A functional matrix metalloproteinase (MMP)-9 polymorphism modifies plasma MMP-9 levels in subjects environmentally exposed to mercury

Mercury (Hg) exposure causes health problems including cardiovascular diseases. Although precise mechanisms have not been precisely defined yet, matrix metalloproteinases (MMPs) may be involved. The gene encoding MMP-9 presents genetic polymorphisms which affect the expression and activity level of this enzyme. Two polymorphisms in the promoter region [C(-1562)T and (CA)(n)] are functionally relevant, and are implicated in several diseases. This study aimed at examining how these polymorphisms affect the circulating MMP-9 levels and its endogenous inhibitor, the tissue inhibitor of metalloproteinase-1 (TIMP-1) in 266 subjects environmentally exposed to Hg. Blood and plasma Hg concentrations were determined by inductively coupled plasma-mass spectrometry (ICP-MS). MMP-9 and TIMP-1 concentrations were measured in plasma samples by gelatin zymography and ELISA, respectively. Genotypes for the C(-1562)T and the microsatellite (CA)(n) polymorphisms were determined. We found a positive association (P<0.05) between plasma Hg concentrations and MMP-9/TIMP-1 ratio (an index of net MMP-9 activity). When the subjects were divided into tertiles with basis on their plasma Hg concentrations, we found that the (CA)(n) polymorphism modified MMP-9 concentrations and MMP-9/TIMP-1 ratio in subjects with the lowest Hg concentrations (first tertile), with the highest MMP-9 levels being found in subjects with genotypes including alleles with 21 or more CA repeats (H alleles) (P<0.05). Conversely, this polymorphism had no effects on subjects with intermediate or high plasma Hg levels (second and third tertiles, respectively). The C(-1562)T polymorphism had no effects on MMP-9 levels. These findings suggest a significant interaction between the (CA)(n) polymorphism and low levels of Hg exposure, possibly increasing the risk of developing diseases in subjects with H alleles. (c) 2010 Elsevier B.V. All rights reserved.

Sub-Chronic Exposure to Methylmercury at Low Levels Decreases Butyrylcholinesterase Activity in Rats

In this study, we examined the effects of low levels and sub-chronic exposure to methylmercury (MeHg) on butyrylcholinesterase (BuChE) activity in rats. Moreover, we examined the relationship between BuChE activity and oxidative stress biomarkers [delta-aminolevulinic acid dehydratase (delta-ALA-D) and malondialdehyde levels (MDA)] in the same animals. Rats were separated into three groups (eight animals per group): (Group I) received water by gavage; (Group II) received MeHg (30 mu g/kg/day) by gavage; (Group III) received MeHg (100 mu g/kg/day). The time of exposure was 90 days. BuChE and ALA-D activities were measured in serum and blood, respectively; whereas MDA levels were measured in plasma. We found BuChE and ALA-D activities decreased in groups II and III compared to the control group. Moreover, we found an interesting negative correlation between plasmatic BuChE activity and MDA (r = -0.85; p < 0.01) and a positive correlation between plasmatic BuChE activity and ALA-D activities (r = 0.78; p < 0.01), thus suggesting a possible relationship between oxidative damage promoted by MeHg exposure and the decrease of BuChE activity. In conclusion, long-term exposure to low doses of MeHg decreases plasmatic BuChE activity. Moreover, the decrease in the enzyme is strongly correlated with the oxidative stress promoted by the metal exposure. This preliminary finding highlights a possible mechanism for MeHg to reduce BuChE activity in plasma. Additionally, this enzyme could be an auxiliary biomarker on the evaluation of MeHg exposure.

