The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones

Abstract Background a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed. Results elderly runners showed a significantly higher T cell proliferative response and IL-2 production than sedentary elderly controls. IL-2 production was similar to that in young adults. Their serum IL-6 levels were significantly lower than their sedentary peers. They also showed significantly lower IL-3 production in comparison to sedentary elderly subjects but similar to the youngs. Anabolic hormone levels did not differ between elderly groups and no clear correlation was found between hormones and cytokine levels. Conclusion highly conditioned elderly men seem to have relatively better preserved immune system than the sedentary elderly men. Long-term endurance training has the potential to decelerate the age-related decline in immune function but not the deterioration in endocrine function.

The juvenile three-spined stickleback : model organism for the study of estrogenic and androgenic endocrine disruption in laboratory and field

Industrial and domestic sewage effluents have been found to cause reproductive disorders in wild fish, often as a result of the interference of compounds in the effluents with the endocrine system. This thesis describes laboratory-based exposure experiments and a field survey that were conducted with juveniles of the three-spined stickleback, Gasterosteus aculeatus. This small teleost is a common fish in Swedish coastal waters and was chosen as an alternative to non-native test species commonly used in endocrine disruption studies, which allows the comparison of field data with results from laboratory experiments. The aim of this thesis was to elucidate 1) if genetic sex determination and differentiation can be disturbed by natural and synthetic steroid hormones and 2) whether this provides an endpoint for the detection of endocrine disruption, 3) to evaluate the applicability of specific estrogen- and androgen-inducible marker proteins in juvenile three-spined sticklebacks, 4) to investigate whether estrogenic and/or androgenic endocrine disrupting activity can be detected in effluents from Swedish pulp mills and domestic sewage treatment plants and 5) whether such activity can be detected in coastal waters receiving these effluents. Laboratory exposure experiments found juvenile three-spined sticklebacks to be sensitive to water-borne estrogenic and androgenic steroid substances. Intersex – the co-occurrence of ovarian and testicular tissue in gonads – was induced by 17β-estradiol (E2), 17α-ethinylestradiol (EE2), 17α-methyltestosterone (MT) and 5α-dihydrotestosterone (DHT). The first two weeks after hatching was the phase of highest sensitivity. MT was ambivalent by simultaneously eliciting masculinizing and feminizing effects. When applying a DNA-based method for genetic sex identification, it was found that application of MT only during the first two weeks after hatching caused total and apparently irreversible development of testis in genetic females. E2 caused gonad type reversal from male to female. E2 and EE2 induced vitellogenin - the estrogen-responsive yolk precursor protein, while DHT and MT induced spiggin – the androgen-responsive glue protein of the stickleback. None of the effluents from two pulp mills and two domestic sewage treatment plants had any estrogenic or androgenic activity. Juvenile three-spined sticklebacks were collected during four subsequent summers at the Swedish Baltic Sea coast in recipients of effluents from pulp mills and a domestic sewage treatment plant as well as remote reference sites. No sings of endocrine disruption were observed at any site, when studying gonad development or marker proteins, except for a deviation of sex ratios at a reference site. The three-spined stickleback – with focus on the juvenile stage – was found to be a sensitive species suitable for the study of estrogenic and androgenic endocrine disruption.

Removal of endocrine disrupting compounds from wastewater: a comparison between a conventional activated sludge with tertiary treatment and membrane bioreactors

Póster presentado en 19th International Congress of Chemical and Process Engineering, Prague, Czech Republic August 28th-September 1st, 2010.

The individual and interactive relationship between long chain omega-3 polyunsaturated fatty acids and physical activity as predictors of cognition in cognitively impaired and non-impaired older adults

Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.

