Prevalence of fibrinous pericarditis in heavy pigs (170 kg) and its association with other pluck lesions at slaughter inspection.

This study determined the prevalence of fibrinous pericarditis and its correlation with other pluck lesions in 658 batches of pigs from 236 intensive farms located in Northern Italy over a 12-month period. All pigs were slaughtered at 170 kg, and a total 57,943 plucks (approximately 90 pigs/batch) were individually assessed for the presence of fibrinous pericarditis, pneumonia, pleuritis, and liver milk spots. There was no seasonal variation in the prevalence of plucks with fibrinous pericarditis and annual mean prevalence was 5.6% (range, 0-26.3% at batch level; median, 4.71%). Farm of origin, evaluated as a random effect, accounted for 17.7% batch variation. Batches with a high prevalence of fibrinous pericarditis (≥7.7%) had higher prevalences of pleural, pulmonary, and liver lesions than those with low-middle prevalence of pericarditis; high prevalence of pericarditis was predictive of pluck lesions (P < 0.001). There was a highly significant association between fibrinous pericarditis and severe pleuritis, and 55% of plucks with the highest score for pleuritis also had ongoing fibrinous pericarditis, with a positive correlation at batch level (r2 = 0.52; P < 0.001). The co-existence of pericarditis and pleuritis (73.5% of all pericarditis cases) suggests that pleuritis plays a role in the pathogenesis of pericarditis. Based on the prevalence fibrinous pericarditis, and the role of pleuritis as a potential comorbidity, abattoir data on pluck lesions with accompanying farm history, could aid the interpretation and management of on-farm health problems, and inform diagnostic protocols.

Prevalence and risk factors for gastric ulceration in pigs slaughtered at 170 kg.

Oesophago-gastric ulcers (OGU) are a production and welfare problem in pigs. Stomach condition was scored for 22 551 pigs in 228 batches over a 7-month period at an abattoir in Italy processing heavy pigs for ham production. Mild or severe ulceration was observed in 20.7% of pigs, of which 13% had scar tissue. Variation between batches was high (0% to 36% prevalence of severe ulcers) and showed a significant effect of farm of origin (P<0.001). Overnight lairage increased the prevalence of mild ulcers (P<0.001), but not severe or scarred ulcers. Scarred ulcers increased in the hottest summer months. Prevalence of ulcers showed only few and weak correlations at batch level with pathologies of the pleura, lungs and liver, but a strong correlation with on-farm mortality of the batch. Analysis of farm risk factors for OGU was assessed by questionnaire with a response rate of 17% of farms. Risk factors retained in a multivariable model included a protective effect of anthelmintic treatment (risk ratio (RR)=5.1, P=0.03), increased risk in farms using Mycoplasma vaccination (RR=5.6, P=0.04) and a tendency for association with type of flooring (P=0.06). Univariable analyses also highlighted possible influences of other stress-inducing factors including lack of enrichment objects and mixing of pigs during fattening, suggesting that the role of on-farm stressors merits further investigation. It is concluded that abattoir screening of OGU in future programmes for the assessment of well-being on farm should encompass only severe lesions and scarring, and results be returned to farmers to facilitate improvement of production and welfare.

Pharmacokinetics, metabolism, excretion and plasma protein binding of 14C-levofloxacin after a single oral administration in the Rhesus monkey.

Levofloxacin's metabolism, excretion, and in vitro plasma protein binding, together with its pharmacokinetics, were studied in the Rhesus monkey in support of an anthrax efficacy study in this species. Three males and three female Rhesus monkeys were dosed with a single oral dose of 14C-levofloxacin at 15 mg kg-1 (2 MBq kg-1). Following dose administration, blood samples were collected up to 48 h post-dose, and urine and faeces were quantitatively collected up to 168 h post-dose. Blood, plasma, urine, and faeces were analysed for total radioactivity. Metabolite profiling and identification was performed using radio-high-performance liquid chromatography (HPLC) and liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS). Additionally, the plasma protein binding of levofloxacin was determined in vitro by means of equilibrium dialysis. Peak plasma levels of total radioactivity and levofloxacin were rapidly reached after oral administration with a total radioactivity blood: plasma ratio close to unity. The elimination half-life of levofloxacin was estimated at about 2 h. Total radioactivity was mainly excreted in urine (about 57-86% of the dose) with faecal excretion accounting for only a minor fraction of the total amount of excreted radioactivity (about 7.4-14.7%). In the plasma, the majority of total radioactivity was accounted for by levofloxacin. In addition, two minor metabolites, i.e. levofloxacin n-oxide and presumably a glucuronide conjugate of levofloxacin, were detected. In the urine, five components were found, with levofloxacin being the major component. Minor metabolites included desmethyl levofloxacin, levofloxacin n-oxide, and a glucuronide conjugate of levofloxacin. In the faeces, the major analyte was a polar metabolite, tentatively identified as a levofloxacin glucuronide. The in vitro plasma protein binding was low (on average 11.2%) and independent of concentration (1.0-10.0 microg ml-1). No sex differences were noted in any of the investigations. The present data indicated that the metabolism and excretion pattern, and also the in vitro plasma protein binding of levofloxacin in the Rhesus monkey, were comparable with those previously reported in man, hereby supporting the use of this animal species in the efficacy evaluation of levofloxacin against inhalation anthrax. The shorter half-life of levofloxacin in the Rhesus monkey relative to man (2 versus 7 h) prompted the development of an alternative dosing strategy for use in the efficacy study.

