F1), H2O:MeOH 80/20 (F2), H2O:MeOH 40/60 (F3) e MeOH 100% (F4) das quais, como indicado pelo monitoramento por CCDC, apenas a fração F1 continha o MFA-Na. Essa fração foi submetida à cromatografia em camada delgada preparativa, para isolamento do princípio ativo o qual, em estudo por espectrometria de infravermelho e em comparação com padrão de MFA-Na, comprovou a presença de mistura de mono, di e trifluoroacetato nas folhas desta planta. No estudo bioquímico, animais intoxicados com o padrão de MFA-Na e com o extrato de A. rigida apresentaram alterações nos níveis séricos de cálcio e citrato, sendo estas moléculas consideradas bioindicadoras de efeito a exposição ao MFA-Na. / The first occurrence of sodium monofluoroacetate in plants was reported in Dichapetalum cymosum. Further, this toxic substance was found in other plant species, as Palicourea marcgravii, which causes \"sudden death\". Amorimia rigida, which is well known and frequent in northeastern Brazil, it is among the poisonous plants that have identical lethal effects in cattle to that caused by the ingestion of plants containing sodium fluoroacetate. These intoxication signs are the same that ones presented by experimentally poisoned animals with this toxic. Significant economic losses can be imputed to A. rigida, therefore our aim was to identify its toxic compound and also to establish its biomarkers of effect. The study by cellulose thin layer chromatography using as mobile phase solution of ethanol /ammonium hydroxide/pyridine/water (95:3:1:1, v/v/v/v) and Nile blue as the derivatizing agent - of the aqueous extract of milled dried plant showed the presence of MFA-Na. The fractionation of the hydroalcoholic extract of A. rigida by XAD-2 column chromatography gave four fractions: 100% H2O (F1), H2O: MeOH 80/20 (F2) H2O: MeOH 40/60 (F3) and 100% MeOH (F4); only F1 fraction contained MFA-Na, according to CCDC monitoring. This fraction was subjected to preparative thin layer chromatography, in order to isolate the toxic principle which, in a study by infrared spectroscopy and by comparison with standard MFA-Na, confirmed being a mixture of mono-, di and trifluoroacetate. In the biochemical study, animals intoxicated by MFA-Na and by A. rigida extract showed serum calcium/citrate imbalances; such alterations may be considered biomarkers of MFA-Na exposure effect.

Made available in DSpace on 2014-06-11T19:31:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-05-16Bitstream added on 2014-06-13T20:22:04Z : No. of bitstreams: 1 zuanaze_rcc_dr_botfmvz.pdf: 2365698 bytes, checksum: 5ed70ccdd25955ad8f5b2e015a21dec7 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação para o Desenvolvimento da UNESP (FUNDUNESP) / O monofluoroacetato de sodio (MFAS) ou composto 1080 e um rodenticida que foi amplamente utilizado para o controle de roedores e predadores domesticos, apos sua descoberta em 1945. Este potente rodenticida age bloqueando o ciclo de Krebs por acao do seu metabolito toxico, o fluorocitrato, e como consequencia, inibe a resposta celular e a producao de ATP. O MFAS foi proibido por lei no Brasil e em diversos paises, mas seu uso indiscriminado continua causando diversos casos de intoxicacoes potencialmente fatais no homem e animais domesticos, principalmente em caes e gatos, representadas por alteracoes neurologicas e cardiacas. Pretendeu-se com este estudo caracterizar o perfil hematologico e bioquimico, as alteracoes histopatologicas e toxicologicas de gatos intoxicados experimentalmente com MFAS, com o objetivo de determinar metodos diagnosticos eficazes. Para tanto, foram utilizadas amostras de sangue de 16 gatos intoxicados experimentalmente com 0,45mg/kg de MFAS, por via oral. Estas amostras foram colhidas por puncao jugular e analisadas quanto ao perfil hematologico, bioquimica serica e analises toxicologicas em cromatografia liquida de alta eficiencia (CLAE), para deteccao e quantificacao do MFAS no soro dos animais. Avaliaram-se tambem as lesoes macro e microscopicas dos animais intoxicados que vieram a obito. Observaram-se leucopenia e trombocitopenia transitorias; hiperglicemia, aumento das enzimas musculares creatinoquinase (CK) e creatinoquinase fracao cardiaca (CK-MB); observaram-se tambem hipocalemia, hipofosfatemia e hipomagnesemia. Os achados macroscopicos e histopatologicos demonstraram lesoes caracteristicas de processos isquemicos e as analises toxicologicas demonstraram um metodo diagnostico simples e eficiente... / Sodium monofluoroacetate (SMFAC) or 1080 compound is a potent rodenticide, largely used since 1945 for rodent and domestic pest control. The toxic effects of SMFAC are caused by fluorocitrato, a toxic metabolite, which has a competitive action with aconitase enzyme, leading to citrate accumulation and interferes in energy production by Krebs cycle blockade. In Brazil, although prohibited by law, there is illegal use, keep causing intoxication in children and domestic animals, specially dogs and cats. The most common intoxication clinical signs are from the cardiac and neurological alterations. In the present study, 16 domestic cats were intoxicated with oral doses of monofluoroacetate (0.45mg/kg). The hematologic and biochemical profiles, and histophatological and blood serum toxicological analysis by high performance liquid chromatography (HPLC) were made to looking for a efficient diagnosis methods. The hematologic profile showed transitory leucopenia and trombocitopenia; the biochemical profile presented hiperglycemia, increase of creatinoquinase enzyme (CK) and creatinoquinase cardiac fraction (CK-MB), hypokalemia and hypophosfatemia were observed. The macrocospic and histopathological findings showed lesions characteristic of degenerative and ischemic processes. The toxicological analysis was shown to be a simple and efficient diagnostic method. SMFAC was detected in 75% of the serum samples analysed, and it was verified an average concentration of 0.32 ìg/mL in them; 4.81% of the serum samples did not show metabolized SMFAC six hours after the induced intoxication of the animals used in this study.

