PCBs are among the most problematic marine contaminants. Converging towards the oceans via the rivers and the atmosphere, they concentrate in sediments where they become a permanent threat to organisms living at their contact. PCBs are extremely resistant, bioaccumulated and some congeners are considered as highly toxic. The North Sea is considered as a highly contaminated area ; however little information is available regarding the impact of PCBs on key benthic organisms of this region. Ubiquist, abundant and generally recognized as a good bioindicator species, the common NE Atlantic sea star Asterias rubens (L.) is an ecosystem-structuring species in the North Sea and was chosen as an experimental model. The present study focused on the characterization of PCB bioaccumulation in A. rubens exposed through different routes (seawater, food, sediments) and on subsequent biological responses, at immune and sucellular levels. The considered responses were respectively (i) the production of reactive oxyggen species (ROS) by sea stars amoebocytes, which constitutes the main line of defence of echinoderms against pathogenic challenges and (ii) the induction of a cytochrome P450 immunopositive protein (CYP1A IPP) which, in vertebrates, is involved in PCB detoxification. Experimental exposures carried out have shown that A. rubens efficiently accumulates PCBs. Exposure concentrations were always adjusted to match those encountered in the field. PCB concentrations reached in sea stars during the experiments matched the values reported in field studies ; therefore our experimental protocol was found to accurately simulate actual field situations. Uptake kinetics were related to the planar conformation of the considered congeners : non-coplanar PCB uptake was described using saturation models, whereas coplanar PCBs (c-PCBs) were bioaccumulated according to bell-shaped kinetics. Non-coplanar congeners generally reached saturation concentrations whithin a few days or a few weeks, which means that sea stars can be used to pinpoint PCB contamination shortly after occurrence. On the other hand, c-PCB concentrations reached a peak followed by a sudden drop, indicating the probable occurrence of c-PCB-targeted metabolization processes in sea stars. Our experimental studies also demonstrated that seawater was by far the most efficient route for PCB uptake in sea stars and that even if PCB levels in seawater are extremely low compared to sediment-associated concentrations, seawater constitutes a non-negligible route for PCB uptake in marine invertebrates. Among the different body compartments, bodywall displayed the highest bioaccumulative potency and can therefore be considered as particularly interesting for field biomonitoring applications. Rectal caeca, which play a central role in digestion and excretion processes in sea stars, have also rised particular interest as results suggest these organs could be involved in the elimination of PCB 77 degradation products. The field work carried out during the present study showed that PCB concentrations measured in A. rubens tissues reflect environmental levels of certain congeners. As it was the case in experimental conditions, A. rubens differentially accumulated PCB congeners according to their planarity. Strong relationships were found between concentrations measured in sediments and those determined in sea stars body wall for certain non-coplanar congeners (e.g. 118 and 138), thus allowing to consider A. rubens as a suitable bioindicator species for medium-chlorinated PCB congeners. On the other hand, sea stars appeared to be able to regulate -to a certain extent- their content in coplanar PCBs. This implies that (i) A. rubens cannot be strictly considered as an indicator organism for c-PCBs and (ii) c-PCBs probably affect essential aspects of sea star biology, potentially leading to deleterious effects. The present study addressed effects of PCB exposure on A. rubens biology, in both experimental and field conditions. In experimental conditions, PCBs were found to significantly alter ROS production by sea stars amoebocytes. This alteration also occurred in a congener-specific way : c-PCBs were found to significantly affect, and probably impair sea stars immune system, whereas non-coplanar congeners had no effect. In the field, the PCB contribution to immunotoxicity could not be determined because none of our studies considered ROS production along with c-PCB concentration measurements. However, the levels of ROS production by sea stars amoebocytes measured in field and experimental conditions were found to potentially lead to altered immunity, and therefore to impair sea stars defence against pathogenic agents. A specially designed ELISA