Orientador: Rosemeire Cristina Linhari Rodrigues Pietro / Coorientador: Flávio Politi / Banca: Ilio Montanari Junior / Banca: Luis Vitor do Sacramento / Resumo: O Brasil é um dos maiores exportadores de carne bovina do mundo, entre 2003 e 2008 a receita com exportações cresceu de um bilhão para mais de cinco bilhões de dólares. Apesar disso, o setor enfrenta perdas consideráveis devido à ocorrência de infestações massivas de ectoparasitas como os carrapatos da espécie Rhipicephalus (Boophilus) microplus. Ainda dentro do agronegócio, outra produção que se encontra em amplo crescimento e demonstrando grande potencial de ganho de espaço no mercado internacional é a ovinocultura, com rebanho estimado em 14 milhões de animais, colocando o Brasil em 18º lugar no ranking mundial de exportações. Porém, existem grandes perdas econômicas devido à existência de infestações com endoparasitas, como o nematódeo gastrintestinail da espécie Haemonchus contortus. Em paralelo à preocupação com os prejuízos financeiros no agronegócio, outra espécie de carrapato, Rhipicephalus sanguineus, desperta interesse dos pesquisadores por ser o vetor de microrganismos causadores de importantes doenças em cães nas regiões tropicais e subtropicais. Devido ao mau uso, acaricidas e nematicidas sintéticos tem ocasionado o fenômeno de resistência, com isso a busca por novas substâncias a partir de espécies vegetais configura-se numa alternativa muito promissora para o controle desses parasitas. A espécie Achyrocline satureioides (Lam.) D.C. (Asteraceae), popularmente conhecida como macela, possui em sua composição compostos fenólicos, sobretudo flavonóis e flavanonas, ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Brazil is one of the largest beef exporter in the world and between 2003 and 2008, revenue from exports grew from one billion to more than five billion dollars. Nevertheless, the sector is facing considerable losses due to the occurrence of massive infestations of ectoparasites such as tick species of Rhipicephalus (Boophilus) microplus. In the agribusiness, another production that is in ample growth and showing great potential for space gain in the international market is the sheep industry, with herd estimated at 14 million animals, placing Brazil in 18th position in the world exports ranking. However, there are great economic losses due to the infestations of endoparasites, such as the gastrointestinal nematodes species of Haemonchus contortus. In parallel to the concern about the financial losses in agribusiness, other tick species, Rhipicephalus sanguineus, arouses interest of researchers for being the vector of microorganisms that causes major diseases to dogs in tropical and subtropical regions. Due to misuse of synthetic antiparasitic, which causes the phenomenon of resistance to them, the search for new substances from plant species sets up a very promising alternative for the biological control. The species Achyrocline satureioides (Lam.) DC (Asteraceae), popularly known as macela, has in its composition phenolic compounds, particularly flavonols and flavanones in the inflorescences. Based on the aspects, this study aimed to analyze the effectiveness of extractives of the first Brazilian cultivar of A. satureoides developed in the CPQBA on ticks R. (B.) microplus and R. sanguineus, as well as on the nematode H. contortus, using in vitro assays. The essential oil and the extracts of inflorescences of macela have shown that this plant has high activity on engorged females of R. (B.)... (Complete abstract click electronic access below) / Mestre

Orientador: Estevam Guilherme Lux Hoppe / Banca: Adjair Antônio do Nascimento / Banca: Paulo Aléscio Canola / Banca: Daniel Cortes Beretta / Banca: José Ribamar Privado Filho / Resumo: O monepantel, anti-helmíntico de uma nova classe, foi desenvolvido e colocado no mercado recentemente, como solução para criações com helmintos de ovinos multirresistentes. Após pouco tempo de utilização, foram relatados casos de resistência contra o produto. Objetivou-se avaliar o perfil de resistência ao monepantel em criações de ovinos em uma microrregião em torno de Jaboticabal-SP e caracterizar experimentalmente a resistência ao monepantel em isolado de Haemonchus contortus. Foi realizado o teste de redução de ovos em dez propriedades ovinocultoras próximas a Jaboticabal/SP, identificando a eficácia do monepantel e levantando o histórico da utilização do produto para determinação de fatores de risco associados à resistência. Obteve-se isolado de H. contortus resistente para teste crítico. Após coleta de fezes dos animais oriundos de propriedade onde o vermífugo foi ineficaz, obteve-se larvas infectantes que foram inoculadas em dois doadores para obtenção de fêmeas de H. contortus. Larvas infectantes deste isolado foram inoculadas em dez animais. Após confirmada a patência, cinco animais receberam monepantel, grupo tratamento, e cinco não receberam, grupo controle. Exames de OPG foram realizados nos dias 0 (dia do tratamento), 2, 4, 