Orientador: Michiko Sakate / Banca: Noeme Sousa Rocha / Banca: Manoel Lima de Menezes / Banca: Mara Regina Stipp Balarin / Banca: Silvana Lima Gorniak / Resumo: O monofluoroacetato de sodio (MFAS) ou composto 1080 e um rodenticida que foi amplamente utilizado para o controle de roedores e predadores domesticos, apos sua descoberta em 1945. Este potente rodenticida age bloqueando o ciclo de Krebs por acao do seu metabolito toxico, o fluorocitrato, e como consequencia, inibe a resposta celular e a producao de ATP. O MFAS foi proibido por lei no Brasil e em diversos paises, mas seu uso indiscriminado continua causando diversos casos de intoxicacoes potencialmente fatais no homem e animais domesticos, principalmente em caes e gatos, representadas por alteracoes neurologicas e cardiacas. Pretendeu-se com este estudo caracterizar o perfil hematologico e bioquimico, as alteracoes histopatologicas e toxicologicas de gatos intoxicados experimentalmente com MFAS, com o objetivo de determinar metodos diagnosticos eficazes. Para tanto, foram utilizadas amostras de sangue de 16 gatos intoxicados experimentalmente com 0,45mg/kg de MFAS, por via oral. Estas amostras foram colhidas por puncao jugular e analisadas quanto ao perfil hematologico, bioquimica serica e analises toxicologicas em cromatografia liquida de alta eficiencia (CLAE), para deteccao e quantificacao do MFAS no soro dos animais. Avaliaram-se tambem as lesoes macro e microscopicas dos animais intoxicados que vieram a obito. Observaram-se leucopenia e trombocitopenia transitorias; hiperglicemia, aumento das enzimas musculares creatinoquinase (CK) e creatinoquinase fracao cardiaca (CK-MB); observaram-se tambem hipocalemia, hipofosfatemia e hipomagnesemia. Os achados macroscopicos e histopatologicos demonstraram lesoes caracteristicas de processos isquemicos e as analises toxicologicas demonstraram um metodo diagnostico simples e eficiente...(Resumo completo, clicar acesso eletrõnico abaixo) / Abstract: Sodium monofluoroacetate (SMFAC) or 1080 compound is a potent rodenticide, largely used since 1945 for rodent and domestic pest control. The toxic effects of SMFAC are caused by fluorocitrato, a toxic metabolite, which has a competitive action with aconitase enzyme, leading to citrate accumulation and interferes in energy production by Krebs cycle blockade. In Brazil, although prohibited by law, there is illegal use, keep causing intoxication in children and domestic animals, specially dogs and cats. The most common intoxication clinical signs are from the cardiac and neurological alterations. In the present study, 16 domestic cats were intoxicated with oral doses of monofluoroacetate (0.45mg/kg). The hematologic and biochemical profiles, and histophatological and blood serum toxicological analysis by high performance liquid chromatography (HPLC) were made to looking for a efficient diagnosis methods. The hematologic profile showed transitory leucopenia and trombocitopenia; the biochemical profile presented hiperglycemia, increase of creatinoquinase enzyme (CK) and creatinoquinase cardiac fraction (CK-MB), hypokalemia and hypophosfatemia were observed. The macrocospic and histopathological findings showed lesions characteristic of degenerative and ischemic processes. The toxicological analysis was shown to be a simple and efficient diagnostic method. SMFAC was detected in 75% of the serum samples analysed, and it was verified an average concentration of 0.32 ìg/mL in them; 4.81% of the serum samples did not show metabolized SMFAC six hours after the induced intoxication of the animals used in this study. / Doutor

Aerial control using 1080 (sodium monofluoroacetate) baits is widely used in New Zealand for the control of introduced brushtail possums (Trichosurus vulpecula), with the aim of protecting national conservation and agricultural values from these damaging pests. This thesis integrates research, completed over 25 years, that was motivated by growing recognition in the 1970s of the extent of possum impacts and the need to improve the effectiveness and efficiency of the control operation. Field research assessed the palatability of three types of cereal-based pellet baits and carrot baits in different regions, habitat types and seasons. Palatability was assessed by the consumption of the different bait types presented independently of each other on 15-30 plots, with rotation of bait types at plots on successive nights to provide equal exposure to each bait type. There was regional variation in possums' bait preferences, possibly reflecting genotypic differences, whereas seasonal variation was less evident. Carrot bait was preferred or equally preferred to cereal bait in 14 out of 20 field trials. The proportion of possums eating baits was then investigated