Anthelmintic treatment of livestock is an important aspect of the control of gastrointestinal parasites. Resistance to anthelmintics is common, and an understanding of resistance requires knowledge of an anthelmintic's mode(s) of action and mechanism(s) of resistance. The parasitic nematode, Haemonchus contortus, has developed resistance to benzimidazoles and avermectins/milbemycins. Proposed mechanisms of resistance are here supported by genetic changes observed in genes whose protein products are believed to interact with these anthelmintics. Statistically significant differences in allele frequencies were observed between untreated and ivermectin- and moxidectin-treated strains in a gene encoding a putative glutamate-gated chloride channel alpha subunit, a proposed target of avermectins/milbemycins. One allele appeared to be associated with resistance. Similar changes in allele frequencies in the same strains occurred in a gene encoding a subunit of a gamma-aminobutyric acid receptor. Significant differences in allele frequencies of a gene encoding a P-glycoprotein were found in strains of H. contortus treated with ivermectin and moxidectin compared to derived, untreated strains. In all treated strains, one allele appeared to be associated with resistance. Similarly, allele frequencies of this gene were significantly different between a cambendazole-treated strain and its derived, untreated strain. These results implicate glutamate-gated chloride channels and gamma-aminobutyric acid receptors in mechanisms of resistance to avermectins/milbemycins and implicate P-glycoprotein in a mechanism of resistance to avermectins/milbemycins and benzimidazoles in H. contortus.

Resistance to the avermectin/milbemycin class of anthelmintics in nematodes has become a serious problem worldwide due to their unrestricted usage. Resistance to these compounds is attributed to the over-expression of the transport protein, P-glycoprotein (P-gp). P-gp acts by pumping drug molecules out from the cell or organism, P-gp efflux activity can be blocked using multidrug resistance (MDR) modulators associated with chemotherapy to enhance their therapeutic effect. A series of experiments was undertaken to determine if the association of the anthelmintics, ivermectin (IVM) and moxidectin (MOX), and MDR modulators would increase the anthelmintics' efficacy against resistant parasites. Using an in vitro migration assay, IVM and MOX in the presence or absence of verapamil (VRP), CL347,099 and cyclosporin A (CyA) were used against IVM- and MOX-selected strains of H. contortus. The modulators alone had no effect on reducing the number of migrating larvae, IVM and MOX had a significant increase in efficacy of 52.7 and 58,3% respectively, when used in association with VRP, above that obtained with the anthelmintics alone. CL347,099 was also able to significantly increase the IVM and MOX efficacy by 24.2 and 38.9%, respectively. The effect of IVM and MOX in combination with VRP and CL347,099 was determined in jirds infected with selected strains of H. contortus. The combinations of VRP with either IVM or MOX significantly reduced worm counts of the selected strains compared with the untreated controls, whereas IVM or MOX alone did not. CL347,099 plus MOX combination was significantly more efficacious than moxidectin alone against the selected strains. To evaluate the effect of VRP on the pharmacokinetic behaviour of the anthelmintics IVM and MOX, the drug combination was given to sheep. The IVM plus VRP treatment resulted in an increase of the pharmacokinetic parameters of IVM. The peak concentration (83%) and area under the curve (54%) were significantly differen

Anthelmintics, antiparasitic agents, have been developed as a main weapon to control parasitic nematodes of domestic ruminants. Unfortunately, the intensive use of anthelmintics leads to the development of drug resistance in parasite populations. Anthelmintic resistance has compromised the control of nematode parasites and has become a major problem in many countries of the world. Resistance to the newest anthelmintics such as ivermectin (IVM) and related anthelmintics in Haemonchus contortus in sheep has been developing rapidly in recent years. The development of drug resistance is an evolutionary process that leads to genetic changes in parasite populations in response to drug exposure. However, the mechanism of ivermectin resistance in nematode parasites is unknown. P-glycoprotein (Pgp) has been well documented in mammalian cells as a membrane transporter by actively extruding a variety of structurally and functionally unrelated hydrophobic cytotoxic drugs out of the cell. This study was to determine whether there is an association between specific alleles at the Pgp locus and IVM or moxidectin (MOX) selection in H. contortus, by investigating the genetic variation of the Pgp homologue in unselected and IVM- and MOX-selected strains of H. contortus. (Abstract shortened by UMI.)

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

Haemonchus contortus, otherwise known as the “Barber Pole Worm”, “The Wire Worm” or simply as the large stomach worm of sheep, has been the subject of much scientific interest for the past quarter of a century. Considerable work has been done which has established this parasite as a factor of economic importance and its presence as a pathological agent in the abomasum of ruminants is generally well recognized. This worm is one of the largest of the Strongyloid group, measuring sometimes an inch in the females and three-quarters inch in the males, and its general anatomy is fairly well known. The literature does not, however, reveal any work which has been done in connection with the development of the reproductive cells of this species. In the present work a study has been made of spermatogenesis and oogenesis with some attention directed to methods of copulation, the passage of the sperm cells upon entrance into the vulva and the anatomical location in the female where the sperms are collected for the purpose of fertilization of the ova. No histologic section, depicting the entrance of the sperm into the ova, has been observed but the developmental stages immediately following this penetration of the ova are shown in this paper. Even though a considerable amount of material has been examined which has afforded opportunity for studying the entire reproductive organs of both male and female worms, several developmental stages which have been reported as occurring in nematodes, have not been observed in this study. Sufficient evidence, however, is herein presented which indicated very clearly and definitely the normal chromosome number. / Master of Science

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This investigation was accomplished in the Experimental Station Tunshi Productive Unit Sheep Goat, located to an altitude of 2747 m.s.n.m. and with an average temperature of 13.1°C, it located to 8 kilometers of Riobamba route to Licto and in the Laboratory of Microbiology of the Cattle Sciences Faculty of the Espoch, during 120 days (November of 1998 to February of 1999). The principal objective was that of to evaluate the effect terapeutics of the plant Spigelia anthelmia against parasitesinternal in lambs, for something which is 20 lambs native males with ages that fluctuated of 6 to 9 months, these animals stayed in estabulación fed with forage of good quality (alfalfa + ray grass) and concentrated. Then of the period of adjustment were effected exams coprologycs quantitative to determine the load parasites initial, then was them applied 4 treatments with 5 repetitions each one, the experimental unit was 1 lamb. For the evaluations of PGI, they were studied the days 1,2,3,4,5,6,15,30,45,60 subsequent to the application; to determine the percentages of efficiency against PGI were studied the days 15, 30, 45 and 60; to determine the efficiency to combat Pulmonary Parasites were evaluated the days 15,30 and 60 subsequent to the application. The laboratory techniques that were employed were that of Mc Master, Flotation, Sedimentation, Migration. The obtained results were submitted to the techniques of the ADEVA and Contrast Ortogonals at the levels of probabilities of 0.05 and 0.01, establishing that the alcaloide Spiegilina contained in the Spigelia anthelmia produced a decrease of HPG of PGI without arriving to zero, this effect would be caused by the decrease of the female adult, its action in eggs, juvenile states, adult males is done not know; this plant did not show positive effects against PP; they were not observed sound effects. For it previously exposed is recommended to prove this plant in different forms of preparations and in not ruminant addressee and to evaluate findings post – mortem and Productive Parameters. To prefer the Panvermín L front to the Virbamec by the cost for the gastrointestinal and pulmonary parasites treatment in lambs native.

No description available.