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P Odin

Publications and source records attributed to P Odin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Pregnancy in Parkinson's disease: a review of the literature and a case report.

Pregnancy is rare in Parkinson's disease (PD). In the literature on studies of antiparkinsonian drugs in animals during pregnancy, there are reports on malformations of the skeletal and circulatory system. However, the majority of studies in animals have not shown any teratogenicity. Amantadine has been teratogenic in rats and selegiline has caused neurochemical and behavioral alterations in rats when coadministered with clorgyline. The published experience with humans consists of 35 pregnancies among 26 women suffering from PD, including this report, and a number of cases treated with antiparkinsonian agents for other reasons. With the exception of the majority of the cases where amantadine was used, complications have been rare. However, there are indications that suggest a possible risk of a woman's parkinsonism worsening in connection with pregnancy. We also report the case of a woman with PD who was treated with L-dopa-benserazide during an uncomplicated pregnancy and gave birth to a healthy boy without experiencing any worsening of her PD.

Abnormalities, Drug-Induced↗
PubMed1998

Expression of platelet-derived growth factor after intrastriatal ibotenic acid injury.

The expression of platelet-derived growth factor (PDGF) was studied in a rat model of Huntington's disease, produced by unilateral intrastriatal ibotenic acid injections. The most pronounced effect registered was that the number of PDGF-immunoreactive cells increased in the lesioned area up to 10 weeks after the surgery. Double immunofluorescence staining indicated that the PDGF-positive cells were astrocytes. The increased PDGF immunoreactivity was associated with only minor changes in total PDGF mRNA and PDGF protein levels in the lesioned area. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated a slight increase in PDGF mRNA after ibotenic acid lesion, but this was not reflected in an increase in PDGF A- and B-chain protein concentration as measured with ELISA. After sham operation an increase in PDGF protein concentration was seen, while the number of PDGF-immunoreactive cells was unchanged. The accumulation of PDGF in the astrocytes might reflect the role of PDGF in a repair process in neurodegenerative processes.

Animals↗
PubMed1998

Subcutaneous apomorphine in late stage Parkinson's disease: a long term follow up.

OBJECTIVES: Despite the recent introduction of new peroral drugs as well as neurosurgical methods for Parkinson's disease, treatment of late stage parkinsonian patients remains difficult and many patients become severely handicapped because of fluctuations in their motor status. Injections and infusions of apomorphine has been suggested as an alternative in the treatment of these patients, but the number of studies describing the effects of such a treatment over longer time periods is still limited. The objective was to investigate the therapeutic response and range of side effects during long term treatment with apomorphine in advanced Parkinson's disease. METHODS: Forty nine patients (30 men, 19 women; age range 42-80 years) with Parkinson's disease were treated for 3 to 66 months with intermittent subcutaneous injections or continuous infusions of apomorphine. RESULTS: Most of the patients experienced a long term symptomatic improvement. The time spent in "off" was significantly reduced from 50 to 29.5% with injections and from 50 to 25% with infusions of apomorphine. The quality of the remaining "off" periods was improved with infusion treatment, but was relatively unaffected by apomorphine injections. The overall frequency and intensity of dyskinesias did not change. The therapeutic effects of apomorphine were stable over time. The most common side effect was local inflammation at the subcutaneous infusion site, whereas the most severe were psychiatric side effects occurring in 44% of the infusion and 12% of the injection treated patients. CONCLUSION: Subcutaneous apomorphine is a highly effective treatment which can substantially improve the symptomatology in patients with advanced stage Parkinson's disease over a prolonged period of time.

Adult↗
PubMed1997

Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease.