Brief for GSDR - Emerging Contaminants in urban stormwater: Challenges and perspectives for sustainable water use

Emerging contaminants (ECs) are chemical compounds commonly present in water. It is only recently that this family of compounds is being recognized as significant water pollutants (. ECs include a wide variety of chemicals such as pharmaceutical and personal care products (PPCPs), pesticides, hydrocarbons and hormones, among others, that once released into the environment exert adverse impacts on the human and wildlife endocrine system. Natural attenuation and conventional treatment processes are not capable of removing these micro-pollutants detected in wastewater influent and effluent and surface and drinking water. The main challenges related with presence of ECs in stormwater in the context of reuse are: a) Development of suitable laboratory test methodologies and protocols for ECs identification and quantification b) Identification of the sources of ECs in the urban environment; c) Understanding their impacts on human and/or ecosystem health; and d). Development of cost-effective removal technologies which are appropriate for large as well as small-scale application.

Efeitos metabólicos e testicular da administração em longo prazo de diferentes dietas hiperlipídicas em ratos adultos

A obesidade e suas complicações metabólicas afetam o sistema endócrino e vários órgãos, tais como os testículos. Portanto, o objetivo deste estudo foi avaliar os efeitos da ingestão de diferentes dietas hiperlipídicas (rica em ácidos graxos saturados e/ou poliinsaturados) na massa corporal, no metabolismo de carboidratos e na morfologia testicular em ratos aos sete meses de idade. 39 ratos machos Wistar (três meses de idade) foram divididos em 4 grupos: SC (standard chow; n = 9), HF-S (dieta hiperlipídica rica em ácidos graxos saturados; n = 10), HF-P (dieta hiperlipídica rica em ácidos graxos poliinsaturados; n = 10), HF-SP (dieta hiperlipídica rica em ácidos graxos saturados e poliinsaturados; n = 10). A massa corporal foi monitorada semanalmente, até o final do experimento. Ao sacrifício (sete meses de idade), amostras de sangue foram coletadas e os testículos foram dissecados, pesados e processados para análises histomorfométrica, imunohistoquímica e bioquímica. Os depósitos de gordura genital foram dissecados e pesados. Os dados foram analisados por ANOVA e pós-teste de Bonferroni, considerando p < 0,05. As dietas hiperlipídicas promoveram aumento na massa corporal dos animais quando comparado ao grupo SC (p < 0,0001). Corroborando com esse resultado, os depósitos de gordura genital dos grupos hiperlipídicos (HF-S, HF-P e HF-SP) apresentaram aumento de 67%, 91% e 90% (p = 0,0004) em relação ao grupo SC, respectivamente. Quanto aos parâmetros séricos, os animais dos grupos HF-S e HF-SP apresentaram hiperglicemia (p = 0,0060), hiperinsulinemia (p = 0,0030), hipercolesterolemia (p = 0,0021). Todos os grupos hiperlipídicos apresentaram hiperleptinemia (p = 0,0019). Os níveis de triglicerídeos e testosterona não diferiram entre os grupos. Em relação ao testículo, os grupos SC, HF-P e HF-SP apresentaram maior altura do epitélio seminífero quando comparado ao grupo HF-S (p = 0,0003). No que diz respeito ao diâmetro dos túbulos seminíferos, verificou-se uma diminuição no grupo HF-SP, em comparação ao grupo SC (p = 0,0010). A proliferação celular foi reduzida no grupo HF-S comparado ao grupo SC (p = 0,0450). Não foram observadas diferenças na massa testicular e na concentração de colágeno. Diante do exposto, a administração de dieta HF, independentemente da qualidade do lipídio, promoveu o sobrepeso em ratos adultos. No entanto, a dieta rica em ácidos graxos saturados (banha de porco) promoveu alterações no metabolismo dos carboidratos e na morfologia testicular, com redução no diâmetro dos túbulos seminíferos, na altura do epitélio seminífero e na proliferação das células da linhagem espermatogênica. Estas alterações estão possivelmente relacionadas à distúrbios na espermatogênese.

Avaliação da presença de metilparabeno e propilparabeno no ambiente aquático e seus potenciais estrogênicos e a toxicidade aguda.

