Low temperature-processed, porous sol-gel glasses represent a new class of materials for the immobilisation of biomolecules. If used to entrap biological recognition elements, these transparent and chemically inert glasses offer a new approach in the development of optical biosensors.

Orientador: Aguinaldo Robinson de Souza / Coorientador: Valdecir Farias Ximenes / Banca: Nelson Henrique Morgon / Banca: Ignez Caracelli / Resumo: A Albumina do Soro Humano (HSA) desempenha um papel importante no transporte de substâncias com propriedades farmacológicas devido a sua alta concentração e especificidade plasmática, colocando-a como uma das proteínas fundamentais responsáveis pela implicação farmacocinética dos fármacos. O derivado de aminoácido dansilglicina (DanGly) é um marcador fluorescente específico para o sítio II na HSA. Além disso, ao se ligar à proteína, a DanGly adquire quiralidade, uma característica que também pode ser usada para caracterizar o sítio de ligação de novos compostos na HSA. Este trabalho teve como objetivo elucidar a indução de quiralidade na DanGly por sua ligação com a HSA. Os espectros de Dicroísmo Circular Eletrônico (ECD) da DanGly (100 μM) na ausência ou presença de HSA (30 μM) em solução fosfato de sódio 50 mM em pH 7,0 foram obtidos num espectropolarímetro Jasco J-815 a 25o C com uma resolução de 1 nm numa velocidade de 50 nm/min. Os ECDs teóricos foram simulados usando a abordagem da Teoria do Funcional da Densidade (DFT) com os funcionais híbridos B3LYP e CAM-B3LYP no conjunto de bases 6-311 ++ G (2d, p) e o Modelo de Solvação baseado em Densidade (SMD) para os solventes etanol, metanol, acetonitrilo, água e tetra-hidrofurano; os cálculos foram realizados com o programa Gaussian09. A formação do complexo DanGly-HSA em tampão resultou no aparecimento de um espectro positivo de ECD centrado em 346 nm. Considerando que o sinal do ICD deve surgir a partir de uma conformação ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Human serum albumin (HSA) plays an important role in the transport of substances with pharmacological properties due to their high plasma concentration and specificity, placing it as the fundamental protein responsible for the pharmacokinetic implication of the drugs. The dansylglycine amino acid derivative (DanGly) is a fluorescent marker specific for the II site on the HSA. In addition, when binding to the protein, DanGly acquires chirality, a feature that can also be used to characterize the binding site of new compounds in albumin. This work aimed to elucidate the induction of chirality in the DanGly by its bonding to the HSA. Experimental Electronic Circular Dichroism (ECD) spectra of DanGly (100 μM) in the absence or presence of HSA (30 μM) in 50 mM sodium phosphate buffer pH 7.0 were obtained in a Jasco J-815 spectropolarimeter at 25o C. The spectra were obtained with a resolution of 1 nm and a scanning speed of 50 nm/min. The theoretical ECDs were simulated using the Density Functional Theory (DFT) approach with the hybrid functional B3LYP and CAM-B3LYP in the base set 6- 311 ++ G (2d, p) and the implicit Solvation Model based on Density (SMD) for the solvents ethanol, methanol, acetonitrile, water and tetrahydrofuran; the calculations were performed with the Gaussian09 program. The DanGly -HSA complex formation in buffer resulted in the appearance of a positive ECD spectrum centered at 346 nm. Considering that the ICD signal should arise from a chiral conformation of... (Complete abstract click electronic access below) / Mestre

BACKGROUND: Hypoalbuminemia (HA) is common in HF, however, its pathophysiology and clinical implications are poorly understood. While multiple studies have been published in the past decade investigating the role of serum albumin in HF, there is still no consensus on the prognostic value of this widely available measure. The objective of this study is to assess the prognostic role of albumin in heart failure (HF) patient. METHODS: Unrestricted searches of MEDLINE, EMBASE, Cochrane databases were performed. The results were screened for relevance and eligibility criteria. Relevant data were extracted and analyzed using Comprehensive Meta-Analysis software. The Begg and Mazumdar rank correlation test was utilized to evaluate for publication bias. RESULTS: A total of 48 studies examining 44,048 patients with HF were analyzed. HA was found in 32% (95% confidence interval [CI] 28.4%-37.4%) HF patients with marked heterogeneity (I2 = 98%). In 10 studies evaluating acute HF, in-hospital mortality was almost 4 times more likely in HA with an odds ratios (OR) of 3.77 (95% CI 1.96-7.23). HA was also associated with a significant increase in long-term mortality (OR: 1.5; 95% CI: 1.36-1.64) especially at 1-year post-discharge (OR: 2.44; 95% CI: 2.05-2.91; I2 = 11%). Pooled area under the curve (AUC 0.73; 95% CI 0.67-0.78) was comparable to serum brain natriuretic peptide (BNP) in predicting mortality in HF patients. CONCLUSION: Our results suggest that HA is associated with significantly higher in-hospital mortality as well as long-term mortality with a predictive accuracy comparable to that reported for serum BNP. These findings suggest that serum albumin may be useful in determining high-risk patients.

