O co-processamento de resíduos em fornos de cimenteiras é uma alternativa de destinação de resíduos que consiste em substituir combustíveis ou matérias primas usados na fabricação do clínquer por diversos resíduos que apresentem poder calorífico e propriedades similares. Os resíduos são co-processados a temperaturas altas, porém podem ocorrer emissões de diversos poluentes devido a variedade de resíduos que podem ser co-processados. Entre esses poluentes estão os Hidrocarbonetos Policíclicos Aromáticos (HPA), que podem ser emitidos nas chaminés dos fornos das cimenteiras, ou também podem estar presentes no ambiente interno das mesmas. Considerando que os HPA são compostos orgânicos que apresentam potencial carcinogênico e/ou mutagênico, e assim oferecem risco à saúde humana, esse estudo tem o objetivo apresentar uma avaliação preliminar da presença e dos níveis de concentração de HPA em uma indústria de cimento que co-processa resíduos. As análises de HPA no ambiente ocupacional foram realizadas seguindo a metodologia proposta do NIOSH (National Institute for Occupational Safety and Health). Para isso utilizou-se como ferramenta analítica a técnica de cromatografia a líquido de alto desempenho (CLAE) com detecção por fluorescência, acompanhada da otimização e avaliação dos principais parâmetros analíticos do método, possibilitando assim a determinação dos 17 HPA prioritários pela NIOSH com confiabilidade analítica. Os resultados indicaram a presença de vários HPA no ambiente de trabalho estudado, porém numa concentração baixa (faixa de ng.m-3) e dentro da faixa de concentração encontrada em trabalhos em ambientes convencionais. Este estudo foi desenvolvido com a colaboração da FUNDACENTRO/MTE. / The co-processing of residues in furnaces of cement industries is an alternative to dispose residues by substituting conventional combustibles and raw materials used for production of clinker by diverse organic residues of similar properties and calorific power. Co-processing is made at high temperatures, but emission of diverse pollutants may occur as a consequence of the large diversity of residues that are processed. Among these pollutants, Polycyclic Hydrocarbons (PAH) may be either emitted in the chimneys of the furnaces, or be present in the interior ambient of these industries. PAH pose risk to human health because they are organic compounds having potential carcinogenic and mutagenic activities. The present study aims to show the results of a preliminary evaluation of the presence and concentration levels of PAH in a cement industry co-processing residues. PAH analyses in the occupational environment were made according the methodology recommended by NIOSH (National Institute of Occupational Safety and Health). High performance chromatography (HPLC) with fluorescence detection was the analytical technique used for analyses. Optimization and evaluation of the major analytical parameters allowed the determination of the 17 PAH prioritized by NIOSH to be made with analytical confidence. Results showed the presence of several PAH in the studied environment, but at low concentrations (in the range of ng.m-3). These concentrations are of similar magnitude to the ones found in conventional environments. The present study was made in collaboration with FUNDACENTRO/MTE.

