Toxic effects of mercury, lead and gadolinium on vascular reactivity

Heavy metals have been used in a wide variety of human activities that have significantly increased both professional and environmental exposure. Unfortunately, disasters have highlighted the toxic effects of metals on different organs and systems. Over the last 50 years, the adverse effects of chronic lead, mercury and gadolinium exposure have been underscored. Mercury and lead induce hypertension in humans and animals, affecting endothelial function in addition to their other effects. Increased cardiovascular risk after exposure to metals has been reported, but the underlying mechanisms, mainly for short periods of time and at low concentrations, have not been well explored. The presence of other metals such as gadolinium has raised concerns about contrast-induced nephropathy and, interestingly, despite this negative action, gadolinium has not been defined as a toxic agent. The main actions of these metals, demonstrated in animal and human studies, are an increase of free radical production and oxidative stress and stimulation of angiotensin I-converting enzyme activity, among others. Increased vascular reactivity, highlighted in the present review, resulting from these actions might be an important mechanism underlying increased cardiovascular risk. Finally, the results described in this review suggest that mercury, lead and gadolinium, even at low doses or concentrations, affect vascular reactivity. Acting via the endothelium, by continuous exposure followed by their absorption, they can increase the production of free radicals and of angiotensin II, representing a hazard for cardiovascular function. In addition, the actual reference values, considered to pose no risk, need to be reducedResearch supported by CAPES and CNPq/FAPES/ FUNCITEC (#39767531/07), Brazil, and MCINN (#SAF 2009-07201) and ISCIII (Red RECAVA, #RD06/0014/0011), Spai

Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems

Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. History More than 2500 A.C., the prehistoric man used the cinabrio (mercury sulfide), due to its red-gold color, to draw on cave walls and perform face painting. Subsequently, mercury has been used in the amalgamation (direct burning of metallic mercury on the gravel, promoting the separation of gold), in photography and as an antiseptic in the treatment of syphilis Exposure to mercury brought harmful effects to health of humans, but changes resulting from human exposure to mercury only called the attention of the scientific society after the accidents in Japan and Iraq Mercury Characteristics Mercury is characterized as a highly malleable liquid at normal temperature and pressure Inorganic Mercury Compounds Elemental Mercury or Metalic Mercury Compounds. In its liquid form, the elemental mercury (Hg 0 ) is poorly absorbed and presents little health risk. However, in the vapor form, metallic mercury is readily absorbed through the lungs and can produce body damage Elemental mercury is used in thermometers and sphygmomanometers because of its uniform volumetric expansion, high surface tension, and lack of vitreous adherence to surfaces. Low electrical resistance and high thermal conductivity allow metallic mercury to be used in electrical and electronic materials. Because of its high oxidation power, metallic mercury is used in electrochemical operations in the chlorine and soda industries. Metallic mercury is also used in metallurgy, mining, and dentistry because of the easy amalgam formation with other metals. In addition, gold extraction with archaic and dangerous methods predispose miners to mercury poisoning. The burning of metallic mercury on the gravel promotes the separation of gold, a process called amalgamation, which causes emission of large amounts of mercury vapor that is inhaled immediately by the miner, since they do not use appropriate personal protective equipment Mercurous Mercury and Mercuric Mercury Compounds. The mercurous mercury in the form of mercurous chloride (Hg 2 Cl 2 ) is little absorbed in the body. It is believed that in the body the form of metallic mercury is changed to elemental mercury and mercuric mercury Mercuric mercury compounds, such as mercury salts, result from the combination of mercury with chlorine, sulfur, or oxygen. Mercuric mercury can be found in different states when combined with other chemical elements, including mercuric chloride (HgCl 2 ), which is highly toxic and corrosive; mercury sulfide (HgS), which is often used as a pigment in paints due to its red color; mercury fulminate (Hg(CNO) 2 ), which is used as an explosive detonator In the cardiovascular system, acute inorganic mercury exposition in vivo promotes reduction of myocardial force development Organic Mercury. Organic mercury compounds, also called organometallic, result from a covalent bond between mercury and the carbon [8] atom of an organic functional group such as a methyl, ethyl, or phenyl group. Methylmercury (CH 3 Hg + ) is by far the most common form of organic Hg to which humans and animals are exposed. CH 3 Hg + in the environment is predominantly formed by methylation of inorganic mercuric ions by microorganisms present in soil and water Journal of Biomedicine and Biotechnology 3 The organomercury antiseptics still used are Merthiolate, Bacteran, and Thimerosal [40]. Thimerosal is an organomercurial compound that since 1930 has been widely used as a preservative in biological material such as vaccines and serums used to prevent microbiological growth Forms of Mercury Exposure Mercury is now considered an environmental pollutant of high risk to public health because of its high toxicity and mobility in ecosystems More natural sources of mercury include volcanic activity, earthquakes, erosion, and the volatilization of mercury present in the marine environment and vegetation Mercury contaminates the environment through a cycle involving the initial emission, the subsequent atmospheric circulation of the vapor form, and the eventual return of mercury to the land and water via precipitation ( Mercury present in seas and rivers after methylation can contaminate fish Transport and Elimination of Mercury Inhaled elemental mercury vapor, for example, is readily absorbed through mucous membranes and the lung and is rapidly oxidized but not as quickly as to prevent the deposition of considerable amount in the brain Then, toxicity for man varies depending on the form of mercury, dose, and rate of exposure. The target organ for inhalted mercury vapor is primarily the brain Oxidized mercury binds strongly to SH groups; this reaction can inactivate enzymes, lead to tissue damage and interfere with various metabolic processes Doses of Mercury and Safety Legislation The chemical form of mercury in the air affects its time of permanence and its dispersion in the atmosphere. The elemental mercury form can persist for more than four years in the air, while its compounds are deposited in a short time at locations near their origin. In the northern hemisphere, their average concentration in the atmosphere is estimated at 2 ng/m 3 and in the southern hemisphere is less than 1 ng/m 3 . In urban areas, there is a great variability of these concentrations being found up to 67 ng/m 3 with a mean of 11 ng/m 3 in Japan In 2004, the Joint FAO (Food and Agriculture Organization of the United National)/WHO Expert Committee on Food Additives (JECFA) established that the safe concentration of methylmercury intake, without the appearance of neurological disorders, is 1.6 mg/kg of body weight. However, in 2006, JECFA stated that this concentration is not safe for intrauterine exposure, because fetuses are more sensitive to the onset of neurological disorders after exposure to methylmercury Currently, the general population is exposed to mercury by the following main sources: the consumption of contaminated fish, the use and manipulation of dental amalgam, thimerosal contained in vaccines, workers in industries of chlorine, caustic soda, miners, and workers in industries of fluorescent lamps In Brazil, the rules for vaccination of the Ministry of Health, published in June 2001, shows that thimerosal is used in many vaccines. These vaccines prevent flu (influenza vaccine), rabies (rabies vaccine), infection with meningococcus serogroup b, and hepatitis B The US Environmental Protection Agency's recommended a reference blood concentration of mercury to be 5.8 ng/mL; concentrations below this level are considered to be safe In the following sections, we will describe results obtained from animals with chronic and acute exposure to mercury. Some of these studies were performed with mercury exposure protocols that led to blood concentrations slightly above the reference values. Nevertheless, these concentrations could be easily found in exposed populations and may even be considered low when compared with concentrations in humans who consume large amounts of fish or who live in areas contaminated with mercury. Effect of Mercury on the Central Nervous System (CNS) Among the compounds of mercury, the methylmercury is primarily responsible for the neurological alterations present in humans and experimental animals. It is believed that the mechanisms are related to the toxic increase in reactive oxygen species (ROS). Oxidative stress is associated with the etiology of neurodegenerative diseases such as amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease Reinforcing the hypothesis that the majority of injuries caused by methylmercury (MeHg) in the central nervous system are related to its ability to increase reactive oxygen species, Studies also demonstrate that mercury has the ability to reduce the number of neuron and cytoarchitecture in individuals with prenatal exposure to mercury In addition, because of its high affinity for sulfhydryl groups in tubulin, methylmercury inhibits the organization of microtubules that are important in CNS development Corroborating these findings, the study conducted by Halbach et al. [90] studied a correlation in Iraqi children between the level of maternal exposure to methylmercury during pregnancy and psychomotor retardation. SandborghEnglund et al. Effect of Mercury on the Cardiovascular System For decades, the toxic effects of mercury were associated mainly with the central nervous system; however, inorganic mercury also produces profound cardiotoxicity The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. Exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction The reduction in glutathione peroxidase with seleniumdependent activity is the result of the decreased bioavailability of selenium, a molecule that is required for enzymatic activity Cardiovascular changes resulting from mercury poisoning are also described in animal models. However, the mechanism involved in the effects of mercury on the cardiovascular system is not fully understood but seems to be dependent on both the dose and time of exposure. Raymond and Ralston [123] studied the hemodynamic effects of an intravenous injection of HgCl 2 (5 mg/kg) in rats and observed that mercury produced cardiac diastolic failure and pulmonary hypertension. Moreover, Naganuma et al. Our group has found that chronic exposure to low doses of mercury (1st dose 4.6 μg/kg followed by 0.07 μg/kg/day for 30 days, im) attained a blood mercury concentration of approximately 8 ng/mL, a concentration similar to the levels found in exposed humans. This exposure produced a negative inotropic effect in perfused hearts, although increasing myosin ATPase activity. Invivo, arterial or ventricular pressures did not change The chronic exposure to low concentrations of mercury was also able to induce endothelial dysfunction in resistance and conductance vessels, most likely because of the decreased nitric oxide (NO) bioavailability due to the increased superoxide anion (O 2 •− ) production from NADPH oxidase Taken together, these data show that chronic low doses of mercury have an important and deleterious effect on vascular function by reducing NO bioavailability. The degree of severity of mercury exposure is comparable to traditional cardiovascular risk factors, such as hypertension diabetes or hypercholesterolemia. Therefore, mercury could be considered an important risk factor for cardiovascular disease that could play a role in the development of cardiovascular events. The association between mercury exposure and an increased risk of developing cardiovascular and neurological diseases is apparent. Thus, continuous exposure to mercury can be dangerous, and current reference values, once considered to be without risk, should be reevaluated and reduced

