Introdução: Os lasers fracionados não ablativos são efetivamente utilizados no rejuvenescimento da pele. As novas tecnologias a laser permitem uma remodelação dérmica seletiva, sem ablação da epiderme. Objetivo: Avaliar a eficácia do laser Erbium Glass (Sellas Evo) fracionado não ablativo 1550nm no rejuvenescimento facial através do estudo da quantificação histomorfométrica de fibras colágenas e elásticas, a expressão da molécula de adesão intercelular 1 (ICAM-1) por imuno-histoquímica , a análise das fases do ciclo celular, o potencial elétrico da membrana mitocondrial, a expressão de interleucina-1 (IL-1), o marcador celular endotelial CD34, o receptor do fator transformador de crescimento beta (TGF-beta), atividade da caspase-3 por citometria de fluxo e as alterações ultraestruturais na pele por microscopia eletrônica de varredura, 4 meses após o tratamento com laser. Materiais e Métodos: Quinze indivíduos (média de 56,4 anos, fototipo II-IV), com fotoenvelhecimento cutâneo na face fizeram 3 tratamentos com laser Erbium Glass fracionado não ablativo 1550nm usando uma fluência de 70 mJ e uma densidade de 100 cm2. Foram avaliados biópsias na região pré-auricular em 15 pacientes no início e 4 semanas após o tratamento final. Os níveis de expressão dos receptores e a atividade do potencial elétrico mitocondrial foram analisados na suspensão de células da derme obtida a partir da digestão por colagenase. A avaliação clínica e fotográfica foi analisada quatro semanas após o final do tratamento. Resultados: Após 4 meses do início do tratamento foi observada melhora clínica moderada, com uma média de satisfação de 8,8, as fibras de colágeno aumentaram em 6,68%, as fibras elásticas mostraram uma diminuição de 12,85%, o ICAM-1 aumentou 4,47% significativamente na área dos vasos. Houve aumento significativo dos níveis de expressão do receptor de IL-1 e TGF-beta após o tratamento com laser Erbium Glass. As respostas proliferativas e a ausência de apoptose dependente da caspase-3 foram observadas nas suspensões de células após o tratamento. Conclusão: Rejuvenescimento facial com laser Erbium Glass fracionado não ablativo 1550nm demonstrou melhora visível no fotoenvelhecimento, assim como, aumento significativo da expressão de IL-1 e receptores de TGF-beta, que estão envolvidos na remodelação e indução da proliferação de componentes da matriz extracelular da pele. O grau de satisfação foi alto especialmente em relação à textura, rugas e discromias / Background: Non-ablative fractional lasers have been effectively used in skin rejuvenation. The new laser technologies allow selective dermal remodeling without ablation of the epidermal surface. Objectives: to evaluate the efficacy of the 1550nm Erbium Glass Laser (Sellas Evo) for facial rejuvenation through study of the histomorphometric quantification of colagen and elastic fibers; the expression of intercellular adhesion molecule 1 (ICAM-1) by immnohistochemistry; and analysis of the cell cycle phases, the electrical potential of the mitochondrial membrane and the expression of interleukin 1 (IL-1), the endothelial cell marker CD34 and transforming growth factor beta (TGF-beta) receptors, caspase-3 activity by flow cytometry and the ultrastructural changes in the skin by scanning electron microscopy 4 months after the laser treatment. Materials and methods: fifteen subjects (mean age 56,4 skin typoes II-IV) with photodamage on the face and wrinkles had 3 treatments with the 1550 nm Erbium Glass Laser using a fluence of 70 mJ and a density of 100 cm2. Pre-auricular biopsies from 15 subjects were