O presente estudo visou reconstruir o histórico de impactos antrópicos na bacia de drenagem do Lago das Garças durante o século XX por meio da deposição de contaminantes no compartimento sedimentar. O Lago das Garças está localizado em uma unidade de conservação, Parque Estadual das Fontes do Ipiranga (PEFI), inserida em área altamente povoada e urbanizada da cidade de São Paulo. Dois testemunhos de sedimento (LG05-03 e LG05-04, com 70 cm e 65 cm, respectivamente) foram amostrados mediante auxílio de mergulhadores no ponto mais profundo do reservatório, sendo, posteriormente, fatiados a cada 1 cm. Em LG05-03 foram quantificadas as distribuições verticais de carbono orgânico total (COT), nutrientes totais (NT e PT), hidrocarbonetos policíclicos aromáticos (HPA), hidrocarbonetos alifáticos (n-alcanos), bem como foi feita a classificação granulométrica. Em LG05-04 foi determinada a deposição de metais pesados (Co, Cr, Cu, Fe, Mn, Ni, Pb e Zn) e a geocronologia através do isótopo radioativo \'ANTPOT. 210 Pb\', usando o modelo CIC (Constant Initial Concentration). Os dados foram analisados por meio de análises estatísticas multivariadas (ACP: Análise de Componentes Principais). Com base nas tendências dos dados e na ACP, foi possível estabelecer três fases principais: Fase I: 64-43 cm (~1894-1975): caracterizada por baixas concentrações de nutrientes e contaminantes, sendo possível recuperar níveis préindustriais destes compostos, propostos como valores de referência regionais. Ainda, com base na razão C/N e em razões entre n-alcanos, notou-se, nesta fase o predomínio de aporte de matéria orgânica de origem alóctone; Fase II: 43-26 cm (~1975-1990): aumento abrupto das concentrações de metais pesados e HPA traçadores de veículos automotores, marcando o aumento da poluição atmosférica devido ao grande crescimento econômico do município e maior circulação de veículos na região. Ainda, foi observado aumento gradual das concentrações de NT e PT, atribuídos aos despejos de esgotos não tratados oriundos da Secretaria de Agricultura e Abastecimento e da Fundação Parque Zoológico; Fase III: 26-0 cm (~1990-2005): aumento mais acentuado das concentrações de nutrientes devido aos despejos de esgotos, acarretando em maior eutrofia do sistema, registrada pelo perfil do n-\'C IND.17\'. Pico das concentrações de HPA traçadores do uso de carvão mineral associado às atividades de uma siderúrgica vizinha (Siderúrgica J.L. Alipeti), bem como queda das concentrações destes traçadores coincidindo com mudanças no processo industrial da empresa. Ainda nesta fase notaram-se aumentos expressivos dos teores e fluxos dos HPA traçadores de veículos automotores, corroborando o cenário de aumento vertiginoso da frota de veículos na última década. Desse modo, este estudo contribuiu com o cenário nacional em termos de manejo de bacias hidrográficas urbanas, incluindo registros desde a época pré-revolução industrial no Brasil (~1894) até os dias atuais, demonstrando o potencial do uso de testemunhos lacustres no resgate de informações relativas à contaminação de ecossistemas aquáticos associadas às atividades antropogênicas. / Present study aimed to reconstruct the human impact history on the Garças Lake Drainage Basin during the 20th Century based on contaminants deposition on the lacustrine sediment. Garças Lake is located in a preservation area, the Parque Estadual das Fontes do Ipiranga (PEFI), located in a highly populated urban area within the city of São Paulo. Two sediment cores (LG05-03 and LG05-04, 70 cm and 65 cm long) were sampled by divers at the deepest site of the lake, which were sliced at 1 cm intervals. Information for LG05-03 included total organic carbon (TOC), total nutrients (TN and TP), polycyclic aromatic hydrocarbons (PAHs), aliphatic hydrocarbons (n-alkanes) and grain size vertical distributions. Deposition of heavy metals (Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn) and the geocronology by \'ANTPOT. 210 Pb\', using CIC model (Constant Initial Concentration), were determined in LG05-04. Data were analyzed by multivariate statistic analysis (PCA, principal components analysis). Based on data trends and PCA, it was possible to recognized three main phases: Phase I: 64-43 cm (~1894-1975) characterized by low nutrients and contaminants concentrations, allowing retrieving preindustrial levels of these compounds, which are proposed as regional reference values. Besides, C/N ratio and n-alkanes ratios demonstrated aloctonous organic matter predominance; Phase II: 43-26 cm (~1975-1990) characterized by the abrupt increase of heavy metals and vehicular PAHs concentration, indicating the atmospheric pollution increase, due to the great economic rise experienced by the city of São Paulo over that time and the higher vehicles circulation in the region. Yet, it was observed a gradual increase in nutrient concentration attributed to the untreated sewage inputs from the São Paulo State Department of Agriculture and Provisioning headquarters and the city Zoo; Phase III: 26-0 cm (~1990-2005) characterized by a marked increase in nutrient concentration related to the untreated sewage inputs, leading to the increase of eutrophication, as registered by the n-\'C IND.17\' distribution. A peak of coal PAHs concentration was also noticed, related to a neighbor steel mill (J.L. Aliperti), followed by a subsequent decrease of these compounds, coincident with industrial procedures changes. Besides, there was an expressive increase in vehicular PAHs concentrations, corroborating the scenery of a drastic raise of vehicles in the last decade. The present study contributed to the national scenario towards urban drainage basin management. It included records since preindustrial time (~1894) up to the present, highlighting the potential use of lacustrine sediment on the retrieval of historical environmental changes of aquatic ecosystems and associated anthropogenic impacts.

