Fenbendazole-related drug residues in milk from treated dairy cows.

Oral administration of [14C] fenbendazole (FBZ) at a dose of 5.0 mg/kg leads to the presence of radiolabel in the milk of lactating dairy cows. However, the maximum mean concentration of total FBZ equivalents quantitated to one-third of the recommended safe concentration in milk (1.67 micrograms/mL). The label is equally distributed to the fat and aqueous portions of the milk. The maximum level, in general, is attained approximately 24-36 h after drug administration, with the highest levels ranging from 24 to 48 h after administration. The residues rapidly deplete, attaining levels of 10-20 ng/mL by day 5, and are essentially undetectable by radiolabel monitoring by day 6. Extraction of the milk by matrix solid phase dispersion indicated that the label was distributed between traces of the parent drug, FBZ, and predominantly, the FBZ sulphoxide (SO) and sulphone (SO2) metabolites. No other radiolabelled peaks were observed. Based on these data the metabolites of FBZ, FBZ-sulphone and FBZ-sulphoxide, could be used as marker residues for monitoring the administration of FBZ to lactating dairy cows.

Influence of nitrogen fertilization and defoliation frequency on nitrogen constituents and feeding value of annual ryegrass.

Two experiments were conducted to determine the seasonal effects of N fertilizer (NF) and defoliation interval (DI) on specific N fractions within annual ryegrass (AR) and overall usage of AR N by growing lambs. In Exp. 1, NF (0, 112, 224, and 336 kg of N/ha) and DI of 2, 4, or 6 wk were factorially applied to AR plots. Both decreasing DI and increasing NF increased N levels in AR in a manner that depended on harvest date (NF or DI x harvest date interaction, P < .05). The proportions of .2% NaOH soluble N or soluble protein N were not affected (P > .05) by NF or DI. Although NF had no effect (P > .05) on in situ disappearance of DM, decreasing the DI seemed to reduce the severity of the season-induced reduction in DM disappearance (DI x harvest date interaction, P = .04). In Exp. 2, NF (0 or 224 kg of N/ha) and a DI of 2 or 6 wk were factorially applied to AR plots. Fresh, frozen AR was fed in semipurified diets (48% of DM as AR) to four wether lambs (23 +/- 1.3 kg) using a 4 x 4 Latin square. Diets including AR had greater ruminal DM and plant N digestibilities when AR had a 2-wk vs a 6-wk DI with NF but had reduced digestibilities when AR had a 2-wk vs a 6-wk DI without NF.(ABSTRACT TRUNCATED AT 250 WORDS)

Suboptimal levels of dietary copper vary immunoresponsiveness in rats.

The effects of severe, moderate, and mild copper deficiencies on cellular and humoral immunity were studied. Fifty male Sprague-Dawley rats, 5 wk of age, were fed diets containing 0.5, 2.0, 3.5, or 5.0 micrograms Cu/g for either 4 or 8 wk. Ten of the rats were fed the control diet, but were pair-fed with the 0.5-micrograms/g treatment group. All rats were immunized once with sheep red blood cells. Mean plasma-copper concentration reflected the dietary levels of copper, and ceruloplasmin activity correlated highly to plasma copper. Rats consuming suboptimal levels of copper responded differently to the deficiencies, so copper status varied among those animals. After 8 wk, cell proliferation, when stimulated by phytohemagglutinin, was dependent on the copper status of the animal. Severely deficient rats had consistently lower lymphocyte stimulation indexes for phytohemagglutinin and concanavalin A, but specific antibody response was not reduced. Immunoglobulin G (IgG) concentrations were variable for all rats, and immunoglobulin M (IgM) concentrations were lower for the severely deficient rats. Suboptimal dietary copper may alter immune function in rats, depending on the ensuing effect on copper status.

Management practices to overcome the incidence of grass tetany.

To minimize the incidence of grass tetany, winter pastures should be established on soils containing Mg-rich minerals, drainage should be improved on five-textured soils, legumes should be included in the sward and soil pH should be at least 5.5. Liming acid soils with dolomitic lime increases forage Mg by supplying Mg and by raising soil pH. Calcitic lime applications also can increase Mg availability to plants on soils with adequate Mg. Low rates of application of soluble Mg salts (less than 100 kg/ha of Mg) effectively increase Mg uptake from noncalcareous soils with low cation exchange capacity. Potassium levels in soils and plants should be kept in the lower range of recommended values. Nitrogen application should be regulated to provide the desired level of forage production. Nitrogen fertilizers, especially the nitrate form, stimulate plant Mg uptake if Mg is available in the soil. The most practical and cost-efficient method of supplementing dietary Mg intake is to provide free-choice Mg. Supplements must be palatable and placed in locations frequently used by cow herds. Including a high-energy feed in the supplement may at times increase its preventive effectiveness by increasing Mg absorption and reducing lipolysis. Regardless of the supplement formulation, Mg intake should be monitored on a regular basis, and formulation or management changes should be initiated if Mg consumption is below required levels. In severe grass tetany outbreaks, foliar application of Mg or administration of Mg via the drinking water may be warranted.

