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A Bousquet-Mélou

Publications and source records attributed to A Bousquet-Mélou.

16 recordsLinked to original sources
PubMed2006

Water deficit stress induces different monoterpene and sesquiterpene emission changes in Mediterranean species. Relationship between terpene emissions and plant water potential.

The effects of water deficit stress and plant water potential (psi) on monoterpene and sesquiterpene leaf emissions from Rosmarinus officinalis, Pinus halepensis, Cistus albidus and Quercus coccifera were studied over 11 days of water withholding (from t(1) to t(11)), after substrates had achieved their field capacity (control pots: t(0)). Volatile compounds were sampled from the same twig per plant all throughout the study, using a dynamic bag enclosure system. Volatiles, collected in Tenax TA, were studied by means of GC-FID and GC-MS. Monoterpene emissions of water stressed plants (t(1)-t(11)) were either similar to those of control seedlings (R. officinalis and Q. coccifera) or higher (P. halepensis and C. albidus). By contrast, sesquiterpene emissions were strongly reduced or inhibited after four days of water withholding, particularly for R. officinalis, thus altering terpene emission composition. Despite the positive effect of water stress on leaf monoterpene emissions of P. halepensis and C. albidus, the significant correlation between these emissions and psi showed a slow decrease of these emissions over long term water deficit periods. This contrasted with the rapid decline of sesquiterpene emissions of R. officinalis according to lower values of psi. These results provide an overall picture of the different responses of monoterpene and sesquiterpene emissions to progressive water loss. They also reveal the utility of using psi for estimating some emission rates of some species according to drought conditions.

Cistus↗
PubMed2004

Population pharmacokinetics of marbofloxacin in horses: preliminary analysis.

Population pharmacokinetic of marbofloxacin was investigated on 21 healthy and 16 diseased horses to assess interindividual variability of drug exposure. Demographic, physiologic and disease covariables were tested using mixed effects models. As a preliminary analysis, this study has demonstrated that none of the tested covariables were significant in regression models for compartmental volumes or clearance of distribution, but the clinical status of the horse (healthy/diseased) was a significant covariable (P < 0.01) for systemic clearance. Clearance had a lower mean and a higher variance for diseased horses than healthy horses, with respectively a mean of 0.209 and 0.284 L/h/kg and a coefficient of variation of 52 and 15%. Consequently, variability of AUC was greater in diseased horses. Considering an AUC/MIC ratio below 60 h as a prediction of poor efficacy, a dosage regimen of 2 mg/kg intravenous was deemed to be inadequate for 19% of diseased horses if the MIC of the bacteria was 0.1 microg/mL. However 93% of diseased horses could achieve a ratio above 125 h, predicting a very good efficacy, for the MIC(90) of Enterobacteriacae (0.027 microg/mL).

Animals↗
PubMed2004

Plasma terminal half-life.

Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose. When the process of absorption is not a limiting factor, half-life is a hybrid parameter controlled by plasma clearance and extent of distribution. In contrast, when the process of absorption is a limiting factor, the terminal half-life reflects rate and extent of absorption and not the elimination process (flip-flop pharmacokinetics). The terminal half-life is especially relevant to multiple dosing regimens, because it controls the degree of drug accumulation, concentration fluctuations and the time taken to reach equilibrium.

Animals↗
PubMed2004

Volumes of distribution.

Volumes of distribution are proportionality constants between total amount of drug in the body and plasma concentrations. As snapshot plasma drug concentrations may be measured in different conditions (at equilibrium, under pseudo-equilibrium condition,...), several volumes of distribution have been defined. The two most relevant are the volume of distribution at equilibrium (V(ss)), and the volume of distribution during pseudo-equilibrium (V(area)). Volumes of distribution are used to compute a loading dose (V(ss)) or the residual amount of drug in the body knowing plasma concentrations (V(area)). Volume of distribution may be interpreted in terms of drug distribution having recourse to physiological models involving drug binding to plasma and tissues. Volumes of distribution should be determined early in drug development programmes and those having a large volume of distribution may be selected to obtain a long terminal half-life even for drugs having a relatively high clearance.

Animals↗
PubMed2004

Bioavailability and its assessment.

Bioavailability is a key pharmacokinetic parameter which expresses the proportion of a drug administered by any nonvascular route that gains access to the systemic circulation. Presented in this review are the different approaches to measurement of bioavailability (absolute and relative), including the case in which intravenous administration is impossible. The rate of drug absorption is also discussed with special emphasis on the possible difficulties encountered using C(max) and T(max) or curve fitting to evaluate the rate of drug absorption.

Animals↗
PubMed2004

Plasma clearance.

