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

In recent muscle metabolic studies, patients with moderate upper motor neuron lesions showed marked difficulty in performing an equal submaximal work load (bilaterally) in two-legged exercise. For a better evaluation of these patients, studies were performed on each leg separately. Six patients with Parkinson's disease and six with moderate hemiparesis were studied. During one-legged submaximal and maximal exercise heart rate, oxygen uptake, and blood lactate were determined. Maximal voluntary contraction in knee and ankle flexion and extension for each leg was measured. Succinate dehydrogenase (SDH) activity in the thigh muscles was determined. During submaximal exercise, oxygen uptake, heart rate and blood lactate increased more in the paretic leg of hemiparetic patients and in the more affected leg of the Parkinson patients. In hemiparetic patients maximal voluntary contraction of flexors and extensors of the knee was significantly reduced in the paretic leg but was reduced even in the nonparetic knee flexors. SDH activity was very low in both legs in all patients and lowest in the paretic and more affected leg, respectively. It is concluded that (a) the general muscle inactivity per se, secondary to the neurological disorder, may lead to a reduced work capacity; (b) the increased heart rate and blood lactate level seem to be correlated to the relative exercise level of each leg; and (c) in patients with impaired muscle function of one or both legs, evaluation of each leg separately with regard to work capacity and muscle metabolism is of value.
 ...
PMID:Work capacity, muscle strength and SDH activity in both legs of hemiparetic patients and patients with Parkinson's disease. 119 56

Oxygen free radicals (OFRs) have been suggested in the pathogenesis of Parkinson's disease (PD). These free radicals exert their cytotoxic effect by peroxidation of lipid membrane resulting in the formation of malondialdehyde (MDA). Polymorphonuclear (PMN) leukocyte is one of the major sources of OFR. However, the oxygen free radical producing activity of PMN leukocytes in patients with PD is not known. We therefore studied the oxygen free radical producing activity of polymorphonuclear leukocytes and MDA levels in the serum of healthy subjects and in patients with Parkinson's disease. The oxygen free radical producing activity of PMN leukocytes in blood and the MDA content in serum were significantly higher in patients with Parkinson's disease than in healthy subjects. These results indicate a possible role of oxygen free radicals in the pathogenesis of Parkinson's disease.
 ...
PMID:Oxygen free radical producing activity of polymorphonuclear leukocytes in patients with Parkinson's disease. 132 91

1-Methyl-4-phenyl-2,3-dihydropyridinium (MPDP+), a metabolic product of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been shown to generate superoxide radicals during its autoxidation process. The generation of superoxide radicals was detected as a 5,5-dimethyl-1-pyrroline-N-oxide (DMPO).O2- spin adduct by spin trapping in combination with EPR techniques. The rate of formation of spin adduct was dependent not only on the concentrations of MPDP+ and oxygen but also on the pH of the system. Superoxide dismutase inhibited the spin adduct formation in a dose-dependent manner. The ability of DMPO to trap superoxide radicals, generated during the autoxidation of MPDP+, and of superoxide dismutase to effectively compete with this reaction for the available O2-, has been used as a convenient competition reaction to quantitatively determine various kinetic parameters. Thus, using this technique the rate constant for scavenging of superoxide radical by superoxide dismutase was found to be 7.56 x 10(9) M-1 s-1. The maximum rate of superoxide generation at a fixed spin trap concentration using different amounts of MPDP+ was found to be 4.48 x 10(-10) M s-1. The rate constant (K1) for MPDP+ making superoxide radical was found to be 3.97 x 10(-6) s-1. The secondary order rate constant (KDMPO) for DMPO-trapping superoxide radicals was found to be 10.2 M-1 s-1. The lifetime of superoxide radical at pH 10.0 was calculated to be 1.25 s. These values are in close agreement to the published values obtained using different experimental techniques. These results indicate that superoxide radicals are produced during spontaneous oxidation of MPDP+ and that EPR spin trapping can be used to determine the rate constants and lifetime of free radicals generated in aqueous solutions. It appears likely that the nigrostriatal toxicity of MPTP/MPDP+ leading to Parkinson's disease may largely be due to the reactivity of these radicals.
 ...
PMID:EPR kinetic studies of superoxide radicals generated during the autoxidation of 1-methyl-4-phenyl-2,3-dihydropyridinium, a bioactivated intermediate of parkinsonian-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 133 Oct 93

