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Dissertations / Theses on the topic 'Nano medicine'
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Lavryk, D. "The use of nano-robots in medicine." Thesis, Sumy State University, 2017. http://essuir.sumdu.edu.ua/handle/123456789/62558.
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Today, more and more people question the treatment without surgery. Thanks to modern research and the efforts of scientists a new possible way to use nano-robots was invented. The first thing to know about nanorobots in medicine is that they're not like the robots you're probably imagining. Scientists who build nanorobots are building tiny packages that can complete tasks in an automated way.
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Feil, Florian. "Single molecule diffusion studies in nanoporous systems: From fundamental concepts to material science and nano-medicine." Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-144120.
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André, Emilie. "Combination of nano and microcarriers for stem cell therapy of Huntington's disease : new regenerative medicine strategy." Thesis, Angers, 2015. http://www.theses.fr/2015ANGE0047/document.
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La combinaison de biomatériaux et cellules souches, a pour but de protéger des cellules endommagées et de ralentir la progression des maladies neurodégénératives, comme la maladie de Huntington (MH). Les cellules souches mésenchymateuses et particulièrement une sous-population, les cellules MIAMI, ont déjà démontré leur efficacité dans la maladie de Parkinson. Il est cependant essentiel d’améliorer leur différenciation neuronale, leur survie et évaluer leur sécrétome. L’objectif principal de ce travail fut de proposer une stratégie innovante de médecine régénératrice pour la MH associant cellules souches, nano et micro médecines. Pour l’évaluer, un nouveau modèle animale ex vivo de la MH a été mis en place. Nous avons ensuite développé et optimisé deux nano-vecteurs, des nanocapsules lipidiques et des nanoparticules solides de SPAN, et les avons associés à un inhibiteur de REST qui est un facteur de transcription qui empêche la différenciation neuronale. La transfection de ce siREST a montré une amélioration du phénotype neuronal. Ces cellules ainsi modifiées furent ensuite induites vers un phénotype GABAergic grâce à des facteurs de croissance. Puis elles ont été associées à un support 3D, les microcarriers pharmacologiquement actif (MPA) permettant une meilleure intégration des cellules après greffe. Les MPA sont des microsphères ayant une surface biomimétique de laminine et libérant de façon contrôlée un facteur trophique le « brain derived neurotrophic factor » (inducteur d’un phénotype neuronal et neuro-protecteur). Des résultats prometteurs ont été obtenus, encourageant à continuer l’évaluation de cette stratégie in vivo dans des modèles génétiques de la MH<br>The combination of biomaterials and stem cells aims to protect damaged cells and slow the progression of neurodegenerative diseases such as Huntington's disease(HD). Mesenchymal stem cells, particularly a subpopulation known as MIAMI cells, have already demonstrated their effectiveness in Parkinson's disease. However, it is essential to improve their neuronal differentiation, survival, and to assess their secretome. The main objective of this work was to propose an innovative regenerative medicine strategy for HD by combining stemcells, micro and nano medicines. To perform this assessment, a new ex vivo animal model of HD has been set up. We then developed and optimized two nanovectors,lipid nanocapsules and solid SPAN nanoparticles,carrying an inhibitor of REST a transcription factor, which prevents neuronal differentiation. The transfection of this siREST showed an improvement in the neuronal phenotype. These modified cells were then induced into a GABAergic phenotype through growth factors. They were then associated with a 3D support, the pharmacologically active microcarriers (PAM) allowing a high rate of engraftment. The PAM are microspheres which have a biomimetic surface of laminin and release a trophic factor BDNF, brain derived neurotrophic factor (inducer of a neural phenotype and neuroprotective) in a controlled manner. Promising results were obtained, further encouraging continuing the evaluation of this strategy in vivo in genetic models of HD
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Memarzadeh, Kaveh. "Investigations into the use of nano-based antimicrobial and osteoconductive coatings for bone implants." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/9001.
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Objectives: Orthopaedic and dental implants are prone to frequent infections. This can lead to detrimental and often irreversible outcomes for many patients. The objective of this study was to develop a novel system using zinc oxide nanoparticles (nZnO) as a coating material that inhibits both bacterial adhesion / growth and promotes osteoblast growth. Methods and Results: Initially bacteria (S. aureus, E. coli, S. epidermidis and P. aeruginosa) were exposed to different concentrations of zinc oxide nanoparticulate suspensions (250 μg/mL, 500 μg/mL, 1000 μg/mL and 2500 μg/mL); with the higher concentrations of the suspensions demonstrating significant bactericidal effects. A novel electrohydrodynamic atomization coating technique (EHDA) was used to deposit mixtures of nZnO and nano-hydroxyapatite (nHA) onto the surface of glass samples (1 cm2). Exposure of the coated samples to phosphate buffered saline (PBS) and adult bovine serum (ABS) and measurement of bactericidal activity demonstrated superior antimicrobial activity for 100% and 75% nZnO composite coated samples. Lactate dehydrogenase (LDH) release from osteoblast-like cells (UMR-106 and MG-63) exposed to both nano-TiO2 and nano-ZnO nanoparticulate suspension supernatants indicated minimal toxicity. Nano-ZnO coated samples did not elicit LDH release with an increase in proliferation and viability of cells was observed. Scanning electron microscopy (SEM) and optical microscopy indicated that all cell types used (mesenchymal stem cells and osteoblast-like cells) were able to maintain their normal morphological state when adhered to the surface of the nano-coated material. Further studies as regards to patterned coated samples showed an exclusive adhesion selection by osteoblast-like cells to nZnO patterned regions that needs to be further investigated. Conclusion: ZnO NPs provide an antimicrobial and biocompatible coating material for medical and dental bone implants.
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Xu, Zizhao. "Development of Lipid-based Nano Formulations of Miriplatin Against Lung Cancer." Scholarly Commons, 2020. https://scholarlycommons.pacific.edu/uop_etds/3699.
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Cancer is the second leading cause of death and is responsible for approximately 9.6 million deaths worldwide in 2018. Among all oncological diseases, lung cancer claims the highest mortality (male: 23.5%; female: 22%) and the second most new cases (male: 13%; female: 12%) in the US. Approximately 40% of newly diagnosed lung cancer patients are in the advanced stage IV, for which platinum-based chemotherapy is the first-line treatment, either by itself or in combination with surgery or radiotherapy.
Cisplatin, the first-generation platinum-based anticancer chemotherapeutic agent, has the highest potency against lung cancer but carries many severe adverse effects. Cisplatin also induces drug resistance during long-term chemotherapy. Many more platinum complexes have been investigated as better alternatives, which led to the approval of carboplatin and oxaliplatin by Food and Drug Administration (FDA). In addition, miriplatin suspended in iodolipds (lipiodolization) was approved in Japan for the treatment of hepatocellular carcinoma (HCC) in 2009. Miriplatin has the same non-leaving group as oxaliplatin but different leaving groups of two myristate chains, which make it highly lipophilic.
Several characteristics of solid tumors in lung cancer constitute a physiochemical barrier to the homogenous distribution and deep penetration of chemotherapy agents. Nanocarriers provide a promising platform to overcome the physiochemical barrier and to reduce the systemic toxicity of anticancer chemotherapy. In this study, miriplatin is formulated with various lipid-based nanocarriers including micelles and solid lipid nanoparticles (SLNs) thanks to its highly lipophilic structure. The goal of this thesis is to develop and evaluate miriplatin-loaded nano formulations against lung cancer.
Miriplatin-loaded formulations were prepared by different methods, including thin film hydration and several scale-up methods including chloroform dripping, chloroform injection, chloroform evaporation, co-solvent evaporation, chloroform slow evaporation and co-solvent slow evaporation. Between the two types of nano formulations under this study, micelles were much smaller (~10 nm in diameter) and more homogeneous (PDI < 0.3), while SLNs were bigger (~ 100 nm in diameter) and more heterogeneous (PDI ~0.8). A quantification method of miriplatin was established using inductively coupled plasma-optical emission spectrometry (ICP-OES). The quantification of platinum recovery from different miriplatin-loaded nano formulations was facilitated by digestion with 70% nitric acid and heating. The co-solvent slow evaporation method to prepare miriplatin-loaded nano formulations improved the platinum recovery prominently from 10% to 70%. Thus, co-solvent slow evaporation has been established as a pharmaceutically viable scale-up method to prepare nano formulations of miriplatin.
Miriplatin-loaded nano formulations of different compositions were negatively stained with uranyl acetate and then imaged by transmission electron microscopy (TEM), which showed the formulations’ size and morphology that were consistent with the size and PDI data from dynamic light scattering studies by the Malvern Zetasizer. In the TEM studies, micelles showed a morphology of spherical dots at around 10 nm in diameter while SLNs showed both spherical and rod structures with a size distribution from 50 to 150 nm.
A three-dimensional multicellular spheroid (3D MCS) model of A549-iRFP cells was used for in vitro evaluation of the nano formulations’ activity against lung cancer. A549-iRFP cells were engineered from the common lung cancer cell line A549 to stably express the near-infrared fluorescent protein (iRFP). The viability of A549-iRFP 3D MCS after exposure to cisplatin or nano formulations was similar to A549 3D MCS. The anticancer activity of miriplatin-loaded nano formulations against 3D MCS was positively associated with the platinum recovery as quantified by ICP-OES. The miriplatin-loaded nano formulations that had been prepared by the co-solvent slow evaporation method showed substantial anticancer activities against A549 3D MCS and A549-iRFP 3D MCS, which were comparable to cisplatin.
Taken together, miriplatin-loaded nano formulations were successfully prepared by co-solvent slow evaporation. The formulations were developed to carry favorable physiochemical properties to enhance the activities of platinum drugs against lung cancer.
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Feil, Florian [Verfasser], and Christoph [Akademischer Betreuer] Bräuchle. "Single molecule diffusion studies in nanoporous systems: From fundamental concepts to material science and nano-medicine / Florian Feil. Betreuer: Christoph Bräuchle." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2012. http://d-nb.info/1023435489/34.
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Fornaguera, Puigvert Cristina. "Development of multifunctional polymeric nanoparticles by nano-emulsion templating as advanced nanocarriers targeting the blood-brain barrier." Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/285368.
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Multifunctional polymeric nanoparticles (NP) represent a promising alternative for the treatment of neurodegenerative diseases using the intravenous route (i.v.). In current treatments, the effects of the intravenously injected drugs are systemic, requiring high drug doses to achieve therapeutic effects, thus causing severe side effects. NP can act specifically in a tissue provided that they are properly designed. An interesting approach is the preparation of NPs by nano-emulsion templating. Nano-emulsions (NE) are fine emulsions, with droplet sizes typically between 20 – 200nm. They can be prepared by the phase inversion composition (PIC) method, a low-energy emulsification method appropriate for pharmaceutical applications, since it can be performed at mild process conditions. Nanoparticles are obtained from nano-emulsions by solvent evaporation. To target the central nervous system (CNS), a specific targeting moiety on the nanoparticle surface is required to cross the blood-brain barrier (BBB), which is a current key goal under intense investigations. The aim of this work was to obtain multifunctional polymeric NP as advanced delivery systems able to cross the BBB. O/W polymeric NE were prepared by the PIC method and polymeric NPs were obtained by solvent evaporation. Polymeric NP with appropriate sizes for the i.v. administration (<1milimicron) were obtained. With the aim to design imaging systems, a model fluorescent dye and magnetic nanoparticles were encapsulated in polymeric NPs. An analgesic and an antiapoptotic drugs were also encapsulated into PLGA NP for therapeutic purposes. High encapsulation efficiencies were found for all tested compounds, attributed to the method of nanoparticle preparation as well as to low solubility of the components in the aqueous dispersion media. In addition, a sustained and controlled release of fluorescent dyes / drugs was achieved. NP surface was functionalized using various elements. On the one hand, it was functionalized with a monoclonal antibody against the transferring receptor, overexpressed in the BBB, to achieve an active targeting to the BBB. On the other hand, NPs were functionalized with oligonucleotides, to be used as non-viral gene delivery systems. Firstly, carbosilane cationic dendrons were covalently attached to nanoparticle surface to achieve a cationic surface. In a further step, antisense oligonucleotides, siRNA and plasmids were electrostatically bound to cationized nanoparticles. In vitro tests showed that the formulated NP did produce neither cytoxicity nor hemolysis. In addition, they were weak activators of the immune system and produced only a slight adsorption of blood proteins. Therefore, they are appropriate to be used by the i.v. route. NPs functionalized with oligonucleotides enhanced gene transfection in cell cultures, up to values comparable to those of commercial values (up to 90%). These NPs are advantageous in terms of toxicity issues over the commercial formulations. Therefore, they represent promising non-viral gene delivery systems. In vivo tests, which measured the central analgesia produced by an encapsulated drug into nanoparticles (loperamide) that is not able to cross the BBB, confirmed a central analgesic effect, reaching a potency of analgesia comparable to positive controls when nanoparticles were functionalized with the antibody. Therefore, the antibody functionalized nanoparticles efficiently crossed the BBB. In conclusion, the designed polymeric nanoparticles, functionalized with the antitransferrin receptor antibody, are able to cross the BBB with high efficiency. These nanoparticles represent promising nanosystems to deliver actives to the central nervous system.<br>Les nanopartícules polimèriques multifuncionals (NPs) representen una alternativa prometedora pel tractament de malalties neurodegeneratives, a través de l’administració intravenosa (i.v.), ja que els tractaments actuals provoquen molts efectes secundaris. Les NPs, en canvi, si estan correctament dissenyades, poden actuar específicament en el teixit diana. Ja que l’òrgan diana és el cervell, és necessari un element de vectorització per poder creuar la barrera hemato-encefàlica (BBB). En aquest context, l’objectiu de la present tesi és l’obtenció de NPs com a sistemes avançats d’alliberament de principis actius que travessin la BBB. Es van obtenir NPs a partir de nano-emulsions (NE) plantilla, emprant l’àcid poli-(làctic-co-glicòlic) com a polímer i el mètode d’inversió de fases a temperatura constant per emulsionar, seguit d’evaporació de solvent per obtenir NPs. Les NPs obtingudes tenen mides apropiades per l’administració i.v.. Es va aconseguir encapsular un fluorescent i NPs magnètiques dins les NPs polimèriques, per fer-les servir com a sistemes d’imatge. També es van encapsular fàrmacs per usar-les com a sistemes terapèutics. En tots els casos, es van aconseguir eficiències d’encapsulació molt elevades i un alliberament del fàrmac controlat i prolongat en el temps. A més, es va aconseguir funcionalitzar la superfície de les NPs amb diferents elements. Es van unir covalentment dendrons catiònics per posteriorment unir oligonucleòtids electrostàticament. També es va afegir una coberta exterior de polietilenglicol per protegir el material genètic. Per altra banda, es va funcionalitzar la superfície de les NPs amb un anticòs específic contra el receptor de la transferrina, sobreexpressat a la BBB. A continuació, es van fer assajos in vitro, que van posar de manifest que les NPs no són citotòxiques ni hemolítiques. També es va estudiar l’eficiència de transfecció cel•lular del material genètic, arribant a eficiències de transfecció equivalents a les dels vectors comercials. Assajos in vivo van permetre confirmar el pas a través de la BBB, sobretot de les NPs funcionalitzades amb l’anticòs. Els resultats obtinguts permeten concloure que s’ha aconseguit dissenyar noves NPs polimèriques a partir de NE, apropiades per l’administració i.v. i amb capacitat de travessar la BBB.
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Jayasinghe, Chaminda. "Synthesis and Characterization of Carbon Nanotube, Threads, Yarns, and Sheets." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1312292744.
