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.     

Fast variability of tera-electron volt gamma rays from the radio galaxy M87

The detection of fast variations of the tera-electron volt (TeV) (10(12) eV) gamma-ray flux, on time scales of days, from the nearby radio galaxy M87 is reported. These variations are about 10 times as fast as those observed in any other wave band and imply a very compact emission region with a dimension similar to the Schwarzschild radius of the central black hole. We thus can exclude several other sites and processes of the gamma-ray production. The observations confirm that TeV gamma rays are emitted by extragalactic sources other than blazars, where jets are not relativistically beamed toward the observer.     

In vitro susceptibility to antimonials and amphotericin B of Leishmania infantum strains isolated from dogs in a region lacking drug selection pressure

The aim of this study was to evaluate the susceptibility to anti-leishmanial agents of 24 strains isolated from dogs living in the urban area of Alger lacking drug selection pressure. Two different Leishmania infantum zymodemes, MON-1 and MON-281, were identified in these dogs. The in vitro susceptibility to the main forms of antimonial and amphotericin were assessed on promastigote and amastigote life stages in culture. The results obtained for both parasite life stages were concordant whatever the molecule tested. Moreover, our data showed that isolates belonging to the relatively rare zymodeme of L. infantum, MON-281, were less susceptible to antimony than MON-1, when at the same time there was no significant difference for amphotericin B.     

Natural enemies of the South American moth, Tuta absoluta, in Europe, North Africa and Middle East, and their potential use in pest control strategies

The South American tomato leafminer, Tuta absoluta Meyrick (Lepidoptera: Gelechiidae), is an invasive Neotropical pest. After its first detection in Europe, it rapidly invaded more than 30 Western Palaearctic countries becoming a serious agricultural threat to tomato production in both protected and open-field crops. Among the pest control tactics against exotic pests, biological control using indigenous natural enemies is one of the most promising. Here, available data on the Afro-Eurasian natural enemies of T. absoluta are compiled. Then, their potential for inclusion in sustainable pest control packages is discussed providing relevant examples. Collections were conducted in 12 countries, both in open-field and protected susceptible crops, as well as in wild flora and/or using infested sentinel plants. More than 70 arthropod species, 20 % predators and 80 % parasitoids, were recorded attacking the new pest so far. Among the recovered indigenous natural enemies, only few parasitoid species, namely, some eulophid and braconid wasps, and especially mirid predators, have promising potential to be included in effective and environmentally friendly management strategies for the pest in the newly invaded areas. Finally, a brief outlook of the future research and applications of indigenous T. absoluta biological control agents are provided.     

Genetic and environmental factors affecting perinatal and preweaning survival of D’man lambs

This study examined the viability of 4,554 D’man lambs born alive at Errachidia research station in south-eastern Morocco between 1988 and 2009. Lamb survival to 1, 10, 30 and 90 days old was 0.95, 0.93, 0.93 and 0.92, respectively. The majority of deaths (85.7 %) occurred before 10 days of age. Type and period of birth both had a significant effect on lamb survival traits, whereas age of dam and sex of lamb did not. The study revealed a curvilinear relationship between lamb’s birth weight and survival traits from birth to 90 days, with optimal birth weights for maximal perinatal and preweaning survival varying according to type of birth from 2.6 to 3.5 kg. Estimation of variance components, using an animal model including direct and maternal genetic effects, the permanent maternal environment as well as fixed effects, showed that direct and maternal heritability estimates for survival traits between birth and 90 days were mostly low and varied from 0.01 to 0.10; however, direct heritability for survival at 1 day from birth was estimated at 0.63. Genetic correlations between survival traits and birth weight were positive and low to moderate. It was concluded that survival traits of D’man lambs between birth and 90 days could be improved through selection, but genetic progress would be low. However, the high proportion of the residual variance to total variance reinforces the need to improve management and lambing conditions.     

Cardiomyocyte calcium cycling in a naturally occurring German shepherd dog model of inherited ventricular arrhythmia and sudden cardiac death

ObjectiveTo further characterize arrhythmic mechanisms in German shepherd dogs (GSDs) affected with inherited ventricular arrhythmias by evaluating intracellular calcium cycling and expression of calcium handling genes.AnimalsTwenty five GSDs, 9 backcross dogs, and 6 normal mongrel dogs (controls) were studied. The GSDs and backcross dogs were from a research colony of inherited ventricular arrhythmias. The control research dogs were purchased.MethodsAction potentials (APs) and pseudo-electrocardiograms (ECG) were recorded from left ventricular (LV) wedge preparations of GSDs and normal dogs. Midmyocardial (Mid) LV cells from GSDs and normal mongrels were isolated by enzymatic digestion. Cells were either field stimulated or voltage clamped and calcium transients were measured by confocal microscopy using the indicator Fluo-3AM. Expression of calcium handling genes was measured by quantitative RT-PCR.ResultsMean calcium transient decay (tau) was not different between affected GSDs and control dogs, but striking cell-to-cell variability for tau was observed within affected GSDs and between affected GSDs and controls (P < 0.0001 each); within-dog variability accounted for 75% of total variability. Calcium sparks and afterdepolarizations occurred in GSD but not control cells. ATP2A2/SERCA2a expression was significantly reduced (P = 0.0063) in affected GSDs and inversely correlated (P = 0.0006) with severity of ventricular arrhythmias.ConclusionsGerman shepherd dogs with inherited ventricular arrhythmias have electrophysiologic abnormalities in calcium cycling associated with reduced ATP2A2/SERCA2a expression. These animals provide a unique opportunity to study calcium remodeling at the genetic and molecular level in familial ventricular arrhythmias.     

Fractional composition of humus in leached chernozems and gleyed podzolized chernozem-like soils of the northern forest-steppe zone

The composition of humus in leached chernozems differs from that in gleyed podzolized chernozem-like soils in the northern forest-steppe zone of European Russia. Leached chernozems have the fulvate-humate humus. Gleyed podzolized chernozem-like soils have the humate-fulvate humus. A more aggressive composition of humus in the latter soils is caused by their overwetting and the development of gley processes under conditions of a stagnant-percolative soil water regime.