Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

32 patients, suffering from Parkinson's disease, had internal fixation of femoral neck fractures. In 24 displaced fractures, 6 nonunions and 3 segmental collapses were seen; and in 8 undisplaced fractures, 1 case of segmental collapse was diagnosed. Healing complications were thus seen in one third. Total hip replacement for healing complication was performed in 3 of 32 patients. 9 patients died within 2 years. No difference in the rate of healing or mortality was detected compared with hip fracture patients without Parkinson's disease. Our study does not support primary arthroplasty for femoral neck fracture in patients with Parkinson's disease.
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PMID:Internal fixation of femoral neck fractures in Parkinson's disease. 32 patients followed for 2 years. 262 88

Forty patients with severe Parkinson's disease (23 men, 17 women) who had been treated for six years with L-dopa-decarboxylase inhibitor, were part of a placebo-controlled double-blind trial to test the effectiveness of bromocriptin. In all patients the effectiveness of L-dopa had been decreasing, 34 patients had L-dopa-induced dyskinesias, 35 "on-off" symptoms. Bromocriptin dosage was gradually increased to a total dose of 30 - 40 mg daily. This led to a 25% reduction in L-dopa requirements. The symptoms of Parkinson's disease were favourably influenced, with rigor, tremor and also walking disturbances responding better than bradykinesia of the hands. At the same time, there was a marked prolongation of the periods of good mobility ("on" time) from 7 to 10.8 hours without influence on other "on-off" symptoms such as paradoxical akinesia. Two patients had to be excluded from the trial because the treatment caused side effects (orthostatic hypotension, exogenous psychotic symptoms). Other side effects, such as nausea and mild forms of collapse, could be controlled by drugs.
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PMID:[Bromocriptin in the treatment of progressive stages of Parkinson's disease (author's transl)]. 679 66

The oxidative stress theory, the mitochondrial (mt) hypothesis, and the apoptosis hypothesis are proposed as the cause of neuronal cell death in Parkinson's disease (PD). However, the direct link between them has remained unknown. Recently, the mt control of nuclear apoptosis is documented that collapse of mt transmembrane potential due to energy crisis leads to release of apoptotic protease activating-factors into cytosol and subsequently nuclear DNA fragmentation. However, an endogenous factor responsible for the energy crisis under physiological conditions is missing. Here we report the missing factor as that mtDNA in the striatum of a parkinsonian patient fragments into 134 types of deleted pieces, being detected by the total detection system for mtDNA deletion. The system has documented that the mtDNA is extremely susceptible to hydroxyl radical damage, hence to oxidative stress, enough to cause the cellular energy crisis. The extensive fragility of mtDNA in brain stem could link the oxidative stress up with the apoptotic neuronal cell-death of PD.
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PMID:Fragile mitochondrial DNA: the missing link in the apoptotic neuronal cell death in Parkinson's disease. 919 54

Hot, humid conditions in tropical regions generally rule out any risk of hypothermia due to cold exposure. In this report, we describe a case of severe hypothermia involving a core temperature of 26 degrees C in a 61-year-old man living in Gabon. Parkinson's disease and chronic alcoholism may have been predisposing factors. The patient was treated by active and passive rewarming (intestinal irrigation with warm water). Sudden circulatory collapse occurred during treatment but the final outcome was successful. This case demonstrates that hypothermia can occur in tropical areas. Emergency diagnosis may be difficult in Black Africa where adequate temperature monitoring equipment is rarely available. Standard mercury thermometers do not allow measurement of temperatures lower than 34 degrees C. African physicians should be aware of the possibility of potentially life-threatening hypothermia and be prepared to initiate proper treatment and surveillance in intensive care.
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PMID:[Severe hypothermia in a tropical setting]. 979 96

