The need to disentangle key concepts from ecosystem-approach jargon.

The ecosystem approach--as endorsed by the Convention on Biological Diversity (CDB) in 2000-is a strategy for holistic, sustainable, and equitable natural resource management, to be implemented via the 12 Malawi Principles. These principles describe the need to manage nature in terms of dynamic ecosystems, while fully engaging with local peoples. It is an ambitious concept. Today, the term is common throughout the research and policy literature on environmental management. However, multiple meanings have been attached to the term, resulting in confusion. We reviewed references to the ecosystem approach from 1957 to 2012 and identified 3 primary uses: as an alternative to ecosystem management or ecosystem-based management; in reference to an integrated and equitable approach to resource management as per the CBD; and as a term signifying a focus on understanding and valuing ecosystem services. Although uses of this term and its variants may overlap in meaning, typically, they do not entirely reflect the ethos of the ecosystem approach as defined by the CBD. For example, there is presently an increasing emphasis on ecosystem services, but focusing on these alone does not promote decentralization of management or use of all forms of knowledge, both of which are integral to the CBD's concept. We highlight that the Malawi Principles are at risk of being forgotten. To better understand these principles, more effort to implement them is required. Such efforts should be evaluated, ideally with comparative approaches, before allowing the CBD's concept of holistic and socially engaged management to be abandoned or superseded. It is possible that attempts to implement all 12 principles together will face many challenges, but they may also offer a unique way to promote holistic and equitable governance of natural resources. Therefore, we believe that the CBD's concept of the ecosystem approach demands more attention.

Is there a cost of parasites to caribou?

SUMMARY: Macroparasites potentially play a significant but often ignored role in the ecology and dynamics of wild ruminant populations. In the Arctic, parasites may impact on host populations by exacerbating the effects of seasonal and limited forage availability on the condition, fecundity and survival of individuals. We studied the effects of abomasal nematode parasites and warble flies, Hypoderma tarandi, on condition and pregnancy of caribou Rangifer tarandus in the Dolphin-Union herd, Nunavut, Canada. By the end of winter, female caribou over 2 years old showed a significant decrease in body weight with increasing nematode burden, and a decrease in back fat depth with increasing warble abundance. These effects were exaggerated in the non-pregnant fraction of the population. High warble larvae burdens were also associated with significantly reduced probability of being pregnant. Our research demonstrates a negative relationship between parasites and caribou condition that may have consequences for their fitness. Additionally, we discuss the possibility that muskox Ovibos moschatus share some parasite species with the caribou and could lead to elevated burdens in the sympatric host. Parasites may have been a contributory factor in a previous winter range-shift of the caribou herd and this may reflect a form of apparent competition between the two ungulate species.

The effect of host movement on viral transmission dynamics in a vector-borne disease system.

Many vector-borne pathogens whose primary vectors are generalists, such as Ixodid ticks, can infect a wide range of host species and are often zoonotic. Understanding their transmission dynamics is important for the development of disease management programmes. Models exist to describe the transmission dynamics of such diseases, but are necessarily simplistic and generally limited by knowledge of vector population dynamics. They are typically deterministic SIR-type models, which predict disease dynamics in a single, non-spatial, closed patch. Here we explore the limitations of such a model of louping-ill virus dynamics by challenging it with novel field data. The model was only partially successful in predicting Ixodes ricinus density and louping-ill virus prevalence at 6 Scottish sites. We extend the existing multi-host model by forming a two-patch model, incorporating the impact of roaming hosts. This demonstrates that host movement may account for some of the discrepancies between the original model and empirical data. We conclude that insights into the dynamics of multi-host vector-borne pathogens can be gained by using a simple two-patch model. Potential improvements to the model, incorporating aspects of spatial and temporal heterogeneity, are outlined.

The effects of co-administration of 3,4-methylenedioxymethamphetamine ("ecstasy") or para-methoxyamphetamine and moclobemide at elevated ambient temperatures on striatal 5-HT, body temperature and behavior in rats.

