Characterization of In Vitro Synthesized Equine Metabolites of the Selective Androgen Receptor Modulators S24 and S4     

Oliver Krug  Andreas Thomas  Simon Beuck  Ina Schenk  Marc Machnik  Wilhelm Schänzer  Ulf Bondesson  Mikael Hedeland  Mario Thevis 《Journal of Equine Veterinary Science》2012

Several selective androgen receptor modulators (SARMs) have been synthesized and investigated in humans, rats, and dogs in the past, but no data are yet available concerning the metabolism of SARMs in horses. The aryl-propionamide-derived drug candidates S24 and S4 (andarine) have a strong androgen receptor binding affinity and show distinctive specific cell answers. Although no SARM drug candidate (aiming for testosterone replacement therapy) has completed clinical trials yet, S4 has been illicitly available via the Internet. These facts led to the prohibition of SARMs by the German equestrian federation, and the (mis)use of such compounds would further represent a doping rule violation in horse racing. In this study, the drug candidates S24 and S4 were subjected to in vitro metabolism experiments with equine liver microsomal preparations from a female Quarter Horse to obtain information about potential target analytes in equine doping control analysis. The enzymatically synthesized metabolites were characterized by liquid chromatography–tandem mass spectrometry and –high-resolution/high-accuracy mass spectrometry. All observed S24 and S4 equine metabolites are in agreement with earlier in vitro and in vivo studies in humans and dogs. Nevertheless, the relative percentage of generated equine metabolites (as determined from the analytes’ response in full-scan chromatography–tandem mass spectrometry and –high-resolution/high-accuracy mass spectrometry measurements) differs considerably from the reported profiles. Although the S24 metabolite pattern is comparably balanced concerning glucuronidated and sulfonated conjugates, the major S4 metabolite was found to be the unconjugated dephenylated compound, with a proportion of more than 90%.  相似文献   

Antimicrobial Resistance of Mastitis Pathogens   总被引：1，自引：0，他引：1  

Stephen P. Oliver  Shelton E. Murinda 《Veterinary Clinics of North America: Food Animal Practice》2012

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Fine-scale spatial genetic structure of sycamore maple (<Emphasis Type="Italic">Acer pseudoplatanus</Emphasis> L.)     

Madhav Pandey  Oliver Gailing  Hans H. Hattemer  Reiner Finkeldey 《European Journal of Forest Research》2012,131(3):739-746

Knowledge of SGS in plants is vital to understand the ecological and evolutionary dynamics of populations and to plan conservation strategies. Some of the major factors that can affect spatial genetic structure (SGS) in plants are the level of gene flow, spatial arrangement and life stages of individuals within populations. Applying six highly variable microsatellite markers, we investigated the effect of these factors on spatial genetic structure selecting two natural populations of sycamore maple, which is an insect-pollinated, autotetraploid and an indigenous hardwood species in Germany and in other central European countries. The two study populations had different shapes (“compact” and “elongated”) and tree densities. Significant SGS extended to ~180 m in the elongated population and to ~35 m in the compact population. Juvenile plants of the compact population showed significant SGS up to 40 m. Estimate of Sp statistic in high-density population was almost double of that in the population with low density. Gene dispersal distance in the low-density population was about 9 times higher than in the population with high density. The similar level of significant SGS in both adult and juvenile plants suggested minimal or no effect of life stages of individuals on SGS in the sycamore maple population. The data presented in this study can provide guidelines for seed collection and to establish populations for the conservation and management of genetic resources of the species.  相似文献   

Water sorption mechanisms of commercial wood adhesive films     

Rupert Wimmer  Oliver Kläusler  Peter Niemz 《Wood Science and Technology》2013,47(4):763-775

As water moves inside the wood, the gluelines might act as barriers that are potentially leading to local moistening. Even low amounts of water may influence the mechanical performance of glued wood products. Dynamic vapor sorption analysis was performed to assess the sorption processes of six commercial wood adhesives. Vapor sorption isotherms were compared with vapor uptake dynamics. Phenol–resorcinol–formaldehyde showed high moisture uptake of 18 %, while vapor diffusion speed was low. Fish glue showed a water uptake of 45 % at otherwise moderate vapor uptake speed. Melamine–formaldehyde resin gained 22 % water, and polyvinyl acetate absorbed 10 %. The latter was also the fastest vapor absorbing adhesive. Polyurethane only absorbed 3.5 % of moisture at medium uptake speed. Mechanisms of water diffusion seem to be driven by (1) the available free volume in the polymer and (2) the interacting ionic groups of the polymer chain. While the free volume could be linked to the accumulated moisture, the ionic group interaction might determine the measured vapor diffusion dynamics.  相似文献   