Six patients with Parkinson's disease were followed for 10 to 72 months after human embryonic mesencephalic tissue from four to seven donors was grafted unilaterally into the putamen (4 patients) or putamen plus caudate (2 patients). After 8 to 12 months, positron emission tomography showed a 68% increase of 6-L-[18F]-fluorodopa uptake in the grafted putamen, no change in the grafted caudate, and minor decreases in nongrafted striatal regions. There was therapeutically valuable improvement in 4 patients, but only modest changes in the other 2, both of whom developed atypical features. Patient 4 was without L-dopa from 32 months and had normal fluorodopa uptake in the grafted putamen at 72 months. Overall, the L-dopa dose was reduced by a mean of 10 and 20%, "off" time was reduced by 34 and 44%, and the "off" phase Unified Parkinson's Disease Rating Scale motor score by 18 and 26%, and the duration of the response to a single L-dopa dose increased by 45 and 58% during the first and second years after surgery, respectively. Rigidity and hypokinesia improved bilaterally, but mainly contralateral to the implant. No consistent changes in dyskinesias were observed. We conclude that transplantation of embryonic mesencephalic tissue leads to highly reproducible survival of dopaminergic neurons, inducing clinically valuable improvements in most recipients.

Adult↗
PubMed1996

Protective effect of platelet-derived growth factor against 6-hydroxydopamine-induced lesion of rat dopaminergic neurons in culture.

The effects of platelet-derived growth factor (PDGF)-AA and -BB on 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic (DA) neurons were studied in cultures of dissociated fetal rat mesencephalon. The 6-OHDA lesion (0.3% for 4 h) caused a selective 75% loss of tyrosine hydroxylase (TH)-positive DA neurons. The neuronal death was significantly decreased (to about 25%) by addition of 1, 10 or 30 (but not 0.1) ng/ml of PDGF-BB 24 h prior to the insult. In contrast, treatment with PDGF-AA (30 ng/ml) for 24 h before the lesion or addition of PDGF-BB (30 ng/ml) simultaneously with or 1 h after 6-OHDA did not promote the survival of TH-positive neurons. We conclude that PDGF-BB can counteract 6-OHDA-induced degeneration of mesencephalic DA neurons.

Animals↗
PubMed1996

Differential trophic effects of basic fibroblast growth factor, insulin-like growth factor-1, and neurotrophin-3 on striatal neurons in culture.

We have examined the trophic effects of basic fibroblast growth factor (bFGF), truncated insulin-like growth factor-1 (tIGF), and neurotrophin-3 (NT-3) on embryonic striatal neurons grown under serum-free culture conditions. Striatal neurons were identified using immunocytochemistry for dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32). In our serum-free striatal cultures, the survival and the development of DARPP-32- containing neurons were dependent on initial plating density: relatively high density cultures yielded disproportionately increased number of harvested DARPP-32- positive neurons. All three growth factors, bFGF (10 ng/ml), tIGF-1 (50 ng/ml), and NT-3 (50 ng/ml), promoted the survival of DARPP-32-positive neurons, with bFGF being significantly more effective than tIGF-1 and NT-3. Exposure to bFGF also significantly increased the total cell number compared to control cultures, whereas there was only a tendency toward more (20-30%) surviving cells in cultures treated with either tIGF-1 or NT-3. With the concentrations used, only bFGF gave rise to a significant increase (80%) in the number of glial fibrillary acidic protein-immunopositive glia as compared to controls. The most pronounced effect on morphological development of DARPP-32-containing neurons was seen with NT-3, which increased the length of neurites, the number of branching points on the neurites, and the soma area. There was no alteration of the morphology of this neuronal population in bFGF-treated cultures. All of these growth factors were seen to be approximately equally efficient at protecting striatal neurons from N-methyl-D- aspartate-induced excitotoxicity. These data indicate that bFGF, tIGF-1, and NT3 exert different trophic activities on striatal neurons in vitro and suggest that these growth factors might also be involved in the regulation of neuronal development and maintenance in the striatum.

Animals↗
PubMed1996

Effects of brain-derived neurotrophic factor on neuronal structure of dopaminergic neurons in dissociated cultures of human fetal mesencephalon.

Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival of cultured fetal mesencephalic dopaminergic neurons of rat and human origin. In the present study, BDNF was tested for its ability to influence neuronal structure of dopaminergic neurons in dissociated cultures of human fetal ventral mesencephalon after 7 days in vitro. Following immunocyto chemical staining for tyrosine hydroxylase, all surviving dopaminergic neurons were counted. Computer-assisted three-dimensional reconstructions of uniform randomly selected neurons cultured with 50 ng/ml BDNF (n = 120) or without BDNF (n = 80) were made. BDNF increased the number of surviving human dopaminergic neurons by 76%. Mean soma profile area was significantly enlarged by 18% in BDNF-treated neurons as compared to controls. Analysis of parameters of neuritic size and complexity in these cultures revealed that combined neuritic length, combined neuritic volume, and neuritic field area were increased by 60%, 125% and 129%, respectively, and the mean number of segments per cell was increased by 41%. A change in neurite complexity in BDNF-treated cultures was further confirmed by the Sholl's concentric sphere analysis. These results demonstrate that BDNF promotes development and differentiation of human fetal dopaminergic neurons in vitro.

Brain-Derived Neurotrophic Factor↗
PubMed1996

Enhanced synthesis of platelet-derived growth factor following injury induced by 6-hydroxydopamine in rat brain.

The kinetics of platelet-derived growth factor messenger RNA synthesis in the substantia nigra and in the striatum, before and after unilateral intranigral 6-hydroxydopamine injection, was studied and compared with that after sham operation by a quantitative reverse transcription-polymerase chain reaction. The kinetics of brain-derived neurotrophic factor messenger RNA was studied as a comparison. Furthermore, the expression of platelet-derived growth factor A- and B-chain proteins was analysed by enzyme-linked immunosorbent assay and immunohistochemistry. In the ipsilateral striatum of 6-hydroxydopamine-lesioned rats, the signal density of messenger RNA for both A- and B-chains had already increased at one day and remained at an elevated level during the observation period of four weeks. In the substantia nigra ipsilateral to the lesion, a strongly increased level of B-chain and, to a lesser extent, of A-chain messenger RNA was already detected at 4h, reaching a maximal level at one day. No significant increase was seen either in sham-operated rats or in the contralateral striatum and substantia nigra. Amounts of platelet-derived growth factor proteins were examined separately by enzyme-linked immunosorbent assay in both sides of the substantia nigra, striatum and cortex. Three days after 6-hydroxydopamine lesions the levels of both platelet-derived growth factor A- and B-chains increased in the ipsilateral striatum, substantia nigra, and cortex. An increase in the A-chain was also observed in the contralateral side of the brain. The signal for brain-derived neurotrophic factor messenger RNA increased in the striatum in the lesioned side and, to a lesser extent, in the contralateral side, as well as in the substantia nigra, where a significant difference was observed when compared with the contralateral side. Semiquantitative immunohistochemical analysis on the substantia nigra confirmed the enhanced platelet-derived growth factor expression, revealing that the majority of the platelet-derived growth factor-producing cells were neurons. In summary, we have shown that platelet-derived growth factor messenger RNA as well as its protein are induced after injury to dopaminergic cells. These data indicate an important role of platelet-derived growth factor in the dopaminergic system.

Animals↗
PubMed1995

Trophic and protective actions of brain-derived neurotrophic factor on striatal DARPP-32-containing neurons in vitro.

We have examined the effects of either brain-derived neurotrophic factor (BDNF), the BB-isoform of platelet-derived growth factor (PDGF-BB), or a combination of these growth factors on the survival and the morphological development of embryonic striatal neurons grown under serum-free culture conditions. Striatal neurons were identified using immunocytochemistry for "dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton" (DARPP-32). BDNF and PDGF-BB promoted the survival of DARPP-32-positive neurons, with the magnitude of their effects being comparable. A combination of these growth factors exerted no significant additive effects on cell survival. BDNF stimulated morphological differentiation of DARPP-32-containing neurons by increasing the length of neurites, the number of branching points on the neurites, and the soma area. By contrast, PDGF-BB increased the neurite length and the cell body area, but not the number of branching points. BDNF also protected striatal neurons from excitotoxicity induced by N-methyl-D-aspartate, whereas PDGF-BB had no effect under the same treatment conditions as those for BDNF. Thus, BDNF is trophic for striatal DARPP-32-containing neurons in vitro by enhancing the survival, morphological differentiation and resistance to excitotoxicity, and its mechanisms of action are probably different from those of PDGF-BB.

Animals↗
PubMed1995

Specific effects of platelet derived growth factor (PDGF) on fetal rat and human dopaminergic neurons in vitro.

