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    Celulose bacteriana como penso curativo

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    Tese de doutoramento em Biomedical EngineeringWounds, in particular traumatic (e.g. burns) and chronic ones, are a major cause of morbidity, impaired life quality and high health care costs. They often result in long hospitalization stays, taking up substantial health resources in developed countries. Conventional treatments are often painful, expensive and may increase the infection risk, compromising the treatments‚Äô time and success. In recent years, there have been efforts to develop new advanced methodologies to heal chronic wounds, including the topic use of growth factors or cell-based therapies. However, in many cases, the therapeutic efficacy is low, the therapies are expensive and require application in a clinical facility. Therefore, development of new therapeutics is absolutely necessary and important to satisfy these unmet clinical needs. So, this work comprised the development of a safe, easy-to-use and non expensive novel dressing, aimed at efficiently addressing these issues, by attaining faster and proper wound healing. The use of bacterial nanocellulose (BNC) has already demonstrated positive results in the treatment of different kinds of wounds. Additionally, BNC is considered a promising drug delivery system. In this work, BNC was conceived as a protective barrier against exogenous agents (particles, microorganisms) that can impair wound healing, and as a drug carrier for the controlled release of hydrophobic drugs, namely of vitamin D3 (Vit D3 ), an inducer of the endogenous expression of antimicrobial peptide (AMP) LL37, known for accelerating the wound healing process. In a first part of this project, the optimization of the static BNC production was performed, aiming at making it viable and economic at large scale. First, an experimental design, based on response surface methodology (RSM) - central composite design (CCD) - was used to optimize the culture medium for BNC production by Komagataeibacter xylinus BPR 2001, using a simple culture medium composition based on byproducts from the food industry. The optimal conditions for BNC production were (% (m/v)): molasses 5.38; CSL 1.91; ammonium sulphate 0.63; disodium phosphate 0.270; citric acid 0.115 and ethanol 1.38 % (v/v). The experimental and predicted maximum BNC production yields were 7.5 ¬Ī0.54 g/L and 6.64 ¬Ī0.079 g/L, respectively, after 9 days at 30 ¬ļC. Furthermore, the effect of the surface area and culture medium depth on the BNC production yield and productivity were evaluated. BNC dry mass production increased with the surface area and with the medium volume (depth) and fermentation time. Also, as long as nutrients were still available in the culture media, the BNC mass productivity was maintained overtime. The pre-inoculum preparation (PIP) step was also optimized with regards to the (a) identification of an inexpensive culture medium for pre-inoculum leading to a high cell density; (b) analysis of the effect of the initial cellular concentration on the static production of BNC and (c) kinetics of cell growth throughout the different steps of pre-inoculum preparation, including static and stirred - laboratorial and pilot-scale ‚Äď fermentations. The best composition for PIP medium was (% (m/v)): Glucose and Fructose syrup 1.5- 2.0; Corn Step Liquor (protein basis) 0.7; citric acid 0.115; Na2HPO4 0.27. The analysis of the cell growth kinetics in the different steps of PIP showed that a careful control on the culture time in each stage is advisable. The time required to reach the exponential phase was very different in each stage of PIP, reducing significantly from the static culture to the stirred culture and for large scale stirred culture, in a 75 L Bioreactor. In a second part of this work, the use of BNC as a drug carrier was addressed. Since Vit D3 is poorly water soluble, and thus not easily incorporated in the highly hydrophilic environment of the BNC membrane, Vit D3 was encapsulated in a self-assembled hyaluronic acid (HA)-based amphiphilic nanogel and then incorporated in the BNC membrane. The carrier was obtained by grafting hexadecylamine (Hexa) into the HA backbone (HA-Hexa). Vit D3 was successfully loaded into the nanogel (HA-Vit D3 ) with an encapsulation efficiency between 60-91 %. The loaded system- HA-Vit D3 - was embedded into BNC, conceived as a transdermal delivery system. The release of Vit D3 was monitored over time using a Franz cell device. Around 70 % of the initial Vit D3 available was released from BNC membranes in the first 48 h. Most importantly, we observed that the released Vit D3 still remained within the HA-Hexa nanogel carrier. Vit D3 is known to stimulate the endogenous production of human cathelicidin (LL37), which is known to accelerate wound healing. Thus, formulations of HA-Vit D3 and HA-LLKKK18 (an analogue of LL37) were tested in vivo, using excision and chronic wound in dexamethasone treated C57BL/6 and db+/db+ mice models, as to evaluate and compare their efficiency in wound repairing. However, the results did not confirm any wound healing improvement.As feridas cr√≥nicas e traum√°ticas (e.g. queimaduras) apresentam uma elevada morbilidade, afetando severamente a qualidade de vida dos pacientes. Os tratamentos convencionais implicam longos per√≠odos de interna√ß√£o hospitalar, com