Aluminum overload in the reverse osmosis dialysis era: does it exist?

BACKGROUND: Aluminum accumulation is a well-described complication in dialysis patients. Improvements in hemodialysis technology have possibly eliminated the occurrence of aluminum overload. Limited evidence suggests that aluminum overload may decline in the era of aluminum removal from dialysis fluids, even with the use of aluminum binders. METHODS: We examined the data from January 2014 to June 1, 2020, identified through our electronic records, to evaluate the desferrioxamine (DFO) test results for aluminum overload. The presentation and treatment of aluminum overload were recorded. RESULTS: Ninety-nine dialysis patients were enrolled for the DFO test. Forty-seven patients (47.5%) were identified as DFO test positive for aluminum overload, of which 14 (14/47) patients had symptoms, including one patient with an unexplained fracture, eight patients with unexplained anemia despite high-dose erythropoiesis-stimulating agents, and five patients with hypercalcemia (serum calcium >11 mg dL-1). None of the patients with aluminum overload developed encephalopathy. Only four of the 47 patients had microcytic anemia. Patients requiring longer treatments (>10 months versus <10 months) had similar basal serum aluminum (p = 0.219) but had an increase in serum aluminum after DFO (p = 0.041). Furthermore, the treatments decreased erythropoietin doses in the aluminum overload group, with serum total alkaline phosphatase levels <60 U L-1 (p = 0.028). CONCLUSION: We concluded that aluminum overload existed in the reverse osmosis dialysis era. In light of non-obvious symptoms, such as anemia and bone turnover change, serum aluminum in dialysis patients should be monitored in countries using aluminum-based phosphate binders, despite reverse osmosis dialysis.

Risk factors for granulomas in children following immunization with aluminium-adsorbed vaccines: A Danish population-based cohort study.

BACKGROUND: Aluminium-adsorbed vaccines may in some children cause severely itching nodules at the injection site, known as vaccination granulomas. OBJECTIVE: To investigate vaccine-, child- and maternal-level risk factors for the development of vaccination granulomas following immunization with aluminium-adsorbed vaccines. METHODS: A Danish population-based cohort study with 553 932 children born in Denmark from 1 January 2009 to 31 December 2018, vaccinated with an aluminium-adsorbed vaccine during the first year of life, followed until 31 December 2020. Poisson regression was used to estimate granuloma rate ratios according to the type of adjuvant, accumulated dose of aluminium, timing of vaccination appointments, sex, gestational age, having siblings with granulomas, maternal age and maternal ethnicity. RESULTS: We identified 1901 vaccination granuloma cases (absolute risk, 0.34%). Among vaccine level factors, revaccination (third vs. first vaccination appointment, adjusted rate ratio [RR] 1.26, 95% confidence interval [CI] 1.03-1.55), the specific adjuvant used (aluminium phosphate vs. hydroxide, RR 0.58, 95% CI 0.48-0.70) and dosage (≥1.0 mg vs. <1.0 mg, RR 1.34, 95% CI 1.19-1.52) were associated with risk of granulomas; the timing of vaccination appointments was not. Among child-level factors, female sex (vs. males, RR 1.12, 95% CI, 1.02-1.22), prematurity (vs. term birth, RR 0.71, 95% CI, 0.54-0.93) and having sibling(s) with granulomas (vs. no siblings with granulomas, RR 46.15, 95% CI, 33.67-63.26) were associated with risk of granulomas. Among maternal-level factors, non-Danish ethnicity (vs. Danish, RR 0.51, 95% CI, 0.42-0.63) and young maternal age (<20 years vs. 20-39 years, RR 0.46, 95% CI 0.25-0.83) were associated with risk of granulomas. CONCLUSIONS: Several risk factors for vaccination granulomas at the vaccine, child and maternal levels, were identified. Reducing the dose of aluminium or replacing aluminium hydroxide with aluminium phosphate could reduce the risk of granulomas. However, this must be balanced against the potential for reduced immunogenicity.

