RESUMEN
Objective: Recent studies have found that selenium (Se) levels were associated with the risk of Parkinson's disease (PD), but the results were contradictory. Therefore, this meta-analysis was conducted to investigate the correlation between Se levels and PD.Methods: PubMed, Embase and Web of Science were searched published up to 28 October 2019. The differences between groups were analyzed by forest plots and results were pooled and assessed using a random-effect model. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to assess the association between Se levels and the risk of PD. Subgroup analysis, meta-regression, and sensitivity analysis were also conducted. Publication bias was estimated using Begg's regression asymmetry test.Results: Finally, 12 articles involving 601 PD patients and 749 controls were included in this meta-analysis. The meta-analysis revealed a significantly higher cerebrospinal fluid (CSF) Se level in PD patients than those in controls (SMD = 1.22; 95%CI [0.05, 2.39]; p = 0.000). No publication bias was found.Conclusion: The meta-analysis indicated that CSF Se levels in PD patients were significantly higher than those in controls.
Asunto(s)
Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/líquido cefalorraquídeo , Selenio/sangre , Selenio/líquido cefalorraquídeo , Oligoelementos/sangre , Oligoelementos/líquido cefalorraquídeo , Antioxidantes/metabolismo , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Humanos , Enfermedad de Parkinson/diagnósticoRESUMEN
BACKGROUND: The aim of the study was to investigate if speciation analysis by liquid chromatography coupled to mass spectrometry could be used to detect organic and inorganic binding forms of selenium in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) and age-matched control subjects (AMC). METHODS: PD patients and control subjects were enrolled from three different neurological departments. CSF samples were collected according to standardized biomarker protocols and subjected to inductively coupled plasma mass spectrometry (ICP-MS) for total selenium determination and ion exchange chromatography (IEC) hyphenated to ICP-MS for selenium speciation analysis. RESULTS: 75 PD patients and 68 age-matched controls were enrolled for speciation analysis. 8 different species could be detected, but only selenoprotein P (SELENOP), human serum albumin-bound Se (Se-HSA), selenomethionine (Se-Met) and an unidentified Se-compound (U2) presented with more than 50% values above the limit of quantification, without showing significant differences between both groups (pâ¯>â¯0.05). The Se-HSA / Se-Met ratio yielded a significant difference between PD and AMC (pâ¯=â¯0.045). The inorganic species Se-IV and Se-VI were only detectable in a minor part of PD and AMC samples. A highly significant correlation between total selenium levels and SELENOP (PD pâ¯<â¯0.0001; AMC pâ¯<â¯0.0001) and Se-HSA (PD pâ¯<â¯0.0001; AMC pâ¯<â¯0.0001) could be demonstrated, respectively. CONCLUSIONS: Speciation analysis yielded new insight into selenium homeostasis in PD but cannot be used to establish a diagnostic biomarker. The small number of detectable values for Se-IV and Se-VI suggests an inferior role of these potentially neurotoxic binding forms in PD pathology in contrast to other neurodegenerative disorders.
Asunto(s)
Enfermedad de Parkinson/líquido cefalorraquídeo , Selenio/líquido cefalorraquídeo , Anciano , Humanos , Espectrometría de Masas , Persona de Mediana Edad , Compuestos de Selenio/líquido cefalorraquídeo , Selenometionina/líquido cefalorraquídeo , Selenoproteína P/líquido cefalorraquídeoRESUMEN
