ORCID Profile
0000-0003-1041-6563
Current Organisation
University of Tasmania
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Publisher: CSIRO Publishing
Date: 2007
DOI: 10.1071/WR06094
Abstract: Cabergoline is a potent inhibitor of prolactin release and a potential fertility control agent for foxes. To understand how cabergoline could behave in baits deployed for fox control, we conducted laboratory and field trials to investigate the stability of cabergoline when (1) in solution, (2) injected into a bait (deep-fried liver and Foxoff®) and (3) exposed to a range of environmental conditions, including burial. Cabergoline, dissolved in a 1% acetic acid solution, and its carboxylic acid hydrolysis product can be assayed using high-performance liquid chromatography. When stored at 4°C and at room temperature, cabergoline in solution was stable for up to 36 days. When stored under cool (≤15°C), dry conditions, cabergoline (800 µg) in commercial Foxoff® and deep-fried ox-liver baits was stable for 28 and 7 days, respectively stability was reduced by increases in temperature (tested up to 40°C) and humidity. Recovery of cabergoline from buried baits exposed to a range of field conditions decreased rapidly in the first week, but after 56 days remained detectable at levels of 6–22% of the injected amounts. This study has important implications for baiting c aigns that use cabergoline for fox control.
Publisher: Springer Science and Business Media LLC
Date: 06-1995
DOI: 10.1007/BF02033457
Publisher: Wiley
Date: 05-1995
DOI: 10.1111/J.1751-0813.1995.TB03505.X
Abstract: This study examined the use of 4 antagonists of chemical restraint in mature female southern elephant seals (Mirounga leonina) that were restrained with ketamine and diazepam, ketamine and xylazine, or tiletamine and zolazepam. The antagonists were: 4-aminopyridine, yohimbine, doxapram and sarmazenil. The effects of the antagonists on the animal's time to first movement forward and recovery, heart rate, respiratory rate and venous blood gas and pH values, and level of chemical restraint were recorded. Sarmazenil (1.0 mg/kg) and doxapram (5.0 mg/kg) partially antagonised 50:1 ketamine: diazepam (ketamine = 3.0 mg/kg, diazepam = 0.06 mg/kg) and tiletamine and zolazepam (tiletamine = 0.5 mg/kg, zolazepam = 0.5 mg/kg). However, the rapid recovery after low doses of anaesthetics means that antagonism is usually unnecessary, and it may increase the likelihood of shaking. Routine antagonism of ketamine and xylazine (ketamine = 3.0 mg/kg, xylazine = 0.5 mg/kg) is more useful given its usually delayed recovery time and potential for thermoregulatory problems. For this purpose yohimbine (0.06 mg/kg) offered advantages over doxapram in giving a smoother recovery with less aggression. 4-aminopyridine (0.2 mg/kg) prolonged chemical restraint by 100:1 ketamine:diazepam (ketamine = 3.0 mg/kg, diazepam = 0.03 mg/kg) and ketamine and xylazine, and should be contraindicated. Doxapram (5.0 mg/kg) was the most useful general antagonist for all groups of drugs but shaking was seen and a lower dose is recommended.
Publisher: Springer Science and Business Media LLC
Date: 10-04-2008
DOI: 10.1007/S10886-008-9463-X
Abstract: The common brushtail possum (Trichosurus vulpecula) is a generalist herbivore whose diet includes Eucalyptus leaves that are well defended by plant secondary metabolites (PSM) such as the terpene 1,8-cineole (cineole). We accustomed possums to a terpene-free diet, then challenged them with the addition of 2% cineole to the diet. Initially, there was a 50% reduction in total overnight food consumption associated with a marked decrease in the mass of the major feeding bout. After nine nights, however, cineole tolerance had developed as total food consumption had returned to the control amount. Compared to the control diet, the cineole diet was eaten in a larger number of smaller bouts, which were also eaten at a slower rate. The experiment was repeated with animals that had been accustomed to day-time feeding to take blood s les during feeding sessions. Feeding variables and blood concentration data for cineole were compared on the first and seventh day of the cineole diet. Although the total food consumed increased 2.5-fold after 7 days of the cineole diet, there was no increase in average blood cineole concentration, measured as the area under the concentration-time curve. This indicates that induction of liver enzymes resulted in greater pre-systemic metabolism of cineole and reduced bioavailability. The maximum tolerated blood concentration of cineole also increased, suggesting some adaptation of the central nervous system to the cineole aversive effects. This appears to be the first report in a vertebrate herbivore that consumption of a dietary PSM leads to metabolism induction and that this contributes to development of tolerance to the PSM. Overall, herbivores adapt to newly encountered dietary PSMs by immediate changes in feeding behavior followed by development of increased metabolism of PSM and probably diminished cellular responsiveness to effects.
Publisher: Springer Science and Business Media LLC
Date: 09-2012
DOI: 10.1007/S10886-012-0192-9
Abstract: Pygmy rabbits (Brachylagus idahoensis) are one of only three vertebrates that subsist virtually exclusively on sagebrush (Artemisia spp.), which contains high levels of monoterpenes that can be toxic. We examined the mechanisms used by specialist pygmy rabbits to eliminate 1,8-cineole, a monoterpene of sagebrush, and compared them with those of cottontail rabbits (Sylvilagus nuttalli), a generalist herbivore. Rabbits were offered food pellets with increasing concentrations of cineole, and we measured voluntary intake and excretion of cineole metabolites in feces and urine. We expected pygmy rabbits to consume more, but excrete cineole more rapidly by using less-energetically expensive methods of detoxification than cottontails. Pygmy rabbits consumed 3-5 times more cineole than cottontails relative to their metabolic body mass, and excreted up to 2 times more cineole metabolites in their urine than did cottontails. Urinary metabolites excreted by pygmy rabbits were 20 % more highly-oxidized and 6 times less-conjugated than those of cottontails. Twenty percent of all cineole metabolites recovered from pygmy rabbits were in feces, whereas cottontails did not excrete fecal metabolites. When compared to other mammals that consume cineole, pygmy rabbits voluntarily consumed more, and excreted more cineole metabolites in feces, but they excreted less oxidized and more conjugated cineole metabolites in urine. Pygmy rabbits seem to have a greater capacity to minimize systemic exposure to cineole than do cottontails, and other cineole-consumers, by minimizing absorption and maximizing detoxification of ingested cineole. However, mechanisms that lower systemic exposure to cineole may come with a higher energetic cost in pygmy rabbits than in other mammalian herbivores.
Publisher: Springer Science and Business Media LLC
Date: 12-2009
Abstract: Injections of mixtures prepared from crushed tablets contain insoluble particles which can cause embolisms and other complications. Although many particles can be removed by filtration, many injecting drug users do not filter due to availability, cost or performance of filters, and also due to concerns that some of the dose will be lost. Injection solutions were prepared from slow-release morphine tablets (MS Contin ® ) replicating methods used by injecting drug users. Contaminating particles were counted by microscopy and morphine content analysed by liquid chromatography before and after filtration. Unfiltered tablet extracts contained tens of millions of particles with a range in sizes from 5 μm to 400 μm. Cigarette filters removed most of the larger particles ( 50 μm) but the smaller particles remained. Commercial syringe filters (0.45 and 0.22 μm) produced a dramatic reduction in particles but tended to block unless used after a cigarette filter. Morphine was retained by all filters but could be recovered by following the filtration with one or two 1 ml washes. The combined use of a cigarette filter then 0.22 μm filter, with rinses, enabled recovery of 90% of the extracted morphine in a solution which was essentially free of tablet-derived particles. Apart from overdose and addiction itself, the harmful consequences of injecting morphine tablets come from the insoluble particles from the tablets and microbial contamination. These harmful components can be substantially reduced by passing the injection through a sterilizing (0.22 μm) filter. To prevent the filter from blocking, a preliminary coarse filter (such as a cigarette filter) should be used first. The filters retain some of the dose, but this can be recovered by following filtration with one or two rinses with 1 ml water. Although filtration can reduce the non-pharmacological harmful consequences of injecting tablets, this remains an unsafe practice due to skin and environmental contamination by particles and microorganisms, and the risks of blood-borne infections from sharing injecting equipment.
