Pharmacokinetics of oral ivabradine in healthy cats

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method for the measurement of the novel heart rate-lowering drug ivabradine and its major metabolite, S-18982, was cross-validated in the plasma of eight healthy cats. Plasma concentrations were then determined after single and repeated oral administration of ivabradine. Individual plasma concentrations versus time from each cat were used in compartmental analysis using the commercially available software WinNonlin. Both ivabradine and S-18982 reached their maximum concentrations of 103.33 and 3.86 ng/mL within 1 h. Following repeated administration, areas under the plasma concentration-time curves for ivabradine and S-18982 did not significantly increase. Two-compartmental and one-compartmental models with first-order input and elimination provided the best fit to the data for ivabradine and S-18982, respectively. Both models were combined to produce a single 4-compartment model characterizing ivabradine and S-18982 pharmacokinetics. The results of this study indicate that repeated oral doses of ivabradine produced plasma drug concentrations suitable for 12-h dosing intervals in healthy cats. Furthermore, the analytical assay and combined ivabradine/S-18982 model provide tools for further evaluation of ivabradine pharmacokinetics and pharmacodynamics in future studies in cats.     

Conception rates in early postpartum ewes bred naturally or by intrauterine insemination

Ewes were treated with a medroxyprogesterone acetate (MAP) sponge for 8 d followed, at sponge removal, with 500 IU pregnant mare serum gonadotropin (PMSG) at d 30, 40 or 50 (d 0 = lambing) to induce estrus. Dry and lactating ewes were divided into equal numbers at each postpartum day and bred at estrus. Conception rates and number of accessory sperm were determined by flushing the oviducts 3 d after mating and examining the recovered ova. There was no effect (P greater than .05) of lactational status on conception rates. Conception rates increased (P less than .05) from d 30 (10%) to d 40 (45%) and from d 40 to d 50 (80%). There were fewer (P less than .05) ova with accessory sperm (5/26) in d-30 ewes compared with d-40 (10/27) or d-50 (12/24) ewes. In Exp. 2, ewes were assigned to two groups after receiving PMSG on d 30: 1) mated naturally or 2) inseminated during laparotomy near the uterotubal junction (UTJ). Dry and lactating ewes were divided evenly within each of the two treatments. Oviducts were flushed and ova were examined for cleavage. The conception rate was 60% in ewes that were inseminated in the UTJ vs 10% in ewes mated to rams (P less than .05). Lactational status had no effect on results. In conclusion, conception rates in postpartum ewes treated with MAP sponge and PMSG increased from postpartum d 30 to d 50 with natural breeding, and d-30 conception rates were increased over natural mating by insemination into the uterine horn near the UTJ.     

Factors affecting the virulence of Ralstonia solanacearum and its colonization on tobacco roots

Tobacco bacterial wilt caused by Ralstonia solanacearum is a serious disease affecting tobacco cultivation in southwest China. The response surface methodology was employed to evaluate the optimal conditions of tobacco bacterial wilt, and green fluorescent protein gene (gfp) labelling was applied to monitor the location and survival dynamics of R. solanacearum (Rs::gfp) on tobacco roots and in soil under these optimal conditions. The results showed that the highest wilt incidence was 91.13%, which occurred when the population reached 6.6 × 10⁶ CFU/g soil, the temperature was 30.55 °C, and the humidity was >81.42%. The Rs::gfp densely colonized the root tips and root hairs, and cells of Rs::gfp were observed intermittently in the elongation zone or at the point of the emerging lateral roots. The Rs::gfp number in the rhizosphere soil was 10.75‐, 73.13‐ and 74.86‐times higher than that in the bulk soil at 10, 15 and 20 days after transplantation, respectively. Increased colonization by Rs::gfp was related to the population of the pathogen, the environmental temperature and the humidity in the soil. These three conditions determined whether R. solanacearum would induce tobacco wilt. This is the first study to investigate factors affecting the virulence of a tobacco wilt bacterial pathogen, which is important for conducting field diagnosis and biocontrol of tobacco bacterial wilt.     

Evaluation of aerobic bacteriologic culture of epidermal collarette specimens in dogs with superficial pyoderma

OBJECTIVE: To evaluate a method of aerobic bacteriologic culture of epidermal collarette specimens from dogs with superficial pyoderma and compare results with those for aerobic bacteriologic culture of abdominal skin specimens in healthy dogs. DESIGN: Prospective study. ANIMALS: 22 dogs with epidermal collarettes and 24 healthy dogs. PROCEDURE: Dry sterile cotton swabs were rolled across epidermal collarettes or hairless areas of abdominal skin in healthy dogs and submitted for aerobic bacteriologic culture. Hemolytic colonies of gram-positive-staining cocci were tested for catalase production, and if results were positive, a coagulase test was performed. Colonies with coagulase activity were tested for the ability to ferment mannitol. Antimicrobial susceptibility testing was performed on all Staphylococcus spp that were isolated. RESULTS: S. intermedius was isolated from collarettes in 18 of 22 dogs with superficial pyoderma but not from healthy dogs. Estimated sensitivity and specificity of the culture method were 81.8% and 100%, respectively. There were no significant differences in the ability to culture S. intermedius, the number of S. intermedius isolates without resistance to antimicrobials, and the number of S. intermedius isolates resistant to penicillin G when comparing dogs with superficial pyoderma for the first time and dogs with recurrent pyoderma, dogs that did or did not receive concurrent antimicrobials, and dogs with and without underlying allergic disease. CONCLUSIONS AND CLINICAL RELEVANCE: Bacteriologic culture of epidermal collarette specimens was a simple and reliable method for identification of S. intermedius in dogs with superficial pyoderma, regardless of history of pyoderma or current antimicrobial use.     

