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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
121

UTVECKLING AV EN NY METOD FÖR ATT EXTRAHERA PROTEINER FRÅN GULA ÄRTOR / DEVELOPMENT OF A NEW METHOD FOR EXTRACTING PROTEINS FROM YELLOW PEAS

Sadek, Douaa January 2023 (has links)
Proteiner spelar en avgörande roll i människokroppen och det är därför viktigt att inta tillräckligt med essentiella aminosyror genom kosten. Tidigare har animaliska källor varit kända för att vara rika på dessa aminosyror, men nu förtiden räcker det inte för att tillfredsställa den globala behov. Dessutom väcker den animaliska proteiner allvarliga frågor om klimatförändringar och etik. Ärtor innehåller en essentiell profil av aminosyror och har många andra fördelar, såsom tillgänglighet, kostnadseffektivitet och förmåga att växa i låga temperaturer. Tidigare studier har visat att regelbunden intag av ärtprotein kan minska risken för hjärt-kärlsjukdomar och diabetes. Studier visade att Naturliga djupa eutektiska lösningsmedel (NADES) kan lösa upp proteiner utan att denaturera de, vilket är ett problem med traditionella lösningsmedel som kan påverka proteinstrukturer. Dessutom är NADES icke-toxiska och biologiskt nedbrytbara lösningar, vilket gör dem mer hållbara och miljövänliga än vanliga vätskor som används vid proteinextraktion. Syftet med studien var att använda NADES för att utveckla en ny metod för att extrahera proteiner från gula ärtor och jämföra denna med etablerade metoder. Dessutom skulle skillnader i proteinutbyte och strukturella förändringar uppskattas genom användning av Size Exclusion Chromatography (SEC) och Sodium Dodecyl Sulfate PolyAcrylamide Gel Elektrofores SDS-PAGE. Tre varianter av NADES framställdes från kolinklorid, citronsyra och olika vattenhalter. NADES 20% användes för extraktion, eftersom det har visat sig vara en lämplig metod för detta ändamål. Resultaten visade att extraktion med NADES är mer komplicerad än referensmetoderna för att proteinerna utfölls vid olika steg under extraktion process. SEC-kromatogram visade proteindenaturering där en tydlig topp erhölls vid senare elueringsvolym. SDS-PAGE analys genomfördes för att identifiera toppar men inge resultat kunde erhålla på grund av låg proteinkoncentration. Från ett optimistiskt perspektiv kan de denaturerade proteinerna fortfarande användas inom livsmedelsindustrin eller NADES kan användas som en pre-extraktionsmetod för att avlägsna föroreningar innan den verkliga extraktionsprocessen påbörjas. Det skulle vara användbart för framtida studier att prova att extrahera med en lägre vattenhalt i NADES eller med en annan typ av NADES. / Protein plays a crucial role in the human body, making it essential to consume sufficient amounts of essential amino acids through diet. Traditionally, animal sources have been known to be rich in these amino acids, but this is not sufficient to meet global demand. Additionally, this raises serious questions about climate change and ethics. Peas have been found to contain an essential profile of amino acids and have many other advantages, such as availability, cost-effectiveness, and the ability to grow in low temperatures. Previous studies have shown that regular consumption of pea protein can reduce the risk of cardiovascular disease and diabetes. Studies have shown that Natural Deep Eutectic Solvents (NADES) can dissolve proteins without denaturing them, which is a problem with traditional solvents that can affect protein structures. In addition, NADES are non-toxic and biodegradable solutions, making them more sustainable and environmentally friendly than common liquids used in protein extraction. The aim of the study was to use NADES to develop a new protein extraction method from yellow peas and compare this with established methods. In addition, differences in protein yield and structural changes were estimated using Size Exclusion Chromatography (SEC) and Sodium Dodecyl Sulfate PolyAcrylamide Gel Elektrofores SDS-PAGE. Three variants of NADES were prepared from choline chloride, citric acid, and different water contents. NADES 20% was used for extraction as it has been found to be a suitable method for this purpose. The results showed that extraction with NADES is more complicated than the reference methods because the proteins precipitated at different stages during the extraction process. SEC chromatogram showed protein denaturation where a clear peak was obtained at later elution volumes. SDS-PAGE analysis was performed to identify peaks, but no results could be obtained due to low protein concentration. From an optimistic perspective, the denatured proteins can still be used in the food industry, or NADES can be used as a pre-extraction method to remove impurities before the actual extraction process begins. It would be useful for future studies to try extracting with a lower water content in NADES or with a different type of NADES.
122