Elevated blood lead levels in a riverside population in the Brazilian Amazon

Lead (Pb) is recognized as one of the most toxic metals. Sources of Pb exposure have been widely documented in North America, and the removal of Pb additives from gasoline was reflected in a dramatic lowering of blood Pb concentration. In Latin America, the removal of Pb from gasoline resulted in decreased exposure, but Pb levels in many areas remain high due to occupational and environmental sources of exposure. While many of the Pb sources have been identified (mining, industries, battery recycling, lead-based paint, ceramics), new ones occasionally crop up. Here we report on blood Pb (B-Pb) levels in remote riverside communities of the Brazilian Amazon. Blood Pb (B-Pb) levels were determined in 448 persons from 12 villages of the Lower Tapajos River Basin, Par, Brazil. Socio-demographic and dietary information, as well as occupational, residential and medical history was collected using an interview-administered questionnaire. B-Pb, measured by ICP-MS, showed elevated concentrations. Mean B-Pb was 13.1 mu g/dL +/- 8.5, median B-Pb was 11.2 mu g/dL and ranged from 0.59 to 48.3 mu g/dL. Men had higher B-Pb compared to women (median: 15.3 mu g/dL vs 7.9 mu g/dL respectively). B-Pb increased with age for women, while it decreased for men. For both genders, B-Pb decreased with education. There were significant differences between villages. Exploratory analyses, using linear partition models, showed that for men B-Pb was lower among those who were involved in cattle-raising, and higher among those who hunted, farmed and fished. The distribution profile of B-Pb directed us towards artisanal transformation of manioc to flour (farinha), which requires heating in a large metal pan, with stirring primarily done by young men. In the village with the highest B-Pb, analysis of Pb concentrations (dry weight) of manioc (prior to transformation) and farinha (following transformation) from 6 houses showed a tenfold increase in Pb concentration (mean: 0.017 +/- 0.016 to 0.19 +/- 0.10 mu g/g). This was confirmed in one of these villages where we sampled manioc paste Oust before roasting) and the roasted farinha (0.05 mu g/g vs 0.20 mu g/g). While there may be other sources (ammunition, sinkers for fishing nets), the high concentrations in farinha, a dietary staple, assuredly makes an important contribution. Further action needs to reduce Pb sources in this region. (C) 2009 Elsevier Inc. All rights reserved.

A plateau detected in lead accumulation in subsurface deciduous enamel from individuals exposed to lead may be useful to identify children and regions exposed to higher levels of lead

In a previous study, we showed 4 times more lead in surface deciduous enamel (1.9-5.9 mu m) of a notoriously contaminated area (Bauru, Sao Paulo State, Brazil) in comparison to samples from a region with no lead contamination described (Ribeirao Preto, Sao Paulo State, Brazil). The samples from the more superficial enamel (1.9-3.18 mu m) showed higher amounts of lead and the highest variability, while in the subsurface enamel (3.18-5.9 mu m) a plateau in lead content was detected in children living in the contaminated environment (around 600 mu g/g). Here we expand our previous study, and use only samples obtained from subsurface enamel (Ribeirao Preto, n = 186; Bauru, n = 20). We tried to distinguish regions with more children with lead above the threshold of 600 mu g/g of lead in enamel. We tested whether differences in the percentage of children with ""high"" lead (>= 600 mu g/g) could be observed among the different Kindergartens studied in Ribeirao Preto. We also tested whether these results were different from the ones provided by conventional comparison of the data. Ribeirao Preto showed almost 4 times less lead than Bauru (p < 0.0001), and a statistically significant difference was found only in Ribeirao Preto between Kindergarten 2 and 5 (p<0.01). Twelve percent of the children from Ribeirao Preto had ""high"" lead, while 55% of the children from Bauru did so. However, when we looked at the percentages of children with ""high"" lead in each Kindergarten, and compared them, a whole new picture emerged, in which we could see children with ""high"" lead concentrated mainly in 3 Kindergartens from Ribeirao Preto, with Kindergarten 5 with 33% of the children with ""high"" lead, being statistically different from all Kindergartens, except 4 and 6. The threshold of 600 mu g/g of lead in subsurface enamel was tentatively settled here after the plateau seen in exposed children, and enabled us to identify locations with more children exposed to a higher amount of lead. (C) 2008 Elsevier Inc. All rights reserved.

