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 contents of indispensable major elements sodium (Na), phosphorus (P), calcium (Ca), magnesium (Mg), trace elements iron (Fe), copper (Cu), nickel (Ni), zinc (Zn), strontium (Sr), vanadium (V), chromium (Cr), manganese (Mn), molybdenum (Mo), and other elements lead (Pb), silicon (Si), aluminium (Al), titanium (Ti), barium (Ba), lanthanum (La), cadmium (Yb), cerium (Ce), scandium (Sc), silver (Ag), in cerebrospinal fluid (CSF) were measured in 13 patients suffering from Parkinson disease before and after autotransplantation of adrenal medulla. It was found that while the patients' objective symptoms were relieved and the contents of monoamine transmitters were changed, the contents of P, V, Co, Cr, in CSF increased significantly (P less than 0.05 or 0.01) at the first, 2nd, 4th, 6th, and 8th week, the contents of Mn in CSF also increased significantly at the first 4th week (P less than 0.05) but decreased significantly at the 8th week the contents of Zn in CSF increased significantly (P less than 0.05) at the 2nd week; Mo increased significantly (P less than 0.05 or 0.01) at the 4th and 8th week B increased significantly (P less than 0.05) at the first week; the contents of Ca, Na, Sr, Ba, Al, Ti, La, Ce, Yb, Sc, Ag in CSF increased significantly (P less than 0.05 or 0.01) at the 8th week, Mg, Fe, Cu Ni, Pb, Si, Cd remained unchanged after operation. The results suggest that the contents of these chemical elements can be affected by this kind of operation, indicating that these elements are involved in the pathogenesis of Parkinsonism.
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PMID:[Determination of multiple chemical elements in CSF in Parkinson disease after intracerebral autotransplantation of the adrenal medulla]. 186 88

The dopaminergic system implicated in human disorders such as Parkinson's disease, schizophrenia and prolactinomas, exerts its effects through several dopamine receptors. The diversity of the dopaminergic system has been revealed by the application of molecular biology techniques to this system, which allowed the identification of five different types of dopamine receptors to date. Even though the structure of these receptors has now been identified, their physiological roles are still under investigation. The coupling of the D1 and D2 dopamine receptor to second messengers has been investigated using cell lines transfected with the cDNAs of these receptors. However, until recently, there was no technique allowing non-invasive real-time measurement of the metabolic activity of cells after agonist stimulation. We present here real-time measurement of events induced by dopaminergic agents on either the D1 or the D2 dopamine receptors using a novel technique employing a silicon-based microphysiometer.
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PMID:Dopaminergic activity measured in D1- and D2-transfected fibroblasts by silicon-microphysiometry. 845 May 4

Although deep-brain stimulation (DBS) can be used to improve some of the severe symptoms of Parkinson's disease (e.g., Bradykinesia, rigidity, and tremors), the mechanisms by which the symptoms are eliminated are not well understood. Moreover, DBS does not prevent neurodegeneration that leads to dementia or death. In order to fully investigate DBS and to optimize its use, a comprehensive long-term stimulation study in an animal model is needed. However, since the brain region that must be stimulated, known as the subthalamic nucleus (STN), is extremely small (500 microm x 500 microm x 1 mm) and deep within the rat brain (10 mm), the stimulating probe must have geometric and mechanical properties that allow accurate positioning in the brain, while minimizing tissue damage. We have designed, fabricated, and tested a novel micromachined probe that is able to accurately stimulate the STN. The probe is designed to minimize damage to the surrounding tissue. The probe shank is coated with gold and the electrode interconnects are insulated with silicon nitride for biocompatibility. The probe has four platinum electrodes to provide a variety of spatially distributed stimuli, and is formed in a novel 3-D plating process that results in a microwire like geometry (i.e., smoothly tapering diameter) with a corresponding mechanically stable shank.
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PMID:Multielectrode microprobes for deep-brain stimulation fabricated with a customizable 3-D electroplating process. 1588 42

