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Biomedical subjects

S Fahn

Publications and source records attributed to S Fahn.

At least 199 records · Page 11Linked to original sources
PubMed1989

Autoradiographic evidence of [3H]neurotensin binding changes in discrete regions of brain in the rat model of persistent spasmodic dyskinesia induced by iminodipropionitrile.

Chronic injection of iminodipropionitrile (IDPN) to rats causes a persistent set of abnormalities which includes hyperlocomotion, hyperexcitability, and dyskinetic movements of the neck. These behavioral changes are very similar to those observed after the acute administration of the dopamine (DA) agonist, amphetamine, in rodents. Because of the anatomical and functional evidence that neurotensin (NT) can modulate DA neurotransmission, the present receptor autoradiographic study investigated the binding of [3H]NT in the brains of IDPN-treated rats. There were significant decreases in binding in the frontal and cingulate cortices, the rhinal sulcus, the dorsolateral aspect of the caudate-putamen, and in the ventral tegmental area. These results provide the first evidence for the possible participation of the NT system in the manifestations of the IDPN-induced syndrome.

Animals↗
PubMed1989

Regional effects of 6-hydroxydopamine (6-OHDA) on free radical scavengers in rat brain.

Superoxide dismutase (SOD), catalase, glutathione (GSH), and glutathione peroxidase (GSH-Px) were measured in the caudate-putamen (CPu), the hippocampus (HIP), and the brainstem (BS) of the brains of control animals and of rats treated with one intracerebroventricular infusion of 6-hydroxydopamine (6-OHDA). Injection of 6-OHDA resulted in significant decreases in the activity of SOD in the CPu, the BS, and in the HIP. There were decreases in catalase in the CPu and in the BS, but not in the HIP. GSH was reduced in the CPu and the BS but not changed in the HIP. There were small decreases in the activity of GSH-Px only in the BS. These changes may be secondary to the production of free radicals after the infusion of 6-OHDA in rat brain.

Animals↗
PubMed1989

Biochemical properties of monoamine-rich human neuroblastoma cells.

The biochemical, pharmacological and immunological characterization of cells derived from human neuroblastoma tumors recently acquired great interest, since these cells may be a putative donor source for transplantation in animal models of neurological disorders. We measured monoamine levels, tyrosine hydroxylase (TH) immunostaining, and the expression of major histocompatibility cell surface antigens (MHC) in 7 human neuroblastoma cell lines. Three cell lines (LAN5, NB69 and CHP126) had high levels of monoamines. TH immunostaining was strongly positive in CHP126 and LAN5, and NB69. MHC were not detected in any of the cells with high catecholamine levels. Treatment with neuroleptics increased the metabolism of dopamine in LAN5 but not in NB69. The implantation of LAN5 cells in immunocompetent, unilaterally 6-hydroxydopamine-lesioned rats decreased the apomorphine-induced contralateral rotation. The effect of the implant was greatest in animals in which LAN5 neuroblastoma cells, pretreated with dibutyryl cyclic adenosine monophosphate (DBcAMP) and prostaglandin E1 (PGE1, were implanted into the cerebral ventricle ipsilateral to the lesion, and then irrigated with DBcAMP administered through a totally implanted drug delivery system. The effect of the implant decreased after the second week. Neuroblastoma cells were found in approximately 50% of the implanted animals. TH immunostaining was weak or absent in the grafted animals. Inflammatory changes were present in the majority of the brains examined. Extensive tumor growth was present in one animal implanted with untreated cells. Grafting of cells treated with DBcAMP and PGE1 plus with mitomycin C and bromodeoxyuridine in animals immunosuppressed with cyclosporin A reduced the apomorphine-induced rotation to 40-60% of baseline levels and this reduction persisted beyond the period of infusion with DBcAMP. Intraventricular infusion of DBcAMP in animals injected with cell culture medium produced a transient reduction of rotation to 70% of baseline. The amphetamine-induced rotation was not significantly reduced during the 4 weeks follow up. Atypical cells, consistent with surviving neuroblastoma cells, were observed in the brain of all transplanted animals. TH immunostaining was weak or negative in most cases. Human neuroblastoma cells may be an alternative donor tissue for the study of the effects of transplantation in animal models of Parkinson's disease.

