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)

Although it is generally accepted that free radicals are involved in the neurodegenerative process occurring in the dopaminergic neurons of the nigro-striatal system in Parkinson's disease, the exact mechanism of neurodegeneration in vivo is still unknown. We propose that the degeneration of dopaminergic nigrostriatal system in this condition may depend on: (a) existence of free dopamine which oxidizes to aminochrome as a consequence of: (i) overproduction of dopamine; (ii) inhibition and/or low expression of synaptic vesicle catecholamine transporter; (iii) inhibition or low expression of monoamine oxidases; (b) one-electron reduction of aminochrome to leukoaminochrome o-semiquinone radical, which induces neurotoxicity, due to inhibition of DT-diaphorase or the existence of a polymorphism with a point mutation (C --> T) in the cDNA 609 expressing an inactive DT-diaphorase. We suggest that DT-diaphorase plays a neuroprotective role in dopaminergic neurons, which is supported by the following observations: (i) Cu-toxicity is dependent on DT-diaphorase inhibition with dicoumarol in RCSN-3 cells derived from the rat substantia nigra; (ii) the cytotoxic effect of monoamine oxidase-A inhibitor amiflamine in RCSN-3 cells is increased by 2.4-fold (p < 0.001) in the presence of the inhibitor of DT-diaphorase, dicoumarol; (iii) concomitant intracerebral administration of manganese (Mn3+) together with the DT-diaphorase inhibitor dicoumarol into the left medial forebrain bundle produced a behavioral pattern characterized by contralateral rotational behavior when the rats were stimulated with apomorphine, in a manner similar to that observed in animals injected unilaterally with 6-hydroxydopamine; (iv) incubation of RCSN-3 cells with salsolinol in the presence of DT-diaphorase inhibitor significantly decreased cell survival by 2.5-fold (p < 0.001).
Pol J Pharmacol
PMID:Oxidation of dopamine to aminochrome as a mechanism for neurodegeneration of dopaminergic systems in Parkinson's disease. Possible neuroprotective role of DT-diaphorase. 1286 11

Among all the extrapiramidal movement disorders Parkinson's disease (PD) is the one most often submitted to neurosurgical treatment. Technical advances in neurosurgery, neuroimaging and neurophysiology, as well as shortcomings of chronic Levodopa medication (i.e. on/off fluctuations, violent dyskinesia and painful dystonia) have greatly contributed to the renewed interest in the surgical treatment of PD. The attainment of a better understanding of the basal ganglia function and of PD pathophysiology has also encouraged centers to treat Parkinson's disease in recent years. This article presents the current model of PD and the rationale for using GPi, thalamus and STN as target sites in stereotactic surgery.
Neurol Neurochir Pol
PMID:[The currently accepted pathophysiological model underlying surgical management of Parkinson disease]. 1291 Aug 41

The renewal of interest in the neurosurgical treatment of Parkinson's disease (PD) also in Poland results from of our improved understanding of functional anatomy of basal ganglia, developments in neurophysiological and neuroimaging techniques, as well as from advances in stereotactic surgery techniques. In view of the growing number of PD patients referred to surgical treatment and the wide variety of interventions offered, the development of clear of PD patient's selection to surgery seems necessary. Various surgical options and possible targets provide different functional benefits, but the almost 10 year's experience makes us aware also of the limitations and possible complications involved. Algorithms worked out by researchers from the most experienced centers include the following selection criteria as a minimal standard of the PD patient's evaluation before surgery: a reliable diagnosis of Parkinson's disease, at least 5 years of PD duration since the onset of symptoms, good responsiveness to L-dopa or apomorphine, exclusion of severe depression and dementia, neuroimaging (MRI) performed before the surgery, and optimal (but ineffective) attempts at available pharmacological therapy prior to the surgery.
Neurol Neurochir Pol
PMID:[Stereotactic surgery in Parkinson disease: patient selection criteria in the light of existing research]. 1291 Aug 42

