Telling about Mercury (Hg) to future docs in Amazon

UFAM-Brazil team is has an interesting diversity is its students skills (see our team section). Majors and minors of all sort: biology, biotechnology, computer science, engineering, mathematics, arts, design and also medicine. The medicine student proposed to the group a nice twist in our outreach: a material orientated for medicine students regarding to Hg contamination.

Hg contamination has lots of implications for the Amazon region as we already discussed here in this Wiki, however doctors and medicine students are not alerted as should be about it and even some diagnosis are misleading over time and people who has symptoms are not properly treated. This occurs mainly because the Hg contamination is a topic “hidden underneath carpet” and not well divulgated or discussed. In Amazon the natural levels of Hg are high due to the soil and water constitution, which bring concerns since the gold harvesting activity is much spread and are based in Hg use, bring the rates of this element beyond the acceptable by the World Human Organization (WHO).

Our Human Practice found out this could be a great chance of talk about the problem and show how is the state of the art in this field including show the Mercury Bacter project.

This approach couldn’t have gone better! The med students loved it, they got to know about the Hg and gold mining issues for environment and human health and they had lots of fun learning about our project and about SynBio!

For that we prepared a concise material about Hg and relations with the medical field to show to the future docs. This material is below in detail. We give one advice to future teams working in environmental topics: these issues are highly related to human health problems and are great to include future docs in your team; they give an interesting perspective to the whole thing! We got so lucky on that… our team mate from medical school also participated and contributed a lot with our Modeling (colocar hyperlink do modeling), so they can be math docs also. ;-)

Following material from our outreach design for the human health community and taught for our university future docs!

Methylmercury Poisoning

Context

Gold digging grew severely in the emergent countries at the end of XX century. In the process of extracting the gold, mercury (Hg) is used a lot, most of the time without the proper care, the pure metal is discarded in the nature where it becomes a potential intoxicating agent. The potential is so high that, even through processes such as oxidation and methylation, through biochemicals and metabolic reactions measured mainly by bacteria.

Figure 1 - Man in gold prospection.

In addition to the disposal process itself in nature, another phenomenon is responsible for the ability of mercury poisoning: bioaccumulation. Its main result is the accumulation of mercury, especially in its methylated form in fish, which has a direct effect on the lives of the local population, which has fish in their food base. As shown in Nogueira et al. (1997), Pinheiro et al. (2000) and Boischio et al. (2000), high levels of mercury found in the hair of both riverine populations as the population of the great capitals of the Amazon, Manaus and Belém as indicating that the risk of contamination with heavy metal is real and must be addressed seriously by public health policies directed toward mercury in the Amazon region.

Figure 2 - Just a little humor...

The attention in public health for methylmercury poisoning (MeHg) through the consumption of contaminated foods, such as fish, only if initiated after acute poisoning events happening in the city of Minamata, Japan, in 1953, which gave rise to current name given to the syndrome of intoxication by methylmercury, known as Minamata disease In this locality, chemical companies had MeHg as a major waste and discarded them in Bay City, Bay of Minamata. The high levels of MeHg led to several cases, once enigmatic, neurological deficits in the population of the city, giving rise to the disease in its most acute form. However, after years, the chemical industry in the region was growing and in order to maintain higher productivity, the industry chose the Minamata River, which flowed into the Shiranui Sea, as the discharge point. This led to a whole contamination of fish in the sea and, like fishing in the locality was unrestrained at the time, entire families on this coast were being exposed to contaminated food and slowly were intoxicating themselves, giving rise to chronic poisoning by 20 years after the wasting begun.

Epidemiology

In conjunction with the local population in the Amazon region, we have the main route of contamination it is the excessive ingestion of fish in the area, these often highly contaminated with high concentrations of mercury due to the phenomenon of bioaccumulation, however, ingestion of fish marine or other seafood are also able to intoxicate, and the presence of MeHg in some pesticides and fungicides. For study purposes, the calculation of the concentration of MeHg in hair of patients is guide for estimating patient exposure to sources of MeHg. A study in the city of Manaus, Amazonas, UFAM_Brazil headquarters staff, by Farias et al. (2012), assesses the levels of Hg and MeHg found in the hair of children in the city. This study showed that the concentration of these metals in the hair of children in Manaus is a higher than average in other regions of the country, and in the riverines this concentration is even higher. In addition, the study was able to confirm the thesis that MeHg levels in hair are directly related to the diet of the population, which is based on fish, great source of MeHg.

