961 resultados para matrix metalloproteinase 2
Resumo:
The extracellular matrix is a three-dimensional network of proteins, glycosaminoglycans and other macromolecules. It has a structural support function as well as a role in cell adhesion, migration, proliferation, differentiation, and survival. The extracellular matrix conveys signals through membrane receptors called integrins and plays an important role in pituitary physiology and tumorigenesis. There is a differential expression of extracellular matrix components and integrins during the pituitary development in the embryo and during tumorigenesis in the adult. Different extracellular matrix components regulate adrenocorticotropin at the level of the proopiomelanocortin gene transcription. The extracellular matrix also controls the proliferation of adrenocorticotropin-secreting tumor cells. On the other hand, laminin regulates the production of prolactin. Laminin has a dynamic pattern of expression during prolactinoma development with lower levels in the early pituitary hyperplasia and a strong reduction in fully grown prolactinomas. Therefore, the expression of extracellular matrix components plays a role in pituitary tumorigenesis. On the other hand, the remodeling of the extracellular matrix affects pituitary cell proliferation. Matrix metalloproteinase activity is very high in all types of human pituitary adenomas. Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.
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Matrix metalloproteinases (MMPs) are a major group of proteases known to regulate extracellular matrix (ECM) turnover and so they have been suggested to be important in the process of lung disease associated with tissue remodeling. This has led to the concept that modulation of airway remodeling including excessive proteolysis damage to the tissue may be of interest for future treatment. Within the MMP family, macrophage elastase (MMP-12) is able to degrade ECM components such as elastin and is involved in tissue remodeling processes in chronic obstructive pulmonary disease including emphysema. Pulmonary fibrosis has an aggressive course and is usually fatal within an average of 3 to 6 years after the onset of symptoms. Pulmonary fibrosis is associated with deposition of ECM components in the lung interstitium. The excessive airway remodeling as a result of an imbalance in the equilibrium of the normal processes of synthesis and degradation of ECM components could justify anti-protease treatments. Indeed, the correlation of the differences in hydroxyproline levels in the lungs of bleomycin-treated mice strongly suggests that a reduced molar pro-MMP-9/TIMP-1 ratio in bronchoalveolar lavage fluid is associated with collagen deposition, beginning as early as the inflammatory events at day 1 after bleomycin administration. Finally, these observations emphasize that effective treatment of these disorders must be started early during the natural history of the disease, prior to the development of extensive lung destruction and fibrosis.
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Le PCK3145 est un peptide de 15 acides amins inhibant la scrtion de MMP-9 et dmontrant une activit anti-tumorale contre le cancer de la prostate. Comme les cancers hmatologiques scrtent MMP-9, nous avons donc valu leffet du PCK3145 sur ces cancers. Nous avons dmontr que les lignes humaines de lymphome non- Hodgkinien (LNH) SR et de mylome multiple RPMI-8226 ainsi que la ligne murine de mastocytome P815 ont une prolifration rduite suite une exposition au PCK3145. Ce peptide diminue galement la clonognicit de ces cellules. In vivo, le PCK3145 diminue significativement la croissance des tumeurs sous-cutanes P815 comparativement au PBS (p<0.001) et aux peptides contrles ( scrambled peptide (p<0.05) et PCK5266 (p<0.01)). De plus, le traitement au PCK3145 diminue le nombre de mtastases au niveau du foie par rapports aux contrles (p<0.05). Les niveaux de MMP-9 dans le sang des souris traites au PCK3145 sont similaires ceux dans le sang des souris sans tumeur. Par contre, chez les souris recevant le PBS ou le scrambled peptide , les niveaux de MMP-9 taient significativement plus levs que dans les souris sans tumeur et les souris traites au PCK3145 (p<0.05). De surcrot, dans un modle de xnogreffe, le PCK3145 diminue significativement la croissance des lymphomes SR par rapport au PBS (p<0.01) et au scrambled peptide (p<0.001). Ces rsultats indiquent que le PCK3145 possde une activit anti-tumorale et pourrait reprsenter un agent intressant pour le traitement de plusieurs cancers hmatologiques.
