Ability of an oral formulation of afoxolaner to protect dogs from Borrelia burgdorferi infection transmitted by wild Ixodes scapularis ticks.

A randomized, blinded, negative controlled study was conducted to determine whether treatment with afoxolaner (NexGard®, Merial, Inc.) would prevent the transmission of Borrelia burgdorferi to dogs by wild caught Ixodes scapularis ticks. Twenty healthy dogs were randomly assigned to two groups of ten dogs each. Ten dogs were treated orally on Day 0 at a dose near the minimum recommended dose of afoxolaner of 2.5mg/kg (actual doses 2.5-3.1mg/kg) and ten control dogs were not treated. On Day 28, each dog was infested with approximately 50 adult unfed wild caught I. scapularis that had a 67% B. burgdorferi infection rate (determined by polymerase chain reaction). On Day 33, live ticks were counted and removed. No ticks were found on treated dogs while control dogs had an average of 21.4 ticks. To detect infection, the B. burgdorferi-specific C6 antibody SNAP® 4Dx® test (IDEXX) was performed on serum collected before infestation (all dogs seronegative on Days -6 and 27) and on Days 48, 63, 77 and 92. The ten treated dogs remained seronegative through the end of the study (Day 92), while nine out of the ten control dogs were infected, as demonstrated by their seroconversion to being positive for the presence of the B. burgdorferi-specific C6 antibody starting on Day 48. In this study, all dogs treated with NexGard® 28days prior to challenge with wild caught I. scapularis ticks were protected from B. burgdorferi infection, while nine out of the ten untreated control dogs were infected.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel, against the ticks, Ixodes ricinus and Ixodes scapularis, on cats.

Five controlled, blinded and randomized studies were conducted to examine the efficacy of a single topical application of a combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel (BROADLINE(®), Merial) against induced infestations with Ixodes ticks on cats. Three studies investigated the efficacy against Ixodes ricinus and two against Ixodes scapularis. In each study, purpose-bred cats were assigned at random to an untreated group or to a treated group. For the studies using I. ricinus, cats were infested with 50 female ticks and a similar number of males 2 days before treatment application, and weekly afterwards on between four and six occasions. For the studies using I. scapularis, cats were infested with a total of 50 ticks (approximately 25 females and 25 males) according to the same schedule as for I. ricinus. Tick counts for the evaluation of efficacy were performed 48 h after treatment and 48 h after the subsequent weekly infestations. Weekly attachment rates to untreated cats of at least 29% for I. ricinus and at least 30% for I. scapularis demonstrated consistently that the ticks were vigorous and that the attachment rates were adequate for efficacy evaluation. In the I. ricinus studies, an efficacy of at least 93% was demonstrated for up to 37 days after the treatment. In the I. scapularis studies, the efficacy level was at least 95% 30 days after the treatment. The product was well tolerated and caused no adverse reaction.

Influence of prepartum pirlimycin hydrochloride or penicillin-novobiocin therapy on mastitis in heifers during early lactation.

A study was conducted in 2 dairy research herds to determine whether prepartum therapy of heifer mammary glands with penicillin-novobiocin or pirlimycin hydrochloride was effective for reducing the percentage of heifers and mammary quarters infected with mastitis pathogens during early lactation. Almost 96% of Jersey heifers (67 of 70) and 71.3% of quarters (199 of 279) were infected 14 d before expected calving. Of the quarters infected at 14 d before expected parturition, 75% (54 of 72) were uninfected following treatment with penicillin-novobiocin; 87% (61 of 70) were uninfected following treatment with pirlimycin, and 56% (32 of 57) were uninfected in the untreated negative control group. The majority of intramammary infections in Jersey heifers were due to coagulase-negative staphylococci (61%), Streptococcus species, primarily Streptococcus uberis (19%), and Staphylococcus aureus (8%). Almost 73% of Holstein heifers (40 of 55) and 34.3% of mammary quarters (73 of 213) were infected 14 d before expected calving. Of the quarters infected at 14 d before expected parturition, 76% (19 of 25) were uninfected following treatment with penicillin-novobiocin; 59% (17 of 29) were uninfected following treatment with pirlimycin, and 26% (5 of 19) were uninfected in the untreated negative control group. The majority of intramammary infections in Holstein heifers were due to coagulase-negative staphylococci (44%) and Staph. aureus (30%). In both herds, the bacteriological cure rate was significantly higher in heifer mammary glands treated with penicillin-novobiocin or pirlimycin hydrochloride than in untreated controls. Prepartum therapy of heifer mammary glands with penicillin-novobiocin or pirlimycin hydrochloride significantly reduced the percentage of heifers and quarters infected with mastitis pathogens during early lactation.

