In search for multi-target ligands as potential agents for diabetes mellitus and its complications—a structure-activity relationship study on inhibitors of aldose reductase and protein tyrosine phosphatase 1b

Diabetes mellitus (DM) is a complex disease which currently affects more than 460 million people and is one of the leading cause of death worldwide. Its development implies numerous metabolic dysfunctions and the onset of hyperglycaemia-induced chronic complications. Multiple ligands can be rationally designed for the treatment of multifactorial diseases, such as DM, with the precise aim of simultaneously controlling multiple pathogenic mechanisms related to the disease and providing a more effective and safer therapeutic treatment compared to combinations of selective drugs. Starting from our previous findings that highlighted the possibility to target both aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP1B), two enzymes strictly implicated in the development of DM and its complications, we synthesised 3-(5-arylidene-4-oxothiazolidin-3-yl)propanoic acids and analogous 2-butenoic acid derivatives, with the aim of balancing the effectiveness of dual AR/PTP1B inhibitors which we had identified as designed multiple ligands (DMLs). Out of the tested compounds, 4f exhibited well-balanced AR/PTP1B inhibitory effects at low micromolar concentrations, along with interesting insulin-sensitizing activity in murine C2C12 cell cultures. The SARs here highlighted along with their rationalization by in silico docking experiments into both target enzymes provide further insights into this class of inhibitors for their development as potential DML antidiabetic candidates

The Effect of Convection on Disorder in Primary Cellular and Dendritic Arrays

Directional solidification studies have been carried out to characterize the spatial disorder in the arrays of cells and dendrites. Different factors that cause array disorder are investigated experimentally and analyzed numerically. In addition to the disorder resulting from the fundamental selection of a range of primary spacings under given experimental conditions, a significant variation in primary spacings is shown to occur in bulk samples due to convection effects, especially at low growth velocities. The effect of convection on array disorder is examined through directional solidification studies in two different alloy systems, Pb-Sn and Al-Cu. A detailed analysis of the spacing distribution is carried out, which shows that the disorder in the spacing distribution is greater in the Al-Cu system than in Pb-Sn system. Numerical models are developed which show that fluid motion can occur in both these systems due to the negative axial density gradient or due the radial temperature gradient which is always present in Bridgman growth. The modes of convection have been found to be significantly different in these systems, due to the solute being heavier than the solvent in the Al-Cu system and lighter than it in the Pb-Sn system. The results of the model have been shown to explain experimental observations of higher disorder and greater solute segregation in a weakly convective Al-Cu system than those in a highly convective Pb-Sn system

Didascalie, disegni e zoologia sul Papiro di Artemidoro

Il presente lavoro intende appronfondire alcune probelmatiche relative alla raffigurazione e alla denominazione degli animali nel mondo antico, partendo dalla straordinaria documentazione linguistica e figurativa offerta dai disegni sul Verso del Papiro di Artemidoro. Si cerchera', nel corso di questa disamina, di fornire alcune puntuali risposte a certe ipotesi che vorrebbero considerare gli animali del Verso una raffigurazione cosmografica, i cui confronti stilistici e formali sono assolutamente inesistenti per tutta l'eta' antica, medievale e modern