evaluated at baseline and 4 weeks after the final treatment. Receptor expression levels and the presence of potentially functional mitochondria were analyzed in a cell suspension obtained from collagenase digestion of the skin. Data from the photo assessments and the subjects\' self-assessed improvements were analyzed 4 weeks after the final treatment.Results: Four months after the last treatmenbt application, clinical improvement was observed, with an average satgisfation score of 8.8, corresponding to moderate improvement. After 4 months of treatment, collagen fibers had increased up to 6.68%, while the average proportion of collagen fibers in the dermis, the elastic fibers, showed a 12.85% decrease of ICAM-1 and a mean increase in vessel area of 4.47%.Significantly enhanced IL-1 and TGF-beta receptor expression levels were identified after Erbium Glass Laser treatment. Proliferative responses and non-apoptosis-dependent caspase-3 activity were both observed in the cell suspensions after dermal treatment. Conclusion: Non-ablative rejuvenation with the 1550 mn Erbium Glass Laser was of the IL-1 and TGF-beta receptors, that are involved in remodeling and induced proliferation components in the extracellular matrix of skin fibers. The subjects were highly satisfied, especially regarding texture, rhytids and dyschromia

Este estudo se propôs a avaliar o efeito do gás sulfídrico (H2S), produzido endogenamente em mamíferos, na sinovite induzida pela injeção intra-articular de carragenina (CGN) no joelho de ratos Wistar (250 g). Ratos foram tratados (-60 min) com indometacina, o inibidor da cistationina <font face=\"Symbol\">g-liase DL-propargilglicine (PGly) ou doador de H2S reagente de Lawesson ( LR).Os parâmetros funcionais e bioquímicos foram avaliados 4h após. Ratos com sinovite exibiram dor, alodinia e edema articular. Na cavidade articular foram mensurados níveis elevados de neutrófilos (> MPO), nitração de resíduos protéicos (3-NT), atividade da iNOS, NOx-, caspase-1, IL-1<font face=\"Symbol\">&#946 e via NF-<font face=\"Symbol\">kB. O LR ou indometacina, mas não PGly, reduziu significativamente a nocicepção, edema e marcadores inflamatórios, exceto iNOS, NOx-, 3-NT e NF-<font face=\"Symbol\">kB. A PGly não modificou a dor e inflamação, mas aumentou o numero de macrófagos e atividade da iNOS (NOx-) e AP-1. Conclui-se que, enquanto a administração exógena do LR produz efeitos antiinflamatórios e anti-nociceptivos, o H2S endógeno exerce pouco efeito anti-sinovite. / In this study we evaluated the effects of exogenous and endogenous H2S on Wistar rat knee synovitis induced by the intra-articular injection of carrageenan (CGN). One hour prior to CGN injection, Rats were pre-treated with indomethacin, an inhibitor of H2S formation (DL-propargylglycine) or an H2S donor Lawessons reagent (LR). CGN evoked knee inflammation, as characterized by impaired gait, secondary allodynia of the hindpaw, joint swelling, neutrophil infiltration, increased MPO, 3-NT residues, inducible NOS (iNOS) activity and NOx-, caspase-1 and NF-<font face=\"Symbol\">kB activation. Pretreatment with LR or indomethacin significantly attenuated the pain and all the inflammatory / biochemical changes, except for the increased iNOS activity, NOx- and 3-NT. PGly potentiated synovial iNOS activity (and NOx-), enhanced macrophage infiltration and AP-1 activation, but had no effect on oedema and pain. Whereas exogenous H2S delivered to the knee joint can produce a significant anti-inflammatory and anti-nociceptive effect, locally produced H2S exerts little immunomodulatory effect.

