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.     

The effects of various plant protection methods on the development of Zymoseptoria tritici and Cephalosporium gramineum,grain yield and protein profile

Septoria leaf blotch progresses rapidly, leading to the development of Zymoseptoria titici forms resistant to fungicides. Cephalosporium stripe is caused by Cephalosporium gramineum. The aim of this study was to evaluate the effectiveness of selected pesticides in limiting the symptoms of both diseases on winter wheat leaves, and to determine their influence on grain yield and the content and composition of protein fractions in wheat kernels. Propiconazoles were most effective in inhibiting the development of Septoria leaf blotch (symptoms were reduced from 54.7% to 78.6%). Strobilurins were less effective due to the presence of isolates with the G143A mutation. Symptoms of Cephalosporium stripe were rarely observed, and protective treatments did not reduce their severity. The highest content of grain protein (14.81%) was found in plants most intensely protected with the fungicides containing fenpropimorph, pyraclostrobin and epoxiconazole. The principal component analysis revealed that the plant protection method influenced the grain protein profile. The accumulation of HMW glutenins and α/β gliadins was mutually interrelated and higher in high-input treatments; control grain was characterized by close relationships between ω-gliadins, LMW glutenins, albumins and globulins, whereas low-input treatments influenced mostly γ-gliadins.     

Natural products as a source of agrochemicals and leads for chemical synthesis

The use of natural products as a source of new agrochemicals and the procedures that can be undertaken to discover such compounds are reviewed using examples from both the literature and our own experiences. The commercial successes obtained to date show that natural products are a powerful source of new agrochemicals. The results from a survey of the views of the agrochemical industry of natural product work indicated a high level of interest, with 16 of the 19 companies that replied being involved in natural product work either through in-house or external programmes of work. Possible approaches to the key challenges of atural product work, for example choice of sources and screens, avoiding known metabolites and obtaining sufficient compound for biological evaluation, are discussed.     

Response of susceptible and resistant peach-potato aphids Myzus persicae (Sulz.) to insecticides in leaf-dip bioassays

The response of susceptible (S), moderately resistant (R₁) and strongly resistant (R₂) peach-potato aphids, Myzus persicae (Sulz.) to organophosphorus, carbamate and pyrethroid insecticides was tested by a leaf-dip bioassay. The aphids were placed on potato leaves (dipped in insecticide solutions 1–2 or 24 h before infestation) and their mortality examined 48 h later. R₁ aphids were virtually susceptible to most of the carbamates, demephion and acephate, but were slightly to moderately resistant (2.1–9.4 times) to permethrin, cypermethrin and (S)-α-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (I), (NRDC 161), to 5,6,7,8-tetrahydro-2-methylquinolin-4-yl dimethylcarbamate (II), (Hoechst 25 682) and demeton-S-methyl. R₂ aphids resisted more strongly or very strongly (between 65 and 1280 times) the pyrethroids, demeton-S-methyl (×94), II (×83) and demephion (×9), and were slightly to moderately (2–5 times) resistant to acephate, pirimicarb, ethiofencarb and 2-(dimethylcarbamoyloxyimino)-3-methoxyimino-N,N- dimethylbutyramide (III), (DPX 3853). Both resistant strains were susceptible to nitrilacarb [4,4-dimethyl-5-(methylcarbamoyloxyimino)pentanenitrile] complex (1:1) with zinc chloride (IV), (AC 85 258). The implications of these results in terms of practical aphid control are discussed.     

The Validation of Pesticide Leaching Models

The validation of pesticide leaching models presents particular problems where the number of model predictions is far in excess of the observed data. Normally, however, there are more frequent field observations for other parameters (notably the site hydrology) than for pesticide concentrations in either water or soil. A five-stage validation procedure which takes advantage of the most frequently available observations and which tests each of the components of the model in a cumulative way, is thus advocated: Stage 1: Parameterisation of the model using only independently measured parameters. Stage 2: Hydrological validation: the validation of the predictions of water movement and water content of the soil. Stage 3: Solute movement validation: where field data are available for solutes other than pesticide, the model should first be validated for them, especially if they are more abundant than the pesticide observations. Conserved solutes such as chloride or bromide are preferred, although nitrate may be used for short periods. Stage 4: Pesticide fate in the soil: models should use parameters of pesticide fate derived from independent studies. Stage 5: Pesticide leaching: only in the last stage are the relatively small number of pesticide observations compared with the model predictions with respect to patterns and orders of magnitude of occurrence. With this scheme, the results of each stage are carried forward to the next, and confidence in the model is built with each stage. This is illustrated using the CRACK-P model and hydrological, nitrate and pesticide data from the Brimstone Farm Experiment Oxfordshire, UK.     

Estimates of stem wood increments in forest resources: comparison of different approaches in forest inventory: consequences for international reporting: case studyof European forests

Key message

Quality and reliability of forest resource assessments depend on the ability of national forest inventories (NFIs) to supply necessary and high-quality data. Over the last decades and especially since the 1990s, the NFIs in European countries have been rapidly developing. Possibilities for obtaining reliable and accurate data on annual increment from different inventory types were evaluated, and sample-based inventories have been found to be superior to standwise inventories in providing reliable data. Simplified methods may be employed when increment cannot be directly estimated from inventory data.