BACKGROUND: Parkinson's disease (PD) is the most common neurodegenerative disease after Alzheimer's dementia. Whereas the exact etiology of PD remains unknown, risk of developing PD seems to be related to a combination of genetic and environmental factors. This also includes abnormal exposure to trace elements of nutritional and toxicological interest. OBJECTIVES: In this systematic review and meta-analysis, we summarized the results of case-control studies comparing levels of selenium, copper, iron, and zinc in PD patients and controls in either blood (whole blood, serum/plasma) or cerebrospinal fluid (CSF). METHODS: We performed a systematic PubMed search selecting studies reporting trace element levels in different specimens of patients and controls. We performed a meta-analysis using a random-effect model to compute the weighted mean differences (WMD) and corresponding 95% CI of selenium, copper, iron, and zinc levels in the blood or CSF of patients and their matched controls. RESULTS: We retrieved 56 papers reporting data for selenium (cases/controls: 588/721), copper (2,190/2,522), iron (2,956/3,469), and zinc (1,798/1,913) contents in CSF and blood. Cases showed considerably higher levels of selenium in CSF compared with controls (+51.6%; WMD 5.49; 95% CI 2.82 to 8.15), while levels in serum were similar (-0.2%; WMD -0.22; 95% CI -8.05 to 7.62). For copper, cases showed slightly higher levels in CSF and slightly lower concentrations in serum (+4.5%; WMD 1.87; 95% CI -3.59 to 7.33, and -4.5%; WMD -42.79; 95% CI -134.35 to 48.76, respectively). A slight increase was also found for CSF iron -levels (+9.5%; WMD 9.92; 1.23 to 18.61), while levels were -decreased in serum/plasma (-5.7%; WMD -58.19; 95% CI -106.49 to -9.89) and whole blood (-10.8%; WMD -95.69; 95% CI -157.73 to -33.65). Conversely, for zinc cases exhibited lower levels both in CSF (-10.8%; WMD -7.34; 95% CI -14.82 to 0.14) and serum/plasma (-7.5%; WMD -79.93; 95% CI -143.80 to -16.06). A longer duration of the disease tends to be associated with overall lower trace element levels in either CSF or blood. CONCLUSIONS: Due to the study findings and the greater relevance of the CSF compartment compared with the circulating peripheral ones, this meta-analysis suggests that overexposure in the central nervous system to selenium, and possibly to copper and iron, may be a risk factor of the disease, while zinc might have a protective -effect.
Asunto(s)
Enfermedad de Parkinson/etiología , Selenio , Oligoelementos , Estudios de Casos y Controles , Humanos , Selenio/efectos adversos , Selenio/sangre , Selenio/líquido cefalorraquídeo , Oligoelementos/efectos adversos , Oligoelementos/sangre , Oligoelementos/líquido cefalorraquídeoRESUMEN
Several human studies imply that the trace element selenium and its species may influence the onset of neurological disease, including Alzheimer's dementia (AD). Nevertheless, the literature is conflicting, with reported associations between exposure and risk in opposite direction, possibly due to biases in exposure assessment. After conducting a cohort study that detected an excess AD risk associated with higher levels of inorganic-hexavalent selenium in subjects with mild cognitive impairment (MCI), we investigated the relation between selenium and AD using a case-control study design. We determined cerebrospinal fluid levels of selenium species in 56 MCI participants already included in the cohort study, considered as referents, and in 33 patients with established AD. AD risk was inversely correlated with inorganic selenium species and with the organic form bound to selenoprotein P. Selenium bound to other organo-selenium species was positively correlated with AD risk, suggesting compensatory selenoprotein upregulation following increased oxidative stress. The finding of an increased AD risk associated with inorganic-hexavalent selenium from the cohort study was not replicated. This case-control study yielded entirely different results than those generated by a cohort study with a partially overlapping participant population, suggesting that case-control design does not allow to reliably assess the role of selenium exposure in AD etiology. This inability appears to be due to exposure misclassification, falsely indicating an etiologic role of selenium deficiency likely due to reverse causation, and involving most selenium species. The case-control design may instead lend insights into the pathologic process underlying disease progression.
