Éditeur(s) : Université des Antilles AREBio Groupe de recherche BIOSPHERES : BIOlogie, Sciences Physiques & Humaines pour les énergies Renouvelables, l
Extrait de : 1er colloque international BIOSPHERES, du 18 au 20 juin 2019. Université des Antilles
Description : In the current ecological, economic and social context, the systematic use of drugs (prescription or self-medication) has direct health and environmental consequences. As a result, it is important to understand their perception by their main consumers. In this sense, social and environmental psychology aims to highlight the socio-psychological factors likely to influence the actors to adopt new practices or not (Zbinden et al., 2011). The present study, conducted in 2016 in CACEM territory, focuses on the analysis of social representations (SR) of drugs of the population from Martinique. The theory of SR allows the analysis of this mediation between man and his physical and social environment because these representations are highly contextualized and depend on the social anchoring of the groups (Doise, 1992).

Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V19084
V19084

South America -- Guyana -- Georgetown
Caribbean

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
A rapid and specific high-performance liquid chromatography method with UV detection (HPLC-UV) for the simultaneous determination of 12 beta-lactam antibiotics (amoxicillin, cefepime, cefotaxime, ceftazidime, ceftriaxone, cloxacillin, imipenem, meropenem, oxacillin, penicillin G, piperacillin, and ticarcillin) in small samples of human plasma is described. Extraction consisted of protein precipitation by acetonitrile. An Atlantis T3 analytical column with a linear gradient of acetonitrile and a pH 2 phosphoric acid solution was used for separation. Wavelength photodiode array detection was set either at 210 nm, 230 nm, or 298 nm according to the compound. This method is accurate and reproducible (coefficient of variation [CV] < 8%), allowing quantification of beta-lactam plasma levels from 5 to 250 μg/ml without interference with other common drugs. This technique is easy to use in routine therapeutic drug monitoring of beta-lactam antibiotics.
ISSN: 0066-4804

hal-00875271
https://hal.archives-ouvertes.fr/hal-00875271
https://hal.archives-ouvertes.fr/hal-00875271/document
https://hal.archives-ouvertes.fr/hal-00875271/file/Simultaneous_Determination-accepted.pdf
PUBMED : 21788467

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
Introduction: Drug transporters are now recognized as major players involved in pharmacokinetics and toxicology. Methods for assessing their activity are important to consider, particularly owing to regulatory requirements with respect to inhibition of drug transporter activity and prediction of drug–drug interactions. In this context, the use of fluorescent-dye-based transport assays is likely to deserve attention.Areas covered: This review provides an overview of the nature of fluorescent dye substrates for ATP-binding cassette and solute carrier drug transporters. Their use for investigating drug transporter activity in cultured cells and clinical hematological samples, drug transporter inhibition, drug transporter imaging and drug transport at the organ level are summarized.Expert opinion: A wide range of fluorescent dyes is now available for use in various aspects of drug transporter studies. The use of these dyes for transporter analyses may, however, be hampered by classic pitfalls of fluorescence technology, such as quenching. Transporter-independent processes such as passive diffusion of dyes through plasma membrane or dye sequestration into subcellular compartments must also be considered, as well as the redundant handling by various distinct transporters of some fluorescent probes. Finally, standardization of dye-based transport assays remains an important on-going issue
ISSN: 1742-5255

hal-01162381
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162381
DOI : 10.1517/17425255.2015.1053462
PUBMED : 26050735