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SILVESTRI, ANTONIA. "Implantable Nanofluidic Membrane and Smart Electronic System for Drug Release Control." Doctoral thesis, Politecnico di Torino, 2021. http://hdl.handle.net/11583/2918000.
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Pearson, Frances E. "Transcutaneous delivery of T cell-inducing viral vector malaria vaccines by microneedle patches." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:2155c639-bcc8-49e0-b415-a5d353aacba3.
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There is an urgent need for improvements to existing vaccine delivery technologies to run parallel with the development of new-generation vaccines. The burdens of needle-based immunisation strategies are exacerbated by poor resource provision in such areas as sub-Saharan Africa, where annual malaria mortality stands at 860,000. Needle-free delivery of vaccine to the skin holds promise for improved immunogenicity with lower doses of vaccine, in addition to significant logistical advantages. Various methods have been described for the transcutaneous delivery of vaccines, including the use of microneedles to overcome the outer stratum corneum of the skin for efficient delivery of liquid or solid, microneedle-coated vaccines into underlying strata rich in antigen-presenting cells. This thesis aims to evaluate two transcutaneous silicon microneedle and microprojection patch technologies for the delivery of live recombinant Adenovirus and Modified Vaccinia Ankara-vectored vaccines encoding pre-erythrocytic malaria antigens in mice. Cellular immunogenicity directed against a well-documented epitope of the Plasmodium berghei circumsporozoite protein is evaluated, as is protection against lethal P. berghei sporozoite challenge. Immunological and logistical benefits of each technology are assessed, as well as mechanisms underlying differences in the generation of a patch-induced immune response to vaccination. These data inform the future development of transcutaneous microneedle patches for the delivery of live vaccine.
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PAIOTTA, ALICE. "Synthesis of Glycoderivatives as Molecular Tools in Medicinal Chemistry and Nano-Medicinal Chemistry." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2018. http://hdl.handle.net/10281/199137.
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Durante il terzo anno di dottorato mi sono occupata della sintesi finale dei glicomimetici del substrato naturale dell’enzima AGM1 GlcNAc-6P o del prodotto GlcNAc-1P.
Le sintesi messe a punto sono necessarie per ottenere prodotti finali utilizzabili come strumenti molecolari chimici per studiare il ruolo dell’HBP nella regolazione della proliferazione e la sopravvivenza delle cellule tumorali.
I prodotti presentati (caratterizzati mediante NMR (1H. COSY, HSQC e 13C) e Massa) sono stati preparati protetti (acetilati sugli ossidrili) per i test cellulari per favorire la loro diffusione attraverso la membrana cellulare e nella forma de-protetta per il test enzimatico, per poterne valutare la potenza inibitoria direttamente sull’enzima AGM1.
La messa a punto del test enzimatico ha come obiettivo la valutazione dell’effettiva capacità inibitoria dei composti sintetizzati. Il test prevede la comparazione della quantità di UDP-GlcNAc prodotto dalla reazione accoppiata dell’enzima AGM1 e AGX1, utilizzando un estratto enzimatico cellulare, in assenza e in presenza dei potenziali inibitori. La quantificazione è stata effettuata mediante l’utilizzo della tecnica cromatografica HPLC, con un metodo ion-pair a fase inversa associato ad un rilevatore UV impostato ad una lamda di 254 nm.
Inizialmente è stata preparata la retta di taratura dell’UDP-GlcNAc costruita partendo da una madre 1.5 mM e attraverso diluzioni sono state effettuate le analisi in triplicato per ogni punto della retta. Sono stati calcolati i valori del limite di rilevabilità (LOD) e di quantificazione (LOQ).
Il test messo a punto prevede la quantificazione della produzione di UDP-GlcNAc a partire dai substrati GlcNAc-6P e UTP utilizzando estratti cellulari lisati. In una prima analisi si è esaminato l’estratto enzimatico per verificare la presenza di UDP-GlcNAc endogena, che non è stata riscontrata. Quindi si è verificata l’effettiva efficacia dell’estratto nel catalizzare la produzione di UDP-GlcNAc a partire dai substrati forniti e si sono messe a punto le condizioni di reazione. Infine, si è proceduto con l’analisi degli inibitori sintetizzati. Dati preliminari non hanno evidenziato una diminuzione del segnale di UDP-GlcNAc, il che farebbe escludere una buona attività inibitoria.
Durante il periodo di Traineeship presso il CycloLab di Budapest ho potuto effettuare l'incapsulamento di un potenziale inibitore enzimatico in ciclodestrine funzionalizzate per il targeting di cellule tumorali.
Alcuni dei composti sintetizzati possiedono caratteristiche chimico-fisiche che rendono il loro passaggio attraverso la membrana cellulare molto difficile: la presenza di gruppi solfati, solfonati e fosforamidati, che possiedono cariche negative, li rendono particolarmente polari. Lo scopo del progetto è quello di sfruttare ciclodestrine (CD) opportunamente funzionalizzate come un “cavallo di Troia” per veicolare gli inibitori enzimatici all'interno delle cellule tumorali.
Al CycloLab mi sono quindi occupata della sintesi dello scaffold di interesse e dell’incapsulamento del potenziale inibitore.<br>The project carried out during the 3 years-Ph.D. has had the objective to identify and synthesize new glycomimetics as molecular tools to study the Hexosamine Biosynthetic Pathway (HBP), which role is to regulate the proliferation and survival of cancer cells. The project has been funded by AIRC and the principal aim was to identify the Adenocarcinoma of the Pancreatic Duct (PDAC) as the target of research. The synthesis of innovative chemical tools helps the understanding of the HBP pathway and its response in PDAC: new potential inhibitors, which are similar to the natural substrate of enzyme, can be recognized but trick the enzyme and block its activity in order to decrease the UDP-GlcNAc production and consequently modify the protein glycosylation. Due to the important role of the HBP in the cells, alteration of this pathway can bring to alteration of N- and O- glycosylation and activate the Unfolded Protein Response (UPR) during the Endoplasmic Reticulum (ER) stress. The description of the research target helps the understanding of the design of molecular tools: the focus point is the inhibition of the enzyme N-acetylglucosamine-phosphate mutase (AGM1): its inhibition could represent the way to induce apoptosis in cancer cells. Through the Molecular Design, a rational design of potential inhibitors has been done. This design is based on the similarity with the structures of the natural substrate of enzyme AGM1, with some modifications. All of the drawn structures have been used for Molecular Docking in order to get a first virtual screening on the compounds library. Starting from preliminary results of theoretical approach, the synthesis of compounds have been done following three different synthetic strategies. All the steps and reaction condition are described in details and are shown the characterization (1H, 13C NMR spectra, m/z) of all the synthetized compound.
The optimization of the analytical method on High Performance Liquid Chromatography is necessary in order to achieve experimental data on the ability of the designed compounds to inhibit the target enzyme, data to be compared to those obtained through a computational theoretical approach. To this aim an HPLC method has been set-up for the quantification of UDP-GlcNAc produced using the cellular extract as enzyme source, and carrying out the reaction with the natural substrates GlcNAc-6P, UTP in the presence or not of the test molecules. Using 10 and 30 µL of extract, three compounds lead to a decrease of production of UDP-GlcNAc. The computational data ”describes” the interaction between the enzyme and the molecules. The calculation of C LogP has confirmed the most apolar character of compound 3B in the acetylated form. Some preliminary evaluation of the effect of compound 2B in a Triple Negative Breast Cancer (TNBC) cell model has been carried out. In conclusion, the study of the target of this research, the HBP pathway, and the focus on the inhibition of AGM1 are the starting point for a complete project, that includes at first the design of a library of compound based on the structural properties of the natural substrate. the “in silico” evaluation of their interaction with the target enzyme, the synthesis and the screening through an enzymatic assay.. The tuning of the strategy of synthesis is important to obtain the compound for the in vitro test. The analytical method with HPLC gives results comparable to the docking scores, and then, after a calculation of C LogP, the test on cells gives the final results of potency of compound 3B (2B the acetylated form). The last part describes the collaboration with CycloLab (Budapest): some compounds of the library possess chemical-physical characteristics that make their passage through cell membrane very harsh: they are very polar and some of them possess negative charges (sulphate, sulphonates, phosphoramidate). This preliminary work is still in progress.
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Bachtarzi, Houria. "Targeting polymer coated adenovirus to tumour-associated vasculature." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:602123e8-814c-4b63-a482-ab8adcfa6594.
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Tumour-associated vasculature provides an accessible target for systemic gene therapy using targeted adenoviruses. The aim of this thesis is to develop strategies for targeting adenovirus infection to tumour-associated endothelium. Adenovirus expressing luciferase (Adluc) was coated with an amino-reactive polymer based on poly [N-(2-hydroxypropyl) methacrylamide] [pHPMA] to ablate normal infection pathways¬. This was a pre-requisite to redirecting virus tropism to infect endothelial cells via specific receptors. Direct attachment to the pHPMA-adenovirus (pcAdluc) of ligands including vascular endothelial growth factor (VEGF165) and a monoclonal antibody (RAFL) recognising VEGF receptor 2 (VEGFR-2) retargeted infectivity to VEGFR-2-positive endothelial cells and not to receptor-negative cells. Specificity of transduction in vitro was shown by competition with excess antibody. In vivo however, the VEGF165-retargeted virus failed to transduce tumour-associated endothelia following systemic administration. Similarly, direct linkage of a monoclonal antibody against E-Selectin (MHES) demonstrated E-Selectin-specific transduction of tumour necrosis factor-α (TNF-α)-activated endothelial cells, although overall levels of infection were not increased compared to unmodified Adluc. A two-component targeting system using protein A or protein G as ‘bridging’ agents was developed to ensure the required orientation of targeting antibodies. Using this system MHES mediated greater transduction of TNF-α-activated endothelial cells than Adluc. Conjugation using protein A also gave non-specific effects which were not seen with protein G. Whereas the unmodified Adluc virus failed to transduce TNF-α-activated endothelium in an umbilical vein model ex vivo, the MHES-protein G-pHPMA-adenovirus (MHES-StrepGpcAdluc) mediated good transduction. Similarly, StrepGpcAdluc retargeted with a chimeric P-Selectin Glycoprotein Ligand-1 (PSGL-1)-Fc fusion protein, showed good circulation kinetics and significant uptake into HepG2 xenografts following intravenous administration. Histological studies suggested selective targeting to tumour-associated endothelial cells. Overall these findings support the assertion that tumour-associated vasculature is an accessible target for systemic gene delivery, and the use of protein G as bridging agent facilitates rapid screening of Fc-bearing ligands for retargeting pcAd infection to tumour-associated endothelium.
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Brisola, Gabriel Motta Pinheiro. "Efeitos da suplementação de β-alanina sobre a potência anaeróbia, habilidade de esforços repetidos e desempenho no polo aquático /". Rio Claro, 2016. http://hdl.handle.net/11449/144686.
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Orientador: Alessandro Moura Zagatto<br>Banca: Marcelo Papoti<br>Banca: Guilherme Giannini Artioli<br>Resumo: O objetivo geral do presente trabalho foi verificar o potencial ergogênico da suplementação por 4 semanas de β-alanina sobre a potência anaeróbia, habilidade de esforços repetidos e desempenho no polo aquático. 22 jogadores de elite do sexo masculino (média±dp: idade = 18±4 anos, peso = 78,5±9,5 kg e altura = 1,79±0,06 m) participaram do estudo, que foi conduzido de modo randomizado, duplo cego e placebo controlado. Os participantes foram divididos em dois grupos (β-alanina e placebo) de 11 atletas cada e foram submetidos a testes específicos (teste de habilidade de esforços repetidos (RSA) e teste máximo de 30s de salto sob o gol (30CJ)) e semi-específicos (teste de 30s máximo em nado atado (30ATADO), teste máximo de 3 minutos (All Out 3min), teste incremental máximo (GXTATADO) e performance de 200m em nado crawl (P200m)) para a modalidade e um jogo simulado para possibilitar o rastreamento das atividades realizadas por meio de filmagem. As avaliações ocorreram pré e após o período de suplementação (4 semanas). Não foram encontrados efeitos significativos de interação entre os grupos para nenhuma variável do presente estudo. No entanto, alguns ligeiros indícios de melhora com a suplementação de β-alanina foram encontrados como: (1) melhora significativa entre os momentos (pré × pós) no número total de sprints durante o jogo simulado de polo aquático; (2) efeito provavelmente benéfico (análise de inferência baseada na magnitude) para o tempo médio, pior tempo e tempo total na... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: The overall aim of this study was to investigate the ergogenic effect of 4 weeks β-alanine supplementation on the anaerobic power, ability to performed repeated efforts and performance of water polo. 22 male elite players (mean±SD age = 18±4 years, weight = 78.5±9.5 kg and height = 1.79±0.06 m) participated in the study, which was conducted in order randomized, double blind and placebo controlled. Participants were divided into two groups (β-alanine and placebo) of 11 athletes each and were subjected to specific tests (repeated sprint ability test (RSA) and maximum 30s jump under the goal test (30CJ)) and semi-specific (30s maximal test in tethered swimming (30TS), maximal 3 min effort (AllOut-3min), tethered swimming graded exercise test (GXTTS) and 200m in front crawl (P200m)) for the modality and a simulated game to enable tracking of the activities carried out by video record. Assessments occurred before and after the supplementation period (4 weeks). There were no significant interaction effects between the groups for any variable of this study. However, some slight improvement indications with β-alanine supplementation were found to: (1) significant improvement between moments (pre × post) the total number of sprints during the simulated game water polo; (2) probably beneficial effect (magnitude-based inference analysis) for the mean time, worst time and total time in the first series of the RSA test (RSA1); (3) significant improvement between moments for mean force and integral of force during the 30TS and P200m; (4) significant improvement between moments for peak power at GXTTS. Therefore, it is concluded that supplementation for 4 weeks of β-alanine can promote only slightly improve some parameters related to swimming ability in water polo as total number of sprints in simulated game, mean time,... Complete abstract electronic access below)<br>Mestre
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Mandal, Subhra. "Polyelectrolyte based NANO-approaches for Cancer therapy or diagnostics." Doctoral thesis, SISSA, 2010. http://hdl.handle.net/20.500.11767/4133.
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The work presented here has been aimed at exploring a polymer nanoparticle based approach to cancer diagnostics and therapy. Cancer is the second leading cause of death in the world. Nanoparticles and polymer science have opened up a new world of opportunities for the development of efficient medical diagnostic methods and of selective cancer therapy. The different (sometimes hierarchical and/or multilayer) structures, shapes and compositions of nanoparticles provide good potential for their application in the biomedical field. With the development of nanotechnology, various types of uncoated and coated nanoparticles are being developed for cancer diagnostics and therapy.
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Palm, Fredrik, and Nelson Frida. "The importance of medical staff placement in CT examination rooms : A study of the scattered radiation doses in CT examination rooms in Da Nang, Vietnam." Thesis, Hälsohögskolan, Högskolan i Jönköping, HHJ, Avd. för naturvetenskap och biomedicin, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-36493.
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Cazzagon, Virginia <1992>. "Development and application of a Risk Management Framework for nano-biomaterials used in medical devices and medicinal products." Doctoral thesis, Università Ca' Foscari Venezia, 2022. http://hdl.handle.net/10579/22058.
