Efficacy of intramammary treatment with procaine penicillin G vs. procaine penicillin G plus neomycin in bovine clinical mastitis caused by penicillin-susceptible,gram-positive bacteria--a double blind field study

The efficacy of intramammary treatments containing procaine penicillin G alone (treatment A) or a combination of procaine penicillin G and neomycin (treatment B) was compared in treating clinical bovine mastitis caused by gram-positive bacteria susceptible in vitro to penicillin G. Both treatments were supplemented with a single intramuscular injection of procaine penicillin G on the first day of treatment. The study was carried out using a double blind design on commercial dairy farms in Southern Finland. A total of 56 quarters were treated with treatment A and 61 with treatment B. The cure rates for both treatments were equal, which suggests that the use of the penicillin G-aminoglycoside combination does not increase the efficacy of the treatment over that achieved by using penicillin G alone in bovine clinical mastitis caused by penicillin-susceptible, gram-positive bacteria.     

Distribution of penicillin G, dihydrostreptomycin, oxytetracycline, and chloramphenicol in serum and subcutaneous chamber fluid

Penetration of penicillin G, dihydrostreptomycin, oxytetracycline, and chloramphenicol into interstitial fluid of calves was estimated using subcutaneously implanted, multiple perforated spherical polypropylene capsules as a model. Antibiotic concentrations were determined in simultaneously withdrawn serum and capsular fluid (CF) samples at intervals after single and multiple intramuscular injections of antibiotics at recommended dose schedules. Peak concentrations of penicillin G in CF were 57% of those in serum, and the drug was eliminated from CF at a slower rate than from serum. Dihydrostreptomycin diffused into CF to a limited degree and was eliminated from CF much more slowly than from serum leading to gradual drug accumulation in CF upon repeated dosing. Multiple injections of oxytetracycline resulted in CF drug levels comparable with those in serum. Concentrations of chloramphenicol in CF were generally similar to free (non-protein bound) serum drug levels. CF concentrations of penicillin G were within the range of the minimal inhibitory concentrations of the drug for pathogenic gram positive micro-organisms and CF levels of dihydrostreptomycin, oxytetracycline, and chloramphenicol were apparently sufficient to inhibit the majority of gram negative pathogens involved in bovine injections. Advantages and limitations of the tissue cage model are briefly discussed.     

Spinal fluid concentrations of mepivacaine in horses and procaine in cows after thoracolumbar subarachnoid analgesia

The CSF concentrations of mepivacaine in 10 Standardbred horses and of procaine in 10 Holstein cows given the drugs by thoracolumbar subarachnoid injection were determined. Mepivacaine hydrochloride was injected into the horses (502 +/- 60.5 kg) at an average dosage of 30 mg (1.5 ml of 20 mg/ml solution). Analgesia was produced 7.5 +/- 4.3 minutes after injection, extended between spinal cord segments T13 and L3 on both sides of the spinal column, and lasted 47 +/- 18.7 minutes at the T18 dermatome. Procaine hydrochloride was injected into cows (614 +/- 51.5 kg) at a dosage ranging between 75 mg and 100 mg (1.5 ml and 2 ml of 50 mg/ml solution). Analgesia was produced 8.2 +/- 2.0 minutes after injection, extended between spinal cord segments T11 and L4 on both sides of the spinal column, and lasted 47 +/- 17.5 minutes at the T13 dermatome. The critical CSF concentrations of local anesthetics required to eliminate response to pinprick stimulation were 204.4 +/- 90.3 micrograms of mepivacaine/ml in horses and 197.0 +/- 86.1 micrograms of procaine/ml in cows. Average CSF concentrations at 120 minutes after injections were made were 16.8 +/- 15.5 micrograms of mepivacaine/ml and 30.6 +/- 17.1 micrograms of procaine/ml. In in vitro experiments to determine the rates of hydrolysis of mepivacaine and procaine in CSF, significant changes (P greater than 0.05) were not seen in the CSF concentrations of mepivacaine in horses and procaine in cattle after a 120-minute incubation (37 C). The analgesic threshold concentrations of mepivacaine in CSF of horses and procaine in CSF of cows were similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

The concentration of penicillin in bovine conjunctival sac fluid as it pertains to the treatment of Moraxella bovis infection. (II) Topical application