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OBJECTIF: Rcemment, nous avons dmontr que la modification du collagne type II (Col II) par le 4-hydroxynonnal (HNE), un produit de la peroxydation lipidique, est augmente dans le cartilage arthrosique sans quon sache la signification de cette augmentation dans la pathogense de larthrose. Lobjectif de cette tude vise dmontrer que cette modification affecte linteraction chondrocytes/matrice extracellulaire (MEC) et en consquence induit des changements phnotypiques et fonctionnels de ces cellules. METHODES: Des plaques de culture ont t pralablement cotes avec du Col II puis traites avec du HNE (0.1-2 mM) except le puits contrle. Les chondrocytes ont t ensuite ensemencs puis incubs pendant 48 heures. La viabilit des cellules est value par le test MTT. Le Western blot est utilis pour mesurer lexpression des molcules dadhsion (lICAM-1 et lintgrine 11), de la cyclooxygenase-2 (COX-2), du Col II ainsi que la phosphorylation de la p38 MAPK, ERK1/2 et NF-B-p65. La RT-PCR en temps rel est utilise pour mesurer lexpression de lARNm de lICAM-1, des intgrines 11, de la COX-2 et de la mtalloprotinases-13 (MMP-13). La dtermination de lexpression de lICAM-1 la surface des cellules est ralise par cytomtrie de flux. Des kits commerciaux ont servi pour mesurer le niveau de la MMP-13, de la prostaglandine E2 (PGE2), de lactivit de la caspase-8 et de la phosphorylation de la p38 MAPK, ERK1/2 et NF-B-p65. RESULTATS: La modification du Col II par 0.2 mM HNE induit significativement lexpression des molcules dadhsion telles que lICAM-1 et lintgrine 11, de la MMP-13 sans avoir un effet sur la morphologie, la survie et le phnotype cellulaires. Nos rsultats montrent aussi une forte augmentation de la phosphorylation de la p38 MAPK, dERK1/2 et de NF-B-p65. Cependant, la modification du Col II par 2 mM HNE affecte la morphologie et la viabilit cellulaires et induit lactivit de la caspase-8. Elle inhibe fortement lexpression des integrines 11 et du Col II ainsi que la phosphorylation de lERK1/2 et de NF-B-p65, mais par contre, induit significativement la production de la COX-2 et son produit la PGE2 ainsi que la phosphorylation de la p38 MAPK. Fait intressant, le prtraitement des complexes HNE/Col II par 0.1 mM de carnosine empche les changements phnotypiques et fonctionnels des chondrocytes. CONCLUSION : Ces nouveaux rsultats suggrent le rle important de la modification du Col II par le HNE dans larthrose, en affectant le phnotype et le fonctionnement cellulaires des chondrocytes. La carnosine, par sa capacit de neutraliser le HNE, a rvl dtre un agent promoteur dans le traitement de larthrose.
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Ldme crbral est une complication associe lencphalopathie hpatique (EH) lors dune insuffisance hpatique chronique (cirrhose du foie). Prsentement, lorigine de sa pathogense, vasognique (rupture de la barrire hmato-encphalique (BHE)) ou cytotoxique (prise anormale dions), na pas encore t dtermine. Il a t dmontr que le co-transporteur Na-K-Cl (NKCC1) du ct luminal des microvaisseaux sanguins crbraux (CMV) joue un rle dans le dveloppement de ldme crbral dans des modles dischmie o la bumetanide, un inhibiteur de NKCC, attnue ldme crbral. Deux modles dEH ont t utiliss pour cette tude i) la ligature de la voie biliaire (BDL) qui prsente lhyperammonimie chronique, ldme crbral et le stress oxydatif systmique ; ii) lanastomose portocave (PCA) qui prsente de lhyperammonimie chronique seulement. Les buts du projet taient de: i) dfinir lorigine du dveloppement de ldme chez les rats BDL en tudiant lextravasation de macromolcules, les jonctions serres et lactivation des mtalloprotinases matricielles de la BHE; ii) observer les effets de lhyperammonimie chronique indpendamment sur la BHE chez les rats PCA; iii) valuer le rle de lhyperammonimie et du stress oxydatif et iv) tudier le rle du NKCC1 dans les CMV dans la pathogense de ldme crbral. Les rsultats du projet dmontrent que ldme est dorigine cytotoxique chez les rats BDL et que lintgrit de la BHE est conserve chez les rats PCA malgr lhyperammonimie. Lexpression gnique du NKCC1 est associe ldme mais pas son expression protique et sa phosphorylation. Enfin, ltude dmontre que lhyperammonimie et le stress oxydatif indpendant ne jouent pas un rle dans la pathogense de ldme mais suggre quils y aient un effet synergique.
