Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cause of the degeneration of dopamine-containing cells in the zona compacta of the substantia nigra in Parkinson's disease remains unknown. The ability of the selective nigral toxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) (via its metabolite MPP+) to destroy nigral dopamine cells selectively by inhibiting complex I of the mitochondrial energy chain may provide a clue. Indeed, recent studies of post-mortem brain tissue have suggested the presence of an on-going toxic process in the substantia nigra in Parkinson's disease leading to excess lipid peroxidation. This appears also to involve a disruption of mitochondrial function since mitochondrial superoxide dismutase activity is increased and there is impairment of complex I. These changes may in turn relate to a selective increase in the total iron content of substantia nigra coupled to a generalised decrease in brain ferritin content. Piribedil is used in the symptomatic treatment of Parkinson's disease and is particularly effective against tremor. Piribedil (and its metabolites) acts as a dopamine D-2 receptor agonist. However, in our studies in contrast to other dopamine agonists, in vivo piribedil interacts with dopamine receptors in the substantia nigra and nucleus accumbens but not those in the striatum. In patients with Parkinson's disease the beneficial effects of piribedil may be limited by nausea and drowsiness. Indeed, in MPTP-treated primates piribedil reverses motor deficits but marked side-effects occur. However, pre-treatment with the peripheral dopamine receptor antagonist domperidone prevents the unwanted effects and piribedil produces a profound and longer-lasting reversal of all components of the motor syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parkinson's disease: pathological mechanisms and actions of piribedil. 163 7

One-month-old male Sprague-Dawley rats were fed a basal vitamin E deficient diet with or without 50 ppm vitamin E supplementation for 7 months. The washed red cells were suspended in a saline-phosphate buffer, pH 7.4, that contained either 0, 0.011 or 0.055 M glucose and were incubated at 37 C with constant shaking. Catalase activity in the red cells of vitamin E deficient rats was decreased 74% (P less than 0.001) at the end of the 22-hour incubation, and only 9% of the initial value was retained at the end of 46 hours. In the red cells of the vitamin E supplemented group, 82% and 48% of catalase activity was retained at the end of 22 and 46 hours, respectively. Glucose in the medium significantly increased catalase activity during the early hours of incubation and retarded the enzyme inactivation at the end of 22 and 46 hours in both groups of animals. The activities of superoxide dismutase and glutathione peroxidase were not significantly altered by the presence of glucose or by the status of dietary vitamin E during the incubation. The results suggest that both glucose and dietary vitamin E provide protection against inactivation of catalase under the experimental conditions.
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PMID:Glucose and dietary vitamin E protection against catalase inactivation in the red cells of rats. 720 46

Cu, Zn-superoxide dismutase (Cu,Zn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase (CAT), peroxidase (POX), glutathione peroxidase(GP) and glutathione reductase (GR) activities were assayed in the brains of genetically selected neurological mutant rabbits pt and their controls. Paralytic tremor (pt) is a spontaneous mutation in rabbit that affects irregular and defective myelination of CNS. Antioxidant enzyme levels were different in three brain regions: brain hemispheres, cerebellum, and brain stem. In brain hemisphere and cerebellum of pt rabbits Mn-SOD and Cu, Zn-SOD activities were elevated. Catalase activity in brain hemispheres and peroxidase activity in the brain stem of pt rabbits were reduced. It was also noticed, that in the pt rabbit the ratio CAT/Cu, Zn-SOD was lower by 20% in the brain hemispheres and by 13% in the cerebellum and the ratio POX/Cu, Zn-SOD was lower by 31.8% in the brain stem. These findings indicated that pt mutations are associated with changes in the antioxidant defense system in the rabbit brain.
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PMID:Antioxidant enzyme activities in different brain areas of the neurological mutant--pt rabbit. 870 86

