DHA-enriched phospholipid diets modulate age-related alterations in rat hippocampus.

Our previous work on rat hippocampus showed that a loss of docosahexaenoic acid (DHA) occurs in the fatty acid composition of phosphatidylethanolamine (PE), plasmenylethanolamine (PmE) and phosphatidylserine (PS) with increasing age. The present study investigated whether a DHA-enriched phospholipid dietary supplement could restore DHA levels and cholinergic activity. Male rats were fed a balanced diet containing both linoleic and alpha-linolenic acids until the age of 2, 18 and 21 months. From 18 to 21 months, one subgroup received a diet supplemented with DHA-enriched phospholipids from egg yolk (E-PL), and another a diet with DHA-enriched phospholipids from pig brain (B-PL). Compared to the control diet, the E-PL diet restored the proportion of polyunsaturated fatty acids (PUFAs: 22:6n-3 and 20:4n-6) in PE and PmE, while enhancing spontaneous and evoked-acetylcholine (Ach) release. The B-PL diet had no effect on PUFAs, but increased basal extracellular levels of Ach in 21-month-old rats as compared to the age-matched control. Our results show that supplementation with DHA-enriched egg PL can enhance Ach release and correct PUFA composition.

Effects of inhaled salbutamol in exercising non-asthmatic athletes.

BACKGROUND: Beta-2 agonists such as salbutamol are used, not only by asthmatic athletes to prevent exercise induced asthma, but also by non-asthmatic athletes as a potentially ergogenic agent. We have investigated whether inhaled salbutamol enhances endurance performance in non-asthmatic athletes. METHODS: A prospective double blind, randomised, three way crossover design was used to study the effects of 200 microg and 800 microg inhaled salbutamol versus a placebo in 12 trained triathletes. The treatments were compared in three identical cycle ergometer sessions at 85% of the predetermined maximal oxygen uptake. Lung function, endurance time, metabolic parameters (glucose, potassium, lactate, free fatty acid, and glycerol), and psychomotor performance were evaluated. RESULTS: Neither endurance time nor post-exercise bronchodilation were significantly different between the treatments. Metabolic parameters were affected by exercise but not by treatment. CONCLUSIONS: Inhaled salbutamol, even in a high dose, did not have a significant effect on endurance performance in non-asthmatic athletes, although the bronchodilating effect of the drug at the beginning of exercise may have improved respiratory adaptation. Our results do not preclude an ergogenic effect of beta2 agonists given by other routes or for a longer period.

[Benzodiazepines and pregnancy]. / Benzodiazépines et grossesse.

The use of benzodiazepines is not negligible in pregnant woman and self-medication is considerable. To investigate the effects on the fetus of benzodiazepines used during pregnancy, we reviewed animal and clinical studies completed with observations of CRPV (Centres Régionaux de Pharmacovigilance). Pooled results indicate that the risk of malformations associated with first-trimester exposure to benzodiazepines remains small. However, in a fetus exposed essentially to long-acting benzodiazepines on a long-term basis, neonatal hypotonicity, failure to feed and/or withdrawal syndrom could be observed.

[Attitude of the clinican toward adverse effects of protease inhibitors]. / Attitude du clinicien face aux effets indésirables des inhibiteurs des protéases.

Since 1996, marketing of new drugs called protease inhibitors has revolutionized the treatment of patients suffering from AIDS. The side-effects of this new therapeutic family are quite well known but we wanted to evaluate the attitude of the clinician: can these adverse effects be corrected by symptomatic treatment, do they regress spontaneously or do they lead to an alternative PI therapy? We therefore carried out a retrospective survey in the Infectious Diseases Department of Poitiers Hospital consisting in research on files of patients (n = 70) treated in this department (hospitalization and consultation) for any clinical or biological abnormality attributable to the PI. For each drug we determined what sort of side-effects could be found and the position adopted by the clinician. For 30 patients the PI was stopped and for 21 of these cases because of drug toxicity (gastrointestinal, neurological, renal and metabolic effects). The biological anomalies are quite well tolerated and regress spontaneously in most cases.