Effects of concentrate‐to‐forage ratios and 2‐methylbutyrate supplementation on ruminal fermentation,bacteria abundance and urinary excretion of purine derivatives in Chinese Simmental steers

This study evaluated the effects of dietary concentrate levels and 2‐methylbutyrate (2MB ) supplementation on performance, ruminal fermentation, bacteria abundance, microbial enzyme activity and urinary excretion of purine derivatives (PD ) in steers. Eight ruminally cannulated Simmental steers (12 months of age; 389 ± 3.7 kg of body weight) were used in a replicated 4 × 4 Latin square design with a 2 × 2 factorial arrangement. Moderate‐concentrate (400 g/kg diet [MC ]) or high‐concentrate (600 g/kg diet [HC ]) diets were fed with or without 2MB (0 g/day [2MB ?] or 15.0 g/day [2MB +]). Dry matter intake and average daily gain increased, but feed conversion ratio decreased with the HC diet or 2MB supplementation. Ruminal pH decreased, but total volatile fatty acid increased with the HC diet or 2MB supplementation. Molar proportion of acetate and acetate‐to‐propionate ratio decreased with the HC diet, but increased with 2MB supplementation. Propionate molar proportion and ruminal NH ₃‐N content increased with the HC diet, but decreased with 2MB supplementation. Neutral detergent fibre degradability decreased with the HC diet, but increased with 2MB supplementation. Crude protein degradability increased with the HC diet or 2MB supplementation. Abundance of Ruminococcus albus , Ruminococcus flavefaciens , Fibrobacter succinogenes and Bufyrivibrio fibrisolvens as well as activities of carboxymethyl cellulase, cellobiase, xylanase and pectinase decreased with the HC diet, but increased with 2MB supplementation. However, abundance of Prevotella ruminicola and Ruminobacter amylophilus as well as activities of α‐amylase and protease increased with the HC diet or 2MB supplementation. Total PD excretion also increased with the HC diet or 2MB supplementation. The results suggested that growth performance, ruminal fermentation, CP degradability and total PD excretion increased with increasing dietary concentrate level from 40% to 60% or 2MB supplementation. The observed diet × 2MB interaction indicated that supplementation of 2MB was more efficacious for improving growth performance, ruminal fermentation and total PD excretion with promoted ruminal bacteria abundance and enzyme activity in the MC diet than in the HC diet.     

Variation in egg yolk cholesterol concentration between and within breeds of the domestic fowl.

1. The pattern of variation for egg yolk cholesterol concentration between 5 commercial egg layer lines and a cross of Gallus domesticus is described. 2. Yolk cholesterol concentration in the cross was lower than in the lines, and 6.7% lower than the midparent value. 3. It is proposed that the reduced yolk cholesterol concentration of the cross may be a consequence of heterosis, although sex-linkage and/or maternal effects cannot be discounted. 4. The difference between the cross and parental lines is consistent with a physiological relationship between yolk cholesterol concentration and rate of egg production, but not between yolk cholesterol concentration and yolk weight.     

A comparison of aggressiveness and deoxynivalenol production between Canadian <Emphasis Type="Italic">Fusarium graminearum</Emphasis> isolates with 3-acetyl and 15-acetyldeoxynivalenol chemotypes in field-grown spring wheat

Twenty four isolates of Fusarium graminearum, half of which were 3-acetyldeoxynivalenol (3-ADON) and half 15-acetyldeoxynivalenol (15-ADON) chemotypes, were tested for their ability to produce deoxynivalenol and to cause Fusarium head blight (FHB) in spring wheat cultivars. The objectives of this study were to determine (1) whether 3-ADON isolates differ in aggressiveness, as measured by the FHB index, and DON production from 15-ADON isolates under field conditions, and (2) whether the performance of resistant host cultivars was stable across isolates. Field tests of all isolates were conducted with three replicates at each of two locations in Canada and Germany in 2008 with three host genotypes differing in FHB resistance level. The resistant host genotype showed resistance regardless of the chemotype or location. The differences between mean FHB indices of 3-ADON and 15-ADON isolates were not significant for any wheat genotype. In contrast, average DON production by the 3-ADON isolates (10.44 mg kg⁻¹) was significantly (P < 0.05) higher than for the 15-ADON isolates (6.95 mg kg⁻¹) at three of the four locations where moderately resistant lines were tested, and at both locations where susceptible lines were evaluated. These results indicate that 3-ADON isolates could pose a greater risk to food safety. However, as the mean aggressiveness and DON production of 3-ADON and 15-ADON chemotypes was similar on highly resistant lines, breeding and use of highly resistant lines is still the most effective measure of reducing the risks associated with DON in wheat.