Asunto(s)
Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/etiología , Selenio/efectos adversos , Selenio/química , Anciano , Enfermedad de Alzheimer/líquido cefalorraquídeo , Estudios de Casos y Controles , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Selenio/administración & dosificación , Selenio/líquido cefalorraquídeoRESUMEN
Insufficient supply of selenium to antioxidant enzymes in the brain may contribute to Alzheimer's disease (AD) pathophysiology; therefore, oral supplementation may potentially slow neurodegeneration. We examined selenium and selenoproteins in serum and cerebrospinal fluid (CSF) from a dual-dose 24-week randomized controlled trial of sodium selenate in AD patients, to assess tolerability, and efficacy of selenate in modulating selenium concentration in the central nervous system (CNS). A pilot study of 40 AD cases was randomized to placebo, nutritional (0.32 mg sodium selenate, 3 times daily), or supranutritional (10 mg, 3 times daily) groups. We measured total selenium, selenoproteins, and inorganic selenium levels, in serum and CSF, and compared against cognitive outcomes. Supranutritional selenium supplementation was well tolerated and yielded a significant (p < 0.001) but variable (95% CI = 13.4-24.8 µg/L) increase in CSF selenium, distributed across selenoproteins and inorganic species. Reclassifying subjects as either responsive or non-responsive based on elevation in CSF selenium concentrations revealed that responsive group did not deteriorate in Mini-Mental Status Examination (MMSE) as non-responsive group (p = 0.03). Pooled analysis of all samples revealed that CSF selenium could predict change in MMSE performance (Spearman's rho = 0.403; p = 0.023). High-dose sodium selenate supplementation is well tolerated and can modulate CNS selenium concentration, although individual variation in selenium metabolism must be considered to optimize potential benefits in AD. The Vel002 study is listed on the Australian and New Zealand Clinical Trials Registry ( http://www.anzctr.org.au /), ID: ACTRN12611001200976.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Antioxidantes , Ácido Selénico , Selenio , Oligoelementos , Anciano , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/líquido cefalorraquídeo , Antioxidantes/administración & dosificación , Antioxidantes/metabolismo , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/metabolismo , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Ácido Selénico/administración & dosificación , Ácido Selénico/sangre , Ácido Selénico/líquido cefalorraquídeo , Selenio/administración & dosificación , Selenio/sangre , Selenio/líquido cefalorraquídeo , Oligoelementos/administración & dosificación , Oligoelementos/sangre , Oligoelementos/líquido cefalorraquídeoRESUMEN
BACKGROUND: Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form. METHODS: We determined concentrations of selenium species in cerebrospinal fluid sampled at diagnosis in 56 participants with mild cognitive impairment of nonvascular origin. We then investigated the relation of these concentrations to subsequent conversion from mild cognitive impairment to Alzheimer's dementia. RESULTS: Twenty-one out of the 56 subjects developed Alzheimer's dementia during a median follow-up of 42 months; four subjects developed frontotemporal dementia and two patients Lewy body dementia. In a Cox proportional hazards model adjusting for age, sex, duration of sample storage, and education, an inorganic selenium form, selenate, showed a strong association with Alzheimer's dementia risk, with an adjusted hazard ratio of 3.1 (95% confidence interval 1.0-9.5) in subjects having a cerebrospinal fluid content above the median level, compared with those with lower concentration. The hazard ratio of Alzheimer's dementia showed little departure from unity for all other inorganic and organic selenium species. These associations were similar in analyses that measured exposure on a continuous scale, and also after excluding individuals who converted to Alzheimer's dementia at the beginning of the follow-up. CONCLUSIONS: These results indicate that higher amounts of a potentially toxic inorganic selenium form in cerebrospinal fluid may predict conversion from mild cognitive impairment to Alzheimer's dementia.
Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Disfunción Cognitiva/líquido cefalorraquídeo , Selenio/líquido cefalorraquídeo , Anciano , Biomarcadores/líquido cefalorraquídeo , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Demencia Frontotemporal/líquido cefalorraquídeo , Humanos , Enfermedad por Cuerpos de Lewy/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Although an increasing role of genetic susceptibility has been recognized, the role of environmental risk factors in amyotrophic lateral sclerosis (ALS) etiology is largely uncertain; among neurotoxic chemicals, epidemiological and biological plausibility has been provided for pesticides, the heavy metal lead, the metalloid selenium, and other persistent organic pollutants. Selenium involvement in ALS has been suggested on the basis of epidemiological studies, in vitro investigations, and veterinary studies in which selenium induced a selective toxicity against motor neurons. OBJECTIVE: Hypothesizing a multistep pathogenic mechanism (genetic susceptibility and environmental exposure), we aimed to study selenium species in ALS patients carrying disease-associated gene mutations as compared to a series of hospital controls. METHODS: Using advanced analytical techniques, we determined selenium species in cerebrospinal fluid sampled at diagnosis in 9 ALS patients carrying different gene mutations (C9ORF72, SOD1, FUS, TARDBP, ATXN2, and TUBA4A) compared to 42 controls. RESULTS: In a patient with the tubulin-related TUBA4A mutation, we found highly elevated levels (in µg/L) of glutathione-peroxidase-bound selenium (32.8 vs. 1.0) as well as increased levels of selenoprotein-P-bound selenium (2.4 vs. 0.8), selenite (1.8 vs. 0.1), and selenate (0.9 vs. 0.1). In the remaining ALS patients, we detected elevated selenomethionine-bound selenium levels (0.38 vs. 0.06). CONCLUSIONS: Selenium compounds can impair tubulin synthesis and the cytoskeleton structure, as do tubulin-related gene mutations. The elevated selenium species levels in the TUBA4A patient may have a genetic etiology and/or represent a pathogenic pathway through which this mutation favors disease onset, though unmeasured confounding cannot be excluded. The elevated selenomethionine levels in the other patients are also of interest due to the toxicity of this nonphysiological selenium species. Our study is the first to assess selenium exposure in genetic ALS, suggesting an interaction between this environmental factor and genetics in triggering disease onset.
