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The aluminum content of biological products containing aluminum adjuvants: determination by atomic absorption spectrometry.

Aluminum compounds are used as adjuvants in certain types of vaccines, toxoids and allergenic extracts for human use. The most common Al compounds used in biological products to enhance the immune response are aluminum potassium sulphate (alum), aluminum hydroxide and aluminum phosphate. This study describes an atomic absorption spectrometric method for the determination of the Al content of Al adsorbed toxoid preparations and allergenic extracts at levels of less than 0.85 mg of Al per half millilitre human dose. Aliquots of the samples which contained Al suspensions were acid digested with nitric and sulphuric acid and analysed in the nitrous oxide-acetylene flame of an atomic absorption spectrometer. The 396.2 nm Al line was used for analysis. The Al content of the National Bureau of Standards (NBS) Standard Reference Material No. 1075a aluminum 2- ethylhexanoate was determined to within 1% of the NBS certificate value by this method. Atomic absorption results for the Al content of tetanus toxoids containing aluminum potassium sulphate and aluminum phosphate were compared with polarographic and inductively coupled argon plasma (ICP) emission spectrometry results. Reproducibility and recovery data for Al are tabulated for a variety of biological products containing aluminum phosphate, aluminum potassium sulphate and aluminum hydroxide adjuvants. In addition, ICP has been used to characterize the Al and P compositions of the precipitates and supernatant solutions which resulted from centrifuging toxoid suspensions that contained the three different Al adjuvants.

Adjuvants, Immunologic↗

Time-dependent actions of aluminates on membrane and action potentials of snail neurons.

Aluminum (Al) is one of the elements, which is frequently subjected to experiments, however, the neurological observations with it are rather conflicting. The cause of this controversiality is not known but relates to some human disorders such as Alzheimer's disease and others as well. We studied the time-dependent actions of AlCl3 base solutions on resting membrane potential (Em), input resistance (Rin) and spike shape in giant neurons of the snail Helix pomatia L. at pH 7.7 and room temperature (22-24 degrees C) by use of intracellular technique. We reported significant differences in the effectiveness of the various Al solutions depending on the time of storage before use in the experiments (0, 2 and 6 days at room temperature). Freshly prepared and applied Al solutions caused a significant and dose-dependent depolarization with a concomitant decrease of Rin and the amplitude of the action potentials, but the 6 days solutions induced a hyperpolarization. Ouabain (0.1 mM) antagonized the hyperpolarization. The pH (7.1 or 7.7) and the time of the storage in combination also modified the direct membrane effects. Our experiments show that Al can induce differential membrane effects depending on the presence of various aluminum compounds. Namely, the predominate aluminum-monomer at pH 7.7 the Al(OH)4- might cause depolarization but the polynuclear aluminum complexes after polymerization of the monomers could hyperpolarize the neuronal membrane. We suppose, that the time-dependent equilibrium of various aluminum complexes plays a role in generating controversies in this field and emphasize again the importance of standardization of the experimental protocol.

Action Potentials↗

Aluminum Phenylphosphonates: A Fertile Family of Compounds.

Six aluminum phenylphosphonates have been synthesized depending upon the synthetic conditions: Al(2)(O(3)PC(6)H(5))(3).2H(2)O (I), Al(2)(O(3)PC(6)H(5))(3) (II), alpha-Al(HO(3)PC(6)H(5))(O(3)PC(6)H(5)).H(2)O (III), beta-Al(HO(3)PC(6)H(5))(O(3)PC(6)H(5)).H(2)O (IV), Al(HO(3)PC(6)H(5))(3).H(2)O (V), and Al(OH)(O(3)PC(6)H(5)) (VI). Thermal analysis, X-ray powder thermodiffractometry, IR spectroscopy, and (27)Al and (31)P MAS NMR data have been obtained to study the structure and thermal stability of these materials. III crystallizes in the orthorhombic system, space group Pbca, with a = 9.7952(1) Å, b = 29.3878(4) Å, c = 9.3537(3) Å, and Z = 8. The structure was solved ab initio, from synchrotron data (lambda approximately 0.4 Å), using direct methods, and refined by Rietveld methods. The final agreement factors were R(wP) = 6.73%, R(P) = 5.24%, and R(F)() = 6.8%. The compound is layered with the aluminum atoms in an octahedral environment of oxygens and two crystallographically independent phosphonate groups, one being protonated. The powder patterns of V and VI have been indexed, and the experimental observations are consistent with layered structures. The unit cell of V contains one octahedral site for Al and three tetrahedral sites for P. Phosphonate I seems to have a three-dimensional tubular structure with aluminum atoms in both octahedral and tetrahedral environments and phosphorus atoms in three different types of sites.

