Interindividual variability in plasma concentrations after systemic exposure of swine to dietary doxycycline supplied with and without paracetamol: a population pharmacokinetic approach

Anorexigenic substances released during infection may hinder the therapeutic efficacy of in-feed antibiotics. Paracetamol (acetaminophen; PARA) inhibits the anorexia of infection and seems to improve the clinical efficacy of doxycycline (DOX) against bacterial respiratory disease in swine herds. In order to verify whether PARA selectively stimulates intake of DOX-medicated feed in diseased pigs, we documented the pharmacokinetics (PK) of DOX when coadministered with PARA and examined the effect of in-feed PARA on the interindividual variability in plasma concentrations after systemic exposure to in-feed DOX in swine herds with respiratory disease. Systemic exposure to DOX was measured with the area under the curve (AUC) of its plasma concentrations over time. First, a rich-sampling PK study of in-feed and i.v. DOX (10 mg/kg of BW) and PARA (30 and 10 mg/kg of BW, respectively) was performed on 5 pigs. The PK profiles of in-feed DOX were used in mathematical simulations to determine 5 optimal sampling times for the farm-based population PK study. A randomized, blind, parallel PK study was performed in 2 herds with bacterial respiratory disease, where liquid feed was fortified with DOX alone (5 mg x kg of BW(-1) x meal(-1)) or combined with PARA (15 mg x kg of BW(-1) x meal(-1)). Medicated meals were given twice, 12 h apart, to group-housed growing pigs (n > 50 pigs x treatment(-1) x herd(-1), totaling 215 pigs). Plasma concentrations of DOX and PARA were measured with HPLC. At variance with our expectations, PARA decreased (P = 0.069) mean AUC of in-feed DOX and did not decrease its variability (P > 0.34). Mean AUC of DOX increased with feed intake and with initial exposure to DOX, and was greater in sick animals. Therefore, symptomatic PARA-induced improvement in bacterial respiratory disease control with DOX is more likely caused by its analgesic/antipyretic effects than by its orexigenic effect. Interindividual variation in the AUC of DOX was large in pigs given group medication, even when sufficient feeding space was allowed and the amount of feed offered was greater than their requirements. Therefore, future studies to improve the efficacy of group antibiotic therapy should focus on feeding behavior characteristics as well as biopharmaceutical properties of medicated feeds.     

Dosage assessment of valnemulin in pigs based on population pharmacokinetic and Monte Carlo simulation

To estimate the valnemulin pharmacokinetic profile in a swine population and to assess a dosage regimen for increasing the likelihood of optimization. This study was, respectively, performed in 22 sows culled by p.o. administration and in 80 growing‐finishing pigs by i.v. administration at a single dose of 10 mg/kg to develop a population pharmacokinetic model and Monte Carlo simulation. The relationships among the plasma concentration, dose, and time of valnemulin in pigs were illustrated as C_i,v = X₀(8.4191 × 10^‐4 × e^?0.2371t + 1.2788 × 10^?5 × e^?0.0069t) after i.v. and C_p.o = X₀(?8.4964 × 10^?4 × e^?0.5840t + 8.4195 × e^?0.2371t + 7.6869 × 10^?6 × e^?0.0069t) after p.o. Monte Carlo simulation showed that T_>MIC was more than 24 h when a single daily dosage at 13.5 mg/kg BW in pigs was administrated by p.o., and MIC was 0.031 mg/L. It was concluded that the current dosage regimen at 10–12 mg/kg BW led to valnemulin underexposure if the MIC was more than 0.031 mg/L and could increase the risk of treatment failure and/or drug resistance.     

Estimates of phenotypic and genetic parameters for birth weight of Brown Swiss calves in Turkey using an animal model

A study was conducted to assess the influence of genetic and environmental factors on Brown Swiss calf birth weight, and to estimate variance components, genetic parameters, and breeding values. Data were collected on 1,761 Brown Swiss calves born from 1990 to 2005 in the Konuklar State Farm in Turkey. Mean birth weight for all calves was 39.3 ± 0.09 kg. Least squares mean birth weights for male and female Brown Swiss calves were 40.3 ± 0.02 and 39.0 ± 0.02 kg, respectively. Variance components, genetic parameters, and breeding values for birth weight in Brown Swiss calves were estimated by restricted error maximum likelihood (REML)–best linear unbiased prediction(BLUP) procedures using an MTDFREML (multiple trait derivative free restricted maximum likelihood) program employing an animal model. Direct heritability (h _d²), maternal heritability (h _m²), total heritability (h _T²), r _am and c _am estimates were 0.12, 0.09, 0.23, −0.58, and −0.06, respectively. The estimated maternal permanent environmental variance expressed as a proportion of the phenotypic variance (c ²) was 0.05. Breeding values were estimated for the trait and used to evaluate genetic trends across the time period investigated. The genetic trend linear regression was not different from zero. No genetic trend for birth weight was expected, since there had been no direct selection pressure on the trait. Absence of a trend confirms that there was no change due to selection pressure on correlated traits. Genetic and environmental parameter estimates were similar to literature values indicating that effective selection methods used in more developed improvement programs would be effective in Turkey as well.     

