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Biomedical subjects

D Lagarde

Publications and source records attributed to D Lagarde.

32 records · Page 2Linked to original sources
PubMed1995

Effects of a vigilance-enhancing drug, modafinil, on rat brain metabolism: a 2D COSY 1H-NMR study.

The effects of modafinil, a vigilance-enhancing drug, on brain metabolism were investigated directly in situ by the 2D COSY 1H-NMR spectroscopy in anesthetized rats. Modafinil (600 mg/kg, i.p.) induced significant increases in both aspartate (72% +/- 15%) and glutamate-glutamine pool (28% +/- 8%) simultaneously with increases in inositol (51% +/- 19%) and creatine-phosphocreatine pool (47% +/- 14%) in comparison with control values (P < 0.05; n = 5). These results suggest that the awakening properties of modafinil could be mediated by metabolic activation.

Animals↗
PubMed1995

Some measures to reduce effects of prolonged sleep deprivation.

Prolonged sleep deprivation is an exceptional situation, encountered in special environments such as sports, civilian and military, and which induces deficits in vigilance and performance. Among the array of measures which may be used to counteract these effects, the authors described a protocol using the combination of small naps, and administration of a pharmacological aid. A detailed description of advantages and drawbacks of each one of these measures is given, illustrated by several examples extracted from different studies. Four aspects of pharmacological aid are reviewed: the effects of amphetamines and amphetamine-like substances, caffeine, eugregoric substances, and the effect of the association small nap + eugregoric substances. The use of these various aids is discussed, and findings show that each one of them finds an application in a specific context.

Amphetamines↗
PubMed1995

Interest of modafinil, a new psychostimulant, during a sixty-hour sleep deprivation experiment.

Modafinil, a new psychostimulant, was evaluated in eight healthy volunteers subjected to 60 hours of sleep deprivation. During continued wakefulness, vigilance was evaluated by self-assessment questionnaires, analogue visual scales, multiple sleep latency tests (MSLT), sleep logs, and continuous ambulatory electroencephalographic recordings (EEG). Modafinil (200 mg) or a placebo was given every 8 hours for three days; the sessions were separated by a 15 day wash out period. Results indicated a satisfactory level of vigilance, both subjective and objective, after the administration of modafinil, characterised by the quasi total absence of microsleep episodes which gradually occurred under placebo conditions. The confirmed wakening potency of modafinil makes this substance suitable for therapeutic use in patients with sleep disorders such as Gelineau's syndrome and hypersomnia.

Adult↗
PubMed1995

[Prevalence of immediate allergy to respiratory allergens in fodder farmers in Doubs].

The Doubs is a damp, semi-mountainous fodder farming department in which occupational respiratory diseases (including asthma) are common in farmers. We studied the prevalence of IgE-mediated allergy (total IgE, Phadiatop and skin prick tests) in a group of 265 exclusive dairy farmers of both sexes of the department and in a control group of non exposed, administrative workers living in the same area. Skin prick tests were: Dermatophagoides pteronyssinus, Acarus siro, cat hair, cow danders, grass pollens, betullacea pollens (trees from the East of France), and hay extracts from the Doubs. Total IgE were higher than 180 KUI/l in 26 (9.9%) farmers and in 15 (10.5%) controls (NS). Phadiatop was positive in 41 (15.7%) farmers and in 27 (19%) controls (NS). Prevalence of positive skin prick tests (at least one) in farmers and controls was respectively 36% and 40% (NS). Farmers were more frequently sensitized to hay extracts (OR = 1.7), cow danders (OR = 1.3) and less frequently to cat hair (OR = 0.63) than controls but the differences were not statistically significant. In conclusion, this study fails to give evidence of a risk of IgE-mediated allergy to work-related and other common inhalation allergens in dairy farmers the Doubs.

Adult↗
PubMed1995

[Analgesia after surgery of the spine in adults and adolescents].

Postoperative pain after spinal surgeries is highly dependent on the number of vertebrae included in the operation and on its invasiveness, opposing two extremes, discectomies and cyphoscoliosis corrections. Opiates by intravenous route remain the reference, either continuously given in predetermined doses, or better using a patient-controlled device. Nonsteroidal and steroidal anti-inflammatory drugs are widely popular for medical approach of sciatalgia and it is quite logical to use them for reducing, even to suppress, opiates after spinal surgeries. Supported by many studies, spinal administration of analgesics (opiates, alpha 2-agonists, corticosteroids) may be of interest in pain treatment of spinal surgeries. In order to prolong locoregional analgesia, a catheter may be inserted into epidural space by caudal route or surgically, before skin closure. Morphine is the most popular agent in this indication. Also, epidural clonidine results in excellent pain relief, but is associated with hypotension and marked sedation. In discectomy, injection of dexamethasone into the operative field has been proposed. Whatever the technique used, early diagnosis of neurological complications of spinal surgery should be not ruled out by postoperative analgesia.