Animals↗
PubMed1989

Vitamin E attenuates the toxic effects of intrastriatal injection of 6-hydroxydopamine (6-OHDA) in rats: behavioral and biochemical evidence.

Unilateral 6-hydroxydopamine (6-OHDA) injections into the striatum lead to the development of apomorphine-induced rotation in rats. The circling behavior was associated with significant decreases in dopamine, dihydroxyphenylacetic acid and homovanillic acid in the ipsilateral striatum. Pretreatments with either D-alpha-tocopherol or all-racemic-alpha-tocopherol caused significant attenuation of both the behavioral and biochemical abnormalities. These results are discussed in terms of their support for the free radical hypothesis of Parkinson's disease and for the role of antioxidants in the treatment of this neurodegenerative disorder.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Idiopathic dystonia among Ashkenazi Jews: evidence for autosomal dominant inheritance.

We studied families to clarify the mode of inheritance of idiopathic torsion dystonia among the Ashkenazim. Probands had symptoms before 28 years of age, had at least one Ashkenazi grandparent, and were ascertained independently of family history and not referred by another relative. All available first- and second-degree relatives were examined, and videotapes were made. Examination notes and blinded review of videotapes led to rating of dystonia as definite, probable, possible, or absent. We determined rates of illness for first- and second-degree relatives and calculated age-adjusted lifetime risks. The methods of maximum likelihood and likelihood ratio goodness-of-fit tests were used to estimate parameters and to test dominant and recessive models of inheritance. We studied 43 probands, 146 (90.1%) of 162 living first-degree relatives, and 96 (40.2%) of 239 living second-degree relatives. Nineteen relatives had definite dystonia, and 2 had probable dystonia. Using definite cases only, the age-adjusted risk for all first-degree relatives was 15.5% and for all second-degree relatives 6.5%, with no significant sex differences; parent, offspring, and sibling risks did not differ significantly. The risks were consistent with autosomal dominant inheritance with a penetrance estimated at 29.4% using definite cases only or 32.2% using definite and probable cases. Assuming a disease frequency of 1/15,000, the gene frequency was estimated to be 1/9000.

Adolescent↗
PubMed1989

Tardive akathisia: an analysis of clinical features and response to open therapeutic trials.

In recent years, there has been increasing recognition that akathisia occurs not only as an acute, self-limited complication of dopamine (DA) antagonist treatment, but also as a persistent form, called tardive akathisia. We represent a retrospective analysis of clinical features and therapeutic trials in 52 cases of this disorder. Although most patients developed this disorder after years of DA antagonist treatment (mean = 4.5 years), a significant proportion (34%) developed it within 1 year. The characteristic motor features included frequent, complex stereotyped movements. The legs were most frequently involved, showing marching in place and crossing/uncrossing. Trunk rocking, respiratory grunting and moaning, and complex hand movements such as face rubbing or scratching also occurred. In the 26 patients who were able to discontinue DA antagonists, akathisia persisted for years (mean = 2.7 years, range of 0.3-7 years) until abatement of symptoms or last follow-up. Younger patients were more likely to have remission or therapeutic suppression of akathisia at follow-up. In our experience, the catecholamine-depleting drugs reserpine and tetrabenazine were the most effective agents for suppressing symptoms, producing improvement in 87 and 58% of patients treated, respectively. However, improvement was limited in many patients, and at last follow-up only 33% of patients had complete abatement of their symptoms. In conclusion, tardive akathisia is a particularly disabling form of tardive dyskinesia, frequently persistent for years and often resistant to therapy.

Adult↗
PubMed1989

Adductor laryngeal dystonia (spastic dysphonia): treatment with local injections of botulinum toxin (Botox).

