Canine CYP2B11 metabolizes and is inhibited by anesthetic agents often co-administered in dogs

Baratta, M. T., Zaya, M. J., White, J. A., Locuson, C. W. Canine CYP2B11 metabolizes and is inhibited by anesthetic agents often co-administered in dogs. J. vet. Pharmacol. Therap. 33 , 50–55.
Medetomidine is a well-established sedative and analgesic for dogs and cats. As a premedicant for anesthesia regimens that also include other agents, medetomidine can also provide a dose-sparing effect. While there are likely several reasons for the dose-sparing effect of medetomidine, the role of metabolic drug–drug interactions at the single enzyme level has not yet been examined. Using a panel of individually expressed canine cytochromes P450 cloned from beagle liver, this report demonstrates that medetomidine is an extremely potent CYP2B11 inhibitor (IC₅₀ < 10 n m ) and that ketamine and midazolam are CYP2B11 substrates with high intrinsic clearances. These in vitro findings suggest that under some circumstances, medetomidine (i.e. 'perpetrator') may inhibit the metabolic clearance of some high metabolic clearance drugs (i.e. 'victims') with which it is commonly co-administered via the CYP2B11 pathway. However, as the dose-sparing effect of medetomidine premedication commonly results in anesthetic dose reduction, any increased plasma concentrations of victim drugs caused by medetomidine would still be lower than if no dose reduction had been made. Further studies are needed to characterize whether medetomidine possesses the potential to cause pharmacokinetic interactions. In conclusion, the ability of recombinant P450s to define canine-specific drug clearance pathways and P450 inhibitors should prove useful in identifying drug combinations that may require dose adjustments in dogs.     

Changing stock of biomass carbon in a boreal forest over 93 years

The growing stock more than doubled from 1.6 to 3.4 million m³ between 1912 and 2005 in forests on an area of 387 km² in southern Finland. The stock expansion continued for 93 years noting interim results, which were available for 1959, 1982, 1994 and 1999. Forested area in the region hardly changed. Carbon sequestration was mainly a result of a long-term recovery from forest degradation, a legacy of land use in the 18th and 19th centuries. Tree demography responded to management change especially of mature stands: Average tree size and stocking density of stands increased. On average the expanding biomass stock sequestered 18 tons C annually per km² (18 g C per m²). In comparison, the emissions of fossil carbon in the region were estimated at 12 tons C per km² (12 g C per m²) on average. However, fossil CO₂ emissions exceeded biomass sequestration in recent decades. The powerful and persistent expansion of the carbon stock was an unintended co-benefit of forestry, which was motivated by the intention to improve timber yield. On the more negative side the change in management introduced clear-cuts, and a loss of diverse elements of the pre-industrial biota.     

Effect of glyphosate on the tripartite symbiosis formed by Glomus intraradices,Bradyrhizobium japonicum,and genetically modified soybean

Most soybeans grown in North America are genetically modified (GM) to tolerate applications of the broad-spectrum herbicide glyphosate; as a result, glyphosate is now extensively used in soybean cropping systems. Soybean roots form both arbuscular mycorrhizal (AM) and rhizobial symbioses. In addition to individually improving host plant fitness, these symbioses also interact to influence the functioning of each symbiosis, thereby establishing a tripartite symbiosis. The objectives of this study were to (1) estimate the effects of glyphosate on the establishment and functioning of AM and rhizobial symbioses with GM soybean, and (2) to estimate the interdependence of the symbioses in determining the response of each symbiosis to glyphosate. These objectives were addressed in two experiments; the first investigated the importance of the timing of glyphosate application in determining the responses of the symbionts and the second varied the rate of glyphosate application. Glyphosate applied at recommended field rates had no effect on Glomus intraradices or Bradyrhizobium japonicum colonization of soybean roots, or on soybean foliar tissue [P]. N₂-fixation was greater for glyphosate-treated soybean plants than for untreated-plants in both experiments, but only when glyphosate was applied at the first trifoliate soybean growth stage. These data deviate from previous studies estimating the effect of glyphosate on the rhizobial symbiosis, some of which observed negative effects on rhizobial colonization and/or N₂-fixation. We did observe evidence of the response of one symbiont (stimulation of N₂-fixation following glyphosate) being dependent on co-inoculation with the other; however, this interactive response appeared to be contextually dependent as it was not consistent between experiments. Future research needs to consider the role of environmental factors and other biota when evaluating rhizobial responses to herbicide applications.     