Adolescent↗
PubMed1994

Evaluation of drowsiness during prolonged sleep deprivation.

Prolonged sleep deprivation is a relatively frequent situation during military training or warfare. A 60-hour sleep deprivation experiment was carried out on eight healthy volunteers of the French Air Force to assess drowsiness. Parameters used to assess drowsiness were questionnaires on behavior, measurement of sleep latency (MSLT), continuous electroencephalogram recording, and number of response failures or control losses observed during repeated psychomotor tests. Results showed a gradual decrement in arousal in all subjects and for all tests. These results, consistent with the literature, confirm the emergence of drowsiness after the 24th hour of uninterrupted wakefulness. This phenomenon had an increasingly negative effect on performance due to "micro-sleep" episodes which substantially reduced psychomotor performance.

Adult↗
PubMed1994

Balanced postoperative analgesia: effect of intravenous clonidine on blood gases and pharmacokinetics of intravenous fentanyl.

Agonist interactions in antinociceptive effects between clonidine and opioids can be used to reduce opioid requirements in surgical patients. However, clonidine can cause marked sedation and associated respiratory dysfunction. Thus, the benefit of using clonidine to reduce opioid use on respiration is questionable. This double-blind randomized study compared the analgesic efficacy, arterial blood gases, and pharmacokinetics of an intravenous (IV) infusion of fentanyl 75 micrograms/h and a mixture of fentanyl 25 micrograms/h plus clonidine 0.3 micrograms.kg-1.h-1 in 32 healthy young adults after surgery for scoliosis correction. Oxygen saturation (FIO2: 0.21) and respiratory rate were monitored as well as supplemental analgesia demands (IV ketoprofen via a patient-controlled device), pain, sedation, and hemodynamics. Oxygen and naloxone (5 micrograms.kg-1.min-1) were administered, respectively, if more than three episodes of oxygen saturation less than 90% were observed within 10 min and if PaCO2 was higher than 50 mm Hg. Pain relief, sedation, and ketoprofen requirements were similar in both groups. The number of episodes of arterial desaturation less than 90% (> 20 s) was 106 for four patients in the fentanyl group (versus none in the clonidine-fentanyl group). Naloxone was required in six patients and oxygen in two patients of the fentanyl group (versus none in the group receiving clonidine). Dopamine, 10 micrograms.kg-1.min-1, was required in one patient of the clonidine-fentanyl group to correct hypotension. Mean arterial blood pressure, plasma clearance, and the elimination rate constant of fentanyl were lower in the clonidine-fentanyl group than in the fentanyl group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Behavioral effects induced by beta CCE in free or restrained rhesus monkeys (Macaca mulatta).

Behavioral effects of the IV injection of beta carboline carboxylic acid ethyl ester (beta CCE) were studied in chair-restrained rhesus monkeys and in rhesus monkeys freely moving in their cages. Observations made during the administration of increasing doses of beta CCE (0.5, 1 and 2 mg/kg) evidence behaviors reflecting a state of anxiety. The similarity of results obtained under the two experimental conditions excludes a potential effect of restraint on the behavioral expression of effects induced by the administered molecule. Convulsions observed in three subjects out of twelve should call for great caution when using this molecule.

Animals↗
PubMed1990

Electroencephalographic effects of modafinil, an alpha-1-adrenergic psychostimulant, on the sleep of rhesus monkeys.

An electroencephalographic (EEG) study on the rhesus monkey, primate model of human sleep, showed the significant wakening effect of a new psychostimulant, Modafinil. The first experiment, with single administration of three increasing doses of Modafinil (3, 6, and 12 mg/kg), was to determine the efficient threshold dose; the second experiment, with repeated administration of 22.5 mg/kg during 4 days, was to determine whether continuous wakefulness could be obtained without apparent behavioral disorders. Results of the first experiment showed a wakening effect above 6 mg/kg, but 12 mg/kg induced a sharp wakening effect with a significant decrease in all sleep stages. The second experiment induced important insomnia in all subjects for 4 days and 4 nights. No behavioral disorder was observed. Modafinil has a wakening effect at the dose of 6 mg/kg in rhesus monkeys and induces quasicontinuous wakefulness for 4 total days and nights with daily administration of 22.5 mg/kg, with no behavioral disorders. Modafinil should therefore find interesting applications in sleep disorder treatments.

Animals↗
PubMed1990

[Primates as a model for the study of sleep in man].

