Absence of evidence of porcine circovirus infection in piglets with congenital tremors.

Porcine circovirus types 1 (PCV1) and 2 (PCV2) have been associated with congenital tremors (CTs) in piglets in the United States. In this study, central nervous system and nonneural tissues of 40 CT piglets from Spain, the United Kingdom, Ireland, and Sweden were investigated for the presence of PCV1 and PCV2 using in situ hybridization and immunohistochemical labeling on paraffin sections. The polymerase chain reaction for PCV2 was also carried out on sera from the Spanish CT cases. No evidence of circovirus nucleic acid or antigen was found in any CT piglet. Although these results do not support the hypothesis that PCV1 or PCV2 are linked to porcine CT, they cannot disprove it.     

Mode of action of the delayed toxicity of O,O,S-trimethyl phosphorothioate in the rat

As preliminary probes to determine the mode of delayed toxic action of O,O,S-trimethyl phosphorothioate (I) in the rat, the effect of I on rat tissue and organs, and on blood, urine, and pharmacokinetic parameters was investigated. Following oral administration, 30 to 200 mg/kg I caused liver necrosis as a major pathological effect. Morphological changes were also observed in the heart, adrenal, tissues of the small intestine, and kidney. Most animals treated with I developed bronchopneumonia after 3 days. Blood samples taken from rats poisoned with 60 mg/kg I showed severe hemoconcentration; however, serum Na⁺, Cl^?, albumin, and total carbonate/bicarbonate varied only slightly. Na⁺ and Cl^? concentrations in the urine showed a steady decline with time following poisoning but K⁺ levels remained relatively constant. Pharmacokinetic studies showed that ¹⁴C levels in the blood following intraperitoneal or intravenous administration of 60 mg/kg [CH₃O¹⁴C]I were not affected when the animals were cotreated with 5% of the antagonist O,O,O-trimethyl phosphorothioate. However, lower levels of ¹⁴C were found in antagonized animals following oral administration.     

Toxicokinetics of carbofuran in house fly, Musca domestica L

The kinetics of accumulation and elimination of lethal doses of [¹⁴C]carbofuran in the hemolymph of the house fly suggest a one-compartment open model. Carbofuran in the hemolymph appeared to be in equilibrium with that in the tissues very soon after treatment.Following topical application of carbofuran, the rate of onset of symptoms of poisoning was correlated with the amount of carbofuran in the hemolymph, and the onset of convulsions only occurred after the concentration of carbofuran in the hemolymph reached μM levels. This value correlated well with neurobioassays of known concentrations of carbofuran perfused in saline onto the isolated thoracic ganglion.Following topical doses, carbofuran concentration in the hemolymph reached a peak within an hour and then gradually declined. At an LD₆₀ dose, the initial decline in carbofuran concentration in the hemolymph over time was significantly slower than the decline after an LD₁₀ dose, suggesting saturation kinetics.Hemolymph was collected from house flies for up to 3 hr following topical application of toxic amounts of carbofuran. Thereafter, hemolymph volume decreased and blood samples could not be collected. Curiously, hemolymph samples could be collected for 5 hr from house flies that were injected with toxic doses of carbofuran.     

Comparison of the effects of injections of nortestosterone phenylpropionate at single and multiple sites in cattle on the detection of its residues in plasma, urine and bile

The synthetic androgen 17 beta-19-nortestosterone (beta-NT) has been used illegally as a growth promoter in cattle production in the European Union. The elimination of beta-NT and its metabolites in plasma and urine was studied in cattle which had received intramuscular injections of its phenylpropionate ester (NTPP) at either single or multiple sites at a dose rate of 1 mg/kg bodyweight. In both groups, the plasma concentrations of beta-NT, measured by enzyme immunoassay, were consistently greater than the assay's limit of quantification (0.24 ng/ml) during days 1 to 7 of the study. The mean (sd) maximum plasma concentration (Cmax) was significantly greater in the multiply injected animals (4.4 [0.48] v 2.7 [0.15] ng/ml), but other plasma pharmacokinetic parameters, AUC, CL, T1/2 beta, Tmax and MRT, were not significantly different in the two groups. The equivalent urinary concentrations exceeded the limit of quantification of the assay (4.5 ng/ml) for up to 24 days after injection. In a second study, the biliary concentrations of beta-NT and its 17 alpha-epimer (alpha-NT) were measured by gas chromatography-high resolution mass spectrometry after cattle were injected intramuscularly at either single or multiple sites with NTPP. Only alpha-NT was detected in bile for up to 62 days after injection at concentrations above the limit of quantification of the assay (0.7 ng/ml). It is concluded that in some animals, intramuscular injections of NTPP at several sites may decrease the period after injection during which free beta-NT and its metabolites are detectable in plasma and urine. After the injection of NTPP, alpha-NT was detected in bile for longer than it was detected in plasma or urine.     