Haplotypes of vitamin D receptor modulate the circulating levels of lead in exposed subjects

Genetic factors influence whole blood lead (Pb-B) concentrations in lead exposed subjects. This study aimed at examining the combined effects (haplotype analysis) of three polymorphisms (BsmI, ApaI and FokI) in vitamin D receptor (VDR) gene on Pb-B and on the concentrations of lead in plasma (Pb-P), which is more relevant to lead toxicity, in 150 environmentally exposed subjects. Genotypes were determined by RFLP, and Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. Subjects with the bb (BsmI polymorphism) or ff (FokI polymorphism) genotypes have lower B-Pb than subjects in the other genotype groups. Subjects with the aa (ApaI polymorphism) or ff genotypes have lower P-Pb than subjects in the other genotype groups. Lower Pb-P, Pb-B, and %Pb-P/Pb-B levels were found in subjects with the haplotype combining the a, b, and f alleles for the ApaI, BsmI, and FokI polymorphisms, respectively, compared with the other haplotype groups, thus suggesting that VDR haplotypes modulate the circulating levels of lead in exposed subjects.

Protective properties of quercetin against DNA damage and oxidative stress induced by methylmercury in rats

Aim of the study was to find out whether consumption of quercetin (QC), an abundant flavonoid in the human diet, protects against DNA damage caused by exposure to organic mercury. Therefore, rats were treated orally with methylmercury (MeHg) and the flavonoid with doses that reflect the human exposure. The animals received MeHg (30 mu g/kg/bw/day), QC (0.5-50 mg/kg/bw/day), or combinations of both over 45 days. Subsequently, the glutathione levels (GSH) and the activities of glutathione peroxidase (GPx) and catalase (CAT) were determined, and DNA damage was measured in hepatocytes and peripheral leukocytes in single cell gel electrophoresis assays. MeHg decreased the concentration of GSH and the activity of GPx by 17 and 12%, respectively and caused DNA damage to liver and blood cells, while with QC no such effects were seen. When the flavonoid was given in combination with MeHg, the intermediate and the highest concentrations (5.0 and 50.0 mg/kg/bw/day) were found to cause DNA protection; DNA migration was reduced by 54 and 65% in the hepatocytes and by 27 and 36% in the leukocytes; furthermore, the reduction in GSH and GPx levels caused by MeHg treatment was restored. In summary, our results indicate that consumption of QC-rich foods may protect Hg-exposed humans against the adverse health effects of the metal.

Effects of methylmercury on male reproductive functions in Wistar rats

In this study we investigated the effects of subacute exposure to methylmercury (MeHg) on male reproductive functions in rats by means of determination of alterations in structural and functional parameters. Adult male Wistar rats received 0, 0.5, 1.0 or 3.0 mg/kg/body weight/day orally, daily MeHg for 14 days. Sperm motility, the relative sperm count and transit time in the caput/corpus epididymis, were all reduced at all doses. The lowest dose increased the number of sperm head abnormalities; daily sperm production was elevated at the intermediate dose; while at the highest dose there was a decrease in serum testosterone levels and a rise in mercury (Hg) content in reproductive organs, liver and kidneys. In conclusion, MeHg exposure produced damages on male reproductive functions which may be attributed, at least in part, to the reduction in serum testosterone levels. These consequences could potentially result in infertility in rats. (C) 2011 Elsevier Inc. All rights reserved.

Melatonin enhances pro-inflammatory cytokine levels and protects against Chagas disease

Pro-inflammatory and modulatory cytokines have an essential role in host defense against human and murine Trypanosoma cruzi infection. Control of T. cruzi parasitism during the acute phase of infection is considered to be critically dependent on direct macrophage activation by cytokines. Melatonin has been proposed to regulate the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. The aims of this work were to evaluate in rats, the influences of exogenous melatonin treatment on T. cruzi-infected host`s immune responses. With this in mind, several immunological parameters were analyzed, including tumor necrosis factor-alpha, gamma-interferon, interleukin-12, nitric oxide (NO) and macrophage count. The melatonin therapy was provided in one of two different treatment regimens, that is, either beginning 7 days prior to infection or concomitant with the infection. Both treatments triggered an up-regulation of the immune response, with the concomitant treatment being more effective; in this case all cytokines studied, with exception of NO, displayed enhanced concentrations and there was a higher number of peritoneal macrophages, which displayed reduced concentrations under melatonin therapy. We conclude that melatonin plays a pivotal role in up-regulating the Th1 immune response thus controlling parasite replication.

