Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reported previously that Go-deficient mice develop severe neurological defects that include hyperalgesia, a generalized tremor, lack of coordination, and a turning syndrome somewhat reminiscent of unilateral lesions of the dopaminergic nigro-striatal pathway. By using frozen coronal sections of serially sectioned brains of normal and Go-deficient mice, we studied the ability of several G protein coupled receptors to promote binding of GTPgammaS to G proteins and the ability of GTP to promote a shift in the affinity of D2 dopamine receptor for its physiologic agonist dopamine. We found a generalized, but not abolished reduction in agonist-stimulated binding of GTPgammaS to frozen brain sections, with no significant left-right differences. Unexpectedly, the ability of GTP to regulate the binding affinity of dopamine to D2 receptors (as seen in in situ [(35)S]sulpiride displacement curves) that was robust in control mice, was absent in Go-deficient mice. The data suggest that most of the effects of the Gi/Go-coupled D2 receptors in the central nervous system are mediated by Go instead of Gi1, Gi2, or Gi3. In agreement with this, the effect of GTP on dopamine binding to D2 receptors in double Gi1 plus Gi2- and Gi1 plus Gi3-deficient mice was essentially unaffected.
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PMID:Most central nervous system D2 dopamine receptors are coupled to their effectors by Go. 1124 20

The availability of the cannabinoid antagonist, SR 141716A, to precipitate withdrawal following repeated cannabinoid administration provides a model to investigate the mechanisms underlying cannabinoid dependence as well as potential treatments to alleviate withdrawal symptoms. The goal of the present study was to determine whether SR 141716A-precipitated withdrawal symptoms in Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-tolerant mice could be alleviated by either readministration of Delta(9)-THC or clonidine, an alpha(2)-receptor agonist. SR 141716A elicited paw tremors in Delta(9)-THC-tolerant mice, but produced a significant increase in head shakes independently of repeated Delta(9)-THC treatment. Readministration of Delta(9)-THC, following SR 141716A-precipitated withdrawal, reversed paw tremors (ED(50)=9.9 mg/kg), but failed to reduce head shaking behavior. Clonidine reversed SR 141716A-precipitated paw tremors (ED(50)=0.18 mg/kg) and blocked head shakes at all doses tested. The reversal effects did not appear to be the result of motor impairment because neither decreases in spontaneous locomotor activity nor motor incoordination, as assessed in the inverted screen test, could account for the effects. These findings suggest that SR 141716A precipitates paw tremors in mice by competing with Delta(9)-THC at the CB(1) receptor, though it also produced head shaking in nondependent animals. Finally, the observation that clonidine alleviated SR 141716A-precipitated paw tremors suggests its potential as a treatment for cannabinoid dependence.
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PMID:Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine. 1142 84

Neuropathic pain, whether of peripheral or central origin, is characterized by a neuronal hyperexcitability in damaged areas of the nervous system. In peripheral neuropathic pain, damaged nerve endings exhibit abnormal spontaneous and increased evoked activity, partly due to an increased and novel expression of sodium channels. In central pain, although not explored in detail, the spontaneous pain and evoked allodynia are also best explained by a neuronal hyperexcitability. The peripheral hyperexcitability is due to a series of molecular changes at the level of the peripheral nociceptor, in dorsal root ganglia, in the dorsal horn of the spinal cord, and in the brain. These changes include abnormal expression of sodium channels, increased activity at glutamate receptor sites, changes in gamma-aminobutyric acid (GABA-ergic) inhibition, and an alteration of calcium influx into cells. The neuronal hyperexcitability and corresponding molecular changes in neuropathic pain have many features in common with the cellular changes in certain forms of epilepsy. This has led to the use of anticonvulsant drugs for the treatment of neuropathic pain. Carbamazepine and phenytoin were the first anticonvulsants to be used in controlled clinical trials. Studies have shown these agents to relieve painful diabetic neuropathy and paroxysmal attacks in trigeminal neuralgia. Subsequent studies have shown the anticonvulsant gabapentin to be effective in painful diabetic neuropathy, mixed neuropathies, and postherpetic neuralgia. Lamotrigine, a new anticonvulsant, is effective in trigeminal neuralgia, painful peripheral neuropathy, and post-stroke pain. Other anticonvulsants, both new and old, are currently undergoing controlled clinical testing. The most common adverse effects of anticonvulsants are sedation and cerebellar symptoms (nystagmus, tremor and incoordination). Less common side-effects include haematological changes and cardiac arrhythmia with phenytoin and carbamazepine. The introduction of a mechanism-based classification of neuropathic pain, together with new anticonvulsants with a more specific pharmacological action, may lead to more rational treatment for the individual patient with neuropathic pain.
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PMID:Anticonvulsants in neuropathic pain: rationale and clinical evidence. 1188 43

