NeuroToxicology 31 (2010) 575–581 Contents lists available at ScienceDirect NeuroToxicology Review The neurotoxicity of environmental aluminum is still an issue Stephen C. Bondy * Program in Environmental Toxicology, Division Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA 92697-1825, USA A R T I C L E I N F O A B S T R A C T Article history: Received 18 September 2009 Received in revised form 24 March 2010 Accepted 10 May 2010 Available online 27 May 2010 Evidence for the neurotoxicity of extended exposure to low levels of aluminum salts is described using an animal model treated with aluminum at low levels reﬂecting those found in some water supplies. Emphasis is given to the potential role of aluminum in acceleration and promotion of some indices characteristic of brain aging. These hallmarks include the appearance of excess levels of inﬂammation in speciﬁc brain areas. Aluminum salts can increase levels of glial activation, inﬂammatory cytokines and amyloid precursor protein within the brain. Both normal brain aging and to a greater extent, Alzheimer’s disease are associated with elevated basal levels of markers for inﬂammation. These are not attributable to obvious exogenous stimuli and may reﬂect the lifespan history of the organism’s immune responses. It is possible that aluminum salts can act as a subtle promoter of such apparently unprovoked responses. s 2010 Elsevier Inc. All rights reserved. Keywords: Aluminum Drinking water brain aging Alzheimer’s disease Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Aluminum is environmentally prevalent and ingested by humans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . There is an epidemiological relation between chronic aluminum exposure and the incidence of Alzheimer’s disease . . . . . . . . . . . Aluminum exposure may also promote the onset of Parkinson’s disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute exposure to aluminum can cause clinical neurotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Elevated levels of intrinsic inﬂammation are associated with neural aging and this is exacerbated in several neurodegenerative diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Low levels of aluminum in drinking water of experimental animals, elevate basal levels of inﬂammatory activity within the CNS Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Introduction This review on the potential neurotoxic hazard posed by aluminum focuses on distinguishing between those aspects of aluminum neurotoxicity that are widely accepted and not controversial, and those aspects that are suggestive but not fully established. The work of this laboratory over the past 12 years is described and this falls into the latter classiﬁcation, adding to the body of evidence increasingly implicating aluminum as a potentially hazardous environmental agent. The most accepted facts relating to aluminum include: (i) it’s widespread prevalence and level of human consumption, (ii) the * Correspondence address: Department of Community and Environmental Medicine, University of California at Irvine, Irvine, CA 92697-1825, USA. Tel.: +1 949 824 8077; fax: +1 949 824 2793. E-mail address: scbondy@uci.edu. 0161-813X/$ – see front matter s 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.neuro.2010.05.009 known neurotoxicity of high levels of aluminum, and (iii) a repeated epidemiological correlation between ingested aluminum and the incidence of Alzheimer’s disease. Another relevant area of widespread consensus is the tendency of the aging brain to express elevated levels of inﬂammation and the further exacerbation of this state in several neurodegenerative diseases. Less accepted is the evidence that aluminum can be a causal factor in promoting Alzheimer’s disease. This area has been handicapped by earlier erroneous reports of heightened levels of aluminum in amyloid plaques. Tissue aluminum levels are notoriously difﬁcult to determine and later more reliable ﬁndings leading to similar conclusions have been overshadowed by these original reports. The main objective of our more recent studies has been to study the effects of extended exposure of experimental animals to levels of aluminum that have relevance for the human population. Demon- stration that these can provoke cerebral inﬂammatory responses resembling those that are found with brain senescence, can provide a mechanistic link to epidemiological reports.

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The neurotoxicity of environmental aluminum is still an issue - eScholarship

This invention relates to novel penetrating compositions including one or more effectors included within a water soluble composition, immersed in a hydrophobic medium The invention also relates to methods of treating or preventing diseases by administering such penetrating compositions to affected subjects.

Compositions capable of facilitating penetration across a biological barrier

A device for delivering a drug by inhalation is disclosed. The device includes a body defining an interior flow-through chamber having upstream and downstream chamber openings, and a drug supply unit contained within the chamber for producing, upon actuation, a heated drug vapor in a condensation region of the chamber. Gas drawn through the chamber region at a selected gas-flow rate is effective to form drug condensation particles from the drug vapor having a selected MMAD between 0.02 and 0.1 MMAD or between 1 and 3.5 gm. A gas-flow control valve disposed upstream of the unit functions to limit gas-flow rate through the condensation region to the selected gas-flow rate. An actuation switch in the device activates the drug-supply unit, such that the drug-supply unit can be controlled to produce vapor when the gas-flow rate through the chamber is at the selected flow rate.

Inhalation device for producing a drug aerosol

Devices and methods of entraining a substance within an airflow are disclosed. Condensation aerosol delivery devices and methods of consistently producing multiple doses of a substance, such as a drug, having high purity, high yield, characterized by a particle size distribution appropriate for pulmonary delivery, and which can be administered to a user in a single dose are also disclosed.

Multiple dose condensation aerosol devices and methods of forming condensation aerosols

An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opiods. In the preferred embodiment, a drug is modified to increase its lipophilicity. In preferred embodiments the modified drug is homogeneously dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and preferably organic solvent insoluble, but enzymatically degradable by enzymes present in the human gastrointestinal tract. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is broken down or dissolved gradually within the GI tract by a combination of enzymatic degradation, surfactant action of bile acids, and mechanical erosion.

