H M Ruottinen, J O Rinne, U H Ruotsalainen, J R Bergman, V J Oikonen, M T Haaparanta, O H Solin, A O Laihinen, U K Rinne
The effect of peripheral catechol-O-methyltransferase (COMT) inhibition with entacapone on striatal uptake of 6-[18F]fluoro-L-dopa (FDOPA) was studied with PET both without and with entacapone in fifteen advanced parkinsonian patients and six healthy controls. Entacapone significantly enhanced the fraction of unmetabolized FDOPA in plasma from 16% to about 50% at 80 minutes after FDOPA injection in all subjects. The striatal to occipital ratios and the striatal FDOPA uptake, expressed as a modified decarboxylation coefficient (k3R0), was significantly increased in healthy controls, whereas in parkinsonian patients the increase was significant only in the caudate. On the other hand, the influx constant (Ki) decreased significantly in the caudate and putamen in parkinsonian patients; in healthy controls the Ki remained virtually unchanged. Effective peripheral COMT inhibition markedly increased the fraction of FDOPA in plasma and thus its availability in the brain for decarboxylation both in patients and control subjects. However, the change in striatal FDOPA uptake was modest in the advanced parkinsonian patients as compared to that in control subjects, because of the advanced disease, decreased storage capacity, or both.
{"title":"Striatal [18F]fluorodopa utilization after COMT inhibition with entacapone studied with PET in advanced Parkinson's disease.","authors":"H M Ruottinen, J O Rinne, U H Ruotsalainen, J R Bergman, V J Oikonen, M T Haaparanta, O H Solin, A O Laihinen, U K Rinne","doi":"10.1007/BF02251225","DOIUrl":"https://doi.org/10.1007/BF02251225","url":null,"abstract":"<p><p>The effect of peripheral catechol-O-methyltransferase (COMT) inhibition with entacapone on striatal uptake of 6-[18F]fluoro-L-dopa (FDOPA) was studied with PET both without and with entacapone in fifteen advanced parkinsonian patients and six healthy controls. Entacapone significantly enhanced the fraction of unmetabolized FDOPA in plasma from 16% to about 50% at 80 minutes after FDOPA injection in all subjects. The striatal to occipital ratios and the striatal FDOPA uptake, expressed as a modified decarboxylation coefficient (k3R0), was significantly increased in healthy controls, whereas in parkinsonian patients the increase was significant only in the caudate. On the other hand, the influx constant (Ki) decreased significantly in the caudate and putamen in parkinsonian patients; in healthy controls the Ki remained virtually unchanged. Effective peripheral COMT inhibition markedly increased the fraction of FDOPA in plasma and thus its availability in the brain for decarboxylation both in patients and control subjects. However, the change in striatal FDOPA uptake was modest in the advanced parkinsonian patients as compared to that in control subjects, because of the advanced disease, decreased storage capacity, or both.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"10 2-3","pages":"91-106"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02251225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20539874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S Higuchi, T Muramatsu, H Arai, M Hayashida, H Sasaki, J Q Trojanowski
Disturbances of the dopamine system are involved in the pathogenesis of idiopathic Parkinson's disease (PD). Although genetic factors may play a role in the etiology of PD, there is little direct evidence implicating a specific gene. We conducted a study to test the hypothesis that allelic variations of the dopamine receptors (D2, D3, D4) and the dopamine transporter (DAT) contribute to the susceptibility to PD. Association analyses of 70 Japanese PD patients and the same number of age-matched controls did not reveal any association between alleles of the D2, D3 or D4 receptor genes or the DAT gene and PD. Thus, our results suggest that factor(s) other than allelic variations of these key proteins in the dopamine system contribute to the susceptibility to PD.