Context

An increasing intensity of forest resource use requires more accurate, detailed and reliable information, not only on forest area and growing stock but also on forest stand productivity, wood increment and its components.

Aims

The main objectives were to assess the capacities of forest inventories, the methods used for estimation of gross increment and its components and their accuracy and to demonstrate an effective method for estimation of increment when direct inventory methods are not available.

Methods

Data about national forest inventory methods were obtained from 30 responses to a questionnaire, distributed amongst national correspondents of all European countries; reports of COST Actions E43 and FP 1001, databases of Temperate and Boreal Forest Resource Assessment (TBFRA) 2000 and State of Europe’s Forests (SoEF) 2011 were used as well. Analysis and comparison of results from different forest inventories were used for evaluation of data reliability. Relationships between growing stock and gross increment in European forests were also analysed, and corresponding models were proposed.

Results

Seventy-nine percent of European forest area is covered by national forest inventories (NFIs) based on sampling methods and the rest on stand-level inventory and other inventory methods. Data obtained by aggregating standwise data usually underestimate growing stock by 15–20 % and gross increment even more. Almost half of the European forest area (47 %) is monitored using permanent plots, measured twice or more, allowing the estimation of gross increment and its components to be made directly.

Conclusion

Implementation of NFIs based on sampling methods, especially with permanent plots, resulted in an improvement of data quality and in most cases an increase of growing stock and gross increment. The estimation of natural losses is the weakest link in today’s NFIs and in the current assessment of European forest resources. The proposed default values for gross increment and its components is an option to be used in countries not having NFI at all or those which have started it only recently.

     

Peptidases of Trichobilharzia regenti (Schistosomatidae) and its molluscan host Radix peregra S. Lat. (Lymnaeidae): construction and screening of cDNA library from intramolluscan stages of the parasite

Trichobilharzia regenti is a neurotropic bird schistosome,causing cercarial dermatitis in humans. In this study, ZAP cDNA expression library from Radix peregra s. lat. hepatopancreases containing intramolluscan stages of T. regenti was constructed and screened using PCR with specific and degenerate primers, designed according to previously described serine and cysteine peptidases of other parasite species. Full-length sequences of cathepsins B1 and L, and two serine peptidases, named RpSP1 and RpSP2, were obtained.The protein-protein BLAST analysis and parallel control reactions with template from hepatopancreases of T. regenti non-infected snails revealed that only cathepsin B1 was of parasite origin. The remaining sequences were derived from the snail intermediate host, which implies that the initial source of parasite mRNA was contaminated by snail tissue.Regardless of this contamination, the cDNA library remains an excellent molecular tool for detection and identification of bioactive molecules in T. regenti cercariae.     

Field experiments to assess approaches for spray drift incident investigation

BACKGROUND: Spray trials were conducted to determine the variation in primary spray drift deposition between trials under very similar conditions, in order to assess the feasibility of developing a computational tool to aid post‐event investigations of pesticide spray incidents. Pesticide deposition was examined by analysis of filter paper and vegetation samples. RESULTS: Considerable variation in the drift profile was found. The overall estimate of the spray drift decay term was ?1.13 (95% confidence interval ?1.02 to ?1.24), with statistically significant differences between plots. Variation in the drift profile between neighbouring essentially identical plots indicates the variation in deposition that might be expected over small distances. Vegetation samples were found to have considerably lower capture efficiency than filter papers. Importantly, degradation of pesticides was found to have little effect on the pesticide drift profile over a 14 day period. CONCLUSIONS: The levels of spatial variation in spray drift deposits between runs and plots observed in this study suggest serious limitations to the inferences that may be drawn from limited numbers of post‐incident samples. In particular, they would limit inferences about the spray conditions that could be drawn from an estimate of the drift profile derived from limited post‐incident samples. © Crown copyright 2009. Reproduced with permission of Her Majesty's Stationery Office. Published by John W iley & Sons, Ltd.     

Induced resistance for plant disease control: maximizing the efficacy of resistance elicitors

ABSTRACT Plants can be induced to develop enhanced resistance to pathogen infection by treatment with a variety of abiotic and biotic inducers. Biotic inducers include infection by necrotizing pathogens and plant-growth-promoting rhizobacteria, and treatment with nonpathogens or cell wall fragments. Abiotic inducers include chemicals which act at various points in the signaling pathways involved in disease resistance, as well as water stress, heat shock, and pH stress. Resistance induced by these agents (resistance elicitors) is broad spectrum and long lasting, but rarely provides complete control of infection, with many resistance elicitors providing between 20 and 85% disease control. There also are many reports of resistance elicitors providing no significant disease control. In the field, expression of induced resistance is likely to be influenced by the environment, genotype, and crop nutrition. Unfortunately, little information is available on the influence of these factors on expression of induced resistance. In order to maximize the efficacy of resistance elicitors, a greater understanding of these interactions is required. It also will be important to determine how induced resistance can best fit into disease control strategies because they are not, and should not be, deployed simply as "safe fungicides". This, in turn, will require information on the interaction of resistance elicitors with crop management practices such as appropriate-dose fungicide use.