The Anguilla spp. migration problem: 40 million years of evolution and two millennia of speculation.

Anguillid eels Anguilla spp. evolved between 20 and 40 million years ago and possess a number of remarkable migratory traits that have fascinated scientists for millennia. Despite centuries of effort, the spawning areas and migrations are known only for a few species. Even for these species, information on migratory behaviour is remarkably sketchy. The latest knowledge on the requirements for successful migration and field data on the migrations of adults and larvae are presented, how experiments on swimming efficiency have progressed the understanding of migration are highlighted and the challenges of swimming at depth considered. The decline of Anguilla spp. across the world is an ongoing concern for fisheries and environmental managers. New developments in the knowledge of eel migration will, in addition to solving a centuries old mystery, probably help to identify how this decline might be halted or even reversed.

[Experience with an automated dispensing system in department of pharmacy]. / Automatisation de la dispensation nominative au sein d'une pharmacie à usage intérieur. Expérience du centre hospitalier Le Vinatier.

Nominative drug dispensation significantly reduces the incidence of medication errors. Computerized automated unit dose drug distribution system could be a safest hospital drug distribution system and allows an improvement of drug distribution in clinical ward. In 2005, at the Vinatier Hospital, an automated ward dispensing device was acquired. This report describes the implementation of this system and the experience of the pharmacy department. The implementation of an automated unit dose system includes expanding computerized order entry system, physicians' training and nurses to use the software, pharmaceutic staff's training to use the new dispensing system and setting under quality assurance the dispensation process.

Fish as a model in investigations about the relationship between oxygen consumption and hydroxyl radical production in permeabilized muscle fibers.

Mitochondrion is the main production site for reactive oxygen species (ROS). In endotherms, the existence of a positive relationship between ROS production and metabolic rate is acknowledged. But, little is known about ectotherms, especially fish, with a metabolic rate dependent on the environmental temperature. The maximal oxygen consumption and the production of highly reactive hydroxyl radicals by permeabilized red muscles of yellow and silver eels and trouts were measured concomitantly and compared to those of rats chosen for their comparable body mass, but different metabolic rate. The positive correlation found in fish between the metabolic rate and the ROS production showed a shift with respect to mammals.

Sex-related differences in aerobic capacities and reactive oxygen species metabolism in the silver eel.

Silver European eels (Anguilla anguilla L.) need to develop important aerobic capacities to cope with their long fasting spawning migration at depth, particularly males which are about half the size of females. Moreover, they have to face potential oxidative stress because reactive oxygen species (ROS) production is linked to the increase in metabolic rate. Thus, aerobic metabolism was globally evaluated in male and female silver eels exposed to a 10.1 MPa hydrostatic pressure (1,000 m depth). Oxygen consumption (MO(2)), ROS production and antioxidant enzyme activities were measured in the muscle fibres. Males showed a trend in both higher rate of aerobic metabolism and ROS production than females. After pressure exposure, ROS production was inversely correlated to metabolic rate only in males. By facilitating MO(2) rise with no harmful effects by ROS, the supposed enhanced aerobic capacities of males could speed up the sustained swimming. In females, the tendency to lower metabolic rate and higher catalase activity would make them less vulnerable to ROS effects. These results are in agreement with the hypothesis for different migration depths between genders.

High hydrostatic pressure improves the swimming efficiency of European migrating silver eel.

To reproduce, European eels must undergo a long migration without feeding. During this migration they have to cope with many environmental factor changes, one of them being hydrostatic pressure. We focus on the effects of hydrostatic pressure on swimming energetics: does the pressure exposure modify swimming efficiency? By using a specially designed Blazka type swimming tunnel able to work under pressure, we have measured oxygen consumption of migrating male silver eels at different swimming speeds (from 0.2 to 1.0 BL/s) first at atmospheric pressure then at 101 ATA hydrostatic pressure. The results show that pressure increases the energetic swimming efficiency by decreasing oxygen consumption for a given swimming speed. Such a pressure effect could represent a remarkable adaptation enabling eels to spare their energy stores and swim for a long time.

Pressure and temperature interactions on aerobic metabolism of migrating European silver eel.

