Thesis (Ph. D.)--Lehigh University, 2005. / Includes vita. Includes bibliographical references (leaves 121-124).

No description available.

Made available in DSpace on 2014-06-11T19:27:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-21Bitstream added on 2014-06-13T18:32:18Z : No. of bitstreams: 1 rodrigues_dc_me_jabo.pdf: 335525 bytes, checksum: 6290737730ffac1a4d1fcdac98f3ce60 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Avermectinas, derivados de um complexo natural de lactonas macrocíclicas obtidas a partir de fermentação do fungo Streptomyces avermitilis, são amplamente utilizadas no controle de endo e ectoparasitoses. A abamectina tem sido recomendada mundialmente apenas para bovinos acima de quatro meses de idade. Estudos farmacocinéticos apontam diferenças plasmáticas entre avermectinas convencionais e aquelas de longa ação. O objetivo deste trabalho foi avaliar a toxicidade da formulação Abamectina 1% e da formulação de ação prolongada Ivermectina 2,25% + Abamectina 1,25% em diferentes concentrações, para bovinos com idade inferior a trinta dias. Foram utilizados 35 bezerros, machos, HPB, distribuídos em sete grupos: GI - solução fisiológica (controle); GII - 200 mcg/kg; GIII - 400 mcg/kg; GIV - 600 mcg/kg de Abamectina; GV - 450 mcg/kg de Ivermectina + 250 mcg/kg de Abamectina; GVI - 900 mcg/kg de Ivermectina + 500 mcg/kg de Abamectina; GVII - 1350 mcg/kg de Ivermectina + 750 mcg/kg de Abamectina. Todos os bovinos foram submetidos a exames clínicos, duas vezes por dia, durante 14 dias. Foram colhidas amostras de sangue e de líquor nos dias 0, 1, 7 e 14 pós-tratamento. Foram mensurados os seguintes parâmetros bioquímicos do sangue: proteína total e as enzimas AST, GGT e Fosfatase alcalina. No líquor foram quantificados: Coloração e aspectos, pH, densidade, celularidade, proteínas totais, glicose, e as enzimas CK. ALT e LDH. Em relação aos parâmetros clínicos verifica-se que embora ocorresse alterações estatisticamente significativas, estas não podem ser correlacionadas com a aplicação da droga. Assim como as mudanças verificadas nos parâmetro bioquímicos do soro e do liquor. / Avermectin, derivatives of a natural complex of gotten macrocyclical lactonas from fermentation of Streptomyces avermitilis, widely are used in the control of endo and ectoparasites. The abamectin has been recommended world-wide only for bovines above of four months of age. Farmacocinéticos studies point plasmatic differences between conventional avermectins and those of long action. The objective of this work was to evaluate the toxicity of the formularization Abamectin 1% and of the formularization of drawn out action I contend Ivermectin 2.25% + Abamectin 1.25% in different concentrations, for bovines with inferior age the thirty days. 35 year-old calves, males, HPB, distributed in seven groups had been used: GI - physiological solution (control); GII - 200 mcg/kg of Abamectin; GIII - 400 mcg/kg of Abamectin; GIV - 600 mcg/kg of Abamectin; GV - 450 mcg/kg of Ivermectin + 250 mcg/kg of Abamectin; GVI - 900 mcg/kg of Ivermectin + 500 mcg/kg of Abamectin; GVII - 1350 mcg/kg of Ivermectin + 750 mcg/kg of Abamectin. All the bovines had been submitted the clinical examinations, two times per day, during 14 days. Samples of blood and líquor in days 0, 1, 7 and 14 had been harvested post-cure. The following parameters had been to mensurar biochemists of the blood: total protein and the enzymes AST, GGT and alkaline Fosfatase. In the liquor they had been quantified: Coloration and aspects, pH, total density, cells, proteins, glucose, and enzymes CK. ALT and LDH. In relation to the clinical parameters one verifies that even so it occurred significant alterations statistics, these cannot be correlated with the application of the drug. As well as the changes verified in the parameter biochemists of the serum and the liquor.