Phagocytosis and Nitric Oxide Levels in Rheumatic Inflammatory States in Elderly Women

Background Very few studies have investigated, in the elderly, the effect of rheumatic inflammatory states on phagocyte function and free radical production. The objective of this article is to evaluate phagocytosis by neutrophils and the production of nitric oxide (.NO) by monocytes in elderly women recruited among patients of the Brazilian Public Health System. Methods: Forty patients aged more than 60 years with rheumatic inflammatory diseases were studied. Phagocytosis was measured by flow cytometry. .NO production was measured by the total nitrite assay and conventional inflammation markers were determined. Data were analyzed with the Mann Whitney nonparametric test and P<0.05 was considered significant. Results. C-reactive protein levels and white blood cell counts were significantly higher in inflammation than in the control group (P<0.05). The phagocytosis fluorescence intensity per neutrophil and the percentual of neutrophils expressing phagocytosis were significantly higher (P<0.05) in the test than in the control group. Furthermore, there was significant .NO overproduction by monocytes, (P<0.05). Conclusion: Phagocytosis and .NO production are affected by rheumatic states. This suggests that the increased .NO levels may play a part in the increased oxidative stress in rheumatic diseases in elderly women. J. Clin. Lab. Anal. 25:47-51, 2011. (C) 2011 Wiley-Liss, Inc.

Isolation and Characterization of a Natriuretic Peptide from Crotalus oreganus abyssus (Grand Canyon Rattlesnake) and its Effects on Systemic Blood Pressure and Nitrite Levels

Studies on the therapeutic potential of venom peptides have significantly advanced the development of new peptide drugs. A good example is captopril, a synthetic peptide drug, which acts as an anti-hypertensive and potentiating bradykinin, inhibiting the angiotensin-converting enzyme, whose precursor was isolated from the venom of Bothrops jararacussu. The natriuretic peptide (NPs) family comprises three members, ANP (atrial natriuretic peptide), BNP (B-type natriuretic peptide) and CNP (C-type natriuretic peptide), and has an important role in blood pressure regulation and electrolyte homeostasis. In this study, we describe, for the first time, the isolation and characterization of a novel natriuretic-like peptide (Coa_NP), isolated from Crotalus Oreganus abyssus venom. The peptide has 32 amino acids and its complete sequence is SKRLSNGCFGLKLDRIGAMSGLGCWRLINESK. The Coa_NP has an average molecular mass of 3510.98 Da and its amino acid sequence presents the loop region that is characteristic of natriuretic peptides (17 amino acids, NP domain consensus; CFGXXXDRIXXXSGLGC). Coa_NP is a natriuretic peptide of the ANP/BNP-like family, since the carboxy terminal region of CNP has its own NP domain. The functional experiments showed that Coa_NP produced biological effects similar to those of the other natriuretic peptides: (1) a dose-dependent decrease in mean arterial pressure; (2) significant increases in plasma nitrite levels, and (3) vasorelaxation in thoracic aortic rings that were pre-contracted with phenylephrine. The structural and biological aspects confirm Coa_NP as a natriuretic peptide isolated from snake venom, thus expanding the diversification of venom components.

Effect of a Pool of Peptides Isolated from Crotalus durissus terrificus (South American Rattlesnake) Venom on Glucose Levels of Mice Fed on a High-Fat Diet

This study investigated the effect of a pool of peptides, isolated from venom of Crotalus durissus terrificus (South American rattlesnake) on glucose concentration in C57BL/6 mice fed on a high-fat diet for 6 weeks. The pool of peptides (molecular mass around of 10 kDa) was obtained using a MidJet apparatus with a cartridge of 10 KDa. The peptide pool was injected intraperitoneally in mice in a single dose (0.5 mg/animal) or multiple doses (0.2 mg/dose). After predetermined times (30, 60, 90 and 120 min) post injections, venous blood samples were collected for enzymatic measurement of serum glucose using a commercial glucose kit (glucose oxidase method). High-fat fed mice showed an increase in blood glucose concentration, in comparison with mice fed on the chow diet. Thirty minutes after a single dose of the peptide pool, high-fat fed animals showed a significant decrease (similar to 47%) in glycemia. However, the glucose level increased again at 60 and 120 min. Conversely, after multiple injections of the pool of peptides administered every 30 min, the blood glucose concentration in the high-fat mice was significantly decreased (similar to 37%) and remained at low levels until 120 min. These results suggest that the tested pool of peptides from Crotalus durissus terrificus contained a peptide (or peptides) with a beneficial role on glucose-lowering action of high-fat fed mice.

