Pharmacokinetics of a high-concentration formulation of buprenorphine (Simbadol) in male dogs

ObjectiveTo describe the pharmacokinetics of buprenorphine in dogs following administration of a high-concentration formulation of buprenorphine.Study designProspective, randomized, crossover study.AnimalsA total of six healthy male intact Beagle dogs, aged 9–13 months and weighing 10.3 ± 1.4 kg (mean ± standard deviation).MethodsDogs were randomized to be administered buprenorphine (0.12 mg kg^–1; Simbadol, 1.8 mg mL^–1) via the intravenous (lateral saphenous) or subcutaneous (dorsal interscapular) route followed by the alternative route of administration after a 14 day interval. Blood was sampled before administration and at set times up to 72 hours after injection. Plasma buprenorphine concentration was measured using liquid chromatography–tandem mass spectrometry.ResultsA three-compartment model with zero or biphasic rapid and slow first-order input in (intravenous or subcutaneous data, respectively) and first-order elimination from the central compartment best fitted the data. The rapid first-order input accounted for 63% of the dosage absorption. Typical values (% interindividual variability) for the three compartment volumes were 900 (33), 2425 (not estimated) and 6360 (28) mL kg^–1. The metabolic and two distribution clearances were 25.7 (21), 107.5 (74) and 5.7 (61) mL minute^–1 kg^–1. The absorption half-life for the fast absorption phase was 8.9 minutes with a 0.7 (103) minute delay. The absorption half-life for the slow absorption phase was 347 minutes with a 226 (42) minute delay. Median (range) bioavailability calculated from noncompartmental analysis was 143 (80–239)%. Calculated terminal half-life was 963 minutes.Conclusions and clinical relevanceThe high-concentration formulation of buprenorphine administered subcutaneously had a large volume of distribution and a rapid absorption phase followed by slower, delayed absorption. The high estimate of bioavailability should be interpreted with caution as values above 100% are most commonly related to experimental issues.     

Cardiovascular function,pulmonary gas exchange and tissue oxygenation in isoflurane-anesthetized,mechanically ventilated Beagle dogs with four levels of positive end-expiratory pressure

ObjectivesTo compare pulmonary gas exchange, tissue oxygenation and cardiovascular effects of four levels of end-expiratory pressure: no positive end-expiratory pressure (ZEEP), positive end-expiratory pressure (PEEP) of maximal respiratory system compliance (PEEPmaxC_rs), PEEPmaxC_rs + 2 cmH₂O (PEEPmaxC_rs+2), PEEPmaxC_rs + 4 cmH₂O (PEEPmaxC_rs+4), in isoflurane-anesthetized dogs.Study designProspective randomized crossover study.AnimalsA total of seven healthy male Beagle dogs, aged 1 year and weighing 10.2 ± 0.7 kg (mean ± standard deviation).MethodsThe dogs were administered acepromazine and anesthesia was induced with propofol and maintained with isoflurane. Ventilation was controlled for 4 hours with ZEEP, PEEPmaxC_rs, PEEPmaxC_rs+2 or PEEPmaxC_rs+4. Cardiovascular, pulmonary gas exchange and tissue oxygenation data were evaluated at 5, 60, 120, 180 and 240 minutes of ventilation and compared using a mixed-model anova followed by Bonferroni test. p < 0.05 was considered significant.ResultsCardiac index (CI) and mean arterial pressure (MAP) were lower in all PEEP treatments at 5 minutes when compared with ZEEP. CI persisted lower throughout the 4 hours only in PEEPmaxC_rs+4 with the lowest CI at 5 minutes (2.15 ± 0.70 versus 3.45 ± 0.94 L minute^–1 m^–2). At 180 and 240 minutes, MAP was lower in PEEPmaxC_rs+4 than in PEEPmaxC_rs, with the lowest value at 180 minutes (58 ± 7 versus 67 ± 7 mmHg). Oxygen delivery index (DO₂I) was lower in PEEPmaxC_rs+4 than in ZEEP at 5, 60, 120 and 180 minutes. Venous admixture was not different among treatments.Conclusion and clinical relevanceThe use of PEEP caused a transient decrease in MAP and CI in lung-healthy dogs anesthetized with isoflurane, which improved after 60 minutes of ventilation in all levels of PEEP except PEEPmaxC_rs+4. A clinically significant improvement in arterial oxygenation and DO₂I was not observed with PEEPmaxC_rs and PEEPmaxC_rs+2 in comparison with ZEEP, whereas PEEPmaxC_rs+4 decreased DO₂I.     