For the assessing the incidence of mood disturbances among the neurological out-patients 3287 of them were examined by 111 neurologists during their routine practice. Early diagnosis, the type of mood disturbances and the depth of depression were estimated by the use of Beck's Depression Inventory, the questionnaire based on The Mini-International Neuropsychiatric Interview and Hamilton Depression Rating Scale, as well. Around half of the patients (50.47%) were suspected on depression, as an early diagnosis. In suspected and diagnosed depressive patients the symptoms as anxiety, low activity precordial pain, headaches, dry mouth, constipation, sleep and appetite troubles were significantly (p < 0.01) more frequent than in euthymic subjects. Among all studied patients the episode of depression were found as a final diagnose in 17.2%, recurrent depressive disorders--in 17.6% and dysthymia--in 2.8% of subjects. In finally diagnosed depressive patients the chronic neurological problems were significantly (p = 0.013) more frequent, as the cause of the visit, than in the euthymic ones. The low mood was equally frequent among the patients with Parkinson's disease, multiple sclerosis and cerebrovascular disorders, as well.
Neurol Neurochir Pol 2003
PMID:[Prevalence of depression in neurological outpatients. DEPEND study]. 1291 Aug 52

The aim of the present study was to find out whether a blockade of adenosine A2A receptors by the selective antagonist, SCH 58261, potentiates the attenuating effect of L-DOPA, the well-known antiparkinsonian drug, on parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano- and electromyographic method, which simultaneously measured muscle resistance of a rat hindfoot to passive extension and flexion in the ankle joint and the electromyographic (EMG) activity of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was produced by reserpine (5 mg/kg ip) injected in combination with alpha-methyl-p-tyrosine (alpha-MT, 250 mg/kg ip). L-DOPA (25 mg/kg ip) or SCH 58261 (0.1 mg/kg ip) administered separately, slightly influenced the reserpine + alpha-MT-induced muscle rigidity. However, only ankle joint extension was affected significantly while the effect on flexion of the rat hindfoot was not significant. Neither L-DOPA nor SCH 58261 given separately modified the reserpine-enhanced tonic or reflex EMG activities in both muscles examined. However, when L-DOPA (25 mg/kg) was given together with SCH 58261 (0.1 mg/kg), a clear synergistic effect was seen on both examined movements and muscles. The present results show that the blockade of adenosine A2A receptors potentiates the antiparkinsonian effect of L-DOPA. Since such an effect was seen in different animal models of Parkinson's disease (PD), it seems that co-administration of SCH 58261 may allow for the lowering of the doses of L-DOPA in clinical practice, which indicates a potential therapeutic value of this compound in the treatment of PD.
Pol J Pharmacol
PMID:Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats. 1292 42

In our search for novel, low-toxic, cell-penetrable and neuroprotective antioxidants, we have designed a number of novel N-propargylamine derivatives of nitroxyl, named "JSAKs". The reactivity and antioxidative potency of two selected JSAKs and their parent nitroxyl against reactive oxygen species (ROS) were examined in vitro, in a cell-free gamma-radiolysis and in model Fenton-type reaction systems and compared with those of deprenyl, the investigated member of adjunct therapies in clinical neurology. The efficiency of JSAKs to suppress the oxidative degradation of a model target (deoxyribose), deprenyl and dopamine, caused by hydroxyl radical (*OH) was also investigated. The data demonstrated that the novel compounds, JSAKs, can act as promising antioxidants and protectors of targets against ROS toxicity, thus, providing a sound chemical basis for further comparative investigations of their activity in vivo. The findings were discussed from a mechanistic point of view as well as in terms of the structure-dependent, comprehensive properties of JSAKs as dual-function compounds: antioxidants and anti-apoptotic propargylamines. The novel class of N-propargylamine nitroxyls, JSAKs, may have potential implications for the experimental therapies of Parkinson's disease, where ROS mediate deleterious effects, because these compounds have an ability to either block or reduce the progression of neurotoxic cascade of brain damage.
Pol J Pharmacol
PMID:Antioxidant properties of newly synthesized N-propargylamine derivatives of nitroxyl: a comparison with deprenyl. 1450 18

