| 1. |
- Aaseth, J, et al.
(författare)
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Prevention of progression in Parkinson's disease
- 2018
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Ingår i: Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. - : Springer Science and Business Media LLC. - 1572-8773. ; 31:5, s. 737-747
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Aaseth, Jan, et al.
(författare)
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Treatment strategies in Alzheimers disease: a review with focus on selenium supplementation
- 2016
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Ingår i: Biometals. - : SPRINGER. - 0966-0844 .- 1572-8773. ; 29:5, s. 827-839
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimers disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (A beta) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce A beta production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral A beta plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.
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| 3. |
- Andersen, Ole, et al.
(författare)
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Nutritional interactions in intestinal cadmium uptake--possibilities for risk reduction.
- 2004
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Ingår i: Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. - : Kluwer Academic Publishers. - 0966-0844 .- 1572-8773. ; 17:5, s. 543-7
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Tidskriftsartikel (refereegranskat)abstract
- Effects of dietary composition and trace element status on fractional intestinal cadmium uptake is reviewed below. Fractional cadmium uptake is of fundamental importance for internal dose, related individual susceptibility to cadmium, induced renal damage and eventually bone disease. Diet composition with regard to macronutrients has some effects on cadmium bioavailability. Major determinants of intestinal cadmium uptake are however diet composition with regard to crude fibres and trace elements, especially iron. Deficiencies may increase intestinal cadmium uptake 5-8 times. Ultimate risk management would be not to raise crops on cadmium polluted soil. Provisionally, assurance of optimal trace element statusin persons exposed to cadmium is essential for risk reduction.
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| 4. |
- Ariöz, Candan, 1983, et al.
(författare)
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The six metal binding domains in human copper transporter, ATP7B: molecular biophysics and disease-causing mutations
- 2017
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Ingår i: Biometals. - : Springer Science and Business Media LLC. - 0966-0844 .- 1572-8773. ; 30:6, s. 823-840
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Tidskriftsartikel (refereegranskat)abstract
- Wilson Disease (WD) is a hereditary genetic disorder, which coincides with a dysfunctional copper (Cu) metabolism caused by mutations in ATP7B, a membrane-bound P-1B-type ATPase responsible for Cu export from hepatic cells. The N-terminal part (similar to 600 residues) of the multi-domain 1400-residue ATP7B constitutes six metal binding domains (MBDs), each of which can bind a copper ion, interact with other ATP7B domains as well as with different proteins. Although the ATP7B's MBDs have been investigated in vitro and in vivo intensively, it remains unclear how these domains modulate overall structure, dynamics, stability and function of ATP7B. The presence of six MBDs is unique to mammalian ATP7B homologs, and many WD causing missense mutations are found in these domains. Here, we have summarized previously reported in vitro biophysical data on the MBDs of ATP7B and WD point mutations located in these domains. Besides the demonstration of where the research field stands today, this review showcasts the need for further biophysical investigation about the roles of MBDs in ATP7B function. Molecular mechanisms of ATP7B are important not only in the development of new WD treatment but also for other aspects of human physiology where Cu transport plays a role. RAHAMS JP, 1994, NATURE, V370, P621
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| 5. |
- Bengtsson, Ulf, et al.
(författare)
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Increased mercury emissions from modern dental amalgams
- 2017
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Ingår i: Biometals. - : SPRINGER. - 0966-0844 .- 1572-8773. ; 30:2, s. 277-283
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Tidskriftsartikel (refereegranskat)abstract
- All types of dental amalgams contain mercury, which partly is emitted as mercury vapor. All types of dental amalgams corrode after being placed in the oral cavity. Modern high copper amalgams exhibit two new traits of increased instability. Firstly, when subjected to wear/polishing, droplets rich in mercury are formed on the surface, showing that mercury is not being strongly bonded to the base or alloy metals. Secondly, high copper amalgams emit substantially larger amounts of mercury vapor than the low copper amalgams used before the 1970s. High copper amalgams has been developed with focus on mechanical strength and corrosion resistance, but has been sub-optimized in other aspects, resulting in increased instability and higher emission of mercury vapor. This has not been presented to policy makers and scientists. Both low and high copper amalgams undergo a transformation process for several years after placement, resulting in a substantial reduction in mercury content, but there exist no limit for maximum allowed emission of mercury from dental amalgams. These modern high copper amalgams are nowadays totally dominating the European, US and other markets, resulting in significant emissions of mercury, not considered when judging their suitability for dental restoration.
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| 6. |
- Del Giudice, Rita, et al.
(författare)
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Effects of iron on the aggregation propensity of the N-terminal fibrillogenic polypeptide of human apolipoprotein A-I
- 2018
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Ingår i: BioMetals. - : Springer Science and Business Media LLC. - 0966-0844 .- 1572-8773. ; 31:4, s. 551-559
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Tidskriftsartikel (refereegranskat)abstract
- Specific mutations in APOA1 gene lead to systemic, hereditary amyloidoses. In ApoA-I related amyloidosis involving the heart, amyloid deposits are mainly constituted by the 93-residue N-terminal region of the protein, here indicated as [1-93]ApoA-I. Oxidative stress is known to be an enhancing factor for protein aggregation. In healthy conditions, humans are able to counteract the formation and the effects of oxidative molecules. However, aging and atmospheric pollution increase the concentration of oxidative agents, such as metal ions. As the main effect of iron deregulation is proposed to be an increase in oxidative stress, we analysed the effects of iron on [1-93]ApoA-I aggregation. By using different biochemical approaches, we demonstrated that Fe(II) is able to reduce the formation of [1-93]ApoA-I fibrillar species, probably by stabilizing its monomeric form, whereas Fe(III) shows a positive effect on polypeptide fibrillogenesis. We hypothesize that, in healthy conditions, Fe(III) is reduced by the organism to Fe(II), thus inhibiting amyloid formation, whereas during ageing such protective mechanisms decline, thus exposing the organism to higher oxidative stress levels, which are also related to an increase in Fe(III). This alteration could contribute to the pathogenesis of amyloidosis.