Publisher: Springer Science and Business Media LLC
Date: 2003
Abstract: We investigated effects of two plant secondary metabolites (PSMs), cineole and gallic acid, on the nightly feeding behavior of the common brushtail possum (Trichosurus vulpecula), a generalist folivore. We tested whether possums altered their feeding behavior in response to increasing levels of cineole, a dietary terpene. Possums were fed artificial diets containing three levels of cineole: zero (basal diet), medium (6.8% of total dry matter, DM), and high (15.3% DM). In another experiment, we introduced gallic acid, a dietary phenolic, into the diets. Possums were offered a Choice PSM diet (cineole and gallic acid diets simultaneously) or a No-Choice PSM diet (containing either cineole or gallic acid). Detoxification products of cineole and gallic acid were examined in urine to determine that different detoxification pathways were utilized in the elimination of each compound. With increasing cineole levels, possums ate less, had smaller feeding bouts, and had a lower rate of intake, but did not extend their total nightly feeding time. Possums offered the Choice PSM diet, compared with the No-Choice diets, ate more, had larger feeding bouts, and tended to increase their rate of intake. Results from the urinary analysis indicated that gallic acid and cineole were not involved in competing detoxification pathways in brushtail possums. There was also a significant sex effect: females ate more overall, ate more per feeding bout, and ate at a higher rate than males. These results indicate that PSMs not only constrain overall intake, but that possums alter their feeding behavior in response to them. Altered feeding patterns may reduce the negative influence of PSMs on intake.
Publisher: Informa UK Limited
Date: 09-2007
DOI: 10.1080/00498250701570277
Abstract: 1,8-Cineole (cineole) is a Eucalyptus leaf toxin that defends against predation by herbivores such as the brushtail possum (Trichosurus vulpecula). The aim of the current study was to characterize the pharmacokinetics of cineole in the possum to improve understanding about how possums can avoid cineole toxicity when eating a Eucalyptus diet. Nine male possums were trapped in the wild and acclimated to captivity a subcutaneous port was then implanted for venous blood s ling. Cineole was administered intravenously (10 and 15 mg kg(-1)) via a lateral tail vein and orally (30, 100 and 300 mg kg(-1)) by gavage, and blood concentrations of cineole and its metabolites were determined by gas chromatography. Cineole had a large terminal volume of distribution (V(z) = 27 l kg(-1)) and a high clearance (43 ml min(-1) kg(-1)), equal to hepatic blood flow. The terminal half-life was approximately 7 h. Oral bioavailability was low (F = 0.05) after low doses, but increased tenfold with dose, probably due to saturable first-pass metabolism. These findings indicate that when possums feed on a cineole diet, they eat until the cineole consumed is sufficient to saturate pre-systemic metabolism, leading to a rapid rise in bioavailability and cineole blood levels, and a cessation of the feeding bout. This is the first report on the pharmacokinetics of a dietary toxin in a wild herbivore, and provides insights into the interactions between the blood concentration of a plant secondary metabolite and the browsing behaviour of a herbivore.
Publisher: Hindawi Limited
Date: 04-1997
DOI: 10.1111/J.1365-2710.1997.TB00005.X
Abstract: Some studies have indicated that over-reliance on inhaled bronchodilator (beta 2-agonist) therapy may worsen asthma control and increase morbidity. The aim of this study was to measure urinary concentrations of salbutamol, the most commonly used bronchodilator, in a relatively large s le of asthmatic patients and examine the potential value of the concentration as an indicator of over-use of salbutamol. The urinary concentrations of the drug were measured in 'spot' urine s les from 102 asthmatic patients (64 community patients and 38 hospital inpatients). A solid-phase extraction technique, using a phenyl-bonded phase and a reversed-phase ion-pair high-performance liquid chromatography assay with UV-detection were developed and used to measure both unchanged salbutamol concentrations and total salbutamol concentrations after enzymatic hydrolysis of the metabolite. In addition, salbutamol concentrations were corrected for urine dilution, with the measured drug expressed per gram of urinary creatinine. The hospital patients were generally older, had greater disease severity, were more likely to be receiving prophylactic therapy and had received more salbutamol in the past 24 h. The urinary concentrations of salbutamol varied enormously between patients. The median concentrations of unchanged and total drug were 0.38 microgram/ml (range 0-34.4 micrograms/ml) and 2.55 micrograms/ml (range 0-49.8 micrograms/ml), respectively. Even when controlling for dosage in the preceding 24 h, there was a 262-fold and 810-fold variation in the urinary concentrations for unchanged and total salbutamol, respectively, among the community patients. Modest correlations were found between salbutamol concentrations and dosage administered in the preceding 24 h (Spearman's r = 0.67 and 0.54 for unchanged and total drug, respectively P < 0.001). The correlations improved only slightly with correction for urine dilution (Spearman's r = 0.69 and 0.57 for unchanged and total drug, respectively P < 0.001). This enormous inter-patient variability, which may be largely due to differences in the pharmacokinetics of salbutamol and inhaler technique, may play a role in the observed worsening of asthma control with the regular use of inhaled bronchodilator drugs and warrants further investigation. Measuring urinary concentrations of salbutamol in spot s les provides only a relatively crude indication of the extent of use of inhaled salbutamol in the preceding 24 h.
Publisher: Elsevier BV
Date: 04-1991
DOI: 10.1016/0378-4347(91)80384-O
Abstract: A novel analytical screening procedure has been developed, using computer-controlled gas chromatography-mass spectrometry (GC-MS), to detect 120 drugs of interest to road safety. This paper describes GC-MS methodology suitable for use on extracts of biological origin, while extraction procedures will be the subject of a future communication. The method was devised to identify drugs in extracts of blood s les, as part of an investigation into the involvement of drugs, other than alcohol, in road accidents. The method could be adapted to screen for other substances. The method depends on a "macro" program which was written to automate the search of GC-MS data for target drugs. The strategy used was to initially search for each drug in the database by monitoring for a single characteristic ion at the expected retention time. If a peak is found in this first mass chromatogram, a peak for a second characteristic ion is sought within 0.02 min of the first and, if found, the ratio of peak areas calculated. Probable drug identification is based on the simultaneous appearance of peaks for both characteristic ions at the expected retention time and in the correct ratio. If the ratio is outside acceptable limits, a suspected drug (requiring further investigation) is reported. The search macro can use either full mass spectra or, for enhanced sensitivity, data from selected ion monitoring (which requires switching between groups of ions during data acquisition). Quantitative data can be obtained in the usual way by the addition of internal standards.
Publisher: Frontiers Media SA
Date: 26-10-2016
Publisher: Elsevier BV
Date: 09-1996
DOI: 10.1016/0300-9629(96)00001-1
Abstract: Six common ringtail possums (Pseudocheirus peregrinus) were intravenously injected with a standard dose of radioactive 3-Methylhistidine (N tau-[Me-14C]MeH). The dose was rapidly and quantitatively excreted by the possums. More than 90% of radioactivity was recovered within 3 days. Thin layer chromatography and mass spectroscopy showed that 97% of recovered radioactivity was associated with unmetabolised N tau-[Me-14C]MeH. These data satisfy two key requirements for the validity of urinary 3-Methylhistidine (N tau-3MeH) excretion as an index of muscle protein catabolism, in P. peregrinus.
Publisher: Elsevier BV
Date: 03-1996
DOI: 10.1016/S0007-1935(96)80075-3
Abstract: A study was conducted to assess the effectiveness of the alpha-2 agonist medetomidine for sedation of pre-moulting, mature female southern elephant seals (Mirounga leonina). Two animals were sedated with a single intramuscular dose of medetomidine (0.013 and 0.027 mg kg-1). A further two groups of five animals received medetomidine (0.017 mg kg-1) combined with ketamine (1.90 mg kg-1) and, 20 min later, either saline or the alpha-2 antagonist atipamezole (0.04 mg kg-1) intravenously. Medetomidine alone did not give sufficient restraint to permit intravenous access. The response appeared to be similar to previous findings with ketamine and xylazine. Administration of atipamezole had little effect upon the level and timecourse of restraint. Ketamine and medetomidine seem to offer few advantages over ketamine and xylazine or other cyclohexamine-drug combinations for routine chemical restraint of southern elephant seals.