Atualmente no cenário mundial a qualidade da água tem gerado muitas preocupações, pois milhares de produtos sintéticos são produzidos para facilitar muitas práticas industriais, domésticas e pessoais e com isso diversas substâncias químicas utilizadas para esses fins são introduzidas no meio ambiente. Os parabenos são substâncias químicas utilizadas pelas indústrias farmacêuticas, de alimentos e cosméticos e que cuja função é a conservação, sendo que há muitos questionamentos em relação a sua segurança, pois alguns relatórios têm mostrado que a exposição a esses parabenos pode modular ou perturbar o sistema endócrino e com isso gerar consequências prejudiciais à saúde humana e aos ambientes aquáticos. Esse estudo teve como objetivo avaliar a presença dos Parabenos Metilparabeno e Propilparabeno no ambiente aquático e os seus potenciais estrogênicos e a toxicidade aguda. A metodologia se desenvolveu a partir do ensaio in vitro YES para a determinação da atividade estrogênica, ensaios de toxicidade aguda em Daphnia similis e em Aliivibrio fischeri e a quantificação dos parabenos na água do Rio Maracanã-RJ através da cromatografia líquida acoplada ao espectrômetro de massa. Os resultados obtidos para a CE50 dos MP e PP, a partir do ensaio in vitro YES, foi de 18,91 mgL-1 e 7 mgL-1 e a magnitude da resposta foi de 10-5 e 10-4 menos potente que 17ß-estradiol para o MP e o PP, respectivamente. A partir do ensaio de toxicidade aguda, os valores de CE50 obtidos em Daphnia similis, foi de 29,42 mgL-1 e 9,94 mgL-1e em Aliivibrio fischeri foi de 3,047 mgL-1 e 1,946 mgL-1, respectivamente, com isso observou-se que o PP é mais tóxicos em todos os organismos testados, sendo mais tóxicos para um e menos para outros. A água do Rio Maracanã não foi tóxica para a Daphnia similis em nenhum dos dois pontos, já para o Aliivibrio fischeri foi tóxica em apenas um ponto. As concentrações encontradas de MP e PP foram maiores no ponto onde, de acordo com os parâmetros físico-químicos, a qualidade da água não está dentro dos padrões exigidos pela legislação, sendo quantificados na ordem de ngL-1, contudo é válido ressaltar que os DEs não são encontrados no meio ambiente separados, eles interagem entre si e provocam efeitos aditivos ou sinérgicos, sendo muito difícil de prever qual o efeito, por isso é importante o conhecimento do potencial estrogênico das substâncias simples, pois em um estudo com uma matriz ambiental, pode-se observar se houve algum efeito aditivo ou sinérgico de outras substâncias.

Monitoramento de desreguladores endócrinos no rio Arroio Fundo na bacia de Jacarepaguá, RJ.

Os desreguladores endócrinos são compostos micropoluentes de ação deletéria que causam efeitos aos animais e aos seres humanos. Estes vêm trazendo a várias décadas, problemas relacionados à má formação ou ainda infertilidade de várias espécies. A presença destes compostos na ordem de ng L-1 já é capaz de gerar efeitos nocivos ao sistema endócrino. Este trabalho visou à determinação da presença e quantidade de alguns destes compostos como 17α-etinilestradiol, bisfenol A e estrona entre outros, nas águas do rio Arroio Fundo, localizado em Jacarepaguá no RJ que possui um índice de qualidade de água ruim. A primeira etapa deste trabalho foi a implementação e validação de metodologia para determinação do 17α-etinilestradiol por cromatografia líquida acoplada a detector de fluorescência onde foram estabelecido limite de detecção, de quantificação e linearidade conforme orientação do Inmetro (2010). Além da avaliação das amostras ambientais através da metodologia estabelecida. Na etapa subsequente foram realizados os experimentos relativos à determinação dos desreguladores endócrinos através da espectrometria de massas por detector tipo tandem quadrupolo, onde também foram realizados os procedimentos de validação e determinação dos compostos bisfenol A e estrona que não foram suscetíveis a efeito de matriz durante a ionização, que acabou impedindo a determinação de outros desreguladores endócrinos. Os resultados indicam que não há redução da presença dos desreguladores endócrinos detectados, e de outros compostos orgânicos também detectados, mas não identificados, entre os pontos a montante e a jusante da Unidade de Tratamento do Rio Arroio Fundo. Todavia em função do grande efeito de matriz oriundo do fato da amostra ser de extrema complexidade, não foi possível realizar uma identificação e quantificação de todos os compostos alvos.

