Study of Spacer Arm Length Influence on Drug Vectorization by Fullerene C 60

This work studies theoretically the effect of spacer arm lengths on the characteristics of a fullerene C 60 -based nanovector. The spacer arm is constituted of a carbon chain including a variable number of methylene groups (n = 2-11). To improve the ability of the fullerene carriage, two arms are presented simultaneously through a malonyl bridge. Then the evolution of selected physicochemical parameters is monitored as a function of the spacer arm length and the angle between the two arms. We show here that while the studied characteristics are almost independent of the spacer arm length or vary monotonically with it, the dipole moment and its orientation vary periodically with the parity of the number of carbon atoms. This periodicity is related to both modules and orientations of dipole moments of the spacer arms. In the field of chemical synthesis, these results highlight the importance of theoretical calculations for the optimization of operating conditions. In the field of drug discovery, they show that theoretical calculations of the chemical properties of a drug candidate can help predict its in vivo behaviour, notably its bioavailability and biodistribution, which are known to be tightly dependent of its polarity

Les facteurs influençant le rendement oléicole : cas de la région de Jijel du Nord-Est algérien

La région de Jijel, dans le Nord-Est algérien, possède un important potentiel naturel oléicole favorisant une activité économique importante autour de ce produit, notamment dans le milieu rural. Néanmoins, la production des exploitations de la région demeure faible et instable dans le temps, malgré les efforts de plantations entrepris depuis 2001. La recherche des causes de cette faiblesse nous a conduits à repérer les principaux facteurs spécifiques ayant un impact significatif sur les rendements. À cet effet, quatre facteurs ont été identifiés comme ayant des effets significatifs sur les rendements des exploitations oléicoles locales : deux s’avèrent liés à la variété et les deux autres à l’environnement. Les facteurs intrinsèques sont l’origine de la variété (locales et hors région) et l’âge des plants. Les deux autres facteurs extrinsèques (liés à l’environnement) sont l’altitude et la pente des terrains ; les exploitations se situant à des altitudes supérieures à 600 mètres, avec des pentes modérées enregistraient des rendements plus importants. Cette étude nous a permis de connaître les exigences agro-écologiques et les principaux facteurs spécifiques à prendre en considération pour une bonne affectation de la ressource oléicole au niveau local

8-oxo-7,8-dihydro-2'-deoxyguanosine as a biomarker of oxidative damage in oesophageal cancer patients: lack of association with antioxidant vitamins and polymorphism of hOGG1 and GST

International audienceThe present report was designed to investigate the origins of elevated oxidative stress measured in cancer patients in our previous work related to a case-control study (17 cases, 43 controls) on oesophageal cancers. The aim was to characterize the relationship between the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), antioxidant vitamins and genetic susceptibility

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Etude du passage membranaire de solutions huileuses du [60] fullerène administrées par voie orale (action sur le stress oxydatif dans un model expérimental d intoxication par le CCI4 chez le rat)

L'objectif de cette thèse a été d'étudier les effets d'une solution huileuse de [60]fullerène sur le stress oxydatif dans un modèle expérimental chez le rat. Les résultats obtenus montrent que ce fullerène peut être absorbé par voie digestive et que ces effets sont remarquables, même à des doses de l'ordre de quelques milligrammes par kilogramme de poids corporel.The objective of this thesis was to study the effects of an oily solution of [60]fullerene on oxidative stress in an experimental model in rats. The results obtained show that the fullerene can be absorbed through the digestive tract and that these effects are notable, even at doses of the order of several milligrams per kilogram of body weightCHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Photosynthèse de dérivés [60]fullerene-acides aminés (mécanisme réactionnel et modulation de nombre d'adduits)