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Gli obiettivi della tesi di dottorato sono lo sviluppo di un framework per la valutazione e gestione dei rischi di nano-biomateriali (NBM) utilizzati in dispositivi medici e prodotti medicinali e l’applicazione di tale framework in casi studio reali. Il framework proposto si compone di due pilastri principali: l’analisi di rischio occupazionale/ambientale, e l’analisi rischi-benefici per i pazienti. Nel contesto dell’analisi di rischio, sono stati analizzati i rischi occupazionali di nanoparticelle di magnetite utilizzate come mezzo di contrasto attraverso l’applicazione di un sistema di supporto alle decisioni (BIORIMA DSS). L’analisi condotta ha rilevato l’assenza di rischi per i lavoratori esposti a questo NBM lungo l’intero ciclo di vita del prodotto e ha permesso di testare l’applicabilità del DSS. Inoltre, è stato sviluppato un approccio Safe-By-Design per garze contenenti nanoparticelle di argento che ha permesso di selezionare l’alternativa migliore tra cinque prodotti in base ad un set di criteri relativi alla sicurezza per la salute umana e l’ambiente. Riguardo all’analisi rischi-benefici, è stata valutata la complessità dell’utilizzo di un agente teranostico contenente nanoparticelle di magnetite per la terapia personalizzata di tumori solidi e i successivi effetti avversi e/o benefici attraverso l’utilizzo dell’approccio System Thinking, dimostrando l’applicabilità di tale approccio in medicina per supportare l’analisi rischi-benefici di screening per nanofarmaci.
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Alshibani, Salah Ramadan. "Screening of Selected Libyan Medicinal Plants for the Synthesis of Metal Nanoparticles and their activity against Streptococcus mutans." University of the Western Cape, 2020. http://hdl.handle.net/11394/7716.
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>Magister Scientiae - MSc<br>Nanotechnology has emerged as an elementary division of modern science and stemmed directly from green chemistry twelve basic concepts, it receives global attention due to its unique character and ample applications. It also has great potential to mitigate the challenges they face in various fields, especially medical sector. Nanodrugs are increasingly considered as a potential candidate to carry therapeutic agents safely into a targeted compartment in an organ, particular tissue or cell. In this study, twenty (20) Libyan plants were selected and evaluated for their potential to synthesis gold and silver nanoparticles. The screening of the different plant extracts was performed using 96 well plate method at 25 °C and 70 °C. The NPs formation was confirmed and characterized using UV- Vis, DLS, HR-TEM and EDX. A well-defined NPs were obtained at high temperature (70 °C). The Au NPs had an average diameter of 92 nm at 25 °C and 66 nm at 70 °C. The zeta potential values were observed to be negative (-14 to -24) and indicate the stability of the Au NPs. The HR-TEM showed polydispersity, which decreased at higher temperature (70 °C). The stability of Au NPs in nutrient broth prior was conducted as well. All the Au NPs under study showed stability, only minimal changes in the UV-Vis spectra can be observed. Two plant extract viz Pistacia atlantica, Junipers phoenicea showed consistent results and forming stable and smaller NPs compared to others, both of the plant extracts and the corresponding NPs were tested against Streptococcus mutans and showed MIC value ~ 49 g/mL. In case of silver NPs, two plant extracts viz J. phoenicea, Rosmarinus officinalis, showed superior results than the others; both plants produced stable and small Ag NPs. The antibacterial activity against S. mutans demonstrated MIC valus ~ 50 g/mL. The synthesised NPs showed a promising bioactivity for developments of new antibacterial agents against S. mutans strains. Dose-dependent activity was observed for the tested NPs.
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Mahoney, Catherine M. "An investigation into maintaining naso-gastric feeding for stroke patients : a mixed methods design." Thesis, Edinburgh Napier University, 2009. http://researchrepository.napier.ac.uk/Output/2744.
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Background: Dysphagia is common after stroke, so feeding through a naso-gastric (NG) tube may be necessary. NG tubes are frequently dislodged, potentially causing feed or fluids to enter the lungs. Interventions to prevent this include taping NG tubes to the face, hand mittens and nasal bridles. Overall Aim The aim of this study was to explore the opinions of staff, patients and relatives about the maintenance of NG tube feeding for stroke patients while investigating current clinical practice. Research Design and Methods: A three-phased mixed method design was used. Phase 1 involved focus groups with multidisciplinary stroke unit staff (n=17); one-to-one interviews, with stroke patients (n=4) and relatives (n=6). Phase 2 incorporated a postal survey sent to a convenience sample (n=528) registered nurses working in the field of stroke across the UK. Phase 3 involved interviews with nurses (n=5) outside the speciality of stroke. Findings: Phase 1 highlighted many categories, including: lack of protocols; ethical and legal concerns; training to insert NG tubes; patient dignity; patient autonomy and potential harms and benefits of interventions used. There were variations in the opinions of staff, patients and relatives concerning the effectiveness and acceptability of methods for securing NG tubes. Phase 2 achieved a response rate of 59% (n=314/528); 22% (n=68/312) of nurses used hand mittens, only 11% (n=34/312) used a protocol; 56% (n=176/314) of nurses had received formal training to insert an NG feeding tube, more senior nurses had been formally trained than junior nurses (p<0.005). Acceptability and effectiveness ratings for tube securing interventions varied: 50% (n=158/312) considered hand mittens to be unacceptable. However, from a total of n=92 responses about their effectiveness, 66% (n=61/92) felt they were effective. Phase 3 produced more detailed results about fear associated with NG feeding; inconsistent approaches to training and ethical and legal issues of patient restraint. Conclusions: Overall this study demonstrates differences in opinion about what constitutes acceptable, effective and legal practice when maintaining NG feeding for stroke patients. It also suggests that the lack of consistent nurse training affects the standards of care patients receive. Furthermore, there is a need for more robust evidence to inform clinical practice. This study culminates in a model of nursing related to the insertion and maintenance of NG feeding for stroke patients.
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Chen, Tong Kai. "Development of Schisantherin A and baicalein nano-formulations with improved oral bioavailability, brain uptake, and anti-Parkinsonian activity." Thesis, University of Macau, 2017. http://umaclib3.umac.mo/record=b3690809.
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Carli, Marta. "Meso- and nano-structured metal-dielectric interfaces for plasmonic nanofocusing." Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3423458.
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With increasing demand for nanoscale optical devices, the ability to confine the light on length scales smaller than those allowed by the diffraction limit of light has begun to attract enormous interest. A possible solution to this problem is offered by Plasmonics.
Under certain conditions, a metal-dielectric interface supports Surface Plasmons (SPs), i.e. electromagnetic excitations strongly coupled to oscillations of free electrons in the metal. Thanks to these excitations, electromagnetic energy can be confined in a sub-wavelength volume close to the metal surface. This opens up the way for a wide range of opportunities and applications, from photovoltaics to biosensing.
The focus of this thesis was to engineer metal-dielectric interfaces in order to excite plasmonic hotspots, i.e. nanometer-sized regions where the electromagnetic field is strongly enhanced. As hinted above, this can be achieved by conveniently meso- and/or nano-structuring the metal surface. The properties of metal-dielectric interfaces emerging from these studies are of particular interest in the field of molecular sensing, but are also of more fundamental interest.
Different classes of devices are proposed. We started from digital plasmonic gratings, studying their excitation modes thoroughly. We then moved to nanostructures supporting a Localized Surface Plasmon Resonance (LSPR), specifically plasmonic nanoantennae, which are of special interest for the enhancement of well-established sensing techniques such as SERS. Coming to nanofocusing, we studied plasmonic wedges – which provide adiabatic nanofocusing at their ridge – as well as bull’s eye/Archimedean spiral structures, which can generate and focus Surface Plasmons carrying orbital angular momentum (OAM). Finally, we proposed a non-trivial integration of the above-mentioned effects, in the form of an Archimedean spiral coupled to nanoantenna resonators.
In parallel, we collaborated with the company A.P.E. Research to develop a new characterization instrument, called EllipsSNOM. It consists in implementing a SNOM head on a J.A. Woollam Co. Inc. Variable Angle Spectroscopic Ellipsometer (VASE). This challenging task was pursued in order to get simultaneous control of the far field and the near field properties of the structures; ellipsometry and SNOM microscopy are indeed both essential techniques to achieve a full characterization of plasmonic nanodevices.<br>All’aumentare della richiesta di dispositivi ottici di scala nanometrica, la possibilità di confinare la luce su scale di lunghezza inferiori a quelle consentite dal limite di diffrazione della luce ha iniziato ad attrarre un enorme interesse. Una possibile soluzione a questo problema è offerta dalla Plasmonica.
In determinate condizioni, un'interfaccia metallo-dielettrico supporta Plasmoni di Superficie (SP), cioè eccitazioni elettromagnetiche fortemente accoppiate alle oscillazioni degli elettroni liberi nel metallo. Grazie a queste eccitazioni, l’energia elettromagnetica può essere confinata in un volume di dimensioni inferiori alla lunghezza d’onda della luce vicino alla superficie metallica. Questo apre la strada a una vasta gamma di opportunità e applicazioni, dal fotovoltaico alla biosensoristica.
L’obiettivo di questa tesi è stato progettare interfacce metallo-dielettrico al fine di eccitare hotspot plasmonici, cioè regioni di dimensioni nanometriche dove il campo elettromagnetico è fortemente potenziato. Come accennato sopra, questo può essere ottenuto meso- e/o nano-strutturando opportunamente la superficie del metallo. Le proprietà delle interfacce metallo-dielettrico che emergono da questi studi sono di particolare interesse nel campo della sensoristica, ma sono anche di interesse più fondamentale.
Sono proposte diverse classi di dispositivi. Siamo partiti da reticoli plasmonici digitali, studiando a fondo i loro modi di eccitazione. Ci siamo poi spostati su nanostrutture che supportano una Risonanza Plasmonica di Superficie Localizzata (LSPR), nello specifico nanoantenne plasmoniche, che sono di particolare interesse per il potenziamento di tecniche sensoristiche ben consolidate come il SERS. Venendo poi al nanofocusing, abbiamo studiato strutture plasmoniche tipo wedges (cunei) – che forniscono nanofocusing adiabatico sulla loro cresta – e strutture tipo bull’s eye/spirali di Archimede, in grado di generare e focalizzare Plasmoni Superficiali che trasportano momento angolare orbitale (OAM). Infine, abbiamo proposto un'integrazione non banale degli effetti sopra citati, in forma di una spirale di Archimede accoppiata a una nanoantenna.
In parallelo, abbiamo collaborato con la ditta A.P.E. Research per sviluppare un nuovo strumento di caratterizzazione, chiamato EllipsSNOM. Esso consiste nell’implementazione di una testa SNOM su un ellissometro spettroscopico J.A. Woollam Co. Inc. Variable Angle Spectroscopic Ellipsometer (VASE). Questo intrigante obiettivo è stato perseguito al fine di ottenere il controllo simultaneo delle proprietà di campo lontano e di campo vicino delle strutture; ellissometria e microscopia SNOM sono infatti entrambe tecniche essenziali per realizzare una completa caratterizzazione dei nanodispositivi plasmonici.
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Salieri, Beatrice <1981>. "The challenges and the limitations in Life Cycle Impact Assessment for metal oxide nanoparticles, a case study on nano- TiO2." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5227/1/Beatrice_Salieri_Tesi.pdf.
Full textAbstract:
Life Cycle Assessment (LCA) is a chain-oriented tool to evaluate the environment performance of products focussing on the entire life cycle of these products: from the extraction of resources, via manufacturing and use, to the final processing of the disposed products. Through all these stages consumption of resources and pollutant releases to air, water, soil are identified and quantified in Life Cycle Inventory (LCI) analysis. Subsequently to the LCI phase follows the Life Cycle Impact Assessment (LCIA) phase; that has the purpose to convert resource consumptions and pollutant releases in environmental impacts. The LCIA aims to model and to evaluate environmental issues, called impact categories. Several reports emphasises the importance of LCA in the field of ENMs. The ENMs offer enormous potential for the development of new products and application. There are however unanswered questions about the impacts of ENMs on human health and the environment. In the last decade the increasing production, use and consumption of nanoproducts, with a consequent release into the environment, has accentuated the obligation to ensure that potential risks are adequately understood to protect both human health and environment. Due to its holistic and comprehensive assessment, LCA is an essential tool evaluate, understand and manage the environmental and health effects of nanotechnology. The evaluation of health and environmental impacts of nanotechnologies, throughout the whole of their life-cycle by using LCA methodology. This is due to the lack of knowledge in relation to risk assessment. In fact, to date, the knowledge on human and environmental exposure to nanomaterials, such ENPs is limited. This bottleneck is reflected into LCA where characterisation models and consequently characterisation factors for ENPs are missed. The PhD project aims to assess limitations and challenges of the freshwater aquatic ecotoxicity potential evaluation in LCIA phase for ENPs and in particular nanoparticles as n-TiO2.<br>L’LCA è una metodologia standardizzata volta alla valutazione delle performance ambientali di un prodotto lungo il suo intero ciclo di vita. Il consumo di risorse e le emissioni di sostanze inquinanti in aria, acqua, suolo sono quantificate nella fase di inventario (LCI).La fase successiva di Life Cycle Impact Assessment ha lo scopo di convertire i consumi di risorse e le emissioni di inquinanti in impatti ambientali. classificate in categorie di impatto.Grazie all’ utilizzo di specifici fattori di caratterizzazione i risultati della fase d’inventario vengono convertiti in un unità comune ed espressi in termini di impact score per ogni categoria d’impatto. L’importanza di studi di LCA nel settore dei nanomateriali (ENM) è stata sottolineata da diversi studi. Nonostante le nanotecnologie, sembrano offrire enormi potenzialità per lo sviluppo di nuovi prodotti e applicazioni con migliori prestazioni energetiche o un ridotto uso di materiali ed energia, vi sono ancora forti incertezze legate ai loro possibili impatti ambientali e sanitari. Negli ultimi dieci anni l'aumento della produzione, l'uso e il consumo di nanoprodotti, ha accentuato l'obbligo di garantire che i rischi potenziali siano adeguatamente compresi per proteggere sia la salute umana e l'ambiente. Grazie al suo approccio olistico l’LCA è stato identificata come uno strumento essenziale per valutare, gli effetti sull'ambiente e sulla salute. Solo pochi studi di LCA sono stati condotti sui nanoprodotti e tra questi solo pochi considerando gli impatti ambientali di tipo tossicologico. La scarsa applicazione della metodologia LCA nel settore della nanotecnologia è principalmente dovuta alle frammentarie conoscenze scientifiche correlati alla valutazione del rischio ambientale.Ad oggi, nella metodologia LCA si risente della completa mancanza di opportuni modelli di caratterizzazione per gli impatto tossicologici. Il progetto di dottorato si propone di valutare i limiti e le sfide nella fase di LCIA per la valutazione degli impattiecotossicologi per nanoparticelle di n-TiO2.
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Salieri, Beatrice <1981>. "The challenges and the limitations in Life Cycle Impact Assessment for metal oxide nanoparticles, a case study on nano- TiO2." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5227/.