Publisher: Elsevier BV
Date: 07-1999
DOI: 10.1016/S0742-8413(99)00035-3
Abstract: Southern elephant seals (Mirounga leonina) are large, potentially dangerous animals which must be restrained before study or treatment. However, chemical restraint is unpredictable, possibly because of differences in body composition during fasting ashore, and circulatory adaptations to enable ing. The pharmacokinetics of ketamine (1.1 mg/kg i.v.) was studied in 15 southern elephant seals which had come ashore on Macquarie Island. The animals were first sedated with pethidine (5 mg/kg i.m.) to allow intravenous access. There was great variability in the calculated pharmacokinetic parameters, possibly due to circulatory changes associated with periods of apnoea which characterise this animal's response to anaesthetics. The median values were similar to those reported for other species: distribution t1/2 = 2.5 min (range 1-11 min) elimination t1/2 = 43 min (range 17-108 min) apparent volume of distribution, 1474 ml/kg (range 830-9301 ml/kg) clearance, 33 ml/min/kg (range 12-57 ml/min/kg). This was the first investigation of drug disposition in any seal species. and the first in any free-ranging wild animal. It is important to obtain pharmacological data in animals in whom drugs are used, but pre-catheterised captive animals may provide less variable data.
Publisher: Springer Science and Business Media LLC
Date: 12-2005
DOI: 10.1007/S10886-005-8393-0
Abstract: The blood concentration of 1,8-cineole and its metabolites was measured in six male brushtail possums while they voluntarily fed on diets laced with varying concentrations of cineole for 3 d. On the third day, blood s les were collected during and after each bout of feeding for 3 hr. Blood cineole was measured by using headspace solid-phase microextraction (SPME), while cineole metabolites were measured by liquid-liquid extraction followed by gas chromatography-mass spectroscopy. Feeding patterns were measured by continual recording of residual food weight and time. Cineole absorption was rapid, resulting in a peak blood concentration at the end of each feeding bout. The blood concentration of cineole did not exceed a critical value (51.8 +/- 14.1 micromol/l) regardless of the concentration in the diet. Food and, therefore, cineole intake was regulated. The amount of food ingested in the first feeding bout decreased from 236 +/- 52 g on the control diet to 36 +/- 20 g on the 4% cineole diet. The amount of cineole ingested in the first bout (1.18 +/- 1.10 g) was the same regardless of the dietary concentration and was controlled by the size of the meal. Total food eaten during the 7-hr feeding session decreased by 64% from 368 +/- 94 g (control diet) to 131 +/- 52 g (4% diet). Total cineole intake increased from 2.47 +/- 0.60 g (1% diet) to 5.05 +/- 2.41 g (4% diet). Cineole metabolites accumulated throughout the s ling period and were generally still rising at the end of blood s ling period. Blood levels of metabolites were at least 10-fold higher than cineole levels. The immediate control of feeding seems to be regulated by blood levels of cineole, whereas metabolites are likely to be more important in regulating the chronic ingestion of cineole.
Publisher: Wiley
Date: 12-1982
DOI: 10.1111/J.1528-1157.1982.TB05075.X
Abstract: Determinants of compliance were examined in 101 hospital outpatients with epilepsy. Self-reported patient compliance was associated with plasma anticonvulsant levels, prescription refill frequencies, and appointment keeping. Factors independently related to compliance were worry about one's health, having generalized tonic-clonic seizures, and the absence of barriers to good compliance. Seizure frequency indirectly contributed to patient compliance through worry about one's health. Removing potential barriers to compliance and counselling patients who have been relatively seizure-free may improve compliance with anticonvulsant therapy.
Publisher: Royal Society of Chemistry (RSC)
Date: 1998
DOI: 10.1039/A805021J
Publisher: Wiley
Date: 08-1984
DOI: 10.1111/J.1528-1157.1984.TB03436.X
Abstract: Fifty-three hospital outpatients with epilepsy were randomly allocated to either a control or an intervention group. Patients in the intervention group were subjected to a combination of compliance-improving strategies: patient counselling, a special medication container, self-recording of medication intake and seizures, and mailed reminders to collect prescription refills and attend clinic appointments. Compliance with anticonvulsant therapy (as measured by plasma anticonvulsant levels and prescription refill frequencies), and seizure frequency, were evaluated in each patient prior to intervention and 6 months afterwards. Patient compliance and clinical control improved significantly in the intervention group patients. Seizure frequency was, on average, halved following intervention. Compliance and seizure frequency were unaltered in the control group. Intervention failed to improve clinic appointment keeping. Poor compliance with drug therapy commonly confounds the treatment of epilepsy. This study shows that compliance can be improved and seizure frequency lessened by strategies that are easily incorporated into the routine management of epileptic patients.
Publisher: Public Library of Science (PLoS)
Date: 30-03-2021
DOI: 10.1371/JOURNAL.PONE.0248961
Abstract: The red fox is a highly adaptable mammal that has established itself world-wide in many different environments. Contributing to its success is a social structure based on chemical signalling between in iduals. Urine scent marking behaviour has long been known in foxes, but there has not been a recent study of the chemical composition of fox urine. We have used solid-phase microextraction and gas chromatography-mass spectrometry to analyze the urinary volatiles in 15 free-ranging wild foxes (2 female) living in farmlands and bush in Victoria, Australia. Foxes here are routinely culled as feral pests, and the urine was collected by bladder puncture soon after death. Compounds were identified from their mass spectra and Kovats retention indices. There were 53 possible endogenous scent compounds, 10 plant-derived compounds and 5 anthropogenic xenobiotics. Among the plant chemicals were several aromatic apocarotenoids previously found in greater abundance in the fox tail gland. They reflect the dietary consumption of carotenoids, essential for optimal health. One third of all the endogenous volatiles were sulfur compounds, a highly odiferous group which included thiols, methylsulfides and polysulfides. Five of the sulfur compounds (3-isopentenyl thiol, 1- and 2-phenylethyl methyl sulfide, octanethiol and benzyl methyl sulfide) have only been found in foxes, and four others (isopentyl methyl sulfide, 3-isopentenyl methyl sulfide, and 1- and 2-phenylethane thiol) only in some canid, mink and skunk species. This indicates that they are not normal mammalian metabolites and have evolved to serve a specific role. This role is for defence in musteloids and most likely for chemical communication in canids. The total production of sulfur compounds varied greatly between foxes (median 1.2, range 0.4–32.3 μg ‘acetophenone equivalents’/mg creatinine) as did the relative abundance of different chemical types. The urinary scent chemistry may represent a highly evolved system of semiochemicals for communication between foxes.
Publisher: Bentham Science Publishers Ltd.
Date: 09-2012
DOI: 10.2174/157488612803251298
Abstract: It is common for injecting drug users (IDU) to prepare injections by crushing tablets which are not designed for parental administration. The injection of insoluble tablet excipients can lead to serious local and systemic medical complications. The aim of the study was to investigate the effectiveness of various types of filters in removing harmful insoluble particles from the injections prepared using crushed oxycodone tablets. Injections were prepared from a sustained-release oxycodone tablet formulation. The filtration of tablet extracts was carried out following procedures used by IDU using makeshift filter and commercially available filters. Particulate contamination and oxycodone content were analysed using light microscopy and spectrophotometer. Unfiltered extracts contained hundreds of thousands of particles of sufficient size to cause harms. Cigarette filters removed large particles but failed to remove small particles. The combination of cigarette filter and syringe filter (0.45 μm or 0.22 μm) reduced the particle count by 90 - 95%. A double membrane syringe filter (0.8/0.2 μm) removed more than 99% of the particles. Recovery of oxycodone was more than 95% with the tested syringe filters. Particulate contamination in injections prepared from crushed tablets can be effectively removed using a combination process of cigarette filter and syringe filters, or a 0.8/0.2 μm syringe filter. Compared to other filters, the 0.8/0.2 μm syringe filter did not block, the filtration was quick and easy to perform, and did not retain oxycodone. The use of a 0.8/0.2 μm syringe filter can provide an important harm reduction measure for IDU.