Zinc in cerebrospinal fluid and serum in some neurological diseases

Palm, Ragnar January 1982 (has links)
The trace elements zinc and copper are essential components of many enzymes, some of which are of importance for the development and function of the central nervous system. Deficiency of the metals has been shown to lead to malformations and to the loss of myelin in animals. Earlier reports of zinc concentrations in the cerebrospinal fluid are few and the results variable. In multiple sclerosis and in epilepsy therapy with phenytoin there are varying reports of changes in serum concentrations of zinc and copper. A method was developed for the determination of zinc in cerebrospinal fluid by flame atomic absorption spectrophotometry utilizing a pulse nebulizer technique. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry with conti nous aspiration. The normal concentrations of zinc in cerebrospi nal fluid was 0.16_+0.03 micromoles per litre (mean +_ S.D.). The zinc concentrations were correlated with protein and albumin concentrations in the cerebrospinal fluid but not with the serum zinc levels. In the patients with increased protein concentrations in the cerebrospinal fluid or with subarachnoid haemorrhage increased zinc levels were found. In 50 patients with multiple sclerosis lower serum concentrations of zinc were found compared to age and sex matched controls. In younger patients low serum levels of copper were also observed. There was no correlation between zinc and protein parameters in the cerebrospinal fluid of multiple sclerosis patients. In untreated epileptic males low serum zinc concentrations were observed. During the first 72 hours of phenytoin therapy increased serum concentrations of zinc and copper were found. during long-term therapy with phenytoin alone or in combination with other antiepileptic drugs there was an increased serum concentration of copper and ceruloplasmin but no change in zinc concentration compared with controls. / <p>Diss. Umeå, Umeå universitet, 1982, härtill 4 uppsatser</p> / digitalisering@umu
123

Mouvements transmembranaires et effet sécrétagogue de l'albumine au niveau du syncytiotrophoblaste humain / Transmembrane movements and secretory effect of albumin at the human syncytiotrophoblast level