We have recently demonstrated that co-administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") with the reversible monoamine oxidase type A (MAO-A) inhibitor moclobemide at an ambient temperature of 22 degrees C significantly increases striatal 5-HT outflow and 5-HT-mediated behaviors. In the present study, using microdialysis, we examined the effects of co-administration of MDMA or para-methoxyamphetamine (PMA) with moclobemide on striatal 5-HT outflow at the elevated ambient temperatures of 30 degrees C. Samples were collected every 30 min for 4 h and analyzed by high-performance liquid chromatography assay with electrochemical detection (HPLC-ED). 5-HT-mediated effects on body temperature and behavior were also recorded. Rats were treated with either saline or 20 mg/kg (i.p.) moclobemide, followed by 10 mg/kg (i.p.) MDMA, 10 mg/kg (i.p.) PMA or saline 60 min later. Both MDMA and PMA produced significant increases in 5-HT outflow (370% peak and 309% peak, respectively, P<0.05). MDMA and PMA significantly increased body temperature (+2.0 degrees C and +2.1 degrees C, respectively, P<0.01) and drug-related behaviors (P<0.05). When MDMA or PMA was co-administered with moclobemide, additional significant increases were seen in 5-HT outflow (850% peak, P<0.01 and 1450% peak, P<0.001, respectively) and only MDMA showed additional significant increase in body temperature (+5.0 degrees C, P<0.001). No additional increases were seen in behavioral activity. When moclobemide was co-administered with MDMA, sustained increases in body temperature were recorded that were significantly higher than with MDMA alone and such increases were not observed in our previous study at normal room temperature. Our results suggest greater risk of MDMA-induced adverse effects on body temperature regulation, compared with PMA, when used in combination with moclobemide at elevated ambient temperatures.

Don't forget to look down - collaborative approaches to predator conservation.

Finding effective ways of conserving large carnivores is widely recognised as a priority in conservation. However, there is disagreement about the most effective way to do this, with some favouring top-down 'command and control' approaches and others favouring collaboration. Arguments for coercive top-down approaches have been presented elsewhere; here we present arguments for collaboration. In many parts of the developed world, flexibility of approach is built into the legislation, so that conservation objectives are balanced with other legitimate goals. In the developing world, limited resources, poverty and weak governance mean that collaborative approaches are likely to play a particularly important part in carnivore conservation. In general, coercive policies may lead to the deterioration of political legitimacy and potentially to non-compliance issues such as illegal killing, whereas collaborative approaches may lead to psychological ownership, enhanced trust, learning, and better social outcomes. Sustainable hunting/trapping plays a crucial part in the conservation and management of many large carnivores. There are many different models for how to conserve carnivores effectively across the world, research is now required to reduce uncertainty and examine the effectiveness of these approaches in different contexts.

The role of parasites in the dynamics of a reindeer population.

Even though theoretical models show that parasites may regulate host population densities, few empirical studies have given support to this hypothesis. We present experimental and observational evidence for a host-parasite interaction where the parasite has sufficient impact on host population dynamics for regulation to occur. During a six year study of the Svalbard reindeer and its parasitic gastrointestinal nematode Ostertagia gruehneri we found that anthelminthic treatment in April-May increased the probability of a reindeer having a calf in the next year, compared with untreated controls. However, treatment did not influence the over-winter survival of the reindeer. The annual variation in the degree to which parasites depressed fecundity was positively related to the abundance of O. gruehneri infection the previous October, which in turn was related to host density two years earlier. In addition to the treatment effect, there was a strong negative effect of winter precipitation on the probability of female reindeer having a calf. A simple matrix model was parameterized using estimates from our experimental and observational data. This model shows that the parasite-mediated effect on fecundity was sufficient to regulate reindeer densities around observed host densities.

DNA evidence that Ostertagia gruehneri and Ostertagia arctica (Nematoda: ostertagiinae) in reindeer from Norway and Svalbard are conspecific.

DNA sequences of ITS-1 and ITS-2 of rDNA were determined for 16 individual adult males each of Ostertagia gruehneri and Ostertagia arctica from Svalbard reindeer (Rangifer tarandus platyrhynchus) and Eurasian tundra reindeer (R. t. tarandus). Each ITS was virtually identical in O. gruehneri and O. arctica and the three mixed bases detected were shared by both species. Our results strongly suggest that O. gruehneri and O. arctica are dimorphic males of the same species.

Identification by polymerase chain reaction (PCR) of Marshallagia marshalli and Ostertagia gruehneri from Svalbard reindeer.

