Efficacy and local tolerance of a low-dose, 7-day matrix estradiol transdermal system in the treatment of menopausal vasomotor symptoms.

OBJECTIVE: To determine the efficacy and local tolerance of a new matrix transdermal drug-delivery system that delivers 0.02 mg of 17 beta-estradiol (E2) daily for 7 days for the relief of vasomotor symptoms. METHODS: A total of 324 surgically or naturally menopausal women, all with prior hysterectomy and moderate to severe vasomotor symptoms (56-140 hot flushes per week, with episodes of sweating, during a baseline observation period), participated in two independent, 12-week, randomized, double-blind, placebo-controlled studies. After a 4-week, treatment-free period, each woman received a continuous regimen of either one E2 transdermal system, two E2 transdermal systems, or placebo transdermal system(s) applied every week for 12 weeks. Efficacy was measured as reduction in hot flush frequency, determined from subject diaries. To measure local tolerance, skin irritation (erythema and edema) was objectively and systematically evaluated under blue light after removal of the transdermal system(s). Serum E2 and estrone concentrations were determined in one of the studies during baseline and on days 1, 9, 30, 58, 79, and 84. RESULTS: Mean hot flush frequency decreased from 80 hot flushes per week at baseline to approximately 13 hot flushes per week (84% decrease) after 12 weeks of transdermal E2 treatment. Compared with placebo, the decrease in hot flush frequency was significant as early as weeks 2 and 3, and was maintained through the end of the study. Few clinically significant skin reactions occurred, and only nine (3%) of the subjects withdrew because of a skin effect. After initial increase, serum E2 concentrations remained stable throughout the study, achieving values of approximately 20 and 40 pg/mL above baseline for one and two E2 transdermal systems, respectively. CONCLUSION: The E2 transdermal system effectively reduced the frequency of moderate to severe vasomotor symptoms as early as the second week of therapy and was very well tolerated. The decrease in hot flush frequency was similar to that reported for oral and other transdermal estrogens, but at lower serum E2 concentrations. This result may be due to the stable E2 blood level achieved with this transdermal system.

Factors affecting the in vitro production of volatile fatty acids by mixed bacterial populations from the bovine rumen.

Factors affecting in vitro ruminal bacterial VFA production were examined. Treatments consisted of high and low initial pH (6.7, 5.7), osmolality (600, 400 mOsm) and concentrations of acetic (40, 0 mM) and propionic acids (20, 0 mM). Response variables measured included the production of acetic, propionic and total VFA, total gas and methane. Initial pH affected (P less than .05) most variables either independently or in combination with one or more of the other factors. Acetic acid production was reduced 40% (P = .03) when initial acetic acid concentrations were 40 mM compared with 0 mM. Also, acetic acid production was less (P less than .01) at low initial pH (5.7) than at high initial pH (6.7). Propionic acid production was greater (P = .05) at high vs low initial acetic acid concentrations. Propionic acid production was greater in response to low vs high initial osmolality, although the magnitude of this difference depended on initial pH (interaction P = .02). Total production of VFA was greater (P less than .01) at high than at low initial pH; however, at low initial pH, no difference (P greater than .05) was observed due to initial osmolality, whereas at high pH, production was greater (interaction P = .04) for low than for high initial osmolality. The diminished production of total VFA at pH 5.7 occurred primarily due to reduced acetic acid production, although increased production of propionic and butyric acids was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of diet on water flux and volatile fatty acid concentrations in the rumen of growing beef steers fed once daily.

In vivo temporal changes in ruminal liquid flow, liquid volume and VFA concentrations were determined in growing steers following once-daily feeding. Crossbred beef steers (n = 8; 278 +/- 8 kg), used in a crossover design, were trained to consume 180% of their maintenance energy intake within 2 h of either a high-forage (54% hay: 46% concentrate; HF) or high-concentrate (28% hay: 72% concentrate; HC) diet. For each animal on each diet, ruminal VFA concentrations, liquid volumes and liquid dilution rates were determined during a 2-h period before feeding and during three consecutive 2-h periods following feeding. Water was withheld during these periods to observe physiologically rather than behaviorally induced changes. At equal energy intakes, diet alone had no effect on VFA concentrations (P greater than .10), although changes in total VFA, acetic and isobutyric acids differed during the time periods following feeding due to diet (diet x time period interaction; P less than or equal to .10). Ruminal volume and dilution rate were altered in a reciprocal manner due to diet, with greater volumes and lower dilution rates observed in HC than in HF steers. Differences among time periods were observed for dilution rate and propionic acid concentrations. In general, these differences can be explained by comparison of the prefeeding time period with the postfeeding time periods. A numerical, but not statistically significant, increase in ruminal volume was observed following feeding. The effects of diet on volume and liquid dilution rate of the rumen must be considered when assessing total nutrients available for animal absorption.