Full textAbstract:
Life Cycle Assessment (LCA) is a chain-oriented tool to evaluate the environment performance of products focussing on the entire life cycle of these products: from the extraction of resources, via manufacturing and use, to the final processing of the disposed products. Through all these stages consumption of resources and pollutant releases to air, water, soil are identified and quantified in Life Cycle Inventory (LCI) analysis. Subsequently to the LCI phase follows the Life Cycle Impact Assessment (LCIA) phase; that has the purpose to convert resource consumptions and pollutant releases in environmental impacts. The LCIA aims to model and to evaluate environmental issues, called impact categories. Several reports emphasises the importance of LCA in the field of ENMs. The ENMs offer enormous potential for the development of new products and application. There are however unanswered questions about the impacts of ENMs on human health and the environment. In the last decade the increasing production, use and consumption of nanoproducts, with a consequent release into the environment, has accentuated the obligation to ensure that potential risks are adequately understood to protect both human health and environment. Due to its holistic and comprehensive assessment, LCA is an essential tool evaluate, understand and manage the environmental and health effects of nanotechnology. The evaluation of health and environmental impacts of nanotechnologies, throughout the whole of their life-cycle by using LCA methodology. This is due to the lack of knowledge in relation to risk assessment. In fact, to date, the knowledge on human and environmental exposure to nanomaterials, such ENPs is limited. This bottleneck is reflected into LCA where characterisation models and consequently characterisation factors for ENPs are missed. The PhD project aims to assess limitations and challenges of the freshwater aquatic ecotoxicity potential evaluation in LCIA phase for ENPs and in particular nanoparticles as n-TiO2.<br>L’LCA è una metodologia standardizzata volta alla valutazione delle performance ambientali di un prodotto lungo il suo intero ciclo di vita. Il consumo di risorse e le emissioni di sostanze inquinanti in aria, acqua, suolo sono quantificate nella fase di inventario (LCI).La fase successiva di Life Cycle Impact Assessment ha lo scopo di convertire i consumi di risorse e le emissioni di inquinanti in impatti ambientali. classificate in categorie di impatto.Grazie all’ utilizzo di specifici fattori di caratterizzazione i risultati della fase d’inventario vengono convertiti in un unità comune ed espressi in termini di impact score per ogni categoria d’impatto. L’importanza di studi di LCA nel settore dei nanomateriali (ENM) è stata sottolineata da diversi studi. Nonostante le nanotecnologie, sembrano offrire enormi potenzialità per lo sviluppo di nuovi prodotti e applicazioni con migliori prestazioni energetiche o un ridotto uso di materiali ed energia, vi sono ancora forti incertezze legate ai loro possibili impatti ambientali e sanitari. Negli ultimi dieci anni l'aumento della produzione, l'uso e il consumo di nanoprodotti, ha accentuato l'obbligo di garantire che i rischi potenziali siano adeguatamente compresi per proteggere sia la salute umana e l'ambiente. Grazie al suo approccio olistico l’LCA è stato identificata come uno strumento essenziale per valutare, gli effetti sull'ambiente e sulla salute. Solo pochi studi di LCA sono stati condotti sui nanoprodotti e tra questi solo pochi considerando gli impatti ambientali di tipo tossicologico. La scarsa applicazione della metodologia LCA nel settore della nanotecnologia è principalmente dovuta alle frammentarie conoscenze scientifiche correlati alla valutazione del rischio ambientale.Ad oggi, nella metodologia LCA si risente della completa mancanza di opportuni modelli di caratterizzazione per gli impatto tossicologici. Il progetto di dottorato si propone di valutare i limiti e le sfide nella fase di LCIA per la valutazione degli impattiecotossicologi per nanoparticelle di n-TiO2.
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Certo, Francesco. "Technological innovations in multimodal management of glioblastoma: from nano-drugs to imaging guided surgery and supra-maximal resection." Doctoral thesis, Università di Catania, 2018. http://hdl.handle.net/10761/4189.
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Primary brain tumors are a major cause of morbidity and mortality in the United States. Approximately one-third of tumors are malignant and the remaining are benign or borderline malignant. High-grade glioma, in particular glioblastoma, management is a great challenge for both neurosurgeons and patients. More than 45% of CNS primary malignant tumours are glioblastoma and their 5 year-survival is only 5% on average. Although biomolecular differences between glioblastoma IDH-WT and IDH-mutant might account for different outcomes, treatment strategies, including surgical EOR, chemiotherapy and radiotherapy, are currently considered important factors associated with PFS and OS.
objective of this thesis is the definition of a neuro-oncological protocol, to be reserved for patients with glioblastoma, which can establish a therapeutic path that starts with a safe and effective surgery and continues with a pharmacological treatment that may lead to the limitations of current antitumor therapy schemes.
Two main research lines have been conducted, with these purposes: the first one, essentially clinical, has been analysed in two consecutive studies, first retrospectively, then prospectively, the results of the application of an intraoperative imaging protocol that foresees the use of Advanced neuronavigation, intraoperative fluorescence and intraoperative CT. The second line of research was instead based on the attempt to obtain a pharmacological preparation which provided for the combination of temozolomide with nano-vectors, able to increase its antiblastic efficacy and to increase its chances of delivery at the intracranial level.
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Melli, Mauro. "Mechanical resonating devices and their applications in biomolecular studies." Doctoral thesis, SISSA, 2010. http://hdl.handle.net/20.500.11767/4646.
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To introduce the reader in the subjects of the thesis, Chapter 1 provides an overview on the
different aspects of the mechanical sensors. After a brief introduction to NEMS/MEMS, the
different approaches of mechanical sensing are provided and the main actuation and detection
schemes are described. The chapter ends with an introduction to microfabrication.
Chapter 2 deals with experimental details. In first paragraph the advantages of using a pillar
instead of common horizontal cantilever are illustrated. Then, the fabrication procedures and the
experimental setup for resonance frequencies measurement are described. The concluding
paragraph illustrates the technique, known as dip and dry, I used for coupling mechanical
detection with biological problems.
In Chapter 3, DNA kinetics of adsorption and hybridization efficiency, measured by means of pillar
approach, are reported.
Chapter 4 gives an overview of the preliminary results of two novel applications of pillar approach.
They are the development of a protein chip technology based on pillars and the second is the
combination of pillars and nanografting, an AFM based nanolithography.
Chapter 5 starts with an introduction about the twin cantilever approach and of the mechanically
induced functionalization. Fabrication procedure is described in the second paragraph. Then the
chemical functionalizations are described and proved. Cleaved surface analyses and the
spectroscopic studies of the mechanically induced functionalization are reported.
In Appendix A there is an overview of the physical models that are used in this thesis.
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Cuenca, Chumpitaz Violeta Angélica. "Percepções femininas sobre a participação do parceiro das decisões reprodutivas e no aborto induzido." reponame:Repositório Institucional da FIOCRUZ, 2003. https://www.arca.fiocruz.br/handle/icict/5163.
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Previous issue date: 2003<br>Trata-se de uma pesquisa qualitativa que teve como objetivo principal identificar a influência e participação do parceiro na decisão de abortar através das percepções e experiências de mulheres que referiram situações de aborto induzido e de relacionamentos estáveis com estes parceiros. Foram realizadas 16 entrevistas semiestruturadas com moradoras de duas favelas da zona norte do Rio de Janeiro, das quais analisamos 20 casos de abortos. Utilizamos a perspectiva relacional de gênero como categoria de análise.Incluímos como temas de análise: as representações de gênero, a contracepção e gravidez indesejada, a tomada da decisão de abortar e a participação masculina na decisão de abortar. Observamos que estas mulheres conciliam significados de uma ideologia de gênero tradicional com outra mais igualitária, principalmente em relação à identidade feminina e ao trabalho da mulher, o que denotaria um processo de transição de gênero. A gravidez indesejada foi construída a partir da visão e interação de ambos os parceiros e condicionada fortemente por fatores de contexto, entre eles, o desemprego. A participação masculina na decisão de abortar é variada (o parceiro se exclui, promove ou recusa o aborto); mas o desejo de não assumir a paternidade parece refletir as características da natureza e qualidade do relacionamento, assim como a situação do parceiro como trabalhador ou provedor da família.
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Silva, Constanza Thaise Xavier. "Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo." Universidade Federal de Goiás, 2016. http://repositorio.bc.ufg.br/tede/handle/tede/6620.
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Previous issue date: 2016-12-13<br>Cutaneous melanoma is a type of skin cancer that originates in melanocytes,
predominantly affecting young and middle-aged adults. Several evidence suggests
that cancer stem cells exist for melanoma. The POU5F1 / OCT4, NANOG genes
have been studied as cancer stem markers. OCT4 and NANOG are involved in the
maintenance of pluripotency and self-renewal of undifferentiated embryonic stem
cells. This study aims to evaluate the epidemiological, clinical-pathological and
expression of the OCT4 and NANOG proteins in cutaneous melanoma samples. We
selected 102 cases for the epidemiological, clinical and pathological study,
diagnosed between the years 2004 to 2008. For survival study, patients with a followup
of up to 60 months were selected, with a recorded death. Of the 102 cases
evaluated, 62.7% were female and 37.3% male; With mean age of 57.2 years and
63.1 years respectively (p= 0.0026). The most prevalent age at diagnosis of
melanoma was between 51 and 70 years (44.1% p= 0.023). In this study, there was
a predominance of lesions located in the trunk (32.3%). Histopathological
examination of the type of tumor growth showed a predominance of the superficial
extensive type in 52.9% of the cases. According to the Breslow index, lesions with
≤1.0 mm predominated in 39.2% of the individuals, followed by lesions> 4.0 mm in
23.5% of the cases. According to the Clark level 29.4% of the cases were classified
in level IV; Followed by 25.5% cases with level V; Clark II in 23.5%; Clark III in
20.6%; And Clark I in only 1 case (1.0%). There were metastases in 47% of the
cases and the main localization sites were: lymph nodes, brain, skin and lung.
Regarding the clinical evolution of the patients, there were 26 cases of deaths due to
melanoma (25.5%). The survival curve calculated at the 60-month follow-up was
73.0%. Univariate analysis revealed significant associations between nuclear
overexpression of OCT4 and the following variables: Breslow index with thickness >
2.1 mm (p = 0.021, OR: 2.64, 95% CI: 1.15-6.05 ); Levels of Clark, IV and V (p =
0.001, OR: 4.11, 95% CI: 1.79-9.46); ulceration present (p≤0.0001; OR: 459.0; 95%
CI: 51.67-4077.27); Presence of metastases (p <0.0001, OR: 40.25, 95% CI: 12.90-
125.62), and death from cutaneous melanoma (p <0.0001). The significant
associations between cytoplasmic hyperexpression of OCT4 and the following
variables were: present ulceration (p = 0.015, OR: 2.73, 95% CI: 1.21-6.16);
Presence of metastases (p = 0.004, OR: 3.34, 95% CI: 1.47 - 7.62) and death from
cutaneous melanoma (p = 0.039, OR 2.67, 95% CI 1.05 - 6,77). And the significant
associations between the cytoplasmic hyperexpression of NANOG and the following
variables were: present ulceration (p≤ 0.0001); Presence of metastases (p ≤ 0.0001)
and death due to cutaneous melanoma (p = 0.030). Our study demonstrated a strong
association of the OCT4<br>O melanoma cutâneo é um tipo de câncer de pele que tem origem nos melanócitos,
afetando predominantemente adultos jovens e de meia-idade. Diversas evidências
sugerem a existência células-tronco tumorais para o melanoma. Os genes
POU5F1/OCT4, NANOG vem sendo estudados como marcadores células-tronco
tumorais. O OCT4 e o NANOG estão envolvidos na manutenção da pluripotência e
autorrenovação das células-tronco embrionárias indiferenciadas. Este estudo tem
por objetivo avaliar os fatores epidemiológicos, clínico-patológicos e expressão da
proteína OCT4 e NANOG em amostras de melanoma cutâneo. Foram selecionados
102 casos para o estudo epidemiológico, clínico e patológico, diagnosticados entre
os anos de 2004 a 2008. Para estudo de sobrevida foram selecionadas pacientes
com seguimento de até 60 meses, com óbito registrado. Dos 102 casos avaliados
foram observados 62,7% do gênero feminino e 37,3% masculino; com média de
idade de 57,2 anos e 63,1 respectivamente (p= 0,0026). A idade de maior
prevalência ao diagnóstico do melanoma foi entre 51 a 70 anos (44,1% p= 0,023).
Nesse estudo, houve predomínio das lesões localizadas no tronco (32,3%). Ao
exame histopatológico quanto ao tipo de crescimento do tumor, houve predomínio
do tipo extensivo superficial em 52,9% dos casos. Segundo o índice de Breslow
predominaram as lesões com ≤1,0mm em 39,2% dos indivíduos, seguidas pelas
lesões >4,0mm em 23,5% dos casos. De acordo com o nível de Clark 29,4% dos
casos foram classificados no nível IV; seguidas por 25,5% casos com nível V; Clark
II em 23,5%; Clark III em 20,6%; e Clark I em apenas 1 caso (1,0%). Houve
metástases em 47% dos casos e os principais sítios de localização foram:
linfonodos, cérebro, pele e pulmão. Em relação à evolução clínica dos pacientes
ocorreram 26 casos de óbitos por melanoma (25,5%). A curva de sobrevida
calculada no seguimento de 60 meses foi de 73,0%. A análise univariada revelou
associações significativas entre a hiperexpressão nuclear de OCT4 e as seguintes
variáveis: índice de Breslow com espessura de > 2,1 mm (p= 0,021; OR: 2,64; IC
95%: 1,15 - 6,05); níveis de Clark, IV e V (p= 0,001; OR: 4,11; IC 95%: 1,79 - 9,46);
ulceração presente (p≤ 0,0001; OR: 459,0; IC 95%: 51,67 - 4077,27); presença de
metástases (p≤ 0,0001; OR: 40,25; IC 95%: 12,90 - 125,62) e óbito por melanoma
cutâneo (p≤ 0,0001). As associações significativas entre a hiperexpressão
citoplasmática de OCT4 e as seguintes variáveis foram: ulceração presente (p=
0,015; OR: 2,73; IC 95%: 1,21 - 6,16); presença de metástases (p= 0,004; OR: 3,34;
IC 95%: 1,47 - 7,62) e óbito por melanoma cutâneo (p= 0,039; OR: 2,67; IC 95%:
1,05 - 6,77). E as associações significativas entre a hiperexpressão citoplasmática
de NANOG e as seguintes variáveis foram: ulceração presente (p≤ 0,0001);
presença de metástases (p≤ 0,0001) e óbito por melanoma cutâneo (p= 0,030).
Nosso estudo demostraram uma forte associação dos genes OCT4 e NANOG como
os piores fatores prognósticos do melanoma cutâneo.
27
Yamani, Zuhoor. "Design of Multi-function Polymeric Nanoparticles for Theranostic Application." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-255348.
Full textAbstract:
Block copolymer nanoparticles (NPs) have gained great attention among researcher for various medical application mainly due to their extraordinary optical, chemical, and biological properties. The current thesis presents design of multifunctional polymeric NPs for imaging and drug delivery system (DDS) with an in-vitro study of their participation in drug release and cell viability. The NPs were synthesized using reversible addition chain fragmentation transfer (RAFT)-mediated emulsion polymerization via polymerization induce self-assembly (PISA) approach. The environment-friendly emulsion polymerization process of n-buytl acrylate (n-BA) in water is highly efficient. The process produced uniform NPs which would have control over the particle size and molecular weight of the compound. Herein we report a novel simultaneous encapsulation of camptothecin (CPT) and Nile red (NR) into poly(ethylene glycol) methyl ether methacrylate-co-N-hydroxyethyl acrylamide-b-poly n-buytlacrylate (PEGA-co-HEAA)-b-P(n-BA) during the particles formation with a small particle size of 66 nm, high conversion ~80% and encapsulation efficiency of ~50%. The In vitro drug release of the CPT from the NPs exhibited an initial burst (70-80%) within 6h. cell viability was evaluated for the NPs against RAW 264.7 cell line, which indicated the designed NPs are biocompatible and not toxic.
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FREDDI, STEFANO. "Gold nanorods characterization for nanomedical applications." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2012. http://hdl.handle.net/10281/28477.
Full textAbstract:
In recent years, several groups have investigated the changes of chemical and physical properties of materials with size in the nanometer scale. These studies have highlighted a number of possible applications for nanostructures, which are now employed, for example, in biology and medicine for imaging, disease detection, diagnosis, sensing and therapy.
In noble metals, the coherent collective oscillation of electrons in the conduction band (Surface Plasmon Resonance, SPR), induces large surface electric fields which greatly enhance the radiative properties of gold and silver NPs when they interact with resonant electromagnetic radiation. The coupling of SPR with the electromagnetic field may lead to a huge enhancement of both the absorption and scattering cross sections.
