The GSTP1 rs1695 Polymorphism Is Associated with Mercury Levels and Neurodevelopmental Delay in Indigenous Munduruku Children from the Brazilian Amazon.

Genetic polymorphisms may influence mercury (Hg) toxicity. The aims of this study were to evaluate individual factors, such as the presence of the GSTP1 rs1695 polymorphism, associated with internal Hg dose and child neurodevelopment in indigenous people from the Brazilian Amazon chronically exposed to Hg. Eighty-two indigenous children were clinically evaluated, hair Hg was measured, and the GSTP1 rs1695 polymorphism was genotyped. The mean age was 4.8 years, the median Hg was 5.5 µg/g, and 93.8% of children exceeded the safe limit (2.0 µg/g). Fish consumption was associated with Hg levels (p = 0.03). The GSTP1 rs1695 A>G polymorphism was in the Hardy-Weinberg equilibrium and the highest prevalence of the GSTP1 AA genotype (80%) was found in Sawré Aboy, which had the highest Hg levels (10 µg/g) among the studied villages. The Hg levels tended to increase over the years in males and in carriers of the GSTP1 AA genotype (0.69 µg/g and 0.86 µg/g, respectively). Nine children failed the neurodevelopmental test, all of whom had Hg > 2.0 µg/g, and 88.9% carried the GSTP1 AA or AG genotypes, previously associated with the highest internal Hg doses and neurocognitive disorders. The genetic counseling of this population is important to identify the individuals at greater risk for neurodevelopmental disorders resulting from chronic Hg exposure.

Single-Nucleotide Polymorphisms Associated with Mercury Levels and Neurological Symptoms: An Overview.

Mercury (Hg) pollution is a global public health concern because of its adverse effects on the environment and health. Single-nucleotide polymorphisms (SNPs) have been associated with Hg levels and outcomes. The aim of this review was to describe the research and discuss the evidence on the genetic susceptibility of Hg-exposed individuals to the development of neurocognitive disorders. A systematic review was performed to identify the genes/SNPs associated with Hg toxicokinetics and that, therefore, affect neurological function in exposed populations. Observational and experimental studies were identified by screening three databases. Thirteen articles were included (quality score 82-100%) and 8124 individuals were evaluated. Hg exposure was mainly fish consumption (77%) and, in 31% of the studies, the Hg levels exceeded the reference limits. Genetic susceptibility to higher Hg levels and neurotoxicity risk in Hg poisoning were associated with eight (ALAD rs1800435, CYP3A4 rs2740574, CYP3A5 rs776746, CYP3A7 rs2257401, GSTP1 rs1695, MT1A rs8052394, MT1M rs2270836, and MT4 rs11643815) and three (MT1A rs8052394, MT1M rs2270837, and MT2A rs10636) SNPs, respectively, and rs8052394 was associated with both outcomes. The MT1A rs8052394 SNP may be used as a susceptibility biomarker to identify individuals at greater risk for higher Hg levels and the development of neurocognitive disorders in metal-exposed populations.

Long-Term Environmental Methylmercury Exposure Is Associated with Peripheral Neuropathy and Cognitive Impairment among an Amazon Indigenous Population.

Widespread contamination of the Amazon basin with mercury has been reported to occur since at least the mid-80s due to heavy gold mining activity. Although initial studies have indicated that this may lead to deleterious neurological consequences to the indigenous populations living in the region, further research is needed to better characterize the neurological burden of such long-term exposure. With this aim, a cross-sectional exploratory study has been conducted with the Yanomami indigenous population residing in a northern Amazon region. All participants underwent a structured interview; detailed neurological examination, including assessment for cognitive, motor, coordination, and sensory functions; and laboratorial testing for serum hemoglobin, blood glucose, and methylmercury levels in hair samples. This study enrolled 154 individuals of 30.9 ± 16.8 years of age, of which 56.1% were female. Mean methylmercury levels in hair were 3.9 ± 1.7 µg/g. Methylmercury levels in hair > 6.0 µg/g were found in 10.3%. Among participants with hair methylmercury levels ≥ 6.0 µg/g, the prevalences of peripheral neuropathy and reduced cognitive performance were, respectively, 78.8% (95%CI 15-177%, p = 0.010) and 95.9% (95%CI 16-230.8%, p = 0.012) higher than those of individuals with lower levels. These results suggest that chronic mercury exposure may lead to significant and potentially irreversible neurotoxicity to Yanomami population living in the northern Amazon basin.

