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Biomedical subjects

P Sebert

Publications and source records attributed to P Sebert.

At least 19 recordsLinked to original sources

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.

Adult↗

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 Unpublished results concerning the mitochondrial function of eels acclimatised at two temperatures and two pressures show that the mitochondrial targets of pressure and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.

Animals↗

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.

Acoustic Stimulation↗

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.

Animals↗

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.

Body Temperature↗

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.

Acclimatization↗

[Normal values of respiratory function tests. Safety of normalized regression equations].

A frequent question in lung function testing is the extent of the margin of error in the measurements. Is the confidence interval (CI) of the usual summary equations for reference values larger than the sum of every possible error including interindividual variations and measurement errors which come from the apparatus, the technician and the patient? The analysis of the data of several authors including our data (lung function laboratory of Brest University hospital) leads to the conclusion that the summary equations of Quanjer et al. (1993) may be used safety as the CI is larger than the sum of all errors. However, this is only true if lung function testing is performed in optimal conditions, i.e. with frequently checked and carefully calibrated apparatus used by professional technicians in cooperating patients.

Adult↗

[Medical value of a respiratory mixture of oxygen and helium (Heliox)].

Lighter and more viscous than air, the oxygen-helium mixtures (heliox), well known to respiration physiologists, are used for functional exploration in the diagnosis of airways obstructions; they are also administered to deep-sea divers. However, it is usually little known that heliox can be used as therapeutic agent in the treatment of acute respiratory distress or severe disorders of ventilation caused by obstruction (e.g. inflammation). Heliox reduces the ventilatory work and increases alveolar ventilation, thereby improving haematosis and carbon dioxide elimination. The English-speaking authors, in particular, have a large experience of oxygen-helium mixtures in the treatment of such pathologies as severe asthma, small airways obstruction, cystic fibrosis, bronchoalveolitis, post-extubation pathologies, pharyngo-laryngeal oedema and drowning. The oxygen-helium mixture, therefore, participates efficiently, simply and inaggressively in the treatment of airway obstruction and acute respiratory distress.

Adult↗

Low doses of insulin as a treatment of tardive dyskinesia: conjuncture or conjecture?

Tardive dyskinesia (TD) induced by antipsychotic drugs represents a great concern for patients and psychiatrists. Considering its pathophysiological mechanisms, there exists a convergence towards the development of postsynaptic dopaminergic hypersensitivity as a possible cause of TD. Hypersensitivity following receptor blockade is the consequence of an increased number of receptors and such a synthesis is energy-dependent. In the brain, under normal conditions, energy is almost exclusively provided by glucose utilization. We thus hypothesized that, if glucose availability were reduced, the metabolically hyperactive structures should represent the best functional target of a reduction in fuel availability. Twenty chronic schizophrenic outpatients (13 males, 7 females), aged 20-67 (mean: 38.3), accepted to participate in this double-blind, placebo-controlled study. They were randomly assigned to either the insulin treatment group (10 patients) or to the insulin-placebo group (10 patients). They received a subcutaneous injection of 10 units of standard insulin or placebo at 10 a.m. From day 1 to day 15, injections were performed daily and, thereafter, every other week for 5 weeks totalizing 20 injections in 90 days. At day 7, the insulin treatment group showed a sharp decrease in the intensity of TD symptoms which persisted throughout the duration of the study. By contrast, no change in TD symptomatology was observed in the insulin-placebo-treated group. Although a direct effect on DA neurones, or at least the participation of such an effect, cannot be excluded, our data favor a role of decreased glucose availability in reversing receptor hypersensitivity.

Adult↗

CO2 chemoreflex drive of ventilation in man: effects of hyperoxia and sex differences.