was used to measure CYP1A IPP in experimental and field conditions. Experimental work has shown that the induction of this protein was related to PCB exposure in a congener-specific fashion : c-PCBs alone were found to strongly induce the production of CYP1A IPP according to a dose-dependent relationship. These results have highlighted many similarities between the dioxin-like responsiveness of CYP1A IPP induction in sea stars and that occurring in vertebrates. This strongly suggests similarities in the toxicity-triggering mechanism of dioxins and c-PCBs. In the field, CYP1A IPP induction was found to be significantly related to PCB levels determined in bottom sediments. It can thus be considered as a valuable biomarker. Further research is however needed to better characterize the influence of physico-chemical and physiological parameters on CYP1A induction to refine the interpretation of the information gathered via this biomarker. Results obtained in our study have lead to questionning international regulations applying to PCB biomonitoring in the marine environment. For instance, we strongly suggest that the selection of congeners to be systematically considered should be revised to include c-PCBs. Indeed, in our experiments PCB toxicity was almost always attributable to the sole c-congeners. Historically, determination of c-PCB concentrations was extremely difficult due to analytical limitations ; however, nowadays, these problems have been overcome and do no more justify their exclusion from monitoring studies. Although A. rubens appeared to be quite resistant to PCB contamination, levels measured in sea stars from the southern North Sea can possibly affect their immune and endocrine systems in a subtle way, but with relatively low risk for this species at the short-term. However, this does not mean that other species in this region undergo similarly low risks, or that sea star-structured ecosystems may not become affected in the long-term

Proteins secreted or shed by tumors can be found in serum. Detecting these proteins by mass spectrometry (MS) is difficult, due to the wide dynamic range of protein concentrations in serum. To circumvent this issue, we mined the conditioned media of epithelial ovarian cancer (EOC) cell lines which is a less complex fluid to work with. We hypothesize that some of the proteins shed or secreted by EOC cell lines are similar to those secreted or shed by EOC tumors and that some of these proteins can be used as biomarkers. We mined the conditioned medium of four ovarian cancer cell lines (HTB75, TOV-112D, TOV-21G and RMUG-S) by two-dimensional liquid chromatography-mass spectrometry. Our study identified 1208, 1252, 885, and 463 proteins from the HTB-75, TOV-112D, TOV-21G, and RMUG-S cell lines respectively. In all, we identified 2039 proteins from which we focused on 420 extracellular and plasma membrane proteins. High abundance proteins such as albumin and immunoglobulins, which are problematic for serum proteomics, did not interfere with our study. Several known markers of EOC including CA-125, HE4, Mesothelin, and KLK6, were identified in this study. The list of 420 extracellular and membrane proteins was cross-referenced with the proteome of ascites fluid to generate a final list of 51 potential candidates. According to Ingenuity Pathway Analysis, two of the top 10 diseases associated with our list of 51 proteins were cancer and reproductive diseases. Of the 51 candidates, 10 proteins were selected for verification in sera from ovarian cancer patients and healthy individuals. Clusterin showed a significant difference between cancer patients and normal, with sera from cancer patients showing higher levels. Another protein, NPC2, did not show a difference in sera between cancer and normals. Protein expression studies using immunohistochemistry showed that NPC2 is highly expressed in ovarian cancer tissue and absent in normal ovarian surface epithelium. In summary, clusterin and NPC2 appear to play a role in ovarian cancer pathobiology and their role in EOC need to be studied further.

Background: Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. Methods/design: This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n=75) or placebo (n=75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. Discussion: The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin in a growing population at risk for multiple diseases.

Several biomarkers (cell viability and phagocytosis) based on earthworm (Lumbricus terrestris) immune cells (coelomocytes), together with whole-worm mortality (LC/LD50's), were used to assess a bioremediation attempt to reduce pentachlorophenol (PCP) toxicity in a former wood processing hazardous waste site (HWS).

