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Biomedical subjects

U K Rinne

Publications and source records attributed to U K Rinne.

At least 19 recordsLinked to original sources
PubMed1992

Effects of a selective partial D1 agonist, CY 208-243, in de novo patients with Parkinson disease.

A selective dopamine D1-receptor agonist, CY 208-243, was administered to 23 de novo patients who had had Parkinson disease (PD) for less than or equal to 3 months. The drug was first used as monotherapy and then in some patients in combination with a dopamine D2-receptor agonist, bromocriptine. Results showed that CY 208-243 exerted a mild antiparkinsonian action, and tremor was the main symptom that consistently improved. The addition of bromocriptine less than or equal to 15 mg to CY 208-243 did not result in additional improvement, but this might be due to the short duration of treatment and the low doses of bromocriptine. The study was prematurely discontinued for safety reasons. We conclude that D1-receptor stimulation may result in improvement of motor disability in PD.

Adult↗
PubMed1992

Decrease in mesencephalic dopamine autoreceptors in experimental herpes simplex encephalitis.

Brain dopamine receptors were determined in experimental herpes encephalitis using an animal model, where herpes simplex virus type 1 was inoculated onto the cornea of rabbits. The animals exhibit an asymmetric posture and circling to the side of inoculation, which appears to be connected to the altered dopamine transmission in the mesostriatal system. In this study striatal and mesencephalic D-1 and D-2 dopamine receptors were measured by radioligand techniques using 3H-SCH 23390 and 3H-spiroperidol as ligands. In the striatal D-1 and D-2 receptors there were no significant differences between HSV-inoculated and control rabbits. In the substantia nigra-ventral tegmental area there was a significant decrease in the D-2 receptors (Bmax) on the side contralateral to the primary virus inoculation and the direction of the rotational behaviour, without any changes in the D-1 receptors. Thus experimental herpes simplex virus infection seems to affect the mesencephalic dopamine autoreceptors, leading to unilateral activation of the mesostriatal dopamine system and rotational behaviour.

Animals↗
PubMed1992

Comparison of lisuride and bromocriptine in the treatment of advanced Parkinson's disease.

Twenty patients with advanced idiopathic Parkinson's disease were studied, all having a deteriorating response to levodopa and suffering from daily fluctuations in disability. A double-blind randomized cross-over study was conducted. Basic levodopa and anticholinergic treatment was continued unchanged in all patients. The dose increment period of 4-8 weeks was followed by a 4 week treatment period on a fixed optimal dose. In both treatment groups the mean optimal daily dose of lisuride was 1.3 mg (range 0.2-2.4 mg) and that of bromocriptine about 15 mg (range 3.75-30.0), without any significant differences between the treatment groups. The addition of lisuride or bromocriptine to levodopa treatment resulted in a significant and equal further improvement of parkinsonian disability. The therapeutic profiles of both lisuride and bromocriptine were similar. There was significantly more improvement in tremor than in other parkinsonian symptoms. Both lisuride and bromocriptine elicited a significant improvement in fluctuations of disability. No significant differences between the treatments were observed. The occurrence of clinical side effects seemed to be similar with both treatment regimens. In advanced parkinsonian patients the therapeutic efficacy of lisuride seems to be equal to that of bromocriptine as far as parkinsonian disability and fluctuations in disability are concerned.

Aged↗
PubMed1992

[18F]-6-fluorodopa PET scanning in Parkinson's disease after selective COMT inhibition with nitecapone (OR-462).

PET studies were performed to investigate the effects of a new cathechol-O-methyltransferase (COMT) inhibitor, nitecapone (OR-462 [3-(3,4-dihydroxy-5-nitrobenzylidene)- 2,4-pentadione]), on the accumulation of dopamine in the striatum and whether it is able to improve [18F]6-fluorodopa imaging of the brain. Altogether, three patients with Parkinson's disease (PD) and three normal volunteers were examined, first without nitecapone and then with an oral dose of 100 mg of nitecapone 1 hour before the IV injection of 3 mCi of [18F]6-fluorodopa. High-pressure liquid chromatography analysis of arterial plasma samples showed a significant reduction in the metabolic conversion rate from [18F]6-fluorodopa to [18F]3-O-methylfluorodopa after the administration of nitecapone. PET studies showed that nitecapone significantly (p less than 0.05) increased the [18F]6-fluorodopa accumulation in the striatum both in PD patients and normal controls; the magnitude of this increase was 20.0 +/- 5.5% (mean +/- SEM). The ratio of radioactivity in the striatum and arterial plasma was increased 39.0 +/- 5.0% (mean +/- SEM) after the administration of nitecapone. Consequently, the quality of PET images after OR-462 was better, which has implications for future [18F]6-fluorodopa studies. In addition, COMT inhibition may have clinical advantages by improving levodopa treatment in PD.