Introdução: Os lasers fracionados não ablativos são efetivamente utilizados no rejuvenescimento da pele. As novas tecnologias a laser permitem uma remodelação dérmica seletiva, sem ablação da epiderme. Objetivo: Avaliar a eficácia do laser Erbium Glass (Sellas Evo) fracionado não ablativo 1550nm no rejuvenescimento facial através do estudo da quantificação histomorfométrica de fibras colágenas e elásticas, a expressão da molécula de adesão intercelular 1 (ICAM-1) por imuno-histoquímica , a análise das fases do ciclo celular, o potencial elétrico da membrana mitocondrial, a expressão de interleucina-1 (IL-1), o marcador celular endotelial CD34, o receptor do fator transformador de crescimento beta (TGF-beta), atividade da caspase-3 por citometria de fluxo e as alterações ultraestruturais na pele por microscopia eletrônica de varredura, 4 meses após o tratamento com laser. Materiais e Métodos: Quinze indivíduos (média de 56,4 anos, fototipo II-IV), com fotoenvelhecimento cutâneo na face fizeram 3 tratamentos com laser Erbium Glass fracionado não ablativo 1550nm usando uma fluência de 70 mJ e uma densidade de 100 cm2. Foram avaliados biópsias na região pré-auricular em 15 pacientes no início e 4 semanas após o tratamento final. Os níveis de expressão dos receptores e a atividade do potencial elétrico mitocondrial foram analisados na suspensão de células da derme obtida a partir da digestão por colagenase. A avaliação clínica e fotográfica foi analisada quatro semanas após o final do tratamento. Resultados: Após 4 meses do início do tratamento foi observada melhora clínica moderada, com uma média de satisfação de 8,8, as fibras de colágeno aumentaram em 6,68%, as fibras elásticas mostraram uma diminuição de 12,85%, o ICAM-1 aumentou 4,47% significativamente na área dos vasos. Houve aumento significativo dos níveis de expressão do receptor de IL-1 e TGF-beta após o tratamento com laser Erbium Glass. As respostas proliferativas e a ausência de apoptose dependente da caspase-3 foram observadas nas suspensões de células após o tratamento. Conclusão: Rejuvenescimento facial com laser Erbium Glass fracionado não ablativo 1550nm demonstrou melhora visível no fotoenvelhecimento, assim como, aumento significativo da expressão de IL-1 e receptores de TGF-beta, que estão envolvidos na remodelação e indução da proliferação de componentes da matriz extracelular da pele. O grau de satisfação foi alto especialmente em relação à textura, rugas e discromias / Background: Non-ablative fractional lasers have been effectively used in skin rejuvenation. The new laser technologies allow selective dermal remodeling without ablation of the epidermal surface. Objectives: to evaluate the efficacy of the 1550nm Erbium Glass Laser (Sellas Evo) for facial rejuvenation through study of the histomorphometric quantification of colagen and elastic fibers; the expression of intercellular adhesion molecule 1 (ICAM-1) by immnohistochemistry; and analysis of the cell cycle phases, the electrical potential of the mitochondrial membrane and the expression of interleukin 1 (IL-1), the endothelial cell marker CD34 and transforming growth factor beta (TGF-beta) receptors, caspase-3 activity by flow cytometry and the ultrastructural changes in the skin by scanning electron microscopy 4 months after the laser treatment. Materials and methods: fifteen subjects (mean age 56,4 skin typoes II-IV) with photodamage on the face and wrinkles had 3 treatments with the 1550 nm Erbium Glass Laser using a fluence of 70 mJ and a density of 100 cm2. Pre-auricular biopsies from 15 subjects were evaluated at baseline and 4 weeks after the final treatment. Receptor expression levels and the presence of potentially functional mitochondria were analyzed in a cell suspension obtained from collagenase digestion of the skin. Data from the photo assessments and the subjects\' self-assessed improvements were analyzed 4 weeks after the final treatment.Results: Four months after the last treatmenbt application, clinical improvement was observed, with an average satgisfation score of 8.8, corresponding to moderate improvement. After 4 months of treatment, collagen fibers had increased up to 6.68%, while the average proportion of collagen fibers in the dermis, the elastic fibers, showed a 12.85% decrease of ICAM-1 and a mean increase in vessel area of 4.47%.Significantly enhanced IL-1 and TGF-beta receptor expression levels were identified after Erbium Glass Laser treatment. Proliferative responses and non-apoptosis-dependent caspase-3 activity were both observed in the cell suspensions after dermal treatment. Conclusion: Non-ablative rejuvenation with the 1550 mn Erbium Glass Laser was of the IL-1 and TGF-beta receptors, that are involved in remodeling and induced proliferation components in the extracellular matrix of skin fibers. The subjects were highly satisfied, especially regarding texture, rhytids and dyschromia

