Pharmacokinetic profiles of the analgesic flupirtine in dogs after the administration of four pharmaceutical formulations

ObjectiveFlupirtine (FLU) is a non-opioid analgesic with no antipyretic or anti-inflammatory effects which is used in the treatment of pain in humans. There is a substantial body of evidence on the efficacy of FLU in humans but this is inadequate for the recommendation of its off-label use in veterinary clinical practice. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after intravenous (IV), oral immediate release (POIR), oral prolonged release (POPR) and rectal (RC) administrations in healthy dogs.Study designFour-treatment, single-dose, four-phase, unpaired, cross-over design (4 × 4 Latin-square).AnimalsSix adult Labrador dogs.MethodsAnimals in groups 1, 2 and 4 received a single dose of 5 mg kg⁻¹ FLU administered by IV, POIR and RC routes. Group 3 received a single dose of 200 mg subject⁻¹ via the POPR route. The wash-out periods were 1 week. Blood samples (1 mL) were collected at assigned times for 48 hours and plasma FLU concentrations were analysed by a validated HPLC method.ResultsAdverse effects including salivation, tremors and vomiting were noted in the IV group and resolved spontaneously within 10 minutes. These effects did not occur in the other groups. The FLU plasma concentrations were detectable in all of the treatment groups for 36 hours following administration. The pharmacokinetic profiles after extravascular administrations showed similar trends. The bioavailability values after POIR, POPR and RC were 41.93%, 36.78% and 29.43%, respectively. There were no significant differences in pharmacokinetic profiles between the POIR and POPR formulations. A 5 mg kg⁻¹ POIR dose or a 200 mg subject⁻¹ POPR dose gave plasma concentrations similar to those reported in humans after clinical dosing.Conclusion and clinical relevanceThis study provides pharmacokinetic data that can be used to design further studies to investigate FLU in dogs.     

Unexpected disproportion observed in species composition between oak mixed stands and their progeny populations

We used morphological analysis to assess species composition of natural regenerations and progeny plantations established from two mixed oak stands in Jamy and Legnica, Poland. Despite equal proportions of pedunculate (Quercus robur) and sessile oak (Quercus petrea) in seed stands, the species composition differed strikingly. In all progeny populations, pedunculate oak dominated, reaching 89.5% and 96.6% in Legnica and Jamy, respectively. However, sessile oak predominated in natural regenerations. Morphological studies indicated a varied number of phenotypically intermediate or mosaic individuals. Among artificial populations, the highest number of putative hybrids was observed in Legnica (average 2.5%) and the lowest in Jamy (average 0.2%). Hybrids in natural regeneration were 1% in Legnica and 8% in Jamy. The disproportionate species composition could result from either unintentional indirect acorn selection during collection or selection in nursery practice. We discuss the role of ecophysiological differences between species in biased species representation in progeny populations.     

Influence of wheat leaf position on leaf rust severity

Summary The relation between flag leaf position and leaf rust severity was investigated in field experiments. Different leaf angles were obtained by attaching ends of flag leaves to strings stretched at different heights along wheat rows. Leaves with angles between lamina and stem of 0° and 45° were significantly less diseased than leaves with horizontal and pendulous positions. In the experiment with seedlings, spore settling and uredia number were significantly lower on erect than on horizontal leaves. The influence of wheat leaf position changes on leaf rust severity was discussed. It has been suggested that breeding of wheat cultivars with erect leaves can improve their resistance to airborne pathogens.     

Examination and presentation of element distribution in soil

Goal, Scope and Background  

The distribution of elements cannot only scatter widely in investigation areas, but also to a small scale in investigation fields. Chemometric methods are useful tools to describe the spatial distribution of the elements and are suitable to characterize the inhomogeneity in the soil. This knowledge can also be beneficial, among other things, for the creation of problem-adapted sampling strategies. The element distribution at one sampling point, the so-called microinhomogeneity considerably affects the representativeness of pollution assessment for a whole investigation area.     

