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)

It is well recognized that 1,2,3,4-tetrahydroisoquinoline (TIQ) is a substance capable of inducing in animals a syndrome, regarded as an animal model of Parkinson's disease. This study was designed to evaluate the effect of the endogenous neurotoxin TIQ on the brain noradrenaline (NA) metabolism in mice and on an arterial blood pressure in rats. It was shown for the first time that TIQ significantly increased NA metabolism, induced NA release and raised the level of its final metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), in mouse brain. The comparative biochemical studies using specific agonist (clonidine) and antagonist (yohimbine) of alpha2-adrenergic receptors ligands have shown that observed biochemical effects were similar to those produced by alpha2-adrenergic antagonist, yohimbine. In functional studies, the systolic and diastolic blood pressure was measured using a non-invasive blood pressure transducer. Both acute and multiple treatment with TIQ produced a strong hypotensive effect, having decreased both systolic and diastolic blood pressure in rats. Development of tolerance to the hypotensive effect was observed after multiple treatment with TIQ. The data coming from these experimental studies apparently suggest an important role of the noradrenergic system in the mechanism of action of endogenous compounds from TIQ group. The results may also support the hypothesis assuming a causal relationship between noradrenergic dennervation, activity of the nigrostriatal dopamine system, and some clinical manifestation of Parkinson's disease.
Pol J Pharmacol
PMID:Role of noradrenergic system in the mechanism of action of endogenous neurotoxin 1,2,3,4-tetrahydroisoquinoline: biochemical and functional studies. 1202 40

Factors underlying pathogenesis of diseases are currently being searched. In recent years increasing number of reports on genetic background of central nervous system diseases have appeared. In the search of factors that can precipitate degeneration of dopaminergic neurons the role of enzymes catabolising xenobiotics (CYP2D6, NAT2) and enzymes metabolising catecholamines (COMT, MAO B) has been postulated. Polymorphism of genes coding for isotypes characterised by different biological activity could be responsible for the propensity for Parkinson's disease, progression and efficacy of pharmacotherapy of the disease.
Neurol Neurochir Pol
PMID:[Role of gene polymorphism of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAOB), cytochrome P450 2D6 (CYP2D6) and N-acetyltransferase 2 (NAT2) in pathogenesis of Parkinson's disease]. 1205 3

Urinary dysfunction in idiopathic Parkinson's disease (IPD) has already been described, however its incidence, urodynamic pattern, dependence on the severity of parkinsonism as well as improvement with levodopa treatment are not exactly known. The aim of the study was to evaluate the frequency of urinary disturbances in patients with idiopathic Parkinson's disease and their relationship to treatment with levodopa. The investigation was carried out on 41 IPD patients aged 37-84 (mean 61.6) years. The neurological examination, including evaluation of parkinsonism according to UP-DRS scale was conducted together with the urological tests, including uroflowmetry and cystometry. Patients with infection of the urinary tract and with prostate hypertrophy were excluded from the study. 32 (78%) patients had urinary symptoms: frequency in 27 cases (65%), urgency in 9 cases (21%), urge incontinence in 1 case and dysuria in 1 case. Disorders in urodynamic examination were found in 26 cases (63%); they were: detrusor hyperactivity in 21 cases (51%), prolonged time of micturition in 18 cases (44%) and decrease of maximum flow rate in 19 cases (46%). Detrusor hyperactivity was more frequent in patients with extended parkinsonian motor signs. The results of the examination indicate frequent urinary disturbances (70%) in IPD, which improve during treatment with increased dose of levodopa.
Neurol Neurochir Pol
PMID:[Micturition disturbances in Parkinson's disease. Clinical and urodynamic evaluation]. 1205 13

