SciCombinator

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Journal: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)

327

The genetic predispositions which describe a diagnosis of familial Alzheimer’s disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer’s disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer’s disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer’s disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer’s disease brain tissue raise the spectre of aluminium’s role in this devastating disease.

Concepts: Alzheimer's disease, Scientific method, Protein, Neuron, Environment, Dementia, Beta amyloid, Amyloid precursor protein

288

Autism spectrum disorder is a neurodevelopmental disorder of unknown aetiology. It is suggested to involve both genetic susceptibility and environmental factors including in the latter environmental toxins. Human exposure to the environmental toxin aluminium has been linked, if tentatively, to autism spectrum disorder. Herein we have used transversely heated graphite furnace atomic absorption spectrometry to measure, for the first time, the aluminium content of brain tissue from donors with a diagnosis of autism. We have also used an aluminium-selective fluor to identify aluminium in brain tissue using fluorescence microscopy. The aluminium content of brain tissue in autism was consistently high. The mean (standard deviation) aluminium content across all 5 individuals for each lobe were 3.82(5.42), 2.30(2.00), 2.79(4.05) and 3.82(5.17) μg/g dry wt. for the occipital, frontal, temporal and parietal lobes respectively. These are some of the highest values for aluminium in human brain tissue yet recorded and one has to question why, for example, the aluminium content of the occipital lobe of a 15year old boy would be 8.74 (11.59) μg/g dry wt.? Aluminium-selective fluorescence microscopy was used to identify aluminium in brain tissue in 10 donors. While aluminium was imaged associated with neurones it appeared to be present intracellularly in microglia-like cells and other inflammatory non-neuronal cells in the meninges, vasculature, grey and white matter. The pre-eminence of intracellular aluminium associated with non-neuronal cells was a standout observation in autism brain tissue and may offer clues as to both the origin of the brain aluminium as well as a putative role in autism spectrum disorder.

Concepts: Central nervous system, Nervous system, Brain, Human brain, Cerebrum, Skull, Autism, Frontal lobe

29

In view of the wide-spread deficiency of iron and zinc in populations dependent on plant foods, it is desirable to improve the bioavailability of the same. Specific dietary spices may alter the ultrastructure and permeability characteristics of intestines. Groups of Wistar rats were fed piperine, capsaicin and ginger containing diets for 8 weeks in order to examine their possible influence on intestinal absorption of iron, zinc and calcium. Everted segments of duodenum, jejunum and ileum portions of small intestines isolated from these rats were examined for ex vivo uptake of iron, zinc and calcium from incubations containing digesta of finger millet. Higher uptake of iron, zinc and calcium by the intestinal segments from spice-fed animals was observed. The increase in the mineral uptake was the highest for calcium with >100% in some cases. The positive influence of dietary capsaicin was more pronounced on zinc uptake as compared to that of iron. Uptake of the glutamic acid standard was 87% and 62% higher in the case of jejunal segments of rats fed piperine and ginger. The higher intestinal uptake of iron and zinc as a result of consumption of pungent spices could encourage a strategy to reduce deficiency of these trace elements prevalent in population dependent on plant based foods.

Concepts: Digestive system, Large intestine, Intestine, Small intestine, Duodenum, Ginger, Jejunum, Spice

28

Despite the introduction of salt iodization programmes as national measures to control iodine deficiency, several European countries are still suffering from mild iodine deficiency (MID). In iodine sufficient or mildly iodine deficient areas, iodine deficiency during pregnancy frequently appears in case the maternal thyroid gland cannot meet the demand for increasing production of thyroid hormones (TH) and its effect may be damaging for the neurodevelopment of the foetus. MID during pregnancy may lead to hypothyroxinaemia in the mother and/or elevated thyroid-stimulating hormone (TSH) levels in the foetus, and these conditions have been found to be related to mild and subclinical cognitive and psychomotor deficits in neonates, infants and children. The consequences depend upon the timing and severity of the hypothyroxinaemia. However, it needs to be noted that it is difficult to establish a direct link between maternal iodine deficiency and maternal hypothyroxinaemia, as well as between maternal iodine deficiency and elevated neonatal TSH levels at birth. Finally, some studies suggest that iodine supplementation from the first trimester until the end of pregnancy may decrease the risk of cognitive and psychomotor developmental delay in the offspring.

Concepts: Pregnancy, Infant, Thyroid-stimulating hormone, Hypothyroidism, Thyroid, Thyroid hormone, Iodine, Triiodothyronine

28

Zinc which is an essential element has very important effects on growth and immune system in patients with thalassemia major ™. The effects of two oral iron chelator agents, desferrioxamine (DFO) and deferiprone (DFP), on zinc levels were investigated in previous studies and they were found to cause zinc deficiency. Zinc level alteration by the new chelator deferasirox (DFX) is not present in the literature. The aim of this study was to examine the effects of different oral chelators on serum and urine zinc levels in TM patients. Zinc levels are compared in the patients who received different chelators: only DFX, combined chelation with DFO plus DFP and the healthy control group. A total of 56 patients with TM were involved in this study: 39 patients received only DFX and 17 patients were given combined treatment DFO+DFP between August 2008 and August 2009. In addition, a control group was established from the healthy population. Blood was taken from all the patients for serum zinc levels and 24hour-urine samples were collected for urine zinc levels. Serum zinc levels were found to be 64.8±14.8μg/dL in DFX group and 66.5±15.1μg/dL in DFO+DFP group. These levels were statistically lower than that in the control group (149±54.3μg/dL) (p<0.05), but there was no statistically difference between the two different chelation groups (p>0.05). The urine zinc levels of DFX and DFO+DFP group were 662.2±428.2μg/day and 1182.3±980.3μg/day respectively (p<0.05). Urinary zinc excretion in the chelation groups (DFX and DFO+DFP) was significantly higher than the control group (395.1±208.9μg/day) (p<0.05). As a conclusion, the new chelation agent, DFX, also leads to zinc deficiency, though its urinary zinc excretion is lower. New studies are required to examine the effects of DFX on zinc extensively. Zinc levels of patients with TM should be followed up regularly and zinc supply should be given at early ages.