Modularität ist ein wiederkehrendes Thema in biologischen Netzwerken, in denen sich unabhängige Elemente wiederholen und neu zusammensetzen, um neue Funktionen zu erzeugen. In der angeborenen Immunität sind supramolekular organisierende Zentren (SMOCs) ein Beispiel für Modularität, die durch eine ligandeninduzierte komplexe Selbstassemblierung gekennzeichnet sind und deren Signalkomponenten in ihrer lokalen Konzentration zunehmen. Das Myddosom ist ein SMOC, das sich als Reaktion auf den Liganden IL-1, ein wichtiges proinflammatorisches Zytokin, zusammensetzt. Der Myddosom-vermittelte IL-1-Signalweg wurde mit biochemischen Methoden umfassend charakterisiert, doch Informationen zur Dynamik sind weiterhin begrenzt. Es gibt widersprüchliche Berichte darüber, wie die Proteine des IL-1-Signalwegs zusammengesetzt werden, und es ist nicht bekannt, ob die Komplexe des IL-1-Signalwegs wieder abgebaut werden. In dieser Arbeit wurde die Dynamik der Myddosom-vermittelten IL-1-Signaltransduktion untersucht, wobei eine völlig neue Hochdurchsatz-Bildanalyse-Pipeline, eine Phasenporträtanalyse, ein neuartiger Mikroskopie-Assay und CRISPR/Cas9-editierte lebende Lymphomzelllinien kombiniert wurden. Hier zeige ich, dass der Aufbau des IL-1-Signalwegs sequenzielle Schritte, eine ligandeninduzierte De-novo-Oligomerisierung, Proteine, die die Oligomergröße regulieren, und zwei Module umfasst: das Myddosom und die NF-κB-Signalosome. Das stromaufwärts gelegene Myddosom-Signalosom (MyD88, IRAK4, IRAK1, TRAF6, TAB2) erscheint zuerst, zeigt keine Erholung in FRAP-Experimenten und zeigt eine positive interne Rückkopplung. Das nachgeschaltete NF-κB-Signalosom (HOIL1, NEMO, RelA, A20) erscheint später, erholt sich nach FRAP und reguliert das Myddosom-Signalosom negativ. Ich zeige auch zum ersten Mal, dass sich der IL-1-Signalweg nach Überschreiten eines kritischen stöchiometrischen Verhältnisses auflöst und dass dynamische Gleichungen den Zusammenbau und den Abbau nachbilden können. Diese Ergebnisse zeigen, wie ein SMOC-abhängiger Signalweg Modularität zur Regulierung einsetzt. Das Verständnis von Signalisierungsmodulen ist von großer Bedeutung für die Aufklärung der regulatorischen Schaltkreise in biologischen Netzwerken. Meine Hochdurchsatz-Pipeline bietet einen vielversprechenden Ansatz, um dieses Ziel zu erreichen. / Modularity is a recurring theme in biological networks where independent elements repeat and shuffle to produce novel functions. In innate immunity, supramolecular organizing centers (SMOCs) are an example of modularity, characterized by ligand-induced complex self-assembly, and signaling components increase in local concentration. The Myddosome is a SMOC that assembles in response to the ligand IL-1, a vital proinflammatory cytokine. The Myddosome-mediated IL-1 signaling pathway has been extensively characterized using biochemical methods, yet dynamic information remains limited. There are conflicting reports of how the IL-1 pathway proteins assemble, and it is unknown whether IL-1 pathway complexes disassemble. This thesis investigated the Myddosome-mediated IL-1 signal transduction dynamics, combining a completely new high-throughput image analysis pipeline, phase portrait analysis, a novel microscopy assay, and CRISPR/Cas9-edited live lymphoma cell lines. Here, I show that the IL-1 pathway assembly has sequential steps, ligand-induced de novo oligomerization, proteins regulating oligomer size, and two modules: the Myddosome and NF-κB signalosomes. The upstream Myddosome signalosome (MyD88, IRAK4, IRAK1, TRAF6, TAB2) appears first, has no FRAP recovery, and shows positive internal feedback. The downstream NF-κB signalosome (HOIL1, NEMO, RelA, A20) appears later, recovers after FRAP, and negatively regulates the Myddosome signalosome. I also show, for the first time, that the IL-1 pathway disassembles after crossing a critical stoichiometric ratio, and that dynamical equations can recapitulate assembly-disassembly. These results demonstrate how a SMOC-dependent pathway uses modularity to achieve regulation. Understanding signaling modules holds significant implications for elucidating the regulatory circuitry in biological networks. My high-throughput pipeline offers a promising approach to achieving this objective.