Publisher: Springer Science and Business Media LLC
Date: 2004
DOI: 10.1023/B:JOEC.0000013180.46747.07
Abstract: The resistance of Eucalyptus to browsing mammals has been related to the level and type of formylated phloroglucinol compounds (FPCs) present in the leaf. The antifeedant activity of FPCs appears to depend on their aldehyde groups, but little else is known of their mode of action. We have sought to elucidate this further by examining the biological reactivity and disposition of jensenone, a model FPC. Neither jensenone nor any metabolites were detected in urine or feces of marsupial brushtail or ringtail possums that had ingested up to 725 mg x kg(-0.75). When jensenone was incubated in rat gastrointestinal segments in vitro, it rapidly disappeared. Jensenone also reacted rapidly with glutathione, cysteine, glycine, ethanolamine, and trypsin, and more slowly with acetylcysteine and albumin. Sideroxylonal, a more complex FPC, exhibited the same reactivity. Torquatone, a related compound that lacks both aldehyde groups and antifeedant activity, was unreactive. Mass spectroscopic analysis indicated that the adducts were Schiff bases formed between the aldehyde groups of FPCs and amine groups of the conjugating molecules. Successive adducts were formed with the two aldehyde groups of jensenone, and the four groups of sideroxylonal. The jensenone bis-glutathione adduct appeared to cyclize to the disulfide form. These findings suggest that the antifeedant effects of FPCs are due to their facile binding to amine groups on critical molecules in the gastrointestinal tract, leading to a loss of metabolic function. The consequent toxic reaction, probably involving chemical mediators such as 5-hydroxytryptamine (5HT), may cause colic, nausea, and a general malaise, resulting in anorexia.
Publisher: Elsevier BV
Date: 11-2002
DOI: 10.1016/S1570-0232(02)00625-6
Abstract: We have developed two solid-phase microextraction (SPME) methods, coupled with gas chromatography, for quantitatively analysing the major Eucalyptus leaf terpene, 1,8-cineole, in both expired air and blood from the common brushtail possum (Trichosurus vulpecula). In-line SPME s ling (5 min at 20 degrees C room temperature) of excurrent air from an expiratory chamber containing a possum dosed orally with 1,8-cineole (50 mg/kg) allowed real-time semi-quantitative measurements reflecting 1,8-cineole blood concentrations. Headspace SPME using 50 microl whole blood collected from possums dosed orally with 1,8-cineole (30 mg/kg) resulted in excellent sensitivity (quantitation limit 1 ng/ml) and reproducibility. Blood concentrations ranged between 1 and 1380 ng/ml. Calibration curves were prepared for two concentration ranges (0.05-10 and 10-400 ng/50 microl) for the analysis of blood concentrations. Both calibration curves were linear (r(2)=0.999 and 0.994, respectively) and the equations for the two concentration ranges were consistent.
Publisher: Elsevier BV
Date: 07-1999
DOI: 10.1016/S0742-8413(99)00035-3
Abstract: Southern elephant seals (Mirounga leonina) are large, potentially dangerous animals which must be restrained before study or treatment. However, chemical restraint is unpredictable, possibly because of differences in body composition during fasting ashore, and circulatory adaptations to enable ing. The pharmacokinetics of ketamine (1.1 mg/kg i.v.) was studied in 15 southern elephant seals which had come ashore on Macquarie Island. The animals were first sedated with pethidine (5 mg/kg i.m.) to allow intravenous access. There was great variability in the calculated pharmacokinetic parameters, possibly due to circulatory changes associated with periods of apnoea which characterise this animal's response to anaesthetics. The median values were similar to those reported for other species: distribution t1/2 = 2.5 min (range 1-11 min) elimination t1/2 = 43 min (range 17-108 min) apparent volume of distribution, 1474 ml/kg (range 830-9301 ml/kg) clearance, 33 ml/min/kg (range 12-57 ml/min/kg). This was the first investigation of drug disposition in any seal species. and the first in any free-ranging wild animal. It is important to obtain pharmacological data in animals in whom drugs are used, but pre-catheterised captive animals may provide less variable data.
Publisher: Informa UK Limited
Date: 03-07-2014
Publisher: Informa UK Limited
Date: 2000
Abstract: 1. The metabolic fate of 1,8-cineole was investigated in the brushtail possum. Six possums were fed an artificial diet to which 0.5% 1,8-cineole (wet weight) was added for 2 days. Urine and faeces were collected after the second day. A s le of each was extracted into ethyl acetate and analysed for metabolites. Both free and total levels of metabolites were identified by GC-MS and LC-MS and quantified by GC-MS. 2. The pattern of metabolite excretion was very complex in the brushtail possum. Nineteen metabolites were found in total. Metabolites were categorized into four groups according to the oxidation they had undergone: hydroxycineoles (n = 3), cineolic acids (n = 2), dihydroxycineoles (n = 3) and hydroxycineolic acids (n = 11). No hydroxycineolic acid metabolites have been previously reported as metabolites of 1,8-cineole. 3. Fractional recovery of the ingested dose (2.4 +/- 0.5 g mean +/- SD) was 0.44 +/- 0.14 (mean +/- SD) in 24 h. Sixty percent of excreted metabolites were hydroxycineolic acids, the most extensively oxidized metabolites. Conjugation with glucuronic acid was inversely related to metabolite polarity, being greatest for hydroxycineoles (41-82%) and minimal for hydroxycineolic acids. 4. Traces of most metabolites were also found in the faeces.
Publisher: Hindawi Limited
Date: 04-1995
DOI: 10.1111/J.1365-2710.1995.TB00629.X
Abstract: This study was conducted to examine the interpatient variability in steady-state plasma concentrations of fluphenazine by repeat depot intramuscular administration, and to determine the relationship between these concentrations and clinical state. Steady-state pre-dose concentrations of fluphenazine in plasma were measured using a sensitive and specific gas chromatography/mass spectrometry (GC/MS) assay in 24 patients with schizophrenia who were receiving continuous treatment with depot intramuscular fluphenazine decanoate. Clinical response was measured using the Andreasen Scale for positive and negative symptoms. Steady-state plasma concentrations of fluphenazine ranged from undetectable (< 0.1 ng/ml) to 27.9 ng/ml, with a median of 0.5 ng/ml. No significant associations were found between plasma concentration and dosage, or age and sex of the patient. Steady-state plasma concentrations in patients taking anticholinergic agents were significantly higher than in patients not receiving such drugs (P < 0.05 by Mann-Whitney U-test). Poorer control, expressed as the sum of the negative symptom scores or the sum of the positive and negative symptom scores, was related to higher log transformed plasma concentration of fluphenazine and higher fluphenazine decanoate dosage. The log transformed plasma concentrations of fluphenazine and the fluphenazine decanoate dosages were weakly related. Patients receiving another antipsychotic drug in addition to fluphenazine decanoate tended to have poorer clinical control and higher dosages of fluphenazine decanoate. These results indicate the useful role that plasma level monitoring can fulfil in identifying patients who are therapy-resistant despite high plasma levels.
Publisher: Springer Science and Business Media LLC
Date: 2000
Publisher: Wiley
Date: 06-09-2015
DOI: 10.1111/DAR.12196
Abstract: The medical complications of injecting preparations from crushed tablets can be severe, and most can be attributed to the injection of insoluble particles and micro-organisms. Previously we have shown that most of the particles can be removed by filtration, but it was not known whether bacteria could also be filtered in the presence of a high particle load. This study aims to determine the feasibility of filtration to remove bacteria from injections prepared from tablets. Injections were prepared from crushed slow-release morphine tablets, in mixed bacterial suspensions of Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa. The injection suspensions were passed through syringe filters of porosity 0.45 or 0.20 μm, or combined 0.8 then 0.2 μm, and the bacterial load was counted. Bacterial concentrations in unfiltered injections were 2.5-4.3 × 10(6) colony forming units mL(-1) . Both the 0.20 and 0.45 μm filters blocked unless a prefilter (cigarette filter) was used first. The 0.2 μm filter and the combined 0.8/0.2 μm filter reduced the bacteria to the limit of detection (10 colony forming units mL(-1) ) or below. Filtration through a 0.45 μm filter was slightly less effective. Use of a 0.2 μm filter, together with other injection hygiene measures, offers the prospect of greatly reducing the medical complications of injecting crushed tablets and should be considered as a highly effective harm reduction method. It is very likely that these benefits would also apply to other illicit drug injections, although validation studies are needed.
