Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphorus magnetic resonance spectroscopy (MRS) was used to study muscle phosphates metabolism in several brain disorders. Those with primary mitochondrial encephalomyopathies showed the typical pattern of impaired oxidative metabolism at rest and during recovery after exercise. In migraine, Parkinson's disease and alternating hemiplegia muscle MRS observations lend support to a possible mitochondrial dysfunction. Similar observations in multiple sclerosis are probably the result of secondary deconditioning. In post polio syndrome and in some of the hereditary ataxias, elevated intracellular inorganic phosphates may be the result of another, yet unknown, metabolic impairment. Thus, muscle phosphate metabolism may be altered in various central nervous system (CNS) disorders by different metabolic impairments. All these possibilities should be taken into account when evaluating MRS results in brain diseases.
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PMID:Muscle high-energy phosphates in central nervous system disorders. The phosphorus MRS experience. 949 67

We compared the referral diagnoses of TIAs and minor strokes made by non-specialists with those of two consultant neurologists, in 565 consecutive cerebrovascular clinic patients, of whom 508 (90%) were referred with a diagnosis of any TIA or stroke. In 373 (73%), the neurologists felt the diagnosis of a cerebrovascular event to be correct. Agreement with the vascular syndrome (CVA vs. TIA) was significantly higher for patients with a referral diagnosis of stroke (136/176) (77%) than it was for patients with a referral diagnosis of TIA (200/332) (60%) (difference in proportions 17%, 95% CI 9-25). In 37 patients (7%) the neurologists confirmed the diagnosis of cerebrovascular disease but not the specific TIA/stroke diagnosis. Vascular surgeons were more likely to be correct in their referral diagnosis of carotid territory cerebrovascular disease (88% correct) than all other sources combined (63% correct) (difference in proportions 25%, 95% CI 11-39), but there was no significant variation in diagnostic accuracy between other individual groups. In 135/508 patients (27%) referred as any TIA or stroke, the diagnosis of cerebrovascular disease was undone. Alternative diagnoses included migraine (3%), epilepsy (1%), hyperventilation (1%), multiple sclerosis (1%) and a case of idiopathic Parkinson's disease, but many symptoms (8%) were unclassifiable. A strict comparison of diagnostic accuracy would have required assessment of patients not referred for specialist opinion, to estimate false-negative as well as false-positive diagnoses. However, in this patient group (which reflects current local practice) TIAs and strokes seem overdiagnosed.
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PMID:Overdiagnosis of TIA and minor stroke: experience at a regional neurovascular clinic. 953 40

Complex visual hallucinations may affect some normal individuals on going to sleep and are also seen in pathological states, often in association with a sleep disturbance. The content of these hallucinations is striking and relatively stereotyped, often involving animals and human figures in bright colours and dramatic settings. Conditions causing these hallucinations include narcolepsy-cataplexy syndrome, peduncular hallucinosis, treated idiopathic Parkinson's disease, Lewy body dementia without treatment, migraine coma, Charles Bonnet syndrome (visual hallucinations of the blind), schizophrenia, hallucinogen-induced states and epilepsy. We describe cases of hallucinosis due to several of these causes and expand on previous hypotheses to suggest three mechanisms underlying complex visual hallucinations. (i) Epileptic hallucinations are probably due to a direct irritative process acting on cortical centres integrating complex visual information. (ii) Visual pathway lesions cause defective visual input and may result in hallucinations from defective visual processing or an abnormal cortical release phenomenon. (iii) Brainstem lesions appear to affect ascending cholinergic and serotonergic pathways, and may also be implicated in Parkinson's disease. These brainstem abnormalities are often associated with disturbances of sleep. We discuss how these lesions, outside the primary visual system, may cause defective modulation of thalamocortical relationships leading to a release phenomenon. We suggest that perturbation of a distributed matrix may explain the production of similar, complex mental phenomena by relatively blunt insults at disparate sites.
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PMID:Complex visual hallucinations. Clinical and neurobiological insights. 979 40

Aside from physiological tremor, essential tremor (ET) is by far the most common cause of tremor in humans, affecting large numbers of individuals in every human population. The crude prevalence of ET has been conservatively estimated to be between 0.4% and 3.9%, although some estimates of the prevalence of ET among the elderly are higher than 20%. Essential tremor is the most prevalent adult-onset movement disorder, and is also regarded as one of the most common neurological disorders of adults, with a prevalence that is similar to or greater than that of stroke, Alzheimer disease, migraine headache, and lumbosacral pain syndromes. Essential tremor is as much as 20 times more prevalent than Parkinson disease.
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PMID:A new twist for stopping the shakes? Revisiting GABAergic therapy for essential tremor. 1040 81