Effect of the duration of use of aluminum cookware on its metal leachability and cytogenotoxicity in Allium cepa assay.

Aluminum cookware are widely used in many parts of the world. Data is increasing on the leaching of toxic metals from aluminum cookware into food and drink. In the present study, cytogenotoxicity of water boiled in three different aluminum pots (new, 3-year-old, and 6-year-old) in onion root tip's dividing cells was evaluated using the Allium cepa assay. The concentrations of Pb, As, Cd, Cu, Ni, and Al in the samples were also analyzed. Onion bulbs were grown in the boiled water samples, while tap water served as the control. Cytological and genetic analyses were carried out after 48 h, while analysis of inhibition of root length was carried out after 72 h. The results showed a significant (p < 0.05) cell proliferation and root growth inhibition compared with the control, which is dependent on the duration of use of the aluminum pots. The boiled water samples also caused modification of the root morphology as well as chromosomal aberrations which include sticky chromosomes, anaphase bridge, and disturbed spindle. The highest cytogenotoxicity was observed in the 6-year-old aluminum pot and the least in the new aluminum pot. Pb, As, Cd, Cu, Ni, and Al analyzed in the samples, with the highest concentrations in the 6-year-old aluminum pot, were believed to be responsible for the cytogenotoxicity observed in the A. cepa assay. The data of this study are indications that the aluminum pot-boiled water contains substances with the potential to be cytotoxic and cause mutations in somatic cells of A. cepa.

Phosphorus deficiency induced by aluminum in a marine nitrogen-fixing cyanobacterium Crocosphaera watsonii WH0003.

Large amounts of aluminum (Al) enter the ocean through atmospheric dust deposition and river runoffs. However, few studies have reported the effects of Al on marine phytoplankton, especially nitrogen-fixing cyanobacteria. By using the isotope tracer method and quantitative reverse transcription PCR (RT-qPCR), we examined the physiological effect of Al (0.2, 2 and 20 µM) on the unicellular marine nitrogen-fixing cyanobacterium Crocosphaera watsonii in Aquil* medium. We show that Al has an inhibitory physiological effect on C. watsonii, including changes in growth rate, nitrogen fixation rate, carbon fixation rate, cell size, fast rise chlorophyll fluorescence kinetics, cellular photosynthetic pigment and C/N/P content, the same as that of the phosphorus deficient treatment. The ratio of cellular elements C:N:P showed that phosphorus was deficient in the cell of C. watsonii after Al treatment (2 and 20 µM). In addition, Al stimulated the expression of phosphorus-related genes pstS, phoH, phoU, ppK and ppX in C. watsonii. All these results suggest that Al-treated C. watsonii is phosphorus-limited, and that the phosphorus deficiency induced by Al may be one mechanism behind aluminum's toxicity.

Curcumin Acts as Post-protective Effects on Rat Hippocampal Synaptosomes in a Neuronal Model of Aluminum-Induced Toxicity.

The neurotoxic effects of aluminum are generally associated with reduced antioxidant capacity, increased oxidative stress and apoptosis, which lead to the induction of neurodegenerative processes. Curcumin has a lipophilic polyphenol character and effects of antioxidant and anti-apoptotic. The present study was undertaken to examine possible aluminum exposure in rats brain synaptosomes and to investigate whether protective and therapeutic effects of curcumin on biochemical and morphological changes in both pre- and post-treated groups. Aluminum chloride (AlCl3) at 50 µM concentration and curcumin at 5 and 10 µg/mL doses were applied to hippocampal synaptosomes of rats according to experimental design. Biochemical effects were evaluated by MTT cytotoxicity, malondialdehyde (MDA) levels, nitric oxide (NO) levels, glutathione (GSH) levels, caspase 3 activities, cytochrome c levels, DNA fragmentation values and protein levels. Morphological examinations were done by TEM analysis. AlCI3 exposure in the synaptosomes enhanced oxidative stress, triggered apoptosis and caused ultrastructural alterations which were well reflected in the TEM images. Curcumin pre-treatment slightly ameliorated the MDA levels, NO levels, cytochrome c levels and caspase 3 activities in AlCI3-exposed synaptosomes, but these results were not statistically significant. Furthermore, curcumin post-treatment significantly improved oxidative damage and morphological alterations, and suppressed cytochrome c and caspase 3 activities. Taken together, our data showed that curcumin had more therapeutic effects than protective effects in AlCI3-induced neurotoxicity. Nevertheless, the therapeutic (post-protective) effects of curcumin should be further investigated in in vivo neurodegenerative models involving behavioral tests.

