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)

Activated microglia are implicated in the pathogenesis of disease-, trauma- and toxicant-induced damage to the CNS, and strategies to modulate microglial activation are gaining impetus. A novel action of the tetracycline derivative minocycline is the ability to inhibit inflammation and free radical formation, factors that influence microglial activation. Minocycline is therefore being tested as a neuroprotective agent to alleviate CNS damage, although findings so far have yielded mixed results. Here, we showed that administration of a single low dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or methamphetamine (METH), a paradigm that causes selective degeneration of striatal dopaminergic nerve terminals without affecting the cell body in substantia nigra, increased the expression of mRNAs encoding microglia-associated factors F4/80, interleukin (IL)-1alpha, IL-6, monocyte chemoattractant protein-1 (MCP-1, CCL2) and tumor necrosis factor (TNF)-alpha. Minocycline treatment attenuated MPTP- or METH-mediated microglial activation, but failed to afford neuroprotection. Lack of neuroprotection was shown to be due to the inability of minocycline to abolish the induction of TNF-alpha and its receptors, thereby failing to modulate TNF signaling. Thus, TNF-alpha appeared to be an obligatory component of dopaminergic neurotoxicity. To address this possibility, we examined the effects of MPTP or METH in mice lacking genes encoding IL-6, CCL2 or TNF receptor (TNFR)1/2. Deficiency of either IL-6 or CCL2 did not alter MPTP neurotoxicity. However, deficiency of both TNFRs protected against the dopaminergic neurotoxicity of MPTP. Taken together, our findings suggest that attenuation of microglial activation is insufficient to modulate neurotoxicity as transient activation of microglia may suffice to initiate neurodegeneration. These findings support the hypothesis that TNF-alpha may play a role in the selective vulnerability of the nigrostriatal pathway associated with dopaminergic neurotoxicity and perhaps Parkinson's disease.
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PMID:Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-alpha. 1640 14

Weight loss is frequent in patients with Parkinson's disease (PD). Reduced energy intake and/or increased energy expenditure have been postulated as the cause. Dysphagia, anorexia, and gastrointestinal dysfunction may be possible causes of reduced energy intake; whereas, rigidity, tremor, and levodopa-induced dyskinesia may increase energy expenditure. Levodopa may enhance glucose metabolism resulting in enhanced energy expenditure. Depression, anti-parkinsonian drugs, and medical complications such as pneumonia and malignancies also may facilitate weight loss in PD. Combinations of various degrees of these factors, especially in advanced PD, may produce weight loss. Such weight loss is associated with malnutrition which may precipitate infection and decubitis; accelerate motor, behavioral, and autonomic impairment; consequently spoiling one's quality of life. Attention must be paid as well to motor symptoms to prevent or reverse weight loss in PD patients.
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PMID:Weight loss in Parkinson's disease. 1713 Dec 27

Advise patients with Parkinson's disease (PD) to consume a balanced diet, with special attention to adequate intake of dietary fiber, fluids, and macro- and micronutrients. Regularly reassess patients' nutritional history and anthropomorphic measures (height and weight), particularly in patients with advanced disease. PD-related psychosocial as well as physical and cognitive limitations increase susceptibility to subacute and chronic malnutrition. Nutritional requirements may change with PD progression or after surgical therapy for PD. Patients and caregivers may benefit from counseling by a dietician who is knowledgeable about the nutritional risks and needs of PD. Regularly inquire about dysphagia symptoms, and consider speech therapy consultation for clinical and modified barium-swallowing evaluations and management recommendations. Although non-oral delivery options of dopaminergic therapy are increasing, severe dysphagia may warrant percutaneous endoscopic gastrostomy tube placement for nutritional support and more reliable PD medication dosing. Analyze vitamin B(12) and D concentrations at regular intervals. Both vitamins are frequently deficient in elderly persons but may not be routinely checked by primary care physicians. Record over-the-counter and nutritional supplement medications at each visit, and assist patients in periodically re-evaluating their potential benefits, side effects, drug interactions, and costs. To date, clinical trials of antioxidant vitamins and nutritional supplements have provided insufficient evidence to support routine use for PD in the clinic. Data from several clinical trials of antioxidant vitamins/nutritional supplements are expected in the near future. Consider altering medication dosing in relation to meals to help with mild to moderate motor fluctuations. Patients with severe motor fluctuations may benefit from adapting the 5:1 carbohydrate-to-protein ratio in their daily meals and snacks. Following a "protein redistribution" diet is logistically more difficult and less palatable, and therefore less frequently recommended. To ensure adequate protein intake, a registered dietician should supervise patients who follow either of these diets.
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PMID:Nutritional therapies in Parkinson's disease. 1744 97

