Pharmacokinetics of R(-) and S(+) carprofen after administration of racemic carprofen in donkeys and horses

OBJECTIVE: To compare plasma disposition of the R(-) and S(+) enantiomers of carprofen after IV administration of a bolus dose to donkeys and horses. ANIMALS: 5 clinically normal donkeys and 3 clinically normal horses. PROCEDURE: Blood samples were collected from all animals at time 0 (before) and at 10, 15, 20, 30, and 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 28, 32, and 48 hours after IV administration of a bolus of carprofen (0.7 mg/kg). Plasma was analyzed in triplicate via high-performance liquid chromatography to determine the concentrations of the carprofen enantiomers. A plasma concentrationtime curve for each donkey and horse was analyzed separately to estimate noncompartmental pharmacokinetic variables. RESULTS: In donkeys and horses, the area under the plasma concentration versus time curve (AUC) was greater for the R(-) carprofen enantiomer than it was for the S(+) carprofen enantiomer. For the R(-) carprofen enantiomer, the AUC and mean residence time (MRT) were significantly less and total body clearance (CIT) was significantly greater in horses, compared with donkeys. For the S(+) carprofen enantiomer, AUC and MRT were significantly less and CIT and apparent volume of distribution at steady state were significantly greater in horses, compared with donkeys. CONCLUSIONS AND CLINICAL RELEVANCE: Results have suggested that the dosing intervals for carprofen that are used in horses may not be appropriate for use in donkeys.     

Root-knot nematode--directed expression of a plant root--specific gene

Root-knot nematodes are obligate plant parasites that induce development of an elaborate feeding site during root infection. Feeding-site formation results from a complex interaction between the pathogen and the host plant in which the nematode alters patterns of plant gene expression within the cells destined to become the feeding site. Expression of TobRB7, a gene expressed only in tobacco roots, is induced during feeding site development. The cis-acting sequences that mediate induction by the nematode are separate from those that control normal root-specific expression. Reporter transgenes driven by the nematode-responsive promoter sequences exhibit expression exclusively in the developing feeding site.     

Molecular findings of disseminated histoplasmosis in two captive snow leopards (Uncia uncia)

This paper reports two cases of disseminated histoplasmosis in captive snow leopards (Uncia uncia). Histoplasmosis was diagnosed based on histopathology, immunohistochemistry, transmission electron microscopy, and molecular findings.     

The correlation of potassium content and moisture in bovine liver samples analyzed for trace mineral concentrations.

Beef cattle in the United States are often found to be deficient in essential trace minerals such as copper and zinc. Established reference ranges for mineral concentrations exist and usually designate a concentration as adequate, marginal, deficient, or excessive. This research investigates a new method of interpreting detected elemental concentrations in bovine liver that will add confidence to the final diagnosis. This is based on the hypothesis that a correlation exists between potassium concentration and moisture in a bovine liver sample. This relationship between potassium and moisture content enables the diagnostician to more accurately predict mineral concentrations and wet weight regardless of sample moisture loss. Correlations were found between potassium content and percentage of moisture in experimental samples, clinical biopsies, and a validation study, to a statistical significance of P < 0.001. Experimental samples had a correlation coefficient of R2 = 0.95 and the mathematical relationship y = 2513.2x(-1.0662). Clinical biopsies had a correlation of R2 = 0.83 and the mathematical relationship y = 2203.4x(-0.991). The validation study had a correlation of R2 = 0.55 and a mathematical relationship y = 2321.4x(-0.952). An exponent of -1 is predicted by conservation of potassium mass. These findings have practical significance in maintaining and improving cattle growth, health, reproduction, and food safety.     

Effects of selenium supply and dietary restriction on maternal and fetal metabolic hormones in pregnant ewe lambs