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells. The pyrethroids allethrin and tetramethrin were found to inhibit various ABC and SLC drug transporters, including multidrug resistance-associated protein (MRP) 2, breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP) 1B1, organic anion transporter (OAT) 3, multidrug and toxin extrusion transporter (MATE) 1, organic cation transporter (OCT) 1 and OCT2, with IC50 values however ranging from 2.6 muM (OCT1 inhibition by allethrin) to 77.6 muM (OAT3 inhibition by tetramethrin) and thus much higher than pyrethroid concentrations (in the nM range) reached in environmentally pyrethroid-exposed humans. By contrast, allethrin and tetramethrin cis-stimulated OATP2B1 activity and failed to alter activities of OATP1B3, OAT1 and MATE2-K, whereas P-glycoprotein activity was additionally moderately inhibited. Twelve other pyrethoids used at 100 muM did not block activities of the various investigated transporters, or only moderately inhibited some of them (inhibition by less than 50%). In silico analysis of structure-activity relationships next revealed that molecular parameters, including molecular weight and lipophilicity, are associated with transporter inhibition by allethrin/tetramethrin and successfully predicted transporter inhibition by the pyrethroids imiprothrin and prallethrin. Taken together, these data fully demonstrated that two pyrethoids, i.e., allethrin and tetramethrin, can act as regulators of the activity of various ABC and SLC drug transporters, but only when used at high and non-relevant concentrations, making unlikely any contribution of these transporter activity alterations to pyrethroid toxicity in environmentally exposed humans.
ISSN: 1932-6203

hal-01477206
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477206
DOI : 10.1371/journal.pone.0169480
PUBMED : 28099443

Éditeur(s) : HAL CCSD
Résumé : International audience
In vitro evaluation of P-glycoprotein (P-gp) inhibitory potential is now a regulatory issue during drug development, in order to predict clinical inhibition of P-gp and subsequent drug-drug interactions. Assays for this purpose, commonly based on P-gp-expressing cell lines and digoxin as a reference P-gp substrate probe, unfortunately exhibit high variability, raising thus the question of developing alternative or complementary tests for measuring inhibition of P-gp activity. In this context, the present study was designed to investigate the use of the fluorescent dye rhodamine 123 as a reference P-gp substrate probe for characterizing P-gp inhibitory potential of 16 structurally-unrelated drugs known to interact with P-gp. 14/16 of these P-gp inhibitors were found to increase rhodamine 123 accumulation in P-gp-overexpressing MCF7R cells, thus allowing the determination of their P-gp inhibitory potential, i.e., their half maximal inhibitor concentration (IC50) value towards P-gp-mediated transport of the dye. These IC50 values were in the range of variability of previously reported IC50 for P-gp and can be used for the prediction of clinical P-gp inhibition according to Food and Drug Administration (FDA) criteria, with notable sensitivity (80%). Therefore, the data demonstrated the feasibility of the use of rhodamine 123 for evaluating the P-gp inhibitory potential of drugs
Pharmaceutics

hal-01305488
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01305488
DOI : 10.3390/pharmaceutics8020012
PUBMED : 27077878

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability. However, such interactions are drug dependent according to their solubility pattern and to the duration of action of acid-suppressive therapy, which is coprescribed. Significant interactions occur by inhibition or induction of CYP450 3A4 which is the main metabolic pathway of TKIs. However, minor metabolic pathways should also be paid attention to. Interactions involving efflux and influx transporters should also be considered occurring for some TKIs. Genetic polymorphism in drug metabolism as well as in drug transport is a factor of variability in drug exposure, which could modulate the magnitude of drug-drug interactions (DDIs). It should be noticed that TKIs can also be at the origin of drug interactions by altering the pharmacokinetics of coprescribed drugs. Since cancer patients are given many drugs either for supportive care or for the treatment of drug toxicity, and to the fact that the oldest patients are polymedicated, a clear understanding of DDIs with TKIs is of interest. The objectives of this review are to provide an overview of the mechanisms of DDIs with TKIs and to provide to physicians and pharmacists recommendations to manage these DDIs in their clinical practice.
ISSN: 0278-0232

hal-01616064
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616064
DOI : 10.1002/hon.2335
PUBMED : 27925256