Abuse-deterrent pharmaceutical compositions of opioids and other drugs

A pharmaceutical composition contains an acid addition salt of a basic drug and a fatty acid or bile acid. The acid addition salts thus formed exhibit enhanced transmucosal and transdermal penetration of the basic drug. The acid addition salts, an inclusion complex containing said salts and a use of said salts are also disclosed.

Pharmaceutical composition containing acid addition salt of basic drug

An inclusion complex comprises (a) an indole selective serotonin (5-HTID) agonist or a pharmaceutically acceptable salt thereof, such as for example sumatriptan, and (b) unsubstituted or substituted beta- or gamma-cyclodextrin, such as for example methyl-beta-cyclodextrin. Pharmaceutical compositions containing the inclusion complex and the use of the inclusion complex in the treatment of migraine and cluster headaches are also disclosed.

Inclusion complex containing indole selective serotonin agonist

A pharmaceutical composition for oral mucosal delivery comprises an active ingredient, an inclusion complex of (a) a selective β2-adrenergic agonist or a pharmaceutically acceptable salt thereof such as salbutamol, and (b) an unsubstituted or substituted beta- or gamma-cyclodextrin, and a pharmaceutically acceptable carrier for oral mucosal delivery. The pharmaceutical composition is of use in the treatment of reversible obstructive airways diseases such as asthma.

Inclusion complexes of beta-2-andrenergics for oral mucosal delivery

Acid mine drainage (AMD) is a worldwide industrial pollution of grave concern. AMD pollutes both water sources and the environment at large with dissolved toxic metals which are detrimental to human health. This paper reports on the preparation of polymeric ion exchange resins decorated with hydrated iron oxides and their application for the ecological removal of toxic metals ions from AMD. The hydrated iron oxide particles were incorporated within commercial chelating ion exchange resins using the precipitation method. The synthesised hybrid resins were then characterized using appropriate spectroscopic and solid-state techniques. The metal ion levels were measured using the inductively coupled plasma-optical emission spectrometer (ICP-OES). The optimization of contact time, pH, and adsorbent dosage were conducted to enhance the efficiency of adsorption of toxic metals onto the hybrid organic/inorganic nanosorbents. Kinetics and adsorption isotherms were constructed to study the adsorption mechanisms of the adsorbents. The results showed that the dispersed Fe-O is hydrated and amorphous within the hybrid materials. The adsorption kinetics followed the pseudo-second-order shown by the high R2 values. The hybrid adsorbents were finally tested on environmental AMD samples and were able to remove toxic metals Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn at various removal degrees. Solution pH played a crucial role in the adsorption of toxic metals on hybrid iron oxide adsorbents. The hybrid TP-260 HFO had higher affinity for toxic metals than other prepared adsorbents thus has a potential for acidic mine water pollution remediation. The adsorbed Al(III) can be recovered using NaCl-NaOH binary solution from the loaded resins.

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Polymeric Ion Exchanger Supported Ferric Oxide Nanoparticles as Adsorbents for Toxic Metal Ions From Aqueous Solutions and Acid Mine Drainage

Environmental pollution due to acid mine drainage (AMD) is a worldwide concern because of its high content of toxic metals and acidity. The toxic metal species present in AMD tends to affect negatively the whole ecological system where it is discharged, and this requires an elective solution to remedy the environment. In this study, hydrated ZrO2 nanoparticles (HZO) were irreversibly dispersed within chelating ion-exchange resins using the precipitation method, resulting in HZO-260, HZO-207, HZO-214, HZO-4195 and HZO-900 organic/inorganic nanosorbents which were used for the removal of metals from AMD. The synthesized nanosorbents were characterized using SEM–EDS, FTIR and XRD. The effect of time, adsorbent dosage and pH on Al(III) adsorption was investigated using the batch technique. The SEM–EDS confirmed the incorporation of HZO within all the parent resins, while XRD showed that the hybrid materials were amorphous. The adsorption of Al(III) occurred through physisorption and was favourable only onto HZO-260 as revealed by the data modelling. Metal levels were determined using the ICP-OES technique. The HZO-260 removed 100% Al(III) in acidic conditions and was successfully regenerated for reuse using a NaCl–NaOH binary solution (pH > 12). HZO-260 removed selected metals (Al, Cr, Mn, Fe, Ni, Co, Cu, Zn, Pb and Cd) from environmental AMD. Therefore, HZO-260 has a promising potential as an adsorbent for AMD remediation.

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Lueta-Ann De Kock

Papers

Pharmaceutical composition containing acid addition salt of basic drug

Inclusion complex containing indole selective serotonin agonist

Inclusion complexes of beta-2-andrenergics for oral mucosal delivery

Polymeric Ion Exchanger Supported Ferric Oxide Nanoparticles as Adsorbents for Toxic Metal Ions From Aqueous Solutions and Acid Mine Drainage

Acid mine drainage pollution remediation using hybrid chelating ion-exchange/HZrO2 nanocomposite adsorbents