IL-36 gamma is a proinflamatory cytokine which belongs to the IL-1 family of cytokines. It is expressed in the skin and by epithelial cells (ECs) lining lung and gut tissue. We used human 3-D organotypic cells, that recapitulate either in vivo human vaginal or cervical tissue, to explore the possible role of IL-36 gamma in host defense against pathogens in the human female reproductive tract (FRT). EC were exposed to compounds derived from virus or bacterial sources and induction and regulation of IL-36 gamma and its receptor was determined. Polyinosinic-polycytidylic acid (poly I:C), flagellin, and synthetic lipoprotein (FSL-1) significantly induced expression of IL-36 gamma in a dose-dependent manner, and appeared to be TLR-dependent. Recombinant IL-36 gamma treatment resulted in self amplification of IL-36 gamma and its receptor (IL-36R) via increased gene expression, and promoted other inflammatory signaling pathways. This is the first report to demonstrate that the IL-36 receptor and IL-36 gamma are present in the human FRT EC and that they are differentially induced by microbial products at this site. We conclude that IL-36 gamma is a driver for epithelial and immune activation following microbial insult and, as such, may play a critical role in host defense in the FRT.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

No description available.

Objetivo: Avaliar o perfil de citocinas pró-inflamatórias e de melatonina no cordão umbilical e no sangue materno de gestantes hígidas de acordo com a via de parto. Métodos: Entre março e setembro de 2010, foi realizado estudo observacional prospectivo no Hospital Universitário da Universidade de São Paulo. Foram dosadas citocinas (IL-1, IL-6, TNF) e melatonina em pacientes sem doenças clínicas ou complicações obstétricas que entraram em trabalho de parto espontâneo. As concentrações de citocinas e de melatonina foram comparadas de acordo com a via de parto, além do período do dia e do local de coleta. O sangue retirado da veia do cordão umbilical (VCU) era obtido imediatamente após o parto, sendo que após uma hora era colhido o sangue da veia braquial materna (VB). Foram excluídas pacientes com infecção, parto prematuro e sofrimento fetal. Resultados: Foram estudadas 50 parturientes, das quais 25 evoluíram para parto vaginal e 25 para cesárea. A idade materna foi em média 26,0 ± 6,7 anos. A idade gestacional no parto foi em média 39,5 ± 1,7 semanas. O peso médio dos recém-nascidos foi 3366,5 ± 340,2 gramas. Todos os casos receberam analgesia durante o parto (analgesia combinada: peridural e raquianestesia). A maioria das pacientes era de nulíparas (31/50 - 62,0%). A duração do trabalho de parto foi semelhante nas pacientes que evoluíram para o parto vaginal (7,6 ± 4,4 horas) e nas que foram submetidas à operação cesariana (8,2 ± 4,4 horas; p=0,87). Houve tendência de níveis mais elevados de melatonina no VCU e na VB em pacientes após parto vaginal, porém sem diferença estatística (p=0,41 e p=0,16). Pacientes que evoluíram para cesariana apresentaram dosagens significativamente maiores de TNF na VB, de IL-1 na VCU e na VB e de IL-6 na VCU que em pacientes que evoluíram para parto vaginal (p= 0,02; p<0,01; p<0,01 e p<0,01; respectivamente). Observou-se variação no ritmo circadiano das dosagens dessas citocinas após cesariana, com correlação significativa entre dosagem de melatonina e de citocinas nessa via de parto. Conclusão: Pacientes submetidas à operação cesariana apresentaram tendência a redução da secreção de melatonina, com aumento significativo da secreção de citocinas pró-inflamatórias, o que pode ser conseqüência do processo inflamatório relacionado ao estresse cirúrgico / Objetive: To evaluate the profile of