Effects of feeding Artemisia filifolia and Helenium flexuosum on rabbit cytochrome P450 isozymes.

Six groups of 4 rabbits each were treated as follows: Control; phenobarbital (PB); 3-methylcholanthrene (3MC); proadifen hydrochloride (SKF-525A); Artemisia filifolia and Helenium flexuosum. Prototype P450 inducers (PB and 3MC) increased basal hepatic cytochrome P450 content by 2-3 fold whereas the P450 inhibitor (SKF-525A) had no effect on basal cytochrome P450 content. PB-induction of hepatic microsomes significantly increased the rate of dealkylation of long alkyl chain alkoxyresorufin ethers, benzyloxyresorufin and pentoxyresorufin 47-fold and 17-fold, respectively, but had little or no effect on short alkyl chains. 3MC-induction of microsomes increased dealkylation of all alkoxyresorufin ethers tested, preferentially dealkylating ethers with short alkyl chain in the order: methoxy > ethoxy > propoxy. Artemisia filifolia or Helenium flexuosum had no effect on basal hepatic cytochrome P450 content. However, microsomal dealkylation activity of short alkyl chain alkoxyresorufin ethers (methoxy, ethoxy and propoxy) was inhibited approximately 50%. When these plants are eaten for several days, they may inhibit biotransformation processes in herbivores through the same isoenzymes induced by 3MC.

In vitro assessment of the efficacy of erythromycin in combination with oxytetracycline or spectinomycin against Pasteurella haemolytica.

The effects of combining erythromycin (Ery) with oxytetracycline (Oxy) or spectinomycin (Sp) on Pasteurella haemolytica were evaluated in vitro using the chessboard (checkerboard) technique. These combinations were selected because all are drugs widely used in bovine respiratory disease treatment, and they represent possible sequential or complementary mechanisms of action. Using the recommended breakpoints of greater than 4 micrograms/ml for Ery, 16 micrograms/ml for Oxy, and 32 micrograms/ml for Sp, of the 33 P. haemolytica isolates, 32 were resistant to Oxy, 27 to Sp, and 14 to Ery. Based on the fractional inhibitory concentration index, Ery and Oxy in combination were synergistic or additive against 32 of 33 isolates. The combination of Ery and Sp was synergistic or additive against 27 of 33 isolates. No instances of antagonism were seen. When the effects were considered within the context of therapeutically achievable serum/tissue concentrations, the effects of Ery and Oxy in combination were only marginal. Thus, against P. haemolytica isolates, Ery and Sp appeared to represent an effective antimicrobial combination, whereas Ery and Oxy were only of marginal efficacy as a combination.

The prophylactic effect of corn supplementation on experimental nitrate intoxication in cattle.

Sodium nitrate was administered through rumen cannulae to produce NO-3 intoxication in four cows (382 to 445 kg body wt) fed prairie grass hay and a protein-mineral supplement. The cows were fed 0, 1.6 or 3.2 kg of dry rolled corn daily for 10 d prior to sodium nitrate administration. Sodium nitrate administration was followed by a marked increase in intraruminal NO-2 and NH3 and blood NO-2 and methemoglobin. Six of eight cows fed 0 and 1.6 kg of corn were given methylene blue to treat severe methemoglobinemia, while none of the cows fed 3.2 kg corn required such therapy. Feeding of 3.2 kg of corn protected against nitrate poisoning by reducing intraruminal nitrite and blood methemoglobin (P less than .05).

Cyanide intoxication in sheep; therapeutics.

Various cyanide antidotes were evaluated by comparing the effects of delay in time of therapy following oral administration of sodium cyanide in sheep. Successful therapy of lethal doses of sodium cyanide could be accomplished with the more potent antidotes for up to 30 minutes following administration of sodium cyanide. Either 660 mg/kg sodium thiosulfate or 1 mg/kg p-aminopropriophenone were effective antidotes for moderate lethal doses (7.6 mg/kg) of sodium cyanide. The conventional low dosage nitrite/thiosulfate (6.7 mg/kg and 67 mg/kg) was much less effective. Larger doses (15.2 mg/kg) of sodium cyanide were effectively antagonized by either 660 mg/kg sodium thiosulfate alone or in combination with 1.5 mg/kg p-aminopropriophenone or 22 mg/kg sodium nitrite. At high cyanide dosage, p-aminopropriophenone alone was less effective than sodium thiosulfate alone. Sodium thiosulfate at high dosage appears to be the antidote of choice. This more closely satisfies the requirements of high efficacy and low toxicity for an antidote. Sodium nitrate or other antidotes may be used in conjunction with sodium thiosulfate, but their use is not necessary for high efficacy.