Desreguladores endócrinos no meio ambiente: efeitos e conseqüências

There is an increasing interest in micropollutants in the environment that can interfere with the endocrine system, affecting health, growth and reproduction of animals and humans. These substances are known as Endocrine Disrupting Chemicals (EDCs) and can be found in domestic sewage, domestic wastewater treatment plant effluents, and in natural and potable waters. There are numerous chemicals classified as EDCs, such as pesticides, chemicals used and produced by chemical industries and natural and synthetic estrogens. EDCs can be related to the increase of the incidence of anomalies in the reproductive system of animals, cancer in humans and reduction of the masculine fertility.

Interferentes endócrinos no ambiente

Although the hypothesis that environmental chemicals may exhibit endocrine disrupting effects is not new, the issue has been a growing level of concern due to reports of increased incidences of endocrine-related disease in humans, including declining male fertility, and more significantly, to adverse physiological effects observed in wildlife where cause and effect relationships are more evident. The list of endocrine disrupting chemicals (EDCs) includes a range of anthropogenic compounds, phytoestrogens, naturally occurring sex steroids and synthetic estrogens. Within the aquatic environment, the presence of EDCs has concerned many scientists and water quality regulators. Discharge of effluents from treatment facilities is likely to be a significant source of input of contaminants to many systems, and the potential for concentration of hydrophilic compounds and transformation products within sludges has implications for their disposal. Then, understanding the processes and the fate of EDCs on the environment, as well as the mechanisms of endocrine disruption, may facilitate controlling or limiting exposure of both humans and the environment to these compounds.

Fotodegradación heterogénea de bisfenol A en agua con dióxido de titanio

Bisphenol A (BPA) is a monomer used in epoxy resin and polycarbonate manufacture. This molecule is considered as an endocrine disruptor that causes different diseases. The human exposition to this non biodegrable substance is increasing in the time; in particular, water is contaminated by industrial remainder flow. In this article heterogeneous photo degradation of a solution of BPA in water solution using a catalytic photo reactor with UV light and titanium dioxide (TiO2) was evaluated. High performance liquid chromatography (HPLC) was used to analyze the photo degradation of BPA solutions. The influence of titanium dioxide amount, BPA concentration, reaction temperature and the catalyst state like suspension and immobilized were also determinated. The highest elimination of BPA was 83.2%, in 240 min, beginning with 0.05 mM of BPA and 100 mg/L of TiO2 in suspension.

Recent research data on the removal of pharmaceuticals from sewage treatment plants (STP)

Pharmaceutical compounds have been detected in sewage treatment plant (STP) effluents, surface waters and, less frequently, in groundwater and drinking water, all over the world. Different sources are responsible for their appearance in the aquatic environment, however, it is widely accepted that the main sources of this type of pollutant are STP effluents. The adverse effects of pharmaceuticals in the environment include aquatic toxicity, development of resistance in pathogenic bacteria, genotoxicity and endocrine disruption. Thus, the discharge of these compounds to the environment in STP effluents should be minimized.

Estrogênios em águas naturais e tratadas da região de Jaboticabal - São Paulo

The aim of this work was to analyze 17 β estradiol and estrone, natural estrogenic hormones present in domestic effluents and animal excreta, in the public water supply system of Jaboticabal, SP. The results have shown the presence of estrogens in 22% of the samples in concentrations from 6,8 ng L-1 (treated water) to 30,6 ng L-1 (riverhead) for 17 β estradiol and 600 ng L-1 of estrone (stream), respectively. We concluded that animal wastes, discharges from the wastewater treatment station, and discharges of domestic effluent without treatment from rural proprieties were probably the cause of this contamination.

Biodegradação de alcoóis, ftalatos e adipatos em um solo tropical contaminado

The adipic and phthalic acid esters are plasticizers, have low water solubility, high partition octanol/water coefficients (Kow) and accumulate in soil and sediments. These compounds are considered teratogenic, carcinogenic and endocrine disruptors chemicals. This study evaluated the bioremediation of tropical soil contaminated with plasticizers process wastes, in aerobic conditions, with and without introduction of acclimated bacteria. It was selected 200 kg of contaminated tropical soil for the biodegradation study. The plasticizers concentrations in soil ranged between 153 mgDOA/kg up to 15552 mgDIDP/kg and after 90 days of biodegradation, the lower removal efficiencies were 72% with a 1-2 log simultaneous bacterial growth.

Determinação de plastificantes em água potável utilizando cromatografia gasosa e espectrometria de massas

This study investigated the levels of plasticizer endocrine disruptors (diethyl phthalate, dibutyl phthalate, and bisphenol A) in drinking water at Paraíba do Sul River region and release of these compounds from bottled water. An analytical method employing solid phase extraction and GC/MS was optimized and validated. The results showed that the method is selective, linear (r² > 0.99), precise (RSD <12%), accurate (recoveries between 62 and 105%), sensitive and robust. Applying the method, the presence of all studied pollutants in drinking water was observed for the three sampled plasticizers. These plasticizers were not found in mineral bottled water, before or after storage.