Die Habilitationsschrift beinhaltet eine zusammenfassende Darstellung unterschiedlicher Marker der biologischen Psychiatrie. Hierzu wurden mittels neuroendokriner und molekulargenetischer Verfahren depressive Patienten, alkoholabhängige Patienten und schizophrene Patienten mit einer seltenen Arzneimittelnebenwirkung untersucht und die jeweiligen Befunde als State- Trait- und Residualmarker charakterisiert. Im Bereich Neuroendokrinologie wurden der Dex/CRH-Test und Liquoruntersuchungen bei depressiven Patienten und die Apomorphin-induzierte HGH-Sekretion bei alkoholabhängigen Patienten durchgeführt. Im Bereich Pharmakogenetik erfolgten molekularbiologische HLA-und Enzymsystemuntersuchungen bei Patienten mit einer Clozapin-induzierten Agranulocytose. Es zeigten sich folgende Charakterisierungen einzelner Substrate: * HHN-Systemveränderungen (messbar über Cortisol- und ACTH-Serumkonzentrationen) sind State-bzw. Residualmarker der Depression. CRH-, AVP-und Somatostatin-Liquorkonzentrationen sind keine biologischen Marker der Depression * Das HGH-"Blunting" alkoholabhängiger Patienten ist ein spezifischer Marker für Alkoholabhängigkeit mit ungünstigem klinischen Verlauf * Spezifische HLA-Haplotypen sind als Traitmarker der Clozapin-induzierten Agranulocytose zu werten. Enzymsystem-Polymorphismen haben keine Bedeutung bei der Entwicklung dieser Arzneimittelnebenwirkung Der spezifischen Charakterisierung einzelner Befunde schließt sich eine Diskussion über deren Bedeutung für die biologische Psychiatrie an. / Neuroendocrine and pharmacogenetic studies were performed in depressive and alcohol-dependent patients as well as schizophrenic patients with clozapine-induced agranulocytosis to characterize different serological or molecular substrates as state-, trait or residualmarker. Depressive patients were assessed using the dexamethasone/corticotropin releasing hormone test and measuring neuropeptide hormone concentrations in cerebrospinal fluid (CSF), whereas dopaminergic responsiveness of alcohol-dependant patients was assessed by the apomorphine-induced human growth hormone (HGH) secretion. HLA-subtyping and screening of relevant polymorphisms of clozapine metabolizing enzyme systems was performed in patients with clozapine-induced agranulocytosis (CA). * HPA-alterations as a function of cortisol-and ACTH serum concentration appear as state- and residual marker of depression. CSF-CRH, -AVP and -SOM do not fulfill marker criteria * HGH blunting may serve as a residual marker of alcoholism with poor clinical outcome * HLA alleles but not polymorphisms of clozapine metabolizing enzyme systems are associated with CA and thus, underline the importance of imunogenetic mechanisms in the pathophysiology of this idiosyncratic drug reaction. In conclusion, the importance of biological markers for psychiatric research and future directions are discussed

Made available in DSpace on 2014-12-17T15:42:05Z (GMT). No. of bitstreams: 1 AndreaFFBpdf.pdf: 4139444 bytes, checksum: afbdb6abf6434ea8e10808e3c84e0350 (MD5) Previous issue date: 2008-12-05 / Petr?leo Brasileiro SA - PETROBRAS / This work aims to detect polycyclic aromatic hydrocarbons (PAHs) through optimized analytical techniques, such as gas chromatography with flame-ionisation detector (CGFID), gas chromatography coupled to mass spectrometry (CGMS), Fluorescence Spectroscopy of Molecular and Purpot of oils and greases (POG). Apply to chemometrics, Factorial Planning 23, in the preparation of samples by liquid-liquid extraction. The sample preparation was used for liquid-liquid extraction and factors in this sample was used for the application of factorial planning 23, such as the use of ultrasound, solvents (dichloromethane, hexane and chloroform) and ratio of solvent / synthetic sample. These factors were assigned two types of levels: positive and negative. It was used to form the cube to better analyze the answers. The responses of the eight