Risk Assessment of Mercury-Contaminated Fish Consumption in the Brazilian Amazon: An Ecological Study.

Mercury is one of the most dangerous contaminants on the planet. In recent years, evidence of mercury contamination in the Amazon has significantly increased, notably due to gold-mining activities. Although mercury contamination in fish has consistently been documented, little is known about the risk associated with fish consumption by populations in urban areas of the Amazon. We sampled 1010 fish sold in public markets in six state capitals and 11 additional cities. Mercury levels were determined for each specimen, and the evaluation of the health risks associated with consuming mercury-contaminated fish was conducted according to the methodology proposed by the World Health Organization (WHO). Our study reveals that more than one-fifth (21.3%) of the fish sold in urban centers had mercury levels above the safe limits (≥0.5 µg/g) established by the Brazilian Health Surveillance Agency (ANVISA). The prevalence of Hg contamination ≥0.5 µg/g was approximately 14 times higher in carnivorous than in noncarnivorous fish. The analysis of the risk attributable to fish consumption reveals that daily mercury intake exceeded the reference dose recommended by the U.S. EPA in all population groups analyzed, reaching up to 7 and 31 times in women of childbearing age and children from 2 to 4 years old, respectively. However, these risks are diverse depending on the type of fish consumed and must be considered to formulate appropriate nutritional guidelines for safe fish consumption by the local community.

Chronic Mercury Exposure and GSTP1 Polymorphism in Munduruku Indigenous from Brazilian Amazon.

Genetic polymorphisms may be involved with mercury levels and signs and symptoms of intoxication from this exposure. Therefore, the aims were to describe the frequency of the GSTP1 polymorphism and to evaluate its effects on mercury levels and neurological signs in three Munduruku indigenous villages in the Brazilian Amazon. One-hundred-and-seven indigenous (over 12 years old) were included and genotyped (rs1695) using a TaqMan validated assay. Then, associations were evaluated by binary logistic regression, using odds ratios (OR) and 95% confidence intervals (CI). Mean age was 27.4 ± 13.9 years old, 52.3% were male, mean hair mercury concentration was 8.5 ± 4.3, exceeding the reference limit (≥6.0 µg/g), and were different among the three villages: 13.5 ± 4.6 µg/g in Sawré Aboy, 7.4 ± 2.3 µg/g in Poxo Muybu and 6.9 ± 3.5 µg/g in Sawré Muybu. The minor allele frequency of GSTP1 G was significantly different among the villages: 57% Sawré Muybu, 21% Poxo Muybu and 15% Sawré Aboy. Finally, after adjustment, GSTP1 GG and GA genotypes were associated with lower levels of Hg (OR = 0.13; CI95% = 0.03-0.49) and abnormal somatosensory signs (OR = 3.7; 95%IC = 1.5-9.3), respectively. In conclusion, monitoring this population is imperative to identify individuals at higher risk of developing signs of chronic mercury exposure based on the genetic profile.

Health Risk Assessment Attributed to Consumption of Fish Contaminated with Mercury in the Rio Branco Basin, Roraima, Amazon, Brazil.