6, 8, 10, 12 e 14 e os animais eutanasiados no dia 14, avaliando o número de H. contortus no abomaso dos animais dos dois grupos. Revelou-se que em duas propriedades o monepantel foi ineficaz, em duas foi eficaz e nas outras seis foi altamente eficaz. Os principais fatores predisponentes detectados foram: intervalos curtos entre vermifugações, não alternância com outras bases químicas, tratamento massivo, raça e intensificação da criação. Observou-se H. contortus resistente após realização do teste crítico com eficácia de 24,65%. Conclui-se que helmintos de ovinos já estão resistentes ao monepantel em criações... / Abstract: Monepantel, anthelmintic of a new class, was recently developed and released to the international market, it was presented as a solution for properties with multirresistant helminthes. However, with little time utilization, were related cases of resistance against this product. The objectives of this work were evaluate the resistance profile of monepantel on sheep creations at a microregion around Jaboticabal-SP and characterize experimentally the monepantel resistance on Haemonchus contortus isolate. Initially, was accomplished egg count reduction test at ten ovine properties located around Jaboticabal-SP, identifying the monepantel efficacy and investigating the history of product use for determination risk factors resistance associated. Posteriorly, a H. contortus resistant isolate was obtained for the critic test. After animals collect stoll of a resistance suspected proprierty, there were obtained infective larvae that were inoculated on two donors for females of H. contortus obtainment and after, infective larvae production for inoculation in ten animals. After patency confirmed, five animals received monepantel, treatment group, and five didn't receive, control group. The treatment day was day 0. Fecal egg counts were performed on days 0, 2, 4, 6, 8, 10, 12 and 14 and the animals were euthanized on day 14, evaluating the H. contortus number in the sheep abomaso of both groups. The results of the fisrt part study revealed the monepantel was ineffective in two properties, was effective in two properties and highly effective on six properties. The risk factors detected were: short interval between anthelmintic treatments, no alternation with other chemical bases, massive treatment, breed, intensification of creation. In a second step, was observed H. contortus resistant after performed the critc test, with an efficacy of 24,65%. We concluded that sheep helminths are already monepantel ... / Doutor

Haemonchus contortus is a blood feeding parasitic nematode infecting ruminants causing anemia and poor health at great economic cost. The ability to pharmaceutically control infection has been challenged by the rapid development and spread of drug resistance. The discovery of new targets is therefore required for sustainable parasite control. UNC-49 is a nematode ligand-gated ion channel that plays an important role in muscle contraction required for normal locomotion. However, little is known regarding its sensitivity to different agonists and how they interact with the binding site. This thesis describes an investigation into the efficacy of a range of classical GABA receptor agonists on Hco-UNC-49 expressed in Xenopus oocytes. The results of our electrophysiological recordings indicate that there is a size requirement for full agonism of the Hco-UNC-49 binding site. Furthermore, a number of molecules that are known to act on vertebrate GABA receptors have no effect on Hco-UNC-49. This suggests that the binding site of nematode GABA receptors does exhibit some unique properties. These findings could possibly be exploited to develop new drugs that specifically target GABA receptors from parasitic nematodes. / UOIT

Haemonchus contortus is a parasitic nematode that is controlled by several nematocides which target ion channels. We have identified two H. contortus ion channel genes, Hcounc- 49B and C that encode two GABA-gated chloride channel subunits. Electrophysiological analysis shows that the Hco-UNC-49B subunit forms a functional homomeric channel in Xenopus laevis oocytes that produces a robust response to GABA and is highly sensitive to picrotoxin. In contrast, Hco-UNC-49C alone does not respond to GABA but can assemble with Hco-UNC-49B to form a heteromeric channel with an increased sensitivity to GABA and a lower sensitivity to picrotoxin. To investigate the subunit requirements for high agonist sensitivity, we generated cross-assembled channels by co-expressing the H. contortus subunits with UNC-49 subunits from the nematode Caenorhabditis elegans (Cel-UNC-49). Co-expressing the Cel-UNC-49B with Hco- UNC-49C produced a heteromeric channel with a low sensitivity to GABA. In contrast, co-expressing Hco-UNC-49B with Cel-UNC-49C produced a heteromeric channel that was highly sensitive to GABA. These results suggest that the Hco-UNC-49B subunit is the key determinant for the high agonist sensitivity of heteromeric channels.