Lambot, Nathalie 17 February 2006 (has links)
Le placenta assure les échanges materno-fœtaux et possède une fonction endocrine autonome. Les hormones placentaire lactogène (hPL) et chorionique gonadotrope (hCG) sont synthétisées par le syncytiotrophoblaste. A ce jour, les mécanismes impliqués dans le contrôle de la sécrétion de ces deux hormones ne sont pas connus. In vitro, l’influx d’ions Ca2+ entraîne une augmentation immédiate et soutenue de la libération d’hPL et d’hCG à partir d’explants de placentas à terme. En outre, l’élévation de la concentration extracellulaire en albumine, principale protéine maternelle circulante en contact direct avec le trophoblaste, stimule de manière immédiate et transitoire la libération d’hPL et d’hCG. L’objectif de nos travaux a été de vérifier la spécificité de l’activité sécrétagogue de l’albumine au niveau du placenta, de caractériser les messagers cellulaires potentiellement impliqués dans la libération d’hPL et d’hCG, et de définir l’interaction entre l’albumine et le trophoblaste, en utilisant des explants provenant de placentas humains à terme. Nos travaux démontrent que la riposte sécrétoire à l’albumine (5%, m/v) est largement mimée par d’autres agents colloïdaux (dextran et polygéline). Cette stimulation colloïdale de la libération d’hPL et d’hCG impliquerait une mobilisation de Ca2+ à partir de réserves intracellulaires. L’intervention de 3 messagers cellulaires a été envisagée: les IPs/DAG, l’AMPc, et le GMPc. Le fluorure de sodium, la forskoline, ou le nitroprussiate sodique, activateurs connus de la production respective des IPs, de l’AMPc, et du GMPc, augmentent de manière significative les taux placentaires de chacun de ces messagers, sans toutefois affecter la libération d’hPL ou d’hCG. De plus, l’élévation de la concentration extracellulaire en albumine (5%, m/v) ne modifie pas les taux des IPs, de l’AMPc et du GMPc dans les explants placentaires, tandis qu’elle stimule la sécrétion hormonale. Ces systèmes de signalisation, bien que fonctionnels au niveau du trophoblaste, ne joueraient donc pas un rôle majeur dans la régulation de la libération d’hPL et d’hCG. Nos résultats mettent en évidence une internalisation rapide d’albumine marquée, avec de l’125I ou de la fluorescéïne, dans le syncytiotrophoblaste. Une large fraction de cette albumine est recyclée, intacte, vers la circulation maternelle selon un processus sensible à l’abaissement de la température et indépendant du cytosquelette. L’albumine marquée restant dans les explants placentaires est partiellement dégradée. Trois mécanismes ont été envisagés pour expliquer ces mouvements d’entrée et de sortie de l’albumine au sein du placenta humain: l’endocytose médiée par l’albondine via les caveolae, le système des coated pits clathrine-dépendant, et l’endocytose médiée par la mégaline. Par immunohistochimie, nous avons montré que, dans le tissu placentaire, la caveoline-1, protéine caractéristique des caveolae, est localisée uniquement dans l’endothelium des capillaires fœtaux. La clathrine, au niveau des coated pits, et la mégaline se trouvent au contraire dans le syncytiotrophoblaste. La méthyl-b-cyclodextrine et l’hydrochlorure de chlorpromazine, inhibiteurs d’une endocytose dépendant de la clathrine, réduisent significativement l’internalisation placentaire de l’albumine marquée. Par contre, le DIDS ou le NPPB, susceptibles de perturber l’endocytose médiée par la mégaline, n’affectent pas la captation d’albumine marquée par les explants placentaires. L’albumine pénétrerait donc dans le syncytiotrophoblaste principalement par un processus clathrine-dépendant. La mégaline ne jouerait ici qu’un rôle mineur dans l’entrée de la protéine. Un tel processus de recyclage de l’albumine pourrait être similaire à celui décrit pour les immunoglobulines G au niveau du syncytiotrophoblaste. Ces mouvement d’entrée et de sortie de l’albumine ne semblent pas associés à la stimulation de la libération d’hPL et d’hCG par l’albumine. Ils pourraient par contre participer significativement, étant donné leur ampleur, à la nutrition fœtale. L’albumine est en effet un transporteur notoire d’ions et d’acides gras, molécules qui pourraient être acheminées au fœtus via le phénomène de recyclage placentaire de l’albumine mis en évidence par ce travail. / The human placenta is the site of all maternal-fetal exchanges, and is also an active endocrine organ. Placental lactogen (hPL) and chorionic gonadotrophin (hCG) hormones are synthesized by the syncytiotrophoblast. So far, the mechanisms involved in the regulation of both hormones secretion remain elusive. In vitro, calcium inflow causes an immediate and sustained rise in the hPL and hCG releases from human term placenta explants. Moreover, increasing the extracellular concentration of albumin, the major maternal plasma protein in direct contact with the human trophoblast, stimulates the hPL and hCG releases in an immediate and transient way. Our study have aimed to check the specificity of this secretory effect of albumin, to investigate the potential cellular messengers involved in the hPL and hCG releases, and to define the interaction between albumin and the throphoblast layer, using human term placenta explants. Our results indicate that the triggering effect of albumin (5%, w/v) is largely mimicked by two other colloidal agents (dextran and polygelin). This “colloidal” stimulation of the hPL and hCG releases would involve the mobilization of calcium from intracellular pools. Three cellular messengers have been considered to mediate this process: the IPs/DAG, the cAMP, and the cGMP. Sodium fluoride, forskolin, or sodium nitroprusside, known activators of respectively the IPs, cAMP, and cGMP production, significantly increase the placental content of each of those messengers, without modifying the hPL and hCG releases. In addition, raising the extracellular concentration of albumin does not cause any change in the placental level of IPs, cAMP, and cGMP, while stimulating the hormonal release. These three signaling pathways are thus functional in human term trophoblast but do not appear to significantly modulate the hPL and hCG secretions. Our findings show that albumin, labeled with 125I or with fluorescein, is rapidly internalized into the syncytiotrophoblast. Thereafter, the intact protein is largely recycled to the maternal circulation, through a temperature-sensitive and cytoskeleton-independent process. The labeled albumin remaining in placental explants is partially degraded. Three different mechanisms could participate to the albumin entry into the human placenta: the albondin-mediated endocytosis via the caveolae, the clathrin-dependent coated pits system, and the megalin-mediated endocytosis. Using immunohistochemistry, caveolin-1, marker of the caveolae, is localized in the endothelium of the fetal capillaries and not in the syncytiotrophoblast. By contrast, clathrin and megalin are observed only in the syncytiotrophoblast. Methyl-b-cyclodextrin, and chlorpromazine hydrochloride, known inhibitors of the clathrin-dependent endocytotic process, significantly reduce the placental uptake of labeled albumin. On the other hand, DIDS or NPPB, able to perturb the megalin-mediated endocytosis, do not affect the labeled albumin uptake. Thus, albumin seems to be internalized into the syncytiotrophoblast mainly through a clathrin-dependent mechanism. Megalin would only play a minor role in this process. Such movements of albumin in the human placenta may be similar to the recycling process reported for IgG at that site. The placental apical recycling of albumin is not associated to the albumin triggering effect on the hPL and hCG releases. This quantitatively significant internalization process may participate to the fetus’ nutrition. Indeed, Albumin carries ions and fatty acid, which could be brought to the fetus via the protein recycling evidenced by our study.
124