{"title":"Polymorphisms of dopamine receptor and transporter genes and Parkinson's disease.","authors":"S Higuchi, T Muramatsu, H Arai, M Hayashida, H Sasaki, J Q Trojanowski","doi":"10.1007/BF02251226","DOIUrl":"https://doi.org/10.1007/BF02251226","url":null,"abstract":"<p><p>Disturbances of the dopamine system are involved in the pathogenesis of idiopathic Parkinson's disease (PD). Although genetic factors may play a role in the etiology of PD, there is little direct evidence implicating a specific gene. We conducted a study to test the hypothesis that allelic variations of the dopamine receptors (D2, D3, D4) and the dopamine transporter (DAT) contribute to the susceptibility to PD. Association analyses of 70 Japanese PD patients and the same number of age-matched controls did not reveal any association between alleles of the D2, D3 or D4 receptor genes or the DAT gene and PD. Thus, our results suggest that factor(s) other than allelic variations of these key proteins in the dopamine system contribute to the susceptibility to PD.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"10 2-3","pages":"107-13"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02251226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20539875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
There has been much speculation of late as to whether antagonists of glutamate receptors can be used to combat the motor difficulties of Parkinson's disease, either as monotherapy, or as polytherapy to boost the effects of conventional L-DOPA treatment. The latter seems to be the more practical approach and the therapeutic implications of such treatment have been discussed in some detail. However, the mechanisms by which glutamate antagonists potentiate the antiparkinsonian actions of L-DOPA, remain cryptic. In this review we have explored the evidence and considered the practicality of using NMDA and non-NMDA receptor blockers to treat parkinsonism, as well as focusing on the ways in which the behavioural synergy between dopamine and glutamate systems could conceivably arise at the cellular level. Particular attention has been paid to the differential interaction between glutamate antagonists and postsynaptic dopamine D1 and D2 receptory mechanisms, since these are currently believed to reflect the activity of the two major basal ganglia output circuits: the so-called direct pathway to the substantia nigra and the indirect pathway to the globus pallidus. Finally, we have considered the new proposal, that inhibiting glutamate transmission in the basal ganglia accelerates the enzymic conversion of L-DOPA to dopamine at presynaptic sites.
{"title":"Antiparkinsonian actions of glutamate antagonists--alone and with L-DOPA: a review of evidence and suggestions for possible mechanisms.","authors":"M S Starr","doi":"10.1007/BF02251229","DOIUrl":"https://doi.org/10.1007/BF02251229","url":null,"abstract":"<p><p>There has been much speculation of late as to whether antagonists of glutamate receptors can be used to combat the motor difficulties of Parkinson's disease, either as monotherapy, or as polytherapy to boost the effects of conventional L-DOPA treatment. The latter seems to be the more practical approach and the therapeutic implications of such treatment have been discussed in some detail. However, the mechanisms by which glutamate antagonists potentiate the antiparkinsonian actions of L-DOPA, remain cryptic. In this review we have explored the evidence and considered the practicality of using NMDA and non-NMDA receptor blockers to treat parkinsonism, as well as focusing on the ways in which the behavioural synergy between dopamine and glutamate systems could conceivably arise at the cellular level. Particular attention has been paid to the differential interaction between glutamate antagonists and postsynaptic dopamine D1 and D2 receptory mechanisms, since these are currently believed to reflect the activity of the two major basal ganglia output circuits: the so-called direct pathway to the substantia nigra and the indirect pathway to the globus pallidus. Finally, we have considered the new proposal, that inhibiting glutamate transmission in the basal ganglia accelerates the enzymic conversion of L-DOPA to dopamine at presynaptic sites.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"10 2-3","pages":"141-85"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02251229","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20539878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To ascertain the extent to which neuronal firing pattern in the subthalamic nucleus (STN) is determined by afferent inputs, a comparison was made between STN neurons recorded in vivo and in vitro (a largely denervated preparation). In vivo, the majority of cells exhibited an irregular firing pattern, although some showed evidence of burst firing. In contrast, all cells had a regular firing pattern in vitro. Electrical stimulation of the striatopallidal complex in vivo induced a short latency inhibition in STN neurons, followed by a burst of spikes. These effects could be reproduced in vitro; hyperpolarising pulses gave rist to a slow depolarising potential upon termination, which was accompanied by a burst of action potentials. Hence, the evidence suggests that afferents play an important role in determining the firing pattern of STN neurons. However, the cells also possess intrinsic membrane properties which allow inputs to trigger either single spikes or bursts.
