107 research outputs found

    Das geographische Institut und die Meeres- und Küstenforschung in Kiel

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    Wirksamkeit der Hypnose auf Schmerzen bei Erwachsenen: systematische Literaturreview

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    Das Ziel dieser systematischen Literaturreview ist es, die Wirksamkeit der Hypnose auf Schmerzen bei Erwachsenen zu überprüfen. Daraus ergibt sich folgende Forschungsfrage: "Wie wird die Wirksamkeit der Hypnose auf Schmerzen bei Erwachsenen in der wissenschaftlichen Literatur beschrieben?

    Isolation and characterization of an inhibitory human monoclonal antibody specific to the urokinase-type plasminogen activator, uPA

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    The serine protease urokinase (uPA, urokinase-type plasminogen activator) is over-expressed in certain tumors and is considered to be the strongest single indicator of poor prognosis in patients with metastatic breast cancer. In this article, we describe the isolation and affinity maturation of a fully human recombinant antibody (termed DS2), specific to the human uPA and capable of inhibiting its enzymatic activity with an IC50 value in the low nanomolar range. The novel antibody cross-reacts with murine uPA. It was expressed both as scFv fragment and in IgG format, allowing a systematic comparative immunofluorescence (IF) analysis of the uPA expression patterns in a large panel of human und murine tumors and of normal human tissues. Although uPA was strongly expressed in virtually all tumor specimens tested, it exhibited only a weak expression in certain normal tissues (mainly in the colon, lung, spleen and bone marrow). IgG(DS2) was not able to inhibit cancer growth in immunocompromised mice bearing subcutaneous human MDA-MB-231 or DoHH-2 tumors. However, an ex vivo IF analysis confirmed the ability of the DS2 antibody to preferentially localize at the tumor site compared with normal organs. Collectively, these data suggest that uPA blocking antibodies may not be indicated for cancer growth inhibition strategies, but may serve as valuable tools for the implementation of pharmacodelivery strategies against a variety of different tumor

    Tumour-targeting properties of antibodies specific to MMP-1A, MMP-2 and MMP-3

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    Purpose: Matrix metalloproteinases (MMPs), a group of more than 20 zinc-containing endopeptidases, are upregulated in many diseases, but several attempts to use radiolabelled MMP inhibitors for imaging tumours have proved unsuccessful in mouse models, possibly due to the limited specificity of these agents or their unfavourable pharmacokinetic profiles. In principle, radiolabelled monoclonal antibodies could be considered for the selective targeting and imaging of individual MMPs. Methods: We cloned, produced and characterized high-affinity monoclonal antibodies specific to murine MMP-1A, MMP-2 and MMP-3 in SIP (small immunoprotein) miniantibody format using biochemical and immunochemical methods. We also performed comparative biodistribution analysis of their tumour-targeting properties at three time points (3h, 24h, 48h) in mice bearing subcutaneous F9 tumours using radioiodinated protein preparations. The clinical stage L19 antibody, specific to the alternatively spliced EDB domain of fibronectin, was used as reference tumour-targeting agent for in vivo studies. Results: All anti-MMP antibodies and SIP(L19) strongly stained sections of F9 tumours when assessed by immunofluorescence methods. In biodistribution experiments, SIP(SP3), specific to MMP-3, selectively accumulated at the tumour site 24 and 48h after intravenous injection, but was rapidly cleared from other organs. By contrast, SIP(SP1) and SIP(SP2), specific to MMP-1A and MMP-2, showed no preferential accumulation at the tumour site. Conclusion: Antibodies specific to MMP-3 may serve as vehicles for the efficient and selective delivery of imaging agents or therapeutic molecules to sites of diseas

    Albumin biofunctionalization to minimize the Staphylococcus aureus adhesion on solid substrates

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    Staphylococcus aureus has become the most common opportunistic microorganism related to nosocomial infections due to the bacteria capacity to form biofilms on biomedical devices and implants. Since bacterial adhesion is the first step in this pathogenesis, it is evident that inhibiting such a process will reduce the opportunity for bacterial colonization on the devices. This work is aimed at optimizing a surface biofunctionalization strategy to inhibit the adhesion of S. aureus on solid substrates. The first part of the work deals with the albumin adsorption-desorption process, studied by a factorial design of experiments to explore a wide range of experimental factors (protein concentration, pH, flow rate and adsorption time) and responses (initial adsorption rate, adsorbed amount, desorbed extent) for hydrophilic and hydrophobic substrates, with a reduced number of experiments. This approach allows the simultaneous evaluation of the factors affecting the albumin adsorption-desorption process to find a qualitative correlation with the amount of alive S. aureus adhered on albumin biofunctionalized substrates. The results of this work point to a relationship between bacterial adhesion and the degree of albumin relaxation on the solid substrate. In fact, the inhibition of bacterial adhesion on albumin biofunctionalized substrates is due to the surface perturbation on the native structure of the protein. On this base, a biofunctionalization strategy was designed using a solution of thermally treated albumin molecules (higher β-sheet or unordered secondary structure elements) to biofunctionalize solid substrates by dipping. With these albumin biofunctionalized substrates S. aureus adhesion was minimized.Fil: Martín, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Pfaffen, Maria Valeria del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Valenti, Laura Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Giacomelli, Carla Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

    Voltammetric quantification of 4-nitrophenol using a multivariate optimized plated bismuth film electrode

