Pharmacokinetic profiles of the active metamizole metabolites after four different routes of administration in healthy dogs

Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary metabolite 4‐methylaminoantipyrine (MAA) and relatively active secondary metabolite 4‐aminoantipyrine (AA). The aim of this study was to assess the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.), intramuscular (i.m.), oral (p.o.), and rectal (RC) routes in dogs. Six dogs were randomly allocated to an open, single‐dose, four‐treatment, four‐phase, unpaired, crossover study design. Blood was collected at predetermined times within 24 hr, and plasma was analyzed by a validated HPLC‐UV method. Plasma concentrations of MAA and AA after i.v., i.m., p.o., and RC administrations of MT were detectable from 5 (i.v. and i.m.) or 30 (p.o. and RC) min to 24 hr in all dogs. The highest concentrations of MAA were found in the i.v., then i.m., p.o., and RC groups. Plasma concentrations of AA were similar for i.v., i.m., and RC, and the concentrations were approximately double those in the PO groups. The AUC_EV/IV ratio for MAA was 0.75 ± 0.11, 0.59 ± 0.08, and 0.32 ± 0.05, for i.m., p.o., and RC, respectively. The AUC_EV/IV ratio for AA was 1.21 ± 0.33, 2.17 ± 0.62, and 1.08 ± 0.19, for i.m., p.o., and RC, respectively. Although further studies are needed, rectal administration seems to be the least suitable route of administration for MT in the dog.     

Pharmacokinetics of acetaminophen after intravenous and oral administration in fasted and fed Labrador Retriever dogs

Acetaminophen (paracetamol) is used in dogs to manage fever and mild pain. The aim of this study was to assess the pharmacokinetics of acetaminophen in both fed and fasted Labrador Retrievers after a single intravenous and oral administration (20 mg/kg). Six healthy dogs underwent three treatments in a randomized block study (a, n = 2; b, n = 2; c, n = 2). In phase one, group a received acetaminophen intravenously, group b and c orally after being fasted and fed, respectively. In phase two and three, groups were swapped, and the experiment was repeated. At the end of the trial, each dog received the same treatment. Acetaminophen plasma concentrations were detected using a validated HPLC‐UV method. The pharmacokinetic analysis was performed using a noncompartmental model. Clearance, volume at steady state and half‐life of acetaminophen in Labrador Retrievers were 0.42 L/kg hr, 0.87 L/kg and 1.35 hr, respectively. No significant statistical differences were found between fasted and fed dogs regarding maximum plasma concentration, time at maximum concentration and bioavailability as measured by the AUC. Feeding does not significantly affect the acetaminophen oral pharmacokinetics.     

Scots pine (Pinus sylvestris L.) roots and soil moisture did not affect soil thermal sensitivity

Through their effects on microbial metabolism, temperature and moisture affect the rate of decomposition of soil organic matter. Plant roots play an important role in SOM mineralization and nutrient cycling. There are reports that rhizosphere soil exhibits higher sensitivity to temperature than root-free soil, and this can have implications for how soil CO₂ efflux may be affected in a warmer world. We tested the effects of 1-week incubation under different combinations of temperature (5, 15, 30 ^°C) and moisture (15, 50, 100% WHC) on the respiration rate of soil planted with Scots pine and of unplanted soil. Soil respiration in both soils was the highest at moderate moisture (p < 0.0001) and, increased with temperature (p < 0.0001). There was also marginally significant effect of soil kind on respiration rate (p < 0.055), but the significant interaction of temperature effect with soil kind effect, indicated, that soil respiration of planted soil was higher than unplanted soil only at 5 ^°C (p < 0.05). The soil kind effect was compared also as Q₁₀ coefficients for respiration rate, showing the relative change in microbial activity with increased temperature. However, there was no difference in the thermal sensitivity of soil respiration between planted and unplanted soils (p = 0.99), irrespective of the level of soil moisture. These findings were similar to the latest studies and confirmed, that in various models, being useful tools in studying of soil carbon cycling, there is no need to distinguish between planted and unplanted soil as different soil carbon pools.     

Distribution of Heterobasidion annosum intersterility groups in Poland

Specimens of Heterobasidion annosum were collected in 104 different stands in 43 regions of Poland. Pure cultures originating from 439 collections were identified in mating tests. Three intersterility groups, P, S and F, of H. annosum were found. Their occurrence in Poland was connected with the natural distribution of the main hosts: Pinus sylvestris, Picea abies and Abies alba, respectively. P was the most common intersterility group of H. annosum in Poland, causing mortality in Scots pine plantations and root rot in older stands. It was also isolated from Betula pendula, P. abies, Larix decidua, Fagus sylvatica and Carpinus betulus. The S group was present in the southern and north‐eastern parts of the country, causing root and butt rot mostly in spruce stands. The F group occurred in the south of Poland, in the mountains, highlands and lowland up to the northern border of the distribution of fir. It was found only on stumps, old dead trees and logs. There was no evidence of damage caused by the F group on A. alba trees.     

Response of spruce stands in national parks of southern Poland to air pollution in 1998–2005

The purpose of this study was to describe changes in the deposition of air pollutants and the response of spruce trees in the period of 1998–2005. The investigation was carried out in twelve sites, mainly national parks. Air pollution level, that is, SO₂, NO₂, and O₃ concentrations in the air, as well as throughfall and soil solution chemical composition was analysed. The reaction of trees was described based on a stand health parameter, that is, defoliation. A decrease in the concentration of SO₂ and NO₂ in the investigated period was observed. In most of the analysed sites, ozone concentrations in the growing season exceeded the level regarded as harmful to plants. Annual loads of nitrogen and sulphur reaching the forest soil exceeded 10 kg/ha. The data collected for the analysed period confirmed that the health status of forests at the investigated sites did not show a general tendency towards improvement. Also, no dependency between the air pollution level and defoliation rate was found.     

