Identification and characterization of the enzymes responsible for the metabolism of the non‐steroidal anti‐inflammatory drugs,flunixin meglumine and phenylbutazone,in horses

The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug–drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450‐mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of recombinant equine P450s. Incubation of phenylbutazone in microsomes generated oxyphenbutazone and gamma‐hydroxy phenylbutazone. Microsomal incubations with flunixin meglumine generated 5‐OH flunixin, with a kinetic profile suggestive of substrate inhibition. In recombinant P450 assays, equine CYP3A97 was the only enzyme capable of generating oxyphenbutazone while several members of the equine CYP3A family and CYP1A1 were capable of catalyzing the biotransformation of flunixin to 5‐OH flunixin. Flunixin meglumine metabolism by CYP1A1 and CYP3A93 showed a profile characteristic of biphasic kinetics, suggesting two substrate binding sites. The current study identifies specific enzymes responsible for the metabolism of two NSAIDs in horses and provides the basis for future study of drug–drug interactions and identification of reasons for varying pharmacokinetics between horses.     

In-hospital development of an aorto-cardiac fistula in a Warmblood gelding with chronic renal disease

A 20-year-old Warmblood gelding presented for evaluation and treatment of ventral oedema and azotaemia of unknown aetiology. On presentation, a diastolic heart murmur was appreciated and echocardiography revealed moderate aortic insufficiency due to chronic degenerative valve disease. The horse was hospitalised and failed to respond to oral and i.v. fluids and diuretics. Following discontinuation of all fluid and diuretic therapy, the horse became acutely agitated and developed monomorphic ventricular tachycardia. The ventricular tachycardia spontaneously converted to normal sinus rhythm, however the heart murmur changed in timing to a right basilar continuous murmur and bounding jugular pulses were noted. Repeat echocardiogram revealed an aorto-cardiac fistula with dissection into the basilar interventricular septum and left-sided chamber volume overload that was not previously present. Attempts at stabilisation were unsuccessful and euthanasia was elected. Post-mortem examination confirmed chronic renal disease of unknown aetiology in addition to an aorto-cardiac fistula originating from the right sinus of Valsalva with subsequent dissection into the basilar interventricular septum.     

Influence of the Expert Effect on Cultural Models

We examined hunters’ perceptions of fauna to see if expert hunters and other hunters perceive wildlife abundance similarly. We used cultural consensus analysis (CCA) to assess the knowledge of 25 hunters in the Bolivian Amazon about the abundance of 38 animals. CCA indicated highly shared beliefs among hunters concerning wildlife abundance (average agreement = .62). However, expert hunters (as judged by their reported successful hunts of rare species, having hunted recently, and consuming more game in their diet) perceived more animals as abundant than did non-experts, although they all shared the same model. Since the expert hunters did not always agree on which species was more abundant, they had low cultural knowledge scores in CCA results. These experts may be unwilling to curtail hunting efforts on key species that they perceive to be abundant.     

Lactation feed disappearance and weaning to estrus interval for sows fed spray-dried plasma

Four experiments involving 265, 410, 894, and 554 sows (Exp. 1 to 4, respectively) were conducted to determine the effect of spray-dried plasma (SDP) at 0 or 0.25% (Exp. 1 and 2) and 0 or 0.50% (Exp. 3 and 4) in lactation diets on average daily feed disappearance (FD), sum of sow BW, fetal and placental loss from d 110 gestation to weaning (SWL), litter size at weaning, litter weight at weaning, and average days from weaning to first estrus (WEI). Experiments 1, 3, and 4 were conducted during summer months, and Exp. 2 was conducted during fall to winter months. Experiment 1 used only parity 1 and parity 2 sows and Exp. 4 used only mature (>2 parities) sows, whereas Exp. 2 and 3 used all parity groups. Sows fed SDP in Exp. 1 had increased (P < 0.01) FD and a tendency for reduced (P = 0.06) SWL and WEI (P = 0.06). Sows fed SDP in Exp. 2 had a tendency for increased (P = 0.09) sow BW at weaning and reduced (P = 0.09) SWL, whereas other variables were not different between diets. Parity 1 and 2 sows fed SDP in Exp. 3 had increased (P < 0.01) FD, but mature sows fed SDP had reduced (P = 0.02) FD. Pig survival and litter size at weaning for all parity groups was not different between diets. The WEI for parity 1 sows fed SDP was reduced (P = 0.02) and tended to be reduced (P = 0.10) for mature sows fed SDP, but was not different between diets for parity 2 sows. More parity 1 sows fed SDP were detected (P = 0.01) in estrus 4 to 6 d after weaning, and fewer were detected (P < 0.01) in estrus 6 d after weaning compared with control parity 1 sows. In Exp. 4, FD was reduced (P < 0.01) for mature sows fed SDP; however, litter weight and average pig BW at weaning was increased (P < 0.01) with more (P < 0.01) marketable pigs (pig BW > 3.6 kg) weaned per litter. Relatively low dietary levels of SDP (0.25 to 0.50%) fed to parity 1 sows farrowed during summer months increased lactation FD and reduced WEI. Mature sows fed SDP during summer months consumed less lactation feed without compromising WEI, but had an increased litter weight, average pig BW, and number of marketable pigs at weaning.     

Inactivation of fenitrothion on stored maize at different moisture contents

Biological activity of fenitrothion on stored maize at various moisture contents and at different times after application was measured by biological assay using adults of Tribolium castaneum (Herbst). Inactivation of actual residues over time was then determined after making the necessary allowance for chemical breakdown. At a given moisture content, the inactivation process was substantially completed during the first 6 weeks after application and loss of effectiveness from 6 weeks onwards resulted mainly from chemical breakdown. At a given time after application, residues were less active at higher moisture content (m.c). Differences in activity between moisture contents were apparent within a few hours of application and continued to increase for up to 3 days, with relatively little change thereafter during storage of 24 weeks. Thus after 24 weeks, residues on maize of 18% m.c. had an activity about 20% that of similarly-aged residues at 10% m.c. and 4% that of freshly-applied residues at 10% m.c. These results were in general accord with changes in the proportion of the residue which was collected from the kernels by a surface wash with methanol, this readily-extractable residue presumably representing the insecticide that may be picked up by insects.     

Factors that alter rumen microbial ecology

Ruminant animals and ruminal microorganisms have a symbiotic relationship that facilitates fiber digestion, but domestic ruminants in developed countries are often fed an abundance of grain and little fiber. When ruminants are fed fiber-deficient rations, physiological mechanisms of homeostasis are disrupted, ruminal pH declines, microbial ecology is altered, and the animal becomes more susceptible to metabolic disorders and, in some cases, infectious disease. Some disorders can be counteracted by feed additives (for example, antibiotics and buffers), but these additives can alter the composition of the ruminal ecosystem even further.