The mutation gly93-->ala of Cu,Zn superoxide dismutase (SOD) is found in patients with familial amyotrophic lateral sclerosis and causes motor neuron disease when expressed in transgenic mice. The progression of clinical and pathological disease was studied in a line of mice designated G1H. Clinical disease started at 91 +/- 14 days of age with fine shaking of the limbs, followed by paralysis and death by 136 +/- 7 days of age. Pathological changes begin by 37 days of age with vacuoles derived from swollen mitochondria accumulating in motor neurons. At the onset of clinical disease (90 days), significant death of somatic motor neurons innervating limb muscles has occurred; mice at end-stage disease (136 days) show up to 50% loss of cervical and lumbar motor neurons. However, neither thoracic nor cranial motor neurons show appreciable loss despite vacuolar changes. Autonomic motor neurons also are not affected. Mice that express wild-type human Cu,Zn SOD remain free of disease, indicating that mutations cause neuron loss by a gain-of-function. Thus, the age-dependent penetrance of motor neuron disease in this transgenic model is due to the gradual accumulation of pathological damage in select populations of cholinergic neurons.
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PMID:Age-dependent penetrance of disease in a transgenic mouse model of familial amyotrophic lateral sclerosis. 884 4

We present the clinical characteristics of autosomal recessive form of juvenile parkinsonism(AR-JP) (MIM 600116) and the result of the linkage analysis using 11 markers on the long arm of chromosome 6. We examined 25 patients of 13 Japanese AR-JP families. They showed female predominance, mean age at onset at 24.4 +/- 10.3 years, slow progression, good response to levodopa and frequent occurrence of wearing-off phenomenon and dopa-induced dyskinesia. Compared to Parkinson's disease(PD), the parkinsonian triad(tremor, rigidity and bradykinesia) were mild, but dystonic posture, postural instability and hyperreflexia were more prominent compared to PD. By the linkage analysis, we obtained a strong evidence for linkage of the AR-JP gene to a 17 cM region of chromosome 6q25.2-27 including the Mn-superoxide dismutase gene(SOD2) with a maximal cumulative multipoint lod score of 9.44 at 0.9 cM telomeric to D6S253.
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PMID:[Clinical characteristics and linkage analysis of autosomal recessive form of juvenile parkinsonism(AR-JP)]. 901 27

Platelets and coagulation are involved in the pathogenesis of blood-borne metastases. The aim of this study is to obtain more information about the mechanisms involved in the initial adhesion of tumor cells to endothelial cells. In short term experiments with tumor cells, suspended in the medium of cultured endothelial cells, we tested whether addition of both platelets and thrombin cause more tumor cell adhesion to endothelial cells, than when either platelets or thrombin are acting alone. HeLa cells or HT29 cells, prelabeled with radioactive 51Cr, human platelets, and thrombin were added to human endothelial cell cultures. Following 15 min of shaking at 37 degrees C, the percentage of tumor cell adhesion was calculated. The percentages of adhering tumor cells with the presence of both platelets and thrombin were greatly increased compared to controls. Addition of hirudin 2 min before thrombin lowered the adhesion percentage of tumor cells. Hirudin added immediately before and 2 min after thrombin gave only minor effects. When the endothelium was treated with superoxide dismutase, catalase, and mannitol, the adhesion of tumor cells was lowered with catalase and superoxide dismutase. The cause of tumor cell-endothelial cell interaction is probably complex. Our results show that activated platelets enhance the tumor cell adhesion, and that generation of active oxygen species may be important in the initial phase of the interaction.
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PMID:Addition of both platelets and thrombin in combination accelerates tumor cells to adhere to endothelial cells in vitro. 911 26

Scrapie, one of the prion diseases, is a transmissible neurodegenerative disease of sheep and other animals. Clinical symptoms of prion diseases are characterized by a long latent period, followed by progressive ataxia, tremor, and death. To study the induction of neurodegeneration during scrapie infection, we have analyzed the activities of various antioxidant enzymes and mitochondrial enzymes in cerebral cortex, brain stem, and cerebellum of scrapie-infected hamsters. The activity of mitochondrial Mn-superoxide dismutase (SOD) was decreased, while the activities of cytosolic Cu/Zn-SOD and catalase were not altered in infected brains. The activities of glutathione peroxidase and glutathione reductase were increased in scrapie-infected hamsters. The decreased activity of Mn-SOD might result in increasing oxidative stress in the mitochondria of infected brain; this concept is supported by our findings of a high level of lipid peroxidation, and low levels of ATPase and cytochrome c oxidase activity in the infected cerebral mitochondria. In addition, structural abnormalities of mitochondria have been observed in the neurons of hippocampus and cerebral cortex of infected brain. These results suggest that mitochondrial dysfunction caused by oxidative stress gives rise to neurodegeneration in prion disease.
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PMID:Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 K scrapie agent. 975 61