Two studies were conducted to evaluate the effectiveness of using copper sulfate (CuSO4) as a drench in Hampshire ewes to control stomach worms (Haemonchus contortus). A study was conducted to assess the effectiveness of CuSO4 to control gastrointestinal nematodes (GIN) over a three year period. Ewes were FAMACHA scored, hematocrit evaluated for packed cell volume (PCV), and fecal egg counts (FEC) were determined from 2007 through 2009. Ewes received only CuSO4 to control GIN. Ewes with FEC exceeding 6,000 eggs/g feces were drenched. A separate study during the summer of 2008 assessed the potential of CuSO4 drench to cause copper toxicity in Hampshire ewes. Eighty-four ewes were blocked to one of two treatments according to parity and balanced for FEC. One group received CuSO4 (D) and the other was not drenched (ND). Jugular blood samples were collected at pre-determined intervals after CuSO4 was administered to D ewes. Serum was analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK). Elevated serum levels indicate copper toxicity. Results suggest CuSO4 has the potential to control stomach worms in Hampshire ewes without causing copper toxicity.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2009. / Härtill 4 uppsatser.

Submitted by ALINE CARVALHO MARTINS null (alinecarvalhomartins@hotmail.com) on 2016-02-29T01:32:05Z No. of bitstreams: 1 Tese defesa com correções.pdf: 2266757 bytes, checksum: a86bbd4a6396a41dc83d25dac4029acf (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-02-29T16:45:46Z (GMT) No. of bitstreams: 1 martins_ac_dr_jabo.pdf: 2266757 bytes, checksum: a86bbd4a6396a41dc83d25dac4029acf (MD5) / Made available in DSpace on 2016-02-29T16:45:46Z (GMT). No. of bitstreams: 1 martins_ac_dr_jabo.pdf: 2266757 bytes, checksum: a86bbd4a6396a41dc83d25dac4029acf (MD5) Previous issue date: 2016-01-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O monepantel, anti-helmíntico de uma nova classe, foi desenvolvido e colocado no mercado recentemente, como solução para criações com helmintos de ovinos multirresistentes. Após pouco tempo de utilização, foram relatados casos de resistência contra o produto. Objetivou-se avaliar o perfil de resistência ao monepantel em criações de ovinos em uma microrregião em torno de Jaboticabal-SP e caracterizar experimentalmente a resistência ao monepantel em isolado de Haemonchus contortus. Foi realizado o teste de redução de ovos em dez propriedades ovinocultoras próximas a Jaboticabal/SP, identificando a eficácia do monepantel e levantando o histórico da utilização do produto para determinação de fatores de risco associados à resistência. Obteve-se isolado de H. contortus resistente para teste crítico. Após coleta de fezes dos animais oriundos de propriedade onde o vermífugo foi ineficaz, obteve-se larvas infectantes que foram inoculadas em dois doadores para obtenção de fêmeas de H. contortus. Larvas infectantes deste isolado foram inoculadas em dez animais. Após confirmada a patência, cinco animais receberam monepantel, grupo tratamento, e cinco não receberam, grupo controle. Exames de OPG foram realizados nos dias 0 (dia do tratamento), 2, 4, 6, 8, 10, 12 e 14 e os animais eutanasiados no dia 14, avaliando o número de H. contortus no abomaso dos animais dos dois grupos. Revelou-se que em duas propriedades o monepantel foi ineficaz, em duas foi eficaz e nas outras seis foi altamente eficaz. Os principais fatores predisponentes detectados foram: intervalos curtos entre vermifugações, não alternância com outras bases químicas, tratamento massivo, raça e intensificação da criação. Observou-se H. contortus resistente após realização do teste crítico com eficácia de 24,65%. Conclui-se que helmintos de ovinos já estão resistentes ao monepantel em criações brasileiras localizadas no estado de São Paulo, especialmente o H. contortus. / Monepantel, anthelmintic of a new class, was recently developed and released to the international market, it was presented as a solution for properties with multirresistant helminthes. However, with little time utilization, were related cases of resistance against this product. The objectives of this work were evaluate the resistance profile of monepantel on sheep creations at a microregion around Jaboticabal-SP and characterize experimentally the monepantel resistance on Haemonchus contortus isolate. Initially, was accomplished egg count reduction test at ten ovine properties located around Jaboticabal-SP, identifying the monepantel efficacy and investigating the history of product use for determination risk factors resistance associated. Posteriorly, a H. contortus resistant isolate was obtained for the critic test. After animals collect stoll of a resistance suspected proprierty, there were obtained infective larvae that were inoculated on two donors for females of H. contortus obtainment and after, infective larvae production for inoculation in ten animals. After patency confirmed, five animals received monepantel, treatment group, and five didn’t receive, control group. The treatment day was day 0. Fecal egg counts were performed on days 0, 2, 4, 6, 8, 10, 12 and 14 and the animals were euthanized on day 14, evaluating the H. contortus number in the sheep abomaso of both groups. The results of the fisrt part study revealed the monepantel was ineffective in two properties, was effective in two properties and highly effective on six properties. The risk factors detected were: short interval between anthelmintic treatments, no alternation with other chemical bases, massive treatment, breed, intensification of creation. In a second step, was observed H. contortus resistant after performed the critc test, with an efficacy of 24,65%. We concluded that sheep helminths are already monepantel resistant in brazilian creations located at São Paulo state, especially Haemonchus contortus.

