Biochemistry in Medicine—Honorary Special Issue Commemorating Research and Work of Professors Jan O. Aaseth and Jan Alexander

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 22419

Special Issue Editors


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Guest Editor
Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
Interests: hemochromatosis; liver diseases; hematology; medical biochemistry; internal medicine

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Guest Editor
Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden
Interests: neurology; clinical neurophysiology; neurodegenerative disorders; amyotrophic lateral sclerosis; multiple sclerosis; neurotoxic metals
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Special Issue Information

Dear Colleagues,

The year 2023 marks the 50th anniversary of the publication of Professor Jan O. Aaseth’s paper in Biochemical Pharmacology (Jellum, E., Aaseth, J., and Eldjarn, L. 22(10), 1179-1188). A couple of years later, Professor Jan Alexander together with colleagues had his first paper in Journal of Chromatography, 126, 487-493. Both researchers were introduced to medical biochemistry by Professor Lorentz Eldjarn. While Dr. Aaseth initially continued his research on mercury toxicity and detoxification, Dr. Alexander continued research on metal interactions with selenium. They defended their theses at the University of Oslo in 1976 and 1983, respectively. While Aaseth completed his specialization in medical biochemistry and in internal medicine and endocrinology at Oslo University Hospital, Dr. Alexander specialized in occupational medicine at the National Institute of Occupational Health. Both researchers are approved EUROTOX-registered toxicologists. Dr. Alexander has held the leadership for Environmental medicine and Food Safety at the Norwegian Institute of Public Health and was appointed as a professor at the Norwegian University of Science and Technology (NTNU), and later at the Norwegian University of Life Sciences (NMBU). He served as an expert for the WHO, as chair of the Norwegian Scientific Committee for Food and Environment and as vice chair of EFSA Scientific Committee. Dr. Aaseth has been head of the units of Medical Biochemistry and Endocrinology at Innlandet Hospital, and appointed as a professor at University of Tromsø, later at Inland Norway University of Applied Sciences.

In 1984, Aaseth became a member of the steering group of the Committee for Geomedicine of the Norwegian Academy of Science and Letters; later, Jan Alexander joined the Committee. Then, in 1985, in close collaboration with colleagues in the Nordic countries, Jan O. Aaseth together with Jan Alexander founded the Nordic Trace Element Society (NTES), a scientific group that organized several international conferences, also in cooperation with the international organization ISTERH where Dr. Aaseth was a board member. Both researchers have been Guest Editors for Special Issues of several international scientific journals. Dr. Aaseth was also the president of the Norwegian Association for the Study of Obesity. Both have published more than 300 scientific papers.

Biomolecules is pleased to host a Special Issue on Biochemistry in Medicine, thereby also honoring Professors Jan O. Aaseth and Jan Alexander for their achievements within this field, which will be the focus of this issue.

Dr. Sonia Distante
Dr. Per M. Roos
Guest Editors

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Keywords

  • medical biochemistry
  • endocrinology
  • neurotoxic metals

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Published Papers (5 papers)

