Aluminum Hydroxide

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Michael S Petrik - One of the best experts on this subject based on the ideXlab platform.

  • Aluminum Hydroxide injections lead to motor deficits and motor neuron degeneration
    Journal of Inorganic Biochemistry, 2009
    Co-Authors: Christopher A Shaw, Michael S Petrik
    Abstract:

    Gulf War Syndrome is a multi-system disorder afflicting many veterans of Western armies in the 1990-1991 Gulf War. A number of those afflicted may show neurological deficits including various cognitive dysfunctions and motor neuron disease, the latter expression virtually indistinguishable from classical amyotrophic lateral sclerosis (ALS) except for the age of onset. This ALS "cluster" represents the second such ALS cluster described in the literature to date. Possible causes of GWS include several of the adjuvants in the anthrax vaccine and others. The most likely culprit appears to be Aluminum Hydroxide. In an initial series of experiments, we examined the potential toxicity of Aluminum Hydroxide in male, outbred CD-1 mice injected subcutaneously in two equivalent-to-human doses. After sacrifice, spinal cord and motor cortex samples were examined by immunohistochemistry. Aluminum-treated mice showed significantly increased apoptosis of motor neurons and increases in reactive astrocytes and microglial proliferation within the spinal cord and cortex. Morin stain detected the presence of Aluminum in the cytoplasm of motor neurons with some neurons also testing positive for the presence of hyper-phosphorylated tau protein, a pathological hallmark of various neurological diseases, including Alzheimer's disease and frontotemporal dementia. A second series of experiments was conducted on mice injected with six doses of Aluminum Hydroxide. Behavioural analyses in these mice revealed significant impairments in a number of motor functions as well as diminished spatial memory capacity. The demonstrated neurotoxicity of Aluminum Hydroxide and its relative ubiquity as an adjuvant suggest that greater scrutiny by the scientific community is warranted.

Christopher A Shaw - One of the best experts on this subject based on the ideXlab platform.

  • Aluminum Hydroxide injections lead to motor deficits and motor neuron degeneration
    Journal of Inorganic Biochemistry, 2009
    Co-Authors: Christopher A Shaw, Michael S Petrik
    Abstract:

    Gulf War Syndrome is a multi-system disorder afflicting many veterans of Western armies in the 1990-1991 Gulf War. A number of those afflicted may show neurological deficits including various cognitive dysfunctions and motor neuron disease, the latter expression virtually indistinguishable from classical amyotrophic lateral sclerosis (ALS) except for the age of onset. This ALS "cluster" represents the second such ALS cluster described in the literature to date. Possible causes of GWS include several of the adjuvants in the anthrax vaccine and others. The most likely culprit appears to be Aluminum Hydroxide. In an initial series of experiments, we examined the potential toxicity of Aluminum Hydroxide in male, outbred CD-1 mice injected subcutaneously in two equivalent-to-human doses. After sacrifice, spinal cord and motor cortex samples were examined by immunohistochemistry. Aluminum-treated mice showed significantly increased apoptosis of motor neurons and increases in reactive astrocytes and microglial proliferation within the spinal cord and cortex. Morin stain detected the presence of Aluminum in the cytoplasm of motor neurons with some neurons also testing positive for the presence of hyper-phosphorylated tau protein, a pathological hallmark of various neurological diseases, including Alzheimer's disease and frontotemporal dementia. A second series of experiments was conducted on mice injected with six doses of Aluminum Hydroxide. Behavioural analyses in these mice revealed significant impairments in a number of motor functions as well as diminished spatial memory capacity. The demonstrated neurotoxicity of Aluminum Hydroxide and its relative ubiquity as an adjuvant suggest that greater scrutiny by the scientific community is warranted.

Stanley L. Hem - One of the best experts on this subject based on the ideXlab platform.