Extended ceftiofur therapy for treatment of experimentally-induced Streptococcus uberis mastitis in lactating dairy cattle.

Streptococcus uberis is an important cause of mastitis in dairy cows throughout the world, particularly during the dry period, the period around calving, and during early lactation. Strategies for controlling Strep. uberis mastitis are poorly defined and are currently inadequate. Objectives of the present study were to evaluate efficacy of ceftiofur, a new broad-spectrum cephalosporin antibiotic, for treatment of experimentally induced Strep. uberis intramammary infections (IMI) in lactating dairy cows during early lactation and to determine whether extended therapy regimens enhanced efficacy of ceftiofur. Efficacy of extended ceftiofur intramammary therapy regimens was investigated in 37 mammary quarters of 23 dairy cows that developed clinical mastitis following experimental infection with Strep. uberis during early lactation. Cows that developed clinical mastitis during the challenge period were allocated randomly to 3 groups representing 3 different ceftiofur treatment regimens: 2-d (n = 7 mammary quarters), 5-d (n = 16 mammary quarters), and 8-d (n = 14 mammary quarters) treatment regimens. For all groups, 125 mg of ceftiofur hydrochloride was administered via intramammary infusion. A bacteriological cure was defined as an experimentally infected quarter that was treated and was bacteriologically negative for the presence of Strep. uberis at 7, 14, 21, and 28 d posttreatment. Percentage of Strep. uberis IMI eliminated was 43, 88, and 100% for the 2-, 5-, and 8-d ceftiofur treatment regimens, respectively. Both the 5- and 8-d ceftiofur extended therapy treatment regimens had significantly higher bacterial cure rates than the standard 2-d ceftiofur treatment regimen. The bacterial cure rate of the 8-d ceftiofur extended therapy group was marginally better (P = 0.052) than the 5-d ceftiofur extended therapy group. Results of this study indicate that ceftiofur therapy was effective for eliminating Strep. uberis experimental IMI, and 5- and 8-d extended ceftiofur therapy regimens were more effective than the standard 2-d treatment.

Efficacy of extended ceftiofur intramammary therapy for treatment of subclinical mastitis in lactating dairy cows.

Little research has focused on treatment of cows with subclinical mastitis during lactation. Ceftiofur is a new broad-spectrum, third-generation cephalosporin antibiotic for veterinary use that inhibits bacterial cell wall synthesis by interfering with enzymes essential for peptidoglycan synthesis. Ceftiofur should be effective against a wide range of contagious and environmental mastitis pathogens. Objectives of the present study were to evaluate the efficacy of ceftiofur for treatment of subclinical mastitis in lactating dairy cows, and to determine if extended therapy regimens enhanced efficacy of ceftiofur. Holstein and Jersey dairy cows (n = 88) from 3 dairy research herds were used. Cows were enrolled in the study based on milk somatic cell counts >400,000/mL and isolation of the same mastitis pathogen in 2 samples obtained 1 wk apart. Cows with one or more intramammary infections (IMI) were blocked by parity and DIM and allocated randomly to 1 of 3 different ceftiofur treatment regimens: 2-d (n = 49 IMI), 5-d (n = 41 IMI), and 8-d (n = 38 IMI) treatment regimens. For all groups, 125 mg of ceftiofur hydrochloride was administered via intramammary infusion. Eighteen cows with 38 IMI were included as an untreated negative control group. A bacteriological cure was defined as a treated infected mammary quarter that was bacteriologically negative for the presence of previously identified bacteria at 14 and 28 d after the last treatment. Efficacy of ceftiofur therapy against all subclinical IMI was 38.8, 53.7, and 65.8% for the 2-, 5-, and 8-d ceftiofur treatment regimens, respectively. Four of 38 (10.5%) IMI in control cows were cured spontaneously without treatment. All 3 ceftiofur treatment regimens were significantly better than the negative control, and the 8-d extended ceftiofur treatment regimen treatment group was significantly better than the standard 2-d treatment group. Pathogen groups had significantly different cure rates from one another. The cure rate for the 8-d extended ceftiofur treatment regimen was 70% for Corynebacterium bovis, 86% for coagulase-negative Staphylococcus species, 36% for Staph. aureus, 80% for Streptococcus dysgalactiae ssp. dysgalactiae, and 67% for Strep. uberis.

