The ability to reliably detect anthelmintic resistance is a crucial part of resistance management. If data between countries are to be compared, the same test should give the same results in each laboratory. As the egg hatch test for benzimidazole resistance is used for both research and surveys, the ability of different laboratories to obtain similar results was studied through testing of known isolates of cyathostomins, Haemonchus contortus, Ostertagia ostertagi, and Cooperia oncophora in programs supported by the EU (Cost B16 and FP6-PARASOL).
Co-administration of piperonyl butoxide (PB) potentiates fenbendazole (FBZ) in small ruminants. The resultant increase in bioavailability of FBZ and its metabolite oxfendazole (OFZ) has important implications for the efficacy of these drugs against benzimidazole (BZD)-resistant strains of Teladorsagia circumcincta. This study evaluated the racemic (achiral) and enantiomeric (chiral) plasma disposition kinetics of OFZ and its metabolites after the co-administration of PB and OFZ in sheep. Six 6-8-month-old, parasite-free, female Dorset sheep (30-40 kg) were used in a two-phase crossover experiment. In phase I, three sheep received 30 mg/kg PB orally, followed by a single intravenous (i.v.) injection of OFZ at 5 mg/kg. The other three animals were treated similarly except that 5 mL of water replaced PB. In phase 2, treatments for the two groups were reversed and were given 14 days after the initiation of phase I. Three analytes OFZ, FBZ and fenbendazole sulphone (FBZSO(2)) were recovered in plasma up to 48 h post-treatment in both experimental groups. Achiral and chiral pharmacokinetic (PK) profiles for OFZ, after the co-administration of PB, were characterized by a significantly greater area under the concentration--time curve (AUC) and a longer mean residence time (MRT). Chiral OFZ distribution ratios were comparable in both treatment groups. Piperonyl butoxide treatment markedly influenced the plasma PK profiles for FBZ and FBZSO(2) following OFZ administration. Production of FBZ was enhanced as reflected by increased (> 60%) AUC, delayed T(max) and a significantly delayed (> 45%) elimination (t(1/2)(el)). Although AUC values for FBZSO(2) were not significantly different between groups, this metabolite was depleted more slowly from plasma (t(1/2)(el) > 60% and MRT > 42%) following PB treatment. This study demonstrated that PB co-administration is associated with an inhibition of OFZ biotransformation, as evidenced by the significantly higher plasma concentrations of OFZ and FBZ, and this could have important implications in terms of anti-parasite therapy against BZD-resistant parasite strains.
The causes of hypothermia in 89 lambs were identified on the basis of history and clinical biochemistry. Excessive heat loss accounted for 24 per cent of the cases, and depressed heat production because of either severe hypoxia during birth, immaturity or starvation accounted for 72 per cent. Exhaustion of energy reserves and hypoglycaemia were marked characteristics of lambs which became hypothermic after 12 hours of age. Most of the lambs were either twins or triplets. The implications of the findings for both the treatment and prevention of hypothermia in newborn lambs are discussed.
The feeding of housed lambs on conserved forages and pelletedrattons is accompanied by a high risk of chronic capper tCu) poisoning (CeF) which might be reduced by sekcting sires for low liver Cu status. Livers were therefore retrieved from Suffolk, Texel and Charollais lambs, slaughtered during the course ofa performance trial, to ascertain sire and possibly breed effects on the rate of Cu accretion in the liver. In total, 160 livers were obtained, 100from Suffolk, 40 from Texel and 20from Charoiiaie lambs, the progeny of 14, eightand eightsires, respectively. Lambs came from three separately managed flocks but were brought together at B weeks of age, weaned onto a common complete diet containing 6·1mg Cu per kg dry matter (DM) and offered ad libitum. One-fifth of each breed grouptvas slaughtered at 14, 18 or22 weeks and the remaining 40% at 26 weeks afage. Mean (s.e. ) liverCu concentrations at those ages were 3220 (450), 4639(464)/ 6426 (468), anti 6513 (370) gmol/kg OMfor Suffolk, and 5843(811), 6579 (857), 8017 (811) and 10406 (589) gmollkg OM for Texel, respectively. The pattern olliver Cu accretion differed, the Suffolk starting at a low value yetreaching a plateau at about 22 weeks of age (significant quadratic regression coefficient), the Texel, continually increasing from a high initial value at an average rate of 53·7 (s.e.10·6)gmol/kg OM per day. There was a significant effect of sire onliver Cuin theSuffolk(P <0·05) with a heritability of 0·85 (s.e. 0·44); in the Suffolk and Texei combined/ the heritability was 0·60 (s.e. 0·33). The data available on theCharollais were too limited to test for sire effects but at 26 weeks of age, where mast information was available, the mean liver Cu concentration was 7285 is.e. 826) }1mollkg DM. At a given age, food intake/ liver weight and live weight were each lowest in the Texel but When expressed as a proportion ofliveweight (LW), bath food intake (43g/kg LW)and liver weight (5·15g OM per kg LW) were similar among breeds (P> 0·05). Thus, differences in lioerCu accretion are unlikely to reflect differences in Cu intake per unit liver weight. There was a tendencyfor liversize perkg LW to decrease as.liver Cu rose in the Texel but not in theSuffolt Continued hepatic Cuaccreiion in the Texel may reflect a breed-specific inability to c()pe with Cu overload. Increases in liver Cu to marginally toxic levels in some Suffolk, some Charollaisand most Texellamoe. and toa level commonly associated with toxicityin one Texellamb, on a ration ofmoderate Cu concentration highlights thedifficulty of controlling risk ofCCPby.manipulating dietary composition. The current EC limit for Cuin ooine diets, 17 mg Cu perkg DM, is clearly too high for the breeds and dietary conditions used in this study. However a safe limit would be hard to achieve andhence the need to exploit sire variation in propensity to accumulate liver Cu to reduce disease risk. gradually introduced to this same ration, with ad libitum access to hay, over several weeks. All lambs were housed together in a single sh...
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