Doxorubicin pharmacokinetics following a single-dose infusion to sulphur-crested cockatoos (Cacatua galerita)

OBJECTIVE: To determine the pharmacokinetics of doxorubicin in sulphur-crested cockatoos, so that its use in clinical studies in birds can be considered. DESIGN: A pharmacokinetic study of doxorubicin, following a single intravenous (i.v.) infusion over 20 min, was performed in four healthy sulphur-crested cockatoos (Cacatua galerita). PROCEDURE: Birds were anaesthetised and both jugular veins were cannulated, one for doxorubicin infusion and the other for blood collection. Doxorubicin hydrochloride (2 mg/kg) in normal saline was infused i.v. over 20 min at a constant rate. Serial blood samples were collected for 96 h after initiation of the infusion. Plasma doxorubicin concentrations were assayed using an HPLC method involving ethyl acetate extraction, reverse-phase chromatography and fluorescence detection. The limit of quantification was 20 ng/mL. Established non-parametric methods were used for the analysis of plasma doxorubicin data. RESULTS: During the infusion the mean +/- SD for the Cmax of doxorubicin was 4037 +/- 2577 ng/mL. Plasma concentrations declined biexponentially immediately after the infusion was ceased. There was considerable intersubject variability in all pharmacokinetic variables. The terminal (beta-phase) half-life was 41.4 +/- 18.5 min, the systemic clearance (CI) was 45.7 +/- 18.0 mL/min/kg, the mean residence time (MRT) was 4.8 +/- 1.4 min, and the volume of distribution at steady state (V(SS)) was 238 +/- 131 mL/kg. The extrapolated area under the curve (AUC(0-infinity)) was 950 +/- 677 ng/mL x h. The reduced metabolite, doxorubicinol, was detected in the plasma of all four parrots but could be quantified in only one bird with the profile suggesting formation rate-limited pharmacokinetics of doxorubicinol. CONCLUSIONS AND CLINICAL RELEVANCE: Doxorubicin infusion in sulphur-crested cockatoos produced mild, transient inappetence. The volume of distribution per kilogram and terminal half-life were considerably smaller, but the clearance per kilogram was similar to or larger than reported in the dog, rat and humans. Traces of doxorubicinol, a metabolite of doxorubicin, were detected in the plasma.     

Drilling to gabbro in intact ocean crust

Sampling an intact sequence of oceanic crust through lavas, dikes, and gabbros is necessary to advance the understanding of the formation and evolution of crust formed at mid-ocean ridges, but it has been an elusive goal of scientific ocean drilling for decades. Recent drilling in the eastern Pacific Ocean in Hole 1256D reached gabbro within seismic layer 2, 1157 meters into crust formed at a superfast spreading rate. The gabbros are the crystallized melt lenses that formed beneath a mid-ocean ridge. The depth at which gabbro was reached confirms predictions extrapolated from seismic experiments at modern mid-ocean ridges: Melt lenses occur at shallower depths at faster spreading rates. The gabbros intrude metamorphosed sheeted dikes and have compositions similar to the overlying lavas, precluding formation of the cumulate lower oceanic crust from melt lenses so far penetrated by Hole 1256D.     

Teaching non-technical (professional) competence in a veterinary school curriculum

Data from focused studies and comprehensive surveys suggest that developing or enhancing non-technical (professional) skills will result in a more satisfied and successful veterinary student or veterinary graduate. The College of Veterinary Medicine at Washington State University has devoted considerable time, effort, and resources to augmenting the non-technical aspects of its curriculum while maintaining the traditional strengths of its DVM program. Here we summarize pertinent research and best-practice recommendations from a variety of sources and outline the steps that have been taken, with the underlying rationales, to integrate the teaching and modeling of non-technical (professional) competence throughout a four-year course of veterinary study.     

An immunocytochemical procedure for protein localization in various nematode life stages combined with plant tissues using methylacrylate-embedded specimens

Plant-parasitic nematodes possess a large number of proteins that are secreted in planta, allowing them to be successful parasites of plants. The majority of these proteins are synthesized mainly in the nematode subventral and dorsal glands as well as in other organs. To improve the immunovisualization of these proteins, we adapted a methacrylate embedding method for the localization of proteins inside nematode tissues, and extracellularly when secreted in planta or within plant cells. An important advantage is that the method is applicable for all nematode stages: preparasitic as well as parasitic stages, including large mature females. Herein, the method has been successfully applied for the localization of four nematode secreted proteins, such as Mi-MAP-1, Mi-CBM2-bearing proteins, Mi-PEL3, and Mi-6D4. In addition, we could also localize 14-3-3 proteins, as well as two cytoskeletal proteins, by double-immunolabeling on preparasitic juveniles. Superior preservation of nematode and plant morphology, allowed more accurate protein localization as compared with other methods. Besides excellent epitope preservation, dissolution of methacrylate from tissue sections unmasks target proteins and thereby drastically increases antibody access.     