combinations were obtained in reading the spectrofluorimetric. The optimization of equipment were used, and they served in the HPA's identification of the samples collected in Rio Potengi. The optimization of the equipment was observed every 16's and PAH in the samples was found that the HPA's came from contamination of the Rio Potengi. The contamination comes through organic household waste, hospital waste, and among other contamination that comes from industries that are installed around the River The factorial design of high validity, it was observed a more effective sample preparation. The factorial design of liquid-liquid extraction showed a way to spend less solvent in less time using an ideal solvent, but also a way to extract more analyte from the matrix itself is water. In planning a smaller form factor extraction was the use of ultrasound, the ratio 1:3 corresponding to a solvent and sample 3 and the best solvent was dichloromethane who presented a viable extraction, not discarding the possibility of using also the hexane. The chloroform and may be toxic not had a good extraction / Este trabalho tem como objetivo detectar hidrocarbonetos polic?clicos arom?ticos (HPAs) atrav?s de t?cnicas anal?ticas otimizadas, tais como: Cromatografia Gasosa com Detector de Ioniza??o de Chama (CGDIC), Cromatografia Gasosa acoplada ? Espectrometria de Massa (CGEM), Espectroscopia de Fluoresc?ncia Molecular e Teor de ?leos e Graxas (TOG). Aplicar a Quimiometria, Planejamento Fatorial 23, na prepara??o de amostras por Extra??o L?quido-L?quido. A prepara??o da amostra utilizada foi ? extra??o l?quido-l?quido e nesta amostragem foi utilizado fatores para aplica??o do planejamento fatorial 23, tais como: a utiliza??o do ultrassom, solventes (diclorometano, hexano e clorof?rmio) e propor??o de solvente/amostra sint?tica. Esses fatores foram atribu?dos dois tipos de n?veis: positivo e negativo. E foi utilizada a forma de cubo para melhor analisar as respostas. As respostas das oito combina??es foram obtidas na leitura do espectrofluor?metro. A otimiza??o dos equipamentos foram utilizados, e eles serviram na identifica??o dos HPA s das amostras coletadas no Rio Potengi. Na otimiza??o do equipamento foi observado todos os 16 HPA s e nas amostras foi encontrados os HPA s que foram provenientes da contamina??o do Rio Potengi. A contamina??o por org?nicos vem atrav?s de lixos dom?sticos, lixos hospitalares, e dentre outras contamina??es que vem de ind?strias que s?o instaladas em torno do Rio. O planejamento fatorial foi de grande validade, pois foi observada uma maneira mais eficaz de prepara??o de amostra. O planejamento fatorial da extra??o liquido-liquido mostrou uma maneira de gastar menos solventes em menos tempo utilizando um solvente ideal, como tamb?m uma forma de extrair mais analito da pr?pria matriz ?gua. No planejamento fatorial a menor forma de extra??o foi a utiliza??o do ultrasom, a propor??o 1:3 que corresponde a um de solvente e 3 de amostra e o melhor solvente foi o diclorometano que apresentou uma vi?vel extra??o, n?o descartando a possibilidade de utiliza??o, tamb?m do hexano. O clorof?rmio al?m de ser t?xico n?o apresentou uma boa extra??o

Centenas de compostos orgânicos são emitidos para a atmosfera por uma variedade de fontes biogênicas e antrópicas. Essa mistura complexa causa preocupação devido ao impacto que esses compostos podem provocar na saúde e no ambiente. Apesar de constituírem 10-70% da massa do aerossol atmosférico, a caracterização dos compostos orgânicos particulados permanece ainda deficitária. A contribuição das principais fontes de emissão para a poluição a nível regional pode ser diagnosticada através da utilização de marcadores moleculares específicos. De acordo com esta necessidade, o objetivo do presente trabalho é a caracterização de compostos orgânicos do aerossol atmosférico coletado em sítios de cidades da América do Sul. As amostragens do material