Genetic trends for objectively measured and subjectively assessed traits in a Dorper sheep flock     

Oliver Tendayi Zishiri  Schalk Willem Cloete  Johannes Jacobus Olivier  Kennedy Dzama 《Tropical animal health and production》2013,45(2):517-524

Genetic trends were constructed to monitor the genetic change for subjectively assessed and objectively measured traits using data emanating from complete records from the National Small Stock Improvement Scheme database and performance records accumulated by a single breeder over a period of 24 years. The objectively measured production traits considered were weaning weight, post-weaning weight (PWW), yearling weight, average daily weight gain to weaning (ADGW), average daily weight gain during post-weaning phase (ADGPW) and average daily weight gain up to yearling age. The subjectively assessed traits (scored on a five-point scale) were conformation, fat distribution, size, type and colour. Direct genetic trends for live weight and growth traits (with the exception of ADGPW) were positive. All the objectively measured traits where maternal effects were significant, except PWW, registered small declines in maternal breeding values. The fastest genetic progress was attained by ADGW, which amounted to 0.29 % of the overall phenotypic mean per annum. Conformation and type exhibited positive but slow increments in direct breeding values at an equivalent annual rate amounting to 0.12 and 0.09 % of the overall phenotypic mean, respectively. Size demonstrated a negative genetic trend of ?0.14 % of the overall phenotypic mean per annum. Genetic trends for fat distribution and colour were negligible. It was concluded that breeders should focus more on the performance recording of objective traits as they are likely to respond favourably to selection pressure.  相似文献   

Carbendazim,at concentrations used on pasture for facial eczema control,reduces development of Trichostrongylus colubriformis when sprayed onto infected sheep faeces     

A-MB Oliver  DM Leathwick  TS Waghorn  CM Miller  DS Atkinson 《New Zealand veterinary journal》2013,61(6):383-387

Abstract

AIM: To determine whether the fungicide, carbendazim, as applied to pastures for controlling facial eczema (FE), would inhibit development of the free-living stages of the gastrointestinal nematode parasite Trichostrongylus colubriformis.

METHODS: Two studies were conducted, using sheep faeces containing eggs of T. colubriformis. In the first, the faeces were either exposed or not to an application of carbendazim sprayed at the recommended rate for FE control. After spraying, dishes containing the faeces were incubated at 20°C for 14 days, and the resulting third-stage infective larvae (L3) extracted by baermannisation and counted. In addition, naturally infested pasture was also sprayed, and the number of L3 present 7 days later was assessed by cutting herbage samples and extracting larvae by soaking in water and baermannisation. In the second, the faeces were incubated at 20°C for 0, 3 or 7 days before being exposed to no, one or two applications of carbendazim. After further incubation for 14, 11 or 7 days, L3 were similarly extracted by baermannisation and counted.

RESULTS: In the first study, there was a 74% reduction in the number of T. colubriformis larvae recovered from faeces exposed to carbendazim compared with faeces not exposed, but there was no reduction in the number of L3 recovered from herbage. In the second study, faeces incubated for 0 or 3 days prior to exposure to a single application of carbendazim yielded 98% or 89% fewer larvae, respectively, than faeces not exposed. Faeces incubated for 7 days prior to exposure yielded similar numbers of larvae to faeces not exposed.

CONCLUSION: Treatment of pastures with carbendazim for FE control is likely to result in reduced development of the larvae of T. colubriformis, and by inference those of other species, where the application coincides with the presence of freshly deposited faeces containing eggs and developing larvae. However, no effect of treatment on L3 was indicated. The significance of this for on-farm nematode parasite control remains to be determined, as does any potential for strategic applications of carbendazim to pasture aimed at reducing numbers of parasite larvae on pasture. The latter should not be contemplated without due consideration of the implications for the development of anthelmintic resistance.  相似文献   

Drench-and-shift is a high-risk practice in the absence of refugia     

TS Waghorn  CM Miller  A-MB Oliver  DM Leathwick 《New Zealand veterinary journal》2013,61(6):359-363

Abstract

AIM: To examine the effect of an anthelmintic treatment to lambs, followed immediately by a shift onto pastures with differing levels of larval contamination, on the development of anthelmintic resistance, in order to support recommendations to farmers regarding drench-and-shift practices for sustainable worm control.

