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)

A matter of debate is the impact of levodopa (LD) application in patients with Parkinson disease (PD) on altered force development and coordination, which are also influenced by the strength of muscles used. The objectives were to compare the motor response, the development of grip strength, and the pharmacokinetic behavior of LD and its main peripheral metabolite 3-O-methyldopa (3-OMD) after intake of 200-mg retarded-release levodopa/carbidopa (LD/CD) and of 150-mg LD/CD/entacapone (LD/CD/EN). Twelve patients with PD received both LD formulations within a standardized setting under double-blind conditions with a crossover design 1 day after the other. Motor symptoms significantly improved, LD plasma concentrations went up, and grip strength increased after both LD/CD and LD/CD/EN administration. There were no significant differences between both conditions with regard to motor response and LD pharmacokinetics. The 3-OMD levels were significantly lower during catechol-O-methyltransferase (COMT) inhibition with entacapone. The LD/CD/EN compound was superior over the retarded-release LD formulation, indicating the impact of LD on grip force. This may be caused by the interference of 3-OMD with the blood-brain barrier transport of LD; therefore, LD delivery is greater during the LD/CD/EN condition. Because the rating scale used does not consider the grip strength, this effect of better blood barrier transport of LD was not reflected. Another hypothesis may be that more acidic metabolites appear during peripheral LD metabolism by means of COMT, whereas COMT inhibition is accompanied by more basic LD metabolites (ie, the tyrosine aminotransferase-dependent substrates dihydroxyphenylpyruvate acetate and trihydroxyphenylacetate). This antiacid scenario may support a better muscle function with a positive impact on muscle excitability and contractibility.
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PMID:Catechol-O-methyltransferase inhibition improves levodopa-associated strength increase in patients with Parkinson disease. 1852 Sep 80

The present study investigates the effects of divalent and trivalent manganese (Mn(2+)/Mn(3+)) mixture inhalation on mice to obtain a novel animal model of Parkinson disease (PD) inducing bilateral and progressive cell death in the substantia nigra compacta (SNc) and correlating these alterations with motor disturbances. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl(2)) and manganese acetate (Mn(OAc)(3)), 1 h twice a week for 5 months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. By doing this, overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn exposure period, animals were killed. The mesencephalon was processed for tyrosine hydroxylase (TH) immunocytochemistry. After 5 months of Mn mixture inhalation, mice developed evident deficits in their motor performance manifested as akinesia, postural instability and action tremor. SNc of the Mn-exposed animals showed an important decrease (67.58%) in the number of TH-immunopositive neurons. Our data provide evidence that MnCl(2) and Mn(OAc)(3) mixture inhalation produces similar morphological and behavioral alterations to those observed in PD providing a useful experimental model for the study of this neurodegenerative disease.
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PMID:Inhalation of divalent and trivalent manganese mixture induces a Parkinson's disease model: immunocytochemical and behavioral evidences. 1856 81

The L-dopa is the immediate precursor of the neurotransmitter dopamine. Unlike dopamine, L-dopa easily enters the central nervous system and is used in the treatment of Parkinson's disease. A sensitive and selective method is presented for the voltammetric determination of L-dopa in pharmaceutical formulations using a carbon paste electrode modified with trinuclear ruthenium ammine complex [(NH(3))(5)Ru(III)ORu(IV)(NH(3))(4)ORu(III)(NH(3))(5)](6+) (Ru-red) incorporated in NaY zeolite. The parameters which influence on the electrode response (paste composition, potential scan rate, pH and interference) were also investigated. The optimum conditions were found to an electrode composition (m/m) of 25% zeolite containing 6.7% Ru, 50% graphite and 25% mineral oil in acetate buffer at pH 4.8. Voltammetric peak currents showed a linear response for L-dopa concentration in the range between 1.2x10(-4) and 1.0x10(-2)moll(-1) (r=0.9988) with a detection limit of 8.5x10(-5)moll(-1). The variation coefficient for a 1.0x10(-3)moll(-1) L-dopa (n=10) was 5.5%. The results obtained for L-dopa in pharmaceutical formulations (tablet) was in agreement with compared official method. In conclusion, this study has illustrated that the proposed electrode modified with Ru-red incorporated zeolite is suitable valuable for selective measurements of L-dopa.
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PMID:Voltammetric determination of L-dopa using an electrode modified with trinuclear ruthenium ammine complex (Ru-red) supported on Y-type zeolite. 1896 37