{"title":"Determinants of neuronal firing pattern in the guinea-pig subthalamic nucleus: an in vivo and in vitro comparison.","authors":"P G Overton, S A Greenfield","doi":"10.1007/BF02256628","DOIUrl":"https://doi.org/10.1007/BF02256628","url":null,"abstract":"<p><p>To ascertain the extent to which neuronal firing pattern in the subthalamic nucleus (STN) is determined by afferent inputs, a comparison was made between STN neurons recorded in vivo and in vitro (a largely denervated preparation). In vivo, the majority of cells exhibited an irregular firing pattern, although some showed evidence of burst firing. In contrast, all cells had a regular firing pattern in vitro. Electrical stimulation of the striatopallidal complex in vivo induced a short latency inhibition in STN neurons, followed by a burst of spikes. These effects could be reproduced in vitro; hyperpolarising pulses gave rist to a slow depolarising potential upon termination, which was accompanied by a burst of action potentials. Hence, the evidence suggests that afferents play an important role in determining the firing pattern of STN neurons. However, the cells also possess intrinsic membrane properties which allow inputs to trigger either single spikes or bursts.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"10 1","pages":"41-54"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02256628","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19598509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The mRNA levels encoding enkephalin and substance P were measured in the rat striatum following cortical ablation, blockade of N-methyl-D-aspartate (NMDA) receptors or inhibition of glutamate release by lamotrigine. Unilateral ablation of the cerebral cortex resulted in a decrease of substance P mRNA levels particularly in the rostral dorsolateral and dorsomedial striatum ipsilateral to the lesion. There was a similar trend for a reduction in levels of enkephalin mRNA. Continuous, intrastriatal infusion of the competitive NMDA receptor antagonist, 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, (CPP, 0.12 and 1.2microg/day) decreased both enkephalin mRNA and substance P mRNA in dose-dependent manner evenly throughout the striatum adjacent to the infusion site. Following subchronic administration of the presumed glutamate release inhibitor, lamotrigine (5 and 20mg/kg IP) there was no significant alterations in either enkephalin mRNA or substance P mRNA levels in the striatum. Both enkephalin mRNA and substance P mRNA expression in the rat striatum appear tonically stimulated through postsynaptic NMDA receptor mediated mechanisms. This contrasts with differential dopaminergic modulation of peptides in striatal output neurons.