particulado (MP10) foram realizadas em duas áreas em Bogotá na Colômbia, uma de influência industrial (BOI) e outra veicular (BOV) em 2007, e em áreas urbanas em São Paulo no Brasil em 2007 (SPA 07) e 2008 (SPA 08), e em Buenos Aires (BAI) na Argentina em 2008. Diferentes classes de compostos orgânicos foram determinadas: n-alcanos e hidrocarbonetos policíclicos aromáticos (HPA) por cromatografia a gás com detecção por ionização em chama (CG-DIC), n-alcanais e n-alcanonas por cromatografia a gás com detecção por espectrometria de massas (CG/EM). A composição e concentração do aerossol atmosférico foram afetadas substancialmente pelo transporte de massas provenientes de regiões com queima de biomassa e pelas condições meteorológicas locais. Em SPA 08, BOI e BAI foram encontradas as maiores concentrações de MP10 onde as amostragens foram realizadas em época de seca, favorecendo a acumulação dos poluentes. A constituição orgânica do MP10 nos sítios estudados reflete a incorporação nas amostras de marcadores moleculares biogênicos como n-alcanos com número ímpar de carbonos. Dentre os traçadores antrópicos, foram identificadas a presença de pristano e fitano, a mistura complexa não-resolvida (MCNR) e HPA de queima de combustíveis fósseis. Em SPA 08 foi identificada a presença do reteno, um traçador da queima de biomassa. As maiores concentrações de n-alcanais e n-alcanonas foram observadas no sítio BOV. Os n-alcanais (< C20) identificados nos sítios deste trabalho podem ser originados a partir da oxidação de alcanos e alcenos, e as n-alcanonas (< C20) podem ter como origem atividades antrópicas, processos oxidativos na atmosfera ou atuação microbiana sobre outros compostos. / Hundreds of organic compounds are emitted to the atmosphere by biogenic and anthropogenic sources. This complex mixture generates concern due to the impact of these compounds on health and environment. In spite of accounting for 10-70% of the atmospheric aerosol mass, particulate-phase organic compounds are not yet well characterized. The contribution of the major emission sources to regional particulate pollution can be diagnosed by using specific molecular markers. According to this necessity, the present work has as objective the characterization of organic compounds from atmospheric aerosol collected in sites of South American cities. The particulate matter (PM10) sampling were accomplished in two areas in Bogota (Colombia), one with industrial (BOI) and other with vehicular (BOV) influence in 2007, and in urban areas in Sao Paulo (Brazil) in 2007 (SPA 07) and 2008 (SPA 08), and in Buenos Aires (BAI), Argentina, in 2008. Different organic classes were determined: n-alkanes and polycyclic aromatic hydrocarbons (PAH) by gas chromatograph with flame ionization detection (GC-FID), n-alkanals and n-alkanones by gas chromatograph with mass spectrometer detection (CG/MS). The aerosol atmospheric composition and concentration were substantially affected by mass transport from biomass burning regions and by the local meteorological conditions. In SPA 08, BOI and BAI were found the highest PM10 concentrations where the samplings were accomplished in dry period, contributing for the pollutants accumulation. The PM10 organic composition at studied sites reflects the incorporation from biogenic molecular markers in the samples like n-alkanes with odd carbon number. Among the anthropogenic tracers, were identified the presence of pristane and phytane, the unresolved complex mixture (UCM) and PAH from fossil fuel combustion. In SPA 08 was observed the presence of retene, a biomass burning tracer. Higher concentration from n-alkanals and n-alkanones were observed at the BOV site. The n-alkanals (< C20) identified at sites from this work may be originated from oxidation of alkanes and alkenes, and n-alkanones (< C20) are derived from anthropogenic activity, atmospheric oxidative processes or microbial action over other compounds.

