The development of acid-base reaction cements as formulations for the controlled release of trace elements.

Novel acid-base reaction cements have been developed for use as controlled release formulations. Many new ones have been discovered and assessed; these include those which are capable of releasing copper, cobalt or selenium singly or in combination. A selection was made of the most suitable formulations for this purpose and these were subjected to field trials.

Reaction cements as materials for the sustained release of trace elements into the digestive tract of cattle and sheep. I. Copper release.

Acid-base reaction cements were produced by reacting copper oxide with phosphoric acid. When placed in the reticulo-rumen of cattle and sheep these cements released copper into the digestive tract for at least 3 months at a rate sufficient to provide the animals' requirements for copper. Lambs given a pellet of cement at 3 months of age had significantly greater concentrations of copper in their livers than similar untreated animals when slaughtered 3-4 months later. It was shown that salts of cobalt and selenium could be incorporated into the cement to provide additional supplementation with these two elements.

Barium selenate injections in cattle: effects on selenium concentrations in plasma and liver and residues at site of injection.

Twenty Angus cross heifers were fed a complete diet which contained 0.07 mg selenium/kg dry matter. Thirteen were injected subcutaneously with barium selenate at a dose rate of approximately 1 mg selenium/kg bodyweight and seven remained untreated. All the heifers were slaughtered during the following 121 days, the last of the treated group 119 days after injection. Glutathione peroxidase activity in blood increased within four weeks of administration and remained high thereafter. The selenium dependent glutathione peroxidase activity did not increase in liver kidney or muscle. The concentrations of selenium in the blood, liver and muscle were increased significantly from 30 days until 119 days. Between 76 and 99 per cent of the selenium injected remained at the site of injection.

The use of controlled-release glass for the controlled delivery of bioactive materials.

CRG can provide a useful supplement to other methods of controlled delivery. Some advantages of this approach are: The constituents of the CRG can be limited to biologically safe ionic species such as Na+, Ca2+ and PO4(3-). The release system is completely soluble in water and no residue remains. There is no evidence of any mechanism for biodegradation of the CRG and so one possible cause of premature or accelerated release is eliminated. The absolute release rate can be selected anywhere in a spectrum covering several orders of magnitude and the rate-controlling process has zero-order kinetics. The release rate can be selected to be pH-sensitive or pH-independent. Complex temporal release-rate patterns can be obtained readily by the choice of geometrical shape or composition profile of the device. The controlled release of organics or other heat-sensitive materials which cannot be incorporated in the glass can be realized by the use of composite structures in which the CRG is the rate-controlling constituent. A number of different functions can be performed by a single CRG-based device. For example, CRG can be used as a biomedical resorbable material in surgery and the CRG structural component can release an AM as it dissolves. Similarly the CRG of the sinter-composite used for organic AM release can itself release any selected inorganic adjuvant. CRG boluses containing either copper or cobalt and weighing approx. either 70 g or 15 g, have been administered to both cattle and sheep. More than 90% of the boluses remained either in the reticulum of trace element remained after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Boluses of controlled release glass for supplementing ruminants with cobalt.

Boluses of controlled release glass containing cobalt and weighing approximately either 60 g or 14.5 g were administered to 22 steers and 21 sheep respectively. The steers were housed and slaughtered at intervals between 17 and 145 days after dosing. The boluses released more than 0.85 mg cobalt daily. In both untreated and dosed animals serum and liver vitamin B12 concentrations were at the upper end of the normal range. Two types of glass were administered to sheep. In five wethers one glass released 0.07 mg cobalt per day, and in 16 grazing lambs a second glass released more than 0.15 mg cobalt per day. Fourteen of the boluses were recovered from the lambs up to 276 days after dosing. The concentration of B12 in serum of lambs increased significantly from a mean +/- sd of 1.64 +/- 0.47 to 2.02 +/- 0.04 ng/ml serum and the concentration in liver from 3.84 +/- 0.85 to 4.99 +/- 0.72 micrograms/g dry weight liver.

Boluses of controlled release glass for supplementing ruminants with copper.

