Submitted by Renata Lopes (renatasil82@gmail.com) on 2018-09-04T11:52:25Z No. of bitstreams: 1 annelisafarahsilvapaesleme.pdf: 3714457 bytes, checksum: 04f67b418a9032046d649343f4ef5330 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-09-04T13:18:39Z (GMT) No. of bitstreams: 1 annelisafarahsilvapaesleme.pdf: 3714457 bytes, checksum: 04f67b418a9032046d649343f4ef5330 (MD5) / Made available in DSpace on 2018-09-04T13:18:39Z (GMT). No. of bitstreams: 1 annelisafarahsilvapaesleme.pdf: 3714457 bytes, checksum: 04f67b418a9032046d649343f4ef5330 (MD5) Previous issue date: 2014-02-14 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Biofilmes associados a dispositivos médicos são responsáveis por 85% das infecções de corrente sanguínea relacionadas a catéteres (ICSRC). O objetivo deste trabalho foi testar duas formulações, como revestimento para catéteres venosos centrais (CVC), as quais tiveram a eficácia antimicrobiana e antiaderente avaliadas in vitro e a eficácia e biocompatibilidade, in vivo. A atividade antimicrobiana foi determinada por método turbidimétrico e a concentração inibitória mínima (CIM) foi estabelecida. A microscopia eletrônica de varredura (MEV) avaliou a propriedade antiaderente dos CVC revestidos com a formulação 1 (CVC-R1) e formulação 2 (CVC-R2), comparados aos não revestidos (CVC-NR). Implantes subcutâneos foram inseridos na área dorsal de ratos. O primeiro ensaio compreendeu análises hematológicas e microbiológicas (hemocultura e colonização das superfícies de CVC), a fim de avaliar a eficácia dos revestimentos. A biocompatibilidade foi avaliada no segundo ensaio pela observação das reações inflamatórias após 7 e 21 dias. Ambas formulações apresentaram atividade antimicrobiana frente a todas as cepas testadas. A desagregação do biofilme, com redução significativa da aderência microbiana, foi observada em ambos CVC revestidos. In vivo, foi observada maior eficácia antibiofilme de CVC-R2, com redução da colonização por Staphylococcus aureus ATCC 25923. As reações teciduais provocadas por CVC-R1 e CVC-R2 foram mais pronunciadas inicialmente, contudo, ao longo do experimento, se tornaram estatisticamente semelhantes às do CVC-NR. Ambas as formulações foram biocompatíveis, com maior velocidade de reparo tecidual no grupo CVC-R2. O uso de CVC- R1 e, especialmente de CVC-R2, pode diminuir a incidência de ICSRC. Acredita-se que CVC-R2 apresenta potencial para ser testado clinicamente. / Device-associated biofilms are responsible for 85% of catheter-related bloodstream infections (CRBSI). The aim of this study was investigate two formulations, as central venous catheters (CVC) coating, which were submitted to in vitro evaluation of antimicrobial and anti-adherent efficacy and in vivo evaluation of efficacy and biocompatibility. The antimicrobial activity was assessed by turbidimetric method and the minimum inhibitory concentration (MIC) was determined. The scanning electron microscopy (SEM) was used to assess the anti-adherent property of CVC coated with formulation 1 (CVC-R1) and formulation 2 (CVC-R2), in comparison to uncoated CVC fragments (CVC-NR). Subcutaneous implants were inserted into the dorsal area of rats. The first assay consisted in hematological and microbiological analysis (hemoculture and CVC surfaces colonization) in order to evaluate the coatings effectiveness. The second assay evaluated the biocompatibility by the observation of inflammatory reactions after 7 and 21 days. Both formulations showed antimicrobial activity against all tested strains. The biofilm disaggregation, with reduction in microbial adherence, was noted in coated catheters. In vivo results showed greater antibiofilm efficacy of CVC-R2 since a reduction of Staphylococcus aureus ATCC 25923 colonization was observed. The tissue reactions of CVC-R1 and CVC-R2 groups were initially more pronounced, however, throughout the experiment, the histological parameters have become statistically similar those found in CVC-NR group. Both formulations were biocompatible and a higher speed of tissue repair in CVC-R2 group was noted. The use of CVC- R1, and especially of CVC-R2, may reduce the development of CRBSI, and thereby, CVC-R2 have potential to be clinically tested.