We present the first reported study of Ruta graveolens toxicity in 7-8-month-old Nubian goats. Oral administration of 5 g/kg bw per day of R. graveolens leaves caused tremor, dyspnoea, frequent urination, incoordination of movement, ataxia and recumbency, with death after 1-7 days. In goats receiving oral doses of 1 g/kg bw per day of the leaves, the course of toxicity was prolonged and the animals had pallor of the visible mucous membranes and loss in condition; one died on day 17, the others being slaughtered on days 41 and 46. The clinical effects were correlated with pathological changes in various organs, alterations in serum aspartate transaminase, creatine kinase, total protein, cholesterol, urea and other serum constituents, haematological values and the concentrations in the tissues of copper, iron, zinc, manganese, calcium and phosphorus.
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PMID:Preliminary observations on experimental Ruta graveolens toxicosis in Nubian goats. 1216 28

This is a critique of a study by Howlett, Nkya, Mmuni, Missalek, published in AIDS (1989), which reports on clinical findings in 200 AIDS patients at the Kilimanjaro Christian Medical Center in Tanzania between 1985-88. For 135 of these patients, the study concentrates on the clinical neurological symptoms of AIDS. General symptoms included weakness (98%); wasting (92%); fever (79%); diarrhea (75%); maculo-papulor rash (71%); and candidiasis (57%). Neurological symptoms included AIDS dementia complex (54%); retinal abnormalities (23%); areflexia (21%); pyramidal tract signs (19%) and tremor and incoordination (19%). This study is the most detailed published examination to date of the clinical neurological symptoms associated with AIDS in African patients. In spite of the weaknesses of the study the paucity of laboratory investigations and the lack of autopsy information and the frequency of different infections affecting the nervous system in African AIDS patients, the study will be referenced in all future works on the neurology of AIDS in Africa. (Author's modified).
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PMID:Neurological disorders in AIDS and HIV disease in the northern zone of Tanzania. 1228 84

Wilson's disease is a rare autosomal recessive disease of copper accumulation and copper toxicity, due to mutations in the ATP7B gene, which leads to a failure of copper excretion in the bile. It presents clinically primarily as liver disease, psychiatric disease, neurological disease, or a combination of these. The neurological disease is a movement disorder, with abnormalities of speech, tremor, incoordination and dystonia being common features. Diagnosis of neurologically presenting patients is usually straightforward, with Kayser-Fleischer rings and a urine copper over 100 microg/day almost invariably present. In the treatment of neurologically presenting patients, penicillamine should always be avoided, because of the high risk of permanent, drug-induced, additional neurological deterioration. A new drug we have developed, tetrathiomolybdate, given for 8-16 weeks, in combination with zinc, is our first choice for treating these patients. In the absence of availability of tetrathiomolybdate, zinc or trientine are the next best choices.
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PMID:Neurologically presenting Wilson's disease: epidemiology, pathophysiology and treatment. 1574 Jan 74

Essential tremor is the most common movement disorder and has an unknown etiology. Here we report that gamma-aminobutyric acidA (GABA(A)) receptor alpha1-/- mice exhibit postural and kinetic tremor and motor incoordination that is characteristic of essential tremor disease. We tested mice with essential-like tremor using current drug therapies that alleviate symptoms in essential tremor patients (primidone, propranolol, and gabapentin) and several candidates hypothesized to reduce tremor, including ethanol; the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801; the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA); the GABA(A) receptor modulators diazepam, allopregnanolone, and Ro15-4513; and the L-type Ca2+ channel antagonist nitrendipine. Primidone, propranolol, and gabapentin reduced the amplitude (power) of the pathologic tremor. Nonsedative doses of ethanol eliminated tremor in mice. Diazepam, allopregnanolone, Ro15-4513, and nitrendipine had no effect or enhanced tremor, whereas MK-801 and CCPA reduced tremor. To understand the etiology of tremor in these mice, we studied the electrophysiological properties of cerebellar Purkinje cells. Cerebellar Purkinje cells in GABA(A) receptor alpha1-/- mice exhibited a profound loss of all responses to synaptic or exogenous GABA, but no differences in abundance, gross morphology, or spontaneous synaptic activity were observed. This genetic animal model elucidates a mechanism of GABAergic dysfunction in the major motor pathway and potential targets for pharmacotherapy of essential tremor.
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PMID:Genetic essential tremor in gamma-aminobutyric acidA receptor alpha1 subunit knockout mice. 1576 40

