Aluminium metabolism

Over the years, problems have arisen as a result of the presence of significant amounts of aluminium in parenteral nutrition solutions in particular they have been held responsible for hypercalciuria and its consequences (54). Parenterally administered aluminium bypasses the gastrointestinal tract, which normally serves as a protective barrier to aluminium entry into the blood. In the past, aluminium contamination of casein hydrolysate, which was used as a source of protein in parenteral nutrition solutions, was associated with low-turnover osteomalacia and with encephalopathy in uremic patients. Premature infants are still at risk of aluminium accumulation as a result of prolonged parenteral nutrition (as are patients receiving plasmapheresis with albumin contaminated in its preparation with aluminium). Metabolic bone disease can result (54). 

Meiri H, Banin E, Roll M, et al Toxic effects of aluminium on nerve cells and synaptic transmission. Prog Neurohiol 40 89-121, 1993 Meshitsuka S, Loeda T, Hara T, et al Abnormal aluminium metabolism in two siblings with progressive CNS calcification (letter). Dev Med Child Neurol 43 287-288, 2001... 

Oshiro S (2003) A New Effect of Aluminium on Iron Metabolism in Mammalian Cells 104 ... 

Other photosensitisers in clinical or pre-clinical trials include zinc phthalocya-nine, aluminium sulphonated phthalocyanines, benzoporphyrins, benzochlorins and purpurin-lS-iV-alkylamides, all of which absorb strongly in the 675-700 nm region. An alternative approach to the photosensitisation in PDT involves the use of 5-aminolaevulinic acid (ALA). This compound itself is not a sensitiser but in human cells it is the key metabolic precursor in the biosynthesis of protoporphyrin IX, which can act as a photosensitiser. Normally the biosynthetic process would continue beyond protoporphyrin IX to the iron containing haem. However, by adding extra ALA and iron chelators, the ferrochelatase action is inhibited and the normal feedback mechanism by-passed resulting in a build up of protoporphyrin IX in the cell. The mechanism is illustrated in Figure 4.24. ... 

Various additional oil-based adjuvants have subsequently been developed. Adjuvant 65, for example, consists of 86% peanut oil, 10% Arlacel A and 4% aluminium monostearate (as a stabilizer). Unlike mineral oil, peanut oil is composed largely of triglycerides, which are readily metabolized by the body. Although adjuvant 65 was initially proved safe and effective in humans, it displayed less adjuventicity than FIA. Its use was largely discontinued, mainly due to the presence in its formulation of Arlacel A. 

Gunse, B., Poschenrieder, C., and Barcelo, J., The role of ethylene metabolism in the short-term responses to aluminium by roots of two maize cultivars different in Al-resistance, Environ. Exp. Bot., 43, 73, 2000. 

Treatments of diseases such as osteoporosis, rickets and osteomalacia, in which there is a disturbance of phosphate levels, is complicated by the interdependence of calcium metabolism. This topic has recently been discussed in relation to clinical medicine21. There is the further difficulty that absorption of phosphate from the bowel can be decreased in the presence of calcium or aluminium salts because of the formation of their insoluble phosphates. Uptake of phosphate by bone is exploited in the treatment of polycythaemia vera by intravenous injection of 32P as sodium phosphate. The resulting irradiation of the neighbouring red bone marrow diminishes the production of red cells. 

Aluminium is the third most abundant element in the earth s crust and is used widely in the manufacture of construction materials, wiring, packaging materials and cookware. The metal and its compounds are used in the paper, glass and textile industries as well as in food additives. Despite the abundance of the metal, its chemical nature effectively excludes it from normal metabolic processes. This is due largely to the low solubility of aluminium silicates, phosphates and oxides that result in the aluminium being chemically unavailable. However, it can cause toxic effects when there are raised concentrations of aluminium in water used for renal dialysis. These effects are not seen when aluminium is at the concentrations usually present in drinking water. There is currently much activity to examine the factors that influence uptake of aluminium from the diet. 

H2-labelled thioridazine 56 (the phenothiazine-type antipsychotic agent) has been obtained recently39 for metabolic and pharmacokinetic studies by a new route (equation 16) from 2-(2-hydroxyethyl)piperidine 57. The key steps in this sequence of reactions involve ruthenium tetroxide oxidation of the 7V,0-diacetylated starting material 58 and subsequent lithium aluminium deuteride reduction of the 2-(2-acetoxyethyl)-6-piper-idinone (59, R = Ac). Treatment of 60 with thionyl chloride produced 2-(2-chloroethyl)-l-methyl[6,6-2H2]piperidine which, on N(10)-alkylation of 2-methylthio-10i/-phenothia-zine, yielded 56. For each of the seven steps in the conversion of 57 to 56 the yield has been at least 76%40. 