Éditeur(s) : HAL CCSD
Résumé : International audience
Gevokizumab is a potent anti-interleukin (IL)-1 beta neutralizing monoclonal antibody (mAb), which may be used for treating inflammatory or autoimmune diseases. The present study was designed to characterize the potential effects of this mAb towards well-established IL-1 beta-mediated repression of hepatic drug detoxifying proteins, like cytochrome P450 (CYP) 3A4 and drug transporters. Primary cultured human hepatocytes were exposed to various concentrations of IL-1 beta in the absence or presence of gevokizumab (5 A mu g/mL); mRNA expression and activity of CYP3A4 and transporters were next determined. Gevokizumab was found to down-modulate, but not abolish, the repression of CYP3A4 and drug transporter mRNAs caused by IL-1 beta in human hepatocytes, through shifting up IL-1 beta half maximal inhibitory concentration (IC50) values by factors ranging from 6.8 to 10.4. The mAb concomitantly shifted IL-1 beta IC50 values towards CYP3A4 activity from 22.0 pg/mL (in the absence of gevokizumab) to 796 pg/mL (in the presence of gevokizumab) and counteracted the decrease of organic anion-transporting polypeptide activity occurring in response to 50 pg/mL IL-1 beta, but not that occurring at higher IL-1 beta concentration (1000 pg/mL). Gevokizumab attenuates, but not abolishes, IL-1 beta-mediated functional repression of CYP3A4 and drug transporters in human hepatocytes, which agrees with the fact that the mAb is considered as a modulator and not a blocker of IL-1 beta signaling. This attenuation of IL-1 beta-mediated down-regulation of hepatic detoxifying proteins by gevokizumab may have to be evaluated in terms of potential therapeutic protein drug-drug interactions when considering future development and therapeutic uses of this IL-1 beta neutralizing mAb.
ISSN: 0378-7966

hal-01616062
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616062
DOI : 10.1007/s13318-017-0406-1

Éditeur(s) : HAL CCSD
Résumé : International audience
The search for safe antimalarial compounds acting against asexual symptom-responsible stages and sexual transmission-responsible forms of Plasmodium species is one of the major challenges in malaria elimination programs. So far, among current drugs approved for human use, only primaquine has transmission-blocking activity. The discovery of small molecules targeting different Plasmodium falcip-arum life stages remains a priority in antimalarial drug research. In this context, several independent studies have recently reported antiplasmodial and transmission-blocking activities of commonly used stains, dyes and fluorescent probes against P. falciparum including chloroquine-resistant isolates. Herein we have studied the antimalarial activities of dyes with different scaffold and we report that the triar-ylmethane dye (TRAM) Brilliant green inhibits the growth of asexual stages (IC 50 2 mM) and has exflagellation-blocking activity (IC 50 800 nM) against P. falciparum reference strains (3D7, 7G8) and chloroquine-resistant clinical isolate (Q206). In a second step we have investigated the antiplasmodial activities of two polysulfonated triarylmethane food dyes. Green S (E142) is weakly active against P. falciparum asexual stage (IC 50 x 17 mM) whereas Patent Blue V (E131) is inactive in both antimalarial assays. By applying liquid chromatography techniques for the culture supernatant analysis after cell washings and lysis, we report the detection of Brilliant green in erythrocytes, the selective uptake of Green S (E142) by infected erythrocytes, whereas Patent Blue V (E131) could not be detected within non-infected and 3D7-infected erythrocytes. Overall, our results suggest that two polysulfonated food dyes might display different affinity with transporters or channels on infected RBC membrane.
International journal for parasitology. Drugs and drug resistance

Droits : http://creativecommons.org/licenses/by-nc-sa/
pasteur-01614675
https://hal-pasteur.archives-ouvertes.fr/pasteur-01614675
https://hal-pasteur.archives-ouvertes.fr/pasteur-01614675/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01614675/file/Leba%20LJ-article%20colorant-version%20publiee.pdf
DOI : 10.1016/j.ijpddr.2017.07.002