Publisher: Informa UK Limited
Date: 2001
DOI: 10.1080/00498250110043535
Abstract: 1. This study reports on the pathways of metabolism and enzyme kinetics of the Eucalyptus terpene, 1,8-cineole, by liver microsomes from the brushtail possum (Trichosurus vulpecula) and koala (Phascolarctos cinereus) (animals that normally include this terpene in their diet), rat and human. 2. The rank order of the ability to metabolize 1,8-cineole with respect to overall 1,8-cineole intrinsic clearance (CL'int = Vmax/Kmax in microl mg protein(-1) min(-1)) was koala (188) > possum (181)>> rat (28) > human (12). This order supports the hypothesis that adaptation to a Eucalyptus diet involves enhanced metabolism of terpenes. 3. The metabolism of 1,8-cineole was also studied in the liver from brushtail possum pretreated with a mixture of terpenes, which have previously been shown to induce cytochrome P450 enzymes. Rats were pretreated with the same mixture of terpenes or phenobarbitone. 4. Terpene pretreatment more than doubled the CL'int of 1,8-cineole by brushtail possum liver microsomes (from 180 to 394 microl mg protein(-1) min(-1)) and increased rat CL'int by nearly 10-fold (from 28 to 259 microl mg protein(-1) min(-1)), but still less than the induced possum value. However, phenobarbitone had the greatest inducing effect, increasing the rat CL'int to 1,825 microl mg protein(-1) min(-1). 5. A regioselective preference of oxidation was evident between adapted and non-adapted species. In rat and human oxidation was preferred at the aliphatic ring carbons over methyl substituents. In possum, many of the available carbons were utilized, however metabolism at methyl substituents was preferred. In the koala, oxidation occurred primarily at the methyl substituents.
Publisher: Informa UK Limited
Date: 1997
DOI: 10.3109/03602539709037582
Abstract: The CDK4/6-Rb axis is a crucial target of cancer therapy and several selective inhibitors of it have been approved for clinical application. However, current therapeutic efficacy evaluation mostly relies on anatomical imaging, which cannot directly reflect changes in drug targets, leading to a delay in the selection of optimal treatment. In this study, we constructed a novel fluorescent probe, CPP30-Lipo/CDKACT4, for real-time monitoring of CDK4 activity and the therapeutic efficacy of its inhibitor in HR
Publisher: Annual Reviews
Date: 12-2005
DOI: 10.1146/ANNUREV.ECOLSYS.36.102003.152617
Abstract: ▪ Abstract Plant secondary metabolites (PSMs) significantly impact the nutritional ecology of terrestrial vertebrate herbivores. Herbivores have a wide range of mechanisms (herbivore offenses) to mitigate the negative effects of PSMs. We discuss several behavioral and physiological offenses used by terrestrial vertebrates. Several newly recognized herbivore offenses such as regulated absorption and regulation of toxin intake are presented. We give a detailed description of the biotransformation system with respect to PSMs. We also summarize recent findings of plant–animal interactions for lizards, birds, and mammals. Finally, we discuss some new tools that can be applied to long-standing questions of plant–vertebrate interactions.
Publisher: Wiley
Date: 04-1984
DOI: 10.1111/J.1445-5994.1984.TB04276.X
Abstract: Factors affecting patient compliance with diet and medication, clinical control, complications, and handicap were studied in 114 subjects with non-insulin-dependent diabetes mellitus who were attending a hospital diabetic clinic. Compliance with diet and hypoglycemic medication was correlated. The perceived importance, and the ease of compliance were the principal correlates of patient compliance. Factors independently related to diabetic control were compliance with diet, and the quality of the patient's diet. Diabetes which was poorly controlled, and which was of several-years' standing, was more likely to involve complications. Both poor control and the presence of complications contributed to handicap. Increased dietary education and counselling, with emphasis placed on the importance and benefits of compliance with prescribed diets, may improve control, decrease the incidence of complications, and ultimately minimise handicap due to diabetes in non-insulin-dependent patients.
Publisher: Springer Science and Business Media LLC
Date: 10-2009
DOI: 10.1007/S10886-009-9702-9
Abstract: Papyriferic acid (PA) is a triterpene that is secreted by glands on twigs of the juvenile ontogenetic phase of resin producing tree birches (e.g., Betula neoalaskana, B. pendula) and that deters browsing by mammals such as the snowshoe hare (Lepus americanus). We investigated the pharmacology of PA as a first step in understanding its antifeedant effect. After oral administration to rats, PA and several metabolites were found in feces but not urine, indicating that little was absorbed systemically. Metabolism involved various combinations of hydrolysis of its acetyl and malonyl ester groups, and hydroxylation of the terpene moiety. The presence of a malonyl group suggested a possible interaction with succinate dehydrogenase (SDH), a mitochondrial enzyme known to be competitively inhibited by malonic acid. The effect of PA on the oxidation of succinate by SDH was examined in mitochondrial preparations from livers of ox, rabbit, and rat. In all three species, PA was a potent inhibitor of SDH. Kinetic analysis indicated that, unlike malonate, PA acted by an uncompetitive mechanism, meaning that it binds to the enzyme-substrate complex. The hydrolysis product of PA, betulafolienetriol oxide, was inactive on SDH. Overall, the evidence suggests that PA acts as the intact molecule and interacts at a site other than the succinate binding site, possibly binding to the ubiquinone sites on complex II. Papyriferic acid was potent (K(iEIS) ranged from 25 to 45 microM in the three species) and selective, as malate dehydrogenase was unaffected. Although rigorous proof will require further experiments, we have a plausible mechanism for the antifeedant effect of PA: inhibition of SDH in gastrointestinal cells decreases mitochondrial energy production resulting in a noxious stimulus, 5-HT release, and sensations of nausea and discomfort. There is evidence that the co-evolution of birches and hares over a large and geographically- erse area in Northern Europe and America has produced marked differences in the formation of PA by birches, and the tolerance of hares to dietary PA. The present findings on the metabolic fate and biochemical effects of PA provide a rational basis for investigating the mechanisms underlying differences among populations of hares in their tolerance of a PA-rich diet.
Publisher: Springer Science and Business Media LLC
Date: 04-05-2006
DOI: 10.1007/S10886-006-9076-1
Abstract: Mammalian herbivores, particularly browsers and folivores, encounter and consume a range of plant chemical defenses [plant secondary metabolites (PSMs)] on a regular basis. The physiological regulation of PSM ingestion and the resulting behavioral responses of mammalian herbivores directly affect their feeding decisions and the subsequent foraging strategies that they adopt. Generalist mammalian herbivores are hypothesized to consume a generalized diet because of physiological limitations of their detoxification systems. The consumption of a generalized diet is proposed to enable toxin (PSM) dilution through the use of multiple detoxification pathways. We tested the predictions of the detoxification-limitation hypothesis by offering two chemically different plant species, Eucalyptus regnans and E. globulus, to a generalist mammalian folivore, the common brushtail possum (Trichosurus vulpecula), as single- and mixed-species diets. By feeding more efficiently, brushtail possums benefited more, through increased intake, on the mixed-species diet than on either of the single-species diets. We argue that frequently switching between chemically erse foliage reduces the physiological constraints imposed by a PSM-rich diet and enables more efficient feeding. The behavioral responses of brushtail possums were consistent with the proposed physiological constraints of a chemically defended diet, offering support for predictions of the detoxification-limitation hypothesis. We suggest that feeding behavior of herbivores may be a useful indicator of the physiological constraints imposed by a chemically defended diet.
Publisher: Springer Science and Business Media LLC
Date: 2003
Abstract: We investigated effects of two plant secondary metabolites (PSMs), cineole and gallic acid, on the nightly feeding behavior of the common brushtail possum (Trichosurus vulpecula), a generalist folivore. We tested whether possums altered their feeding behavior in response to increasing levels of cineole, a dietary terpene. Possums were fed artificial diets containing three levels of cineole: zero (basal diet), medium (6.8% of total dry matter, DM), and high (15.3% DM). In another experiment, we introduced gallic acid, a dietary phenolic, into the diets. Possums were offered a Choice PSM diet (cineole and gallic acid diets simultaneously) or a No-Choice PSM diet (containing either cineole or gallic acid). Detoxification products of cineole and gallic acid were examined in urine to determine that different detoxification pathways were utilized in the elimination of each compound. With increasing cineole levels, possums ate less, had smaller feeding bouts, and had a lower rate of intake, but did not extend their total nightly feeding time. Possums offered the Choice PSM diet, compared with the No-Choice diets, ate more, had larger feeding bouts, and tended to increase their rate of intake. Results from the urinary analysis indicated that gallic acid and cineole were not involved in competing detoxification pathways in brushtail possums. There was also a significant sex effect: females ate more overall, ate more per feeding bout, and ate at a higher rate than males. These results indicate that PSMs not only constrain overall intake, but that possums alter their feeding behavior in response to them. Altered feeding patterns may reduce the negative influence of PSMs on intake.
