Search Results (18)

The Cluster of Differentiation 5-like protein (CD5L) is produced by tissue-resident macrophages. It is an innate immune mediator protein with a multitude of functions, such as binding of invading microorganisms and oxidised LDL, and it is associated with clinical conditions, i.e., atherosclerosis and inflammation. The circulating CD5L level has been reported to correlate to selenium status and thyroid hormone activity. In order to test this hypothesis, we analysed CD5L in serum samples from a randomized controlled trial (RCT) with selenium and coenzyme Q₁₀ supplementation and examined associations between CD5L and thyroid hormones, health-related quality-of-life (Hr-QoL), and mortality in an elderly population low in selenium. Circulating levels of CD5L and thyroid hormones were determined in 359 elderly community-living individuals enrolled in an RCT at inclusion and after 48 months of supplementation (179 received selenium and coenzyme Q₁₀, and 180 placebo). Hr-QoL was recorded at both time-points using Short Form 36. Pre-intervention plasma selenium was low, mean 67 µg/L. CD5L correlated positively to free tri-iodothyronine (fT3) and showed an inverse relation with thyroid stimulating hormone (TSH). Low CD5L concentrations at inclusion in the placebo group were associated with increased cardiovascular mortality during 10 years of follow-up, and impaired Hr-QoL at 48 months. Selenium and coenzyme Q₁₀ supplementation significantly increased CD5L and fT3 levels, in association with a better health outcome. The data indicate that circulating CD5L positively responds to selenium and coenzyme Q₁₀ supplementation, correlates with thyroid hormone status, and associates with positive health indices. The observed effect may be due to increased selenium-dependent deiodinase isozyme expression that converts thyroxine (T4) to T3 locally and supports thyroid hormone activities. Whether the observed associations with Hr-QoL and cardiovascular mortality are a direct effect of circulating CD5L or local thyroid hormone activity is unclear and should be further investigated. Full article

Background: The effectiveness of bariatric surgery in reducing remnant cholesterol (RC) levels, particularly when obesity is accompanied by elevated glycated hemoglobin (HbA1c), is insufficiently investigated. In this study, we aimed to examine the impacts of two common bariatric procedures, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), as regards their effects on RC and HbA1c levels. Methods: Adult morbidly obese subjects were included and assigned to receive either RYGB or SG. The levels of RC and HbA1c were determined 6 and 12 months after surgery and compared to preoperative levels to assess the efficacy of these surgical methods. In the statistical evaluation of covariations between RC and other biomarkers, previously determined C-reactive protein (CRP), triglycerides, apolipoprotein B, apolipoprotein A1, and low- and high-density lipoprotein cholesterol 6 and 12 months after surgery were included. A linear mixed regression model for repeated analyses was used. Results: The RC levels were markedly reduced both after RYGB and SG but without significant differences between the RYGB and the SG surgery. Furthermore, the RC values were strongly associated with the levels of CRP and HbA1c. Conclusions: A significant lowering of RC values after bariatric surgery appeared paralleled by concomitant reductions in HbA1c values and CRP levels. Together, these effects lead to a lower risk of cardiovascular disease. Full article

Cyanide (CN) is a well-known mitochondrial poison. CN poisoning may result from acute or long-term exposure to a number of CN compounds. Recent insight into the chemical affinities of the CN anion has increased our understanding of its toxicity and the mechanisms of antidotal actions, which, together with information on various exposure sources, are reviewed in the present article. A literature search in Scopus, Embase, Web of Science, PubMed, and Google Scholar for the period 2001–2024 revealed that the CN anion after exposure or degradation of CN compounds is distributed to vulnerable copper and iron-containing targets, especially in mitochondria, thus blocking the electron transport chain. Intake of cyanogenic compounds may exert subacute or chronic toxic effects, also because of the interaction with cobalt in vitamin B₁₂. Antidotal agents exert their effects through the affinity of CN for cobalt- or iron-containing compounds. Research on CN interactions with metalloproteins may increase our insight into CN toxicity and efficient antidotal regimens. Full article

Members of three generations of a Norwegian family (N = 9) with a rare demyelinating disease were studied. Neuropsychological testing was performed using the Mini Mental Status Examination (MMSE), Wechsler Intelligence Scale-III (WAIS-III), and Hopkins Verbal Learning Test-Revised (HVLT-R). EEGs were recorded with grand averaging spectrograms and event-related potentials (ERPs) in rest and cued GO/NOGO task conditions. The results were within the normal range on the MMSE. Full-scale WAIS-III results were in the range of 69–113, with lower scores in verbal understanding than in perceptual organization, and low scores also in indications of working memory and processing speed difficulties. The HVLT-R showed impairment of both immediate and delayed recall. Quantitative EEG showed an increase in low alpha (around 7.5 Hz) activity in the temporofrontal areas, mostly on the left side. There was a deviation in the late (>300 ms) component in response to the NOGO stimuli. A strong correlation (r = 0.78, p = 0.01) between the Hopkins Verbal Learning Test (delayed recall) and the amplitude of the NOGO ERP component was observed. The EEG spectra showed deviations from the healthy controls, especially at frontotemporal deviations. Deviations in the ERP component of the NOGO trials were related to delayed recall in the Hopkins Verbal learning test. Full article