Changes in monsoon patterns not only affect ecosystems and societies but also the global climate system in terms of heat energy and humidity transfer from the equator to higher latitudes. However, understanding the mechanisms that drive monsoon variability on longer timescales remains a challenge, partly due to sparse paleoenvironmental and paleoclimatic data. This thesis, which contributes new hydroclimate data sets for the Asian monsoon region, seeks to advance our understanding of the mechanisms that contributed to Southeast Asian summer monsoon variability in the past. Moreover, it explores how past climatic conditions may have impacted societies and ecosystems. In this study lake sediment and peat sequences from northeastern and southern Thailand have been investigated using organic geochemistry, and more specifically the stable carbon and hydrogen isotopic composition of specific biomarkers (n-alkanes, botryococcenes, and highly branched isoprenoids). The hydrogen isotopic composition of leaf waxes (δDwax) in Thailand was shown to relate to the amount of precipitation and the extent of the El Niño Southern Oscillation.  Higher values of δDwax can be interpreted as reflecting relatively dry climatic conditions, whereas lower values relate to wetter conditions. The hydroclimate reconstruction for northeastern Thailand, based on the sedimentary record of Lake Kumphawapi, suggests higher moisture availability between ca. 10,700 cal. BP and ca. 7,000 cal. BP likely related to a strengthened early Holocene summer monsoon. Moisture availability decreased during the mid-Holocene, but seems to have increased again around 2,000 years ago and has fluctuated since. The high-resolution Lake Pa Kho peat sequence, which allows for a sub-centennial reconstruction of moisture availability, indicates that the wettest period occurred between ca. 700 and ca. 1000 CE whereas driest intervals were from ca. 50 BCE to ca. 700 CE and from ca. 1300 to ca. 1500 CE. Hydroclimate comparison of Pa Kho’s δDwax record with other paleoclimate records from the Asian-Pacific region suggests that El Niño-like conditions led to Northeastern Thailand being wetter, whereas La Niña-like conditions led to drier conditions. Regional hydroclimate variability also greatly influenced the Angkor Civilization, which flourished between ca. 845 and ca. 1450 CE. The shift from drier to wetter conditions coincided in time with the rise of the Angkor Civilization and likely favored the intense agriculture needed to sustain the empire. The gradual decline in moisture availability, which started after ca. 1000 years CE, could have stretched the hydrological capacity of Angkor to its limit. It is suggested that Angkor’s population resorted to unconventional water sources, such as wetlands, as population growth continued, but summer monsoon rains weakened. The 150-year long record of Lake Nong Thale Prong in southern Thailand offers insights into decadal-scale hydroclimatic changes that can be connected to the instrumental record. δDwax-based hydroclimate was drier from ~1857 to 1916 CE and ~1970 to 2010 CE and wetter from ~1916 to 1969 CE. Drier climatic conditions between ~1857 and 1916 CE coincided with oligotrophic lake waters and a dominance of the green algae Botryococcus braunii. Higher rainfall between ~1916 and 1969 CE concurred with an increase in diatom blooms while eutrophic lake water conditions were established between ~1970–2010 CE. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Submitted. Paper 3: Manuscript.</p> / Monsoon project

La moule zébrée Dreissena polymorpha constitue une espèce sentinelle intéressantes en raison de traits bioécologiques (e.g. régime filtreur, mode de vie sessile, large aire de répartition) autorisant une utilisation pratique de cet organisme dans la surveillance de différents types d'hydrosystèmes (de Lafontaine et al., 2000). Les nombreuses études menées sur la dreissène ont d'ailleurs permis de développer depuis une dizaine d'années un ensemble de marqueurs biologiques destinés à évaluer l'impact des diverses activités anthropiques (activités agricoles, domestiques et industrielles) sur la qualité des milieux aquatiques. Ces biomarqueurs constituent des paramètres biologiques individuels (ou infra-individuels) dont la modulation par rapport à une valeur de référence est révélatrice d'une exposition, présente ou passée, à un ou plusieurs contaminants de l'environnement (e.g. pesticides, métaux lourds) (Lagadic et al., 1997a). Souvent associés à des mécanismes de défense de l'organisme (e.g. système de défense antioxydant, système de détoxication des métaux), les marqueurs usuels ne permettent toutefois pas d'évaluer concrètement les effets d'un stress toxique sur la " fitness " d'un individu (i.e. fécondité, survie) et au-delà sur le maintien de sa population (Forbes et al., 2006). La caractérisation de marqueurs génétiques associés au métabolisme énergétique pourrait constituer une solution potentielle à cet écueil dans la mesure où les fonctions d'entretien et de reproduction d'un individu sont sous l'étroite dépendance de sa capacité à exploiter les ressources alimentaires disponibles dans son milieu. L'étude de biomarqueurs énergétiques potentiels tels que les réponses enzymatiques digestives pourrait dès lors constituer une approche intéressante à développer dans le cadre de stratégies de biosurveillance multimarqueurs (Lagadic et al., 1994 ; De Coen et al., 1998b). Le prrésent travail de thèse a eu ainsi pour principal objectif d'analyser l'intérêt informatif potentiel des réponses enzymatiques