Dose determination and confirmation of a long-acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease.

The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil(R) 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1-8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study 3 this dose was judged to be at the beginning of an efficacious dose range for the treatment of BRD when compared with tilmicosin. In Study 4, day 28 treatment success rates were higher for CCFA-SS at 4.4-8.8 CE/kg BW than for tilmicosin (P=0.002) or the noneffective CCFA-SS dose of 1.1 mg CE/kg BW (P < 0.001). Based on decision criteria for Study 4, the effective dose was determined to be 4.4-5.5 mg CE/kg BW. These clinical studies demonstrated that a single dose of CCFA-SS (100 mg CE/mL) administered subcutaneously (s.c.) in the neck at 4.4-5.5 mg CE/kg BW is an effective treatment for BRD in feedlot cattle. However, this route of administration is no longer being considered for this formulation because of the ceftiofur residues that are present at the injection site for extended periods of time.

Comparison of plasma pharmacokinetics and bioequivalence of ceftiofur sodium in cattle after a single intramuscular or subcutaneous injection.

Ceftiofur sodium, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance. This study was designed to compare the bioequivalence of the sodium salt in cattle after a single intramuscular (i.m.) or subcutaneous dose (s.c.) of 2.2 mg ceftiofur equivalents/kg body weight. The criteria used to evaluate bioequivalence were (1) the area under the curve from time of injection to the limit of quantitation (LOQ) of the assay (AUC0-LOQ), and (2) time concentrations remained above 0.2 microg/mL (t>0.2). Twelve crossbred beef cattle were enrolled in a three-period, two-treatment crossover trial, with a minimum 2-week washout period between doses of 2.2 mg ceftiofur equivalents/kg. Blood samples were collected serially for up to 72 h post-injection. Plasma samples were then analyzed using a validated assay that measures ceftiofur, and all desfuroylceftiofur-related metabolites, by high-performance liquid chromatography (HPLC) as the stable derivative, desfuroylceftiofur acetamide. A maximum plasma concentration (Cmax) of 13.9+/-3.55 microg/mL was observed from 0. 67-2.0 h after i.m. administration, whereas a Cmax of 13.6+/-3.85 microg/mL was observed from 0.67-3.0 h after s.c. administration. The AUC0-LOQ was 108+/-35.0 microg. h/mL after i.m. dosing, compared with 105+/-29.8 microg. h/mL after s.c. dosing. The pre-established criterion for equivalence of the AUC0-LOQ for the i.m. and s.c. routes of administration was satisfied. The t>0.2 was 49.2+/-8.55 h after i.m. administration, compared with 47.0+/-9.40 h after s.c. administration. The pre-established criterion for equivalence of the t>0.2 for i.m. and s.c. administration was satisfied. The equivalence of AUC0-LOQ and t>0.2 for i.m. and s.c. administration of 2.2 mg ceftiofur equivalents (CE)/kg doses of ceftiofur sodium suggest similar therapeutic efficacy and systemic safety for the two routes of administration.

Prevention of bacteremia in dogs undergoing dental scaling by prior administration of oral clindamycin or chlorhexidine oral rinse.

Dogs with periodontitis were used to determine the efficacy of an oral regimen of clindamycin versus chlorhexidine acetate oral rinse in reducing the total number of bacteria and the incidence of bacteremia before and after dental scaling. Aerobic and anaerobic bacteria, isolated from blood and gingival swab cultures, were identified to genus using an automated system.

A multilocation clinical trial in lactating dairy cows affected with clinical mastitis to compare the efficacy of treatment with intramammary infusions of a lincomycin/neomycin combination with an ampicillin/cloxacillin combination.