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The emerging orbicular batfish (Platax orbicularis) aquaculture is the most important fish aquacultureindustry in French Polynesia. However, bacterial infections are causing severe mortality episodes.Therefore, there is an urgent need to find an effective management solution. Besides the supplyingdifficulty and high costs of veterinary drugs in French Polynesia, batfish aquaculture takes place close tothe coral reef, where use of synthetic persistent drugs should be restricted. Medicinal plants andbioactive algae are emerging as a cheaper and more sustainable alternative to chemical drugs. We havestudied the effect of local Polynesian plants and the local opportunistic algae Asparagopsis taxiformis onbatfish when orally administered. Weight gain and expression of two immune-related genes (lysozyme ge Lys G and transforming growth factor beta - TGF-b1) were studied to analyze immunostimulant activityof plants on P. orbicularis. Results showed that several plants increased Lys G and TGF-b1 expressionon orbicular batfish after 2 and 3 weeks of oral administration. A. taxiformis was the plant displaying themost promising results, promoting a weight gain of 24% after 3 weeks of oral administration andsignificantly increasing the relative amount of both Lys G and TGF-b1 transcripts in kidney and spleen ofP. orbicularis.
ISSN: 1050-4648

hal-01381334
https://hal-univ-perp.archives-ouvertes.fr/hal-01381334
DOI : 10.1016/j.fsi.2016.09.011

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Hepatic drug transporters are now recognized as major actors of hepatobiliary elimination of drugs. Characterization of their regulatory pathways is therefore an important issue. In this context, the present study was designed to analyze the potential regulation of human hepatic transporter expression by protein kinase C (PKC) activation. Treatment by the reference PKC activator phorbol 12-myristate 13-acetate (PMA) for 48 h was shown to decrease mRNA expression of various sinusoidal transporters, including OATP1B1, OATP2B1, NTCP, OCT1 and MRP3, but to increase that of OATP1B3, whereas mRNA expression of canalicular transporters was transiently enhanced (MDR1), decreased (BSEP and MRP2) or unchanged (BCRP) in human hepatoma HepaRG cells. The profile of hepatic transporter mRNA expression changes in PMA-treated HepaRG cells was correlated to that found in PMA-exposed primary human hepatocytes and was similarly observed in response to the PKC-activating marketed drug ingenol mebutate. It was associated with concomitant repression of OATP1B1 and OATP2B1 protein expression and reduction of OATP, OCT1, NTCP and MRP2 activity. The use of chemical PKC inhibitors further suggested a contribution of novel PKCs isoforms to PMA-mediated regulations of transporter mRNA expression. PMA was finally shown to cause epithelial-mesenchymal transition (EMT) in HepaRG cells and exposure to various additional EMT inducers, i.e., hepatocyte growth factor, tumor growth factor-β1 or the HNF4α inhibitor ≡I6015, led to transporter expression alterations highly correlated to those triggered by PMA. Taken together, these data highlight PKC-dependent regulation of human hepatic drug transporter expression, which may be closely linked to EMT triggered by PKC activation
ISSN: 0006-2952

hal-01216205
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01216205
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01216205/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01216205/file/Protein%20kinase%20C-dependent%20regulation.pdf
DOI : 10.1016/j.bcp.2015.10.007

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Cigarette smoke condensate (CSC) has previously been shown to impair activity and expression of hepatic drug transporters. In the present study, we provided evidence that CSC also hinders activity of organic anion transporters (OATs), notably expressed at the kidney level. CSC thus cis-inhibited OAT substrate uptake in OAT1- and OAT3-transfected HEK293 cells, in a concentration-dependent manner (IC50=72.1μg/mL for OAT1 inhibition and IC50=27.3μg/mL for OAT3 inhibition). By contrast, OAT4 as well as the renal organic cation transporter (OCT) 2 were less sensitive to the inhibitory effect of CSC (IC50=351.5μg/mL and IC50=226.2μg/mL, for inhibition of OAT4 and OCT2, respectively). OAT3 activity was further demonstrated to be blocked by some single chemicals present in cigarette smoke such as the heterocyclic amines AαC (IC50=11.3μM) and PhIP (IC50=1.9μM), whereas other major cigarette smoke components used at 100μM, like nicotine, the nitrosamine NNK and the polycyclic aromatic hydrocarbons benzo(a)pyrene and phenanthrene, were without effect. AαC and PhIP however failed to trans-stimulate activity of OAT3, suggesting that they were not substrates for this transporter. Taken together, these data establish OAT1 and OAT3 transporters as targets of cigarette smoke chemicals, which may contribute to smoking-associated pharmacokinetics alterations.
ISSN: 0887-2333

hal-01579604
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579604
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579604/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579604/file/Sayyed%20et%20al.%20-%20Inhibition%20of%20organic%20anion%20transporter%20%28OAT%29%20acti.pdf
DOI : 10.1016/j.tiv.2017.06.014

