Metals as a common trigger of inflammation resulting in non-specific symptoms: diagnosis and treatment.

BACKGROUND: The multiple symptoms of chronic fatigue syndrome (CFS) and fibromyalgia resemble those described in patients suffering from autoimmune/inflammatory syndrome induced by adjuvants (ASIA). It has been suggested that chronic metal-induced inflammation might play a role both in CFS and fibromyalgia as well as in ASIA. Humans are exposed to metals mainly through the release of metal ions from corroding dental restorations and orthopedic implants, food, vaccines and jewelry. Metals readily bind to sulphur and other groups in the mitochondria, enzymes and cell proteins. Metal-bound proteins are recognized by the immune system of susceptible subjects and might trigger an abnormal immune response, including allergy and autoimmunity. OBJECTIVES: To study three subjects with CFS and two with fibromyalgia, all of whom suspected metal exposure as a trigger for their ill health. METHODS: We measured delayed-type hypersensitivity to metals (metal allergy) using a validated lymphocyte transformation test, LTT-MELISA. All patients except one were sensitized to metals present in their dental restorations. The remaining patient reacted to metals in his skull implant. The removal of sensitizing metals resulted in long-term health improvement. Nine healthy controls matched for gender and age showed only marginal reactivity to the metals tested. CONCLUSIONS: Patients with CFS and fibromyalgia are frequently sensitized to metals found in the environment or used in dentistry and surgery. This allergy to metals might initiate or aggravate non-specific symptoms in metal-sensitized patients.

[The metallic profile: a new biological concept]. / Une nouvelle approche biologique: le profil métallique.

Considerable advances have been made in metals and metalloids analysis over the past decade. This analysis is a basic stage in deficiency or toxicity assessment. A recently introduced technique, inductively coupled plasma mass spectrometry (ICP-MS) is progressively replacing atomic absorption. This analysis permits multi-elementary determinations, many ten or so elements, among periodic classification, with an optimal gain in sensitivity in many biological matrices: i.e. whole blood, plasma, urine, hair, nail, and biopsy samples. Moreover, this method allows semi-quantitative determination with an additional thirty supplementary elements, which enables the toxicologist to sufficiently estimate the toxic levels and metal exposure. The authors demonstrate that the ICP-MS could be very useful for a wide range of clinical applications. Furthermore, this procedure offers new exploration possibilities in various fields such as clinical chemistry but also clinical toxicology, forensic toxicology as well as workplace testing or environmental exposure and permits epidemiologic studies. This analytical method in fact also provides a new biologic approach. To our knowledge we are the first to propose the metallic profile.

A categorization of metal anticancer compounds based on their mode of action.

The development of new metal anticancer compounds is a challenge for inorganic chemists. We have to face the fact that four decades of research in this field have only produced a small number of clinically used compounds, most often developed through serendipity rather than through rational chemical design. Nevertheless, by virtue of the wealth of knowledge acquired in these years, medicinal inorganic chemistry is probably mature for making significant steps forward and there are great expectations for future developments. With the aim of contributing to the rationalization of this field, we suggest here a categorization of metal anticancer compounds into five classes based on their mode of action: (i) the metal has a functional role, i.e. it must bind to the biological target; (ii) the metal has a structural role, i.e. it is instrumental in determining the shape of the compound and binding to the biological target occurs through non-covalent interactions; (iii) the metal is a carrier for active ligands that are delivered in vivo; (iv) the metal compound is a catalyst; and (v) the metal compound is photoactive and behaves as a photo-sensitizer. Selected examples for each category are given. The few metal anticancer drugs that are in clinical use are all believed to be functional compounds. Our classification, that is clearly focused on the metal compound and is independent from the nature of its bio-target(s)-most often still unknown-has the purpose of providing an intellectual tool that might be helpful in the rational development of new drugs.

Preliminary risk assessment of trace metal pollution in surface water from Yangtze River in Nanjing Section, China.

In order to investigate the contamination levels of trace metals, surface water samples were collected from six regions along Yangtze River in Nanjing Section. The concentrations of trace metals (As, B, Ba, Be, Cd, Cr, Cu, Fe, Pb, Li, Mn, Mo, Ni, Sb, Se, Sn, Sr, V and Zn) were determined using inductively coupled plasma-atomic emission spectrometry (ICP-AES). Total concentrations of the metals in the water samples ranged from 825.1 to 950.4 microg/L. The result was compared with international water quality guidelines. Seven metals levels were above the permissible limit as prescribed by guidelines. A preliminary risk assessment was then carried out to determine the human health risk via calculating Hazard Quotient and carcinogenic risk of the metals. Hazard Quotients of all metals were lower than unity, except As. The carcinogenic risk of As and Cd was higher than 10(-6), suggesting that those two metals have potential adverse effects on local residents.