Aluminum in vaccines: Does it create a safety problem?

For almost a century, aluminum (Al) in the form of Al oxyhydroxide (a crystalline compound), Al hydroxyphosphate (an amorphous Al phosphate hydroxide), Al phosphate, and Al potassium sulfate has been used to improve the immunogenicity of vaccines. Al is currently included in vaccines against tetanus, hepatitis A, hepatitis B, human papillomavirus, Haemophilus influenzae type b, and infections due to Streptococcus pneumoniae and Neisseria meningitidis. Official health authorities consider the inclusion of Al in most of the presently recommended vaccines to be extremely effective and sufficiently safe. However, the inclusion of Al salts in vaccines has been debated for several years because of studies that seem to indicate that chronic Al exposure through vaccine administration can interfere with cellular and metabolic processes leading to severe neurologic diseases. Children, who in their first years of life receive several vaccine doses over a reduced period of time, would be most susceptible to any risk that might be associated with vaccines or vaccine components. The main aim of this paper was to discuss the data presently available regarding Al neurotoxicity and the risk for children receiving vaccines or other pharmaceutical preparations containing Al. Analysis of the literature showed that no apparent reason exists to support the elimination of Al from vaccines for fear of neurotoxicity. The only problem that deserves attention is the suggested relationship between Al oxyhydroxide-containing vaccines and macrophagic myofaciitis or myalgic encephalomyelitis/chronic fatigue syndrome. Currently, definitive conclusions cannot be drawn on these risks and further studies must be conducted. Until then, Al remains the best solution to improve vaccine efficacy.

Evidence Refuting the Existence of Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA).

Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was described in 2011. Over time the condition and its triggers have broadened to include several autoimmune disorders, the macrophagic myofasciitis syndrome, the Gulf war syndrome, the sick building syndrome, siliconosis, and the chronic fatigue syndrome. The aluminum-containing adjuvants in the hepatitis B vaccine and the human papillomavirus vaccine in particular have been stated to be the major causes of the disorder. Here, we review the specificity of the diagnostic criteria for ASIA. We also examine relevant human data, pertaining to causation, particularly from patients undergoing allergen-specific immunotherapy (IT). Patients undergoing allergen-specific IT receive 100 to 500 times more injected aluminum over 3 to 5 years, compared with hepatitis B and human papillomavirus vaccine recipients. In a large pharmacoepidemiological study, in contrast to case series of ASIA, patients receiving aluminum-containing allergen IT preparations were shown to have a lower incidence of autoimmune disease. In another clinical trial, there were no increases in exacerbations in a cohort of patients with systemic lupus erythematosus immunized with the hepatitis B vaccine. Current data do not support the causation of ASIA by vaccine adjuvants containing aluminum, which should be of reassurance to patients undergoing routine immunizations as well as to those undergoing allergen-specific IT.

Preparación de las nutriciones parenterales pediátricas / Preparation of pediatric parenteral nutrition solutions

No disponible

Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

[Metallosis: A Rare Cause of Autoimmune Hemolytic Anemia]. / Metalose: Causa Rara de Anemia Hemolítica Autoimune.