During their migration for reproduction, European eels have to cope with many environmental factors changes. The main changes concern hydrostatic pressure and temperature that are important environmental and physiological factors when considering life in the deep sea. We focus on the consequences of pressure (from 0.1 to 12.1MPa by 1MPa steps) and temperature (9, 15, 22 degrees C) shifts on the oxygen consumption (MO(2)) at the whole animal level. Because of their morphological differences, we are also interested in males and females to evaluate the best conditions for migration. Firstly, whatever temperature, males present higher aerobic capacities than females at atmospheric pressure. Secondly, an increase in temperature increases the pressure effects in males (synergy) but decreases them in females (opposite effects). We raise the hypothesis that two different migration strategies could be used in the water column in order to reach the breeding area: males could tend to privilege pressure and cold waters (deep water) and females, on the other hand, could opt for warmer temperature surface waters.

Pressure and temperature interactions on aerobic metabolism in migrating silver eels: results in vitro.

The European eel (Anguilla anguilla) migrates (6000 km) from European coast towards the supposed spawning area: the Sargasso Sea. This intensive and sustained swimming activity is performed without feeding and by using essentially red muscle i.e. aerobic metabolism. Temperature and hydrostatic pressure vary during migration and have known effects on energy metabolism, mainly on mitochondrial functioning. We raise the question about the existence of a pressure-temperature combination that optimizes energy metabolism. We have measured the maximal oxygen consumption (MO2) of red muscle fibres of silver eel (migrating stage) in a temperature range (5 to 25 degrees C) covering what can be reasonably expected during the migration. We have combined (random order) three temperatures (5, 15, 25 degrees C) with 5 different pressures steps from 0.1 to 10.1 MPa (corresponding to depths from surface to 1000 m). The results show that when an adequate temperature is chosen as a reference, pressure effects and pressure sensitivity depend on the temperature. Based on the fact that energy budget is limited in migrating eels, we consider that the best conditions are low temperature and high pressure.

Does hydrostatic pressure have an effect on reactive oxygen species in the eel?

Eels are submitted to hydrostatic pressure (HP) during their spawning migration (about 6000 Km). Before migration, they change from the yellow to the silver stage (silvering process). The effects of HP in relation to the silvering process have been studied on aerobic metabolism and more precisely on reactive oxygen species (ROS) metabolism. HP acclimatization of yellow eels improves oxidative phosphorylation together with supposed concomitant changes in electron leak and ROS production. Therefore hydroxyl radical (OH*) production, superoxyde dismutase and catalase activities, malondialdehyde content and in parallel oxygen consumption were measured in the red muscle of long-term pressure exposed and control group yellow and silver eels. At atmospheric pressure, yellow eels exhibited significantly higher oxygen consumption and OH* production than silver eels; and significantly lower malondialdehyde content. This could be due to the increase in membrane fluidity induced by the silvering process. Long-term HP exposure decreases yellow eel oxygen consumption which becomes similar to that of the silver stage. In parallel there is a decrease in OH* production and concomitantly antioxidant enzyme activities follow the same tendency. Thus the respiratory chain improvement in pressure acclimatized yellow eels is accompanied by a ROS production decrease which could mean an electron leak decrease.

A comparative study of reactive oxygen species in red muscle: pressure effects.

In ectotherms as well as in endotherms, the mitochondrial respiratory chain is the major source of reactive oxygen species (ROS) including the highly reactive, hydroxyl radical (OH*). It is known that the different steps involved in ROS production and the antioxidant systems are comparable in ectotherms and endotherms. But regulatory mechanisms in ROS production are less known especially in fish submitted to environmental changes. Firstly, we performed a ROS muscle metabolism interspecies study, using trout and eels as ectotherms and rats as endotherms, measuring OH* production, superoxide dismutase and catalase activities and in parallel oxygen consumption (MO2). Secondly, we studied the effects of an environmental factor (hydrostatic pressure) on ROS metabolism in both fish species. The results show that, at atmospheric pressure, fish have a higher OH*/MO2 ratio than rats which exhibit a higher superoxide dismutase activity. In fish exposed to hydrostatic pressure, this ratio is reversed so that for the same MO2 value, fish produce less OH* under hydrostatic pressure than at atmospheric pressure.