Journal Article↗

[The causes, diagnosis and treatment of aluminum toxicity in patients with chronic renal failure undergoing dialysis].

To study the causes, diagnosis and treatment of aluminum toxicity in patients with chronic renal failure, the serum aluminum concentration was determined in 27 normal subjects, 28 patients of various kinds of diseases with normal renal function and 81 patients of chronic renal failure with hemodialysis in 65 and without in 16, of whom 41 patients were determined the aluminum concentration in the bone tissue. Clinical symptoms were carefully observed in all patients and desferrioxamine (DFO) test was performed in 17 patients, of whom 10 were treated with DFO. The results showed that treatment with improperly processed water and administration of aluminum compound were the major causes of aluminum toxicity in uremic patients. Aluminum toxicity may induce anemia, encephalopathy and bone disease, but its clinical features were nonspecific and the diagnosis may require several serum aluminum determinations or DFO test. DFO can chelate aluminum in a variety of tissues so that the latter may be released into the blood circulation. The DFO test may be used to assess the actual aluminum load in the bone tissue. The changes in serum aluminum concentration after intravenous infusion of DFO correlated closely with bone aluminum level, suggesting that the DFO test may be useful for the diagnosis of aluminum toxicity. The DFO therapy may be indicated for, 1, patients with uremia having hyperaluminumnemia due to treatment with improperly processed water and intake of aluminum-containing agents. 2. those who had serum aluminum concentration of higher than 200 micrograms/L and positive DFO test and 3. patients whose aluminum concentration in the bone tissue was 10 times greater than normal values. In this study, DFO was given intravenously in a dose of 20-40 mg/kg, twice a week. Satisfactory results were obtained in 3 to 6 months and there were no severe side effects when the agent was administered slowly.

Aluminum↗

[Aluminum and magnesium burden of dialysis patients using antacids. A comparative study].

Aluminum toxicity is becoming more and more evident as a complication of maintenance dialysis treatment. The aluminum contamination of the dialysate bath solution no longer plays an important role. The main source of aluminum overloading turns out to be the ingestion of aluminum-containing antacids as phosphate binders in the impaired renal aluminum excretion. In 19 dialysis patients an antacid poor in aluminum (Magaldrate) was compared with one rich in aluminum (compound M 70). The serum concentrations of aluminum, magnesium, phosphorus and calcium were investigated over a period of 14 days. After M 70 the aluminum and magnesium levels were markedly more elevated than after Magaldrate. Calcium remained unchanged with both compounds. Phosphorus was diminished only by M 70. The results of this short term study on dialysis patients are also important for patients with normal renal function, in particular in cases of uncontrolled long term treatment with antacids rich in aluminum.

Adolescent↗

Effect of embedded metal compound on porosity of silica colloids prepared by spray reaction of silicon tetrachloride.

Attempts to prepare macroporous silica particles and metal-compound-nanoparticle-embedded silica microspheres were carried out using reactions between silicon tetrachloride and ultrasonic generating microdroplets including metal (Na, K, Al, Ni, Ti, Pt) compounds. Samples were collected by dry and wet processes. In the case of using nickel and aluminum compounds, acid-treated samples were also prepared. The obtained samples were characterized by scanning electron microscopy, X-ray fluorescence spectroscopy, powder X-ray diffractometry, mercury porosimetry, and the nitrogen adsorption method. The macroporous silica particles were prepared by removing the salt crystals, such as NaCl and KCl, formed in the silica frame. For acid-resistant metals, platinum- and titanium-compound nanoparticles are easily embedded in silica microspheres using these metal-compound solutions. For acid-soluble metals, aluminum- and nickel-compound-nanoparticle-embedded silicas were prepared by applying neutralization of the collection water. Micropores and mesopores were produced in wet-process samples. Acid treatment induced the increase of micropore volumes.