The cause of dopaminergic cell death in Parkinson's disease (PD) remains unknown, but may involve oxidative stress and mitochondrial complex I deficiency. Opening of the permeability transition pore and disruption of the mitochondrial transmembrane potential are known to be common events in the apoptotic pathway. Cyclosporin A and its non-immunosuppressant analogue, N-methyl-4-valine cyclosporin inhibit the opening of the mitochondrial megachannel. Complex I inhibitors, including MPP+, are known to induce both apoptosis in cell culture and parkinsonism in man and other primates. The present study using propidium iodide and FITC-TUNEL staining to identify apoptotic cells, demonstrates that rotenone, MPP+ and tetrahydroisoquinoline induce apoptosis in PC12 cells. Apoptosis induced by these agents was decreased by cyclosporin A and N-methyl-4-valine cyclosporin. Thus, apoptosis induced by inhibitors of mitochondrial complex I is probably mediated by permeability pore opening and collapse of the mitochondrial membrane potential. This observation may allow the development of novel neuroprotective strategies in disorders that may involve mitochondrial dysfunction and apoptotic cell death.
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PMID:Cyclosporin inhibition of apoptosis induced by mitochondrial complex I toxins. 979 6

Oxidative stress is thought to contribute to dopaminergic cell death in Parkinson's disease (PD). The neurotoxin 6-hydroxydopamine (6-OHDA), which is easily oxidized to reactive oxygen species (ROS), appears to induce neuronal death by a free radical-mediated mechanism, whereas the involvement of free radicals in N-methyl-4-phenylpyridinium (MPP+) toxicity is less clear. Using free radical-sensitive fluorophores and vital dyes with post hoc identification of tyrosine hydroxylase-positive neurons, we monitored markers of apoptosis and the production of ROS in dopaminergic neurons treated with either 6-OHDA or MPP+. Annexin-V staining suggested that 6-OHDA but not MPP+-mediated cell death was apoptotic. In accordance with this assignment, the general caspase inhibitor Boc-(Asp)-fluoromethylketone only blocked 6-OHDA neurotoxicity. Both toxins exhibited an early, sustained rise in ROS, although only 6-OHDA induced a collapse in mitochondrial membrane potential temporally related to the increase in ROS. Recently, derivatives of buckminsterfullerene (C60) molecules have been shown to act as potent antioxidants in several models of oxidative stress (Dugan et al., 1997). Significant, dose-dependent levels of protection were also seen in these in vitro models of PD using the C3 carboxyfullerene derivative. Specifically, C3 was fully protective in the 6-OHDA paradigm, whereas it only partially rescued dopaminergic neurons from MPP+-induced cell death. In either model, it was more effective than glial-derived neurotrophic factor. These data suggest that cell death in response to 6-OHDA and MPP+ may progress through different mechanisms, which can be partially or entirely saved by carboxyfullerenes.
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PMID:Distinct mechanisms underlie neurotoxin-mediated cell death in cultured dopaminergic neurons. 995 6

A genetic defect in complex I of the mitochondrial electron transport chain (ETC) is implicated in the etiology of Parkinson's disease (PD), and has been studied in hybrid mitochondrial transgene cells based on the SH-SY5Y neuroblastoma. We sought to characterize further the mechanisms and time course of cell death in cultures of human SH-SY5Y neuroblastoma cells exposed to the ETC complex I inhibitor methylpyridinium ion (MPP+). We verify previous reports that apoptosis occurs after MPP+ exposure in SH-SY5Y cells. Nuclear pyknosis, the end stage of apoptosis, is evident after 18-hr exposure to 5 mM MPP+ and reversible until 10 hr, providing a temporal window within which to look for molecular and physiological correlates of MPP+-induced apoptosis. We then looked for mitochondrial correlates of MPP+ induced apoptosis in SH-SY5Y cells. Using flow cytometry, we found that MPP+ -induced increased reactive oxygen species (ROS) and lactate production consistent with inhibition of the ETC. Rho(o) cells, lacking a functional ETC, showed no ROS production, compensatory lactate production or apoptosis after exposure to MPP+. Finally, we show a collapse in ROS production and mitochondrial potential that is temporally correlated with irreversibility of MPP+ -induced apoptosis.
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PMID:Characterization and time course of MPP+ -induced apoptosis in human SH-SY5Y neuroblastoma cells. 1008 84