The aim of this study was to assess the health risk attributable to the consumption of mercury-contaminated fish for the urban and non-urban populations living in the Roraima state, Amazon, Brazil. Seventy-five fish specimens distributed across twenty different species, comprising four trophic levels (i.e., herbivore, omnivore, detritivore, and carnivore), were collected at four locations in the Branco River Basin. The fish samples were sent to the Toxicology Laboratory at Evandro Chagas Institute to determine the total-Hg levels by using the cold vapor atomic system (CVAAS). The total-Hg levels ranged from 0 to 3.159 µg/g. The average concentration in non-carnivorous species (n = 32) was 0.116 µg/g, and among carnivorous fish (n = 43), it was 0.869 µg/g. The weighted average of contamination levels for all samples was 0.545 µg/g. The health risk assessment was conducted according to the methodology proposed by the World Health Organization and different scenarios of human exposure were considered, based on three levels of fish consumption (low: 50 g/day; moderate: 100 g/day and high: 200 g/day). Women of childbearing age ingest 5 to 21 times more mercury than the dose considered safe by the U.S. EPA and intake a dose from 2 to 9 times higher than the safe dose proposed by FAO/WHO. Children under 5 years of age ingest from 18 to 75 times the dose proposed by the U.S. EPA and from 8 to 32 more mercury than the limit proposed by FAO/WHO. In summary, regardless of the level of fish consumption, type of residency (urban or non-urban), and the subset of the population analyzed, anyone who consumes fish from the locations sampled is at high risk attributable to mercury ingestion, with the only exception of adult men, who consume an average of 50 g of fish per day.

Comparison of Salivary Electrolytes Profile in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma.

OBJECTIVES: to determine salivary electrolyte concentration of oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) patients. A related systematic review was performed. METHODS: Observational study. Unstimulated saliva from 18 patients with OSCC, 18 with OPMD, and 18 without oral lesions was collected. A biochemical analysis was performed to evaluate the salivary concentrations of potassium (K), phosphorus (P), sodium (Na), calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), and iron (Fe). Kruskal-Wallis test was performed, and p < 0.05 was interpreted as statistically significant. The literature search for the systematic review retrieved 9 studies that associated salivary electrolyte levels with presence and progression of OSCC. RESULTS: A highly significant increase was found in the salivary Mg levels in the OPMD group (5.41 µg/mL) in comparison with the OSCC (3.71µg/mL) and control group (3.51 µg/mL) (p = 0.041). No differences were observed in other salivary levels elements. The results of the systematic review revealed that one article indicated a decrease, and three papers reported an increase in salivary Na levels in patients with OPMD and OSCC. Two articles indicated a decrease in salivary K levels in OSCC, and the other two reported high Mg levels in OPMD and OSCC. CONCLUSION: High salivary Mg levels can be a potential biomarker indicating the presence of OPMD, however, the evidence is still contradictory and more studies are required.

Economic Impacts on Human Health Resulting from the Use of Mercury in the Illegal Gold Mining in the Brazilian Amazon: A Methodological Assessment.

Artisanal small-scale gold mining (ASGM) in the Amazon results in the dumping of tons of mercury into the environment annually. Despite consensus on the impacts of mercury on human health, there are still unknowns regarding: (i) the extent to which mercury from ASGM can be dispersed in the environment until it becomes toxic to humans; and (ii) the economic value of losses caused by contamination becomes evident. The main objective of this study is to propose a methodology to evaluate the impacts of ASGM on human health in different contexts in the Brazilian Amazon. We connect several points in the literature based on hypotheses regarding mercury dispersion in water, its transformation into methylmercury, and absorption by fish and humans. This methodology can be used as a tool to estimate the extent of environmental damage caused by artisanal gold mining, the severity of damage to the health of individuals contaminated by mercury and, consequently, can contribute to the application of fines to environmental violators. The consequences of contamination are evaluated by dose-response functions relating to mercury concentrations in hair and the development of the following health outcomes: (i) mild mental retardation, (ii) acute myocardial infarction, and (iii) hypertension. From disability-adjusted life years and statistical life value, we found that the economic losses range from 100,000 to 400,000 USD per kilogram of gold extracted. A case study of the Yanomami indigenous land shows that the impacts of mercury from illegal gold mining in 2020 totaled 69 million USD, which could be used by local authorities to compensate the Yanomami people.

An Assessment of Health Outcomes and Methylmercury Exposure in Munduruku Indigenous Women of Childbearing Age and Their Children under 2 Years Old.