Checklist of the dipterofauna (Insecta) from Roraima, Brazil, with special reference to the Brazilian Ecological Station of Maracá

Roraima is a Brazilian state located in the northern portion of the Amazon basin, with few studies regarding its biodiversity. The Ecological Station of Maracá (Brazil, state of Roraima) harbors the third largest Brazilian pluvial island and is composed of a transitional landscape of savanna and Amazon rainforest components. Despite its ecological importance and strategic localization, few studies covered the dipterofauna of this locality. An updated checklist addressing 41 families of true flies (Diptera) occurring in Roraima is presented based on the literature and the specimens collected during a field expedition that occurred in 2015. This checklist brings several improvements such as new records of 165 taxa to the state of Roraima, 29 taxa to Brazil, and 259 morphotypes, mostly likely representing undescribed species

Intestinal barrier interactions with specialized CD8 T Cells

Copyright: © 2017 Konjar, Ferreira, Blankenhaus and Veldhoen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The trillions of microorganisms that reside in the gastrointestinal tract, essential for nutrient absorption, are kept under control by a single cell barrier and large amounts of immune cells. Intestinal epithelial cells (IECs) are critical in establishing an environment supporting microbial colonization and immunological tolerance. A large population of CD8+ T cells is in direct and constant contact with the IECs and the intraepithelial lymphocytes (IELs). Due to their location, at the interphase of the intestinal lumen and external environment and the host tissues, they seem ideally positioned to balance immune tolerance and protection to preserve the fragile intestinal barrier from invasion as well as immunopathology. IELs are a heterogeneous population, with a large innate-like contribution of unknown specificity, intercalated with antigen-specific tissue-resident memory T cells. In this review, we provide a comprehensive overview of IEL physiology and how they interact with the IECs and contribute to immune surveillance to preserve intestinal homeostasis and host-microbial relationships.Members of the Veldhoen laboratory are supported by European Union H2020 ERA project (N°667824—EXCELLtoINNOV), publication costs were provided by LISBOA-01-0145-FEDER-007391, projeto cofinanciado pelo FEDER através POR Lisboa 2020—Programa Operacional Regional de Lisboa, do PORTUGAL 2020, e pela Fundação para a Ciência e a Tecnologia.info:eu-repo/semantics/publishedVersio

Information vs Engagement in parliamentary websites – a case study of Brazil and the UK

Parliamentary websites have become the main window of parliament to the outside world. More than a gimmick, they are an essential element in the promotion of a relationship between parliament and citizens. This paper develops a comparative analysis of the websites of the lower chambers of the Brazilian and the British parliaments, respectively the Chamber of Deputies and the House of Commons. We structure this analysis around three dimensions: 1) information about the institution; 2) information about parliamentary activity; and 3) tools to promote engagement with the public. The choice of two very different case studies enables us to consider more clearly the specific purposes of these parliamentary websites. We consider in particular if these parliaments' institutional differences affect their websites. The websites' analysis is complemented by semi-structured elite interviews with parliamentary staff who manage the services provided by these websites. Our analysis shows that both websites achieve much higher levels of complexity in the information area than in engagement. But it also shows that the Brazilian parliament website includes far more tools designed for public interaction than its UK counterpart. The indexes and interviews show that both institutions are highly committed to disseminating data and information to citizens. This is seen as a path towards achieving higher accountability and improving knowledge about parliamentary processes and, consequently, improving public image and levels of trust. Whilst there is a strong focus on the provision of information, there is still little evidence of enabling citizen participation in the legislative process. This is partly due to a tension between conceptions of representative democracy and those of participatory democracy. The articulation between these different types of democracy still has a long way to be resolved, although parliaments are slowly introducing participatory tools