Asunto(s)
Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/genética , Mutación/genética , Selenio/líquido cefalorraquídeo , Tubulina (Proteína)/genética , Ataxina-2/genética , Proteína C9orf72 , Niño , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Proteína FUS de Unión a ARN , Superóxido Dismutasa-1RESUMEN
BACKGROUND: The homeostasis of essential trace elements such as selenium and manganese may be altered in patients with severe diseases of various etiologies (trauma brain injuries, tumors, leukemias, lymphomas, neurological diseases). METHODS: Concentration of manganese and selenium were determined in cerebrospinal fluid by electrothermal atomic absorption spectrometry in 50 hospitalized children with various clinical ethiologies including oncological, neurological, and brain related diseases. RESULTS: The concentrations of manganese in cerebrospinal fluid of children were 0.97±0.67 µg/L. The concentrations of selenium were 13.3±3.5 µg/L. The concentrations were similar as published in adults. The values did not correlated with the age, gender and severity of the disease. CONCLUSION: We evaluated values of selenium and manganese in cerebrospinal fluid of seriously diseased children.
Asunto(s)
Manganeso/líquido cefalorraquídeo , Selenio/líquido cefalorraquídeo , Adolescente , Encefalopatías/líquido cefalorraquídeo , Niño , Preescolar , Enfermedad Crítica , Femenino , Humanos , Lactante , Límite de Detección , Modelos Lineales , Masculino , Neoplasias/líquido cefalorraquídeo , Espectrofotometría AtómicaRESUMEN
Selenium (Se) protects cells against oxidative stress damage through a range of bioactive selenoproteins. Increased oxidative stress is a prominent feature of Alzheimer's disease (AD), and previous studies have shown that Se deficiency is associated with age-related cognitive decline. In this study, we assessed Se status in different biofluids from a subgroup of participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. As Se in humans can either be an active component of selenoproteins or inactive via non-specific incorporation into other proteins, we used both size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and tandem mass spectrometry to characterize selenoproteins in serum. We observed no differences in total Se concentration in serum or cerebrospinal fluid of AD subjects compared to mildly cognitively impairment patients and healthy controls. However, Se levels in erythrocytes were decreased in AD compared to controls. SEC-ICP-MS analysis revealed a dominant Se-containing fraction. This fraction was subjected to standard protein purification and a bottom-up proteomics approach to confirm that the abundant Se in the fraction was due, in part, to selenoprotein P. The lack of change in the Se level is at odds with our previous observations in a Brazilian population deficient in Se, and we attribute this to the Australian cohort being Se-replete.