We are unceasingly exposed to potentially harmful microorganisms. The battle against threatening infectious agents includes activation of both the innate and of the adaptive immune systems. Illness responses are elicited and include inflammation, fever, decreased appetite, lethargy and increased sensitivity to painful stimuli in order to defeat invaders. While many of these signs of disease are controlled by the central nervous system, it has remained an enigma how signals from the peripheral immune system reach the brain through its blood-brain barrier, which precludes macromolecules, including cytokines, from diffusing into the brain parenchyma. Previous findings indicate the existence of a pathway across the blood-brain barrier, which includes binding of the cytokine interleukin-1 (IL-1) to its receptor in the brain vessels, thereby inducing the production of the prostaglandin E2 (PGE2) synthesizing enzymes cyclooxygenase-2 (Cox-2) and microsomal prostaglandin E synthase-1 (mPGES-1), which ultimately synthesize PGE2. PGE2 subsequently binds to any of the four prostaglandin E2 (EP) -receptors. Previous results from our laboratory have suggested that this pathway plays a critical role in the febrile response to infectious stimuli. The present thesis aims at further investigating the molecular events underlying immune-to-brain signalling, with special emphasis on fever, hypothalamic-pituitary-adrenal (HPA) -axis activation and anorexia and their connection to signalling molecules of the cytokine and prostaglandin families, respectively. In paper I, the molecular processes linking the proinflammatory cytokine interleukin-6 (IL-6) and PGE2 in the febrile response were investigated. Both IL-6 and PGE2 have been shown to be critical players in the febrile response, although the molecular connections are not known, i.e. if IL-6 exerts its effects up- or downstream of PGE2. Mice deficient in IL-6 were unable to respond to bacterial lipopolysaccharide (LPS) with a febrile response, but displayed similar induction of Cox-2 and mPGES-1, and similar concentrations of PGE2 in the cerebrospinal fluid as wild-type mice. Paradoxically, the IL-6 deficient mice responded with a dose-dependent elevation of body temperature in response to intracerebroventricularly injected PGE2. Furthermore, IL-6 per se was not pyrogenic when injected peripherally in mice, and did not cause increased levels of PGE2 in cerebrospinal fluid. IL-6 deficient mice were not refractory to the action of PGE2 because of excess production of some hypothermia-producing factor, since administration of a Cox-2 inhibitor in LPS-challenged IL-6 deficient mice did not unmask any hypothermic response, and neutralization of tumor necrosis factor α (TNFα), associated with hypothermia, did not produce fever in LPS-challenged IL-6 deficient mice. These data indicate that IL-6 rather than exerting its effects up- or down-stream of PGE2 affects some process in parallel to PGE2, perhaps by influencing the diffusion and binding of PGE2 onto its target neurons. In papers II and III, we injected the proinflammatory cytokine IL-1β in free-fed wild-type mice, in mice with a deletion of the gene encoding mPGES-1, or in mice deficient in the EP1, EP2 and EP3. Food intake was continuously measured during their active period, revealing that mPGES-1 deficient mice were almost completely resistant to anorexia induced by IL-1β. However, all of the investigated EP receptor deficient mice exhibited a normal profound anorexic response to IL-1β challenge, suggesting that the EP4 is the critical receptor that mediates IL-1β-induced anorexia. We also investigated the role of mPGES-1 in anorexia induced by lipopolysaccharide (LPS) in mPGES-1 deficient mice. The profound anorexic response after LPS-challenge was similar in mPGES-1 deficient and wild-type mice. To further investigate the anorectic behaviour after LPS injection, we