Metodjämförelse mellan IMMAGE 800 och BN ProSpec för U-albumin, U-IgG, U-kappa och U-lambda

Al-Hadad, Mohamed January 2010 (has links)
<p>Njurarna är ett organsystem med viktiga funktioner som exempelvis utsöndring av flertalet vattenlösliga substanser. För att sjukdomssymtom ska uppträda krävs mer än tre fjärdedelars bortfall av njurfunktionen, eftersom njurarna har en enorm reservkapacitet. Genom att analysera bland annat proteinerna albumin, immunoglobulin G, kappa och lambda i urin utreds om njurfunktionen fungerar som den ska. Analys av dessa proteiner kan ske med analysinstrumenten IMMAGE 800 från Beckman Coulter och BN ProSpec från DADE BEHRING. Båda dessa analysinstrument använder sig av metoden nefelometri, som är en metod där ljusspridning i en vätska eller gas kan mätas.</p><p>Syftet med föreliggande studie var att analysera urinprover på både IMMAGE 800 och BN ProSpec och sedan jämföra resultaten. Under denna studie kalibrerades standardkurvor, genomfördes kvalitetskontroller och 37 prov analyserades. Samma prov analyserades flera gånger, både under samma dag och vid ett antal kommande dagar för att erhålla precisionen. Korrelationskoefficienten blev 0,999 för U-albumin; 0,998 för U-IgG; 0,947 för U-kappa och 0,883 för U-lambda. ProSpec kan således användas vid analys av U-albumin, U-IgG, U-kappa och U-lambda då den uppfyller EQUALIS kvalitetsmål.</p>
125

Development of Luminescent Quantum Dot-Enabled Nano- and Microplatforms for Multiplex Detection of Biomarkers

Williams, Kristen S 19 May 2017 (has links)
Luminescent semiconductor quantum dots (QDs) are extensively researched for use in biological applications. They have unique optical and physical properties that make them excellent candidates to replace conventional organic dyes for cellular labeling, multiplexing, nucleic acid detection, and as generalized probes. The primary focus of this dissertation was to utilize quantum dots for improvement in immunoassays. Specifically, atherosclerosis biomarkers were detected simultaneously in an effort to demonstrate advances in early detection diagnostics. Quantum dot-antibody bioconjugates were prepared by encapsulation into mesoporous silica and functionalized with thiol and amine groups to enable bioconjugation. Functionalization of the mesoporous silica quantum dot composites facilitated biocompatibility for use with biological buffers in immunoassays. These bioconjugates were used in a sandwich immunoassay to detect atherosclerosis biomarkers IL-15 and MCP-1. Sandwich assays employ capture antibodies immobilized onto a well plate to bind as much of the antigen as possible. The capture antibodies increased binding by at least 4 times the amount of antigen bound to the surface of a direct detection assay. The sandwich immunoassay was able to detect 1 pg/mL of IL-15 and 50 pg/mL of MCP-1 biomarkers. Human serum albumin nanoparticles (HSAPs) were synthesized via a desolvation and crosslinking method. Human serum albumin is a versatile protein being used in a variety of applications. Quantum dots were loaded into HSAPs as potential detection probes for immunoassays. Efficient loading was not achieved, and the assay was unable to improve current detection limits. Controlled release studies were explored using HSAPs loaded with superparamagnetic iron oxide nanoparticles and a fluorescent drug analog. Exposure to a magnetic field resulted in degradation of the HSAPs. The fluorophore was released and measured to examine how cancer drugs might be controlled through a magnetic field. Gold nanorods and an anticancer drug, Sorafenib, were also encapsulated into HSAPs for treatment of renal cell carcinoma in vivo. Laser irradiation treatment combined with Sorafenib resulted in 100% tumor necrosis and total elimination of any viable tumor present. HSAPs have demonstrated remarkable potential as drug delivery nanocarriers.
126

Computational and micro-analytical techniques to study the in vitro and in silico models of novel therapeutic drugs