Submitted by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-16T14:30:50Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Fernanda_Demoliner.pdf: 883689 bytes, checksum: 17b2361f24d2dcbcf6fa64f2b8eb26cc (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-16T20:23:53Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Fernanda_Demoliner.pdf: 883689 bytes, checksum: 17b2361f24d2dcbcf6fa64f2b8eb26cc (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-05-16T20:24:07Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Fernanda_Demoliner.pdf: 883689 bytes, checksum: 17b2361f24d2dcbcf6fa64f2b8eb26cc (MD5) / Made available in DSpace on 2018-05-16T20:24:07Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Fernanda_Demoliner.pdf: 883689 bytes, checksum: 17b2361f24d2dcbcf6fa64f2b8eb26cc (MD5) Previous issue date: 2015-03-20 / Sem bolsa / A adesão e formação de biofilmes de micro-organismos a superfícies de equipamentos e utensílios no processamento de alimentos resulta em grave problema para a indústria, pois atua como fonte de contaminação do alimento, por serem mais resistentes a ação de sanitizantes e antimicrobianos. O objetivo deste trabalho foi avaliar a capacidade de Pseudomonas spp. e Listeria spp., provenientes de cortes de carnes de frango e de búfalo de frigoríficos e do comércio varejista da região sul do Rio Grande do Sul, de formar biofilmes em superfície de placas de poliestireno e aço inoxidável, bem como verificar a resistência destes a sanificantes e a antimicrobianos. Foram utilizados 69 isolados bacterianos provenientes de cortes de carnes de frango e de búfalo, sendo 19 de espécies de Listeria e 50 de Pseudomonas spp. Os isolados foram avaliados quanto à formação de biofilme em microplacas de poliestireno e em corpos de prova de aço inoxidável. Os isolados formadores de biofilme em aço inoxidável foram testados quanto à ação de sanitizantes: cloro orgânico e quaternário de amônio (200 ppm) e submetidos ao teste de resistência antimicrobiana. A formação biofilme em microplacas de poliestireno foi de 73,7 % para isolados de Listeria spp. e de 32 % para isolados de Pseudomonas spp. Todos os isolados de Listeria spp. e 72% dos isolados de Pseudomonas spp. formaram biofilmes em corpos de prova de aço inoxidável. O quaternário de amônio foi mais eficaz que o cloro orgânico na redução de biofilme de Listeria spp. e Pseudomonas spp. Os isolados pertencentes ao gênero Listeria apresentaram maior resistência à penicilina (94,7 %), à clindamicina (84,2 %), à oxacilina (73,7 %) e à cefepime (57,9 %), sendo que 94,7 % foram resistentes a dois ou mais antimicrobianos. Meropenem foi o antimicrobano menos efetivo para Pseudomonas spp. Também foram encontrados 84% dos isolados de Pseudomonas spp. multirresistentes a antimicrobianos. Conclui-se que os isolados provenientes de cortes de carnes de frango e de bubalino foram formadores de biofilme em poliestireno e aço inoxidável e apresentaram resistência a antimicrobianos, o que confere riscos a saúde do consumidor. / The adhesion and microorganisms biofilm formation on surfaces of equipment and utensilsin food processingresults inserious problem for the industry because it actsas a source of contamination are less resistant to sanitizers and antimicrobial action. The objective of this study was to evaluate the ability of Pseudomonas spp. and Listeria spp. present in chicken and buffalo meat, to form biofilms on the surface of polystyrene plates and stainless steel as well as verify their resistance to sanitizers and antimicrobials. Sixty nine bacterial isolates were used, 19 species of Listeria and 50 species of Pseudomonas spp. The isolates were evaluated to their biofilm formation capacity in polystyrene microplates and stainless steel. Isolated stainless steel biofilm formers were tested for sanitizing action of organic chlorine and quaternary ammonium (200 ppm) and submitted antimicrobial resistance testing. The ability to form biofilmon polystyrene microplates was 73,7 % in isolates of Listeria spp. and 32 % for Pseudomonas spp. All isolates of Listeria spp. and 72 % of Pseudomonas spp. showed the ability to form biofilm on stainless steel specimens. The sanitizing organic chlorine and quaternary ammonium were effective to reduce Listeria spp. and Pseudomonas spp. biofilm formation in stainless steel. Quaternary ammonium was more effective than organic chlorine to reduce Listeria spp. biofilm formation from buffalo meat. Isolates belonging to the Listeria generous showed greater resistance to penicillin (94.7 %), clindamycin (84.2 %), oxacillin (73.7 %) and cefepime (57.9 %), and 94.7 % were resistant to two or more antimicrobial. Meropenem was the less effective antimicroban of or Pseudomonas spp. It was also found that 84 % of isolates of Pseudomonas spp. were multirresistentes to antimicrobianos. The isolates from chicken meat cuts and buffalo were biofilm-forming polystyrene and stainless steel and were resistant to antimicrobials, which gives risk to consumer health.

Objetivo: Avaliar se a adição de nanopartículas de prata ao cimento MTA branco irá melhorar a ação antimicrobiana sobre Enterococcus faecalis e prevenir a aderência deste microrganismo ao material. Método: Teste de contato direto utilizando corpos de prova dos materiais: MTA branco (n=10) grupo B, MTA cinza (n=10) grupo C, MTA branco + NPAg em pó a 1% em peso (n=10) grupo P, MTA branco + solução de NPAg 50ppm (n=10) grupo L, que foram mantidos a 35˚C por 72 horas na suspensão de Enterococcus faecalis em SBF (0.085 UA; 660nm). Alíquotas de 100μL foram tomadas da suspensão a cada 24 horas, realizadas as diluições seriadas e semeadas em triplicata em placa de Petri contendo meio Nutriente acrescido de azul de bromotimol a 0,001%. As placas foram incubadas a 35˚C por 48 horas e então realizadas as contagens de UFC. Ao final de 72 horas, corpos de prova em resina (n=10), que haviam sido mantidos na mesma suspensão juntamente com os demais grupos, tiveram a suspensão renovada, tendo sido ajustada para 0.1 UA (660nm). Permaneceram por mais 72 horas em estufa a 35˚C e então foram submetidos ao teste de aderência. Resultados: Para a comparação intergrupos considerando a variação do número de UFC em dois períodos houve diferença significante entre o grupo P e demais grupos no intervalo (T0-24h) e no intervalo (48-72h) para o grupo C comparado ao grupo L e P (Teste Anova teste t; α=0.01). Conclusões: Os cimentos MTA cinza e branco, com ou sem nanopartículas, apresentaram ação antimicrobiana sobre Enterococcus faecalis em todos os períodos do teste de contato direto; A adição da nanopartícula de prata em pó promoveu um efeito antimicrobiano em menor tempo sobre o Enterococcus faecalis, no teste de contato direto; O MTA branco, com nanopartículas não permitiu a aderência bacteriana ao final de 72 horas em contato com a suspensão bacteriana de Enterococcus faecalis. / Aim: To evaluate if the addition of silver nanoparticles to white MTA cement will improve the antimicrobial action of Enterococcus faecalis and prevent adherence of this microorganism to the material. Method: Direct contact test using samples of materials: white MTA (n=10) B group, gray MTA (n=10) C group, white MTA + NPAG powder to 1wt% (n=10) P group, white MTA + solution NPAG of 50ppm (n=10) L group were kept at 35˚C for 72 hours in Enterococcus faecalis in SBF(0.085AU; 660nm). Aliquots of the suspension were taken every 24 hours, serial dilutions carried out in triplicate and plated on Petri dishes containing nutrient medium plus bromothymol blue 0.001%. The plates were incubated at 35˚C for 48 hours and then the CFU counts performed. At the end of 72 hours resin specimens (n=10) which had been kept at the same suspension together with the remaining groups all had renewed suspension having been adjusted to 0.1AU (660nm). Lasted for over 72 hours in an oven at 35˚C and then were tested for adhesion. Results: Comparing between those groups consider the variation of numbers of CFU in two periods there was significant differente between the P group and other groups in the interval (T0-24h) and range (48-72h) for group C compared with group L and P (Anova test - t test; α=00:01). Conclusions: The gray and white MTA, with or without nanoparticles showed antimicrobial activity on Enterococcus faecalis at all periods of direct contact test; the silver nanoparticle powder addition promoted an antimicrobial effect in less time on the Enterococcus faecalis in test direct contact; white MTA with nanoparticles prevented bacterial adherence at the end of 72 hours in contact with the bacterial suspension of Enterococcus faecalis.

Ce travail de thèse est consacré à la préparation de glycopolymères porteurs de groupements pendants mannoside d’heptyle et à l’évaluation de la capacité de ces ligands multivalents à inhiber la fixation bactérienne sur les cellules humaines. Nous avons synthétisé, par polymérisation radicalaire contrôlée, une série de glycopolymères linéaires ou en étoile présentant des masses molaires, des densités en mannoside et des microstructures modulables dans le but d’évaluer l’influence de ces paramètres sur les processus d’interactions avec diverses souches de bactéries E coli (AIEC LF82 et UTI 89). Nous avons tout d’abord mis en évidence par diffusion dynamique et statique de la lumière, la formation d’agrégats entre ces glycopolymères et FimH, la lectine à l’origine de la fixation de souches de bactéries E coli, traduisant des interactions fortes entre les motifs mannosides et les sites de reconnaissance au mannose de la lectine. Nous avons ensuite évalué l’aptitude de ces ligands multivalents à bloquer l’adhésion bactérienne d’AIEC LF82 (impliquée dans la maladie de Crohn) sur des cellules épithéliales intestinales T84. Il a été démontré en conditions in vitro que l’ajout de 10 nM ou 100 nM d’unités mannoside (respectivement en pré- ou post-incubation) réduit de moitié l’adhésion des bactéries sur les cellules épithéliales. L’effet anti-adhésif de ces glycopolymères a été confirmé par des tests ex vivo réalisés sur des intestins isolés de souris transgéniques CEABAC10. Enfin, nous avons exploité la technique de nanoprécipitation pour l’élaboration de nanocapsules de glycopolymères à cœur huileux. Le procédé développé permet la synthèse de nanocapsules de dimensions contrôlées, porteuses de groupements fonctionnels (fluorophores, ligands) ou de particules métalliques et l’encapsulation de molécules actives à cœur en une seule étape. / This PhD work focuses on the preparation of glycopolymers bearing pendent heptyl mannose groups and the evaluation of the capability of such multivalent ligands to inhibit bacterial adhesion to human cells. Aiming at understanding the impact of various structural parameters on glycopolymer/ E coli interactions (AIEC LF82 et UTI 89 strains of E. coli), a series of linear and star-shaped glycopolymers with tunable molecular weight, mannoside density and microstructure (block copolymers, gradient copolymers, random copolymers) has been constructed. The association of the glycopolymers with FimH adhesin, a lectin which possesses a mannose-specific receptor site and is responsible for recognition and binding to host cells, was first confirmed by static and dynamic light scattering experiments. The propensity of the glycopolymers to prevent attachment of E. coli (AIEC LF82 involved in Crohn’s disease) to intestinal epithelial cells (T84 cells) was further investigated through adhesion assays. It was shown that under in vitro conditions, the addition of 10 nM or 100 nM of glycopolymer on a mannose unit basis (in pre-incubation and post-incubation respectively) decreases by half the bacterial adhesion to intestinal epithelial cells. The anti-adhesive effect of these multivalent ligands was further confirmed in ex vivo conditions for colonic loops of transgenic CEABAC10 mice (Crohn’s disease model mouse). Finally we took advantage of the nanoprecipitation process to generate glyconanocapsules with oily core. The employed strategy allowed for preparing well-defined nanocapsules bearing groups of interest (tags, ligands) or metal particles within the shell and loaded with active molecules in the core in one step.

No / This article describes how an insight into the chemical and physical cues that affect bacterial adhesion and biofilm formation can provide ideas for creating successful antifouling or antimicrobial surfaces. To facilitate the design of new materials, the role of physical and chemical properties on bacterial adhesion is reviewed. The current approaches to reduce bacterial adhesion to various polymeric surfaces are discussed, as well as how multidisciplinary research on surface design and engineering may have an impact on both fundamental and applied microbiological science and technology.

No / This chapter describes the current approaches to reduce bacterial adhesion to various biomaterial surfaces, focusing on nonfouling surfaces through patterning and hydrophobicity plasma-assisted surface treatment and deposition; incorporation of antimicrobials, antibiotics, antibiofilms, and natural extracts that are either immobilized or released; dual function antimicrobial surfaces; incorporation of nonpathogenic bacteria, bacteriophages, and biofilm dispersal agents but also reduced bacterial adhesion through tissue integration. To facilitate the design of new materials, the role of physical, chemical, and biological surface properties on bacterial adhesion is reviewed in each case, as an insight into the chemical and physical cues that affect bacterial adhesion and biofilm formation can provide ideas for creating successful antifouling or antimicrobial surfaces. The application of these surfaces is explored based on the clinical needs and the market gaps. How multidisciplinary research on surface design and engineering may have an impact on both fundamental understanding of bacterial adhesion to biomaterials and applied biomaterial science and technology is finally discussed.

Fímbrias do tipo IV estão associadas a diversos fenótipos em bactérias gram-negativas, e o presente estudo consistiu na caracterização da fímbria Pil e investigação de seu papel na adesão bacteriana de isolados de EPEC atípica. Por PCR e RT-PCR foram investigadas a presença e a funcionalidade do operon Pil e os resultados demonstraram que este está sendo transcrito somente nos isolados BA558 e BA956. Os genes pilS e pilV foram clonados em vetor de expressão para obtenção das proteínas Pil recombinantes e produção de anticorpos policlonais. A análise qualitativa dos testes de inibição da adesão utilizando os soros anti-PilS e anti-PilV juntos demonstraram que o isolado BA558 apresentou mudança de fenótipo de adesão. Esses resultados nos permitem concluir que o operon Pil está funcional em BA558 e BA956, e a expressão da fímbria Pil nessas cepas não está relacionada à formação de biofilme e autoagregação, porém a proteína fimbrial PilS juntamente com a adesina PilV parecem exercer uma função acessória importante na interação de BA558 às células HEp-2. / Type IV fimbriae are associated with several phenotypes in gram-negative bacteria. The aim of this study was the characterization of the Pil fimbria and its role in the interaction of atypical EPEC isolates in bacterial adhesion. Using PCR and RT-PCR, we investigated the presence and functionality of the pil operon genes. The results showed that these genes are transcribed only in the BA558 and BA956 isolates. The pilS and pilV genes were cloned into an expression vector for recombinant proteins and polyclonal antibodies production. Qualitative analysis of the adherence inhibition assays using both rabbit sera changed to localized-like the phenotype of BA558 isolate adhesion. Together, these results allow us to conclude that the Pil operon is functional only in the BA558 and BA956 isolates and that the expression of Pil fimbriae in aEPEC is not related to biofilm formation and autoaggregation but, the fimbrial PilS protein together with PilV adhesin seem to play an important accessory function in the interaction between the BA558 and epithelial cells in vitro.

L'adhésion bactérienne est la première étape du processus de formation d'un biofilm et est un enjeu majeur de la recherche depuis plusieurs dizaines d'années. Les biofilms ont des conséquences parfois dramatiques dans des domaines comme la santé, l'agroalimentaire ou la purification des eaux usées. Toutefois, l'adhésion bactérienne reste un phénomène mal compris. Dans cette thèse, l'adhésion bactérienne est étudiée sur des surfaces modèles très bien organisées et structurées, de chimie de surface variable à l'échelle moléculaire. Une méthodologie de caractérisation adaptée aux monocouches déposées sur wafers de silicium est proposée. Des surfaces modèles composées de monocouches mixtes auto-assemblées de densités variables de NH2 dans un continuum de CH, sont développées et optimisées. Ces surfaces contrôlées, de densités de 0% NH2 à 100% NH2 dans CH3, sont utilisées comme outil pour étudier l'adhésion bactérienne en conditions de culture « batch »et « temps réel ». Les résultats montrent un impact significatif sur l'adhésion bactérienne de faibles différences chimiques à l'échelle moléculaire. Les résultats des expériences menées en conditions « batch » permettent de déterminer deux zones « plateau » dans lesquelles l'adhésion bactérienne ne varie pas significativement malgré des variations importantes de la concentration en groupements amine sur la surface. Une zone de transition entre les zones « plateau » est mise en évidence, dans laquelle une faible modification de la concentration en groupement amine mène à l'augmentation / diminution significative du nombre de bactéries adhérées. Cette tendance est montrée pour deux souches différentes de bactérie. / Bacterial adhesion is the first step of biofilm formation and in the focus of research interest since several decades. Biofilms cause many problems, sometimes dramatic, for example in health, food packing or waste water purification. Despite of high interest, bacterial adhesion process is only poorly understood yet. In this work, bacterial adhesion was investigated on well-organized and structured model surfaces with various chemistries at molecular scale. For that purpose a characterization methodology was developed to sufficiently analyze monolayers on silicon wafers, and controlled mixed monolayers surfaces with different densities of NH 2 backfilled with CH3 were developed and optimized. These controlled surfaces with different densities of 0 % NH2 up to 100% NH2 were eventually used as tool to study bacterial adhesion in batch and real time conditions. The results demonstrate a significant impact on bacterial adhesion of weak difference in the surface chemistry at molecular scale. In the batch experiments, two so-called "plateaus" zones were determined, in which bacterial adhesion is not significantly different despite the change of the amine concentration on the surface. On the contrary, one transition zone exists between the "plateaus" in which a slight chunge.in the amine concentration leads to a significant increase / decrease of the bacterial adhesion. The same trend of bacteria behavior was observed for different bacterial strains.

Les infections bactériennes lorsqu’elles se développent à partir d’implants sont très difficiles à traiter, l’issue courante étant un retrait pur et simple de l’implant incriminé. Dans ce cadre, les revêtements des biomatériaux ont un rôle important à jouer pour, d’une part, prévenir l’adhésion bactérienne et d’autre part, éliminer les bactéries présentes. Ces revêtements antibactériens doivent par ailleurs permettre une intégration tissulaire des biomatériaux aux cellules rencontrées sur le site de l’implantation. Dans ce travail une nouvelle famille de revêtements antibactériens a été développée. Ils contiennent et libèrent de manière contrôlée un agent bioactif. Ils sont constitués de multicouches de polymère plasma d'anhydride maléique déposées à la surface de fibres de polypropylène tressées et constituant le matériau à implanter. Entre chaque dépôt de polymère plasma (agissant comme couche barrière), des nanoparticules d'argent sont piégées formant ainsi des réservoirs d’agent antibactérien. En raison des différences de propriétés mécaniques entre les films minces plasma et le substrat massique élastique (i.e. tissu de fibre de polypropylène), la résistance à la traction génère des fissures dans les couches polymère plasma, qui sont utilisées comme canaux de diffusion pour les substances bioactives (dans notre cas les ions argent). Avant étirement, la libération spontanée des ions argent par simple diffusion aux travers des couches barrières peut être contrôlée en jouant sur le taux de réticulation des couches plasma. Au cours de l'étirement, le contrôle réversible de l'ouverture des fissures permet une libération maîtrisée des ions argent. Dans le domaine des textiles et d'autres biomatériaux souples, cette stratégie est prometteuse en raison des contraintes mécaniques qui se produisent naturellement sur le site de l'implantation.L'impact de différents types de procédures de stérilisation couramment utilisés (autoclave et irradiation par faisceau d’électrons) sur les propriétés du matériau développé a également été étudié. En particulier, l’incidence sur la chimie de surface, la dispersion des nanoparticules d'argent et la formation de fissures sous étirement a été regardée. La méthode de stérilisation par faisceau d’électrons permet de conserver les propriétés finales recherchées. Enfin, les propriétés antibactériennes du nouveau matériau ont été étudiées. L'effet du relargage des ions argent sur des bactéries Escherichia coli planctoniques, l'adhésion bactérienne et la formation de biofilm sur le système étiré et non-étiré a été évalué. L’intégrité membranaire des bactéries adhérées et des bactéries dans les biofilms a été suivie au cours de l'étude comme indicateur de l’état physiologique des bactéries. Les résultats ont suggéré que la sensibilité des bactéries aux concentrations faibles d'ions d'argent libérés aboutit à la formation de différents types de structures de biofilms sur les matériaux étudiés. L’ensemble des résultats obtenus donne une base solide pour le développement de matériaux intelligents capables de contrôler la libération du principe actif sur le site de l'infection. Nos résultats montrent qu’une faible dose d’argent peut suffire à contrôler l’infection en agissant sur la structure des biofilms formés. / Despite strict operative procedures to minimize microbial contaminations, bacterial infection of implants significantly raises postoperative complications of surgical procedures. One of the promising approaches is to adjust and control antimicrobial properties of the implant surface. New types of antibacterial coatings prepared via plasma polymer functionalization step have been developed. These coatings contain and release in a control way a bioactive agent. Controlled release was achieved by the fabrication of plasma polymer multilayer systems, which consist of two layers of Maleic Anhydride Plasma Polymer deposited on the surface of Polypropylene made surgical mesh. In between plasma polymer layers, silver nanoparticles are trapped as an antibacterial agent reservoir. Owing to differences between mechanical properties of the plasma-polymer thin films and the elastic bulk substrates, tensile strengths generate cracks within the plasma polymer, which might be used as diffusive channels for bioactive substances, here silver ions. The cracks can be controlled mechanically in a reversible way. The tailoring of the spontaneous release of bioactive agent is achieved by the modification of the second plasma polymer deposition conditions. In addition, during mechanical stimulation of the designed material, control over silver ion release is achieved through an elongation-dependent releasing process allowed by the reversible control of the cracks. In the field of textiles and other soft biomaterials, this strategy is promising due to the mechanical stresses that naturally occur at the implant location. In regard of possible application of the developed system as a future biomaterial, the impact of different types of commonly used sterilization procedures on the properties of developed material was studied. The effects of autoclaving and electron beam sterilization methods on the surface chemistry, the dispersion of embedded silver nanoparticles in the plasma polymer and the cracks formation of the developed material was verified. Results showed the compatibility of the developed system with electron beam sterilization method. The antibacterial properties of the new material have been evaluated. The effect of developed system on planktonic bacteria, bacterial adhesion and biofilm formation on stretched and unstretched system was studied. The membrane integrity of the adhered bacteria and bacteria in biofilms was followed during the study as an indicator of the physiologic state of bacteria. Results suggested that the sensitivity of bacteria to low concentrations of released silver ions resulted in the formation of different types of structures of the biofilms on the studied materials. The results give a strong base on the future of intelligent, silver containing materials that control the release at the site of infection. Our results show that low doses of silver may be sufficient to control infection by acting on the structure of bacterial biofilms.