Mitochondrial membrane potential (delta psi(m)) was determined in intact isolated nerve terminals using the membrane potential-sensitive probe JC-1. Oxidative stress induced by H2O2 (0.1-1 mM) caused only a minor decrease in delta psi(m). When complex I of the respiratory chain was inhibited by rotenone (2 microM), delta psi(m) was unaltered, but on subsequent addition of H2O2, delta psi(m) started to decrease and collapsed during incubation with 0.5 mM H2O2 for 12 min. The ATP level and [ATP]/[ADP] ratio were greatly reduced in the simultaneous presence of rotenone and H2O2. H2O2 also induced a marked reduction in delta psi(m) when added after oligomycin (10 microM), an inhibitor of F0F1-ATPase. H2O2 (0.1 or 0.5 mM) inhibited alpha-ketoglutarate dehydrogenase and decreased the steady-state NAD(P)H level in nerve terminals. It is concluded that there are at least two factors that determine delta psi(m) in the presence of H2O2: (a) The NADH level reduced owing to inhibition of alpha-ketoglutarate dehydrogenase is insufficient to ensure an optimal rate of respiration, which is reflected in a fall of delta psi(m) when the F0F1-ATPase is not functional. (b) The greatly reduced ATP level in the presence of rotenone and H2O2 prevents maintenance of delta psi(m) by F0F1-ATPase. The results indicate that to maintain delta psi(m) in the nerve terminal during H2O2-induced oxidative stress, both complex I and F0F1-ATPase must be functional. Collapse of delta psi(m) could be a critical event in neuronal injury in ischemia or Parkinson's disease when H2O2 is generated in excess and complex I of the respiratory chain is simultaneously impaired.
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PMID:Depolarization of in situ mitochondria due to hydrogen peroxide-induced oxidative stress in nerve terminals: inhibition of alpha-ketoglutarate dehydrogenase. 1038 74

The precursor of the non-Abeta-component of Alzheimer's disease (AD) amyloid (NACP, alpha-synuclein) aggregates into insoluble filaments of Lewy bodies (LBs) in Parkinson's disease (PD) and dementia with LBs (DLB). The microtubule-associated protein tau is an integral component of filaments of neurofibrillary tangles (NFTs). NFTs are occasionally found in brains of PD and DLB; however, the presence of NFTs or tau-epitopes within LB-containing neurons is rare. Double-immunofluorescence study and peroxidase-immunohistochemical study in serial sections, performed to examine the co-localization of tau- and NACP-epitopes in the brainstem of PD and DLB, demonstrated that four different epitopes of tau including phosphorylation-dependent and independent ones were present in a minority of LBs, but more often than previously considered. A tau (tau2)-epitope was localized to filaments in the outer layers of brainstem-type LBs by immunoelectron microscopy. Therefore, we conclude that tau is incorporated into filaments in certain LBs. Extensive investigation has enabled us to classify this co-localization into four types: type 1, LBs with ring-shaped tau-immunoreactivity; type 2, LBs surrounded by NFTs; type 3, NACP- and tau-immunoreactive filamentous and granular masses; and type 4, NACP- and tau-immunoreactive dystrophic neurites. This study raises a new question whether aggregation and hyperphosphorylation of tau in PD and DLB are triggered by the collapse of intraneuronal organization of microtubules due to NACP-filament aggregation in neuronal perikarya and axons.
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PMID:Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. 1052 10

In Parkinson's disease, apoptosis was proposed to cause cell death in nigral dopamine neurons. An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, stereo-selectively induced apoptosis in human neuroblastoma SH-SY5Y cells. In this paper the intracellular mechanism of apoptosis was studied using N-methyl(R)salsolinol, 6-hydroxydopamine and peroxynitrite as inducers of apoptosis. Apoptotic cascade was initiated by opening of mitochondrial permeability transition pore, as shown by collapse of mitochondrial membrane potential, deltapsim. Apoptosis was executed by caspase 3 activation, followed by DNA fragmentation, which was antagonized by overexpressed Bcl-2. Propargylamines were found to protect the cells from apoptosis, and rasagiline, a selective irreversible inhibitor of type B monoamine oxidase was the most potent to prevent the cell death. Rasagiline preserved deltapsim, which was proved also in isolated mitochondria, and rasagiline completely suppressed the activation of caspases and DNA fragmentation. These results suggest that mitochondria regulate apoptotic process, which may be a target of neuroprotection by rasagiline.
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PMID:Neurotoxins induce apoptosis in dopamine neurons: protection by N-propargylamine-1(R)- and (S)-aminoindan, rasagiline and TV1022. 1120 38


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