Amylopectinosis in fetal and neonatal Quarter Horses

Three Quarter Horses, a stillborn filly (horse No. 1), a female fetus aborted at approximately 6 months of gestation (horse No. 2), and a 1-month-old colt that had been weak at birth (horse No. 3), had myopathy characterized histologically by large spherical or ovoid inclusions in skeletal and cardiac myofibers. Smaller inclusions were also found in brain and spinal cord and in some cells of all other tissues examined. These inclusions were basophilic, red-purple after staining with periodic acid-Schiff (both before and after digestion with diastase), and moderately dark blue after staining with toluidine blue. The inclusions did not react when stained with Congo red. Staining with iodine ranged from pale blue to black. Their ultrastructural appearance varied from amorphous to somewhat filamentous. On the basis of staining characteristics and diastase resistance, we concluded that these inclusions contained amylopectin. A distinctly different kind of inclusion material was also present in skeletal muscle and tongue of horse Nos. 1 and 3. These inclusions were crystalline with a sharply defined ultrastructural periodicity. The crystals were eosinophilic and very dark blue when stained with toluidine blue but did not stain with iodine. Crystals sometimes occurred freely within the myofibers but more often were encased by deposits of amylopectin. This combination of histologic and ultrastructural features characterizes a previously unreported storage disease in fetal and neonatal Quarter Horses, with findings similar to those of glycogen storage disease type IV. We speculate that a severe inherited loss of glycogen brancher enzyme activity may be responsible for these findings. The relation of amylopectinosis to the death of the foals is unknown.     

Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in alpacas

The aim of this study was to determine the pharmacokinetics and prostaglandin E₂ (PGE₂) synthesis inhibiting effects of intravenous (IV) and transdermal (TD) flunixin meglumine in eight, adult, female, Huacaya alpacas. A dose of 2.2 mg/kg administered IV and 3.3 mg/kg administered TD using a cross‐over design. Plasma flunixin concentrations were measured by LC‐MS/MS. Prostaglandin E₂ concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE₂ concentrations decreased after IV flunixin meglumine administration but there was minimal change after TD application. Mean t_1/2λz after IV administration was 4.531 hr (range 3.355 to 5.571 hr) resulting from a mean Vz of 570.6 ml/kg (range, 387.3 to 1,142 ml/kg) and plasma clearance of 87.26 ml kg^?1 hr^?1 (range, 55.45–179.3 ml kg^?1 hr^?1). The mean C_max, T_max and t_1/2λz for flunixin following TD administration were 106.4 ng/ml (range, 56.98 to 168.6 ng/ml), 13.57 hr (range, 6.000–34.00 hr) and 24.06 hr (18.63 to 39.5 hr), respectively. The mean bioavailability for TD flunixin was calculated as 25.05%. The mean 80% inhibitory concentration (IC₈₀) of PGE₂ by flunixin meglumine was 0.23 µg/ml (range, 0.01 to 1.38 µg/ml). Poor bioavailability and poor suppression of PGE₂ identified in this study indicate that TD flunixin meglumine administered at 3.3 mg/kg is not recommended for use in alpacas.     

Pharmacokinetics of single doses of maropitant citrate in adult horses

The neurokinin‐1 (NK) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood and likely under‐recognized in horses. Use of NK‐1 receptor antagonists in horses has not been reported. The purpose of this study was to determine the pharmacokinetic profile of maropitant in seven adult horses after single intravenous (IV; 1 mg/kg) and intragastric (IG; 2 mg/kg) doses. A randomized, crossover design was performed. Serial blood samples were collected after dosing; maropitant concentrations were measured using LC‐MS/MS. Pharmacokinetic parameters were determined using noncompartmental analysis. The mean plasma maropitant concentration 3 min after IV administration was 800 ± 140 ng/ml, elimination half‐life was 10.37 ± 2.07 h, and volume of distribution was 6.54 ± 1.84 L/kg. The maximum concentration following IG administration was 80 ± 40 ng/ml, and elimination half‐life was 9.64 ± 1.27 hr. Oral bioavailability was variable at 13.3 ± 5.3%. Maropitant concentrations achieved after IG administration were comparable to those in small animals. Concentrations after IV administration were lower than in dogs and cats. Elimination half‐life was longer than in dogs and shorter than in cats. This study is the basis for further investigations into using maropitant in horses.     

