Caracterización de línea celular de paratiroides humana (RCPTH) y evaluación de tumorigenicidad en ratones NOD/SCID / Characterization of human parathyroid cell line (RCPTH) and tumorigenicity evaluation in NOD/SCID

Background: Cell therapy could be an alternative for the treatment of hypoparathyroidism. Therefore efforts have been made to establish a cell line of parathyroid cells. Aim: To establish a continuous functional and non-tumorigenic human parathyroid cell line. Material and Methods: Nineteen tissue samples from 15 patients subjected to parathyroidectomy due to primary or secondary hyperparathyroidism were obtained. Functional, morphological and tumorigenic properties of the obtained cells were analyzed. Results: After two months of culture in conditions of immortalization, cells had an exponential growth without experiencing senescence. Therefore, more than 200 sub cultures have been performed. The cell line was denominated RCPTH. Morphological characterization showed monolayer growth with contact inhibition and a duplication time of 30 hours. On light microscopy, pleomorphism and low number of mitoses were observed. Cells accumulated glycogen, expressed calcium sensing receptor and had positive PTH cytoplasmic clusters. The line secreted PTH initially but subsequently, PTH production became undetectable. The cell line did not have tumor or metastatic growth. Conclusions: A parathyroid cell line has been established. The lack of PTH production is a problem that will require the search for mechanisms to activate it.

Papel de los polimorfismos -238 y -308 del promotor del factor de necrosis tumoral alfa en la patogenia y respuesta al tratamiento anti- factor de necrosis tumoral alfa en artritis reumatoide / The influence of -238 and -308 TNF alpha polymorphisms on the pathogenesis and response to treatment in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects 0.8 percent of the world population, it affects the synovial membrane of joints and the clinical presentation encompasses a wide spectrum, ranging from a mild to a severe and erosive disease that causes joint and cartilage destruction which finally provokes irreversible structural damage and patient disability. In the last years, there have been important advances in the pathogenesis of this disease, the efforts have been concentrated on pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha). This protein guides numerous events in the synovial and systemic inflammatory process and is encoded in the Major Histocompability Complex (MHC), one of the most polymorphic of the genome. Polymorphisms affecting the TNFalpha gene and its regulatory regions are associated with RA prevalence and course. There is a possible association between these polymorphisms and the clinical response to the use of monoclonal antibodies anti-TNFalpha. The possibility that the determination of genotypes -238 and -308 may have prognostic and therapeutic consequences is debated nowadays (Rev Méd Chile 2005; 133: 1089-95).

Terapias emergentes en artritis reumatoide / Emergent therapies for rheumatoid arthritis

The use of biological agents such as etanercept, infliximab, adalimumab and anakinra has been recently approved for the treatment of rheumatoid arthritis. All are effective controlling signs and symptoms and inhibiting disease progression. To overcome the problems generated by their high costs and possible participation in reactivating latent infections, other therapeutic tools are being developed. Gene therapy using expression vectors carrying genes coding for specific proteins, may interfere in key points involved in the pathogenesis of the disease. Intra-articular administration of cDNA coding for soluble TNF receptors, IL-1, or IL-1Ra decreases signs of the disease in animal models. Vectors, expressing inhibitors of signal transduction pathways involving to NF-kB and JAK-STAT-3, are effective in modulating joint inflammation in mice. The use of antigen-pulsed antigen presenting cells or dendritic cells (DC) bound to apoptosis-inducing molecules, specifically eliminates autoreactive T cells. Other novel approach attempts the development of T regulatory-inducing tolerogenic DC-based vaccines that inhibit autoreactive T cells, through the secretion of suppressing cytokines or by other mechanisms to be elucidated. Oral tolerance induction to auto-antigens is also a successful experimental strategy under study. Current research aims to control peripheral tolerance in rheumatoid arthritis patients.

Nuevas armas inmunológicas para la medicina del siglo XXI: Terapia biológica basada en el uso de anticuerpos monoclonales de última generación / New immunological weapons for Medicine at XXI century: biological therapy based on the use of last generation monoclonal antibodies

The fusion of a murine B cell and a myeloma cell generates a hybridoma that produces monoclonal antibody (mAb). These murine mAb induce the HAMA (human anti-mouse antibodies) response. Murine mAb have been modified by genetic engineering, producing molecules with a higher proportion of human protein. At present, chimeric, humanized and fully human mAb are available. mAb block interactions between target molecules and their ligands or trigger the lyses of mAb-coated tumor cells. Numerous mAb have been developed using the recombinant DNA technology and several are available in the market. Trastuzumab, against HER2/neu, is useful in breast cancer; rituximab, against CD20 in B lymphocytes is useful in lymphoma; alemtuzumab, against CD52 is used in lymphoma and leukemia; daclizumab and basiliximab block the IL-2 receptor interaction and reduce acute rejection in kidney transplantion; abciximab, an antagonist of GPIIb/IIIa platelet receptor, is used in patients undergoing acute coronary syndromes. In autoimmunity diseases, blocking tumor necrosis factor by infliximab and adalimumab has demonstrated excellent results. Thus, infliximab is useful in the treatment of rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis while adalimumab is the first fully human mAb available for RA. Infliximab and adalimumab reduce signs and symptoms in RA and they also interfere with progression of joint damage. Finally, the direct benefits of antagonist treatment can occur at the expense of a major adverse effect in some other biological function (Rev Méd Chile 2003; 131: 1445-53).