Metabolic profile testing.

Metabolic profiles have been used in efforts to predict periparturient problems and fertility, to diagnose metabolic disease, and to assess nutritional status. Results have been varied. Until knowledge and technology provide improved blood constituent panels, the metabolic profile should not be the first step in the diagnostic process. Rather, such profiles should follow an assessment of management practices and an evaluation of diet. However, these profiles may help to confirm the diagnosis, to convince dairy farmers that management changes are desirable, or to monitor improvement in herd animals. At this point, their major contribution has been to increase our understanding of the factors contributing to changes in blood constituent concentrations, which, in turn, has led to more efficient means of diagnosis. Except in cases of gross mismanagement, these profiles do not offer a "quick fix." In many of the reported cases in which diagnosis of herd problems was attributed to the metabolic profile, the clinician should have been able to identify the problem before the profile was conducted. Profiles are to be recommended when the cause of an existing problem is still not identified or resolved after a complete evaluation. The profile may aid in identifying a factor that has been overlooked. Profiles are not for clinicians who do not have an interest in upgrading their understanding of the factors involved, or who do not have a source of knowledgeable advice.

Correction of subnormal fertility with copper and magnesium supplementation.

Two hundred and four Holstein cows and heifers were randomly assigned to mineral supplement groups 30 d prior to expected calving. Supplement treatment groups were Cu, Mg, Cu plus Mg, and no mineral supplement. The total diet of supplemented groups averaged 15 mg/kg of Cu and .30% of Mg. Pastures consisted of bermudagrass, bahiagrass, and millet during the summer and oats and ryegrass mixture during the winter. Corn and sorghum silage were also fed. Blood samples were taken just prior to initiation of mineral supplementation and at wk 1, 2, 4, 6, and 8 postpartum. Hemoglobin and packed cell volume were determined and plasma was assayed for Cu and Mg. First service conception rates were 57% for the Cu plus Mg treatment and 27, 38, and 33% for treatments 1, 2, and 4, respectively. Ninety-two percent of the cows in the Cu plus Mg-group conceived by 210 d postpartum as opposed to an average of 75% for the other groups. Plasma Mg was different among cows grouped on a fertility basis and hemoglobin was correlated with days to conception. Plasma Mg was correlated with hemoglobin. Both were inversely related to postcalving infection and uterine involution. In summary, cows supplemented with both Cu and Mg showed improved fertility, whereas those supplemented with Cu or Mg alone did not.

Pharmacokinetics of pentobarbital and thiamylal as combined anesthetics in sheep.

This study was performed to investigate the possible mechanisms underlying prolongation of anesthesia times in sheep caused by the sequential administration of thiamylal and pentobarbital. Sodium thiamylal was injected as an intravenous bolus dose (13.2 mg/kg) followed in 7 min by sodium pentobarbital (14.3 mg/kg) by the same route to seven sheep. Separate studies were conducted for each of the two drugs administered separately to the same animals at the same doses. Mean anesthesia times (to the return of the palpebral reflex) were 7.89 min (thiamylal), 5.39 min (pentobarbital) and 34.1 min (the sequential combination). The kinetic parameters Vd(area), Vd(ss), t 1/2 beta, and ClB for either drug were not affected by the other when given in combination. The t 1/2 alpha was shorter, and the Vc was smaller, for pentobarbital when administered with thiamylal, while there were no changes in thiamylal disposition for the combination regimen. Computer-generated curves, associated with the two-compartment open model showing the fraction of dose in each compartment as a function of time, illustrated that pentobarbital rapidly achieved higher concentrations in the peripheral compartment after prior thiamylal administration. Protein-binding studies showed that this could not be attributed to displacement of pentobarbital from plasma albumin by thiamylal. Calculation of total and free drug concentrations at the time of awakening showed that, when the drugs were combined, the concentration of each drug was less than half of that observed at awakening when they were studied separately. It can be concluded that the prolonged sleeping times associated with the sequential combination of the two agents were not due to an alteration in kinetic parameters of either drug caused by the other, but rather to an additive effect of the subanesthetic concentrations of the two drugs when combined. The fact that sleeping times were supra-additive is attributed to a shift of awakening time from the distribution (alpha) phase, when given independently, to the elimination (beta) phase when administered in combination.

