Stanford Moore, William Stein, and Anfinsen were awarded the Nobel Prize in Chemistry in 1972 for \"their contribution\n to the understanding of the connection between chemical structure and catalytic activity of the active center of the ribonuclease\n molecule.\" In his Nobel Lecture, Anfinsen provided a sketch of the rich history of research that provided the foundation\n for his work on protein folding and the \"Thermodynamic Hypothesis,\" and outlined potential avenues of current and\n future scientific exploration.

https://web.iitd.ac.in/~amittal/1973_Anfinsen_Science.pdf

Principles that Govern the Folding of Protein Chains

The main threats to human health from heavy metals are associated with exposure to lead, cadmium, mercury and arsenic. These metals have been extensively studied and their effects on human health regularly reviewed by international bodies such as the WHO. Heavy metals have been used by humans for thousands of years. Although several adverse health effects of heavy metals have been known for a long time, exposure to heavy metals continues, and is even increasing in some parts of the world, in particular in less developed countries, though emissions have declined in most developed countries over the last 100 years. Cadmium compounds are currently mainly used in re-chargeable nickel-cadmium batteries. Cadmium emissions have increased dramatically during the 20th century, one reason being that cadmium-containing products are rarely re-cycled, but often dumped together with household waste. Cigarette smoking is a major source of cadmium exposure. In non-smokers, food is the most important source of cadmium exposure. Recent data indicate that adverse health effects of cadmium exposure may occur at lower exposure levels than previously anticipated, primarily in the form of kidney damage but possibly also bone effects and fractures. Many individuals in Europe already exceed these exposure levels and the margin is very narrow for large groups. Therefore, measures should be taken to reduce cadmium exposure in the general population in order to minimize the risk of adverse health effects. The general population is primarily exposed to mercury via food, fish being a major source of methyl mercury exposure, and dental amalgam. The general population does not face a significant health risk from methyl mercury, although certain groups with high fish consumption may attain blood levels associated with a low risk of neurological damage to adults. Since there is a risk to the fetus in particular, pregnant women should avoid a high intake of certain fish, such as shark, swordfish and tuna; fish (such as pike, walleye and bass) taken from polluted fresh waters should especially be avoided. There has been a debate on the safety of dental amalgams and claims have been made that mercury from amalgam may cause a variety of diseases. However, there are no studies so far that have been able to show any associations between amalgam fillings and ill health. The general population is exposed to lead from air and food in roughly equal proportions. During the last century, lead emissions to ambient air have caused considerable pollution, mainly due to lead emissions from petrol. Children are particularly susceptible to lead exposure due to high gastrointestinal uptake and the permeable blood-brain barrier. Blood levels in children should be reduced below the levels so far considered acceptable, recent data indicating that there may be neurotoxic effects of lead at lower levels of exposure than previously anticipated. Although lead in petrol has dramatically decreased over the last decades, thereby reducing environmental exposure, phasing out any remaining uses of lead additives in motor fuels should be encouraged. The use of lead-based paints should be abandoned, and lead should not be used in food containers. In particular, the public should be aware of glazed food containers, which may leach lead into food. Exposure to arsenic is mainly via intake of food and drinking water, food being the most important source in most populations. Long-term exposure to arsenic in drinking-water is mainly related to increased risks of skin cancer, but also some other cancers, as well as other skin lesions such as hyperkeratosis and pigmentation changes. Occupational exposure to arsenic, primarily by inhalation, is causally associated with lung cancer. Clear exposure-response relationships and high risks have been observed.

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Hazards of heavy metal contamination.

Heavy metals are naturally occurring elements that have a high atomic weight and a density at least five times greater than that of water. Their multiple industrial, domestic, agricultural, medical, and technological applications have led to their wide distribution in the environment, raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the US Environmental Protection Agency and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity.

/pdf/heavy-metal-toxicity-and-the-environment-32mfkxp6nb.pdf

Heavy metal toxicity and the environment.

Oxidative mechanisms in the toxicity of metal ions

Reactive oxygen species (ROS) are produced as a normal product of plant cellular metabolism. Various environmental stresses lead to excessive production of ROS causing progressive oxidative damage and ultimately cell death. Despite their destructive activity, they are well-described second messengers in a variety of cellular processes, including conferment of tolerance to various environmental stresses. Whether ROS would serve as signaling molecules or could cause oxidative damage to the tissues depends on the delicate equilibrium between ROS production, and their scavenging. Efficient scavenging of ROS produced during various environmental stresses requires the action of several nonenzymatic as well as enzymatic antioxidants present in the tissues. In this paper, we describe the generation, sites of production and role of ROS as messenger molecules as well as inducers of oxidative damage. Further, the antioxidative defense mechanisms operating in the cells for scavenging of ROS overproduced under various stressful conditions of the environment have been discussed in detail.

https://downloads.hindawi.com/archive/2012/217037.pdf

Reactive Oxygen Species, Oxidative Damage, and Antioxidative Defense Mechanism in Plants under Stressful Conditions

This review covers the toxicology of mercury and its compounds. Special attention is paid to those forms of mercury of current public health concern. Human exposure to the vapor of metallic mercury dates back to antiquity but continues today in occupational settings and from dental amalgam. Health risks from methylmercury in edible tissues of fish have been the subject of several large epidemiological investigations and continue to be the subject of intense debate. Ethylmercury in the form of a preservative, thimerosal, added to certain vaccines, is the most recent form of mercury that has become a public health concern. The review leads to general discussion of evolutionary aspects of mercury, protective and toxic mechanisms, and ends on a note that mercury is still an "element of mystery."