  • In-Vitro Adsorption of Cholate Anion at pH 7.5 by Aluminum Hydroxide
    Drug Development and Industrial Pharmacy, 2008
    Co-Authors: Lisa Eaton, Joe L. White, Stanley L. Hem
    Abstract:

    AbstractThe in-vitro adsorptive capacities of Aluminum Hydroxide gel, dried Aluminum Hydroxide gel, and boehmite for cholate anion were determined at pH 7.5, 37°C and compared to cholestyramine. The adsorptive capacity of Aluminum Hydroxide gel was similar to cholestyramine. However, spray drying reduced the adsorptive capacity by approximately 50%. Boehmite, a crystalline Aluminum oxyHydroxide, had an adsorptive capacity similar to dried Aluminum Hydroxide gel. The results support the hypothesis that adsorption of bile salts contributes to the constipation which is sometimes associated with Aluminum Hydroxide therapy.

  • mechanism of adsorption of hepatitis b surface antigen by Aluminum Hydroxide adjuvant
    Vaccine, 2004
    Co-Authors: Seema Iyer, Harm Hogenesch, R Robin S Robinett, Stanley L. Hem
    Abstract:

    Hepatitis B surface antigen (HBsAg) differs from many antigens because of its associated lipid bilayer that is largely composed of phospholipids. In general, phosphate groups adsorb strongly to hydroxylated mineral surfaces by ligand exchange. The purpose of this study was to investigate the mechanism of adsorption of hepatitis B surface antigen to Aluminum Hydroxide adjuvant with emphasis on the role of phospholipids in this adsorption. The adsorption of HBsAg by Aluminum Hydroxide adjuvant exhibits a high affinity adsorption isotherm. The Langmuir equation was used to calculate the adsorptive capacity (1.7 microg/microg Al), which is the amount of HBsAg adsorbed at monolayer coverage and the adsorptive coefficient (6.0 ml/microg), which is a measure of the strength of the adsorption force. The relatively high value of the adsorptive coefficient indicates that adsorption is due to a strong attractive force. Ligand exchange between a phosphate of the antigen and a surface hydroxyl of the adjuvant provides the strongest adsorption mechanism. The adsorption capacity of HBsAg was not affected by increased ionic strength indicating that electrostatic attraction is not the predominant adsorption force. Adsorption was also not affected by the addition of ethylene glycol indicating that hydrophobic interactions were not the predominant adsorption force. The strength of the adsorption force was indicated by the resistance of HBsAg to elution when exposed to interstitial fluid. Less than 5% of the HBsAg adsorbed to Aluminum Hydroxide adjuvant in a model vaccine was eluted during a 12 h in vitro exposure to interstitial fluid at 37 degrees C. Less than 1% of the adsorbed HBsAg in two commercial vaccines was eluted by in vitro exposure to interstitial fluid for 48 h at 37 degrees C. Thus, it was concluded that adsorption of HBsAg by Aluminum Hydroxide adjuvant is predominantly due to ligand exchange between the phospholipids in HBsAg and surface hydroxyls in Aluminum Hydroxide adjuvant.

  • effect of the degree of phosphate substitution in Aluminum Hydroxide adjuvant on the adsorption of phosphorylated proteins
    Pharmaceutical Development and Technology, 2003
    Co-Authors: Seema Iyer, Harm Hogenesch, Stanley L. Hem
    Abstract:

    Aluminum Hydroxide adjuvant was pretreated with six concentrations of potassium dihydrogen phosphate to produce a series of adjuvants with various degrees of phosphate substitution for surface hydroxyl. The adsorption of three phosphorylated proteins (alpha casein, dephosphorylated alpha casein, and ovalbumin) by the phosphate-treated Aluminum Hydroxide adjuvants was studied. The phosphorylated proteins were adsorbed by ligand exchange of phosphate for hydroxyl even when an electrostatic repulsive force was present. However, the extent (adsorptive capacity) and strength (adsorptive coefficient) of adsorption was inversely related to the degree of phosphate substitution of the Aluminum Hydroxide adjuvant. Exposure of vaccines containing Aluminum Hydroxide adjuvant and phosphorylated antigens to phosphate ion in the formulation or during manufacture should be minimized to produce maximum adsorption of the antigen.