Falls in Parkinson's disease may pose a significant threat for patients. This is not only a clinical problem, but also an economic one. The effects of falls may cause deterioration of the quality of life for both patients and their caretakers. The causes of falls are not clinically uniform: the falls are caused by various factors and require a differential diagnosis. The purpose of this paper is to analyse the above mentioned causes, as well as to draw clinicians' attention to the possibility of effective therapy for certain disorders that cause such falls in patients with Parkinson's disease. 51 patients with recognized Parkinson's disease were examined, including 25 persons who reported falls that had occurred within the past 6 months and 26 persons who had no falls. In both groups there were patients with different types of the disease (tremulous, akinetic-hipertonic and mixed). The clinical status of the patients was assessed using the Hoehn and Yahr scale. In each patient Schellong test and EEG examinations were performed. It has been established that the occurrence of falls is related to the duration of the disease (on average 9.6 years in the group with falls versus 6.2 years in the group without falls) and the daily levodopa dosage (on average 806.0 mg in the group with falls versus 499.0 mg in the group without falls). The proportion of patients with abnormalities in the EEG (revealed mainly as slowing of EEG background activity) was notably higher in the group with falls. The comparison of such groups from the point of view of sex, age, stage of the disease and the occurrence of asymptomatic orthostatic hypotension did not reveal any statistically significant differences. The analysis of the causes of falls in the examined patients revealed that in 8 cases they fell due to unstable posture, 4--due to freezing or festination, 1--due to symptomatic orthostatic hypotension, 1--due to co-existing neurological disorders, 2--due to the heart arrhythmia (requiring implantation of pacemaker), in 8 persons--due to toppling falls and in 1 patients the falls could not be classified.
Neurol Neurochir Pol
PMID:[Analysis of causes for falls in people with Parkinson's disease]. 1205 16

Impairment of swallowing is a common symptom in advanced stage of Parkinson's disease and severe defect of this function may cause aspiration pneumonia, problems with food intake and cachexy. The aim of this study was to assess the reflex and oral, pharyngeal, oesophageal phase of swallowing. Eleven patients with Parkinson's disease and 9 healthy subjects were investigated by electromyography (EMG) and oesophageal scintigraphy. The study demonstrates delayed triggering of swallowing reflex (543 +/- 84 ms in patients with PD vs. 230 +/- 66 ms in controls, p < 0.05) and prolongation of laryngeal movement (1880 +/- 140 ms vs. 1349 +/- 154 ms, p < 0.05). The prolongation of the oesophageal phase of swallowing with predilection to retention of water in lower one/third part of esophagus (12.45 +/- 2.45 s vs. 6.45 +/- 1.18 s, p < 0.001) was observed. The dysphagia limit, that is the maximum amount of water swallowed at once, was also evaluated (all normal subjects are able to swallow 20 ml water or more at once). In the studied patients with Parkinson's disease it was 4.5 +/- 0.86 ml. These results evidently and objectively indicate the presence of swallowing disorders in Parkinson's disease. Dysphagia was observed in all studied patients, although only 8 of them complained about it. In other 3 cases the impairment of swallowing was subclinical and it was connected with prolongation of oesophageal phase.
Neurol Neurochir Pol
PMID:[Swallowing disorders in Parkinson's disease]. 1218 1

The assessment of the levels of IgG antibodies against Bordetella pertussis in serum using ELISA test was performed in 59 patients (including 30 patients with Parkinson's disease--PD, 15 patients with other non-inflammatory neurological diseases, and 14 controls). The average age in the groups was 64.0, 64.4, and 58.7 years, respectively. Positive results were found in 17/30 patients with PD, 8/15 subjects with other non-inflammatory neurological diseases and in 7/14 controls. The above results are surprising and demonstrate a high incidence of subclinical whooping cough among the adult population. No statistically significant difference has been found between patients with Parkinson's disease and patients with other neurological diseases. A tendency is observed for a higher percentage of negative results among controls in comparison with patients with Parkinson's disease and other non-inflammatory neurological diseases.
Pol Merkur Lekarski 2002 Sep
PMID:[Frequency of Bordetella pertussis antibodies in serum of patients with Parkinson's disease]. 1247 66

