Diseases from metals

Lead (Pb) is a relahvely common metal, mined chiefly as the sulphide (galena) in many cormtries - USA, Australia, USSR, Canada and Mexico . 

In this country we use about 330000 tonnes of lead annually, much of which comes from recycled scrap. 

Lead has a great variety of uses, e.g. (percentages approximated from annual production figures issued by World Bureau of Metal Statistics, London)  

as a fume or dust hazard. is therefore met in many industries. The 

Inorganic lead can enter the body by inhalation or ingestion. Up to about 50% of that inhaled is absorbed and only about 10% of that ingested. It is then transported in the blood stream and deposited in all tissues, but about 90% of it is stored in the bone. It is a cumulative poison excretion is slow and occurs mainly in the urine and faeces. 

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Numerous and disparate copper criteria are proposed for protecting the health of agricultural crops, aquatic life, terrestrial invertebrates, poultry, laboratory white rats, and humans (Table 3.8) however, no copper criteria are now available for protection of avian and mammalian wildlife, and this needs to be rectified. Several of the proposed criteria do not adequately protect sensitive species of plants and animals and need to be reexamined. Other research areas that merit additional effort include biomarkers of early copper stress copper interactions with interrelated trace elements in cases of deficiency and excess copper status effects on disease resistance, cancer, mutagenicity, and birth defects mechanisms of copper tolerance or acclimatization and chemical speciation of copper, including measurement of flux rates of ionic copper from metallic copper. 

Figure 18.16 Hypothetical model for the metallobiology of AP in Alzheimer s disease. (From Bush, 2003. Copyright 2003, with permission from Elsevier.) The proposed sequence of events (1) concentration of iron and copper increase in the cortex with aging. There is an overproduction of APP and AP in an attempt to suppress cellular metal-ion levels. (2) Hyper-metallation of AP occurs which may facilitate H202 production. (3) Hyper-metallated AP reacts with H202 to generate oxidized and cross-linked forms, which are liberated from the membrane. (4) Soluble AP is released from the membrane and is precipitated by zinc which is released from the synaptic vesicles. Oxidized AP is the major component of the plaque deposits. (5) Oxidized AP initiates microglia activation. (6) H202 crosses cellular membranes to react with Cu and Fe, and generate hydroxyl radicals which oxidize a variety of proteins and lipids.

Dust can be stirred up by treading or other movement and can permeate the atmosphere and be inhaled. The dust that one can see can give rise to irritation and even dermatitis, but the dust that is inhaled can accumulate in the lungs and elsewhere and give rise to a variety of diseases from lead poisoning to metal fume fever. 

Figure 12.19 Phosphatidylinositol bisphosphate cycle and treatment of bipolar disease. The metal ion lithium inhibits inositol monophosphate phosphatases and, therefore, inhibits the flux from IP3 to inositol, so that the concentration of the latter decreases. This can restrict formation of phosphatidylinositol the bisphosphate (PIP ) so that the amount in the membrane decreases and the phospholipase no longer catalyses a zero order reaction. The extent of the decrease in the IP3 concentration will depend on how far the process is removed from zero order. This may explain the well-known variability in the response of patients to lithium which is probably dependent on the patient taking the precise dose of the drug (Chapter 14).

There is a common feature in the two major neurodegenerative diseases In both Alzheimer s disease (AD) and Parkinson s disease (PD) there is an imbalance of metal metabolism leading to oxidative stress-induced neuronal apoptosis. It is well known that there is no cure or efficient treatment available for these diseases. Is there a way to prevent these diseases From this review... 

The toxicity, health effects, and related symptoms of poisoning caused by different metals and metal compounds in humans is modulated by many factors. In a large number of instances, poisoning from metal compounds is because of the persistence of the metal dusts and fumes present in the workplace, as well as the properties of each metal, the pattern or route of exposure, the form and nature of the metal, and the quantity or concentration of the metal compound ingested, inhaled, or absorbed into the system. The health status of a worker modulates its toxicity. Toxic metals cause severe poisoning and skin diseases such as melanosis, leukomelanosis, keratosis, nonpitting edema, gangrene, and skin cancer. 

For hospital patients with infections, and after accidental injury or postsurgery, the systemic inflammatory response wiU affect the concentration of essential elements in circulating blood independently of nutritional status. For example, the APR causes increased permeability of capillaries and transfer of certain plasma carrier proteins and their trace metals into interstitial space. Hepatic synthesis of some plasma proteins, the so-called acute phase proteins, is also induced, so that these proteins increase in concentration in plasma, together with any metals that they carry (e.g., ceruloplasmin and copper). Moreover, there are marked changes in the kinetics of elements, with altered rates of transfer to and from the tissue. Knowledge of the effect of disease on metal kinetics and distribution is therefore essential. ... 

Polymer-based heart valves are widely used as replacements for diseased or damaged human heart valves. Most mechanical heart valves are made from metals, silicone, or polyesters, although some work has gone into incorporating biocompatible coatings such as PEO into these systems. 

West T, Weinstein J, Bray J, Shell disease and metal content of blue crabs, Callinectes sapidus, from the Albemarle-Pamlico estuarine system, North Carolina, Archives of Environmental Contamination and Toxicology, 1992, 23, 355-362. 

Anemia results from insufficient oxygen supply, often because of a decrease in hemoglobin (Hb) blood levels. Approximately 65 to 70 percent of total body iron resides in Hb. In the U.S., many foods, especially those derived from flour, are enriched in iron. In third-world countries, however, scarcity of dietary iron is a major contributor to anemia. This information illustrates one important fact about disease that results from metal deficiency, namely, the need for an adequate supply of essential metals in food. A related aspect, one of greater interest for bioinorganic chemistry, is the requirement that metals be adequately absorbed by cells, appropriately stored, and ultimately inserted into the proper environment to carry out the requisite biological function. For iron, these tasks. 

Inhaling large amounts of zinc (as zinc dust or fumes from smelting or welding) can cause a specific short-term disease called metal fume fever. Flowever, very little is known about the long-term effects of breathing zinc dust or fumes. 

Observational studies At least six types of metals are involved in aluminium smelting. The calculated reference doses for inhalation in a study in an aluminium production plant in Thailand maximum daily doses in those who were exposed to the metals are shown in Table 1 [1 ]. Workers who had been exposed to metals had a 31 times higher risk of developing diseases from aluminium than those who had not been exposed. 

Pollution caused by effluents from chemical works is not a new problem, and the discharges emanating from some of the earlier chemical factories (for example the Leblanc alkali works) were quite horrendous by modem standards. One example of a twentieth century pollution problem is provided by Minamata disease. This was caused by the discharge of mercury, used as a catalyst in a plastics factory, into Minamata Bay in Japan. Some of those who ate fish caught in the bay suffered damage to the nervous system, and some children bom to mothers who had eaten the fish had serious birth defects. Although mercury was identified as the cause of the problem in 1953, it was not understood how such low concentrations of the metal could cause such serious problems. It was only in 1969 that it was realised that the real culprit was dimethylmercury, which had been formed from metallic mercury by bacteria in the mud at the bottom of the bay. 

Grinding operations have, in the past, involved lung hazards (hard metal disease) from the abrasives in the wheel. Again, effective fixed or portable collection devices exist for grinders. 

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