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Ces travaux visent tendre les applications de la rsonance de plasmons de surface (SPR) Lobjectif est doffrir des outils diagnostics plus rapides, efficaces et simple dutilisation pour diagnostiquer ou effectuer le suivi de conditions cliniques. Pour se faire, un nouveau type dinstrumentation SPR bas sur lutilisation dun prisme dinversion (dove) a permis datteindre une limite de dtection (LOD) de 10-6 unit dindice de rfraction (RIU), une valeur comparable aux instruments commerciaux complexes tout en demeurant peu dispendieux, robuste et simple dutilisation. Les travaux prsents dans cet ouvrage visent, dans un second temps, rduire les interactions nonspcifiques (NSB) entre la surface des biocapteurs SPR et les composants de la matrice biologique complexe telles que: lurine, le lysat cellulaire, le srum et le sang. Ces dernires induisent des rponses empchant lutilisation de biocapteurs SPR en milieux complexes. Les acides amins (AA) offrent une grande varit de proprits physico-chimiques permettant la mise au point de monocouches auto-assembles (SAM) aux proprits diverses. Initialement, 19 des 20 acides amins naturels ont t attachs lacide 3-mercaptopropionique (3-MPA) formant des SAMs peptidomimtiques. La quantit dinteractions nonspcifiques engendres par ces diffrentes surfaces a t mesure en exposant ces surfaces au srum sanguin bovin complet variant de 400 ng/cm jusqu 800 ng/cm. La dtection laide de ces surfaces de la -lactamase (une enzyme responsable de la rsistance aux antibiotiques au niveau M) a dmontr la possibilit demployer ces surfaces pour btir des biocapteurs SPR. Des peptides de longueur allant de 2 5 rsidus attachs 3-MPA ont t synthtiss sur support solide. Cette tude a dmontr que laugmentation de la longueur des peptides forms dAA rsistants aux NBS accroit leur rsistance jusqu 5 rsidus. Le compos le plus performant de ce type (3-MPA-(Ser)5-OH) a permis datteindre 180 ng/cm. Cette valeur est similaire celle des meilleures surfaces disponibles commercialement, notamment les surfaces de polyethylne glycol (PEG) 100 ng/cm. Des surfaces de 3-MPA-(Ser)5-OH ont permis ltalonnage de la -lactamase et sa quantification directe dans un lysat cellulaire. La LOD pour ces biocapteurs est de 10 nM. Une troisime gnration de surfaces peptidiques binaires a permis la rduction de la NSB jusqu un niveau de 2310 ng/cm une valeur comparable aux meilleures surfaces disponibles. Ces surfaces ont permis ltalonnage dun indicateur potentiel du cancer la metalloprotinase-3 de matrice (MMP-3). Les surfaces formes de peptides binaires (3-MPA-H3D2-OH) ont permis la quantification directe de la MMP-3 dans le srum sanguin complet. Une quatrime gnration de surfaces peptidiques a permis de rduire davantage le niveau de NSB jusqu une valeur de 12 11 ng/cm. Ces surfaces ont t modifies en y attachant une terminaison de type acide nitriloactique (NTA) afin dy attacher des biomolcules marques par six rsidus histidines terminaux. Ces surfaces ont permis le dveloppement dune mthode rapide de balayage des ligands ciblant le cluster of differenciation-36 (CD36). Ltude dlectroformation des monocouches de peptide a permis de dterminer les conditions de formation optimales dune couche de 3-MPA-HHHDD-OH permettant ainsi la formation de monocouches rsistantes au NSB en moins de 6 minutes en appliquant un potentiel de formation de 200mV vs Ag/AgCl.
