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)

We report a reliable method for determining DOPA levels in plasma and cerebrospinal fluid. The method is based on complete conversion of DOPA to dopamine and quantification by HPLC-ECD of the dopamine formed. Lower limit of detection was 0.5 nmol/l. No differences in plasma DOPA levels were found between normal children (0-15 yr, n = 60), normal adults (n = 39) and patients with essential hypertension (n = 40) or Parkinson's disease (no DOPA therapy, n = 30). In normal individuals and in patients with essential hypertension venous plasma levels were higher than arterial levels (10.2 vs 9.3 nmol/l, p less than 0.001, V/A ratio 1.11 (SD 0.08), n = 15). Sympathetic stimuli (standing, tilting, bicycle exercise, tyramine) did not influence DOPA levels. In untreated depressed patients (n = 10) and in non-parkinsonian neurological patients (n = 12) cerebrospinal fluid levels of DOPA were 4.5 (SD 2.4) and 5.2 (SD 1.3) nmol/l respectively. A direct method for the measurement of DOPA by HPLC-ECD after deproteinization of plasma is also described and compared with the conversion method. Good agreement was found when plasma DOPA levels exceeded 0.25 mumol/l (y(conversion method) = 0.943x (direct method) + 0.118; n = 60; r = 0.985). The direct method, because of greater simplicity and the possibility of simultaneous measurement of the DOPA metabolite 3-O-methyldopa, is the method of choice with plasma samples from DOPA-treated patients. In non-DOPA treated individuals the conversion method is superior and has proved to be an accurate and sensitive method for the determination of DOPA levels in plasma and cerebrospinal fluid.
 ...
PMID:Determination of 3,4-dihydroxyphenylalanine (DOPA) in plasma and cerebrospinal fluid by high performance liquid chromatography with electrochemical detection. 314 24

Brain imaging is performed using radiopharmaceuticals by single photon emission computed tomography (SPECT) and positron emission tomography (PET). SPECT and PET radiopharmaceuticals are classified according to blood-brain-barrier permeability, cerebral perfusion and metabolism receptor-binding, and antigen-antibody binding. The blood-brain-barrier (BBB) SPECT agents, such as 99mTcO4-, [99mTc]DTPA, 201TI and [67Ga]citrate are excluded by normal brain cells, but enter into tumor cells because of altered BBB. These agents were used in the earlier period for the detection of brain tumors. SPECT perfusion agents such as [123I]IMP, [99mTc]HMPAO, [99mTc]ECD are lipophilic agents and therefore, diffuse into the normal brain. These tracers have been successfully used to detect various cerebrovascular diseases such as stroke, Parkinson disease, Huntington's disease, epilepsy, dementia, and psychiatric disorders. Xenon-133 and radiolabeled microspheres have been used for the measurement of cerebral blood flow (CBF). Important receptor-binding SPECT radiopharmaceuticals include [123I]QNE, [123I]IBZM, and [123I]iomazenil. These tracers bind to specific receptors in the brain, thus displaying their distribution in various receptor-related cerebral diseases. Radioiodinated monoclonal antibodies were used for the detection of brain tumors. PET radiopharmaceuticals for brain imaging are commonly labeled with positron-emitters such as 11C, 13N, 15O, and 18F, although other radionuclides such as 82Rb, 62Cu and 68Ga also were used. The brain uptake of [13N]glutamate, [68Ga]EDTA and [82Rb]RbCl depends on the BBB permeability, but these are rarely used for brain imaging. Several cerebral perfusion agents have been introduced, of which [15O]water, [13N]ammonia, and [15O]butanol have been used more frequently. Regional CBF has been quantitated by using these tracers in normal and different cerebral disease states. Other perfusion agents include [15O]O2, [11C]CO, [11C]CO2, [18F]fluoromethane, [15O]O2, [11C]butanol, and [62Cu]PTSM. Among the PET cerebral metabolic agents, [18F]fluorodeoxyglucose (FDG) is most commonly used to detect metabolic abnormalities in the brain. Various brain tumors have been graded by [18F]FDG PET. This technique was used to detect epileptic foci by showing increased uptake in the foci during the ictal period and decreased uptake in the interictal period. Differentiation between recurrent tumors and radiation necrosis and the detection of Alzheimer's disease have been made successfully by [18F]FDG PET. Other PET metabolic agents such as [11C]deoxyglucose, and [11C]methylmethionine have drawn attention in the detection of brain tumors. [18F]fluorodopa is a cerebral neurotransmitter agent, which has been found very useful in the detection of Parkinson disease that shows reduced uptake of the tracer in the striatum of the brain.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Radiopharmaceuticals for brain imaging. 781 3