The paper is a review of current experience with use of gabapentin--a new antiepileptic drug--in neurologic conditions others than epilepsy. Mechanism of action of the drug is not fully elucidated yet. However it proved to be effective in therapy of chronic pain, especially in neuropathic pain, neuralgia, low back pain, reflex sympathetic dystrophy and erythromelalgia. Gabapentin is also effective in pain and spasticity in multiple sclerosis. Clinical studies of gabapentin in movement disorders, such as Parkinson disease, essential tremor and atrophic lateral sclerosis are discussed in the paper. It can be summarized that gabapentin is a valuable medication and the use thereof in neurology is not limited to epilepsy.
Neurol Neurochir Pol
PMID:[GABApentin--new therapeutic possibilities]. 1252 21

It is well established that in the CNS, endogenous adenosine plays a pivotal role in neurodegeneration. A low, nanomolar concentration of adenosine is normally present in the extracellular fluid, but it increases dramatically during enhanced nerve activity, hypoxia or ischemia. In these pathological conditions, adenosinergic transmission-potentiating agents, which elevate adenosine level by either inhibiting its degradation (adenosine deaminase and kinase inhibitors) or preventing its transport, offer protection against ischemic or excitotoxic neuronal damage. The directly acting adenosine A1 receptor agonists are known to mediate neuroprotection, mostly by the blockade of Ca2+ influx, which results in the inhibition of glutamate release and reduction of its excitatory effects at a postsynaptic level. More recent data have shown that antagonists of adenosine A2A receptors markedly reduce cerebral ischemic damage in animal models of focal and global ischemia. Moreover, these compounds attenuate the neuronal loss induced by excitatory amino acids (EAA). A neuroprotective effect of adenosine A2A receptor antagonists was also shown in animal models of Parkinson's disease (MPTP, 6-OHDA, methamphetamine). Hence, it might be suggested that adenosine A2A receptor antagonists may represent a novel strategy in the therapeutic approach to pathologies characterized by acute or chronic neurodegenerative events, since they not only reverse motor impairment but can act as neuroprotective compunds by promoting cell survival.
Pol J Pharmacol
PMID:Neuroprotective role of adenosine in the CNS. 1252 85

Based on a literature review, the application of Acetylcholinesterase inhibitors, IAchE (donepezil, rivastigmine, galantanine) in the treatment of various illnesses which have cholinergic system disability and dementia in their course--(dementia with Lewy bodies, vascular dementia, Parkinson's disease, Multiple Sclerosis, Down Syndrome), delirium symptoms (e.g. Korsakoff psychosis), hyperkinesis, attention and memory disorders--is presented. Promising results in the treatment of late dyskinesias, in schizophrenia with impaired cognitive function, as well as in the additional treatment of various psychotic states are noted. It should be stressed that in Poland, the IAchE have been approved only in the treatment of slight to moderate dementia in the course of Alzheimer's disease.
Psychiatr Pol
PMID:[Acetylcholinesterase inhibitors--beyond Alzheimer's disease]. 1264 32

The cause of chronic nigral cell death in Parkinson's disease (PD) and the underlying mechanisms remain elusive. The selective action of exogenous and endogenous neurotoxic substances can provide partial explanation of these processes. 1-Methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) is an exogenous neurotoxin producing parkinsonism in humans, monkeys and various animals as the result of MAOB-catalyzed conversion of it to the 1-methyl-4-phenyl-pyridinium ion (MPP+), which selectively kills the nigrostriatal dopaminergic neurons. On the other hand, various isoquinoline derivatives were found in the brain, and they are considered to be the endogenous neurotoxins with neurochemical properties similar to those of MPTP, which cause PD. Among them, 1,2,3,4-tetrahydroisoquinoline (TIQ), 1-benzyl-TIQ, and 1-methyl-5,6-dihydroxy-TIQ (salsolinol) have the most potent neurotoxic action. Since PD is a slowly progressing neurodegenerative disease, it has been suggested that it could be connected with excitotoxicity and apoptosis. Therapeutic strategies should focused on the search for the drugs exhibiting antiapoptotic potential such as: antioxidants, MAOB inhibitors, dopaminergic drugs and free radical scavengers.
Pol J Pharmacol
PMID:Endogenous risk factors in Parkinson's disease: dopamine and tetrahydroisoquinolines. 1286 10


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