Conversion of Cortisone to Cortisol and Prostaglandin F2α Production by the Reproductive Tract of Cows at the Late Luteal Stage In Vivo

Previous in vitro studies demonstrated that bovine endometrium has the capacity to convert inactive cortisone to biologically active cortisol (Cr) and that Cr inhibits cytokine‐stimulated prostaglandin F_2α (PGF) production. This study was carried out to test the hypothesis that bovine reproductive tract has the capacity to convert cortisone to Cr in vivo and to evaluate the effects of intravaginal application of exogenous cortisone on uterine PGF secretion during the late luteal stage. The temporal relationships between PGF and Cr levels in uterine plasma were also determined. Catheters were inserted into jugular vein (JV), uterine vein (UV), vena cava caudalis (VCC) and aorta abdominalis (AA) of six cows on Day 15 of the oestrous cycle (ovulation = Day 0) for frequent blood collection. On Day 16, the cows were divided randomly into two groups and infused intravaginally with vaseline gel (10 ml; control; n = 3) or cortisone dissolved in vaseline gel (100 mg; n = 3). Blood samples were collected at ?2, ?1, ?0.5, 0, 0.5, 1, 1.5, 2, 3, 4, 5 and 6 h after treatments (0 h). Intravaginal application of cortisone increased plasma concentrations of Cr between 0.5 and 1.5 h in UV, at 0.5 h in VCC, at 1 h in JV and at 1.5 h in AA. The plasma concentrations of PGF in UV and of PGF metabolite in JV were greater at 0.5 and 1 h in the cortisone‐treated animals than in control animals. The levels of PGF in UV blood plasma decreased after Cr reached its highest levels. The overall findings suggest that the female reproductive tract has the capacity to convert cortisone to Cr in vivo. Based on the temporal changes of PGF and Cr levels in the uterine plasma, a biphasic response in PGF secretion was found to be associated to the Cr increase induced by the cortisone treatment at the late luteal stage in non‐pregnant cows.     

Pharmacokinetic evaluation of tramadol and its major metabolites after single oral sustained tablet administration in the dog: a pilot study

The study evaluated the pharmacokinetics of tramadol and its major metabolites O-desmethyltramadol (M1), N-desmethyltramadol (M2) and N-O didesmethyltramadol (M5) following a single oral administration of a sustained release (SR) 100mg tablet to dogs. Plasma tramadol concentration was greater than the limit of quantification (LOQ) in three dogs, M1 was quantified only in one dog while M2 and M5 were quantified in all of the dogs. The median values of C(max) (maximum plasma concentration), T(max) (time to maximum plasma concentration) and T(1/2) (half-life) for tramadol were 0.04 (0.17-0.02)mirog mL(-1), 3 (4-2) and 1.88 (2.211-1.435)h, respectively. M5 showed median values of C(max), T(max) and T(1/2) of 0.1 (0.19-0.09)microg mL(-1), 2 (3-1) and 4.230 (6.583-1.847)h, respectively. M2 showed median values of C(max), T(max) and T(1/2) of 0.22 (0.330-0.080)microg mL(-1), 4 (7-3) and 4.487 (6.395-1.563)h, respectively. The findings suggest that the SR formulation of tramadol may not have suitable pharmacokinetic characteristics to be administered once-a-day as an effective and safe treatment for pain in the dog.     

The relations of broad nematode resistance to quality characteristics as a consequence of marker-assisted selection in potato breeding programs

Cultivating resistant varieties of potato is the most effective and environmentally sound method of protecting potato crops against pests and diseases. Potato cyst nematodes (PCN) are major nematode pests causing severe constraints in potato production worldwide. There are five pathotypes of Globodrea rostochiensis (Ro1–Ro5) and three of G. pallida Pa1–Pa3. Cultivation of potato varieties with broad nematode resistance may influence the growth of the wide spectrum of PCN pathotypes, but there is limited availability of such varieties on the market. The use of molecular markers allows for the effective selection of resistant genotypes at early stages of breeding. However, the impact of early selection for nematode resistance on the agronomic value of the final selected clones is a cause of concern for potato breeders. This study investigates the relationships between the presence of the combined resistance genes H1, Gro1-4 and GpaV_vrn, which confer resistance to the nematodes, and certain agricultural traits. Clones with broad nematode resistance conferred by the genes H1, Gro1-4 and GpaV_vrn presented yields and tuber morphology traits similar to those of the clones without identified resistance genes.     

Genetic diversity and population structure of Polish Arabian horses assessed through breeding and microsatellite data

Polish Arabian horses are one of the most important populations of this breed in the world. Their post‐war history can be divided into two periods, with the dominant role of state studs until 1989, and the increasing significance of private breeding in the next years. The goal of the study was to evaluate genetic diversity and structure of the population under a new breeding policy. The analyses of breeding and microsatellite data from 1996 to 2012 provide a coherent picture of the population with constant flow of horses only in one direction from state to private studs. An increase in the number of broodmares was observed, from 396 mares in 1996 to 1021 mares in 2012. The proportion of foreign sires used in Polish studs also increased, from 7.1% to 37.0%. An increasing number of alleles and progressive differentiation in mares were observed. STRUCTURE analysis indicated that the Polish horses were clearly separated from foreign horses used in Polish breeding, although only one of the 75 alleles found can be considered as typically Polish. The high heterozygosity is an important feature of the Polish population; however, the decrease of heterozygosity in state broodmares was noted. This issue needs to be studied further.