Orientador: Alvimar José da Costa / Banca: Gilson Pereira de Oliveira / Banca: Vando Edésio Soares / Resumo: Avermectinas, derivados de um complexo natural de lactonas macrocíclicas obtidas a partir de fermentação do fungo Streptomyces avermitilis, são amplamente utilizadas no controle de endo e ectoparasitoses. A abamectina tem sido recomendada mundialmente apenas para bovinos acima de quatro meses de idade. Estudos farmacocinéticos apontam diferenças plasmáticas entre avermectinas convencionais e aquelas de longa ação. O objetivo deste trabalho foi avaliar a toxicidade da formulação Abamectina 1% e da formulação de ação prolongada Ivermectina 2,25% + Abamectina 1,25% em diferentes concentrações, para bovinos com idade inferior a trinta dias. Foram utilizados 35 bezerros, machos, HPB, distribuídos em sete grupos: GI - solução fisiológica (controle); GII - 200 mcg/kg; GIII - 400 mcg/kg; GIV - 600 mcg/kg de Abamectina; GV - 450 mcg/kg de Ivermectina + 250 mcg/kg de Abamectina; GVI - 900 mcg/kg de Ivermectina + 500 mcg/kg de Abamectina; GVII - 1350 mcg/kg de Ivermectina + 750 mcg/kg de Abamectina. Todos os bovinos foram submetidos a exames clínicos, duas vezes por dia, durante 14 dias. Foram colhidas amostras de sangue e de líquor nos dias 0, 1, 7 e 14 pós-tratamento. Foram mensurados os seguintes parâmetros bioquímicos do sangue: proteína total e as enzimas AST, GGT e Fosfatase alcalina. No líquor foram quantificados: Coloração e aspectos, pH, densidade, celularidade, proteínas totais, glicose, e as enzimas CK. ALT e LDH. Em relação aos parâmetros clínicos verifica-se que embora ocorresse alterações estatisticamente significativas, estas não podem ser correlacionadas com a aplicação da droga. Assim como as mudanças verificadas nos parâmetro bioquímicos do soro e do liquor. / Abstract: Avermectin, derivatives of a natural complex of gotten macrocyclical lactonas from fermentation of Streptomyces avermitilis, widely are used in the control of endo and ectoparasites. The abamectin has been recommended world-wide only for bovines above of four months of age. Farmacocinéticos studies point plasmatic differences between conventional avermectins and those of long action. The objective of this work was to evaluate the toxicity of the formularization Abamectin 1% and of the formularization of drawn out action I contend Ivermectin 2.25% + Abamectin 1.25% in different concentrations, for bovines with inferior age the thirty days. 35 year-old calves, males, HPB, distributed in seven groups had been used: GI - physiological solution (control); GII - 200 mcg/kg of Abamectin; GIII - 400 mcg/kg of Abamectin; GIV - 600 mcg/kg of Abamectin; GV - 450 mcg/kg of Ivermectin + 250 mcg/kg of Abamectin; GVI - 900 mcg/kg of Ivermectin + 500 mcg/kg of Abamectin; GVII - 1350 mcg/kg of Ivermectin + 750 mcg/kg of Abamectin. All the bovines had been submitted the clinical examinations, two times per day, during 14 days. Samples of blood and líquor in days 0, 1, 7 and 14 had been harvested post-cure. The following parameters had been to mensurar biochemists of the blood: total protein and the enzymes AST, GGT and alkaline Fosfatase. In the liquor they had been quantified: Coloration and aspects, pH, total density, cells, proteins, glucose, and enzymes CK. ALT and LDH. In relation to the clinical parameters one verifies that even so it occurred significant alterations statistics, these cannot be correlated with the application of the drug. As well as the changes verified in the parameter biochemists of the serum and the liquor. / Mestre

No description available.

