Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration

Aspergillosis is a condition causing serious morbidity and mortality in captive penguins and other bird species. It can be treated with antifungal drugs, such as voriconazole. However, the pharmacokinetics of voriconazole are variable between different animal and bird species. Therefore, the pharmacokinetics of voriconazole were investigated in this study in Magellanic penguins. Pharmacokinetic models were constructed and applied to predict the pharmacokinetics of voriconazole during long‐term treatment in Magellanic penguins, since the voriconazole treatment duration in chronic aspergillosis cases can last up to several months. Plasma voriconazole concentration–time data from adult Magellanic penguins (Spheniscus magellanicus; n = 15) following a single oral (PO) dose of either 2.5 mg/kg or 5 mg/kg in a herring in three separate study periods 7–12 months apart were collected. Mean plasma voriconazole concentrations were above the targeted MIC for Aspergillus fumigatus for 2 hr following a single 2.5 mg/kg voriconazole dose while the plasma concentrations exceeded the MIC for least 24 hr following a 5 mg/kg dose. Nonlinear mixed‐effects modeling was used to fit two pharmacokinetic models, one with first‐order and another with saturable elimination, to the single‐dose data. Fits were good for both, as long as dose was included as a covariate for the first‐order model so that clearance was lower and the half‐life longer for animals receiving the 5 mg/kg dose. Although the single‐dose data suggested saturated elimination at higher concentrations, the model with saturable elimination did not predict plasma voriconazole concentrations well for a clinical aspergillosis case receiving long‐term treatment, possibly because of induction of metabolizing enzymes with chronic exposure. Pharmacokinetic models should accurately predict plasma drug concentrations for different dosage regimens in order to be applicable in the field. Future studies should focus on determining clearance at steady‐state to be able to refine the pharmacokinetic models presented here and improve model performance for long‐term oral voriconazole administration in Magellanic penguins.     

Exploring drivers of the usage of anticoagulant rodenticides on UK farms

Anticoagulant rodenticides (ARs) are considered inhumane, show increasingly limited efficacy due to acquired resistance, and carry environmental consequences associated with non-target species uptake. In a questionnaire study of 499 UK farms that all deployed chemical rodenticide we found a high mean reliance (79%), on second generation ARs with just over half of the respondents using no other rodent control methods. Additional methods where deployed, alone or in combination, included predation (41%), kill-trap deployment (16%) and shooting (1%). Nearly 40% of all respondents deployed rodenticides year-round. There was no evidence to suggest that “tidy-farm” measures, such as clearing food spills and minimising on-farm rodent harbourage sites aimed at minimising rodent-associated problems, were associated with a lower likelihood of year-round deployment; in fact trends in our analyses suggested the opposite. We therefore encourage operators to fully evaluate the true necessity of rodenticide deployment before AR use.     

HT-2 and T-2 toxins in Norwegian oat grains related to weather conditions at different growth stages

High concentrations of the mycotoxins HT-2 and T-2 (HT2?+?T2), primarily produced by Fusarium langsethiae, have occasionally been detected in Norwegian oat grains. In this study, we identified weather variables influencing accumulation of HT2?+?T2 in Norwegian oat grains. Oat grain samples from farmers’ fields were collected together with weather data (2004–2013). Spearman rank correlation coefficients were calculated between the HT2?+?T2 contamination in oats at harvest and a range of weather summarisations within estimated phenological windows of growth stages in oats (tillering, flowering etc.). Furthermore, we developed a mathematical model to predict the risk of HT2?+?T2 in oat grains. Our data show that adequate predictions of the risk of HT2?+?T2 in oat grains at harvest can be achieved, based upon weather data observed during the growing season. Humid and cool conditions, in addition to moderate temperatures during booting, were associated with increased HT2?+?T2 accumulation in harvested oat grains, whereas warm and humid weather during stem elongation and inflorescence emergence, or cool weather and absence of rain during booting reduced the risk of HT2?+?T2 accumulation. Warm and humid weather immediately after flowering increased the risk, while moderate to warm temperatures and absence of rain during dough development, reduced the risk of HT2?+?T2 accumulation in oat grains. Our data indicated that HT2?+?T2 contamination in oats is influenced by weather conditions both pre- and post-flowering. These findings are in contrast with a previous study examining the risk of deoxynivalenol contamination in oat reporting that toxin accumulation was mostly influenced by weather conditions from flowering onwards.     