pro-inflammatory cytokines and the melatonin level in maternal and umbilical cord blood samples in accordance with the mode of delivery. Methods: Between March 2010 and September 2010, a prospective observational study was conducted at University Hospital of University of São Paulo. Cytokines (IL-1, IL-6, TNF) and melatonin levels were analyzed from maternal brachial vein (BV) and umbilical cord vein (UCV) obtained from healthy patients that started spontaneous labor. The levels of cytokines and melatonin were evaluated in accordance to the mode of delivery as well as the day period and the local of blood sample (UCV - immediately after delivery and BV - one hour after delivery). Patients with infection, preterm labor and fetal distress were excluded. Results: A total of 50 patients were evaluated in the present study: 25 underwent vaginal delivery and 25 c-section. Mean maternal age was 26.0 ± 6.7 years. Mean gestational age at delivery was 39.5 ± 1.7 weeks. The average of newborn weight was 3366.5 ± 340.2 grams. All patients had combined epidural and raquianesthesia. The majority of the patients was nullipara (31/50 62.0%). The labor duration was similar in patients that underwent vaginal delivery (7.6 ± 4.4 hours) or c-section (8.2 ± 4.4 hours, p=0.87). There was a tendency of increased levels of melatonin in the UCV and BV samples after vaginal deliveries, but with statistical significance (p=0.41 and p=0.16). Patients that underwent c-section had increased levels of TNF at the BV, IL-1 at the UCV and BV and IL-6 at the UCV than in patients that underwent vaginal delivery (p= 0.02; p<0.01; p<0.01 and p<0.01; respectively). Circadian variations of the cytokines and the melatonin levels were observed in patients that underwent c-section, with significant correlation between the levels of cytokines and melatonin. Conclusion: Patients that underwent c-section had a tendency of reduced melatonin level, with significant increase in the cytokine levels, which may be consequent of the inflammatory process related to the surgical stress.

Objetivo: Avaliar o perfil de citocinas pró-inflamatórias e de melatonina no cordão umbilical e no sangue materno de gestantes hígidas de acordo com a via de parto. Métodos: Entre março e setembro de 2010, foi realizado estudo observacional prospectivo no Hospital Universitário da Universidade de São Paulo. Foram dosadas citocinas (IL-1, IL-6, TNF) e melatonina em pacientes sem doenças clínicas ou complicações obstétricas que entraram em trabalho de parto espontâneo. As concentrações de citocinas e de melatonina foram comparadas de acordo com a via de parto, além do período do dia e do local de coleta. O sangue retirado da veia do cordão umbilical (VCU) era obtido imediatamente após o parto, sendo que após uma hora era colhido o sangue da veia braquial materna (VB). Foram excluídas pacientes com infecção, parto prematuro e sofrimento fetal. Resultados: Foram estudadas 50 parturientes, das quais 25 evoluíram para parto vaginal e 25 para cesárea. A idade materna foi em média 26,0 ± 6,7 anos. A idade gestacional no parto foi em média 39,5 ± 1,7 semanas. O peso médio dos recém-nascidos foi 3366,5 ± 340,2 gramas. Todos os casos receberam analgesia durante o parto (analgesia combinada: peridural e raquianestesia). A maioria das pacientes era de nulíparas (31/50 - 62,0%). A duração do trabalho de parto foi semelhante nas pacientes que evoluíram para o parto vaginal (7,6 ± 4,4 horas) e nas que foram submetidas à operação cesariana (8,2 ± 4,4 horas; p=0,87). Houve tendência de níveis mais elevados de melatonina no VCU e na VB em pacientes após parto vaginal, porém sem diferença estatística (p=0,41 e p=0,16). Pacientes que evoluíram para cesariana apresentaram dosagens