dc.contributor.advisor	Hamilton, Don L.	en_US
dc.contributor.advisor	Thompson, Julie -.	en_US
dc.contributor.committeeMember	Alcorn, Jane	en_US
dc.contributor.committeeMember	Clark, Chris R.	en_US
dc.contributor.committeeMember	Dowling, Patricia M.	en_US
dc.creator	Sampieri, Francesca	en_US
dc.date.accessioned	2013-07-27T12:00:10Z
dc.date.available	2013-07-27T12:00:10Z
dc.date.created	2013-04	en_US
dc.date.issued	2013-07-26	en_US
dc.date.submitted	April 2013	en_US
dc.description.abstract	Lawsonia intracellularis causes proliferative enteropathies in juvenile mammals. The porcine (PPE) and equine (EPE) diseases are worldwide. Rabbits and hamsters are naturally susceptible, the latter being a classic modeling-host for PPE. None is known for EPE, besides foals. An in vitro evaluation of antimicrobial efficacy against L. intracellularis is difficult. This study aimed to validate a laboratory animal EPE model and to investigate pharmacokinetics (PK) and efficacy of gallium maltolate (GaM) as an alternative antimicrobial therapy. Infected animals were inoculated with cell-cultured L. intracellularis and infection was verified with clinically utilized diagnostic tests. Initially, 2 groups of EPE-infected rabbits were compared to 1 uninfected group. After inoculation (PI), EPE-infected rabbits showed mild clinical signs; detectable seroconversion, fecal shedding, gross lesions in intestinal tissues (IT), and early immuno-histochemistry labeling of L. intracellularis antigen. Thus, a humane EPE-rabbit model was achieved. Subsequently, EPE-infected hamsters were compared to uninfected and PPE-infected hamsters; whereas, PPE-infected rabbits were compared to EPE-infected rabbits. EPE-hamsters did not develop infection, unlike PPE-infected controls; and PPE-rabbits did not develop IT lesions or seroconversion comparable to EPE-rabbits. Therefore rabbits were chosen as the EPE modeling-host for the GaM studies. First, GaM PK and IT concentrations of Ga and Fe were measured. Then, GaM efficacy was compared to a current EPE antimicrobial treatment. During sampling, the intra-arterial catheters in the rabbits’ ears were protected with a novel moleskin-cover, allowing repeated sampling while minimally restrained. The PK study was based on the comparison of EPE-infected and uninfected rabbits, after a single treatment with GaM, collection of serial blood samples and IT samples. The only differing PK parameter, between groups, was a decrease in the terminal phase rate constant of the EPE-rabbits, so a 48h dosing interval was chosen for the efficacy study. In the efficacy study, 3 groups of EPE-infected rabbits were treated with GaM, doxycycline and a placebo, respectively. No differences were noted between treatments, in terms of lesions and fecal shedding. GaM appears no more efficacious than doxycycline in EPE- rabbits. In conclusion, albeit GaM tolerance appeared adequate in rabbits, results do not support its use in EPE-infected animals.	en_US
dc.identifier.uri	http://hdl.handle.net/10388/ETD-2013-04-997	en_US
dc.language.iso	eng	en_US
dc.subject	Gallium maltolate	en_US
dc.subject	rabbit	en_US
dc.subject	hamster	en_US
dc.subject	horse	en_US
dc.subject	Lawsonia intracellularis	en_US
dc.subject	equine proliferative enteropathy	en_US
dc.subject	pharmacokinetics	en_US
dc.subject	efficacy	en_US
dc.subject	animal models.	en_US
dc.title	Investigation on gallium maltolate pharmacokinetics and efficacy, as antimicrobial alternative in an equine proliferative enteropathy infection model.	en_US
dc.type.genre	Thesis	en_US
dc.type.material	text	en_US
thesis.degree.department	Veterinary Biomedical Sciences	en_US
thesis.degree.discipline	Veterinary Biomedical Sciences	en_US
thesis.degree.grantor	University of Saskatchewan	en_US
thesis.degree.level	Doctoral	en_US
thesis.degree.name	Doctor of Philosophy (Ph.D.)	en_US

Investigation on gallium maltolate pharmacokinetics and efficacy, as antimicrobial alternative in an equine proliferative enteropathy infection model.

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