[Chronic lead poisoning in children today. A pathology of poverty and social exclusion]. / Le saturnisme chronique chez l'enfant aujourd'hui. Une pathologie de la pauvreté et de l'exclusion.

Despite the recognition of lead poisoning in children as a major public health problem in France since the 1980's, the setting-up of systematic detection of lead poisoning at a national level has not yet been done. The main source of intoxication in children is in paintings containing ceruse in housing built before 1948. Moderate chronic poisoning, although leading to irreversible lesions, particularly of the central nervous system, remains usually unnoticed. The biological diagnosis is mainly based upon blood lead level, completed by the protoporphyrine-zinc level. Large scale identification of dangerous housing and the control of rehabilitation are the only means available to decrease the incidence of lead posioning. Targeted screening is difficult because it concerns children excluded from classical health care systems. Prevention and long-term treatment requires elimination of the source of lead intoxication after an environmental inquiry. This raises the problems of rehousing and follow-up of intoxicated children.

[Prospective study on admissions for iatrogenic adverse effects in the emergency service of hospital university center in Poitiers]. / Enquête prospective sur les admissions pour iatrogénie médicamenteuse dans le service d'accueil des urgences du centre hospitalier universitaire de Poitiers.

Hospital admissions resulting from an adverse drug reaction have been studied in the emergency unit of the university hospital in Poitiers during a 27-day period. This prospective study consisted in documenting all observations considered as an ADR by the medical practitioner in charge of the patient. There were 1235 hospital admissions to the emergency unit during the study period. Thirty-one (2.5 per cent) of admissions were considered to be drug-related. Women were more often affected than men. Patients with ADR were classified taking into account the type of pathology and the drug responsible for the effect. Dermatological and gastrointestinal reactions were predominant. Antibiotic and analgesic drugs were the most common drug groups implicated in causing an ADR.

[Study of voluntary drug intoxication in an emergency unit]. / Etude des intoxications médicamenteuses volontaires reçues dans une unité d'accueil des urgences.

Voluntary drug intoxications are not systematically recorded. Main aspects of this important problem have been studied in the unit responsible for medico-psychological emergencies in the university hospital of Poitiers. Files of all patients admitted to the unit from January to December 1994 have been analysed and 598 patients were included in our study. Of these, 67 per cent were females. 31 per cent were 20 to 29 years old and for the most part unemployed (62.5 per cent). Drugs most commonly used are benzodiazepines (39 per cent), alone or often associated with alcohol (33 per cent). A fatal outcome was observed in one patient. In many cases (50 per cent) this was not the first episode of voluntary intoxication; 53 per cent of the patients were discharged from hospital after a psychiatric consultation. For many years, voluntary drug intoxication frequency has increased continually. All cases have a specific intention that we have to clarify in order to take effective preventive measures to prevent recidivism.

The effects of 600 mg of slow release caffeine on mood and alertness.

BACKGROUND: Caffeine is the most widely used psychostimulant. PURPOSE: This study evaluated the pharmacokinetics and effects of mood and alertness of a single oral administration of 600 mg of a slow release caffeine (SRC) on a large group of healthy subjects. METHOD: In this double-blind, parallel-group study, 120 young adult males were randomly assigned to either a caffeine group (CG, n = 100) or a placebo group (PC, n = 20). After a normal sleep, each subject took 600 mg of a SRC or a placebo. Circulating caffeine was determined by salivary caffeine assays after acetylation phenotype categorization. Mood, alertness and nocturnal sleep were evaluated by visual analog scales (VAS). RESULTS: This SRC was well tolerated probably due to its relative low plasmatic Cmax (10.37 micrograms.ml-1). Between CG and PG, there were no differences for alertness, contentedness and sleep quality of the night after treatment (N2) compared to the previous night (N1). VAS scores showed a decrease in calmness in the CG (p < 0.01). Sleep latency in N2 was significantly increased with caffeine (p < 0.01). Calmness, sleep onset latency, quality of sleep onset and overall rating of N2 compared to N1 were correlated with caffeine levels, which were only influenced by tobacco consumption. CONCLUSIONS: Although a single oral dose of 600 mg of a SRC is well tolerated, further evaluation must be done on alertness and pharmacokinetics with fatigued subjects and with females using oral contraceptives.

