Pharmacokinetics and i.m. bioavailability of ceftiofur in Asian elephants (Elephas maximus)

Captive elephants are prone to infections of the feet, lungs, and skin. Often treatment regimens are established with no pharmacokinetic data on the agents being used for treatment in these species. A pharmacokinetic study using ceftiofur (1.1 mg/kg) was conducted in four adult female captive Asian elephants (Elephas maximus) at Busch Gardens in Tampa, Florida. Elephants were given both i.v. and i.m. administrations in a complete crossover design with a 3-week washout period between treatments. Blood samples were collected prior to drug administration and at 0.33, 0.67, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 h postadministration. Ceftiofur analysis was performed using a validated liquid chromatography/mass spectrophotometric (LC/MS) assay. Plasma concentrations for the i.m. samples were lower than expected. The mean C(max) following i.m. administration was 1.63 microg/mL with a corresponding T(max) of 0.55 h. Following i.v. administration, the median V(d(ss)) was 0.51 L/kg and a median Cl(p) of 0.069 L/kg/h. Mean i.m. bioavailability was 19%. The results indicate that ceftiofur used at 1.1 mg/kg i.m. could be useful in elephants when given two to three times a day or alternatively, 1.1 mg/kg i.v. once daily, depending upon the MIC of the pathogen.     

Effects of wet corn gluten feed and intake level on diet digestibility and ruminal passage rate in steers

Twelve ruminally cannulated Jersey steers (BW = 534 kg) were used in an incomplete Latin square design experiment with a 2 x 2 factorial arrangement of treatments to determine the effects of wet corn gluten feed (WCGF) and total DMI level on diet digestibility and ruminal passage rate. Treatments consisted of diets formulated to contain (DM basis) steam-flaked corn, 20% coarsely ground alfalfa hay, and either 0 or 40% WCGF offered once daily for ad libitum consumption or limited to 1.6% of BW (DM basis). Two consecutive 24-d periods were used, each consisting of 18 d for adaptation, 4 d for collection, and a 2-d in situ period. Rumens of all steers were evacuated once daily at 0, 4, 8, and 12 h after feeding. Chromic oxide (10 g/[steer*d]) was fed as a digestibility marker, and steers were pulse-dosed with Yb-labeled alfalfa hay to measure ruminal particulate passage rate. Dacron bags containing 5 g of steam-flaked corn, WCGF, or ground (2-mm screen) alfalfa hay were placed into the rumens of all steers and removed after 3, 6, 12, or 48 h. Wet corn gluten feed increased percent apparent total-tract digestion of OM (P < 0.01), NDF (P < 0.01), and starch (P < 0.03), decreased (P < 0.01) ruminal total VFA concentration, increased (P < 0.01) ruminal NH3 concentration, and increased (P < 0.01) ruminal pH. Wet corn gluten feed also increased (P < 0.01) ruminal passage rate of Yb. Limit feeding decreased (P < 0.01) percent apparent total-tract digestion of both OM and NDF, ruminal total VFA concentration (P < 0.01), and ruminal fill (P < 0.01), but increased (P < 0.01) ruminal NH3 concentration. Apparent total-tract digestion of starch was not affected (P = 0.70) by level of DMI. A DMI level x hour interaction (P < 0.01) occurred for ruminal pH. Limit feeding increased ruminal pH before and 12 h after feeding, but decreased ruminal pH 4 h after feeding compared with diets offered ad libitum. A diet x DMI level interaction (P < 0.02) occurred for in situ degradation of alfalfa hay, with dietary addition of WCGF increasing (P < 0.02) the extent of in situ alfalfa hay degradation in steers fed for ad libitum consumption. This study suggests that WCGF increases OM and NDF digestion, and that limit feeding diets once daily might depress OM and NDF digestion, possibly due to decreased stability of the ruminal environment.     

Unraveling the life history of successful invaders

Despite considerable current interest in biological invasions, the common life-history characteristics of successful invaders remain elusive. The widely held hypothesis that successful invaders have high reproductive rates has received little empirical support; however, alternative possibilities are seldom considered. Combining a global comparative analysis of avian introductions (>2700 events) with demographic models and phylogenetic comparative methods, we show that although rapid population growth may be advantageous during invasions under certain circumstances, more generally successful invaders are characterized by life-history strategies in which they give priority to future rather than current reproduction. High future breeding expectations reduce the costs of reproductive failure under uncertain conditions and increase opportunities to explore the environment and respond to novel ecological pressures.     

Inhibition of telomerase in canine cancer cells following telomestatin treatment

Telomere shortening in normal somatic cells has been proposed as a major barrier to unlimited cellular proliferation. Telomerase is an enzyme capable of maintaining telomere length, and thus bypassing this barrier. In human beings, telomerase activity is restricted to cancer cells and cells of stem or germ cell lineages. Dogs represent a potentially useful clinical model for the development of telomerase‐based therapies because telomerase activity is also restricted to cancer cells and stem cells in this species. We examined the ability of telomestatin to inhibit telomerase activity in telomerase‐positive D17 and CMT7 canine cancer cell lines. At a concentration of 2 μM, telomestatin treatment resulted in a decrease in telomerase activity, telomere shortening, growth inhibition and apoptosis in telomerase‐positive cancer cells. These effects were not seen in telomerase‐negative skin fibroblasts or negative controls. These results confirm that telomestatin specifically inhibits telomerase activity in canine cancer cells and strengthens the usefulness of dogs as a model for testing telomerase‐based therapies.     

