To test the efficacy and safety of creatine (Cr) monohydrate in mitochondrial diseases, 16 patients with chronic progressive external ophthalmoplegia or mitochondrial myopathy were randomized in a crossover design to receive double-blind placebo or 20 g Cr/day for 4 weeks. Cr was well tolerated, but there were no significant effects with regard to exercise performance, eye movements, or activities of daily life. The power of this pilot study was limited and future multicenter trials are needed.

Previous studies have suggested that target-derived nerve growth factor (NGF) is essential for the survival of cholinergic basal forebrain neurons. Thus, axotomy of septohippocampal neurons in adult rats resulting in the withdrawal of target-derived NGF caused a dramatic loss of choline acetyltransferase (ChAT)-immunoreactive neurons in the medial septum-diagonal band complex. We have recently shown that this loss of immunolabelled neurons does not indicate cell death, since many septohippocampal cholinergic neurons recover their immunoreactivity for ChAT after a long survival time despite disconnection from target-derived neurotrophins. One possibility would be that these surviving ChAT-immunoreactive neurons have gained access to other, probably local, NGF sources. Here we provide evidence that the recovery of ChAT immunoreactivity after axotomy is not accompanied by a similar recovery of NGF receptor expression in these neurons. In situ hybridization for p75NTR mRNA and trkA mRNA 6 months after bilateral fimbria-fornix transection revealed a substantial loss of labelled cells. In addition, there was a persisting loss of p75NTR-immunoreactive and NGF-immunoreactive medial septal neurons. Cholinergic neurons in controls did not express NGF mRNA, but were heavily immunostained for NGF protein due to receptor-mediated uptake. These data suggest that at least some cholinergic septohippocampal neurons re-express ChAT either independently of NGF or with a reduced need for NGF.

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Roughest (Rst) is a cell adhesion molecule of the immunoglobulin superfamily with pleiotropic functions during the development of Drosophila melanogaster. It has been shown to be involved in cell sorting before apoptosis in the developing compound eye, in fusion processes of embryonic muscle development and in axonal pathfinding. In accordance with its multiple functions, the rst gene shows a dynamic expression pattern throughout the development of Drosophila. In order to understand the transcriptional regulation of rst expression we have identified rst cis regulatory sequences in an enhancer detection screen. By dissection of the identified rst cis regulatory sequences we identified several distinct rst regulatory modules. Among others these include elements for expression in interommatidial cells of the pupal eye disc at a time when apoptotic decisions are made in these cells and elements for expression in the embryonic mesoderm. The expression of rst in the embryonic mesoderm is regulated by at least two separate modules.

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