The immune system can play both detrimental and beneficial roles in the nervous system. Multiple arms of the immune system, including T cells, B cells, NK cells, mast cells, macrophages, dendritic cells, microglia, antibodies, complement and cytokines participate in limiting damage to the nervous system during toxic, ischemic, hemorrhagic, infective, degenerative, metabolic and immune-mediated insults and also assist in the process of repair after injury has occurred. Immune cells have been shown to produce neurotrophic growth factors and interact with neurons and glial cells to preserve them from injury and stimulate growth and repair. The immune system also appears to participate in proliferation of neural progenitor stem cells and their migration to sites of injury. Neural stem cells can also modify the immune response in the central and peripheral nervous system to enhance neuroprotective effects. Evidence for protective and reparative functions of the immune system has been found in diverse neurologic diseases including traumatic injury, ischemic and hemorrhagic stroke, multiple sclerosis, infection, and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis). Existing therapies including glatiramer acetate, interferon-beta and immunoglobulin have been shown to augment the protective and regenerative aspects of the immune system in humans, and other experimental interventions such as vaccination, minocycline, antibodies and neural stem cells, have shown promise in animal models of disease. The beneficent aspects of the immune response in the nervous system are beginning to be appreciated and their potential as pharmacologic targets in neurologic disease is being explored.
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PMID:Protective autoimmunity in the nervous system. 1900 Jul 12

Oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as Parkinson's disease, Alzheimer's disease, epilepsy and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a role in the pathogenesis of these diseases. Lindenenyl acetate, isolated by bioassay-guided fractionation of the MeOH extract of the roots of Lindera strychnifolia, showed potent neuroprotective effects on glutamate-induced neurotoxicity by inducing the expression of HO-1 and increasing the activity of HO in mouse hippocampal HT22 cells. Furthermore, lindenenyl acetate caused the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements (ARE) in mouse hippocampal HT22 cells. In addition, we found that treatment of the cells with extracellular signal-regulated kinase (ERK) inhibitor (U0126) reduced lindenenyl acetate-induced HO-1 expression. Lindenenyl acetate also increased ERK phosphorylation. These results suggest that lindenenyl acetate increases cellular resistance to glutamate-induced oxidative injury in mouse hippocampal HT22 cells, presumably through the ERK pathway-Nrf2/ARE-dependent HO-1 expression.
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PMID:Cytoprotective effects of lindenenyl acetate isolated from Lindera strychnifolia on mouse hippocampal HT22 cells. 1944 2

Parkinson's disease (PDI is a neurodegenerative disorder of unknown etiology. Both genetic and environmental factors are thought to be implicated to some extent. The ACE gene insertion/deletion (I/D) polymorphism has been associated with common neurodegenerative disorders that share similar clinical and neuropathological features with PD (Alzheimer's disease). In this study we set out to examine the role of the ACE gene insertion/deletion (I/D) polymorphism in Parkinson's disease (PD).We conducted a case-control association study among 77 PD patients and 50 non-PD controls from Greece. The genotype frequencies for II, ID, and DD were 39, 48, and 13%, respectively, in the PD group and 32, 50, and 18% in the control group. Although the DD frequency was higher in the case group statistical significance was not reached. We conclude that although disease modifying effects cannot be excluded, the ACE insertion/deletion polymorphism is unlikely to be an important determinant of susceptibility to PD in this population.
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PMID:The insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) in Parkinson's disease. 1945 13

The mechanism underlying the motor fluctuations that develop after long-term L-dopa therapy is not fully known. It has been speculated that malabsorption of L-dopa from the small intestine occurs. It was reported that gastric retention in Parkinson's disease (PD) patients with motor fluctuations is increased as compared with that in PD without fluctuations. Because L-dopa therapy may worsen the symptoms of delayed gastric emptying (GE), it was not clear whether the delayed GE of PD patients with motor fluctuation was affected by L-dopa therapy. We assessed GE in PD patients with and without motor fluctuations. We investigated GE in 40 patients with PD under long-term L-dopa therapy, 20 fluctuators with "delayed-on" and "noon" phenomena, 20 nonfluctuators, and 20 healthy volunteers. GE was examined by the 13C-acetate breath test ((13)CABT) [the half emptying time (HET), the peak time of the (13)C-%-dose-excess curve (T(max))], with expirations collected for 4 h after a test meal and analyzed for (13)CO(2) using an infrared (IR) spectrophotometer. The T(max) of GE as assessed using the (13)C-ABT was significantly delayed in all PD patients as compared with controls (P = 0.002). The HET was significantly delayed in all PD patients as compared with controls (P < 0.001). The T(max) and HET were not significantly delayed in PD patients with motor fluctuations as compared with PD patients without motor fluctuations. These results demonstrated that GE is commonly delayed in PD patients with long-term L-dopa therapy. Delayed GE does not differ between PD patients with and without motor fluctuations. This finding demonstrated that the motor fluctuation in PD may not be influenced by GE.
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PMID:Is there a difference in gastric emptying between Parkinson's disease patients under long-term L-dopa therapy with and without motor fluctuations? An analysis using the 13C-acetate breath test. 1957 60