METHODS: Newly weaned Romney lambs (n=72) were dosed with third-stage infective larvae (L3) of two nematode parasite species, Teladorsagia (=Ostertagia) circumcincta and Trichostrongylus colubriformis, comprising benzimidazole-resistant and -susceptible isolates, calculated to yield, after treatment with albendazole, a 95% reduction in faecal nematode egg count (FEC). Once infections became patent (Day 0), lambs were randomised into nine groups of eight animals, treated with albendazole at the manufacturer's recommended dose rate, and moved to individual pastures each previously prepared to have one of three different levels of parasite larval infestation (Treatment 1 = low contamination, Treatment 2 = medium contamination, and Treatment 3 = high contamination), and grazed on those pastures before receiving a second treatment with albendazole at Day 47. Anthelmintic resistance status in each group of lambs was measured using FEC reduction (FECR) and egghatch assays (EHA) after the first anthelmintic treatment, and FECR after the second treatment.

RESULTS: Egg-hatch assays demonstrated significant differences between treatments. The concentration of anthelmintic required to kill 50% of the eggs (LC₅₀) for Treatment 1, comprising the least contaminated pastures, was significantly higher than for Treatments 2 and 3 on Days 33 and 40. Treatment 1 also had a significantly lower FECR at the final anthelmintic treatment, and significantly lower FEC than the other two treatments from Days 26 to 47.

CONCLUSIONS: The results demonstrated that the populations of T. circumcincta and T. colubriformis in lambs treated with anthelmintic had significantly higher levels of albendazole resistance at the end of the grazing period in lambs moved onto pastures with relatively low levels of parasite contamination than those moved onto pastures with relatively higher contamination, confirming drench-and-shift onto ‘clean’ pasture as a high-risk practice for the selection for anthelmintic resistance. While this does not necessarily preclude the use of this practice it does emphasise the importance of taking appropriate remedial action to minimise the risk.  相似文献   

Parainfluenza type 3 virus in cattle with upper respiratory disease     

R.E. Oliver B.V.Sc.  G.W. Horner B.V.Sc. M.Sc.  R. Hunter F.I.M.L.T.  W. Niederer B.V.Sc. 《New Zealand veterinary journal》2013,61(7):135-137

Abstract

Extract

Parainfluenza type 3(Pl₃) virus has been associated with upper respiratory disease of cattle in many countries (Hoerlein et al., 1959 Bögel, K. 1961. Virologische Undersuchungsbefunde bei Kalbern mit respiratoris-chem Syndrom unter besonderer Berucksichtigung der Parainfluenza 3 Myxovirus. Mh. Tierheilk, 13: 129–129. 162. [Cited by Jolly, R. D., (1967), N.Z. vet. J., 15: 43–4.] [Google Scholar]; Bögel, 1961 Campbell, R. S. F. 1972. “Virus diseases of cattle. Virology and Virus Disease”. In Proc. No. 16 of Course for Veterinarians, 132–132. University of Sydney.  [Google Scholar]; Reisinger, 1962 Carter, Margery E. and Hunter, R. 1970. Isolation of parainfluenza type 3 virus from sheep in New Zealand. N.Z. vet. J., 18: 226–227. [Taylor &; Francis Online] , [Google Scholar]; Jolly and Ditchfield, 1965 Curtis, R. A. and Sutton, R. H. 1972. Chronic granular rhinitis (nasal catarrh) of cattle. N.Z. vet. J., 20: 125–125. [Taylor &; Francis Online] , [Google Scholar]). However, PI₃ virus has not been isolated from cattle with respiratory disease in New Zealand although a serological study found that 89.3% of cows had significant levels of antibody against PI₃ virus (Pastier and Hansen, 1966). In most cases infections are subclinical, and there is little evidence to suggest that PI₃ virus is an important cause of disease in New Zealand cattle (Jolly, 1967 Fastier, L. B. and Hansen, N. F. 1966. The occurrence of antibodies to bovine virus diarrhoea, infectious bovine rhinotracheitis and parainfluenza 3 viruses in sera from New Zealand cattle. N.Z. vet J., 14: 27–32. [Taylor &; Francis Online] , [Google Scholar]). This communication records an outbreak of upper respiratory disease in cattle from which PI₃ virus was isolated.  相似文献   