A polymerase chain reaction (PCR) assay to identify two common abomasal nematodes Marshallagia marshalli and Ostertagia gruehneri of Svalbard reindeer was developed. Species-specific PCR primers were designed from internal transcribed spacer (ITS)-2 sequences of rDNA and validated using morphologically identified adult male and female nematodes. Using the species-specific primers, a 110 bp fragment was amplified from M. marshalli and its minor morph Marshallagia occidentalis and a 149 bp fragment was amplified from Ostertagia gruehneri and its minor morph Ostertagia arctica. No PCR products were amplified from the third rare species, Teladorsagia circumcincta, or DNA from the reindeer host. The assay provides a useful tool to estimate species composition for both sexes in this nematode community.

The population dynamics of Ostertagia gruehneri in reindeer: a model for the seasonal and intensity dependent variation in nematode fecundity.

The gastrointestinal nematode Ostertagia gruehneri is a parasite of reindeer that can have a significant impact on host population dynamics. To gain a better understanding of the population dynamics of O. gruehneri, we parameterise a model for its fecundity that describes the observed seasonal and intensity dependent pattern of faecal egg counts well. The faecal egg count model is combined with a model for the seasonal faecal production rate of Svalbard reindeer to obtain quantitative estimates of the fecundity of O. gruehneri. The model is used to evaluate the relative contribution to pasture contamination of variation in the abundance of O. gruehneri and variation in reindeer densities. It is concluded that due to the intensity dependence in nematode fecundity, variation in reindeer population densities is likely to be the most important of these factors for pasture contamination.

Analysis of genetically modified plant gene expression using GUS fluorimetry.

A fluorimetric assay method for the analysis of beta-glucuronidase (GUS) reporter gene expression in genetically modified plants is described. Optimization of this method for woody plants and a statistical approach suitable for comparisons of gene expression in different transformants or tissues of the same plant is described. Example data from elm (Ulmus procera) SR4 regenerant plants, shown to be genetically modified by PCR and DNA-DNA hybridizations, in which higher GUS expression levels are found in stems than in leaves demonstrates the utility of this approach.

Combined cardiac effects of cocaine and the anabolic steroid, nandrolone, in the rat.

Despite reports of an increase in the incidence of simultaneous cocaine and anabolic steroid abuse, potential adverse interactions between these two drugs on the cardiovascular system are largely unquantified. Cocaine has been reported to induce coronary vasoconstriction, cardiac arrhythmias and conduction delays. Anabolic steroids have been associated with cardiac hypertrophy and hypertension. Utilising both in vivo (radiotelemetry) and in vitro (isolated Langendorff-perfused heart) techniques, our aim was to determine whether anabolic steroids cause cardiac hypertrophy and alter cardiac function, and consequently alter the response of the heart to cocaine. It was found that 15 days of treatment of rats with nandrolone decanoate (20 mg/kg, s.c.) was not sufficient to cause hypertrophy, alter cardiac function or the spread of electrical activity through the heart. However, nandrolone pretreatment was found to significantly potentiate the heart rate response to cocaine (45 mg/kg, i.p.) in vivo. This study indicates that nandrolone significantly elevates the heart rate response to high dose cocaine without changing heart morphology. The mechanism of this interaction remains uncertain.

Precipitated withdrawal following codeine administration is dependent on CYP genotype.

The role of metabolic polymorphism in the development of physical dependence to codeine was assessed in cytochrome P450 2D2 (CYP2D2) deficient Dark Agouti and CYP2D2 intact Sprague-Dawley rats by assessment of the severity of naloxone precipitated withdrawal after codeine and morphine administration. Plasma morphine concentrations after codeine were significantly higher (P<0.01) in Sprague-Dawley than in Dark Agouti rats with metabolic ratios of 0.71 +/- 0.27 and 0.07 +/- 0.04, respectively. Withdrawal after codeine resulted in significantly greater hypothermia (3.5-4 degrees C, P<0.0001) in Sprague-Dawley animals compared to the other groups. Body weight loss was similar for all groups ranging from 6.2 +/- 0.4 to 8.2 +/- 0.6 g. When strain and treatment data were combined, a relationship between body temperature and plasma morphine concentration could be described by the inverse Hill equation (r(2)=0.76, EC(50)=556 +/- 121 ng/ml, n=2.9 +/- 1.5). These data indicate that dependence and withdrawal after codeine administration are dependent on its bioconversion to morphine.

Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat.