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Plasmodium vivax malaria is an important public health issue in the Amazon region, and it accounts for approximately 84 % of cases of the disease. Migration across the border between Brazil and French Guiana contributes to the maintenance of the disease. The aim of this study was to evaluate the therapeutic and parasitological responses of patients with P. vivax malaria treated with chloroquine and primaquine in the socio-environmental context of cross-border interactions between Brazil and French Guiana. The factors controlled were diagnostic agreement, adherence, adjustment of primaquine doses for patient weight, and quality of the drugs used. A prospective study was conducted in 2011 with 103 individuals aged 10-60 years with a positive diagnosis of P. vivax treated with chloroquine (10 mg base/kg on the first day, followed by 7.5 mg/kg on the second and third days) and primaquine for 7 days, who were followed for 28 days. The primaquine doses were adjusted for the patients' weight. A number of factors were determined: epidemiological characteristics, origin of patients, signs and symptoms, initial parasitaemia and parasitaemia clearance time, blood concentrations of chloroquine and primaquine, quality of anti-malarial drugs and diagnostic agreement. Ninety-five patients were followed for 28 days. There was a 100 % agreement in microscopic diagnosis between field laboratory and reference centre. The adhesion to the treatment was 100 %. Of these patients, 32.6 % received a weight-adjusted dose of primaquine. The chloroquine and primaquine tablets were consistent with the optimal quality limits for human consumption. The investigated patients achieved optimal blood exposure to anti-malarial drugs. The parasitological and therapeutic response was adequate in 99.0 % of cases. In the municipality of Oiapoque, the therapeutic regime used for the treatment of P. vivax malaria using chloroquine combined with primaquine remains effective, when external factors are controlled, such as the quality of anti-malarial drugs, the adhesion to the treatment prescribed, the correct diagnostic and the adjustment of primaquine dose for patient body weight.
ISSN: 1475-2875

Droits : http://creativecommons.org/licenses/by/
pasteur-01229355
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01229355/file/s12936-015-0925-7.pdf
PUBMEDCENTRAL : PMC4600333