Gumede, Njabulo Joyfull January 2016 (has links)
Submitted in fulfillment of the requirements for the Doctor of Philosophy degree in Chemistry, Durban University of Technology, Durban, South Africa, 2016. / In drug discovery and development projects, metabolism of new chemical entities (NCEs) is a major contributing factor for the withdrawal of drug candidates, a major concern for other chemical industries where chemical-biological interactions are involved. NCEs interact with a target macro-molecule to stimulate a pharmacological or toxic response, known as pharmacodynamics (PD) effect or through the Adsorption, Distribution, Metabolism, and Excretion (ADME) process, triggered when a bio-macromolecule interacts with a therapeutic drug. Therefore, the drug discovery process is important because 75% of diseases known to human kind are not all cured by therapeutics currently available in the market. This is attributed to the lack of knowledge of the function of targets and their therapeutic use in order to design therapeutics that would trigger their pharmacological responses. Accordingly, the focus of this work is to develop cost saving strategies for medicinal chemists involved with drug discovery projects. Therefore, studying the synergy between in silico and in vitro approaches maybe useful in the discovery of novel therapeutic compounds and their biological activities. In this work, in silico methods such as structure-based and ligand-based approaches were used in the design of the pharmacophore model, database screening and flexible docking methods. Specifically, this work is presented by the following case studies: The first involved molecular docking studies to predict the binding modes of catechin enantiomer to human serum albumin (HSA) interaction; the second involved the use of docking methods to predict the binding affinities and enantioselectivity of the interaction of warfarin enantiomers to HSA. the third case study involved a combined computational strategy in order to generate information on a diverse set of steroidal and non-steroidal CYP17A1 inhibitors obtained from literature with known experimental IC50 values. Finally, the fourth case study involved the prediction of the site of metabolisms (SOMs) of probe substrates to Cytochrome P450 metabolic enzymes CYP 3A4, 2D6, and 2C9 making use of P450 module from Schrödinger suite for ADME/Tox prediction. The results of case study I were promising as they were able to provide clues to the factors that drive the synergy between experimental kinetic parameters and computational thermodynamics parameters to explain the interaction between drug enantiomers and thetarget protein. These parameters were correlated/converted and used to estimate the pseudo enantioselectivity of catechin enantiomer to HSA. This approach of combining docking methodology with docking post-processing methods such as MM-GBSA proved to be vital in estimating the correct pseudo binding affinities of a protein-ligand complexes. The enantioselectivity for enantiomers of catechin to HSA were 1,60 and 1,25 for site I and site II respectively. The results of case study II validates and verifies the preparation of ligands and accounting for tautomers at physiological pH, as well as conformational changes prior to and during docking with a flexible protein. The log KS = 5.43 and log KR = 5.34 for warfarin enantiomer-HSA interaction and the enantioselectivity (ES = KS/KR) of 1.23 were close to the experimental results and hence referred to as experimental-like affinity constants which validated and verified their applicability to predict protein-ligand binding affinities. In case study III, a 3D-QSAR pharmacophore model was developed by using 98 known CYP17A1 inhibitors from the literature with known experimental IC50 values. The starting compounds were diverse which included steroidal and non-steroidal inhibitors. The resulting pharmacophore models were trained with 69 molecules and 19 test set ligands. The best pharmacophore models were selected based on the regression coefficient for a best fit model with R2 (ranging from 0.85-0.99) & Q2 (ranging from 0.80-0.99) for both the training and test sets respectively, using Partial Least Squares (PLS) regression. On the other hand, the best pharmacophore model selected was further used for a database screening of novel inhibitors and the prediction of their CYP17A1 inhibition. The hits obtained from the database searches were further subjected to a virtual screening workflow docked to CYP17A1 enzyme in order to predict the binding mode and their binding affinities. The resulting poses from the virtual screening workflow were subjected to Induced Fit Docking workflow to account for protein flexibility during docking. The resulting docking poses were examined and ranked ordered according to the docking scores (a measure of affinity). Finally, the resulting hits designed from an updated model from case study III were further synthesized in an external organic chemistry laboratory and the synthetic protocols as well as spectroscopic data for structure elucidation forms part of the provisional patent specification. A provisional patent specification has been filed (RSA Pat. Appln. 2015/ 07849). The case studies performed in this thesis have enabled the discovery of non-steroidal CYP17A1 inhibitors. / D
127

Conjugados de ovalbumina e albumina bovina com desferrioxamina e suas interações com íons metálicos / Conjugates of ovalbumin and bovine albumin with desferrioxamine and their interactions with metallic ions