Relationship between fertility and blood glucose and cholesterol concentrations in Holstein cows.

Jugular blood samples were collected prepartum and postpartum from 97 Holstein cows and heifers. Samples were analyzed for total serum cholesterol and plasma glucose. Plasma samples taken 4, 11, 18, and 25 days postpartum were also analyzed for progesterone. Concentrations of cholesterol, glucose, and progesterone were evaluated in relation to summer- and winter-calving seasons, milk production, lactation number, days-to-conception, number of postcalving uterine infusions given, and time relative to calving. A temperature-humidity index was used as a covariate in the analysis to adjust the data for climatic effects so that seasonal effects other than temperature and humidity could be determined. Average plasma glucose was within the normal range (62 +/- 8 mg/dl). It increased before calving and then declined to a minimum value between 11 and 25 days postpartum. Glucose then increased after 25 days for the summer-calving group and remained relatively stable for the winter-calving cows. Blood glucose concentrations were inversely related to milk production. Negative correlations existed between milk production and plasma glucose at days 4, 11, 18, 25, and 39 postpartum. First-lactation heifers had higher blood glucose levels than cows in their second or later lactation. Blood glucose concentrations were not related to days-to-conception over both seasons. Average serum cholesterol was within the normal range (125 +/- 29 mg/dl). It decreased before calving and then increased for 88 days after calving. Summer-calving cows had higher serum cholesterol concentrations prepartum and winter-calving cows had higher concentrations from 39 through 88 days postpartum. Cholesterol concentrations were directly related to milk production from 25 through 88 days postpartum.(ABSTRACT TRUNCATED AT 250 WORDS)

Selenium concentrations in feeds and effects of treating pregnant Holstein cows with selenium and vitamin E on blood selenium values and reproductive performance.

Holstein cows (n = 104) and heifers (n = 35) were used to determine the effects of treatment with selenium (Se) and vitamin E on whole blood Se values and fertility. At 21 +/- 3 days before parturition, 55 cows and 19 heifers were injected with 680 IU of vitamin E and 50 mg of Se as sodium selenite. Treatment had no effect on days to first estrus, days to first service, days to conception, services per conception, or number of uterine infusions required. Blood samples were obtained from 33 nontreated cows and heifers and 32 treated animals at 21 and 14 days (+/- 3) before calving and at 7 and 14 days (+/- 3) after calving. Mean whole blood Se level at -21 days (day 0 was day of parturition) and before Se-vitamin E treatment was 0.109 micrograms/ml. At days -14, 7, and 14, blood Se was significantly higher in the treated than the non-treated animals. Blood Se was lower on all sampling days in cows calving in July through November than in cows calving in December through April. Heifers in their 1st lactation had lower blood Se concentrations than did cows in their 2nd or later lactation. In feeds sampled at 2-week intervals, mean concentrations of Se in Bahia grass, mixed ryegrass and oats, corn silage, and sorghum silage were less than 0.1 micrograms/g on a dry matter basis. Bermuda grass, alfalfa hay, and concentrates contained greater than 0.1 micrograms of Se/g. Large variation existed in Se concentrations of individual feedstuffs.

Plasma copper concentration and packed cell volume and their relationships to fertility and milk production in Holstein cows.

Jugular blood samples were obtained from 55 summer-calving and 40 winter-calving Holstein cows fed diets which averaged 7.4 micrograms of Cu/g. Samples were collected within 3 days of 30, 11, and 4 days before calving and 4, 11, 18, 25, 39, 60, 88, 116, and 147 days after calving. Packed cell volume and plasma Cu concentrations were determined. Blood components were analyzed in relationship to season, milk production, lactation number, number of days to conception, number of postcalving uterine infusions, and time relative to calving. The environmental temperature-humidity index was used as a covariate in the analysis, so that seasonal effects represented feeding or production differences between seasons and were not due to the direct effects of climate. Plasma Cu concentrations were within the usual laboratory limits (1.05 +/- 0.20 microgram/ml). These values were unrelated to PCV in the summer-calving cows, but were slightly related in the winter-calving cows (r = 0.11). Plasma Cu values increased around the time of calving, with the maximum level (1.13 microgram/ml) occurring on postpartum day 11. Plasma Cu concentration was higher in cows that conceived within 80 days of calving than in cows which conceived at 120 days or more. Differences in plasma Cu among fertility groups were most evident during postpartum days 25 to 60. However, the relationship between plasma Cu concentrations and fertility was not consistent. Significant interactions existed for season X fertility groups and milk production groups X fertility groups. Plasma Cu concentration was significantly higher for the summer-calving cows and was inversely related to milk production level.(ABSTRACT TRUNCATED AT 250 WORDS)