The neurotrophic effects of the BB isoform of platelet-derived growth factor (PDGF) on rat and human fetal mesencephalic dopaminergic neurons have been characterized in vitro. A dose-response analysis demonstrated maximal responses at 30 ng/ml of PDGF-BB. This concentration resulted in a marked increase in the survival and neurite outgrowth from rat and human tyrosine hydroxylase-(TH) positive, presumed dopaminergic neurons after 7 days in vitro. The effects of PDGF-BB on survival of TH-positive neurons were comparable to those of brain-derived neurotrophic factor (BDNF), whereas neurite outgrowth was more pronounced after addition of BDNF. The combination of BDNF and PDGF-BB yielded no additive effects. Double immunohistochemical staining of rat cultures demonstrated PDGF beta-receptors on about 90% of the TH-positive neurons. PDGF-BB treatment of rat mesencephalic cultures induced an upregulation of c-fos and TH mRNA with maximal levels after 0.5-2 h as assessed by quantitative PCR analysis. An increased number of Fos protein-positive cells was detected immunohistochemically after 4 h of PDGF-BB treatment. The present results provide further evidence for specific and direct effects of PDGF-BB on gene expression, survival and neurite outgrowth of mesencephalic dopaminergic neurons of rat and human origin.

Animals↗
PubMed1995

Protective effects of BDNF and NT-3 but not PDGF against hypoglycemic injury to cultured striatal neurons.

Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and platelet-derived growth factor (PDGF) exert trophic effects on striatal neurons in vitro, which raises the possibility that these growth factors might also counteract neuronal death provoked by various insults. We have found that BDNF and NT-3, but neither PDGF-AA nor -BB, added 24 h before the insult ameliorated hypoglycemic neuronal damage induced by 15 or 24 h of glucose deprivation in rat striatal cell cultures. BDNF and NT-3 afforded neuronal protection even when administered 8 or 4 h, respectively, after the onset of hypoglycemia. In normoglycemic striatal cultures exposed to these neurotrophins for several days, there was a slight, nonsignificant increase of the number of surviving microtubule-associated protein-2-positive cells (20-30%) compared to untreated control cultures, but no change of glial cells. Exposure of the cultures to BDNF or NT-3 produced a significant increase in the number of neurons expressing detectable levels of the calcium-binding protein, calbindin, suggesting that a stabilization of calcium homeostasis might be implicated in the neuroprotection. Immunocytochemical analysis revealed that the majority (70-80%) of neurons in the striatal cultures expressed TrkB and TrkC, the functional receptors for BDNF and NT-3, respectively, implying that the effects of the neurotrophins are most likely direct. These data indicate that BDNF and NT-3 can protect striatal neurons against hypoglycemia in vitro and raise the possibility that these neurotrophins could counteract striatal neuronal death induced by hypoglycemic and ischemic insults in vivo.

Animals↗
PubMed1995

Pen injected apomorphine against off phenomena in late Parkinson's disease: a double blind, placebo controlled study.

The effect, therapeutic dose range, and pharmacokinetics of apomorphine, given as subcutaneous injections by a single use pen, were evaluated in the treatment of off phenomena in 22 patients with idiopathic Parkinson's disease. At study entry a placebo controlled apomorphine test was performed, and apomorphine doses were then individually titrated (mean 3.4 (range 0.8-6.0) mg) and compared with placebo in a double blind cross over phase. With apomorphine compared with placebo the mean daily duration of off periods was reduced by 51% as assessed by the patients and by 58% as assessed by the staff. The severity of off periods was also significantly reduced. The effect was unchanged after a maintenance phase of eight weeks. At study termination 13 of 14 patients were able to inject themselves and 11 of 14 patients found that their feeling of freedom had increased. The most common adverse events were nausea, subcutaneous nodules, and increased frequency of involuntary movements. Pharmacokinetics were linear and did not change with repeat dosing. The tmax ranged from five to 45 minutes (16 patients). It is concluded that pen injected apomorphine is a valuable treatment for patients with advanced Parkinson's disease with on-off phenomena.

Adult↗
PubMed1994

Selective sub-dissection of the striatal primordium for cultures affects the yield of DARPP-32-containing neurones.