INTRODUCTION: Hemolytic anemia may be associated with multiple etiologies, including toxic substances, such as metals, which is a rare cause. CASE STUDY: 55-year-old male, who underwent a total arthroplasty of the right hip (uncemented prostheses with ceramic-ceramic articulation with an acetabular component consisting of a dome composed of an alloy of titanium, aluminum and vanadium into which fitted a ceramic 'insert'). Approximately 4 years after surgery the patient complained of noise originating from the prosthesis which occurred on movement. A surgical revision was performed and showed the presence of dark thick intracapsular fluid, fracture of the ceramic acetabular 'insert' and signs of wear of the acetabular metal dome. Extensive washing was carried out and the fractured ceramic 'insert' was replaced for a polyethylene 'insert'. Two months later he was referred to the Emergency Room due to worsening of his general health, floating in the right hip and mucocutaneous jaundice. Laboratory tests suggested autoimmune hemolytic anemia. Arthrocentesis was performed and a large volume of metal fluid was drained off. The CT scan showed a large heterogeneous pelvic cystic collection seeded with prosthesis fragments, suggestive of metallosis. Hemolytic anemia was explained as toxicity of the particles and metal ions caused by the wear of the prosthesis. The patient was started on a high-dose steroid treatment. Afterwards, when he was stable, prosthesis components replacement and drainage of pelvic debris fluid were carried out. DISCUSSION: After the fracture of the ceramic 'insert' the ceramic head began to articulate directly with the metallic acetabular component, causing noise and wear with release of particles and ions. This caused a cystic pelvic abscess, which went unnoticed on the first surgical revision. Surgical debridement lead to the cystic collection extending into the adjacent tissues and the systemic circulation, triggering serious systemic effects, such as autoimmune hemolytic anemia. The potential toxicity of each of the metal elements of this prosthesis is unknown, and there are still no available laboratory tests for its detection. CONCLUSION: Metallosis is a rare cause of autoimmune hemolytic anemia.

Introdução: A anemia hemolítica pode estar associada a múltiplas etiologias, nomeadamente a tóxicos, como os metais, sendo esta uma causa rara.Caso Clínico: Homem de 55 anos de idade, sujeito a artroplastia total da anca direita (prótese não cimentada com articulação cerâmica-cerâmica, cujo componente acetabular era constituído por uma cúpula metálica composta por uma liga de titânio, vanádio e alumínio na qual encaixava um insert cerâmico). Cerca de quatro anos após esta intervenção cirúrgica referia ruídos na prótese com os movimentos. Foi sujeito a revisão cirúrgica tendo-se constatado a presença de líquido espesso intracapsular de cor escura, fractura do insert acetabular cerâmico e sinais de desgaste da cúpula metálica acetabular. Procedeu-se a lavagem abundante e substituição do insert cerâmico fracturado por um insert de polietileno. Dois meses depois recorreu ao Serviço de Urgência por degradação do estado geral, flutuação na anca direita e icterícia muco-cutânea. Analiticamente evidenciava valores compatíveis com anemia hemolítica autoimune. Foi feita punção articular com saída de abundante líquido metalótico. A tomografia computorizada revelou extensa colecção heterogénea quística intrapélvica com múltiplos fragmentos de prótese no seu interior, sugestivos de metalose. A anemia hemolítica foi interpretada como consequência da toxicidade das partículas e iões metálicos oriundos do desgaste da prótese. Iniciou corticoterapia em altas doses e posteriormente quando houve condições procedeu-se à substituição de todos os componentes da prótese e drenagem do material acumulado intra-pélvico.Discussão: Após a fractura do insert cerâmico a cabeça cerâmica passou a articular directamente com o componente acetabular metálico, originando os ruídos e desgaste com libertação de partículas e iões. Este material formou uma coleção quística intrapélvica, que passou despercebida na primeira revisão cirúrgica. O desbridamento cirúrgico pôs em comunicação esta coleção com os tecidos adjacentes e com a circulação sistémica, desencadeando efeitos sistémicos graves, como anemia hemolítica auto-imune. Desconhece-se o potencial de toxicidade de cada um dos elementos metálicos desta prótese, não estando ainda disponíveis testes laboratoriais de detecção.Conclusão: A metalose é uma causa rara de anemia hemolítica auto-imune.

