The adjuvant aluminum fate - Metabolic tale based on the basics of chemistry and biochemistry.

Aluminum is inevitable component of many vaccines. The benefit of the vaccines is undeniable but effects of aluminum toxicity might be underestimated and neglected. In this review, we highlighted the mechanims of aluminum toxicity, which is still in debate. So far, all the papers that disscused the adverse aluminum effects pointed two mechanisms responsible for Al toxicity, direct Al toxicity and aluminum induced cell damage via the oxidative metabolism. According to our knowledge, which is based on basic principles of biochemistry and inorganic chemistry, we suggested that aluminum highly interferes with iron metabolism eventually resulting in iron-mediated cell damage. More importantly, in this paper, we offered easily feasible solutions, in order to avoid aluminum toxicity in the future. We suggest that as it once was, Calcium Phosphate again to be used as the adjuvant or better solution that the vaccine adjuvants should be based on zinc compounds or even better would be non-metal adjuvants, such as microcrystalline tyrosine and monosodium urate. Until an adequate adjuvant is provided, we suggest instant postponement of vaccination with vaccines which use aluminum as the adjuvant until the 12 months of age.

Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis.

The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. CONCLUSION: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liver damage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.