Adult↗
PubMed1991

A post-mortem study on striatal dopamine receptors in Parkinson's disease.

Striatal dopamine D1 and D2 receptors were investigated in 49 patients with Parkinson's disease (PD) and 33 age-matched controls with [3H]SCH 23390 and [3H]spiroperidol as ligands respectively. A full Scatchard analysis giving Bmax and Kd values was performed. In the caudate nucleus, a small but significant decrease in the number of D1 and D2 receptors was seen, whereas in the putamen the number of dopamine receptors was unchanged. Treatment with neuroleptics was found to increase the number of D2 receptors both in the caudate nucleus and putamen. The number of neither D1 nor D2 receptors correlated neither with the duration of disease or levodopa treatment of the patients nor with the post-mortem delay or storage time of the samples. Furthermore, no association was found between either D1 or D2 receptor number and clinical variables of the patients. The activity of choline acetyltransferase (ChAT) was found to be unchanged in the striatum, whereas a marked decline was seen in the hippocampus and cortical areas, indicating that intrinsic striatal cholinergic neurons are not affected in PD. The present results suggest that there is a modest decline in the number of striatal dopamine D2 receptors in advanced patients with PD at the end stage of the disease.

Aged↗
PubMed1991

Brain monoamine metabolism and rotational behaviour induced by experimental herpes simplex virus encephalitis.

The motor behaviour and brain concentrations of dopamine, noradrenaline, serotonin and their metabolites have been examined in rabbits with experimental herpes simplex virus (HSV) brain infection achieved by unilateral corneal inoculation. The animals showed altered motor behaviour, consisting of a posture tilting to the side of inoculation and circling in the same direction, that began on day 4-5 post inoculation, and was most vigorous on day 7 post inoculation. Compared with controls, the concentration of 5-hydroxyindoleacetic acid was increased in the caudate nucleus on both sides and that of serotonin was decreased in the nucleus accumbens on the side of inoculation. The circling of the animals correlated positively with the ratio of homovanillic acid concentrations between the left and right caudate nucleus, although the actual concentrations did not differ from the controls. The posture asymmetry correlated with the ratio of the left and right nucleus accumbens homovanillic acid concentrations. The results demonstrate that experimental HSV infection in the brain alters motor behaviour, in association with changes in brain dopamine and serotonin metabolism in the major ascending monoamine systems.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Debrisoquine oxidation in Parkinson's disease.

Variations in the activities of xenobiotic metabolizing liver enzymes may be involved in the pathophysiology of diseases, including Parkinson's disease. We therefore studied the activity of the debrisoquine metabolizing enzyme in 97 patients with newly diagnosed Parkinson's disease. The urine debrisoquine metabolic ratios (MR) of the patients were compared with a group of 176 healthy subjects. There were 4 poor metabolizers (4.1%) among the parkinsonians. This proportion did not differ from that found in the group of healthy subjects (51%). In contrast to earlier finding, the parkinsonian poor metabolizers (PM) had the onset of the disease later than the parkinsonian extensive metabolizers (EM). In the parkinsonian patients, it was observed that the excretion of debrisoquine and 4-OH-debrisoquine into urine correlated inversely with the actual age and age at disease onset. Our results indicate that in patients with Parkinson's disease, debrisoquine hydroxylation is comparable with healthy subjects.

Adult↗
PubMed1991

Progression and survival in Parkinson's disease.

Parkinson's disease is a progressive disorder and no permanent cure has ever been documented. The clinical onset, which usually occurs at an age of 55-65 years, is probably preceded by a preclinical period of two or more decades. The progression rate of the disease is extremely variable in different patients; in individual patients on the other hand, the progression of motor symptoms is fairly constant. The tremor-dominant type of the disease usually has a more favourable prognosis than the hypokinetic type. Onset at an older age may be associated with a faster progression rate and the development of cognitive failure. In natural conditions, the average duration of Parkinson's disease is 10 years, although with a considerable range. The disease shortens life expectancy, which can be restored at least partially by treating patients with levodopa and other modern drugs. The highest benefit in increasing life expectancy is obtained when the treatment is initiated at a relatively early stage of the disease.

Adult↗
PubMed1991

New strategies in the treatment of early Parkinson's disease.

