Enantioselective pharmacokinetics of ketoprofen in calves after intramuscular administration of a racemic mixture

The pharmacokinetic properties of ketoprofen were determined in 4‐week‐old calves after intramuscular (i.m.) injection of a racemic mixture at a dose of 3 mg/kg body weight. Due to possible enantioselective disposition kinetics and chiral inversion, the plasma concentrations of the R(?) and S(+) enantiomer were quantified separately, using a stereospecific HPLC‐UV assay. A distinct predominance of the S(+) enantiomer was observed, as well as significantly different pharmacokinetic parameters between R(?) and S(+) ketoprofen. More in specific, a greater value for the mean area under the plasma concentration–time curve (AUC_0→∞) (46.92 ± 7.75 and 11.13 ± 2.18 μg·h/mL for the S(+) and R(?) enantiomer, respectively), a lower apparent clearance (Cl/F) (32.8 ± 5.7 and 139.0 ± 25.1 mL/h·kg for the S(+) and R(?) enantiomer, respectively) and a lower apparent volume of distribution (V_d/F) (139 ± 14.7 and 496 ± 139.4 mL/kg for the S(+) and R(?) enantiomer, respectively) were calculated for the S(+) enantiomer, indicating enantioselective pharmacokinetics for ketoprofen in calves following i.m. administration.     

Fertilizing Capacity of Frozen Epididymal Sperm Collected from Dogs

The collection of epididymal sperm may be a valuable tool for canine reproduction especially since it can enable collection of cells after death of a valuable dog. The aim of the present study was to evaluate the viability of epididymal sperm after freeze-thawing. Epididymides were obtained from four adult dogs by elective orchiectomy. The caudal portion of the epididymides and part of the deferential ducts were squeezed by means of an anatomic clamp into a Petri dish containing either 0.9% saline solution (Group 1) or Ringer solution without lactate (Group 2). Samples were centrifuged at 800 ×  g for 10 min, the supernatant was removed and the pellet was diluted in one step with a Tris/citric acid/OEP (Orvus Es Paste) extender containing 7% glycerol and subjected to semen freezing. Oocytes were obtained from canine ovaries, after ovariohysterectomy. Only oocytes that were approximately 100 μm in diameter, with a dark ooplasm surrounded by three- or four-well formed cumulus cell layers were used for sperm testing. Frozen semen samples were thawed in a water bath at 70°C for 8 s and analysed at room temperature for sperm motility and velocity. Oocytes were incubated with spermatozoa in humidified atmosphere containing 5% CO₂ at 38°C for 18 h. Morphological and functional characteristics of spermatozoa were similar in both groups. However, the percentage of sperm cells bound to oocytes was significantly higher in Group 2 than in Group 1. This result suggests that the Ringer solution without lactate was a more suitable medium for collecting epididymal canine sperm than 0.9% saline.     

Kisspeptin,c‐Fos and CRFR Type 2 Co‐expression in the Hypothalamus after Insulin‐Induced Hypoglycaemia

Normal reproductive function is dependent upon availability of glucose and insulin‐induced hypoglycaemia is a metabolic stressor known to disrupt the ovine oestrous cycle. We have recently shown that IIH has the ability to delay the LH surge of intact ewes. In the present study, we examined brain tissue to determine: (i) which hypothalamic regions are activated with respect to IIH and (ii) the effect of IIH on kisspeptin cell activation and CRFR type 2 immunoreactivity, all of which may be involved in disruptive mechanisms. Follicular phases were synchronized with progesterone vaginal pessaries and at 28 h after progesterone withdrawal (PW), animals received saline (n = 6) or insulin (4 IU/kg; n = 5) and were subsequently killed at 31 h after PW (i.e., 3 h after insulin administration). Peripheral hormone concentrations were evaluated, and hypothalamic sections were immunostained for either kisspeptin and c‐Fos (a marker of neuronal activation) or CRFR type 2. Within 3 h of treatment, cortisol concentrations had increased whereas plasma oestradiol concentrations decreased in peripheral plasma (p < 0.05 for both). In the arcuate nucleus (ARC), insulin‐treated ewes had an increased expression of c‐Fos. Furthermore, the percentage of kisspeptin cells co‐expressing c‐Fos increased in the ARC (from 11 to 51%; p < 0.05), but there was no change in the medial pre‐optic area (mPOA; 14 vs 19%). CRFR type 2 expression in the lower part of the ARC and the median eminence was not altered by insulin treatment. Thus, disruption of the LH surge after IIH in the follicular phase is not associated with decreased kisspeptin cell activation or an increase in CRFR type 2 in the ARC but may involve other cell types located in the ARC nucleus which are activated in response to IIH.     