Development of a One-Step Real-Time Polymerase Chain Reaction Assay for Diagnosis of Phytophthora ramorum

ABSTRACT Phytophthora ramorum is a recently described pathogen causing bleeding cankers, dieback, and leaf blight on trees and shrubs in parts of Europe and North America, where the disease is commonly known as sudden oak death. This article describes the development of a single-round real-time polymerase chain reaction (PCR) assay based on TaqMan chemistry, designed within the internal transcribed spacer 1 region of the nuclear ribosomal (nr)RNA gene for detection of P. ramorum in plant material. Unlike previously described methods for the molecular detection of P. ramorum, this assay involves no post amplification steps or multiple rounds of PCR. The assay was found to have a limit of detection of 10 pg of P. ramorum DNA, and could detect P. ramorum in plant material containing 1% infected material by weight within 36 cycles of PCR. The assay also was used to test DNA from 28 other Phytophthora spp. to establish its specificity for P. ramorum. A quick and simple method was used to extract DNA directly from host plant material, and detection of P. ramorum was carried out in multiplex with an assay for a gene from the host plant in order to demonstrate whether amplifiable DNA had been extracted. Amplifiable DNA was extracted from 84.4% of samples, as demonstrated by amplification of host plant DNA. The real-time protocol was used to test 320 plant samples (from 19 different plant species) from which DNA extraction had been successful, and was shown to give results comparable with a traditional isolation technique for diagnosis of P. ramorum in plant material from common U.K. hosts.     

The occurrence of Fusarium crown and root rot of tomato in Israel

Based upon symptomatology and the results of pathogenicity tests, it has been shown that the Fusarium crown and root rot organism of tomato — previously reported only from North America and Japan — is present in Israel.     

On the spatial distribution of citrus tristeza virus disease

The spatial spread of citrus tristeza virus (CTV) disease was studied using data from two infected groves. Statistical analysis indicated a spatial grouping of infected trees. A gamma distribution was fitted to the empirical distribution of the distances between nearest infected neighbors. The findings suggest that, after locating a newly infected tree, additional inspections to detect CTV should be carried out mainly on trees within 14 m of that tree.     

The prevalence and nature of cardiac arrhythmias in horses following general anaesthesia and surgery

Background

The prevalence and nature of arrhythmias in horses following general anaesthesia and surgery is poorly documented. It has been proposed that horses undergoing emergency surgery for gastrointestinal disorders may be at particular risk of developing arrhythmias. Our primary objective was to determine the prevalence and nature of arrhythmias in horses following anaesthesia in a clinical setting and to establish if there was a difference in the prevalence of arrhythmias between horses with and without gastrointestinal disease undergoing surgery. Our secondary objective was to assess selected available risk factors for association with the development of arrhythmias following anaesthesia and surgery.

Methods

Horses with evidence of gastrointestinal disease undergoing an exploratory laparotomy and horses with no evidence of gastrointestinal disease undergoing orthopaedic surgery between September 2009 and January 2011 were recruited prospectively. A telemetric electrocardiogram (ECG) was fitted to each horse following recovery from anaesthesia and left in place for 24 hours. Selected electrolytes were measured before, during and after surgery and data was extracted from clinical records for analysis. Recorded ECGs were analysed and the arrhythmias characterised. Multivariable logistic regression was used to identify risk factors associated with the development of arrhythmias.

Results

Sixty-seven horses with gastrointestinal disease and 37 without gastrointestinal disease were recruited. Arrhythmias were very common during the post-operative period in both groups of horses. Supra-ventricular and bradyarrhythmias predominated in both groups. There were no significant differences in prevalence of any type of arrhythmias between the horses with or without gastrointestinal disease. Post-operative tachycardia and sodium derangements were associated with the development of any type of arrhythmia.

Conclusions

This is the first study to report the prevalence of arrhythmias in horses during the post-operative period in a clinical setting. This study shows that arrhythmias are very common in horses following surgery. It showed no differences between those horses with or without gastrointestinal disease. Arrhythmias occurring in horses during the post-anaesthetic period require further investigation.     

Deklaration und Wirklichkeit bei pflanzlichen Erzeugnissen

The German Union of Consumers in Bonn demands firmly from the German Federal Government that a long felt need is filled in the new German Food Laws. Until present, there are no regulation for residues of toxic environmental biocides such as Cadmium, Lead, Mercury in fodder and foodstuffs. The Union also calls for restrictive regulations on another field. The fallacious propaganda of food-producers advertising certain products as ‘Pure Nature’, ‘Bio’, ‘Vita’, ‘Without Residues’ etc. is most unrealistic and mislead the consumer. Toxic residues of heavy metals and certain presticides are ubiquitous and can not be avoided in foodstuffs. Examples are given by the author.