A study was conducted to compare the efficacy in lactating dairy cows of intramammary infusions in quarters affected with clinical mastitis between a formulation containing 330 mg lincomycin and 100 mg neomycin in a 10-mL aqueous solution (LINCOCIN FORTE S, Pharmacia & Upjohn) and a formulation containing 75 mg ampicillin and 200 mg cloxacillin in an oil suspension (AMPICLOX, Pfizer Animal Health). This study was designed as a multicentre clinical trial involving investigators in France, Germany and Belgium and carried out according to the European Commission guidelines on Good Clinical Practices. Cows in the herds were monitored for clinical mastitis. When evidence of clinical mastitis was detected in a single quarter, a pretherapy milk sample was collected from the affected quarter. After milk sampling, the cow was assigned to one of the two treatment groups at random and treated with an intramammary infusion of one syringe of either LINCOCIN FORTE S or AMPICLOX for three successive milkings in the mastitic quarter. At 4-5, 13-15 and 20-22 days after first infusion, the veterinarian returned to the farm to conduct a clinical examination and collect milk samples from the affected quarter. Milk samples were cultured for the presence of mastitis organisms and somatic cell count (SCC) was measured. Following a 10-month study period, 256 cases were enrolled in the study. A total of 232 and 189 cases were analysed for clinical cure and for clinical-plus-bacteriological cure, respectively. The proportions of cases cured clinically and cured clinically-plus-bacteriologically were compared between the two treatment groups. Somatic cell count differences between treatment groups were also tested. The clinical cure rate for LINCOCIN FORTE S (62.5%) was significantly better than for AMPICLOX (51.8%) (P = 0.035). The clinical-plus-bacteriological cure rate was also significantly better for LINCOCIN FORTE S (38.1%) than for AMPICLOX (21.7%) (P = 0.005). Among bacteriologically cured cases, the SCC declined in both treatment groups but the SCC was significantly higher for the AMPICLOX group than for the LINCOCIN FORTE S group (P = 0.036). In conclusion, clinical cure rate, clinical-plus-bacteriological cure rate, and SCC level were significantly better with LINCOCIN FORTE S than for AMPICLOX.

Effects of age on the pharmacokinetics of single dose ceftiofur sodium administered intramuscularly or intravenously to cattle.

The effects of maturation on the intravenous (IV) and intramuscular (IM) pharmacokinetics of ceftiofur sodium following a dose of 2.2 mg ceftiofur equivalents/kg body weight were evaluated in 16 one-day-old Holstein bull calves (33-53 kg body weight initially; Group 1) and 14 six-month-old Holstein steers (217-276 kg body weight initially; Group 2). Group 1 calves were fed unmedicated milk replacer until 30 days of age and were then converted to the same roughag/concentrate diet as Group 2. Groups 1-IV and 2-IV received ceftiofur sodium IV, and Groups 1-IM and 2-IM received ceftiofur sodium IM. Group 1 calves were dosed at 7 days of age and at 1 and 3 months of age; group 2 calves were dosed at 6 and 9 months of age. Blood samples were obtained serially from each calf, and plasma samples were analysed using an HPLC assay that converts ceftiofur and all desfuroylceftiofur metabolites to desfuroylceftiofur acetamide. Cmax values were similar in all calves, and were no higher in younger calves than in older calves. Plasma concentrations remained above 0.150 microgram ceftiofur free acid equivalents/mliter for 72 h in 7-day-old calves, but were less than 0.150 microgram/mliter within 48 h following IV or IM injection for 6- and 9-month-old calves. Intramuscular bioavailability, assessed by comparing the model-derived area under the curve (AUCmod) from IM and IV injection at each age, appeared to be complete. After IV administration, the AUCmod in 7-day-old and 1-month-old calves (126.92 +/- 21.1 micrograms.h/mliter and 135.0 +/- 21.6 micrograms.h/mliter, respectively) was significantly larger than in 3-, 6- and 9-month-old calves (74.0 +/- 10.7 micrograms.h/mliter, 61.0 +/- 17.7 micrograms.h/mliter and 68.5 +/- 12.8 micrograms.h/mliter, respectively; P < 0.0001). The Vd(ss) decreased linearly within the first 3 months of life in cattle (0.345 +/- 0.0616 L/kg, 0.335 +/- 0.919 L/kg and 0.284 +/- 0.0490 L/kg, respectively; P = 0.031), indicative of the decreasing extracellular fluid volume in maturing cattle. The ClB was significantly smaller in 7-day-old and 1-month-old calves (0.0178 +/- 0.00325 L/h.kg and 0.0167 +/- 0.00310 L/h.kg, respectively) than in 3-, 6- and 9-month-old calves (0.0303 +/- 0.0046 L/h.kg, 0.0398 +/- 0.0149 L/h.kg and 0.0330 +/- 0.00552 L/h.kg, respectively; P < or = 0.001). This observation may be indicative of maturation of the metabolism and/or excretion processes for ceftiofur and desfuroylceftiofur metabolites. The approved dosage regimens for ceftiofur sodium of 1.1-2.2 mg/kg administered once daily for up to 5 consecutive days will provide plasma concentrations above the MIC for bovine respiratory disease pathogens for a longer period of time in neonatal calves than in older calves. Peak plasma concentrations of ceftiofur and desfuroylceftiofur metabolites were no higher in neonatal calves than in more mature cattle, highly suggestive that peak tissue concentrations would be no higher in neonatal calves than in more mature cattle.

