The steady-state pharmacokinetics and bioequivalence of carprofen administered orally and subcutaneously in dogs

Eighteen male Beagle dogs were randomized to oral (p.o.) or subcutaneous (s.c.) carprofen administration in a two-sequence, two-period crossover design with a 10-day washout between periods. Twenty-five milligrams of carprofen was administered p.o. or s.c. every 12 h for 7 days. Plasma concentrations of carprofen collected after the first and last treatments were determined by high-performance liquid chromatography. Carprofen concentration data were natural log transformed and geometric means were calculated for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC0--12) following the first dose and Cmax and AUC0--12 following administration of the last dose. Formulations were considered bioequivalent if the 90% confidence interval (CI) of the mean difference for each variable between formulations were within -20% and 25% of the oral formulation. The mean Cmax and AUC0--12 were 16.9 microg/mL and 73.1 microg. h/mL, respectively, following a single oral dose and 8.0 microg/mL and 64.3 microg x h/mL, respectively, following a single s.c. injection. The 90% CI for Cmax (-56.8 to -48.7%) was outside of the bioequivalence criteria whereas the 90% CI for AUC0--12 (-16.3 to -7.5%) was within the bioequivalence criteria. At steady-state, the mean Cmax and AUC0--12 were 18.7 microg/mL and 101.9 microg x h/mL, respectively, following p.o. administration and 14.7 microg/mL and 111.0 microg x h/mL, respectively, following s.c. injection. The 90% CI was outside the bioequivalence criteria for Cmax (-30.8 to -10.8) but within the bioequivalence criteria for AUC0--12 (2.3-15.9%). The results of this study indicate that peak plasma concentrations of carprofen differ when administered p.o. and s.c., but that total drug exposure following a single dose and at steady-state are bioequivalent.     

Site-Directed Disruption of the fimA and fimF Fimbrial Genes of Xylella fastidiosa

ABSTRACT Xylella fastidiosa causes Pierce's disease, a serious disease of grape, citrus variegated chlorosis, almond and oleander leaf scorches, and many other similar diseases. Although the complete genome sequences of several strains of this organism are now available, the function of most genes in this organism, especially those conferring virulence, is lacking. Attachment of X. fastidiosa to xylem vessels and insect vectors may be required for virulence and transmission; therefore, we disrupted fimA and fimF, genes encoding the major fimbrial protein FimA and a homolog of the fimbrial adhesin MrkD, to determine their role in the attachment process. Disruption of the fimA and fimF genes in Temecula1 and STL grape strains of X. fastidiosa was obtained by homologous recombination using plasmids pFAK and pFFK, respectively. These vectors contained a kanamycin resistance gene cloned into either the fimA or fimF genes of X. fastidiosa grape strains Temecula1 or STL. Efficiency of transformation was sufficiently high ( approximately 600 transformants per mug of pFFK DNA) to enable selection of rare recombination events. Polymerase chain reaction and Southern blot analyses of the mutants indicated that a double crossover event had occurred exclusively within the fimA and fimF genes, replacing the chromosomal gene with the disrupted gene and abolishing production of the corresponding proteins, FimA or FimF. Scanning electron microscopy revealed that fimbriae size and number, cell aggregation, and cell size were reduced for the FimA or FimF mutants of X. fastidiosa when compared with the parental strain. FimA or FimF mutants of X. fastidiosa remained pathogenic to grapevines, with bacterial populations slightly reduced compared with those of the wild-type X. fastidiosa cells. These mutants maintained their resistance to kanamycin in planta for at least 6 months in the greenhouse.     

Effects of Date of Inoculation on the Within-Plant Movement of Xylella fastidiosa and Persistence of Pierce's Disease Within Field Grapevines

ABSTRACT The effects of date of inoculation on the development of Pierce's disease (PD) were evaluated in California grapevines during 1997 through 2000 at four locations. Some vines that had been inoculated either by using blue-green sharpshooters (Graphocephala atropunctata) as vectors or mechanically by needle puncture with the PD causal bacterium Xylella fastidiosa became infected during each month and at each location where infection was attempted. Vines inoculated on the earliest inoculation dates (April to May) developed more extensive and severe PD symptoms, and only 54% of these vines recovered from PD after the following winter, compared with vines that had been inoculated during June through August, of which 88% recovered from PD after the following winter. For the 1999 inoculations, the number of vines infected at a central California site (Parlier) was higher than the number of vines infected at a north coastal site (Hopland). For the best-fitting regression equation, percent recovery of vines infected with X. fastidiosa increased significantly with date of inoculation (r(2) = 0.737) at all sites excluding Hopland. The Hopland site had the highest percentage of vines that recovered from PD (100%). At most sites, only early infection (April and May) resulted in chronic disease unless the vines were inoculated at the bases instead of the distal tips of canes. Vines inoculated early in the growing season (April and May) have less chance to recover from Pierce's disease than vines inoculated later (July and August).     

