Pharmacokinetic profiles of metamizole (dipyrone) active metabolites in goats and its residues in milk

Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human and veterinary medicine. The aim of this study was to assess two major active metabolites of MET, 4‐methylaminoantipyrin (MAA) and 4‐aminoantipyrin (AA), in goat plasma after intravenous (IV) and intramuscular (IM) administration. In addition, metabolite concentration in milk was monitored after IM injection. Six healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a crossover design study. The blood and milk samples were analyzed using HPLC coupled with ultraviolet detector and the plasma vs concentration curves analyzed by a noncompartmental model. In the goat, the MET rapidly converted into MAA and the mean maximum concentration was 183.97 μg/ml (at 0.08 hr) and 51.94 μg/ml (at 0.70 hr) after IV and IM administration, respectively. The area under the curve and mean residual time values were higher in the IM than the IV administered goats. The average concentration of AA was lower than MAA in both groups. Over 1 μg/ml of MAA was found in the milk (at 48 hr) after MET IM administration. In conclusion, IM is considered to be a better administration route in terms of its complete absorption with long persistence in the plasma. However, this therapeutic option should be considered in light of the likelihood of there being milk residue.     

Plasma and cerebrospinal fluid interleukin-1β during lipopolysaccharide-induced systemic inflammation in ewes implanted or not with slow-release melatonin

Background: Interleukin-1β(IL-1β) is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cerebrospinal fluid(CSF) is peripheral circulation, while over time, cytokines produced in the brain are more important. Melatonin has been shown to decrease pro-inflammatory cytokines concentration in the brain. In ewes, melatonin is used to advance the onset of a breading season. Little is known about CSF concentration of IL-1β in ewes and its correlation with plasma during inflammation as well as melatonin action on the concentration of IL-1β in blood plasma and the CSF, and brain barriers permeability in early stage of lipopolysaccharide(LPS)-induced inflammation.Methods: Systemic inflammation was induced through LPS administration in melatonin-and sham-implanted ewes. Blood and CSF samples were collected before and after LPS administration and IL-1β and albumin concentration were measured. To assess the functions of brain barriers albumin quotient(QAlb) was used.Expression of IL-1β(Il1B) and its receptor type Ⅰ(Il1r1) and type Ⅱ(Il1r2) and matrix metalloproteinase(Mmp) 3 and 9 was evaluated in the choroid plexus(CP).Results: Before LPS administration, IL-1β was on the level of 62.0 ± 29.7 pg/mL and 66.4 ± 32.1 pg/mL in plasma and 26.2 ± 5.4 pg/mL and 21.3 ± 8.7 pg/mL in the CSF in sham-and melatonin-implanted group, respectively.Following LPS it increased to 159.3 ± 53.1 pg/mL and 197.8 ± 42.8 pg/mL in plasma and 129.8 ± 54.2 pg/mL and139.6 ± 51.5 pg/mL in the CSF. No correlations was found between plasma and CSF IL-1β concentration after LPS in both groups. The QAlb calculated before LPS and 6 h after was similar in all groups. Melatonin did not affected m RNA expression of Il1B, Il1r1 and Il1r2 in the CP. The m RNA expression of Mmp3 and Mmp9 was not detected.Conclusions: The lack of correlation between plasma and CSF IL-1β concentration indicates that at the beginning of inflammation the local synthesis of IL-1β in the CP is an important source of IL-1β in the CSF. Melatonin from slow-release implants does not affect IL-1β concentration in plasma and CSF in early stage of systemic inflammation.     

Studies of composition and major protein level in milk and colostrum of mares

The aim of the study was to determine the changes in composition and physicochemical features (pH, density, thermostability and acidity) of mare colostrum and milk, and of protein fraction contribution (serum albumin, β-casein, γ-casein, α-lactalbumin, G class immunoglobulins) depending on lactation stage. The research material was colostrum and milk samples from 12 Arabian mares. Colostrum samples were collected within 2 h after parturition and milk samples were collected twice, in the 3rd and 6th weeks of lactation. The level of basic milk components decreased significantly (only lactose content increased) as compared to colostrum. Total bacteria count and somatic cell count decreased significantly with an increase in resistance and urea level. The changes observed were connected to differentiated contribution of particular protein fractions and their relative proportions. Lower levels of γ-casein (P ≤ 0.05), β-casein, serum albumin as well as α-lactalbumin were observed in colostrum as compared to those in milk. Any relationship between lactation stage and β-casein content was observed. Serum albumin and α-lactalbumin content increased in subsequent milkings. The level of G class immunoglobulins decreased significantly and its highest level was noted in colostrum. Any significant differences between the 3rd and 6th lactation weeks were obtained.     