Selective and on-demand drenching of lambs: Impact on parasite populations and performance of lambs     

DM Leathwick  TS Waghorn  CM Miller  DS Atkinson  NA Haack  A-M Oliver 《New Zealand veterinary journal》2013,61(6):305-312

AIM: To determine whether drenching regimes for lambs by which a proportion (10%) of the heaviest animals was selectively left untreated, or animals are only drenched ‘on demand’ when faecal nematode egg counts (FEC) exceeded a threshold level, would result in measurable increases in parasite larval challenge in the autumn and/or decreases in the performance of lambs.

METHODS: A replicated study compared three drenching strategies in which mobs of lambs (n=360 in total) received either: a five-drench preventive programme, administered to all animals (Treatment 1); a five-drench preventive programme, but the 10% heaviest animals left untreated each time (Treatment 2); or drench treatments administered only when FEC exceeded 500 eggs per gram of faeces (epg) (Treatment 3). After the five-drench programme, animals in Treatments 1 and 2 were treated according to FEC as for Treatment 3. A triple-combination drench containing ivermectin, oxfendazole and levamisole, administered orally, was used for all treatments. There were nine farmlets, allowing three replicates of each treatment, in a completely randomised design. Parasite infestations on pasture were measured in autumn by pasture plucks, and worm burdens were monitored in tracer lambs, while the performance of lambs was assessed by liveweight gains, fleece weights, and body condition and dag scores.

RESULTS: Increased numbers of Haemonchus contortus and Trichostrongylus colubriformis larvae on pasture were found in the autumn on farmlets treating selectively or on-demand (Treatments 2 and 3). No differences were detected in other parasite species. Mean liveweight gains did not differ between treatments but some differences were detected between drenched and undrenched lambs in Treatment 2. Mean body condition and mean dag scores of lambs in Treatment 3 tended to be lower and higher, respectively, than those of lambs in Treatment 1; Treatment 2 was generally intermediate.

CONCLUSIONS: Drenching strategies for lambs designed to slow the development of anthelmintic resistance, by increasing the pool of susceptible worms available to dilute resistant survivors after treatment, resulted in increased numbers of H. contortus and T. colubriformis but not other species of parasite on pasture. The increased parasite challenge to lambs in the autumn was associated with small production losses, which may be acceptable to farmers wishing to implement such strategies. It is clear that further work is required on the interaction between management practices and the population dynamics of parasites, especially with regard to creating pools of susceptible genotypes to slow the development of drench resistance.  相似文献   

In vitro activity of almond skin polyphenols for scavenging free radicals and inducing quinone reductase     

Chen CY  Blumberg JB 《Journal of agricultural and food chemistry》2008,56(12):4427-4434

Observational studies and clinical trials suggest nut intake, including almonds, is associated with an enhancement in antioxidant defense and a reduction in the risk of cancer and cardiovascular disease. Almond skins are rich in polyphenols (ASP) that may contribute to these putative benefits. To assess their potential mechanisms of action, we tested the in vitro effect of ASP extracted with methanol (M) or a gastrointestinal juice mimic (GI) alone or in combination with vitamins C (VC) or E (VE) (1-10 micromol/L) on scavenging free radicals and inducing quinone reductase (QR). Flavonoid profiles from ASP-M and -GI extracts were different from one another. ASP-GI was more potent in scavenging HOCl and ONOO (-) radicals than ASP-M. In contrast, ASP-M increased and ASP-GI decreased QR activity in Hepa1c1c7 cells. Adding VC or VE to ASP produced a combination- and dose-dependent action on radical scavenging and QR induction. In comparison to their independent actions, ASP-M plus VC were less potent in scavenging DPPH, HOCl, ONOO (-), and O 2 (-) (*). However, the interaction between ASP-GI plus VC promoted their radical scavenging activity. Combining ASP-M plus VC resulted in a synergistic interaction, inducing QR activity, but ASP-GI plus VC had an antagonistic effect. On the basis of their total phenolic content, the measures of total antioxidant activity of ASP-M and -GI were comparable. Thus, in vitro, ASP act as antioxidants and induce QR activity, but these actions are dependent upon their dose, method of extraction, and interaction with antioxidant vitamins.  相似文献