After demonstrating the value of the animal model for the study of sleep in man, the author successively considers, in the first part of this investigation, the main characteristics of sleep in non human primates. Circadian rhythm, EEG, neuropharmacological, neuro-anatomical and zootechnical criteria are reviewed. The second part of the investigation describes an application of the use of rhesus monkeys as model to study sleep in the pharmacology of wakefulness. Two techniques, night actography and electroencephalography, which are part of a protocol to evaluate the efficiency and innocuity of new psychostimulants are described and discussed.

Animals↗
PubMed1990

[Effects of 1,25 dihydroxyvitamin d3 on the morphology and alkaline phosphatase activity of ROS 17/2,8 osteoblastic cells: influence of time and dose].

Osteosarcoma-derived osteoblastic cells were exposed to 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) either to 0.001-1,000 nmol.l-1 for 4 days or to 10 nmol.-1 for 1-21 days. Between 0.01 and 10 nmol.l-1, a dose-dependent increase in alkaline phosphatase (AP) activity was found, which rose to a maximum level at 10 nmol.l-1 (+55%). At higher doses (100 and 1,000 nmol.l-1), 1,25(OH)2D3 induced a decrease in AP activity of 40%. After 1 day at 10 nmol.l-1 a slight increase in AP activity was noted (+20%) which augmented with the duration of exposure. This stimulatory effect was highest after 8 days (+130%). In contrast, after 15 and 21 days, AP activity decreased by 30%. Under 1,25(OH)2D3, microtubules were observed mainly in the perinuclear region.

Alkaline Phosphatase↗
PubMed1988

Construction and characterization of hybrid hepatitis B antigen particles carrying a poliovirus immunogen.

The hepatitis B surface antigen (HBsAg) has the unique property of assembling with cellular lipids into spherical or elongated particles of 22 nm diameter which are secreted by mammalian cells expressing HBsAg. We have studied the structural requirements for particle formation and secretion by creating in-phase insertions into different regions of the S gene of the hepatitis B virus, coding for HBsAg. Modified genes were integrated into an appropriate vector and expressed in mouse L cells. Various single and double inserts in the two major hydrophilic domains of HBsAg were compatible with particle synthesis and secretion. The level of secretion was influenced by the length of the insert, its primary structure, and the site of insertion into the HBsAg molecule. One of the inserted sequences was a synthetic DNA fragment encoding a continuous type 1 poliovirus neutralization epitope (the C3 epitope). Mammalian cells expressing the modified hepatitis B virus S gene secreted hybrid particles carrying the poliovirus antigen. The hybrid polio-HBsAg particles reacted with a monoclonal antibody specific for the C3 epitope and induced poliovirus neutralizing antibodies at low, but significant, titers in mice and at high titers in rabbits. However, the immune response to HBsAg was weaker to hybrid particles than to unmodified HBsAg particles. By cotransfection with two different plasmids carrying either modified or unmodified genes, we obtained phenotypically mixed particles containing both polio-HBsAg and HBsAg molecules. Inoculated into rabbits, the mixed particles induced high antibody titers against both poliovirus and HBsAg.

Amino Acid Sequence↗
PubMed1983

Long term regeneration of cis-platinum and X ray treated human tumor nodules maintained in continuous organotypic culture.

A simple method for maintaining tumor cells in continuous three-dimensional culture, derived from Wolff's organotypic technique, has been used to study the effects of cis-platinum and X rays on growth inhibition, regrowth and long term regeneration of cultures maintained in low traumatizing conditions (absence of enzymatic dissociation of the cells and the possibility of avoiding subculturing, if necessary). The tumor nodules were derived from cells of the A 549 lung carcinoma cell line. The nodules developed an alveolar structure. After 1 h treatment with 15 micrograms/ml cis-platinum the growth of the nodules was slightly inhibited during the first 10 days, and then resumed normal growth. After treatment with 100 micrograms/ml cis-platinum, growth inhibition lasted longer and regrowth was observed after about 30 days. Treatment with 300 micrograms/ml of cis-platinum induced cell necrosis and loss of alveolar structures. Forty days later, regeneration occurred; two months after the drug treatment, the reconstituted nodules could be routinely subcultured. A single 15 Gy X ray dose (inducing a 0.005% survival in A 549 monolayer cells, n = 8; D0 = 1.4 Gy; Dq = 1.48) caused an early growth inhibition of about 25%. The alveolar structures disappeared. Alveolar structures reappeared in 17% of the nodules 50 days after irradiation. A slight regrowth was observed 90 days after the irradiation. A 549 nodules supported an about 20-fold higher cis-platinum concentration than monolayer cells. An almost lethal X ray dose (15 Gy, inducing a survival of 0.005%) for monolayer cells induced a prolonged lag phase in nodules followed by a slight but regular regrowth. These results support the idea that cells maintained in three dimensional culture are more resistant to radiation and drug-induced injury than monolayer cells. The organotypic culture method may be a useful tool for determining the activity of antitumoral agents.

Adenocarcinoma↗