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Research

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6 pages, 608 KiB  
Communication
Hereditary Transthyretin Amyloidosis (hATTR) with Polyneuropathy Clusters Are Located in Ancient Mining Districts: A Possible Geochemical Origin of the Disease
by Per M. Roos and Sebastian K. T. S. Wärmländer
Biomolecules 2024, 14(6), 652; https://doi.org/10.3390/biom14060652 - 3 Jun 2024
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Abstract
Hereditary transthyretin amyloidosis (hATTR) with polyneuropathy (formerly known as Familial Amyloid Polyneuropathy (FAP)) is an endemic amyloidosis involving the harmful aggregation of proteins, most commonly transthyretin (TTR) but sometimes also apolipoprotein A-1 or gelsolin. hATTR appears to be transmitted as an autosomal dominant [...] Read more.
Hereditary transthyretin amyloidosis (hATTR) with polyneuropathy (formerly known as Familial Amyloid Polyneuropathy (FAP)) is an endemic amyloidosis involving the harmful aggregation of proteins, most commonly transthyretin (TTR) but sometimes also apolipoprotein A-1 or gelsolin. hATTR appears to be transmitted as an autosomal dominant trait. Over 100 point mutations have been identified, with the Val30Met substitution being the most common. Yet, the mechanism of pathogenesis and the overall origin of hATTR remain unclear. Here, we argue that hATTR could be related to harmful metal exposure. hATTR incidence is unevenly distributed globally, and the three largest defined clusters exist in Japan, Portugal, and Sweden. All three disease regions are also ancient mining districts with associated metal contamination of the local environment. There are two main mechanisms for how harmful metals, after uptake into tissues and body fluids, could induce hATTR. First, the metals could directly influence the expression, function, and/or aggregation of the proteins involved in hATTR pathology. Such metal–protein interactions might constitute molecular targets for anti-hATTR drug design. Second, metal exposure could induce hATTR -associated genetic mutations, which may have happened several generations ago. These two mechanisms can occur in parallel. In conclusion, the possibility that hATTR could be related to metal exposure in geochemically defined regions deserves further attention. Full article
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12 pages, 724 KiB  
Article
A Vegetarian Diet Significantly Changes Plasma Kynurenine Concentrations
by Anne-Lise Bjørke-Monsen, Kristin Varsi, Arve Ulvik, Sunniva Todnem Sakkestad and Per Magne Ueland
Biomolecules 2023, 13(2), 391; https://doi.org/10.3390/biom13020391 - 18 Feb 2023
Cited by 7 | Viewed by 2279
Abstract
Tryptophan is an essential amino acid and a precursor of a number of physiologically important metabolites, including serotonin, melatonin, tryptamine, and kynurenines. We assessed tryptophan, kynurenines, and vitamin B2 and B6, as well as biomarkers of liver function and inflammation, in a group [...] Read more.
Tryptophan is an essential amino acid and a precursor of a number of physiologically important metabolites, including serotonin, melatonin, tryptamine, and kynurenines. We assessed tryptophan, kynurenines, and vitamin B2 and B6, as well as biomarkers of liver function and inflammation, in a group of 158 female omnivores and vegetarians aged 18–40 years. The majority of women were omnivores, and 22% were vegetarians. Vegetarians had 25% lower serum ALT, significantly higher pyridoxal concentrations, and significantly lower plasma concentrations of most kynurenines, varying from 8% lower concentrations of median plasma kynurenine to 42% lower concentrations of plasma xanthurenic acid, compared to omnivores. No significant differences were observed in vitamin B2 status or in inflammation markers, C-reactive protein and neopterin between the groups. Vegetarians had lower levels of several plasma kynurenines compared to omnivores. The reason for this is unknown; however, lower ALT concentrations, suggesting a better liver status, and a more favourable vitamin B6 status might be contributing factors. Full article
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Review

