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)

The plasma soluble melanins (PSM) form spontaneously in vitro and in vivo and their formation involves oxidative polymerization and copolymerization of dopa, catecholamines, homogentisic acid, 3-hydroxyanthranilic acid, p-aminophenol, p-phenylenediamine, and other end(ex)ogenous ortho and para polyhydroxy-, (poly)hydroxy(poly)amino- and polyamino-phenyl compounds. The build up of PSM is visible within 2-3 h after the start of incubation at 37 degrees C with 1 mg/ml of plasma. PSM also form similarly in blood and these processes cause hemolysis. The mean quantity of PSM in normal human plasma is 1.61+/-0.1 (S.D.) mg/ml (n = 20) and in normal human urine is 1.1+/-1.2 g/24 h collection (n = 8). They contribute to the yellow color of plasma and urine. Antioxidants delay the formation of PSM. The deposited melanins also form from these precursors. Reactive oxygen side products (ROSP) are generated during and after melanogenesis. Melanins in vivo are generally associated with proteins or with proteins and lipids. The PSM-protein-lipid complexes are called plasma soluble lipofuscins (PSL), because they have histochemical and fluorescence properties similar to those of solid lipofuscins. The soluble and deposited melanins (SDM) and their intermediates have similar toxic chemical reactivities. The oxidizing quinoid (they can produce partially and completely substituted conjugates) and the semiquinoid free radical intermediates are also moieties in most human melanin structures. Soluble melanins formed from dopa, or dopamine, or norepinephrine in weak alkaline solution have been shown to be toxic to human CD4+ lymphoblastic cells (MT-2) at higher than 10 microg/ml concentrations. Alkaptonuria with high levels of homogentisic acid in the plasma is a potentially fatal disease, exhibiting the toxic effects of the homogentisic acid melanin (soluble and deposited), its intermediates and the ROSP. Patients with alkaptonuria develop arthritis and often suffer from other diseases too, including cardiovascular disease (frequent cause of death) and kidney disease. Pheochromocytoma, with high levels of catecholamines in the plasma is another potentially fatal disease. The catecholamine PSM of pheochromocytoma have very light yellow or practically no colors, due to the concentrations and chemical structures. Pheochromocytomas can cause hypertension, cardiovascular disease (frequent cause of death), kidney disease, stroke, cancer, amyloid formation and can mimic many other diseases, including acute pancreatitis, carcinoid, neuroblastoma, psychiatric illness, hypercalcemia, retinal vascular lesions, and diabetes mellitus. Pheochromocytoma is potentially fatal even in patients without hypertension. Following trauma and surgery, heavily pigmented eyes are apt to experience greater inflammation than lightly pigmented eyes. In Parkinson's disease those neurons are lost first in the substantia nigra and locus ceruleus which contain the greatest amounts of neuromelanins. The antihypertensive alphamethyldopa causes Parkinson's syndrome. It forms PSM in a short time in vitro. The side effects of L-dopa (immobility episodes alternate with normal or involuntary movements; psychotic abnormalities) suggest that the SDM, their intermediates and the ROSP present naturally in vivo are involved in the cause of Parkinson's disease and Alzheimer's disease. There is a large overlap between these two diseases. (ABSTRACT TRUNCATED)
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PMID:The probable involvement of soluble and deposited melanins, their intermediates and the reactive oxygen side-products in human diseases and aging. 1124 35

We report the case of a 62-year-old woman with parkinson's disease and depression. Her symptoms included episodes of flushing, palpitations and hypertension, giving rise to the suspicion of the existence of a phaeochromocytoma. The levels of adrenaline and vanillymandelic acid in the urine were moderately elevated, the noradrenaline level was high- normal. Upon further examination, there was no evidence of a phaeochromocytoma or a carcinoid tumor. In the literature, there are reports of pseudophaeochromocytoma in patients receiving levodopa. Elevated levels of catecholamins and their metabolites can be caused by the metabolic process of levodopa and levodopa can influence the outcome of laboratory tests. The patient's depression resolved and the flushing disappeared after treatment with antidepressants and after changing the Parkinson regime.
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PMID:[Pseudophaeochromocytoma in a Patient with Parkinson's Disease and Depression] 1313 Mar 38

We report the case of a 62-year-old woman with parkinson's disease and depression. Her symptoms included episodes of flushing, palpitations and hypertension, giving rise to the suspicion of the existence of a phaeochromocytoma. The levels of adrenaline and vanillymandelic acid in the urine were moderately elevated, the noradrenaline level was high-normal. Upon further examination, there was no evidence of a phaeochromocytoma or a carcinoid tumor. In the literature, there are reports of pseudophaeochromocytoma in patients receiving levodopa. Elevated levels of catecholamins and their metabolites can be caused by the metabolic process of levodopa and levodopa can influence the outcome of laboratory tests. The patient's depression resolved and the flushing disappeared after treatment with antidepressants and after changing the Parkinson regime.
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PMID:[Pseudopheochromocytoma in Parkinson disease and depression]. 1450 40

Pergolide is an ergot derivative dopamine agonist used in the treatment of Parkinson's disease and restless legs syndrome. Ergot derivatives are known to be associated with fibrotic conditions, including a carcinoid-like, fibrotic, valvular heart disease (VHD). Recently, pergolide was identified in association with the development of VHD. This article includes a summary of the literature published on pergolide-associated VHD, a description of the potential mechanisms of drug-induced VHD, and the clinical implications for the management of patients taking pergolide.
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PMID:Pergolide-associated valvular heart disease. 1684 52

