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)

Bromocriptine (BRC) has been mainly used for the inhibition of lactation, treatment of menstrual disorders, Parkinson disease, breast tumours, infertility and brain tumours as a dopamine agonist in clinics. But current BRC formulations have some side effects and bioavailability problems because of hepatic first pass effect. Transdermal application could be an alternative route to overcome all these problem and penetration properties of BRC has not been studied yet. Therefore, it was aimed to investigate the effectiveness of transdermal formulation of BRC which is applicable to the skin. For this purpose, a number of BRC gel formulations (Carbopol-934 (C-934), chitosan (CH) and Gantrez-SP215 (G-SP215) were developed and the effectiveness and bioavailability of the formulations were compared in rabbits. Commercial BRC tablets (Parlodel) were also given to rabbits orally and plasma levels were compared. The effects of two different penetration enhancers, sodium taurocholate (ST) and ethoxydiglycol-Transcutol) (TR) on the BRC penetration were also investigated. The skin samples from the dorsal part of the rabbit were removed after CH gel application and investigated under electron microscope to understand the effects of the gel on the penetration and the possible penetration mechanisms through skin were also discussed. In conclusion, CH gel formulation was found to be the best formulation and comparable blood BRC concentrations were obtained when applied to the rabbit skin. Higher blood levels were obtained with the use of CH. The main penetration process was found to be through transcellular route but some other mechanisms were also found to be incorporated, after microscopic investigation. CH gel was found to be a useful carrier for BRC administration through dermal route and the penetration enhancing effect and the mechanism of CH gel were first established in this study. It was concluded that transdermal delivery of BRC may be a very promising alternative route to the oral route for the treatment.
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PMID:Transdermal administration of bromocriptine. 1267 32

We reviewed literature on malignant syndrome occurring in patients with Parkinson's disease (PD) during the course of drug therapy. Clinical features were high fever, marked rigidity, consciousness disturbance, autonomic dysfunction, and elevation of serum creatine kinase. The clinical features were essentially similar to those of neuroleptic malignant syndrome. The immediate triggering event was, most often, discontinuation or reduction of anti-parkinsonian drugs, particularly of levodopa. But no anti-parkinsonian drug was the exception to the induction of malignant syndrome. Serious complications were severe pneumonia, disseminated intravascular coagulation, and acute renal failure. Early treatment with intravenous fluid infusion and external body cooling are essential for good recovery. Bromocriptine and dantrolene sodium were used frequently. It has been claimed that they are effective; however, randomized controlled studies are needed to explicitly prove the efficacy of these drugs in malignant syndrome associated with PD.
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PMID:Malignant syndrome in Parkinson's disease: concept and review of the literature. 1464 3

We report the results of a collaborative study on malignant syndrome (MS) that developed in patients being treated with levodopa and other anti-parkinsonian drugs. We analyzed clinical features, laboratory findings, precipitating events, and risk factors for poor outcome. The study was conducted in five centers in Japan. Patients who developed MS between January 1991 and December 1997 were included. The enrollment criteria used were the same as those for neuroleptic MS proposed by Levenson et al. (1985).A total of 99 episodes were encountered in 93 patients (72 with Parkinson's disease and 21 with secondary parkinsonism); one patient had four recurrences of MS and three patients had two recurrences. High fever was the most frequent clinical manifestation of MS followed by worsening of parkinsonism, and then altered levels of consciousness. Serum creatine kinase was abnormally elevated in all the patients studied. Life-threatening complications were rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure. The most frequent precipitating event was discontinuation or dose reduction of anti-parkinsonian drugs, particularly levodopa. No drug was the exception in the precipitation of MS. Intercurrent infection was the next most common precipitating event. MS developed without drug withdrawal or infection in some patients. In five patients, severe "wearing off" phenomenon was the only event preceding the onset of MS. Hot weather and dehydration appeared to be the cause in three patients. Among the total of 99 episodes, patients recovered to the pre-MS state following 68 episodes (68.7%); in the remaining 31.3%, patients failed to recover to their previous state. Older age, higher Hoehn and Yahr stage during the symptomatic phase of MS, higher akinesia score, and the absence of wearing off phenomenon prior to developing MS were associated with poor outcome. The most frequently used treatments of MS were intravenous fluid, levodopa, dantrolene sodium, and intragastric bromocriptine. Early introduction of treatment is important. Any elevation of body temperature during the course of anti-parkinsonian drug treatment should be considered as MS until proved otherwise.
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PMID:A collaborative study on the malignant syndrome in Parkinson's disease and related disorders. 1273 13