CO2 single breaths have been performed in 7 men and 7 women in conditions of normoxia (FICO2 congruent to 0.13; FIO2 congruent to 0.21; FIN2 congruent to 0.66) and of hyperoxia (FICO2 congruent to 0.13; FIO2 congruent to 0.87). Ventilatory responses of the subjects and modifications of breathing pattern in the course of the CO2 tests were also explored in the two conditions. The results (mean +/- SEM) show that, whatever the oxygenation, men and women exhibit the same ventilatory response during a CO2 test from a qualitative point of view but with a smaller intensity in women (men: 0.37 +/- 0.088 LBTPS.min-1.Torr-1; women: 0.15 +/- 0.025 LBTPS.min-1.Torr-1; p less than 0.05). Considering men and women together, CO2 tests induced an increase of minute volume VE (p less than 0.001), VT (p less than 0.01) and rate of breathing (NS) but this response is decreased in hyperoxic conditions (p less than 0.05) mainly in men (men: 0.19 +/- 0.043 LBTPS.min-1.Torr-1; women: 0.11 +/- 0.023 LBTPS.min-1.Torr-1). These results show that sensitivity to transient hypercapnia and its interaction with hyperoxia are weaker in women than in men.

Adult↗

[Abnormalities of respiratory function in civil defence firefighter-submarine divers. Respective role of diving and occupational exposure related to occupational firefighter's functions].

Lung function was studied in 20 firemen-submarine divers (mean age 36 +/- 1.2 years) of the French civil defence undergoing the medical check-up compulsory for professional divers (lung function tests are not systematically performed in ordinary firemen). Compared with the CECA standards: (1) vital capacity (VC) was increased, residual volume (RV) was decreased and total lung capacity (TLC) was unchanged; (2) with the exception of peak respiratory flow, all expiratory flow values (FEV1, MEF50, MEF25) were decreased; (3) the permeability factor (KCO) was decreased. These functional abnormalities were moderately worse in subjects who smoked. Some abnormalities (increased VC, decreased RV) are typical of diving activities, but the deterioration of effort-dependent expiratory flow values and alveolar-capillary diffusion must be ascribed to specific nuisances (fumes, polluants, toxic substances) associated with fireman's activities. Monitoring lung function in all professional firemen therefore seems to be necessary, if not indispensable.

Adult↗

Effects of long-term exposure to hydrostatic pressure per se (101 ATA) on eel metabolism.

Oxygen consumption, MO2, has been measured in yellow freshwater eels (Anguilla anguilla L.) exposed in normoxic conditions for 31 days at a hydrostatic pressure of 101 ATA (atmosphere absolute; 1 ATA = 0.1 MPa) using a high pressure water circulation system. The results (series I) show that from a maximal value observed at the end of compression, MO2 decreases exponentially with time (tau congruent to 1.4 days) then reaches a steady state (MO2 = 0.67 +/- 0.05 mmol.h-1.kg-1) at a lower level than observed at 1 ATA before compression (MO2 = 1.04 +/- 0.03 mmol.h-1.kg-1). These observations are in agreement with the hypothesis that shallow water fish are able to adapt to pressure; the possible mechanisms of this adaptation are discussed. Results from a second experimental series show that fish previously submitted to pressure for 1 month (then decompressed to 1 ATA) adjust faster to a new pressure exposure (4 days later) than fish that have never experienced pressure exposure. This observation suggests that the mechanisms triggered by long-term pressure exposure could persist, at least in part, for several days after decompression to atmospheric pressure.

Anguilla↗

[L-tyrosine: a long term treatment of Parkinson's disease].

That l-dopa represents a major advance in Parkinson treatment should not hide that a number of problems remain unanswered: on-off effects, transient improvements... Based on the beneficial effects of l-tyrosine in dopamine dependent depressions and narcolepsy, five naive patients diagnosed after sleep polygraphy criteria and five l-dopa and/or dopamine agonist treated patients were prescribed l-tyrosine as a long-term treatment. For some patients, 3 years of L-tyrosine treatment was followed by better clinical results and many fewer side effects than with L-DOPA or dopamine agonists. However, the theoretical long-term sparing neurons potentiality of approach requires further studies.

Aged↗

Effects of breathing an O2-H2 (20%-80%) mixture on the energy metabolism of the eel at 1 ATA.

The hypothesis of a specific effect of hydrogen on living organisms was investigated. Three tissues were studied: brain, muscle, and liver. Nucleotide concentrations (ATP, ADP, AMP, IMP, NAD) were determined using an HPLC method, and energy charge (EC) was calculated. These measurements were performed at atmospheric pressure for 50 or 132 h. Experiments were carried out using 15 control eels that breathed aerated water and 15 eels that breathed water saturated with oxygen (20%) and hydrogen (80%). No significant variation was found of the measured concentrations in muscle or liver, irrespective of the exposure duration to H2. In contrast, hydrogen induced in brain tissue a significant increase of AMP (p less than 0.005) and significant decreases of ATP (p less than 0.005) and EC (p less than 0.001). It should be noted that the EC decrease is already significant (p less than 0.05) after 50 h of exposure to H2. These modifications in energetic nucleotides were coupled with a small decrease of NAD (NS) in the three tissues explored. From the present results, obtained from eels at atmospheric pressure, it appeared that hydrogen could induce a perturbation of energy metabolism at the brain level. Its origin could be a partial saturation of respiratory chain carriers with exogen H2.