Non-steroidal anti-inflammatory drugs and variceal bleeding: a case-control study.

BACKGROUND/AIM: The aim of this case-control study was to assess the risk of bleeding from esophageal varices associated with aspirin and non-steroidal anti-inflammatory drug consumption. METHODS: Between January 1992 and May 1994, patients admitted for bleeding from esophageal or gastric lesions related to portal hypertension were matched with a control patient of the same age and sex, who was free of gastrointestinal bleeding. A structured interview was conducted with the cases and controls to determine drug consumption during the 2 weeks preceding admission. Fifty-nine cases and 59 controls were recruited. RESULTS/CONCLUSIONS: Use of aspirin was more prevalent among the cases than the controls (odds ratio 3.81; 95% confidence interval 1.36-11.64; p = 0.004). This difference remained significant in the subgroups of patients with a first episode of variceal bleeding (odds ratio 3.9; 95% confidence interval 1.2-13.9, p = 0.01), but was not significant in the subgroups of patients with a recurrent episode of variceal bleeding. The use of aspirin was associated with a high risk of a first episode of variceal bleeding, suggesting that patients with portal hypertension should avoid taking these drugs.

[Follow-up of antidepressive therapy in psychiatric clinical practice]. / Le suivi thérapeutique des antidépresseurs en pratique clinique psychiatrique.

The therapeutic drug monitoring of antidepressant drugs is of interest to adapt dosage regimens to reduce the number of non-responder patients, to reduce drug side effects and to detect non-compliant patients. A therapeutic range is defined for many of these drugs and their linear or non-linear kinetics are important parameters in clinical practice to define the posology. Some patients, because of when there is drug biotransformation polymorphism, are exposed to drug accumulation a deficit in isoenzymes of cytochrome P450. The existence of these isoenzymes explains the possibility of non-linear kinetics and drug interactions.

[Cytochrome p450 IID6, its role in psychopharmacology]. / Le cytochrome P450 IID6, son rôle en psychopharmacologie.

Cytochrome P450 IID6 has got typical features (genetical polymorphism, competitive inhibition, saturability) which can be at the origin of pharmacokinetic modifications of molecules using it for their metabolism. In the field of pharmacology, many molecules are substrates or inhibitors of this cytochrome. They are presented. The results of a study of the dextromethorphan variation test performed before and after 28 days of clomipramine therapy with depressed patients are explained. They show a significant decreasing of the cytochrome P450 IID6 oxidation capacities between both of these times. A patient has passed from the phenotype "effective metabolizer" to the one of "poor metabolizer" with clomipramine.

Lack of interaction between a new antihistamine, mizolastine, and lorazepam on psychomotor performance and memory in healthy volunteers.

1. The possible interaction between a new H1 antihistamine, mizolastine, and lorazepam was assessed in a randomised, double-blind, cross-over, placebo-controlled study involving 16 healthy young male volunteers who received mizolastine 10 mg or placebo once daily for 8 days with a 1 week wash-out interval. The interaction of mizolastine, at steady-state, with a single oral dose of lorazepam or placebo was assessed on days 6 or 8 of each treatment period. 2. Psychomotor performance and cognitive function were evaluated using objective tests (critical flicker fusion threshold, choice reaction time, tapping, arithmetic calculation, body sway) and self-ratings (visual analogue scale, ARCI) before and at 2, 4, 6 and 8 h after dosing. Short-term memory (Sternberg memory scanning immediate free recall of a word list) and long-term memory (delayed free recall and recognition of words and pictures) were assessed before and at 3 h after dosing. Pharmacodynamic interactions were evaluated by repeated measures ANOVA in a 2 x 2 factorial interaction model. 3. Mizolastine, 10 mg once daily, at steady-state, was devoid of sedation and detrimental effect on skilled performance and memory. 4. In contrast, a single 2 mg dose of lorazepam produced marked impairment of psychomotor performance, cognitive functions (significant reduction in flicker fusion threshold, tapping and arithmetic calculation and increase in reaction times and body sway) and subjective sedation from 2 to 8 h after dosing. In addition, lorazepam induced an anterograde amnesia, characterised by a decrease in delayed free recall and recognition, and a deficit in short term memory.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of the interaction between a partial agonist and a full agonist of benzodiazepine receptors, based on psychomotor performance and memory, in healthy volunteers.

