Exploring the occurrence of thioflavin-T-positive insulin amyloid aggregation intermediates

The aggregation of proteins is considered to be the main cause of several neurodegenerative diseases. Despite much progress in amyloid research, the process of fibrillization is still not fully understood, which is one of the main reasons why there are still very few effective treatments available. When the aggregation of insulin, a model amyloidogenic protein, is tracked using thioflavin-T (ThT), an amyloid specific dye, there is an anomalous occurrence of double-sigmoidal aggregation kinetics. Such an event is likely related to the formation of ThT-positive intermediates, which may affect the outcome of both aggregation kinetic data, as well as final fibril structure. In this work we explore insulin fibrillization under conditions, where both normal and double-sigmoidal kinetics are observed and show that, despite their dye-binding properties and random occurrence, the ThT-positive intermediates do not significantly alter the overall aggregation process.

A PRELIMINARY STUDY OF THE EFFECT OF ANESTHETIC AGENTS ON THE RHEOLOGICAL PARAMETERS OF GLYCATED ERYTHROCYTES

This paper presents a preliminary study of the effects of the anesthetics propofol, remifentanil, and vecuronium bromide on the rheological properties of glycated erythrocytes in vitro, modeling the glycation by hyperglycemia observed in diabetes. Viscoelastic and aggregation kinetic parameters of erythrocytes were determined using an erythrocyte rheometer and an optical chip aggregometer developed in our laboratory. The results showed significant alterations in the membrane surface viscosity, the elastic modulus, and the erythrocyte deformability index for the different anesthetics studied. Also, the kinetics aggregation parameters showed different types of alterations due to the effect of anesthetics. This preliminary study suggests that the use of these anesthetics in diabetic patients could induce hemorheological alterations that disturb the microcirculation. For this reason, it is recommended to deepen these investigations to prevent complications in surgical procedures.

Salt mediated unusual switching in the aggregation kinetic profile of human carbonic anhydrase

Aggregation pathway of human carbonic anhydrase II in the presence of salt.