Loss of the Y chromosome in Philadelphia-positive cells predicts a poor response of chronic myeloid leukemia patients to imatinib mesylate therapy.

In chronic myeloid leukemia (CML), cytogenetic abnormalities found in addition to the t(9;22) translocation may impact the response to therapy. Loss of the Y chromosome is generally overlooked in this context, owing to its relatively frequent occurrence in healthy elderly patients. In this multicenter retrospective study, the outcome after imatinib treatment of 30 CML patients with karyotype showing Y chromosome loss (Y-) was compared to 30 Y+ control males diagnosed and treated at the same time in the same institutions. Y- patients had significantly delayed cytogenetic and molecular responses, lower event-free survival and shorter overall survival than Y+ patients. The negative impact of this abnormality was particularly marked when it occurred in a sub-clone (clonal evolution) rather than in all mitoses. These data indicate that loss of the Y chromosome should be taken into account in the prognostic evaluation of chronic myelogenous leukemia patients.

Aluminum L-glutamate complex in rat brain cortex: in vivo prevention of aluminum deposit by magnesium D-aspartate.

Our previous experiments in the rat showed that aluminum L-glutamate complex (Al L-Glu) crosses the blood-brain barrier and accumulates in selective brain areas and that Al salts may increase D-aspartic acid forms in living brain proteins, probably by inducing more thermodynamically stable structures than L isomers. As magnesium blocks NMDA receptors, D-aspartic acid was used in the present study in the form of magnesium salt to prevent the excitotoxicity of dicarboxylic amino acids. Effects on brain amino acids and Al cortex levels in mature rats were studied after chronic treatment with Al L-Glu or Na L-Glu alone or in association with magnesium D-aspartate (Mg D-Asp). Results demonstrate that treatment with Mg D-Asp induces a decrease in the Al concentration in brain cortex of Al L-Glu-treated rats. In aluminum-free treated controls, treatment with Mg D-Asp in association with Na L-Glu also induces a decrease in Al concentration in brain cortex. These data indicate that Mg D-Asp administration protects rat brain cortex from Al accumulation and suggest that this treatment may be useful in preventing brain Al intoxication.

Progressive alteration of neuronal dopamine transporter activity in a rat injured by an intranigral injection of MPP+.

MPTP or its metabolite MPP+ are used to produce a Parkinsonism syndrome in a variety of animal species. The present study describes the effects of intranigral MPP+ administration either at 10 or 40 microg on the neuronal dopamine transporter (DAT) activity measured in rat striatal synaptosomes at different times after lesion. The 40 microg MPP+ injection induced a maximal toxic effect on day 7. However, 10 microg MPP+ progressively inhibited DA uptake on the injured side. V(max) decreased in a time-dependent manner and the lowest value was observed on day 21 after lesion. At this time, the K(m) value began to increase and was continuously accentuated until day 45 as compared to the contralateral side. Treatments either with the antioxidant alpha-tocopherol acetate or the MAO inhibitor pargyline, given daily for 7 days after lesion, partially prevented the 40 microg MPP(+)-induced inhibition of DA uptake. Conversely, both treatments given daily for 21 days after lesion completely prevented the alteration of DAT activity in the ipsilateral striatum induced by 10 microg MPP+. The absence of protection when both treatments were stopped 2 weeks before DA uptake measurements indicated that free radicals and DA oxidized products were continuously accumulated and gradually affected the functionality of the DAT. These results demonstrate that a rat intranigral lesion with 10 microg MPP+ led to a progressive impairment of DAT activity.