PubMed HealthSearch

Biomedical subjects

A Renaud

Publications and source records attributed to A Renaud.

At least 19 recordsLinked to original sources

Effects of SDZ NVI-085, a putative subtype-selective alpha 1-agonist, on canine cataplexy, a disorder of rapid eye movement sleep.

Canine narcolepsy is an animal model of the human rapid eye movement sleep disorder. Dogs exhibit bouts of sleep attacks and muscle atonia (cataplexy) that are induced by emotions and thought to be abnormal rapid eye movement sleep episodes. We have previously demonstrated that cataplexy is strongly inhibited by increases in noradrenergic activity. This effect is mediated through central alpha 1-adrenoceptors, presumably of the alpha 1B subtype. In this study, we demonstrate with the canine model that SDZ NVI-085, a new compound with alerting effects, is a potent anticataplectic agent that may act through stimulation of an alpha 1-adrenoceptor subtype.

Adrenergic alpha-Agonists

Simple equilibrium dialysis-high-performance liquid chromatographic method for the in vitro assessment of 5-methoxypsoralen bound to human albumin.

Increasingly used in therapeutics, 5-methoxypsoralen (5-MOP), a linear furocoumarin, associated with UVA irradiation (PUVA), is now an established treatment for skin diseases such as vitiligo, mycosis funcoides and particularly psoriasis. Successful PUVA therapy depends on a sufficiently high peak 5-MOP plasma concentration coinciding with the UVA irradiation. However, as with most drugs, only the free plasma fraction is able to enter the target cells and has a pharmacological effect. In this work, the binding of 5-MOP to human albumin was studied in vitro, using a dialysis chamber. Bound and free 5-MOP fractions were quantified by a modification of Stolk's high-performance liquid chromatographic method. Dialysis was performed at 37 degrees C and pH 7.4 for 2 h, against a 4% albumin solution in phosphate buffer. The 5-MOP concentrations used were from 5 x 10(-5) to 5 x 10(-2) g/l in 1 x 10(-1) g/l steps. The 5-MOP bound strongly to human albumin in an unsaturable way. The mean 5-MOP binding to albumin was 95.3%. These results are in accordance with those published by Artuc et al. and not with those of Veronese et al., who found a lower saturable fixation (91%). These two research groups used tritiated 5-MOP. The technique used in this work is simple and inexpensive. It can be employed easily in vivo, e.g., for the assessment of 5-MOP free fractions in different therapeutic conditions.

5-Methoxypsoralen

Effects of sleep disturbances on subsequent physical performance.

The purpose of the study was to compare the cardiovascular, respiratory and metabolic responses to exercise of highly endurance trained subjects after 3 different nights i.e. a baseline night, a partial sleep deprivation of 3 h in the middle of the night and a 0.25-mg triazolam-induced sleep. Sleep-waking chronobiology and endurance performance capacity were taken into account in the choice of the subjects. Seven subjects exercised on a cycle ergometer for a 10-min warm-up, then for 20 min at a steady exercise intensity (equal to the intensity corresponding to 75% of the predetermined maximal oxygen consumption) followed by an increased intensity until exhaustion. The night with 3 h sleep loss was accompanied by a greater number of periods of wakefulness (P less than 0.01) and fewer periods of stage 2 sleep (P less than 0.05) compared with the results recorded during the baseline night. Triazolam-induced sleep led to an increase in stage 2 sleep (P less than 0.05), a decrease in wakefulness (P less than 0.05) and in stage 3 sleep (P less than 0.05). After partial sleep deprivation, there were statistically significant increases in heart rate (P less than 0.05) and ventilation (P less than 0.05) at submaximal exercise compared with results obtained after the baseline night. Both variables were also significantly enhanced at maximal exercise, while the peak oxygen consumption (VO2) dropped (P less than 0.05) even though the maximal sustained exercise intensity was not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Narcolepsy].

Explore the source record for details and available documents.

Animals

[Sleep].

Explore the source record for details and available documents.

Humans

Chronopharmacokinetics of 5-methoxypsoralen.