Asunto(s)
Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/líquido cefalorraquídeo , Disfunción Cognitiva/sangre , Disfunción Cognitiva/líquido cefalorraquídeo , Selenio/sangre , Selenio/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/genética , Estudios de Cohortes , Eritrocitos/metabolismo , Femenino , Humanos , Masculino , ProteómicaRESUMEN
This study was performed to characterise selenium (Se) and Se species in cerebrospinal fluid (CSF) of sheep and its relation to the respective Se concentrations in serum. Paired samples from 10 adult sheep were used for the study. Five sheep were fed a diet with a marginal Se concentration of <0.05mg Se/kg diet dry weight (dw, Se(-)), and five animals were fed the same diet supplemented with sodium selenite revealing a concentration of 0.2mg Se/kg diet dw (Se(+)). The feeding strategy was conducted for two years; The results on metabolic effects were published previously. At the end of the feeding period, paired samples of serum and CSF were collected and analysed using ion exchange chromatography inductively coupled plasma-dynamic reaction cell-mass spectrometry (IEC-ICP-DRC-MS) technique for total Se concentration and concentrations of Se species. Albumin concentrations were analysed additionally. The feeding strategy caused significant differences (p<0.01) in serum Se concentrations with 33.1±5.11µg Se/l in the Se(-) group and 96.5±18.3µg Se/l in the Se(+) group, respectively. The corresponding total Se concentrations in CSF were 4.38±1.02µg Se/l and 6.13±1.64µg Se/l in the Se(-) and the Se(+) group, respectively, missing statistical significance (p=0.077). IEC-ICP-DRC-MS technique was able to differentiate the Se species selenoprotein P-bound Se (SePP), selenomethionine, glutathione peroxidase-bound Se (Se-GPx), selenocystine, thioredoxin reductase-bound Se, ovine serum albumin-bound Se (Se-OSA), SeIV and SeVI in ovine serum and CSF. Quantitatively, SePP is the main selenoprotein in ovine serum followed by Se-GPx. The CSF/blood ratio of albumin (QAlbumin) reflected a physiological function of the blood-CSF barrier in all sheep. QSe-species were higher than QAlbumin both feeding groups, supporting the hypothesis of local production of Se species in the brain. Significant positive regression lines for CSF vs. serum were found for albumin and Se-OSA only, suggesting a role of albumin to convey Se across the blood-CSF barrier. The ovine model, together with the IEC-ICP-DRC-MS technique to characterise the Se species, might be a worthwhile model for further studies as repeated sample collection as well as modification of the nutritional status is feasible and effective.
Asunto(s)
Selenio/sangre , Selenio/líquido cefalorraquídeo , Ovinos/sangre , Ovinos/líquido cefalorraquídeo , Animales , Glutatión Peroxidasa/metabolismo , Humanos , Selenoproteína P/metabolismo , Albúmina Sérica/metabolismo , Reductasa de Tiorredoxina-Disulfuro/metabolismoRESUMEN
BACKGROUND: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on α-tocopherol (α-TP)-deficient diet. OBJECTIVE: Intramuscular α-TP and selenium (Se) administration at 4 days of age would have no significant effect on serum or cerebrospinal fluid (CSF) α-TP in healthy foals. Serum and CSF α-TP, but not Se, would be significantly decreased in NAD/EDM-affected foals during first year of life. ANIMALS: Fourteen Quarter horse foals; 10 healthy foals supplemented with 0.02 mL/kg injectable α-TP and Se (n = 5) or saline (n = 5) at 4 days of age and 4 unsupplemented NAD/EDM-affected foals. METHODS: Complete neurologic examinations were performed, blood and CSF were collected before (4 days of age) and after supplementation at 10, 30, 60, 120, 180, 240, and 360 days of age. Additional blood collections occurred at 90, 150, 210, and 300 days. At 540 days, NAD/EDM-affected foals and 1 unsupplemented healthy foal were euthanized and necropsies performed. RESULTS: Significant decreases in blood, CSF α-TP and Se found in the first year of life in all foals, with most significant changes in serum α-TP from 4-150 days. Dam α-TP and Se significantly influenced blood concentrations in foals. Injection of α-TP and Se did not significantly increase CSF Se, blood or CSF α-TP in healthy foals. NAD/EDM-affected foals had significantly lower CSF α-TP through 120 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Injection of α-TP and Se at 4 days of age does not significantly increase blood or CSF α-TP. Despite all 14 foals remaining deficient in α-TP, only the 4 genetically predisposed foals developed NAD/EDM.