Sodium benzyl penicillin, procaine penicillin and benethamine penicillin were applied into the bovine conjunctival sac as an aqueous solution or in ointment form in order to study the concentration-time profiles. The series of treatments was repeated in five animals in a random sequence. Penicillin concentration in conjunctival sac fluid (CF) was determined using the agar-well-diffusion assay technique. The data obtained were transformed to linear regression slopes. Similarity of the slopes within treatments (in five different eyes) enabled the construction of four common lines by co-variance analysis to represent each treatment. The regression coefficients of the four common lines were then compared to study the difference between treatments. Topical application of 5,000 iu sodium benzylpenicillin in aqueous solution at a concentration isotonic with 0.9% saline, produced a duration of therapeutic concentration (DTC) in CF of 12.6 +/- 1.5 h. When the same salt or other less water-soluble ones were formulated at the same concentration in an ointment base, the DTC was significantly prolonged. For all treatments, peak concentrations in CF were recorded at the first sampling and ranged between 7 iu/ml and 14 iu/ml. Sodium benzylpenicillin or procaine penicillin, both in the ointment base, produced DTCs of 38.8 +/- 2.1 h and 37 +/- 4.0 h, respectively, while the ointment formulation of benethamine penicillin produced a DTC of 56 +/- 4.5 h. The prolonged duration observed in the eye ointments can be partly accounted for by the viscous nature of the base. Other differences may be dependent on relative water solubility of each penicillin product and complexity of the surface mucosae of the eye.     

Concentrations of sulphadimidine, oxytetracycline and penicillin G in serum, synovial fluid and tissue cage fluid after parenteral administration to calves

Drug concentrations in serum, synovial fluid and tissue cage fluid (TCF) in calves were measured after single i.m. doses of oxytetracycline hydrochloride (OTC), procaine penicillin G (PPG) and potassium penicillin G (KPG) and single i.v. doses of sulphadimidine (SDM) and OTC. For all drugs, concentration-time curves in serum and synovial fluid were not identical but they had similar profiles, with peak levels occurring at about the same time. Concurrent concentrations were lower in synovial fluid than in serum. For each drug, elimination half-lives from synovial fluid and from serum were similar, except for penicillin G after KPG administration which had a significantly longer half-life from synovial fluid than from serum (P less than 0.05). Of the two penicillin G preparations, PPG gave a significantly higher synovial fluid:serum area under curve (AUC) ratio than did KPG; 0.76 +/- 0.10 and 0.54 +/- 0.12, respectively (P less than 0.05). For OTC, the synovial fluid:serum AUC-ratio was 0.33 +/- 0.12 after i.m. and 0.34 +/- 0.08 after i.v. administration. Drug concentration-time curves of TCF had different profiles compared with serum, with relatively low and delayed peak levels and slow elimination from TCF. TCF:serum AUC-ratios did not differ significantly for i.m. and i.v. administration of OTC; 0.10 +/- 0.10 and 0.19 +/- 0.03 respectively (P greater than 0.05). Potassium penicillin G (KPG), however, gave a significantly higher TCF:serum AUC-ratio than PPG; 0.55 +/- 0.21 and 0.19 +/- 0.07, respectively (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma pharmacokinetics and synovial fluid concentrations after oral administration of single and multiple doses of celecoxib in greyhounds

OBJECTIVE: To determine the plasma pharmacokinetics and synovial fluid concentrations after oral administration of single and multiple doses of celecoxib in Greyhounds. ANIMALS: 7 adult Greyhounds. PROCEDURES: Dogs received celecoxib (median dose, 11.8 mg/kg [range, 11.5 to 13.6 mg/kg], PO, q 24 h) for 10 days. Blood samples were collected prior to administration of celecoxib and serially for 24 hours after the 1st and 10th doses were administered. A synovial joint catheter was placed into a stifle joint in each dog for collection of synovial fluid samples. Concentrations of celecoxib in plasma and synovial fluid were quantified by use of a validated liquid chromatography/mass spectrometry method. Identification of hydroxy- and carboxyl-celecoxib in plasma and synovial fluid was also performed. Pharmacokinetic parameters were determined by use of noncompartmental analysis. RESULTS: Administration of multiple doses of celecoxib resulted in a significant decrease (40%) in median area under the curve (AUC) values and a corresponding decrease in median maximum concentrations (Cmax; 2,620 to 2,032 ng/mL) between the 1st and 10th doses. Synovial fluid concentrations were less than the corresponding plasma concentrations at all times except 24 hours after administration of the 10th dose of celecoxib. CONCLUSIONS AND CLINICAL RELEVANCE: Celecoxib distributes into the synovial fluid of Greyhounds. Although the exact mechanism for the decreases in AUC and Cmax is not known, results suggested that the plasma pharmacokinetics of celecoxib are different after administration of multiple doses in Greyhounds. These findings warrant further investigation on the absorption, distribution, metabolism, and elimination of celecoxib in Greyhounds and other breeds of dogs.     