Adductor spastic dysphonia (SD) is a laryngeal dystonia characterized by a choked, constrained voice pattern with breaks in vocal flow. Treatment with a variety of therapies including speech and pharmacotherapy have minimal benefit; only one-third of patients undergoing recurrent laryngeal nerve section have benefitted at 3 years. We have used local injections of botulinum toxin (Botox) bilaterally into vocalis muscles in 42 patients with SD. Injections were through a teflon-coated hollow electromyography (EMG) recording needle. Unilateral small doses (2.5-3.75 U) were of no clinical benefit. Bilateral small doses resulted in sustained improvement lasting 84.4 +/- 9.3 days. The degree of improvement was 61.1 +/- 4.6%. Common side-effects included a brief period of breathy hypophonia (8.5 +/- 2.5 days) and a mild sensation of choking/aspiration of fluids (1.7 +/- 0.6 days); there were no serious adverse effects. Vocal cord paralysis was not necessary for benefit. Follow-up vocalis muscle EMGs revealed denervation. All patients responded to retreatment (longest follow-up 3.5 years). Patients with prior recurrent laryngeal nerve surgery and residual uncomplicated dysphonia had similar results. Our results indicate that local injection of low-dose Botox is the treatment of choice for SD.

Adult↗
PubMed1989

Monoamine oxidase inhibitory properties of milacemide in rats.

Milacemide is a glycine prodrug with reported antiepileptic antimyoclonic properties. In this study, milacemide increased "wet dog shakes" in rats pretreated with 5-Hydroxytryptophan (5-HTP) and carbidopa. Moreover, it worsened the serotonin behavior syndrome precipitated by 5-HTP and the monoamine oxidase inhibitor tranylcypromine. The serotonin syndrome was also elicited by the combination of milacemide and 5-HTP without tranylcypromine. In vitro, milacemide inhibited both monoamine oxidase A and B from the frontal cortex of rats, to a greater extent for MAO B. This drug is currently under investigation in humans as an antiepileptic agent and precautions for the consequences of monoamine oxidase inhibition should be considered when the drug is used in high doses.

5-Hydroxytryptophan↗
PubMed1989

Milacemide increases 5-hydroxytryptamine and dopamine levels in rat brain--possible mechanisms of milacemide antimyoclonic property in the p,p'-DDT-induced myoclonus.

Milacemide, a glycine prodrug that is able to enter the brain readily, has been shown to have an antimyoclonic property in the p,p'-DDT-induced myoclonus syndrome. Milacemide increased regional 5-HT and dopamine and decreased 5-HIAA, DOPAC and HVA levels in naive rats. In p,p'-DDT-treated rats, 5-HT levels were unchanged at the time the rats experienced spontaneous myoclonus in all brain regions except in the striatum, where it increased. 5-HIAA levels increased but did not reach significant levels except in the striatum. Dopamine, DOPAC, HVA and norepinephrine were unchanged. When rats were treated concurrently with both p,p'-DDT and milacemide, regional 5-HT levels were increased and NE levels in the brainstem and cerebellum decreased. Depletion of brain serotonin by pretreatment with PCPA or with 5,7-DHT, or blocking 5-HT receptors with different 5-HT antagonists, failed to eliminate the antimyoclonic property of milacemide. This antimyoclonic effect of milacemide may be mediated through other mechanisms besides its ability to increase brain 5-HT levels. Possible mechanisms to be considered are its antiepileptic property, and its ability to increase brain glycine levels. Milacemide may have potential for therapeutic trials in patients with myoclonus.

Acetamides↗
PubMed1989

The protein synthesis inhibitor, anisomycin, causes exacerbation of the iminodipropionitrile-induced spasmodic dyskinetic syndrome in rats.

The effects of anisomycin on dyskinetic head movements, circling, and locomotor activity were investigated in the IDPN-induced syndrome. Intracerebroventricular (ICV) injections of anisomycin in conjunction with IDPN caused exacerbation of all aspects of the syndrome, although circling and vertical head dyskinesias (retrocollis) were the most affected. Animals treated with only anisomycin showed persistent retrocollis but not laterocollis or circling. Biochemical studies confirmed the increases in the concentration of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) previously observed in the striata of IDPN-treated rats two weeks after stopping administration of the drug. Rats treated with anisomycin alone also showed significant increases in striatal 5-HT and 5-HIAA concentrations which were somewhat higher on the side of the ICV infusions. Coadministration of IDPN and anisomycin did not cause any further increases in 5-HT or 5-HIAA. These results suggest that inhibition of protein synthesis by IDPN may be one of the processes involved in the development of the persistent dyskinetic syndrome.

