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)

Ten free monoamines and their metabolites in plasma and cerebrospinal fluid (CSF) were simultaneous measured in 6 levodopa-untreated (LU), 18 levodopa-treated (LT) and 37 levodopa-withdrawn (LW) Chinese patients with Parkinson's disease (PD) and 26 controls. We found that the levels of these substances in LW patients were not significantly different from those in LU patients. In LU- and LW-PD patients, CSF epinephrine (EPI) was higher (P < 0.05) than that of the controls. 3-methoxy-DOPA (3-OMDOPA) might not inhibit the accumulation of 3,4-dihydroxyphenylalanine (DOPA) and dopamine metabolites in CSF. Levodopa treatment might change the dopaminergic and serotoninergic neuronal systems, but not the noradrenergic or adrenergic neuronal systems, in CNS of PD patients. Benserazide (a peripheral decarboxylase inhibitor) in Madopar might decrease the levels of serotonin (5-HT) and norepinephrine (NE), but not those of DOPA and homovanillic acid (HVA), in plasma. HVA, NE and EPI in plasma were not good indices for those in CSF. Otherwise, our results were consistent with some other studies by showing a significantly lower level (P < 0.01) of HVA in CSF of LU- and LW-PD patients than that of the controls, while no difference for NE, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindole acetic acid (5-HIAA) or 3-OMDOPA was noted. The severity of clinical disability was related to the deficiency of CSF HVA and DOPAC in LU- and LW-PD patients; however, there was no relationship between clinical symptoms of tremor, rigidity-bradykinesia, autonomic dysfunction, dementia, depression or levodopa-induced dyskinesia and CSF monoamines or their metabolites.
 ...
PMID:Monoamines and their metabolites in plasma and lumbar cerebrospinal fluid of Chinese patients with Parkinson's disease. 833 58

Dopa-induced "peak dose" dyskinesia (DID) observed during the treatment of Parkinson's disease patients has traditionally been linked primarily to dopamine D1 receptor-mediated mechanisms. However, in MPTP-induced parkinsonian monkeys with DID, the administration of selective dopamine D1 or D2 agonists will, in the case of D1 agonists result in similar antiparkinsonian effect but with much less dyskinesia. Thus, once primed, enhanced D1 neural transmission might in fact benefit DID. In drug-naive MPTP monkeys, the high dyskinetic potential of several selective D2 agonists and the more favorable outcome on dyskinesia resulting from the continuous stimulation of D2 receptors (leading to D2 receptor down regulation) are important clues suggesting the primary role played by D2 receptor-mediated mechanisms in the dyskinesia priming process. Further clinical studies using drugs selective for the various dopamine receptor subtypes and of different efficacy half-lives are needed to validate our primate data.
 ...
PMID:DOPA-induced "peak dose" dyskinesia: clues implicating D2 receptor-mediated mechanisms using dopaminergic agonists in MPTP monkeys. 874 15

The Long-Term Dopa Syndrome (LTDS) is one of the main problems in the management of advanced parkinsonian patients. A transient L-Dopa withdrawal (Drug Holiday, DH) can be useful to improve the drug response after DH, even if this approach presents risks due to patient akinesia. We tried to verify if Apomorphine sc administration during DH (DH with Apomorphine, DHA) can: a) reduce the risks connected with DH: b) maintain the benefits of DH: c) standardize the duration of DH. Twenty-five parkinsonian patients with LTDS were treated with Apomorphine sc during DH (14 days). No patient had any severe side effects. The follow-up at 180 days, conducted using the Unified Parkinson's Disease Rating Scale, demonstrated a significant improvement in the clinical conditions of about 70% of the patients, allowing a 27.1% reduction in daily L-dopa dosage. DHA can represent a valid therapeutical approach for parkinsonian patients with LTDS.
 ...
PMID:Apomorphine SC treatment in parkinsonian patients with long-term L-dopa syndrome during L-dopa drug holiday. 874 22