significativo consumo de recursos dos sistemas de sa√ļde nos pa√≠ses desenvolvidos. Al√©m disso, s√£o dolorosos, caros e podem aumentar o risco de infe√ß√£o, comprometendo a dura√ß√£o e o sucesso dos tratamentos. Recentemente, t√™m sido desenvolvidos esfor√ßos para o desenvolvimento de novas metodologias avan√ßadas para o tratamento de feridas cr√≥nicas, incluindo a aplica√ß√£o t√≥pica de fatores de crescimento ou terapias baseadas em c√©lulas. Em muitos casos, estas novas abordagens s√£o caras, devendo ser realizadas numa unidade hospitalar, e a sua efic√°cia terap√™utica √© baixa. Assim, o desenvolvimento de novas solu√ß√Ķes para satisfazer esta necessidade cl√≠nica ainda n√£o satisfeita √© absolutamente necess√°rio. Com este trabalho pretende se desenvolver um penso curativo eficiente, inovador, f√°cil de usar e n√£o dispendioso, atrav√©s de uma abordagem segura, visando uma cicatriza√ß√£o mais r√°pida e adequada da ferida. A nanocelulose bacteriana (BNC) demonstrou j√° resultados positivos no tratamento de diferentes tipos de feridas, assim como foi j√° demonstrado tamb√©m o seu potencial como sistema de entrega de f√°rmacos. Neste trabalho, a BNC foi utilizada como ve√≠culo para a liberta√ß√£o controlada de mol√©culas hidrof√≥bicas, nomeadamente a vitamina D3 (Vit D3 ), que √© um indutor da express√£o end√≥gena do pept√≠do antimicrobiano LL37, conhecido por acelerar o processo de cicatriza√ß√£o de feridas. Al√©m disso, a BNC funciona como uma barreira protetora contra agentes ex√≥genos (poeiras, microorganismos) que podem prejudicar a cicatriza√ß√£o de feridas. Numa primeira parte, foram desenvolvidos trabalhos visando tornar a produ√ß√£o em grande escala de BNC em cultura est√°tica econ√≥mica e vi√°vel. Nesse sentido, foi usado um desenho experimental, baseado na metodologia de superf√≠cie de resposta (RSM) - planeamento composto central (CCD) - para otimizar o meio de cultura, usando subprodutos da ind√ļstria alimentar. Foi utilizada a estirpe Komagataeibacter xylinus BPR 2001, a 30 ¬ļC. Foram identificadas as seguintes condi√ß√Ķes √≥timas para a produ√ß√£o de BNC (% (m/v)): mela√ßo 5,38, xarope de milho (CSL) 1,91; sulfato de am√≥nio 0,63; fosfato diss√≥dico 0,270; √°cido c√≠trico 0,115 e etanol 1,38 % (v/v). Os rendimentos m√°ximos experimentais e previstos de produ√ß√£o de BNC foram 7,5 ¬Ī0,54 g/L e 6,64 ¬Ī0,079 g/L, respetivamente, ap√≥s 9 dias. Adicionalmente, foram avaliados o efeito da √°rea superficial e da profundidade/altura do meio de cultura no rendimento e produtividade em BNC. Verificou-se que a produ√ß√£o de BNC aumenta com a √°rea superficial, com o volume de meio de cultura (profundidade) e com o tempo de fermenta√ß√£o. Al√©m disso, observou-se que a produtividade de BNC se mant√©m constante at√© se esgotarem os nutrientes no meio de cultura. Para a etapa de prepara√ß√£o pr√©-in√≥culo (PIP), a otimiza√ß√£o consistiu em diferentes estudos, especificamente: (a) otimiza√ß√£o dum meio de cultura de custos reduzidos, que permita a obten√ß√£o de uma elevada densidade celular; (b) avalia√ß√£o do efeito da concentra√ß√£o celular inicial na produ√ß√£o est√°tica de BNC e (c) estudo da cin√©tica de crescimento celular ao longo das diferentes etapas de PIP. A melhor composi√ß√£o para o PIP foi (% (m/v)): xarope de glucose e frutose 1,5- 2,0; CSL 0,7; √°cido c√≠trico 0,115 e Na2HPO4 0,27. Os estudos de cin√©tica de crescimento celular para as diferentes etapas do PIP evidenciam a necessidade dum controle cuidadoso do tempo de cultura em cada etapa do PIP. O tempo necess√°rio para atingir a fase exponencial foi muito diferente em cada fase do PIP, reduzindo significativamente da cultura est√°tica, para a cultura agitada, e para cultura agitada em larga escala num bioreator de 75 L. A segunda parte do trabalho relaciona-se com o desenvolvimento da BNC como sistema de entrega de f√°rmacos. A Vit D3 √© pouco sol√ļvel em √°gua e, portanto, n√£o √© facilmente incorporada no ambiente altamente hidrof√≠lico como o da membrana de BNC. Para esse efeito foi usado um nanogel anfif√≠lico auto-organizado obtido pela liga√ß√£o de hexadecilamina (Hexa) na cadeia do √°cido hialur√≥nico (HA). A Vit D3 foi ent√£o encapsulada no nanogel de (HA-Hexa) e em seguida impregnada na membrana de BNC, com uma efici√™ncia de encapsula√ß√£o entre 60-91 %. A liberta√ß√£o da Vit D3 foi monitorizada ao longo do tempo, usando uma c√©lula de Franz e realizando estudos de permea√ß√£o. Observou-se a liberta√ß√£o de cerca de 70 % da Vit D3 , ainda dentro do nanogel de HA-Hexa, das membranas de BNC em 48h. Finalmente, foi testada a utiliza√ß√£o de HA-Vit D3 e de HA-LLKKK18 (um p√©ptido an√°logo √† LL37) em modelos de feridas de excis√£o e cr√≥nicas em ratinhos tratados com dexametasona e diab√©ticos tipo II (db + / db +) C57BL/6. No entanto, os resultados n√£o revelaram uma maior efici√™ncia na cicatriza√ß√£o de feridas na presen√ßa das referidas formula√ß√Ķes.Ao Projeto BioTecNorte (NORTE-01-0145-FEDER-000004), n¬ļ 003435: ‚ÄúBUILD ‚Äď Bacterial cellulose Leather‚ÄĚ, financiado pelo Fundo Europeu de Desenvolvimento Regional (FEDER) atrav√©s do Programa Operacional do Regional do Norte (NORTE 2020) e ao projeto SkinChip: Disruptive cellulose-based microfluidic device for 3D skin modelling, PTDC/BBB-BIO/1889/2014 e ainda √† Funda√ß√£o para a Ci√™ncia e Tecnologia no √Ęmbito do financiamento estrat√©gico da unidade UID / BIO / 04469/2019 e pela atribui√ß√£o da bolsa de doutoramento SFRH/BD/89547/2012

