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.     

Cultivar variation in apple peel and whole fruit phenolic composition

The quali-quantitative distribution of phenolic compounds varies considerably between apple flesh and peel, but the concentration of phenolics is substantially higher in the peel than flesh. Because the peel comprises only a small percentage of the entire fruit weight, its significance as a donor of phenolics is disputable. We assessed the contribution of the peel to the total phenolic yield of 19 apple cultivars. Calculations were based on the weight of the whole fruit and the peel (which is frequently discarded) and the concentration of individual phenolic compounds. On average, 8, 24, 32, 50 and 66% of chlorogenic acid, (+)-catechin, (−)-epicatechin, phloridzin, and rutin, respectively, were present in the peel, which constitutes about 6–8% of the whole apple weight. With the exception of chlorogenic acid, 50% or more, on average, of the above phenolics were present in the peel of ‘Granny Smith’, ‘Idared’, ‘Red Rome’, ‘Jonamac’ and ‘Gloster’ apples; the highest percentage was found in ‘Starking Delicious’ apple peel (82%). The lowest peel contribution to total phenolic content per whole apple ranged between 26 and 29% and was observed in ‘Pilot’, ‘McIntosh’ and ‘Prima’ apples. Presented results may be useful for further investigations of the relationship between phenolics and agronomical parameters or future selection of apple genotypes having improved nutritional quality when consumed as fresh or as processed apple products.     

Impact of long‐term dietary exposure to lead on some reproductive parameters of a female Common carp (Cyprinus carpio L.)

During a long‐term 3‐year dietary exposure of mature carp females to lead, its bioaccumulation in the brain, changes in the neurohormonal activity at the level of the hypothalamus and the pituitary gland as well as the growth and maturation of ovaries were analysed. Moreover, an analysis of the effectiveness of hormone‐stimulated spawning during two subsequent spawning seasons was carried out. The results of the analyses show that chronic exposure of maturing and mature carp females to lead in feed results in its accumulation in the brain (1.365 μg g^?1). This impairs the endocrine activity of the hypothalamus, which is manifested by, among others, an increased secretion of dopamine and impaired spontaneous secretion of luteinizing hormone (LH). The observed decrease in the concentration of gonadotropin in blood inhibits vitellogenesis, which is manifested by a lower degree of the maturity of oocytes, lower fecundity (as measured by egg number, egg weight, egg maturity and egg survival) and lower gonadosomatic index values. The final negative impact of lead is the impairment of reproductive functions, as manifested by a smaller number of spawning females and in their lower fecundity during spawning.     

Early infection of Fagus sylvatica by Heterobasidion annosum sensu stricto

Heterobasidion annosum sensu stricto is the most important damaging agent in Scots pine stands planted on the former agricultural lands in Poland. The routine action in pine stands which have lost stability because of H. annosum root rot is to change stand management, including species conversion. In many cases, the Fagus sylvatica is used for this purpose. This study was the first assessment of widespread infection by H. annosum in young F. sylvatica plantations. Disease symptoms included atrophy and yellowing of leaves, wilting and the presence of pathogen sporocarps around the root collars of young trees. Heterobasidion annosum s. s. was observed on both 4‐ and 17‐year‐old beech. Based on annual increments, the disease could be present for 3–4 years before tree death. A high incidence of H. annosum in pine stumps of previous stands (80–100%) and dry periods in recent years may be the main reasons for such common infection of F. sylvatica. This work also showed that mice and frost were not the main killing factors F. sylvatica in plantations.     

Beta-Glucan as Wall Material in Encapsulation of Elderberry (Sambucus nigra) Extract

Plant Foods for Human Nutrition - The aim of the study was to investigate the potential of using β-glucan as wall material to microencapsulate the elderberry extract. Firstly, the extract was...     

Short- and long-term consequences on biochemical markers after fundectomy in pigs supplemented with 3-hydroxy-3-methylbutyrate and alpha-ketoglutarate

The aim of this study was to investigate short-term 4 and 14 weeks after fundectomy) and long-term (at the age of 8 months) postoperative effects of 3-hydroxy-3-methylbutyrate and/or alpha-ketoglutarate on selected serum biochemical markers in fundectomized pigs. Experimental fundectomy was performed in 30 castrated male pigs of the Pu?awska breed who received placebo or 3-hydroxy-3-methylbutyrate and/or alpha-ketoglutarate up to the age of 8 months. Plasma amino acid concentrations and selected blood parameters were analyzed. Main vital organs were weighed. Our study showed that the supplementations with alpha-ketoglutarate and/or 3-hydroxy-3-methylbutyrate to fundectomized pigs significantly prevented the reduction of stomach, liver and spleen weights. However, results of this study, either positive or negative, cannot categorically establish a beneficial effect of AKG and HMB nutritional support after fundectomy in pigs.     

Toward a More Embedded Production System? Automotive Supply Networks and Localized Capabilities in Poland

The article addresses the embeddedness of automotive production in Poland in terms of supply networks. A comprehensive analysis of more than 550 suppliers, supported by company interviews, shows that foreign‐owned producers become embedded in Poland in the automotive supplier networks they have largely created themselves. Numerous local suppliers gain access to export markets and become integrated in a Europe‐wide production system. This trend has been accompanied by significant upgrading of foreign affiliates and domestic firms in terms of product quality, cost efficiency, adaptability, and fast response, but far less in nonproduction competences such as R&D. It is argued that the competences of automotive suppliers in Poland are built upon the localized capabilities, which are a product of the dynamic interplay between the activity of foreign firms and the changing local environment comprising various stakeholders. The localized capabilities constitute elements of a company's sunk costs and are embedding automotive producers in Poland. At the same time, the dependence on decisions and innovations from abroad and the limited development of local design and brands may constrain the future role of suppliers from the semiperipheral economy of Poland.