Identification and determination of pirlimycin residue in bovine milk and liver by high-performance liquid chromatography-thermospray mass spectrometry.

Determinative and confirmatory methods of analysis for pirlimycin (I) residue in bovine milk and liver have been developed based on HPLC-thermospray (TSP) MS. Milk sample preparation consisted of precipitating the mill proteins with acidified acetonitrile followed by a solvent partitioning with a mixture of n-butyl chloride and hexane extraction of I from the aqueous phase into methylene chloride (MC), and solid-phase extraction clean-up. For liver, samples (2 g) were extracted with 0.25% trifluoroacetic acid in acetonitrile. The aqueous component was released from the organic solvent with n-butyl chloride. The aqueous solution was reduced in volume by evaporation, basified with ammonium hydroxide, then extracted with MC. The MC was evaporated to dryness and the dried residue reconstituted in 2.0 ml of 0.1 M ammonium acetate for analysis. A chromatographically resolved stereoisomer of I with TSP-MS response characteristics identical to I was used as an internal standard (I.S.) for quantitative analysis based on the ratio of peak areas of I to I.S. in the protonated molecular-ion chromatogram at m/z 411.2. The method for milk was validated by the analysis of control milk samples spiked with I at concentrations from 0.05 to 0.8 micrograms/ml. The overall recovery of pirlimycin across this concentration range was 95.4% +/- 8.7%. The limit of quantitation (LOQ) and limit of confirmation (LOC) of the method were validated to be 0.05 micrograms/ml and 0.10 micrograms/ml, respectively. The method for liver was validated by the analysis of control liver samples spiked with I at concentrations ranging from 0.025 to 1.0 micrograms/g. The overall recovery of pirlimycin was 97.6% +/- 5.1% in this concentration range. The validated limit of quantitation (LOQ) and limit of confirmation (LOC) of the method were 0.025 micrograms/g and 0.10 micrograms/g, respectively. Four diagnostic ions for I were monitored for confirmation: the pseudo-molecular ions (M+H)+ at m/z 411.2 (35Cl) and m/z 413.2 (37Cl), and fragment ions at m/z 375.2 and 158.1. Confirmatory criteria were defined for these assays.

Survey of intramammary infections in dairy heifers at breeding age and first parturition.

A survey was conducted to determine and contrast prevalence of IMI in nulligravid and primigravid dairy heifers pre- and postpartum. Contrasts were made to evaluate the risk factors of location of dairy, trimester of gestation, and season of sampling on IMI. Twenty-eight dairies in California, Louisiana, Vermont, and Washington were studied. Lacteal secretions were collected aseptically from heifers at breeding age (8 to 19 mo) from one side of the gland and again at 4 d postpartum from all quarters. Of the quarters sampled, 65.6% prepartum and 64.0% postpartum were free of IMI. The percentages of quarters with IMI from coagulase-negative staphylococci or Staphylococcus aureus IMI were 27.1 and 9% prepartum and 21.8 and 2.9% postpartum. Staphylococcus aureus IMI were most prevalent in Louisiana during the months other than summer. Location, herd, and season significantly influenced prevalence of IMI. The prevalence of IMI was greatest during the last trimester of pregnancy, ranging from 49.2% in the winter to 36.8% in the summer. The significant effects of herd location and season suggest that management variables influence prevalence of heifer IMI. Because prevalence of IMI was greatest during the last trimester of pregnancy compared with prevalence during earlier stages of pregnancy, the heifer may be most susceptible to this disease during this period of first gestation.

The visual appearance and somatic cell count of mammary secretions collected from primigravid heifers during gestation and early postpartum.