P300 was evoked by a visual oddball and an S1-S2 task in 22 non-demented Parkinson's disease (PD) patients (13 in the early stage, nine in the late stage) and 18 normal controls. Reaction time was also measured. All patients undertook the (99)Tc-ECD SPECT examination. Quantitative regional cerebral blood flow (rCBF) was obtained by overlying SPECT image on the 3D-magnetic resonance image. In the PD patients in the late stage, P300 latency to S2-same and reaction time were significantly prolonged, while rCBF at bilateral frontal, temporal, and the right parietal lobes was decreased. P300 latency to S2-same was significantly correlated with the rCBF at bilateral temporal lobes. Reaction time was significantly correlated with the rCBF at the right frontal and parietal lobes, as well as the temporal and occipital lobes. The results suggest that P300 changes in non-demented PD in the late stage could be related to the temporal lobe dysfunction.
 ...
PMID:The correlation between P300 alterations and regional cerebral blood flow in non-demented Parkinson's disease. 1071 9

The results reported herein address the question of synaptogenesis between adrenal chromaffin cells and striatal neurons. The release of dopamine from chromaffin cells in the presence of striatal neurons was also examined. Co-culture of newborn rat chromaffin cells and striatal neurons at 1:1 ratio was made. Cultures were examined morphologically using immunocytochemistry and ultrastructural techniques (transmission electron microscopy), while quantitation of dopamine in the culture media by HPLC-ECD was also determined. Neurite outgrowth from chromaffin cells was enhanced in the presence of striatal neurons and numerous synaptic-like contacts between these two cell types were observed. Higher concentration of dopamine was also present in the co-culture medium as compared with those containing only chromaffin cells. The development of synapses between these two types of cells may give support to the functionality of transplants in human cases of Parkinson disease (PD).
 ...
PMID:Immunocytochemical, ultrastructural and neurochemical evidences on synaptogenesis and dopamine release of rat chromaffin cells co-cultured with striatal neurons. 1074 6

High-frequency stimulation of the internal pallidum is an effective surgical approach for patients with advanced Parkinson's disease suffering from motor fluctuations and L-dopa induced dyskinesia. To study the acute effects of internal pallidum stimulation, changes in cerebral blood flow were measured by means of a single-day split-dose protocol using 99Tc(m)-ECD SPET. Nine patients with advanced Parkinson's disease and with a clinical picture predominated by tremor and drug-induced dyskinesia, were imaged before and immediately after electrostimulation. Brain perfusion data were mirrored to the same electrode side (five left and four right implants), co-registered and analysed statistically on a voxel-by-voxel basis (Statistical Parametric Mapping) and by an automated volume-of-interest approach. Acute stimulation of the internal pallidum induced a significantly decreased perfusion in the ipsilateral thalamus and striatum, as well as in the right parietal cortex. For the subgroup of seven patients with effective motor score improvements, a significant correlation between thalamic and striatal perfusion changes and UPDRS III motor score was present (P = 0.04). These results suggest that effective stimulation of the internal globus pallidus may produce symptom relief through decreased activity in pallido-thalamo-cortical circuits.
 ...
PMID:99Tc(m)-ECD SPET perfusion changes by internal pallidum stimulation in Parkinson's disease. 1120 14

Cognitive abnormalities have been reported in a large percentage of patients with Parkinson's disease (PD). Often cognitive changes are sub-clinical and involve frontal lobe function. In other occasions they develop into full dementia. Functional neuroimaging may help characterize these abnormalities. We have studied brain perfusion with SPECT and the tracer ECD in 44 PD patients, 22 presenting with normal cognitive function and 22 with clinical and neuropsychological signs of dementia. Compared with 21 healthy controls, demented PD patients showed significant perfusion decrements in all cortical areas, particularly temporal and parietal regions; in the non-demented cohort reductions were limited to the frontal lobe area. These results suggest that brain perfusion abnormalities are present in PD patients. It is speculated that different pathological mechanisms underlie perfusion differences.
 ...
PMID:Perfusion ECD/SPECT in the characterization of cognitive deficits in Parkinson's disease. 1148 94

Four patients with Parkinson's disease (PD) achieved excellent improvement of their unilateral tremor by chronic deep brain stimulation (DBS) of the contralateral ventral intermediate (Vim) nucleus of the thalamus. Repeated measurements of cerebral blood flow were obtained 14 days apart off and on stimulation using 99mTc-ECD SPECT. Subjects were scanned at rest and the data were compared with those of normal healthy volunteers. During stimulation, there were highly significant deactivations in the motor area and supplementary motor area on the electrode side and in the prefrontal area and the anterior cingulum bilaterally. No cerebellar deactivation was detected. We conclude that the mechanism responsible for suppression of parkinsonian tremor by thalamic stimulation is deactivation of thalamocortical activity.
 ...
PMID:Deactivation of thalamocortical activity is responsible for suppression of parkinsonian tremor by thalamic stimulation: a 99mTc-ECD SPECT study. 1171 67