Adenosine Monophosphate↗

Effects of hydrostatic pressure per se (101 ATA) on energetic processes in fish.

Nucleotides concentrations (ATP, ADP, AMP) have been measured in brain and muscle of eels exposed to 101 ATA of hydrostatic pressure (HP) for 3 hr. Survival times (ST) and oxygen arterial content (CaO2) have been measured in trouts exposed to HP = 101 ATA. The results show that at HP = 101 ATA, AMP increases (P less than 0.05) and ATP decreases (-12%; NS) in muscle but are not modified in brain; ST values are similar in normoxic and hyperoxic conditions, and CaO2 are similar at 1 ATA and 101 ATA of HP. It is concluded that HP tends to decrease aerobic production of energy. This phenomenon is not due to a failure in O2 transport from ambient medium to the cell but to a possible perturbation of the aerobic cellular processes leading to energy production (Krebs cycle and/or respiratory chain coupled to oxidative phosphorylation.

Adenine Nucleotides↗

[Cardiovascular effects of salbutamol in rabbits anesthetized with sodium pentobarbital].

1) Heart rate, instantaneous carotid blood flow (electromagnetic probe) and arterial blood pressure were recorded for 60 minutes in rabbits anesthetized with sodium pentobarbital (40 mg/kg). Anesthetic induction was made one hour before starting the measurements to allow animal preparation. These measurements were performed on three experimental groups--(A) group: anesthetized animals without any treatment (control group); (A + SA) group: anesthetized animals + intravenous (I.V.) infusion of salbutamol (300 micrograms/kg); (A + SE) group : anesthetized animal + I.V. infusion of a saline solution in the same volume and time conditions than for (A + SA) group, that is to say (10 ml within 10 min): this series was conducted to explore the specific effects of hypervolemia. 2) Comparing the SE and SA groups, it appeared, within 30 to 120 seconds, that I.V. infusion of salbutamol induced a decrease in systolic and diastolic blood pressures and a significant increase in heart rate and carotid blood flow. While heart rate and blood pressures returned progressively to their control values (A group), carotid blood flow was still higher 60 minutes after starting salbutamol infusion. 3) The possible mechanisms involved in the observed cardiovascular responses to salbutamol are discussed. The predominant effect is probably the hypotension resulting from a peripheral vasodilatation by direct stimulation of beta 2-adrenergic receptors in vascular smooth muscle. The increase in heart rate and carotid blood flow may be explained by a two fold mechanisms: direct stimulation of the beta-adrenergic receptors (beta 1 and/or beta 2) and consequences of the vasodilatation.

Albuterol↗

[Changes in the respiratory function in Gougerot-Sjögren syndrome].

Tests for lung function assessment were performed in 36 subjects (34 women, 2 men; mean age 56 +/- 2.2 years) presenting with Sjögren's syndrome of 8.4 +/- 1.0 years duration. The tests used in the study were: spirography with measurement of residual volume, flow volume curve, total dynamic resistances, diffusing capacity of the lung (steady state and breath hold methods), estimation of alveolar ventilation and, in some subjects, dynamic lung compliance. Sjögren's syndrome was assessed by anatomo pathological methods and divided into primary (n = 9) and secondary (n = 27). Secondary Sjögren's syndrome (SGS II) was associated mainly with a connective tissue disease (rheumatoid arthritis in 23 cases). The results of lung function tests showed distal airway obstruction associated with a decrease in lung diffusing capacity due to functional disturbance of the alveolar capillary membrane. Moreover, the greater alteration of lung function observed in SGS II could be explained by: a direct correlation between duration of SGS and alteration of lung function, and an alteration of the parietal ventilatory mechanics, at least in subjects with rheumatoid arthritis.

Arthritis, Rheumatoid↗