Characterization of aerosols containing microcystin

Toxic blooms of cyanobacteria are ubiquitous in both freshwater and brackish water sources throughout the world. One class of cyanobacterial toxins, called microcystins, is cyclic peptides. In addition to ingestion and dermal, inhalation is a likely route of human exposure. A significant increase in reporting of minor symptoms, particularly respiratory symptoms was associated with exposure to higher levels of cyanobacteria during recreational activities. Algae cells, bacteria, and waterborne toxins can be aerosolized by a bubble-bursting process with a wind-driven white-capped wave mechanism. The purposes of this study were to: evaluate sampling and analysis techniques for microcystin aerosol, produce aerosol droplets containing microcystin in the laboratory, and deploy the sampling instruments in field studies. A high-volume impactor and an IOM filter sampler were tried first in the laboratory to collect droplets containing microcystins. Samples were extracted and analyzed for microcystin using an ELISA method. The laboratory study showed that cyanotoxins in water could be transferred to air via a bubble-bursting process. The droplets containing microcystins showed a bimodal size distribution with the mass median aerodynamic diameter (MMAD) of 1.4 and 27.8 mum. The sampling and analysis methods were successfully used in a pilot field study to measure microcystin aerosol in situ.     

Roles of bootstrap resampling,measure of central tendency,and method for calculating thermal units when developing phenology models for pest management

The successful development of phenology models from field studies depends on many factors, some of which are entirely under the control of pest managers. For example, one such factor is the choice of method for calculating thermal units. In this study, we have demonstrated that four methods for calculating thermal units provided for acceptable predictions of one phenological event of one insect species, while another method for calculating thermal units did not. The measure of central tendency (mean or median) that is used to estimate lower developmental temperatures and required thermal summations is another factor that pest managers can control when developing phenology models from field studies. Here, we show that predictions that were made when using phenology models based on median lower developmental temperatures and median required thermal summations were superior to predictions that were made when using phenology models based on mean lower developmental temperatures and mean required thermal summations. The use of bootstrap vs. non-bootstrap estimates of lower developmental temperatures and required thermal summations is yet another factor that pest managers can control when developing phenology models from field studies. In this study, we found that calculating and using bootstrap estimates of lower developmental temperatures and required thermal summations in phenology models did not improve the predictions of one phenological event for one insect species. The implications of these and other findings are discussed.     

Breakfast habits affect overall nutrient profiles in adolescents

OBJECTIVE: To describe breakfast consumption patterns, on a nutrient and food item level, in Belgian adolescents. DESIGN: A 7-day estimated food record was administered in a cross-sectional survey. SETTING: Secondary schools in Ghent, Belgium. SUBJECTS: A total of 341 adolescents (13-18 years old), multistage clustered sampling. RESULTS: The energy contribution of breakfast to daily energy intake was on average 15.7% in boys and 14.9% in girls. Significantly more overweight girls and significantly more girls following vocational training were categorised as eating a low-quality breakfast. In boys, the energy contribution of polysaccharides was significantly higher in consumers of good-quality breakfasts. The intake of all selected micronutrients was significantly higher in consumers of good-quality breakfasts. In girls, the total energy intake and the proportional intake of proteins and polysaccharides were significantly higher in consumers of good-quality breakfasts, while the proportional contribution of total fat, monounsaturated and polyunsaturated fatty acids was significantly lower in these girls. The intake of all micronutrients was significantly higher in girls consuming a good-quality breakfast. In all adolescents, consumers of a good-quality breakfast had significantly higher intakes of bread, fruit, vegetables, milk and milk products, and fruit juice, while intake of soft drinks was significantly lower than in consumers of low-quality breakfasts. CONCLUSIONS: Consumers of a good-quality breakfast had a better overall dietary pattern - on a nutrient and food group level - than consumers of a low-quality breakfast. A daily breakfast, including whole-grain products, fruit and (semi-) skimmed milk products or an alternative source of calcium, is recommended.     