In line with the 1000-day initiative and the Sustainable Development Goals (SDG) 2 and 3, we present a cross-sectional analysis of maternal health, infant nutrition, and methylmercury exposure within hard-to-reach indigenous communities in the state of Pará, Brazilian Amazon. We collected data from all women of childbearing age (i.e., 12-49) and their infants under two years old in three Munduruku communities (Sawré Muybu, Sawré Aboy, and Poxo Muybu) along the Tapajos River. We explored health outcomes through interviews, vaccine coverage and clinical assessment, and determined baseline hair methylmercury (H-Hg) levels. Hemoglobin, infant growth (Anthropometric Z scores) and neurodevelopment tests results were collected. We found that 62% of women of childbearing age exceeded the reference limit of 6.0 µg/g H-Hg (median = 7.115, IQR = 4.678), with the worst affected community (Sawré Aboy) registering an average H-Hg concentration of 12.67 µg/g. Half of infants aged under 24 months presented with anemia. Three of 16 (18.8%) infants presented H-Hg levels above 6.0 µg/g (median: 3.88; IQR = 3.05). Four of the 16 infants were found to be stunted and 38% of women overweight, evidencing possible nutritional transition. No infant presented with appropriate vaccination coverage for their age. These communities presented with an estimated Infant Mortality Rate (IMR) of 86.7/1000 live births. The highest H-Hg level (19.6 µg/g) was recorded in an 11-month-old girl who was found to have gross motor delay and anemia. This already vulnerable indigenous Munduruku community presents with undernutrition and a high prevalence of chronic methylmercury exposure in women of childbearing age. This dual public health crisis in the context of wider health inequalities has the potential to compromise the development, health and survival of the developing fetus and infant in the first two critical years of life. We encourage culturally sensitive intervention and further research to focus efforts.

Neurological Impacts of Chronic Methylmercury Exposure in Munduruku Indigenous Adults: Somatosensory, Motor, and Cognitive Abnormalities.

There has been increasing evidence about mercury (Hg) contamination in traditional populations from the Amazon Basin due to illegal gold mining. The most concerning health impact is neurotoxicity caused by Hg in its organic form: methylmercury (MeHg). However, the severity and extent of the neurotoxic effects resulting from chronic environmental exposure to MeHg are still unclear. We conducted a clinical-epidemiological study to evaluate the neurological impacts of chronic MeHg exposure in Munduruku indigenous people, focusing on somatosensory, motor, and cognitive abnormalities. All participants were subjected to a systemized neurological exam protocol, including Brief Cognitive Screening Battery (BCSB), verbal fluency test, and Stick Design Test. After the examination, hair samples were collected to determine MeHg levels. Data collection took place between 29 October and 9 November 2019, in three villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy) from Sawré Muybu Indigenous Land, Southwest of Pará state. One hundred and ten individuals >12 years old were included, 58 of which were men (52.7%), with an average age of 27.6 years (range from 12 to 72). Participants' median MeHg level was 7.4 µg/g (average: 8.7; S.D: 4.5; range: 2.0-22.8). In Sawré Aboy village, the median MeHg level was higher (12.5 µg/g) than in the others, showing a significant statistical exposure gradient (Kruskal-Wallis test with p-value < 0.001). Cerebellar ataxia was observed in two participants with MeHg levels of 11.68 and 15.68 µg/g. Individuals with MeHg exposure level ≥10 µg/g presented around two-fold higher chances of cognitive deficits (RP: 2.2; CI 95%: 1.13-4.26) in BCSB, and in the verbal fluency test (RP: 2.0; CI 95%: 1.18-3.35). Furthermore, adolescents of 12 to 19 years presented three-fold higher chances of verbal development deficits, according to the fluency test (RP: 3.2; CI 95%: 1.06-9.42), than individuals of 20 to 24 years. The worsened motor and cognitive functions are suggestive of neurotoxicity due to chronic MeHg exposure. In conclusion, we believe monitoring and follow-up measures are necessary for chronic mercury exposed vulnerable people, and a basic care protocol should be established for contaminated people in the Brazilian Unified Health System.

Impacts of the Goldmining and Chronic Methylmercury Exposure on the Good-Living and Mental Health of Munduruku Native Communities in the Amazon Basin.