Estimating direct healthcare costs attributable to laboratory‐confirmed Lyme disease in Ontario,Canada: A population‐based matched cohort study using health administrative data

The objective of this study was to determine healthcare costs attributable to laboratory‐confirmed Lyme disease (LD) from the healthcare payer perspective in Ontario, Canada. A cost‐of‐illness study was conducted for incident LD subjects from 1 January 2006 through 31 December 2013 ascertained from provincial laboratory and reportable disease databases, linked to health administrative data. All LD subjects included were laboratory‐confirmed, according to provincial case definitions. Incident LD subjects were propensity‐score matched to uninfected subjects on age, sex, comorbidities and urban/rural status. We used phase‐of‐care methods to calculate attributable costs for two phases of illness: initial care (≤30 days following “index date”) and continuing care (>30 days after index date to the end of the follow‐up period). A total of 663 incident, confirmed LD subjects were identified from 2006 through 2013. Mean age was 44.2 ± 20.1 years; 339 (51.1%) were female; and 31 (4.7%) were hospitalized ≤30 days after index date. Six hundred fifty‐eight (99.2%) LD subjects were matched to uninfected subjects; mean follow‐up time was 3.3 years. Mean attributable costs per case during the initial care phase and continuing care were $277 (95% CI: $197, $357) and ?$5 (?$27, $17), respectively. Attributable costs per LD subject aged 5–14 years were $440 ($132, $747), greater than the costs observed for other age strata. Expected 1‐year attributable costs were $832, given continuing care costs were negligible. Limitations to our study include estimating costs using a cohort of only laboratory‐confirmed LD cases, introducing selection bias for diagnosed and treated patients who may have a lower risk of developing sequelae. In conclusion, the initial care phase of LD is associated with increased healthcare costs, but without significant costs attributable to LD infection after 30 days. Estimates of costs attributable to LD are important for healthcare resource prioritization and the evaluation of novel interventions.     

Effects of L‐citrulline supplementation on heat stress physiology,lactation performance and subsequent reproductive performance of sows in summer

Lactating sows are susceptible to heat stress (HS). Part of the thermoregulatory response to HS is to increase peripheral blood flow, which is mediated in part by the vasodilator, nitric oxide (NO). Therefore, the aim of this experiment was to determine the effect of supplementation of L‐citrulline, a NO precursor, on symptoms of HS, lactation performance and subsequent reproductive performance of sows in summer. A total of 221 summer farrowing mixed parity sows were fed either a control diet or supplemented with 1% L‐citrulline upon entry to the farrowing house (6 ± 1.8 days for mean ± standard deviation [SD] before farrowing) until weaning (26 ± 1.5 days). The average daily minimum and maximum temperature in the farrowing house was 21.0 ± 1.88 and 29.2 ± 3.82°C (mean ± SD). Rectal temperature, respiration rate, and plasma and urinary nitrite and nitrate (NOx) of sows were measured on the 19th day post‐farrowing. Supplemental L‐citrulline in the diet did not affect the number of piglets born alive, feed intake of sows, body weight or backfat thickness of sows at weaning, or litter weight gain. L‐citrulline tended to reduce piglet pre‐weaning mortality rate from 18.6% to 15.6% (p = 0.058). L‐citrulline reduced the respiration rate of sows compared to the control diet at 17:00 hr (Time × Diet, p < 0.001); however, rectal temperature was not affected. L‐citrulline tended to increase urinary NOx concentrations (127 vs. 224 µM, p = 0.057) but not plasma NOx concentrations. L‐citrulline did not affect farrowing rate or number of piglets born alive in the subsequent parity. In conclusion, L‐citrulline supplementation reduced respiration rate of lactating sows and reduced piglet pre‐weaning mortality rate in summer. Whether the effects were due to a NO‐dependent mechanism requires further validation.