Made available in DSpace on 2014-06-11T19:33:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-06-21Bitstream added on 2014-06-13T20:05:15Z : No. of bitstreams: 1 domingues_lf_dr_jabo.pdf: 549039 bytes, checksum: d86406f020ba0aeb857e62d02337188a (MD5) / As medidas de controle de parasitas de ruminantes são baseadas quase que exclusivamente no uso de antiparasitários comerciais, provocando o rápido desenvolvimento da resistência. O objetivo deste estudo foi verificar o efeito carrapaticida, in vitro, sobre Rhipicephalus (Boophilus) microplus de bovinos, e o efeito anti-helmíntico, in vitro e in vivo, sobre Haemonchus contortus de ovinos. Nos testes realizados sobre R. (B.) microplus, o extrato aquoso de abacaxi e a bromelina foram avaliados em oito concentrações. Fêmeas ingurgitadas foram imersas nos tratamentos e acondicionadas em incubadora para observação da sobrevivência, postura e eclodibilidade das larvas. Para o teste com larvas, cerca de 100 larvas foram colocadas em papéis-filtro impregnados, incubados e as leituras realizadas após 24 horas. O ensaio in vitro foi baseado nos testes de eclodibilidade dos ovos (TEO) e no de desenvolvimento larvar (TDL). No teste in vivo, 36 ovinos infectados artificialmente com H. contortus foram divididos em seis grupos (n=6). No G1 foi administrado 2 g/kg PV do EACA durante três dias, no G2 - 2 g/kg PV do resíduo industrial do abacaxi durante 60 dias, no G3 – 180 mg/animal da bromelina em dose única, G4 – controle negativo I (dos grupos G1 e G2), G5 – controle positivo (10 mg/kg PV de fosfato de levamisol) e G6 – controle negativo II (do grupo G3). Foram realizadas contagens de ovos por grama de fezes (OPG) até o dia 28 após o tratamento. Os resultados do estudo do abacaxi sobre o carrapato demonstraram que, no teste de fêmeas ingurgitadas, as concentrações mais efetivas foram 125, 250 e 500 mg/mL: 33, 48 e 59% para o EACA e 27, 51 e 55%, para a bromelina. As CL50 e CL90 foram, respectivamente, as seguintes: 276 e 8691 mg/mL para o EACA, e 373 e 5172 mg/mL para a bromelina. Nenhuma das diluições estudadas apresentou eficácia contra... / The measures to control parasites in ruminants are almost exclusively based on use of commercial chemical compounds, causing rapid development of resistance. The objective of this study was to investigate the acaricidal effect, in vitro, on Rhipicephalus (Boophilus) microplus in cattle and the anthelmintic effect, in vitro and in vivo, on Haemonchus contortus in sheep. In the tests on R. (B.) microplus, an aqueous extract of pineapple and bromelain were evaluated at eight concentrations. Engorged females were dipped and placed in a incubator for observation of survival, oviposition and egg hatching. For the larvae, about 100 larvae were placed on filter papers impregnated, incubated and readings were taken after 24 hours. The in vitro experiment used the egg hatch test (EHT) and larval development test (LDT). In the in vivo test, 36 sheep artificially infected with H. contortus were divided into six groups (n=6). In the G1 – 2 g/kg BW of AEPS for three days; G2 – 2 g/kg BW of the industrial pineapple residue during 60 days.; G3 – 180 mg/animal of bromelain in a single dose, G4 – negative control I (of groups G1 and G2), G5 – positive control (10 mg/kg BW of levamisole phosphate); and G6 – negative control II (of group G3). The eggs per gram (EPG) of feces were counted until the day 28 after treatment. In the test with engorged cattle ticks, the greatest efficacies were at dilutions of 125, 250 and 500 mg/mL: 33, 48 and 59% for the AEPS and 27, 51 and 55% for bromelain. The LC50 and LC90 were respectively as follows: 276 and 8691 mg/mL for the AEPS, and 373 and 5172 mg/mL for the bromelain. None of the dilutions studied was effective against R. (B.) microplus larvae. In the experiment with the nematode H. contortus, the LC50 and LC90 in the EHT were respectively 31 and 81 mg/mL for the AEPS and 0.50 and 2 mg/mL for the bromelain... (Complete abstract click electronic access below)