在皮质消融、阻断n -甲基- d -天冬氨酸(NMDA)受体或拉莫三嗪抑制谷氨酸释放后,测定大鼠纹状体中编码脑啡肽和P物质的mRNA水平。大脑皮质单侧消融导致P物质mRNA水平下降,特别是在与病变同侧的吻侧背外侧纹状体和背内侧纹状体。脑啡肽mRNA水平的降低也有类似的趋势。连续在纹状体内灌注竞争性NMDA受体拮抗剂3-((+/-)-2- carboxypperazin -4-yl)-丙基-1-膦酸(CPP, 0.12和1.2微克/天),以剂量依赖的方式均匀地降低了邻近输注部位纹状体的脑啡肽mRNA和P物质mRNA。在亚慢性给药假定的谷氨酸释放抑制剂拉莫三嗪(5和20mg/kg IP)后,纹状体中脑啡肽mRNA或P物质mRNA水平均无显著变化。大鼠纹状体中脑啡肽mRNA和P物质mRNA的表达均通过突触后NMDA受体介导的机制被强直刺激。这与纹状体输出神经元中多肽的差异多巴胺能调节形成对比。
{"title":"Glutamatergic regulation of striatal peptide gene expression in rats.","authors":"J Jolkkonen, P Jenner, C D Marsden","doi":"10.1007/BF02251230","DOIUrl":"https://doi.org/10.1007/BF02251230","url":null,"abstract":"<p><p>The mRNA levels encoding enkephalin and substance P were measured in the rat striatum following cortical ablation, blockade of N-methyl-D-aspartate (NMDA) receptors or inhibition of glutamate release by lamotrigine. Unilateral ablation of the cerebral cortex resulted in a decrease of substance P mRNA levels particularly in the rostral dorsolateral and dorsomedial striatum ipsilateral to the lesion. There was a similar trend for a reduction in levels of enkephalin mRNA. Continuous, intrastriatal infusion of the competitive NMDA receptor antagonist, 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, (CPP, 0.12 and 1.2microg/day) decreased both enkephalin mRNA and substance P mRNA in dose-dependent manner evenly throughout the striatum adjacent to the infusion site. Following subchronic administration of the presumed glutamate release inhibitor, lamotrigine (5 and 20mg/kg IP) there was no significant alterations in either enkephalin mRNA or substance P mRNA levels in the striatum. Both enkephalin mRNA and substance P mRNA expression in the rat striatum appear tonically stimulated through postsynaptic NMDA receptor mediated mechanisms. This contrasts with differential dopaminergic modulation of peptides in striatal output neurons.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"10 2-3","pages":"187-98"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02251230","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20539879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J Thome, A Baumer, J Kornhuber, M Rösler, P Riederer
The alpha1-antichymotrypsin and apolipoprotein-E polymorphisms were investigated in patients suffering from Alzheimer's syndrome and non-demented psychiatric inpatients as controls. The apolipoprotein E allele 4, well known as risk factor, tended to be elevated in the index group. The frequency of the alpha1-antichymotrypsin allele A was significantly increased in patients with Alzheimer's syndrome: 0.647 vs. 0.483 (chi-square test, p < 0.05). We conclude that, apart from the apolipoprotein E allele 4, the alpha1-antichymotrypsin allele A possibly represents a second genetic factor increasing individual's risk for Alzheimer's syndrome.
{"title":"Alpha-1-antichymotrypsin bi-allele polymorphism, apolipoprotein-E tri-allele polymorphism and genetic risk of Alzheimer's syndrome.","authors":"J Thome, A Baumer, J Kornhuber, M Rösler, P Riederer","doi":"10.1007/BF02251232","DOIUrl":"https://doi.org/10.1007/BF02251232","url":null,"abstract":"<p><p>The alpha1-antichymotrypsin and apolipoprotein-E polymorphisms were investigated in patients suffering from Alzheimer's syndrome and non-demented psychiatric inpatients as controls. The apolipoprotein E allele 4, well known as risk factor, tended to be elevated in the index group. The frequency of the alpha1-antichymotrypsin allele A was significantly increased in patients with Alzheimer's syndrome: 0.647 vs. 0.483 (chi-square test, p < 0.05). We conclude that, apart from the apolipoprotein E allele 4, the alpha1-antichymotrypsin allele A possibly represents a second genetic factor increasing individual's risk for Alzheimer's syndrome.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"10 2-3","pages":"207-12"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02251232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20539881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R M Marié, L Barré, P Rioux, P Allain, B Lechevalier, J C Baron
Post-mortem neurochemical studies in Parkinson's disease (PD) have shown that, in addition to the typical nigro-striatal dopamine denervation, there exists a concomitant neocortical monoamine fibre deafferentation (of variable severity) whose role in motor, and especially in associated cognitive and affective impairment, remains elusive. We have extensively examined whether PET imaging with 11C-S-Nomifensine (11C-NMF), a radioligand of the dopamine and norepinephrine presynaptic reuptake sites which has been used so far to investigate the striatum, could provide a method for assessing in vivo the neocortical monoamine terminal loss in PD; previously, this has been a little addressed and controversial issue. To this end, we prospectively selected a highly homogeneous sample of nine non-demented, non-depressed idiopathic PD patients with mild to marked side-to-side asymmetry in motor impairment. In addition to recovering the previously-reported correlations with putaminal 11C-NMF specific uptake asymmetries, the clinical motor asymmetries also significantly correlated in the clinically expected direction to neocortical (especially frontal) 11C-NMF asymmetries, suggesting the monoamine neocortical denervation might play a direct role in motor impairment in PD. These results demonstrate that it is possible to assess in vivo the neocortical monoamine terminal loss, and to elucidate its potential role in the complex cognitive and affective impairment, in both PD and atypical degenerative parkinsonism.