Publisher: Springer Science and Business Media LLC
Date: 2003
Abstract: Glucuronuria is normal in marsupial folivores such as the koala (Phascolarrctos cinereus), which excretes 2-3 g glucuronic acid daily. Although this has long been attributed to the metabolites of Eucalyptus terpenes, we have found that these are mostly excreted in the unconjugated form. We now report on the aglycones that account for most of the glucuronic acid in koala urine. Urine (24 hr) was collected from six male koalas (8.8 +/- 0.4 kg, mean +/- SE) that were maintained on E. cephalocarpa foliage. Urine s les were analyzed by liquid and gas chromatography (LC and GC) coupled with mass spectrometry (MS). Glucuronides were readily identified by LC-MS/MS, which generated characteristic product ions at m/z 113 and 175. From the corresponding parent glucuronide ions, the masses of the aglycones were calculated. Confirmation of identity was by GC-MS after hydrolysis with beta-glucuronidase and comparison with standard compounds. Quantitation was by GC. The major non-terpene aglycones were 4-methylcatechol, resorcinol, salicyl alcohol, and two unidentified C7H8O2 phenols. Smaller amounts of benzoic acid, benzyl alcohol, orcinol, p-cresol, phenol, and phloroglucinol were detected. We have previously reported that terpene metabolites account for about 10% urinary glucuronides in the same koalas fed E. cephalocarpa. The present study found that an additional 60% urinary glucuronic acid is conjugated with non-terpene, mainly phenolic, aglycones. It seems likely that these phenolic compounds are present in leaves as glycosides and are chiefly responsible for the glucuronuria in koalas.
Publisher: Elsevier BV
Date: 08-2001
DOI: 10.1016/S1532-0456(01)00214-9
Abstract: The in vivo metabolic fate of 1,8-cineole was investigated in six male koalas. Koalas were fed ad lib a diet of Eucalyptus cephalocarpa leaf with a 1,8-cineole concentration of 2.53+/-0.70% dry mass of leaf, corresponding to a 1,8-cineole intake of 2.4+/-1.1 mmol/kg (3.1+/-1.3 g). Urine and faeces were collected for 24 h and metabolites identified by GC-MS and LC-MS. Metabolites were quantified before and after hydrolysis with beta-glucuronidase to give free and total levels, respectively. Fractional recovery of ingested 1,8-cineole was 1.3+/-0.4 and 1.4+/-0.4 (mean+/-S.D.) for free and total measurements, respectively. Seven metabolites were identified and quantified: 9- and 7-hydroxycineole, 9- and 7-cineolic acid, 7-hydroxy-9-cineolic acid, 9-hydroxy-7-cineolic acid and 7,9-dicineolic acid. The hydroxycineolic acids dominated the metabolite profile (85%). 7,9-Dicineolic acid, a novel metabolite of 1,8-cineole, accounted for almost 10% of the recovered dose making it the second most abundant metabolite after 7-hydroxy-9-cineolic acid (77%). Together, the less oxidised metabolites, the hydroxycineoles and cineolic acid, accounted for only 5% of the cineole consumed. Significant conjugation only occurred with four minor, less oxidised, alcohol and carboxylic acid metabolites. We have shown that the koala detoxifies and eliminates 1,8-cineole primarily by extensive oxidation without utilising conjugation pathways.
Publisher: Springer Science and Business Media LLC
Date: 2001
Abstract: Salicin was administered orally to six brushtail possums by incorporation in food for six days at three dose levels (0.05, 0.5, and 1.5% wet weight), giving mean +/- SD daily intakes of 0.31 +/- 0.09, 2.76 +/- 0.75, and 6.04 +/- 1.12 mmol salicin. Metabolites were identified by mass spectrometry and assayed by HPLC. Salicyl alcohol glucuronide accounted for 56-64% of urinary metabolites over the three doses, salicyluric acid 15-26%, salicin 10-18%, and there were smaller amounts of free (2-4%) and conjugated (0-6%) salicylic acid. beta,2-Dihydroxyphenylpropionic acid was a minor metabolite. The hydrolysis of dietary salicin enabled reconjugation of its aglycone, salicyl alcohol, with a more polar sugar, glucuronic acid, thus enhancing its renal excretion and resulting in little net loss of substrates for conjugation and a low measurable metabolic cost of excretion.
Publisher: Wiley
Date: 06-2007
Publisher: Elsevier BV
Date: 1984
DOI: 10.1016/0378-4347(84)80079-1
Abstract: This work describes a method for the quantitative determination of the labile, toxic N-hydroxy metabolite of phenacetin in urine. A thin-layer chromatography step was used for the preliminary purification of extracts, and the specificity of the assay was based on the monitoring of specific metastable decompositions in a forward geometry double-focussing mass spectrometer, in a manner analogous to conventional tandem mass spectrometry. This precluded the need for a gas chromatographic separation, thus minimizing thermal decomposition which can occur with these compounds, as well as enabling very rapid analyses.
Publisher: Oxford University Press (OUP)
Date: 07-02-2019
Abstract: Like all animals, the red fox uses chemical signals for social communication. The supracaudal or tail gland smells of violets, attributed to the presence of carotenoid degradation products, or apocarotenoids, which commonly occur as aromatics in flowers. We have more fully characterized the scent chemistry of the fox tail gland. Volatile chemicals were analyzed by gas chromatography-mass spectrometry (GC-MS) and identified from their electron ionization mass spectra and Kovats retention indices. The 3 previously reported apocarotenoids were confirmed, and many additional compounds found. These include the apocarotenoids β-cyclocitral, β-homocitral, β-ionone, cyclic β-ionone, β-ionone-5,6-epoxide, α-ionene, α-ionone, 2,6,6-trimethylcyclohexanone (IUPAC 2,2,6-), 2,6,6-trimethyl-2-cyclohexen-1-one, 6-methyl-5-hepten-2-one (sulcatone), and geranyl acetone. Notably, sulcatone is a semiochemical in several species. 3,3-Dimethyl-2,7-octanedione was identified as a probable apocarotenoid which is likely to be a significant fox scent chemical. The γ-lactone of 4-hydroxyhexadecanoic acid (hexadecan-4-olide) was also found, one of a group of known mammalian signaling compounds. This rich mixture of volatile apocarotenoids implies an adequate consumption of plant carotenoids, which are known to be necessary for optimal health. Dietary carotenoids color the skin and feathers of some birds, used as a visual signal to conspecifics, and the floral aroma of the fox tail gland may provide an olfactory signal to other foxes.
Publisher: Elsevier BV
Date: 11-1999
DOI: 10.1016/S0742-8413(99)00085-7
Abstract: The mixed function oxidase (MFO) activity and content was studied in the liver of common brushtail possums fed for 10 days on a diet containing a mixture of terpenes found in Eucalyptus leaves on which possums commonly browse. The MFOs were compared to the MFOs in possums fed a control diet of fruits and cereals only. The terpenes chosen were 1,8-cineole, p-cymene, alpha-pinene and limonene. The selected terpenes caused induction of P450 enzymes, as shown by a 53% higher cytochrome P450 content and a 45% increase in aminopyrine demethylase activity in the test animals. Aniline hydroxylase activity was significantly increased, with levels of 2.95 and 1.43 nmol min(-1) mg(-1) microsomal protein in the test and control animals, respectively. There was also a significant increase in androstenedione 16alpha-hydroxylase activity in the test group, 0.85 as compared to 0.50 nmol mg(-1) min(-1) in the control group. Western blot studies using human CYP2E1 and rat CYP2C11 and CYP2C6 antibodies gave CYP2E, CYP2C11 and CYP2C6 immunoreactive bands of greater intensity in the test animals as compared to the control group. This study has shown experimentally that dietary terpenes cause enzyme induction in folivorous marsupials. It also confirms the importance of knowledge of diet when studying xenobiotic metabolising enzymes, particularly in wild animals such as the brushtail possum.