Concepts: Blood, Mathematics, Red blood cell, Thalassemia, Zinc, Chelation, Chelation therapy, Deferoxamine

22

This study provides the dietary intakes of six trace elements (cadmium, chromium, copper, manganese, selenium and zinc), generally characterized by both nutritional and toxicological features depending on their exposure. Being diet the most relevant source of exposure to trace elements in non-professionally exposed subjects, we measured content of these trace elements in foods composing the typical Italian diet using inductively coupled plasma-mass spectrometry, and assessing dietary habits using a validated semi-quantitative food frequency questionnaire we eventually estimated dietary daily intake of trace elements in a Northern Italian community. In the 890 analyzed food samples, the main contributors to cadmium intake are cereals, vegetables and sweets, while cereals, beverages and vegetable are to primary source of manganese. The primary contributors for copper are cereals, fresh fruits and vegetables, while for chromium are beverages, cereals and meat. The main source of selenium intake are cereals and meat, followed by fish, seafood and milk and dairy products, while of zinc intake are meat, cereals, milk and dairy products. In our Italian population sample, the estimated median (interquartile range) dietary daily intakes are 5.00 (3.17-7.65), 56.70 (36.08-86.70) and 66.53 (40.04-101.32) μg/day for cadmium, chromium and selenium, and corresponding figures are 0.98 (0.61-1.49), 2.34 (1.46-3.52) and 8.50 (5.21-12.48) mg/day for copper, manganese and zinc. The estimated intakes are generally within the average intake reported in other European populations, and in such cases well above the daily dietary intakes recommended by national international agencies, avoiding the risk of excess or deficiency. The present estimated intake data can be used to examine a specific trace element of interest and would afford enhanced health protection from those trace elements characterized by both nutritional and toxicological effects.

Concepts: Nutrition, Milk, Metal, Diet, Seafood, Italy, Chemical elements, Biology and pharmacology of chemical elements

10

The brain pathology in autism spectrum disorders (ASD) indicates marked and ongoing inflammatory reactivity with concomitant neuronal damage. These findings are suggestive of neuronal insult as a result of external factors, rather than some type of developmental mishap. Various xenobiotics have been suggested as possible causes of this pathology. In a recent review, the top ten environmental compounds suspected of causing autism and learning disabilities were listed and they included: lead, methyl-mercury, polychorinated biphenyls, organophosphate pesticides, organochlorine pesticides, endocrine disruptors, automotive exhaust, polycyclic aromatic hydrocarbons, polybrominated diphenyl ethers, and perfluorinated compounds. This current review, however, will focus specifically on mercury exposure and ASD by conducting a comprehensive literature search of original studies in humans that examine the potential relationship between mercury and ASD, categorizing, summarizing, and discussing the published research that addresses this topic. This review found 91 studies that examine the potential relationship between mercury and ASD from 1999 to February 2016. Of these studies, the vast majority (74%) suggest that mercury is a risk factor for ASD, revealing both direct and indirect effects. The preponderance of the evidence indicates that mercury exposure is causal and/or contributory in ASD.

Concepts: Brain, Causality, Factor analysis, Polycyclic aromatic hydrocarbon, Autism, Aromatic hydrocarbon, Biphenyl, Chelation therapy

3

Suicide is a major public health concern affecting both the society and family life. There are data indicating that higher level lithium intake with drinking water is associated with lower suicide rate. This pilot study examined the relationship between lithium levels in drinking water and suicide rates in Lithuania. Twenty-two samples from public drinking water systems were taken in 9 cities of Lithuania. The lithium concentration in these samples was determined by inductively coupled plasma mass spectrometry (ICP-MS). The suicide data were obtained from the Lithuania Database of Health Indicators, and comprised all registered suicides across all ages and gender within the 5-year period from 2009 to 2013. The study demonstrated an inverse correlation between levels of lithium (log natural transformed), number of women for 1000 men and standardized mortality rate for suicide among total study population. After adjusting for confounder (the number of women for 1000 men), the lithium level remained statistically significant in men, but not in women. Our study suggested that higher levels of lithium in public drinking water are associated with lower suicide rates in men. It might have a protective effect on the risk of suicide in men.

Concepts: Epidemiology, Demography, Suicide, Water supply network

3

Thimerosal is an organic-mercury (Hg)-containing compound (49.55% Hg by weight) historically added to many multi-dose vials of vaccine as a preservative and still added to some vaccines today. Concerns about the toxic effects from Thimerosal-containing childhood vaccines and the risk of an atypical autism diagnosis were evaluated in this study.

Concepts: Vaccine, Vaccination, United States, Autism, Mercury

3

Serum levels of zinc and copper have been proposed to associate with sleep duration. Mechanisms, such as inflammatory processes, have been suggested to relate this association. However, earlier studies have been conducted in small sample sizes. Human studies investigating the suggested associations while controlling for potential confounding factors are lacking.

Concepts: Inflammation, Sample size, Zinc, Copper, The Association, C-reactive protein, Long, Short