Oceanografia e Química: unindo conhecimentos em prol dos oceanos e da sociedade

The marine environment is certainly one of the most complex systems to study, not only because of the challenges posed by the nature of the waters, but especially due to the interactions of physical, chemical and biological processes that control the cycles of the elements. Together with analytical chemists, oceanographers have been making a great effort in the advancement of knowledge of the distribution patterns of trace elements and processes that determine their biogeochemical cycles and influences on the climate of the planet. The international academic community is now in prime position to perform the first study on a global scale for observation of trace elements and their isotopes in the marine environment (GEOTRACES) and to evaluate the effects of major global changes associated with the influences of megacities distributed around the globe. This action can only be performed due to the development of highly sensitive detection methods and the use of clean sampling and handling techniques, together with a joint international program working toward the clear objective of expanding the frontiers of the biogeochemistry of the oceans and related topics, including climate change issues and ocean acidification associated with alterations in the carbon cycle. It is expected that the oceanographic data produced this coming decade will allow a better understanding of biogeochemical cycles, and especially the assessment of changes in trace elements and contaminants in the oceans due to anthropogenic influences, as well as its effects on ecosystems and climate. Computational models are to be constructed to simulate the conditions and processes of the modern oceans and to allow predictions. The environmental changes arising from human activity since the 18th century (also called the Anthropocene) have made the Earth System even more complex. Anthropogenic activities have altered both terrestrial and marine ecosystems, and the legacy of these impacts in the oceans include: a) pollution of the marine environment by solid waste, including plastics; b) pollution by chemical and medical (including those for veterinary use) substances such as hormones, antibiotics, legal and illegal drugs, leading to possible endocrine disruption of marine organisms; and c) ocean acidification, the collateral effect of anthropogenic emissions of CO2 into the atmosphere, irreversible in the human life time scale. Unfortunately, the anthropogenic alteration of the hydrosphere due to inputs of plastics, metal, hydrocarbons, contaminants of emerging concern and even with formerly "exotic" trace elements, such us rare earth elements is likely to accelerate in the near future. These emerging contaminants would likely soon present difficulties for studies in pristine environments. All this knowledge brings with it a great responsibility: helping to envisage viable adaptation and mitigation solutions to the problems identified. The greatest challenge faced by Brazil is currently to create a framework project to develop education, science and technology applied to oceanography and related areas. This framework would strengthen the present working groups and enhance capacity building, allowing a broader Brazilian participation in joint international actions and scientific programs. Recently, the establishment of the National Institutes of Science and Technology (INCTs) for marine science, and the creation of the National Institute of Oceanographic and Hydrological Research represent an exemplary start. However, the participation of the Brazilian academic community in the latest assaults on the frontier of chemical oceanography is extremely limited, largely due to: i. absence of physical infrastructure for the preparation and processing of field samples at ultra-trace level; ii. limited access to oceanographic cruises, due to the small number of Brazilian vessels and/or absence of "clean" laboratories on board; iii. restricted international cooperation; iv. limited analytical capacity of Brazilian institutions for the analysis of trace elements in seawater; v. high cost of ultrapure reagents associated with processing a large number of samples, and vi. lack of qualified technical staff. Advances in knowledge, analytic capabilities and the increasing availability of analytical resources available today offer favorable conditions for chemical oceanography to grow. The Brazilian academic community is maturing and willing to play a role in strengthening the marine science research programs by connecting them with educational and technological initiatives in order to preserve the oceans and to promote the development of society.

Avaliação da remoção de fármacos e de desreguladores endócrinos em águas de abastecimento por clarificação em escala de bancada

In this work, the efficiency of clarification treatment (coagulation, flocculation and sedimentation) with polyaluminum chloride (PAC) and aluminum sulfate (SA) as coagulants was evaluated in the removal of 7 microcontaminants (diclofenac - DCF, sulfamethoxazole - SMX, ethinylestradiol - EE2, bisphenol-A - BPA, estradiol - E2, estrone - E1 and estriol - E3) in water of low and high turbidity. The clarification treatment led to poor removal rates (40% at most) for all microcontaminants except SMX which exhibited intermediate removal efficiency (67 to 70%). Overall, PAC application yielded better performance compared to SA.

