The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Chinchang Huang - One of the best experts on this subject based on the ideXlab platform.
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chronic Manganism a long term follow up study with a new dopamine terminal biomarker of 18f fp dtbz 18f av 133 brain pet scan
Journal of the Neurological Sciences, 2015Co-Authors: Chinchang Huang, Chuyun Huang, Eusden Tsao, Chiaju Hsieh, Yihsin Weng, Ingtsung HsiaoAbstract:Abstract Recent experimental studies revealed that dopamine neuron dysfunction in chronic Manganism may be due to a reduced capacity of dopamine release in the striatum. The findings imposed further difficulty in the differential diagnosis between Manganism and IPD. We conducted a long-term clinical follow-up study of 4 Manganism patients, applying a new tracer 18 F-9-fluoropropyl-(+)-dihydrotetrabenazine ( 18 F-AV-133) with positron emission tomography (PET). Twenty age-matched subjects including 4 Manganism patients, 8 idiopathic Parkinson's disease (IPD) patients, and 8 healthy controls were enrolled for comparison. Volumes of interest of the bilateral putamen, caudate nuclei and occipital cortex as the reference region were delineated from individual magnetic resonance images. The clinical features of the Manganism patients still progressed, with increased scores on the Unified Parkinson Disease Rating Scale. The 18 F-AV-133 uptake in the IPD patients decreased at the bilateral striatum, compared with the healthy controls. In the Manganism patients, there was no decreased uptake of radioactivity involving the bilateral striatum, except Patient 4, who had a stroke with decreased uptake in the right posterior putamen. The 18 F-AV-133 PET finding reveals that nigrostriatum neurons are not degenerated in chronic Manganism and can provide a useful neuroimage biomarker in the differential diagnosis.
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Chronic Manganism: A long-term follow-up study with a new dopamine terminal biomarker of 18F-FP-(+)-DTBZ (18F-AV-133) brain PET scan.
Journal of the Neurological Sciences, 2015Co-Authors: Chuyun Huang, Eusden Tsao, Chiaju Hsieh, Yihsin Weng, Ingtsung Hsiao, Chinchang HuangAbstract:Abstract Recent experimental studies revealed that dopamine neuron dysfunction in chronic Manganism may be due to a reduced capacity of dopamine release in the striatum. The findings imposed further difficulty in the differential diagnosis between Manganism and IPD. We conducted a long-term clinical follow-up study of 4 Manganism patients, applying a new tracer 18 F-9-fluoropropyl-(+)-dihydrotetrabenazine ( 18 F-AV-133) with positron emission tomography (PET). Twenty age-matched subjects including 4 Manganism patients, 8 idiopathic Parkinson's disease (IPD) patients, and 8 healthy controls were enrolled for comparison. Volumes of interest of the bilateral putamen, caudate nuclei and occipital cortex as the reference region were delineated from individual magnetic resonance images. The clinical features of the Manganism patients still progressed, with increased scores on the Unified Parkinson Disease Rating Scale. The 18 F-AV-133 uptake in the IPD patients decreased at the bilateral striatum, compared with the healthy controls. In the Manganism patients, there was no decreased uptake of radioactivity involving the bilateral striatum, except Patient 4, who had a stroke with decreased uptake in the right posterior putamen. The 18 F-AV-133 PET finding reveals that nigrostriatum neurons are not degenerated in chronic Manganism and can provide a useful neuroimage biomarker in the differential diagnosis.
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the natural history of neurological Manganism over 18 years
Parkinsonism & Related Disorders, 2007Co-Authors: Chinchang Huang, Chinsong Lu, Roushayn Chen, Michael Schulzer, Donald B CalneAbstract:Abstract We investigated the clinical features and progression of four patients with chronic manganese intoxication, 18 years after cessation of exposure. Because the results were to be compared with previous observations, we employed the same scoring system. The clinical manifestations were foot dystonia, wide based gait, rigidity, and difficulty in walking backwards. Resting tremor was rarely seen, but tongue tremor was found in 2 patients. The asymmetry initially present in 2 patients persisted 18 years later. Measurements had previously revealed rapid progression in the initial 10 years. We found a plateau over the following decade.
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long term progression in chronic Manganism ten years of follow up
Neurology, 1998Co-Authors: Chinchang Huang, C S Lu, R S Chen, Donald B CalneAbstract:We studied the long-term clinical course of five patients with chronic manganese intoxication. The mean scores of the King9s College Hospital Rating Scale for Parkinson9s disease increased from 15.0 ± 4.2 in 1987 to 28.3 ± 6.70 in 1991 and then to 38.1 ± 12.9 in 1995. The deterioration was most prominent in gait, rigidity, speed of foot tapping, and writing. Tissue concentrations of manganese in blood, urine, scalp hair, and pubic hair returned to normal. Follow-up MRIs did not show paramagnetic high-signal intensity on T1-weighted images. The data indicate that clinical progression in patients with manganese parkinsonism continues even 10 years after cessation of exposure.
