No description available.

Avermectins and milbemycins are commonly used in agro-ecosystems for the control of parasites in domestic livestock. As integral members of agro-ecosystems with importance in maintaining pasture health through dung burial behaviour, dung beetles are an excellent, non-target, bio-indicator taxon for examining potential detrimental effects of pesticide application. The current study uses the dung beetle species, Euoniticellus intermedius (Reiche), as a bio-indicator to test the relative toxicity of four different anthelmintics in dung residues. There have been numerous laboratory and field trials on these four anthelmintics but there has never been a laboratory trial comparing ivermectin, eprinomectin, doramectin and moxidectin under precisely the same conditions. The effects of avermectin and milbemycin toxicity are not confined to parasitic nematodes and arthropods, but also extend to a large variety of beneficial invertebrate species, which use the dung as a microhabitat and breeding resource. Over time, pesticide usage indirectly affects the rate of dung degradation through adverse effects on dung beetles. This potential problem constitutes the main focus of this study. The present and previous studies have indicated no significant effect on the survival of adults but a significant reduction in reproductive rate and reproductive success. Over time, reduced reproductive rate would result in decreased population sizes in the dung beetle community and, ultimately, a decrease in the rate of dung degradation and dung burial. It is, thus, vitally important to create awareness about the importance of dung beetles and sound farming practices for healthy agro-ecosystems. / Dissertation (MSc)--University of Pretoria, 2014. / lk2014 / Zoology and Entomology / MSc / Unrestricted

No description available.

Compared to mammals, nematodes appear to exhibit a unique GABAergic nervous system. Haemonchus controtus is a parasitic nematode that infects ruminants worldwide. Hco-UNC-49 is a H. contortus GABA-gated chloride channel and is an orthologue to the UNC-49 channel from the free-living nematode Caenorhabditis elegans. Previous research by our group has shown that while the UNC-49 channels from the two nematodes share similar sequence homology they do not share identical sensitivity to GABA. To further investigate the characteristics of the Hco-UNC-49 channel, this study tested the effects of various modulators, insecticides and anti-parasitic drugs on channel function. Most notably, the molecules penicillin G, propofol and pregnenolone sulfate all had similar effects on Hco-UNC-49 as reported previously for Cel-UNC-49. On the other hand, Hco-UNC-49 appears to be less sensitive to picrotoxin inhibition compared to what has been reported for Cel-UNC-49. Novel effects of a number of anthelmintics were also observed. For example, the anthelmintics ivermectin and moxidectin both enhanced Hco-UNC-49 GABA responses, while piperazine was able to directly activate Hco-UNC-49 at high concentrations. These results suggest that Hco-UNC-49 is likely an in vivo target for these anthelmintics. / UOIT

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.

Anthelmintic resistance is a major problem in livestock, and while it has been slower to emerge in cattle, there are reports of its occurrence. Three broad-spectrum anthelmintics are available for use, and one mechanism of resistance that is common to all is target site alteration. Glutamate-gated chloride channels (GluCls) are an important target for macrocyclic lactone anthelmintics (MLs), while beta-tubulin represents the benzimidazole (BZ) target. The objectives of this thesis were to determine whether GluCls are involved in ML resistance in the cattle parasite Cooperia oncophora , and whether beta-tubulin is involved in BZ and ML resistance. Two isolates of C. oncophora were used. In a fecal egg-count reduction test, ivermectin was found to be 100% effective against one isolate (IVS), and only 77.8% effective against the second isolate (IVR). Two full-length GluCl cDNAs, encoding GluClalpha3 and beta subunits, were cloned. These subunits share high sequence identity with similar GluCl subunits from Haemonchus contortus and Caenorhabditis elegans. Genetic variability analysis of the two genes showed significant differences in allele frequencies between IVS and IVR worms at the GluClalpha3 gene, but not the GluClbeta gene, suggesting that the GluClalpha3 gene is involved in ivermectin resistance. Sequencing of full-length GluCl subunit cDNAs from IVS and IVR worms revealed the presence of mutations in the N-terminal domains. Mutations in the GluClalpha3 caused modest but significant reductions in glutamate, ivermectin and moxidectin sensitivity, while mutations in the GluClbeta abolished glutamate sensitivity. Of the three mutations identified in the IVR GluClalpha3, the L256F mutation accounted for the difference in glutamate and ivermectin response between IVS and IVR GluClalpha3 channels. Two beta-tubulin isotypes cloned from C. oncophora were found to share a high homology with beta-tubulin isotypes from other trichostrongylids. Gen

The aim of this research was to determine the influence of route of administration, drug formulation and modified-liver metabolism on the pharmacokinetic and metabolic patterns of benzimidazole anthelmintics in ruminants. Both route of administration and formulation dramatically affected the bioconversion of netobimin (NTB) pro-drug, N-methoxycarbonyl-N$ sp prime$-(2-nitro-5-propylphenylthio)-${ rm N} sp{ prime prime}$-(2-ethyl sulphonic acid) guanidine, and the bioavailability and disposition kinetics of its active albendazole (ABZ) metabolites in both sheep and cattle. The efficacy of NTB conversion by the gastrointestinal (GI) microflora, was markedly lower after subcutaneous (SC) administration of NTB pro-drug compared with enteral administrations in both species. Although trisamine and zwitterion formulations of NTB were bioequivalent after SC treatment, the zwitterion suspension was two-fold more bioavailable in terms of ABZ metabolites, after oral administration to cattle. ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO$ sb2$), the main metabolites found in plasma, were reversibly exchanged between plasma and GI compartments and concentrated in the abomasum. ABZ, ABZSO and ABZSO$ sb2$ were detected in the GI tract for 72 h post-NTB administration to cattle. In vitro, ABZ was oxidized into ABZSO and ABZSO$ sb2$ by liver microsomes and ruminal and ileal fluids. However, only ABZSO was reduced (back to ABZ) by these GI fluids. The rate of ABZ sulphoxidation by liver microsomes was significantly lower in cattle compared to sheep. However, while the oxidizing activity was greater in GI fluids of cattle, the reducing activity was prevalent in those of sheep. This was consistent with the higher ABZSO$ sb2$/ABZSO ratio and the markedly faster disposition of both metabolites in cattle compared to sheep. The co-administration of NTB with different oxidation-impairing compounds, largely methimazole (MTZ), in both species, resulted in an increased bioavailability and/o

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2004. / Härtill 6 uppsatser.