Hydrostatic pressure effects on eel mitochondrial functioning and membrane fluidity.

Aerobic metabolism which is required for long swimming activities during the eel's spawning migration at depth, is a potential target for pressure effects due to its components located in the inner mitochondrial membrane (respiratory chain and oxidative phosphorylation). Previous studies have evidenced that eels are able to acclimatize to pressure through membrane fluidity adjustment. However these studies were performed on the premigratory stage (yellow stage), which never encounters high pressure. Metamorphosis (silvering) seems to preadapt eels (at the silver stage) to most of the environmental changes they will encounter during migration. Is it also true for pressure resistance? This study shows that yellow eels exhibit a higher pressure sensitivity than silver eels (compression effects). The acclimatization period (21 days at 10.1 MPa) cancels the differences in pressure sensitivity and in aerobic metabolism observed at 0.1 MPa between the two stages. The mechanisms, which take place in yellow eels during acclimatization to high pressure, appear to be already present in silver eels before pressure exposure. Indeed at 0.1 MPa, silver eels exhibit higher membrane fluidity and proportions of membrane polyunsaturated fatty acids. Metamorphosis, by improving membrane fluidity, seems to allow silver eels to cope with hydrostatic pressure without spending energy in acclimatization processes.

Lateralization of the effects of the benzodiazepine drug oxazepam on medial olivocochlear system activity in humans.

Benzodiazepines (Bzd) are known to interact with GABAergic inhibitory neurotransmission. Previous research on their effect on human auditory efferent pathways--through evoked otoacoustic emissions suppression by contralateral acoustic stimulation (CAS)--indicated a decrease in medial olivocochlear (MOC) efferent system inhibitory activity, after oral intake of oxazepam--representative of the Bzd drug class. To date, this pharmacological effect was only assessed in the right ear. Since a leftward asymmetry of Bzd receptors localization in human auditory cortex has been described recently, we explored in this study the hypothesis of an asymmetrical action of Bzd on MOC efferent functioning. The results revealed a significant difference of Bzd effect probing the right ear versus the left ear, with CAS-induced suppression being less effective in the right than left ear after oxazepam intake. This finding raises the question of possible neurochemical left-right asymmetry in the descending auditory pathways. The potential localization of this asymmetry is discussed.

Pressure and temperature interactions on cellular respiration: a review.

Thermodynamic equations show that pressure and temperature can, theoretically, act in synergy or in opposite directions depending on their respective variations. Hence, they interact to establish rates of biological processes (pressure/temperature interactions, PTI). For such studies, it is interesting to use aquatic ectotherms, in particular fish, because it is easy to submit them to temperature and/or pressure changes. This review focuses on the effects of temperature and pressure changes on the energy metabolism of fish, mitochondrial oxygen consumption and functioning, showing that the observed effects do not always match the predictions made by equations or models. Unpublished results concerning the mitochondrial function of eels acclimatised at two temperatures and two pressures show that the mitochondrial targets of pressure and temperature are probably not the same. The possible mechanisms and consequences of PTI are discussed.

Influence of benzodiazepines on auditory perception.

The aim of this study was to test for an influence of benzodiazepine (BZD) on various perceptual and/or cognitive auditory processes. Loudness, auditory selective attention, and the ability of subjects to form perceptual streams out of alternating tone sequences were tested. Nine subjects were tested before, 1, 3, 7, and 24 h after a single-dose oxazepam vs placebo administration in a crossover design. A sample of blood allows us to measure plasma oxazepam concentration. The results revealed a significant reduction in stream segregation expressed as d' scores 1 h after oxazepam intake in the test subjects. No significant change occurred across time in the same subjects when they were administrated a placebo in another session. Furthermore, oxazepam had no substantial and systematic influence either on auditory selective attention or on loudness perception. Altogether, these results suggest that the perceptual organization of sound sequences involves inhibitory neural mechanisms, which can be affected by BZDs. This outcome is consistent with existing models of auditory stream segregation and may be paralleled with earlier findings on the effect of BZDs on perceptual binding in the visual modality.

A global approach to energy metabolism in an experimental model of sepsis.

