Selegiline increases heme oxygenase-1 expression and the cytotoxicity produced by dopamine treatment of neuroblastoma SK-N-SH cells

Increased dopamine catabolism may be associated with oxidative stress and neuronal cell death in Parkinson's disease. The present study was carried out to examine the effect of dopamine on the expression of heme oxygenase-1 and -2 (HO-1 and HO-2) in human neuroblastomas (SK-N-SH cell line) and the effects of selegiline and antioxidants on this expression. Cells were kept with close control of pH and were incubated with varying concentrations of dopamine (0.1-100 µM) for 24 h. HO-1 and HO-2 cDNA probes were prepared by reverse transcription-polymerase chain reaction amplification. The mRNA expression of HO-1 and HO-2 was measured by Northern blot analysis. The levels of HO-1 mRNA increased after dopamine treatment, in a dose-dependent manner, in all cell lines studied, whereas levels of the two HO-2 transcripts did not. The HO-1 and HO-2 protein expression was analyzed by Western blotting. HO-1 protein was undetectable in untreated SK-N-SH cells and increased after treatment with dopamine. In contrast, the HO-2 protein (36 kDa) was detected in untreated cells and the levels did not change as a result of treatment. alpha-Tocopherol (10-100 µM) and ascorbic acid (100 µM) did not attenuate the effects of dopamine. Selegiline (10 µM) produced significant increase (P < 0.01) in the induction of HO-1 by dopamine (more than six times the control values). The increased expression of HO-1 following dopamine treatment indicates that dopamine produces oxidative stress in this cell line.

Investigation by Parkinson’s Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson’s disease: further results of randomised trial and confidential inquiry

Objective: To determine whether the excess mortality observed in patients who received both levodopa and selegiline in a randomised trial could be explained by revised diagnosis of Parkinson’s disease, autonomic or cardiovascular effects, more rapid disease progression, or drug interactions.

Mortality in people taking selegiline: observational study

Objective: To evaluate mortality among patients with Parkinson’s disease receiving different treatment.

Death following acute poisoning by moclobemide

A fatality due to ingestion of a reversible inhibitor of monoamine-oxidase A (MAO-A) is reported. Moclobemide is generally considered as a safe drug far less toxic than tricyclic anti-depressants. However, severe intoxications may result from interactions with other drugs and food such as selective serotonin reuptake inhibitors (SSRIs), anti-Parkinsonians of the MAOI-type (e.g. selegiline) or tyramine from ripe cheese or other sources. In the present case, high levels of moclobemide were measured in peripheral blood exceeding toxic values reported so far in the scientific literature. The body fluid concentrations of moclobemide were of 498 mg/l in peripheral whole blood, 96.3 mg/l in urine while an amount of approximately 33 g could be recovered from gastric contents. The other xenobiotics were considered of little toxicological relevance. The victim (male, 48-year-old) had a past history of depression and committed one suicide attempt 2 years before death. Autopsy revealed no evidence of significant natural disease or injury. It was concluded that the manner of death was suicide and that the unique cause of death was massive ingestion of moclobemide.

Early impairment of cognitive functions in Parkinson's disease

Background: Impairment in non-motor functions such as disturbances of some executive functions are also common events in Parkinson's disease patients. Objective: To verify the performance of Parkinson's disease patients in activities requiring visuoconstructive and visuospatial skills. Method: Thirty elderly patients with mild or moderate stages of Parkinson's disease were studied. The assessment of the clinical condition was based on the unified Parkinson's disease rating scale (56.28; SD=33.48), Hoehn and Yahr (2.2; SD=0.83), Schwab and England (78.93%), clock drawing test (7.36; SD=2.51), and mini-mental state examination (26.48; SD=10.11). Pearson's correlation and stepwise multiple regression were used for statistical analyses. Results: The patients presented deterioration in visuospatial and visuoconstructive skills. Conclusion: The clock drawing test proved to be a useful predictive tool for identifying early cognitive impairment in these individuals.

Síndrome da disfunção cognitiva em cães

Cognitive dysfunction syndrome (CDS) is a progressive degenerative disorder of older dogs, characterized by a decline in cognitive function. The main clinical signs consistent with CDS are: disorientation, changes in socio-environmental interaction, sleep-wake cycle disturbance, changes in hygiene habits, urinate and/or defecate in unusual places, decreased physical activity, anxiety and eating disorders. There are no specific diagnostic tests for this condition in vivo, but alterations in neurological examination, cognitive tests and magnetic resonance imaging can be observed. The diagnosis is confirmed by histopathological examination of brain tissue. Diets rich in antioxidants, environmental enrichment with exercise and the use of selegiline and L-deprenyl have been recommended for the treatment of CDS.

Gallium-transferrin binding in treated and untreated Parkinson's disease

The binding of gallium (Ga) to transferrin (Tf) was studied in plasma from control patients, in patients with untreated Parkinson's disease (PD) and in patients with PD treated either with levodopa (L-dopa) alone or in combination with selegiline. Mean percentage Ga-Tf binding was significantly reduced in untreated and treated PD compared with controls. Binding, however, was significantly greater in treated than in untreated patients. There was no difference in binding between patients treated with L-dopa alone and those treated with L-dopa and selegiline. The data support the hypothesis that oxidation reactions may be of pathogenic significance in PD.