Asunto(s)
Enfermedades de los Caballos/sangre , Distrofias Neuroaxonales/veterinaria , Selenio/líquido cefalorraquídeo , alfa-Tocoferol/líquido cefalorraquídeo , Animales , Animales Recién Nacidos , Femenino , Predisposición Genética a la Enfermedad , Enfermedades de los Caballos/líquido cefalorraquídeo , Enfermedades de los Caballos/genética , Caballos , Masculino , Distrofias Neuroaxonales/sangre , Distrofias Neuroaxonales/líquido cefalorraquídeo , Distrofias Neuroaxonales/genética , Distrofias Neuroaxonales/prevención & control , Selenio/administración & dosificación , Selenio/sangre , Selenio/farmacología , alfa-Tocoferol/administración & dosificación , alfa-Tocoferol/sangre , alfa-Tocoferol/farmacologíaRESUMEN
Selenium is an important trace element for brain function. Our objective was to analyse cerebrospinal fluid (CSF) selenium (Se) in 89 paediatric patients. We also studied correlations between Se and other biochemical variables (age, CSF protein concentrations and glutathione peroxidase activity and plasma Se values). Cerebrospinal fluid Se values showed a significant negative correlation with the age of patients (r = -0.476; p < 0.0001), and positive with CSF total protein concentrations and GPX activity (r = 0.446, p < 0.001; r = 0.431; p = 0.001, respectively). No association was observed between plasma and CSF Se concentrations. Median CSF Se values were 32 times lower when compared with those for plasma. In conclusion, CSF Se concentrations depend on age and total CSF protein values. The association observed between CSF Se and GPX activity suggests that Se quantification might be a reflection of some Se-dependent protein function. Cerebrospinal fluid Se values were independent of serum Se concentrations.
Asunto(s)
Selenio/líquido cefalorraquídeo , Adolescente , Niño , Preescolar , Humanos , Lactante , Recién NacidoRESUMEN
The well-known beneficial health effects of Se have demanded the development of rapid and accurate methods for its analysis. A flow injection (FI) method with inductively coupled plasma mass spectrometry (ICP-MS) as a selenium-selective detector was optimized. Flow injection was carried out using a Knauer 1100 smartline inert series liquid chromatograph coupled with a Perkin Elmer DRC II ICP-mass spectrometer. For sample injection a Perkin Elmer electronic valve equipped with a 25microL sample loop was employed. Before measurement, standards or samples were administered with 1microg/L rhodium as internal standard for correction of changes in detector response according to changes in sample electrolyte concentration. The method characterization parameters are: LOD (3sigma criterion): 26ng/L, LOQ (10sigma criterion): 86ng/L, linearity: 0.05->10microg/L, r(2)=0.9999, serial or day-to-day precision at 2microg/L: 4.48% or 5.6%. Accuracy was determined by (a) recovery experiments (CSF spiked with 2microg/L Se); (b) comparison of FI-ICP-MS measurement with graphite furnace atomic absorption (GFAAS) measurements of 1:10 diluted serum samples; (c) Se determination in urine and serum control materials. Recovery (a) was 101.4%, measurement comparison with GFAAS (b) showed 98.8% (5 serum samples, 1:10 diluted in the range of 0.5-1.3microg/L, compared to GFAAS determination, which was set to 100%), and accuracy was 96.8% or 105.6% for the serum or urine control material. Analysis time per sample was short and typically below 2min for the complete measurement, including sample introduction, sample-line purge and quadruplicate Se determination. This method was used to determine Se in cerebrospinal fluid (CSF) and plasma (here parallel to GFAAS) in 35 paired serum and CSF samples. Se determination gave values in the range of 42-130microg/L for serum and 1.63-6.66microg/L for CSF. The median for Se in 35 individual CSF samples was 3.28microg/L, the mean (+/-SD) was 3.67 (1.35)microg/L, whilst for individual serum samples the median was 81microg/L and the mean (+/-SD) was 85 (26)microg/L. When relating the paired Se concentrations of CSF samples to respective serum samples it turned out that Se-CSF (behind blood brain barrier (BBB)) is independent on Se-serum concentration (before BBB).
Asunto(s)
Análisis de Inyección de Flujo/métodos , Espectrometría de Masas/métodos , Microquímica/métodos , Selenio/sangre , Selenio/líquido cefalorraquídeo , Barrera Hematoencefálica/fisiología , Calibración , Humanos , Isótopos , Reproducibilidad de los Resultados , Espectrofotometría Atómica/métodosRESUMEN
We have quantitated CSF and serum levels of Selenium, iron, copper and zinc by Atomic absorption spectrophotometer in 36 patients with parkinson's disease all on L-dopa therapy. Out of these 19 showed on or positive response to L-dopa where as 21 patients showed on and off response. These data were compared with 21 healthy controls. The results showed that serum levels of iron, copper and zinc remained unchanged where as in CSF, significant decrease in zinc was found in both on and on/off PD patients indicating the deficiency of zinc which continues in the worsening clinical condition of off patients. The level of copper remained unchanged in both on and on/off PD patients. Iron and selenium increase in CSF of both patients which is a clear evidence of relationship between increased iron and selenium level in brain which could be correlated with decrease in dopamine levels and oxidative stress in PD Patients.