Castro, Camila Cristina de Lima 31 January 2017 (has links)
O ferro é essencial para a vida do ser humano, desempenhando um papel fundamental no metabolismo. Contudo, quando não armazenado em compartimentos biológicos adequados, o metal apresenta um potencial tóxico ao organismo, uma vez que contribui para a formação de espécies reativas de oxigênio. A sobrecarga de ferro é uma condição desfavorável para portadores de algumas disfunções genéticas, como a hemocromatose, ou de anemias crônicas que requeiram transfusões de sangue periódicas, como é o caso da talassemia. Os fármacos atuais que controlam a patologia, como a desferrioxamina (DFO), requerem infusão subcutânea lenta, causando desconforto em pacientes e podendo trazer um série de complicações, como insuficiência hepática e renal. A modificação dessas moléculas com biopolímeros é uma proposta para minimizar efeitos colaterais e aumentar a biodisponibilidade do fármaco no organismo. Dentre esses biopolímeros, destacam-se as albuminas proveniente do soro bovino (BSA) e do ovo (OVA), que têm baixa toxicidade, baixo custo e abundância de sítios reativos, que quando modificados, favorecem reação com a desferrioxamina. Como resultado, houve a reação dos biopolímeros com a desferrioxamina, com mudanças em suas estruturas secundárias e possível dimerização, resultando na formação de conjugados possuem afinidade com íon ferro e capacidade antioxidante semelhante ao fármaco original, características que tornam os compostos bons candidatos a uma alternativa à terapia de quelação. Os conjugados BSA-DFO e OVA-DFO podem reagir, além do ferro, com gadolínio, fazendo com o que os complexos tenham uma potencial aplicação como agentes de contraste em ressonância magnética de imagem (MRI). Neste trabalho, vimos que o complexo entre Gd(III) e BSA-DFO apresentou uma relaxatividade de 52,92 s-1 mM-1 para T2 e 45,37 s-1 mM-1 para T1 , um valor bem superior aos fármacos disponíveis no mercado, que apre-sentam relaxatividade entre 4 e 5 s-1 mM-1, o que foi explicado por sua elevada massa molecular, indicando que poderia ter bons efeitos na qualidade de MRI, com menores doses. / Iron is essential for human life, playing a fundamental role in metabolism. However, when not stored in appropriate biological compartments, the metal presents a toxic potential to the body, contributing to the formation of reactive oxygen species (ROS). Iron overload is an unfavorable condition for people with certain genetic disorders, such as hemochromatosis, or chronic anemias that require periodic blood transfusions, as thalassemia. Current drugs that control the pathology, as desferrioxamine, require slow subcutaneous infusion, causing discomfort in patients and may lead to a number of complications, such as hepatic and renal failures. As a result, the biopolymers were reacted with desferrioxamine, with changes in their secondary structures and possible dimerization, resulting in the formation of conjugates with iron ion affinity and antioxidant capacity similar to the original drug, characteristics that make the compounds good candidates for an alternative chelation therapy As a result, the reaction of the biopolymers with desferrioxamine caused a change in the secondary structure, with possible formation of dimers and showing different mobility when exposed to an electric potential difference. Not all polymer chains have reacted with DFO, however BSA-DFO complex has antioxidant capacity similar to the original drug. The BSA-DFO and OVA-DFO conjugates can react, in addition to iron, with gadolinium, making the complexes potential contrast agents for magnetic resonance imaging (MRI). In this work, the complex between Gd(III) and BSA-DFO presented a relaxativity of 52,92 s-1 mM-1 for T2 and 45,37 s-1 mM-1 for T1, values higher than the available drugs in the market (4 - 5 s-1 mM-1) which was explained by the high molecular weight, indicating a good effects on the quality of MRI, with lower doses.
128

Investigação química de complexos de coordenação dos antibióticos enrofloxacina e norfloxacina combinados ao íon Ru(III) e suas interações com biomoléculas alvo / Chemical Investigation of coordination compounds with enrofloxacin and norfloxacin antibiotics combined to Ru (III) ion and their interations with target biomolecule.