Deficiency of the meso-diencephalic dopamine (mdDA) neuron specific transcription factor Pitx3 in aphakia (ak) mice results in the loss of the substantia nigra compacta (SNc). Concomitantly, reduced spontaneous locomotor behavior, symptoms reminiscent to those in Parkinson's disease, has been reported. However, the ak mouse line originates from the 1960s and has been compared to C57BL/6J inbred controls. Therefore, to define Pitx3 gene function in baseline and novelty-induced locomotor behavior and mdDA neuronal activity, we analyzed Pitx3-deficiency in a controlled genetic and epigenetic background. The analysis implicated that, in contrast to the controversial and previously reported hypo-activity in ak mice, Pitx3-/- mice showed normal dark phase motor activity levels. Our data also revealed that ak and Pitx3-/- mice both display a similar neuro-anatomical and physiological phenotype, and, interestingly, showed increased spontaneous home cage activity levels during their habitual sleep phase. Further behavioral analysis revealed that both ak and Pitx3-/- mice have reduced transitions but increased consolidation of specific locomotor behaviors, such as rearing and horizontal movement. Thus, Pitx3 is not involved in the expression of nighttime motor activity levels, but is critical for selective mdDA neuronal activity and associated with increased consolidation of movement.
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PMID:Phenotypic segregation of aphakia and Pitx3-null mutants reveals that Pitx3 deficiency increases consolidation of specific movement components. 1791 45

Freezing of gait appears to result from a number of fundamental problems in patients with Parkinson disease. Automaticity is impaired, putting more stress on voluntary mechanisms. Internal drivers of movement are impaired, likely because of deficient basal ganglia function. Deficiency of internal forces to initiate movement is a major factor in freezing. This deficiency gives a greater influence to external or sensory factors. The sensory factors can both help or hinder freezing. Analogous to the problem with set-shifting, there is also some difficulty in regulation of internal versus external factors and in regulation of different external factors.
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PMID:The intrinsic and extrinsic aspects of freezing of gait. 1866 25

The rise in Infantile Autism, learning problems, cognitive decline with age, Alzheimer's, Parkinson's Diseases and the SIDS epidemic, has a common cause in the rising dietary deficit in Omega-3 brain-food. This paper suggests that aside from the wider concept of Autism Spectrum Disorders (ASD) and Pervasive Developmental Disorders (PDD), the rise in Infantile Autism (IA) in the last decade is the effect of deficient brain-food (Omega-3). The consequent delay of development prolongs the 2nd regressive event in infancy to pruning of the centre in the Medial Frontal Lobe System that connects Hippocampus and Cingulum. With a consequently defective Supplementary Motor Area (SMA), the Delayed Response Function is affected leading to persistent psychosis. Post-Pubertal Episodic Psychoses are associated with acute reduction of excitation, a risk of breakdown of circuitry, insufficient fill-in mechanisms, and silent spots. An acute psychosis occurs if the silent spots comprise of SMA. Only two brain areas have continuous neurogenesis, indicating their important functions: the Hippocampus and Olfactory Bulb that belongs to the Lateral Frontal Lobe System essential to survival. Concerned with necessity of action in response to the environment, it relies upon short-term memory and Acute Feedback Mechanisms influenced by emotion and motivation from the external world. In contrast, the Medial Frontal Lobe network is controlled by Feed-Forward Predictive Mechanisms related to storage of information. The Delayed Response Function is mastered at 7 months, when 2nd event occurs with pruning of axons and dendrites. An abolished or defective Delayed Response Function seriously incapacitates an individual: A defective "Social Brain" with an inability for conscious action and to communicate, predominates in IA. There is a near lack of speech, despite normal vision and hearing in the minority without marked adversity in pregnancy, at delivery or in infancy. I propose that the recent rise in IA despite no rise in adversity signifies a rising deficiency in brain-food. That this is so is suggested by a changing clinical picture: no Mental Retardation in an IA majority. Deficit in Olfaction is pathognomonic in schizophrenia since 30 yrs and distinguishes the Asperger Syndrome. If brain-food deficiency alone sufficiently prolongs pruning to cause absent activity in SMA in infancy, less mentally retarded IA from other causes might be observed. Deficit in brain-food was evident in the Sudden Infant Death Syndrome: birthweight averaged 200-300 g lower than sibs, Omega-3 levels in brainstem were lower than controls. Only 20 % SIDS died in first hypoxic episode, suggesting such episodes are more frequent than we imagined. Children with learning-behaviour problems have similarly depressed birthweight. A general deficiency in Omega-3 contributes to the lacking reduction in Schizophrenia, despite early puberty predominates. Olfactory Bulb is first affected in the Alzheimer's and Parkinson's Disease. Cognitive decline with age, Hippocampal dysfunctions rise markedly irrespective of disease, but the major mental illnesses and Infantile Autism in particular, benefit from "brain-food" that might also prevent a development of these disorders. To secure optimal brain function in the coming generations, there is a need to change the diet now from its emphasis on protein for body growth to food for the brain. This means there is a need to increase fish and sea food consumption.
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PMID:Infantile autism: a chronic psychosis since infancy due to synaptic pruning of the supplementary motor area. 1932 37

