Methotrexate-Coated Complexes of Plasmid DNA and Polyethylenimine for Gene Delivery.

Folate receptors are overexpressed on the surface cancer cells. We successfully constructed a new gene delivery vector of methotrexate (MTX)-coated plasmid DNA-polyethylenimine (pDNA-PEI) complexes (PEI complexes) by electrostatic binding. The stable anionic nanoparticle was optimized at MTX charge ratios of 120 or more. pDNA-PEI-MTX complexes (MTX complexes) demonstrated gene expression efficiency as high as cationic pDNA-PEI complexes in the mouse melanoma cell line, B16-F10. The MTX complexes were taken up by the cell-specific uptake mechanisms via the folate receptor. MTX-coated complexes are useful as endocytosis ligands. The MTX120 complexes exhibited no blood aggregation. The transgene efficiency of MTX120 complexes in the liver and spleen after their intravenous administration was higher than that of PEI complexes. Therefore, MTX complexes are expected as a new gene vector in the future.

Therapeutic time window for musicokinetic therapy in a persistent vegetative state after severe brain damage.

OBJECTIVE: To determine the therapeutic time window in which musicokinetic therapy (MKT) could be of potential benefit for a persistent vegetative state (PVS), this study analysed the relationship between the timing of MKT and changes in PVS score following MKT. METHODS: Twenty-six patients who fulfilled the definition of PVS were treated consecutively by MKT employing a trampoline with live music performance for 3 months. The PVS score ranges from 0-30 and the condition which meets the definition of PVS is never scored greater than 20. RESULTS: As compared to patients with brain damage caused by trauma (n=12) or subarachnoid haemorrhage (SAH; n=9), those caused by other cerebrovascular accidents (n=3) or anoxic encephalopathy (n=2) appeared to demonstrate a much smaller improvement in their PVS score. When the patients caused by trauma or SAH were analysed in isolation, the effects of MKT were clearly better in those patients in whom the MKT was initiated within 6 months after brain damage. Among nine patients caused by trauma or SAH who had been in a PVS for more than 12 months, however, six (66.7%) demonstrated improvement of their PVS score by 5 or more and four (33.3%) reached a post-MKT score of greater than 20. CONCLUSIONS: These findings suggest that, contrary to the commonly held belief, the therapeutic time window for MKT is far greater than 6 months, insofar as patients with brain damage caused by trauma or SAH are concerned. Although the benefits of MKT were not proven directly, this inference is consistent with the hypothesis that MKT can induce an improvement in the clinical condition of PVS patients.