Myasthenia gravis is usually caused by autoantibodies to the acetylcholine receptor (AChR). The AChR is clustered and anchored in the postsynaptic membrane of the neuromuscular junction (NMJ) by a cytoplasmic protein called rapsyn. We previously showed that resistance to experimental autoimmune myasthenia gravis (EAMG) in aged rats correlates with increased rapsyn concentration at the NMJ. It is possible, therefore, that endogenous rapsyn expression may be an important determinant of AChR loss and neuromuscular transmission failure in the human disease, and that upregulation of rapsyn expression could be used therapeutically. To examine first a potential therapeutic application of rapsyn upregulation, we induced acute EAMG in young rats by passive transfer of AChR antibody, mAb 35, and used in vivo electroporation to over-express rapsyn unilaterally in one tibialis anterior. We looked at the compound muscle action potentials (CMAPs) in the tibialis anterior, at rapsyn and AChR expression by quantitative radioimmunoassay and immunofluorescence, and at the morphology of the NMJs, comparing the electroporated and untreated muscles, as well as the control and EAMG rats. In control rats, transfected muscle fibres had extrasynaptic rapsyn aggregates, as well as slightly increased rapsyn and AChR concentrations at the NMJ. In EAMG rats, despite deposits of the membrane attack complex, the rapsyn-overexpressing muscles showed no decrement in the CMAPs, no loss of AChR, and the majority had normal postsynaptic folds, whereas endplates of untreated muscles showed typical AChR loss and morphological damage. These data suggest not only that increasing rapsyn expression could be a potential treatment for selected muscles of myasthenia gravis patients, but also lend support to the hypothesis that individual differences in innate rapsyn expression could be a factor in determining disease severity.

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The relative importance of flood pulse dynamics and megafan behaviour for the Sábalo (Prochilodus lineatus) catches in the neotropical Pilcomayo River is studied. The Sábalo catches can mainly be explained by decreased river discharges in the preceding years resulting in smaller inundated areas during rainy season floods and thereby in a decreased area of feeding grounds for the fishes. The decreased river discharges and the related decline of Sábalo catches in the 1990's can be linked to the 90-95 El Niño event. In 2007 the Sábalo catches were comparable to the catches before the "El Niño" event. The connectivity (continuity) between the main river and flood plain areas, which is influenced by sedimentation processes, is also of great importance and very probably plays a more important role since the late 1990's.Se ha estudiado la importancia relativa de la dinámica del pulso de inundación y el comportamiento del sistema megafan para las capturas del Sábalo (Prochilodus lineatus) en el río Pilcomayo. Las capturas del Sábalo puede explicarse fundamentalmente por los bajos caudales del río en los años anteriores, resultando en menores superficies de las zonas inundadas durante la temporada de lluvia y por lo tanto en una área menor de alimentación para los peces. La disminución del caudal del río y la declinación relativa de capturas de Sábalo en los años 1990 pueden estar relacionadas con el 90-95 evento de El Niño. En 2007, la captura de Sábalo fue comparable a las capturas antes del evento de "El Niño". La conectividad (continuidad) entre el río principal y las llanuras aluviales, que son influenciadas por los procesos de sedimentación, son también de gran importancia y muy probablemente juegan un papel muy importante desde finales de los años '90.

Experimental autoimmune myasthenia gravis (EAMG) can be induced in a large number of animal species by active immunization (AI) AChR, by passive transfer (PT) of anti-AChR antibodies, by autologous bone marrow transplantation and cyclosporin (BMT-Cy), or spontaneously. Depending on the model used, different immunological mechanisms are operational. In the AI model, the T cell is pivotal in directing the anti-AChR antibody production towards pathogenic, that is, cross-linking and complement-fixing antibodies. Injection of anti-AChR antibodies alone suffices to induce EAMG, excluding the role of specific cell-mediated immune responses in the effector phase of the disease. Aged animals are resistant to the induction of AI and PT EAMG. This resistance is localized at the postsynaptic membrane containing more AChR-anchoring proteins, including S-laminin and rapsyn in aged animals. In BMT-CyA EAMG, a dysregulation of the immune system in the absence of immunization is capable of inducing myasthenia. The role of these animal models in relation to pathogenesis and immunotherapy is discussed.

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