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sympathetic skin response and rr interval variation in Manganism and a comparison with parkinson s disease
Parkinsonism & Related Disorders, 1996Co-Authors: Chinchang Huang, Donald B CalneAbstract:Abstract Autonomic dysfunction in five patients with Manganism was investigated by sympathetic skin response (SSR) and RR interval variation (RRIV). A comparison was made with 10 patients with Parkinson's disease (PD) and 10 normal controls. The subjects were agematched and in PD disease stage-matched. Autonomic symptoms were more common in PD than in Manganism. In SSR, the latency was prolonged in PD and Manganism, while the amplitude was reduced only in PD. The RRIV was decreased in PD and Manganism, but the reduction in RRIV was more severe in PD than in Manganism. The present data indicate that autonomic disturbance may occur in Manganism, but is less frequent and less severe when compared with PD.
Alan S Hazell - One of the best experts on this subject based on the ideXlab platform.
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potential for stem cell treatment in Manganism
Neurochemistry International, 2018Co-Authors: Thatiane Cristina De Moura, Szeifoul Afadlal, Alan S HazellAbstract:Abstract Development of Manganism (also known as manganese neurotoxicity) is a major complication of manganese exposure in which neurological dysfunction is linked to accumulation of the metal in brain. Due to neuronal cell death in basal ganglia structures, particularly the globus pallidus, functional recovery is limited. Bearing a resemblance to Parkinson's disease, effective treatment for Manganism is currently limited. However, the rapidly developing field of stem cell research offers new hope for the treatment of illnesses in which neurodegeneration is a major feature. The first part of this review will focus on the clinical features and pathophysiology of cerebral damage resulting from exposure to manganese, including the role of astrocytes, disruption of energy metabolism, involvement of oxidative stress, excitotoxicity, and inflammation, with the second part exploring how stem cells may provide an important therapeutic strategy for patients with this major neurologic disorder.
Robert J Cousins - One of the best experts on this subject based on the ideXlab platform.
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intestine specific deletion of metal transporter zip14 slc39a14 causes brain manganese overload and locomotor defects of Manganism
American Journal of Physiology-gastrointestinal and Liver Physiology, 2020Co-Authors: Tolunay Beker Aydemir, Trista Lee Thorn, Courtney H Ruggiero, Marjory Pompilus, Marcelo Febo, Robert J CousinsAbstract:Mn-induced parkinsonism is recognized as rising in frequency because of both environmental factors and genetic vulnerability; yet currently, there is no cure. We provide evidence in an integrative ...
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intestine specific deletion of metal transporter zip14 slc39a14 causes brain manganese overload and locomotor defects of Manganism
bioRxiv, 2020Co-Authors: Tolunay Beker Aydemir, Trista Lee Thorn, Courtney H Ruggiero, Marjory Pompilus, Marcelo Febo, Robert J CousinsAbstract:Impaired manganese (Mn) homeostasis can result in excess Mn accumulation in specific brain regions and neuropathology. Maintaining Mn homeostasis and detoxification is dependent on effective Mn elimination. Specific metal transporters control Mn homeostasis. Human carriers of mutations in the metal transporter ZIP14 and whole-body Zip14 KO (WB-KO) mice display similar phenotypes, including spontaneous systemic and brain Mn overload, and motor dysfunction. Initially, it was believed that Mn accumulation due to ZIP14 mutations caused by impaired hepatobiliary Mn elimination. However, liver-specific Zip14 KO mice (L-KO) did not show systemic Mn accumulation or motor deficits. ZIP14 is highly expressed in the small intestine and is localized to the basolateral surface of enterocytes. Thus we hypothesized that basolaterally-localized ZIP14 in enterocytes provides another route for elimination of Mn. Using wild type and intestine-specific ZIP14 KO (I-KO) mice, we have shown that ablation of intestinal Zip14 is sufficient to cause systemic and brain Mn accumulation. The lack of intestinal ZIP14- mediated Mn excretion was compensated for by the hepatobiliary system; however, it was not sufficient to maintain Mn homeostasis. When supplemented with extra dietary Mn, I-KO mice displayed some motor dysfunctions, brain Mn accumulation based on both MRI imaging and chemical analysis, thus demonstrating the importance of intestinal ZIP14 as a route of Mn excretion. A defect in intestinal Zip14 expresssion likely could contribute to the Parkinson-like Mn accumulation of Manganism. New & NoteworthyMn-induced parkinsonism is recognized as rising in frequency due to both environmental factors and genetic vulnerability, yet currently, there is no cure. We provide evidence in an integrative animal model that basolaterally localized ZIP14 regulates Mn excretion and detoxification and that deletion of intestinal ZIP14 leads to systemic and brain Mn accumulation, providing robust evidence for the indispensable role of intestinal ZIP14 on Mn excretion.