Plasma (total, systemic...) clearance is determined by all the individual metabolizing/eliminating organ clearances and involves mainly liver and kidney clearances. Plasma clearance (a volume per time, i.e. a flow) expresses the overall ability of the body to eliminate a drug by scaling the drug elimination rate (amount per time) by the corresponding plasma concentration level. The interpretation of plasma clearance and inter-species comparisons are made easier by computing the overall body extraction ratio (from 0 to 1), which is the ratio of the body clearance divided by cardiac output. Plasma clearance is the most important pharmacokinetic parameter because it is the only one which controls the overall drug exposure (for a given bioavailability) and it is the parameter which allows computation of the dosage required to maintain an average steady-state plasma concentration.

Animals↗
PubMed2002

The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics.

Pharmacokinetic-pharmacodynamic (PK/PD) surrogate indices (AUIC, AUC/MIC, C(max)/MIC, T>MIC) for measuring antibiotic efficacy are presented and reviewed. As clinical trials are not sufficiently sensitive to establish a dosage regimen which guarantees total bacteriological cure (Pollyanna phenomenon), PK/PD indexes have been proposed from in vitro, ex vivo, and in vivo infection models and subsequently validated in retrospective or prospective human clinical trials. The target value for time-dependent antibiotics (beta-lactams, macrolides) is a time above the MIC (T>MIC) of 50-80% of the dosage interval, while for concentration-dependent antibiotics (quinolones and aminoglycosides), the area under the inhibitory curve (AUIC, or more simply AUC/MIC of about 125h) is the best surrogate indicator of activity. Using the latter drugs, high concentrations achieved early during therapy are desirable to prevent the development of resistance. A C(max)/MIC ratio greater than 10-12 seems to be an appropriate target for aminoglycosides.

Animals↗
PubMed2001

Licking behaviour and environmental contamination arising from pour-on ivermectin for cattle.

Pour-on formulations of endectocides are extensively used to treat and control systemic parasitic diseases in cattle, worldwide. The purpose of the present study was to investigate the influence of the natural licking behaviour of cattle on the plasma and faecal disposition of topically administered ivermectin. Twelve Holstein cattle were given one single intravenous (i.v.) (200 microg/kg) and topical (500 microg/kg) administration of ivermectin at a 5-month interval. For the pour-on administration, the animals were allocated into two groups (n=6): one control group (lickers) and one group where licking was prevented (non-lickers). Ivermectin plasma (total) clearance (270+/-57.4 ml/kg/day) was very homogeneous among the 12 cattle. In contrast, major differences between lickers and non-lickers were observed following pour-on administration. Prevention of licking resulted in an extended terminal plasma half-life (363+/-16.2 vs. 154+/-7.4 h in lickers) and in a lower and less variable systemic availability of ivermectin (19+/-4.9 vs. 33+/-18.5% in lickers). More importantly, nearly 70% of the pour-on dose was recovered as parent drug in the faeces of lickers vs. only 6.6% in non-lickers. Altogether, these results are consistent with an oral rather than percutaneous absorption of topical ivermectin in control animals, the non-systemically available fraction of ingested ivermectin providing a major contribution (80%) to the drug faecal output. The consequences of licking on the disposition of pour-on ivermectin are discussed in terms of environment, given the known ecotoxicity of this drug, and of cross-contamination. Animals licking themselves and each other could result in unexpected residues in edible tissues of untreated animals and in possible subtherapeutic drug concentrations, a factor in drug resistance. According to the Precautionary Principle, these considerations elicit concern over the use of topical drug formulations in cattle.

Administration, Topical↗
PubMed1999

Pregnancy modifies the alpha2-beta-adrenergic receptor functional balance in rabbit fat cells.

The sympathetic nervous system controls lipolysis in fat by activation of four adrenergic receptors: beta1, beta2, beta3, and alpha2. During pregnancy, maternal metabolism presents anabolic and catabolic phases, characterized by modifications of fat responsiveness to catecholamines. The contributions of the four adrenergic receptors to adipocyte responsiveness during pregnancy have never been studied. Our aim was to evaluate the influence of pregnancy on adrenergic receptor-mediated lipolysis in rabbit white adipocytes. Functional studies were performed using subtype-selective and non-selective adrenergic receptor agonists. Overall adrenergic responsiveness was measured with the physiological agonist epinephrine. Non-adrenergic agents were used to evaluate different steps of the lipolytic cascade. The alpha2- and beta1/beta2-adrenergic receptor numbers were determined with selective radioligands. Non-adrenergic agents revealed that pregnancy induced an intracytoplasmic modification of the lipolytic cascade in inguinal but not in retroperitoneal adipocytes. Pregnancy induced an increase in beta1- and specially beta3-mediated lipolysis. The amounts of adipocyte beta1/beta2- and alpha2-adrenergic receptors were increased in pregnant rabbits. Epinephrine effects revealed an increased contribution of alpha2-adrenergic receptor-mediated antilipolysis in adipocytes from pregnant rabbits. These results indicate that pregnancy regulates adipocyte responsiveness to catecholamines mainly via the alpha2- and beta3-adrenergic pathways. Pregnancy induces an intracytoplasmic modification of the lipolytic cascade, probably via hormone-sensitive lipase, with differences according to fat location.-Bousquet-Mélou, A., C. Muñoz, J. Galitzky, M. Berlan, and M. Lafontan. Pregnancy modifies the alpha2-beta-adrenergic receptor functional balance in rabbit fat cells.

