Effect of high doses of a sustained-release bovine somatotropin on antibody formation in dairy cows.

Eighty-two lactating Holstein cows received either one, three, or five concurrent, intramuscular injections of a unit dose (.6 g) of zinc methionyl bST (some-tribove) or five doses of the vehicle. Injections were administered at 14-d intervals from 60 d postpartum until the end of lactation or necropsy. Thirty-eight cows continued on the same treatment for a 2nd yr. Blood bST antibodies developed within the first 7 wk of treatment, and the number of cows with anti-bST binding generally declined with time. Thirteen out of 59 cows receiving bST developed binding activity > 25% (positives) during the 1st yr. At the .6-g dose level, no binding was detected after wk 15. Seven of the 13 positive cows were among the group randomly selected to continue on study during yr 2. In the 2nd yr, only 2 out of 24 bST-treated cows were positive. Binding activity was associated with the IgG fraction in serum. Binding capacities of antibodies ranged from .625 to 3.04 mg of bST/L, and affinities ranged from 1.14 x 10(8) to 3.14 x 10(8) L/mol. Cows considered to be clinically positive had performance similar to those of their herdmates having binding < 25%. No evidence of a pathologic effect of antibodies existed in treated cows, their calves, or fetuses. The presence of anti-bST antibodies did not affect milk production of the cow or growth of the calves conceived during bST treatment.

Response of dairy cows to high doses of a sustained-release bovine somatotropin administered during two lactations. 1. Production response.

This study evaluated the effect of sometribove (zinc methionyl bST) in a sustained-release formulation administered to lactating cows at concentrations up to 3.0 g every 14 d over two lactations. Eighty-two lactating Holstein cows in their first, second, or third lactation were assigned to the study. Cows received .6, 1.8, or 3.0 g of bST in one, three, or five intramuscular injections of a unit dose (.6 g) every 2 wk. Controls received five injections of the vehicle (equivalent volume to the 3.0-g treatment) every 2 wk. Injections were administered from 60 +/- 3 d postpartum until dry-off or necropsy. Thirty-eight animals were continued on treatment for a second consecutive lactation. During the 1st yr of treatment, bST increased mean 3.5% FCM by 7.2, 9.4, and 8.4 kg/d over control production (21.1 kg/d). During the 2nd yr, milk response to .6, 1.8, and 3.0 g of bST averaged 10.6, 3.6, and 4.9 kg/d over controls (24.8 kg/d). The incidence of clinical mastitis increased in the 3.0-g group relative to controls during the 2nd yr. Thus, salable FCM averaged 8.1, 9.1, and 6.2 kg/d above controls (yr 1) and 12.1, 4.7, and -2.8 kg/d (yr 2) for the .6-, 1.8-, and 3.0-g groups. Salable FCM was unaffected by mastitis at a proposed commercial dose (.6 g). Milk fat, protein, lactose, calcium, phosphorus, zinc, magnesium, and ash concentrations were unaffected by bST treatment. Calculated energy, calcium, phosphorus, and protein balances also were unaffected except for early decreases of up to 5 Mcal/d, and 40, 20, and 600 g/d, respectively, until feed intake increased. Milk serum bST concentrations greater than the assay limit of sensitivity (1 ng/ml) were routinely measurable only at doses of 1.8 and 3.0 g. Results confirmed that bST concentrations in milk serum are exceedingly small. Overall, supraphysiological doses of sometribove increased milk production with little effect on composition. No toxic effects of bST were observed.

Factors affecting insulin-like growth factor-I concentration in bovine milk.

To establish the naturally occurring range of insulin-like growth factor-I concentrations in bovine milk, samples from individual cows (n = 409) managed on five Missouri dairy herds were assayed. Parity, stage of lactation, and farm affected milk insulin-like growth factor-I concentration. Milk insulin-like growth factor-I concentration was higher in early lactation than mid and late lactation with concentrations in multiparous cows exceeding those in primiparous cows. Insulin-like growth factor-I concentration was negatively correlated to milk production the day of sample collection (r = -.15) and not correlated to predicted 305-d milk yields. Unprocessed bulk tank milk samples (n = 100) from a commercial processing plant had a mean concentration of insulin-like growth factor-I in milk of 4.32 ng/ml with a range of 1.27 to 8.10 ng/ml. This distribution was similar to the range detected in samples from individual cows, but values were lower than those reported for human milk. Concentration of insulin-like growth factor-I in milk was not altered by pasteurization (at 79 degrees C for 45 s). However, insulin-like growth factor-I was undetectable in milk heated to temperatures (121 degrees C for 5 min) required for infant formula preparation or in commercially available infant formula. These data indicated that insulin-like growth factor-I is a normal but quantitatively variable component of bovine milk that is not destroyed by pasteurization but is undetectable in infant formula. Concentration of insulin-like growth factor-I in bovine milk is lower than concentrations reported for human milk yet similar to those reported for human saliva.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue culture cytotoxicity assay for cyclophosphamide metabolites in rat body fluids.

An in vitro cytotoxicity assay for cyclophosphamide metabolites in rat body fluids is described. Of the two tissue culture tumor cell lines employed, the Walker-256 rat carcinosarcoma was more sensitive to metabolite levels than the L-1210 mouse lymphocytic leukemia. The Walker-256 system detected cyclophosphamide metabolite levels two orders of magnitude lower than the commonly used 4-(p-nitrobenzyl)pyridine analytical procedure.