Michael Aschner - One of the best experts on this subject based on the ideXlab platform.
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Manganese neurotoxicity.
Annals of the New York Academy of Sciences, 2020Co-Authors: Allison W Dobson, Keith M Erikson, Michael AschnerAbstract:Manganese is an essential trace element and it is required for many ubiquitous enzymatic reactions. While manganese deficiency rarely occurs in humans, manganese toxicity is known to occur in certain occupational settings through inhalation of manganese-containing dust. The brain is particularly susceptible to this excess manganese, and accumulation there can cause a neurodegenerative disorder known as Manganism. Characteristics of this disease are described as Parkinson-like symptoms. The similarities between the two disorders can be partially explained by the fact that the basal ganglia accumulate most of the excess manganese compared with other brain regions in Manganism, and dysfunction in the basal ganglia is also the etiology of Parkinson's disease. It has been proposed that populations already at heightened risk for neurodegeneration may also be more susceptible to manganese neurotoxicity, which highlights the importance of investigating the human health effects of using the controversial compound, methylcyclopentadienyl manganese tricarbonyl (MMT), in gasoline to increase octane. The mechanisms by which increased manganese levels can cause neuronal dysfunction and death are yet to be elucidated. However, oxidative stress generated through mitochondrial perturbation may be a key event in the demise of the affected central nervous system cells. Our studies with primary astrocyte cultures have revealed that they are a critical component in the battery of defenses against manganese-induced neurotoxicity. Additionally, evidence for the role of oxidative stress in the progression of Manganism is reviewed here.
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Role of Astrocytes in Manganese Neurotoxicity Revisited
Neurochemical Research, 2019Co-Authors: Tao Ke, Marta Sidoryk-wegrzynowicz, Edward Pajarillo, Asha Rizor, Félix Alexandre Antunes Soares, Michael AschnerAbstract:Manganese (Mn) overexposure is a public health concern due to its widespread industrial usage and the risk for environmental contamination. The clinical symptoms of Mn neurotoxicity, or Manganism, share several pathological features of Parkinson’s disease (PD). Biologically, Mn is an essential trace element, and Mn in the brain is preferentially localized in astrocytes. This review summarizes the role of astrocytes in Mn-induced neurotoxicity, specifically on the role of neurotransmitter recycling, neuroinflammation, and genetics. Mn overexposure can dysregulate astrocytic cycling of glutamine (Gln) and glutamate (Glu), which is the basis for Mn-induced excitotoxic neuronal injury. In addition, reactive astrocytes are important mediators of Mn-induced neuronal damage by potentiating neuroinflammation. Genetic studies, including those with Caenorhabditis elegans ( C. elegans ) have uncovered several genes associated with Mn neurotoxicity. Though we have yet to fully understand the role of astrocytes in the pathologic changes characteristic of Manganism, significant strides have been made over the last two decades in deciphering the role of astrocytes in Mn-induced neurotoxicity and neurodegeneration.
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Manganese-induced parkinsonism and Parkinson’s disease: Shared and distinguishable features
International Journal of Environmental Research and Public Health, 2015Co-Authors: Gunnar F. Kwakye, Somshuvra Mukhopadhyay, Aaron B. Bowman, Monica Maria Bastos Paoliello, Michael AschnerAbstract:Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as Manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson’s disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for Manganism and idiopathic Parkinson’s disease (PD).
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manganese induced parkinsonism and parkinson s disease shared and distinguishable features
International Journal of Environmental Research and Public Health, 2015Co-Authors: Gunnar F. Kwakye, Somshuvra Mukhopadhyay, Aaron B. Bowman, Monica Maria Bastos Paoliello, Michael AschnerAbstract:Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as Manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking. In addition, we review some of the shared similarities, pathologic and clinical distinctions between Mn-induced parkinsonism and Parkinson’s disease. Where possible, we review the influence of Mn toxicity on dopamine, gamma aminobutyric acid (GABA), and glutamate neurotransmitter levels and function. We conclude with a survey of the preventive and treatment strategies for Manganism and idiopathic Parkinson’s disease (PD).