Publisher: Springer Science and Business Media LLC
Date: 23-05-2006
DOI: 10.1007/S10886-006-9081-4
Abstract: Plant secondary metabolites (PSMs) are a major constraint to the ingestion of food by folivorous and browsing herbivores. Understanding the way in which mammalian detoxification pathways are adapted to deal with PSMs is crucial to understanding how PSMs influence ingestive behavior of herbivores and hence their fitness and the impact that they have on vegetation. Pharmacological concepts can provide insights into the relationship between the absorption and metabolic fate of PSMs and ingestive behavior. Lipophilic PSMs will be absorbed into the bloodstream and must be removed fast enough to prevent their accumulation to toxic levels. Elimination depends on their metabolism, usually by cytochrome P450 enzymes, to more polar metabolites that can be excreted by the kidney. The concentration of PSM in blood (C) is a better measure of exposure to a toxin compared to the amount ingested because there can be great variability in the rate and degree of absorption from the gut. C rises and falls depending on the relative rates of absorption and elimination. These rates depend in part on metabolic and transport processes that are saturable and liable to inhibition and induction by PSMs, indicating that complex interactions are likely. Herbivores can use diet choice and the rate and amount of PSM consumption to prevent C from reaching a critical level that produces significant adverse effects.
Publisher: Informa UK Limited
Date: 1985
DOI: 10.3109/00498258509045046
Abstract: The metabolism of phenacetin to reactive intermediates in humans was estimated from the excretion of thio adducts in urine. N-Hydroxyphenacetin, a precursor of reactive metabolites, was also quantified. Following an oral dose of phenacetin (10 mg/kg) to humans, these metabolites in 24 h urine were: paracetamol-3-cysteine, 4.4% dose paracetamol-3-mercapturate, 3.9% 3-thiomethylparacetamol, 0.4% N-hydroxyphenacetin, 0.5%. Rats showed a considerable increase in N-hydroxyphenacetin excretion after chronic dosing with phenacetin at high dosage (500 mg/kg) for one month. chronic dosing with a low dose (50 mg/kg) did not increase N-hydroxyphenacetin excretion, but a marked increase occurred on concomitant administration of aspirin and caffeine.
Publisher: Elsevier BV
Date: 03-1996
DOI: 10.1016/S0007-1935(96)80075-3
Abstract: A study was conducted to assess the effectiveness of the alpha-2 agonist medetomidine for sedation of pre-moulting, mature female southern elephant seals (Mirounga leonina). Two animals were sedated with a single intramuscular dose of medetomidine (0.013 and 0.027 mg kg-1). A further two groups of five animals received medetomidine (0.017 mg kg-1) combined with ketamine (1.90 mg kg-1) and, 20 min later, either saline or the alpha-2 antagonist atipamezole (0.04 mg kg-1) intravenously. Medetomidine alone did not give sufficient restraint to permit intravenous access. The response appeared to be similar to previous findings with ketamine and xylazine. Administration of atipamezole had little effect upon the level and timecourse of restraint. Ketamine and medetomidine seem to offer few advantages over ketamine and xylazine or other cyclohexamine-drug combinations for routine chemical restraint of southern elephant seals.
Publisher: Informa UK Limited
Date: 2002
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1080/00498250210124138
Abstract: 1. p-Cymene is an aromatic monoterpene found in the leaves of Eucalyptus spp. and is ingested in the diet of two marsupial folivores, the brushtail possum (Trichosurus vulpecula) and koala (Phascolarctos cinereus). The metabolism of p-cymene by liver microsomes from the possum, koala and rat (an animal whose diet is not terpene-rich) was examined. 2. The major p-cymene metabolite in each species was cuminyl alcohol, with smaller amounts of other side-chain alcohols being formed. No phenolic metabolites were detected. Possum and koala microsomes further oxidized cuminyl alcohol to cumic acid. 3. Pretreatment with a terpene diet more than doubled the V(max) for cuminyl alcohol formation by possum microsomes. This is similar to a previous finding by our group with 1,8-cineole and indicates that a terpene-containing diet results in induction of the enzymes responsible for terpene metabolism. 4. The rank order of the ability to metabolize p-cymene, measured by intrinsic clearance (Cl(int) = V(max)/K(m) [microl mg protein(-1) min(-1)]) was: terpene-treated possum (128)>control possum (107)>koala (69)>rat (38). 5. The findings support the hypothesis that animals that have adapted to a diet of Eucalypus leaf have a greater capacity than generalist feeders to metabolize dietary terpenes.
Publisher: Springer Science and Business Media LLC
Date: 06-1995
DOI: 10.1007/BF02033457
Publisher: Wiley
Date: 1995
DOI: 10.1080/09595239500185121
Abstract: Drink drivers arrested in Tasmania are routinely asked by police where they had last been drinking, and these data were examined for 716 drivers arrested in Southern Tasmania during a 4-month period in 1992. Nearly half (43%) of arrested drink drivers cited in idual hotels as the place where they had last been drinking. This enabled a citation score to be assigned to each of the 82 hotels in metropolitan Hobart. The distribution of citation scores was highly skewed, with eight hotels accounting for 45% of hotel citations, and two accounting for 20%. The hotels' citation scores were compared in relation to the rank order of their licence fees, since better measures of patronage proved unobtainable. Some hotels with small total alcohol sales did appear to have an unexpectedly large number of citations, suggesting less than responsible serving practices. Hoteliers' comments were sought on the interpretation of citation scores, and incorporated into a discussion of the limitations of the data in determining the extent of in idual hotel responsibility for drink drivers. Important questions remaining include (1) what is the validity of citations made by drink drivers at the time of arrest (2) what appropriate and quantifiable denominator can be used to adjust the number of citations to the level of patronage and (3) what level of citations is too high and requires action?
Publisher: Wiley
Date: 28-04-2015
DOI: 10.1007/S11745-015-4025-9
Abstract: The paracloacal glands are the most prevalent scent glands in marsupials, and previous investigation of their secretions in the brushtail possum (Trichosurus vulpecula) has identified many odorous compounds together with large amounts of neutral lipids. We have examined the lipids by LC-MS, generating ammonium adducts of acylglycerols by electrospray ionisation. Chromatograms showed a complex mixture of coeluting acylglycerols, with m/z from about 404 to 1048. Plots of single [M + NH4](+) ions showed three groups of lipids clearly separated by retention time. MS-MS enabled triacylglycerols and diacylglycerol ethers to be identified from neutral losses and formation of diacylglycerols and other product ions. The earliest-eluting lipids were found to be triacylglycerol estolides, in which a fourth fatty acid forms an ester link with a hydroxy fatty acid attached to the glycerol chain. This is the first report of triacylglycerol estolides in animals. They form a complex mixture with the triacylglycerols and diacylglycerol ethers of lipids with short- and long-chain fatty acids with varying degrees of unsaturation. This complexity suggests a functional role, possibly in social communication.
Publisher: Springer Science and Business Media LLC
Date: 14-09-2012
DOI: 10.1007/S10886-012-0188-5
Abstract: The common brushtail possum (Trichosurus vulpecula) is the most widespread browsing marsupial in Australia, where it occupies woodland, agricultural, and urban environments. Following its introduction into New Zealand in the 19th century it has become a major feral pest, threatening native forests. The adaptability of the possum is thought to be due in part to its social organization, in which chemical communication is important. Possums have cloacal glands and exhibit related marking behavior. This study sought to characterize the chemicals involved in scent marking. Swabs were taken of the cloacal region of 15 possums (5 females, 10 males) from north-eastern Tasmania and analyzed by gas chromatography-mass spectrometry. There was a large number of compounds present, including 81 branched and unbranched, and saturated and unsaturated, fatty acids (C(4)-C(15)) and alcohols (C(6)-C(26)) 27 esters of 2,6- and 2,7-dimethyloctanol 29 esters of formic acid 39 sulfur compounds including S(8) and a series of dialkyl disulfides, trisulfides, and tetrasulfides (C(4)-C(10)) and several alkylglycerol ethers. Many of these cloacal compounds are new to biology. There was considerable in idual variability in the relative amounts of compounds found, and no evident sex differences, although the study was not designed to test this. This pattern suggests that these compounds may be acting collectively as a signature mixture of semiochemicals, carrying information on the in idual, its kinship, and physiological and social status. This is the first detailed description of putative semiochemicals in any marsupial species.