The aim of our study was to assess the frequency of depression in group of patients with Parkinson's disease (PD) who fulfilled the diagnostic criteria of PD, had normal CT scans and responded well to L-dopa treatment. The sample consisted of 73 consecutive patients (34 women and 39 men), mean age 65.7 (41-81) years, mean duration of disease 6.7 years. Besides neurological examination, in all the patients the degree of motor impairment was evaluated using the UPDRS, H-Y, and SE scales. Moreover, a sociodemographic questionnaire, psychological tests (MADRS, MMSE), and a quality of life scale (PDQ-39) were used. Depression (MADRS scores > 19) was found in 25 (34.2%) of the patients, with major depression (scores > 28) diagnosed in 7 patients (9.5%) and moderate depression (scores between 20 and 28)--in 18 cases (24.6%). In comparison to non-depressed patients, those with depression were older by 0.9 years on the average, their onset of the disease occurred later by 1.7 years, and their mean duration of the disease was longer by 2.6 years. These differences were not statistically significant. Dementia (MMSE scores < or = 23) did not differentiate between the two groups: it was found in 27 depressed patients (37.4%) and in 26 (35.6%) of those without depression. Patients in the depressed group suffered statistically more often from sleep disorders (19 vs. 14; p < 0.001). In this group motor impairment was significantly more marked, as measured by the UPDRS (32.2 vs. 46.8; p < 0.001) and H-Y (2.54 vs 2.98; p < 0.007), and their quality of life as measured by PDQ-39 questionnaire was significantly lower (36.4 vs. 82.24; p < 0.00002). Our data indicate the presence of depression in 34.2% of the sample, i.e. a somewhat lower prevalence rate than that reported in other studies. This may be due to the fact that only outpatient population was analysed, and outpatients are seldom categorized as degree 4 and 5 on the H-Y scale. Depression on PD patients was correlated with their more severe motor disability and considerably lower quality of life. This may suggest a relationship with progression of the disease and more pronounced changes in cerebral neurotransmitters (i.e. endogenous origin), or PD patient's response to their limited mobility and isolation in later stages of the disease (i.e. reactive origin). However, the two factors--endogenous and reactive--may be overlapping, since a majority of PD patients suffer from mild to moderate depression.
Neurol Neurochir Pol
PMID:[Depression in patients with Parkinson's disease]. 1455 83

Deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus (Vim) has been recently introduced by Benabid and his colleagues as a new surgical procedure in the treatment of tremor-dominant Parkinson's disease (PD). The advantage of DBS Vim over lesioning (thalamotomy) is its reversibility and adjustability with the same clinical effect, but without the need to make a destructive thalamic lesion. In this procedure high-frequency stimulation is employed to simulate a thalamic lesion using an implanted electrode connected to a subcutaneously placed neuropacemaker. Four patients with tremor-dominant PD were included in the study. There were 3 men and one women. Three stimulators were implanted in the left and one in the right cerebral hemisphere. The patients were evaluated using clinical scales, before and up to 24 months after surgery. Adverse effects associated with chronic Vim stimulation were mild and reversible. Chronic thalamic stimulation is effective for drug-resistance parkinsonian tremor suppression, with few adverse side-effects. The method results in a significant improvement of function.
Neurol Neurochir Pol
PMID:[Deep brain stimulation of the Vim nucleus of the thalamus in the treatment of parkinsonian tremor]. 1455 90

The following article presents current views on the possibility of pharmacological treatment of Parkinson's disease (PD). Research conducted on drugs with potentially neuroprotective effects has changed the way we viewed the treatment of early stages of PD. Beginning treatment with the application of dopamine agonists decreases the risk of the occurrence of motor complications, particularly high with young individuals. The treatment of advanced stages of the disease currently requires the application of levodopa combined with other medicines, such as dopamine agonists or catechol-O-methyl transferase (COMT) inhibitors. Selecting treatment options should be individualized for each patient; it should take into account the variability of the clinical picture dependent on the progression of the disease, and the possibility of the occurrence of undesirable adverse effects of the drugs prescribed.
Neurol Neurochir Pol
PMID:[The current therapies for parkinson's disease. Part I: pharmacological treatment]. 1459 60

Surgical treatment of Parkinson's disease (PD) is indicated in patients with severe neurological symptoms (tremor, bradykinesia, rigidity)--who do not benefit from nor tolerate pharmacological therapy. Surgery for PD modifies the motor system function by lesioning or electrostimulation of thalamic, pallidal or subthalamic nuclei. The technological progress together with refined CNS monitoring enabled wider application of deep brain stimulation (DBS). The efficacy of DBS is comparable with lesioning techniques (thalamotomy or pallidotomy) however bears less adverse effects. Both lesioning and DBS are generally well tolerated by patients. The side effects are mostly transient and neurological complications, if occur, usually do not affect quality of patient's life. Unfortunately, the modern surgery for PD is still very expensive and demanding for a large team of specialists and high technology.
Neurol Neurochir Pol
PMID:[Current therapies for parkinson's disease. Part II: surgical treatment]. 1459 61


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