digestives de la dreissène dans l'évaluation des risques associés à la présence de contaminants dans les milieux aquatiques. / The zebra mussel Dreissena polymorpha is a useful sentinel species because of bio-ecological traits (e.g. filtering activity, sessile lifestyle, range-wide distribution) allowing practical use of this organism for monitoring of various types of water systems (de Lafontaine et al., 2000). The numerous studies led on the zebra mussel allowed to develop, over the last ten years, a set of biomarkers to assess the impact of various human activities (agricultural, domestic and industrial ones) on the quality of aquatic environments. These biomarkers are individual (or infra-individual) biological parameters whose variation from a reference value is indicative of an exposure, past or present, to one or several environmental contaminants (e.g. pesticides, heavy metals) (Lagadic et al., 1997a). Often associated with individual defense systems (e.g. antioxydant defense system, metal detoxication system) 'core' biomarkers do not allow, however, to effectively assess the impacts of toxicants on individual " fitness " (i.e. fecundity, survival) and beyond, on the maintenance of population (Forbes et al., 2006). Characterization of generic markers associated with energy metabolism could be a potential solution to this problem since the maintenance and reproduction functions of an individual are closely related to its ability to exploit food resources. The study of potential energy biomarkers such as digestive enzyme responses could therefore be an interesting approach to develop as part of multimarker biomonitoring studies (Lagadic et al., 1994 ; De Coen et al., 1998b). The main objective of the present PhD thesis was to analyze the potential informative interest of zebra mussel's digestive enzyme responses in evaluating the potential risks associated with the presence of contaminants in aquatic environnments.

L’endocardite infectieuse est une maladie grave dont sont victimes chaque année près de 2000 personnes en France et 17000 aux Etats-Unis. Malgré les progrès thérapeutiques, le taux de décès reste encore élevé avec des chiffres d’environ 20% pour la seule période hospitalière. Ces échecs sont en partie la conséquence d’un diagnostic souvent trop tardif et d’une évaluation pronostique insuffisante. En effet, il semble que la stratégie pour réduire la mortalité repose sur l’utilisation de nouveaux outils pour un diagnostic et une stratification du risque plus rapides, une diminution du délai d’instauration du traitement antibiotique, un transfert des patients à haut risque vers des centres médico-chirurgicaux spécialisés, des indications chirurgicales plus larges et un suivi prolongé.Depuis plusieurs années nous avons développé un programme de recherche basé sur une étroite collaboration entre les chercheurs de l’UMR 6236-CNRS et les médecins et chirurgiens des services de cardiologie et de chirurgie cardiaque. Cette thèse rapporte les résultats de cette recherche translationnelle sur la prise en charge des endocardites, synthèse de l’expérience clinique et fondamentale acquise par notre équipe. Nous avons démontré que la standardisation des processus de diagnostic et de décisions chirurgicales au sein d’une équipe multidisciplinaire permet de réduire la mortalité. Afin d’améliorer encore cette prise en charge, des innovations telles que l’utilisation de nouveaux marqueurs biologiques représente une approche importante. A partir d’une analyse du profil transcriptionnel propre à l’endocardite, nous avons pu identifier plusieurs gènes fortement impliqués dans la physiopathologie de la maladie. Ainsi, ces travaux montrent que la métalloproteinase-9 de la matrice extracellulaire, la S100A11 et l’aquaporine-9 constitueraient de nouveaux biomarqueurs pour le diagnostic et la prédiction des complications des endocardites. / Infective endocarditis is a serious disease affecting around 2000 patients in France and 17000 in the United-States. Despite therapeutic progress, in-hospital mortality remains high, around 20%. This is mainly the consequence of a too late diagnosis and insufficiencies in the risk stratification. In fact, novel perspectives on the management of endocarditis are emerging and offer a hope for decreasing the rate of residual deaths by accelerating the process of diagnosis and risk stratification, a reduction of delays of instauration of antimicrobial therapy, the rapid transfer of high-risk patients to specialised medio-surgical centres, the development of new surgical modalities, and close long-term follow-up.Since many years, we have developed, in our institution, a research program based on a close collaboration between the researchers of the UMR 6236-CNRS and the physicians and the surgeons of the Cardiology and Cardiac Surgery Departments. This thesis reports the results of this translational research on the management of endocarditis. We have demonstrated that the standardization of the diagnostic process and of the surgical indications reduces infective endocarditis-related mortality in infective endocarditis. To improve the management, innovations such as the use of new biomarkers represent a critical new approach for this disease. From a transcriptional based approach, we have identified several new genes strongly involved in the pathophysiology of infective endocarditis. Thus, our works shows that the matrix metalloproteinase-9, S100A11 and aquaporin-9 would be potential new biomarkers for the diagnosis and the prediction of complications during infective endocarditis.

