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Biomedical subjects

R Sandyk

Publications and source records attributed to R Sandyk.

At least 271 records · Page 15Linked to original sources
PubMed1988

Serotonergic mechanisms in levodopa-induced "on-off" and sleep disorders in Parkinson's disease.

Serotonergic mechanisms have been implicated in levodopa-induced psychiatric toxicity reactions in Parkinson's disease (PD). Although CNS serotonin levels are reduced in Parkinsonian patients, the contribution of this abnormality to the pathophysiology of the motor symptoms of the disease are largely unknown. The following report concerns a 62-year-old female Parkinsonian patient with levodopa-induced "On-Off", depression and sleep disturbances, the severity of which was dramatically reduced by administration of low dosage amitriptyline (a serotonergic agent). The report suggests that impaired central serotonergic functions may be implicated in the pathophysiology of the levodopa-induced "On-Off" and that pharmacologic manipulations of serotonergic functions may be useful in the management of this motor side effect of chronic levodopa therapy.

Amitriptyline↗
PubMed1988

New vistas in chronic schizophrenia.

In view of the distinct possibility that the disturbed glucose regulation in the frontal area and basal ganglia of chronic schizophrenia is very germane to the successful treatment of this condition, a survey is given of the many factors that have to be considered in developing a therapy that takes into account this new information. The suggestion is made that the balance between cAMP and cGMP in the cells affected are dysregulated so that there is an excessive activity of the cAMP generating system which eventually leads to the pathological picture found in this condition. To restore the normal metabolic balance, use will have to be made of the various substances that are known to enhance the cGMP generating system in the cell, thereby restoring a more normal metabolic integrity. In this connection, the use of high doses of insulin under cover of hyperglycaemia and also the addition of D-ribose could become the cornerstone of a series of treatments to enhance the action of currently used medications in this often intractable illness.

Acute Disease↗
PubMed1988

Neuroleptic-mediated hypothalamic deregulation of central insulin and peripheral glucose metabolism in tardive dyskinesia: a hypothesis.

In the following communication we discuss evidence that impaired peripheral and central glucose and insulin metabolism may be significant in the pathophysiology of neuroleptic-induced tardive dyskinesia. Such an association between alterations in glucose metabolism and pathophysiology of tardive dyskinesia may open new avenues in the prevention and pharmacological management of this often therapy-resistant chronic neurological disorder.

Animals↗
PubMed1988

Failure of amantadine hydrochloride to alter immune responses in the experimental allergic encephalomyelitis model of neuroautoimmune disease.

Amantadine hydrochloride has been reported efficacious in the symptomatic management of patients with multiple sclerosis (MS). To characterize further the potential effects of amantadine in MS, we studied the drug's effect on immunological parameters in the experimental allergic encephalomyelitis (EAE) model. Nine Lewis rats were used; 3 served as controls and 6 were EAE-induced. Three of the EAE-induced rats received amantadine (AMT) (0.3 g/kg/day) at the onset of EAE symptoms. Sera were collected post-AMT treatment and assayed for antimyelin basic protein antibody (anti-MBP) and 2'3'-cyclic nucleotide 3'-phosphohydrolase activity (CNP). The mean differences in the immunological parameters between treated and nontreated EAE-induced groups were not significant. These findings fail to demonstrate a specific effect of amantadine on immunologic responses tested in the EAE model, and do not support the notion that the effects of amantadine in MS are linked to basic alterations in immune responses.

Amantadine↗
PubMed1988

Serotonin in involuntary movement disorders.

Several recent studies have emphasized that serotonergic pathways in the CNS are intimately involved in the modulation of motor behavior, and in the pathophysiology of human involuntary movement disorders. These observations are supported by recent reports demonstrating large serotonergic innervation of the striatum and substantia nigra, and a close interaction between the activity of serotonergic neurons with the dopamine system in the striatum and nigra. In the following communication we summarize evidence demonstrating defective serotonergic functions in a number of human movement disorders and discuss their management with serotonergic drugs.

Basal Ganglia↗
PubMed1988

Enkephalinergic mechanisms in the "compensated" phase of Parkinson's disease.

Loss of 70-80% of striatal dopamine (DA) content has been regarded crucial to the onset of Parkinson's Disease (PD) (Bernheimer et al., 1973). Several compensatory mechanisms have been shown to develop in the nigrostriatal DA system which could possibly contribute to the maintenance of DA-ergic transmission at the early stages of the disease. Hornykiewicz (1966) proposed that the preclinical phase of Parkinsonism might be due to compensatory changes that permit residual DA-ergic neurons to subserve functions previously carried out by the entire nigrostriatal projection. One such compensatory mechanism may include increase in transmitter release from the remaining DA-ergic terminals (Agid et al., 1973), increase in the density of the biosynthetic enzymes of DA synthesis (Zigmond et al., 1984), and increase in the number of the D2 DA postsynaptic receptors (Bokobza et al., 1984). However, with further progression of striatal DA loss, these compensatory mechanisms become insufficient in maintaining adequate DA-ergic transmission and the clinical symptoms of the disease become apparent.