Beta-carbolines have been suggested to be involved in the pathogenesis of Parkinson's disease as a result of their structural similarity to the neurotoxin N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The chloral-derived beta-carboline derivative 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) causes cell loss in neuronal and glial cell cultures and induces a slowly developing neurodegenerative process in rats. In our experiments, effects of TaClo and its derivatives 2-methyl-TaClo (2-Me-TaClo), and 1-dichloromethylene-1,2,3,4-tetrahydro-beta-carboline (1-CCl(2) -THbetaC) on tyrosine hydroxylase (TH) activity were investigated in TH assays using homogenate preparations of the rat nucleus accumbens and recombinant human TH (hTH1). TH activity was determined in vitro by measuring l-DOPA production with HPLC-ECD. Using homogenate preparations, TaClo, 2-Me-TaClo, and 1-CCl(2) -THbetaC inhibited TH in concentrations of 0.1 mm, while 1-CCl(2) -THbetaC in low concentrations enhanced TH activity. When TH was activated by PACAP-27, TaClo, 2-Me-TaClo, or 1-CCl(2) -THbetaC also inhibited activated enzyme activity in high concentrations. However, in the case of 2-Me-TaClo and 1-CCl(2) -THbetaC a biphasic effect was observed with a marked increase of TH activity in the nanomolar range. In our experiments using recombinant hTH1, TaClo, 2-Me-TaClo, or 1-CCl(2) -THbetaC did not modify enzyme activity. After activation of hTH1 by PKA all the tetrahydro-beta-carbolines investigated in this study decreased l-DOPA formation. We suggest that these beta-carbolines modulate dopamine synthesis by interacting with a protein kinase TH-activating system.
 ...
PMID:Modification of tyrosine hydroxylase activity by chloral derived beta-carbolines in vitro. 1206 40

We studied the effects of 0.2 Hz repetitive transcranial magnetic stimulation (rTMS) successively performed 6 times for 2 weeks in 12 patients with idiopathic Parkinson's disease (PD). Ten patients received rTMS to the bilateral frontal cortex (frontal rTMS) and six patients received rTMS to the bilateral occipital cortex (occipital rTMS). Before and after rTMS, we evaluated regional cerebral blood flow (rCBF) using 99m-Tc-ECD single photon emission computed tomography (SPECT) and clinical tests. In an analysis with statistic parametric mapping, both frontal and occipital rTMS reduced rCBF in the cortical areas around the stimulated site. The activities of daily living (ADL) and motor scores of Unified Parkinson's Disease Rating Scale (UPDRS), pronation-supination movements, and buttoning up significantly improved after frontal rTMS than before it, while occipital rTMS had no significant effects in clinical tests.The findings of the present study suggest that successive 0.2 Hz rTMS has outlasting inhibitory effects on neuronal activity around the stimulated cortical areas. Because there were no significant relations between improved clinical tests and reduced rCBF, we speculate that the indirect effects of 0.2 Hz rTMS on subcortical structures are related to improved parkinsonian symptoms. Further studies recruiting large numbers of subjects are required to confirm the efficacy of 0.2 Hz rTMS on PD.
 ...
PMID:Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease. 1268

Deep brain Stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor complications who can no longer be improved by adjustment of medical therapy. Selection of surgery candidates and follow-up after surgery are critical for good outcome. Functional neuroimaging can help in the clinical assessment of these patients. We have used single photon emission computed tomography (SPECT) and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the subthalamic nucleus (STN) in 20 patients with advanced PD. We found a significant increase in the anterior cingulate/supplementary motor cortex in the 12 good responders (change in off unified UPDRS >50%). Conversely, patients with poor response (n=8; change in off UPDRS-III <50% following DBS) revealed a significant worsening of cortical hypoperfusion particularly in the prefrontal areas. No flow decrements were detected in the basal ganglia and in the thalamus in both groups during DBS stimulation suggesting that DBS does not have a "lesion like" effect. If DBS stimulates and does not inactivate STN projection neurons, flow reduction in the poor responders may be secondary to increased inhibitory basal ganglia output.
 ...
PMID:Functional neuroimaging (PET and SPECT) in the selection and assessment of patients with Parkinson's disease undergoing deep brain stimulation. 1290 Jul 31


1 2 3 Next >>