Methemoglobin Reduction in Crocodile Blood: Are High Levels of MetHb Typical of Healthy Reptiles?

In 82 wild-caught Crocodylus porosus, levels of NADH-MetHb reductase and GSH seem adequate to maintain hemoglobin in its reduced functional state. Studies of C. porosus erythrocytes in vitro show reduction of metHb in the presence of lactate, glucose and plasma, but not pyruvate. These findings, together with recent data which show low metHb in a variety of reptiles, cast doubt on the accepted view that high levels of MetHb are typical of healthy reptiles. One explanation for the sharp contrast between earlier and more recent data could be technical. We found low metHb in Crocodylus johnstoni, Chelodina longicollis and Sphenomorphus quoyi. However, high and variable values reminiscent of many of the earlier data were obtained by omitting final centrifugation prior to spectrophotometry. Interestingly, this step is not part of the standard clinical method but is necessary in analyses of blood with nucleated red cells. These observations suggest that high metHb may not be typical of reptiles after all.

Correlation of habitual physical activity levels with flow mediated dilation of the brachial artery in 5-10 year old children

Endothelial dysfunction is an early key event of atherogenesis. Both fitness level and exercise intervention have been shown to positively influence endothelial function. In a cross-sectional study of 47 children, the relationship between habitual physical activity and flow-mediated dilation (FMD) of the brachial artery was explored. Habitual physical activity levels (PALs) were assessed using a validated stable isotope technique, and FMD of the brachial artery was measured via high-resolution ultrasound. The results showed that habitual physical activity significantly correlated with FMD (r=0.39, P=0.007), and remained the most influential variable on dilation in multivariate analysis. Although both fitness level and exercise intervention have previously been shown to positively influence FMD, this is the first time that a relationship with normal PALs has been investigated, especially, at such a young age. These data support the concept that physical activity exerts its protective effect on cardiovascular health via the endothelium and add further emphasis to the importance of physical activity in childhood.

Children’s respiratory health and daily particulate levels in ten non-urban communities

We conducted a study to assess the association between the acute respiratory health of children and the levels of particulates in communities near and away from active opencast coal mines. The study enrolled children aged 1–11 years from the general population of five socioeconomically matched pairs of nonurban communities in northern England. Diaries of respiratory events were collected for 1405 children, and information was collected on the consultations of 2442 children with family/general practitioners over the 6-week study periods during 1996–1997, with concurrent monitoring of particulate levels. The associations found between daily PM10 levels and respiratory symptoms were frequently small and positive and sometimes varied between communities. The magnitude of these associations were in line with those from previous studies, even though daily particulate levels were low, and the children were drawn from the general population, rather than from the population with respiratory problems. The associations among asthma reliever use, consultations with general practitioners, and daily particulate levels were of a similar strength but estimated less precisely. The strength of association between all respiratory health measures and particulate levels was similar in communities near and away from opencast coal mining sites.

Transformations of taste: Americanisation, generational change and Australian cultural consumption

Researchers within the field of cultural imperialism as well as the more recently developed globalisation paradigm have tended to dwell upon the economic or corporate dimensions of global cultural flows and have been largely indifferent to the domain of the everyday cultural tastes and forms of cultural consumption that exist in particular national contexts. This article seeks to redress this focus through an examination of one particular instance of cultural imperialism, the widely held belief in ?he Americanisation of Australian society. Using data from a major research project inquiring into Australian everyday culture the article focuses on the changes in cultural tastes and preferences that are evident in three generational cohorts: contemporary young adults, a segment of the 'baby-boom' generation now in middle age, and a group of older Australians born in the years following World War I and the 1920s. The article documents a trend in which overseas influences, particularly those originating from America, appear to be increasingly shaping Australians' tastes in a wide range of cultural domains. Nevertheless, despite these changes in cultural taste Australians of ail ages retain a strong sense of a distinctive national identity. Such findings have implications for an understanding of cultural globalisation as a process of hybridisation and intermixing.