Éditeur(s) : HAL CCSD
Résumé : International audience
Despite the recent interest in psychiatric illness in prison, the psychopathology of the Remire-Montjoly prison population remains largely unknown. Subject to significant population movements, French Guiana and its prison houses a very mixed population in which recent history has left a strong mark (earthquake in Haïti, civil war in Suriname, violence related to gold mining population and drug trafficking). These negative life events appear as potential vectors of psychological trauma. Additionally, strong links have been established in the literature between post-traumatic stress disorder (PTSD) and many other psychiatric disorders, including suicidal behavior and addictions. Under these conditions, we felt it essential to focus on the identification of PTSD in this sensitive population.Through adapted reception interviews, we tried to identify the PTSD, to describe by means of socio-demographic factors the studied population and to detect psychiatric comorbidities. The screening tool was the M.I.N.I. 5.0, which identifies 17 psychiatric disorders including the PTSD, based on the DSM IV definition. The target population was the prison incomers, agreeing to participate in the study, aged more than 18 years old and imprisoned between 18 January 2013 and 31 December 2013. To this date, 549 inmates were included in the study.The main result of this study was a prevalence of PTSD of 17% for incomers in detention. We found that the PTSD+ population is more likely to be female (15% against 7% p = 0.0246), which is consistent with the literature data. The M.I.N.I. 5.0 showed a higher prevalence of psychiatric disorders in the PTSD+ group. This association was confirmed in several types of pathology like mood disorders including: major depressive episode and manic or hypomanic episode, suicidal risk, some anxiety disorders including: panic disorder, obsessive-compulsive disorder and generalized anxiety disorder. Strong association was found for current major depressive episode, current manic or hypomanic episode and suicidal risk (p < 0.005).The prevalence of PTSD is very high in this study, about 24 times higher than in a general population survey using the same screening tool.A large number of comorbidities have been identified, which corresponds to those described in the literature. The specific issues of psychiatry in prison lead us to examine more specifically the significance of the results about suicide risk. A comprehensive suicide risk (sum of medium and high risk screened by the M.I.N.I.) was found in significantly more PTSD+ inmates (17% versus 7%, p = 0.005). This study supports the need for routine screening of PTSD among incomers in detention. This disease is both worrying and common in this population but the real issues are the comorbidities. Suicidal potential is among the most important issues in detention. Its evaluation should be completed by an early recognition of a PTSD.
Soumis à des mouvements de population importants, la Guyane Française et son centre pénitentiaire abritentune population métissée chez qui l’histoire récente a laissé une empreinte forte (tremblement de terre en Haïti,guerre civile au Suriname, violence liée à l’orpaillage et au trafic de stupéfiants). Ces événements de vienégatifs apparaissent comme autant de vecteurs potentiels de psychotraumatismes. Dans ces conditions, il nous a paru essentiel de mettre l’accent sur le repérage du TSPT (Trouble de Stress Post-traumatique) dans cette population sensible. A l'aide d’entretiens d’accueil dédiés nous nous sommes proposé de repérer les TSPT, de décrire sur un plan sociodémographique la population étudiée et de rechercher les comorbidités psychiatriques. Le résultat principal de cette étude était une prévalence du TSPT de 17% chez les arrivants en détention. Le MINI 5.0 a montré une prévalence plus élevée des pathologies psychiatriques dans le groupe présentant un TSPT avec un lien très fort (p<0.005) pour l’épisode dépressif majeur actuel, l’épisode (hypo)maniaque actuel et le risque suicidaire. Cette étude appuie la nécessité d’avoir un dépistage systématique du TSPT chez les arrivants en détention. Cette pathologie est à la fois fréquente dans cette population et invalidante mais ce sont ses comorbidités, dont le potentiel suicidaire, qui font tout l’enjeu d’un repérage précoce.
ISSN: 0383-6320

inserm-01421075
http://www.hal.inserm.fr/inserm-01421075
http://www.hal.inserm.fr/inserm-01421075/document
http://www.hal.inserm.fr/inserm-01421075/file/2016%2C%20Arnal%20-%20Post-Traumatic%20Stress%20Disorder%20among%20Incomers%20in%20Remire-Montjoly%20Prison%2C%20French%20Guiana.pdf
PUBMED : 27570960

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Human hepatocytes cultured in a monolayer configuration represent a well-established in vitro model in liver toxicology, notably used in drug transporter studies. Polarized status of drug transporters, i.e., their coordinated location at sinusoidal or canalicular membranes, remains however incompletely documented in these cultured hepatocytes. The present study was therefore designed to analyze transporter expression and location in such cells. Most of drug transporters were first shown to be present at notable mRNA levels in monolayer-cultured human hepatocytes. Cultured human hepatocytes, which morphologically exhibited bile canaliculi-like structures, were next demonstrated, through immunofluorescence staining, to express the influx transporters organic anion transporting polypeptide (OATP) 1B1, OATP2B1 and organic cation transporter (OCT) 1 and the efflux transporter multidrug resistance-associated protein (MRP) 3 at their sinusoidal pole. In addition, the efflux transporters P-glycoprotein and MRP2 were detected at the canalicular pole of monolayer-cultured human hepatocytes. Moreover, canalicular secretion of reference substrates for the efflux transporters bile salt export pump, MRP2 and P-glycoprotein as well as sinusoidal drug transporter activities were observed. This polarized and functional expression of drug transporters in monolayer-cultured human hepatocytes highlights the interest of using this human in vitro cell model in xenobiotic transport studies.
ISSN: 0887-2333

hal-01141725
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141725
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141725/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141725/file/Polarized%20location%20of%20SLC.pdf
DOI : 10.1016/j.tiv.2015.03.019