This article reviews new drugs and recent knowledge or indications for old drugs for the treatment of neurological disorders. Drugs for disorders such as migraine, epilepsy, Parkinson's disease, Alzheimer's disease, ischemic stroke, amyotrophic lateral sclerosis and multiple sclerosis are considered.
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PMID:[New drugs in neurology]. 1040 81

Histamine H3 receptors exist in the presynapse of histaminergic nerve terminals, and they regulate the synthesis and release of histamine. A high density of histamine H3 receptors is observed in the cerebral cortex, the amygdala, the striatum, the hippocampus, the thalamus and the hypothalamus. In this review, we describe signal transduction mechanisms of histamine H3 receptors and discuss the structure-activity relationship of histamine H3-receptor ligands, including new compounds that possess high selectivities and affinities. Possible roles of histamine H3 receptors on neurobehavioral disorders such as Alzheimer's disease, Down syndrome, attention deficit hyperactive disease, epilepsy, stress, anxiety, Parkinson's disease, etc. were also described. Recent pharmacological studies revealed that BP2.94, a histamine H3 receptor agonist, has anti-inflammatory and analgesic action. BP2.94 may be useful for the treatment of migraine and is now in clinical trial. Histamine H3 receptor antagonists such as GT2016 and FUB181 may provide clinical candidates for the treatment of dementia, attention deficit hyperactive disorder and epilepsy.
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PMID:[The roles of histamine H3 receptors in the behavioral disorders and neuropsychopharmacological aspects of its ligands in the brain]. 1051 50

There are two families of dopamine (DA) receptors, called D1 and D2, respectively. The D1 family consists of D1- and D5-receptor subtypes and the D2 family consists of D2-, D3-, and D4-receptor subtypes. The amino acid sequences of these receptors show that they all belong to a large superfamily of receptors with seven transmembrane domains, which are coupled to their intracellular signal transduction systems by G-proteins. The implications of DA receptors in neuropsychiatry and cardiovascular and renal diseases are discussed. Neuropsychiatry indications include Parkinson's disease, schizophrenia, migraine, drug dependence, mania and depression, and Gilles de la Tourette syndrome. The underlying dysfunction of dopaminergic systems and the potential benefits of dopaminergic therapy in these different indications are critically examined. With respect to the pharmacological treatment of Parkinson's disease, a range of DA agonists are in various stages of preclinical and clinical development. D2-receptor agonist activity is predominant in most effective antiparkinsonian DA agonists. However, in practice, it is difficult to treat patients for several years with DA agonists alone; therapeutic benefit is not sustained. Rather, the use of a combination of DA agonists and levodopa is considered preferable. Reports of the efficacy of DA partial agonists await confirmation, and recent clinical investigations also suggest the potential of D1 receptor agonists as antiparkinson drugs. Regarding migraine pathogenesis, clinical and pharmacological evidence suggests that DA is involved in this disorder. Most prodromal and accompanying symptoms may be related to dopaminergic activation. Several drugs acting on DA receptors are effective in migraine treatment. Furthermore, migraine patients show a higher incidence of dopaminergic symptoms following acute DA agonist administration, when compared with normal controls. In cardiology, the therapeutic benefits of DA agonists are noted in the treatment of heart failure. Low doses of DA are widely used for its specific dopaminergic effects on renal function, which are suggested to be beneficial, and for its alpha- and beta-adrenergic-mediated responses that occur with higher doses. However, studies have been unable to demonstrate that DA can prevent acute renal failure or reduce mortality. It appears that the significant progress that is being made in the molecular understanding of DA receptors will continue to have a tremendous impact in the pharmacological treatment of neuropsychiatric, cardiovascular, and renal diseases.
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PMID:Dopamine receptors--physiological understanding to therapeutic intervention potential. 1059 3

