| 1. |
- Bergdahl, Ingvar A, et al.
(författare)
-
Plasma-lead concentration: investigations into its usefulness for biological monitoring of occupational lead exposure.
- 2006
-
Ingår i: American journal of industrial medicine. - New York : Wiley. - 0271-3586 .- 1097-0274. ; 49:2, s. 93-101
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The lead concentration in plasma is correlated to that in whole blood with a two to fourfold variation. It has never been investigated if this variation is inter-individual. METHODS: Lead and hemoglobin were determined in blood and plasma from 13 lead workers with a history of relatively high blood-lead concentrations, sampled three times during 1 day. The variation in the distribution of lead between cells and plasma was studied, but not the variation in the lead concentrations as such. RESULTS: Blood hemoglobin decreased with rising plasma lead (0.9-3.0 microg/L). Regarding the distribution of lead, no effect of current exposure during the day or of recent meals appeared. As much as 84% of the overall variance of the distribution of lead between cells and plasma could be attributed to individual factors. After adjustment for erythrocyte volume fraction this decreased to 67%. Plasma samples with elevated hemoglobin concentrations (due to in vitro hemolysis) had somewhat elevated lead concentrations. CONCLUSIONS: Plasma lead is not significantly altered by variation in a single day's exposure and, therefore, the choice of time of the day is not critical for sampling. However, plasma lead is negatively correlated to blood hemoglobin and mild hemolysis (not visible by the eye) in a sample may increase plasma lead with up to 30%. Finally, plasma provides lead exposure information that differs from whole blood, but it is not clear which one of these is the biomarker with the closest relation to exposure and/or effects.
|
|
| 2. |
- Boström, Fredrik, et al.
(författare)
-
Cerebrospinal fluid total tau is associated with shorter survival in dementia with Lewy bodies.
- 2009
-
Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:4, s. 314-9
-
Tidskriftsartikel (refereegranskat)abstract
- A pathology typical of dementia with Lewy bodies (DLB) has been demonstrated to increase mortality to a greater extent than the pathology of Alzheimer's disease (AD). However, mortality in DLB has also been shown to increase with concomitant AD pathology. Furthermore, in a recent publication, we showed that there is a robust and specific increase in CSF calcium and magnesium in DLB patients compared to both AD patients and controls. Thus, in order to explore the influence of CSF AD markers and trace element concentrations on mortality in DLB, we undertook a longitudinal prospective study of 47 clinically diagnosed DLB patients and 157 AD patients as well as 49 healthy volunteers. Both AD and DLB patients showed an increased mortality compared to the healthy controls (relative risk: 10 and 8, respectively; p < 0.001). Increased levels of CSF total tau were associated with increased mortality among the DLB patients (p < 0.05), but not among the AD patients or controls. Gender, age, MMSE score, Abeta42 concentration and phosphorylated tau, and CSF trace element concentrations did not influence survival in the obtained models.
|
|
| 3. |
- Boström, Fredrik, et al.
(författare)
-
CSF Mg and Ca as diagnostic markers for dementia with Lewy bodies.
- 2008
-
Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:8, s. 1265-1271
-
Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence implicates a role for altered metal homeostasis in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, few investigations have addressed this issue in dementia with Lewy bodies (DLB). The aim of the present study was to investigate metal concentrations in cerebrospinal fluid (CSF) and plasma from patients with DLB and other neurodegenerative disorders. To that end, CSF and plasma samples were collected from 29 patients with DLB, 174 patients with AD, 90 patients with AD with minor vascular components, and 51 healthy volunteers. Total concentrations of Mg, Ca, Mn, Fe, Cu, Zn, Rb, Sr, and Cs were determined using mass spectrometry. Patients with DLB had elevated Ca and Mg levels in CSF and Mg levels in plasma as compared to all other groups (p<0.001). Furthermore, a combination of CSF-Mg and CSF-Ca could distinguish DLB from AD with a sensitivity of 93% and a specificity of 85%. Cu levels in both CSF and plasma tended to be higher in DLB compared to the other groups, but these trends failed to reach significance after correction for multiple comparisons. Mn, Fe, Zn, Rb, and Sr concentration in CSF or plasma were similar in all groups. The observed elevations of CSF-Mg, CSF-Ca and CSF-Cu may contribute to or be associated with the neurodegenerative process in DLB. Furthermore, determination of CSF-Mg and CSF-Ca concentration may be a valuable tool in distinguishing DLB from AD.
|
|
| 4. |
- Custodio, Hipolito M, et al.
(författare)
-
Genetic influences on the retention of inorganic mercury.
- 2005
-
Ingår i: Archives of environmental & occupational health. - 1933-8244. ; 60:1, s. 17-23
-
Tidskriftsartikel (refereegranskat)abstract
- Mercury is eliminated as glutathione (GSH) conjugates. GSH production is mediated by glutamyl-cysteine ligase (GCL), and conjugation by glutathione S-transferases (GST). This study tested if polymorphisms in GCL and GST genes modify mercury retention in humans exposed to elemental mercury vapor. Total mercury concentrations in whole blood, plasma and urine, and genotypes for GCLC, GCLM, GSTA1, GSTM1, GSTP1, and GSTT1 were determined in 309 gold miners, gold buyers and controls. The presence of the GCLM-588T allele was associated with increased blood, plasma and urine mercury levels. These results indicate that genotypes with decreased GSH availability for mercury conjugation affect the metabolism of inorganic mercury.
|
|
| 5. |
- Edlund, Maria, 1972, et al.