Diurnal variations in drug pharmacokinetics are a well known phenomenon. Chronopharmacology studies now appear to be attracting increasing interest with a view to establishing an optimum therapeutic prescription. In order to determine possible chronobiological variations of 5-methoxypsoralen (5-MOP) pharmacokinetic, 5-MOP blood concentrations were quantified in 8 healthy subjects after drug ingestion at different times during the day. Stolk's High Performance Liquid Chromatography technique was used to assess the 5-MOP serum concentrations. Each subject underwent three pharmacokinetic studies after oral ingestion of 5-MOP (1.2 mg/kg), in conjunction with a standardized low-lipid meal. The first pharmacokinetic study was started in the morning, the second in the afternoon and the third in the evening. Drug intake was at intervals of 2 days, to avoid drug accumulation. The results showed that the evening intake of the drug induced a higher 5-MOP maximum concentration and a higher 'area under curve' than morning or afternoon ingestion. This study suggests an optimized PUVA therapy, when performed in the evening.

5-Methoxypsoralen

[Disturbance of sports performance after partial sleep deprivation].

The changes in cardiac and ventilatory responses were measured in 7 endurance athletes during physical exercise on a bicycle ergometer, taking place after a control night and after a night with partial sleep deprivation in the middle of the night. The results show that, despite the maximal work load was not modified with control, heart rate, ventilation and VE/VO2 ratio (ERO2) were greater at the submaximal (75% of the VO2 max) and maximal work load and oxygen consumption decreased at maximal work, after the night of partial sleep deprivation as compared to the control. These findings suggest that acute sleep loss may contribute to alter the endurance performance by impairment of aerobic pathways.

Adult

Evaluation of the effect of heparin and tetracycline on the cohesion of the dermal-epidermal junction.

In an attempt to demonstrate the effect of tetracycline or heparin therapy on the dermo-epidermal junction, the suction blister time was measured at the beginning and at the end of the study in 18 female Sprague-Dawley hairless rats, using the suction blister method. Suction blister time was defined as the time taken for the first sign of a vesicle to appear in the hole in the diaphragm of a suction chamber. 200 IU heparinate calcium was administered daily for 6 days in 6 rats. Six other rats received 27.5 mg tetracycline chlorhydrate daily for 6 days. The others did not receive any drug. Significant statistical differences in suction blister time before and after administration of the drugs were found in the heparin group (p less than 0.05), and in the tetracycline group (p less than 0.05), compared with the control group. Heparin and tetracycline were found to increase suction blister time significantly. These results suggest an increased cohesion in the dermo-epidermal junction due to heparin and tetracycline.

Animals

[Dobutamine during anesthesia of patients at risk for heart failure. A controlled prospective multicenter study of 93 surgical patients over 64 years of age].

Most anaesthetic agents cause cardiac depression possibly hazardous in the elderly, especially in presence of a poor cardiac reserve. Ninety-three patients undergoing non cardiac surgery lasting more than 90 min. were entered in a double-blind multicentre randomized trial. They were 65 year old or more and unaffected by evolutive angina pectoris. After insertion of a Swan Ganz catheter and an arterial cannula, anaesthesia was induced by thiopentone, fentanyl and 02/nitrous oxide (50%). Forty-five patients were infused dobutamine 7 micrograms.kg-1.min-1 (group D) from 10 min. after induction till the completion of surgery. Forty-eight patients received a placebo (group P). Haemodynamic parameters were recorded throughout anaesthesia and at its emergence. After induction, heart rate, pulmonary capillary wedge pressure and mean pulmonary artery pressure did not change significantly; mean arterial pressure, cardiac index, stroke index and left ventricular stroke work index decreased by 21, 33, 28 and 42% respectively (p less than 0.001); systemic and pulmonary arterial resistances increased by 12 and 37% respectively (p less than 0.001). In group P, these changes persisted throughout the procedure but, 30 min after extubation, cardiac index returned to control levels due to a 25% increase in heart rate; in this group 4 patients presented with both perioperative low cardiac output and persistent postoperative confusion. With dobutamine, haemodynamic parameters returned to preoperative values and heart rate increased by 12 b.min-1. More arrhythmias and hypertensive episodes but less hypotensions occurred in group D. Substantial haemodynamic changes occur during anaesthesia and surgery in elderly patients. Dobutamine corrects the peroperative decrease in cardiac output and blood pressure, and might prevent postoperative neurological disorders.

Aged