Recombinant bovine somatotropin improves growth performance in finishing beef steers.

The objectives of this study were to determine the efficacy of various doses of rbST on ADG and feed efficiency (FE) and to describe carcass composition changes in finishing beef steers. In Exp. 1, 96 crossbred beef steers (393 kg) received daily i.m. injections of buffer or 33, 100, or 300 micrograms/kg of BW of rbST (0ST, 33ST, 100ST, 300ST). In Exp. 2, 200 crossbred beef steers (417 kg) received daily i.m. injections of buffer or 8.25, 16.5, 33, or 66 micrograms/kg of BW or rbST (0ST, 8.25ST, 16.5ST, 33ST, 66ST). Treatments were administered until steer BW per pen averaged 540 kg in Exp. 1 and 560 kg in Exp. 2. An 86% concentrate: 14% roughage diet was fed once daily (CP: 16.5% in Exp. 1, 20.2% in Exp. 2). In Exp. 1, growth performance of steers receiving rbST was dose-dependent; ADG changed linearly (P = .01), DMI decreased linearly (P = .03), and FE changed quadratically (P less than .03). The 33ST steers responded with improved ADG and FE, 100ST with improved FE, and 300ST with lower ADG and poorer FE, compared with 0ST. In Exp. 2, the ADG response was quadratic (P = .01), DMI decreased linearly (P = .003), and FE improved quadratically (P = .004) with increasing dose of rbST. Steers receiving 16.5ST and 33ST responded with improved ADG and FE, whereas steers receiving 8.25ST and 66ST responded with improved FE but not ADG relative to 0ST steers. In Exp. 1 and 2, rbST administration altered carcass composition by increasing carcass protein and decreasing carcass fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of ceftiofur hydrochloride for treatment of experimentally induced colibacillosis in neonatal swine.

Ceftiofur hydrochloride was tested for effectiveness against induced colibacillosis in neonatal swine. In this model, pigs less than 12 hours old were inoculated via stomach tube with a virulent, K99+, nalidixic acid-resistant strain of Escherichia coli. Six hours after challenge exposure, 1 dose of ceftiofur was administered either IM or orally in experiment 1 and orally only in experiment 2. Mortality, shedding of bacteria, fecal consistency scores, and body weight changes were monitored for 10 days. In experiment 1 (n = 383 pigs), all treatments at dosage that ranged between 0.5 and 64.0 mg of ceftiofur/kg of body weight significantly (P less than 0.001) reduced mortality, bacterial shedding, and diarrhea and increased weight gain, compared with findings in untreated controls. There were no detectable differences between oral and IM routes, except that there was greater reduction in bacteria shedding associated with the oral route of administration. In experiment 2 (n = 505 pigs), ceftiofur was administered orally either once at 6 hours after challenge exposure or twice at 6 and at 48 hours after the first dose. Dosage of ceftiofur was 0, 5, 10, 20, 30, or 60 mg/kg administered once, or half the same dose was administered at each of 2 times. At the optimal dosage (10 mg/kg), a single dose was as effective as 2 doses. The single administration at all dosages reduced mortality, bacterial shedding, and diarrhea scores and increased body weight gain, compared with findings in untreated pigs (P less than 0.01). In this induced infection model, the optimal treatment dosage was determined to be 10 mg/kg administered once.

New microbiological method for determining spectinomycin in pelleted and meal feeds using trifluoroacetic acid as primary extractant.

A new microbiological method, identified as the spectinomycin trifluoroacetic (SPE-TFA) method, was compared with the current AOAC method for analyzing spectinomycin in meal and pelleted feeds fortified with LS-20 premix. Feeds containing 3 concentrations of drugs and a zero level were tested in a correlation study. The data showed no significant differences in the percent of theory assayed between meal and pelleted samples using the SPE-TFA method, but the percent of theory found using the AOAC method was significantly lower for the pelleted samples than for the meal samples. The within-sample variation of the AOAC assay was also not the same for all samples; the SPE-TFA assay variation was relatively constant for all samples. The SPE-TFA method produced an overall average recovery of 98% with a range of 89-109% compared with an 85% recovery ranging from 64 to 102% for the AOAC method. In addition to producing better recoveries, the SPE-TFA method features a more sensitive response line, and final test solutions have viscosities and clarity more comparable to the standard solutions than those produced by the current AOAC method.