帕金森病(PD)的死后神经化学研究表明,除了典型的黑质纹状体多巴胺脱神经外,还存在伴随的新皮质单胺纤维脱神经(严重程度不同),其在运动,特别是相关的认知和情感障碍中的作用尚不清楚。11c - s -诺米芬(11C-NMF)是多巴胺和去甲肾上腺素突触前再摄取位点的放射性配体,目前已用于纹状体的研究,我们已经广泛研究了11c - s - nmf的PET成像是否可以提供一种评估PD患者体内新皮质单胺末端损失的方法;以前,这是一个很少被提及和有争议的问题。为此,我们前瞻性地选择了一个高度均匀的样本,包括9名非痴呆、非抑郁的特发性PD患者,这些患者在运动损伤方面有轻微到明显的侧对侧不对称性。除了恢复先前报道的与壳层11C-NMF特异性摄取不对称的相关性外,临床运动不对称也与新皮层(特别是额叶)11C-NMF不对称在临床预期的方向上显著相关,这表明单胺类新皮层去神经控制可能在PD的运动损伤中起直接作用。这些结果表明,有可能在体内评估新皮质单胺末端丧失,并阐明其在帕金森病和非典型退行性帕金森病中复杂认知和情感障碍中的潜在作用。
{"title":"PET imaging of neocortical monoaminergic terminals in Parkinson's disease.","authors":"R M Marié, L Barré, P Rioux, P Allain, B Lechevalier, J C Baron","doi":"10.1007/BF02252963","DOIUrl":"https://doi.org/10.1007/BF02252963","url":null,"abstract":"<p><p>Post-mortem neurochemical studies in Parkinson's disease (PD) have shown that, in addition to the typical nigro-striatal dopamine denervation, there exists a concomitant neocortical monoamine fibre deafferentation (of variable severity) whose role in motor, and especially in associated cognitive and affective impairment, remains elusive. We have extensively examined whether PET imaging with 11C-S-Nomifensine (11C-NMF), a radioligand of the dopamine and norepinephrine presynaptic reuptake sites which has been used so far to investigate the striatum, could provide a method for assessing in vivo the neocortical monoamine terminal loss in PD; previously, this has been a little addressed and controversial issue. To this end, we prospectively selected a highly homogeneous sample of nine non-demented, non-depressed idiopathic PD patients with mild to marked side-to-side asymmetry in motor impairment. In addition to recovering the previously-reported correlations with putaminal 11C-NMF specific uptake asymmetries, the clinical motor asymmetries also significantly correlated in the clinically expected direction to neocortical (especially frontal) 11C-NMF asymmetries, suggesting the monoamine neocortical denervation might play a direct role in motor impairment in PD. These results demonstrate that it is possible to assess in vivo the neocortical monoamine terminal loss, and to elucidate its potential role in the complex cognitive and affective impairment, in both PD and atypical degenerative parkinsonism.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"9 1","pages":"55-71"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02252963","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18611477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
One hundred and fifty patients suffering from Parkinson's disease were analysed for the expression of the motor symptoms during optimum response to levodopa therapy (subscale III of the Unified-Parkinson's Disease Rating Scale). Patients were grouped according to age (< or = 64, 65-74, > or = 75 years). Disease duration and daily levodopa dosage were similar in the three groups. Pooled residual scores for posture and gait impairment (PGI), tremor (T), rigidity (R) and distal motor impairment (DMI; hand and foot movements) increased with age (Kruskal-Wallis ANOVA). The parkinsonian scores were significantly higher than the scores of 150 age-matched normal controls (Mann-Whitney U test). The differences between the patients' scores and the scores of the age-matched controls increased with age. In spite of a significant increase in the daily levodopa dosage with disease duration (linear regression), PGI aggravated age-dependently, and DMI age-independently with symptom duration (Spearman rank correlation). In contrast, T and R did not increase with disease duration.