Adipocytes↗
PubMed1996

Evidence for numerous brown adipocytes lacking functional beta 3-adrenoceptors in fat pads from nonhuman primates.

Brown adipose tissue (BAT) is involved in the control of energy balance and has been demonstrated to be activated through beta 3-adrenoceptor (beta 3-AR) occupation in rodents. The ability to specifically activate energy expenditure via this receptor is of great interest for the treatment of obesity. Nevertheless, the extent of BAT and the presence of a functional beta 3-AR in humans are now debated, and this situation is difficult to clarify for evident practical and ethical reasons. We investigated the occurrence of brown adipocytes in fat deposits of prepubertal baboons using antibodies raised against uncoupling protein (UCP) in Western blotting and immunocytology experiments. UCP was detected in all types of fat pads studied and was revealed in multilocular cells. Pericardiac and axillary adipose tissues displayed large amounts of UCP and can be assimilated to typical BAT. Most of the other pads looked like white adipose tissue, but exhibited areas with clusters of brown adipocytes and, thus, can be assimilated to the convertible adipose tissue as previously described in rodents. The presence of beta 3-ARs was evaluated by both beta 2-agonist-stimulated lipolysis and messenger ribonucleic acid (mRNA) expression studies. There was no significant lipolytic effect of any of the beta 3-AR agonists tested (SR 58611A, BRL 37344, CGP 12177, or CL 316243) in either white or brown tissues. PCR analysis demonstrated that beta 3-AR mRNA expression is not related to the UCP content of fat pads and that beta 3-AR expression is low. This study demonstrates the presence of great proportions of brown adipocytes in adipose tissue and the heterogeneity of the fat pads in baboons. The lack of a metabolic effect of beta 3-agonists combined with the weak expression of beta 3-AR mRNAs raise the question of the role of beta 3-ARs in adipose tissues of primates.

Adipose Tissue, Brown↗
PubMed1995

Desensitization of beta-adrenergic responses in adipocytes involves receptor subtypes and cAMP phosphodiesterase.

Acute exposure of isolated adipocytes to isoproterenol induces the desensitization of lipolytic responses to norepinephrine and selective beta 1-, beta 2- and beta 3-adrenoceptor agonists, as well as the adrenocorticotropic hormone 1-24 fragment (ACTH). Forskolin and 8-bromo-cAMP responses are also desensitized. When lipolysis was measured in the presence of OPC 3911 [N-cyclohexyl-N-2-hydroxyethyl-4(6-(1,2-dihydro-2- oxoquinolyloxy))butyramide], a specific inhibitor of the cAMP phosphodiesterase of adipocytes, the desensitization of all lipolytic agents--except the beta 2-adrenoceptor agonist--was abolished. Isoproterenol induced a similar loss (35%) of both membrane beta 1- and beta 2-adrenoceptors and an uncoupling of beta 1-adrenoceptors, but did not modify the weak coupling of control beta 2-adrenoceptors. These data suggest that isoproterenol induced (i) an activation of the cAMP phosphodiesterase, which is solely responsible for the desensitization of norepinephrine response as well as beta 1- and beta 3-adrenoceptor mediated responses and (ii) an additional desensitization of the sole beta 2-adrenergic signaling system which suggests a subtype-selective pattern of regulating processes.

Adipocytes↗
PubMed1995

Differential activation of beta 1-, beta 2- and beta 3-adrenoceptors by catecholamines in white and brown adipocytes.

This review summarizes the experiments performed by various groups to determine how the activation of the different beta-adrenoceptors (beta-ARs) is ordinated when they are present in the same fat cell and involved in the same biological event. When expressed after the transfection of their genes in Chinese hamster ovary cell (CHO cells), beta 1- and beta 2-ARs present a higher affinity for catecholamines than beta 3-ARs. In vitro, the lipolytic effect induced by low concentrations of catecholamines in dog and rat white fat cells is due to the selective activation of beta 1- and/or beta 2-ARs. Higher concentrations only are able to activate beta 3-ARs. Similar results have been obtained in rat brown adipocytes. On the other hand, the lipolytic effect of catecholamines in human and primate adipocytes does not involve a beta 3-AR component whatever the concentration used. In vivo experiments in the dog have also shown that lipomobilization induced by low doses of isoprenaline only involved beta 1- and beta 2-AR activation, this effect being blocked by beta 1-/beta 2-antagonist pretreatment. However, in the same blockade conditions, perfusion of a 10-fold higher dose of isoprenaline revealed a beta 3-AR contribution in the lipomobilizing effect. These data showed that brown and white adipocyte beta 3-ARs possess a lower affinity for catecholamines than beta 1- and beta 2-ARs and are only recruited by high concentrations of the amines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗
PubMed1995

[Lipid mobilization, physiopathological and pharmacological aspects].