This paper is an exploratory study that examines the illegal goldmining impacts on Munduruku communities' "Good-Living" (Xipan Jewewekukap) and explores the possible relationship between chronic methylmercury (MeHg) exposure and the worsening mental health conditions in three villages in the Middle-Tapajós River, Brazilian Amazon. The region has been experiencing a long-lasting threat of goldminers' invasions. A total of 109 people were interviewed and evaluated. Total mercury (THg) exposure levels were evaluated through hair samples analysis, from which MeHg exposure levels were calculated. The Geriatric Depression Scale-Short Form (GDS-SF) was used as a screening tool in order to assess mental health indicators. Brief non-structured interviews were carried out to investigate how goldmining is impacting the communities Good-Living. A Poisson regression model was used to estimate the possible association between mental health indicators (assessed through the GDS-SF) and the following independent variables: (i) mercury exposure level (<10.0 µg/g vs. ≥10.0 µg/g), (ii) self-reported nervousness, (iii) self-reported irritability, (iv) age group, and (v) monthly income. The analysis revealed high levels of mercury in hair samples (median: 7.4 µg/g, range 2.0-22.8; 70% and 28% of the participants had THg levels ≥6.0 and ≥10.0 µg/g, respectively) and pointed to a tendency in which higher levels of methylmercury exposure (Hg ≥ 10.0 µg/g) could be linked to worse mental health indicators. Although the GDS-SF has presented limitations due to the Munduruku sociocultural context, our findings suggest a tendency of worse mental health indicators in participants presenting high levels of MeHg exposure. Despite this limitation, the qualitative approach indicates an evident association between the impacts of goldmining and the Munduruku people's decreasing autonomy to maintain a Good-Living on their own terms, pointing to the importance of carrying out new investigations, especially considering longitudinal studies with qualitative methodologies and ethnographic approaches.

Intergenerational Association of Short Maternal Stature with Stunting in Yanomami Indigenous Children from the Brazilian Amazon.

To describe the factors associated to stunting in <5-year-old Yanomami Brazilian children, and to evaluate the association of short maternal stature to their offspring's stunting. A cross-sectional study carried out in three villages in the Yanomami territory. We performed a census, in which all households with children < 5-years-old were included. The length/height-for-age z-score <-2 standard deviations was used to classify the children as stunted. Short maternal height was defined as <145 cm for adult women, and <-2 standard deviations of the height-for-age z-score for adolescent women. We used adjusted Poisson regression models to estimate prevalence ratios (PR) along the 90% confidence interval. We evaluated 298 children. 81.2% of children suffered from stunting and 71.9% of the mothers from short stature. In the bivariate analysis, a significant association of stunting with short maternal stature, gestational malaria and child's place of birth were observed. Considering the variables of the children under five years of age, there were significant associations with age group, the child's caregiver, history of malaria, pneumonia, and malnutrition treatment. In the adjusted hierarchical model, stunting was 1.22 times greater in the offspring of women with a short stature (90% CI: 1.07-1.38) compared to their counterparts. Brazilian Amazonian indigenous children living in a remote area displayed an alarming prevalence of stunting, and this was associated with short maternal height, reinforcing the hypothesis of intergenerational chronic malnutrition transmission in this population. In addition, children above 24 months of age, who were born in the village healthcare units and who had had previous treatment in the past for stunting presented higher rates of stunting in this study.

Mercury Exposure in Munduruku Indigenous Communities from Brazilian Amazon: Methodological Background and an Overview of the Principal Results.

