Vaccination mitigates the impact of PRRSv infection on the pharmacokinetics of ceftiofur crystalline-free acid in pigs.

The pharmacokinetics of intramuscularly administered ceftiofur crystalline-free acid (CCFA) were determined in pigs that were clinically healthy (n = 8), vaccinated with a Porcine reproductive and respiratory syndrome modified live virus (PRRS MLV) (n = 10), challenged with wild-type porcine reproductive and respiratory syndrome virus (PRRSv) VR-2385 (n = 10), or vaccinated with PRRS MLV and later challenged with wild-type PRRSv VR-2385 (n = 10). Animals were given a single dose of CCFA intramuscularly at 5 mg/kg body weight. Blood was collected at 0 (pretreatment), 0.25, 0.5, 1, 6, 12, 24, 48, 96, 144, 192, and 240 h postinjection. Plasma was analyzed using liquid chromatography-mass spectrometry. Plasma concentration-time curves for each group were evaluated with noncompartmental modeling. When compared to control animals, those receiving the PRRSv wild-type challenge only had a lower AUC0-last , higher Cl/F, and higher Vz/F. The PRRSv wild-type challenge only group had the longest T1/2λ . The Cmax did not differ among all four treatments. Control animals had no statistically significant differences from animals vaccinated with PRRS MLV alone or animals vaccinated with PRRS MLV and later challenged with wild-type PRRSv. Our results suggest that PRRSv wild-type infection has the potential to alter CCFA pharmacokinetics and PRRS MLV vaccination may attenuate those changes.

Neonatal Mortality, Vesicular Lesions and Lameness Associated with Senecavirus A in a U.S. Sow Farm.

A 300-sow farrow-to-finish swine operation in the United States experienced a sudden and severe increase in mortality in neonatal piglets with high morbidity followed by vesicular lesions on the snout and feet of adult females and males. Affected live piglets were submitted for diagnostic investigation. Samples tested polymerase chain reaction (PCR) negative for foot-and-mouth disease virus, porcine delta coronavirus, porcine epidemic diarrhoea virus, porcine rotavirus types A, B and C, transmissible gastroenteritis virus, and porcine reproductive and respiratory syndrome virus. Senecavirus A (SV-A) formerly known as Seneca Valley virus was detected by real-time reverse-transcription polymerase chain reaction (rRT-PCR) from serum, skin and faeces of piglets and from serum and faeces of sows. SV-A was isolated in cell culture from piglet samples. SV-A VP1 gene region sequencing from piglet tissues was also successful. A biosecurity and disease entry evaluation was conducted and identified potential biosecurity risks factors for the entry of new pathogens into the operation. This is the first case report in the United States associating SV-A with a clinical course of severe but transient neonatal morbidity and mortality followed by vesicular lesions in breeding stock animals. Veterinarians and animal caretakers must remain vigilant for vesicular foreign animal diseases and report suspicious clinical signs and lesions to state animal health authorities for diagnostic testing and further investigation.

Development and refinement of a technique for short-term intravascular auricular vein catheter placement in mature sows.

Intravenous drug administration in adult swine is difficult to perform due to inaccessible superficial veins and thick subcutaneous fat layers. However, successful intravenous drug administration is critical for many biomedical applications including pharmacokinetic studies as extravascular drug administration can influence the drug's absorption and elimination rate. The purpose of this study was to develop and refine an effective technique for indwelling auricular vein catheter placement in the conscious mature sow. We developed a protocol using a topical anesthetic cream and minimal physical restraint to place indwelling catheters in the auricular vein of six multiparous sows. This method was quick (3 min 20 s ± 8 s [mean ± SE per catheter]), effective (11/12 catheters successfully placed) and reliable, allowing a large drug volume (20-22 mL) to be administrated successfully during the trial without relying on prolonged restraint or general anesthesia of the sow.

Resonance Raman spectroscopy of methylamine dehydrogenase from bacterium W3A1.

Resonance Raman spectroscopy has been used to probe the structure of the covalently bound quinone cofactor in methylamine dehydrogenase from the bacterium W3A1. Spectra were obtained on the phenylhydrazine and 2-pyridylhydrazine derivatives of the native enzyme, on the quinone-containing subunit labeled with phenylhydrazine, and on an active-site peptide also labeled with phenylhydrazine. Comparisons of these spectra to the corresponding spectra of copper-containing amine oxidase derivatives indicate that the quinones in these two classes of quinoproteins are not identical. The resonance Raman spectra of the native enzyme and small subunit have also been measured. 16O/18O exchange permitted the carbonyl modes of the quinone to be identified in the resonance Raman spectrum of oxidized methylamine dehydrogenase: a band at 1614 cm-1, together with a shoulder at 1630 cm-1, are assigned as modes containing substantial C = O stretching character. D2O/H2O exchange has pronounced effects on the resonance Raman spectrum of the oxidized enzyme, suggesting that the quinone may have numerous hydrogen bonds to the protein or that it is unusually sensitive to the local environment. Resonance Raman spectra of the isolated small subunit, and its phenylhydrazine derivative, are considerably different from the corresponding spectra of the intact protein. An attractive explanation for these observations is that the quinone cofactor in methylamine dehydrogenase from W3A1 is located at the interface between the large and small subunits, as found for the enzyme from Thiobacillus versutus [Vellieux, F. M. D., Huitema, F., Groendijk, H., Kalk, K. H., Frank, J. Jzn., Jongejan, J. A., & Duine, J. A. (1989) EMBO J. 8, 2171-2178].(ABSTRACT TRUNCATED AT 250 WORDS)

Methylamine oxidase from Arthrobacter P1 as a prototype of eukaryotic plasma amine oxidase and diamine oxidase.

Methylamine oxidase (MAOx) from Gram-positive soil bacterium Arthrobacter P1 catalyzes the oxidation of CH3NH2 to H2C = O and NH4+ via reduction of O2 to H2O2. Past work indicates that MAOx is similar to mammalian plasma amine oxidase (PAO) and diamine oxidase (DAO), plant DAO, and yeast peroxisomal amine oxidase (YAO). All have Mr congruent to 170,000 and are composed of 2 identical subunits, each of which contains 1 atom of Cu(II) and one molecule of quinonoid cofactor. Herein, we report further evidence as to the striking similarity of these enzymes, and describe properties of MAOx which offer insights into understanding the eukaryotic oxidases. It is our belief that the structure of the quinone cofactor, and the Cu(II) site in MAOx are identical to these sites in PAO and DAO.