Hereditary hemochromatosis: An opportunity for gene therapy

Levels of body iron should be tightly controlled to prevent the formation of oxygen radicals, lipoperoxidation, genotoxicity, and the production of cytotoxic cytokines, which result in damage to a number of organs. Enterocytes in the intestinal villae are involved in the apical uptake of iron from the intestinal lumen; iron is further exported from the cells into the circulation. The apical divalent metal transporter-1 (DMT1) transports ferrous iron from the lumen into the cells, while the basolateral transporter ferroportin extrudes iron from the enterocytes into the circulation. Patients with hereditary hemochromatosis display an accelerated transepithelial uptake of iron, which leads to body iron accumulation that results in cirrhosis, hepatocellular carcinoma, pancreatitis, and cardiomyopathy. Hereditary hemochromatosis, a recessive genetic condition, is the most prevalent genetic disease in Caucasians, with a prevalence of one in 300 subjects. The majority of patients with hereditary hemochromatosis display mutations in the gene coding for HFE, a protein that normally acts as an inhibitor of transepithelial iron transport. We discuss the different control points in the homeostasis of iron and the different mutations that exist in patients with hereditary hemochromatosis. These control sites may be influenced by gene therapeutic approaches; one general therapy for hemochromatosis of different etiologies is the inhibition of DMT1 synthesis by antisense-generating genes, which has been shown to markedly inhibit apical iron uptake by intestinal epithelial cells. We further discuss the most promising strategies to develop gene vectors and deliver them into enterocytes.

Vertebroplastía percutánea en el manejo del dolor de las fracturas vertebrales por compresión / Percutaneous cement vertebral augmentation in vertebral compression fractures: an update

Las fracturas vertebrales por compresión son de alta prevalencia y se relacionan principalmente a osteoporosis y cáncer. Frecuentemente tienen consecuencias devastadoras en la calidad de vida de los pacientes. Aquellos pacientes que no responden al tratamiento conservador se pueden beneficiar de una técnica mínimamente invasiva, la vertebroplastía, para reforzar la vértebra fracturada con cemento y así controlar el dolor. La vertebroplastía es un procedimiento ambulatorio con baja tasa de efectos colaterales cuando la realiza un médico con experiencia y el entrenamiento adecuado. Su tasa de éxito va del 65 al 95 por ciento, dependiendo de la indicación. Sólida evidencia científica se requiere aún para apoyar su amplio uso clínico.

Vertebral compression fractures are highly prevalent. Osteoporosis and cancer are the main causes. As a consequence patients endure excruciating breakthrough pain and debilitating experience that affect their quality of life. Those individuals that do not respond to classic treatment might benefit of vertebral cement augmentation. This is a totally ambulatory procedure aimed to control pain and stabilize the bone. Percutaneous approach is usually undertaken. Long lasting pain relief results in 65 to 95 percent of patients with a very low profile of complications when the procedure is done by experienced practitioners. Randomized, blinded and prospective studies are still required.

Protein recovery, separation and purification: selection of optimal techniques using an expert system

The paper discusses the utilization of new techniques ot select processes for protein recovery, separation and purification. It describesa rational approach that uses fundamental databases of proteins molecules to simplify the complex problem of choosing high resolution separation methods for multi component mixtures. It examines the role of modern computer techniques to help solving these questions