The lipolysis in adipose tissue is controlled by the hormone-sensitive lipase activity which is dependent on the intracellular cAMP level. In human adipose tissue, cAMP level is increased by catecholamines (through beta-adrenoceptor stimulation) or decreased by insulin, catecholamine (through alpha 2-adrenoceptor stimulation), neuropeptide Y, prostaglandins and adenosine. The mobilization of lipids from adipose tissue is an adaptative mechanism in response to starvation or hypocaloric diet, which involves reduction of the antilipolytic effect of insulin and the increase of catecholamine sensitivity. The regulatory pathways of lipolysis and their adaptation to caloric reduction are not defective in obesity state. Pharmacological approaches proposed for the activation of lipolysis are limited; they mainly consist either to stimulate the fat cell beta-adrenoceptors (beta-sympathomimetic drugs) or to indirectly activate the sympathetic nervous system (ephedrine and its derivatives, methylxanthines, alpha 2-antagonists). However, the side effects elicited by these drugs frequently limit their clinical use.

Adenylyl Cyclase Inhibitors↗
PubMed1995

Control of lipolysis in intra-abdominal fat cells of nonhuman primates: comparison with humans.

The mechanisms that control lipolysis in intra-abdominal fat cells from various primate species, the marmoset (Callithrix jacchus), the baboon (Papio papio), and the macaque (Macaca fascicularis), were compared to those of human intraabdominal fat cells. Selective beta 1- or beta 2-adrenoceptor agonists induced lipolysis in all species. Selective beta 3-agonists (BRL 37344, CL 316243, and SR 58611) acted as partial agonists in marmoset but were inefficient in other primates, including humans. alpha 2-Adrenoceptor number ([3H]RX 8210002 binding) equalized (baboon) or exceeded (other primates) beta 1/beta 2-adrenoceptors ([3H]CGP 12177 binding). Baboon fat cell membranes expressed similar amounts of coupled beta- and alpha 2-adrenoceptors. In all species, norepinephrine- or epinephrine-induced lipolysis did not reach the lipolytic effect of isoproterenol but their effects were enhanced after alpha 2-adrenoceptor blockade. N6-phenylisopropyladenosine (PIA) induced a full antilipolytic effect in baboon, macaque, and human adipocytes through adenosine receptors ([3H]DPCPX binding). Peptide YY (PYY) weakly inhibited lipolysis in baboon. Adrenocorticotropic hormone (ACTH) was inactive whereas parathyroid hormone (PTH) partially stimulated lipolysis in primates. Histamine was partially lipolytic in marmoset only. This study emphasizes the similarities of the mechanisms controlling the lipolysis in nonhuman primate and in human adipocytes and suggests that the baboon and the macaque should provide unique models for the study of the regulation of lipolysis.

Abdomen↗
PubMed1994

beta-Adrenergic control of lipolysis in primate white fat cells: a comparative study with nonprimate mammals.

The beta-adrenoceptor subtypes involved in the control of lipolysis in white fat cells of rat, dog, marmoset (Callithrix jacchus), baboon (Papio papio), macaque (Macaca fascicularis), and human were compared. In all species [3H]CGP-12177 binding (up to 3 nM) indicated the existence of a homogeneous population of binding sites in fat cell membranes, and competition studies showed that beta 1- and beta 2-adrenoceptors were present. Selective beta 1 or beta 2-adrenoceptor agonists induced lipolysis. The efficiencies of isoproterenol and norepinephrine were similar. The use of selective beta 3-adrenoceptor agonists revealed that BRL-37344 and CL-316243 were full agonists, whereas CGP-12177 and SR-58611A were partial agonists in rat and dog white fat cells. beta 3-Agonists partially stimulated lipolysis in the marmoset, while CGP-12177 was weakly active in the baboon. In macaque and human fat cells, beta 3-agonists were ineffective. The lipolytic effect of norepinephrine involves beta 1-and/or beta 2-adrenoceptors in baboon, macaque, and human. The baboon and macaque constitute valuable models for studying the beta-adrenergic control of lipolysis.

Adipocytes↗