Aluminium assay and evaluation of the local reaction at several time points after intramuscular administration of aluminium containing vaccines in the Cynomolgus monkey.

Aluminium hydroxide and aluminium phosphate have been widely used as vaccine adjuvants with a good safety record for several decades. The recent observation in human deltoid muscle of macrophage aggregates containing aluminium hydroxide spicules and termed Macrophagic Myofasciitis (MMF) has encouraged research on aluminium salts. This study was conducted in order to further investigate the clearance of aluminium at the vaccine injection site and the features of induced histopathological lesions. Two groups of 12 monkeys were immunised in the quadriceps muscle with Diphtheria-Tetanus vaccines, which were adjuvanted with either aluminium hydroxide or aluminium phosphate. Three, six or twelve months after vaccination, four monkeys from each group were sacrificed and histopathological examination and aluminium assays were performed on quadriceps muscle sections. Histopathological lesions, similar to the MMF described in humans, were observed and were still present 3 months after aluminium phosphate and 12 months after aluminium hydroxide adjuvanted vaccine administration. An increase in aluminium concentration, more marked in the area of the lesions, was also observed at the 3- and 6-month time points. These findings were localised at the injection site and no similar changes were observed in the distal or proximal muscle fragments. We conclude from this study that aluminium adjuvanted vaccines administered by the intramuscular route trigger histopathological changes restricted to the area around the injection site which persist for several months but are not associated with abnormal clinical signs.

Elemental maps in human allantochorial placental vessels cells: 2. MgCl2 and MgSO4 effects.

Extracellular magnesium salts are known to interfere with ionic channels in the cellular membranes. The membrane potential, a regulator of vascular tone, is a function of the physiological activities of ionic channels (particularly, K+ and Ca2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-Particule Induced X-ray Emission (PIXE) analysis was applied to determine the ionic composition of vascular smooth muscle cells (VSMC) and of vascular endothelial cells (VEC) in the placental human allantochorial vessels in a physiological medium (Hanks' solution) modified by the addition of 2 mM MgCl2 or 2 mM MgSO4 which block the calcium-sensitive K+ channels (K(Ca)), the ATP-sensitive K+ channels (K(ATP)) and the voltage-sensitive K+ (K(df)) and Ca2+ channels. In VSMC (media layer), the addition of MgCl2 induced no modification of the K, Cl, P, S and Ca concentrations but increased the Na and Mg concentrations and the addition of MgSO4 only significantly increased the Mg concentration, the other ion concentrations remaining constant. In endothelium (VEC), MgCl2 or MgSO4 addition implicated the same observations as in VSMC. These results confirmed the blockage of K(df), K(Ca), K(ATP) and Ca channels in VSMC and VEC by magnesium salts, the relationship between Mg2+ ions and internal Na and demonstrated the possible intervention of a Na+/Mg2+ exchanger.