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Larthrose (OA) est une maladie dgnrative trs rpondue touchant les articulations. Elle est caractrise par la destruction progressive du cartilage articulaire, linflammation de la membrane synoviale et le remodelage de los sous chondral. Ltiologie de cette maladie nest pas encore bien dfinie. Plusieurs tudes ont t menes pour lucider les mcanismes molculaires et cellulaires impliqus dans le dveloppement de lOA. Les effets protecteurs du rcepteur activ par les prolifrateurs de peroxysomes gamma (PPAR) dans l'OA sont bien documents. Il a t dmontr que PPAR possde des proprits anti-inflammatoires et anti-cataboliques. Aussi, plusieurs stimuli ont t impliqus dans la rgulation de lexpression de PPAR dans diffrents types cellulaires. Cependant, les mcanismes exacts responsables de cette rgulation ainsi que le profil de lexpression de ce rcepteur au cours de la progression de lOA ne sont pas bien connus. Dans la premire partie de nos travaux, nous avons essay dlucider les mcanismes impliqus dans laltration de lexpression de PPAR dans cette maladie. Nos rsultats ont confirm limplication de linterleukine-1 (IL-1), une cytokine pro-inflammatoire, dans la rduction de lexpression de PPAR au niveau des chondrocytes du cartilage articulaire. Cet effet concide avec l'induction de lexpression du facteur de transcription rponse prcoce de type 1 (Egr-1). En plus, la diminution de l'expression de PPAR a t associe au recrutement d'Egr-1 et la rduction concomitante de la liaison de Sp1 au niveau du promoteur de PPAR. Dans la deuxime partie de nos travaux, nous avons valu le profil dexpression de ce rcepteur dans le cartilage au cours de la progression de cette maladie. Le cochon dinde avec OA spontane et le chien avec OA induite par rupture du ligament crois antrieur (ACLT) deux modles animaux dOA ont t utiliss pour suivre lexpression des trois isoformes de PPARs : PPAR alpha (), PPAR bta () et PPAR gamma () ainsi que la prostaglandine D synthase hmatopotique (H-PGDS) et la prostaglandine D synthase de type lipocaline (L-PGDS) deux enzymes impliques dans la production de lagoniste naturel de PPAR, la 15-Deoxy-delta(12,14)-prostaglandine J(2) (15d-PGJ2). Nos rsultats ont dmontr des changements dans lexpression de PPAR et la L-PGDS. En revanche, lexpression de PPAR, PPAR et H-PGDS est reste stable au fil du temps. La diminution de lexpression de PPAR dans le cartilage articulaire semble contribuer au dveloppement de lOA dans les deux modles animaux. En effet, le traitement des chondrocytes par de siRNA dirig contre PPAR a favoris la production des mdiateurs arthrosiques tels que l'oxyde nitrique (NO) et la mtalloprotase matricielle de type 13 (MMP-13), confirmant ainsi le rle anti-arthrosique de ce rcepteur. Contrairement ce dernier, le niveau d'expression de la L-PGDS a augment au cours de la progression de cette maladie. La surexpression de la L-PGDS au niveau des chondrocytes humains a t associe la diminution de la production de ces mdiateurs arthrosiques, suggrant son implication dans un processus de tentative de rparation. En conclusion, lensemble de nos rsultats suggrent que la modulation du niveau dexpression de PPAR, de la L-PGDS et dEgr-1 au niveau du cartilage articulaire pourrait constituer une voie thrapeutique potentielle dans le traitement de lOA et probablement dautres formes d'arthrite.
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BackgroundIncreased production of reactive oxygen species (ROS) throughout the vascular wall is a feature of cardiovascular disease states, but therapeutic strategies remain limited by our incomplete understanding of the role and contribution of specific vascular cell ROS to disease pathogenesis. To investigate the specific role of endothelial cell (EC) ROS in the development of structural vascular disease, we generated a mouse model of endothelium-specific Nox2 overexpression and tested the susceptibility to aortic dissection after angiotensin II (Ang II) infusion. Methods and ResultsA specific increase in endothelial ROS production in Nox2 transgenic mice was sufficient to cause Ang IImediated aortic dissection, which was never observed in wild-type mice. Nox2 transgenic aortas had increased endothelial ROS production, endothelial vascular cell adhesion molecule-1 expression, matrix metalloproteinase activity, and CD45+ inflammatory cell infiltration. Conditioned media from Nox2 transgenic ECs induced greater Erk1/2 phosphorylation in vascular smooth muscle cells compared with wild-type controls through secreted cyclophilin A (CypA). Nox2 transgenic ECs (but not vascular smooth muscle cells) and aortas had greater secretion of CypA both at baseline and in response to Ang II stimulation. Knockdown of CypA in ECs abolished the increase in vascular smooth muscle cell Erk1/2 phosphorylation conferred by EC conditioned media, and preincubation with CypA augmented Ang IIinduced vascular smooth muscle cell ROS production. ConclusionsThese findings demonstrate a pivotal role for EC-derived ROS in the determination of the susceptibility of the aortic wall to Ang IImediated aortic dissection. ROS-dependent CypA secretion by ECs is an important signaling mechanism through which EC ROS regulate susceptibility of structural components of the aortic wall to aortic dissection.