Haemonchus contortus is a nematode parasite that infects sheep and goats, and other ruminants, causing substantial economic loss throughout the world. Anthelmintic drugs are the primary method to control these parasites; however, resistance to all broad spectrum anthelmintics, including the newer avermectins and milbemycins, has been developing rapidly in nematode parasites. The mechanism of avermectin resistance is unknown, but previous studies indicate that at least four genes are involved. A single nucleotide polymorphism (SNP) in the Haemonchus contortus HG1 gene has been linked to ivermectin (IVM) and moxidectin (MOX) resistance. This gene encodes a GABA-gated chloride channel thought to control body muscle movement in H. contortus and mediates IVM and MOX paralysis. The present study was designed to determine whether there is an association between variation in this gene and the ability of H. contortus larvae to move in the presence and absence of MOX. The present study also investigated the difference between a laboratory strain (PF23) and an ivermectin resistant field strain (VHR29). Fourteen different MOX concentrations (ranging from 0.078nm to 156uM) and at least 200 third stage (L3) larvae for each concentration were investigated for each strain. An L3 larval motility assay was used to determine the movement phenotype of individual larva. Pyrosequencing was used to identify the genotype of each individual larva. The present study found that in the PF23 strain, the resistant heterozygote genotype GA protected against the effects of MOX, and that the protection was dose dependent. This was not the case, however, in the VHR29 field strain. For this strain, no protective effect of the HG1 variation was observed with moxidectin treatment. One reason for this may be that field strains are selected under higher drug pressure which favors a monogenic response. The present study has shown that while the HG1 variation does play a role in larval movement and resistance to MOX, this effect may be minor compared to other effects selected in the field.

The objectives of this study are to estimate the degree to which a glutamate-gated chloride channel gene (HcGluCla) contributes to survival of moxidectin treatment and to study the relative dominance of those alleles. The phenotype of individual adult H. contortus with respect to feeding was determined using an inulin uptake assay. Genotype was determined using a diagnostic PCR assay. In the absence of moxidectin, homozygous susceptible genotypes fed significantly more than homozygous resistant genotypes. The effect of the susceptible allele was dominant. In the presence of moxidectin, feeding in the susceptible homozygotes was reduced to the level found in the resistant homozygotes, which were unaffected by the drug. These results suggest that the function of the two alleles is different and that they also respond differently to the drug, the resistant allele being unaffected by the drug. / The selection coefficient, s, is the selective difference between the resistant and susceptible genotypes with regard to feeding. Parasites with the resistant allele were seen to feed less in the absence of the drug, i.e., the effect is recessive. In the presence of the drug, there was no difference between resistant and susceptible parasite feeding. These results suggest that resistance may have hidden complexities. (Abstract shortened by UMI.)

Avermectins and milbemycins are believed to exert their anthelmintic effects by binding to glutamate-gated chloride channels (GluCls). Two GluCl subunits have been localized in the pharynx in Caenorhabditis elegans , and the pharynx has been implicated as a major target for avermectins in C. elegans. The HcGluCla gene encoding an alpha-type GluCl subunit has been cloned from Haemonchus contortus previously, however the localization of this gene has not been identified. To begin to investigate the expression site of this HcGluCla gene we have isolated a 1439bp 5'-flanking region and the entire genomic organization of this gene. The 1439bp 5'-flanking region and the first exon and intron and part of the second exon of the HcGluCla gene were fused to the green fluorescent protein reporter gene and microinjected into the gonads of C. elegans. After microinjection of the construct into C. elegans, four stable transformed lines were established and assayed for GFP expression. The transformed animals exhibited fluorescence in the two pairs of MC and M2 pharyngeal neurons, but no expression was detected in the muscle cells. This result provides evidence that the pharynx is a major site for the mode of action of avermectins and milbemycins on parasitic nematodes, such as H. contortus.

Sustainable parasite control in livestock depends on anthelmintic drugs. The nematode Haemonchus contortus, the most important intestinal parasite of sheep and goats has developed resistance to all classes of anthelmintics including moxidectin, the most potent of the macrocyclic lactones. Pyrosequencing was used to screen H. contortus laboratory and field strains for single nucleotide polymorphisms (SNPs) associated with resistance in three genes, and determine their involvement in field resistance to macrocyclic lactones. Specific SNPs increased in frequency in ivermectin/moxidectin laboratory selected strains for all three genes. These did not protect a resistant field strain from a field dose of ivermectin and were not the major mechanism of resistance in the field strain. A gamma-aminobutyric acid chloride receptor SNP may be a potential marker for moxidectin resistance in the field. This study indicates results obtained from laboratory strains selected with sub-therapeutic doses of drug may not reflect the situation in the field.

No description available.