Genetic resistance of carp (Cyprinus carpio L.) to Trypanoplasma borreli: influence of transferrin polymorphisms

In serum most of the iron molecules are bound to transferrin (Tf), which is a highly polymorphic protein in fish. Tf is an essential growth factor for mammalian trypanosomes. We performed a series of experiments with Trypanoplasma borreli to detect putative correlations between different Tf genotypes of common carp (Cyprinus carpio L.) and susceptibility to this blood parasite. Five genetically different, commercially exploited carp lines (Israelian 'D', Polish 'R2' and 'K', Ukrainian 'Ur', Hungarian 'R0') and a reference laboratory cross ('R3xR8') were challenged with T. borreli and parasitaemia measured to determine susceptibility to the parasite. Among the commercial carp lines, Israelian 'D' carp were identified as most and Polish 'R2' carp as least susceptible, and used to produce a next generation and reciprocal crosses. These progenies were challenged with T. borreli and parasitaemia measured. We demonstrated significant effects of genetic background of the carp lines on susceptibility to T. borreli. This genetic effect was preserved in a next generation. We also observed a significant male effect on susceptibility to T. borreli in the reciprocal crosses. Serum samples from a representative number of fish from two infection experiments were used for Tf genotyping by polyacrylamide gel electrophoresis (PAGE), identifying DD, DG and DF as most frequent Tf genotypes. We could detect a significant association of the homozygous DD genotype with low parasitaemia in the least susceptible 'R2' (and 'K') carp lines and the lack of a such an association in the most susceptible 'D' carp line. Upon examination of parasite growth in vitro in culture media supplemented with 3% serum taken from fish with different Tf genotypes, we could show a faster decrease in number of parasites in culture media with serum from DD-typed animals.     

The endocrine regulation of aging by insulin-like signals

Reduced signaling of insulin-like peptides increases the life-span of nematodes, flies, and rodents. In the nematode and the fly, secondary hormones downstream of insulin-like signaling appear to regulate aging. In mammals, the order in which the hormones act is unresolved because insulin, insulin-like growth factor-1, growth hormone, and thyroid hormones are interdependent. In all species examined to date, endocrine manipulations can slow aging without concurrent costs in reproduction, but with inevitable increases in stress resistance. Despite the similarities among mammals and invertebrates in insulin-like peptides and their signal cascade, more research is needed to determine whether these signals control aging in the same way in all the species by the same mechanism.     

GUIDE VALUES FOR ANTHURIUM (ANTHURIUM CULTORUM BIRDSEY) GROWN IN EXPANDED CLAY

Coefficients of variation and guide values of nutrients were determined for Anthurium cultorum Birdsey cvs. ‘Baron’, ‘Choco’, ‘Pistache’, ‘President’, ‘Midori’, and ‘Tropical’ grown in expanded clay (inert medium) using drip fertigation. Fully developed leaves after freshly-cut flowers were collected as index parts for chemical analyses at two-month intervals over the period of three years (2002–2004). Investigations were conducted at two specialized commercial farms, recording optimal yielding in terms of quantity and quality. A standard nutrient solution for anthurium hydroponics was used in fertigation. Mean guide values for six analyzed cultivars of Anthurium cultorum Birdsey are (in d.m. leaves): 1.40–1.70% nitrogen (N), 0.30–0.40% phosphorus (P), 3.60–4.50% potassium (K), 1.40–1.80% calcium (Ca), 0.20–0.30% magnesium (Mg), 0.30–0.40% sulfur (S), 46.0–60.0 ppm iron (Fe), 35.0–47.0 ppm manganese (Mn), 54.0– 72.0 ppm zinc (Zn), 5.10–6.50 ppm copper (Cu), and 64.0–83.0 ppm boron (B). Guide values for cvs. ‘Baron’, ‘Choco’, ‘Pistache’, ‘President’, ‘Midori’ and ‘Tropical’ are given in the text of this paper. A diversification was shown in guide values for analyzed cultivars in relation to certain macro- and microelements. Coefficients of variation were determined for nutrient contents in index parts of plants. A very high variation (%) was found for Mn 47.5 and Zn 41.8, high for Mg 38.5, P 32.6, S 30.6, medium for Fe 29.2, Ca 28.0, Cu 23.3 and B 20.3, while low for K 11.4 and N 9.9.     

Construction of integrated linkage map of a recombinant inbred line population of white lupin (Lupinus albus L.)

We report the development of a Diversity Arrays Technology (DArT) marker panel and its utilisation in the development of an integrated genetic linkage map of white lupin (Lupinus albus L.) using an F₈ recombinant inbred line population derived from Kiev Mutant/{"type":"entrez-protein","attrs":{"text":"P27174","term_id":"14195583","term_text":"P27174"}}P27174. One hundred and thirty-six DArT markers were merged into the first genetic linkage map composed of 220 amplified fragment length polymorphisms (AFLPs) and 105 genic markers. The integrated map consists of 38 linkage groups of 441 markers and spans a total length of 2,169 cM, with an average interval size of 4.6 cM. The DArT markers exhibited good genome coverage and were associated with previously identified genic and AFLP markers linked with quantitative trait loci for anthracnose resistance, flowering time and alkaloid content. The improved genetic linkage map of white lupin will aid in the identification of markers for traits of interest and future syntenic studies.