There is controversy as to whether there are clinical subgroups in Parkinson's disease (PD). Six tremor-dominant and six bradykinesia-dominant patients identified among 29 cases with PD were compared in terms of erythrocyte superoxide dismutase (SOD) activity and several clinical variables. Erythrocyte SOD activity in tremor-dominant patients was higher than in bradykinesia-dominant patients. According to our preliminary results obtained from small number of patients, the difference of SOD activity in clinically distinct subgroups suggests there may be separate clinical subgroups of PD which can be differentiated by a biological marker.
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PMID:Erythrocyte superoxide dismutase activity differs in clinical subgroups of Parkinson's disease patients. 1181 68

Citrullinemia is an inborn error of the urea cycle caused by deficient argininosuccinate synthetase, which leads to accumulation of L-citrulline and ammonia in tissues and body fluids. The main symptoms include convulsions, tremor, seizures, coma, and brain edema. The pathophysiology of the neurological signs of citrullinemia remains unclear. In this context, we investigated the in vitro effects of L-citrulline and ammonia in cerebral cortex from 30-day-old rats on oxidative stress parameters, namely thiobarbituric acid-reactive substances (TBA-RS), chemiluminescence, mitochondrial membrane protein thiol content, intracellular content of hydrogen peroxide, total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR) as well as on the activities of the antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase). L-Citrulline significantly diminished TRAP (26%) and TAR (37%), while ammonia decreased TAR (30%). Ammonia increased SOD activity (65%) and L-citrulline did not affect the activities of any antioxidant enzymes. We also observed that L-citrulline and ammonia did not alter lipid peroxidation parameters, levels of hydrogen peroxide, and mitochondrial membrane protein thiol content. Taken together, these results may indicate that L-citrulline and ammonia decreased the antioxidant capacity of the brain, which may reflect a possible involvement of oxidative stress in the neuropathology of citrullinemia.
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PMID:Citrulline and ammonia accumulating in citrullinemia reduces antioxidant capacity of rat brain in vitro. 1677 71

Infants and children may undergo severe oxidative stress due to disease state, pre-existing nutritional status, frequent use of oxygen, and lower levels of antioxidant defenses. Antioxidant defenses, made up of intracellular and extra-cellular components, work synergistically to prevent oxidative damage. Total antioxidant activity (TAA) was analyzed by method of ferric reducing antioxidant power assay (FRAP). Patients admitted in Pediatric Dept, RNT Medical College, Udaipur, India were selected for these studies. TAA level in neonates with hypoxic-ischemic-encephalopathy (HIE) stage III and in poor outcome cases was significantly low. Erythrocyte SOD activity level was low in pre-term neonates. TAA level in severely malnourished children at the time of hospital admission was low. This low antioxidant level in severely malnourished children could be multi-factorial viz. low zinc, selenium, vitamin A & C deficiency, recurrent infections, elevated free iron and chronic starvation stage. Delayed recovery of oxidant injury may lead to delayed incomplete recovery at cellular level. In a study of 29 tuberculosis patients TAA level was found to be low in tubercular patients compared with control. TAA level decreased more in CNS tuberculosis compared with other system tuberculosis. In a study of nutritional tremor syndrome TAA, ascorbic acid and alpha-tocopherol levels were low during pre-tremor phase compared with tremor phase (ATS). Pre-term neonates have incompletely developed antioxidant defenses and are deficient in vitamin E, which is normally derived from maternal circulation at the end of 3rd trimester. Therefore, decreased TAA level in HIE with poor outcome indicates addition of antioxidants in therapeutic strategy. Since rise in TAA in antioxidant supplemented group of severely malnutrition children was higher with good outcome compared with nonsupplemented group it would be prudent to supplement antioxidant during nutritional management. These studies have shown that health benefits can be obtained by children with a reduced risk of disease from supplements of antioxidant nutrients. The amounts of optimal supplements in these disorders, whether pharmacologic or large, are to be determined. Further work is needed to show whether modest increases in nutrient intakes in children with these disorders will delay or prevent the complications and improve the outcome. Therefore, available evidence regarding health benefits to be achieved by supplementing antioxidant nutrients is encouraging. Free radical injury and antioxidant deficiency is more common than what we think. Severely malnourished children and children suffering from chronic infections and diseases are at several fold increased risk of antioxidant deficiency and likely to suffer from free radical injury. Appropriate interventions are required in reducing the risk associated with these observations.
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PMID:Free radicals: emerging challenge in environmental health research in childhood and neonatal disorders. 1696 76


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