Short-term effects of ecadotril in dogs with induced congestive heart failure

OBJECTIVE: To evaluate short-term hemodynamic effects of ecadotril in a model of congestive heart failure in dogs. ANIMALS: 6 conscious adult male dogs. PROCEDURES: Instruments were placed in dogs to measure left ventricular, aortic, and atrial blood pressures. Heart failure was induced by repeated coronary embolization with latex microspheres. Four times, and in random order, dogs were given vehicle or active drug (3, 10, or 30 mg/kg of body weight) orally. Hemodynamic variables, urine flow, and urinary electrolyte excretion were measured before and 30, 90, and 150 minutes, and 10 and 21 hours after drug administration. RESULTS: Changes in urine flow, heart rate, mean arterial pressure, or peak positive and negative rate of change in ventricular pressure were not apparent. Urinary sodium excretion significantly increased in response to the low and high doses of ecadotril but not in response to the 10 mg/kg dose. Left ventricular end diastolic pressure (LVEDP) consistently decreased in dose- and time-dependent manner. Maximal group-averaged reductions in LVEDP were 5.2, 8.1, and 10 mm Hg for the low, middle, and high doses, respectively. The magnitude of the decrease in LVEDP was not related to cumulative change in urine flow. CONCLUSIONS AND CLINICAL RELEVANCE: Orally administered ecadotril reduced left ventricular filling pressures in these dogs by a mechanism that does not require a substantial diuretic effect. Ecadotril may be effective for alleviating clinical signs in dogs with left-sided heart failure and may be particularly beneficial for use in dogs that are refractory to traditional diuretic therapy.     

Vertical Frontlimb Ground Reaction Forces of Sound and Lame Warmbloods Differ From Those in Quarter Horses

Lameness is a highly prevalent condition in horses and is the principal cause of removal from athletic activity in this species. In evidence-based veterinary medicine studies to evaluate non-setoidal anti-inflammatory drug (NSAID) therapies, force plates are commonly used to objectively assess improvement of lameness. The objective of this study was to determine whether breed differences would influence force plate measurements in sound and lame riding horses. Force plate measurements of lame (n = 20) and sound (n = 18) Warmblood and lame (n = 15) and sound (n = 8) Quarter Horses were compared. Lameness was visually scored using the grade 0–5 American Association of Equine Practitioners (AAEP) lameness scale. Trotting sound Warmbloods loaded their frontlimbs with 118% body weight (BW) and their hindlimbs with 96% BW, whereas Quarter Horses only used 101% BW in the front and 92% BW in the hindlimbs (P < .05). Furthermore, it appeared and was estimated that, at trot, front-limb-lame Warmblood horses showed higher peak vertical force (PVF) values (grade 2: 89% BW; grade 3: 69% BW), than front-limb-lame Quarter Horses with similar lameness scores (grade 2: 78% BW; grade 3: 66% BW). In conclusion, peak vertical forces (PVF expressed in % BW) of either lame or sound horses seem to be influenced by breed differences between Warmblood and Quarter Horse riding horses. Possible conformation and gait differences enabled trotting Quarter Horses to demonstrate lower absolute PVF values than Warmbloods, whereas trotting lame Warmbloods showed a relatively larger decrease in frontlimb loading and thus in PVF than lame Quarter Horses at a trot. Thus, in studies in which objective lameness observations are recorded, breed differences should be taken into account when specific grades of lameness of a group of horses are to be objectively compared with another group.     

Seasonal patterns of light-saturated photosynthesis and leaf conductance for mature and seedling Quercus rubra L. foliage: differential sensitivity to ozone exposure

Extrapolation of the effects of ozone on seedlings to large trees and forest stands is a common objective of current assessment activities, but few studies have examined whether seedlings are useful surrogates for understanding how mature trees respond to ozone. This two-year study utilized a replicated open-top chamber facility to test the effects of subambient, ambient and twice ambient ozone concentrations on light-saturated net photosynthesis (P(max)) and leaf conductance (g(l)) of leaves from mature trees and genetically related seedlings of northern red oak (Quercus rubra L.). Gas exchange measurements were collected four times during the 1992 and 1993 growing seasons. Both P(max) and g(l) of all foliage followed normal seasonal patterns of ontogeny, but mature tree foliage had greater P(max) and g(l) than seedling foliage at physiological maturity. At the end of the growing season, P(max) and g(l) of the mature tree foliage exposed to ambient ( approximately 80-100 ppm-h) and twice ambient ( approximately 150-190 ppm-h) exposures of ozone were reduced 25 and 50%, respectively, compared with the values for foliage in the subambient ozone treatment ( approximately 35 ppm-h). In seedling leaves, P(max) and g(l) were less affected by ozone exposure than in mature leaves. Extrapolations of the results of seedling exposure studies to foliar responses of mature forests without considering differences in foliar anatomy and stomatal response between juvenile and mature foliage may introduce large errors into projections of the response of mature trees to ozone.     

Quantitative structure-antifungal activity relationships of some benzohydrazides against Botrytis cinerea

Fourteen benzohydrazides have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The best antifungal activity was observed for the N',N'-dibenzylbenzohydrazides 3b-d and for the N-aminoisoindoline-derived benzohydrazide 5. A quantitative structure-activity relationship (QSAR) study has been developed using a topological substructural molecular design (TOPS-MODE) approach to interpret the antifungal activity of these synthetic compounds. The model described 98.3% of the experimental variance, with a standard deviation of 4.02. The influence of an ortho substituent on the conformation of the benzohydrazides was investigated by X-ray crystallography and supported by QSAR study. Several aspects of the structure-activity relationships are discussed in terms of the contribution of different bonds to the antifungal activity, thereby making the relationships between structure and biological activity more transparent.