Toxicity preventing activity (TxPA) is a recently identified substance in serum which counteracts the toxic effect of very low density lipoproteins upon endothelial cells in vitro. In two clinical studies, TxPA was low in individuals with angiographically demonstrable coronary artery disease. An atherogenic index which combines TxPA with lipoprotein cholesterol values classifies individuals with coronary artery disease with an accuracy of greater than 93%. TxPA precipitates with 0.15 M trichloroacetic acid and above 3 M (NH4)2SO4. Activity is present in Cohn fractions IV4 and V and is stabilized by antioxidants. TxPA co-lutes with the albumin peak on gel filtration chromatography and as a subcomponent of albumin on ion-exchange chromatography. Isoelectric focusing resolves albumin into two major peaks with pI values of 4.8 and 5.6. The TxPA is identified as the pI 5.6 albumin peak.

No description available.

Modern diagnostic method magnetic resonance imaging (MRI) usually uses contrast agents T1-type, which are based on Gd3+ complexes. Due to severe toxicity of free Gd3+ , it is desired to have thermodynamically stable and kinetically inert complexes with fast elimination from the body. This work summarizes information about a novel contrast agent based on ligand DO3AP (1,4,7,10-tetraazacyclododecane-1-methyl(alkyl)phosphinic-4,7,10- triacetic acid) with pendant hydrophobic dibenzylamino group which is able to interact hydrophobically with the macromolecule of serum albumin. The stability of supracomplex is dependent on pH value, i.e. on the protonation of the pendant amino group of the complex (pKA = 5.6) and this interaction was confirmed from 1 H-NMRD profile and fluorescent analysis. The compound was tested for its angiographic properties in vivo on rat model. Furthermore, other complexes of the ligand with trivalent lanthanides (Nd3+ , Eu3+ , Tb3+ , Dy3+ , Er3+ ) were characterized by various methods (XRD, luminescence, UV-VIS, 1 H-, 17 O- and 31 P-NMR). The cleavage of the benzyl groups affords ligand whose Ln3+ complexes possess pH dependent PARACEST effect. These complexes were characterized by XRD, luminescence and 1 H- and 31 P-NMR. Moreover, the novel ligands with modified length of pendant...

Graduation date: 1996

Für die visuelle Wahrnehmung im Gehirn spielt die ungestörte Funktion von Neuronen und Gliazellen in der Netzhaut eine entscheidende Rolle. Viele schädigende Prozesse wie Entzündungen, Ischämien oder Traumata können zur Ödementstehung in der Netzhaut führen. Da die Netzhaut entwicklungsgeschichtlich einen vorverlagerten Teil des Zwischenhirns darstellt, lassen sich die pathophysiologischen Zusammenhänge, die zur Entstehung eines Netzhautödems führen, auch auf die Ödementstehung im Gehirn übertragen. Diese Arbeit beschäftigt sich mit dem Phänomen der Zellvolumenregulation von Müllerzellen – den hauptsächlich in der Netzhaut anzutreffenden Gliazellen – und leistet damit einen Beitrag zur Grundlagenerforschung der Ödementstehung in neuronalen Geweben. Die im Rahmen von Ödementstehungen regelmäßig zu beobachtenden Gefäßpermeabilitätserhöhungen führen in neuronalen Geweben auch zur Extravasation von Albumin. Unter diesem Gesichtspunkt untersucht die vorliegende Arbeit den Einfluss von bovinem Serumalbumin auf die Müllerzellen und die damit verbundenen Mechanismen am Modell der Netzhaut von Ratten.

Für die visuelle Wahrnehmung im Gehirn spielt die ungestörte Funktion von Neuronen und Gliazellen in der Netzhaut eine entscheidende Rolle. Viele schädigende Prozesse wie Entzündungen, Ischämien oder Traumata können zur Ödementstehung in der Netzhaut führen. Da die Netzhaut entwicklungsgeschichtlich einen vorverlagerten Teil des Zwischenhirns darstellt, lassen sich die pathophysiologischen Zusammenhänge, die zur Entstehung eines Netzhautödems führen, auch auf die Ödementstehung im Gehirn übertragen. Diese Arbeit beschäftigt sich mit dem Phänomen der Zellvolumenregulation von Müllerzellen – den hauptsächlich in der Netzhaut anzutreffenden Gliazellen – und leistet damit einen Beitrag zur Grundlagenerforschung der Ödementstehung in neuronalen Geweben. Die im Rahmen von Ödementstehungen regelmäßig zu beobachtenden Gefäßpermeabilitätserhöhungen führen in neuronalen Geweben auch zur Extravasation von Albumin. Unter diesem Gesichtspunkt untersucht die vorliegende Arbeit den Einfluss von bovinem Serumalbumin auf die Müllerzellen und die damit verbundenen Mechanismen am Modell der Netzhaut von Ratten.

Call number: LD2668 .T4 1956 L66 / Master of Science