Publisher: Oxford University Press (OUP)
Date: 06-2003
Abstract: The correlation between low level time-weighted average (TWA) atmospheric xylene exposure (p.p.m.) and urinary methylhippuric acid (MHA) expressed per gram of creatinine was examined. Subjects were recruited from workplaces that utilized xylene. Ambient monitoring of o-, m- and p-xylene isomers was carried out using passive diffusion vapour monitors. Adjusted (post-shift minus pre-shift) and post-shift urinary levels of xylene metabolites (2-, 3- and 4-MHA) were determined by GC-MS. Twenty subjects were recruited into the study. Total xylene TWA exposures were 3.36 +/- 3.63 p.p.m. (mean +/- SD) with a range of 0.03-14.44 p.p.m. The r(2) values for the regression equations between xylene exposure and in idual and total adjusted MHA isomers were 0.390, 0.709, 0.677 and 0.631 for o-, m-, p- and total xylenes, respectively, which was greater than the respective correlations between non-adjusted s les. In conclusion, biological monitoring of occupational xylene exposure at levels <15 p.p.m. using urinary MHA showed a good correlation with atmospheric levels and is a valid complement to ambient monitoring. Even though occupational xylene exposure in the workplaces studied was generally low, MHA was found in the pre-shift urine of all workers and the use of adjusted values showed modest improvements in correlations. Recent exposure prior to s ling, either from occupational or non-occupational sources, should be considered when biological monitoring of xylene is undertaken. Extrapolation of data from this study predicted a MHA concentration in post-shift urine of 1.3 g/g creatinine after exposure to a TWA of 100 p.p.m. xylene.
Publisher: Wiley
Date: 08-2006
DOI: 10.1890/0012-9658(2006)87[2103:CDODPI]2.0.CO;2
Abstract: Most herbivores eat more and survive better when they have access to a variety of foods. One explanation involves the detoxification of plant secondary metabolites (PSMs). By feeding from a variety of plants that contain different classes of PSMs, animals can use multiple detoxification pathways and presumably consume more food. Although popular, this theory is difficult to test because it requires knowledge of the detoxification pathways of each PSM in the diet. We established that common brushtail possums (Trichosurus vulpecula) use various combinations of oxidation, hydrolysis, and conjugation with glucuronic acid (GA) or glycine to detoxify six PSMs. Compared to their ingestion of a single PSM, possums ate more when offered a choice between two diets containing PSMs that require apparently independent detoxification pathways (benzoate and 1,8-cineole, benzoate and p-cymene, benzoate and orcinol, benzoate and salicin, or orcinol and 1,8-cineole). However, possums still did not eat as much of these diets as they did of a basal diet free of PSMs. This suggests that detoxification pathways are never independent, but are separated instead by degrees. In contrast, possums offered a choice of two PSMs that require competing detoxification pathways (1,8-cineole and p-cymene, 1,8-cineole and salicin, or orcinol and salicin) ate no more than when offered diets containing one of the compounds. There was an exception: even though both rutin and orcinol are detoxified via conjugation with GA, the feeding behavior of possums did not suggest competition for detoxification pathways. This implies that the supply of GA is not limiting. This study provides the first convincing evidence that herbivorous mammals can eat more by selecting mixed diets with a ersity of PSMs that make full use of their detoxification potential. It also emphasizes that other behavioral and physiological factors, such as transient food aversions, influence feeding behavior.
Publisher: Wiley
Date: 10-1995
DOI: 10.1080/09595239500185481
Abstract: From 1990 to 1991 in the Hobart region there was a marked fall in both hotel patronage and the proportion of patrons subsequently driving with their blood alcohol concentration above the legal limit. This was associated with smaller falls in the number of drink drivers charged and alcohol-related road accidents, which continued in the following year. It appears that the pattern of drinking and driving is changing, presumably in response to random breath testing and tougher penalties for offences.
Publisher: Hindawi Limited
Date: 06-1997
DOI: 10.1046/J.1365-2710.1997.94875948.X
Abstract: This study was conducted to examine the effect of cardiopulmonary bypass surgery on the total and unbound plasma concentrations of fentanyl and the total plasma concentrations of alcuronium. Total fentanyl concentrations were measured by gas chromatography, the plasma protein binding of fentanyl by ultrafiltration, and alcuronium concentrations by high-performance liquid chromatography. Sixteen patients were studied. On initiation of cardiopulmonary bypass (CPB), there were mean decreases of 58.8 +/- 7.1% and 47 +/- 3.2% for total concentrations of fentanyl in plasma and haemoglobin in blood, respectively. The magnitude of these reductions in in idual patients was significantly related (Spearman p = 0.65, P < 0.05). The unbound fraction of fentanyl rose from 0.23 to 0.34 after the start of CPB. The total fentanyl concentration remained relatively stable during bypass until near the end of CPB when the mean total concentration increased, coinciding with rewarming. The size of the increase was related to the body mass index (BMI) of the patient (Spearman p = 0.85, P < 0.01). The estimated elimination half-life of fentanyl using the grouped data was 4.7 h. The total alcuronium concentration in plasma fell by 29% on initiation of CPB and there was no increase on rewarming. The estimated elimination half-life of alcuronium using the grouped data was 234 min. Despite marked declines in the plasma concentrations of both drugs on initiation of CPB, suitable levels of anaesthesia were maintained throughout the procedure.
Publisher: Springer Science and Business Media LLC
Date: 08-1993
DOI: 10.1007/BF00982297
Publisher: Wiley
Date: 09-2006
DOI: 10.1890/0012-9658(2006)87[2236:SSOTPO]2.0.CO;2
Abstract: Generalist mammalian browsers and folivores feed on a range of chemically different plant species, which may assist them in diluting toxins and ersifying nutrient consumption. The frequency and order in which their diets are mixed are important determinants of intake. As a result, the degree of plant heterogeneity in an environment, and the spatial scale at which this occurs, should directly influence herbivore foraging decisions. We tested whether altering the Spatial scale of plants, and thus plant secondary metabolites (PSMs), affected foraging efficiency of a generalist folivore, the common brushtail possum (Trichosurus vulpecula). First, we demonstrated that possums were able to consume more from a mixed diet of two chemically different species, Eucalyptus globulus and E. tenuiramis, than when either of these species was offered alone. We then tested whether altering the spatial scale between E. globulus and E. tenuiramis, as small- or large-scale plant heterogeneity "patches," affected possum foraging behavior and, ultimately, their foraging efficiency. Possums increased their foraging efficiency when the spatial scale of plant heterogeneity was small rather than large. We argue that the ability to regularly switch diets, when plant spatial distribution is at a small scale, reduces the negative effects of PSM ingestion. We predict that the heterogeneity of plant patches, in relation to PSM distribution, and the scale at which this occurs across a landscape, are critical factors that influence foraging efficiency and, ultimately, fitness of mammalian herbivores. This research provides a fundamental link between plant chemistry, foraging, and habitat heterogeneity.
Publisher: Springer Science and Business Media LLC
Date: 04-2004
DOI: 10.1023/B:JOEC.0000028430.92739.83
Abstract: Eucalyptus leaf-eating marsupials such as the brushtail possum (Trichosurus vulpecula) ingest large amounts of terpenes, especially 1,8-cineole (cineole)--the major component of many eucalyptus oils. Brushtail possums were acclimated to a non-Eucalyptus diet with increasing concentrations of cineole (0.5-4.0% wet weight) added over 18 d. We measured food and cineole consumption and urinary metabolites of cineole. Food intake decreased with cineole content, indicating that it was constrained by the maximum tolerable intake of cineole that was 3.8 +/- 0.2 g kg(-1) or 5.2 +/- 0.3 g kg(-0.75) (mean +/- SE, N = 6). The pattern of metabolites was similar at all cineole intakes (56% hydroxycineolic acids, 27% cineolic acids, 13% hydroxycineoles, and 4% dihydroxycineoles). In another experiment, possums maintained on artificial diet were abruptly presented with 4% cineole for 5 d. Food intake fell by 45 +/- 6% (mean +/- SE, N = 6) and mean cineole intake was 2.9 +/- 0.3 g kg(-1). There was evidence of induction of secondary oxidative pathways, as hydroxycineoles were the major metabolites (48% total) on the first day, but rapidly dropped to 15% on subsequent days as the acid metabolites increased. These findings indicate that ingestion of cineole is not constrained by selective saturation of in idual enzymes involved in its multiple pathways of oxidation, but rather the total detoxification capacity appears to limit feeding on a cineole diet.
Publisher: Springer Science and Business Media LLC
Date: 1999
Start Date: 2004
End Date: 2007
Funder: Australian Research Council
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