Efeitos comportamentais e endócrinos do tratamento com a vareniclina em um modelo experimental de exposição à nicotina durante a adolescência

A nicotina é considerada o principal componente psicoativo do tabaco e esta induz seus efeitos farmacológicos centrais atuando em receptores nicotínicos colinérgicos (nAChRs). A maturação dos sistemas colinérgicos é consolidada durante o período da periadolescência, o que sugere que o cérebro do adolescente é vulnerável aos efeitos de estimulantes colinérgicos. Dados os efeitos deletérios do consumo de tabaco, incluindo a dependência, têm sido desenvolvidas estratégias terapêuticas para facilitar a interrupção do uso. A mais recente é o uso da vareniclina, um agonista parcial dos nAChRs α4β2. Pouco se sabe sobre os efeitos da exposição à nicotina na adolescência e menos ainda dos efeitos de curto e longo prazos dos tratamentos disponíveis para a reversão da dependência ainda durante este período. Neste sentido, os objetivos desse trabalho foram o de estudar os comportamentos associados à ansiedade e busca por novos estímulos e a função adrenal em animais expostos à fumaça do cigarro durante a adolescência e subsequentemente tratados com procedimento para reversão de dependência à nicotina. Esse estudo utilizou 150 camundongos Suíços adolescentes (de ambos os sexos). Os animais foram expostos à solução aquosa de nicotina (50g/ml - NIC) ou de sacarina (2% - SAC) v.o. do 30o dia de vida pós-natal (PN) à PN45 e submetidos aos seguintes tratamentos por gavagem de PN45 à PN56: 1) vareniclina (0,1 ou 1,0 mg/kg/dia, VAR1 e VAR2 respectivamente); 2) veículo (VEH); 3) nicotina na dose utilizada entre PN30 e PN45 (NIC). Sete grupos experimentais foram utilizados: SACVEH, SACVAR1, SACVAR2, NICVEH, NICVAR1, NICVAR2 e NICNIC. Em PN55, os animais foram submetidos ao teste do labirinto em cruz elevado (LCE) por 5 min, e duas depois ao teste do campo vazado (CV) também por 5 min. Os tecidos coletados em PN56 (após o sacrifício dos animais) foram: adrenal esquerda para a verificação do conteúdo de catecolaminas, adrenal direita para avaliação da expressão da tirosina hidroxilase e soro para a dosagem de corticosterona. Os nossos resultados demonstraram que no final da vigência do tratamento não foram encontradas diferenças entre os grupos no comportamentos associados à ansiedade do LCE e nos associados à busca por novos estímulos no CV. Por outro lado, a análise do número de orifícios explorados no centro do CV, também utilizado como medida de ansiedade, sugerem que a vareniclina por si só e a exposição continuada à nicotina são ansiogênicas mas que que o tratamento com vareniclina após a exposição à nicotina mantém os resultados dentro da normalidade. Do ponto de vista endócrino, o conteúdo adrenal de catecolaminas foi corrigido pelo tratamento com vareniclina, os níveis séricos de corticosterona foram aumentados pela exposição à nicotina enquanto o tratamento com vareniclina aumentou a expressão de tirosina hidroxilase. Nosso estudo indica que, no final da vigência do tratamento, tanto aspectos comportamentais como endócrinos estão significativamente afetados em nosso modelo de exposição à nicotina durante a adolescência e tratamento subsequente com vareniclina. Estudos futuros deverão avaliar estes parâmetros em períodos posteriores, com o objetivo de verificar se as alterações observadas persistem na vida adulta.