Structure–activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae

BACKGROUND: Dengue fever is a severe public health problem for several countries. In order to find effective larvicides to aid control programs, the structure‐activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae were evaluated. Additionally, the composition and larvicidal activity of Syzygium aromaticum essential oil was assessed. RESULTS: Four compounds representing 99.05% of S. aromaticum essential oil have been identified. The essential oil was active against Ae. aegypti larvae (LC₅₀ = 62.3 and 77.0 ppm, field‐collected and Rockefeller larvae respectively). The larvicidal activity of eugenol, the major compound of the essential oil, was further evaluated (LC₅₀ = 93.3 and 71.9 ppm, field‐collected and Rockefeller larvae respectively). The larvicidal activity and structure‐activity relationships of synthetic derivatives of eugenol were also assessed. The larvicidal activity of the derivatives varied between 62.3 and 1614.9 ppm. Oxidation of eugenol allylic bond to a primary alcohol and removal of the phenolic proton resulted in decreased potency. However, oxidation of the same double bond in 1‐benzoate‐2‐methoxy‐4‐(2‐propen‐1‐yl)‐phenol resulted in increased potency. CONCLUSION: Structural characteristics were identified that may contribute to the understanding of the larvicidal activity of phenylpropanoids. The present approach may help future work in the search for larvicidal compounds. Copyright © 2012 Society of Chemical Industry     

Synovial fluid and plasma concentrations of ceftiofur after regional intravenous perfusion in the horse

OBJECTIVE: To determine radiocarpal (RC) joint synovial fluid and plasma ceftiofur concentrations after regional intravenous perfusion (RIP) and systemic intravenous (IV) administration. STUDY DESIGN: Experimental cross-over study. ANIMALS: Five normal adult horses. METHODS: One RC joint was randomly selected for RIP and the contralateral RC joint was sampled to determine intrasynovial ceftiofur concentrations after IV administration. Wash-out between IV and RIP was > or = 14 days. After surgical introduction of an intraarticular catheter, ceftiofur (2 g) was administered under general anesthesia either IV or by RIP after tourniquet application. Plasma and synovial fluid were collected over 24 hours. Samples were analyzed using high-performance liquid chromatography with ultraviolet detection and the results were statistically analyzed using a linear mixed effect model. RESULTS: Mean synovial fluid ceftiofur concentrations were consistently higher after RIP than after IV administration and were > 1 mug/mL (minimal inhibitory concentration [MIC] for common pathogens) for >24 hours. Mean synovial fluid peak concentration of ceftiofur after RIP and IV administration was 392.7+/-103.29 microg/mL at 0.5 hours postinjection (HPI) and 2.72+/-0.31 mug/mL at 1 HPI, respectively. Large variations in synovial fluid and plasma ceftiofur concentrations were observed between horses regardless of administration technique. RIP did not cause adverse effects. CONCLUSIONS: Under the present experimental conditions RIP with ceftiofur (2 g) induced significantly higher intraarticular antibiotic concentrations in the RC joint in comparison with IV administration. Moreover, after RIP, synovial fluid ceftiofur concentrations remain above the MIC for common pathogens (1 microg/mL) for > 24 hours. No adverse effects from the technique or the antibiotic were observed. CLINICAL RELEVANCE: RIP with high doses of ceftiofur may be a beneficial adjunctive therapy when treating equine synovial infections which are caused by cephalosporin susceptible microorganisms.     

Pharmacokinetics of dexamethasone after intravenous and intramuscular administration in broiler chickens

The aim of this study was to determine the pharmacokinetics of dexamethasone in broiler chickens. Dexamethasone sodium phosphate (0.3 mg/kg bodyweight) was injected IV or IM and blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 h after administration. Dexamethasone in the plasma samples was measured using a liquid chromatography–tandem mass spectrometry method and the pharmacokinetics analysed according to a one-compartmental model.The maximum plasma concentration after IM administration occurred at 0.37 h. The elimination half-life for dexamethasone was 0.46 h and 0.70 h following IV and IM administration, respectively, which was shorter than other species, while the clearance (1.26 L/h kg) was higher than has been reported for other species (<0.5 L/h kg). The volume of distribution (～1 L/kg) was similar to values reported for other species and the bioavailability of dexamethasone after IM administration was 100%. The results from this study will be useful in investigating whether inflammatory disease may affect the pharmacokinetic parameters of dexamethasone in chickens.