The SPR, tunable in the visible (for spherical gold NPs) and near-infrared region (for anisotropic gold NPs) of the electromagnetic spectrum, can also interact, with the fluorescence emission of dyes and substantially modify their brightness and excited-state lifetime. One of the considerations that has inspired the present project is the expect that any change in the dielectric constant of the NP surface, induced, for example, by a biorecognition process that occurs on the surface itself, can produce a change in the emission properties of the fluorophores.
SPR effect becomes also important when combined with two-photon excitation (TPE), which consists in the simultaneous absorption of two photons, each carrying about half the energy necessary to excite the molecule. In fact, the luminescence (TPL) induced by TPE is enhanced (when coupled with an appropriate plasmon resonance) by many orders of magnitude in gold nanorods respect to a standard fluorophore. These properties promise to improve the usefulness of these nanoparticles for in-vivo imaging in the NIR region of the electromagnetic spectrum and have inspired the second part of the project.
The aim of the first part has been studied the interaction of gold nanoparticles a few nanometers in size with fluorophores and to exploit the changes of the dye excited-state lifetime and brightness induced by our interaction in solution under physiological conditions. I have investigated the system based on 5 and 10 nm gold NPs coupled (via a biotin-streptavidin linker) to a fluorophore (FITC) and to a specific protein antibody. The binding of protein to the gold NPs through antigen-antibody recognition modifies the dye excited-state lifetime, which change can then be used to measure the protein concentration.
In particular, we have tested the nanodevice measuring the change of the fluorophore excited-state lifetime after the binding of the model protein bovine serum albumine (BSA) and p53 protein, a marker for early cancer diagnosis and prognosis (both in standard solution and in total cell extracts). These studies have been published in {J. Phys. Chem. C 2009 113(7) 2722-2730} and {J. Biom. Nanotech. 2009 5 683-691}.
In the second part of the project I focused on the use of anisotropic gold nanoparticles as probe in cellular imaging. I have studied the optical properties of gold nanorods synthesized with standard surfactant CTAB (cetyl trimethylammonium bromide) and asymmetric branched gold nanoparticles synthesized with zwitterionic surfactant LSB (laurylsulphobetaine). The sample have been analyzed with a number of structural techniques to obtain a complete characterization: absortpion spectra, TEM images, Fluorescence Correlation Spectroscopy (FCS) and Dynamic Light Scattering (DLS) experiments in suspensions. From the analysis of the data, I have gained information on the nanoparticles shapes, dimension and aggregation numbers. In particular, three different populations have been found: nanospheres with diameter lower than 20 nm, nanostars characterized by large trapezoidal branches, and asymmetric branced nanoparticles with high aspect ratio (≈ 4-5) (published {Chem. Comm., 2011; 47; 1315-1317}). Moreover, TPL (two-photon luminescence) was finally exploited to study by optical microscopy the problems of internalization and toxicity of gold nanoparticles by different cell line (macrophages, HEK and A549). Presently, is in preparation a manuscript on TPL, cellular uptake and cytotoxicity of branched gold NPs.
In the last year I have demonstrated the potential use of NPs, gold nanorods and magnetic nanoparticles (MNPs), as a novel contrast reagent for selective thermal therapy of cancer cells using a near-infrared low energy laser and an AC magnetic field, respectively. Photothermal therapy for cancer have been widely investigated as a minimally invasive treatment modality in comparison with other methods. The appeal of gold NRs as contrast agents is amplified by their additional capability to absorb photons and to convert into heat by nonradiative processes (phonon-phonon interaction). Magnetic nanoparticles heat inductively due to magnetic losses associated with three mechanisms: hysteresis, N\'eel relaxation and Brownian relaxation; moreover they are considered as a low toxicity material with gold and biological compatibility. These two kinds of NPs (gold and magnetic nanoparticles) are delivered to cancer cells and heated to induce apoptosis (programmed cell death).
Within this last part of the project, I have first evaluated the increase in temperature of NR and MNP solutions, using a direct visualization by means of a sensitive thermocamera. Then I have developed a nano-sensor to measure the local temperature on the surface of the nanoparticles under excitation. The rationale is to bind an organic chromophore whose excited state lifetime (ESLT) is particularly sensitive to the temperature, and to refer to its lifetime which is an intensive parameter. Rhodamine B is such a fluorophore, with a temperature dependence of the excited state lifetime ≈ 0.029 ± 0.001 ns/°C, as we also measure here. Moreover this nanoconstruct can target tissues or single cells and used for imaging before the therapy.
Part of these experimental results have been successfully composed to numerical simulations of light induced heating of gold nanorods, using the Two Temperature Model (TTM) in order to calculate raising in temperature due to laser irradiation.
Finally, I have developed methods and knowledge in the field of the use of NPs made of gold or oxide ({Nanotoxicology, 2011; doi:10.3109/17435390}) in biological and medical research and applications.
These studies have produced four publications and two additional manuscripts are under preparation on the cytotoxicity of these NPs and their use for imaging and phototherapy.
29
Alaei, Zohreh. "Molecular Dynamics Simulations of Axonal Membrane in Traumatic Brain Injury." Thesis, KTH, Skolan för teknik och hälsa (STH), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-211109.
Full textAbstract:
The following project presents in silico investigation of axonal damage in Diffuse Axonal Injury (DAI). When axons face a shear force, orientation of the lipids in the axonal membrane gets disrupted. Depending on the value of the force, a tensile strain causes the axons to get partially or fully deformed and in some cases a pore forms in the membrane. Using Molecular Dynamic (MD) simulation and a coarse grain model, a series of bilayers with various bilayer structure (single bilayer, parallel bilayer and cylindrical bilayer) and similar composition to biological axonal membrane were simulated. This was initially done to investigate the strain rate dependency of the bilayers, and their viscoelastic ability on returning to their original shape from their deformed forms. To achieve this, various deformation velocities were applied to the bilayers reaching 20% strain and relaxing the bilayer after. Additionally, the bilayers were deformed further until they reached a pore. It was found that the bilayers can almost recover from their deformed forms to their original length when they were deformed at 20% strain level. In conjunction, no correlation between the deformation velocity and lipid deformation was observed. Further, it was found that bilayers with different lipid percentage to axonal bilayer has different strain values for water penetration and for pore formation. The strain value for cylindrical bilayer was found very high compared to the strain values found in vitro. The strain for pore formation of parallel and single bilayer was found to be around 80% to 90% and for water penetration was found to be 70% for single bilayer and 50% for parallel bilayer. A slight difference in strain for pore formation between single and parallel bilayer was found which showed the bilayer structure can play a role in simulation results. The effect of the length in the simulations results was also observed where shorter bilayers showed lower strain for pore formation compared to longer bilayers.
30
Pajuelo, Rios Oscar Gabriel. "Efecto de un suplemento deportivo sobre los marcadores bioquímicos musculares y el rendimiento físico en ratones sometidos a nado forzado." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2017. https://hdl.handle.net/20.500.12672/7390.
Full textAbstract:
Publicación a texto completo no autorizada por el autor<br>Determina el efecto de un suplemento sobre los marcadores bioquímicos musculares y el rendimiento físico en ratones sometidos a nado forzado. Desarrolla un estudio analítico, experimental, transversal y prospectivo. Utilza 35 ratones Mus musculus machos adultos de 8 semanas de edad, con un peso promedio de 35,43 g, los cuales fueron distribuidos de manera aleatoria en 5 grupos (n=7) para recibir el siguiente tratamiento vía peroral: grupo I y II: suero fisiológico 10 mL/kg; y los grupos III, IV y V recibieron el suplemento deportivo a dosis de 150, 300 y 800 mg/kg de peso. Posteriormente se sometió a los grupos II, III, IV y V al test de nado forzado hasta el agotamiento. Para determinar el rendimiento físico se tomó el tiempo (minutos) de nado forzado hasta el agotamiento, con respecto a los marcadores bioquímicos se tomó la actividad enzimática del Lactato deshidrogenasa (LDH) y lipoperoxidación a nivel muscular. Encuentra que el suplemento presenta un efecto de incremento en la resistencia física de los grupos IV y V en comparación del grupo II, también se observó una reducción en la actividad la lactato deshidrogenasa (LDH) en los grupos III y IV en comparación del grupo número II, además con respecto a la lipoperoxidación se encontró una reducción en los grupos III, IV y V en comparación del grupo II. Concluye que el suplemento presenta un efecto favorable en la resistencia física y sobre los marcadores bioquímicos musculares.<br>Tesis
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Mikati, Nadine. "The Effect of Project ProHEART- Promoting Healthy Eating and Activity using Robot-assisted Training- on Healthy Eating Habits and Physical Activity in School-Aged Children." FIU Digital Commons, 2016. http://digitalcommons.fiu.edu/etd/2620.
Full textAbstract:
The objective of this study was to determine the effectiveness of a 6 week afterschool nutrition and physical activity intervention administered by a registered dietitian with the help of a humanoid robot targeting elementary school aged children aged 6-12 years. The study was conducted across four Young Men’s Christian’s Association (YMCA) sites in Miami-Dade County, Florida (N= 114, Mean age: 8.16 ±1.57 years) using a pretest-posttest quasi-experimental design via randomly assigned intervention (two sites; n=63) and comparison groups (two sites; n=51). The validated Coordinated Approach to Child Health (CATCH) kids club questionnaire and the validated Previous Day Physical Activity Recall (PDPAR) were used to assess nutrition and physical activity knowledge, attitudes/beliefs and behavior change. The Inbody 230 instrument (Biospace, California) was used to calculate body composition and weight. Body Mass Index (BMI) percentiles and associated BMI z-scores for age and gender were calculated based on the Center for Disease Control and Prevention (CDC) growth charts. Data measures were collected at baseline (week 0) and one-week post intervention (week 7). Statistical analysis included independent t-test, paired t-test, chi-squared test, Wilcoxon signed ranks test and logistic regression. Results indicated that nutrition knowledge score significantly increased from 67.43% ±21.03 to 81.31% ±18.47 in the intervention group (p
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Beauthier, Jean-Pol. "Contribution à l'approche anthropologique et médico-légale des sutures viscérocrâniennes utiles dans l'estimation de l'âge au décès (Sutures palatines, fronto-naso-maxillaires et zygomatiques)." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210228.
Full textAbstract:
Les sutures crâniennes ont été régulièrement étudiées au fil des siècles puisque déjà Vésale établissait une relation entre l’âge et la synostose suturale.<p><p>Leur imprécision a quelque peu confiné l’observation de ces sutures dans un certain oubli, justifié en partie.<p><p>Il est clair que leur fiabilité quant à l’estimation de l’âge au décès reste discutable et ce, pour diverses raisons.<p><p>Leur observation est difficile et dès lors sujette à subjectivité dans l’appréciation de leurs stades de fusion.<p><p>De plus, leur apparence sur le crâne sec peut être altérée par divers artéfacts de conservation (cire, vernis…).<p><p>Outre l’observation des classiques sutures ectocrâniennes de voûte et l’utilisation des méthodes habituelles en la matière (méthode de Acsádi et Nemeskéri, méthode de Masset), nous avons orienté notre étude vers des sutures peu voire pas exploitées, à savoir les sutures palatines, les sutures fronto-naso-maxillaires et les sutures de l’os zygomatique.<p><p>Ces trois groupes suturaux ont la particularité d’évoluer de manière très lente vers la fusion, à tel point que peu d’individus en présentent une oblitération complète.<p><p>Face au vieillissement de la population et de par notre expérience médico-légale et anthropologique d’étude de pièces osseuses de personnes âgées, nous avons estimé qu’il était utile de se pencher sur des collections particulières de sujets d’âge avancé, afin d’apprécier l’évolution morphologique de ces sutures faciales.<p><p>Si certaines personnes fort âgées gardent malgré tout des caractéristiques suturales peu évoluées, il existe dans l’ensemble, une progression suturale quasiment constante en fonction de l’âge.<p><p>Nous avons tenté de la cerner, en attribuant à ces sutures, des degrés bien définis de cette progressive fusion et par là, l’aboutissement à un coefficient moyen d’oblitération suturale, se traduisant aisément en pourcentage d’oblitération ou pouvant être introduit dans des équations de régression.<p><p>Tout en connaissant les limites de cette approche, nous pouvons estimer qu’elle peut rendre des services lors de l’étude de restes humains squelettisés, notamment s’ils appartiennent à des personnes fort âgées, dès lors qu’à ces stades de vieillissement, peu de méthodes restent encore applicables. D’autre part, l’approche en pourcentage d’oblitération suturale rend également des services lorsque les crânes étudiés sont fragmentés. C’est la situation que nous rencontrons actuellement lors de l’étude d’une très importante collection anthropologique à l’Institut royal des Sciences naturelles de Belgique.<p><p>Cette observation suturale pourra également – à l’avenir – trouver un terrain d’approche fort utile par l’étude des sutures en CT-Scan ou en micro-CT.<p><p>Enfin, grâce à ces techniques modernes d’imagerie médicale, les sutures trouvent un regain d’intérêt dans une application toute particulière, qui est celle de l’identification comparative, puisqu’il apparaît que le « dessin sutural » s’avère tout à fait propre à chaque individu.<p><p>/<p><p>Cranial sutures were regularly studied during centuries since Vésale already established a relationship between age at death and sutural fusion. <p><p>Their inaccuracy somewhat confined the observation of these joints in a certain lapse of memory, partly justified. <p><p>Various reasons clearly indicate that their reliability for age at death estimation remains debatable. <p><p>Their observation is difficult and consequently prone to subjectivity in the appreciation of their stages of fusion. <p><p>Moreover, their appearance on dry cranium can be modified by various artefacts from preserving methods (wax, varnished…). <p><p>In addition to the traditional observation of ectocranial sutures (with the usual methods such as Acsádi and Nemeskéri method and Masset method), we have directed our study towards not much exploited sutures, namely the palatine sutures, the fronto-naso-zygomatic sutures and the sutures of the zygomatic bone. <p><p>These three sutural groups are characteristic by evolving very slowly to fusion, and than, only few individuals present a complete obliteration of the latter. <p><p>Because of general population ageing and our medicolegal and anthropological experience of skeletal remains in elderly, we estimated the usefulness in studying particular collections of old people, in order to appreciate the morphological evolution of these facial joints. <p><p>Despite some very old people who present little evolved sutural characteristics, we consider as a whole, an almost constant sutural progression according to age. <p><p>We tried to define degrees of this progressive fusion and by the way, the result with a sutural obliteration average coefficient, can be easily translate as a percentage obliteration or able to be introduced into regression equations. <p><p>The limits of this approach are well known but we estimate that it is possible to help the examination of human skeletal remains in elderly, although at these stages of ageing, some methods remain still applicable. In addition, the approach expressed as a percentage of sutural obliteration is also very helpful when craniums are fragmented. This situation is currently observed on the anthropological collections at the Royal Belgian Institute of Natural Sciences. <p><p>Furthemore in the future, the sutural observation will find an interesting and useful approach by the study of the joints in CT-Scan or micro-CT. <p><p>At least, thanks to these modern techniques of medical imagery, the sutures find a renewed interest in a very particular application, such as comparative identification. It appears that the "sutural drawing" proves completely specific to each individual. <p><p><br>Doctorat en sciences médicales<br>info:eu-repo/semantics/nonPublished
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SIRONI, LAURA. "Nanoparticles for in-vitro and in-vivo biosensing and imaging." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2011. http://hdl.handle.net/10281/19278.
Full textAbstract:
In the last two decades several groups have investigated the changes of chemical and physical properties of materials with size in nanometric scales. These studies have highlighted a number of possible applications for nanostructures, which are now employed, for example, in biology and medicine for imaging, disease detection, diagnosis, sensing and therapy.