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| 7. |
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| 8. |
- Edvinsson, Marie, et al.
(författare)
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Trace element balance is changed in infected organs during acute Chlamydophila pneumoniae infection in mice
- 2008
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Ingår i: Biometals. - : Springer Science and Business Media LLC. - 0966-0844 .- 1572-8773. ; 21:2, s. 229-237
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Tidskriftsartikel (refereegranskat)abstract
- Most infectious diseases are accompanied by changed levels of several trace elements in the blood. However, sequential changes in trace elements in tissues harbouring bacterial infections have not been studied. In the present study the respiratory pathogen Chlamydophila pneumoniae (C. pneumoniae), adapted to C57BL/6J mice, was used to study whether the balance of trace elements is changed in infected organs. Bacteria were quantitatively measured by real-time PCR in the blood, lungs, liver, aorta, and heart on days 2, 5, and 8 of the infection. Concentrations of 13 trace elements were measured in the liver, heart, and serum by inductively coupled plasma mass-spectrometry (ICP-MS). Infected mice developed expected clinical signs of disease and bacteria were found in lungs, liver, and heart on all days. The number of bacteria peaked on day 2 in the heart and on day 5 in the liver. The copper/zinc (Cu/Zn) ratio in serum increased as a response to the infection. Cu increased in the liver but did not change in the heart. Iron (Fe) in serum decreased progressively, whereas in the heart it tended to increase, and in the liver it progressively increased. C. pneumoniae may thus cause a changed trace element balance in target tissues of infection that may be pivotal for bacterial growth.
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| 9. |
- Essén, Sofia, et al.
(författare)
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Quantification of hydroxamate siderophores in soil solutions of podzolic soil profiles in Sweden
- 2006
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Ingår i: Biometals. - : Springer Science and Business Media LLC. - 0966-0844 .- 1572-8773. ; 19:3, s. 269-282
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Tidskriftsartikel (refereegranskat)abstract
- Concentrations up to 2 and 12 nM of the hydroxamate siderophores ferrichrome and ferricrocin, respectively, were identified in soil solutions of podzolic forest soils at four sites in both northern and southern Sweden. No ferrichrysin was detected. As with the dissolved organic carbon and low molecular mass organic acids, the highest concentrations of the siderophores were found in the upper layers i.e. the mor layer, the eluvial and upper illuvial horizons. At the southern sites, the concentrations of ferrichrome and ferricrocin were both of similar magnitude and did not differ between the two sites. In contrast, soil solutions at the two northern sites contained more ferricrocin than ferrichrome; the ferricrocin concentrations were also higher at the northern sites than at the southern sites. Analyses were performed by high performance liquid chromatography with a porous graphitic carbon column on which ferrichrome, ferricrocin and ferrichrysin were separated. Detection by electrospray ionization mass spectrometry (ESI-MS) combined with on-line sample pre-concentration, by means of column-switching, enabled detection limits of 0.1-0.2 nM for ferrichrome, ferrichrysin and ferricrocin. The structural identities of the siderophores were further verified by MS/MS fragmentation. Fragmentation of ferrichrome, ferricrocin and ferrichrysin occured mainly via peptide cleavage. The most intense fragments were typified by the loss of one of the three iron(III) chelating hydroxamate residues, i.e N5-acyl-N5-hydroxy ornithine.
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| 10. |
- Gama, Ntombenhle, et al.
(författare)
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Gold(I) complex of 1,1'-bis(diphenylphosphino) ferrocene-quinoline conjugate: a virostatic agent against HIV-1.
- 2016
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Ingår i: BioMetals. - : Springer Science and Business Media LLC. - 1572-8773 .- 0966-0844. ; 29:3, s. 389-397
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Tidskriftsartikel (refereegranskat)abstract
- HIV infection is known for replicating in proliferating CD(+) T-cells. Treatment of these cells with cytostatic (anti-proliferation) compounds such as hydroxyurea interferes with the cells's ability support HIV replication. Combinations of such cytostatic compounds with proven anti-retroviral drugs (like ddI) are known as virostatic, and have been shown to aid in the control of the infection. The use of two different drugs in virostatic combinations however, carries the risk of adverse effects including drug-drug interactions, which could lead to augmented toxicities and reduced efficacy. Here, a novel digold(I) complex of ferrocene-quinoline (3) was investigated for cytostatic behaviour as well as anti-viral activity which if demonstrated would eliminate concerns of drug-drug interactions. The complex was synthesized and characterized by NMR, FT-IR and mass spectroscopy and the molecular structure was confirmed by X-ray crystallography. Bio-screening involved viability dyes, real time electronic sensing and whole virus assays. The complex showed significant (p = 0.0092) inhibition of virus infectivity (83 %) at 10 ug/mL. This same concentration caused cytostatic behaviour in TZM-bl cells with significant (p < 0.01) S and G2/M phase cell cycle arrest. These data supports 3 as a virostatic agent, possessing both anti-viral and cytostatic characteristics. In the absence of 3, TZM-bl cells were infected by a pseudovirus and this was demonstrated through luminescence in a luciferase assay. Pre-incubation of the virus with 3 decreased luminescence, indicating the anti-viral activity of 3. Complex 3 also showed cytostatic behavior with increased S-phase and G2/M phase cell cycle arrest.
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