Effectiveness of α-tocopherol and selenium supplements in preventing lupinosis-associated myopathy in sheep

Objective To compare the effectiveness of combined selenium and α-tocopherol acetate treatments in preventing lupinosis-associated myopathy in sheep.
Design Measurement of plasma muscle and liver enzymes, and histopathological examination of muscle and liver in the treatment groups.
Procedure The treatments were: subcutaneous injections of selenomethionine and vitamin E (sc(SeM+E)) , an intraruminal selenium pellet and oral doses of vitamin E and intramuscular injections of selenomethionine combined with either oral doses of vitamin E (imSeM+orE) or intramuscular injections of vitamin E in an oily carrier. Another group received no supplements, while a control group was given selenium pellets on day 0 and fortnightly oral doses of vitamin E from day 0 to 72. To produce lupinosis-associated myopathy, the sheep were fed a diet low in vitamin E and given repeated injections of a crude extract of Diaphorthe toxica. Groups sc(SeM+E) and imSeM+orE were stressed by dosing with protected polyunsaturated fatty acids from day 56 onwards.
Results Lupinosis-associated myopathy was induced in all unsupplemented sheep. In these sheep the storage of Se increased and that of vitamin E decreased. The subcutaneous treatment was highly effective in preventing lupinosis-associated myopathy and also produced the highest vitamin E concentrations in plasma and liver. Supplemental vitamin E was more efficacious than supplemental Se. Concentrations of vitamin E in the livers of sheep given intramuscular vitamin E were higher than expected based on plasma concentrations. Oral doses of vitamin E proved the least effective method of increasing concentrations in liver. Lupinosis did not affect Se concentrations in liver or muscle.
Conclusion The sc(SeM+E) treatment is highly effective in preventing lupinosis-associated myopathy but needs to be further assessed when selenium and vitamin E are both limiting in the diet.     

Effect of non-linear plasma protein binding on unbound and total plasma phenylbutazone concentrations in cows

Boudinot, F.D., Williams, R.J. & Smith, J. A. Effect of non-linear plasma protein binding on unbound and total plasma phenylbutazone concentrations in cows. J. vet. Pharmacol. Therap. 13, 132–136.
The influence of plasma protein binding on unbound and total phenylbutazone concentrations in cows was examined employing data from the literature. Protein binding parameters (number of binding sites and affinity constants) were generated by computer analysis to characterize the concentration-dependent plasma protein binding of phenylbutazone. Unbound plasma phenylbutazone concentrations were calculated from total plasma drug concentrations observed after administration of a single dose of phenylbutazone to cows. Pharmacokinetic parameters for unbound phenylbutazone were obtained. Parameters characterizing die plasma protein binding and pharmacokinetics of unbound phenylbutazone derived from single-dose administration were then used to predict unbound and total drug concentrations after multiple-dose administration of phenylbutazone. Total plasma phenylbutazone concentrations predicted from single-dose pharmacokinetic parameters agreed well with observed values following multiple-dose administration of the drug. Thus, the results of this analysis demonstrate that the non-linear pharmacokinetics of phenylbutazone in the cow can be attributed to the concentration-dependent plasma protein binding of the drug.
F. Douglas Boudinot, Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.     

The pharmacokinetics of oral and intravenous allopurinol and intravenous oxypurinol in the horse

The pharmacokinetics of oral and intravenous allopurinol was studied in five horses and compared with intravenous oxypurinol. The plasma concentration vs. time curves, following intravenous administration of 5 mg/kg, were best described by the biexponential equations Cp = 106.58e^-25.141+ 159.93e^-10.96tfor allopurinol and Cp = 321.09e^-972t+ 82.39e^-0.44tfor oxypurinol. Allopurinol was rapidly removed from the plasma, compared to oxypurinol, with an elimination half-life ( t _1/2β) of 0.09 h and an area under the curve ( AUC ) of 19.8 μmol·h/L after intravenous administration, while the t _1/2β and AUC of oxypurinol were 1.09 h and 231 μmol·h/L, respectively. The bioavailability of allopurinol was low (14.3%), although no allopurinol was detected in the plasma of two horses after oral administration. However, the AUC of drug and metabolite after intravenous administration of allopurinol was equivalent to that of intravenously injected oxypurinol. The results suggest that allopurinol is rapidly metabolised in vivo and that the majority of the pharmacological activity of allopurinol in the horse may result from the action of the active metabolite, oxypurinol.     

Brown fat: thermogenic effector of arousal in hibernators

Earlier indications that brown fat has a thermogenic role in rats exposed to cold suggested that certain comparable functions in hibernating marmots be investigated. From the results it appears that arousal of the animal by cold is induced by sympathetically activated thermogenesis in areas of brown fat so located, relative to the vasculature, that heat is transferred to the thoracic structures and cervical spinal regions.     

Cardiorespiratory Effects of Four Opioid-Tranquilizer Combinations in Dogs

The cardiorespiratory effects of four opioid-tranquilizer combinations were evaluated in six dogs. The four combinations were administered to each dog in a randomized order. Buprenorphine (BUP; 0.01 mg/kg IV) or oxymorphone (OXY; 0.1 mg/kg IV) was followed in 10.4 ± 1.3 minutes by midazolam (MID; 0.3 mg/kg IV) or acepromazine (ACE; 0.05 mg/kg IV). Nalbuphine (0.16 mg/kg IV) was administered 94.1 ± 2.3 minutes after the tranquilizer was given. Heart rate (HR) and mean arterial blood pressure (MAP) decreased significantly ( P < .05) after each combination. MAP was significantly lower with combinations using ACE. Most dogs panted after opioid administration; this was associated with increased minute volume (V_M) and decreased tidal volume (V_T). After administration of the tranquilizer, mean breathing rate and V_M index (V_MI) were significantly lower with ACE combinations. There were no significant changes in pH and blood gas variables after BUP-ACE. The other three combinations were associated with significant ( P < .05) decreases in pH and increases in Paco₂. Mean Pao₂ decreased significantly ( P < .05) with OXY combinations but not BUP combinations. Dysrhythmias (atrial or ventricular escape complexes) were seen with each combination. HR increased significantly ( P < .05) after nalbuphine in dogs receiving OXY, but not BUP. Dogs receiving OXY became more alert after nalbuphine on six of 12 occasions, whereas dogs receiving BUP became less alert on six of 12 occasions. OXY-ACE provided the most chemical restraint/sedation and BUP-MID provided the least.