RESUMEN
Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma levels. Further analysis showed that patients with advanced AMD had elevated sC5b-9 compared to those with non-advanced AMD, although this was not associated with the P167S polymorphism. Electron microscopy of membrane attack complexes (MACs) generated using recombinantly produced wild type or P167S C9 demonstrated identical MAC ring structures. In functional assays, the P167S variant displayed a higher propensity to polymerize and a small increase in its ability to induce hemolysis of sheep erythrocytes when added to C9-depleted serum. The demonstration that this C9 P167S AMD risk polymorphism displays increased polymerization and functional activity provides a rationale for the gene therapy trials of sCD59 to inhibit the terminal pathway of complement in AMD that are underway.
Asunto(s)
Complemento C9/genética , Predisposición Genética a la Enfermedad/genética , Degeneración Macular/genética , Mutación , Anciano , Animales , Células CHO , Estudios de Casos y Controles , Estudios de Cohortes , Complemento C9/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Proteínas del Sistema Complemento/genética , Proteínas del Sistema Complemento/metabolismo , Cricetinae , Cricetulus , Femenino , Cobayas , Hemólisis , Humanos , Degeneración Macular/sangre , Degeneración Macular/metabolismo , Masculino , Polimerizacion , Factores de Riesgo , OvinosRESUMEN
UNLABELLED: Debate is heating up whether or not to require girls to be vaccinated against the human papillomavirus (HPV), a leading cause of cervical cancer (CC). Prolepsis against this plague is mainly focused on early detection with Pap test (screening) and recently with administrating HPV vaccines in youths. OBJECTIVE: To discuss the increased bioethical role of contemporary gynecologist in the young population, with the aim to contribute to the decrease of this malignancy. MATERIALS AND METHODS: The authors searched the web (data-warehouse: articles, forums, etc., and data-mining: sequence analysis and classification) for HPV vaccination and related bioethical issues. RESULTS: HPV vaccines have already caused debates on whether they must be mandatory and on whether they cause a pseudo-safeness mental state, making youths "forget" necessary annual Pap tests or even worse, urging them in promiscuity, resulting in an increased occurrence of CC. CONCLUSIONS: Greece, in order to appropriately apply the Constitutional Law 5 Section 5 (All persons have the right to the protection of their health...), needs to train contemporary gynecologists in adequate youth consultation and proper family approaches regarding HPV vaccination issues. Enhancing the gynecologist's role, vaccination's effectiveness (sensitivity and specificity) will be increased and on the other hand, a rule of social law will be established in the country.