Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis.

Impaired function/differentiation of progenitor cells might provide an explanation for the limited remyelination observed in the majority of chronic multiple sclerosis lesions. Here, we establish that in the normal adult human CNS, the transcription factors Nkx2.2 and Olig2 are strongly expressed in progenitor cells while mature oligodendrocytes are characterized by low levels of Olig2 or Nkx2.2. In vitro studies confirmed the expression of Olig2 in oligodendroglial progenitor cells and mature oligodendrocytes while astrocytes, microglial cells and neurons were negative for Olig2. In early multiple sclerosis lesions, we found Olig2-positive progenitor cells throughout all lesion stages and in periplaque white matter (PPWM). The number of progenitors in PPWM was significantly increased compared with the white matter from controls. In chronic multiple sclerosis lesions progenitor cells were still present, however, in significantly lower numbers than in early multiple sclerosis lesions. A subpopulation of progenitor cells in early multiple sclerosis lesions and PPWM but not in control cases co-expressed NogoA, a marker of mature oligodendrocytes. The co-expression of these two markers suggested that these cells were maturing oligodendrocytes recently recruited from the progenitor pool. In contrast, in chronic multiple sclerosis lesions maturing progenitors were only rarely present. In summary, we provide evidence that a differentiation block of oligodendroglial progenitors is a major determinant of remyelination failure in chronic multiple sclerosis lesions.

Catalytic kinetic determination of ultratrace amounts of nitrite with detection by linear scan voltammetry at a DME.

Nitrite has a very strong catalytic effect on the bromate oxidation of Methyl Orange in dilute sulphuric acid medium. The oxidation product of methyl orange exhibits a well derivative voltammetric wave at -0.41 V vs. SCE in sodium hydroxide medium. The linear scan voltammetric behaviour for the product at a DME has been studied, and it was selected as indicator component for the indicator reaction. Based on these studies, a novel and highly sensitive and selective catalytic reaction-voltammetric method for nitrite is proposed. A detection limit of 2 x 10(-9)M and calibration graph from 4 x 10(-7) to 4 x 10(-7)M nitrite are obtained. Nitrite in water samples was determined by this method, with satisfactory results.