Animals↗
PubMed1988

Neurochemical perspectives of the narcoleptic syndrome.

Narcolepsy has been defined as a disorder of excessive sleep often associated with cataplexy, sleep paralysis and hypnagogic hallucinations. Although the pathophysiology of the narcoleptic syndrome is not well understood, derangement in the functions of CNS catecholamines and serotonin (5-HT) have been implicated. In the present paper we summarize evidence to suggest a role for the endogenous opioids in the regulation of normal sleep and in the pathophysiology of the narcoleptic syndrome.

Humans↗
PubMed1988

Intraspinal opiates for treatment of intractable pain in the terminally ill cancer patient.

The discovery of opiate receptors and then their endogenous ligands in 1974 (Snyder et al., 1974) has elucidated a vast pharmacology of opiates providing a basis for their diverse clinical applications. With the awareness of quality of life as a primary goal in terminal cancer patients, widespread attention has been drawn to the direct delivery of long-term intraspinal analgesics to cancer patients for who all medical pain control regimens have failed (Coombs & Saunders, 1974). Intraspinal administration of opiates and nonopiate analgesics is not only appealing on theoretical grounds but provides a minimally invasive method to insure otherwise unobtainable pain relief while eliminating obtundation and systemic side-effects associated with conventional therapy (Cobb et al., 1984; Harbaugh et al., 1982; Leavens et al., 1982; Malone et al., 1985; Onofrie et al., 1981; Poletti et al., 1981). Although intraspinal opiates have been used in the treatment of postoperative and benign-pain syndromes (Asari et al., 1981; Cousins & Mather, 1984), in our discussion we review the basic science, current techniques and possible future improvements in spinal analgesia in the control of chronic cancer pain.

Humans↗
PubMed1987

The effects of L-tryptophan on haloperidol-induced movement disorder in the rat.

An animal model of haloperidol-induced tardive dyskinesia was studied in relation to the dietary manipulation of tryptophan and its effect on the movement disorder. This study showed a significant negative behavioral response to the neuroleptic drug, haloperidol. Increased dietary tryptophan (1.0 vs. 0.3%) significantly reduced the frequency of drug-induced head movements. Brain serotonin levels were elevated by the drug treatment. Brain serotonin levels correlated significantly with the behavioral response. Contrary to expectation, brain dopamine levels did not correlate with the behavioral response. These findings suggest a possible serotonergic involvement in neuroleptic-induced tardive dyskinesia and an amelioration of the disorder through tryptophan supplementation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

The hypothalamus in Parkinson disease.

It is currently believed that Parkinson disease (PD) is due to a degenerative process that independently damages multiple areas of the central and peripheral nervous system. Loss of nigrostriatal dopamine is now widely recognized as being directly related to the motor symptoms in Parkinson's disease. Parkinsonian patients also exhibit symptoms and signs suggestive of hypothalamic dysfunction (e.g. dysautonomia, impaired heat tolerance). The latter clinical features are supported by pathological, biochemical and endocrinological findings. Lewy body formation has been demonstrated in every nucleus of the hypothalamus, specifically the tuberomamillary and posterior hypothalamic. Preferential involvement of the hypothalamus was also noted in patients after post-encephalitic parkinsonism. Loss of dopamine (30-40%) in the hypothalamus of affected patients has been shown in recent studies, and is compatible with the reported abnormalities of growth hormone release in response to L-dopa administration, elevated plasma levels of MSH, and reduced CSF levels of somatostatin and beta-endorphins in these patients. Deranged immunological mechanisms have been found in PD patients including the presence of autoantibodies against sympathetic ganglia neurons, adrenal medulla and caudate nucleus. On the evidence of on pathological studies demonstrating the early vulnerability of the hypothalamus in aging and PD, and the known role of the hypothalamus in immune modulation, we expect that it will be shown that primary damage of the hypothalamus leads to subsequent secondary degeneration of structures receiving direct projections from the hypothalamus. Within this framework, the dopaminergic systems may be damaged, since striatal dopamine synthesis and receptor sensitivity have been shown to be regulated by ACTH and alpha-MSH through direct arcuate nucleus-striatal projections.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System↗