The aim of the present review is to discuss the roles of vitamin K (phylloquinone or menaquinones) and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for the maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated, these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. An adequate vitamin K status is required for the carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanisms, such as menaquinone 4 acting as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through the dietary adequacy of vitamin K. Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3, we find that an adequate supply of vitamin K, on top of an optimal vitamin D status, seems to add to the benefit of maintaining bone health. More research related to synergism and the possible mechanisms of vitamins D3 and K interaction in bone health is needed. Full article

The observation that the extent of artery calcification correlates with the degree of atherosclerosis was the background for the alternative treatment of cardiovascular disease with chelator ethylenediamine tetraacetate (EDTA). Recent studies have indicated that such chelation treatment has only marginal impact on the course of vascular disease. In contrast, endogenous calcium chelation with removal of calcium from the cardiovascular system paralleled by improved bone mineralization exerted, i.e., by matrix Gla protein (MGP) and osteocalcin, appears to significantly delay the development of cardiovascular diseases. After post-translational vitamin-K-dependent carboxylation of glutamic acid residues, MGP and other vitamin-K-dependent proteins (VKDPs) can chelate calcium through vicinal carboxyl groups. Dietary vitamin K is mainly provided in the form of phylloquinone from green leafy vegetables and as menaquinones from fermented foods. Here, we provide a review of clinical studies, addressing the role of vitamin K in cardiovascular diseases, and an overview of vitamin K kinetics and biological actions, including vitamin-K-dependent carboxylation and calcium chelation, as compared with the action of the exogenous (therapeutic) chelator EDTA. Consumption of vitamin-K-rich foods and/or use of vitamin K supplements appear to be a better preventive strategy than EDTA chelation for maintaining vascular health. Full article

Skogholt’s disease is a rare neurological disorder that is only observed in a small Norwegian kindred. It typically manifests in adulthood with uncharacteristic neurological symptoms from both the peripheral and central nervous systems. The etiology of the observed cerebral white matter lesions and peripheral myelin pathology is unclear. Increased cerebrospinal fluid (CSF) concentrations of protein have been confirmed, and recently, very high concentrations of CSF total and phosphorylated tau have been detected in Skogholt patients. The symptoms and observed biomarker changes in Skogholt’s disease are largely nonspecific, and further studies are necessary to elucidate the disease mechanisms. Here, we report the results of neurochemical analyses of plasma and CSF, as well as results from the morphometric segmentation of cerebral magnetic resonance imaging. We analyzed the biomarkers Aβ_1––42, Aβ_1–40, Aβ_x–38, Aβ_x–40, Aβ_x–42, total and phosphorylated tau, glial fibrillary acidic protein, neurofilament light chain, platelet-derived growth factor receptor beta, and beta-trace protein. All analyzed CSF biomarkers, except neurofilament light chain and Aβ_1/x–42, were increased several-fold. In blood, none of these biomarkers were significantly different between the Skogholt and control groups. MRI volumetric segmentation revealed decreases in the ventricular, white matter, and choroid plexus volumes in the Skogholt group, with an accompanying increase in white matter lesions. The cortical thickness and subcortical gray matter volumes were increased in the Skogholt group. Pathophysiological changes resulting from choroidal dysfunction and/or abnormal CSF turnover, which may cause the increases in CSF protein and brain biomarker levels, are discussed. Full article

Background: Ageing is associated with cardiovascular disease (CVD). As no single biomarker reflects the full ageing process, we aimed to investigate five CVD- and age-related markers and the effects of selenium and coenzyme Q10 intervention to elucidate the mechanisms that may influence the course of ageing. Methods: This is a sub-study of a previous prospective double-blind placebo-controlled randomized clinical trial that included 441 subjects low in selenium (mean age 77, 49% women). The active treatment group (n = 220) received 200 µg/day of selenium and 200 mg/day of coenzyme Q10, combined. Blood samples were collected at inclusion and after 48 months for measurements of the intercellular adhesion molecule (ICAM-1), adiponectin, leptin, stem cell factor (SCF) and osteoprotegerin (OPG), using ELISAs. Repeated measures of variance and ANCOVA evaluations were used to compare the two groups. In order to better understand and reduce the complexity of the relationship between the biomarkers and age, factor analyses and structural equation modelling (SEM) were performed, and a structural model is presented. Results: Correlation analyses of biomarker values at inclusion in relation to age, and relevant markers related to inflammation, endothelial dysfunction and fibrosis, demonstrated the biomarkers’ association with these pathological processes; however, only ICAM1 and adiponectin were directly correlated with age. SEM analyses showed, however, that the biomarkers ICAM-1, adiponectin, SCF and OPG, but not leptin, all had significant associations with age and formed two independent structural factors, both significantly related to age. While no difference was observed at inclusion, the biomarkers were differently changed in the active treatment and placebo groups (decreasing and increasing levels, respectively) at 48 months (p ≤ 0.02 in all, adjusted), and in the SEM model, they showed an anti-ageing impact. Conclusions: Supplementation with selenium/Q10 influenced the analysed biomarkers in ways indicating an anti-ageing effect, and by applying SEM methodology, the interrelationships between two independent structural factors and age were validated. Full article