pre-starved the animals for 22 hours before injecting them with LPS. In this paradigm, the anorexia was less profound in mPGES-1 knock-out mice. Our results suggest that while the inflammatory anorexia elicited by peripheral IL-1β seems largely to be dependent on mPGES-1-mediated PGE2 synthesis, similar to the febrile response, the LPS-induced anorexia is independent of this mechanism in free-fed mice but not in pre-starved animals. In papers IV and V, the role of prostanoids for the immune-induced HPA-axis response was investigated in mice after genetic deletion or pharmacological inhibition of prostanoid-synthesizing enzymes, including Cox-1, Cox-2, and mPGES-1. The immediate LPS-induced release of ACTH (adrenocorticotropic hormone and corticosteroids was critically dependent on Cox-1 derived prostanoids and occurred independently of Cox-2 and mPGES-1 derived PGE2. In contrast, the delayed HPA-axis response was critically dependent on immune-induced PGE2, synthesized by Cox-2 and mPGES-1, and occurred independently of Cox-1 derived enzymes. In addition, in the mPGES-1 deficient mice, the synthesis of CRH hnRNA and mRNA was decreased in the paraventricular nucleus of the hypothalamus after LPS-challenge, indicating that the delayed hormone secretion was mediated by PGE2-induced gene-transcription of CRH in the hypothalamus. The expression of the c-fos gene and Fos protein, an index of synaptic activation, was maintained in the paraventricular nucleus and its brainstem afferents both after unselective and Cox-2 selective inhibition as well as in Cox-1, Cox-2, and mPGES-1 knock-out mice. This suggests that the immune-induced neuronal activation of autonomic relay nuclei occurs independently of prostanoid synthesis and that it is insufficient for eliciting stress hormone release.

Background: Subtle and inconsistent differences in hypothalamic-pituitary-adrenal (HPA) axis activity have been reported for patients with panic disorder. While these patients show little or no alterations in basal ACTH and cortisol levels, it has been hypothesized that HPA hyperresponsivity was a trait in panic patients when exposed to novel and uncontrollable stimulation. Methods: Thirty-four patients (23 females, mean age 35 yrs) diagnosed with panic disorder were compared to 34 healthy controls matched for age, gender, smoking status, and use of oral contraceptives. Both groups were exposed twice to a potent laboratory stress protocol, the Trier Social Stress Test (TSST) on consecutive days. Free salivary cortisol levels and heart rate responses were repeatedly measured before and following the TSST. In addition, the cortisol awakening response (CAR) was assessed to further investigate HPA reactivity in PD patients. Results: While the TSST induced similar heart rate stress responses in both groups, cortisol responses were clearly absent in the panic patients with normal responses in the controls (F(1.96, 66) = 20.16; p < 0.001). No differences in basal cortisol levels were observed in the extended baseline period. The same cortisol stress non-response patterns were observed when patients with/without comorbid depression, or with/without psychotropic medication were compared. In contrast to their non-response to the psychosocial stressor, panic patients showed a significant CAR. Conclusion: These findings provide strong evidence to suggest that PD patients present with a striking lack of cortisol responsivity to acute uncontrollable psychosocial stress under laboratory conditions. This unresponsiveness of the HPA axis appears to be rather specific, since a normal CAR in the morning could be documented in these patients. Thus, the present results do not support the hypothesis that PD patients show a trait HPA hyperresponsiveness to novel and uncontrollable stimulation. In contrast, the data provide support for a hyporesponsive HPA axis under emotional stress in PD patients.