Modern molecular biology has revealed vast numbers of large and complex proteins and genes that regulate body function. By contrast, discoveries over the past ten years indicate that crucial features of neuronal communication, blood vessel modulation and immune response are mediated by a remarkably simple chemical, nitric oxide (NO). Endogenous NO is generated from arginine by a family of three distinct calmodulin- dependent NO synthase (NOS) enzymes. NOS from endothelial cells (eNOS) and neurons (nNOS) are both constitutively expressed enzymes, whose activities are stimulated by increases in intracellular calcium. Immune functions for NO are mediated by a calcium-independent inducible NOS (iNOS). Expression of iNOS protein requires transcriptional activation, which is mediated by specific combinations of cytokines. All three NOS use NADPH as an electron donor and employ five enzyme cofactors to catalyze a five-electron oxidation of arginine to NO with stoichiometric formation of citrulline. The highest levels of NO throughout the body are found in neurons, where NO functions as a unique messenger molecule. In the autonomic nervous system NO functions NO functions as a major non-adrenergic non-cholinergic (NANC) neurotransmitter. This NANC pathway plays a particularly important role in producing relaxation of smooth muscle in the cerebral circulation and the gastrointestinal, urogenital and respiratory tracts. Dysregulation of NOS activity in autonomic nerves plays a major role in diverse pathophysiological conditions including migraine headache, hypertrophic pyloric stenosis and male impotence. In the brain, NO functions as a neuromodulator and appears to mediate aspects of learning and memory. Although endogenous NO was originally appreciated as a mediator of smooth muscle relaxation, NO also plays a major role in skeletal muscle. Physiologically muscle-derived NO regulates skeletal muscle contractility and exercise-induced glucose uptake. nNOS occurs at the plasma membrane of skeletal muscle which facilitates diffusion of NO to the vasculature to regulate muscle perfusion. nNOS protein occurs in the dystrophin complex in skeletal muscle and NO may therefore participate in the pathophysiology of muscular dystrophy. NO signalling in excitable tissues requires rapid and controlled delivery of NO to specific cellular targets. This tight control of NO signalling is largely regulated at the level of NO biosynthesis. Acute control of nNOS activity is mediated by allosteric enzyme regulation, by posttranslational modification and by subcellular targeting of the enzyme. nNOS protein levels are also dynamically regulated by changes in gene transcription, and this affords long-lasting changes in tissue NO levels. While NO normally functions as a physiological neuronal mediator, excess production of NO mediates brain injury. Overactivation of glutamate receptors associated with cerebral ischemia and other excitotoxic processes results in massive release of NO. As a free radical, NO is inherently reactive and mediates cellular toxicity by damaging critical metabolic enzymes and by reacting with superoxide to form an even more potent oxidant, peroxynitrite. Through these mechanisms, NO appears to play a major role in the pathophysiology of stroke, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.
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PMID:Endogenous nitric oxide synthesis: biological functions and pathophysiology. 1063 Jun 82

Contingent negative variation /CNV/ is a slow negative potential described first in 1964 by Walter et al. It is a correlate of cerebral activity in the frontal lobes connected with expectation of stimulus and frontal cortex preparation for the stimulus to come. CNV develops in the time between the warning signal /S1/ and the commanding signal /S2/. CNV contains two main components connected directly with brain function: the first one, so called early component, is connected with the process of orientation or warning /it is called also orientation wave/, the second one /late component/ is connected with the preparation for movement /expectation wave or preparatory wave/. The clinical application of CNV is for the evaluation of the correlation of potential changes with changes in cognitive functions occurring in various diseases. Numerous studies reported recently have confirmed the applicability of CNV on the diagnosis of dementia, Parkinson's disease, epilepsy, schizophrenia, anxiety states, chronic pains, including migraine.
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PMID:[Clinical applications of late negative evoked potentials--contingent negative variation (CNV)]. 1110 87

As brainstem mechanisms and dopaminergic neurotransmission are involved in migraine pathophysiology, we decided to investigate the course of migraine in Parkinson's disease (PD), the paradigm of brainstem dopaminergic disease. We screened 237 consecutive PD out-patients by direct interview to assess the prevalence of lifetime and current migraine. Moreover, we compared the course of migraine in PD patients with that of otherwise healthy age- (+/- 3 years) and sex-paired migraine controls in a cross-sectional study. PD patients showed a lifetime migraine prevalence of 27.8% and a current migraine prevalence of 13.1%. A positive family history of migraine was less frequent in PD patients than in controls. The frequency of current migraine was significantly lower in PD patients than in controls (47.0% vs. 68.2%; odds ratio = 0.41, 95% confidence interval = 0.19-0.89). Approximately two-thirds of PD patients reported an improvement in or remission of migraine after PD onset. Effects of menopause on migraine course were similar in patients and controls. These findings suggest that PD might somehow shorten the clinical course of migraine. Possible explanations include a prolonged prophylactic effect by chronic dopaminergic therapy or a positive effect of PD pathophysiology, namely nigral degeneration, on migraine mechanisms.
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PMID:Dopamine and migraine: does Parkinson's disease modify migraine course? 1153 7


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