Rates of change in liver copper concentration in cattle given a copper-deficient diet,with or without pre-treatment with tetrathiomolybdate,for evaluation of two parenteral copper supplements

AIM: To minimise the impact of initial variation in liver copper (Cu) on assessments of Cu supplements for cattle in depletion/repletion experiments.

METHODS: Efficacy of two Cu injections was assessed with 18 calves, weighing 200–250 kg, given a Cu-deficient barley diet, containing 4.1 mg Cu/kg dry matter (DM) and added molybdenum (3 mg/kg) and sulphur (3 g/kg). Initial liver biopsy Cu ranged from 3.15–14.17 mmol/kg DM and nine calves with the highest values were given three subcutaneous injections of 235 mg tetrathiomolybdate (TTM) after 42–46 days depletion to lower liver Cu. Untreated (L) and TTM-treated (H) calves were ranked separately for liver Cu after 50 days depletion and allocated to one of three treatments: 100 mg Cu given subcutaneously as CuCaEDTA in either a paraffin (CuP) or aqueous base (CuA) after 56 days depletion (Day 0) or no injection (O). Thereafter, plasma and liver biopsy Cu were measured every 2–4 weeks for 16 weeks. Responses in liver Cu to Cu injections were compared with and without log_e transformation and by linear regression.

RESULTS: Prior to Cu injection, the fractional decline in liver Cu concentration (FDLCu) after 50 days depletion was 0.64 (SE 0.066) and 0.80 (SE 0.090) in H and L calves, respectively (p=0.09) and mean liver Cu did not differ on Day ?6 (6.65 (SE 0.516) and 4.91 (SE 0.681) mmol/kg DM, respectively). Mean plasma Cu was higher in H than L calves on Day 0 (16.6 (SE 0.52) and 13.3 (SE 0.49) μmol/L, respectively (p<0.001)). Rates of decline in log_e liver Cu between Days 0–84 in treatments L and H were: 0.0138 and 0.0071 for Groups O; 0.0033 and 0.0016 for Groups CuP; 0.0073 and 0.0049 for Groups CuA (pooled SE 0.0014) mmol/kg DM/day, respectively. Between Days 84–114, FDLCu was uniformly high across experiments and groups (0.59 (SE 0.042)). Cu injections did not affect plasma Cu, which remained 3.1 (SE 0.41) umol/L higher in Experiment H than in L (p=0.017).

CONCLUSIONS: The use of rates of change in liver copper concentrations improved the assessment of efficacy for two parental copper supplements and that of pre-treatment with tetrathiomolybdate, which, contrary to expectation, slowed Cu turnover by mechanisms that remain unclear.     

The distribution and prevalence of Theileria buffeli in cattle in Queensland

The distribution and prevalence of Thelleria buffeli in Queensland cattle were investigated using serum samples and blood films collected primarily for brucellosis surveillance and tick fever diagnosis. Serums from 8654 cattle from 357 farms throughout Queensland were examined by an indirect fluorescent antibody test for antibody to T buffeli. In addition, 347 peripheral blood films collected from 147 farms in south-eastern Queensland were examined for piroplasms of T buffeli. The overall herd and animal prevalences for T buffeli were 75% and 41%, respectively. There was significant variation among regions in both herd and animal prevalences (P less than 0.001). Herd and animal prevalences were highest in the north and east decreasing westward. The results indicate that T buffeli is more widespread in Queensland than previously thought.     

Residual effects of Mycobacterium avium infection on susceptibility of sheep to copper toxicity and efficacy of treatment with tetrathiomolybdate

Posthaemolytic copper poisoning (post-HCP) in one of six, one-year-old, uninfected sheep (group O) on a Mycobacterium avium experiment prompted an evaluation of copper status and hepatotoxicity in 17 surviving cohorts. Group O had higher mean plasma Cu and δ-glutamyl transferase (GGT) activity and more variable bile acid (BA) concentrations and glutamate dehydrogenase activities (GDH) than two groups infected with M avium soon after birth. Ammonium tetrathiomolybdate (TTM; 3 x 1.7 mg/kg LW) was given subcutaneously over seven days and the pelleted, complete diet replaced by hay, low in copper. Plasma BA immediately declined and was followed by GDH, but erythrocyte superoxide dismutase activity (ESOD) became severely inhibited and took 18 days to recover. Plasma BA and GDH rose sharply after 18 days in uninfected sheep and they became hypercupraemic. TTM treatment was repeated from day 42 and had removed all group differences by day 110 but only after further inhibition of ESOD. M avium infections probably lessened the severity of pre-HCP by reducing copper retention but may predispose grazing livestock to hypocupraemia. The capacity of TTM to reduce liver Cu has probably been overestimated and side effects on cuproenzyme activity underestimated.     