This study focused on the design, biometric simulation and optimization of an intracranial nano-enabled scaffold device (NESD) for the site-specific delivery of dopamine (DA) as a strategy to minimize the peripheral side-effects of conventional forms of Parkinson's disease therapy. The NESD was modulated through biometric simulation and computational prototyping to produce a binary crosslinked alginate scaffold embedding stable DA-loaded cellulose acetate phthalate (CAP) nanoparticles optimized in accordance with Box-Behnken statistical designs. The physicomechanical properties of the NESD were characterized and in vitro and in vivo release studies performed. Prototyping predicted a 3D NESD model with enhanced internal micro-architecture. SEM and TEM revealed spherical, uniform and non-aggregated DA-loaded nanoparticles with the presence of CAP (FTIR bands at 1070, 1242 and 2926 cm(-1)). An optimum nanoparticle size of 197 nm (PdI=0.03), a zeta potential of -34.00 mV and a DEE of 63% was obtained. The secondary crosslinker BaCl(2) imparted crystallinity resulting in significant thermal shifts between native CAP (T(g)=160-170 degrees C; T(m)=192 degrees C) and CAP nanoparticles (T(g)=260 degrees C; T(m)=268 degrees C). DA release displayed an initial lag phase of 24 h and peaked after 3 days, maintaining favorable CSF (10 microg/mL) versus systemic concentrations (1-2 microg/mL) over 30 days and above the inherent baseline concentration of DA (1 microg/mL) following implantation in the parenchyma of the frontal lobe of the Sprague-Dawley rat model. The strategy of coupling polymeric scaffold science and nanotechnology enhanced the site-specific delivery of DA from the NESD.
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PMID:Design, biometric simulation and optimization of a nano-enabled scaffold device for enhanced delivery of dopamine to the brain. 1970 30

Chemical neurotransmission has been the subject of intensive investigations in recent years. Acetylcholine is an essential neurotransmitter in the central nervous system as it has an effect on alertness, memory and learning. Enzymatic hydrolysis of acetylcholine in the synaptic cleft is fast and quickly metabolizes to choline and acetate by acetylcholinesterase. Hence the concentration in the extracellular fluid of the brain is low (0.1-6 nm). Techniques such as microdialysis are routinely employed to measure acetylcholine levels in living brain systems and the microdialysis sample volumes are usually less than 50 microL. In order to develop medicine for the diseases associated with cognitive dysfunction like mild cognitive impairment, Alzheimer's disease, schizophrenia and Parkinson's disease, or to study the mechanism of the illness, it is important to measure the concentration of acetylcholine in the extracellular fluid of the brain. Recently considerable attention has been focused on the development of chromatographic-mass spectrometric techniques to provide more sensitive and accurate quantification of acetylcholine collected from in-vivo brain microdialysis experiments. This review will provide a brief overview of acetylcholine biosynthesis, microdialysis technique and liquid chromatography mass spectrometry, which is being used to quantitate extracellular levels of acetylcholine.
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PMID:Quantification of acetylcholine, an essential neurotransmitter, in brain microdialysis samples by liquid chromatography mass spectrometry. 1987 95

This investigation was designed to determine whether l-DOPA treatment improves the motor alterations observed after divalent and trivalent manganese (Mn) mixture inhalation on mice to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl(2)) and manganese acetate (Mn(OAc)(3)), 1h twice a week for 5 months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. Overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn exposure period, 10 mice were orally treated with 7.5mg/kg L-DOPA. After 5 months of Mn-mixture inhalation striatal dopamine content decreased 71%, mice developed evident deficits in motor performance manifested as akinesia, postural instability and action tremor; these alterations were reverted with L-DOPA treatment. Our results suggest that the motor alterations induced by the inhalation of the combination of MnCl(2)/Mn(OAc)(3) are related to nigrostriatal dopaminergic function providing new light on the understanding of manganese neurotoxicity as a suitable Parkinson disease experimental model.
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PMID:L-DOPA treatment reverses the motor alterations induced by manganese exposure as a Parkinson disease experimental model. 2007 2


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