Proyecto Vainica: valoración e intervención nutricional e insuficiencia cardiaca

Desde el comienzo del milenio diversos estudios muestran la “paradoja de la obesidad en pacientes con insuficiencia cardiaca”. Existe una epidemiología inversa: la obesidad predispone para desarrollar enfermedades cardiovasculares e insuficiencia cardiaca, pero un índice de masa corporal elevado mejora la supervivencia a dos y cinco años. Esta paradoja se ha extendido con posterioridad, a otras enfermedades de carácter crónico y ha sido un tema controvertido en la comunidad científica. Posteriormente, diversos estudios han ido migrando la orientación, relacionando el pronóstico no con el índice de masa corporal en sí, sino con el estado nutricional y el adelgazamiento no intencionado. De modo que el foco de interés está ahora en el estado nutricional de los pacientes y no en su índice de masa corporal. El peso –y por tanto el índice de masa corporal- es un parámetro cambiante en los pacientes con insuficiencia cardiaca, ya que por la naturaleza de su patología, pueden presentar un volumen hídrico aumentado y son susceptibles a descompensaciones edemo-asciticas. Los episodios de descompensación son habitualmente tratados con diuréticos, con el objetivo de eliminar el exceso de líquido, lo que hace que el peso fluctúe rápidamente, a expensas de la reducción del exceso de volumen hídrico. No existe consenso o marcador universalmente aceptado para definir la malnutrición. Por ello, coexisten múltiples métodos de cribado y valoración nutricional. No destacándose ninguno como “gold estándar”..

Relevance of Internal Friction and Structural Constraints for the Dynamics of Denatured Bovine Serum Albumin

A general property of disordered proteins is their structural expansion that results in a high molecular flexibility. The structure and dynamics of bovine serum albumin (BSA) denatured by guanidinium hydrochloride (GndCl) were investigated using small-angle neutron scattering (SANS) and neutron spin–echo spectroscopy (NSE). SANS experiments demonstrated the relevance of intrachain interactions for structural expansion. Using NSE experiments, we observed a high internal flexibility of denatured BSA in addition to center-of-mass diffusion detected by dynamic light scattering. Internal motions measured by NSE were described using concepts based on polymer theory. The contribution of residue-solvent friction was accounted for using the Zimm model including internal friction (ZIF). Disulfide bonds forming loops of amino acids of the peptide backbone have a major impact on internal dynamics that can be interpreted with a reduced set of Zimm modes

Chain Confinement and Anomalous Diffusion in the Cross over Regime between Rouse and Reptation

By neutron spin echo (NSE) and pulsed field gradient (PFG) NMR, we study the dynamics of a polyethylene-oxide melt (PEO) with a molecular weight in the transition regime between Rouse and reptation dynamics. We analyze the data with a Rouse mode analysis allowing for reduced long wavelength Rouse modes amplitudes. For short times, subdiffusive center-of-mass mean square displacement ⟨rcom2(t)⟩ was allowed. This approach captures the NSE data well and provides accurate information on the topological constraints in a chain length regime, where the tube model is inapplicable. As predicted by reptation for the polymer ⟨rcom2(t)⟩, we experimentally found the subdiffusive regime with an exponent close to μ=12, which, however, crosses over to Fickian diffusion not at the Rouse time, but at a later time, when the ⟨rcom2(t)⟩ has covered a distance related to the tube diameter

Effect of Hierarchical Cluster Formation on the Viscosity of Concentrated Monoclonal Antibody Formulations Studied by Neutron Scattering

Recently, reversible cluster formation was identified as an underlying cause of anomalously large solution viscosities observed in some concentrated monoclonal antibody (mAb) formulations, which poses a major challenge to the use of subcutaneous injection for some mAbs. A fundamental understanding of the structural and dynamic origins of high viscosities in concentrated mAb solutions is thus of significant relevance to mAb applications in human health care, as well as being of scientific interest. Herein, we present a detailed investigation of an IgG1-based mAb to relate the short-time dynamics and microstructure to significant viscosity changes over a range of pharmaceutically relevant physiochemical conditions. The combination of light scattering, small-angle neutron scattering, and neutron spin echo measurement techniques conclusively demonstrates that, upon addition of Na₂SO₄, these antibodies form strongly bound reversible dimers at dilute concentrations that interact with each other to form large, loosely bound, transient clusters when concentrated. This hierarchical structure formation in solution causes a significant increase in the solution viscosity