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Introduction: Orthodontic tooth movement uses mechanical forces that result in inflammation in the first days. Myeloperoxidase (MPO) is an enzyme found in polymorphonuclear neutrophil (PMN) granules, and it is used to estimate the number of PMN granules in tissues. So far, MPO has not been used to study the inflammatory alterations after the application of orthodontic tooth movement forces. The aim of this study was to determine MPO activity in the gingival crevicular fluid (GCF) and saliva (whole stimulated saliva) of orthodontic patients at different time points after fixed appliance activation. Methods: MPO was determined in the GCF and collected by means of periopaper from the saliva of 14 patients with orthodontic fixed appliances. GCF and saliva samples were collected at baseline, 2 hours, and 7 and 14 days after application of the orthodontic force. Results: Mean MPO activity was increased in both the GCF and saliva of orthodontic patients at 2 hours after appliance activation (P<0.02 for all comparisons). At 2 hours, PMN infiltration into the periodontal ligament from the orthodontic force probably results in the increased MPO level observed at this time point. Conclusions: MPO might be a good marker to assess inflammation in orthodontic movement; it deserves further studies in orthodontic therapy. (Am J Orthod Dentofacial Orthop 2010;138:613-6)
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Objectives: We investigated effects of chronic exposure (2 months) to ambient levels of particulate matter (PM) on development of protease-induced emphysema and pulmonary remodeling in mice. Methods: Balb/c mice received nasal drop of either papain or normal saline and were kept in two exposure chambers situated in an area with high traffic density. One of them received ambient air and the other had filters for PM. Results: mean concentration of PM10 was 2.68 +/- 0.38 and 33.86 +/- 2.09 mu g/m(3), respectively, in the filtered and ambient air chambers (p<0.001). After 2 months of exposure, lungs from papain-treated mice kept in the chamber with ambient air presented greater values of mean linear intercept, an increase in density of collagen fibers in alveolar septa and in expression of 8-isoprostane (p = 0.002, p < 0.05 and p = 0.002, respectively, compared to papain-treated mice kept in the chamber with filtered air). We did not observe significant differences between these two groups in density of macrophages and in amount of cells expressing matrix metalloproteinase-12. There were no significant differences in saline-treated mice kept in the two chambers. Conclusions: We conclude that exposure to urban levels of PM worsens protease-induced emphysema and increases pulmonary remodeling. We suggest that an increase in oxidative stress induced by PM exposure influences this response. These pulmonary effects of PM were observed only in mice with emphysema. (C) 2009 Elsevier Inc. All rights reserved.
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Aims Periodontal disease (PD) and airway allergic inflammation (AL) present opposing inflammatory immunological features and clinically present an inverse correlation. However, the putative mechanisms underlying such opposite association are unknown. Material and Methods Balb/C mice were submitted to the co-induction of experimental PD (induced by Actinobacillus actinomycetemcomitans oral inoculation) and AL [induced by sensitization with ovalbumin (OVA) and the subsequent OVA challenges], and evaluated regarding PD and AL severity, immune response [cytokine production at periodontal tissues, and T-helper transcription factors in submandibular lymph nodes (LNs)] and infection parameters. Results PD/AL co-induction decreased PD alveolar bone loss and periodontal inflammation while experimental AL parameters were unaltered. An active functional interference was verified, because independent OVA sensitization and challenge not modulate PD outcome. PD+AL group presented decreased tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, -gamma, IL-17A, receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand and matrix metalloproteinase (MMP)-13 levels in periodontal tissues, while IL-4 and IL-10 levels were unaltered by AL co-induction. AL co-induction also resulted in upregulated T-bet and related orphan receptor gamma and downregulated GATA3 levels expression in submandibular LNs when compared with PD group. Conclusion Our results demonstrate that the interaction between experimental periodontitis and allergy involves functional immunological interferences, which restrains experimental periodontitis development by means of a skewed immune response.