1. This study was prompted by recent deaths that have occurred after recreational administration of the substituted amphetamine para-methoxyamphetamine (PMA). Because relatively little is known regarding its mechanism(s) of action, its effects on physiological, behavioural and neurochemical parameters were compared with the well known effects of 3,4-methylenedioxymethamphetamine (MDMA). 2. Equivalent doses of PMA (5-20 mg/kg) produced greater hypothermia than MDMA at an ambient temperature of 20 degrees C. At 30 degrees C, PMA continued to evoke hypothermia except the highest dose where hyperthermia ensued. MDMA altered body temperature only at the highest dose where hyperthermia also resulted. 3. At both 20 and 30 degrees C, MDMA stimulated locomotor activity whereas PMA had modest effects and then, only at high doses. 4. In vivo chronoamperometry was used to measure the effect of MDMA and PMA on release, and inhibition of uptake, of serotonin (5-HT) and dopamine (DA) in the dorsal striatum of anaesthetised rats. As expected, MDMA evoked release of DA and inhibited uptake of both DA and 5-HT. By contrast, PMA was a relatively weak releasing agent and did not inhibit DA uptake. However, PMA potently inhibited uptake of 5-HT. 5. Taken together these data suggest that the acute adverse effects of PMA are more likely to be associated with alterations in serotonergic rather than dopaminergic neurotransmission.

Mechanisms of fatal opioid overdose.

There has been increasing recognition of the problem of fatal opioid overdose. This review examines the pharmacological basis of respiratory depression following opioid administration. Respiration is controlled principally through medullary respiratory centres with peripheral input from chemoreceptors and other sources. Opioids produce inhibition at the chemoreceptors via mu opioid receptors and in the medulla via mu and delta receptors. While there are a number of neurotransmitters mediating the control of respiration, glutamate and GABA are the major excitatory and inhibitory neurotransmitters, respectively. This explains the potential for interaction of opioids with benzodiazepines and alcohol: both benzodiazepines and alcohol facilitate the inhibitory effect of GABA at the GABAA receptor, while alcohol also decreases the excitatory effect of glutamate at NMDA receptors. Heroin and methadone are the major opioids implicated in fatal overdose. Heroin has three metabolites with opioid activity. Variation in the formation of these metabolites due to genetic factors and the use of other drugs could explain differential sensitivity to overdose. Metabolites of methadone contribute little to its action. However, variation in rate of metabolism due to genetic factors and other drugs used can modify methadone concentration and hence overdose risk. The degree of tolerance also determines risk. Tolerance to respiratory depression is less than complete, and may be slower than tolerance to euphoric and other effects. One consequence of this may be a relatively high risk of overdose among experienced opioid users. While agonist administration modifies receptor function, changes (usually in the opposite direction) also result from use of antagonists. The potential for supersensitivity to opioids following a period of administration of antagonists such as naltrexone warrants further investigation. While our understanding of the pharmacological basis of opioid-related respiratory depression has advanced, better understanding of the role of heroin metabolites, the metabolism of methadone, drug interactions and tolerance would all be of considerable value in knowing how best to respond to this problem.

The influence of restraint on blood pressure in the rat.

We examined the influence of procedures used in blood pressure measurement on blood pressure and the effects of antihypertensive agents. Subjects were spontaneously hypertensive rats (SHR) and their Wistar/Kyoto (WKY) controls. Blood pressure was recorded by telemetry. Twenty-four h baseline pressure were measured, and the effect of minor handling on blood pressure and heart rate was examined. The influence of restraint such as is used for tail-cuff blood pressures was examined. The effects of three different antihypertensive drugs was also examined in the SHR. In the home-cage environment, the SHRs showed higher systolic blood pressures, but had similar hypertensive responses to minor handling as the WKYs. Both strains had elevated heart rate and blood pressure when restrained in the manner used for tail-cuff readings. The antihypertensive effects of captopril and losartan in the SHR were unchanged when the animals were restrained but the hypotensive effect of hydralazine was greater. These results confirm that significant changes in heart rate and blood pressure can occur as a result of the minor procedures frequently used in blood pressure recording in both SHR and WKY rats. This suggests that telemetry may have significant advantages as a method for continuous blood pressure monitoring. The pharmacological profile of antihypertensive drugs may well be different in animals where telemetry is employed and are not subject to the stresses involved in previous methods of monitoring blood pressure.

Mu receptor binding of some commonly used opioids and their metabolites.

