Brain-natriuretic peptide and cyclic guanosine monophosphate as biomarkers of myxomatous mitral valve disease in dogs

Elevations in the plasma concentrations of natriuretic peptides correlate with increased severity of myxomatous mitral valve disease (MMVD) in dogs. This study correlates the severity of MMVD with the plasma concentrations of the biomarkers N-terminal fragment of the pro-brain-natriuretic peptide (NT-proBNP) and its second messenger, cyclic guanosine monophosphate (cGMP). Furthermore, the l-arginine:asymmetric dimethylarginine (ADMA) ratio was measured as an index of nitric oxide availability. The study included 75 dogs sub-divided into five groups based on severity of MMVD as assessed by clinical examination and echocardiography.Plasma NT-proBNP and cGMP concentrations increased with increasing valve dysfunction and were significantly elevated in dogs with heart failure. The cGMP:NT-proBNP ratio decreased significantly in dogs with heart failure, suggesting the development of natriuretic peptide resistance. Although the l-arginine:ADMA ratio decreased with increasingly severe MMVD, this was largely due to the older age of the dogs with heart failure.     

The influence of modulation of P-glycoprotein and /or cytochrome P450 3A on the pharmacokinetics and pharmacodynamics of orally administered morphine in dogs

The influence of pretreatment with ketoconazole [cytochrome P450 3A (CYP3A) + P-glycoprotein (P-gp) inhibitor], elacridar (selective P-gp inhibitor) and rifampicin (CYP3A + P-gp inducer) on oral morphine pharmacokinetics and pharmacodynamics was investigated in experimental dogs. Seven beagles were used in a four-way crossover design. Morphine hydrochloride was administered orally (2.5 mg/kg) alone (control group CON) or after pretreatment with ketoconazole (group KETO), elacridar (group ELA) or rifampicin (group RIF). Morphine plasma concentrations were analysed by liquid chromatography-tandem mass spectrometry. Sedation scores (none, mild, moderate or severe) were evaluated subjectively. Dogs were significantly (P < 0.05) more sedated after ketoconazole pretreatment. There were no significant differences between group CON and the other pretreatment groups in pharmacokinetic parameters taking both sexes into account. Sex differences were apparent in some pharmacokinetic parameters of morphine. The area under the plasma concentration time curve (AUC(0-∞) ) was significantly higher, and the total body clearance was significantly lower in male compared to female dogs in all treatment groups. Ketoconazole, rifampicin and elacridar pretreatment had no significant effects on morphine pharmacokinetics, although dogs in the ketoconazole group showed higher sedation scores.     

To what extent is altitudinal variation of functional traits driven by genetic adaptation in European oak and beech?

The phenotypic responses of functional traits in natural populations are driven by genetic diversity and phenotypic plasticity. These two mechanisms enable trees to cope with rapid climate change. We studied two European temperate tree species (sessile oak and European beech), focusing on (i) in situ variations of leaf functional traits (morphological and physiological) along two altitudinal gradients and (ii) the extent to which these variations were under environmental and/or genetic control using a common garden experiment. For all traits, altitudinal trends tended to be highly consistent between species and transects. For both species, leaf mass per area displayed a positive linear correlation with altitude, whereas leaf size was negatively correlated with altitude. We also observed a significant increase in leaf physiological performance with increasing altitude: populations at high altitudes had higher maximum rates of assimilation, stomatal conductance and leaf nitrogen content than those at low altitudes. In the common garden experiment, genetic differentiation between populations accounted for 0-28% of total phenotypic variation. However, only two traits (leaf mass per area and nitrogen content) exhibited a significant cline. The combination of in situ and common garden experiments used here made it possible to demonstrate, for both species, a weaker effect of genetic variation than of variations in natural conditions, suggesting a strong effect of the environment on leaf functional traits. Finally, we demonstrated that intrapopulation variability was systematically higher than interpopulation variability, whatever the functional trait considered, indicating a high potential capacity to adapt to climate change.     

An association between triazine resistance and powdery mildew resistance in Epilobium ciliatum and Senecio vulgaris

The response of four naturally occurring biotypes of Epilobium ciliatum and four sources of Senecio vulgaris to the herbicide atrazine were compared with their susceptibility to the powdery mildews Sphaerotheca epilobii and Erysiphe cichoracearum. Biotypes that were resistant to atrazine were also resistant to mildew. Mechanisms that might explain the association between atrazine resistance and mildew resistance are discussed, along with possible implications of these findings for farmland ecology and for the production of herbicide- and mildew-resistant crop plants.     

Development of a clinical severity index for dogs with acute pancreatitis

Objective-To establish a clinical severity index that correlates severity of body system abnormalities with outcome in dogs with acute pancreatitis (AP) and determine the usefulness of serum C-reactive protein (C-RP) concentration as an objective measure of AP severity. Design-Retrospective cohort study. Animals-61 client-owned dogs with ultrasonographically or histologically confirmed AP. Procedures-Medical records of AP-affected dogs were reviewed, and signalment, physical examination findings, clinicopathologic data, and outcome (death or discharge from the hospital) were evaluated. The correlation of specific abnormalities in endocrine, hepatic, renal, hematopoietic, cardiovascular, and respiratory systems; local pancreatic complications; and intestinal integrity were evaluated, and a clinical severity index was developed for AP in dogs. The severity index score was compared with outcome and, for 12 dogs, with serum C-RP concentration. Results-The clinical severity index had a good correlation with outcome and interval from hospital admission until end point (days until outcome), but there was no difference in days until outcome between survivors and nonsurvivors. All 12 dogs evaluated had high serum C-RP concentration, but this variable was not related to outcome; however, within a 2-day period after onset of clinical signs, serum C-RP concentration in survivors and nonsurvivors differed significantly. Conclusions and Clinical Relevance-Among AP-affected dogs, the clinical severity index may be useful for treatment comparisons and prediction of intensive management requirements. Serum C-RP concentration was best related to AP severity within a 2-day period after onset of clinical signs, but daily measurement may be more useful for monitoring progress.