Doses Of Aluminum Hydroxide Research Articles

ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type.

The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of Aluminum hydroxide (Alum) against SHIV-Cs of varying neutralization sensitivity in macaques. Low doses of Alum induced higher mucosal V2-specific IgA that increased the risk of Tier 2 SHIV-C acquisition. High Alum dosage, in contrast, elicited serum IgG to V2 that correlated with a decreased risk of Tier 1 SHIV-C acquisition. MF59 induced negligible mucosal antibodies to V2 and an inflammatory profile with blood C-reactive Protein (CRP) levels correlating with neutralizing antibody titers. MF59 decreased the risk of Tier 1 SHIV-C acquisition. The relationship between vaccine efficacy and the neutralization profile of the challenge virus appear to be linked to the different immunological spaces created by MF59 and Alum via CXCL10 and IL-1β, respectively.

Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration

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.

Calcium carbonate as a phosphate binder in dialysis patients: Evaluation of an enteric-coated preparation and effect of additional aluminium hydroxide on hyperaluminaemia

Calcium carbonate has been successfully used as a phosphate binder in patients with chronic renal failure; however, a high frequency of hypercalcaemia has been reported. To study the effects of calcium carbonate preparations with different dissolution characteristics on the incidence of this side effect, we conducted a double-blind, crossover trial in 21 patients undergoing chronic haemodialysis. Aluminum hydroxide therapy was replaced with calcium carbonate. The subjects then randomly received either an enteric-coated or a gastric-coated preparation. Calcium carbonate (3.1-3.6 g/d) controlled serum phosphate concentrations as effectively as aluminium hydroxide (2.9 g/d). Concurrently, there was a significant rise in mean serum calcium and a fall in serum concentrations of both parathyroid hormone and osteocalcin, the latter suggesting a decrease in bone turnover. Overall, hypercalcaemic episodes developed in 9 patients (43%) and occurred at a considerable frequency (33 episodes per 100 patient-months) during treatment with the gastric-coated formulation. Following conversion to enteric-coated calcium carbonate (3.6 g/d) patients had fewer occurrences of hypercalcaemia (12 episodes per 100 patient-months, P less than 0.05) and, as compared to the gastric-coated preparation, increases in serum calcium greater than 3.00 mmol/l were not observed at all. Hyperaluminaemia was regressive during therapy with calcium carbonate, but addition of small doses of aluminium hydroxide caused a large rise in serum aluminium concentrations after infusion of desferrioxamine, indicating an enhanced rate of absorption or aberrant compartmentalization of aluminium. We conclude that calcium carbonate can control hyperphosphataemia in dialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease

Abstract Background. The control of hyperphosphatemia is a major clinical problem in patients with chronic renal failure receiving regular dialysis treatment. Despite continuing concern about aluminum toxicity, aluminum-containing antacids are still used in many of these patients as phosphate-binding agents. Although maximal acceptable doses of aluminum hydroxide have been recommended, the safety and efficacy of these guidelines have not been evaluated. Methods. Seventeen children and young adults (mean [±SD] age, 14.1 ±3.7 years) undergoing regular peritoneal dialysis were randomly assigned to treatment with either aluminum hydroxide (n = 7; maximal dose, 30 mg per kilogram of body weight per day) or calcium carbonate (n = 10; dose range, 2.5 to 12 g per day, according to serum phosphorus levels). Aluminum retention was assessed by serial measurements of plasma aluminum, deferoxamine-infusion tests, and measurements of bone aluminum content during a mean (±SD) follow-up of 13±2 months. The evolution of b...

Aluminum metabolism in rats: effects of vitamin D, dihydrotachysterol, 1,25-dihydroxyvitamin D and phosphate binders.

In order to study the effects of vitamin D on aluminium balance when different forms of vitamin D and phosphate binders are used simultaneously for therapeutic purposes, 30 Sprague-Dawley weanling rats, weighing 44-66 g, were randomly assigned to 5 groups: (A) control, (B) aluminum hydroxide, (C) dihydrotachysterol at 16 micrograms/kg/day, (D) 1,25-dihydroxyvitamin D at 16 ng/kg/day and (E) vitamin D at 2,000 IU/kg/day. Aluminum hydroxide (60 mg/kg/day) in the feed was provided to all except the control group. The vitamin D or metabolites were fed by stomach tube daily for a period of 10 days. At the end of the study, the mean (+/- SEM) serum aluminum concentration, as determined by flameless atomic absorption spectrophotometry, was 5.0 +/- 2.4 micrograms/l; there were no significant differences in these results between groups. During the last three days of the study, 24-hour urine and stool collections were made with the usual precautions against trace mineral contamination. The means (+/- SEM) of aluminum balances for groups A, B, C, D and E were -388 +/- 261, 1,121 +/- 331; 2,316 +/- 304; 2,387 +/- 245, and 1,968 +/- 337 micrograms/day, respectively. We conclude that at therapeutic doses of aluminum hydroxide and vitamin D or its metabolites, hyperaluminemia was not observed. However, the positive aluminum balances imply retention, and the use of vitamin D, especially its potent metabolites dihydrotachysterol and 1,25-dihydroxyvitamin D, intensified this risk.

The effects of antacids on enteric-coated salicylate preparations.

A volunteer study was undertaken in which the effect of the co-administration of therapeutic doses of aluminium hydroxide and magnesium trisilicate on the excretion of aspirin derived from enteric-coated preparations was studied. A significant alteration in the pattern of salicylate excretion was seen, but the mechanism of the interaction cannot be deduced from the present study. It was concluded that the interaction was of potential therapeutic importance, and further studies based on this pilot investigation have been initiated.