Obesity has become a worldwide epidemic accompanied by adverse health effects. The limited efficiency of traditional weight reduction regimens has led to a substantial increase in the use of bariatric surgery. Today, sleeve gastrectomy (SG) and Roux-en-Y-gastric bypass (RYGB) are the most used procedures. The present narrative review focuses on the risk of developing postoperative osteoporosis and summarizes some of the most relevant micronutrient deficiencies associated with RYGB and SG. Preoperatively, the dietary habits of obese individuals might lead to precipitated deficiencies in vitamin D and other nutrients affecting bone mineral metabolism. Bariatric surgery with SG or RYGB can aggravate these deficiencies. The various surgical procedures appear to affect nutrient absorption differently. Being purely restrictive, SG may particularly affect the absorption of vitamin B₁₂ and also vitamin D. In contrast, RYGB has a more profound impact on the absorption of fat-soluble vitamins and other nutrients, although both surgical methods induce only a mild protein deficiency. Despite adequate supplementation of calcium and vitamin D, osteoporosis may still occur after the surgery. This might be due to deficiencies in other micronutrients, e.g., vitamin K and zinc. Regular follow-ups with individual assessments and nutritional advice are indispensable to prevent osteoporosis and other adverse postoperative issues. Full article

The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead (Pb) in poisoned individuals. However, DMSA, PSH, EDTA (ethylenediamine tetraacetate), and deferoxamine (DFOA) are water-soluble agents with limited access to the central nervous system (CNS). Strategies for mobilization of metals such as manganese (Mn), iron (Fe), and Cu from brain deposits may require the combined use of two agents: one water-soluble agent to remove circulating metal into urine, in addition to an adjuvant shuttler to facilitate the brain-to-blood mobilization. The present review discusses the chemical basis of metal chelation and the ligand exchange of metal ions. To obtain increased excretion of Mn, Cu, and Fe, early experiences showed promising results for CaEDTA, PSH, and DFOA, respectively. Recent experiments have indicated that p-amino salicylate (PAS) plus CaEDTA may be a useful combination to remove Mn from binding sites in CNS, while the deferasirox–DFOA and the tetrathiomolybdate–DMSA combinations may be preferable to promote mobilization of Fe and Cu, respectively, from the CNS. Further research is requested to explore benefits of chelator combinations. Full article

Short telomeres have been associated with ageing and cardiovascular disease. The influence on leukocyte telomere length (LTL) of long-term intervention with combined selenium and coenzyme Q₁₀ is unknown. Our aim was to determine whether 42 months of selenium and coenzyme Q₁₀ supplementation prevented telomere attrition and further cardiovascular mortality. The investigation is an explorative sub-study of a double-blind, placebo-controlled, randomized trial. Swedish citizens low in selenium (n = 118), aged 70–80 years, were included. Intervention time was 4 years, with 10 years’ follow-up time. LTL was relatively quantified with PCR at baseline and after 42 months. At baseline, LTL (SD) was 0.954 (0.260) in the active treatment group and 1.018 (0.317) in the placebo group (p = 0.23). At 42 months, less shortening of LTL was observed after active treatment compared with placebo (+0.019 vs. −0.129, respectively, p = 0.02), with a significant difference in change basing the analysis on individual changes in LTL (p < 0.001). Subjects suffering future death presented with significantly shorter LTL at 42 months than survivors [0.791 (0.190) vs. 0.941 (0.279), p = 0.01], with a significant difference in change of LTL according to cardiovascular mortality and survival (p = 0.03). To conclude, preservation of LTL after selenium and coenzyme Q₁₀ supplementation associated with reduced cardiovascular mortality. Full article

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

The efficacy of various bariatric procedures on the mitigation of the obese dyslipidemia remains debated, and the impact of these measures on lipoprotein(a) (Lp(a)) levels is unknown. In this study we aimed to compare the two most commonly used procedures: gastric bypass (RYGB) and sleeve gastrectomy (SG). Adult patients with morbid obesity were assigned to receive either RYGB or SG. The levels of non-HDL cholesterol, LDL/HDL-ratio and Lp(a) at examinations conducted 6 and 12 months postoperatively were determined and compared to preoperative levels to estimate the efficacy of the two surgical methods. All results 6 and 12 months after surgery were used in the comparisons with the preoperative results. A linear mixed regression model for repeated analyses was used. The Lp(a) and the non-HDL cholesterol levels were considerably reduced in the RYGB group, in contrast to the minor changes in the SG group. In addition, the LDL/HDL ratio was significantly more reduced in the RYGB group when compared to the SG group. Conclusively, RYGB was found to be more efficient than SG for the mitigation of obese dyslipidemia, including preoperative high Lp(a)-levels. This might have important individual and societal implications, especially regarding the potential to reduce the risk of cardiovascular disease and the related societal costs. Full article