Proteomic analysis of amniotic and allantoic fluid from buffaloes during foetal development

The objective of this study was to describe the dynamic changes in protein composition and protein abundance in amniotic and allantoic fluids from buffaloes during gestation. Amniotic and allantoic fluids were collected during the first, second and third trimesters of gestation. The foetuses were measured and weighed. Fluid samples were centrifuged at 800 g for 10 min and then at 10,000 g for 60 min at 4°C. The supernatant was collected to determine the total protein concentration. Based on total protein concentration, an aliquot (50 μg) was used for in‐solution tryptic digestion, and mass spectrometry analysis (nano‐LC‐MS/MS) was performed. A multivariate statistical analysis of the proteomic data was conducted. Across the different stages of buffalo gestation, fifty‐one proteins were found in the amniotic fluid, and twenty‐one were found in the allantoic fluid. A total of twelve proteins were common among the stages, and four presented significant differences (VIP score α > 1). Fibronectin and alpha‐1‐antiproteinase were more abundant in the amniotic fluid than in the allantoic fluid. Alpha‐2‐macroglobulin and alpha‐2‐HS‐glycoprotein were more abundant in the allantoic fluid than in the amniotic fluid. Alpha‐2‐macroglobulin participates in remodelling and growth of the uterus at beginning of the gestation (first trimester), and these findings indicate that can serve as a potential tool for the early diagnosis of pregnancy in buffaloes.     

Response of water and nutrient fluxes to improvement fellings in a tropical montane forest in Ecuador

Management of natural forests might be one option to reduce the high deforestation rate in Ecuador. We therefore evaluated the response of water and nutrient cycles in a natural tropical montane forest to improvement fellings with the aim of favoring economically valuable target trees which will later be harvested with additional ecosystem impacts not considered here.     

Smartphone adoption and use in agriculture: empirical evidence from Germany

Precision Agriculture - Smartphone technology is promising for the future development of agriculture, as it can facilitate and improve many operational procedures and can also be combined with...     

Root morphology of maize under homogeneous or spatially separated supply of ammonium and nitrate at three concentration ratios

Maize (Zea mays L. cv. Anjou 256) seedlings were grown hydroponically for 10 d in a split‐root system (3mM N; pH 5.5) under either a homogeneous supply (HS) or a simultaneous, but spatially separated supply (SS) of NH₄ ⁺ andNO₃ ^‐. Treatments comprised three NH₄ ⁺:NO₃ ^‐ ratios (1:4, 1:1, 4:1). Shoot dry matter and various root traits (dry matter, number of laterals, length of main axes, total root length and total root surface area) were determined. For all NH₄ ⁺:NO₃ ^‐ ratios, shoot dry matter, root dry matter, total root length, and root surface area, were greater under HS than under SS. Under both SS and HS, increasing NH₄ ⁺:NO₃ ^‐ ratios resulted in decreased shoot and root dry matter production, but did not alter the shoot:root dry matter ratio. Under SS, root dry matter, root length, and root surface area was greater on the NO₃ ^‐‐fertilized side than on the NH₄ ⁺ ‐fertilized side. The allocation of root dry matter, root length, and root surface area to the NH₄ ⁺ or NO₃ ^‐ compartments was unaffected by changes in the NH₄ ⁺:NO₃ ^‐ ratio. Enhanced NH₄ ⁺ nutrition has detrimental effects on top growth, but roots are apparently unable to avoid excessive NH₄ ⁺ uptake by proliferating in zones where NO₃ ^‐ is the only form of N.     

Relationship between grain yield and grain nitrogen concentration in winter triticale

Summary Ten hexaploid winter triticale lines were grown for two cropping periods at three locations in western Switzerland. Averaged across the six environments, the differences between lines were statistically significant (P=0.05) for grain yield, above-ground biomass, N uptake, grain N yield, nitrogen harvest index, grain N concentration and straw N concentration. There were significant line x environment interactions for all traits. Grain yield and grain N concentration were inversely related (r=–0.74^**). Diagrams in which grain yields were plotted against grain N concentration were used to identify lines with a consistently unusual combination of grain yield and grain N concentration. Despite comparable grain yields, Line 3 had a high grain N concentration, while that of Line 7 was low. Line 3 was superior to Line 7 in both N uptake and N harvest index. Averaged across environments and lines, the N harvest index was 0.73 which corresponds to N harvest indices reported for bread wheat in the same region. We considered the feasibility of developing triticale lines which would outperform the best recent ones in N uptake and partitioning. However, we doubted that this would bring about a marked increase in grain N concentration, because, in the long run, the expected genetic progress in grain yield will lead to a dilution of grain protein by grain carbohydrate increments.Abbreviations GNC grain N concentration - GNY grain N yield - GY grain yield - HI above-ground dry matter harvest index - NHI nitrogen harvest index - SNC straw N concentration - TB total above-ground biomass - TPN total plant N     

Controlling the release of pollen from genetically modified maize and increasing its grain yield by growing mixtures of male-sterile and male-fertile plants

There is public concern about the consequences of pollen dispersal from genetically modified (GM) crops. There lease of viable pollen from GM maize can be controlled by growing mixtures of cytoplasmic male-sterile plants and male-fertile non-transformed pollinator plants. Our experiments indicate that such associations can bring about grain yields as high or even higher than those produced by pure male-fertile maize crops, especially when the male-sterile component is pollinated non-isogenically. The grain yield benefits from cytoplasmic malesterility and xenia as well as the fact that seed of male-sterile varieties can be produced cheaply and reliably in large quantities would facilitate the implementation of the proposed system in agricultural practice. This revised version was published online in July 2006 with corrections to the Cover Date.