Journal Article↗

Dietary aluminum chloride reduces the amount of intestinal calbindin D-28K in chicks fed low calcium or low phosphorus diets.

The mechanism of aluminum (Al) toxicity may involve disturbances in calcium (Ca) metabolism. Aluminum compounds have been reported to reduce vitamin D-dependent Ca absorption in chicks, rats and humans. To investigate the mechanism by which Al reduces Ca absorption, we studied the effect of dietary aluminum chloride (AlCl3) on the relative amounts of intestinal calbindin D-28K in chicks fed diets varying in Ca and phosphorus concentration. AlCl3 was added so that Al constituted 0, 0.15 or 0.3 g/100 g of diets that were either adequate, low in Ca, low in P, or contained supplemental P. Diets were fed for 2 wk. Intestinal calbindin D-28K levels were assayed using SDS-PAGE and 45Ca binding to Western blots. Added dietary Al greatly reduced the amount of intestinal calbindin in chicks fed adequate diets, low Ca diets, or low P diets. When diets with supplemental P were fed, little calbindin was evident with or without added Al. Tibia ash, body weight and food intake were also reduced (P < 0.05) by added Al. These results indicate that dietary AlCl3 inhibits vitamin D-dependent Ca absorption by reducing the amount of intestinal calbindin D-28K. Aluminum, therefore, may interfere with the body's ability to regulate intestinal calbindin D-28K levels. This could have implications for other tissues that contain substantial levels of calbindin D-28K.

Aluminum Chloride↗

In vivo and in vitro effects of aluminum on the activity of mouse brain acetylcholinesterase.

Cholinesterases are a large family of enzymatic proteins widely distributed throughout both neuronal and non-neuronal tissues. In Alzheimer's disease (AD), analytical as well as epidemiological studies suggest an implication of an abnormal focal accumulation of aluminum in the brain. In this devastating disease, aluminum may interfere with various biochemical processes including acetylcholine metabolism, and can thus act as a possible etiopathogenic cofactor. Acetylcholinesterase (AChE) exists in several molecular forms that differ in solubility and mode of membrane attachment rather than in catalytic activity. Mice were treated orally with aluminum chloride or aluminum lactate (Al(lac)(3)), and AChE activity in their brain homogenates was then assayed. Results showed that this in vivo treatment augmented the activity of the enzyme. An activating effect was also observed in vitro, when the aluminum compounds were added directly to mouse brain homogenates. However, the activating effect observed in vivo was much more marked than that observed in vitro. In addition, the activation produced by Al(lac)(3) was higher than that obtained after aluminum chloride treatment. Kinetics measurements of AChE activity in the absence and presence of treatment with aluminum both in vivo and in vitro are reported. The influence of the metal speciation on enzymatic activity is discussed in relation to a possible implication of aluminum in some neurodegenerative diseases.

Acetylcholine↗

Temperature effects on flocculation, using different coagulants.

Temperature is known to affect flocculation and filter performance. Jar tests have been conducted in the laboratory, using a photometric dispersion analyser (PDA) to assess the effects of temperature on floc formation, breakage and reformation. Alum, ferric sulphate and three polyaluminium chloride (PACI) coagulants have been investigated for temperatures ranging between 6 and 29 degrees C for a suspension of kaolin clay in London tap water. Results confirm that floc formation is slower at lower temperatures for all coagulants. A commercial PACl product, PAX XL 19, produces the largest flocs for all temperatures; and alum the smallest. Increasing the shear rate results in floc breakage in all cases and the flocs never reform to their original size. This effect is most notable for temperatures around 15 degrees C. Breakage, in terms of floc size reduction, is greater for higher temperatures, suggesting a weaker floc. Recovery after increased shear is greater at lower temperatures implying that floc break-up is more reversible for lower temperatures.