The Amazonian indigenous peoples depend on natural resources to live, but human activities' growing impacts threaten their health and livelihoods. Our objectives were to present the principal results of an integrated and multidisciplinary analysis of the health parameters and assess the mercury (Hg) exposure levels in indigenous populations in the Brazilian Amazon. We carried out a cross-sectional study based on a census of three Munduruku indigenous villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy), located in the Sawré Muybu Indigenous Land, between 29 October and 9 November 2019. The investigation included: (i) sociodemographic characterization of the participants; (ii) health assessment; (iii) genetic polymorphism analysis; (iv) hair mercury determination; and (v) fish mercury determination. We used the logistic regression model with conditional Prevalence Ratio (PR), with the respective 95% confidence intervals (CI95%) to explore factors associated with mercury exposure levels ≥6.0 µg/g. A total of 200 participants were interviewed. Mercury levels (197 hair samples) ranged from 1.4 to 23.9 µg/g, with significant differences between the villages (Kruskal-Wallis test: 19.9; p-value < 0.001). On average, the general prevalence of Hg exposure ≥ 6.0 µg/g was 57.9%. For participants ≥12 years old, the Hg exposure ≥6.0 µg/g showed associated with no regular income (PR: 1.3; CI95%: 1.0-1.8), high blood pressure (PR: 1.6; CI95%: 1.3-2.1) and was more prominent in Sawré Aboy village (PR: 1.8; CI95%: 1.3-2.3). For women of childbearing age, the Hg exposure ≥6.0 µg/g was associated with high blood pressure (PR: 1.9; CI95%: 1.2-2.3), with pregnancy (PR: 1.5; CI95%: 1.0-2.1) and was more prominent among residents in Poxo Muybu (PR: 1.9; CI95%: 1.0-3.4) and Sawré Aboy (PR: 2.5; CI95%: 1.4-4.4) villages. Our findings suggest that chronic mercury exposure causes harmful effects to the studied indigenous communities, especially considering vulnerable groups of the population, such as women of childbearing age. Lastly, we propose to stop the illegal mining in these areas and develop a risk management plan that aims to ensure the health, livelihoods, and human rights of the indigenous people from Amazon Basin.

Health Risk Assessment of Mercury Exposure from Fish Consumption in Munduruku Indigenous Communities in the Brazilian Amazon.

Fish serves as the principal source of animal protein for the indigenous people of the Amazon, ensuring their food and nutritional security. However, gold mining causes mercury (Hg) contamination in fish, and consequently increases health risks associated with fish consumption. The aim of this study was to assess the health risk attributed to the consumption of mercury-contaminated fish by Munduruku indigenous communities in the Middle-Tapajós Region. Different fish species were collected in the Sawré Muybu Indigenous Land to determine mercury levels. The health risk assessment was carried out according to the World Health Organization (WHO 2008) methodology and different scenarios were built for counterfactual analysis. Eighty-eight fish specimens from 17 species and four trophic levels were analyzed. Estimates of Hg ingestion indicated that the methylmercury daily intake exceeds the U.S. EPA (United States Environmental Protection Agency) (2000) reference dose from 3 to 25-fold, and up to 11 times the FAO (Food and Agriculture Organization)/WHO (2003) dose recommendation. In all situations analyzed, the risk ratio estimates were above 1.0, meaning that the investigated Munduruku communities are at serious risk of harm as a result of ingestion of mercury-contaminated fish. These results indicate that, at present, fish consumption is not safe for this Munduruku population. This hazardous situation threatens the survival of this indigenous population, their food security, and their culture.

Genetic Polymorphism of Delta Aminolevulinic Acid Dehydratase (ALAD) Gene and Symptoms of Chronic Mercury Exposure in Munduruku Indigenous Children within the Brazilian Amazon.

Genetic polymorphisms involved in mercury toxicokinetics and toxicodynamics may be associated with severe mercury toxicity. This study aimed to investigate the impact of an ALAD polymorphism on chronic mercury exposure and the health situation of indigenous children from the Brazilian Amazon. One-hundred-and-three indigenous children (under 15 years old) were included and genotyped (rs1800435) using a TaqMan validated assay. The mean age was 6.6 ± 4.5 years old, 60% were female, 49% presented with anemia, and the mean hair mercury concentration was 7.0 ± 4.5 (1.4-23.9) µg/g, with 49% exceeding the reference limit (≥6.0 µg/g). Only two children were heterozygous ALAD, while the others were all wild type. Minor allele frequency (ALAD G) and heterozygous genotype (ALAD CG) were 1% and 2%, respectively. The two children (12 and 14 years old) with the ALAD polymorphism had mercury levels above the average as well as had neurological symptoms related to chronic mercury exposure, such as visual field alterations, memory deficit, distal neuropathy, and toe amyotrophy. Both children also reported frequent consumption of fish in the diet, at least three times a week. In conclusion, our data confirm that an ALAD polymorphism can contribute to mercury half-life time, harmful effects, and neuropsychological disorders in indigenous children with chronic mercury exposure to gold mining activity.

