A Panel of Oxidative Stress Markers in Parkinson's Disease.

BACKGROUND: Oxidative stress may be the cause or effect of several pathogenetic processes such as neurodegenerative diseases. The aim of this paper was to evaluate the diagnostic efficacy in Parkinson's disease (PKD) of a panel of oxidative stress markers selected from the many proposed by the most recent literature. METHODS: 23 molecules including both plasma and urinary oxidative markers such total radical oxygen species, homocysteine, biological antioxidant potential, glutathione, superoxide dismutase, uric acid, total bilirubin, iron, ferritin, coenzyme Q10, 3-nitrotyrosine, total lipoperoxides, 4-hydroxy-nonenal, and 8-hydroxy-deoxy-guanosine were determined both in PKD and aged control subjects. For each analyte and group, the respective reference intervals were determined. Statistical analysis was used to assess the existence of significant differences between intervals in order to indicate which markers can better characterize PKD and distinguish it from the control population. RESULTS: Some parameters were different in both groups when compared to those observed in younger subjects, supporting the hypothesis that aging is associated with an increase of oxidative stress. A peculiar increase of oxidative damage on nucleic acids was found in PKD, as well as a less efficient turnover of the DNA and an increase of protein peroxidation. CONCLUSIONS: Our results demonstrate that in PKD there is an increase of oxidative attack on nucleic acids and that the protein nitration is a characteristic phenomenon. These observations are in good agreement with the hypothesis that in PKD oxidative damage occurs that counter-regulatory systems attempt to balance, but inefficiently.

Plasma and urinary HPLC-ED determination of the ratio of 8-OHdG/2-dG in Parkinson's disease.

BACKGROUND: Oxidative stress may be directly or indirectly involved in the pathogenesis of Parkinson's disease (PD). 8-hydroxy-2'deoxyguanosine (8-OHdG) is the major product of DNA oxidative damage but its determination in plasma or urine may have controversial significance. The concentration of 8-OHdG not only depends on its oxidation rate but also on the efficacy of the DNA repairing systems. METHODS: We studied the ratio between 8-OHdG and 2-dG (the corresponding not hydroxylated base 2'-deoxyguanosine) in plasma and urine as a marker of oxydative stress in PD. This enabled the determination of the real DNA damage in terms of oxidation rate regardless of the efficacy of the DNA repairing mechanisms. RESULTS: We optimized two different analytical methods: one for 8-OHdG and the other for 2-dG, both based on a common preliminary solid-phase extraction step (SPE) followed by two different HPLC analytical separations with electrochemical detection (HPLC-ED). The reliability of these methods was confirmed by analysing plasma and urine samples collected in parkinsonian patients and in age-matched healthy control subjects. CONCLUSIONS: In urine samples, the measurement of 8-OHdG alone as well as the ratio 8-OHdG/2-dG were significantly different in healthy controls and PD patients. In plasma samples, only the ratio 8-OHdG/2-dG was significantly higher in PD compared to healthy controls showing that the ratio 8-OHdG/2-dG is a reliable diagnostic tool in studies on DNA oxydative damage.

Biochemistry of neuromodulation in primary headaches: focus on anomalies of tyrosine metabolism.

Recent studies have suggested that abnormalities of dopamine and trace amines (tyramine, octopamine, and synephrine), products of tyrosine metabolism, may constitute the metabolic events that predispose to the occurrence of cluster headache (CH) and migraine attacks. This hypothesis is supported by the following evidences: the discovery of trace amine associated receptors (TAARs), expressed on the olfactory epithelium, amigdala, hypothalamus, periacqueductal gray, and the biochemical anomalies of dopamine and trace amines. The possible effects of these biochemical abnormalities on TAARs and dopamine receptors, located in different areas of CNS, may explain the behaviour (restlessness, anxiety and, at times, hypersexuality) and the autonomic signs during the painful attacks of CH, and the premonitory symptoms of migraine crisis (thirst, craving, yawning, alteration of smell, depression etc.).

Treatment of aura: solving the puzzle.

Migraine with aura (MwA) sufferers, at times, need specific treatments. This is the case when the auras are frequent, prolonged and cause anxiety and distress. Abnormal release of glutamate, which may trigger auras, and abnormal platelet behaviour, which constitutes a possible predisposing factor to MwA, are possible targets for MwA-specific prophylactic therapy. Here we present results obtained using lamotrigine (two open trials), an agent known to inhibit glutamate release, and picotamide, an antiplatelet drug, in the prophylactic treatment of MwA sufferers. Lamotrigine significantly reduced the frequency of MwA attacks, and picotamide together with lamotrigine reduced the duration and/or the occurrence of auras. In comparison to lamotrigine, the therapy with picotamide may have some advantages such as the use of the therapeutic dose from the first day of treatment (lamotrigine needs one month or more to reach such a dose) and the possibility to prevent cerebral ischaemic events and migraine stroke, a rare but severe complication of MwA attacks.

Contributions of biochemistry to the pathogenesis of primary headaches.

We briefly summarise biochemical anomalies of serotonin, norepinephrine, glutamic and aspartic acids, the main neurotransmitters of inhibitory and excitatory neuronal circuitries, found in primary headaches and their relationship with pathogenesis of migraine and cluster headache (CH). In addition, the high levels of circulating tyramine, octopamine and synephrine (elusive amines), recently reported in both migraine types and CH, are discussed in relation to the other "classic" amines findings. In particular it is suggested how abnormal levels of elusive amines may participate in the pathophysiology of migraine and CH acting through their specific trace amine receptors and alpha and beta receptors. The possible hypothesis that emerges from the analysis of these biochemical findings is that an imbalance of systems, with opposite neurophysiological functions related to the pain and other yet unknown functions, may constitute the biochemical phenotype of migraine with and without aura, and CH.

Biogenic amines in the vomeronasal organ.

The vomeronasal organ of frog and mouse was investigated for the presence and content of serotonin and catecholamines by means of high-performance liquid chromatography. Measurable amounts of serotonin, adrenaline and noradrenaline were found in the vomeronasal organ of adult individuals of both species. The amine content varied with sex of adult frogs and mice and sexual maturity of mice. In preliminary experiments, acute exposure to male urine containing pheromone affected the amine content in the vomeronasal organ of adult female mice. These data suggest that functional sex dimorphism is present in the vomeronasal organ, and biochemical changes therein take place according to stage of sexual maturity. The role of biogenic amines in the vomeronasal organ deserves further study.

Treatment of parkinsonian conditions with a controlled-release form of levodopa--preliminary study.

Results obtained in 22 patients with Parkinson's disease in whom treatment with standard Madopar was replaced by Madopar HBS, a CR formulation of the same product, are presented. All the patients presented with dyskinesia and akinesia phenomena related in part to the L-dopa treatment and in part to the disease itself. In 20 patients replacement of the standard agent by HBS led to a distinct improvement in the clinical condition and a significant reduction of the 'on-off' phenomenon. However, with the new formulation the dosage had to be increased by 86% on average as compared with standard Madopar. In 6 of the 22 patients treatment with the HBS formulation has continued for over 6 months and is still giving very good results.