significativamente maiores de TNF na VB, de IL-1 na VCU e na VB e de IL-6 na VCU que em pacientes que evoluíram para parto vaginal (p= 0,02; p<0,01; p<0,01 e p<0,01; respectivamente). Observou-se variação no ritmo circadiano das dosagens dessas citocinas após cesariana, com correlação significativa entre dosagem de melatonina e de citocinas nessa via de parto. Conclusão: Pacientes submetidas à operação cesariana apresentaram tendência a redução da secreção de melatonina, com aumento significativo da secreção de citocinas pró-inflamatórias, o que pode ser conseqüência do processo inflamatório relacionado ao estresse cirúrgico / Objetive: To evaluate the profile of pro-inflammatory cytokines and the melatonin level in maternal and umbilical cord blood samples in accordance with the mode of delivery. Methods: Between March 2010 and September 2010, a prospective observational study was conducted at University Hospital of University of São Paulo. Cytokines (IL-1, IL-6, TNF) and melatonin levels were analyzed from maternal brachial vein (BV) and umbilical cord vein (UCV) obtained from healthy patients that started spontaneous labor. The levels of cytokines and melatonin were evaluated in accordance to the mode of delivery as well as the day period and the local of blood sample (UCV - immediately after delivery and BV - one hour after delivery). Patients with infection, preterm labor and fetal distress were excluded. Results: A total of 50 patients were evaluated in the present study: 25 underwent vaginal delivery and 25 c-section. Mean maternal age was 26.0 ± 6.7 years. Mean gestational age at delivery was 39.5 ± 1.7 weeks. The average of newborn weight was 3366.5 ± 340.2 grams. All patients had combined epidural and raquianesthesia. The majority of the patients was nullipara (31/50 62.0%). The labor duration was similar in patients that underwent vaginal delivery (7.6 ± 4.4 hours) or c-section (8.2 ± 4.4 hours, p=0.87). There was a tendency of increased levels of melatonin in the UCV and BV samples after vaginal deliveries, but with statistical significance (p=0.41 and p=0.16). Patients that underwent c-section had increased levels of TNF at the BV, IL-1 at the UCV and BV and IL-6 at the UCV than in patients that underwent vaginal delivery (p= 0.02; p<0.01; p<0.01 and p<0.01; respectively). Circadian variations of the cytokines and the melatonin levels were observed in patients that underwent c-section, with significant correlation between the levels of cytokines and melatonin. Conclusion: Patients that underwent c-section had a tendency of reduced melatonin level, with significant increase in the cytokine levels, which may be consequent of the inflammatory process related to the surgical stress.

L'interleukine-6 (IL-6) est une cytokine associée aux maladies auto-immunes de la glande thyroïde et qui pourrait aussi avoir un rôle dans le développement de l'hypertrophie cardiaque pathologique. Dans les cellules thyroïdiennes FRTL-5 et dans les cardiomyocytes de rats adultes, nous montrons que la sécrétion et l'expression de l'ARNm de l'IL-6, stimulées par l'interleukine-1 (IL-1), sont augmentées de manière synergique par la voie de l'AMPc/PKA. Dans les cellules FRTL-5, cet effet synergique s'exerce aussi au niveau de l'activation du promoteur de l'IL-6 et implique les sites AP-1 et CRE ainsi que les facteurs de transcription c-Fos et Fra2. L'IL-6 et son récepteur membranaire stimulent les voies de signalisation impliquant STAT3 et ERK-5 dans les cellules FRTL-5. Dans les cardiomyocytes, STAT3 est activé par l'IL-6 uniquement en présence de son récepteur soluble. Nous montrons que ce mécanisme de conduit à la stimulation de marqueurs associés au processus hypertrophique pathologique.