The effect of dietary molybdenum on hypocupraemic ewes treated by subcutaneous copper

An attempt has been made to assess the importance of systemic sites of interaction from the effect of dietary molybdenum (Mo) on the protection afforded by a single sc injection of copper (Cu) to 29 initially hypocupraemic 5-year-old ewes, maintained on a low Cu diet. They were fed a diet of 1 kg/day containing 1.3 mg of Cu/kg supplemented with sodium sulphate which provided 1.7 gm of sodium per kg. Group A was given no further supplement. Group B was given added Mo, 25 mg/kg. Group C was given added Cu, 10 mg/kg. After 7 months, several animals in each group were injected sc with a single dose of 46.5 mg of Cu in the form of copper calcium edetate (Coprin). Blood samples were taken at intervals from the injected ewes over a 250-day period. All ewes were mated after 12 months on the diet. Injected ewes were approaching the 4th month of gestation when the last blood sample was taken at 250 days. Total Cu in plasma was determined by atomic absorption spectometry. Direct reacting Cu in plasma, cerulosplasmin oxidase activity, and hemoglobin were also estimated. Plasma Cu concentrations had increased to normal levels in 14 days in Group A after the Cu injections. Group B animals showed a greater increase, mean values exceeding those of Groups A and C, between Days 28-129 (p less than .01). Plasma Cu levels declined in ewes not given supplementary Cu after the 177th day. The final values for Groups A and B were similar to those found before injection. The direct reacting Cu in each group was increased after 7 days (p less than .05). This effect was most marked in the Mo supplemented ewes (Group B). The effect of Mo persisted until the final bleeding. Direct reacting Cu was only a minor part of the early response in total plasma copper of Group B ewes. Dietary Mo did not inhibit the incorporation of injected Cu into ceruloplasmin. The Mo-supplemented ewes were in poorer condition than copper-supplemented ewes. All groups gained in weight after the injections. The sc injection of Cu at 5 months prior to mating imporved fertility in Groups A and B. There was no evidence that dietary Mo impa ired the metabolism of parenteral Cu. However, it is known to deplete r uminants of Cu when the diet provides the only source of Cu. It is ther efore thought that the site of the Cu with Mo interaction is in the gut. If infertility due to Cu deficiency is suspected in a flock, an injection of Cu immediately prior to mating may improve conception rate and provide sufficient Cu to reduce the incidence of swayback.     

The Effects of Breed,Neonatal Age and Pregnancy on the Plasma Copper Status of Goats in Oman

There is a history of copper deficiency in grazing Omani livestock and the copper status of three economically important goat breeds, Jabal Akhdar (JA), Batina (B) and Dhofari (D) were therefore compared in October/November (cool season) and June (dry season) in a penned flock given a plentiful dietary supply of copper. In the cool season, 62 lactating does (5 JA, 12 B and 33 D), their 0–5-day-old kids (17 JA, 19 B and 22 D) and 25 dry does (17 JA, 5 B and 3 D) were blood sampled. In the dry season, the does sampled were either barren (15 JA, 16 B and 13 D) or pregnant (9 JA, 13 B and 33 D). The samples were analysed for total copper (TCu) and trichloroacetic acid (TCA)-soluble copper (TCA-sol Cu). There were no effects of breed on TCu or TCA-sol Cu in the cool season, the overall means being 0.75 (SE 0.049) and 0.59 (SE 0.052) mg/L. The mean TCu was low in kids at birth (0.59 mg/L) but had increased to 0.86 mg/L by 4 days of age (p<0.001); breed differences were found (p<0.002), the pooled values for JA, B and D being 0.77, 0.59 and 0.68 (SE 0.033–0.044) mg/L, respectively. By the dry season, the mean TCu had risen in barren does to 0.96 (0.045) mg/L but not in pregnant does (0.76 (0.047) mg/L; p<0.002) and breed differences had emerged, the mean for D being 20% lower than those for JA and B (p<0.05). The highest TCu values were found in the 7-month-old kids in June (1.17 (0.039) mg/L) but the breeds did not then differ. Some effects on TCA solubility were found but were considered unreliable. Breed effects may have been diminished by the generous supply of copper and early stage of lactation studied.     

Relationships between the concentrations of trichloroacetic acid-soluble copper and caeruloplasmin in the serum of cattle from areas with different soil concentrations of molybdenum

The concentrations of trichloroacetic acid (tca)-soluble copper and caeruloplasmin were determined in 345 serum samples taken from cattle in March 1998 by eight Scottish Agricultural College veterinary disease surveillance centres serving areas with soils ranging from being 'high' in molybdenum (Thurso) to 'low' (Perth and St Boswells). The mean concentrations varied significantly between the centres, with Thurso having the lowest values for both variables. There were strong linear regressions (r>0.8) between caeruloplasmin and tca-soluble copper for each centre but no significant differences in slope or intercept between the areas with the highest and lowest soil molybdenum, and the pooled regression accounted for 88 per cent of the variation. The distribution of the ratios of caeruloplasmin to tca-soluble copper, unlike those of the individual variables, was not normal, and 70 per cent of the values fell within 10 per cent of the mean ratio of 20.3 mg/micromol and close to the 22 mg/micromol copper expected in pure caeruloplasmin. Low ratios were generally associated with low tca-soluble copper. Ratios above 24 were found in 8 per cent of the samples and were probably attributable to acute-phase reactions and the non-specificity of the assay for caeruloplasmin.     

Species interactions reverse grassland responses to changing climate

Predictions of ecological response to climate change are based largely on direct climatic effects on species. We show that, in a California grassland, species interactions strongly influence responses to changing climate, overturning direct climatic effects within 5 years. We manipulated the seasonality and intensity of rainfall over large, replicate plots in accordance with projections of leading climate models and examined responses across several trophic levels. Changes in seasonal water availability had pronounced effects on individual species, but as precipitation regimes were sustained across years, feedbacks and species interactions overrode autecological responses to water and reversed community trajectories. Conditions that sharply increased production and diversity through 2 years caused simplification of the food web and deep reductions in consumer abundance after 5 years. Changes in these natural grassland communities suggest a prominent role for species interactions in ecosystem response to climate change.