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Migration, invasion and protease activity are essential for tumor progression and metastasis. Metastatic cells rely on invadopodia to degrade and invade extracellular matrix (ECM). Invadopodia are membrane protrusions with enzymes required for ECM degradation. These protrusions contain cortactin and membrane type I matrix metalloproteinase (MT1-MMP) superimposed to areas of digested matrix. Here we characterized invadopodia in a cell line (CAC2) derived from human adenoid cystic carcinoma. We carried out fluorescent-substrate degradation assay to assess in situ protease activity of CAC2 cells. Digestion spots in fluorescent substrate appear as black areas in green background. Cells were cultured on Matrigel-gelatin-FITC and fixed after 1 h and 3 h. CAC2 cells were double labeled to actin and cortactin. Cells were also double stained to actin and MT1-MMR Samples were studied by laser scanning confocal microscopy. In all time points CAC2 cells showed actin, cortactin, and MT1-MMP colocalized with digestion spots in fluorescent substrate. We searched for other proteases involved in invadopodia activity. We have previously demonstrated that MMP9 influences adenoid cystic carcinoma behavior. This prompted us to investigate role played by MMP9 on invadopodia formation. CAC2 cells had MMP9 silenced by siRNA. After I h in fluorescent substrate, cells with silenced MMP9 showed clear decrease in matrix digestion compared with controls. No differences were found in cells with silenced MMP9 grown for 3 h on fluorescent substrate. Our results showed that CAC2 cells exhibit functional invadopodia containing cortactin and MT1-MMR Furthermore, MMP9 would be required in the initial steps of invadopodia formation. Microsc. Res. Tech. 73:99-108, 2010. (C) 2009 Wiley-Liss, Inc.
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Titanium dioxide with and without the addition of neodymium ions was prepared using sol-gel and precipitation methods. The resulting catalysts were characterized by thermal analysis, X-ray diffraction and BET specific surface area. Neodymium addition exerted a remarkable influence on the phase transition temperature and the surface properties of the TiO(2) matrix. TiO(2) samples synthesized by precipitation exhibit an exothermic event related from the amorphous to anatase phase transition at 510 degrees C, whereas in Nd-doped TiO(2) this transition occurred at 527 degrees C. A similar effect was observed in samples obtained using sol-gel method. The photocatalytic reactivity of the catalysts was evaluated by photodegradation of Remazol Black B (RB) under ultraviolet irradiation. Nd-doped TiO(2) showed enhanced photodegradation ability compared to undoped TiO(2) samples, independent of the method of synthesis. In samples obtained by sol-gel, RB decoloration was enhanced by 16% for TiO(2) doped with 0.5% neodymium ions. (C) 2010 Elsevier B.V. All rights reserved.