Figure 3 - Indigenous Child.

Figure 4 - Typical meal based on fish from the river.

Pharmaco-toxicokinetics

After ingestion of contaminated food, about 95% of the levels found MeHg are absorbed quite rapidly in gastro-intestinal tract through alternative forms linked to amino acids such as MeHg-cysteine and MeHg-glycine. Once adsorbed onto and into the bloodstream just over 90% of MeHg is inside the red blood cells in a ratio of approximately 10-20:1.

The circulation to the liver, where it can spread to all tissues of the body. Acquiring a form of thiol conjugate that possesses similar to the amino acid methionine way MeHg can overcome the blood-brain barrier, so they are easily accumulated in nervous tissue, since its biotransformation into Hg²⁺ is slow explaining levels higher MeHg in the CNS (Central Nervous System) in the rest of the body. The MeHg can also cause damage to the kidney tissue quite rapidly, reaching stable levels within 3 hours after intoxication.

Figure 5 - Blood-Brain Barrier.

Finally, MeHg can be either excreted into bile as urine, representing respectively 90% and 10% of excretion pathways MeHg its half-life in blood is around 40-50 days, while the half-life considering the body as a whole is around 70-80 days. However, regarding the excretion through the bile duct, it is much less developed in infants due to its immaturity of the gut enterocytes, reabsorption of what was occurring secreted into bile.

Physio-pathology and clinical signals

The ability to cross the blood-brain barrier is the main feature which makes MeHg dangerously toxic. Their actions in the CNS are due to their ability to form sulfo-metal bonds with sulfhydryl groups of certain groups of cytoskeletal proteins in nerve cells, such as tubulin, affecting the normal formation of the central nervous system due to changes in capabilities division and migration of such cells, even MeHg is also toxic to the subject to its CNS. This fact explains why many studies prove that MeHg is more toxic during the prenatal period and during childhood, and is considered a powerful teratogenic agent.

Figure 6 – MeHg, a powerful teratogenic agent.

Figure 7 - Microtubules Structure.

Figure 8 - Neuron with its cells and associated structures.

The damage and cell loss, both as neurons of glia cells, due to the toxic effect of MeHg are represented macroscopically with loss of cortical areas of the CNS, both the telencephalon cerebellum as leading to disastrous consequences depending on the region that was affected. Besides the adverse effect on the CNS are also neurotoxic effects noted in the region of spinal ganglia, with a special preference for the dorsal column sensory ganglia.

Figure 9 - Specimen with diffuse brain lesions and atrophy process characteristics of mercury poisoning.

Poisoning can be divided into: acute or chronic high-dose or chronic low doses of MeHg exposure exhibitions. The cases of exposure to high doses are known primarily related to two fated incidents involving intoxication by mass MeHg as the aforementioned case of Minamata Bay, Japan period 1953-1956, and in the rural environment of the early Iraq 1970s the consequences derived from contact with excessive amounts of MeHg, especially of neurological character, were observed steeper when there was exposure during the prenatal period through maternal contamination. Cases where mothers were asymptomatic or had mild signs of intoxication were not unusual, giving birth to offspring with severe neurological disorders such as mental retardation, deafness, blindness, cerebral palsy, cerebellar ataxia, strabismus, dysarthria, among others. Poisoning by high levels of MeHg is rare nowadays.

Chronic poisoning due to exposure to low doses of MeHg are targets of ongoing studies, we still do not reach on an agreement, to assess their true risk (Clifton 2007). However, the teratogenicity of MeHg in the formation of the CNS is unquestionable in the scientific community, which explains the intense activities to try to relate exposure to low levels of MeHg and neurophysiological, neuropsychiatric disorders or neuroanatomical. To our reality in the study UFAM_Brazil team, river dwellers of the Amazonian areas would be much more common to show signs of chronic intoxication by low levels of MeHg, which therefore means that we have more attention to this type of case. According Ekino et al (2007), serious mental disorders and motor development in fetuses that were contaminated with MeHg through maternal exposure and the ability to overcome the uterus-placenta were observed. Such disturbances were connected bilaterally with:

• Swallow Deficit

• Speech Deficit

• Walking Deficit

• Deficit in other coordinated or involuntary movements

• Epileptic seizures

All due to acute injuries in the encephalon, causing loss of brain mass in determined cortex areas. Besides pure neurological symptoms, many neuropsychiatric symptoms were seen on children that were conceived by mothers who were exposed to large amounts of MeHg during their prenatal lives, such as:

• Akinetic mutism

• Extreme shame

• Communication difficulties

• Lack of initiative

• Lack of facial expression

Figure 10 - Extreme shyness may be related to MeHg intoxication.