(författare)
-
A prospective cohort study investigating an exposure-response relationship among vibration-exposed male workers with numbness of the hands
- 2014
-
Ingår i: Scandinavian Journal of Work Environment & Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 40:2, s. 203-209
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to investigate the exposure response relationship of hand-arm vibration (HAY) exposure to neurological symptoms (numbness) of the hand in a cohort of vibration-exposed workers. Methods The baseline cohort comprised 241 office and manual workers with and without exposure to HAY. Numbness (the symptom or event) in the hand was assessed for all subjects at baseline and follow-ups after 5, 10, and 16 years. The workers were stratified into quartiles with no exposure in the first quartile and increasing intensity of exposure in quartiles 2-4 (groups 1-3). Data analysis was performed using survival analysis (time-to-event). Information on cumulative exposure and years of exposure to event was collected via questionnaires. Measurements were performed in accordance with the International Organization for Standardization (ISO) 5349-1. Results The hazard ratio (HR) of risk of event (numbness) differed statistically significantly between the non-exposed group (group 0) and the two higher exposure groups (groups 2 and 3). There was also a significant ratio difference between the lowest exposure group (group 1) and the two higher groups. The ratio for group 1 was 1.77 [95% confidence interval (95% CI) 0.96-3.26] compared with 3.78 (95% CI 2.15-6.62) and 5.31(95% CI 3.06-9.20) for groups 2 and 3, respectively. Conclusion The results suggest a dose response relationship between vibration exposure and numbness of the hands. This underlines the importance of keeping vibration levels low to prevent neurological injury to the hands.
|
|
| 6. |
- Edlund, Maria, 1972, et al.
(författare)
-
Physical capacity and psychological mood in association with self-reported work ability in vibration-exposed patients with hand symptoms.
- 2012
-
Ingår i: Journal of occupational medicine and toxicology (London, England). - : Springer Science and Business Media LLC. - 1745-6673. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: The aim of this study was to investigate whether self-reports of work ability correlated to the results of quantitative tests measuring physical capacity and a questionnaire assessing psychological mood in vibration-exposed patients with hand symptoms. METHODS: The participants comprised 47 patients (36 men and eleven women) with exposure to hand vibration and vascular and/or neurological symptoms in the hands. They performed several quantitative tests (manual dexterity, hand grip strength, finger strength) and completed the Work Ability Index (WAI) and Hospital Anxiety and Depression Scale (HADS) questionnaires. RESULTS: Correlation analysis revealed statistically significant associations between the WAI results, the HADS indices, hand grip and finger strength, and manual dexterity measured using the Purdue Pegboard(R). Multiple regression analysis revealed age and HADS indices as the strongest predictors of work ability. CONCLUSIONS: The patient's age and psychological mood may be stronger predictors of work ability compared with results from tests measuring physical capacity of the hands in vibration-exposed patients with hand symptoms. When using the WAI as an instrument for assessing work ability in these patients, health care providers need to be more aware of the impact of the psychological mood.
|
|
| 7. |
- Gerhardsson, Lars, 1952, et al.
(författare)
-
Cerebrospinal fluid/plasma quotients of essential and non-essential metals in patients with Alzheimer's disease.
- 2011
-
Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 118:6, s. 957-62
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, the quotients (Q) between metal concentrations in cerebrospinal fluid (CSF) and plasma were studied in subjects with Alzheimer's disease (AD) and referents to investigate if the leakage through the blood-CSF barrier (BCB) increased with increased duration and severity of the disease. Concentrations of 18 metals (Mg, Ca, Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Hg, and Pb) were determined by ICP-MS in plasma and cerebrospinal fluid in 264 patients with AD, and in 54 healthy referents. The quotients Q (Mn), Q (Rb), Q (Sb), Q (Pb) and Q (Hg) were significantly lower (p≤0.003) and Q (Co) significantly higher (p≤0.001) in subjects with AD as compared with the controls. Subjects in a subgroup with more severe AD, showed the same pattern. The metal leakage into CSF did not increase with increased duration and/or severity of the disease. The permeability of BCB varied considerably between the studied metals with low median quotients (Q≤0.02) for Cd, Cu, Sb, Se and Zn and higher median quotients for Ca (Q~0.5) and Mg (Q~1.3), probably partly depending on differences in size and lipophilicity of metal-carrier complexes and specific carrier mechanisms.
|
|
| 8. |
- Gerhardsson, Lars, 1952, et al.
(författare)
-
Concentrations of metals, beta-amyloid and tau-markers in cerebrospinal fluid in patients with Alzheimer's disease.