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    In this study the multivariate optimization of bismuth film deposition (BiFE) on glassy carbon electrode, together with square wave voltammetry parameters for nitrophenol quantification, is described for the first time. For this purpose, response surface methodology and desirability function were applied to a Box-Behnken design. For the BiFE deposition procedure, the relationship between the reduction current peak (ip) and standard deviation values with time, potential deposition, and Bi(III) concentration were analyzed; meanwhile, for frequency, step, and amplitude only the relationship with ip was considered. The pH influence in nitrophenol determination was carried on by univariate analysis. After parameters optimization a limit of detection of 3.4 × 10-6 mol L-1 was observed.Fil: Núñez, Rodrigo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Moreno Betancourth, Jessica María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Ortiz, Patricia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Pfaffen, Maria Valeria del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

    Spectroscopic characterization and investigation of the dynamic of charge compensation process of supramolecular films derived from tetra-2-pyridyl-1,4-pyrazine ligand

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    This work describes the infrared spectroscopy characterization and the charge compensation dynamics in supramolecular film FeTPPZFeCN derived from tetra-2-pyridyl-1,4-pyrazine (TPPZ) with hexacyanoferrate, as well as the hybrid film formed by FeTPPZFeCN and polypyrrole (PPy). For supramolecular film, it was found that anion flux is greater in a K+ containing solution than in Li+ solution, which seems to be due to the larger crystalline ionic radius of K+. The electroneutralization process is discussed in terms of electrostatic interactions between cations and metallic centers in the hosting matrix. The nature of the charge compensation process differs from others modified electrodes based on Prussian blue films, where only cations such as K+ participate in the electroneutralization process. In the case of FeTPPZFeCN/PPy hybrid film, the magnitude of the anions’s flux is also dependent on the identity of the anion of the supporting electrolyte.Este trabalho descreve a caracterização espectroscópica por infravermelho e o estudo da dinâmica de compensação de cargas do filme supramolecular FeTPPZFeCN derivado do ligante tetra-2-piridil-1,4-pirazina (TPPZ) com hexacianoferrato, bem como o filme híbrido envolvendo FeTPPZFeCN e uma matriz de polipirrol (PPy). Para o filme supramolecular, foi observado um aumento no fluxo de ânion em solução contendo K+ em relação ao Li+, que parece estar relacionado ao tamanho do raio iônico cristalino do K+. O processo de eletroneutralização é discutido em termos de interação eletrostática entre cátions e centros metálicos na matriz hospedeira. A natureza do processo de compensação de carga difere de outros eletrodos modificados derivados do azul da Prússia, onde somente cátions tais como K+ participam no processo de eletroneutralização. No caso do filme híbrido FeTPPZFeCN/PPy, a magnitude do fluxo de ânions é também dependente da identidade do ânion em diferentes eletrólitos de suporte.FAPESPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)SP

    Neo-Suprahepatic cava: A case report of a modified technique for domino liver transplantation

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    Domino liver transplantation, introduced in 1997, originally consisted of a graft from a patient with familial amyloidotic polyneuropathy used as a donor for a compatible recipient, thus increasing the pool of hepatic grafts for liver transplantation. The aim of this report was to present a modification on the technique for outflow reconstruction in domino liver transplantation first proposed by Liu et al and Cescon et al. In this description we proposed a new technique that differs from the one mentioned above by performing a neo-suprahepatic cava, constructed using only an iliac vein graft, facilitating the anastomosis as if it was a regular cadaveric liver transplant.Fil: Padín, J. M.. Fundación Favaloro; ArgentinaFil: Pfaffen, G.. Fundación Favaloro; ArgentinaFil: Pérez Fernández, I.. Fundación Favaloro; ArgentinaFil: Sandi, M.. Fundación Favaloro; ArgentinaFil: Ramisch, D.. Fundación Favaloro; ArgentinaFil: Barros Schelotto, P.. Fundación Favaloro; ArgentinaFil: Gondolesi, Gabriel Eduardo. Fundación Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Interplay among electrostatic, dispersion and steric interactions: Spectroscopy and quantum chemical calculations of π-hydrogen bonded complexes

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    π-hydrogen bonding interactions are ubiquitous in both materials and biology. Despite their relatively weak nature great progress has been made in their investigation by experimental and theoretical methods, but this becomes significantly more complicated when secondary intermolecular interactions are present. In this study the effect of successive methyl substitution on the supramolecular structure and interaction energy of indole⋯methylated benzene (ind⋯n-mb, n = 1–6) complexes is probed through a combination of supersonic jet experiment and benchmark quality quantum chemical calculations. It is demonstrated that additional secondary interactions introduce a subtle interplay among electrostatic and dispersion forces, as well as steric repulsion, which fine-tunes the overall structural motif. Resonant Two-Photon Ionization (R2PI) and IR-UV double resonance spectroscopy techniques were used to probe jet-cooled ind⋯n-mb (n = 2, 3, 6) complexes, with red-shifting of the N–H IR stretching frequency showing that increasing the degree of methyl substitution increases the strength of the primary N–H⋯π interaction. Ab initio harmonic frequency and binding energy calculations confirm this trend for all six complexes. Electronic spectra of the three dimers are broad and structureless, with quantum chemical calculations revealing that this is likely due to multiple tilted conformations of each dimer possessing similar stabilization energies

    Ferritins: furnishing proteins with iron

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    Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins
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