Berry polyphenol absorption and the effect of northern berries on metabolism, ectopic fat accumulation, and associated diseases

The prevalence of obesity and type 2 diabetes has increased at an alarming rate in developed countries. It seems in the light of current knowledge that metabolic syndrome may not develop at all without NAFLD, and NAFLD is estimated to be as common as metabolic syndrome in western population (23 % occurrence). Fat in the liver is called ectopic fat, which is triacylglycerols within the cells of non-adipose tissue. Serum alanine aminotransferase (ALT) values correlate positively with liver fat proportions, and increased activity of ALT predicts type 2 diabetes independently from obesity. Berries, high in natural bioactive compounds, have indicated the potential to reduce the risk of obesity-related diseases. Ectopic fat induces common endocrine excretion of adipose tissue resulting in the overproduction of inflammatory markers, which further induce insulin resistance by multiple mechanisms. Insulin resistance inducing hyperinsulinemia and lipolysis in adipocytes increases the concentration of free fatty acids and consequently causes further fat accumulation in hepatocytes. Polyphenolic fractions of berries have been shown to reverse inflammatory reaction cascades in in vitro and animal studies, and moreover to decrease ectopic fat accumulation. The aim of this thesis was to explore the role of northern berries in obesity-related diseases. The absorption and metabolism of selected berry polyphenols, flavonol glycosides and anthocyanins, was investigated in humans, and metabolites of the studied compounds were identified in plasma and urine samples (I, II). Further, the effects of berries on the risk factors of metabolic syndrome were studied in clinical intervention trials (III, IV), and the different fractions of sea buckthorn berry were tested for their ability to reduce postprandial glycemia and insulinemia after high-glucose meal in a postprandial study with humans (V). The marked impact of mixed berries on plasma ALT values (III), as well as indications of the positive effects of sea buckthorn, its fractions and bilberry on omental adiposity and adhesion molecules (IV) were observed. In study V, sea buckthorn and its polyphenol fractions had a promising effect on potprandial metabolism after high-glucose meal. In the literature review, the possible mechanisms behind the observed effects have been discussed with a special emphasis on ectopic fat accumulation. The literature review indicated that especially tannins and flavonoids have shown potential in suppressing diverse reaction cascades related to systemic inflammation, ectopic fat accumulation and insulin resistance development.

Fibroblast Growth Factor 8 and its Receptors in The Growth and Angiogenesis of Experimental Breast Cancer . With Special Reference to Thrombospondin-1 as a Novel Target Gene for FGF-8

The growth of breast cancer is regulated by hormones and growth factors. Recently, aberrant fibroblast growth factor (FGF) signalling has been strongly implicated in promoting the progression of breast cancer and is thought to have a role in the development of endocrine resistant disease. FGFs mediate their auto- and paracrine signals through binding to FGF receptors 1-4 (FGFR1-4) and their isoforms. Specific targets of FGFs in breast cancer cells and the differential role of FGFRs, however, are poorly described. FGF-8 is expressed at elevated levels in breast cancer, and it has been shown to act as an angiogenic, growth promoting factor in experimental models of breast cancer. Furthermore, it plays an important role in mediating androgen effects in prostate cancer and in some breast cancer cell lines. We aimed to study testosterone (Te) and FGF-8 regulated genes in Shionogi 115 (S115) breast cancer cells, characterise FGF-8 activated intracellular signalling pathways and clarify the role of FGFR1, -2 and -3 in these cells. Thrombospondin-1 (TSP-1), an endogenous inhibitor of angiogenesis, was recognised as a Te and FGF-8 regulated gene. Te repression of TSP-1 was androgen receptor (AR)-dependent. It required de novo protein synthesis, but it was independent of FGF-8 expression. FGF-8, in turn, downregulated TSP-1 transcription by activating the ERK and PI3K pathways, and the effect could be reversed by specific kinase inhibitors. Differential FGFR1-3 action was studied by silencing each receptor by shRNA expression in S115 cells. FGFR1 expression was a prerequisite for the growth of S115 tumours, whereas FGFR2 expression alone was not able to promote tumour growth. High FGFR1 expression led to a growth advantage that was associated with strong ERK activation, increased angiogenesis and reduced apoptosis, and all of these effects could be reversed by an FGFR inhibitor. Taken together, the results of this thesis show that FGF-8 and FGFRs contribute strongly to the regulation of the growth and angiogenesis of experimental breast cancer and support the evidence for FGF-FGFR signalling as one of the major players in breast cancers.