We are all exposed to aluminium from the metal utensils we use and also from the occasional use of medicinal preparations such as antacids, but it is poorly absorbed and the risk is probably very small. Dialysis patients with renal disease were found to be at risk of brain damage due to the aluminium derived from the equipment. Realization of this led to a lowering of the exposure of such patients, which decreased the occurrence of toxic effects of aluminium. Patients on dialysis with end stage renal disease, in whom some accumulation of aluminium occurred, showed evidence of metabolic abnormalities and in psychomotor function. 

Aluminium is toxic in patients on chronic hemodialysis and peritoneal dialysis and in those taking oral aluminium-containing medications. Aspects of aluminium safety (9) and metabolism (10) have been reviewed. The association between aluminium in drinking water and Alzheimer s disease continues to be discussed and remains controversial (11). 

Calcium is normally considered to be safe in parenteral nutrition, and relatively high quantities are often included in neonatal and pediatric formulations. However, there is a risk of hjrpercalciuria. The pathogenesis of hjrpercal-ciuria is not readily explicable on the basis of endocrine or metabolic effects, but it has been postulated to be due to excessive calcium or vitamin D intake or aluminium overload. 

Metabolic bone disease in children receiving parenteral nutrition manifests primarily as osteopenia and, on occasion, fractures (5). The etiology is multifactorial calcium and phosphate deficiency play a major role in the preterm infant but the part played by aluminium toxicity in this population is unknown. Lack of reference values of bone histomorphometry in the premature infant, as well as lack of reference data for biochemical markers of bone turnover in these patients, contributes to the uncertainty. Other factors that may play a role in the pathogenesis of bone disease associated with parenteral nutrition include lack of periodic enteral feeding underljdng intestinal disease, including malabsorption and inflammation the presence of neoplasms and drug-induced alterations in calcium and bone metabohsm. However, the true incidence and prevalence of parenteral nutrition-associated bone abnormalities in pediatric patients are unknown. 

Vargas JH, Klein GL, Ament ME, Ott SM, Sherrard DJ, Horst RL, Berquist WE, Alfrey AC, Slatopolsky E, Coburn JW. Metabolic bone disease of total parenteral nutrition course after changing from casein to amino acids in parenteral solutions with reduced aluminium content. Am J Clin Nutr 1988 48(4) 1070-8. 

The a- and -isomers of endosulfan can be reduced with lithium aluminium hydride in tetrahydrofuran to furnish the same endosulfan diol (55) which has been observed as one of its metabolic products (56). Depending on whether acetylation or silylation is used to make the diol more GC-responsive, lower limits of detectability are of the order 0.03 or 0.02 ppm, respectively (Table I). 

The production of a mineral substance as a direct consequence of the metabolic processes of a bacterium will be discussed later. However, the system involved here is a very simple one compared with one likely to be encountered in a soil, primarily in the absence of iron and aluminium. 

Surveys have shown a general correlation between the pH and fish status in lakes, and the physiological response of fish to acidic water is now well known ( ). Acid water affects the uptake of sodium and chloride ions through the cell membranes in the gills, and leads to a disturbance of the electrolyte balance ( ). The concentration of reactive (uncomplexed) aluminium ions in acidified waters is particularly detrimental (30), apparently because this interferes with the metabolic uptake of electrolytes from the water, while calcium ions have an ameliorating effect (31) ... 

The use of calcined clay as a filler has shown to lead to the release of soluble aluminium from rubber closures into the parenteral solution (Milano et al., 1982). Various techniques for the determination of soluble aluminium in rubber closures have been proposed (Mondimore and Moore, 1983). There has been concern about aluminium since the 1970s, when a link was identified between high aluminium levels in tap water used for renal dialysis equipment and accumulation of the element in the brain. The injection of parenteral solutions into the body effectively bypasses the normal defence mechanisms and under these circumstances may present a challenge to the normal metabolic processes (Massey and Taylor, 1989). In response to these challenges, suppliers have developed rubber formulations that are essentially free from materials containing aluminium compounds. 

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