Some properties of alfalfa mosaic virus isolated from Buddleia davidii in the UK

Alfalfa mosaic virus (AMV) and cucumber mosaic virus (CMV) were isolated from clones of Buddleia davidii collected at Long Ashton Research Station for assessment of horticultural characteristics. The AMV isolate investigated in this study (AMV-B) infected 18 species and cultivars of herbaceous test plants. The in vitro properties of AMV-B were determined. The virus was purified by permeation chromatography on controlled-pore glass beads and an antiserum prepared. AMV-B appeared to be serologically indistinguishable from AMV isolate 15/64. The sizes and shapes of the virus particles were those of classical AMV components. The capsid protein was a single polypeptide of Mr 24 375. Buddleia seedlings inoculated with AMV-B showed only mild chlorosis and slight distortion of leaves.     

Control of Glomerella cingulata f.sp. camelliae with fungicides

A critical test of fungicidal activity against the wound pathogen Glomerella cingulata f.sp. camelliae on camellias involved the application of a conidial suspension to scratches on detached leaves, treated with fungicide 24 h previously. In this test, prochloraz at 250–500 μg/ml a.i. in both EC and manganese WP formulations was highly effective, inhibiting leaf rotting by 90–100% compared with 55% or less in some tests with benomyl, chlorothalonil and captafol at 500–1000 μg/ml and captan at 1200 μg/ml. Prochloraz gave similar protection to leaves when applied to whole plants. Protection was less, especially on older leaves, when wounding and inoculating were delayed by 7 or more days after treatment. Prochloraz did not prevent all infection through comparatively large wounds, e.g. leaf scars, made on stems 24 h after treatment.
Poor control of the disease in a nursery was not due to resistance of the pathogen to benomyl; in vitro tests failed to detect full resistance at this time. Under nursery conditions a statutory policy of destroying infected plants and spraying the remainder with prochloraz or prochloraz manganese (both at 500 μg/ml), alternating with benomyl (500 μg/ml) on a weekly basis apparently prevented spread of the disease to healthy plants.     

On difficulties with allelopathy methodology

Summary. The main techniques and the common experimental methods used in studying allelopathy are reviewed. Problems associated with both methodology and conclusions drawn based on certain techniques are discussed. The accuracy obtained using these techniques is evaluated and show that some of the techniques could be a misleading tool. Some changes are suggested.     

The significance of VA-Mycorrhiza to future arable farming in the Netherlands

Present conditions of high inputs and narrow rotations render the importance of vesicular-arbuscular mycorrhiza (VAM) in arable farming in the Netherlands rather low. Changes expected in the near future under the influence of economic pressures and environmental problems may change this situation. This is discussed in the light of some such expected changes in Dutch arable farming.     

Designing resistance management programs: How can you choose?

A list of often-discussed resistance management tactics is critically reviewed. Alteration of insecticides across generations, non-persistent formulations, and the use of pesticides conferring only low magnitudes of resistance seem to be among the most promising tactics for general use in resistance management. Justifying the first two choices usually requires little more than data on product persistence in terms of toxic effect on susceptible individuals under field conditions. The last tactic requires additional information on resistance ratios for resistant and susceptible genotypes under field exposure. The efficacy of pesticide mixtures is highly dependent on equal persistence of both compounds used in the mixture. The number of genes involved in resistance and the fitness disadvantages they may confer in the absence of use appear to be of relatively little significance in choosing management tactics.     

The use of entomogenous fungi for pest control and the role of toxins in pathogenesis

Fungi have been suggested as agents for the biological control of insects for over a century, but their use remains extremely limited. This paper examines the biology of entomogenous fungi, highlighting their need for moisture, and reviews studies on the Entomophthoraceae, Beauveria bassiana, Beauveria brongniartii, Metarhizium anisopliae and Verticillium lecanii. It is suggested that current studies should be directed towards the control of pests living in humid micro-climates and that moisture-retaining formulations should be developed to reduce the reliance of fungi on moisture. Many entomogenous fungi produce insecticidal toxins in submerged culture and these compounds are of interest as a source of new toxophores. The most extensively studied toxins are the cyclic depsipeptides from M. anisopliae, termed destruxins, and their possible role in pathogenesis is discussed. Beauveria bassiana also produces the cyclic peptides termed beauvericin, beauverolides, and bassianolide. Toxins produced by V. lecanii, and the Entomophthoraceae are also described.