Éditeur(s) : HAL CCSD
Résumé : International audience
Coming from Crimea, the Black Death spread to Western Europe and North Africa during the 1340s. From 1346 to 1352, the plague killed an estimated 25-40% of Europeans of all age-groups [1] , i.e., 30 to 60% of Europe population. One of the earliest and most widely accepted explanations was that God was punishing humanity for their sins. One remedy for the curse was to do penitence. Thus in 1348 there rapidly arose a mass movement of flagellation [2]. In fact flagellation could not really help against such threat. The Black Death or Bubonic plague is caused by Yersinia pestis, a Eubacteria discovered in 1894 by Alexandre Yersin. It is transmitted by the bite of the flea Xenopsylla cheopsis. This flea lives by feeding the blood of many species besides man but its most preferred relationship is with the black rat (Rattus rattus). Fossilized remains of the plague flea have been found in large numbers in Amarna, Egypt [3, 4] about 1350 BC, and thus could be directly linked to the events described in the Book of Samuel [5, 6]. During the epidemic of Bubonic plague in London in 1665-1666, the known treatments were made use of, e.g. the so-famous Theriac or Venice Treacle which is used from the time of ancient Rome as a remedy against poison [7]. Since then, more specialized and novel treatments have been developed. However, since the characterization of Yersinia pestis, numerous drugs have been developed against it, e.g. gentamicin or doxycycline [8]. These researches had been carried out using more elaborated biochemical, biophysical and biological approaches.
Infectious disorders drug targets

Droits : info:eu-repo/semantics/OpenAccess
inserm-00395256
http://www.hal.inserm.fr/inserm-00395256
http://www.hal.inserm.fr/inserm-00395256/document
http://www.hal.inserm.fr/inserm-00395256/file/editorial.pdf
http://www.hal.inserm.fr/inserm-00395256/file/inserm-00395256_edited.pdf

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Whilst it used to affect mostly intravenous drug users and patients who underwent valvular surgery with suboptimal infection control procedures, fungal endocarditis is now mostly observed in patients with severe immunodeficiency (onco-haematology), in association with chronic central venous access and broad-spectrum antibiotic use. The incidence of fungal endocarditis has probably decreased in most developed countries with access to harm-reduction policies (i.e. needle exchange programmes) and with improved infection control procedures during cardiac surgery. Use of specific blood culture bottles for diagnosis of fungal endocarditis has decreased due to optimisation of media and automated culture systems. Meanwhile, the advent of rapid techniques, including fungal antigen detection (galactomannan, mannan/anti-mannan antibodies and β-1,3-d-glucans) and PCR (e.g. universal fungal PCR targeting 18S rRNA genes), shall improve sensitivity and reduce diagnostics delays, although limited data are available on their use for the diagnosis of fungal endocarditis. New antifungal agents available since the early 2000s may represent dramatic improvement for fungal endocarditis: (i) a new class, the echinocandins, has the potential to improve the management of Candida endocarditis owing to its fungicidal effect on yeasts as well as tolerability of increased dosages; and (ii) improved survival in patients with invasive aspergillosis with voriconazole compared with amphotericin B, and this may apply to Aspergillus sp. endocarditis as well, although its prognosis remains dismal. These achievements may allow selected patients to be cured with prolonged medical treatment alone when surgery is considered too risky.
ISSN: 0924-8579

hal-01118441
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118441
DOI : 10.1016/j.ijantimicag.2014.07.003
PUBMED : 25178919