    The place where curses are manufactured : four poets of the Vietnam War

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    The Vietnam War was unique among American wars. To pinpoint its uniqueness, it was necessary to look for a non-American voice that would enable me to articulate its distinctiveness and explore the American character as observed by an Asian. Takeshi Kaiko proved to be most helpful. From his novel, Into a Black Sun, I was able to establish a working pair of 'bookends' from which to approach the poetry of Walter McDonald, Bruce Weigl, Basil T. Paquet and Steve Mason. Chapter One is devoted to those seemingly mismatched 'bookends,' Walt Whitman and General William C. Westmoreland, and their respective anthropocentric and technocentric visions of progress and the peculiarly American concept of the "open road" as they manifest themselves in Vietnam. In Chapter, Two, I analyze the war poems of Walter McDonald. As a pilot, writing primarily about flying, his poetry manifests General Westmoreland's technocentric vision of the 'road' as determined by and manifest through technology. Chapter Three focuses on the poems of Bruce Weigl. The poems analyzed portray the literal and metaphorical descent from the technocentric, 'numbed' distance of aerial warfare to the world of ground warfare, and the initiation of a 'fucking new guy,' who discovers the contours of the self's interior through a set of experiences that lead from from aerial insertion into the jungle to the degradation of burning human feces. Chapter Four, devoted to the thirteen poems of Basil T. Paquet, focuses on the continuation of the descent begun in Chapter Two. In his capacity as a medic, Paquet's entire body of poems details his quotidian tasks which entail tending the maimed, the mortally wounded and the dead. The final chapter deals with Steve Mason's JohnnY's Song, and his depiction of the plight of Vietnam veterans back in "The World" who are still trapped inside the interior landscape of their individual "ghettoes" of the soul created by their war-time experiences

    Educació postural: avaluació dels coneixements de la salut de l'esquena en activitats de la vida diària en estudiants d'Educació Secundària