Polymerase chain reaction detection of Salmonella spp. in fecal samples of pet birds

The aims of this study were 1) to determine the prevalence of Salmonella in clinically ill birds in aviaries in Ankara, Turkey, and 2) to compare conventional culture and polymerase chain reaction (PCR) for detection of Salmonella in feces from clinically ill pet birds. In the study, 185 fecal samples (feces and/or swabs) collected from the pet birds kept in the seven different aviaries in the city of Ankara were investigated for the existence of Salmonella spp. by bacterial isolation and PCR. The conventional isolation and identification methods were performed for Salmonella isolation from fecal cultures. Suspected colonies were confirmed with the Salmonella polyvalent O antiserum and serogrouped with Salmonella group-specific antiserum. PCR was performed after the fecal swabs were incubated for 18 hr in 10 ml of tetrathionate broth. Three (1.63%) out of 185 fecal samples were found to harbor Salmonella spp. by conventional identification tests and were found to belong to serogroup B. Five (2.7%) swab samples were found to harbor Salmonella DNA by PCR tests. As a conclusion, PCR following incubation of clinical samples in pre-enrichment broth seemed to be a fast and practicable method for Salmonella spp. diagnosis when compared to protracted labor-intensive conventional culture techniques.     

Effects of dietary lysine and energy density on performance and carcass characteristics of finishing pigs fed ractopamine

Two hundred sixteen crossbred barrows and gilts (84.3 kg BW) were used to test the effects of dietary energy density and lysine:energy ratio (Lys:ME) on the performance, carcass characteristics, and pork quality of finishing pigs fed 10 ppm ractopamine. Pigs were blocked by BW and gender, allotted to 36 pens (six pigs per pen), and pens were assigned randomly within blocks to dietary treatments (as-fed basis) arranged in a 2 x 3 factorial design, with two levels of energy (3.30 or 3.48 Mcal/kg) and three Lys:ME (1.7, 2.4, or 3.1 g lysine/Mcal) levels. Pigs were fed experimental diets for 28 d, and weights and feed disappearance were recorded weekly to calculate ADG, ADFI, and G:F. Upon completion of the feeding trial, pigs were slaughtered and carcass data were collected before fabrication. During carcass fabrication, hams were analyzed for lean composition using a ham electrical conductivity (TOBEC) unit, and loins were collected, vacuum-packaged, and boxed for pork quality data collection. Energy density had no (P > 0.22) effect on ADG or ADFI across the entire 28-d feeding trial; however, pigs fed 3.48 Mcal of ME were more (P < 0.02) efficient than pigs fed 3.30 Mcal of ME. In addition, ADG and G:F increased linearly (P < 0.01) as Lys:ME increased from 1.7 to 3.1 g/Mcal. Carcasses of pigs fed 3.48 Mcal of ME were fatter at the last lumbar vertebrae (P < 0.08) and 10th rib (P < 0.04), resulting in a lower (P < 0.03) predicted fat-free lean yield (FFLY). Conversely, 10th-rib fat thickness decreased linearly (P = 0.02), and LM depth (P < 0.01) and area (P < 0.01) increased linearly, with increasing Lys:ME. Moreover, FFLY (P < 0.01) and actual ham lean yield (P < 0.01) increased as Lys:ME increased in the diet. Dietary energy density had no (P > 0.19) effect on pork quality, and Lys:ME did not (P > 0.20) affect muscle pH, drip loss, color, and firmness scores. Marbling scores, as well as LM lipid content, decreased linearly (P < 0.01) as Lys:ME increased from 1.7 to 3.1 g/Mcal. There was a linear (P < 0.01) increase in shear force of cooked LM chops as Lys:ME increased in the finishing diet. Results indicate that 3.30 Mcal of ME/kg (as-fed basis) is sufficient for optimal performance and carcass leanness in pigs fed ractopamine. The Lys:ME for optimal performance and carcass composition seems higher than that currently used in the swine industry; however, feeding very high Lys:ME (> 3.0 g/Mcal, as-fed basis) to ractopamine-fed pigs may result in decreased marbling and cooked pork tenderness.     