Mammary secretions, obtained before and after calving, were examined for visual appearance, SCC, and bacteriology as part of a larger study determining the prevalence of IMI in 1588 primigravid heifers. Appearance of secretions was categorized into five groups: thin and watery, honey-like, serumy, milky, or thickened colostrum. Precalving secretions were further characterized as low viscosity (thin and watery, serumy, or milky) or high viscosity (honey-like and thickened colostrum). Postcalving secretions were further characterized as normal (milky, thickened colostrum) or abnormal (thin and watery, serumy, or honey-like). Infected precalving quarters (81%) had low viscosity secretions. Quarters that were uninfected precalving (75%) had high viscosity secretions. Greater than 90% of all postcalving milk samples appeared to be normal, regardless of geographic location, season, or bacterial infection status. Only 77% of the samples from quarters infected with contagious and noncontagious mastitis pathogens had normal appearance. Precalving SCC from bacteriologically negative quarters were lower than SCC from infected quarters. Similarly, postcalving SCC were lower from the bacteriologically negative quarters than from the infected quarters. Infected quarters had higher mean SCC than the uninfected quarters during both pre- and postcalving periods.

The effect of slaframine on salivary output and subacute and acute acidosis in growing beef steers.

Experiments were conducted to determine 1) the effect of injecting slaframine (SF) on salivary output in growing beef steers and 2) whether increased salivary output after SF injection would inhibit the decrease in ruminal pH that occurs after experimentally induced subacute and acute ruminal acidosis. In Exp. 1 and 2, we measured ruminal pH and salivary output in ruminally and esophageally cannulated beef steers fed an 88% concentrate diet. Injections of 66 or 100 micrograms of SF/kg BW increased salivary flow approximately 50% compared with controls. Those doses were tested in subacute and acute acidosis models using ruminally cannulated beef steers in Exp. 3 and 4, respectively. In these experiments, salivation was assessed indirectly using a visual scoring system. In the subacute acidosis model, SF reduced (P < .10) the decrease in ruminal pH (1.1, .7, and .6 pH units for control, 66, and 100 micrograms of SF/kg BW doses, respectively), and excessive salivation was observed in all SF-injected steers. In the acute acidosis model, there were no differences (P > .10) in ruminal pH at 12 h after injection between control and SF-treated steers. Mean ruminal lactate concentrations for all treatment groups were between 87 and 112 mM. Although treatment with 66 micrograms of SF/kg BW reduced (P < .10) ruminal lactate concentrations, all ruminal lactate concentrations were indicative of acute acidosis. These results indicate that SF will reduce the decrease in ruminal pH associated with subacute acidosis in growing beef steers, but SF does not attenuate acute ruminal acidosis.

Effect of recombinant porcine somatotropin and dietary protein on pancreatic digestive enzymes in the pig.

This study was conducted to determine the effect of daily recombinant porcine somatotropin (rpST) injection (0 or 120 micrograms/kg BW) and dietary CP level of the feed (14 or 26% CP) on pancreatic characteristics of growing pigs. Daily injection of rpST did not affect pancreatic weight (P = .885) but did decrease pancreatic amylase content (P = .005). The ratios of amylase:protein and amylase:trypsin were also lowered by daily rpST injection (P = .002 and P = .0002, respectively). There were protein x rpST and protein x rpST x sex interactions for the ratio of amylase:chymotrypsin. The CP content of the diet had a greater effect than the injection of rpST on pancreatic characteristics. Pigs consuming the 26% CP diet had significantly higher pancreatic weight (P = .003) and greater total pancreatic chymotrypsin (P = .006) than pigs consuming the 14% CP diet. The ratios of trypsin and chymotrypsin to DNA were also higher in pigs fed the 26% CP diet (P = .007 and P = .005, respectively). These responses were not influenced by sex. Recombinant porcine somatotropin seemed to have a slight effect on porcine pancreatic characteristics; however, dietary protein had a greater effect on pancreatic characteristics in market-weight hogs.

Immune response in pigs to Aujeszky's disease viruses defective in glycoprotein g1 or gX.

Two Aujeszky's disease virus glycoprotein genes, gX and g1, have been used to produce deletion mutants which have then been developed into vaccines. These deletions then allow differentiation between pigs infected with wild type virus and those given the vaccine. It is not clear whether the glycoproteins encoded for by these genes are needed to induce a full protective immune response, in which case deletion mutants would suffer from lack of potency. To test this, commercially available Aujeszky's virus vaccines which lacked either gX or g1 were compared and isogenic constructs were made which differed only in the absence or presence of gX and, or, g1. These constructs and vaccines were used to vaccinate the natural host of Aujeszky's disease, the pig, and potency was measured using challenge with wild type virus. In all cases vaccines which lacked g1 performed significantly less well than those in which g1 was present, whereas deletions of gX had no significant effect on vaccine performance.