Antibiotic susceptibility of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> isolated from subclinical bovine mastitis cases and in vitro efficacy of bacteriophage

Staphylococcus aureus is an opportunistic pathogen that may cause severe infections in livestock, and represents the major cause of mastitis in dairy cows. Currently, instead of using antibiotics, new strategies are sought to reduce this clinical health problem. The aim of this study was to determine the efficacy of phage therapy to kill S. aureus strains obtained from farms located at the State of Guanajuato, México. Thirty-six S. aureus strains from cow milk with subclinical mastitis were isolated and identified, and the susceptibility to antibiotics and four phages also isolated in this work was tested. It was found that more of 90% of S. aureus isolates were not susceptible to six or more antibiotics, and 100% were resistant to penicillin, dicloxacillin, cefotaxime, ampicillin and cephalothin, and 81 and 77%, to tetracycline and cefuroxime, respectively. Fortunately, 100% of S. aureus isolates were susceptible to phages used in this work, which was detected as clear zones using specific phage. It was shown for the first time, that phages used in this study are active against pathogenic S. aureus and might be incorporated into the therapy as an important tool for the control of staphylococcal bovine mastitis, specially to antibiotic-resistant S. aureus strains isolated in farm located at the state of Guanajuato, México; and its use might be extended to other regions inside or outside the country.     

Life threatening metabolic disorders after application of a sodium phosphate containing enema in the dog and cat.]

Application of a sodium phosphate containing enema caused life-threatening metabolic disorders in a Dachshund and two cats. Clinical signs were characterised by dehydration and various neurological deficits including seizures. Most striking laboratory abnormalities were hypernatremia, hypocalcemia, hyperphosphatemia, and polycythemia. Despite intensive treatment the dog died, whereas the cats recovered completely. In face of possible severe and potentially fatal metabolic abnormalities sodium phosphate enemas, such as Practo-Clyss, should be used with caution or not at all in cats and small dogs.     

Effects of realimentation after nutrient restriction during mid‐ to late gestation on pancreatic digestive enzymes,serum insulin and glucose levels,and insulin‐containing cell cluster morphology

This study examined effects of stage of gestation and nutrient restriction with subsequent realimentation on maternal and foetal bovine pancreatic function. Dietary treatments were assigned on day 30 of pregnancy and included: control (CON; 100% requirements; n = 18) and restricted (R; 60% requirements; n = 30). On day 85, cows were slaughtered (CON, n = 6; R, n = 6), remained on control (CC; n = 12) and restricted (RR; n = 12), or realimented to control (RC; n = 11). On day 140, cows were slaughtered (CC, n = 6; RR, n = 6; RC, n = 5), remained on control (CCC, n = 6; RCC, n = 5) or realimented to control (RRC, n = 6). On day 254, the remaining cows were slaughtered and serum samples were collected from the maternal jugular vein and umbilical cord to determine insulin and glucose concentrations. Pancreases from cows and foetuses were removed, weighed, and subsampled for enzyme and histological analysis. As gestation progressed, maternal pancreatic α‐amylase activity decreased and serum insulin concentrations increased (p ≤ 0.03). Foetal pancreatic trypsin activity increased (p < 0.001) with advancing gestation. Foetal pancreases subjected to realimentation (CCC vs. RCC and RRC) had increased protein and α‐amylase activity at day 254 (p ≤ 0.02), while trypsin (U/g protein; p = 0.02) demonstrated the opposite effect. No treatment effects were observed for maternal or foetal pancreatic insulin‐containing cell clusters. Foetal serum insulin and glucose levels were reduced with advancing gestation (p ≤ 0.03). The largest maternal insulin‐containing cell cluster was not influenced by advancing gestation, while foetal clusters grew throughout (p = 0.01). These effects indicate that maternal digestive enzymes are influenced by nutrient restriction and there is a potential for programming of increased foetal digestive enzyme production resulting from previous maternal nutrient restriction.     

Acute cortisol responses and wound healing in lambs after ring castration plus docking with or without application of a castration clamp to the scrotum

OBJECTIVE: To test whether the cortisol response to ring castration plus docking is reduced by additional application of a castration clamp across the full width of the scrotum distal to the ring. DESIGN: A physiological study with controls. PROCEDURE: Lambs, 3 to 6 weeks of age, were castrated using a ring or ring plus castration clamp applied for 6 or 10 s and docked using a ring. Blood samples were taken before and regularly for about 4 h after treatment and analysed for plasma cortisol concentrations. The healing of the scrotal wounds was monitored for 6 weeks after castration. RESULTS: The plasma cortisol concentrations were lower only at 60 min after treatment in lambs castrated with a clamp placed on the scrotum for 10 s after ring castration and docking than in lambs castrated and docked by ring alone. Scrotal wounds healed more quickly after ring plus clamp than after ring only castration. CONCLUSIONS: The castration clamp had at most a marginal effect on the cortisol response to ring castration and docking of 3- to 6-week-old lambs, but it did seem to improve the rate of healing.     