Macroscopic Anatomy of the Lower Respiratory System in Mole rats (Spalax leucodon)

The morphologic and morphometric features of the lower respiratory system in mole rats were examined. It was seen that the low respiratory system of this species leading a special life under highly hypoxic/hypercapnic conditions underground is structurally similar to other mammals living on land in terms of the parts examined; trachea was formed by 29.5 ± 4 oval‐formed cartilaginous tracheals arranged backwards and became gradually more stenotic diameter from cranial to the caudal of the neck. The trachea was separated in two principal bronchus at the fourth thoracal intercostal spatium level. The angle between the two main principal bronchi was 60.5 ± 2.35°. The lung constituted 1.29 ± 0.03% of the body weight and the right lung was heavier than the left lung. Fissura inter‐lobaris was deep and separated the lung lobes wholly, and the right lung was separated in four lobes, whereas the left lung was not separated into the lobes. Also, the medial lobe of the left lung was the lightest lobe.     

Volatile fatty acid profile for grass hay or alfalfa hay fed to alpacas (Vicugna pacos)

The purpose of this study was to determine the diurnal composition and concentration of volatile fatty acids (VFA) and to determine VFA composition and concentration differences between stomach compartment 1 (C1) and caecum of alpacas fed grass and alfalfa hay. The study was divided into two experiments. In Experiment 1 (EXP 1), 10 male alpacas (3+ years old, 65 kg BW) were divided into two groups, housed in drylot pens, provided ad libitum water and fed alfalfa (AH) or grass hay (GH) for 30 days. The alpacas were slaughtered and the digestive tract collected, divided into sub‐tract sections, weighed and digesta sampled for pH, dry matter (DM) and NDF. Volatile fatty acid composition and concentration were determined on C1 and caecal material. Four adult male (3+ years old, 60 kg BW), C1 fistulated alpacas were housed in metabolism crates and divided into two forage groups for Experiment 2 (EXP 2). Alpacas were fed the forages as in EXP 1. Diurnal C1 VFA samples were drawn at 1, 3, 6, 9, 12, 18 and 24 h post‐feeding. There were no differences between forages for tract weight, C1 and caecum digesta DM or NDF. Differences were noted (p < 0.05) for pH between forages and sub‐tract site. Volatile fatty acids concentrations were different (p < 0.05) for forage and site, and total VFA was higher for AH than GH (110.6 and 79.1 mm ) and C1 than caecum (40.7 and 27.6 mm ). Proportion of VFA was significant (p < 0.05) for forage and site, C1 acetate highest for GH (84.8 vs. 74.0 mm ) and caecum acetate 83.7 and 76.2 mm for GH and AH respectively. These data demonstrate the level of VFA produced in C1 and the caecum of alpacas and the diurnal VFA patterns. Composition of VFA is similar to other ruminant species.     

Clinical Leptospira interrogans serogroup Australis serovar lora infection in a stud farm in the Netherlands

Summary

A Leptospira interrogans serogroup australis serovar lora infection in a stud farm is reported. During three successive years (1984–1986) clinical leptospirosis with a severe often rapid, fatal course was seen in 12 foals.

Clinical examination revealed severe respiratory distress, depression and pyrexia. Other symptoms were diarrhea (2), jaundice (1), and an unsteady gait (1). Morphological characteristics of the disease were massive pulmonary haemorrhage and haemorrhagicthrombotic or extracapillary glomerulonephritis with tubulonephrosis and interstitial oedema. In most foals high or increasing MAT titres to serovar bratislava were found; from one foal Leptospira interrogans serovar lora was isolated.

Serological examination of all 56 mares at the farm (August 1986) revealed antibodies to serovar bratislava in 64 per cent of the animals. These findings support the idea that Leptospira interrogans serovar bratislava and closely related strains (in this study serovar lora) may be adapted to and maintained by the horse population.     

Bioassay evaluation of the systemic properties of carboxin in lemon seedlings

Carboxin was toxic to the fungus Deuterophoma tracheiphila. Uptake and translocation of carboxin (2,3-dihydro-6-methyl-5-phenylcarbamoyl-1,4-oxathiin) in lemon seedlings were assessed in plant extracts by a bioassay technique. Root uptake and translocation to stem and leaves were demonstrated from both an aqueous solution and drenched soil. Leaf uptake was lower than root uptake, and could be enhanced by removing the epicuticular wax. Chromatographic tests suggested that the compound responsible for fungitoxicity within plant tissues may have been carboxin itself.