The calicheamicin gene cluster and its iterative type I enediyne PKS

The enediynes exemplify nature's ingenuity. We have cloned and characterized the biosynthetic locus coding for perhaps the most notorious member of the nonchromoprotein enediyne family, calicheamicin. This gene cluster contains an unusual polyketide synthase (PKS) that is demonstrated to be essential for enediyne biosynthesis. Comparison of the calicheamicin locus with the locus encoding the chromoprotein enediyne C-1027 reveals that the enediyne PKS is highly conserved among these distinct enediyne families. Contrary to previous hypotheses, this suggests that the chromoprotein and nonchromoprotein enediynes are generated by similar biosynthetic pathways.     

Comment on "Synthesis of ultra-incompressible superhard rhenium diboride at ambient pressure"

Chung et al. (Reports, 20 April 2007, p. 436) reported the synthesis of superhard rhenium diboride (ReB2) at ambient pressure. We show that ReB2, first synthesized at ambient pressure 45 years ago, is not a superhard material. Together with the high cost of Re, this makes the prospect for large-scale industrial applications of ReB2 doubtful.     

Functional divergence of former alleles in an ancient asexual invertebrate

Theory suggests it should be difficult for asexual organisms to adapt to a changing environment because genetic diversity can only arise from mutations accumulating within direct antecedents and not through sexual exchange. In an asexual microinvertebrate, the bdelloid rotifer, we have observed a mechanism by which such organisms could acquire the diversity needed for adaptation. Gene copies most likely representing former alleles have diverged in function so that the proteins they encode play complementary roles in survival of dry conditions. One protein prevents desiccation-sensitive enzymes from aggregating during drying, whereas its counterpart does not have this activity, but is able to associate with phospholipid bilayers and is potentially involved in maintenance of membrane integrity. The functional divergence of former alleles observed here suggests that adoption of asexual reproduction could itself be an evolutionary mechanism for the generation of diversity.     

Grain and Tortilla Quality in Landraces and Improved Maize Grown in the Highlands of Mexico

The maize produced in the highlands of Mexico (>2,400 masl) is generally not accepted by the flour and masa and tortilla industry. The objective of this work was to evaluate the grain quality and tortilla properties of maize landraces commonly grown in the highlands of Mexico and compare them with improved germplasm (hybrids). Germplasm analysis included 11 landraces, 32 white hybrids, and six yellow hybrids. Grain quality was analyzed for a range of physical and chemical factors, as well as for alkaline cooking quality. Landrace grains tended to be heterogeneous in terms of size, hardness and color. All landraces had soft-intermediate grains with an average flotation index (FI) of 61%. In contrast, hybrid grains were homogenous in size and color, and harder than landrace grains, with a FI of 38%. Protein, free sugars, oil and phenolic content in landraces were higher than in the hybrids. Significant correlations were found between phenolic content and tortilla color (r = −0.60; p < 0.001). Three landraces were identified as appropriate for the masa and tortilla industry, while all the hybrids evaluated fulfilled the requirements of this industry.     

Composition of forage and grain from second-generation insect-protected corn MON 89034 is equivalent to that of conventional corn (Zea mays L.)

Insect-protected corn hybrids containing Cry insecticidal proteins derived from Bacillus thuringiensis have protection from target pests and provide effective management of insect resistance. MON 89034 hybrids have been developed that produce both the Cry1A.105 and Cry2Ab2 proteins, which provide two independent modes of insecticidal action against the European corn borer ( Ostrinia nubilalis ) and other lepidopteran insect pests of corn. The composition of MON 89034 corn was compared to conventional corn by measuring proximates, fiber, and minerals in forage and by measuring proximates, fiber, amino acids, fatty acids, vitamins, minerals, antinutrients, and secondary metabolites in grain collected from 10 replicated field sites across the United States and Argentina during the 2004-2005 growing seasons. Analyses established that the forage and grain from MON 89034 are compositionally comparable to the control corn hybrid and conventional corn reference hybrids. These findings support the conclusion that MON 89034 is compositionally equivalent to conventional corn hybrids.     