Potential interactions between the imidazopyridine anxiolytic alpidem and the full benzodiazepine agonist lorazepam were assessed in a randomized, double-blind, four-way cross-over, placebo-controlled study in 16 healthy young male volunteers. Each volunteer received alpidem, 50 mg, or a placebo twice daily for 8 days with a 1- week wash-out interval. The interaction between alpidem, at the steady state, and a single oral dose of lorazepam 2 mg or a placebo was assessed after concomitant administration on days 7 or 9 of each treatment period. Psycho motor performance and cognitive function were evaluated before and 2, 4, 6 and 8 h post-dose, using objective tests [critical flicker fusion threshold (CFF), choice reaction time (CRT), digit-symbol substitution (DSST), body sway and short-term memory (Sternberg memory scanning)] and self-ratings [line analogue rating scales: (LARS)]. Long-term memory (delayed free recall and recognition of pictures) was assessed before the dose and 2 and 4 h post-dose. Pharmacodynamic interactions were evaluated by applying repeated measures ANOVA to a 2 x 2 factorial interaction model. Alpidem, 50 mg twice daily at the steady state, was free of any clinically relevant detrimental effects on skilled performance, information processing or memory. In contrast, a single 2 mg dose of lorazepam induced marked impairment of psychomotor performance and cognitive function (significant reductions in CFF and DSST and increases in CRT and body sway), as well as subjective sedation from 2 to 8 h post-dose, depending on the test used. In addition, lorazepam induced anterograde amnesia, characterized by a decrease in delayed free recall and recognition, and a deficit in short-term memory. Finally, alpidem 50 mg did not potentiate the detrimental effects of lorazepam 2 mg. On the contrary, alpidem significantly antagonized the lorazepam-induced CRT increase and anterograde amnesia, and produced similar trends on most of the other cognitive parameters; thus, the results obtained with the combination of alpidem and lorazepam consistently indicated less impairment than those measured after lorazepam alone. These results are consistent with the suggested partial agonsist properties of alpidem at the benzodiazepine receptor and indicate that such properties can be assessed in humans based on antagonism of the effects of a full agonist.

[A case of metabolic interaction: amitriptyline, fluoxetine, antitubercular agents]. / Un cas d'interaction métabolique: amitriptyline, fluoxétine, antituberculeux.

Polytherapy is often used in clinical practice. The drug associations may lead to pharmacokinetic and/or pharmacodynamic interactions, with clinical implications. The authors reported a quantified illustration of 2 types of interactions in a depressed patient: between antidepressants, amitriptyline and fluoxetine, between these antidepressants and antituberculosis. Firstly, when fluoxetine was added to amitriptyline, it was observed, as expected, an increase of the tricyclic and its metabolite plasma levels, despite a decrease of its dosage. Secondly, when antituberculosis were added to the 2 antidepressants, it was observed a decrease of the tricyclic drug plasma levels. These levels remained below the therapeutic window even when the tricyclic antidepressant dosage was increased. It seems that the fluoxetine interaction disappeared. The competition between the inhibitory effect of fluoxetine and the induction of rifampicin, on the metabolism of amitriptyline is discussed.