The aetiology of Parkinson's disease (PD) is still unknown, but some hypotheses have focused on the imbalances in body levels of metals as co-factors of risk. To assess whether hair could be a reliable marker of possible changes, calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), silicon (Si) and zinc (Zn) were determined in hair from 81 patients affected by PD and 17 age-matched controls. Care was taken to eliminate external contamination of the hair by thorough washing. Digestion of the matrix was achieved by an acid-assisted microwave procedure. Quantification of the elements was performed by inductively coupled plasma atomic emission spectrometry. Results indicated significantly lower levels of Fe in the hair of patients (p=0.018) compared with controls. Ca and Mg levels were slightly lower while Zn levels were higher in patients, although these differences were not significant; neither were variations in Cu and Si. Ca and Mg were at least 1.5 times higher in females than in males in both controls and patients. In addition, Ca correlated positively with Mg in both groups and in both sexes (p-value always less than 0.03), and negatively with age in patients (p<0.01). Finally, element levels did not correlate with either the duration or the severity of the disease or with anti-Parkinson treatment.
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PMID:Calcium, copper, iron, magnesium, silicon and zinc content of hair in Parkinson's disease. 1632 36

Manganese and its inorganic compounds are widely used in many industries and have been accepted as occupational neurotoxins that have caused a distinct and disabling clinical entity, manganism, in several types of work, notably where exposure is by way of dust. There is inconclusive and inconsistent evidence that, in these occupations, subclinical neurological effects, detectable only by neurobehavioural studies, may be caused by low doses. This has prompted a re-evaluation of occupational exposure limits. Some countries, including the UK, already demand much higher levels of protection against exposure than 5 years ago. Welding is the most common source of occupational exposure as manganese is an essential component of steel and so its compounds are inevitable components of fume emitted from steel welding processes. There it is found in respirable particles, often as complex oxides (spinels), sometimes within a core protected by a silicon oxide shell - as distinct from the much simpler form of particle formed by disintegration in processes such as mining and ore milling where manganism has been diagnosed convincingly. Millions of workers are at risk of exposure to manganese-containing compounds in fumes from electric arc welding of steel. In recent years it has been asserted that neurological and neurobehavioural disorders may develop consequent to exposure to steel welding fumes and that employment as a welder is associated with the unusually early onset of Parkinson's disease. Causal relationships have been postulated. Welders have been recorded as having been exposed to high levels of manganese-containing fume, especially where they have worked in confined, unventilated spaces, although this appears from limited data to be the exception rather than the rule. Even then the dose received is generally less than in mining or ore crushing. When care is taken to exclude exposures from hardfacing and burning and cutting arc processes, where manganese may form a high percentage of the fume, manganese compounds usually form a relatively low percentage of the composition of welding fume particles, <2.0%, much outweighed by iron. Although these manganese-compound-containing welding fume particles are insoluble in water, the manganese compounds in particles that are retained in the alveoli may be absorbed, at least in part. Manganese concentrations in biological material samples in some exposed groups reflect this relative to unexposed workers. Some of the transfer systems for absorption and transport, including across the blood-brain barrier, are used in competition with iron which is present in abundance in welding fume. This may reduce absorption of manganese in welders and thus reduce the opportunity for sufficient doses to cause neurotoxicological consequences. Scrutiny of the literature covering the last 40 years has revealed only five cases that meet sufficient criteria for manganism to just cross the diagnostic threshold, and even then they carry a degree of doubt with them. This low incidence alone gives notice that welders have not been and are not at high risk of clinically apparent damage from exposure to manganese. If this needs to be further emphasised, there is the fact that the literature contains no confirmed cases of manganism in welders. Assertions of abnormal results in neurobehavioural studies of welders have raised the possibility of there being a subclinical form of manganism with loss of fine motor control as one of its features. While observations of such changes in workers in other industries have caused regulators in some countries to apply more stringent controls of exposure, as yet the results lack convincing consistency and there is no indication of any dose-effect relationship. If welding fume can have these motor effects it would be a heavy and perhaps career-ending blow to those affected. It would not be prudent to dismiss the warnings sounded by the results of studies of welders, no matter how flawed these investigations are, but wiser and better to act with vigour to reduce exposure and monitor the effectiveness of this additional protection whilst conducting high quality research to allow sound conclusions to be drawn as to whether there actually is a subclinical disorder. Idiopathic Parkinson's disease is a common disorder affecting 1-2% of those in the general population aged >65 years. It has been suggested, on flawed and contested evidence, not that welding causes the disease but rather that employment as a welder carries with it the risk of developing this disease at a younger age than if that trade had not been followed. Manganese in welding fume has been nominated as the neurotoxin. This may be biologically feasible if manganese destroys insufficient receptor cells to produce clinical manganism but sufficient to enhance the effects of a reduced supply of dopamine to give the manifestations of already developing idiopathic Parkinson's disease earlier in the course of destruction of the substantia nigra than if all receptors were intact.
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PMID:Is electric arc welding linked to manganism or Parkinson's disease? 1649 6