Master of Science / Department of Geology / Matthew W. Totten / The Spivey-Grabs-Basil oil field is a highly developed field in south-central Kansas, having large variability in its production and in the Pineville Tripolite facies. The Pineville Tripolite is the primary producing formation of this field having major isopach variations, possibly influencing production. The hypothesis that the field is highly compartmentalized is from the varied production, isopach and structure of the field. This study investigated the Pineville Tripolite facies in the Spivey-Grabs-Basil Oil Field, with the Basil area the predominant focus, and its possible compartmentalization by looking at the gas chromatograms and their biomarker signatures. This field has had several studies investigating the geophysical attributes, depositional setting and large-scale compartmentalization. Post depositional sea-level changes and possibly syntectonics exposed the Reeds Spring to a sub-aerial environment where meteoric alteration created immense porosity and the Pineville Tripolite facies. Geochemical data shows evidence that this section of the field is sourced from both a marine shale and carbonate source at peak oil maturity, deposited in an anoxic environment. Biodegradation appears very slight, with most alterations transpiring in the alkane ranges only, leaving all other susceptible hydrocarbons unaltered. Compartments within the field are harder to identify when comparing geological data to oil data. Isopach data shows altered thickness of the Pineville Tripolite from well to well, as do Pineville structure values. The isopach and structural data point to possible areas for compartments, but it is from oil geochemical data that compartments become more visible. API gravities and GOR show motley values, but do indicate two significant areas of segregation. The deepest, most southern end of the study showed lighter gravity oils than the middle, suggesting possible fill and spill between the two. However, biomarker abundance indicates three possible compartments. The southern compartment has many more biomarker volumes than do the middle compartment, both divided by a reservoir pinch-out. The third most northeastern well has high biomarker abundance, but shows no geological separators from the other wells. Production from this field may be improved by investigating the biomarkers to allocate these compartments and possible barriers close to wells.

The aim of this thesis is to in various ways explore protein expression in human normal tissue and in cancer and to apply that knowledge in biomarker discovery. In Paper I the prognostic significance of RNA-binding motif protein 3 (RBM3) is explored in malignant melanoma. To further evaluate the prognostic significance of RBM3 expression was assessed in 226 incident cases of malignant melanoma from the prospective populationbased cohort study Malmö Diet and Cancer Study using tissue microarray technique (TMA). RBM3 was shown to be down regulated in metastatic melanoma and high nuclear expression in the primary tumor was an independent marker of prolonged over all survival. As a tool to facilitate clinical biomarker studies the Human Protein Atlas has created a tissue dictionary as an introduction to human histology and histopathology. In Paper II this work is introduced. A cancer diagnosis can be a complex process with difficulties of establishing tumor type in localized disease or organ of origin in generalized disease. Immunohistochemically assisted diagnosis of cancer is common practice among pathologists where its application combined with known protein expression profiles of different cancer types, can strengthen or help dismiss a suspected diagnosis. In Paper III the diagnostic performance of 27 commonly used antibodies are tested in a predominantly metastatic, multicancer cohort using TMA technique. Overall these 27 diagnostic markers showed a low sensitivity and specificity for its intended use, highlighting the need for novel, more specific markers. Breast, ovarian, endometrial and ovarian cancers affect predominantly women. Differential diagnostics between these cancer types can be challenging. In Paper IV an algorithm, based on six different IHC markers, to differentiate between these cancer types is presented. A new diagnostic marker for breast cancer, namely ZAG is also introduced. In Paper V the transcriptomic landscape of the adrenal gland is explored by combining a transcriptomic approach with a immunohistochemistry based proteomic approach. In the adrenal gland we were able to detect 253 genes with an elevated pattern of expression in the adrenal gland, as compared to 31 other normal human tissue types analyzed. This combination of a transcriptomic and immunohistochemical approach provides a foundation for a deeper understanding of the adrenal glands function and physiology.