Poisoning by chronic exposure to low doses of MeHg also has the ability to cause harm to adults, even if not to the same severity in relation to fetal intoxication. According to yet Ekino et al. (2007), patients whose MeHg exposure time was prolonged at low doses reported cases in the distal regions of paresthesia of extremities, and around the lip region, even if exposure to the toxic agent has already ended 30 years.

The somatosensory disorders are thus the main manifestation of neuropathies derived from MeHg poisoning. Their distribution pattern is a "stocking-glove", similar to the pattern found in peripheral neuropathies, however, due to the presence of the normal reflexes of the tensions of the members of patients whose chief complaint was paresthesia, canceled the diagnosis of this hypothesis, since it occurs in fact, diffuse lesion in the somatosensory cortex, represented by Brodmann areas 1, 2, 3. To measure such disturbances are measured thresholds of touch and two-point discrimination.

Figure 11 - Standard neuropathies Stocking-Glove.

Figure 12 – Brodmann map.

The threshold of touch, in general, becomes high in general in the whole body, including distal and proximal regions, again in contrast with the characteristics of peripheral neuropathy, only where there is an increased threshold at the ends. The threshold for two-point discrimination, or epicritical touch, was found to be twice also generalized way. Regions such as the tongue, lips, fingers and thumb represent areas with the greatest loss of sensitivity due to the fact these possess large areas in the cortex devoted to their sensitivity. Besides affecting the somatosensory cortex, MeHg poisoning is also capable of causing damage to the granular layer of the cerebellum, generating a phenomenon called cerebellar ataxia, which is characterized by lack of coordination of voluntary muscle movement, balance and planning movements. Finally, damage to various areas of the cortex, such as the primary visual area in the occipital lobe, or primary auditory area in the temporal lobe may cause damage corresponding to the area in which they are working and causing symptoms such as loss of visual acuity, acoustic, among others.

REFERENCES

1. BOISCHIO, A. A. P.; CERNICHIARI, E.; HENSHEL, D. Segmental hair mercury evaluation of a single family along the Upper Madeira Basin, Brazilian Amazon. Cad. Saúde Pública, Rio de Janeiro, v. 16, n. 3, p. 681-686, jul./set. 2000.

2. CLIFTON, J. C. Mercury Exposure and Public Health. Pediatr. Clin. N. Am., v. 54, p. 237–269, 2007.

3. EKINO, S. et al. Minamata disease revisited: An update on the acute and chronic manifestations of methyl mercury poisoning. Journal of the Neurological Sciences, v. 262, p. 131–144, 2007.

4. FARIAS, L. A. et al. Mercury and methylmercury concentration assessment in children’s hair from Manaus, Amazonas State, Brazil. Acta Amazonica, v. 42, n. 2, p. 279–286.

5. HACON S. et al. An overview of mercury contamination research in the Amazon basin with an emphasis on Brazil. Cad. Saúde Pública, Rio de Janeiro, v. 24, n. 7, p. 1479-1492, jul. 2008.

6. NOGUEIRA, F. et al. Total mercury in hair: a contribution to the evaluation of mercury exposure levels in Poconé, Mato Grosso, Brazil. Cad. Saúde Pública, Rio de Janeiro, v. 13, n. 4, p. 601-609, out./dez. 1997.

7. PASSOS, C. J. S.; MERGLER, D. Human mercury exposure and adverse health effects in the Amazon: a review. Cad. Saúde Pública, Rio de Janeiro, sup. 4, v. 24, p. 503-520, 2008.

8. PINHEIRO, M. C. N. et al. Methylmercury human exposure in riverine villages of Tapajos basin, Pará State, Brazil. Revista da Sociedade Brasileira de Medicina Tropical, v. 33, n. 3, p. 265-269, mai./jun. 2000.

9. PINHEIRO, M. C. N. et al. Total mercury in hair samples of inhabitants of Tapajós river, Pará State, Brazil. Revista da Sociedade Brasileira de Medicina Tropical, v. 33, n. 2, p. 181-184, mar./abr. 2000.

10.SANTOS, E. O. et al. Correlation between blood mercury levels in mothers and newborns in Itaituba, Pará State, Brazil. Cad. Saúde Pública, Rio de Janeiro, sup. 4, v. 23, p. 622-629. 2007.