Nanocrystalline TiN/NiTi thin films have been grown on silicon substrate by dc magnetron sputtering to improve the corrosion and mechanical properties of NiTi based shape memory alloys without sacrificing the phase transformation effect. Interestingly, the preferential orientation of the TiN films was observed to change from (1 1 1) to (2 0 0) with change in nature of sputtering gas from 70% Ar+30% N(2) to 100% N(2). In present study the influence of crystallographic orientation of TiN on mechanical and corrosion properties of TiN/NiTi thin films was investigated. TiN (2 0 0)/NiTi films were found to exhibit high hardness, high elastic modulus, and thereby better wear resistance as compared to pure NiTi and TiN (1 1 1)/NiTi films. Electrochemical test revealed that TiN coated NiTi film exhibits better corrosion resistance in 1M NaCl solution as compared to uncoated NiTi film. The application of TiN/NiTi films in the electrochemical sensing of dopamine, which has a critical physiological importance in Parkinson's disease, has been demonstrated. A comparison of voltammetric response of dopamine at silicon based electrodes modified with different nanocrystalline coatings indicated that these films catalyze the oxidation of dopamine.
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PMID:Fabrication and nanoindentation properties of TiN/NiTi thin films and their applications in electrochemical sensing. 1926 58

Brain machine interface (BMI) devices offer a platform that can be used to assist people with extreme disabilities, such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease. Silicon (Si) has been the material of choice used for the manufacture of BMI devices due to its mechanical strength, its electrical properties and multiple fabrication techniques; however, chronically implanted BMI devices have usually failed within months of implantation due to biocompatibility issues and the fact that Si does not withstand the harsh environment of the body. Single crystal cubic silicon carbide (3C-SiC) and nanocrystalline diamond (NCD) are semiconductor materials that have previously shown good biocompatibility with skin and bone cells. Like Si, these materials have excellent physical characteristics, good electrical properties, but unlike Si, they are chemically inert. We have performed a study to evaluate the general biocompatibility levels of all of these materials through the use of in vitro techniques. H4 human neuroglioma and PC12 rat pheochromocytoma cell lines were used for the study, and polystyrene (PSt) and amorphous glass were used as controls or for morphological comparison. MTT [3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide] assays were performed to determine general cell viability with each substrate and atomic force microscopy (AFM) was used to quantify the general cell morphology on the substrate surface along with the substrate permissiveness to lamellipodia extension. 3C-SiC was the only substrate tested to have good viability and superior lamellipodia permissiveness with both cell lines, while NCD showed a good level of viability with the neural H4 line but a poor viability with the PC12 line and lower permissiveness than 3C-SiC. Explanations pertaining to the performance of each substrate with both cell lines are presented and discussed along with future work that must be performed to further evaluate specific cell reactions on these substrates.
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PMID:Atomic force microscopy analysis of central nervous system cell morphology on silicon carbide and diamond substrates. 1958 42