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33 pages, 1676 KiB  
Review
The Role of Trace Elements and Minerals in Osteoporosis: A Review of Epidemiological and Laboratory Findings
by Anatoly V. Skalny, Michael Aschner, Ekaterina V. Silina, Victor A. Stupin, Oleg N. Zaitsev, Tatiana I. Sotnikova, Serafima Ia. Tazina, Feng Zhang, Xiong Guo and Alexey A. Tinkov
Biomolecules 2023, 13(6), 1006; https://doi.org/10.3390/biom13061006 - 17 Jun 2023
Cited by 15 | Viewed by 4762
Abstract
The objective of the present study was to review recent epidemiological and clinical data on the association between selected minerals and trace elements and osteoporosis, as well as to discuss the molecular mechanisms underlying these associations. We have performed a search in the [...] Read more.
The objective of the present study was to review recent epidemiological and clinical data on the association between selected minerals and trace elements and osteoporosis, as well as to discuss the molecular mechanisms underlying these associations. We have performed a search in the PubMed-Medline and Google Scholar databases using the MeSH terms “osteoporosis”, “osteogenesis”, “osteoblast”, “osteoclast”, and “osteocyte” in association with the names of particular trace elements and minerals through 21 March 2023. The data demonstrate that physiological and nutritional levels of trace elements and minerals promote osteogenic differentiation through the up-regulation of BMP-2 and Wnt/β-catenin signaling, as well as other pathways. miRNA and epigenetic effects were also involved in the regulation of the osteogenic effects of trace minerals. The antiresorptive effect of trace elements and minerals was associated with the inhibition of osteoclastogenesis. At the same time, the effect of trace elements and minerals on bone health appeared to be dose-dependent with low doses promoting an osteogenic effect, whereas high doses exerted opposite effects which promoted bone resorption and impaired bone formation. Concomitant with the results of the laboratory studies, several clinical trials and epidemiological studies demonstrated that supplementation with Zn, Mg, F, and Sr may improve bone quality, thus inducing antiosteoporotic effects. Full article
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13 pages, 951 KiB  
Review
The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases
by Knut Hestad, Jan Alexander, Helge Rootwelt and Jan O. Aaseth
Biomolecules 2022, 12(7), 998; https://doi.org/10.3390/biom12070998 - 18 Jul 2022
Cited by 65 | Viewed by 7036
Abstract
Emerging evidence suggests that neuroinflammation is involved in both depression and neurodegenerative diseases. The kynurenine pathway, generating metabolites which may play a role in pathogenesis, is one of several competing pathways of tryptophan metabolism. The present article is a narrative review of tryptophan [...] Read more.
Emerging evidence suggests that neuroinflammation is involved in both depression and neurodegenerative diseases. The kynurenine pathway, generating metabolites which may play a role in pathogenesis, is one of several competing pathways of tryptophan metabolism. The present article is a narrative review of tryptophan metabolism, neuroinflammation, depression, and neurodegeneration. A disturbed tryptophan metabolism with increased activity of the kynurenine pathway and production of quinolinic acid may result in deficiencies in tryptophan and derived neurotransmitters. Quinolinic acid is an N-methyl-D-aspartate receptor agonist, and raised levels in CSF, together with increased levels of inflammatory cytokines, have been reported in mood disorders. Increased quinolinic acid has also been observed in neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and HIV-related cognitive decline. Oxidative stress in connection with increased indole-dioxygenase (IDO) activity and kynurenine formation may contribute to inflammatory responses and the production of cytokines. Increased formation of quinolinic acid may occur at the expense of kynurenic acid and neuroprotective picolinic acid. While awaiting ongoing research on potential pharmacological interventions on tryptophan metabolism, adequate protein intake with appropriate amounts of tryptophan and antioxidants may offer protection against oxidative stress and provide a balanced set of physiological receptor ligands. Full article
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11 pages, 468 KiB  
Review
Gadolinium in Medical Imaging—Usefulness, Toxic Reactions and Possible Countermeasures—A Review
by Lennart Blomqvist, Gunnar F. Nordberg, Valeria M. Nurchi and Jan O. Aaseth
Biomolecules 2022, 12(6), 742; https://doi.org/10.3390/biom12060742 - 24 May 2022
Cited by 36 | Viewed by 6518
Abstract
Gadolinium (Gd) is one of the rare-earth elements. The properties of its trivalent cation (Gd3+) make it suitable to serve as the central ion in chelates administered intravenously to patients as a contrast agent in magnetic resonance imaging. Such Gd-chelates have [...] Read more.
Gadolinium (Gd) is one of the rare-earth elements. The properties of its trivalent cation (Gd3+) make it suitable to serve as the central ion in chelates administered intravenously to patients as a contrast agent in magnetic resonance imaging. Such Gd-chelates have been used for more than thirty years. During the past decades, knowledge has increased about potential harmful effects of Gd-chelates in patients with severe renal dysfunction. In such patients, there is a risk for a potentially disabling and lethal disease, nephrogenic systemic fibrosis. Restricting the use of Gd-chelates in persons with severely impaired renal function has decreased the occurrence of this toxic effect in the last decade. There has also been an increasing awareness of Gd-retention in the body, even in patients without renal dysfunction. The cumulative number of doses given, and the chemical structure of the chelate given, are factors of importance for retention in tissues. This review describes the chemical properties of Gd and its medically used chelates, as well as its toxicity and potential side effects related to injection of Gd-chelates. Full article
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