Late effects of cancer at a young age: Registry-based studies of the health of cancer patients and their off-spring

Modern cancer therapy has resulted in increased survival among patients diagnosed with cancer at a young age. These improvements have led to the investigation of late morbidity and mortality associated with cancer and its treatments. The aim of this study was to evaluate late effects of cancer treated at a young age on the health of patients and their offspring. Utilising the nationwide population-based registries in Finland, we evaluated the risk of hypothyroidism and the probability of parenthood in cancer survivors as well as preterm birth, neonatal outcomes, and the risk of cancer among offspring of patients. The survivor cohort, identified from the Finnish Cancer Registry, consisted of 25,784 cancer patients diag-nosed between ages 0 and 34 in 1953–2004. By linkage to the population register, siblings of these patients were identified for comparison. The prevalence of hypothyroidism was higher among former childhood cancer (aged 0–16) patients than in the general population. The probability of parenthood following early onset cancer was overall significantly reduced compared to siblings. Offspring of female cancer survivors were at an increased risk of preterm birth, this risk being highest among patients diagnosed in childhood and early adulthood (aged 20–34 years). The offspring were not, however, at a significantly increased risk of neonatal death or stillbirth, though they were more likely to need monitoring or intensive care in the neonatal period. The risk of sporadic cancer among offspring of male and female cancer survivors was not elevated in comparison to the general population. The study showed that former cancer patients are at risk of certain adverse endocrine and reproductive health outcomes and should be followed for timely intervention. The offspring of cancer survivors do not appear to be at risk for adverse health outcomes.

Localização de insulinoma pela injeção seletiva intra-arterial de cálcio

Insulinomas are rare endocrine tumors with an estimated incidence of 1(one) per million. Optimal therapy for all islet tumors of the pancreas is curative surgical resection. However, previous reports have show that, in the absence of preoparative localization, insulinoma may not be found intraoperatively in about 20% of patients. With current imaging technology, including serial computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography, localization of insulinomas less than 2cm remains inadequate. This case report shows that selective intraarterial calcium injection with hepatic venous sampling for insulin levels measured is a efficient technique for the localization of insulinomas.

Identification and characterization of new genes and pathways regulating spermatogonial cell fate

Spermatogenesis, i.e sperm production in the seminiferous tubules of the testis, is a complex process that takes over one month to complete. Life-long ability of sperm production ultimately lies in a small population of undifferentiated cells, called spermatogonial stem cells (SSCs). These cells give rise to differentiating spermatogonia, which are committed to mature into spermatozoa. SSCs represent a heterogeneous population of cells and many aspects of their basic biology are still unknown. Understanding the mechanisms behind the cell fate decision of these cells is important to gain more insights into the causes of infertility and testis cancer. In addition, an interesting new aspect is the use of testis-derived stem cells in regenerative medicine. Our data demonstrated that adult mouse testis houses a population of Nanog-expressing spermatogonia. Based on mRNA and protein analysis these cells are enriched in stage XII of the mouse seminiferous epithelial cycle. The cells derived from this stage have the highest capacity to give rise to ES cell-like cells which express Oct4 and Nanog. These cells are under tight non- GDNF regulation but their fate can be dictated by activating p21 signalling. Comparative studies suggested that these cells are regulated like ES cells. Taken together these data imply that pluripotent cells are present in the adult mammalian testis. CIP2A (cancerous inhibitor of PP2A) has been associated with tumour aggressiveness and poor prognosis. In the testis it is expressed by the descendants of stem cells, i.e. the spermatogonial progenitor cells. Our data suggest that CIP2A acts upstream of PLZF and is needed for quantitatively normal spermatogenesis. Classification of CIP2A as a cancer/testis gene makes it an attractive target for cancer therapy. Study on the CIP2A deficient mouse model demonstrates that systemic inhibition of CIP2A does not severely interfere with growth and development or tissue or organ function, except for the spermatogenic output. These data demonstrate that CIP2A is required for quantitatively normal spermatogenesis. Hedgehog (Hh) signalling is involved in the development and maintenance of many different tissues and organs. According to our data, Hh signalling is active at many different levels during rat spermatogenesis: in spermatogonia, spermatocytes and late elongating spermatids. Localization of Suppressor of Fused (SuFu), the negative regulator of the pathway, specifically in early elongating spermatids suggests that Hh signalling needs to be shut down in these cells. Introduction of Hh signalling inhibitor resulted in an increase in germ cell apoptosis. Follicle-stimulating hormone (FSH) and inhibition of receptor tyrosine kinases resulted in down-regulation of Hh signalling. These data show that Hh signalling is under endocrine and paracrine control and it promotes germ cell survival.

Tumor carcinóide de estômago tipo 1

Gastric carcinoid occurs in less than 1% of gastric neoplasias and around 2% of carcinoids tumors. They are classified into three forms: type 1, associated with atrophic gastritis, type 2, associated with multiple endocrine neoplasia 1 and Zollinger Ellison syndrome, and type 3, a sporadic tumor. This study report a case of gastric carcinoid type 1, which manifested with chronic anemia, dyspeptic symptoms and hypergastrinemia. A 44 years old female patient, presented multiple lesions with diameter between 3 and 20 mm, with lynphonodal metastases. A total gastrectomy was performed associated with lymphnodes ressection and Y Roux reconstruction.