Adjuvants and lymphoma risk as part of the ASIA spectrum.

The emerging epidemic of Hodgkin and non-Hodgkin lymphomas worldwide continues to defy our understanding and forces the search for the causative factors. Adjuvants are known to act as triggers of immune and inflammatory responses. Animal experiments have demonstrated that long-term inflammation is related to aggravation of the immune network resulting in cellular and humoral responses leading to autoimmunity and lymphoma development. Chronic stimulation of the immune system is thought to be the key mechanism through which infectious diseases as well as autoimmune diseases can lead to lymphomagenesis. Many adjuvants can act similarly perturbing immune system's function, inducing a state of prolonged immune activation related to chronic lymphatic drainage. Several mechanisms were proposed by which adjuvants induce inflammation, and they are discussed herein. Some of them are triggering inflammasome; others bind DNA, lipid moieties in cells, induce uric acid production or act as lipophilic and/or hydrophobic substances. The sustained inflammation increases the risk of genetic aberrations, where the initial polyclonal activation ends in monoclonality. The latter is the hallmark of malignant lymphoma. Thus, chronic adjuvant stimulation may lead to lymphoma.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects.

In 2011 a new syndrome termed 'ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants' was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with post-vaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance.

Zinc protection against aluminium induced altered lipid profile and membrane integrity.

The aim of the present study was to investigate the effects of Zinc (Zn) supplementation on lipid profile and fluidity of cerebrum and cerebellum membranes of rats treated with aluminium (Al). Sprague dawley male rats were divided into four different treatment groups viz: Control, aluminium treated, zinc treated and aluminium+zinc treated. Aluminium (AlCl3) was administered orally at a dose of 100mg/kgb.wt./day (dissolved in drinking water). Zinc as zinc sulphate was supplemented to rats at a dose of 227mg/l in drinking water. A significant decrease in the levels of total lipids, glycolipids, phospholipids, cholesterol and gangliosides contents were observed in both the cerebrum and cerebellum following Al exposure, which were found to be significantly increased following Zn supplementation. On the contrary, Al treatment caused a significant increase in the formation of conjugated dienes, which were observed to be reduced on Zn co-treatment. Further, Al treatment significantly elevated the fluorescence polarization, anisotropy and order parameter, which however were normalized upon Zn co-administration. Hence, the present study depicts the potential of Zn in moderating the changes caused by Al on membrane composition and fluidity in rat brain.

Calcium chloride and sodium phosphate in neonatal parenteral nutrition containing TrophAmine: precipitation studies and aluminum content.

OBJECTIVES: The objectives were to determine concentrations of calcium chloride (CaCl) and sodium phosphate (NaPhos) that can be safely added to TrophAmine-based parenteral nutrition (PN) and to measure aluminum (Al) concentrations in PN solutions containing CaCl and NaPhos vs those containing calcium gluconate (CaGlu) and potassium phosphate (KPhos). METHODS: In study A, PN solutions containing varying amounts of TrophAmine, CaCl, and NaPhos were compounded and then evaluated visually for precipitation. In study B, Al concentrations were measured in PN solutions containing CaCl and NaPhos (S1), CaGlu and NaPhos (S2), or CaGlu and KPhos (S3). RESULTS: Study A showed that a maximum phosphorus concentration of 15 mmol/L could be added to a solution containing 12.5 mmol/L of calcium without evidence of precipitation when the amino acid (AA) concentration reached ≥3 g/dL (3%). In study B, the mean (range) Al concentrations were S1 = 2.2 (1.9-2.4), S2 = 8.5 (7.8-9.3), and S3 = 11.7 (10.8-12.2) µmol/L (means of 6.0, 22.9, and 31.5 micrograms/dL, respectively). CONCLUSIONS: The data can provide a guide for compounding neonatal PN solutions containing TrophAmine, CaCl, and NaPhos. More studies are needed to determine the long-term effects of substituting CaCl for CaGlu in PN solutions for neonates. Substituting CaCl and NaPhos for CaGlu and KPhos significantly decreases Al concentrations in PN and potential Al exposure of neonatal patients.

