Tuesday, November 19, 2013

A Comparison of the Deleterious Impact of Human Exposure to Methylmercury and PCBs

In a scientific paper entitled, Neurobehavioral toxicity of methylmercury and PCBs Effects-proļ¬les and sensitive populations authored by Dr. Christopher Newland from the Department of Psychology, Auburn University that appeared in the Journal of Environmental Toxicology and Pharmacology, the investigator compares the toxicology of methylmercury and polychlorinated biphenyls (PCBs) in human populations.
Both methylmercury and PCBs are known to be potent neurotoxic agents that have deleterious consequences in terms of the sensory, motor and cognitive abilities of those who have suffered sufficient exposure.

PCBs represent a class of compounds in which over 200 separate substances are members.  There appears to be a wide range of varying toxic effects among these substances depending upon their precise molecular structure.  However, they all bind to the aryl hydrocarbon receptor (ahr) found on the surface of mammalian cells.  Disruption of the usual binding to the Ah receptor can play havoc with the healthy functioning of the nervous system and can account for the wide-ranging toxic effects of PCBs.

Methylmercury is the toxic form of mercury that human populations are usually exposed to.  When ingested it is rapidly absorbed by the gut into the bloodstream and can penetrate the blood-brain barrier by two routes.  It can passively pass through this barrier due to its lipid solubility.  Secondarily, it can actively combine with the amino acid cystein that is one of the 20 amino acids that are the building blocks for the synthesis of proteins.  Once bound it readily penetrates the blood-brain barrier carried by a methionine transporter. The blood-brain barrier is the physiological barrier that usually protects the brain from any foreign and potentially harmful substances that may be circulating in the bloodstream.  Once within the brain the methyl group is enzymatically removed leaving the highly toxic mercury that can persist for a prolonged period of time.
According to the author, “methylmercury exposure affects the visual, auditory, and somatosensory systems.”
In addition, “Methylmercury exposure during adulthood produces a progressive and irreversible constriction of the visual field a pattern of toxicity not associated with developmental exposures. Methylmercury exposure during gestation or lactation affects higher-order visual function.”  Motor damage including nystagmus – rapid involuntary movement of the eyes -  that suggests damage to the cerebellum and cerebral palsy that suggests damage to the cerebral cortex have been shown in victims of the Minamata exposure in Japan as previously described.

Since PCBs and methylmercury contaminants are both found in fish and since seafood is the usual route of exposure of these dangerous chemicals for humans, it would be efficacious, from a public health standpoint, to examine the synergistic effects of these compounds on human health.   

Wednesday, November 13, 2013

The Legacy of Mercury Poisoning in Japan

It has been almost sixty years since medical investigators first pinpointed the nature of an apparently new illness that struck the residents of Minamata, Japan.  This disease came to be referred to as Minamata Disease.   It all seemed to have begun during the spring and summer of 1956 with the appearance of what was referred to at the time as a strange disease that impacted fishing families living in villages in and around Minamata Bay. 

The symptoms that the victims of this ailment presented were numb hands and feet, sudden difficulty in walking and a definitive impairment in speech.  Extreme cases resulted in convulsions and death.  Of the 54 cases that presented with this disease in 1956, 31% died.   This was a disturbing statistic.  This galaxy of symptoms suggested a neurological basis for the disease.

By the year’s end researches at Kumamoto University had identified the etiology of the illness as being heavy metal poisoning from the ingestion of contaminated local fish and shellfish.   This diagnosis was consistent with the evidence; heavy metals are known to play havoc with the nervous system as exemplified by lead poisoning.  It remained to discover the origin of the contamination and the offending metal.
Investigators focused on the Shin Nippon Chisso Hiryo chemical plant facility that had been known to discharge its untreated waste directed into the local waterways.   The plant owners managed to delay a thorough investigation for a number of years.  Ultimately the chemical culprit was discovered – methyl mercury, a highly toxic substance.

It was not until May of 1968 that the plant halted production of acetaldehyde that employed a mercury catalyst in its chemical synthesis.  This overdue decision finally halted its use of mercury.  Furthermore, even though it was shown that there existed a persistent contamination of  methylmercury  on the seafloor,  Minamata Bay was not closed for fishing until 1975.

To this day, the research continues regarding the long term effects of the ingestion of low levels of methyl mercury from contaminated seafood.  The controversy has not subsided regarding who has been victimized and who is liable for the costly toll on individual lives.

Friday, November 1, 2013

Viral-and Bacterial Co-infection

An unfortunate side effect of infection with the flu virus is a secondary bacterial pneumonia often called a co-infection.  This complication can prove to be very deleterious especially among at-risk populations such as the elderly.  The actual cause of this apparent increased susceptibility has not been well defined.
There are two disparate routes through which the immune system can exert its effect.  The more readily understood strategy is referred to as resistance in which the immune system is mobilized to detect the offending pathogen and eliminate it.  There is, however, another route that the immune system can take and that is tolerance in which the immune system adapts to a certain level of tissue damage inflicted by the offending organism.  Interestingly enough, the deleterious impact of infectious disease can be the result of either failed resistance or failed tolerance.

Usually, a deadly outcome of a microbial infection is relegated to either high virulence or decidedly poor resistance on the part of the host immune system.  However, there is another possible explanation.   The damage produced by an invading pathogen can be directly related to the toxins it produces, or to the inflammatory response precipitated by the immune system that can lead to tissue damage.  This latter effect is referred to as “extrinsic virulence.”  Insufficient tissue protection and subsequent repair of damaged tissue can also contribute to the lethality of the infectious process.
Dr. Amanda Jamieson and her colleagues at the Howard Hughes Medical Institute and Department of Immunobiology at the Yale University School of Medicine chose to study the co-infection of the influenza virus with Legionella pneumophila using a mouse model as a way of determining whether it is resistance or tolerance on the part of the host immune system that determines lethality.

Through their detailed studies, they found that susceptibility to co-infection occurred even when the bacterial infection was controlled by the immune system.  From this, they were able to conclude that the failure of host defenses was directly related to a diminished capacity to tolerate tissue damage.

This is a very interesting finding that may have practical implications regarding the clinical approach to patients whose health is seriously impacted by co-infection.