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    Is neuromelanin changed in Parkinson's disease? Investigations by magnetic spectroscopies

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    Human mesencephalic neuromelanin (NM) is characterized by an irregular, undefined structure, making its characterization by usual physico-chemical methodologies quite difficult. NM isolated from controls and from Parkinson's Disease (PD) patients was compared by high-resolution solid-state nuclear magnetic resonance (NMR). The pigment from PD patients appeared to be mainly composed of highly cross-linked, protease-resistant lipo-proteic material, with disappearance of melanin NMR resonances, suggesting melanin breakout due to oxidative stress conditions. Moreover, alpha-synuclein was detected in NM of PD patients and controls after cleavage of the melanin backbone under solubilizing conditions. NM stores iron ions as oxyhydroxide iron clusters containing thousands of iron atoms. Electron Paramagnetic Resonance (EPR) investigations and magnetic susceptibility measurements confirmed the occurrence of magnetic coupling among iron atoms, whereas in synthetic melanin the occurrence of isolated Fe3+ ions was evident. NM from PD patients showed a lower total magnetization, possibly suggesting a progressive Fe migration from its storage environment (i.e., NM) to the cytosol

    Brain stem auditory evoked potentials and blink reflexes in quiescent multiple sclerosis

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    Brain stem auditory evoked potentials (BAEP) and blink reflexes (BR) were studied in 25 patients with multiple sclerosis (MS), the diagnosis being definite according to McAlpine's criteria, in the quiescent phase, without signs of brain stem involvement. BAEP abnormalities were found in 64% of the cases and BR abnormalities in 60%. A good correlation between the two tests was found in most patients. The abnormalities consisted of delayed latencies and/or high intraindividual variability in shape and latency of BAEP and BR components. It seems that demyelination of brain stem pathways results not only in conduction slowing but also in more serious dysfunction of the generators of the evoked components

    Residual substantia nigra neuromelanin in Parkinson's disease is cross-linked to alpha-synuclein

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    The pigmentation of substantia nigra pars compacta dopaminergic neurons is due to the presence of neuromelanin, an irregular macromolecular pigment belonging to the family of melanins. Depletion of neuromelanin in Parkinson's disease is typically indicated by loss of brown color in this area. Unlike that from controls, the pigment extracted from substantia nigra of parkinsonian patients seems to be mainly composed by highly cross-linked, protease-resistant proteic material and the neuromelanin macromolecule appears to be a minor presence. In the present paper we describe the isolation by SDS-PAGE of this proteic component after cleavage of the melanin backbone under solubilizing conditions. A single band is observed, which has been identified as α-synuclein by western blotting. As expected, the same process performed on a control specimen did not show occurrence of any major proteic component. Nevertheless, extraction from a 91 years old control with Lewy bodies displayed minor α-synuclein immunoreactive aggregates, whereas inclusion of free α-synuclein was not observed at all. Results reported here support the view that α-synuclein accumulates within substantia nigra neurons and is entrapped in pigment granules during neuromelanin biosynthesis, i.e. before the melanin depletion characteristic of Parkinson's disease starts

    Acute neurologic complications of hemodialysis. Study of 14,000 hemodialyses in 103 patients with chronic renal failure

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    We have examined and subjected to statistical analysis the transient acute neurological complications arising in the course of hemodialysis in 103 patients with chronic renal failure (13,969 hemodialysis sessions). Our data show that such complications are multiform. Some of the symptoms are aspecific: headache, nausea and/or vomiting, muscle cramps. We have found these symptoms in over 96% of patients, often combined with extraneurological symptoms and phenomena, such as cardiocirculatory shock or increased blood pressure. The other symptoms denote real cerebral impairment: convulsions, consciousness disturbances, psychomotor agitation. They are present in 36% of the patients, but only 10.5% of the patients show a combination of at least two symptoms. In these patients the so-called "Disequilibrium syndrome" is present: its percentage in our case-series is similar to that reported in literature
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