Transfer of U, Al and Mn in the water-soil-plant (Solanum tuberosum L.) system near a former uranium mining area (Cunha Baixa, Portugal) and implications to human health.

Knowledge about metals in crops, grown in contaminated soils around mine sites, is limited and concerns about exposure to hazardous elements through the consumption of contaminated foodstuff, are high. In this study a field experiment was carried out in two agricultural soils located near a former uranium mine area (Cunha Baixa, Portugal). The purpose of the study was to assess the effect of irrigation water quality on soil-potato (Solanum tuberosum L.) crop system and to evaluate if the consumption of the crop represents health risk to the local villagers. The soils were divided in two plots: one irrigated with contaminated water (U: 1.03-1.04mg/L; Al: 7.5-8.00mg/L; Mn: 4.52mg/L) and the other with uncontaminated water (U: 14-10µg/L; Al: 17-23µg/L; Mn: 2.4-5.7µg/L). After irrigation and potato growth, only soil characteristics, as salinity and total U and Mn concentrations were significantly different from those measured at the beginning of the experiment. Within the potato plants, elements were mostly translocated and concentrated in the aerial part: stems and leaves (U: 73-87%; Al: 85-96%; Mn: 85-94%), which minimize the risk of contamination of the edible tissue. In potato tubers, the highest average concentrations (121-590µg U/kg; 25-64mg Al/kg; 12-13mg Mn/kg dry weight) were registered at soil plots irrigated with contaminated water. Uranium and Al were mostly concentrated in the potato peel (88-96 and 76-85%, respectively), and Mn (67-78%) in the pulp, which reinforces the importance of removing peel to minimize human exposure. The risk analysis calculated for non-cancer health effects (hazard quotient), related only to the exposure through the consumption of this basic foodstuff, revealed safety for Cunha Baixa village residents (adults and children) even when potato crop was grown on U enriched soils and irrigated with contaminated water.

Aluminum adjuvant dose guidelines in vaccine formulation for preclinical evaluations.

Aluminum (Al) salt-based adjuvants are present in a large variety of licensed vaccines and their use is widely considered for formulations in clinical trials. Although the regulatory agencies have clearly stated the acceptable levels of Al salts in vaccines for human use, there are no general indications for preclinical research. This brief commentary reviews the current status of Al concentrations in licensed vaccines, the related potential toxicity in preclinical species, and proposes a general guideline for selection of suitable Al salt levels in preclinical models, focusing on the formulation development for recombinant protein antigens. A table with conversion factors is included in order to provide a tool for calculation of doses with different Al salts.

Oral silicon supplementation: an effective therapy for preventing oral aluminum absorption and retention in mammals.

Silicon is an essential element for some lower forms of life. However, it is not generally considered an essential nutrient for mammals and the mechanisms underlying its potential essentiality remain partially unknown. In recent years, a possible association between the aluminum and silicon levels in drinking water and Alzheimer's disease (AD) has been suggested. It has been reported that silicon might have a protective effect for limiting oral aluminum absorption. This review is focused primarily on the potential role of silicon in preventing oral aluminum absorption and retention in mammals. The results of a number of studies suggest that dietary silicon supplementation could be of therapeutic value for preventing chronic aluminum accumulation in the brain, and hence, be a potential therapy for AD. However, it must be noted that controversy remains about whether aluminum accumulation in the brain is a cause or a consequence of AD. It is suggested that further investigation of this issue is warranted.

Memory performance, brain excitatory amino acid and acetylcholinesterase activity of chronically aluminum exposed mice in response to soy isoflavones treatment.