The objective of these studies was to evaluate the effects of dietary restriction and Se on maternal and fetal metabolic hormones. In Exp. 1, pregnant ewe lambs (n = 32; BW = 45.6 +/- 2.3 kg) were allotted randomly to 1 of 4 treatments. Diets contained (DM basis) either no added Se (control), or supranutritional Se added as high-Se wheat at 3.0 mg/kg (Se-wheat), or sodium selenate at 3 (Se3) and 15 (Se15) mg/kg of Se. Diets (DM basis) were similar in CP (15.5%) and ME (2.68 Mcal/kg). Treatments were initiated at 50 +/- 5 d of gestation. The control, Se-wheat, Se3, and Se15 treatments provided 2.5, 75, 75, and 375 microg/kg of BW of Se, respectively. Ewe jugular blood samples were collected at 50, 64, 78, 92, 106, 120, and 134 d of gestation. Fetal serum samples were collected at necropsy on d 134. In Exp. 2, pregnant ewe lambs (n = 36; BW 53.8 +/- 1.3 kg) were allotted randomly to treatments in a 2 x 2 factorial arrangement. Factors were nutrition (control, 100% of requirements vs. restricted nutrition, 60% of control) and dietary Se (adequate Se, 6 microg/kg of BW vs. high Se, 80 microg/kg of BW). Selenium treatments were initiated 21 d before breeding, and nutritional treatments were initiated on d 64 of gestation. Diets were 16% CP and 2.12 Mcal/kg of ME (DM basis). Blood samples were collected from the ewes at 62, 76, 90, 104, 118, 132, and 135 d of gestation. Fetal blood was collected at necropsy on d 135. In Exp.1, dietary Se source and concentration had no effect (P > 0.17) on maternal and fetal serum IGF-I, triiodothyronine (T(3)), or thyroxine (T(4)) concentrations. Selenium supplementation increased (P = 0.06) the T(4):T(3) ratio vs. controls. In Exp. 2, dietary Se had no impact (P > 0.33) on main effect means for maternal and fetal serum IGF-I, T(3), or T(4) concentrations from d 62 to 132; however, at d 135, high-Se ewes had lower (P = 0.01) serum T(4) concentrations than adequate-Se ewes. A nutrition by Se interaction (P = 0.06) was detected for the T(4):T(3) ratios; ewes fed restricted and adequate-Se diets had greater (P = 0.10) T(4):T(3) ratios compared with the other treatments. Nutrient-restricted ewes had lower (P < 0.05) serum IGF-I, T(3), and T(4) concentrations. Fetal serum IGF-I concentrations were lower (P = 0.01) in restricted-vs. control-fed ewes; however, fetal T(3) and T(4) concentrations were unaffected (P > 0.13) by dietary Se or maternal plane of nutrition. These data indicate that dietary Se may alter maternal T(4):T(3) ratios. In addition, nutrient restriction during gestation reduces maternal IGF-I, T(3), and T(4) and fetal IGF-I concentrations.     

Infection trials in pigs with a human isolate of Brucella ( isolate 02/611 'marine mammal type' )

AIM: To determine if pigs could support infection of a human Brucella isolate (Brucella 02/611) from New Zealand, and to study seroconversion to this isolate using a competitive ELISA. METHODS: Ten weaner piglets were challenged with 4.8 x 10(8) cfu of organisms by the oral and ocular routes. Culture was attempted on blood samples taken prior to challenge, and 4, 7, 9, 11, 14, 21 and 28 days post-challenge, and on tissue samples taken at the termination of the trial, 1 month after challenge. Sera were analysed for antibody using an ELISA. For reference comparison, similar trials were conducted in two pigs using an isolate of Brucella suis biovar 1, and two pigs using an isolate of B. suis biovar 3. RESULTS: Brucella 02/611 organisms were re-isolated from one lymph node each from three pigs; all other samples were negative. Low and transient antibody titres were detected using a competitive ELISA in three pigs, two of which were culture negative. Organisms of B. suis reference strains were re-isolated from multiple samples from each of the four animals. CONCLUSION: Brucella 02/611 does not seem to replicate readily in pigs. It is unlikely that pigs were the original maintenance hosts for Brucella 02/611.     

Molecular characterization of three recombinant isolates of avian leukosis virus obtained from contaminated Marek's disease vaccines

Three natural recombinant avian leukosis viruses (ALV; PDRC-1039, PDRC-3246, and PDRC-3249) expressing a subgroup A gp85 envelope protein and containing long terminal repeats (LTR) of endogenous ALV-E viruses were isolated from contaminated commercial Marek's disease vaccines, cloned, and completely sequenced. Their full genomes were analyzed and compared with representative strains of ALV. The proviral DNA of all three isolates displayed 99.3% identity to each other, suggesting a possible common ancestor, even though the contaminating viruses were obtained from three separate vaccine serials produced by two different vaccine manufacturing companies. The contaminating viruses have a genetic organization typical of replication-competent alpharetroviruses. The proviral genomes of PDRC-1039 and PDRC-3246 are 7497 bp long, and the PDRC-3249 is three base pairs shorter because of a deletion of a threonine residue within the gp85 coding region. The LTR, gag, pol, and the transmembrane (TM) region (gp37) of the env gene of all three viruses displayed high identity to endogenous counterpart sequences (>98%). Only the surface (SU) region (gp85) of the env gene displayed high identity with exogenous ALV-A (98.7%). Locus-specific polymerase chain reaction (PCR) analysis for ALV endogenous sequences (ev loci) in the chicken embryo fibroblasts used to produce the original vaccine vials identified the presence of ev-1, ev-2, ev-3, ev-4, and ev-6 in all three vaccines. Homologous recombination most likely took place to involve the SU region of the env gene because the recombinant viruses only differ in this particular region from the consensus ALV-E. These results suggest that the contaminating ALV isolates probably emerged by recombination of ALV-A with endogenous virus sequences before vaccine preparation.     

A possible new inherited myopathy in a young Labrador retriever

A 5-month-old, male, Labrador retriever was evaluated for progressive weakness and muscle atrophy. Histologic evaluation of fresh frozen muscle revealed distinct cytoarchitectural changes and central mitochondrial accumulations indistinguishable from those found in the inherited myopathy described in Great Danes. Multiple male littermates and half-siblings were similarly affected.