Paradigm shift for preparing versatile M2+-free gels from unmodified sodium alginate

This manuscript describes a new route to prepare rapidly Ca2+-free hydrogels from unmodified sodium alginate by simply mixing with small organic molecules such as poly(carboxylic acid) compounds as cross-linker agents instead of classical divalent metal salts such as CaCl2. Dimethyl sulfoxide (DMSO) was also found to induce the rapid gelation of aqueous alginate solutions. The gelation process takes place at room temperature, and depending on the composition, gels with good thermal (90-100 °C) and mechanical properties compared to classical metal-containing analogs are obtained. DMSO-based gels showed remarkable self-supporting and thixotropic properties, which can be tuned by the biopolymer concentration. Furthermore, oxalic acid-based gels show superior elasticity than HCl, CaCl2 and DMSO-based gels. The possibility to prepare monoliths, beads, and films of these gels provide them with significant versatility. In particular, films made of alginate and oxalic acid show good potential as synergistic anticancer drug delivery carrier. Computational studies using both quantum mechanical and classical force-field methodologies reveal that hydrogen bonding networks between water and DMSO molecules located close to the alginate chains are responsible for the stability of DMSO-based gels. In contrast, the cohesion of oxalic acid-based gels is a consequence of the coexistence of multiple ionic associations involving oxalate, alginate, and Na+ counterions, which stabilize the system and keep all the interacting species grouped.Peer ReviewedPostprint (author's final draft

Fabry Nephropathy: An Evidence-Based Narrative Review.

Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency. A correct diagnosis of FD, although challenging, has considerable implications regarding treatment, management, and counseling. The diagnosis may be confirmed by demonstrating the enzyme deficiency in males and by identifying the specific GLA gene mutation in male and female patients. Treatment with enzyme replacement therapy, as part of the therapeutic strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline, particularly in the early stages of the disease. Emergent treatments for FD include the recently approved chaperone molecule migalastat for patients with amenable mutations. The objective of this report is to provide an updated overview on Fabry nephropathy, with a focus on the most relevant aspects of its epidemiology, diagnosis, pathophysiology, and treatment options.S

Impacto de la perfusión hipotérmica pulsativa en el injerto renal de donante subóptimo: nuestra experiencia inicial

Objetivo: Estudios recientes han demostrado que el mantenimiento de la viabilidad de riñones con criterios expandidos durante su preservación sea un reto. La máquina de perfusión hipotérmica pretende mitigar el efecto del almacenamiento en frío sobre la calidad del órgano cuando el tiempo de isquemia fría es prolongada o el donante subóptimo. Objetivo: Evaluar las complicaciones que presentan los pacientes trasplantados renales con preservación estática fría o perfusión hipotérmica pulsátil. Material y Método: Estudio observacional retrospectivo durante 2010-2012 donde se incluyeron todos los trasplantes renales realizados en un hospital de tercer nivel. Las variables de estudio: estancia hospitalaria, horas de isquemia, necesidad de diálisis y número de sesiones post trasplante y el dispositivo de almacenamiento, edad y patologías asociadas al donante. Resultados: Se realizaron 175 trasplantes donde 70 procedieron de donantes =65 años. Se perfundieron en máquina 30 riñones y en 40 se utilizó la preservación estática. Nuestros hallazgos respecto al uso de la máquina de perfusión conllevan un descenso en la estancia media hospitalaria y una menor necesidad de hemodiálisis postrasplante. Conclusiones: Debido al alto porcentaje de órganos procedentes de donantes de edad avanzada y difíciles de preservar, resulta fundamental buscar técnicas de perfusión intravascular continua para una preservación más efectiva del órgano

Paradigm shift for preparing versatile M2+-free gels from unmodified sodium alginate

This manuscript describes a new route to prepare rapidly Ca2+-free hydrogels from unmodified sodium alginate by simply mixing with small organic molecules such as poly(carboxylic acid) compounds as cross-linker agents instead of classical divalent metal salts such as CaCl2. Dimethyl sulfoxide (DMSO) was also found to induce the rapid gelation of aqueous alginate solutions. The gelation process takes place at room temperature, and depending on the composition, gels with good thermal (90-100 °C) and mechanical properties compared to classical metal-containing analogs are obtained. DMSO-based gels showed remarkable self-supporting and thixotropic properties, which can be tuned by the biopolymer concentration. Furthermore, oxalic acid-based gels show superior elasticity than HCl, CaCl2 and DMSO-based gels. The possibility to prepare monoliths, beads, and films of these gels provide them with significant versatility. In particular, films made of alginate and oxalic acid show good potential as synergistic anticancer drug delivery carrier. Computational studies using both quantum mechanical and classical force-field methodologies reveal that hydrogen bonding networks between water and DMSO molecules located close to the alginate chains are responsible for the stability of DMSO-based gels. In contrast, the cohesion of oxalic acid-based gels is a consequence of the coexistence of multiple ionic associations involving oxalate, alginate, and Na+ counterions, which stabilize the system and keep all the interacting species grouped.Peer Reviewe

Fabry nephropathy: an evidence-based narrative review

Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency. A correct diagnosis of FD, although challenging, has considerable implications regarding treatment, management, and counseling. The diagnosis may be confirmed by demonstrating the enzyme deficiency in males and by identifying the specific GLA gene mutation in male and female patients. Treatment with enzyme replacement therapy, as part of the therapeutic strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline, particularly in the early stages of the disease. Emergent treatments for FD include the recently approved chaperone molecule migalastat for patients with amenable mutations. The objective of this report is to provide an updated overview on Fabry nephropathy, with a focus on the most relevant aspects of its epidemiology, diagnosis, pathophysiology, and treatment options