A controlled release glass was formulated into boluses weighing approximately 17 g or 75 g and administered to 19 lambs and 20 steers respectively. The animals were at pasture during the summer months. The lambs were slaughtered between 57 and 219 days after dosing when the mean concentration of copper in their livers had increased to 107.8 +/- 33.4 mg copper/kg fresh weight compared with 55.9 +/- 23.0 mg copper/kg fresh weight in undosed controls. The steers were slaughtered more than 140 days after dosing; the mean concentrations of copper in plasma had increased and the mean concentration of copper in liver was significantly greater than in undosed control steers (14.1 +/- 4.8 mg copper/kg fresh weight liver in dosed steers, 4.7 +/- 1.4 mg copper/kg in control steers) and was similar to the concentration in steers which had received 200 mg copper as copper calcium edetate (18.2 +/- 4.2 mg copper/kg fresh weight). In sheep the minimum rate of release of copper into the reticulorumen was 2.1 mg/day and in steers 11 mg/day.

Parenteral methods of supplementation with copper and selenium.

Parenteral treatments can provide a rapid successful method of supplementing ruminants with copper and selenium, and avoid the possible interactions between an oral supplement and other dietary constituents. The copper preparations studied contained copper complexed with calcium edetate (EDTA) or copper methionate , copper oxide or copper oxyquinoline sulphonate. The recommended doses of these commercial preparations contain different amounts of copper only part of which is transferred to the liver stores from which it can be released during the following months. The recommended dose of copper oxyquinoline sulphonate contains only 12 mg copper and the duration of its protective effect is short. Only a small proportion of the copper in copper methionate and copper oxide is transferred to the liver whereas nearly all the copper in a single dose of the EDTA complex (50 mg copper for sheep) is transferred to the liver stores. Although no longer recommended for use in sheep the copper EDTA complex can be administered to cattle to provide up to 1 mg copper/kg bodyweight. Selenium deficiency in both cattle and sheep can be corrected by the subcutaneous administration of up to 0.15 mg selenium/kg bodyweight as sodium selenate. However, if a dietary deficiency persists copper and selenium treatments are effective for only a few months. To avoid the need for repeated treatments, slowly dissolving or controlled release systems have been developed. Subcutaneous depots of barium selenate have been used (1 mg selenium/kg bodyweight) but large residues remained at the site of injection for up to three months. Initial trials with controlled release glasses containing copper have shown that they maybe useful for routine parenteral therapy.

Effects of selenium and copper supplementation on the growth of beef steers.

During the grazing seasons of 1978 and 1979, 126 Hereford cross Friesian and 25 Charolais cross Friesian steers were used in controlled trials of the effects of injecting them with copper and, or, selenium. In both seasons the unsupplemented steers had low blood concentrations of copper, selenium and glutathione peroxidase, whereas the supplemented steers maintained their serum copper concentrations within the normal range and had significantly higher whole blood concentrations of selenium and glutathione peroxidase than the unsupplemented animals. Supplementing the steers with 400 mg copper during 1978 increased their growth rate by 0.032 kg/day and supplementing them with 200 mg copper during 1979 increased it by 0.080 kg/day. Supplementing the steers in each year with two doses of selenium, each of 0.15 mg selenium/kg bodyweight, increased their growth rate by 0.041 kg/day in 1978 and by 0.060 kg/day in 1979. There was no interaction between the selenium and copper treatments and the total increases in liveweight gains due to both supplements were around 11 kg in 1978 and 16 kg in 1979.

A field trial of 1alpha-hydroxycholecalciferol (1alpha-OH D3) in the prevention of milk fever.

The efficacy of 1alpha-OH cholecalciferol for the prevention of milk fever has been tested in a controlled field trial using 597 cows on 19 farms all of which had previously had a high incidence of milk fever. Of 293 cows receiving 1alpha-OH cholecalciferol 34 had milk fever and of 304 control cows 51 had milk fever. Although there was an apparent efficacy of 31 per cent the difference in incidence was not statistically significant. There was no effect if 1alpha-OH cholecalciferol was administered less than 24 hours before the cows succumbed to milk fever. However, if 1alpha-OH cholecalciferol was administered more than 24 hours and less than one week before the occurrence of milk fever the efficacy increased to 61 per cent and the effect was highly significant.

Use of 1alpha-OH cholecalciferol in preventing post parturient hypocalcaemia and its potential value for the prevention of milk fever in dairy cows.

Cows which received 250 mug 1alpha-hydroxy cholecalciferol (1alpha-OH D3) intramuscularly within two hours after calving suffered significantly less post-parturinet hypocalcaemia and hypophosphataemia than control cows. There was a small depression in plasma magnesium concentrations in the treated cows. 1alpha-OH D3 shows potential for the prevention or treatment of milk fever.