Pilocarpine and digestive efficiency in beef cattle fed a high-concentrate diet.

The effect of pilocarpine HCl, a parasympathetic muscarinic agonist, on digestive characteristics was evaluated in growing beef steers fed a high-grain diet. Oral doses of 0, 2 or 4 mg/kg BW were administered daily to each of eight steers immediately prior to offering an 88% concentrate: 12% hay diet in this three-period crossover design (19 d/period). Treatments did not improve digestibilities of dry matter, organic matter and nitrogen, ruminal liquid volume and fractional dilution rate, body weight gain or feed efficiency. Although daily voluntary feed intake was not altered by treatment (P = .25), there was a dose-dependent slowing of the rate at which feed was consumed (P less than .01). Also, ruminal fluid pH was increased with increasing dose (5.36, 5.55 and 6.11 respectively; P = .10). These observations indicate that the digestive improvements due to pilocarpine reported to occur in mature, nongrowing cattle consuming a high-forage diet are not observed in growing steers fed a production-type diet.

Propionic acid disappearance from the foregut and small intestine of the beef steer.

Studies were conducted to determine the disappearance of propionic acid from the rumen and across the small intestine. Four crossbred beef steers, fitted with ruminal, duodenal and ileal cannulas, were given pulsed-continuous infusions of a nonabsorbable liquid phase marker (CrEDTA) and buffered propionic acid to achieve ruminal propionate productions (RPP) of 142 (basal), 567 and 997 mmol/h. Liquid flows from the rumen, and at the duodenum and ileum (2.75, 3.57 and .92 liters/h, respectively) were not affected by RPP (P greater than .23), although significant differences existed between sites (P = .001), reflecting a net addition of liquid between the rumen and duodenum and a net removal of liquid within the small intestine. Propionate disappearance from the rumen was 40 to 57% irrespective of RPP, with the complement passing from the rumen. Of the propionate that exited the rumen, 93 to 97% disappeared prior to entering the duodenum. Overall removal of RPP prior to the duodenum was 97 to 99% irrespective of RPP. Passage of propionic acid at the duodenum and at the ileum did not differ (P greater than .76) across all RPP, and the overall mean passages did not differ from zero (P greater than .34); similar results were observed for other VFA. These observations indicate that essentially all RPP is removed prior to entering the small intestine. Additionally, net propionate disappearance across the small intestine was undetectable and likely biologically irrelevant. Therefore, VFA absorption does not appear to be a limiting biological process in the beef steer.

Disappearance and passage of propionic acid from the rumen of the beef steer.

Studies were conducted to define steady state pH, propionic acid concentrations and fluid turnover in the rumen of steers fed every 3 h and to determine whether rates of ruminal propionic acid disappearance were linearly related to their in situ production rates. Ruminally fistulated beef steers (326 +/- 11 kg; n = 3) were fed eight times daily a 54% mixed hay: 46% corn-based concentrate diet to meet maintenance energy requirements. Maximal acceptable variations from the mean at steady state conditions of pH, propionic acid concentrations and specific activity, and liquid flow (Cr marker concentrations) were defined as 4%, 20%, 30% and 10%, respectively, across 4 h of observation. In situ production of propionic acid, determined by pulse-continuous infusion of 1-14C-propionic acid, was 142 mmol/h (CV = 8.4%). The ruminal half-life of propionic acid was estimated to be 1.5 h and the liquid flow rate was 3.8 liters/h. Propionic acid production rates subsequently were elevated by continuous intraruminal infusion of buffered propionic acid. Irrespective of production (basal and infusion) rate, approximately 66% disappeared (i.e., presumed absorption) and 34% passed from the rumen to the lower tract in the liquid phase. Ruminal disappearance of propionate was linearly related with its production rate, and propionate concentrations and production rates also were linearly related. Liquid passage was linearly related to production rate, but there was insufficient evidence to conclude that fractional dilution rate or ruminal volume were similarly related. When ruminal production of propionic acid is elevated, the rumen has additional absolute capacity to remove propionate, but the fractional removal appears to be constant. The digestive tract distal to the rumen is likely an important site of propionate absorption in cattle when propionate production is high.