Animals↗
PubMed1989

Clinical variants of idiopathic torsion dystonia.

Some patients with dystonic movements and postures not known to be caused by environmental or degenerative disorders can be segregated from classical-appearing idiopathic torsion dystonia on the basis of distinctive clinical and pharmacologic features. Many of them should be considered within the family of dystonia, as clinical variants of idiopathic torsion dystonia, while others are better classified as being part of other families of dyskinesias. In the former group are paradoxical dystonia, myoclonic dystonia, diurnal dystonia, and dopa-responsive dystonia. The latter group consists of dystonic tics and the various entities comprising paroxysmal dystonia, namely kinesigenic, nonkinesigenic and hypnogenic dystonia.

Diagnosis, Differential↗
PubMed1989

Botulinum toxin injection for the treatment of oromandibular dystonia.

Dystonia is a neurologic disorder characterized by abnormal, involuntary movements causing twisting and turning postures; it is postulated to be a disorder of central motor processing. The dystonias, when classified by region of the body involved, have been characterized as focal, segmental, and generalized. Focal dystonia can affect jaw mechanics, leading to forceful contraction of the jaw muscles and resulting in inappropriate deviation of the jaw. Localized injections of botulinum toxin have been used successfully in the management of other focal or segmental dystonias. We have treated 20 oromandibular dystonia patients with botulinum toxin. Six patients had only jaw and tongue involvement; 11 had blepharospasm and jaw involvement; and three had jaw involvement as part of a more generalized dystonia. Five patients had been diagnosed originally and treated as having temporomandibular joint syndrome. All but one of the patients had improvement of their symptoms with the toxin injections. The patients averaged 47% improvement with the injections.

Aged↗
PubMed1989

Methylprednisolone treatments alter apomorphine-induced circling in the rat model of 6-hydroxydopamine-induced striatal denervation.

Intrastriatal injection of 6-hydroxydopamine causes significant depletion of dopamine which is associated with contralateral apomorphine-induced rotation in rats. Pretreatment with methylprednisolone (MP) causes almost complete elimination of the apomorphine-induced behavioral responses. In addition, there were significant differences between the lateralization effects of the neurotoxin on the levels of striatal dopamine. These results suggest that MP may have ameliorative effects against the motoric behavioral changes associated with the intrastriatal injection of 6-OHDA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Non-chromaffin tissue plus nerve growth factor reduces experimental parkinsonism in aged rats.

The mechanisms by which intrastriatal grafts of chromaffin tissue alleviate the signs of clinical and experimental parkinsonism remain elusive. In the present report, we have demonstrated that, in conjunction with intraventricular infusion of nerve growth factor (NGF), ventricular grafts of either non-chromaffin or adrenal medullary tissue are equally effective in reducing apomorphine-induced circling in rats whose substantia nigra have been permanently lesioned with 6-hydroxydopamine. These treatments were much more effective than implantation of adrenal medulla without NGF. In addition, the effects persisted indefinitely, though at a reduced level, after discontinuation of the NGF infusion. The results suggest that trophic factors may be crucial to the beneficial effects of intracerebral transplanted tissues.

Adrenal Medulla↗
PubMed1988

The iminodipropionitrile (IDPN) model of persistent spasmodic dyskinesias: regional serotonin metabolism in rat brain.

Chronic administration of iminodipropionitrile (IDPN) in rats causes a persistent behavioral syndrome which consists of lateral and vertical twitches, random circling, and hyperactivity. These abnormalities are very similar to those induced by the acute injection of serotonin (5-HT) agonists. The present study reveals significant increases in the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the caudate-putamen and in the nucleus accumbens during treatment with IDPN. In the striatum, these changes lasted up to one month after the last injection of the drug. There were less prominent increases in 5-HT and decreases in 5-HIAA in the brainstem of these animals. These data are consistent with our previous study in which we found significant decreases in the number of 5-HT2 receptors in both the striatum and the accumbens of rats which were suffering from the IDPN-induced syndrome for a period of one month. These results are discussed in terms of their support for a possible role of the serotonin system in both the appearance and the persistence of this dyskinetic syndrome.

Animals↗