We have studied the effect of selectively dissecting the lateral (LGE) and medial (MGE) ganglionic eminences of the striatal primordium on the yield of DARPP-32-immunoreactive striatal neurones in serum-free cultures maintained for 2 or 5 days. The LGE cultures yielded an approximately four-fold higher number of DARPP-32-positive neurones compared with the MGE cultures, without an accompanying difference in total cell numbers. In both types of culture, there was a 70% reduction in DARPP-32 positive neurones from 2 to 5 days in vitro. In conclusion, the LGE is a rich source of striatal precursors and the present culture system provides a good model for the study of factors that may prevent striatal neuronal death.

Animals↗
PubMed1994

Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease.

Two patients with idiopathic Parkinson's disease (Patients 3 and 4 in our series) were followed up to 3 years after grafting of human embryonic dopamine-rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant amelioration of parkinsonian symptoms and increased 6-L-[18F]-fluorodopa uptake in the grafted putamen, as assessed with positron emission tomography. Three years after grafting the patients still exhibited increased fluorodopa uptake in the grafted putamen and significant clinical improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the "off" phase, and by a prolongation of the effect of a single dose of L-dopa. Between 1 and 3 years after surgery, Patient 3 showed only minor changes of parkinsonian symptoms on the side contralateral to the graft, whereas there was a worsening on the ipsilateral side. Fluorodopa uptake decreased in the nongrafted putamen but was unchanged in the grafted putamen. Patient 4 continued to improve after the first postoperative year and L-dopa was withdrawn after 32 months. The reduction of parkinsonian symptoms on the side contralateral to the graft became more pronounced between 1 and 3 years after surgery. Fluorodopa uptake further increased in the grafted putamen, whereas no change was detected on the non-grafted side. These results indicate that grafts of embryonic dopamine neurons can survive, grow, and exert functional effects up to at least 3 years after surgery in the parkinsonian brain, despite an ongoing disease process leading to degeneration of the intrinsic dopamine system.

Brain Tissue Transplantation↗
PubMed1994

Platelet-derived growth factor exerts trophic effects on rat striatal DARPP-32-containing neurons in culture.

The objective of the present study was to determine if either of the two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, exerts trophic effects in vitro on developing rat strial neurons. Striatal neurons were identified using immunocytochemistry for dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton (DARPP-32). In control cultures without PDGF, the mean number of DARPP-32-positive neurons decreased by 47% at days 3 to 5 in vitro. PDGF-BB, but not PDGF-AA, significantly increased the number of DARPP-32-positive neurons both at day 3 (by 42%) and day 5 (by 149%). Total cell number was similar in control and PDGF-BB-treated cultures, suggesting that, in striatal cultures, the action of PDGF-BB is relatively specific for DARPP-32-positive neurons. The DARPP-32-positive neurons in PDGF-BB-treated cultures had longer neurites and larger soma areas than those in control and in PDGF-AA-treated cultures. Our data provide evidence that PDGF-BB exerts a trophic action on striatal DARPP-32-positive neurons in vitro by promoting cell survival and morphological differentiation, although a stimulatory effect on intraneuronal DARPP-32 levels also is possible. The findings raise the possibility that PDGF-BB might also be involved in the development and maintenance of striatal neurons in vivo, and could be used to counteract striatal degeneration in models of Huntington's disease.

Animals↗
PubMed1994

Clinical application of cell transplantation and neurotrophic factors in CNS disorders.

Cell transplantation and administration of neurotrophic factors are now being explored as new therapeutic strategies to restore and preserve function in the diseased human central nervous system. Neural grafts show long-term survival and restore function in patients with Parkinson's disease, but the symptomatic relief needs to be increased. Cell transplantation also seems justified in patients with Huntington's disease and, possibly, in demyelinating disorders. Clinical trials with neurotrophic factors have been initiated in amyotrophic lateral sclerosis, dementia and Huntington's disease, and may later be started in Parkinson's disease and after acute brain insults. However, it remains to be shown if neurotrophic factors can rescue damaged cells in the brain and spinal cord of patients with these disorders.

Animals↗