Reis, Felipe Costa Claro 28 July 2014 (has links)
Este trabalho tem como objetivo sintetizar e caracterizar um novo complexo mononuclear de rutênio (III) e enrofloxacina (enro, fármaco antibacteriano da família das fluoroquinolonas), [Ru(enro)3].nH2O. Foram testadas várias rotas sintéticas e apenas a partir de uma delas obteve-se o composto desejado. O produto foi caracterizado pelas técnicas espectroscópicas de absorção na região do UV-visível e do infra-vermelho. Através desta última técnica foi possível determinar o modo pelo qual a enrofloxacina se coordena ao íon rutênio: a coordenação ocorre de modo bidentado através do oxigênio da piridona e do oxigênio do grupamento carboxilato. Outro objetivo deste trabalho foi investigar a interação do complexo mononuclear de rutênio (III) e norfloxacina, [Ru(nor)3].nH2O, com a albumina de soro humano (HSA), através da técnica de luminescência. Mais especificamente pelo estudo da supressão da luminescência dos resíduos de triptofano, aplicando-se o modelo de tratamento da supressão bimolecular de Stern-Volmer. O estudo de supressão de fluorescência mostrou, por meio de espectros de emissão da HSA, que com o aumento da concentração do complexo [Ru(nor)3].nH2O na solução de HSA, ocorre uma redução gradual da luminescência da HSA, devido a alterações da conformação da proteína, que sugerem alteração do microambiente próximos aos resíduos de triptofano. A partir do tratamento dos dados pode-se determinar tanto K_sv quanto a constante cinética do processo de supressão, que mostraram uma dependência com a temperatura sugerindo como mecanismo predominante de supressão o mecanismo dinâmico. Porém essa conclusão foi revista a partir da determinação dos tempos de vida do estado excitado da HSA, e pode-se concluir que o mecanismo predominante à temperatura ambiente é o mecanismo estático, porém com o aumento da temperatura ocorre a predominância do mecanismo do tipo dinâmico. Através da determinação dos parâmetros termodinâmicos, concluiu-se que as interações entre a HSA e o complexo são espontâneas, e forças de van der Waals e ligações de hidrogênio estão envolvidas na ligação entre a HSA e o supressor. / This work aims to synthesize and characterize a new mononuclear ruthenium (III) complex and enrofloxacin (enro, antibacterial drug of the fluoroquinolone family), [Ru(enro)3].nH2O. Several synthetic routes were tested, but only from one of them it was obtained the desired compound. The product was characterized by spectroscopic techniques of absorption in UV-visible and infra-red regions. Through this last technique, it was possible to determine the coordination mode of enrofloxacin to the ruthenium ion: the coordination occurs in a bidentate way through the pyridone oxygen and the oxygen of the carboxylate group. Another aim of this study was to investigate the interaction of mononuclear ruthenium (III) complex and the norfloxacin, [Ru(nor)3].nH2O, with the human serum albumin (HSA), through the technique of luminescence. More specifically, by the study of the quenching of luminescence of tryptophan residues, by applying the Stern-Volmers model of treatment of bimolecular suppression. The fluorescence quenching study showed, through the emission spectra of HSA, that increasing the complex concentration in HSA solution, there is a gradual reduction of the luminescence of HSA, due to the conformational changes of the protein that suggests the change of microenvironment near tryptophan residues. From the data processing it is possible to determine both K_sv and the kinetic constant of the suppression process, which showed temperature dependence, suggesting as the predominant mechanism of quenching the dynamic mechanism. However, this conclusion has been revised from the determination of the lifetimes of the excited state of HSA, and it can be concluded that the predominant mechanism at room temperature is the static mechanism, but with the temperatures increase, it occurs the predominance of the dynamic type mechanism. By determining the thermodynamic parameters, it was concluded that the interactions between HSA and the complex are spontaneous, and Van der Waals forces and hydrogen bonds are involved in the binding between HSA and suppressor.
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Caracterização do aço inoxidável austenítico UNS S31254 em meio de NaCI 0,11 mol L-1 visando seu emprego em implantes ortopédicos / Electrochemical characterization of UNS S31254 austenitic stainless steel in 0.11 mol L-1 NaCl medium in order to propose its application in orthopaedic implants