O objetivo deste estudo foi avaliar os parâmetros clínicos periodontais: profundidade clínica de sondagem, nível clínico de inserção e sangramento a sondagem e os níveis de IL-17, M-CSF, GM-CSF, MCP-1, ICAM-1 IL-8, IL-10, IL-1?, TNF-?, IL-4 no fluido gengival de pacientes portadores de periodontite agressiva, comparando esses valores aos dados obtidos de sujeitos periodontalmente saudáveis, além de comparar os dados clínicos e imunológicos iniciais aos obtidos após um ano de tratamento nos pacientes com periodontite agressiva. Foram selecionados 37 pacientes portadores de periodontite agressiva e oito pacientes periodontalmente saudáveis, utilizados como grupo controle. Após a realização do exame clínico periodontal em todos os dentes, foi escolhido um sítio profundo de cada paciente com paeriodontite e um sítio raso dos pacientes saudáveis para coleta do fluido gengival. Todos os pacientes receberam tratamento periodontal que consistiu de orientação de higiene bucal, raspagens, remoção de fatores de retenção do biofilme bacteriano, polimento e uso de antibióticos. As amostras obtidas foram processadas e analisadas com um painel de 10 citocinas através de um ensaio multiplex. As análises estatísticas mostraram que não houve diferença estatisticamente significante entre os doentes e os saudáveis em relação a GM-CSF, IL-4, IL-8 e MCP-1. Quando foi feita a comparação longitudinal dos pacientes com periodontite agressiva, houve aumento após o tratamento para GM-CSF, ICAM-1, IL-4, IL-10, IL-17, MCP-1 e TNF-?. Com isso, pode-se concluir que mesmo após o tratamento periodontal com consultas trimestrais de manutenção e melhora dos parâmetros clínicos nos pacientes com PA que tinham um baseline mais inflamado, foi observado que alguns biomarcadores continuaram elevados, o que pode significar que esses pacientes continuam a apresentar atividade de doença ou que alguns desses biomarcadores não têm significância clínica para esses pacientes. / The aim of this study was to evaluate the periodontal clinical parameters: clinical probing depth, clinical attachment level and bleeding on probing and the IL-17, M-CSF, GM-CSF, MCP-1, ICAM-1, IL-8, IL-10, IL-1?, TNF-? and IL-4 levels in gingival crevicular fluid of aggressive periodontitis subjects, comparing these values with some data obtained from periodontal healthy patients, and also comparing clinic and immunologic initial data with the obtained after one year of treatment of aggressive periodontitis. The sample had 37 patients with aggressive periodontitis and 8 subjects clinically healthy, as control group. After the full periodontal examination, each patient with periodontitis had a deep site chosen, and a shallow site of the healthy ones, for collecting gingival fluid. All patients received periodontal treatment with oral hygiene, scaling, removal of retention factors, polishing and antibiotics. The obtained samples were processed and analyzed with a panel of 10 cytokines through a multiplex test. The statistical analyzes showed that there was no significant statistical difference between subjects with PA and healthy subjects with regard to GM-CSF, IL-4, IL-8 and MCP-1 levels.When longitudinal comparison of the subjects was made, it was noted some increase for GM-CSF, ICAM-1, IL-4, IL-10, IL-17, MCP-1 and TNF-?. Then, it can be concluded that, even after the periodontal treatment with trimestral maintenance and improvement on the clinical parameters, some biomarkers are still elevated, what can mean one of those possibilities: or the patients are still presenting some activity of the disease, or that some of these biomarkers don\'t have any clinical significance for this patients.