Membrane metallo-endopeptidase is dispensable for repair after nerve injury.

Membrane metallo-endopeptidase (MME), also known as neprilysin (NEP), has been of interest for its role in neurodegeneration and pain due to its ability to degrade ß-amyloid and substance-P, respectively. In addition to its role in the central nervous system, MME has been reported to be expressed in the peripheral system, specifically in the inner and outer border of myelinating fibers, in the Schmidt-Lantermann cleft and in the paranodes. Recently, mutations of this gene have been associated with Charcot-Marie-Tooth Type 2 (CMT2). Peripheral nerve morphometry in mice lacking MME previously showed minor abnormalities in aged animals in comparison to CMT2 patients. We found that MME expression was dysregulated after nerve injury in a Neuregulin-1 dependent fashion. We therefore explored the hypothesis that MME may have a role in remyelination. In the naïve state in adulthood we did not find any impairment in myelination in MME KO mice. After nerve injury the morphological outcome in MME KO mice was indistinguishable from WT littermates in terms of axon regeneration and remyelination. We did not find any difference in functional motor recovery. There was a significant difference in sensory function, with MME KO mice starting to recover response to mechanical stimuli earlier than WT. The epidermal reinnnervation, however, was unchanged and this altered sensitivity may relate to its known function in cleaving the peptide substance-P, known to sensitise nociceptors. In conclusion, although MME expression is dysregulated after nerve injury in a NRG1-dependent manner this gene is dispensable for axon regeneration and remyelination after injury.

Dispersion of daidzein with polyvinylpyrrolidone effects on dissolution rate and bioavailability.

OBJECTIVE: To study on the dispersion of daidzein with polyvinylpyrrolidone (PVP) and its effects on the aqueous solubility, dissolution rate and bioavailability of daidzein. METHODS: The solid dispersion of daidzein at various daidzein to PVP ratios were obtained via the solvent evaporation method and characterized by differential scanning calorimetry and fourier transform infrared spectroscopy. In addition,the bioavailability of free daidzein as well as its solid dispersion were studied in mice. RESULTS: It was found that the daidzein solubility in the solid dispersion form was 8 times greater than that of the free drug in water at (37 +/- 0.1) degrees C. Meanwhile,the daidzein dissolution rate was significantly increased after dispersing with PVP. The results of the bioavailability showed that both Cmax and AUC value of daidzein solid dispersion were about 5 times larger than unprocessed daidzein, implying that the rate-limiting step in daidzein absorption may be the dissolution process. CONCLUSIONS: The results in this work reveal the substantial advantages of adopting polyvinylpyrrolidone dispersion as an oral preparation to improve daidzein bioavailability.