by, firstly, developing a technique for tracing bait acceptance using rhodamine B, a UV-fluorescent dye. In four field trials, more than 95% of possums accepted three types of dye-marked bait, eliminating bait refusal as a major reason for low kills in winter control operations. In a fifth trial, conducted in summer, only 68% of possums accepted bait suggesting that seasonal availability of favoured foods may influence bait acceptance. Since possums must encounter baits before deciding whether to eat them, field studies were undertaken to assess the coverage achieved in normal aerial baiting operations. Large gaps, up to 400 m in width, were often found between baiting swaths; these could allow some possums to survive. A controlled field experiment, using acceptance of rhodamine-dyed bait as a measure of effectiveness, showed that bait distribution was least accurate where flight paths were not marked. Where gaps of 100 m between flight paths were deliberately created, bait acceptance was slower and less than where coverage was complete. Sowing baits at 3 kg/ha was as effective as at 10 kg/ha, indicating the potential for substantially reducing operational costs by using machinery capable of faultlessly distributing baits at low rates. Navigational guidance systems were evaluated and found to improve the accuracy of bait distribution. During 1993-1997, when a lower sowing rate of 5 kg/ha was adopted operationally by regional managers, control effectiveness was unchanged but annual savings of around $9 million accrued. Because of the lack of suitable sowing machinery, a bucket was developed to permit faultless distribution of baits at lower rates, demonstrating the possibility of yet further cost-savings. The possibility of seasonal food availability affecting bait acceptance was investigated in three different forest habitats. Dyed baits were aerially distributed on 100 ha at each site in each season over two years. In each trial, fat-based condition indices of possums were calculated and the abundance of possum-preferred plant foods described. Bait acceptance was consistently high (85-100%) in the 24 trials, and was not influenced by either condition or availability of preferred foods. It seems likely that seasonal variation in operational effectiveness is caused by either the availability of sharply seasonal, scarce foods that possums may feed on intensively for brief periods, or by warmer temperatures that render 1080 less effective. The influence of 1080 on acceptance of (rhodamine-dyed) baits was investigated in a field trial. Examination of possums for dye-marking showed that 25% of possums refused to eat either a lethal quantity of bait or any bait at all, compared with 98% of possums eating non-toxic bait. This indicated that 1080 is aversive to possums, which is a potential major reason for their surviving control operations. Pen trials were therefore conducted to further examine the problem and to seek solutions. Toxic carrot baits were rejected by 27.5% of possums, equally by smell and taste aversion, whereas toxic cereal pellets were rejected by 34%, mainly by taste aversion. Orange and cinnamon were shown to be among the most preferred of 42 flavours tested and, when applied to toxic baits, 1080 was effectively masked. Bait refusal was reduced to ≤7%, the same as that recorded for possums presented with flavoured non-toxic baits. For long-term control of possum populations, aerial 1080 baiting can be used sequentially with other poisoning methods. However, the compatibility of these methods is dependent on the likelihood of possums developing bait shyness if sublethally dosed. Studies were therefore conducted to characterise and compare the four main toxicants used (1080, cyanide, cholecalciferol and brodifacoum) for induction and mitigation of bait shyness. Shyness was induced in approximately 80% of possums sublethally dosed with cyanide, 60% with 1080, 20% with cholecalciferol, and 0% with brodifacoum. Cyanide and 1080 shyness were found to persist in many possums for at least 12 and 24 months, respectively. Use of alternative bait types, and of baits containing an alternative slow-acting toxin (brodifacoum) were shown to be effective ways of overcoming shyness. This, and other related research, is reviewed to provide operational specifications that maximise the likelihood that all targeted possums will (i) encounter bait, (ii) eat it, and (iii) die. The likely future use of aerial 1080 baiting is described and the technological, economic, environmental and social constraints on its sustainability are discussed. Finally, the uptake of the research by possum managers is considered, and areas identified in the thesis where information is incomplete are summarised as prioritised topics for further research.