It has been reported that the F-Dopa (FD) uptake in patients with idiopathic Parkinson's disease (PD) decreased significantly in the caudate and putamen when compared to controls. The FD uptake severely decreased in the putamen, while it was relatively spared in the caudate nucleus. We also previously reported that atypical parkinsonism with no or little tremor showed a homogeneously reduced FD uptake in both the caudate and the putamen. In this study we evaluated the caudate and the putaminal FD uptakes in relation to the three main symptoms in PD. The FD uptake was measured by PET with 6-L-[18F]fluorodopa in 17 patients with PD. The caudate and the putaminal FD uptake ratios to the cerebellum at 120 min were evaluated. The caudate and the putaminal FD uptake ratios in the patients with PD decreased as their clinical stages advanced. These decreases also correlated with the degree of rigidity and bradykinesia. However, such decreases did not correlate with the degree of tremor. The caudate-putamen index (CPI)(%), which was calculated by a formula based on the difference in the uptakes of the caudate and putamen divided by the caudate uptake, indicated 11.6 +/- 3.6, 16.5 +/- 5.5 and 18.3 +/- 4.1 in the group of no, mild and moderate tremor, respectively, and increased as the degree of tremor advanced. The CPI in the group of moderate tremor significantly increased from that in the group of no tremor (P < 0.04). However, the CPI did not correlate with the clinical stage, the degree of rigidity or the degree of bradykinesia. The FD/PET study therefore effectively demonstrated the severity of the clinical symptoms of rigidity and bradykinesia in patients with PD in correlation with a decrease in the FD uptakes in the caudate and the putamen, and it also demonstrated that the severity of tremor might have a different mechanism from that of such other symptoms as rigidity and bradykinesia.
 ...
PMID:Differences in the reduced 18F-Dopa uptakes of the caudate and the putamen in Parkinson's disease: correlations with the three main symptoms. 881 66

GTP cyclohydrolase I (GTPCH) has recently been identified as the first causative gene for Dopa-responsive dystonia (DRD). DRD typically presents with dystonia in the lower limbs in childhood, but may produce an akinetic-rigid syndrome in middle and old age. We have sequenced the GTPCH gene in 29 Parkinsonian patients without a positive family history for DRD, but who shared at least one feature of the akinetic-rigid presentation of DRD: 23 patients had at least one living relative who also suffered from an akinetic-rigid syndrome; 2 patients had an abnormally mild course of their parkinsonism which was extremely dopa-responsive. DNA was also analysed from 4 brain samples of patients who were clinically diagnosed as suffering from Parkinson's disease, but then did not show any pathological findings at post mortem. No changes in the sequence of the GTPCH gene were detected. We conclude that so far there is no evidence that mutations of the GTPCH gene are responsible for the development of parkinsonism in patients without a positive family history of DRD.
 ...
PMID:The GTP-cyclohydrolase I gene in atypical parkinsonian patients: a clinico-genetic study. 888 Jun 88