{"title":"Effect of age and disease duration on parkinsonian motor scores under levodopa therapy.","authors":"G Ransmayr, G Künig, M Neubauer, M Wagner, M Falk","doi":"10.1007/BF02259659","DOIUrl":"https://doi.org/10.1007/BF02259659","url":null,"abstract":"<p><p>One hundred and fifty patients suffering from Parkinson's disease were analysed for the expression of the motor symptoms during optimum response to levodopa therapy (subscale III of the Unified-Parkinson's Disease Rating Scale). Patients were grouped according to age (< or = 64, 65-74, > or = 75 years). Disease duration and daily levodopa dosage were similar in the three groups. Pooled residual scores for posture and gait impairment (PGI), tremor (T), rigidity (R) and distal motor impairment (DMI; hand and foot movements) increased with age (Kruskal-Wallis ANOVA). The parkinsonian scores were significantly higher than the scores of 150 age-matched normal controls (Mann-Whitney U test). The differences between the patients' scores and the scores of the age-matched controls increased with age. In spite of a significant increase in the daily levodopa dosage with disease duration (linear regression), PGI aggravated age-dependently, and DMI age-independently with symptom duration (Spearman rank correlation). In contrast, T and R did not increase with disease duration.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"9 2-3","pages":"177-88"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02259659","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19509280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A Espino, M Calopa, S Ambrosio, J Ortolà, J Peres, M A Navarro
Somatostatin-like immunoreactivity levels (SLI) in cerebrospinal fluid (CSF) were determined in twenty-three patients with untreated parkinsonian syndrome (15 with Idiopathic Parkinson's disease (IPD) and 8 with other forms of parkinsonism) at the moment of clinical diagnosis (mean duration of disease 1.1 +/- 0.2 years), and in 26 subjects without neurological symptoms. None of the IPD patients had a diagnosis of dementia at the moment of inclusion in the study. CSF-SLI content was found to be significantly higher in patients with parkinsonian syndrome (107.9 +/- 9.8 pg/ml) than in control subjects (73.5 +/- 8.4 pg/ml). The increase was also significant when controls were compared with IPD patients. In addition, a positive correlation between SLI and homovanillic acid was found in CSF of all patients. A test of learning memory was used to evaluate the mental state of patients and a significant increase in CSF-somatostatin levels was observed in patients with Idiopathic Parkinson's disease and severe affectation of memory. These results indicate that in the early steps of untreated parkinsonian syndrome, somatostatin concentration in cerebrospinal fluid may increase, probably due to the neurodegenerative depletion of somatostatin from striatal or cortical neurons.
