The effect of a monensin ruminal delivery device on performance of cattle grazing pasture.

A total of 28 trials utilizing 2,262 steers and heifers were conducted to evaluate a sustained monensin2 ruminal delivery device (RDD) on the daily gain of grazing cattle. Five series of trials, with four to eight trials per series within a grazing season, were conducted to evaluate the daily gain response under different environmental conditions and locations. Pastures grazed included both summer (cool- and warm-season grasses and native range) and winter (rye, ryegrass and wheat) growing pastures. The experimental design for all trials in each of five series was a randomized complete block with initial weight or breed as the blocking factor. The treatments compared in series I, III, IV and V (20 trials) were a control and a single RDD, whereas in series II (eight trials), a 2 x 2 factorial was utilized that compared RDD and estradiol 17-beta controlled release implants. In the five series of trials, the monensin RDD increased daily gain .04 (P = .002), .03 (P = .07), .09 (P = .01), .05 (P = .10) and .08 kg (P = .04) compared with the controls. Use of the RDD provided an effective method of achieving consistent monensin delivery and weight gain improvement without requiring the extra labor needed to administer monensin via hand-feeding or self-feeding supplements, blocks or loose mineral.

Factors affecting retention of estradiol-17 beta silicone rubber implants in ears of steers.

A series of trials were conducted to identify the factors causing loss of estradiol-17 beta (E2-beta) silicone rubber implants from the ears of cattle and to evaluate methods of reducing this loss. Surface application of cattle feces to the ears before implanting resulted in an increase in loss of implants compared with the loss from dry, clean ears (30.6 vs 8.6%; P less than .05). Washing ears with a povidone-iodine antiseptic solution before implanting or treating implant sites with an antibiotic after implanting reduced (P less than .05) implant loss when ears were coated with the fecal slurry. Coating silicone rubber implants with .5 to 2 mg of oxytetracycline hydrochloride (OTC) reduced (P less than .0001) implant loss from 39.8 to 13.8% when ears were coated with fecal slurry. When silicone rubber implants with a 1.5-mg coating of OTC were implanted in cattle before submerging in a dipping vat, implant loss was reduced from 6.2 to 2.7%. In studies designed to evaluate mechanical factors affecting implant loss, implants that were placed in the middle of the ear in tight skin moved .79 cm toward the insertion site during a 14-d period after administration compared with 2.82 cm when placed in the base of the ear. When placed in the middle of the ear in tight skin, only 2 of 399 (.5%) implants were lost from steers submerged in a dipping vat immediately following implantation compared with 42 of 394 (10.7%) when placed in the base of the ear (P less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical field trials with tilmicosin phosphate in feed for the control of naturally acquired pneumonia caused by Actinobacillus pleuropneumoniae and Pasteurella multocida in swine.

OBJECTIVE: To determine and evaluate the efficacy of the dose range of tilmicosin phosphate fed to pigs for control of pneumonia attributable to Actinobacillus pleuropneumoniae during episodes of clinical disease in commercial herds. DESIGN: 12 trials were run in 9 geographic locations in herds with a history of pneumonia caused by A pleuropneumoniae. ANIMALS: Clinically normal male and female pigs of various body weights. PROCEDURE: Two doses of tilmicosin phosphate (200 and 400 micrograms/g) and a 0 dose were administered in the feed for 21 days. Variables for determining efficacy were daily independent composite clinical impression score, individual pig weight, mortality, percentage of pneumonic involvement, and frequency of isolation of bacterial pathogens. RESULTS: Medicated pigs had significantly lower mortality attributed to pneumonia than did nonmedicated pigs. In trials with confirmed pneumonia caused by A pleuropneumoniae or Pasteurella multocida, weight gain, feed conversion, and clinical impression scores were significantly improved in the pigs receiving 200 or 400 micrograms/g of tilmicosin, compared with nonmedicated pigs. CONCLUSIONS: The clinical field trials reported here confirm that tilmicosin in the feed at 200 micrograms/g is effective for control of swine pneumonia attributable to A pleuropneumoniae or P multocida. CLINICAL RELEVANCE: Under the moderate natural challenge conditions encountered, tilmicosin at 400 micrograms/g was not different from tilmicosin at 200 micrograms/g.

Lactation response and body composition of cows receiving somatotropin and three ratios of forage to concentrate.

Ninety multiparous Holstein cows were used to determine the effect of ration energy density and bST on lactation performance and whole body chemical composition. Seventy-eight cows, averaging 43.6 d postpartum, were assigned for 168 d to TMR with forage: concentrate ratios of 40:60, 50:50, and 60:40 (DM basis). Half of the cows on each ration received subcutaneously either 0 or 640 mg bST/28 d. Whole body chemical composition was determined by comparative slaughter in 12 cows (means = 35.9 d postpartum) prior to initiation of treatment and in 35 cows after either 84 or 168 d of treatment. Net energy intake was greater for 40:60 and 50:50 than for 60:40. Milk fat percentage was reduced in cows fed 40:60. Ration did not affect milk, 3.5% FCM, and DMI. There were no differences among rations for total body fat, protein, water, and calories. The bST increased milk and 3.5% FCM but had no effect on DM and net energy intakes. Yield of 3.5% FCM by cows receiving bST and fed 40:60 was 1.9 kg/d more and for 50:50 it was 2.7 kg/d more than for those fed 60:40. Administration of bST reduced total body fat and calories but did not affect protein and water. Partitioning of calories to milk at the expense of fat deposition is the primary mechanism for the galactopoietic action of bST.