Persistent hiccups may have a considerable impact on general health through disturbance of diet, sleep, and mood. They can cause exhaustion, malnutrition, dehydration, wound dehiscence, and even death in extreme cases. We report a complex clinical case of intractable hiccups in a patient with cancer of the pancreas and Parkinson's disease and some of the problems encountered when attempting symptom control. We also discuss a potential therapeutic response to a novel agent, amantadine, unlicensed in the treatment of hiccups.
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PMID:Novel use of amantadine: to treat hiccups. 1973 5

In Europe, neuropsychiatric diseases currently make up approximately a third of the total burden of disease. In 2004, 27% of the overall population was affected by at least one of the most frequent neuropsychiatric diseases such as Alzheimer's dementia, Parkinson's disease, stroke or depression. The annual costs of care exceed those of cancer, cardiovascular conditions and diabetes. In order to delay the onset or course of neurodegenerative diseases, the available potential should be utilized. As well as improving quality of life of patients and relatives, this may reduce the great financial burden caused by neurodegenerative disorders. However, the availability of established drugs or therapeutic agents is very limited. This paper reviews the state of current knowledge as to how homocysteine metabolism is relevant for neurodegenerative and other neuropsychiatric diseases, with particular emphasis on the evidence for prophylactic and therapeutic strategies. In the European countries, many people do not take the recommended daily minimum amount of folate and vitamin B12. Deficiency of these vitamins and secondary changes in the concentrations of associated metabolites, such as methylmalonic acid and homocysteine, may contribute to the onset and progression of neuropsychiatric diseases. This paper reviews the evidence regarding whether substitution of folate and vitamin B12 is beneficial, for example, in cerebrovascular disease, dementia and depression.
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PMID:Homocysteine, folate and vitamin B12 in neuropsychiatric diseases: review and treatment recommendations. 1976 53

Dysarthria and dysphagia occur frequently in Parkinson's disease (PD). Reduced speech intelligibility is a significant functional limitation of dysarthria, and in the case of PD is likely related articulatory and phonatory impairment. Prosodically-based treatments show the most promise for addressing these deficits as well as for maximizing speech intelligibility. Communication-oriented strategies also may help to enhance mutual understanding between a speaker and listener. Dysphagia in PD can result in serious health issues, including aspiration pneumonia, malnutrition, and dehydration. Early identification of swallowing abnormalities is critical so as to minimize the impact of dysphagia on health status and quality of life. Feeding modifications, compensatory strategies, and therapeutic swallowing techniques all have a role in the management of dysphagia in PD.
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PMID:Speech and Swallowing in Parkinson's Disease. 1994 86

Approximately 10% of patients diagnosed clinically with early Parkinson's disease (PD) have normal dopaminergic functional imaging (Scans Without Evidence of Dopaminergic Deficit [SWEDDs]). An important subgroup of SWEDDs are those with asymmetric rest tremor resembling parkinsonian tremor. Clinical and pathophysiological features which could help to distinguish SWEDDs from PD have not been explored. We therefore studied clinical details including non-motor symptoms in 25 tremulous SWEDDs patients in comparison to 25 tremor-dominant PD patients. Blinded video rating was used to compare examination findings. Electrophysiological tremor parameters and also response to a cortical plasticity protocol using paired associative stimulation (PAS) was studied in 9 patients with SWEDDs, 9 with tremor-dominant PD (with abnormal dopamine transporter single photon emission computed tomography findings), 8 with segmental dystonia, and 8 with essential tremor (ET). Despite clinical overlap, lack of true bradykinesia, presence of dystonia, and head tremor favored a diagnosis of SWEDDs, whereas re-emergent tremor, true fatiguing or decrement, good response to dopaminergic drugs, and presence of non-motor symptoms favored PD. A single tremor parameter could not differentiate between groups, but the combination of re-emergent tremor and highest tremor amplitude at rest was characteristic of PD tremor. SWEDDs and segmental dystonia patients exhibited an abnormal exaggerated response to the PAS protocol, in contrast to a subnormal response in PD and a normal response in ET. We conclude that despite clinical overlap, there are features that can help to distinguish between PD and SWEDDs which may be useful in clinical practice. The underlying pathophysiology of SWEDDs differs from PD but has similarities with primary dystonia.
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PMID:Distinguishing SWEDDs patients with asymmetric resting tremor from Parkinson's disease: a clinical and electrophysiological study. 2092 66


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