Noble metals (especially gold and silver nanoparticles) are particularly versatile for these applications due to the phenomenon known as surface plasmon resonance (SPR), an in-phase oscillations of all the conduction band electrons that resonates with the light wave electric field. The resonance frequency depends on the size, shape, orientation and dielectric constant of the nanoparticle. This coupling of SPR with the electromagnetic field leads to a large enhancement of all the nanoparticle radiative properties, such as absorption and scattering. The extinction cross section of these nanoparticles is 10^5-10^6 larger than that of organic dyes and in contrast to common molecular chromophores they are extremely photostable and, depending on the shape, they convert efficiently light into heat. The SPR, tunable in the visible (for spherical NPs) and near-infrared region (for anisotropic Nps) of the electromagnetic spectrum, can also interact, for gold nanoparticles a few nanometers in size, with the fluorescence emission of dyes and substantially modify their brightness and excited-state lifetime. Depending on the fluorophores-NP distance and the NPs anisotropy one can obtain fluorescence enhancement or quenching. In both cases we expect that any change in the dielectric constant of the NP surface, induced, for example, by a biorecognition process that occurs on the surface itself, can produce a change in the emission properties of the fluorophores.
SPR effect becomes also particularly important when combined with two-photon excitation (TPE), which consists in the simultaneous absorption of two photons, each carrying about half the energy necessary to excite the molecule. TPE offers a series of unique features for biological investigation both in vitro and in vivo. First, the two-photon absorption bands of the dyes commonly used in biological studies are wider than their one-photon analogous allowing the simultaneous excitation of multiple fluorophores with a single excitation wavelength. Second, the stimulating light beam has a high penetration depth because of the long infrared wavelengths used, allowing experiments in turbid media. Third, excitation takes place only at the plane of focus, due to the scaling of the probability of simultaneous photon absorption with the square of the light intensity. As a consequence TPE avoids the simultaneous absorption of photons outside the specimen drastically reducing both photo-toxicity and fluorophore bleaching. These advantages make nowadays TPE a well established tool for scientific biological and medical research and can be coupled to anisotropic gold nanoparticles.
In fact, the luminescence (TPL) induced by TPE is enhanced (when coupled with an appropriate plasmon resonance) by many orders of magnitude in non spherically symmetric NPs of noble metal with respect to the single photon excitation on smooth noble metal surfaces. These properties promise to improve the usefulness of these nanoparticles for in-vivo imaging in the NIR region of the electromagnetic spectrum. According to these considerations we have developed our project on two lines related to the use of gold nanoparticles for sensing and non linear imaging. The aim of the first part of this research project is to exploit changes of the dye excited-state lifetime and brightness induced by its interaction with the gold surface plasmons for detection of tiny amounts of protein in solution under physiological conditions. The system we investigated is based on 10 and 5 nm diameter gold NPs coupled (via a biotin- streptavidin linker) to the FITC dye and to a specific protein antibody. The interaction of the fluorophore with the gold surface plasmon resonances, mainly occurring through quenching, affects the excited state lifetime that is measured by fluorescence burst analysis in highly diluted suspensions. The binding of protein to the gold NPs through antigen-antibody recognition further modifies the dye excited-state lifetime, which change can then be used to measure the protein concentration. In particular, we have tested the nanodevice measuring the change of the fluorophore excited-state lifetime after the binding of the model protein bovine serum albumin (BSA); then we have applied the nanoassay in order to recognize the p53 protein, whose detection in the body is highly valuable as marker for early cancer diagnosis and prognosis, both in standard solutions and in total cell extracts. The selectivity of the construct with respect other globular proteins has been also addressed. The data indicate that the FITC excited-state lifetime is a very sensitive parameter in order to detect tiny amounts of protein in solution with an estimated limit of detection of about 5 pM, mostly determined by the statistical accuracy of the lifetime measurement.
In the second part of the project we focused on the exploitation of anisotropic gold nanoparticles as probes in cellular imaging. We have then studied their photoluminescence (TPL) properties under two photon excitation. We have focused on gold nanorods that can easily be obtained by synthesis with the standard surfactant CTAB (cetyl trimethylammonium bromide). The synthesis of asymmetric branched gold nanoparticles, obtained using for the first time in the seed growth method approach a zwitterionic surfactant, laurylsulphobetaine (LSB), has been developed in collaboration with the University of Pavia (Prof. P.Pallavicini). We have shown that LSB concentration in the growth solution allows to control the dimension of the NPs and the SPR position, that can be tuned in the 700-1100 nm Near Infrared range. The samples have been analyzed with a number of structural techniques to obtain a complete characterization: absorption spectra in the UV-Visible region, TEM images of the suspensions, Fluorescence Correlation Spectroscopy (FCS) and Dynamic Light Scattering (DLS) experiments in suspensions. From these data we reached information on the nanoparticles shapes, dimensions and aggregation. In particular, three different populations have been found: nanospheres with diameter lower than 20 nm, nanostars characterized by large trapezoidal branches, and asymmetric branched nanoparticles with high aspect ratio (3-4). A full characterization of the NPs TPL was performed for imaging applications by employing two photon excitation (TPE). The dependence of the TPL intensity on the power, wavelength and polarization of the incident light intensity was studied and TPL was exploited to study the cellular uptake of the nanoparticles in different cell lines (macrophages and HEK cells).
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Segervald, Jonas. "Fabrication and Optimization of a Nanoplasmonic Chip for Diagnostics." Thesis, Umeå universitet, Institutionen för fysik, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-163998.
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To increase the survival rate from infectious- and noncommunicable diseases, reliable diagnostic during the preliminary stages of a disease onset is of vital importance. This is not trivial to achieve, a highly sensitive and selective detection system is needed for measuring the low concentrations of biomarkers available. One possible route to achieve this is through biosensing based on plasmonic nanostructures, which during the last decade have demonstrated impressive diagnostic capabilities. These nanoplasmonic surfaces have the ability to significantly enhance fluorescence- and Raman signals through localized hotspots, where a stronger then normal electric field is present. By further utilizing a periodic sub-wavelength nanohole array the extraordinary optical transmission phenomena is supported, which open up new ways for miniaturization. In this study a nanoplasmonic chip (NPC) composed of a nanohole array —with lateral size on the order of hundreds of nanometer— covered in a thin layer of gold is created. The nanohole array is fabricated using soft nanoimprint lithography on two resists, hydroxypropyl cellulose (HPC) and polymethyl methacrylate (PMMA). An in depth analysis of the effect of thickness is done, where the transmittance and Raman scattering (using rhodamine 6G) are measured for varying gold layers from 5 to 21 nm. The thickness was proved to be of great importance for optimizing the Raman enhancement, where a maximum was found at 13 nm. The nanohole array were also in general found beneficial for additionally enhancing the Raman signal. A transmittance minima and maxima were found in the region 200-1000 nm for the NPCs, where the minima redshifted as the thickness increased. The extraordinary transmission phenomena was however not observed at these thin gold layers. Oxygen plasma treatment further proved an effective treatment method to reduce the hydrophobic properties of the NPCs. Care needs be taken when using thin layers of gold with a PMMA base, as the PMMA structure could get severely damaged by the plasma. HPC also proved inadequate for this projects purpose, as water-based fluids easily damaged the surface despite a deposited gold layer on top.
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Cheng, Tzu Yun, and 程子芸. "Characterization of Functionalized Self-Assembling Nano-peptides for Regenerative Medicine Applications." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/20449839762495464953.
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碩士<br>國立清華大學<br>材料科學工程學系<br>100<br>With the property of sol-gel transition in physiological condition and numerous advantages from peptide-based material, self assembling peptide (SAP) has been regarded as a promising 3D hydrogel scaffold or cell/gene (drug) carrier for the applications in tissue engineering and drug delivery system. The additional functional motifs with various modification ratios and multi-extended diversity can be conjugated and extended at the terminal residue sequence of specific-designed SAPs to enrich SAP possessing therapeutic functionality for different biopharmaceutical applications and serve as medical disease treatment modality. In this study, we specifically enriched RADA16, one of the widely used SAPs, with different functional motifs and evaluated the medical applications of the functionalized SAPs in hemostasis, liver tissue regeneration and brain neural tissue repair in the central nervous system.
In the first part of this study, the physiochemical properties and gelation mechanism of SAPs were in detail investigated. The pKa1, pKa2, and isoelectric point (pI) was obtained by pH titration curve. The peptide showed net-charged at neutral pH value. The protein secondary structure of β-sheet arrangement was confirmed by circular dichroism (CD) spectroscopy. The morphology of nanofibers about 25nm diameter was observed by atomic force microscopy (AFM). The gelation behavior in terms of mechanical property of hydrogel was determined by oscillatory rheology test. As for in vitro experiments, the relative low cytotoxicity of peptide hydrogel was examined by Live/Dead assay and the high cell proliferation ability was shown in 3D hydrogel culture by MTS assay. The results demonstrated that the encapsulated neural stem cells well survived with 3D culture in SAP hydrogel. We also found that even with extended motifs, the gelation behavior, physical and chemical properties of functionalized SAPs were still preserved. It is believed that the functionalized SAPs can be a promising material for follow-up tissue engineering applications.
In hemostasis and liver tissue regeneration study, specifically extended fragments of functional motifs derived from fibronectin and laminin, GRGDS and YIGSR, was designed to evaluate the capability of these functional SAPs in the effect of immediate hemostasis and accelerative liver tissue regeneration. The results showed that hemostasis can be achieved within 10 seconds and the histological analyses demonstrated by H/E stain and immunohistochemistry revealed that SAPs with these extended functional motifs significantly enhanced liver tissue regeneration in rat liver wound model. It is reported that SAPs enriched with the extended functional motifs not only maintained their spontaneous self-assembly property but also extensively advanced the potential therapeutic effect in hemostasis and liver tissue regeneration.
In the study of brain neural tissue repair in the central nervous system, the functionalized RADA16-IKVAV peptide hydrogel was used to encapsulate neural stem cells (NSCs) for investigation of the effectiveness in brain tissue regeneration. The results showed that after 6 weeks transplantation, the regenerative extracellular matrix (ECM) of brain neural tissue was noticed. The specific neuronal protein markers, such as βIII tubulin, MAP2, NF-H were positively stained in the region of wound defect area, suggesting regenerative process of neuronal cells in the brain cerebral cortex.
In summary, we have successfully developed functionalized SAPs with multiple extended motifs, including RADA16-GRGDS, RADA16-YIGSR and RADA16-IKVAV, and their physiochemical properties were also carefully evaluated for the comparison with RADA16 nanopeptides. These functionalized SAPs can not only be used alone as 3D nanoscale scaffold for immediate hemostasis and accelerative liver tissue wound healing, but also be incorporated with neural stem cells for the improvement of brain tissue repair in the central nervous system.
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LO, LI-TA, and 羅立達. "Whitening Nano-Fiber Masks Composed of Traditional Chinese Medicine： Manufacturing Design and Characteristic Evaluations." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/41228165475770490704.
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碩士<br>中臺科技大學<br>生物科技暨醫學工程研究所<br>105<br>This study proposes composite masks with avirulence, humectancy, and whitening properties. Polymeric materials, including polyvinyl pyrrolidone (PVP), gelatin (GEL), and Morus alba (MA), are combined with spunlace nonwoven fabrics in order to form cosmetic care products. This study can be divided into three stages. In the 1st stage： natural Chinese herbal medicine are extracted and evaluated for whitening efficacy. In the 2nd stage, PVP/GEL/MA nanofiber membranes are prepared. In the last stage, membranes are then combined with nonwoven fabrics. Natural Chinese herbal medicine, including Sophora japonica, Spatholobus suberectus, Morus alba, and Polygonatum odoratum are respectively immersed in pure water and 95% ethanol solution in order to have the Chinese herbal medicine extracts. The extracts are tested in terms of extractability, biocompatibility, and MTT assay, thereby characterizing the properties of the four Chinese herbal medicine. Tyrosinase inhibition ratio is used to examine the water-extraction Morus alba (MA) extract to be the optimal whitening extract. Moreover, the PVP/GEL/MA solution is electrospun into spunlance nonwoven, forming PVP/GEL/MA composite masks.
The test results show that MA herbal extract at a concentration of 0.5 mg/ml has good inhibition ratio against tyrosinase, and the MTT assay result is 88 %, indicating a good biocompatibility with L929 fibroblasts. The electrospinning film has a smooth fiber formation when a 20 wt% PVA/GEL mixture is used. The addition of GEL and MA increases both the viscosity and electrical conductivity of the mixtures. The electrospun nanofibers are slim without bead-shaped and have a diameter of 210 nm with the settings of a voltage of being 20kV, a collect distance of being 15 cm, and an electrospinning rate being 0.5 mg/hr. Based on the contact angle meter restuls, the combination of PVP/GEL/MA film and spunlance nonwoven results in a water contact angle of 29.2°, suggesting a good hydrophility. The water vapor transmission rate of PVP/GEL/MA mask is 600-800 g/m2day, which is close to that of the human skin (350 g/m2day), which means the masks have good air-permeable property and suitable for the skin. Moreover, according to the tyrosinase inhibition measurement, the masks have a drug delivery period of 25 minutes at a release rate of 75 %, and an inhibition ratio of 81.42±1.6%. Namely, the whitening effect of the proposed composite masks is slightly higher than that of ready-made masks. In addition, the proposed composite masks have an MTT assay result at 88.79%, which shows that PPVP/GEL-MA composite masks does not obstruct the cell growth and have good biocompatibility. All test results confirm that the PVP/GEL/MA composite membranes have good whitening efficacy and biocompatibility.
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Tso-WeiHuang and 黃佐維. "Graphene oxide whitens teeth by reduction-oxidation reaction: A novel application of nano-medicine in dentistry." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/t8pchq.
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Kreutzer, Bruna. "Polymeric Micelles to improve Salinomycin delivery to cancer cells." Master's thesis, 2018. http://hdl.handle.net/10316/84418.