Over recent years I have been studying whether dopamine agonist treatment alone, or in early combination with levodopa, might institute a better long-term treatment in Parkinson's disease than levodopa alone. Indeed, early combination of levodopa with bromocriptine, pergolide or lisuride has indicated that this kind of treatment results in better management of Parkinson's disease with fewer fluctuations in disability, especially end-of-dose disturbances and dyskinesias, than treatment with levodopa alone. Furthermore, similar results were obtained by using lisuride in combination with selegiline and levodopa. However, during long-term treatment the changes in parkinsonian disability were equal in all treatment groups with or without selegiline. Thus, the possible efficacy of selegiline in slowing down the progression of Parkinson's disease requires further investigations. As a new treatment strategy it appears advisable to initiate the dopaminergic treatment in early Parkinson's disease by using initially selegiline and a dopamine agonist and by adding levodopa when the therapeutic response is insufficient. Another alternative would be to start with selegiline alone, then add a dopamine agonist and, finally, levodopa.

Brain↗
PubMed1991

Selegiline (deprenyl) treatment and death of nigral neurons in Parkinson's disease.

We studied the effect of selegiline (deprenyl) treatment on the number of Lewy bodies and neuron counts in the substantia nigra in patients with Parkinson's disease (PD). The number of medial nigral neurons was greater and the number of Lewy bodies fewer in those PD patients who had been treated with selegiline in combination with levodopa as compared with patients who had received levodopa alone. This suggests that selegiline treatment may retard the death of nigral neurons, but alternative explanations, such as the reduction of levodopa dosage in selegiline-treated patients, are possible.

Aged↗
PubMed1990

PET demonstrates different behaviour of striatal dopamine D-1 and D-2 receptors in early Parkinson's disease.

Striatal dopamine D-1 receptor binding was investigated in vivo with positron emission tomography (PET) in five patients with early Parkinson's disease using [11C]-SCH 23390. All patients had predominantly unilateral symptoms and showed a significant reduction in the accumulation of [18F]-6-F-DOPA in the striatum contralateral to the symptoms. None of the patients had received any antiparkinsonian medication. The striatal and cerebellar radioactivity was measured and corresponding striatum/cerebellum ratios were counted. The mean striatum/cerebellum ratio of [11C]-SCH 23390 binding was symmetric between the hemispheres. By contrast, the striatum/cerebellum ratio of [11C]raclopride binding, labelling dopamine D-2 receptors, was increased significantly in the hemisphere contralateral to the symptoms as compared with the opposite hemisphere. Thus, the present results show that the behaviour of striatal D-1 and D-2 receptors is different in early Parkinson's disease.

Adult↗
PubMed1990

Positron emission tomography demonstrates dopamine D2 receptor supersensitivity in the striatum of patients with early Parkinson's disease.

Striatal dopamine D2 receptor binding was studied in vivo with positron emission tomography in seven patients with early Parkinson's disease using [11C]-raclopride. The patients had unilateral symptoms and none of them had received levodopa treatment. The accumulation of [11C]-raclopride in the striatum was rapid and reached a steady state at approximately 40 min after injection. The binding of [11C]-raclopride was measured in the striatum and cerebellum: The total striatal radioactivity in both hemispheres was counted and the respective striatum/cerebellum ratios were calculated. The striatum/cerebellum ratio of [11C]-raclopride binding was significantly (p less than 0.01) increased in the hemisphere contralateral to the parkinsonian symptoms as compared with the opposite hemisphere. Thus, this study demonstrates that there is denervation supersensitivity in dopamine D2 receptor binding in early Parkinson's disease.

Adult↗
PubMed1990

Brain substance P receptors in Parkinson's disease.

The distribution of SP receptors was studied both in the normal human brain and in the parkinsonian brain by means of tritiated SP. The highest levels of binding were found in the striatal areas and in the NbM. The distribution was similar to that found in laboratory animals in earlier studies. In PD the binding was significantly reduced in the NbM and parietal cortex as compared with controls. The level of SPLI was reduced in both parts of the SN, in the NbM, and in the GPi.

Aged↗
PubMed1989

Brain muscarinic receptor subtypes are differently affected in Alzheimer's disease and Parkinson's disease.

The muscarinic receptor subtypes determined by displacing [3H]quinuclidinyl benzylate by carbachol showed distinct profiles in Alzheimer's disease (AD) and in Parkinson's disease (PD). A decrease in the M2-receptor count was seen in the hippocampus in AD as compared to controls, while PD patients had unaltered binding. By contrast, PD patients had increased M2-binding in the frontal and temporal cortex, whereas unchanged binding was seen in AD. In PD the total number of cortical muscarinic receptors was negatively associated with the activity of ChAT, but had a positive correlation with the degree of dementia of the patients.

Aged↗