The binding affinity to the mu receptor of some opioids chemically related to morphine and some of their metabolites was examined in rat brain homogenates with 3H-DAMGO. The chemical group at position 6 of the molecule had little effect on binding (e.g. morphine-6-glucuronide Ki = 0.6 nM; morphine = 1.2 nM). Decreasing the length of the alkyl group at position 3 decreased the Ki values (morphine less than codeine less than ethylmorphine less than pholcodine). Analgesics with high clinical potency containing a methoxyl group at position 3 (e.g. hydrocodone, Ki = 19.8 nM) had relatively weak receptor binding, whilst their O-demethylated metabolites (e.g. hydromorphone, Ki = 0.6 nM) had much stronger binding. Many opioids may exert their pharmacological actions predominantly through metabolites.

Morphine formation from codeine in rat brain: a possible mechanism of codeine analgesia.

The O-demethylation of codeine to morphine was demonstrated in rat brain homogenate. Maximal formation occurred at 10 minutes, with a Vmax of 5.93 +/- 0.16 nmol/g brain/h and Km of 37.82 +/- 4.99 microM. The formation was significantly (P less than 0.05) greater in the microvessel-rich brain fraction. Intraperitoneal injection of codeine in the rat resulted in brain concentrations of morphine which could not be solely attributed to transfer of morphine from the blood stream across the blood-brain barrier. Morphine formed in the brain after codeine administration may be an important mechanism for codeine-induced analgesia.

The renin angiotensin system and nociception in spontaneously hypertensive rats.

This study investigated the effects of captopril, hydralazine and losartan on the locomotor activity, tailflick and hot plate latencies in spontaneously hypertensive rats (SHR) and their genetic controls the Wistar-Kyoto rat (WKY). The increased hot plate latencies normally exhibited by the spontaneously hypertensive rat were reduced or abolished by captopril (95 mg/kg/day p.o.) and losartan (18 mg/kg/day p.o.) treatment, but were unaffected by hydralazine (19 mg/kg/day p.o.). There were no observable effects of any of the drugs on tailflick latencies or locomotor activity. The results highlight a potential role for angiotensin II in analgesia that is independent of blood pressure change.

The effects of central and peripheral angiotensin on hypertension and nociception in rats.

Spontaneously hypertensive rats (SHRs) rats have been reported to have decreased sensitivity to pain, but as yet a mechanism has not been identified. This study investigated the effects of subcutaneous and intracerebroventricular (ICV) infusions of angiotensin II on blood pressure, locomotor activity, and tailflick and hot plate latencies in the Wistar-Kyoto (WKY) and outbred Wistar rat. Peripheral but not central administration of angiotensin II (567 micrograms/kg/day) increased hot plate latencies in WKY and Wistar rats to a level equivalent to that observed in the SHR. Peripheral administration of norepinephrine (50 and 100 mg/kg/day) to WKYs increased blood pressure but had no effect on hotplate latency. ICV administration of losartan (1 & 3 mg/kg/day) to SHRs had no effect on blood pressure or nociception. The results indicate that angiotensin II has a role in the altered pain perception observed in the SHR and that its site of action is peripheral.

Acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA) in Sprague-Dawley and Dark Agouti rats.

Ingestion of MDMA ("ecstasy") by humans can cause acute toxicity manifested by hyperthermia and death. Demethylenation of MDMA is catalyzed by cytochrome P-450 2D6 (CYP2D6) and cytochrome P-450 2D1 (CYP2D1) in humans and rats, respectively, and is polymorphically expressed. It has been proposed that CYP2D6 deficiency may account for the unexplained toxicity of MDMA. The female Dark Agouti rat is deficient in CYP2D1, and serves as a model for the human poor metabolizer. We investigated thermogenic and locomotor actions of MDMA in adult female Sprague-Dawley (CYP2D1 replete) and Dark Agouti rats. MDMA (2, 5, and 10 mg/kg) and saline were injected subcutaneously at ambient temperatures of 22 and 31 degrees C. There was no difference in core temperature responses between the two rat strains. Hypothermia occurred in the first 30 min and temperature elevation thereafter. MDMA increased locomotor activity in Sprague-Dawley but not in Dark Agouti rats. However, MDMA had pronounced lethal effects at 31 degrees C ambient in the Dark Agouti rats only. We conclude that the poor metaboliser phenotype may predispose to lethality, but the mechanism is as yet unknown.