Alum Compounds↗

Glomerular lesions in male rabbits treated with aluminium lactate: with special reference to microaneurysm formation.

Novel glomerular lesions were seen in male rabbits after intravenous administration of aluminum lactate. Eight rabbits in the treated group were given 0.1 mmol/kg of aluminum lactate 5 days a week for 4 weeks. The control group of 8 rabbits was given 0.3 mmol/kg of sodium lactate by the same injection protocol. In the treated group, the mesangial cells in the glomerular tufts in 6 of 8 rabbits were distended with grayish blue granular material, which was identified by laser microprobe mass spectrometry and acid solochrome azurine stain as an aluminum compound. Other consistent findings in the glomeruli included microaneurysm in 6 of 8 rabbits and segmental sclerosis in 6 of 8 rabbits. Less frequently observed glomerular changes included crescent formation, necrosis with calcification, fibrosis of the Bowman's capsule, cystic dilation of the Bowman's space, and exudation of erythrocytes into the Bowman's space. The mechanism by which aluminum lactate induces the glomerular changes is not certain. However, the pathogenesis may involve the deposition of aluminum in the mesangial cells, resulting in mesangiolysis which in turn causes microaneurysm. The sclerotic change is interpreted as a sequela of microaneurysm. The findings suggest that aluminum induces glomerular lesions in rabbits. This may serve as a good animal model to study mesangiolysis and microaneurysm formation.

Aluminum↗

[Trials of casual treatment of silicosis].

Silica-induced lung injury and the development of silicosis is one of the major occupational diseases. Accumulation and deposition of respirable dust containing silica mineral particles in the lung produces chronic lung disease characterized by granulomatous and fibrotic lesions. Knowledge of precise mechanisms, which induce this process is still limited, hence problems faced in the treatment of silicosis, especially the casual one. This article describes various trials of casual silicosis treatment with tetrandrine (Tet), isolated from the root of Stephania tetrandra, tumor necrosis factor (TNF) antagonists, polyvinyl-pyridine-N-oxide (PVNO), aluminum compounds, corticosteroids or bronchoalveolar lavage (BAL). The existing methods are not sufficient, which warrants further investigations. At present, prevention of the disease and treatment of its complications are most important.

Adrenal Cortex Hormones↗

Adhesion-mediated enhancement of the adjuvant activity of alum.

Alum, the only adjuvant currently licensed for use in humans, fails to adsorb influenza virus haemagglutinin (BHA) and is a poor adjuvant for this antigen. A specific monoclonal anti-BHA antibody adsorbed to alum promoted adhesion of the antigen to the adjuvant. The 'alum-anti-BHA-BHA' complex was found to be 1500-fold more immunogenic in mice and 5-fold more immunogenic in rabbits than a mixture of alum and BHA lacking the anti-BHA antibody. The biotin-binding protein, avidin, also mediated adsorption of biotinylated BHA to alum, and enhanced its immunogenicity to a comparable extent. These results indicate that the adjuvant activity of alum can be markedly enhanced by promoting a physical association between the antigen and the adjuvant.

Adhesiveness↗

Aluminum toxicity in childhood.

Aluminum intoxication is an iatrogenic disease caused by the use of aluminum compounds for phosphate binding and by the contamination of parenteral fluids. Although organ aluminum deposition was noted as early as 1880 and toxicity was documented in the 1960s, the inability to accurately measure serum and tissue aluminum prevented delineation of its toxic effects until the 1970s. Aluminum toxicity has now been conclusively shown to cause encephalopathy, metabolic bone disease, and microcytic anemia.

Aluminum↗

Effects of aluminum on neuronal signal transduction: mechanisms underlying disruption of phosphoinositide hydrolysis.

1. Aluminum is neurotoxic in humans and animals and alters formation of inositol phosphate (IP) second messengers following in vivo or in vitro exposure. 2. Several components of the IP signalling system including G-proteins, phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC) and Ca2+ homeostasis are susceptible to inhibition/disruption by aluminum compounds. 3. Recent evidence suggests that, despite its effects on other components, competitive inhibition by aluminum of phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis by PI-PLC underlies its effects on agonist-stimulated IP generation.

Aluminum↗