Oxygen free radicals and other oxygen derived species (Superoxide, O2-; Hydroperoxide, HOO; Singlet oxygen, 1O2-; Hydroxyl radical, OH; and Hydrogen peroxide, H2O2) including lipid peroxides have been suggested as important causative agents of aging and several human diseases, including cancer, multiple sclerosis, Parkinson's disease, autoimmune disease, ischemia, anemia, senile dementia, asbestosis and in thalassemia. This paper aims to communicate some of the theories and rationales in aging process and thalassemia.
 ...
PMID:Role of lipid peroxidation and antioxidants in aging process and thalassemia. 134 11

Radicals are species containing one or more unpaired electrons, such as nitric oxide (NO.). The oxygen radical superoxide (O2.-) and the nonradical hydrogen peroxide (H2O2) are produced during normal metabolism and perform several useful functions. Excessive production of O2.- and H2O2 can result in tissue damage, which often involves generation of highly reactive hydroxyl radical (.OH) and other oxidants in the presence of "catalytic" iron or copper ions. An important form of antioxidant defense is the storage and transport of iron and copper ions in forms that will not catalyze formation of reactive radicals. Tissue injury, e.g., by ischemia or trauma, can cause increased metal ion availability and accelerate free radical reactions. This may be especially important in the brain because areas of this organ are rich in iron and CSF cannot bind released iron ions. Oxidative stress on nervous tissue can produce damage by several interacting mechanisms, including increases in intracellular free Ca2+ and, possibly, release of excitatory amino acids. Recent suggestions that free radical reactions are involved in the neurotoxicity of aluminum and in damage to the substantia nigra in patients with Parkinson's disease are reviewed. Finally, the nature of antioxidants is discussed, it being suggested that antioxidant enzymes and chelators of transition metal ions may be more generally useful protective agents than chain-breaking antioxidants. Careful precautions must be used in the design of antioxidants for therapeutic use.
 ...
PMID:Reactive oxygen species and the central nervous system. 140 8

Down's Syndrome (DS), the most frequent of congenital birth defects, results from the trisomy of the chromosome numbered 21 in all cells of affected patients. This disease is characterized by developmental anomalies, mental retardation and features of rapid aging, particularly in the brain where the occurrence of Alzheimer's disease (AD) is observed in all trisomy 21 patients over the age of 35. Elucidation of the biological mechanisms leading to brain aging in DS might provide new insight into the understanding of brain aging and AD in normal people. Copper-zinc superoxide dismutase (CuZnSOD) is one of the genes encoded by chromosome 21. As a consequence of gene dosage excess, CuZnSOD activity and protein are increased by 50% in all DS tissues. The level of CuZnSOD protein and mRNA is particularly high in hippocampal pyramidal neurons susceptible to degenerative processes in AD and in dopaminergic melanized-neurons vulnerable in Parkinson's disease. Increased CuZnSOD activity in these age-related neurodegenerative disorders might result in H2O2 overproduction and subsequently promote peroxidative damages within cells. Increase of seleno-dependent glutathione peroxidase (Se-GPx) in DS cells supports this concept. In order to test this hypothesis, cell and animal models of CuZnSOD overexpression have been designed. In cells transfected with the human CuZnSOD gene, and increased Se-GPx activity is observed, a situation which mimics DS. In mice transgenic for the human CuZnSOD, the expression pattern of the transgene in the brain is similar to that in humans, and we can observe an increased peroxidation in this tissue. These data, like others in the literature, support the hypothesis that excess CuZnSOD induces an imbalance in the regulation of oxygen-derived free radical production which might result in peroxidative brain damage and possibly contribute to accelerated aging and age-related neuropathology.
 ...
PMID:Cellular clones and transgenic mice overexpressing copper-zinc superoxide dismutase: models for the study of free radical metabolism and aging. 145 Jun 8