  • Measuring the surface area of Aluminum Hydroxide adjuvant
    Journal of Pharmaceutical Sciences, 2002
    Co-Authors: Cliff T Johnston, Shan-li Wang, Stanley L. Hem
    Abstract:

    Abstract The traditional method of determining surface area, nitrogen gas sorption, requires complete drying of the sample prior to analysis. This technique is not suitable for Aluminum Hydroxide adjuvant because it is composed of submicron, fibrous particles that agglomerate irreversibly upon complete removal of water. In this study, the surface area of a commercial Aluminum Hydroxide adjuvant was determined by a gravimetric/FTIR method that measures the water adsorption capacity. This technique does not require complete drying of the adjuvant. Five replicate determinations gave a mean surface area of 514 m 2 /g and a 95% confidence interval of 36 m 2 /g for a commercial Aluminum Hydroxide adjuvant. The X‐ray diffraction pattern and the Scherrer equation were used to calculate the dimensions of the primary crystallites. The average calculated dimensions were 4.5 × 2.2 × 10 nm. Based on these dimensions, the mean calculated surface area of the commercial Aluminum Hydroxide adjuvant was 509 m 2 /g, and the 95% confidential interval was 30 m 2 /g. The close agreement between the two surface area values indicates that either method may be used to determine the surface area of Aluminum Hydroxide adjuvant. The high surface area, which was determined by two methods, is an important property of Aluminum Hydroxide adjuvants, and is the basis for the intrinsically high protein adsorption capacity. © 2002 Wiley‐Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1702–1706, 2002

  • Detoxification of endotoxin by Aluminum Hydroxide adjuvant.
    Vaccine, 2001
    Co-Authors: Yi Shi, Fred E. Regnier, Harm Hogenesch, Stanley L. Hem
    Abstract:

    Langmuir adsorption isotherms of endotoxin and Aluminum-containing adjuvants at pH 7.4 and 25°C revealed that Aluminum Hydroxide adjuvant has a greater adsorption capacity (283 μg/mg Al) and adsorption coefficient (1.3×104 ml/μg) than Aluminum phosphate adjuvant (3.0 μg/mg Al, 0.20 ml/μg). The difference in endotoxin adsorption was related to two adsorption mechanisms: electrostatic attraction and covalent bonding. The isoelectric point (iep) of endotoxin is approximately 2. An electrostatic attractive force will be present with Aluminum Hydroxide adjuvant (iep=11.4), and an electrostatic repulsive force will operate with Aluminum phosphate adjuvant (iep=4.6). Endotoxin contains two phosphate groups in the lipid A portion. Covalent bonding occurs with surface Aluminum in Aluminum Hydroxide adjuvant but is inhibited by surface phosphate in Aluminum phosphate adjuvant. In-vitro desorption experiments using components of interstitial fluid showed that endotoxin adsorbed by Aluminum Hydroxide adjuvant was not desorbed by interstitial anions (5 mM phosphate or 2.7 mM citrate) or interstitial proteins (25 mg albumin/ml). The effect of Aluminum-containing adjuvants on the systemic response of Sprague–Dawley rats to a 15 μg/kg subcutaneous dose of endotoxin was determined by measuring the serum concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). TNF-α and IL-6 were observed in the group which received an endotoxin solution or endotoxin and Aluminum phosphate adjuvant. No TNF-α or IL-6 was detected in the group that received endotoxin and Aluminum Hydroxide adjuvant. Aluminum Hydroxide adjuvant detoxifies endotoxin by adsorbing it in the vaccine and then not releasing it in interstitial fluid upon administration.

Haruo Tachizawa - One of the best experts on this subject based on the ideXlab platform.