Lactation response of dairy cows receiving bovine somatotropin and fed rations varying in crude protein and undegradable intake protein.

Our experiment evaluated lactation and metabolic responses of Holstein cows injected with somidobove (recombinant bST) and fed one of four isocaloric rations containing either 14 (low) or 17% (high) CP and undegradable intake protein of 33 (low) or 40% (high) of CP. Multiparous cows (n = 37) in early lactation, averaging 37 kg/d of milk, received somidobove (640 mg per injection) at 28-d intervals for 112 d and one of four protein rations: low-low, low-high, high-low, and high-high. Nine other multiparous controls were fed low-low ration with no somidobove. On the low-low ration, somidobove significantly increased milk yield by 2.3 kg/d, but not 3.5% FCM (1.7 kg/d), intakes of DM or CP, or milk composition. Milk and 3.5% FCM increased by 1.7 and 2.1 kg/d in cows fed high undegradable intake protein but there was no effect on milk composition, BW, or DM intake. Ration CP had no effect on production variables in cows receiving somidobove. Serum urea was higher in cows fed high CP rations; undegradable intake protein was without effect. Plasma leucine was higher in cows fed high undegradable intake protein. Administration of somidobove to cows fed low-low rations reduced plasma methionine, serum albumin, hemoglobin, and albumin:globulin ratio. Milk production of high producing dairy cows receiving somidobove may be limited by the amount of protein available at the small intestine.

Milk production in lactating buffalo receiving recombinantly produced bovine somatotropin.

Thirty healthy Murrah buffalo (Bubalus bubalis) in their second to fourth lactations were selected from the herd at the National Dairy Research Institute, Karnal, Haryana, India, for use in a 35-d study to determine the effects of recombinantly produced bovine somatotropin on milk production, milk composition, and dry matter intake. Treatments were daily injections of 0, 25, or 50 mg somatotropin per animal for 14 d. All buffalo consumed green chopped fodder ad libitum plus a predetermined quantity of concentrate mixture to each animal, based on individual milk production during the 14-d pretreatment period. The quantity of concentrate mixture fed to each buffalo was not altered during the study. Net increase in milk volume for groups receiving 25 and 30 mg somatotropin was 16.8 and 29.5% over controls. Milk composition, DM intake, and body weights were not affected by treatment.

Lactation response of dairy cows receiving bovine somatotropin via daily injections or in a sustained-release vehicle.

Three experiments were conducted to characterize metabolic and milk production responses of dairy cows receiving recombinantly derived bovine somatotropin administered either by daily injection or in a sustained-release vehicle. In Experiment 1, somatotropin (25 mg/d) purified by two methods was given by daily injection for 14 d and resulted in 3.5 and 3.8 kg/d more milk than controls. Percentages of fat and total solids in milk were also increased by somatotropin. Eleven hematology indices and 12 metabolites, minerals, and enzyme activities in serum were unaffected by somatotropin. In Experiments 2 and 3, somatotropin was administered in a sustained-release vehicle during an 84-d treatment period. In Experiment 2, administration of 960 mg of somatotropin at 28-d intervals increased milk and SCM yields by 4.1 and 3.3 kg/d compared with yields of controls. There were no significant differences in other production parameters. In Experiment 3, 320, 640, and 960 mg somatotropin were each administered in the sustained-release vehicle at intervals of 14, 21, and 28 d. An uninjected group served as control. Cows receiving somatotropin averaged 3.5 to 5.9 kg/d more milk than controls across all injection intervals. Among doses, milk yield was greater at 960 mg than at 320 or 640 mg. There were no significant differences in milk or SCM among injection groups. These experiments demonstrate the comparable efficacy of somatotropin when given by daily injections or in a sustained-release vehicle.

The effects of a sustained-release recombinant bovine somatotropin (somidobove) on udder health for a full lactation.

The lactational effect of somidobove (recombinant bST) injections on dairy cows in a full lactation was measured in 193 primiparous and 159 multiparous Holsteins. Experimental animals, distributed across six study sites, were administered a sustained-release formulation of somidobove by subcutaneous injection every 28 d beginning 36 to 49 DIM. Randomization at each site determined which of the following somidobove treatments cows received: 0 mg (control), 160 mg (primiparous only), 320 mg, 640 mg, or 960 mg (multiparous only). In addition to lactation response, cows on study were monitored for mastitis. Clinical mastitis was detected by examination of quarter foremilk at each milking. Milk from 300 of 352 cows was monitored for new IMI by routine collection and culture of duplicate quarter milk samples. Somatic cell counts were conducted on individual composite milk samples collected weekly throughout the experiment. No evidence existed of an association between somidobove administration and the incidence or duration of clinical mastitis. Furthermore, somidobove administration was not associated with an increase in new IMI or prevalence of infection by common mastitis pathogens or pathogen groups. Somatic cell counts were low in all treatment groups, but a dose-related trend was found for increased SCC in both primiparous and multiparous cows.