Disturbances in energy metabolism during sepsis are not clearly understood. The aim of the study was to globally assess the energy drive in septic rat myocytes, studying both glycolysis rates and mitochondrial maximal activities together, using recent in vitro techniques. Measurements were assessed before (H0) and 4 h after sepsis induction (H4). Hyperlactatemia was observed in all septic animals ([lactate] = 1.2 +/- 0.3 mmol/L at H0 versus 3.3 +/- 0.6 mmol/L at H4; p < 0.001). An enhanced glycolysis rate was observed in both aerobic ( J(A) = 7.2 +/- 0.9 at H0 versus 18.2 +/- 4.1 nmol glucose/min/g at H4; p < 0.05) and anaerobic ( J(B) = 7.5 +/- 1.2 at H0 versus 15.4 +/- 3.4 micromol glucose/min/g at H4; p < 0.05) fluxes, associated with a selective significant pyruvate-malate-dependent oxygen consumption rate decrease (V O(2)-PM = 0.144 +/- 0.008 at H0 versus 0.113 +/- 0.007 micromol O(2)/h/mg at H4; p < 0.05). This oxygen consumption decrease can be interpreted either as a complex I and/or a complex I-ubiquinone relation alteration. Our results are consistent with the hypothesis that an altered mitochondrial function during sepsis is responsible, at least in part, for hyperlactatemia, which is thus a consequence of an increased glycolysis rate.

Why can the eel, unlike the trout, migrate under pressure.

In order to elucidate the difference between pressure resistance in trout (Onchorhyncus mykiss) and eel (Anguilla anguilla), oxygen consumption of red muscle permeabilised cells and mitochondria were measured at 101 ATA hydrostatic pressure per se. Such an experiment involved the setting up of a special system allowing measurements under high pressure. The results show that hydrostatic pressure strongly alters the oxidative phosphorylation in trout but not in eel, which exhibits mitochondrial pressure resistance. It is hypothesised that the eel has a supranormal mitochondria functioning at atmospheric pressure in order to cope with the high pressure environment encountered during its migration.

In vitro reactivity of ventral aorta to acetylcholine and noradrenaline in yellow freshwater eel (Anguilla anguilla L.) acclimatized to 10.1 MPa hydrostatic pressure.

We examined in vitro vascular reactivity of eels previously acclimatized to 10.1 MPa hydrostatic pressure (HP) for 21 days. The isometric tension developed by ventral aortic rings was measured at atmospheric pressure. Dose-response curves for either acetylcholine (ACh) or noradrenaline (NA), as well as contractions evoked by 80 mM K+, were compared with time-matched experiments conducted on rings obtained from control eels. Results showed that neither the optimal tension nor the maximal force of the K+-evoked contraction were significantly modified, suggesting that acclimatization to high HP did not change the vascular smooth muscle contractile machinery. The dose-response curve to ACh was not significantly changed. Conversely, although NA always relaxed aortic rings, the response of acclimatized eels was significantly reduced over the entire range of the agonist concentration tested (10(-8) to 10(-3) M), except for the lowest one (10(-9) M). The maximal amplitude of the NA-induced relaxation was significantly reduced in aortic rings from acclimatized eels as compared with non-acclimatized samples (339.3 +/- 86.5 vs. 744.3 +/- 72.1 mg x mg(-1) dry weight, P < 0.005). Our results suggest that acclimatization to high HP could selectively alter the control of vascular tone by catecholamines.

High pressure and glycolytic flux in the freshwater Chinese crab, Eriocheir sinensis.

The hexose part of glycolysis has been studied in the freshwater Chinese crab Eriocheir sinensis exposed to high pressure (101 ATA, i.e. 1000 m depth) at 14 degrees C and in normoxic conditions. Glycolytic fluxes (from glucose, JA and from Glucose 6 Phosphate, JB) have been determined using NADH depletion during the conversion of dihydroxy acetone phosphate into alpha-glycerol phosphate. Measurements have been performed at 14 and 19 degrees C. Pressure exposure induces an increase of glycolytic flux and a decrease of the time needed for the transition from aerobic to anaerobic glycolysis. As a consequence pressure-exposed crabs have a higher potential to increase glycolytic flux than control animals at atmospheric pressure. It is concluded that high pressure known to alter numerous enzymes individually, can also modify an overall metabolic pathway.