The use of 3,4-dihydroxy-6-[(18)F]-fluoro-L-phenylalanine ((18)F-FDOPA) with positron emission tomography initially centered on studying central motor disorders and evaluating patients with Parkinsonian symptoms, based on its uptake into presynaptic dopaminergic terminals in the putamen and caudate nuclei of the brain. The roles of this tracer have since expanded to include monitoring disease progression, potentially contributing to drug development, and even questioning the current gold standard for making the diagnosis of Parkinson's disease. As with some other amino acids, (18)F-FDOPA has also been effective for visualizing brain tumors, either at time of diagnosis or when monitoring for recurrence, with high sensitivity and overall accuracy. (18)F-FDOPA may be especially useful for imaging patients with low-grade gliomas, as well in the evaluation of patients with neuroendocrine tumors such as carcinoid and pheochromocytoma, in which its role as a precursor for amine neurotransmitter/neurohormones serves as a basis for its differential uptake.
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PMID:3,4-dihydroxy-6-[18f]-fluoro-L-phenylalanine positron emission tomography in patients with central motor disorders and in evaluation of brain and other tumors. 1792 Mar 51

Serotonin plays a significant role in the development of carcinoid heart disease, which primarily leads to fibrosis and contraction of right-sided heart valves. Recently, strong evidence has emerged that the use of specific drug classes, such as ergot alkaloids (for migraine headaches), 5-hydroxytryptamine (5-HT or serotonin) uptake regulators or inhibitors (for weight reduction), and ergot-derived dopamine agonists (for Parkinson's disease), can result in left-sided heart valve damage that resembles carcinoid heart disease. Recent studies have suggested that both right-sided and left-sided drug-induced heart valve disease involves increased serotoninergic activity and in particular activation of the 5-HT receptors, including the 5-HT2B receptor subtype, which mediate many of the central and peripheral functions of serotonin. G-proteins that inhibit adenylate cyclase activity mediate the activity of the 5-HT2B receptor subunit, which is widely expressed in a variety of tissues, including liver, lung, heart, and coronary and pulmonary arteries; it has also been reported in embryonic mouse heart, particularly on mouse heart valve leaflets. In this review, the authors discuss the salient features of serotoninergic manifestations of both carcinoid heart disease and drug-induced cardiac valvulopathy, with an emphasis on echocardiographic diagnosis.
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PMID:Role of serotoninergic pathways in drug-induced valvular heart disease and diagnostic features by echocardiography. 1955 85

Medications based on ergoline-derived dopamine and serotonin agonists are associated with off-target toxicities that include valvular heart disease (VHD). Reports of drug-induced VHD resulted in the withdrawal of appetite suppressants containing fenfluramine and phentermine from the US market in 1997 and pergolide, a Parkinson's disease medication, in 2007. Recent evidence suggests that serotonin receptor activity affected by these medications modulates cardiac valve interstitial cell activation and subsequent valvular remodeling, which can lead to cardiac valve fibrosis and dysfunction similar to that seen in carcinoid heart disease. Failure to identify these risks prior to market and continued use of similar drugs reaffirm the need to improve preclinical evaluation of drug-induced VHD. Here, we present two complimentary assays to measure stiffness and contractile stresses generated by engineered valvular tissues in vitro. As a case study, we measured the effects of acute (24 h) pergolide exposure to engineered porcine aortic valve interstitial cell (AVIC) tissues. Pergolide exposure led to increased tissue stiffness, but it decreased both basal and active contractile tone stresses generated by AVIC tissues. Pergolide exposure also disrupted AVIC tissue organization (i.e., tissue anisotropy), suggesting that the mechanical properties and contractile functionality of these tissues are governed by their ability to maintain their structure. We expect further use of these assays to identify off-target drug effects that alter the phenotypic balance of AVICs, disrupt their ability to maintain mechanical homeostasis, and lead to VHD.
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PMID:Acute pergolide exposure stiffens engineered valve interstitial cell tissues and reduces contractility in vitro. 2717 67

Heart valve diseases (HVDs) arise from a number of different processes that affect both the structure and function of the valve apparatus. Despite diverse aetiologies, treatments for HVDs are limited to percutaneous or surgical interventions. The search for medical therapies to prevent or slow the progression of HVDs has been hampered by our poor understanding of the progression from subclinical to symptomatic phases, and our limited knowledge of the molecular signals that control the susceptibility of valve interstitial cells to pathological remodeling. Clinical evidence has suggested a link between certain neurotransmitters and valvular diseases of the heart. The fenfluramine-phentermine appetite suppressants popular in the 1980s were linked to mitral valve dysfunction, and ergot-derived dopamine agonists for Parkinson's disease have been associated with an increased risk of mitral and aortic valve regurgitation. The effect does not appear to be limited to medications, as valvular pathologies have also been observed in patients with carcinoid tumours of serotonin-producing enterochromaffin cells. The role of neurotransmitter molecules in valve pathology has not been adequately characterized and may represent a target for future medical therapies. Here we present current evidence from both clinical and basic science suggesting a link between neurotransmitters and HVDs, opening the door to future research in this area.
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PMID:Serotonin and catecholamines in the development and progression of heart valve diseases. 2886 37