Oxidant stress, due to the formation of hydrogen peroxide and oxygen-derived free radicals, can cause cell damage due to chain reactions of membrane lipid peroxidation. Because the substantia nigra is rich in dopamine, which can undergo both enzymatic oxidation via monoamine oxidase and nonenzymatic autoxidation, hydrogen peroxide and oxyradicals (superoxide anion radical and hydroxyl radical) are generated in this midbrain nucleus. Although proof that oxidant stress actually causes the loss of monoaminergic neurons in patients with Parkinson's disease is lacking, there is a considerable body of evidence from studies in both animals and humans that support the concept. (1) Neurotoxins that selectively destroy the dopaminergic neurons in the nigra, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), appear to act via oxidant stress. (2) The substantia nigra of patients with Parkinson's disease reveals evidence of oxidant stress by the findings of increased lipid peroxidation and decreased reduced glutathione. (3) Total iron is increased and ferritin is reduced in the substantia nigra pars compacta in patients with Parkinson's disease. This combination suggests that this transition metal is in a low molecular weight form, capable of catalyzing nonenzymatic oxidative reactions, especially the conversion of hydrogen peroxide to hydroxyl radical, which is the most reactive of the oxygen radicals. (4) Neuromelanin, a product of dopamine autoxidation, can serve as a reservoir for iron, promoting the generation of oxyradicals. (5) Antioxidant defense mechanisms appear to be reduced in the parkinsonian substantia nigra with the findings of decreased activities of glutathione peroxidase and catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The oxidant stress hypothesis in Parkinson's disease: evidence supporting it. 147 73

Several links exist between the two mechanisms of neuronal degeneration (i.e., oxygen radical production and mitochondrial damage) proposed to have a role in Parkinson's disease. Indeed, mitochondria are critical targets for the toxic injury induced by oxygen radicals, and experimental evidence suggests that mitochondrial damage may cause an increased generation of oxygen radicals. A potentially important link between these two mechanisms of neurodegeneration is glutathione. Because of the scavenging activity of glutathione against accumulation of oxygen radicals, its decrease in the brains of parkinsonian patients has been interpreted as a sign of oxidative stress; however, this change may also result from or lead to mitochondrial damage. It is conceivable therefore that regardless of whether oxidative stress or mitochondrial damage represents the initial insult, these toxic mechanisms may both contribute to neuronal degeneration via changes in glutathione levels.
 ...
PMID:Glutathione in Parkinson's disease: a link between oxidative stress and mitochondrial damage? 151 Mar 68

Although the cause of neuronal death in Parkinson's disease remains unknown, a hyperoxidation phenomenon has been implicated as a potential cytotoxic mechanism. Catecholaminergic neurons containing neuromelanin, an autoxidation byproduct of catecholamines, are more vulnerable in Parkinson's disease than nonmelanized catecholaminergic neurons. High levels of CuZn superoxide dismutase mRNA have been observed in the substantia nigra, suggesting that high levels of oxygen free radicals are indeed produced in the structure. Catecholaminergic neurons surrounded by a low density of glutathione peroxidase cells are more susceptible to degeneration in Parkinson's disease than those well protected against oxidative stress. The nigral content in iron, a compound that exacerbates the production of free radicals in catecholaminergic neurons, is increased in Parkinson's disease. Altogether these data suggest that hyperoxidation may participate in the selective vulnerability of catecholaminergic neurons in Parkinson's disease.
 ...
PMID:Why are nigral catecholaminergic neurons more vulnerable than other cells in Parkinson's disease? 151 Mar 86

Oxygen consumption and enzyme activity were evaluated in platelet mitochondria from 17 patients with Parkinson's disease. In comparison with age-matched controls, no consistent abnormality could be discerned in complex I, complex II-III, or complex IV oxygen consumption, or in the enzyme activity of these respiratory chain complexes. Neither chronic therapy with levodopa/carbidopa alone nor in combination with deprenyl significantly affected any measure of mitochondrial respiratory function. There was no discernible relationship between patient age or disease severity and any parameter of mitochondrial respiration. Moreover, blood lactate levels following glucose loading were not different in patients and controls. These results fail to support the occurrence of a generalized defect in any mitochondrial respiratory function in Parkinson's disease.
 ...
PMID:Effect of aging and dopaminomimetic therapy on mitochondrial respiratory function in Parkinson's disease. 162 Jan 40


1 2 3 4 5 6 7 8 9 10 Next >>