Afonso, Monica Luisa Chaves de Andrade 27 September 2006 (has links)
Foi feita a caracterização eletroquímica do aço inoxidável austenítico UNS S31254 em meio de NaCl 0,11 mol L-1 na ausência e presença de soro albumina bovina (BSA) visando seu emprego em implantes ortopédicos. Foram empregadas como técnicas: medidas de potencial de circuito aberto, curvas de polarização, cronoamperometria, EIE, XPS, MEV, EDS e EEO. O comportamento eletroquímico do aço 254 foi comparado com o de outros aços empregados em implantes ortopédicos (ISO 5832-9, ASTM F138, e AISI 316L) na ausência e presença de BSA. O aço 254 se mostrou semelhante ao ISO 5832-9: encontra-se passivado desde o potencial de corrosão até o de transpassivação; a presença de inclusões de óxidos de cálcio e alumínio no aço 254 foi considerada a responsável por um potencial de transpassivação 100 mV menos positivo do que o observado com o aço ISO 5832-9. Foi detectada. além de óxido de Cr(III), a presença de Mo na forma Mo(VI) no filme passivo do aço 254. A ação da BSA, ora passivante ora catalisadora, depende de sua concentração, da natureza do substrato metálico, e do potencial na interfase metal-solução. A BSA modifica o mecanismo de oxidação do aço 254 e inibe seletivamente a dissolução dos seus elementos constituintes, em particular, níquel e cromo. / The electrochemical characterization of UNS S31254 has been made in 0.11 mol L-1 NaCl medium in the absence and presence of bovine serum albumin (BSA) in order to propose its application in orthopaedic implants. The techniques employed were: open circuit potential measurements, polarization curves, chronoamperometry, EIS, XPS, SEM, EDS and EEO. The electrochemical behavior of 254 SS was compared to that observed for ISO 5832-9, ASTM F138 and AISI 316L stainless steels, used in orthopedic implants, in the absence and presence of BSA. 254 SS is similar to ISO 5832-9 SS: it is passivated on the potential range between the corrosion and the transpassivation potentials; the presence of calcium and aluminum oxides can be responsible for the shift of about 100 mV to less positive potentials on the transpassivation potential when compared to ISO 5832-9 SS. The presence of Mo(VI) was detected beside Cr(III) as passivating film for 254 SS. BSA action depends on its concentration, the nature of the metallic substract and on the potential in the metal-solution interphase. BSA changes the oxidation mechanism of 254 SS and promotes the selective dissolution of the elements particularly nickel and chromium.
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Aplicabilidade da estimativa da hemoglobina glicada a partir da albumina glicada em pacientes com diabetes mellitus tipo 2 e diferentes graus de comprometimento renal

Aguiar, Ana Paula Costa de January 2017 (has links)
O diabetes mellitus (DM) é uma doença crônica com alto índice de morbidade e mortalidade, sendo considerado um dos maiores problemas de saúde pública do século 21, afetando aproximadamente 415 milhões de pessoas. As complicações em longo prazo do DM incluem a doença renal, a qual pode levar à falência renal, a retinopatia com perda potencial da visão e neuropatia, bem como o risco de amputações. A hemoglobina glicada (A1c) é considerada o parâmetro de referência na avaliação do controle glicêmico de pacientes com DM. No entanto, a mensuração da A1c pode não ser adequada para avaliar as variações em curto prazo do controle glicêmico, devido ao longo tempo de vida dos eritrócitos (120 dias). Existem ainda algumas limitações do uso deste teste, como em pacientes com hemoglobinas variantes, persistência hereditária à hemoglobina fetal, anemia hemolítica, anemia renal, entre outros. A avaliação da glicação da albumina é considerada, por alguns autores, como um melhor marcador para o controle glicêmico do que a A1c, em situações onde a A1c é de difícil interpretação devido à presença de interferentes, uma vez que a glicação da albumina não é afetada pela alteração no tempo de sobrevida das hemácias, como ocorre com a A1c. Atualmente, não há nenhum teste de albumina glicada (AG) disponível na rotina prática no Brasil, sendo um método limitado à pesquisa. No entanto, vários estudos mostram dados promissores em relação à AG e o controle do DM em situações específicas. Assim, a AG tem sido considerada um marcador alternativo no controle glicêmico e há necessidade de maior investigação sobre a utilização deste teste na prática clínica. / Diabetes mellitus (DM) is a chronic disease with high morbidity and mortality, being considered one of the biggest public health problems of the 21st century, affecting approximately 415 million people. Long-term complications of DM include renal disease, which can lead to kidney failure, retinopathy with potential loss of vision and neuropathy, as well as the risk of amputations. Glycated hemoglobin (A1c) is considered the reference in the assessment of glycemic control in patients with diabetes mellitus (DM). However, A1c measurement may not be adequate to evaluate the short-term variations of glycemic control due to the long lifespan of erythrocytes (120 days). There are also some limitations of using this test, such as in patients with variant hemoglobins, hereditary persistence to fetal hemoglobin, hemolytic anemia, renal anemia, among others. The evaluation of albumin glycation is considered by some authors to be a better marker for glycemic control than A1c in situations where A1c is difficult to interpret due to the presence of interferents, since albumin glycation is not affected by alteration in the survival time of red blood cells, as occurs with A1c. Currently, there is no glycated albumin (GA) test available in routine practice in Brazil, being a method limited to the research. However, several studies show promising data about GA in DM control in specific situations. Therefore, GA has been considered an alternative marker in glycemic control and there is a need of further investigation into the use of this test in clinical practice.

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