Ocular inserts for application of drugs to bovine eyes—in vivo and in vitro studies on the release of gentamicin from collagen inserts

SUMMARY Retention trials with collagen ocular inserts are described followed by gentamicin concentrations achieved in vitro and in vivo with the inserts. Concentrations in the precorneal film during the 24 h after insertion approximated the minimum inhibitory concentrations for gentamicin. The potential of sustained release drug delivery systems for the therapy of infectious bovine keratoconjunctivitis is discussed.     

Resumption of ovary activity and normal estrus cycles in postpartum cows after inclusion of placenta‐containing additives in the diet

Food additives made of placenta tissues of healthy cattle, included in the diet of cows 23–38 days before calving and/or in different intervals of the postpartum period, stimulated the resumption of ovary activity and the manifestation of normal estrus cycles (with ovulation) in cows. The cow fertilization rates during 80 days after calving was 50–80%. These values increased more than twofold in comparison with the fertility level of cows fed a normal diet. The level of fertilization after inclusion of placenta‐containing additives in the diet of cows 5 days before ovulation, in estrus cycles that took place during 6 months after calving, increased 38 % on average, in comparison with that of cows fed a normal diet.     

The pharmacokinetics of methocarbamol and guaifenesin after single intravenous and multiple‐dose oral administration of methocarbamol in the horse

A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration–time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three‐compartment model. Mean extrapolated peak (C₀) plasma concentrations were 23.2 (±5.93) μg/mL. Terminal half‐life, volume of distribution at steady‐state, mean residence time, and systemic clearance were characterized by a median (range) of 2.96 (2.46–4.71) h, 1.05 (0.943–1.21) L/kg, 1.98 (1.45–2.51) h, and 8.99 (6.68–10.8) mL/min/kg, respectively. Oral dose of MCBL was characterized by a median (range) terminal half‐life, mean transit time, mean absorption time, and apparent oral clearance of 2.89 (2.21–4.88) h, 2.67 (1.80–2.87) h, 0.410 (0.350–0.770) h, and 16.5 (13.0–20) mL/min/kg. Bioavailability of orally administered MCBL was characterized by a median (range) of 54.4 (43.2–72.8)%. Guaifenesin plasma concentrations were below the limit of detection in all samples collected after the single intravenous dose of MCBL whereas they were detected for up to 24 h after the last dose of the multiple‐dose oral regimen. This difference may be attributed to first‐pass metabolism of MCBL to GGE after oral administration and may provide a means of differentiating the two routes of administration.     

The pharmacokinetics and pharmacodynamics of alfaxalone in cats after single and multiple intravenous administration of Alfaxan® at clinical and supraclinical doses

This study aimed to determine the pharmacokinetic parameters and pharmacodynamics of alfaxalone in a 2‐hydroxypropyl‐β‐cyclodextrin alfaxalone formulation (Alfaxan^®, Jurox Pty Ltd, Rutherford, NSW, Australia) in cats after single administration at clinical and supraclinical dose rates and as multiple maintenance doses. First, a prospective two‐period cross‐over study was conducted at single clinical and supraclinical doses. Second, a single group multiple dose study evaluated the effect of maintenance doses. Eight (five female and three male) domestic cats completed the cross‐over experiment and six female cats completed the multiple dose study. In the first experiment, alfaxalone was administered intravenously (IV) at 5 or 25 mg/kg with a washout period of 14 days. In the second experiment, alfaxalone was administered IV at 5 mg/kg followed by four doses each of 2 mg/kg, administered at onset of responsiveness to a noxious stimulus. Blood was collected at prescribed intervals and analysed by LCMS for plasma alfaxalone concentration. Noncompartmental pharmacokinetics were used to analyse the plasma alfaxalone data. The plasma clearance of alfaxalone at 5 and 25 mg/kg differed statistically at 25.1 and 14.8 mL/kg/min respectively. The elimination half lives were 45.2 and 76.6 min respectively. Alfaxalone has nonlinear pharmacokinetics in the cat. Nevertheless, for cats dosed with sequential maintenance doses, a regression line through their peak plasma concentrations indicated that there was no clinically relevant pharmacokinetic accumulation. The duration of nonresponsiveness after each maintenance dose was similar at approximately 6 min, indicating a lack of accumulation of pharmacodynamic effect. The cardiovascular and respiratory parameters measured in cats after administration of the labelled doses of Alfaxan^® were stable. In conclusion, the pharmacokinetics of alfaxalone in cats are nonlinear. At clinical dose rates, however, neither alfaxalone nor its effects accumulated to a clinically relevant extent. Further, in the un‐premedicated cat the induction and maintenance of surgical anaesthesia was free of untoward events after a dose of 5 mg alfaxalone/kg body weight followed by four sequential doses of 2 mg/kg as needed (i.e., approximately 7 to 8 mg/kg/h).