Dietary switching of collembola in grassland soil food webs

Soil food webs are characterised by complex direct and indirect effects among the organisms. Consumption of microorganisms by soil animals is considered as an important factor that contributes to the stability of communities, though cascading effects within the food web can be difficult to detect. In a greenhouse experiment, an addition of a high number the fungal feeding collembola Folsomia quadrioculata was applied to grassland soil food webs in monocultures of three plant species: Plantago lanceolata (forb), Lotus corniculatus (legume) and Holcus lanatus (grass). The abundance of microorganisms, determined as the abundances of phospholipid fatty acids (PLFAs) and the abundances of resident invertebrates, nematodes and collembolans, did not change due to the addition of F. quadrioculata. Trophic positions of collembolans were determined by analyses of natural abundances of ¹⁵N stable isotopes. The use of food resources by microorganisms and collembolans was determined by ¹³C analysis of microbial PLFAs and solid samples of collembolans. δ¹³C values of the resident collembola Folsomia fimetaria were lower in the presence of F. quadrioculata than in the control food webs indicating a use of more depleted ¹³C food resources by F. fimetaria. The δ¹⁵N values of F. fimetaria did not change at the addition of F. quadrioculata thus no change of trophic levels was detected. The switch of F. fimetaria to a different food resource could be due to indirect interactions in the food web as the two collembolan species were positioned on different trophic positions, according to different δ¹⁵N values.     

Consumption of 'extra' foods (energy-dense, nutrient-poor) among children aged 16-24 months from western Sydney, Australia

OBJECTIVE: This study evaluates the contribution of energy-dense, nutrient-poor 'extra' foods to the diets of 16-24-month-old children from western Sydney, Australia. DESIGN: An analysis of cross-sectional data collected on participants in the Childhood Asthma Prevention Study (CAPS), a randomised trial investigating the primary prevention of asthma from birth to 5 years. We collected 3-day weighed food records, calculated nutrient intakes, classified recorded foods into major food groups, and further classified foods as either 'core' or 'extras' according to the Australian Guide to Healthy Eating. SETTING: Pregnant women, whose unborn child was at risk of developing asthma because of a family history, were recruited from all six hospitals in western Sydney, Australia. Data for this study were collected in clinic visits and at participants' homes at the 18-month assessment. PARTICIPANTS: Four hundred and twenty-nine children participating in the CAPS study; 80% of the total cohort. RESULTS: The mean consumption of 'extra' foods was approximately 150 g day(-1) and contributed 25-30% of the total energy, fat, carbohydrate and sodium to the diets of the study children. 'Extra' foods also contributed around 20% of fibre, 10% of protein and zinc, and about 5% of calcium. Children in the highest quintile of 'extra' foods intake had a slightly higher but not significantly different intake of energy from those in the lowest quintile. However, significant differences were evident for the percentage of energy provided by carbohydrate and sugars (higher) and protein and saturated fat (lower). The intake of most micronutrients was also significantly lower among children in the highest quintile of consumption. The intake of 'extra' foods was inversely associated with the intake of core foods. CONCLUSIONS: The high percentage of energy contributed by 'extra' foods and their negative association with nutrient density emphasise the need for dietary guidance for parents of children aged 1-2 years. These preliminary data on commonly consumed 'extra' foods and portion sizes may inform age-specific dietary assessment methods.     

Genetic Diversity in Argentine Andean Potatoes by Means of Functional Markers

Andean Potato is a major crop for farmers in the Andes and represents an important gene pool for potato improvement. We present the population structure and genetic diversity of 88 Andigena accessions collected in Northwestern Argentina based on functional markers (25 SSR) distributed along 12 chromosomes. Polymorphic information content ranged from 0.40 to 0.87. A Bayesian approach, a Principal Coordinate Analysis and a Cluster Analysis revealed the presence of: I) a major group containing most of the Andean accessions and II) a smaller group including the out-group cv. Spunta and the sequenced genotype DM. Several group specific alleles were detected. AMOVA showed that 81% of the variability was within each group. Eleven of the SSRs analyzed are linked or within genes reported to regulate traits of nutritional and industrial interest. Additionally, the allelic variant of a photoperiod dependent tuberization regulator gene, StCDF1.2, was exclusively detected in accessions clustered in group II.