{"title":"CSF somatostatin increase in patients with early parkinsonian syndrome.","authors":"A Espino, M Calopa, S Ambrosio, J Ortolà, J Peres, M A Navarro","doi":"10.1007/BF02259660","DOIUrl":"https://doi.org/10.1007/BF02259660","url":null,"abstract":"<p><p>Somatostatin-like immunoreactivity levels (SLI) in cerebrospinal fluid (CSF) were determined in twenty-three patients with untreated parkinsonian syndrome (15 with Idiopathic Parkinson's disease (IPD) and 8 with other forms of parkinsonism) at the moment of clinical diagnosis (mean duration of disease 1.1 +/- 0.2 years), and in 26 subjects without neurological symptoms. None of the IPD patients had a diagnosis of dementia at the moment of inclusion in the study. CSF-SLI content was found to be significantly higher in patients with parkinsonian syndrome (107.9 +/- 9.8 pg/ml) than in control subjects (73.5 +/- 8.4 pg/ml). The increase was also significant when controls were compared with IPD patients. In addition, a positive correlation between SLI and homovanillic acid was found in CSF of all patients. A test of learning memory was used to evaluate the mental state of patients and a significant increase in CSF-somatostatin levels was observed in patients with Idiopathic Parkinson's disease and severe affectation of memory. These results indicate that in the early steps of untreated parkinsonian syndrome, somatostatin concentration in cerebrospinal fluid may increase, probably due to the neurodegenerative depletion of somatostatin from striatal or cortical neurons.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"9 2-3","pages":"189-96"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02259660","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19509281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The influence of R(-) apomorphine, S(+) apomorphine and dopamine on the oxidation kinetics of two polyunsaturated fatty acids (PUFA) (cholesteryl linoleate (CL) and Trilinolein (TL)) was investigated. The oxidation was initiated by free radicals generated through thermal decomposition of 2.2'-Azobis(2-methyl-propionitrile) (AMPN) in phosphate buffer (pH 7.4) thermostated at 50 degrees C. The hydroperoxides formed were determined by iodine titration using a diode array spectrophotometer at 290nm. Both enantiomers of apomorphine as well as dopamine exerted an inhibitory effect. Tocopherol (alpha-tocopherol) and ascorbic acid were used as controls. The former inhibited while ascorbic acid facilitated the oxidation reaction. These results are discussed in relation with the possible role of oxidative injury in parkinsonism and the usefulness of apomorphine in elevating "on-off" episodes. On this basis, the non-dopaminergic enantiomer of apomorphine (S(+)-isomer) is put foward to test the importance of its radical scavenging properties in parkinsonism which could eventually lead to a therapeutic alternative with less side effects.
{"title":"Free radical scavenging properties of apomorphine enantiomers and dopamine: possible implication in their mechanism of action in parkinsonism.","authors":"E E Sam, N Verbeke","doi":"10.1007/BF02251227","DOIUrl":"https://doi.org/10.1007/BF02251227","url":null,"abstract":"<p><p>The influence of R(-) apomorphine, S(+) apomorphine and dopamine on the oxidation kinetics of two polyunsaturated fatty acids (PUFA) (cholesteryl linoleate (CL) and Trilinolein (TL)) was investigated. The oxidation was initiated by free radicals generated through thermal decomposition of 2.2'-Azobis(2-methyl-propionitrile) (AMPN) in phosphate buffer (pH 7.4) thermostated at 50 degrees C. The hydroperoxides formed were determined by iodine titration using a diode array spectrophotometer at 290nm. Both enantiomers of apomorphine as well as dopamine exerted an inhibitory effect. Tocopherol (alpha-tocopherol) and ascorbic acid were used as controls. The former inhibited while ascorbic acid facilitated the oxidation reaction. These results are discussed in relation with the possible role of oxidative injury in parkinsonism and the usefulness of apomorphine in elevating \"on-off\" episodes. On this basis, the non-dopaminergic enantiomer of apomorphine (S(+)-isomer) is put foward to test the importance of its radical scavenging properties in parkinsonism which could eventually lead to a therapeutic alternative with less side effects.</p>","PeriodicalId":16466,"journal":{"name":"Journal of Neural Transmission - Parkinson's Disease and Dementia Section","volume":"10 2-3","pages":"115-27"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF02251227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20539876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}