Lactate Kinetics in veterinary Critical Care: A Review

Elevation in blood lactate concentration, with or without accompanying metabolic acidosis, is a hallmark finding in patients with circulatory compromise, and is also consistently noted in other conditions affecting critically ill or injured individuals. Little is reported in a veterinary literature regarding lactate measurement in the emergency and critical care setting, despite impressive reports of the clinical usefulness of lactate measurement in people. The purpose of this article is to review lactate kinetics and the clinical utility of lactate measurement. Limitations to lactate evaluation will also be discussed.     

Mechanism of Na+/H+ antiporting

Na+/H+ antiporters are central to cellular salt and pH homeostasis. The structure of Escherichia coli NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function. Three conserved aspartates are key to our proposed mechanism: Asp164 (D164) is the Na+-binding site, D163 controls the alternating accessibility of this binding site to the cytoplasm or periplasm, and D133 is crucial for pH regulation. Consistent with experimental stoichiometry, two protons are required to transport a single Na+ ion: D163 protonates to reveal the Na+-binding site to the periplasm, and subsequent protonation of D164 releases Na+. Additional mutagenesis experiments further validated the model.     

Oral glucose leads to a differential response in glucose,insulin, and GLP-1 in lean versus obese cats

The response to oral glucose was examined in 10 obese and 9 lean age-matched, neutered cats. In all cats, oral administration of 2 g/kg glucose was followed by a prompt increase in glucose, insulin, and glucagon-like peptide (GLP)-1. There were significant differences between lean and obese cats in the areas under the curve for glucose, insulin, and GLP-1. However, the responses were variable, and a clear distinction between individual lean and obese cats was not possible. Therefore, this test cannot be recommended as a routine test to examine insulin resistance in individual cats as it is used in people. A further disadvantage for routine use is also the fact that this test requires gastric tubing for the correct administration of the glucose and associated tranquilization to minimize stress and that it was associated with development of diarrhea in 25% of the cats. GLP-1 concentrations were much lower in obese than lean cats. The low GLP-1 concentrations in obese cats might indicate a contribution of GLP-1 to the lower insulin sensitivity of obese cats, but this hypothesis needs to be further investigated.     

A comparison of two combinations of xylazine-ketamine administered intramuscularly to alpacas and of reversal with tolazoline

ObjectiveTo evaluate the anesthetic and cardiorespiratory effects of two doses of intramuscular (IM) xylazine/ketamine in alpacas, and to determine if tolazoline would reduce the anesthetic recovery time.Study designProspective randomized crossover study.AnimalsSix castrated male alpacas.MethodsEach alpaca received a low dose (LD) (0.8 mg kg⁻¹ xylazine and 8 mg kg⁻¹ ketamine IM) and high dose (HD) (1.2 mg kg⁻¹ xylazine and 12 mg kg⁻¹ ketamine IM) with a minimum of one week between trials. Time to sedation, duration of lateral recumbency and analgesia, pulse rate, respiratory rate, hemoglobin oxygen saturation, arterial blood pressure, blood-gases, and the electrocardiogram were monitored and recorded during anesthesia. With each treatment three alpacas were randomly selected to receive tolazoline (2 mg kg⁻¹ IM) after 30 minutes of lateral recumbency.ResultsOnset of sedation, lateral recumbency and analgesia was rapid with both treatments. The HD was able to provide ≥30 minutes of anesthesia in five of six alpacas. The LD provided ≥30 minutes of anesthesia in three of six alpacas. Respiratory depression and hypoxemia occurred with the HD treatment during the first 10 minutes of lateral recumbency: two animals were severely hypoxemic and received nasal oxygen for 5 minutes. Heart rate decreased, but there were no significant changes in arterial blood pressure. Tolazoline significantly shortened the duration of recumbency with the HD.ConclusionsThe HD provided more consistent clinical effects in alpacas than the LD. Intramuscular tolazoline shortened the duration of lateral recumbency in alpacas anesthetized with the HD combination.Clinical relevanceBoth doses of the combination were effective in providing restraint in alpacas and the duration of restraint was dose dependent. Supplemental oxygen should be available if using the HD and IM administration of tolazoline will shorten the recovery time.     

Use of 25-hydroxyvitamin D3 and dietary calcium to improve tenderness of beef from the round of beef cows

The objective of this trial was to determine how 25-hydroxyvitamin D(3) (25-OH D(3)) supplementation, altering supplemental dietary calcium, or their combination influence postmortem biochemical and tenderness changes in muscles from the round of mature cows. Twenty-seven Angus cows (3 to 7 yr old) were allotted randomly to 9 pens with 3 cows per pen. Treatments were arranged in a 3 x 3 factorial design with 3 dosages of 25-OH D(3) (0, 250, or 500 mg of 25-OH D(3) administered as a 1-time oral bolus 7 d before slaughter) and 3 percentages of supplemental limestone (0.5, 0.75, and 1.0%) replenished in the diet for 3 d before slaughter and after a 2-wk limestone withdrawal. Plasma samples were obtained during the feeding period. Upon slaughter, adductor, gracilus, pectineus, sartorius, semimembranosus, vastus intermedius, and vastus lateralis muscles were obtained and aged for 1, 3, or 7 d. Calcium concentrations were increased in plasma when 250 or 500 mg of 25-OH D(3) were administered (P 相似文献