We report on an elderly couple who presented with a syndrome that included severe generalised tremor and incoordination after eating soup from a damaged can. Black mould contaminating the can was subcultured and the fungus Penicillium crustosum was identified. This fungus usually produces a potent neurotoxin called penitrem A. The couple displayed symptoms consistent with penitrem A ingestion, all of which resolved fully. Penitrem A intoxication has been well documented in animals, but not in humans.
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PMID:Tremor syndrome associated with a fungal toxin: sequelae of food contamination. 1593 87

This study describes a comprehensive method to assess neurological deficits after brain ischemia produced by sequential common carotid artery sectioning (SCAS) in aged mice, and a scale to determine the degree of functional incapacity of ischemic animals. The method involves an initial phase of undisturbed observation and a later manipulative phase during which each animal is subjected to a sequence of very simple manipulations. Sham-operated animals demonstrated 96% survival throughout the study period (72 h), whereas the 24, 48 and 72 h survival rates of SCAS-mice were 48, 38 and 36%, respectively. In the surviving SCAS-mice, we detected a total of 23 neurological alterations throughout the observation period (72 h); the most frequent alterations were: motor incoordination, abnormal body position, hypomobility, decreased body tone and muscular strength, tremor, hunched back, passivity, forelimb flexion and ataxic gait. Based on these alterations, we used a global scale that comprises 10 progressive grades beyond 0 (normal), extending to status 10 (death due to SCAS), with higher scores indicating greater deficit. The median neurological scores for sham-operated animals were 1.36, 1.48 and 1.32 at 24, 48 and 72 h, respectively, whereas total neurological scores in SCAS-mice of 6.1, 6.8 and 7.4, at 24, 48 and 72 h, respectively, were substantially greater than those observed in sham-operated animals. The simplicity of the procedure, herein described, to measure the functional neurological condition of ischemic animals, and the remarkable level of functional impairment produced by SCAS offer the possiblity to test the efficacy of putative stroke therapies and to monitor progress of deficits over time in groups of animals.
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PMID:A simplified procedure for the quantitative measurement of neurological deficits after forebrain ischemia in mice. 1605 13

We developed and tested the clinimetric properties of a scale for psychogenic movement disorders (PMDs). PMDs are disabling but lack any generally accepted treatment strategies. To develop treatments, means of assessing disease severity must be provided. No scale to assess PMDs existed. The PMD scale developed here rates 10 phenomena (rest tremor, action tremor, dystonia, chorea, bradykinesia, myoclonus, tics, athetosis, ballism, cerebellar incoordination), 2 functions (gait, speech), and 14 body regions. To study interrater agreement, three movement disorder neurologists independently rated 88 videotapes of PMD patients. Data analysis was performed using a kappa coefficient of agreement, Kendall's coefficient of concordance, Spearman correlations, and intraclass correlation coefficients. Validity and scale responsiveness were tested as well. All phenomena and speech and gait dysfunction occurred in the patient sample. A wide range of affected body regions, severity, and incapacitation was captured. Ratings showed excellent interrater reliability for presence or absence of each phenomenon (kappa range, 0.63 to 0.86). Kendall's concordance coefficients for phenomenology, function, and total PMD scores were 0.92, 0.93, and 0.91. Spearman correlations between raters ranged from 0.86 to 0.90. The scale was responsive to changes that occurred as a result of a neuropsychiatric intervention. The PMD scale adequately captures the complex movements of PMDs and can be used to assess PMDs and test the efficacy of intervention strategies.
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PMID:Rating scale for psychogenic movement disorders: scale development and clinimetric testing. 1610 25


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