Impact of ATP-binding cassette, subfamily B, member 1 pharmacogenetics on tacrolimus-associated nephrotoxicity and dosage requirements in paediatric patients with liver transplant

Importance of the field: Tacrolimus is the most commonly used immunosuppressive agent following solid-organ transplantation in children. Its clinical use, however, is complicated by side effects (mainly nephrotoxicity), narrow therapeutic index and pharmacokinetic variability which can result in an increased risk of treatment failure or toxicity. Studies examining inter-individual differences in the expression of the ABCB1 (ATP-binding cassette, subfamily B, member 1) gene (which encodes the drug transporter, P-gp) and its genetic polymorphisms have attempted to elucidate variations in tacrolimus response and disposition in children.

Effect of target slaughter weight on production efficiency, carcass traits and behaviour of restrictively-fed gilts and intact male finisher pigs

The effect of 3 slaughter weights (85.95 or 105 kg) on performance and carcass traits of 481 pigs in single-gender groups of 13 (18 groups of gilts and 19 groups of intact males) was evaluated. Pigs (39.5 +/- 3.3 kg) were fed a liquid diet 3 times daily in a long trough. The behaviour of pigs slaughtered at 105 kg was recorded at 50, 60 and 70 days after the start of the experiment (5 groups of gilts and 4 groups of intact males). Behaviour (active, inactive, feeding) and posture (standing, lying, dog-sitting) of all pigs was recorded at 5-min intervals for 30 min prior to and 1 h after each feeding event. Slaughtering pigs at 95 kg and 105 kg delayed production by 7 and 16 days, respectively, compared to slaughtering at 85 kg (P0.05). Muscle depth increased with increasing slaughter weight (P

Population dynamics of the liver fluke, Fasciola hepatica: the effect of time and spatial separation on the genetic diversity of fluke populations in the Netherlands

An evaluation of the genetic diversity within Fasciola hepatica (liver fluke) may provide an insight into its potential to respond to environmental changes, such as anthelmintic use or climate change. In this study, we determined the mitochondrial DNA haplotypes of >400 flukes from 29 individual cattle, from 2 farms in the Netherlands, as an exemplar of fasciolosis in a European context. Analysis of this dataset has provided us with a measure of the genetic variation within infrapopulations (individual hosts) and the diversity between infrapopulations within a herd of cattle. Temporal sampling from one farm allowed for the measurement of the stability of genetic variation at a single location, whilst the comparison between the two farms provided information on the variation in relation to distance and previous anthelmintic regimes. We showed that the liver fluke population in this region is predominantly linked to 2 distinct clades. Individual infrapopulations contain a leptokurtic distribution of genetically diverse flukes. The haplotypes present on a farm have been shown to change significantly over a relatively short time-period.

The effect of triclabendazole ("Fasinex") on protein synthesis by the liver fluke, Fasciola hepatica

The effect of the active sulphoxide metabolite of the anthelmintic triclabendazole (TCBZ-SX, 15-50 mu g ml(-1)) on the incorporation of radioactively labelled [C-14] leucine by adult Fasciola hepatica tissue slices was measured by liquid scintillation counting. In addition, the ability of the microfilament-disrupting drug, cytochalasin B, and the microtubule-disrupting drug, tubulozole-C, to inhibit protein synthesis, was assessed by similar methods and compared with TCBZ-SX. The established protein synthesis inhibitors, cycloheximide and actinomycin D were used as positive controls. All the drugs showed a significant inhibition of protein synthesis, albeit to different extents; however, TCBZ-SX was the most potent, with no significant difference between its effect and that of cycloheximide or actinomycin D. Moreover, the concentration of TCBZ-SX, above 15 mu g ml(-1), had little further influence on incorporation of [C-14] leucine. This investigation demonstrates the inhibitory effect of TCBZ-SX, cytochalasin B and tubulozole-C on protein synthesis in F. hepatica and confirms the qualitative observations made in several previous ultrastructural studies.