Modelling irregular and multimodal tree diameter distributions by finite mixture models: an approach to stand structure characterisation

Tree structural diversity is assessed by modelling stand diameter at breast height (DBH) distribution. The aim of this study was to verify the suitability of a mixture of two- and three-component Weibull and gamma models for describing irregular and multimodal DBH distributions. Investigations were carried out in natural Abies alba Mill. and Fagus sylvatica L. stands, representing the growing-up stage, in the Świętokrzyski National Park (Central Poland) and in the Pieniny National Park (Southern Poland). Sample plots (0.25–0.5 ha in area) were selected from a database used for forest dynamics analysis. The parameters of the mixture model were estimated using maximum likelihood estimation (MLE) and a combination of an expectation–maximisation (EM) algorithm with a Newton-type (NT) method. The multistart method (MM) of choosing initial values was used. The DBH distributions in mixed Abies–Fagus forests of complex structure were accurately approximated by two- and three-component mixture models. The root mean square error (RMSE) values varied from 3.4515 to 7.6682 for the Weibull mixture and from 3.6457 to 7.1419 for the gamma mixture. The results indicated that the mixture Weibull and gamma models were, in general, equally suitable for modelling irregular and multimodal DBH distributions. Finite mixture models may be used to characterise tree structural diversity, especially in uneven-aged stands of complex structure.     

Effects of dietary phytoestrogens on plasma testosterone and triiodothyronine (T3) levels in male goat kids

Background

Exposure to xenoestrogens in humans and animals has gained increasing attention due to the effects of these compounds on reproduction. The present study was undertaken to investigate the influence of low-dose dietary phytoestrogen exposure, i.e. a mixture of genistein, daidzein, biochanin A and formononetin, on the establishment of testosterone production during puberty in male goat kids.

Methods

Goat kids at the age of 3 months received either a standard diet or a diet supplemented with phytoestrogens (3 - 4 mg/kg/day) for ~3 months. Plasma testosterone and total and free triiodothyronine (T₃) concentrations were determined weekly. Testicular levels of testosterone and cAMP were measured at the end of the experiment. Repeated measurement analysis of variance using the MIXED procedure on the generated averages, according to the Statistical Analysis System program package (Release 6.12, 1996, SAS Institute Inc., Cary, NC, USA) was carried out.

Results

No significant difference in plasma testosterone concentration between the groups was detected during the first 7 weeks. However, at the age of 5 months (i.e. October 1, week 8) phytoestrogen-treated animals showed significantly higher testosterone concentrations than control animals (37.5 nmol/l vs 19.1 nmol/l). This elevation was preceded by a rise in plasma total T₃ that occurred on September 17 (week 6). A slightly higher concentration of free T₃ was detected in the phytoestrogen group at the same time point, but it was not until October 8 and 15 (week 9 and 10) that a significant difference was found between the groups. At the termination of the experiment, testicular cAMP levels were significantly lower in goats fed a phytoestrogen-supplemented diet. Phytoestrogen-fed animals also had lower plasma and testicular testosterone concentrations, but these differences were not statistically significant.

Conclusion

Our findings suggest that phytoestrogens can stimulate testosterone synthesis during puberty in male goats by increasing the secretion of T₃; a hormone known to stimulate Leydig cell steroidogenesis. It is possible that feedback signalling underlies the tendency towards decreased steroid production at the end of the experiment.     

Synthesis and herbicidal activity of isoxazole-substituted 1-aminoethylphosphonates and 1-hydroxyethylphosphonates

Isoxazole-substituted 1-aminoethyl- and 1-hydroxyethyiphosphonates were synthesized by a multi-step procedure and were screened for herbicidal activity against Lepidium sativum L. and Cucumis sativus L. All the synthesized compounds exhibited notable herbicidal activity.     

Effect of coniferyl alcohol addition on removal of chlorophenols from water effluent by fungal laccase

The effect of coniferyl alcohol on removal of chlorinated phenols from a water environment byRhizoctonia praticola andCerrena unicolor laccases was studied. At optimal conditions in which 7 mM coniferyl alcohol and laccase were added to chlorinated phenols over 20h, about 34% of the radioactivity of 4-chlorophenol, 57% of 2,4-dichlorophenol, 66% of 2,4,5-trichlorophenol, and 85% of pentachlorophenol were removed from the supernatants, compared to the level without laccase activity. After 12-h incubation periods at the optimal concentrations of coniferyl alcohol and laccase (added simultaneously), the fast first phase of chlorophenol removal was complete in 1 h, and eventually coniferyl alcohol enhanced the removal of 4-chlorophenol by 40%, 2,4-dichlorophenol by 54%, 2,4,5-trichlorophenol by 60%, and pentachlorophenol by 76%.