The 5-HTT gene (SLC6A4) is regulated by a common polymorphism in the promoter region (5-HTTLPR), which has functional consequences. Two major alleles have been observed and shown to have differential transcriptional activity with the long (L) allele having greater gene expression than the short (S) allele. 5-HTTLPR appears to modulate depression, anxiety and personality traits such as neuroticism. Additionally, a significant influence of 5-HTTLPR genotype on amygdala reactivity in response to fearful stimuli has been reported. Moreover, 5-HTTLPR seems to impact on the role of stressful life events (SLEs) in the development of depression. An elevated risk of depression and suicidal behaviors has been found in carriers of at least one low expressing S allele who had experienced SLEs, suggesting a gene x environment interaction. However, a recent meta-analysis showed that several findings failed to replicate this finding. Since genetic polymorphisms of the dopaminergic and serotonergic neurotransmission interact at the molecular, analyses with another polymorphism of the dopaminergic system, the dopamine D4 receptor (DRD4) was included to consider these likely gene-gene interactions (epistasis). The aim of this series of studies was to investigate the role 5-HTTLPR and SLEs on the endocrine stress response in different age samples. While newborns have been examined by a heel prick, stress responses were provoked in children (8-12 yrs) and younger adults (19-31 yrs) and older adults (54-68 yrs.) with the Trier Social Stress Test (TSST). The Life History Calendar (LHC) and Life Events Questionnaire (LEQ) were used to acquire data on SLEs. While in newborns the S/S genotype showed a significantly higher acute endocrine stress response than L/L or S/L genotypes, no significant difference between genotype groups was found in children. In the younger adult sample, the genotype impacted on cortisol stress responsiveness was reversed. Adults carrying the more active L allele of the 5-HTTLPR polymorphism showed a significantly larger cortisol response to the TSST than individuals carrying at least one of the lower expressing S allele. In older adults, no significant difference between genotype groups was found. However, results point in the same direction with showing highest cortisol response in individuals with L/L genotype. These data suggest that the association between 5-HTTLPR and endocrine stress reactivity seems to alter across lifespan, more specific the effects of genotype turns around. In addition, a significant interaction effect of 5-HTTLPR and SLEs has been found in the sample of younger adults, i.e. that early SLE as well as a severe number SLEs across the entire lifespan seem to modulate the interaction between HPA axis activity and 5-HTTLPR genotype. Additionally, a DRD4 by 5-HTTLPR interaction emerged which point to independent and joint effects of these polymorphisms on stress responsivity with regard to the concept of genegene interaction.

No description available.

Over the years stress has been a term lacking one clear and specific definition. In general, the term stress has been used mostly as an explanation of a response or reaction to a stressor. A stressor can be of both physiological and behavioral character. The experience of stress can occur both due to a real or a perceived stressor. In this literature review, the concept of stress is viewed with insights from biological, psychological, and social perspectives. The stress response is described biologically with the central nervous system (CNS), the brain, and the hypothalamic-pituitary-adrenal (HPA) axis. Social and psychological stress are concepts related to how stress is perceived by the mind and due to social surroundings which is described in relation to social support, self-efficacy, the locus of control and cognitive appraisal. Dealing with stress can be done through coping which refers to the individual capacity to handle a stressor and has generally been divided into two categories, active/passive coping and problem-focused/emotion-focused coping. Depending on the individual resources to cope with a stressor and the ability to decrease the stress response when needed, the long-term effects of stress can therefore vary between individuals. It has been found that positive coping (known as reducing stress) can increase the anterior cingulate cortex (ACC) volume and decrease anxiety and depression. The prefrontal cortex (PFC), the hippocampus, and the amygdala are closely linked to the ACC and affect emotions, learning, and memory related to the stress response.