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Metales Pesados/sangre , Metales Pesados/líquido cefalorraquídeo , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/líquido cefalorraquídeo , Selenio/sangre , Selenio/líquido cefalorraquídeo , Anciano , Análisis de Varianza , Antiparkinsonianos/uso terapéutico , Estudios de Casos y Controles , Cobre , Femenino , Humanos , Hierro , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Espectrofotometría Atómica/métodos , ZincRESUMEN
We compared CSF and serum selenium levels, measured by atomic absorption spectrophotometry, in 27 patients with Alzheimer's disease (AD) (13 females, 14 males, mean +/- SD age 73.6 +/- 7.4 years) without major clinical signs of undernutrition, and 34 matched controls (18 females, 16 males, mean +/- SD age 70.7 +/- 7.8 years). CSF and serum selenium levels did not differ significantly between AD-patient (11.4 +/- 7.8 ng/ml and 28.5 +/- 13.0 ng/ml, respectively) and control groups (13.3 +/- 7.0 ng/ml and 22.5 +/- 17.5 ng/ml). These values were not correlated with age, age at onset, duration of the disease, and scores of the MiniMental State Examination in the AD group. Weight and body mass index were significantly lower in AD patients than in controls. These results suggest that CSF selenium concentrations are apparently unrelated with the reported oxidative stress processes in patients with AD.
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Enfermedad de Alzheimer/líquido cefalorraquídeo , Selenio/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Femenino , Humanos , Masculino , Concentración Osmolar , Valores de Referencia , Espectrofotometría Atómica , Vitamina A/sangreRESUMEN
We compared CSF and serum levels of selenium and chromium, measured by atomic absorption spectrophotometry, in 28 patients with Parkinson's disease (PD) and 43 matched controls. The CSF and serum levels of these trace metals did not differ significantly between PD patients and controls. CSF selenium and chromium levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group. Although antiparkinsonian therapy did not influence significantly the CSF levels of selenium, PD patients not treated with levodopa had significantly higher CSF selenium levels than controls (p < 0.01). It is possible that increased CSF selenium levels could indicate an attempt of protection against oxidative stress. The normality of CSF and serum chromium levels suggest that these values are not related with the risk for PD.
Asunto(s)
Cromo/líquido cefalorraquídeo , Enfermedad de Parkinson/líquido cefalorraquídeo , Selenio/líquido cefalorraquídeo , Anciano , Antiparkinsonianos/uso terapéutico , Estudios de Casos y Controles , Cromo/sangre , Femenino , Humanos , Masculino , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/tratamiento farmacológico , Selenio/sangreRESUMEN
Two children with severe neurodevelopmental retardation and elevated liver function tests developed intractable seizures during the first year of life. Detectable neurometabolic conditions have been ruled out. At the time of seizures evidence for systemic selenium deficiency could be documented. The youngest patient, who manifested intractable fits from the fourth day of life, died at the age of ten months. Neuropathologic examination was consistent with Progressive Neuronal Degeneration of Childhood (PNDC) with liver disease or formerly known as Alpers disease. In the oldest child, whose diet was normally balanced, fits started from the age of 11 months and features of long-standing selenium deficiency became apparent from the age of 1 1/2 years and consisted of liver function disturbances, depigmented hair and osteoarthropathy. Oral substitution with selenium supplements in both children (3-5 micrograms/kg body weight) resulted in reduction of seizures and improvement of the EEG recordings after two weeks while liver function became normal. Two of the seleno-dependent enzymes Glutathione Peroxidase (GPX) and Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPX) are speculated to play a key-role in the defence of neuronal cells against oxygen radical formation and peroxidative processes. Our findings support the hypothesis that the presence of selenium depletion in the brain amongst patients with epilepsy constitutes an important triggering factor for the origin of intractable seizures and subsequent neuronal damage.