- 2009
-
Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:1, s. 88-94
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: In this study, metal concentrations were related to the levels of well-known Alzheimer markers in cerebrospinal fluid (CSF), such as amyloid-beta (Abeta), total tau (T-tau) and phosphorylated-tau (P-tau). METHODS: Concentrations of 19 metals (Mg, Ca, V, Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Hg and Pb by inductively coupled plasma-mass spectrometry) and the levels of Abeta, T-tau and P-tau in CSF were determined (xMAP technology) in 264 patients with Alzheimer's disease (AD), and in 54 healthy referents. RESULTS: The AD subjects showed positive correlations between CSF-T-tau and CSF-P-tau versus CSF-Mn (r(s) = 0.22, p = 0.004; r(s) = 0.18, p = 0.021). CSF-T-tau, however, showed a negative correlation with CSF-Cs (r(s) = -0.17; p = 0.027). In subjects with severe AD, CSF-Abeta showed a strong positive correlation with CSF-Cs (r(s) = 0.49; p = 0.026), while CSF-T-tau showed a strong negative correlation with CSF-Cs (r(s) = -0.49; p = 0.026). Also, CSF P-tau was negatively associated with CSF-Cs (r(s) = -0.41; p = 0.06). CONCLUSION: The different relationships between the CSF-levels of Abeta and tau-markers versus the levels of CSF-Mn and CSF-Cs may be due to different binding affinity between these metals and metal binding proteins in the CSF and the surrounding brain.
|
|
| 9. |
- Gerhardsson, Lars, 1952
(författare)
-
Diagnosis and treatment of metal poisoning general aspects
- 2021
-
Ingår i: Handbook on the Toxicology of Metals: Volume I: General Considerations. - 9780128232927 ; , s. 663-684
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Metal poisoning may or may not be apparent from the clinical features induced. The exposure pattern in terms of time, concentration, and route of exposure is a determinant of the clinical effect. Short-term high-level and long-term low-level exposure by ingestion are seen more often in the domestic environment and inhalation exposure is seen more often in occupational settings. Acute and chronic clinical effects of metal toxicity may involve the gastrointestinal, respiratory, cardiovascular, renal, hemopoietic, skin, and central nervous systems. In the diagnosis of metal poisoning, the presenting features may be nonspecific, with clinical examination giving no indication of the cause of illness. A full occupational history is required, along with knowledge of the work processes involved, and a detailed history is required where poisoning may occur in the domestic environment, particularly when poisoning results from the long-term absorption of cumulative metals. However, metal accumulation and poisoning may occur in the absence of environmental exposure, as, for example, transfusional siderosis in thalassemias, iron overload in idiopathic hemochromatosis, and copper accumulation in Wilson disease. In addition to history and clinical examination, trace metal analysis in body fluids, tissues, and environmental samples is required, together with biochemical and physiological investigation. In the treatment of metal poisoning, priorities should be to prevent further absorption by removal from exposure; minimize absorption from the gastrointestinal tract; provide general supportive therapy to maintain respiration, circulation, and water and electrolyte balance; and control nervous system effects. Elimination of the absorbed poison may be promoted by diuresis, blocking enterohepatic circulation, hemodialysis, or exchange transfusion. A number of therapeutic agents counteract the effects of an absorbed toxic metal by combining to form a less toxic compound that may be excreted more effectively by displacing it from its receptor site or by promoting translocation into a tissue where it cannot exert its toxic effects. Toxic metal antagonists, i.e., chelating agents, compete for toxic metals with ligands essential for their physiological function by forming a stable complex with the metal in the form of a heterocyclic ring. Chelating agents possess electron donor groups with a high affinity for the metal to be removed, thus causing its release from complexes with proteins or other endogenous ligands in a form that can be readily excreted. Chelation is indicated in the treatment of metal poisoning and metal storage diseases, in blood transfusion in iron overload, and to aid the elimination of metallic nuclides. However, chelation may result in depletion of essential metals or redistribution of toxic metals to other tissues such as the brain. Chelators themselves may also have toxic effects. Classical chelators, e.g., the polyaminopolycarboxylic acid ethylenediaminetetraacetic acid and the thiols dimercaprol [British anti-Lewisite (BAL), 2, 3-dimercaptopropanol] and d-penicillamine are of limited use today. Recent research activities have shown that meso-2, 3-dimercaptosuccinic acid (DMSA; succimer) and 2, 3-dimercaptopropane-1-sulfonate (DMPS; Dimaval, unithiol) are effective in the treatment of lead, arsenic, mercury, and to some extent also in polonium poisoning. Succimer and Dimaval have a significantly lower toxicity than BAL and DMPS can be administered both orally and intravenously. Due to its low toxicity, Succimer may turn out to be the drug of choice for the treatment of Wilson disease, with trientine or thiomolybdate as therapeutic alternatives. Deferoxamine (desferrioxamine, Desferal) is the drug of choice for antidotal management of acute iron overdose. Other orally given agents such as deferasirox (Exjade) and deferiprone (Ferriprox) can be used for the treatment of iron poisoning from metabolic sources and transfusional siderosis. These two agents can be administered in combination. In addition, the combination f deferiprone perorally and deferoxamine subcutaneously have shown promising results for the treatment of these conditions.
|
|
| 10. |
|
|