[Carcinogenicity of metallic elements: general considerations about their identification and monitoring and about their main mechanisms of action. Part 1: general aspects]. / Elementi metallici cancerogeni: meccanismi di azione, identificazione, classificazione, valutazione del rischio Parte 1: aspetti generali.

Some general aspects about identification and classification for metallic elements considered carcinogenic at different degree of risk and for different species such as Nickel, Arsenic, Chromium, Cadmium, Beryllium, Cobalt, Vanadium, Lead and Molybdenum are presented in this first paper. The main mechanisms of biological and toxicological action will be presented in a second related paper. The classification suggested by IARC, ACGIH, DFG and UE are in a good agreement only for some of the above mentioned metallic elements and consequently open questions remain in selecting the most adequate environmental and biological indicators and the related reference or limit values for planning risk assessment and health surveillance. The carcinogenic metals may have different effects on cellular functions including proliferation, apoptosis, cellular differentiation and transformation. leading to different cellular effects in relation to its chemical and physical properties and interactions with biomolecules. In the identification of metallic elements to be considered and of correct indicators both environmental and biological for exposure assessment appears to be necessary to identify the species of metallic element classified as carcinogenic in order to achieve an effective preventive measures and to plan appropriate health and epidemiological surveillance programmes.

Metal speciation, phytochemicals and Helicobacter pylori infection.

Helicobacter pylori (HP) acquired in childhood is an important risk factor for gastric carcinoma. Once colonization is established, infection may be carried for life. The relationship between food intake and HP infection, the presence of metals and phytochemicals closely associated with oxidative stress within everyday diet are important topics to be considered. The possible anti-HP effects of phytochemicals, prooxidant effects exerted in the presence of metal species, intimate relations between some metals and HP, bivalent effects of some metal species in cancer, interactions between metal species and phytochemicals in HP infection are the topics, which require further research. Formulas or diets enriched with phytochemicals and metals against HP and, which are devoid of metals known to favour the growth of HP, may be suggested as the supplements to the classical treatment regimens. The importance of collective consideration of HP, metal species and phytochemicals should be emphasized.

Metallohistins: a new class of plant metal-binding proteins.

Two small multimeric histidine-rich proteins, AgNt84 and Ag164, encoded by two nodule-specific cDNAs isolated from nodule cDNA libraries of the actinorhizal host plant Alnus glutinosa, represent a new class of plant metal binding proteins. This paper reports the characterization of the purified in vitro-expressed proteins by size exclusion chromatography, circular dichroism, equilibrium dialysis, metal affinity chromatography coupled with mass spectrometry, and nuclear magnetic resonance spectroscopy. These analyses reveal that each polypeptide is capable of binding multiple atoms of Zn2+, Ni2-, Co2+, Cu2+, Cd2+ and Hg2+. A reversible shift in histidine Cepsilon1 and Cdelta2 protons in NMR analysis occurred during titration of this protein with ZnCl2 strongly suggesting that histidine residues are responsible for metal binding. AgNt84 and Ag164 are not related to metal binding metallothioneins and phytochelatins and represent a new class of plant metal binding proteins that we propose to call metallohistins. Possible biological roles in symbioses for AgNt84 and Ag164, and their potential for use in bioremediation are discussed.

Epidemiology and the identification of metals as human carcinogens.

Classification of substances as probable human carcinogens under the current IARC classification scheme is dependent on epidemiological evidence. The epidemiological data relating to the four metals currently identified as probable human carcinogens, in the metallic form or in the compounds, are reviewed and the weaknesses identified. These weaknesses lie mainly in exposure assessment. The weaknesses may be overcome to some extent by the use of metademographic methods as applied recently to the respiratory cancers that occurred at the Clydach Nickel Refinery in the first 30 years of this century. The general conclusion is that the epidemiological data relating to metals are unsatisfactory bases for the IARC classifications. There is a need to revise these classifications and to make them more precise by identifying exactly the substances which have caused human cancers.

Metals, silica and AHS content of equisetum bogotense HBK and equisetum giganteum L.(HORSETAIL) / Metales

Sio2, Li,Na,K,Ca,Mg,Cu,Zn,Fe,Pb, and ash content in equisetum bogotense HBK and equisetum giganteum L.(equisetaceae) in aerial parts were determined. These plants are used in natural and homoeopathic medice because of their therapeutic properties