Changes in plasma thyroid hormones and cortisol levels in crucian carp (Carassius auratus) exposed to the extracted microcystins

The endocrine response of crucian carp injected intraperitoneally with extracted microcystins (MC) was investigated in this study. Fish were injected intraperitoneally either with 0.75% NaCl (control) and Microcystis extract corresponding to 150 and 600 mu g microcystins per kg body weight. The plasma levels of triiodothyronine (T-3), thyroxine (T-4), free triiodothyronine (FT3), free thyroxine (FT4), and cortisol were determined at 0, 1, 3, 12, 24. and 48 h post-administration of MC-containing extract. Treated fish displayed abnormal behaviors, Such as a startle response and disoriented swimming, as well as changes in ventilation rates. Plasma cortisol concentrations of fish in both dose groups significantly increased after administration of extracted MC and remained high throughout the experiment, which suggested that MC elicited a stress response in treated fish. The profiles of cortisol changes in treated fish appeared to be dose dependent, indicating that fish in the high dose group experienced greater MC-incluced disturbance. Mortality occurred after 12 h in the high dose group. Plasma levels of T-4, T-3, FT4, and FT3 did not vary significantly between the control fish. In contrast to this, fish exposed to MC-containing extract showed significant declines in T-3, FT4, and FT3 levels in a dose-depenclent manner throughout the experiment. Plasma T4 levels, however, did not vary significantly in the low dose group, whereas they decreased significantly it 48 h post injection in the high dose group. This study demonstrates that administration of microcystins-containing extract causes a stress response and reduces the plasma levels of thyroid hormones in crucian carp. These results illustrate that microcystins exerted potent effects on the endocrine system of crucian carp, through activating their hypothalamus-pituitary- interrenal axis and disturbing thyroid function. (c) 2008 Elsevier Ltd. All rights reserved.

Timidity: A useful emotional mechanism for robot control?

M J Neal and J Timmis. Timidity: A useful mechanism for robot control? Informatica - special issue on perception and emotion based control, 4(27):197-204, 2003.