Interactions of phytate and myo-inositol phosphate esters (IP1-5) including IP5 isomers with dietary protein and iron and inhibition of pepsin

Phytic acid (IP(6)) and myo-inositol phosphate esters (IP(1-5)), including IP(5) isomers prepared chemically and enzymatically with bacterial and fungal phytases, were examined for their effects on protein aggregation of soy protein and β-casein, interaction with Fe(3+), and pepsin activity. The results indicated that the aggregating capabilities of IP esters (IP(1-6)) on the 2 proteins decreased dramatically from IP(6) to IP(5) and became negligible with IP(1-4). Among the IP(5) isomers tested, InsP(5)(1,2,3,4,5) produced by 6-phytase was slightly less powerful in aggregating protein than InsP(5)(1,2,4,5,6) produced by 3-phytase (P = 0.001). For protein hydrolysis, IP esters of IP(3-4) still showed inhibition of pepsin though to a lesser extent than IP(5-6). The in vitro data with IP(1-5) generated with microbial 3- and 6-phytases indicate that, for complete alleviation of pepsin inhibition, IP(6) needs to be broken down to IP(1-2.) In contrast to the aggregation with protein, the reactivity of IP(1-6) toward Fe(3+) decreased proportionally from IP(6) to IP(3.) Based on the radical decrease in turbidity of IP(6) -protein complex observed, as a result of IP(6) dephosphorylation to IP(5), a novel qualitative and semi-quantitative phytase plate assay was established using IP(6)-protein complex incorporated into an agarose petri-dish as substrate. Phytase activity was shown as the development of clear halos on the agarose plate with time. This simple phytase plate assay method can be used at animal farms, control laboratories, and even for the screening of engineered phytase variants. The current study, thus, stresses the importance of the efficient hydrolysis of IP(6) at lower pH range to alleviate the negative effect of phytic acid and its degradation products on protein and Fe(3+) digestion.     

Effect of mastitis during the first lactation on production and reproduction performance of Holstein cows

The aim of this study was to evaluate the effect of postpartum mastitis between first calving and subsequent conception on production and reproduction performance as well as culling of Holstein cows. A data set of 9,183 first lactation cows was used. Results showed that the first cumulative 100?days' milk production and the milk yield standardized to 305?days were affected by the interval from calving to first mastitis (P??0.05). Calving year, calving difficulty score, and cumulative first 60?days milk production had significant impacts on mastitis risk (P?相似文献   

The multiple burdens of zoonotic disease and an ecohealth approach to their assessment

Individual interviews were conducted in 137 households using semi-structured questionnaires to determine the influence of socioeconomic factors on production constraints faced by indigenous chicken producers in the rural areas of South Africa. The major constraints to village chicken production were mortality (95 % of the households) followed by feed shortage (85 %) and low chicken sales (72 %). The logistic regression model showed that households that owned imported/crossbred chickens practiced extensive production system without housing structures and did not have vaccines were more likely to experience high levels of chicken mortality. Poor and youth-headed households with no supplements and vaccines had high probability of Newcastle disease. The probability of a household to experience chicken feed shortage was lower in households that owned indigenous chickens than those that owned imported/crossbred chickens (odds ratio, 11.68; 95 % confidence interval, 1.19–27.44). Youth-headed households that had small flocks and no access to veterinary services were not likely to sell chickens. It was concluded that gender, age, wealth status, production system, chicken flock size, type of chicken breed owned, accessibility of veterinary services, availability of supplements, vaccines and shelter influence village chicken farmer’s production constraints such as feed availability, chicken mortality, prevalence of diseases and chicken sales.     

LDSO: a program to simulate pedigrees and molecular information under various evolutionary forces

Simulations are a major tool to evaluate new statistical methods and optimize experimental designs in the genomic era. However, this can only be achieved when the simulations are close enough to reality, as well as diverse enough to be realistic. For mapping studies, it is thus critical to re-create as much as possible the forces generating linkage (mutation, random drift, changes in population sizes, selection and pedigree structure) and the mechanisms producing trait genetic architecture (additivity, dominance, epistasis). We present here a computer program (ldso) simulating these phenomena. Optional outputs provide statistics on the linkage disequilibrium (LD) structure and the identity by descent between chromosomal segments, facilitating further data analyses. Furthermore, ldso enables the simulation of genomic data in known pedigrees, which sticks as precisely as possible to recent population history and structures of the long-range LD, allowing optimization of fine-mapping strategies.