We report a consensus statement of the collaborative research group on the prevention and treatment of malignant syndrome (MS) in Parkinson's disease. The syndrome is quite similar to neuroleptic MS. Although sudden withdrawal of levodopa was the most frequent cause, many other precipitating events were found such as intercurrent infections, dehydration, hot weather, discontinuation of other anti-parkinsonian drugs, and "wearing off" phenomenon. Awareness of this syndrome is most important for its early detection and the prompt commencement of treatment. MS should be suspected whenever the body temperature rises above 38 degrees C without an apparent cause. Treatment consists of ample intravenous fluid, cooling the body, anti-parkinsonian drugs (particularly levodopa and bromocriptine), dantrolene sodium, and antibiotics if infection is present. Rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure constitute serious complications.
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PMID:Prevention and treatment of malignant syndrome in Parkinson's disease: a consensus statement of the malignant syndrome research group. 1273 15

Within the central nervous system uncontrolled production of large amounts of nitric oxide (NO) by activated glial cells might be the common pathogenesis of several neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. In the present investigation, we measured the effect of a novel antioxidant gamma-L-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl]oxy]carbonyl]-3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-L-cysteinyl-glycine sodium salt (ESeroS-GS) on NO production in cultured rat astrocytes. Upon stimulation with 1 microg/mL lipopolysaccharide plus 100 U/mL interferon-gamma which induced the expression of inducible nitric oxide synthase, cultured astrocytes generated large amounts of NO as measured by nitrite assay and ESR technique. The endogenous NO caused oxidative damage in astrocytes, which was confirmed by the accumulation of both cytosolic and extracellular peroxides, the decrease in the cellular glutathione level, and the formation of thiobarbituric acid reactive substrates. Production of endogenous NO resulted in cell death finally. Pretreatment with the novel antioxidant ESeroS-GS effectively decreased the expression of iNOS gene, inhibited the formation of endogenous NO, and prevented NO-induced oxidative damage and cell death in astrocytes. The results suggest that ESeroS-GS might be used as a potential agent for the prevention and therapy of diseases associated with the overproduction of NO by activated astrocytes.
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PMID:The antioxidant ESeroS-GS inhibits NO production and prevents oxidative stress in astrocytes. 1281 68

alpha-Synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are neurodegenerative disorders in which abnormal inclusions containing alpha-synuclein accumulate in selectively vulnerable neurons and glia. In this report, immunohistochemistry demonstrates ubiquitin in subsets of alpha-synuclein inclusions in dementia with Lewy bodies and multiple system atrophy. Biochemistry demonstrates that alpha-synuclein in the sodium dodecyl sulfate-soluble fractions of diseased brains is ubiquitinated, with mono- and di-ubiquitinated species predominating over polyubiquitinated forms. Similar immunohistochemical and biochemical characteristics were observed in an A53T mutant human alpha-synuclein transgenic mouse model of neurodegenerative alpha-synucleinopathies. Furthermore, in vitro ubiquitination of alpha-synuclein fibrils recapitulated the pattern of alpha-synuclein ubiquitination observed in human disease and the A53T alpha-synuclein mouse model. These results suggest that ubiquitination of alpha-synuclein is not required for inclusion formation and follows the fibrillization of alpha-synuclein.
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PMID:Ubiquitination of alpha-synuclein is not required for formation of pathological inclusions in alpha-synucleinopathies. 1281 14