Asthma: role of the angiotensin-(1-7)/Mas (MAS1) pathway in pathophysiology and therapy.

The incidence of asthma is a global health problem and requires studies aimed for the development of new treatments to improve its clinical management, reducing personal and economic burdens on the health system. Therefore, the discovery of mediators that promote anti-inflammatory and pro-resolutive effects are highly desirable to improve lung function and quality of life of asthmatic patients. In that regard, experimental studies have shown that the angiotensin-(1-7)/Mas receptor (MAS1) of the renin-angiotensin system is a potential candidate for the treatment of asthma. Therefore, we have reviewed findings related to the function of the angiotensin-(1-7)/Mas pathway in regulating the processes associated with inflammation, including leukocyte influx, fibrogenesis, pulmonary dysfunction and the resolution of inflammation in asthma. Thus, a knowledge of the role of the angiotensin-(1-7)/Mas can help pave the way for the development of new treatments for this disease, which has high morbidity and mortality, through new types of experiments and clinical trials.

Salivary characteristics may be associated with burning mouth syndrome?

BACKGROUND: Burning mouth syndrome (BMS) it is characterized by burning and uncomfortable sensations with no clinical alterations or laboratory findings. The evaluation of the salivary characteristics of people with BMS can help the understanding of the pathogenesis of this condition. This case-control study aimed to trace the salivary profile of women with burning mouth syndrome (BMS). MATERIAL AND METHODS: 40 women with BMS and 40 control women were recruited. Unstimulated salivary flow rate (uSFR), pH, salivary cortisol levels, salivary viscosity, and oral health impact profile (OHIP-14 questioner) were determined. P< 0.05 was considered statistically significant. RESULTS: For uSFR, mean values obtained for BMS and for control group respectively were 0.35 and 0.61 mL/min; for pH, 7.23 and 7.34; for cortisol levels, 0.36 and 0.15 µg/dL; for viscosity values, 31.1 and 45.01 mPas and for OHIP-14 scores, 21.7 and 5.7. To uSFR, cortisol levels, viscosity values and OHIP-14 scores, differences were statistically significant. Salivary cortisol levels and OHIP-14 scores were correlated positively (rho = 0.624; p< 0.05). CONCLUSIONS: BMS women have lower uSFR and salivary viscosity and higher salivary cortisol levels that were associated with worse quality of life, compared with the control group. Key words:Xerostomia, Burning mouth syndrome, Viscosity.

Oral Formulation of Angiotensin-(1-7) Promotes Therapeutic Actions in a Model of Eosinophilic and Neutrophilic Asthma.

The presence of eosinophils and neutrophils in the lungs of asthmatic patients is associated with the severity of the disease and resistance to corticosteroids. Thus, defective resolution of eosinophilic and neutrophilic inflammation is importantly related to exacerbation of asthma. In this study, we investigated a therapeutic action of angiotensin-(1-7) (Ang-(1-7)) in a model of asthma induced by ovalbumin (OVA) and lipopolysaccharide (LPS). Balb-c mice were sensitized and challenged with OVA. Twenty-three hours after the last OVA challenge, experimental groups received LPS, and 1 h and 7 h later, mice were treated with oral formulation of Ang-(1-7). On the next day, 45 h after the last challenge with OVA, mice were subjected to a test of motor and exploratory behavior; 3 h later, lung function was evaluated, and bronchoalveolar lavage fluid (BALF) and lungs were collected. Motor and exploratory activities were lower in OVA + LPS-challenged mice. Treatment with Ang-(1-7) improved these behaviors, normalized lung function, and reduced eosinophil, neutrophil, myeloperoxidase (MPO), eosinophilic peroxidase (EPO), and ERK1/2 phosphorylation (p-ERK1/2) in the lungs. In addition, Ang-(1-7) decreased the deposition of mucus and extracellular matrix in the airways. These results extended those of previous studies by demonstrating that oral administration of Ang-(1-7) at the peak of pulmonary inflammation can be valuable for the treatment of neutrophil- and eosinophil-mediated asthma. Therefore, these findings potentially provide a new drug to reverse the natural history of the disease, unlike the current standards of care that manage the disease symptoms at best.