The Toxicology of Mercury and Its Chemical Compounds

Essentiality Toxicity Carcinogenicity Lead(Pb) Exposure Toxicokinetics Toxicity Neurologic, Neurobehavioral, and Developmental Effects in Children Mechanisms of Effects on the Developing Nervous System Peripheral Neuropathy Hematologic Effects Renal Toxicity Lead and Gout Effects on Cardiovascular System Immunotoxicity Bone Effects Reproductive Effects Birth Outcomes Carcinogenicity Other Effects Dose Response Treatment Organic Lead Compounds Mercury (Hg) Exposure Disposition and Toxicokinetics Metabolic Transformation Cellular Metabolism Toxicology Biological Indicators Treatment Nickel (Ni) Exposure Toxicokinetics Essentiality Toxicity Nickel Carbonyl Poisoning Dermatitis Indicators of Nickel Toxicity

/pdf/toxic-effects-of-metals-2t2btb1i7f.pdf

Toxic effects of metals

ercury has been used commercially and medically for centuries. In the past it was a common constituent of many medications. It is still used in hospitals in thermometers and blood-pressure cuffs and commercially in batteries, switches, and fluorescent light bulbs. Large quantities of metallic mercury are employed as electrodes in the electrolytic production of chlorine and sodium hydroxide from saline. These uses still give rise to accidental and occupational exposures. 1 Today, however, exposure of the general population comes from three major sources: fish consumption, dental amalgams, and vaccines. Each has its own characteristic form of mercury and distinctive toxicologic profile and clinical symptoms. Dental amalgams emit mercury vapor that is inhaled and absorbed into the bloodstream. Dentists and anyone with an amalgam filling are exposed to this form of mercury. Liquid metallic mercury (quicksilver) still finds its way into homes, causing a risk of poisoning from the vapor and creating major cleanup costs. Humans are also exposed to two distinct but related organic forms, methyl mercury (CH 3 Hg + ) and ethyl mercury (CH 3 CH 2 Hg + ). Fish are the main if not the only source of methyl mercury, since it is no longer used as a fungicide. In many countries, babies are exposed to ethyl mercury through vaccination, since this form is the active ingredient of the preservative thimerosal used in vaccines. Whereas removal of certain forms of mercury, such as that in blood-pressure cuffs, will not cause increased health risks, removal of each of the three major sources described in this article entails health risks and thus poses a dilemma to the health professional. Exposure to mercury from dental amalgams and fish consumption has been a concern for decades, but the possible risk associated with thimerosal is a much newer concern. These fears have been heightened by a recent recommendation by the Environmental Protection Agency (EPA) that the allowable or safe daily intake of methyl mercury be reduced from 0.5 µg of mercury per kilogram of body weight per day, the threshold established by the World Health Organization in 1978, 2 to 0.1 µg of mercury per kilogram per day. 3 Table 1 summarizes the clinical toxicologic features of mercury vapor and methyl and ethyl mercury. It also includes data on inorganic divalent mercury, since this is believed to be the toxic species produced in tissues after inhalation of the vapor. 5 It is also responsible for kidney damage after exposure to ethyl mercury, since ethyl mercury is rapidly converted to the inorganic form. 13 Inorganic mercury as both mercuric and mercurous salts was also the chief cause of acrodynia, a childhood disease that is now mainly of historical interest. 14 The clinical symptoms of acrodynia consist of painful, red, swollen fingers and toes in association with photophobia, irritability, asthenia, and hypertension. It is believed to be a hypersensitivity reaction. m

/pdf/the-toxicology-of-mercury-current-exposures-and-clinical-3hdhs96jay.pdf

The toxicology of mercury--current exposures and clinical manifestations.

https://science.sciencemag.org/content/sci/181/4096/230.full.pdf

Methylmercury Poisoning in Iraq

The three modern "faces" of mercury are our perceptions of risk from the exposure of billions of people to methyl mercury in fish, mercury vapor from amalgam tooth fillings, and ethyl mercury in the form of thimerosal added as an antiseptic to widely used vaccines. In this article I review human exposure to and the toxicology of each of these three species of mercury. Mechanisms of action are discussed where possible. Key gaps in our current knowledge are identified from the points of view both of risk assessment and of mechanisms of action.

Thomas W. Clarkson

Papers

The Toxicology of Mercury and Its Chemical Compounds

Toxic effects of metals

The toxicology of mercury--current exposures and clinical manifestations.

Methylmercury Poisoning in Iraq

The three modern faces of mercury.