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    Objectiu: Dissenyar i validar un q√ľestionari sobre coneixements de la salut i la cura de l‚Äôesquena en activitats de la vida di√†ria en joves Tamb√© analizar diferents models de puntuaci√≥ de les respostes. Metodologia: Es va seguir un m√®tode general de prospectiva (Delphi), amb el consens d‚Äôun grup de sis experts. Estudi de consistencia interna i fiabilitat en una mostra de 89 xics i 80 xiques. Amb les dades obteses aplicaci√≥ de cinc models de puntuaci√≥ basats en donar un pes diferent a les respostes. Consist√®ncia interna del q√ľestionari calculada amb l'Alfa de Cronbach amb cadasc√ļ dels models. Estudi de la fiabilitat amb l'an√†lisi de mesures repetides test-retest i l‚Äôestudi de l‚Äôerror de mesura amb la representaci√≥ gr√†fica dels valors descrita per Bland i Altman. Es calcularen les desviacions est√†ndard de les difer√®ncies, la prova t per a una mostra amb les difer√®ncies, els coeficients de correlaci√≥ intraclasse i els seus intervals de confian√ßa del 95%, l‚Äôerror est√†ndard de mesura, el canvi m√≠nim detectable i el coeficient de reproductibilitat. Efecte s√≤l/sostre calculat amb els percentatges de resposta m√©s alts i m√©s baixos en les puntuacions del primer passe. Per a l'an√†lisi de la capacitat discriminat√≤ria de les puntuacions obtingudes es van utilitzar les mitjanes totals del primer passe, es va reagrupar la variable en quatre grups per quartils i es va aplicar una ANOVA d'un factor entres el quartil 1 y el quartil 4. Resultats: An√†lisi de la validesa tots els valors obtesos sobre la consist√®ncia interna s√≥n iguals o majors a .6 Als diferents models, l'Alfa de Cronbach va oscil¬∑lar entre .6 i .7. En la representaci√≥ de les puntuacions mitjanes de totes dues passades i el c√†lcul del pendent de la seua funci√≥ lineal hi ha una relaci√≥ positiva entre les mesures. El valor del pendent, en tots els models al voltant de .7 excepte en el model C que va ser de .56. L‚Äô√≠ndex de determinaci√≥ va mostrar un nivell de coher√®ncia de les mesures reals amb les te√≤riques moderat Coeficient de correlaci√≥ entre les puntuacions i el coeficient de correlaci√≥ intraclasse igual o major a .75. Error de mesura i l√≠mits d'acord de les puntuacions calculats a partir de la desviaci√≥ t√≠pica de la difer√®ncia de les mitjanes van indicar una probabilitat molt baixa de ser diferents entre ells. L'efecte s√≤l/sostre va indicar que aquest efecte no es va produir L'an√†lisi de regressi√≥ de les mitjanes i difer√®ncies de les puntuacions totals de tots els models va indicar un augment significatiu de les difer√®ncies en les puntuacions a mesura que el valor mitj√† d'aquestes va augmentar. Les difer√®ncies entre tots els models van ser significatives. Conclusions: Es presenta un q√ľestionari per a mesurar els coneixements sobre la postura corporal i la cura de l'esquena en activitats de la vida di√†ria en adolescents validat. Es determina que les mateixes dades, es poden analitzar utilitzant diferents models, proporcionant cadascun d#aquests informaci√≥ diferent

    Building body identities - exploring the world of female bodybuilders

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    This thesis explores how female bodybuilders seek to develop and maintain a viable sense of self despite being stigmatized by the gendered foundations of what Erving Goffman (1983) refers to as the 'interaction order'; the unavoidable presentational context in which identities are forged during the course of social life. Placed in the context of an overview of the historical treatment of women's bodies, and a concern with the development of bodybuilding as a specific form of body modification, the research draws upon a unique two year ethnographic study based in the South of England, complemented by interviews with twenty-six female bodybuilders, all of whom live in the U.K. By mapping these extraordinary women's lives, the research illuminates the pivotal spaces and essential lived experiences that make up the female bodybuilder. Whilst the women appear to be embarking on an 'empowering' radical body project for themselves, the consequences of their activity remains culturally ambivalent. This research exposes the 'Janus-faced' nature of female bodybuilding, exploring the ways in which the women negotiate, accommodate and resist pressures to engage in more orthodox and feminine activities and appearances

    Ash Wednesday - 2 March 2022

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    Mechanically Tuneable Physical Nanocomposite Hydrogels from Polyelectrolyte Complex Templated Silica Nanoparticles for Anionic Therapeutic Delivery

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    Hydrogels have shown great promise for drug delivery and tissue engineering but can be limited in practical applications by poor mechanical performance. The incorporation of polymer grafted silica nanoparticles as chemical or physical crosslinkers in in situ polymerised nanocomposite hydrogels has been widely researched to enhance their mechanical properties. Despite the enhanced mechanical stiffness, tensile strength, and self-healing properties, there remains a need for the development of simpler and modular approaches to obtain nanocomposite hydrogels. Herein, we report a facile protocol for the polyelectrolyte complex (PEC) templated synthesis of organic-inorganic hybrid poly(ethylenimine) functionalised silica nanoparticles (PEI-SiNPs) and their use as multifunctional electrostatic crosslinkers with hyaluronic acid (HA) to form nanocomposite hydrogels. Upon mixing, electrostatic interactions between cationic PEI-SiNPs and anionic HA resulted in the formation of a coacervate nanocomposite hydrogel with enhanced mechanical stiffness that can be tuned by varying the ratios of PEI-SiNPs and HA present. The reversible electrostatic interactions within the hydrogel networks also enabled self-healing and thixotropic properties. The excess positive charge present within the PEI-SiNPs facilitated high loading and retarded the release of the anionic anti-cancer drug methotrexate from the nanocomposite hydrogel. Furthermore, the electrostatic complexation of PEI-SiNP and HA was found to mitigate haemotoxicity concerns associated with the use of high molecular weight PEI. The method presented herein offers a simpler and more versatile strategy for the fabrication of coacervate nanocomposite hydrogels with tuneable mechanical stiffness and self-healing properties for drug delivery applications

    Desarrollo de materiales bioactivos con potencial aplicación odontológica mediante impregnación asistida por CO2 supercrítico

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    Tesis (DCI)--FCEFN-UNC, 2021En esta tesis se estudi√≥ el proceso de incorporaci√≥n de eugenol en fibras de poliamida 6 (PA6) mediante la impregnaci√≥n asistida por CO2 supercr√≠tico para desarrollar un material con propiedades antimicrobianas con una potencial aplicaci√≥n odontol√≥gica. Para este prop√≥sito, se construy√≥ un equipo de alta presi√≥n en el que se llevaron a cabo m√ļltiples ensayos de impregnaci√≥n de eugenol y de sorci√≥n de CO2 en un hilo dental comercial de PA6 en distintas condiciones de presi√≥n y temperatura (40 ‚Äď 60 ¬įC y 8 ‚Äď 12 MPa). Con el fin de encontrar las mejores condiciones del proceso de impregnaci√≥n, se evalu√≥ la influencia de diferentes variables operativas (presi√≥n, temperatura, tiempo de contacto y velocidad de despresurizaci√≥n) sobre la cantidad de eugenol impregnada en el material. Adem√°s, se estudiaron los principales fen√≥menos difusivos que ocurren en el proceso de impregnaci√≥n del eugenol en condiciones supercr√≠ticas. Para ello, se hicieron ensayos de cin√©tica de sorci√≥n del CO2 y del eugenol en PA6 a diferentes condiciones de presi√≥n y temperatura y se determin√≥ el coeficiente de difusi√≥n aparente para ambas especies en este pol√≠mero. Por otra parte, se evaluaron las propiedades finales del material impregnado, analizando las propiedades mec√°nicas, t√©rmicas y morfol√≥gicas del material original, presurizado con CO2 e impregnado con eugenol. Adicionalmente se evalu√≥ la actividad antimicrobiana del material impregnado frente a dos bacterias comunes (Escherichia coli y Staphylococcus aureus). Asimismo, se estudi√≥ la migraci√≥n del compuesto activo impregnado en aire y en saliva artificial, obteniendo datos importantes para el potencial desarrollo de un producto comercial, como la estimaci√≥n de la vida √ļtil, el tipo de envase, y tipo de aplicaci√≥n del producto. Finalmente, se hizo un dise√Īo y dimensionamiento de un proceso industrial para la impregnaci√≥n de eugenol en bobinas de fibras de PA6 en CO2 supercr√≠tico, a partir de los datos de eficiencia de impregnaci√≥n y par√°metros difusivos del hilo impregnado con eugenol previamente obtenidos, realizando el dise√Īo de la bobina, el equipo impregnador y los c√°lculos de sus principales requerimientos de masa y energ√≠a.Fil: Mosquera Ruiz, Jos√© Euliser. Universidad Nacional de C√≥rdoba. Facultad de Ciencias Exactas, F√≠sicas y Naturales; Argentina.Fil: Mosquera Ruiz, Jos√© Euliser. Consejo Nacional de Investigaciones Cient√≠ficas y T√©cnicas. Instituto de Investigaci√≥n y Desarrollo en Ingenier√≠a de Procesos y Qu√≠mica Aplicada; Argentina
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