Among heterogeneous diseases manifested by parkinsonism beginning early in life, there is a disease presenting with marked diurnal fluctuation of symptoms, called autosomal recessive early-onset parkinsonism with diurnal fluctuation (AR-EPDF). To identify the characteristics of this condition as a disease entity, we examined the clinical manifestations of AR-EPDF patients (Group I, n = 42) in comparison with those of early-onset parkinsonism patients without diurnal fluctuation (Group II, n = 34). Family history suggesting autosomal recessive inheritance was noted in 85.7% of Group I patients and 17.6% of Group II. The male-to-female ratio was 1: 1.8 in Group I, and 1:0.89 in Group II. Age at onset showed a standard distribution with an average of 25.6 years (SD: +/- 7.7) in Group I and an average of 32.7 with an increasing pattern toward 40 years in Group II. The initial symptom was dystonic gait disturbance in 42.9% of Group I and 5.9% of Group II, parkinsonian gait in 19.9% of Group I and 2.9% of Group II, and tremor in 28.6% of Group I and 41.2% of Group II. The main clinical feature was parkinsonism in both groups. Diurnal fluctuation of parkinsonism was remarkable in all but one (97.6%) of Group I, while it was not observed in Group II. Dystonic postures were noted in 79.4% of Group I and in 37.1% of Group II; hyperactive tendon reflexes in 74.3% of Group I patients and in 20% of Group II. Autonomic symptoms were mild in both groups. None of the Group I patients had dementia while two of Group II did. Levodopa was markedly effective in both groups. Dopa-induced dyskinesia was observed in 96.8% of Group I and in 61.8% of Group II. As for progression of the disease, the Hoehn-Yahr stage of patients on medication was evaluated as 2.2 +/- 0.7 (mean +/- SD) in Group I and 3.1 +/- 1.1 in Group II for a period of 10 to 20 years of onset, 2.5 +/- 0.8 in Group I and 3.3 +/- 0.5 in Group II for 20 to 30 years, and 3.2 +/- 0.9 in Group I and 4.3 +/- 0.6 in Group II after 30 years. There were significant differences between the two groups in the frequency of positive family history, in the mean and distribution of age at onset, in the incidence of dystonic gait as the initial symptom, and in the incidences and medians of the variables including dystonia, hyperreflexia and dopa-induced dyskinesia, as well as in the progression of the disease. Thus, we have successfully characterized the clinical features of AR-EPDF and demonstrated that diurnal fluctuation is a cardinal symptom of this disease. Reported pathologic studies on AR-EPDF showed the nigral lesion characterized by non-Lewy body type degeneration and the occurrence of melanin-poor neurons. These pathologic findings as well as the clinical manifestations differentiate AR-EPDF from Parkinson's disease and from autosomal-dominant familial parkinsonism. Low melanin-content of the nigral neurons is also a striking feature of hereditary progressive dystonia with diurnal fluctuation, in which unlike AR-EPDF there is no neuronal loss in the substantia nigra.
 ...
PMID:[Autosomal recessive early-onset parkinsonism with diurnal fluctuation (AR-EPDF)--clinical characteristics]. 895 46

Autoxidation of dopamine or L-DOPA (3,4-dihydroxyphenylalanine) generates reactive oxygen species (ROS), i.e., hydrogen peroxide, superoxide, and hydroxyl radical, which are potentially cytotoxic. Increased formation of ROS has been proposed to be involved in the pathogenesis of many human diseases, including Parkinson's disease. Several reports suggest that R(-)-deprenyl (an MAO-B inhibitor and anti-Parkinsonian drug) may directly or indirectly exert antioxidant effects and thus protect neurons. We have assessed the toxic effects of dopamine and L-DOPA toward catecholaminergic neuroblastoma SH-SY5Y cells and whether R(-)-deprenyl and several structurally related compounds possess antioxidant effects in this system. The results show that both dopamine and L-DOPA are quite cytotoxic toward SH-SY5Y cells. R(-)-deprenyl rather than reducing this dopamine-induced toxicity actually enhances it. Structural analogues of R(-)-deprenyl, such as 4-methyldeprenyl, (-)-methylamphetamine, and clorgyline, exhibited similar effects. Some different MAO-B inhibitors, namely, the aliphatic N-methylpropargylamines, e.g., (+/-)-M-2-PP [N-(2-pentyl)-N-methylpropargylamine] and N-[2-hexyl]-N-methylpropargylamine, which can also protect and rescue neurons in several in vivo and in vitro models, did not exacerbate the cytotoxicity of dopamine. Neither R(-)-deprenyl nor (+/-)-M-2-PP affected the L-DOPA-induced cytotoxicity toward SH-SY5Y cells.
 ...
PMID:R(-)-deprenyl potentiates dopamine-induced cytotoxicity toward catecholaminergic neuroblastoma SH-SY5Y cells. 900 48