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Dissertação de Mestrado em Biotecnologia Farmacêutica apresentada à Faculdade de Farmácia<br>Introdução: A abordagem de utilizar nano medicina para tratar dentre outras doenças, o cancro vem sendo utilizada e estudada cada vez mais para ultrapassar as barreiras encontradas na terapia convencional. A utilização do polímero anfifílico não tóxico como o Pluronic F127 para a formação de nano partículas traz grandes vantagens por formar micelas de substâncias biologicamente ativas com tamanhos de 10 a 100 nm que tem como objetivo entregar fármacos pouco solúveis as células, além de terem a habilidade de entrar passivamente via aumento de permeabilidade e retenção das células tumorais aumentando assim a biodisponibilidade e acúmulo do fármaco nas células de interesse, diminuindo efeitos adversos causados por quimioterápicos. A Salinomicina (SAL) é um antibiótico isolado de Streptomyces albus que recentemente mostrou ser um novo candidato ao tratamento de cancro por inibir seletivamente células estaminais presentes no cancro responsáveis pelo ressurgimento da doença e resistência aos fármacos quimioterápicos.Objetivos: O objetivo principal deste estudo é o design de micelas poliméricas (PM) para distribuição de SAL para células cancerígenas e sua caracterização em termos de diâmetro médio (MD), carga de superfície (ZP) e índice de poli dispersão (PDI). A capacidade de encapsulaçao de MP SAL é determinada e sua eficácia in vitro em relação ao modelo NSCLC foi avaliada e comparada com a atividade livre do fármaco.Métodos: A formação de micelas foi feita pela técnica de reidratação de filme, onde o solvente orgânico contendo uma mistura de fármaco e polímero é evaporado a fim de formar um filme polimérico. Esse filme então é reidratado com água e agitado e há a formação de micelas. Ensaios in vitro como MTT, wound healing e imunocitoquímica foram realizados em triplicata com cultura celular em placas de 96 e 24 poços seguidos de tratamentos com fármaco livre (SAL), fármaco encapsulado (PM SAL) em micelas bem como micelas vazias (Plain PM) em diferentes tempos de incubação. Para a imunocitoquímica, anticorpos anti Pg-p e Vimentina foram utilizados a fim de observar no microscópio de fluorescência os níveis de expressão destas proteínas.Resultados: A caracterização das micelas confirmou que o polímero utilizado foi capaz de formar micelas com tamanhos e índice de poli dispersão esperados (<100nm e < 0,4 respectivamente) já o potencial zeta foi diretamente alterado a medida que a concentração de polímero aumentava, ou seja, quanto maior a concentração de polímero mais próximo da neutralidade a carga de superfície. Para os resultados de MTT, SAL em sua forma não encapsulada mostrou ter efeito dose e tempo dependente em células de cancro de pulmão após 48 horas e além disso, mostrou ser mais eficaz do que em sua forma encapsulada.Nos ensaios de invasão celular (wound healing) SAL e PM SAL mostraram efeitos semelhantes na retenção de migração celular após 24 horas. Nos resultados de imunocitoquímica, SAL e PM SAL mostraram resultados muito semelhantes em inibir a expressão de Pg-p. Por fim, quanto a expressão de vimentina, pode-se observar que quando a concentração de fármaco foi aumentada para 20 uM, houve uma diminuição mais acentuada da expressão de vimentina nas células tratadas com PM SAL. Conclusão: As micelas poliméricas apresentaram as características propostas para a entrega de SAL. Nos ensaios de viabilidade celular, não demonstraram ter efeito citotóxico mais acentuados do que em sua forma livre, porém as PM SAL resistiram ao processo biológico e sua eficácia foi demonstrada na inibição da migração celular, na evasão da Pg-p e inibição da vimentina. Isto indica que as PM SAL podem ser um eficiente coadjuvante no tratamento de NSCLC. Estudos posteriores serão necessários mais para entender melhor a internalização das micelas assim como se faz necessária a funcionalização com anticorpos para que as micelas sejam direcionadas para as células de interesse.<br>Introduction: The approach of using nano medicine to treat several diseases, for cancer has been increasingly used and studied to overcome the barriers found in conventional therapy. The use of the non-toxic amphiphilic polymer such as Pluronic F127 for the formation of nano particles brings great advantages by forming micelles of biologically active substances with sizes from 10 to 100 nm. This technique aims to deliver poorly soluble drugs to the cells, in addition to achieve the ability to passively enter via enhanced permeability and retention (EPR) of tumour cells thereby increasing the bioavailability and accumulation of the drug in the cells of interest, decreasing adverse effects caused by chemotherapeutics. Salinomycin (SAL) is an isolated Streptomyces albus antibiotic that has recently been shown to be a new candidate for cancer treatment by selectively inhibit cancer stem cells responsible for disease resurgence and resistance to chemotherapeutic drugs.Objectives: The main goal of this study is the design of polymeric micelles (PM) for SAL delivery to cancer cells and their characterization in terms of medium diameter (MD), surface charge (ZP) and poly dispersion index (PDI). MP SAL loading capacity is determined and it’s in vitro in effect against NSCLC model was assessed and compared with the free drug activity.Methods: The preparation of micelles was done by the film rehydration technique, where the organic solvent containing a mixture of drug and polymer is evaporated to form a polymer film. This film is then rehydrated with water and vortex to form micelles. In vitro assays such as MTT, wound healing and Immunocytochemistry were performed in triplicate with cell culture in 96 and 24 plates followed by treatments with free drug (SAL), encapsulated drug (PM SAL) in micelles and empty micelles (Plain PM) in different incubation time points. For immunocytochemistry, anti-Pg-p and vimentin antibodies were used to observe the levels of expression of these proteins in the fluorescence microscope.Results: The micelles characterization confirmed that the polymer was able to form micelles with expected MD and PDI (<100nm and <0.4 respectively), ZP was directly altered as a function on the polymer concentration. For the MTT results, SAL in its non encapsulated form has shown to have dose and time dependent effect on lung cancer cells after 48 hours and furthermore proved to be more effective than in its encapsulated form. The wound healing results SAL and PM SAL had similar effects on retention of cell migration after 24 hours. In the results of immunocytochemistry, SAL and PM SAL seems to have very similar results in inhibiting Pg-p expression. Finally, as for Vimentin expression, it can be seen that, when the drug concentration was increased to 20 uM, there was more marked decrease in Vimentin expression in the cells treated with PM SAL.Conclusion: The polymeric micelles has presented the characteristics proposed for SAL delivery. In the cell viability assays, PM SAL were not shown to have more marked cytotoxic effect than in their free form, but PM SALs resisted the biological process and their efficacy was demonstrated in inhibition of cell migration, Pg-p evasion and inhibition of vimentin expression. This indicates that PM SAL can be an efficient adjunct in the treatment of NSCLC. Further studies will be needed for better understanding of the micelles internalization process, also the functionalization with antibodies is necessary to directing the micelles to the cells of interest.
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Santos, Pedro Miguel Marques Dias. "Relatórios de Estágio e Monografia intitulada "Medicamentos de base nanotecnológica na terapia anti-tumoral, no mercado e em ensaios clínicos"." Master's thesis, 2018. http://hdl.handle.net/10316/84538.
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Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia<br>No âmbito da Unidade Curricular de Estágio Curricular do Mestrado Integrado em Ciências Farmacêuticas da Faculdade de Farmácia da Universidade de Coimbra, o presente documento apresenta, sob a forma de análise SWOT (Strengths, Weaknesses, Opportunities and Threats), o relatório de estágio em Indústria Farmacêutica, relativo ao estágio realizado na Farmalabor, em Condeixa-a-Nova, com início a 8 de janeiro e término a 29 de março de 2018, bem como o relatório de estágio em Farmácia Comunitária, realizado na Farmácia de Celas, em Coimbra, entre os dias 2 de abril e 15 de julho de 2018. O presente documento inclui ainda a monografia intitulada “Medicamentos de base nanotecnológica na terapia anti-tumoral, no mercado e em ensaios clínicos”.O cancro é hoje uma das principais causas de mortalidade a nível global. A quimioterapia convencional apresenta várias limitações, como a entrega não específica dos agentes terapêuticos, levando muitas vezes a problemas de toxicidade. Nos últimos anos, o crescimento rápido da nano-medicina na área da oncologia tem demonstrado inúmeros avanços através do desenvolvimento de várias nano-terapias. Estas terapias recorrem a nano-transportadores com o objetivo de proporcionar um tratamento direcionado, alterando o perfil de farmacocinética das terapias convencionais e entregando o fármaco no local-alvo do tumor, de forma a diminuir os efeitos adversos e aumentar a eficácia terapêutica. Baseados em estratégias de passive targeting, active targeting e libertação por resposta a estímulos, estes nano-medicamentos têm alcançado resultados extraordinários em ensaios clínicos, tendo sido alguns já aprovados pelas entidades reguladoras do medicamento, ambicionando alcançar um enorme peso no futuro da terapia anti-tumoral.<br>Within the scope of the course unit of Curricular Internship of the Integrated Master’s degree in Pharmaceutical Sciences of the Faculty of Pharmacy of the University of Coimbra, the present document exhibits, in the form of a SWOT analysis (Strengths, Weaknesses, Opportunities and Threats), the report of the Pharmaceutical Industry Internship, performed at Farmalabor, in Condeixa-a-Nova, from 8th of January to 29th of March 2018, and the report of the Community Pharmacy Internship, performed at Farmácia de Celas, in Coimbra, from 2nd of April to 15th of July 2018. The present document also includes the monograph entitled “Nanotechnology-based drugs in anticancer therapy, on the market and in clinical trials”.Cancer is now a leading cause of global mortality. Conventional chemotherapy has several limitations, such as non-specific delivery of therapeutic agents, often leading to toxicity problems. In the last few years, the rapid growth of nanomedicine in the field of oncology has demonstrated numerous advances through the development of various nanotherapies. These therapies rely on nanocarriers to provide targeted treatment by altering the pharmacokinetic profile of conventional therapies and delivering the drug to the target site of the tumor to decrease adverse effects and increase therapeutic efficacy. Based on strategies of passive targeting, active targeting and stimuli-responsive and triggered release, these nanomedicines have achieved extraordinary results in clinical trials, and some have already been approved by regulatory authorities, aiming to achieve a huge weight in the future of anticancer therapy.
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Davis, Ari B. "Expression of cohesin proteins and nano-architectural changes in rectal mucosa to assess risk of colon cancer based on field carcinogenesis." Thesis, 2014. https://hdl.handle.net/2144/14662.
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With 50,310 related deaths this year, colorectal cancer (CRC) has emerged as the second largest cause of cancer related deaths among Americans. While 70 million Americans are considered at-risk of developing CRC, it is highly curable if detected early. Cohesin proteins, which hold sister chromatids together during replication, have emerged as a potential biomarker in multiple cancer lines. Because of their probable role in DNA replication, DNA repair, chromatin nano-architecture, and gene expression, this paper assessed whether cohesion proteins could be used as a potential biomarker for colorectal cancer risk stratification. While cohesin protein mutations have been reported in different cancers and involved in chromosomal instability, its role in early cancer formation has yet to be observed. Using immunohistochemical and Quantitative Real Time PCR analysis, this thesis assessed the protein and RNA expression levels of cohesin proteins SA-1, NIPBL, and SMC3 from human biopsies at different stages and locations of colorectal cancer development. The results showed that SA-1, a structural cohesion subunit, was significantly (p<0.01) down regulated in cancerous compared to normal tissue. The SA-1 protein was also down regulated in the involved mucosa adjacent to CRC polyps. The cohesion loading protein, NIPBL, was also significantly (p<0.01) under expressed in cancerous versus normal tissue. The RNA expression analysis of rectal mucosa showed that SMC3 and SA-1 was over expressed two fold in patients harboring hyperplastic and adenomous polyps, giving evidence that cohesin proteins are differentially expressed throughout the field of carcinogenesis. Our results demonstrate for the first time that cohesion dysregulation is an early event in human colorectal cancer development and may serve as an important biomarker of field carcinogenesis.
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Mahapatra, Sudarshan. "Synthesis, Structure And Photocatalysis Of Orthovanadates, Novel Approaches For The Crystallization Of Anhydrous Nucleobases And Ab Initio Structure Determination Of A Drug Intermediate From Powder X-ray Diffraction Data." Thesis, 2008. https://etd.iisc.ac.in/handle/2005/910.
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The thesis begins with a brief introduction and relevant literature references. The novelty of synthesis, methodology and results of the work reported in the thesis and highlighted subsequently. The thesis consist of three parts, Part A of the thesis consist of five chapters describing new methods of synthesis of orthovanadates, mainly dealing with the structure and photocatalytic properties of synthesized materials. Part B of the thesis consist of two chapters dealing with an unique crystallization methodology for subliming and low melting organic compounds and the crystal structure determination via single crystal X-ray diffraction. Part C consists of one chapter presenting the ab-initio approach of structure determination via powder X-ray diffraction methods.
Chapter 1 of the thesis presents the synthesis of three zircon type lanthanide orthovanadates, LnVO4 (Ln = Ce, Pr and Nd) via a new solution based approach at room temperature and photodegradation of a variety of water pollutants have been investigated. Chapter 2 describes the importance of microwave synthesis to produce nano particles of the zircon type lanthanide orthovanadates LnVO4. The importance of the surface area in photocatalysis is evaluated. Chapter 3 consist of the synthesis of a series of new compounds, Ln0.95φ0.05Mo0.15V0.85O4 (Ln = Ce, Pr and Nd) via solid state method. The photocatalytic activities of these compounds are investigated both under UV exposure and sunlight. Chapter 4 presents the synthesis of MxCe1-xVO4+ (M = Li, Ca and Fe) with x = 0.1, 0.25 and 0.05 respectively. Different kinds of dyes and organics are degraded under UV radiation and the specificity towards the same are evaluated. Chapter 5 describes a comparative photocatalytic conversion of cyclohexane and benzene to cyclohexanol, cyclohexanone and phenol respectively by LnVO4, LnMo0.15V0.85O4 and MxCe1-xVO4+ (Ln = Ce, Pr and Nd, M= Li, Ca and Fe with x = 0.1, 0.25 and 0.05 respectively). Kinetics of above photoconversions are established by proposing a mechanism and determining the rate constants. Chapter 6 describes the development of a novel apparatus for the crystallization of anhydrous adenine, whose structure has not been solved over the last few decades. The crystal structure is solved via single crystal X-ray diffraction. Chapter 7 presents a modified design for crystallization of low melting organic compounds and co-crystals. A new polymorph of anhydrous thymine has been grown with this apparatus and its structure has been analyzed and compared with the known form of thymine. Chapter 8 presents the ab-initio approach of structure determination via powder X-ray diffraction methods. The methodology of using the direct space approach for the determination of the crystal structure of N-(2-fluorophenyl) benzamide (a drug intermediate), which could not yield good quality single crystals, is outlined.
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Mahapatra, Sudarshan. "Synthesis, Structure And Photocatalysis Of Orthovanadates, Novel Approaches For The Crystallization Of Anhydrous Nucleobases And Ab Initio Structure Determination Of A Drug Intermediate From Powder X-ray Diffraction Data." Thesis, 2008. http://hdl.handle.net/2005/910.
Full textAbstract:
The thesis begins with a brief introduction and relevant literature references. The novelty of synthesis, methodology and results of the work reported in the thesis and highlighted subsequently. The thesis consist of three parts, Part A of the thesis consist of five chapters describing new methods of synthesis of orthovanadates, mainly dealing with the structure and photocatalytic properties of synthesized materials. Part B of the thesis consist of two chapters dealing with an unique crystallization methodology for subliming and low melting organic compounds and the crystal structure determination via single crystal X-ray diffraction. Part C consists of one chapter presenting the ab-initio approach of structure determination via powder X-ray diffraction methods.
Chapter 1 of the thesis presents the synthesis of three zircon type lanthanide orthovanadates, LnVO4 (Ln = Ce, Pr and Nd) via a new solution based approach at room temperature and photodegradation of a variety of water pollutants have been investigated. Chapter 2 describes the importance of microwave synthesis to produce nano particles of the zircon type lanthanide orthovanadates LnVO4. The importance of the surface area in photocatalysis is evaluated. Chapter 3 consist of the synthesis of a series of new compounds, Ln0.95φ0.05Mo0.15V0.85O4 (Ln = Ce, Pr and Nd) via solid state method. The photocatalytic activities of these compounds are investigated both under UV exposure and sunlight. Chapter 4 presents the synthesis of MxCe1-xVO4+ (M = Li, Ca and Fe) with x = 0.1, 0.25 and 0.05 respectively. Different kinds of dyes and organics are degraded under UV radiation and the specificity towards the same are evaluated. Chapter 5 describes a comparative photocatalytic conversion of cyclohexane and benzene to cyclohexanol, cyclohexanone and phenol respectively by LnVO4, LnMo0.15V0.85O4 and MxCe1-xVO4+ (Ln = Ce, Pr and Nd, M= Li, Ca and Fe with x = 0.1, 0.25 and 0.05 respectively). Kinetics of above photoconversions are established by proposing a mechanism and determining the rate constants. Chapter 6 describes the development of a novel apparatus for the crystallization of anhydrous adenine, whose structure has not been solved over the last few decades. The crystal structure is solved via single crystal X-ray diffraction. Chapter 7 presents a modified design for crystallization of low melting organic compounds and co-crystals. A new polymorph of anhydrous thymine has been grown with this apparatus and its structure has been analyzed and compared with the known form of thymine. Chapter 8 presents the ab-initio approach of structure determination via powder X-ray diffraction methods. The methodology of using the direct space approach for the determination of the crystal structure of N-(2-fluorophenyl) benzamide (a drug intermediate), which could not yield good quality single crystals, is outlined.