L objectif de cette thèse a été de développer une plateforme fullerènique (C60 acides aminés) pour la vectorisation de principes actifs. L étude systématique des conditions expérimentales et celle du mécanisme de photo-addition du glycinoate de méthyle sur le C60, nous a permis de contrôler le nombre d adduits et d optimiser le rendement de leur production. Des essais préliminaires ont montré la faisabilité du greffage de molécules antibiotiques sur la plateforme fullerèniqueThe objective of this thesis was to develop derivatives of C60 based on amino-acids for the targeting of biological molecules. The systematic study of experimental conditions and the mechanism of photo-addition reaction of glycine methyl ester on the C60, has allowed us to control the number of adducts and optimize their production. Preliminary tests have shown the possibility of grafting molecules of antibiotics on the fullerene.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Dosage des amines biogènes, ptérines et folates dans le liquide céphalo-rachidien (expérience française à l'hôpital Armand Trousseau-La Roche Guyon)

PARIS-BIUP (751062107) / SudocSudocFranceF

Etude du comportement in vivo de nanotubes de carbone simple paroi normaux et ultracourts

Les nanotubes de carbone simple paroi ultracourts (NTUC) présentent un intérêt particulier pour certaines applications biomédicales. Cependant, les données toxicologiques concernant ces nanostructures restent contradictoires. Ici, nous avons comparé le comportement in vivo de nanotubes de carbone simple paroi (NCPS) en fonction de la dose, de la longueur et des défauts de surface, après administration chez la souris. Dans un essai de toxicité aiguë, les NCPS ont été administrés per os à une dose allant de 50 à 1000 mg/kg de poids corporel. Aucun trouble de croissance ou effet létal n ont été observés. Néanmoins, après administration par voie ip, les NCPS, indépendamment de leur longueur ou de la dose administrée, peuvent s agréger in situ et former des structures fibreuses. Lorsque ces structures dépassent 10 m, elles provoquent la formation de granulomes. Les petits agrégats ne provoquent pas ce phénomène, mais ils persistent à l'intérieur des cellules 5 mois après administration. Cependant, les NCPS courts (< 300 nm) et bien individualisés échappent au système réticuloendothélial et sont excrétés par les reins et la voie biliaire. Ces derniers résultats suggèrent qu'il est possible d'utiliser les NCPS dans le domaine biomédical. Par ailleurs, il a été rapporté, qu'il existe un lien étroit entre le contenu carboné des macrophages alvéolaires (MA) et le déclin de la fonction pulmonaire. Or, le contenu carboné de ces MA, n'a été caractérisé que par microscopie optique. Dans la seconde partie de cette thèse, nous avons recherché et caractérisé à l'aide de techniques analytiques appropriées, la présence de particules carbonées (PC) dans les MA d'enfants parisiens. Nous montrons ici que la majeure partie des PC présentes dans les MA appartient à la famille des fullerènes y compris les NTCs. Cependant, dans les MA, les PC sont très rares et impossible à distinguer par microscopie optique des corps lamellaires, normalement présents dans les pneumocytes de type II.Carbon nanotube (CNT) materials are of special interest as potential tools for biomedical applications. However, available toxicological data concerning single-walled carbon nanotubes (SWNTs) remain contradictory. Here, we compared the effects of SWNTs as a function of dose, length and surface chemistry in Swiss mice. In an acute toxicity test, SWNTs were administered orally at a dose level up to 1000 mg/kg bodyweight (b.w.). Neither death nor growth or behavioral troubles were observed. After intraperitoneal administration, SWNTs, irrespective of their length or dose (50-1000 mg/kg b.w.), can coalesce inside the body to form fiber-like structures. When structure lengths exceeded 10 m, they irremediably induced granuloma formation. Smaller aggregates did not induce granuloma formation, but they persisted inside cells for up to 5 months after administration. Short (<300 nm) well-individualized SWNTs can escape the reticuloendothelial system and are excreted through the kidneys and bile ducts. These findings suggest that if the potential of SWNTs for medical applications is to be realized, they should be engineered into discrete, individual particles. Moreover, it has been shown recently, that there is a link between airborne fine particulate matter and decline in lung function. We report here that a large portion of the carbonaceous particles engulfed by the airway macrophages of Parisian asthmatic infants and children are aggregated fullerene-like structures, including CNTs. Furthermore, the presence of SWNTs in the macrophages has been confirmed by their characteristic near-infrared fluorescence emission spectrum. These findings suggest that humans are being routinely exposed to anthropogenic CNTs.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF