Quaternary ammonium compounds to prevent oral biofilm formation

Bacteriële besmetting is een voortschrijdend probleem binnen de samenleving. Vooral bacteriën die zijn georganiseerd in een biofilm kunnen resulteren in diverse kostbare en ernstige problemen voor de samenleving. Hoofdstuk 1 geeft een kort overzicht van biofilmformatie en bijbehorende problemen. Er werd toegelicht waarom het lastig is biofilms te bestrijden waarna een materiaal met antimicrobiële eigenschappen werd geïntroduceerd. Quaternaire ammoniumverbindingen (QAC) werden onderzocht om biofilms effectief te kunnen bestrijden. QACs verwerkt in een biomateriaal kunnen biofilms bestrijden door middel van afgifte of door middel van direct contact. Hoofdstuk 2 concentreert zich op antimicrobiële materialen met een QAC. Orale biofilm, bacteriële kolonisatie, is één van de belangrijkste factoren in het ontstaan van cariës. Recente preventieve pogingen hebben zich gericht op het ontwikkelen van materialen met antimicrobiële activiteit door dan wel een antimicrobiële component in de matrix in te mengen of door modificaties van het materiaaloppervlak. Voor het ingemengde antimicrobiële middel geldt dat er eerst een “burst release” van de antimicrobiële stof is, gevolgd door een veel lagere afgifte in de tijd. Dit hoofdstuk bespreekt de literatuur over modificaties die aan het oppervlak worden bevorderd door organosilaanverbindingen of methacrylaat monomeren die quaternair ammonium bevatten als functionele groep en gebruikt kunnen worden in biomedische en tandheelkundige toepassingen. In hoofdstuk 3 werd het antibiofilm effect van een jodide quaternair ammoniummethacryloxy silicaat (IQAMS) gemengd in Transbond XT, een licht uithardend composiet voor het cementeren van orthodontische apparatuur, geëvalueerd. Fouriertransformatie infraroodspectroscopie bevestigde IQAMS-vorming en scanning-elektronenmicroscopie gekoppeld aan energie-dispersieve röntgenspectroscopie liet zien dat de coating met QAC van IQAMS homogeen over het oppervlak en homogeen in het composiet waren verdeeld. Onderzoek met Streptococcus mutans vertoonde een verbeterd antibiofilm effect, veel lagere kolonievormende eenheden (CFU), voor de met IQAMS gecoate composieten dan wanneer IQAMS in het composiet was gemengd. Dit verschil werd toegekend aan de lage beschikbaarheid van quaternaire ammoniumgroepen aan het oppervlak van het composiet na de lichtuitharding wanneer IQAMS werd ingemengd, waardoor het antibiofilm effect werd verminderd. Bovendien leidde het inmengen van IQAMS in het composiet tot een lichte afname van de uiteindelijke hechtingsterkte en afschuifsterkte ten opzichte van het commerciële composiet. Aldus kan het gesynthetiseerde IQAMS als een coating op het composiet dienen als preventieve maatregel bij het gebruik van orthodontische apparatuur. In hoofdstuk 4 zijn de quaternaire ammonium bevattende materialen voor dentale toepassing verder onderzocht. Wanneer adequaat poetsen door gecementeerde orthodontische apparatuur wordt belemmerd, is lokale biofilm accumulatie een veel voorkomend probleem. Om dit probleem aan te pakken, werden polyhydroxyurethaan (PHU) coatings met een quaternair ammoniumzout (QAS) ontwikkeld voor toepassing op roestvrijstalen oppervlakken. Twee hybride polyhydroxyurethanen werden ontworpen waaraan een quaternair ammoniumzout werd gebonden door een sol-gel-proces. Materiaal synthese en het aanbrengen van de coating werd met succes bereikt zoals bevestigd door FTIR-ATR, NMR, XPS en GIXS. De coating was sterk bacteriocide tegen S. mutans door afgifte van antimicrobieel QAS, evenals door het bacteriocide effect bij contact van de S. mutans met de QAS coating. Helaas was het QAS bevattende percolaat ook cytotoxisch voor fibroblasten L929. Om het cytotoxische effect te verminderen werden twee methoden onderzocht: een kortdurende (2 uur) ionenuitwisseling met natriumfosfaat en langdurig (3 dagen) spoelen met gedemineraliseerd water. Geen van de behandelingen beïnvloedde de antimicrobiële eigenschappen van de coating. In tegenstelling tot de kortdurende ionenuitwisselsmethode, verminderde 3 dagen wassen met water de cytotoxiciteit na 7 dagen uitlekken in medium. Concluderend, PHU-QAS coating, indien gespoeld, is een betrouwbare behandeling om antimicrobiële eigenschappen aan roestvrij stalen orthodontische apparatuur te geven. Op basis van de prestaties van QAC bevattende coatings, richt hoofdstuk 5 zich op de opname van QAC in een commercieel dentaal sealant om toegepast te worden als coating op het oppervlak van restauraties. Het doel van deze studie was om een commerciële sealant te evalueren met betrekking tot de mechanische weerstand tegen slijtage door poetsen en de antimicrobiële werking van de sealant wanneer een QAC werd toegevoegd. Tandenpoets cycli, SEM en S. mutans biofilmvorming werden uitgevoerd op 4 oppervlakken: restauratieve composiet Z350 XT, composiet met BisCover sealant, composiet met QAC-coating en composiet met de BisCover sealant die QAC bevat. De morfologie van de gepoetste en niet gepoetste oppervlakken werd kwalitatief vergeleken met SEM en de antimicrobiële werking werd gemeten door biofilm formatie en CFU/cm2 bepaling. De antimicrobiële activiteit van QAC puur was gelijk aan QAC toegepast als een coating en QAC toegevoegd aan BisCover sealant. Na poetsen (vergelijkbaar met 2,5 maand tandenpoetsen) werd de antimicrobiële activiteit verminderd, maar CFU/cm2 van de QAC-coating groep was significant lager dan van de andere oppervlakken. SEM-afbeeldingen lieten zien dat QAC bevattend BisCover beter bestand was tegen poetsen. Hoofdstuk 6 bevat een kritische analyse van de uitgevoerde onderzoeken en licht toe waarom er aanpassingen zijn gedaan in vervolg onderzoeken. Ook aspecten die nog kunnen worden onderzocht, zoals cytotoxiciteit en bacteriële resistentie tegen QAC werden gesuggereerd als vervolgonderzoekBacterial contamination is a topic of great concern for scientific community, especially bacteria organized into biofilms can lead to deleterious and costly problems to society. Materials with antimicrobial activity for dental or medical application came into this scenario as good alternative to tackle bacteria related issues. The antimicrobial activity can be achieved by different manners, this thesis focuses on materials containing quaternary ammonium compounds, known for its efficacy against great variety of bacteria. Also, aiming a future application in dentistry to diminish the risk of caries, the inclusion of quaternary ammonium compounds was assessed in commercialized dental materials. New coatings containing quaternary ammonium were as well developed to be applied on metallic orthodontic devices. These series of studies indicate a possible path for preventing dental caries with the aid of antimicrobial materials

Physical, chemical and antimicrobial properties evaluation of a resin based material for braces cementation containing different concentrations of quaternary ammonium

Orientadores: Flávio Henrique Baggio Aguiar, Ubirajara Pereira Rodrigues FilhoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: A fixação de acessórios ortodônticos na cavidade bucal favorece maior acúmulo de biofilme dental. Para minimizar o risco do desenvolvimento de lesões cariosas, materiais utilizados para fixação destes acessórios acrescidos de grupamentos químicos funcionais com efeito antimicrobiano têm sido desenvolvidos. Desta forma, os objetivos deste estudo foram: 1) Sintetizar e caracterizar um organossilano modificado por amônias quaternárias (ORMOSIL-QAMS); 2) Avaliar as propriedades físico-químicas da resina Transbond XT Light Cure Adhesive (3M Unitek) acrescida de 10% e 15% em massa de ORMOSIL-QAMS e 3) Avaliar o efeito antimicrobiano do acréscimo de 10% e 15%, em massa, de ORMOSIL-QAMS à resina Transbond XT ou aplicando-o como material de recobrimento. O ORMOSIL-QAMS foi sintetizado por uma reação de hidrólise e condensação (sol-gel). Na primeira etapa, alcoxissilanos contendo amônias quaternárias foram obtidos. Em seguida, uma rede silicato englobando os alcoxissilanos foi criada, levando à formação do ORMOSIL-QAMS. O produto da síntese foi caracterizado por espectroscopia de infravermelho e fluorescência de Raios-X. Os testes de grau de conversão (DC) (n=7); sorção de água (Wsp) (n=9); solubilidade (Wsl) (n=9); resistência coesiva (UTS) (n=10) e resistência ao cisalhamento (SBS) (n=10) foram realizados após 24 h da confeccção dos espécimes para os grupos: T ¿ Resina Transbond XT Light Cure Adhesive; T10% - Resina Transbond XT contendo 10%, em massa de ORMOSIL-QAMS; T15% - Resina Transbond XT contendo 15% em massa, de ORMOSIL-QAMS. Para avaliar o efeito antimicrobiano um grupo de estudo foi adicionado: TC ¿ Resina Transbond XT recoberta por duas camadas de ORMOSIL-QAMS. A formação de biofilme de Streptococcus mutans UA159 foi realizada em corpos-de-prova de resina correspondente a cada grupo, utilizando meio de cultura Brain Heart Infusion (BHI) com 1% de sacarose por 24 h a 37°C e 5% de CO2. Os dados de propriedades físico-químicas foram submetidos à análise ANOVA e Tukey pós-teste (?=0,05). Os dados obtidos do ensaio de formação de biofilme foram submetidos à análise não paramétrica Kruskall-Wallis e pós-teste Student-Newman-Keuls (?=0,05). A espectroscopia por infravermelho confirmou a presença da rede silicato e dos grupos de amônia quaternária. A fluorescência de Raios-x detectou a presença dos elementos silício e iodo. O DC dos compósitos não diferiu (p>0,05). Quanto maior a quantidade de ORMOSIL-QAMS inserido na resina composta, menores taxas de sorção de água e solubilidade foram observadas (p0,05). Apenas a aplicação do ORMOSIL-QAMS como material de recobrimento apresentou atividade antimicrobiana. Concluiu-se que a adição de ORMOSIL-QAMS reduziu a resistência coesiva e ao cisalhamento da resina para fixação de bráquetes. No entanto, a utilização como material de resobrimento de superfície promoveu redução significativa da formação biofilme 24 h de S. mutansAbstract: Despite the great need and applicability of orthodontic treatment, most of them include cementation of orthodontic brackets and other metal accessories on tooth surface. Recently, the chemical composition of dental materials has been explored to obtain some specific properties. With regard to composite resins for bonding fixed appliances in orthodontics, antibacterial property is desirable due to cleaning difficulties and biofilm accumulation. Thus the aim of this study was to develop an organosilane with quaternary ammonium group (ORMOSIL-QAMS) and assess chemical and physical properties of Transbond XT Light Cure Adhesive containing 10 wt% and 15 wt% ORMOSIL-QAMS. Furthermore, the study aimed to evaluate its antimicrobial effect incorporated (10 wt% and 15 wt%) to Transbond XT Light Cure Adhesive (3M Unitek) or used as a coating material. A reaction of hydrolysis and condensation (sol-gel) was employed to develop ORMOSIL-QAMS. On the first step, alkoxysilanes containing quaternary ammonium group were obtained. Then a silicate network wrapping the quaternary ammonium was created, leading to the formation of ORMOSIL-QAMS. Synthesis product was characterized by infrared spectroscopy and X-Ray fluorescence. Degree of conversion (DC) (n=7); water sorption (Wsp) (n=9); solubility (Wsl) (n=9); ultimate tensile strength (UTS) (n=10) and shear bond strength (SBS) (n=10) tests were done after 24 h of storage, for the following groups: T ¿ composite resin Transbond XT; T10% - Transbond XT containing 10 wt% of ORMOSIL-QAMS; T15% - Transbond XT containing 15 wt% of ORMOSIL-QAMS. For antibacterial properties one group was added: TC ¿ Transbond XT covered by two layers of ORMOSIL-QAMS. Streptococcus mutans UA159 were grown for 24 h in Brain-Heart-Infusion (BHI) supplemented with 1% sucrose at 37 °C and 5% CO2. Physico-chemical properties data were subjected to ANOVA and Tukey¿s post hoc test (?=0.05). The antibacterial test values were subjected to non-parametric Kruskal-Wallis and Student-Newman-Keuls test (? = 0.05). The DC did not differ between groups (p>0.05). Water sorption and solubility decreased as the percentage of ORMOSIL-QAMS inserted increased (p0.05). Only the coating application resulted in less S. mutans biofilm formation in 24 hours (p<0.05). Based on this study it is possible to conclude that incorporating ORMOSIL-QAMS to Transbond XT adversely affected shear bond strength and ultimate tensile strength properties. Additionally, ORMOSIL-QAMS presented the expected antimicrobial activity when applied as coating on the sample surface, diminishing S. mutans biofilm formation considerablyMestradoDentísticaMestra em Clínica Odontológica2013/15518-5FAPES

Application of the residue number system to the matrix multiplication problem

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references.Not availabl

Involvement of Bruton's Tyrosine Kinase in FcεRI-dependent Mast Cell Degranulation and Cytokine Production

We investigated the role of Bruton's tyrosine kinase (Btk) in FcεRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcεRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcεRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcεRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcεRI signal transduction in mast cells

Randomized, crossover questionnaire survey of acceptabilities of controlled-release mesalazine tablets and granules in ulcerative colitis patients

Background/Aims Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. Methods UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. Results A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). Conclusions CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication

Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004

We analyze the data of TAMA300 detector to search for gravitational waves from inspiraling compact star binaries with masses of the component stars in the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the years 2000-2004, are used for the event search. We combine the results of different observation runs, and obtained a single upper limit on the rate of the coalescence of compact binaries in our Galaxy of 20 per year at a 90% confidence level. In this upper limit, the effect of various systematic errors such like the uncertainty of the background estimation and the calibration of the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was correcte

Observation results by the TAMA300 detector on gravitational wave bursts from stellar-core collapses

We present data-analysis schemes and results of observations with the TAMA300 gravitational-wave detector, targeting burst signals from stellar-core collapse events. In analyses for burst gravitational waves, the detection and fake-reduction schemes are different from well-investigated ones for a chirp-wave analysis, because precise waveform templates are not available. We used an excess-power filter for the extraction of gravitational-wave candidates, and developed two methods for the reduction of fake events caused by non-stationary noises of the detector. These analysis schemes were applied to real data from the TAMA300 interferometric gravitational wave detector. As a result, fake events were reduced by a factor of about 1000 in the best cases. The resultant event candidates were interpreted from an astronomical viewpoint. We set an upper limit of 2.2x10^3 events/sec on the burst gravitational-wave event rate in our Galaxy with a confidence level of 90%. This work sets a milestone and prospects on the search for burst gravitational waves, by establishing an analysis scheme for the observation data from an interferometric gravitational wave detector