Pharmacokinetics of pioglitazone after multiple oral dose administration in horses

Pioglitazone is a thiazolidinedione class of antidiabetic agent with proven efficacy in increasing insulin sensitivity in humans with noninsulin-dependent diabetes mellitus, a syndrome of insulin resistance sharing similarities with equine metabolic syndrome. The purpose of this study was to determine the pharmacokinetics of pioglitazone in adult horses following multiple oral dose administration. Pioglitazone hydrochloride (1 mg/kg) was administered orally for 11 doses at 24-h intervals, and plasma samples were collected. Initially, a pilot study was performed using one horse; and thereafter the drug was administered to six horses. Samples were analyzed by liquid chromatography with tandem mass spectrometry, and pharmacokinetic parameters were calculated using noncompartmental modeling. The maximum plasma concentration was 509.1 ± 413.5 ng/mL achieved at 1.88 ± 1.39 h following oral administration of the first dose, and 448.1 ± 303.5 ng/mL achieved at 2.83 ± 1.81 h (mean ± SD) following the eleventh dose. Apparent elimination half-life was 9.94 ± 4.57 and 9.63 ± 5.33 h after the first and eleventh dose, respectively. This study showed that in healthy horses, pioglitazone administered at a daily oral dose of 1 mg/kg results in plasma concentrations and total drug exposure approximating, but slightly below, those considered therapeutic in humans.     

Observations on the indirect transmission of virulent ovine footrot in sheep yards and its spread in sheep on unimproved pasture

SUMMARY: Virulent ovine footrot was transmitted accidentally to a group of 23 adult Merino sheep (flock B) after holding for 1 hour in sheep yards, which earlier the same day had contained another flock (flock A) with < 1% prevalence of sheep with footrot lesions. Sheep in flock B were rendered susceptible to virulent footrot by grazing 600 mm high unimproved pasture dominated by paspalum ( Paspalum dilatatum ) and kangaroo grass ( Themeda australis ) during warm, humid and wet weather. In addition to moisture, interdigital abrasions caused by the pasture might have predisposed the interdigital skin to infection with Dichelobacter nodosus .     

Restriction-endonuclease analysis of Australian isolates of Leptospira interrogans serovar hardjo from cattle with agalactia and abortion

SUMMARY Polyacrylamide gel electrophoresis and agarose gel electrophoresis were used to resolve restriction endonuclease digests of 20 Australian isolates of Leptospira interrogans cultured from urine samples of cattle with agalactia and abortion. The restriction endonuclease profiles of 19 isolates closely matched the profiles of L interrogans serovar hardjo subtype hardjobovis reference strains. The remaining isolate had a different restriction profile from subtype hardjobovis and subtype hardjoprajitno reference strains and was serologically identified as serovar pomona. Silver staining of polyacrylamide gels gave enhanced resolution of restriction fragments compared with the traditional method of ethidium bromide staining of agarose gels.     

Investigations into the toxicity of Echium plantagineum in sheep: 1. Field grazing experiments

A field grazing trial was undertaken to monitor the health and production of crossbred sheep grazing pasture where Echium plantagineum constituted a considerable proportion of the available forage. The trial, conducted for 19 months over successive grazing seasons, demonstrated a significant difference in production, with sheep on the E. plantagineum pasture being lighter and growing less wool compared with sheep on Echium-free pasture. No mortalities involving pyrrolizidine alkaloid poisoning were recorded in sheep grazing E. plantagineum, although there was histological evidence of moderately severe liver damage associated with high liver copper concentrations in at least one sheep following the grazing of large quantities of the plant.