Asunto(s)
Peroxidación de Lípido/fisiología , Selenio/deficiencia , Espasmos Infantiles/fisiopatología , Atrofia , Encéfalo/patología , Esclerosis Cerebral Difusa de Schilder/patología , Esclerosis Cerebral Difusa de Schilder/fisiopatología , Electroencefalografía/efectos de los fármacos , Femenino , Radicales Libres , Glutatión Peroxidasa/fisiología , Humanos , Lactante , Recién Nacido , Masculino , Degeneración Nerviosa/fisiología , Examen Neurológico , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Especies Reactivas de Oxígeno/metabolismo , Selenio/administración & dosificación , Selenio/líquido cefalorraquídeo , Espasmos Infantiles/patologíaRESUMEN
Following a wet digestion of 0.5-2.0 ml cerebrospinal fluid in an open system using 2.0 ml nitric acid and 1.0 ml perchloric acid (240 degrees C) and a reduction step with 1.0 ml hydrochloric acid, Selenium can be determined polarographically after adding 100 micrograms Copper(II)-ions to the analyte (15 ml; water/perchloric acid). Selenium concentrations in cerebrospinal fluid of children younger than one year (2.49 +/- 1.67 ng/ml) are significantly higher (p = 0.0074) than those of older children (1.28 +/- 0.97 ng/ml). Independent of the childrens age and diseases the Selenium concentrations correlate distinctly with cell numbers and protein contents. A correlation between Selenium content and cell numbers alone could not be proved. The non-significant differences between the Selenium concentrations in cerebrospinal fluids of children with hydrocephalus, leukemia (with or without involvement of the central nervous system), and other diseases, respectively, may be interpreted by considering the protein content of the cerebrospinal fluid and the age of the children.
Asunto(s)
Encefalopatías/líquido cefalorraquídeo , Selenio/líquido cefalorraquídeo , Adolescente , Factores de Edad , Neoplasias Encefálicas/líquido cefalorraquídeo , Niño , Preescolar , Femenino , Humanos , Hidrocefalia/líquido cefalorraquídeo , Lactante , Recién Nacido , Leucemia Linfoide/líquido cefalorraquídeo , Leucemia Mieloide Aguda/líquido cefalorraquídeo , Linfoma no Hodgkin/líquido cefalorraquídeo , MasculinoRESUMEN
Following a wet digestion of 0.5-2.0 ml cerebrospinal fluid in an open system using 2.0 ml nitric acid and 1.0 ml perchloric acid (240 degrees C) and a reduction step with 1.0 ml hydrochloric acid, Selenium can be determined polarographically after adding 100 micrograms Copper(II)-ions to the analyte (15 ml; water/perchloric acid). Selenium concentrations in cerebrospinal fluid of children younger than one year (2.49 +/- 1.67 ng/ml) are significantly higher (p = 0.0074) than those of older children (1.28 +/- 0.97 ng/ml). Independent of the children age and diseases the Selenium concentrations correlate distinctly with cell numbers and protein contents. A correlation between Selenium content and cell numbers alone could not be proved. The nonsignificant differences between the Selenium concentrations in cerebrospinal fluids of children with hydrocephalus, leukemia (with or without involvement of the central nervous system), and other diseases, respectively, may be interpreted by considering the protein content of the cerebrospinal fluid and the age of the children.
Asunto(s)
Encefalopatías/líquido cefalorraquídeo , Selenio/líquido cefalorraquídeo , Adolescente , Neoplasias Encefálicas/líquido cefalorraquídeo , Niño , Preescolar , Femenino , Humanos , Hidrocefalia/líquido cefalorraquídeo , Lactante , Leucemia/líquido cefalorraquídeo , Masculino , Meningitis/líquido cefalorraquídeoRESUMEN
We measured the concentrations of nine trace elements in cerebrospinal fluid of 11 patients with malignant brain tumors, 11 with benign brain tumors, and 10 control patients, using flameless atomic absorption spectrophotometry. The mean and standard deviation for these concentrations (microgram/L) in the control group were 5.1 +/- 2.9 (silver), 326.6 +/- 171.2 (aluminum), 38.5 +/- 32.2 (gold), 36.6 +/- 23.7 (bismuth), 1.5 +/- 1.3 (cadmium), 39.8 +/- 24.7 (copper), 15.7 +/- 11.5 (lead), 20.9 +/- 3.8 (antimony), and 19.1 +/- 13.3 (selenium). Concentrations of silver and lead were markedly increased in patients with malignant cerebral neoplasms. The malignant-tumor/control patient concentration ratios were 2.31 for silver and 2.11 for lead. We observed no significant differences between the results for the benign tumor patients and the control group.