Determination of lidocaine and its two N-desethylated metabolites in dog and horse plasma by high-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry

peer reviewedA sensitive method for the quantification of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in animal plasma using high-performance liquid chromatography combined with electrospray ionization mass spectrometry is described. The sample preparation includes a liquid-liquid extraction with methyl tert-butylmethyl ether after addition of 2 M sodium hydroxide. Ethyl methylglycinexylidide (EMGX) is used as an internal standard. For chromatographic separation, an ODS Hypersil column was used. Isocratic elution was achieved with 0.0 1 M ammonium acetate and acetonitrile as mobile phases. Good linearity was observed in the range of 2.5-1000 ng ml(-1) for lidocame in both dog and horse plasma. For MEGX, linear calibration curves were obtained in the range of 5-1000 ng ml(-1) and 20-1000 ng ml(-1) for dog and horse plasma, respectively. In dog and horse plasma good linearity was observed in the range of 200-1500 ng ml(-1) for GX. The limit of quantification (LOQ) in dog plasma for lidocaine, MEGX and GX was set at 2.5 ng ml(-1), 20 ng ml(-1) and 200 ng ml(-1), respectively. For horse plasma a limit of quantification of 2.5 ng ml(-1), 5 ng ml(-1) and 200 ng ml(-1) was achieved for lidocaine, MEGX and GX, respectively. In dog plasma, the limit of detection (LOD) was found to be 0.8 ng ml(-1), 2.3 ng ml(-1) and 55 ng ml(-1) for lidocaine, MEGX and GX, respectively. In horse plasma the LOD's found for lidocame, MEGX and GX, were 1.1 ng ml(-1), 0.5 ng ml(-1) and 13 ng ml(-1), respectively. The method was shown to be of use in pharmacokinetic studies after application of a transdermal patch in dogs and after an intravenous infusion in horses. (c) 2007 Elsevier B.V. All rights reserved

Impact of urban geology on model simulations of shallow groundwater levels and flow paths

This study examines the impact of urban geology and spatial discretization on the simulation of shallow groundwater levels and flow paths at the city scale. The study uses an integrated hydrological model based on the MIKE SHE code that couples surface water and 3D groundwater simulations with a leaky sewer system. The effect of the geological configuration was analyzed by applying three geological models to an otherwise identical hydrological model. The effect of spatial discretization was examined by using two different horizontal discretizations for the hydrological models of 50 and 10 m, respectively. The impact of the geological configuration and spatial discretization was analyzed based on model calibration, simulations of high water levels, and particle tracking. The results show that a representation of the subsurface infrastructure, and near-terrain soil types, in the geological model impacts the simulation of the high water levels when the hydrological model is simulated in a 10 m discretization. This was detectable even though the difference between the geological models only occurs in 7 % of the volume of the geological models. When the hydrological model was run in a 50 m horizontal discretization, the impact of the urban geology on the high water levels was smoothed out. Results from particle tracking show that representing the subsurface infrastructure in the hydrological model changed the particles' flow paths and travel time to sinks in both the 50 and 10 m horizontal discretization of the hydrological model. It caused less recharge to deeper aquifers and increased the percentage of particles flowing to saturated-zone drains and leaky sewer pipes. In conclusion, the results indicate that even though the subsurface infrastructure and fill material only occupy a small fraction of the shallow geology, it affects the simulation of local water levels and substantially alters the flow paths. The comparison of the spatial discretization demonstrates that, to simulate this effect, the spatial discretization needs to be of a scale that represents the local variability in the shallow urban geology.</p

3D urban subsurface modelling and visualisation : a review of good practices and techniques to ensure optimal use of geological information in urban planning