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Manganese Neurotoxicity: a Focus on Glutamate Transporters
Annals of Occupational and Environmental Medicine, 2013Co-Authors: Pratap Karki, Michael AschnerAbstract:Manganese (Mn) is an essential element that is required in trace amount for normal growth, development as well maintenance of proper function and regulation of numerous cellular and biochemical reactions. Yet, excessive Mn brain accumulation upon chronic exposure to occupational or environmental sources of this metal may lead to a neurodegenerative disorder known as Manganism, which shares similar symptoms with idiopathic Parkinson’s disease (PD). In recent years, Mn exposure has gained public health interest for two primary reasons: continuous increased usage of Mn in various industries, and experimental findings on its toxicity, linking it to a number of neurological disorders. Since the first report on Manganism nearly two centuries ago, there have been substantial advances in the understanding of mechanisms associated with Mn-induced neurotoxicity. This review will briefly highlight various aspects of Mn neurotoxicity with a focus on the role of astrocytic glutamate transporters in triggering its pathophysiology.
Donald B Calne - One of the best experts on this subject based on the ideXlab platform.
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the natural history of neurological Manganism over 18 years
Parkinsonism & Related Disorders, 2007Co-Authors: Chinchang Huang, Chinsong Lu, Roushayn Chen, Michael Schulzer, Donald B CalneAbstract:Abstract We investigated the clinical features and progression of four patients with chronic manganese intoxication, 18 years after cessation of exposure. Because the results were to be compared with previous observations, we employed the same scoring system. The clinical manifestations were foot dystonia, wide based gait, rigidity, and difficulty in walking backwards. Resting tremor was rarely seen, but tongue tremor was found in 2 patients. The asymmetry initially present in 2 patients persisted 18 years later. Measurements had previously revealed rapid progression in the initial 10 years. We found a plateau over the following decade.
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long term progression in chronic Manganism ten years of follow up
Neurology, 1998Co-Authors: Chinchang Huang, C S Lu, R S Chen, Donald B CalneAbstract:We studied the long-term clinical course of five patients with chronic manganese intoxication. The mean scores of the King9s College Hospital Rating Scale for Parkinson9s disease increased from 15.0 ± 4.2 in 1987 to 28.3 ± 6.70 in 1991 and then to 38.1 ± 12.9 in 1995. The deterioration was most prominent in gait, rigidity, speed of foot tapping, and writing. Tissue concentrations of manganese in blood, urine, scalp hair, and pubic hair returned to normal. Follow-up MRIs did not show paramagnetic high-signal intensity on T1-weighted images. The data indicate that clinical progression in patients with manganese parkinsonism continues even 10 years after cessation of exposure.
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sympathetic skin response and rr interval variation in Manganism and a comparison with parkinson s disease
Parkinsonism & Related Disorders, 1996Co-Authors: Chinchang Huang, Donald B CalneAbstract:Abstract Autonomic dysfunction in five patients with Manganism was investigated by sympathetic skin response (SSR) and RR interval variation (RRIV). A comparison was made with 10 patients with Parkinson's disease (PD) and 10 normal controls. The subjects were agematched and in PD disease stage-matched. Autonomic symptoms were more common in PD than in Manganism. In SSR, the latency was prolonged in PD and Manganism, while the amplitude was reduced only in PD. The RRIV was decreased in PD and Manganism, but the reduction in RRIV was more severe in PD than in Manganism. The present data indicate that autonomic disturbance may occur in Manganism, but is less frequent and less severe when compared with PD.
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Manganism and idiopathic parkinsonism similarities and differences
Neurology, 1994Co-Authors: Donald B Calne, Chinchang Huang, C S Lu, W OlanowAbstract:: From the comparison we have made between PD and Manganism, we draw the following conclusions: 1. There are similarities between PD and Manganism, notably the presence of (a) generalized bradykinesia and (b) widespread rigidity. 2. There are also dissimilarities between PD and Manganism, notably the following in Manganism: (a) less-frequent resting tremor, (b) more frequent dystonia, (c) a particular propensity to fall backward, (d) failure to achieve a sustained therapeutic response to levodopa, and (e) failure to detect a reduction in fluorodopa uptake by PET. Further studies are likely to yield more discriminants between PD and Manganism. For example, PET with raclopride may be useful in early cases of Manganism, and MRI may be helpful in patients with advanced Manganism.
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levodopa failure in chronic Manganism
Neurology, 1994Co-Authors: Chinsong Lu, Chinchang Huang, Donald B CalneAbstract:We report a placebo-controlled study of levodopa in four patients with extrapyramidal deficits caused by chronic manganese intoxication. Their parkinsonism and dystonia had progressed slowly over a period of 5 years after they left the site of exposure. Initially the patients appeared to respond to levodopa in open observations, but this apparent benefit was not sustained. This short-term, double-blind study indicates that their parkinsonism and dystonia failed to respond to levodopa.