Glycolysis in the human muscle: a new approach.

The flow response time theory allows the global assessment of a metabolic pathway. This study describes the first application of this concept to explore glycolysis on human skeletal muscle extracts. The muscle extract is used to convert glucose or glucose-6-phosphate into glycerol-phosphate through the first part of glycolysis. The functioning of the experimental model is assayed by a continuous recording of the reduced nicotinamide adenine dinucleotide decay in a spectrophotometer. This measurement method was applied to normal and pathologic human skeletal muscles. The aerobic (J(A)) and anaerobic (J(B)) fluxes and the time (t99) needed for the transition from J(A) to J(B) were measured under a wide clinical temperature range (30 degrees C to 40 degrees C). The two studied muscle types (gluteus maximus and tibialis anterior) have similar glycolytic flux values, with an identical functional modality. The thermal response of glycolysis is not linear, with a high thermal sensitivity in the hypothermic range (30 degrees C to 38 degrees C) and a thermal insensitivity in the hyperthermic range (37 degrees C to 40 degrees C). On the same type of muscle (tibialis anterior), a pathologic process can induce different variations in the glycolysis patterns, but further data are needed to clear this point. The flow response time concept allows an accurate assessment of glycolysis in the human skeletal muscle, whether normal or pathologic. This approach is interesting for evaluating the global influence of different stimulations on a metabolic pathway, such as temperature variation.

Improvement in the efficiency of oxidative phosphorylation in the freshwater eel acclimated to 10.1 MPa hydrostatic pressure.

Previous studies have suggested that the efficiency of oxidative phosphorylation in the freshwater eel (Anguilla anguilla) is increased after acclimation to high hydrostatic pressure. Analysis at atmospheric pressure of the respiratory chain complexes showed that, after 21 days at 10.1 MPa, the activity of complex II was decreased to approximately 50 % (P<0.01) of the control value and that cytochrome c oxidase (complex IV) activity was significantly increased to 149 % of the control value (P<0.05). ADP/O ratios calculated from mitochondrial respiration measurements were significantly increased after acclimation to high hydrostatic pressure (2.87 versus 2.52, P<0.001) when measured in the presence of pyruvate plus malate at atmospheric pressure. These results clearly show an increased oxidative phosphorylation efficiency in response to high-pressure acclimation.

A longitudinal study of lung impairment in patients with primary Sjögren's syndrome.

OBJECTIVE: A longitudinal evaluation of lung involvement in primary Sjögren's syndrome (SS). METHODS: Eighteen non-smoking women fulfilling the European criteria for primary SS were followed for 55 months (range 26-137 mos.). These were consecutive patients with exclusion for current smokers and patients with lung diseases. Every patient underwent clinical examination, chest radiographs and lung function tests (spirography, flow/volume loop and CO lung diffusing capacity measurements). No patient was given any immunosuppressive or mucolytic therapy. RESULTS: Cough, dyspnea on exertion and recurrent bronchitis were observed in 50, 40 and 20% of the patients respectively and their frequency did not change with time. Chest radiographs were and remained normal. At presentation, lung volumes and diffusing capacity were in the normal range, whereas expiratory flows in the small airways tended to be in the low range. With time, the peak expiratory flow (PEF) significantly increased (95.8 +/- 4.6 v 103.5 +/- 4.6, mean +/- SE, % of predicted, Wilcoxon, p < 0.05) whereas the lung transfer factor for CO (TLCO) and the transfer coefficient (KCO = TLCO/alveolar volume) decreased (92.9 +/- 4.0 v 87.0 +/- 4.0 and 89.7 +/- 2.4 v 84.2 +/- 2.6 respectively, p < 0.05 for both). The TLCO decrease, corrected for the duration of follow-up, correlated with the titers of IgA circulating immune complexes (CIC) at presentation and to a lesser extent with the occurrence of cough. CONCLUSION: During the follow-up of these primary SS patients, respiratory symptoms did not change, the recurrent respiratory infection rate was low, and no cases of pulmonary hypertension or lymphoma was observed. The diffusion capacity decrease was associated with IgA CIC titers at presentation. This impairment could contribute to dyspnea during its evolution over a lifetime but is too slight to explain the dyspnea on exertion seen in most of our patients.