The six elements commonly known as metalloids are boron, silicon, germanium, arsenic, antimony, and tellurium. Metalloid containing compounds have been used as antiprotozoal drugs. Boron-based drugs, the benzoxaboroles have been exploited as potential treatments for neglected tropical diseases. Arsenic has been used as a medicinal agent and arsphenamine was the main drug used to treat syphilis. Arsenic trioxide has been approved for the treatment of acute promyelocytic leukemia. Pentavalent antimonials have been the recommended drug for visceral leishmaniasis and cutaneous leishmaniasis. Tellurium (IV) compounds may have important roles in thiol redox biological activity in the human body, and ammonium trichloro (dioxoethylene-O, O'-)tellurate (AS101) may be a promising agent for the treatment of Parkinson's disease. Organosilicon compounds have been shown to be effective in vitro multidrug-resistance reverting agents.
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PMID:Metalloid compounds as drugs. 2401 24

Amyotrophic lateral sclerosis (ALS) on Guam previously attained incidence rates 50 to 100 times that of the continental United States and Europe and accounted for one in five deaths among Chamorros over age 25. A second neurological disorder in high incidence, parkinsonism-dementia (PD), and the early appearance in those populations of neurofibrillary tangles such as are seen in Alzheimer's disease and normal ageing have also been noted. Incidence and mortality rates of both diseases have declined dramatically during the past 30 years, and today, the risk of developing either disease among Guamanian Chamorros is only several times higher than in non-Guamanian populations. The decline is most likely a consequence of increased acculturation over the past three decades, with a concomitant decrease in isolation, changes in dietary habits and local water supplies, and much less dependence on locally grown foodstuffs. Similar declines are evident in the remaining two Pacific foci of high- incidence ALS, namely the Kii Peninsula focus in Japan and southern West New Guinea where western contact and introduction of new foodstuffs have occurred.The accumulating epidemiological, genetic and environmental evidence, as well as the development of new and promising experimental animal models, support the hypothesis that a basic metabolic defect, provoked by chronic nutritional deficiencies of calcium, lead to increased intestinal absorption of toxic metals and the co-deposition of calcium, aluminium and silicon in neurons of patients with ALS and PD. This elemental deposition is thought to result in aberrant microtubule assembly and/or abnormal post-translational modification of the amyloid precursor protein leading to widespread formation of neurofibrillary tangles, the hallmark pathological features in these disorders. The naturalistic paradigms of these foci in the Western Pacific have provided insights to understanding not only ALS and PD but other neurological disorders, such as classical ALS, Parkinson's disease, Alzheimer's disease and early neuronal ageing.
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PMID:Models of environmentally induced neurological disease: epidemiology and etiology of amyotrophic lateral sclerosis and parkinsonism-dementia in the Western Pacific. 2420 80

Intracranial implants elicit neurodegeneration via the foreign body response (FBR) that includes BBB leakage, macrophage/microglia accumulation, and reactive astrogliosis, in addition to neuronal degradation that limit their useful lifespan. Previously, monocyte chemoattractant protein 1 (MCP-1, also CCL2), which plays an important role in monocyte recruitment and propagation of inflammation, was shown to be critical for various aspects of the FBR in a tissue-specific manner. However, participation of MCP-1 in the brain FBR has not been evaluated. Here we examined the FBR to intracortical silicon implants in MCP-1 KO mice at 1, 2, and 8 weeks after implantation. MCP-1 KO mice had a diminished FBR compared to WT mice, characterized by reductions in BBB leakage, macrophage/microglia accumulation, and astrogliosis, and an increased neuronal density. Moreover, pharmacological inhibition of MCP-1 in implant-bearing WT mice maintained the increased neuronal density. To elucidate the relative contribution of microglia and macrophages, bone marrow chimeras were generated between MCP-1 KO and WT mice. Increased neuronal density was observed only in MCP-1 knockout mice transplanted with MCP-1 knockout marrow, which indicates that resident cells in the brain are major contributors. We hypothesized that these improvements are the result of a phenotypic switch of the macrophages/microglia polarization state, which we confirmed using PCR for common activation markers. Our observations suggest that MCP-1 influences neuronal loss, which is integral to the progression of neurological disorders like Alzheimer's and Parkinson disease, via BBB leakage and macrophage polarization.
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PMID:The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during chronic neuroinflammation. 2488 Oct 26


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