Single-mode regime of square-lattice photonic crystal fibers.

The modal cutoff of square-lattice photonic crystal fibers with a finite number of air-hole rings has been accurately investigated to our knowledge for the first time. By analyzing the leaky behavior of the second-order mode, we have obtained a phase diagram that describes the regions of single-mode and multimode operation as well as the endlessly single-mode regime. Furthermore, starting from these results, we have obtained the cutoff normalized frequency according to two different formulations of the V parameter previously adopted for fibers with a triangular lattice. A final comparison of the cutoff properties of fibers characterized by a square lattice and a triangular lattice has been carried out.

Pharmacokinetics, metabolism and excretion of the glycine antagonist GV150526A in rat and dog.

1. The pharmacokinetics, metabolic fate and excretion of 3-[-2(phenylcarbamoyl) ethenyl-4,6-dichloroindole-2-carboxylic acid (GV150526), a novel glycine antagonist for stroke, in rat and dog following intravenous administration of [C14]-GV150526A were investigated. 2. Studies were also performed in bile duct-cannulated animals to confirm the route of elimination and to obtain more information on metabolite identity. 3. Metabolites in plasma, urine and bile were identified by HPLC-MS/MS and NMR spectroscopy. 4. GV150526A was predominantly excreted in the faeces via the bile, with only trace metabolites of radioactivity in urine (< 5%). Radioactivity in rat bile was predominantly due to metabolites, whereas approximately 50% of the radioactivity in dog bile was due to parent GV150526. 5. The principal metabolites in bile were identified as glucuronide conjugates of the carboxylic acid, whereas in rat urine the main metabolite was a sulphate conjugate of an aromatic oxidation metabolite. Multiple glucuronide peaks were observed and identified as isomeric glucuronides and their anomers arising from acyl migration and muta-rotation.

First time in human for GV196771: interspecies scaling applied on dose selection.

The utility of interspecies scaling in early drug development has been extensively debated. The authors discuss the dose selection strategy for a first time into man (FTIM) study for GV196771, a new glycine antagonist, using techniques of interspecies scaling. The FTIM dose selection strategy was based on predicted plasma profiles of GV196771 in humans using allometric scaling and considerations of safety and pharmacological activity in animals. Allometric techniques were first retrospectively applied to data obtained in humans and animals for GV150526, a glycine antagonist with similar pharmacokinetic characteristics to GV196771. GV196771 and GV150526 are extensively protein bound; thus, protein binding differences among species were considered in the scaling. Using the scaled pharmacokinetic parameters, compartmental modeling was performed to prospectively simulate concentration profiles for the oral administration of GV196771. This article will discuss the outcome of the prospective dose selection strategy for GV196771 compared to the actual concentration profiles observed in the FTIM study.

Sanfetrinem and sanfetrinem-cilexetil: disposition in rat and dog.

1. The absorption, distribution, metabolism and excretion of sanfetrinem have been investigated in the rat and dog after intravenous (i.v.) administration of the radiolabelled parent compound, and oral dosing of the hexetil ester prodrug, 14C-sanfetrinem-cilexetil. 2. Sanfetrinem-cilexetil was rapidly absorbed and hydrolysed pre-systemically to sanfetrinem. The oral bioavailability was 32% in rat and 15% in dog. 3. Drug-related radioactivity was distributed in all tissues with high levels present in bladder, kidney and liver. The volume of distribution was approximately that of extracellular fluid. There was no indication of any significant binding or retention to any tissues, including those containing melanin. 4. Protein binding of sanfetrinem determined in rat and dog plasma was constant over a wide range of concentrations equivalent to 14-18% in dog and about 67% in rat plasma. 5. Two metabolites were identified in urine after i.v. administration: the open beta-lactam ring derivative (GV173923) and the dimeric compound (GV196359). 6. After i.v. dosing the terminal half-life of the unchanged drug was 12 min in rat and 35 min in dog. The half-life of the total radioactivity was longer due to low levels of metabolites. Of the dose, > 90% was excreted in the urine both in rat and dog, and 69% of the dose was excreted as unchanged sanfetrinem in rat urine. The radioactivity excreted in the bile accounted for 3-7% of the dose.