This report is the result of COST Action TU1206 Working Group 2, Work package 2.3, and focusses on 3D urban subsurface modelling and visualisation. The major aims of this report are: 1) evaluating current techniques and identify good practices / best efforts in 3D geological modelling and visualisation of the urban subsurface, based on case studies, and 2) co-developing (subsurface specialists & model users) requirements for optimal use of 3D geological modelling information in specific planning and policy contexts. Three major topics have been considered: • Constructing and maintaining 3D urban geological models • Modelling man-made ground • Visualising 3D urban subsurface model results To improve the use of subsurface modelling in urban planning in the future, the following challenges have been identified: • The complexity of the urban subsurface, including man-made ground, combined with the level of detail of information asked for in many urban planning issues demand that geologists look beyond their traditional data sources. • Combined 3D property modelling of the small-scale heterogeneity of man-made deposits and natural deposits requires new modelling approaches. • Management of the shallow urban subsurface requires model tools that can be frequently updated to reflect the frequently changing properties and functions of the urban subsurface. • There is a need for dynamic (4D) urban subsurface models that can be used for real-time monitoring and incorporation of time-series data on subsurface properties. • It would be cost-effective to have an actively maintained, scalable geological framework model of a city available that forms a common basis for the various kinds of dedicated models of parts of the city. • To give subsurface information a firm position in urban planning and management, geological information will have to be presented in the right format, and at the right time. It is absolutely necessary to include the subsurface infrastructure and to combine the model with above-ground information

Addressing food and nutrition insecurity in the Caribbean through domestic smallholder farming system innovation

Structural conditions underlying the development of CARICOM’s two-tiered agricultural innovation system depict diverse drivers of change over time, versus institutional inertia of export-oriented formal institutions and the neglect of informal domestic markets. Key principles of taking an agroecological approach would include: supporting diversity and redundancy, building connectivity, managing slow variables and feedbacks, improving understanding of socioecological systems as complex adaptive systems, and encouraging polycentric governance systems. In this paper, we review the conditions that have been undermining sustainable food and nutrition security in the Caribbean, focusing on issues of history, economy, and innovation

Endocarditis in horses: a retrospective study of five cases

peer reviewe

Doppler Echocardiographic Reference Values in Healthy Donkeys

peer reviewe

Does Acepromazine reduce the cardiovascular toxicity of Norepinephrine in the horse

peer reviewe

A case of Vitamin K3 induced renal toxicosis in a horse

peer reviewe

Clinical aspects of alfaxalone use in rabbits. Partial results.

peer reviewedAlfaxalone, a synthetic neuroactive steroid, has been shown to induce smooth general anesthesia in wild and companion rabbits. The aim of the study was to test the effect of alfaxolone in experimental rabbits without concomitant oxygen supplementation.Respiratory status was assessed by measuring the duration of the post-induction apnea, the respiratory rate, the oxygen saturation of hemoglobin in the peripheral blood (SpO2) and the end-tidal CO2 (EtCO2) Cardiac function was assessed by monitoring heart rate using a pulse oximeter. The degree of anesthesia was monitored by evaluating ear and paw pinch reflex, as well as ocular signs such as nystagmus, exophtalmia and the loss of palpebral and corneal reflexes

Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway

BACKGROUND—As granulocyte/macrophage colony stimulating factor (GM-CSF) mediated delay of granulocyte apoptosis contributes to the accumulation of inflammatory cells at the site of inflammation in many diseases, we sought to determine whether asthma is also associated with a GM-CSF dependent increase in lung granulocyte survival. Moreover, because GM-CSF mediates its effects through activation of signal transducer and activator of transcription 5 (STAT5), we also investigated the potential role of STAT5 in allergic inflammation.
METHODS—Blood granulocytes were recovered from six healthy and six heaves affected horses, a model of asthma. Lung granulocytes were obtained by bronchoalveolar lavage (BAL) from the same horses. Granulocytes were cultured in the presence or absence of anti-GM-CSF receptor antibodies for different times and apoptosis was determined using the Annexin-V/propidium iodide detection method. Nuclear protein extracts from cultured granulocytes were analysed for STAT5 binding activity by electrophoretic mobility shift assay.
RESULTS—BAL fluid granulocytes from heaves affected horses demonstrated a significant delay in apoptosis compared with blood granulocytes from the same horses and blood and BAL fluid granulocytes from healthy horses. Conversely, the rate of apoptosis in blood granulocytes from healthy and heaves affected horses was comparable. The enhanced survival of BAL fluid granulocytes from affected horses was suppressed in the presence of antibodies directed against GM-CSF receptors. Increased levels of active STAT5 were found in BAL fluid granulocytes from heaves affected horses and were markedly reduced after treatment with anti-GM-CSF receptor antibodies.
CONCLUSIONS—These data indicate that granulocyte survival is enhanced in the lung of heaves affected horses and suggest a role for a GM-CSF activated STAT5 pathway in delaying apoptosis of lung granulocytes in this model of asthma.