Valeria Marina Nurchi

Brain copper, iron, magnesium, zinc, calcium, sulfur and phosphorus storage in Wilson's disease.

PROJECT Wilsons disease (WD) is an inherited disorder of copper metabolism characterised by juvenile liver cirrhosis and by neurological symptoms. Copper levels in brain in WD have been reported to be 10 to 15 fold normal values, depending on the different brain regions. Being very few data on copper distribution in central nervous system in WD available, it seemed of interest to study the concentration of copper and of other trace elements (Zn, P, Mg, Ca, Fe and S) in the brain of a patient died for WD. PROCEDURE a 56 year old woman affected by WD was admitted to our hospital with signs of hepatic failure and died few days later. At autopsy, a brain slice extending from the left to the right hemisphere was divided in 28 samples. On each sample Copper, Iron, Magnesium, Phosphorus, Sulphur, Zinc and Calcium were determined by Induced Coupled Plasma Atomic Emission Spectroscopy. RESULTS the mean concentration of copper, ranging from 88 to 158 microg/g of dry tissue in all the brain specimens was higher than literature reference values, while that of the other tested elements was considerably lower. CONCLUSIONS 1) In the brain of WD patient examined the status of trace elements was extensively altered. Further studies are necessary to correlate the concentration of trace elements with pathological lesions and with clinical pictures. 2) The elements considered in our study showed an uneven distribution in different brain areas.

Chelating Agents as Therapeutic Compounds—Basic Principles

While principles of chelation were briefly outlined in chapter: General Chemistry of Metal Toxicity and Basis for Metal Complexation, the basic requisites of chelating agents to be used in the clinical treatment of metal intoxication are discussed in more detail in the present chapter. In particular, the stability of the formed complexes between chelating agents and toxic metal ions, the selectivity of chelating agents, the kinetic aspects, and the factors affecting the absorption, and the bioavailability of chelating agents are presented. In the second part of the chapter, the drugs approved by Food and Drug Administration (USA) or by EU for their use in the clinical chelation therapy are singularly illustrated, reporting their principal chemical, biological, and pharmacological features.

Warns against unapproved ‘chelation therapy’

At Eurobic11 in Granada we presented a Keynote Lecture on chelation therapy, a consolidated medical procedure used primarily to hinder the effects of toxic metal ions on human tissues. Its application spans a broad spectrum of serious disorders, ranging from acute metal intoxication to genetic metal-overload. The use of chelating agents is compromised by a number of serious side effects, mainly attributable to perturbed equilibrium of essential metal ion homeostasis and dislocation of complexed metal ions to dangerous body sites. For this reason, chelation therapy has been limited to specific critical and otherwise untreatable conditions and it needs to be monitored within an appropriate clinical context. In this meeting we want warn against the widespread fraudulent use of the term ‘‘chelation therapy’’ to take advantage of and make profit from people with tragic health problems. We believe that scientists working in this field have the corollary obligation to deter these frauds and to inform the scientific community of the possible side effects and complications of chelation therapy. This duty is all the more important if we consider the detrimental and even life threatening consequences that can occur in subjects with no clear clinical and laboratory evidence of metal intoxication. The aim of this communication is to present how this ‘‘false chelation therapy’’ developed and in which diseases it is currently applied. This research was supported by the Regione Autonoma Sardegna [CRP-27564].AW 1 Vanadium: its role in life and environmental issues Dieter Rehder Department of Chemistry, University of Hamburg, Martin-LutherKing-Platz 6, 20146 Hamburg, Germany. rehder@chemie.unihamburg.de Vanadium is the second-to-most abundant transition metal in sea water. Marine macroalgae employ vanadate, built into the active centre of vanadate-dependent haloperoxidases VHPOs, in the peroxidation of halides (Hal) to Hal species. Hal can generate halomethanes that are released into the atmosphere [1] where they are involved in ozone depletion; see Figure. VHPOs are also present in some terrestrial fungi, in lichen and in Streptomyces bacteria. The biocidal (antifouling) and oxidative power of VHPOs have initiated research into applications, including active centre models, in medicinal (disinfection) and industrial (oxidation catalysis) fields [2]. In the context of possible medicinal applications of vanadium compounds it is worth noting that vanadate HVO4 2is an antagonist of phosphate: Vanadate appears to have a cardioand neuro-protective potential, and oxidovanadium(IV) and –(V) chelates have been show to exert in vitro and in vivo anti-cancer, anti-viral and anti-bacterial activity [3]. The most prominent issue in a medicinal context is the insulinenhancing action of vanadyl chelates such as VO(acac)2 and VO(maltol)2. Vanadium can enter the cytosol directly as vanadate, or in the form of VO coordinated to transferrin and serum albumin. Its possible primary mode of action is the regulation of the tyrosine phosphorylation level of the insulin receptor (and thus the glucose signalling path) by interacting with protein tyrosine phosphatase 1B [2, 3].