1) Objectives: - To systematically evaluate the effectiveness of pharmacist care compared with usual care (UC) on improving adherence to antidepressants in depressed outpatients. - To evaluate the effectiveness and cost‐effectiveness of a community pharmacist intervention (CPI) compared to UC in the improvement of adherence to antidepressants and patient wellbeing in a primary care population initiating treatment with antidepressants. 2) Methods: A systematic review and meta‐analysis of randomized controlled trials (RCTs) that evaluated the impact of pharmacist interventions on improving adherence to antidepressants was conducted. RCTs were identified through electronic databases and manual search. Methodological quality was assessed and methodological details and outcomes were extracted in duplicate. A RCT comparing patients with depressive disorder receiving a low intensity CPI (87) with patients receiving UC (92) was performed in Barcelona. The intervention consisted of an educational programme focused on improving knowledge about medication, improving patients’ compliance and reducing stigma. Measurements took place at baseline, 3 and 6 months. Adherence was continuously registered from the computerized pharmacy records. Secondary outcomes included clinical severity of depression (PHQ‐9), health‐related quality of life (HRQOL) (EuroQol‐5D) and satisfaction with the treatment received. Direct and indirect costs were assessed using the Client Service Receipt Inventory. Unit costs were derived from official local sources. Quality‐Adjusted Life‐Years (QALYs) were calculated using the EuroQol‐5D Spanish tariffs. 3) Results: Six RCTs were identified in the systematic review; most of them were conducted in the USA. A total of 887 depressed patients who were initiating or maintaining treatment with antidepressants and who received pharmacist care (459 patients) or UC (428 patients) were included in the review. The most commonly reported interventions were patient education and monitoring, monitoring and management of toxicity and side effects and compliance promotion. Overall, no statistical heterogeneity or publication bias was detected. The pooled odds ratio was 1.64 (95% CI 1.24‐2.17). Subgroup analysis showed no statistically significant differences in results. Results from the RCT showed that patients in the CPI group were more likely to remain adherent at 3 and 6‐month follow‐up but the difference was not statistically significant. No statistically significant differences were observed in clinical symptoms or satisfaction with the pharmacy service. However, patients in the CPI group showed greater statistically significant improvement in HRQOL compared to UC patients, both in the ITT and PP analyses. Overall costs were higher in the CPI group than in UC patients, mainly because of differences in productivity losses. There were no statistically significant differences between groups in QALYs. From the societal perspective, the incremental cost‐effectiveness ratio (ICER) for CPI compared with UC was €9,335 per extra adherent patient. The incremental cost‐utility ratio (ICUR) was €38,896 per QALY gained. If willingness to pay (WTP) is €50,000 per one extra adherent patient, per extra remission of symptoms or per QALY, the probability of the CPI being cost‐effective was 0.71, 0.52 and 0.56, respectively. From the healthcare perspective, the ICER was €862 per extra adherent patient. ICUR was €3,542. The probability of the intervention being cost‐effective was 0.75 if WTP is €12,000 for an extra adherent patient and €40,000 for QALY gained. The probability of the CPI being cost‐effective in remission of depressive symptoms was 0.55 for a WTP of €50,000. 4) Conclusions: A pharmacist intervention could be a good strategy to improve patients’ adherence to antidepressants in primary care but evidence supporting the pharmacist intervention in depressed patients is still limited, especially in community pharmacies and outside the USA. A low intensity CPI proved to be ineffective in improving patients’ adherence to antidepressants or clinical symptomatology. However, it was effective in improving the patient’s HRQOL. The CPI was not cost‐effective in comparison with UC in the improvement of adherence, depressive symptoms and QALYs.