Memory performance, brain excitatory amino acid and acetylcholinesterase activity of chronically aluminum (Al) exposed mice in response to soy isoflavones (SI) treatment was investigated in the study. Forty eight mice were allotted randomly into a control group, an Al exposed group (100 mg/kg Al) and an Al exposed group treated with SI (100 mg/kg Al + 60 mg/kg SI) for 60 days. Chronic Al exposure significantly impaired long memory performance in mice as assessed using a passive avoidance task test (χ(2) analysis, p < 0.05). Interestingly, SI treatment markedly improved the memory performance score in the Al exposed mice. This improvement was associated with a total reversal of Al-induced increases in acetylcholinesterase activity in the cerebral cortex and hippocampus of mice. The Al exposure also led to significant decreases in brain levels of aspartic and glutamic acids, two excitatory amino acid neurotransmitters; whereas SI treatment partially reversed the decreased aspartic and glutamic acid contents in the hippocampus. The results suggest that SI can improve long memory performance in the Al exposed mice, possibly by modulating the metabolism of brain acetylcholine and amino acid neurotransmitters.

Aluminium and strontium in calcium supplements and antacids: a concern to haemodialysis patients?

Trace elements, most notably aluminium and strontium, have been noted for their role in the development of secondary bone disorders in haemodialysis patients. Due to the large dosages of calcium required for the maintenance of dialysis patients, this study investigated whether the source of calcium chosen for supplementation, including the form of administration (i.e. chewable forms or capsules), has an influence on the total amount of strontium and aluminium ingested daily. A convenience sample of various calcium supplement tablets and antacids was acquired, and strontium and aluminium quantification was performed by wavelength-dispersive X-ray fluorescence spectrometry. The use of readily available oyster shell-based calcium was found potentially to increase the total amount of ingested strontium substantially with concentrations reaching (2.26 +/- 0.05) (mg Sr).(g Ca)(-1), while the use of antacids or chewable supplements was found to contain concentrations reaching as high as (1.2 +/- 0.3) (mg Al).(g Ca)(-1) in the supplements analysed within this work. It is recommended that the choice of calcium supplement prescribed to individuals undergoing haemodialysis be closely regulated and noted as a possible factor in the prevalence of bone disorders reported in these patients.

Aluminum content of parenteral nutrition in neonates: measured versus calculated levels.

BACKGROUND AND OBJECTIVE: Aluminum (Al) is associated with significant central nervous system toxicity and bone and liver damage. Because Al is a contaminant of parenteral nutrition (PN) components including calcium and phosphate additives, premature infants are at potentially high risk for toxicity. The US Food and Drug Administration (FDA) has mandated PN component product labeling and recommended maximum Al daily exposure limits. The objective of this article is to determine the actual Al content of neonatal PN solutions, compare these values to the calculated amounts from manufacturers' PN product labels, and ascertain whether the actual Al exposure exceeds the FDA recommended maximum of 5 microg . kg(-1) . day(-1). MATERIALS AND METHODS: Samples from 40 neonatal patient PN solutions were selected for sampling and Al content determination. Samples were also taken from 16 manufacturer's component products used in PN formulation. All of the samples were sent to Mayo Laboratories for Al content measurement. The calculated Al concentrations in PN samples were determined from the manufacturer's labeled content. RESULTS: Both measured and calculated Al concentrations exceeded the FDA recommended safe limit of <5 microg . kg(-1) . day(-1). The actual measured Al content was significantly lower than the calculated Al content in both the patient PN solutions and the component product samples. CONCLUSIONS: Al exposure exceeded the FDA recommended maximum limit for all patient samples; however, the actual measured Al content of all the samples was significantly less than the calculated Al content based on manufacturer's labels. These findings suggest that manufacturers label their products with actual Al content at the time of product release rather than at time of expiration. Periodic monitoring of Al levels should be considered with prolonged PN therapy. Changes in manufacturing processes, including the use of better raw materials, are essential to reduce Al contamination to meet FDA mandates.