Alterações do Funcionamento da Glândula da Tiróide

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

DIESE Final Report

The DIESE program (Determination of relevant Indicators for Environmental monitoring: A Strategy for Europe) brought together seven French and British research teams, a private company and the agencies responsible for the management of water bodies of the two countries (ONEMA and the Environmental Agency) in a joint effort to document the ecotoxicological effects related to the presence of chemicals in the environment. To contribute to a better understanding and management of the environment, the program has expanded its efforts to (1) use existing knowledge, or new information acquired during the research program, to identify important biological problems affecting wildlife, (2) increase our understanding of toxicological mechanisms involved and thus be able to identify the causes of the identified dysfunctions and (3) to hone our expertise and vigilance systems in order to better monitor changes in the environment and make appropriate diagnoses. The first part of the program identified clear biological effects, and using biological tests representative of the mechanisms of action of compounds, identified the responsible compounds present in the environment. In connection with the feminization observed in many fish species in European streams, a search for estrogenic and anti-androgenic compounds was conducted. A new test identifying estrogenic compounds has been developed in roach and the ER-Calux test for anti-androgenic effects has been implemented. The results showed that, in addition to biocides such as triclosan and chlorophène, many aromatic hydrocarbon compounds are likely to disturb the physiology of living organisms by interacting with the androgen receptor. Six of these were identified in sediment extracts: benzanthrone, fluoranthene, 1,2- benzodiphenylene sulfide, benzo[a]pyrene, benz[a] anthracene, and 9-phenylcarbazole. The second part of the program aimed at documenting and understanding the mechanisms of action of chemicals leading to physiological changes. This work represents a particular challenge when dealing with molluscs, as knowledge about their physiology and endocrinology is still fragmentary. Thus, new technologies including metabolomic and transcriptomic analyses have been implemented in order to obtain a comprehensive picture of the effects on molluscs. Metabolomic research demonstrated that estrogenic compounds are able to alter the metabolism of eicosanoids and amines, while transcriptomic strategies identified genes whose expression is altered in intersex clams. Because these genes mainly appear as “male” genes, the results suggest that these profound physiological changes result from demasculinisation of male clams. Proteomic studies have also been carried out to elucidate the mechanisms of action of pollutants on fish physiology. These studies generally included a set of molecular marker measurements in an integrative and ecological perspective. The results showed that not only male fish physiology is altered but also female reproductive status is impaired. Moreover, it appeared that other alterations of the fish endocrine system, such as androgenic effects, are at work and that the immune system is also subject to chemical pressure including effects from environmental estrogens. Notably, the immune system, like the endocrine system, seems to show periods of particular sensitivity during development. Measurements on growth and on the general metabolism emphasize the importance of environmental conditions in the physiology of aquatic organisms and in particular the inter-site variability due to temperature,hypoxic conditions, and fish development strategies. They thus provide a unique perspective that allow us to better understand the context and consequences of natural conditions on the population. In a third part of the program, the research conducted had the objective of developing and testing a biomarker strategy to support the environmental management methodologies. Two lanes of specific studies have been followed. The first was to implement, over all or part of the study area, robust biomarkers to establish maps that highlight the water bodies at risk and provide information on sources of compounds and associated disturbances. The second part of the work aimed at exploring methodologies to take advantage of biomarker measurements and to integrate them in a very simple and clear index. Partial or comprehensive maps of the Channel area were produced to report the presence of mutagenic or anti-androgenic compounds in the sediments, intersex fish and clams, and imposex. These maps may remain to be completed and work will be necessary to confront this information in order to learn relevant lessons for management of the environment, a goal that the DIESE program has contributed to by providing some necessary and original information.

Neuroendocrine tumors. A European view

A center in Belfast, Northern Ireland, has established a register for tumors of the gastroenteropancreatic endocrine system. Carcinoid tumors occur most frequently. Of the non-carcinoid tumors, insulinomas, gastrinomas, and unknown types have the highest incidence, with other types being extremely rare. The potentially remediable nature of the tumors is stressed, and frequently a good quality of life can be experienced even in the presence of metastatic disease. The syndromes are probably underdiagnosed as they present with clinical features for which there are more common explanations, and appropriate diagnostic methods are therefore not used. The management of the syndromes is reviewed with particular emphasis on the treatment of patients with inoperable disease. Histamine (H2)-receptor antagonist therapy has made an impact in Zollinger-Ellison syndrome, and streptozotocin and somatostatin analogues can control tumor growth and endocrine syndromes, respectively.

Effects of the mycotoxin patulin at the level of nuclear receptor transcriptional activity and steroidogenesis in vitro

Patulin (PAT) is a mycotoxin produced by various species of fungi, with Penicillium expansum being the most commonly occurring. Apples and apple products are the main sources of PAT contamination. This mycotoxin has been shown to induce toxic effects in animals, a few of which include reproductive toxicity and interference with the endocrine system. Here the endocrine disrupting potential of PAT has been investigated in vitro to identify disruption at the level of oestrogen, androgen, progestagen and glucocorticoid nuclear receptor transcriptional activity, and to assess interferences in estradiol, testosterone and progesterone steroid hormone production. At the receptor level, 0.5-5000ng/ml (0.0032-32μM) PAT did not appear to induce any specific (ant) agonistic responses in reporter gene assays (RGAs); however, nuclear transcriptional activity was affected. A >6 fold increase in the glucocorticoid receptor transcriptional activity was observed following treatment with 5000ng/ml PAT in the presence of cortisol. At the hormone production level, despite cytotoxicity being observed after treatment with 5000ng/ml PAT, estradiol levels had increased >2 fold. At 500ng/ml PAT treatment, an increase in progesterone and a decrease in testosterone production were observed. The findings of this study could be considered in assessing the health risks following exposure to PAT.