The diverse damaging effects of dopamine (DA) oxidation products on brain subcellular components including mitochondrial electron transport chain have been implicated in dopaminergic neuronal death in Parkinson's disease. It has been shown in this study that DA (50-200 microM) causes dose-dependent inhibition of Na+, K+-ATPase activity of rat brain crude synaptosomal-mitochondrial fraction during in vitro incubation up to 2 h. The enzyme inactivation is prevented by catalase and the metal-chelator (diethylenetriamine penta-acetic acid) but not by superoxide dismutase or hydroxyl-radical scavengers like mannitol and dimethylsulphoxide (DMSO). Further, reduced glutathione and cysteine, markedly prevent DA-mediated inactivation of Na+, K+-ATPase. Under similar conditions of incubation, DA (200 microM) leads to the formation of quinoprotein adducts (protein-cysteinyl catechol) with synaptosomal-mitochondrial proteins and the phenomenon is also prevented by glutathione (5 mM) or cysteine (5 mM). The available data imply that the inactivation of Na+, K+-ATPase in this system involves both H2O2 and metal ions. The reactive quinones by forming adducts with protein thiols also probably contribute to the process, since reduced glutathione and cysteine which scavenge quinones from the system protect Na+, K+-ATPase from DA-mediated damage. The inactivation of neuronal Na+, K+-ATPase by DA may give rise to various toxic sequelae with potential implications for dopaminergic cell death in Parkinson's disease.
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PMID:Dopamine oxidation products inhibit Na+, K+-ATPase activity in crude synaptosomal-mitochondrial fraction from rat brain. 1286 86

A 64-year-old male with treated Parkinson's disease underwent mechanical valve replacement for aortic valve regurgitation. The antiparkinsonian drugs for internal use were interrupted on the morning of the operative day. After the operation, the patient developed fervescence, muscle rigidity, hidropoiesis and a rise in creatine kinase. The patient was diagnosed as neuroleptic malignant syndrome and given medication dantrolene sodium and antiparkinsonian drugs on the 5th postoperative day. The symptom of neuroleptic malignant syndrome disappeared on 12 postoperative days. As the stress of open heart surgery with extracorporeal circulation trigger off neuroleptic malignant syndrome, the patient with Parkinson's disease need early beginning of antiparkinsonian drugs on account of prevention of neuroleptic malignant syndrome after operation.
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PMID:[Neuroleptic malignant syndrome after aortic valve replacement; report of a case]. 1367 24

Although it is well known that high-frequency stimulation (HFS) of the subthalamic nucleus (STN) alleviates the cardinal symptoms of Parkinson's disease, the underlying mechanisms are not fully understood. We investigated the effect of stimulation from low to high frequencies on rat STN neurons in naive and dopamine-depleted slices using whole-cell, current-clamp techniques and on-line artifact suppression. Stimulation at 10 Hz evoked 10 Hz single spikes but did not significantly modify ongoing STN activity. In contrast, at therapeutically relevant frequencies (80-185 Hz), stimulation had a dual effect: it fully suppressed STN spontaneous activity and generated a robust pattern of recurrent bursts of spikes, with each spike being time-locked to a stimulus pulse. Neither the suppression of spontaneous activity nor the generation of spikes was prevented by the antagonists of the metabotropic and ionotropic receptors of glutamate and gamma-aminobutyric acid. Tetrodotoxin, the Na+ channel blocker, suppressed all HFS-evoked spikes, whereas nifedipin, an L-type Ca2+-channel blocker, abolished the membrane oscillations underlying bursts. Therefore, we conclude that HFS drives the STN neuronal activity by directly activating the neuronal membrane. We suggest that this pattern may remove the deleterious activity of the basal ganglia network in the parkinsonian state and drive target neurons to a high-frequency state of activity, dependent on the characteristics of STN efferent synapses and resonant properties of target membranes.
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PMID:Dual effect of high-frequency stimulation on subthalamic neuron activity. 1450 74

The membrane composition and the isoprenoid pathway metabolites important in maintaining cell membrane integrity was studied in neurological and psychiatric disorders. The results indicate alteration in cholesterol:phospholipid ratio of the RBC membrane which is increased in glioma, schizophrenia, and bipolar mood disorder (MDP); decreased in multiple sclerosis and Parkinson's disease; and not significantly altered in epilepsy. The concentration of total glycosaminoglycans (GAG), hexose, and fucose decreased in the RBC membrane and increased in the serum. The RBC membrane Na+-K+ ATPase activity was reduced and serum HMG CoA reductase activity was increased. There were increased serum levels of digoxin, cholesterol, and dolichol and decreased levels of ubiquinone. The serum magnesium and tyrosine levels were reduced and tryptophan increased. The results indicate a defect in membrane formation and a decreased membrane Na+-K+ ATPase activity in all the disorders studied. The results are discussed, and a hypothesis regarding the relationship between these disorders and defective membrane architecture and membrane Na+-K+ ATPase inhibition is presented.
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PMID:Isoprenoid pathway-related membrane dysfunction in neuropsychiatric disorders. 1458 55


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