Éditeur(s) : HAL CCSD Taylor & Francis (Routledge)
Résumé : International audience
The French Antilles (Martinique, Saint Martin and Guadeloupe) and French Guiana are the French territories most affected by the HIV epidemic. Some population groups such as men who have sex with men (MSM), especially those involved in transactional sex, are thought to be particularly vulnerable to HIV but few data exist to help characterize their health-related needs and thus implement relevant prevention interventions. To fill this knowledge gap, we used data collected from an HIV/AIDS Knowledge, Attitudes, Behaviours and Practices survey conducted in 2012 among MSM living in the French Antilles and French Guiana and recruited through snowball sampling. Our objectives were to compare social and demographic characteristics and sexual behaviours between MSM engaging in transactional sex and MSM not engaging in transactional sex and to identify factors associated with transactional sex involvement using a logistic regression model. A total of 733 MSM were interviewed, 21% of whom reported to undergo transactional sex. Their behaviour and social and demographic characteristics were different from other MSMs’ and they were more exposed to factors that are recognized to potentiate HIVvulnerability, at the individual, community, network and structural levels. The variables positively associated with sex trade involvement were having ever consumed drug (OR = 2.84 [1.23–6.52]; p = .002), having a greater number of sex partners than the median (OR = 8.31 [4.84–14.30]; p < .001), having experienced intimate partner violence (OR = 1.72 [0.99–3.00]; p = .053) and having undergone physical aggression because of sexual orientation (OR = 2.84 [1.23–6.52];p = .014). Variables negatively associated with sex trade involvement were being older (OR = 0.93 [0.90–0.97] per year; p = .001), having a stable administrative situation (OR = 0.10 [0.06–0.19]; p < .001), having a stable housing (OR = 0.29 [0.15–0.55]; p < .001) and being employed full-time (OR = 0.29 [1.23–6.52]; p = .002).
ISSN: 0954-0121

inserm-01407263
http://www.hal.inserm.fr/inserm-01407263
http://www.hal.inserm.fr/inserm-01407263/document
http://www.hal.inserm.fr/inserm-01407263/file/AIDS%20Care%20final%20version.pdf
DOI : 10.1080/09540121.2016.1234680

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
INTRODUCTION: Hydroxyurea is an antimetabolite drug used in the treatment of myeloproliferative disorders. Common adverse effects include haematological, gastrointestinal cutaneous manifestations, and fever. Hydroxyurea-induced pneumonitis is unusual. CASE REPORT: A female patient was treated with hydroxyurea for polycythemia vera. She was admitted 20 days after commencing treatment with a high fever, productive cough, clear sputum and nausea. A chest CT-scan showed diffuse ground-glass opacities. Microbiological investigations were negative. The symptoms disappeared a few days after discontinuation of the drug and rechallenge led to a relapse of symptoms. CONCLUSION: Our case and 15 earlier cases of hydroxyurea-induced pneumonitis are reviewed. Two patterns of this disease may exist: an acute febrile form occurring within 1 month of introduction of hydroxyurea and a subacute form without fever. Even if uncommon, one should be aware of this complication of hydroxyurea.
Revue des Maladies Respiratoires

hal-01072996
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01072996
DOI : 10.1016/j.rmr.2013.09.001
PUBMED : 24878159

Éditeur(s) : Soc General Microbiology
Résumé : The Plasmodium falciparum kinome includes a family of four protein kinases (Pfnek-1 to -4) related to the NIMA (never-in-mitosis) family, members of which play important roles in mitosis and meiosis in eukaryotic cells. Only one of these, Pfnek-1, which we previously characterized at the biochemical level, is expressed in asexual parasites. The other three (Pfnek-2, -3 and -4) are expressed predominantly in gametocytes, and a role for nek-2 and nek-4 in meiosis has been documented. Here we show by reverse genetics that Pfnek-1 is required for completion of the asexual cycle in red blood cells and that its expression in gametocytes in detectable by immunofluorescence in male (but not in female) gametocytes, in contrast with Pfnek-2 and Pfnek-4. This indicates that the function of Pfnek-1 is non-redundant with those of the other members of the Pfnek family and identifies Pfnek-1 as a potential target for antimalarial chemotherapy. A medium-throughput screen of a small-molecule library provides proof of concept that recombinant Pfnek-1 can be used as a target in drug discovery.
Microbiology-sgm (1350-0872) (Soc General Microbiology), 2011-10 , Vol. 157 , P. 2785-2794

Droits : 2011 SGM Printed in Great Britain / This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
http://archimer.ifremer.fr/doc/00175/28578/26965.pdf
DOI:10.1099/mic.0.049023-0
http://archimer.ifremer.fr/doc/00175/28578/