Tmax: an unconfounded metric for rate of absorption in single dose bioequivalence studies.

PURPOSE: While peak drug concentration (Cmax) is recognized to be contaminated by the extent of absorption, it has long served as the indicator of change in absorption rate in bioequivalence studies. This concentration measure per se is a measure of extreme drug exposure, not absorption rate. This paper redirects attention to Tmax as the absorption rate variable. METHODS: We show that the time to peak measure (Tmax), if obtained from equally spaced sampling times during the suspected absorption phase, defines a count process which encapsulates the rate of absorption. Furthermore such count data appear to follow the single parameter Poisson distribution which characterizes the rate of many a discrete process, and which therefore supplies the proper theoretical basis to compare two or more formulations for differences in the rate of absorption. This paper urges limiting the use of peak height measures based on Cmax to evaluate only for dose-dumping, a legitimate safety concern with any formulation. These principles and techniques are illustrated by a bioequivalence study in which two test suspensions are compared to a reference formulation. RESULTS: Appropriate statistical evaluation of absorption rate via Tmax supports bioequivalence, whereas the customary analysis with Cmax leads to rejection of bioequivalence. This suggests that the inappropriate use of Cmax as a surrogate metric for absorption rate contributes to the unpredictable and uncertain outcome in bioequivalence evaluation today.

Why rate of absorption inferences in single dose bioequivalence studies are often inappropriate.

PURPOSE: Peak drug concentration (Cmax) measures the extremity of drug exposure and is a secondary indicator of the extent of absorption after area under the concentration time curve (AUC). Cmax serves as the indicator of absorption rate in bioequivalence (BE) studies in the US (1). The use of Cmax, not the time to Cmax (Tmax), as the metric to assess absorption rate causes erratic inferences in BE studies, and incorrect conclusions for some. We can improve BE efficiency (i.e., get the answer right the first time), by properly analyzing the time to Cmax (Tmax) instead of Cmax. METHODS: We have previously redirected attention to Tmax as the unconfounded absorption rate variable, instead of Cmax, and have called for equally spaced sampling times during the suspected absorption phase to improve the performance of the rate metric (2). Equal spacing converts Tmax easily into a count variable and we illustrated an appropriate statistical analysis for counts. This paper provides some measurement theory concepts to help judge which is the more appropriate analysis, and also provides parametric confidence limits for Tmax treatment differences. Three separate BE studies are then analyzed by both methods. RESULTS: By focusing on the differences in conclusions, or inferences, this paper identifies three major issues with the current FDA "recommended" analysis of BE studies. First, Cmax, a continuous variable peak-height or extent measure has usurped Tmax's function and performs erratically as a substitute measure for the rate of absorption. Second, Tmax, should be analyzed as a discrete attribute, not as a continuous variable. Third, since several extent measures (AUC, Cmax), not one, are actually being analyzed, an adjustment for multiple testing is mandatory if we are to maintain the size of the test at the desired alpha level (13), and not inadvertently use a narrower bioequivalence window than is intended. These actions all can have serious unintended consequences on inferences, including making inappropriate ones.

Pyelonephritis therapy in rats: random association with excreted urinary antibacterial activity.

In vitro activities or excreted urinary activities of 56 generic and experimental drugs against two organisms commonly associated with human pyelonephritis, Escherichia coli and Proteus mirabilis, are not correlated with the in vivo activities of these compounds as measured by reduction of viable organisms in kidneys in experimental pyelonephritis.

Effect of somidobove sustained release administration on the lactation performance of dairy cows.

Lactation performance was determined on 190 multiparous Holsteins from five herds supplemented with 0, 320, 640, or 960 mg of somidobove every 28 d. The experiment consisted of 21 d of pretreatment and treatment periods of various lengths, depending upon stage of lactation of animals at first administration. Somidobove beginning in early (28 to 45 d in milk), mid (111 to 166 d in milk), or late (166 to 334 d in milk) stages of lactation consisted of 9, 6, or 3 administrations. Milk and 3.5% FCM yields were increased by each dose of somidobove in all stages. Milk composition and dry matter and energy intakes were similar among treatments within stage. Milk to DMI ratio and milk energy to net energy intake ratio were improved by somidobove. Gain was positive for all treatments, but less in somidobove-supplemented cows. Lower body weight and condition score at the completion of somidobove treatment resulted. For early cows, days to first estrus and days to first breeding were similar; however, total number of inseminations for cows receiving somidobove was twofold greater than control, resulting in a longer calving interval. Results demonstrated efficacy of somidobove administered every 28 d to lactating dairy cattle for increased milk yield.