  • Effect of Aluminum Hydroxide, an Antacid, on the Pharmacokinetics of New Quinolones in Humans
    Drug Metabolism and Pharmacokinetics, 2007
    Co-Authors: Kohya Shiba, Atsushi Saito, Tadashi Miyahara, Haruo Tachizawa, Teruo Fujimoto
    Abstract:

    Effect of Aluminum Hydroxide on the pharmacokinetics of new quinolones, ofloxacin, enoxacin and norfloxacin, was investigated in cross-over study using five healthy male volunteers. Serum levels of the three drugs were decreased significantly up to 10 hours later by the concurrent administration of Aluminum Hydroxide. Cmax and AUC of the respective drug were decreased significantly by combined administration with Aluminum Hydroxide. Urinary excretion rates of the drugs within 24 hours were also decreased significantly by the concurrent administration of Aluminum Hydroxide. This combination effect of Aluminum Hydroxide on the pharmacokinetics of new quinolones was largest in case of norfloxacin and smallest in ofloxacin. Thus, these results suggest that the combination effect of Aluminum Hydroxide may be induced by the inhibition of absorption of new quinolones in the gastrointestinal tract.

  • Studies on the Mechanism of Pharmacokinetic Interaction of Aluminum Hydroxide, an Antacid, with New Quinolones in Rats
    Drug Metabolism and Pharmacokinetics, 2007
    Co-Authors: Osamu Okazaki, Tadashi Kurata, Haruo Tachizawa
    Abstract:

    The studies on the mechanism of pharmacokinetic interaction of Aluminum Hydroxide with new quinolones, ofloxacin, enoxacin and norfloxacin, were performed in rats. New quinolones (20 mg/kg) were administered orally with or without Aluminum Hydroxide or Aluminum chloride (50 mg/kg). Co-administration of Aluminum Hydroxide induced a significant decrease in Cmax of enoxacin and norfloxacin, and in the AUC values of the three drugs. This effect was enhanced by co-administration of Aluminum chloride. The combination of Aluminum Hydroxide caused a significant increase in the intestinal contents and decrease in urinary excretion of new quinolones. The formation of the stable chelate of new quinolones with Al3+ ions formed from Aluminum Hydroxide in the same acidic solution as gastric juice was observed. Thus, it is concluded that the co-administration of Aluminum Hydroxide affects the pharmacokinetics of new quinolones, probably, by the inhibition of the intestinal absorption of new quinolones by the chelate formation of these compounds with Al3+ ions released from Aluminum Hydroxide in the gastric juice.

Yu. G. Trifonov - One of the best experts on this subject based on the ideXlab platform.

  • Structure of Aluminum Hydroxide powders obtained as a byproduct of hydrogen fuel production
    Glass and Ceramics, 2013
    Co-Authors: A. D. Shlyapin, A. Yu. Omarov, V P Tarasovskii, Yu. G. Trifonov
    Abstract:

    The structure of Aluminum Hydroxide powders obtained as byproducts of hydrogen fuel production was investigated. One of the main initial components comprised Aluminum-magnesium chips with 0.6, 6 and 12 wt.% magnesium. The phase composition and morphology of the powder particles were studied by x-ray phase and petrographic analysis. It was determined that the Aluminum Hydroxide powder obtained holds promise for obtaining corundum ceramic.

  • Study of Aluminum Hydroxide powder prepared by chemical dispersion of Aluminum and its alloy
    Refractories and Industrial Ceramics, 2013
    Co-Authors: A. D. Shlyapin, A. Yu. Omarov, A. Kh. Khairi, Yu. G. Trifonov
    Abstract:

    Aluminum Hydroxide is a secondary product during operation of a hydrogen generator. An alkaline reaction proceeding between Aluminum or Aluminum alloy and caustic soda may be considered as a chemical dispersion method with preparation of nanodispersed Aluminum Hydroxide powder. Particle fineness and morphology, and also Aluminum Hydroxide powder phase composition, are different with different preparation methods, and therefore x-ray-phase, petrographic, and dimensional analyses are performed for three powder samples. Two powder samples are studied, prepared by chemical dispersion of Aluminum (sample 1) and silumin AK7 (sample 2). Results for industrially produced Aluminum Hydroxide powder, prepared by the Bayer method (sample 3) are studied for comparison.