Selective degeneration of dopaminergic neurons by MPP(+) and its rescue by D2 autoreceptors in Drosophila primary culture.

Drosophila melanogaster is widely used to study genetic factors causing Parkinson's disease (PD) largely because of the use of sophisticated genetic approaches and the presence of a high conservation of gene sequence/function between Drosophila and mammals. However, in Drosophila, little has been done to study the environmental factors which cause over 90% of PD cases. We used Drosophila primary neuronal culture to study degenerative effects of a well-known PD toxin MPP(+) . Dopaminergic (DA) neurons were selectively degenerated by MPP(+) , whereas cholinergic and GABAergic neurons were not affected. This DA neuronal loss was because of post-mitotic degeneration, not by inhibition of DA neuronal differentiation. We also found that MPP(+) -mediated neurodegeneration was rescued by D2 agonists quinpirole and bromocriptine. This rescue was through activation of Drosophila D2 receptor DD2R, as D2 agonists failed to rescue MPP(+) -toxicity in neuronal cultures prepared from both a DD2R deficiency line and a transgenic line pan-neuronally expressing DD2R RNAi. Furthermore, DD2R autoreceptors in DA neurons played a critical role in the rescue. When DD2R RNAi was expressed only in DA neurons, MPP(+) toxicity was not rescued by D2 agonists. Our study also showed that rescue of DA neurodegeneration by Drosophila DD2R activation was mediated through suppression of action potentials in DA neurons.

Integrated Oxygenator FX05.

In recent years, there has been a trend to incorporate arterial filters into cardiopulmonary bypass (CPB) oxygenators. The FX oxygenators are the first examples of integrating a filter around the fibers of the oxygenator. To assess the efficacy of the FX05 oxygenator, in comparison with our existing CPB setup (RX05 oxygenator + arterial filter), we randomly assigned 40 patients undergoing CPB, with calculated flows <1.5 L/min, to FX05 or RX05 + arterial filter (19 FX and 21 RX). Embolic load was assessed using the emboli detection and classification quantifier, with sensors placed prefilter and postfilter/oxygenator at identical distances for both devices. A total of 6,270 FX readings and 6,183 RX readings were obtained. Because of the extremely skewed nature of the data, the prefilter embolic volumes were divided into deciles, and each decile was analyzed separately. Our results show that the devices perform similarly; both filter out a high percentage of the prefilter embolic load. Our data support that in the clinical setting, the FX05 is as effective at removing emboli as the RX05 with an arterial filter (CXAF02) which, in conjunction with the prime volume reduction and circuit simplification, has warranted our conversion to the FX series of oxygenators.