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MEROLA, Gustavo. "Analysis of emerging drugs of abuse by using miniaturized techniques." Doctoral thesis, 2013. http://hdl.handle.net/11562/531550.
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L'uso di droghe a scopo voluttuario è vecchio come il mondo. Nel corso dei secoli secoli, piante come coca (Erythroxylon coca), kath (Catha edulis), oppio (Papaver somniferum), sono state utilizzate per ottenere effetti psicoattivi. In seguito, le conoscenze di chimica organica hanno portato alla sintesi di nuove droghe d’abuso e questa è una tendenza che continua ancora oggi. Per contrastare la diffusione e l'uso di queste droghe emergenti un contributo importante è dato dalle scienze forensi. Le scienze forensi includono tutte le applicazioni scientifiche che possono essere utilizzate per sostenere a tutti i livelli il rispetto della legge. L'analitica forense è un campo di ricerca in rapida espansione, come testimoniano le numerose pubblicazioni e review disponibili nella letteratura scientifica. Vale la pena notare tuttavia che la maggior parte dei avori relativi alle analisi forensi, sono incentrati su tecniche cromatografiche (GC e HPLC) che possono fornire risultati veloci e facilmente comparabili, grazie a numerose procedure standardizzate. Poiché vi è una grande richiesta, ai laboratori di polizia scientifica, affinché si mettano a punto metodi analitici più veloci, efficienti e meno costosi, la miniaturizzazione è emersa come tendenza sempre più popolare anche nelle scienze forensi. Tecniche di separazione quali elettroforesi capillare (CE) e nano-cromatografia liquida (nano-LC) sono state applicate con successo all'analisi di sostanze illegali, sia nei reperti che nei fluidi biologici. Rispetto alle tecniche convenzionali, quelli miniaturizzate offrono alcuni vantaggi quali alta efficienza e selettività, analisi più rapide, minore diluizione del campione, necessità di ridotti volumi di campione e reagenti, nonché minime quantità di materiali di impaccamento. Grazie a tutte queste caratteristiche, tali tecniche possono essere vantaggiosamente applicate anche alle scienze forensi. In realtà l'applicabilità di queste tecniche analitiche rapide ed efficienti non è ancora in gran parte sfruttata in tossicologia forense. Il presente lavoro è finalizzato, nella prima parte a confermare ulteriormente l’affidabilità e l’applicabilità di queste tecniche nei laboratori forensi. La seconda parte del lavoro, invece, ha lo scopo di confermare CE e nano-LC quali strumenti preziosi per lo screening, l'identificazione e la quantificazione di analiti di interesse forense.<br>The use of recreational drugs is old as time. For centuries, plants, like coca (Erythroxylon coca), kath (Catha edulis), opium (Papaver somniferum), were used to achieve central nervous system (CNS)-psychoactive effects. Later, the knowledge in organic chemistry led to the synthesis of new drugs of abuse and this is an on-going trend nowadays. To contrast the use of these emerging drugs of abuse an important contribute is given by forensic sciences. Forensic sciences include all the applications of science which can be used to support at any level the enforcement of the law. Forensic analysis is a rapidly expanding field of analytical research as witnessed by the numerous publications and specific scientific reviews available in the scientific literature. It is worth noting however, that the majority of works concerning forensic analysis are related to chromatographic techniques (GC and HPLC) which can provide fast and easily comparable results, due to widespread standardized procedures. Owing to the great demand of forensic laboratories for faster, efficient and less costly analytical methods, miniaturization has emerged as an increasing popular tool also in forensic sciences. Separation techniques including capillary electrophoresis (CE) and nano-liquid chromatography (nano-LC) have been successfully applied to the analysis of illegal drugs both in seized materials and in biological fluids. Compared to conventional techniques, the miniaturized ones offer some unique advantages such as high efficiency and selectivity, shorter analysis time, lower sample dilution, need of smaller volumes of samples and reagents as well as small amounts of packing materials. For all these features these techniques can be applied advantageously also to forensic sciences. Indeed the applicability of these rapid and cost-effective analytical techniques are not yet largely exploited in forensic toxicology. In this perspective, to provide further confirmation of the reliability and applicability of these techniques in forensic laboratories, this work is started and aimed in its first part.
The second part, instead, is aimed at confirming CE and nano-LC as valuable tools for screening and identification and for precise and sensitive quantification of analytes of forensic interest.
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Vidal, Bruno. "How early inflammatory events affect bone nano properties at rheumatoid arthritis onset." Doctoral thesis, 2016. http://hdl.handle.net/10451/28404.
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Tese de doutoramento, Ciências Biomédicas (Ciências Biopatológicas), Universidade de Lisboa, Faculdade de Medicina, 2017<br>Rheumatoid arthritis (RA) is a chronic, systemic and immune-mediated inflammatory disease that mainly affects the synovial membrane of multiple small joints. As a consequence, RA results in cartilage and bone damage, leading to functional impairment and an increase in morbidity and mortality. Early diagnosis and adequate treatment are critical to prevent RA progression, as joint destruction can occur immediately after its onset. The most characteristic feature of RA is synovial hyperplasia, which is mediated by several immune cells, such as T-cells, B-cells, neutrophils, macrophages and by a complex cytokine network, especially interleukin (IL)-1β, tumor necrosis factor (TNF) and IL-6. RA inflammatory environment induces osteoclastogenesis, promoting disturbances in skeletal bone remodeling, which ultimately leads to the development of secondary osteoporosis and consequent bone fragility. An opportunity for a more effective treatment intervention was identified in early RA, when permanent damage can be prevented and a higher number of patients can achieve remission. Early treatment intervention might also interfere systemically with bone biology preventing bone micro and nano architectural damage. The development of therapeutic strategies able to control both inflammation and bone degradation, with a high rate of disease remission, low incidence of side effects and low production costs is still an unmet medical need in RA. Our hypothesis is that the impact of inflammation on bone micro and nano properties (intrinsic bone tissue properties, independent of the overall bone architecture and directly dependent on the way bone cells, collagen and calcium crystals interact) occurs almost immediately, upon first symptoms, and that these effects can be prevented by early intervention with drugs able to control inflammation and capable of interfering also with bone metabolism. This thesis characterizes the early events of bone damage in RA and explores the effect of novel treatment interventions in this context. Accordingly, in the first part of this thesis, we used an adjuvant induced arthritis (AIA) rat model and observed a synovial sublining layer infiltration, increased lining layer cells, bone erosions and cartilage surface damage present since the early stages of arthritis, as well as increased levels of IL-6. This inflammatory environment promotes osteoclastogenesis, which is related to the observed local bone erosion and may interfere systemically with bone skeletal remodeling. Indeed, AIA animals showed an increased bone turnover, as depicted by increased CTX-I (Carboxy-terminal telopeptide of type I collagen) and P1NP (amino terminal propeptides of type I collagen) levels since the early stages of arthritis. Bone histology was consistent with this early onset spur of bone remodeling. Arthritic animals showed concentric lamellas in secondary osteons (SO), which are the consequence of intense bone remodeling. On the contrary, healthy animals presented more parallel-lamellae (PL) structures than SO structures and these PL structures are 10% harder than SO structures, representing the mature bone structure (normal bone remodeling). Thus, arthritic bone tissue was composed of a larger number of younger, less mineralized and less hard structures, explaining the reduced hardness that we have observed by nanoindentation. Moreover, an increased area occupied by osteocyte lacunae was detected early on in the arthritis process. This apparent change of osteocyte morphology might be related to bone necrosis, leading to mineral loss, decreased hardness and possibly mechanical weakness. In addition, we have also demonstrated that arthritis induces mineral and collagen loss in trabecular bone since the early phase of arthritis development. At a higher organizational level data, micro computed tomography (micro-CT) revealed in arthritic animals a lower fraction of cortical and trabecular bone volume with reduced trabecular thickness together with a higher trabecular separation, in comparison with controls. Results also demonstrated cortical differences in polar moment of inertia, suggesting mechanical weakness in arthritic groups since the early phase of arthritis. Furthermore, cortical and trabecular porosity were increased in the arthritic groups compared to healthy controls. We also confirmed these observations by classic histomorphometry, which demonstrated a decreased structural integrity in arthritic animals. Coherent with these structural defects, our results also showed that in very early arthritis bone has low mechanical competence. Altogether, these results revealed that inflammation promotes bone nano and micro structural disturbances, leading to bone fragility since the early stages of arthritis. In addition, we also provided the basis for using the AIA animal model of arthritis as an adequate model for studying the impact of inflammation on bone and for assessing candidate compounds for the control of arthritis and its associated bone damage. The quest for new RA treatments, more effective at inflammation and bone damage control, safer and less expensive is still a major need. Previously, we had demonstrated that celastrol, acts by downregulating IL1β and TNF production, was a promising RA therapeutic candidate. Herein we have demonstrated that celastrol was able to reduce the number of synovial B and T-cells as well as fibroblasts and CD68 macrophages. Accordingly, we showed that celastrol protects cartilage and bone from inflammation-induced focal damage. At a systemic level, we observed a reduction in bone turnover together with preservation of bone structural and mechanical properties. Moreover, celastrol therapy showed superior effects if administrated in an early phase of arthritis development, which highlights the importance of an early treatment to limit inflammation-induced bone damage. Tofacitinib was also tested in order to assess the effects on micro and nano structural and mechanical properties of bone in an AIA rat model of arthritis. Tofacitinib is a selective inhibitor of janus kinase 1 (JAK1) and janus kinase 3 (JAK 3). Results showed significant reduced arthritis manifestations, synovial tissue inflammation and bone erosions, accompanied by a reduced bone turnover rate and a predominance of parallel structures on bone tissue. At tissue level, measurements performed by nanoindentation showed that tofacitinib increased bone cortical and trabecular hardness. However, micro-CT and 3-point bending tests revealed that tofacitinib did not revert the effects of arthritis on cortical and trabecular bone structure and mechanical properties. This effect on bone might be related to the mechanism of action of tofacitinib which has complex and conflictual molecular interactions with bone. We suggest that these interactions have an overall negative effect not totally compensated by the benefits resulting from the control of inflammation. On the other hand, tofacitinib may require more exposure time to have an impact on bone quality. Overall, the results of the present thesis support the hypothesis that the impact of inflammation on bone micro and nano properties occurs almost immediately, upon the appearance of first symptoms. Moreover, these observed effects can be prevented by very early intervention with drugs able to control inflammation and capable of interfering with bone metabolism.<br>Pfizer – ASPIRE 2013 Prize; ECTS/AMGEN Bone Biology 2014 Prize
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PALADINI, GIUSEPPE. "Branched polyethyleneimine/TEMPO-oxidized cellulose nanofibers xerogels for water remediation: a structural and dynamical study by small angle neutron scattering (SANS) and Fourier-transform infrared spectroscopy (FTIR)." Doctoral thesis, 2019. http://hdl.handle.net/11570/3147621.
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In the present thesis, cellulose sponges prepared using 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) oxidized and ultra-sonicated cellulose nanofibers (TOUS-CNFs) as three-dimensional scaffolds, and branched polyethyleneimine (bPEI) as crosslinking agent, underwent to a systematic Small Angle Neutron Scattering (SANS) and Fourier-Transform Infrared Spectroscopy (FTIR) investigation, by varying the amount of cross-linker, water content and temperature. The aim was to provide an experimental evidence of nano-porosity in the TOUS-CNFs network of these nanosponges (CNS) by investigating the water nano-confinement geometries in the adsorbent material. Moreover, we also verified how the breaking/reformation of specific intermolecular hydrogen bond interactions between water and the chemical groups present in the architecture of the CNS can contribute to regulate the water adsorption process observed at macroscopic level. Concerning SANS measurements, the analysis of the experimental data, performed in terms of a Correlation Length Model (CLM), allowed us to extract the short-range correlation length ξ, interpreted as a very first indirect estimation of the effective nano-dimension of the cavities produced by the cross-linking of the reticulated cellulose nanofibers. From the model, a power-law (n) and Lorentzian (m) exponents have been also obtained, respectively associated to the density of TOUS-CNFs at high (larger than hundreds of Å) and low (∼ 10 - 100 Å) spatial scale. These parameters turned out to be all sensitive to the structural variations induced by the progressive uptake of water on the bPEI/TOUS-CNFs sponges with different ratios. Finally, the effect of the addition of citric acid in the CNS formulation was investigated, confirming its role in increasing cross-linking density and sponge rigidity. In addition, a preliminary investigation of the molecular connectivity and the extent of hydrogen-bond patterns of water molecules confined in the bPEI/TOUS CNFs sponges was also performed by FTIR spectroscopy. The proposed spectroscopic method exploits the combined analysis of the vibrational spectra of polymers hydrated with water and deuterated water, which allows us to separate and selectively investigate the temperature-evolution of the HOH bending mode of engaged water molecules. As main results, we find a strong experimental evidence of a liquid-like behaviour of water molecules confined in the sponge nano-cavities and we observe a characteristic destructuring effect on the hydrogen-bonds network of confined water induced by thermal motion. The obtained results appear crucial in order to rationalize the design of these sponges and to track the changes in the ability of the final products as efficient nano-confinement systems for water decontamination.
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Eff, Christopher. "Effects of Proton Pump Inhibitors on the bioactivation of dietary nitrate during submaximal exercise." Thesis, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:gih:diva-5456.
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Abstract Aim: The purpose of the study is to show the influence of Proton Pump Inhibitors (PPI in form of esomeprazole) on the bioactivation of dietary nitrate (sodium-nitrate solution) in submaximal exercise, through affecting the gastric pH. Method: Randomized, doubled-blinded, placebo-controlled and crossover study with six subjects (mean ± SD, age 29 ± 5years, height 170 ± 5 centimeters, weight 70 ± 5 Kg, BMI 24,36 ± 1,75 Kg/m2 blood pressure 119/ 77 ± 6 mmHg, 3 male and 3 female). They were tested in two different trials. Every trial consisted of two parts. One part was cycling on 4 different submaximal stages (80W/60RPM, 80W/90RPM, 120W/60RPM, 120W/90RPM) for 5 minutes each, with 90 minutes rest in between. The same protocol was repeated. In the beginning of the resting time a sodium nitrate solution (NaNO3-, 10mg/kg body weight) was ingested. VO2, VCO2, RER, VE, Lactate, Glucose, heart rate and blood pressure were recorded. Venous blood samples were taken. Whether esomeprazole (10mg) or a placebo were taken 24h, 12h and directly before being tested in both trials. Subjects were pleased to have a nitrate poor diet starting when taking the pills. An information sheet was provided. Results: No significant differences were found between the post values and the treatment. Tendencies of a higher oxygen consumption when taking esomeprazole (2,62%) in comparison to placebo (0,11%) were observed. Systolic BP decreased by 3,91% with the placebo while it decreased just 2,04% with esomeprazole after intake. Sex-specific differences occurred in the metabolism of esomeprazole and dietary nitrate. RER showed a significant post nitrate difference between the female and male participants with t=.006 and a significance in predietary nitrate intake. VE in female (40,79 ± 7,20 L/min) and (50,03 ± 10,09 L/min) in male were as well significant (t=.017). Conclusion: Tendencies of effects of PPI are seen in the post-values of VO2 and BP after intake of dietary nitrate. Gender-differences are shown in RER and VE. More research is needed to see the impact of dietary nitrate on the human body under submaximal load.