Short latency somatosensory evoked potentials were measured in 10 patients with Parkinson's disease before and after the administration of Apomorphine 5 mg sc. Eight of these subjects were reassessed after one month of treatment with Levo-Dopa. These potentials were measured in other nine subjects before and after one month of treatment with Selegiline 10 mg od. There was a significant increase of frontal potential N30 in nine of 10 subjects that received apomorphine, in seven of eight patients treated with Levo-dopa and seven of nine patients treated with Selegiline. No changes in N20 parietal potential were observed. During apomorphine test, changes in N30 potential preceded clinical improvement in six patients and occurred simultaneously in three patients. No changes with apomorphine in N30 potential were observed in two healthy males. There was no relationship between electrophysiological changes and duration of disease or motor fluctuations. It is concluded that short latency somatosensory evoked potentials are an objective means of measuring dopaminergic response in patients with Parkinson's disease.
 ...
PMID:[Somatosensory evoked potentials and symptomatic response to dopaminergic drugs in Parkinson's disease]. 900 41

Clinicopathological identification of juvenile parkinsonism(JP) was described in reference to Dopa-responsive syndrome or to dopamine-dependent disorders. Recently, hereditary progressive dystonia(HPD), a dopamine-dependent disorder, was identified as a nosological entity from JP and Parkinson's disease(PD) by discovery of mutations of the gene. JP includes young onset Parkinson's disease(YOPD) and idiopathic JP with much younger-onset cases. YOPD belongs to PD-nosology based on clinical and pathological findings of our own autopsied cases. However, the idiopathic JP' might involve independent pathophysiological changes. Namely, cases of the JP are associated with atypical pathological findings with lack of Lewy body or hypoplasia of the substantia nigra and specific clinical manifestations of autosomal recessive trait and of dystonic feature and diurnal fluctuation of the symptoms.
 ...
PMID:[Definition and nosological concept of juvenile parkinsonism]. 901 26

Intracranial implantation of polymer-encapsulated PC-12 cells has been shown to improve motor behavioral performance in animal models of Parkinson's disease. The purpose of this blinded study was to examine whether such improvement is associated with the active uptake and metabolism of dopamine precursors by intracerebrally implanted polymer-encapsulated PC-12 cells. In an in vitro experiment we demonstrate that 3H-dopamine uptake by PC-12 cells was 10(8) fmol/min x 10(6) cells, and that this uptake can be specifically blocked 88% by the addition of 10nM of nomifensine. In the in vivo experiments, polymer-encapsulated PC-12 cells were implanted in four MPTP-treated monkeys into the left deep parietal white matter (R1) or left striatum (R2-4). A fifth MPTP-treated monkey (R5) served as a control and received left striatal implants of empty capsules. 18-F-Dopa Positron Emission Tomography (PET) imaging was performed on each monkey before and after implantation surgery by blinded investigators. PET images obtained 5-13 wk after implantation demonstrated well delineated focal areas of high 18F-dopa uptake in R1, R2, and R4. The focal area of high 18F-dopa uptake in R1 precisely coregistered on a brain magnetic resonance image to the site of implantation. R3 (in whom the polymer-encapsulated PC-12 cells demonstrated poor cell survival upon explantation) and R5 (empty capsules) failed to demonstrate any area of increased 18F-dopa uptake in their PET images. Histological examination of the host brain revealed no sprouting of dopaminergic nerve terminals around the implantation sites of the polymer-encapsulated PC-12 cells. These results indicate that the previously noted behavioral improvement after intrastriatal implantation of polymer encapsulated PC-12 cells is at least in part due to their highly specific uptake and metabolism of dopamine precursors. Furthermore, these data suggest that polymer-encapsulated PC-12 cells can store, reuptake, and functionally replenish dopamine and therefore, may be an effective treatment for Parkinson's disease.
 ...
PMID:Polymer-encapsulated PC-12 cells demonstrate high-affinity uptake of dopamine in vitro and 18F-Dopa uptake and metabolism after intracerebral implantation in nonhuman primates. 933 98


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