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Introduo: Nveis de fator de necrose tumoralalfa (TNF-), N-peptdeo do pr-colgeno III (PIIINP) e metaloproteinase de matriz 1 (MMP-1), marcadores biolgicos de remodelamento ventricular, esto elevados em pacientes com insuficincia cardaca (IC), talvez refletindo elevadas presses de enchimento. A correlao destes marcadores com variveis clnicas e hemodinmicas permanece pouco compreendida, particularmente no contexto ambulatorial da IC. Objetivo: Avaliar nveis sricos de marcadores biolgicos de remodelamento ventricular em pacientes com IC, comparando tratamento guiado por ecocardiografia (ECO), buscando reduo de presses de enchimento, versus tratamento convencional (CLNICO), baseado em sinais e sintomas. Mtodos: Ensaio clnico randomizado. Pacientes estveis com IC e frao de ejeo menor do que 40% foram alocados entre os grupos de tratamento e submetidos a ecocardiograma e coletas de sangue no incio do estudo e em 180 dias. TNF- e MMP- 1 foram medidos por ELISA, e PIIINP, por radioimunoensaio. Resultados: Incluiu-se 80 pacientes, com 59 15 anos e frao de ejeo de 26 7%; 25% isqumicos e 52% masculinos. Houve reduo dos marcadores biolgicos intragrupos, no havendo diferena entre os tratamentos. No grupo CLNICO, os nveis de TNF-, MMP-1 e PIIINP apresentaram diferenas estatisticamente significativas entre os momentos basal e final (respectivamente, 3,11 2,90 versus 1,24 0,60 pg/mL p < 0,0003; 2,66 1,00 versus 1,16 0,40 ng/mL p < 0,0001; 6,12 2,60 versus 3,89 1,60 g/L p < 0,0001). De maneira semelhante, tal diferena tambm foi observada no grupo ECO para os trs marcadores (respectivamente, 3,90 4,90 versus 1,40 1,30 pg/mL p < 0,0001; 2,50 0,90 versus 1,09 0,40 ng/mL p < 0,0001; 6,09 2,60 versus 3,50 1,30 g/L p<0,0001). Ao final da interveno, no entanto, no foi observada diferena significativa dos valores de TNF- , MMP-1 e PIIINP entre os dois grupos de tratamento (p = 0,7; p = 0,8; e p = 0,2; respectivamente). A combinao dos valores basais das variveis biolgicas gerou um escore que se associou significativamente com o comportamento final das presses atrial direita e sistlica da artria pulmonar. Pacientes com marcadores biolgicos basais no quartil 75% mantiveram nveis superiores de presses atrial direita (13 mmHg; p = 0,034) e sistlica de artria pulmonar (60 mmHg; p = 0,007) ao final do seguimento. Concluso: Independente do tratamento alocado, houve reduo dos nveis de marcadores biolgicos ao final do seguimento; no entanto, nveis basais mais elevados destes marcadores foram preditores de menor reduo das presses em trio direito e sistlica da artria pulmonar. Os dados sugerem que indicativos de intenso processo de remodelamento ventricular se associam progresso da IC e a presses de enchimento elevadas.
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Introduo: a incidncia dos melanomas permanece em ascenso em diversos pases. Os nevos melanocticos podem ser seus precursores ou marcadores de risco. A radiao ultravioleta o principal fator de risco ambiental para o seu desenvolvimento. Estudos com nevos irradiados mostram que a radiao ultravioleta B (UVB) pode causar alteraes morfolgicas e bioqumicas semelhantes s de um melanoma in situ. As metaloproteinases da matriz (MMP) so enzimas proteolticas e, particularmente, as MMP-2 e 9 (gelatinases A e B) parecem estar associadas invaso tumoral, formao de metstases e de neoangiognese em melanomas. O objetivo do presente estudo avaliar os efeitos da UVB nas expresses imunoistoqumicas de MMP-2 e 9 nas diferentes linhagens celulares de nevos melanocticos. Mtodos: quarenta e dois nevos melanocticos tiveram suas metades irradiadas com dose de 2 DEM (dose eritematosa mnima) de UVB e foram excisados uma semana aps. As expresses imunoistoqumicas das MMP-2 e -9 foram comparadas, quanto sua intensidade, por trs avaliadores diferentes entre os lados irradiados e no irradiados em queratincitos, melancitos de epiderme e derme superior, clulas endoteliais e fibroblastos. Os dados foram analisados pelo teste t pareado para as diferenas de expresso e pelo ICC para avaliao da homogeneidade entre as respostas dos observadores. Resultados: com relao expresso imunoistoqumica de MMP-2, todas as linhagens celulares mostraram aumento no lado irradiado, especialmente os melancitos epidrmicos. Quanto MMP-9, somente nos queratincitos, no se observou aumento de expresso do lado irradiado, ficando essa evidente nas demais linhagens celulares avaliadas. Concluses: A UVB na dose de 2 DEM aumenta a expresso imunoistoqumica das MMP-2 e 9 em quase todas as linhagens celulares dos nevos melanocticos avaliados at uma semana aps a irradiao, com exceo feita queratincitos, com a MMP-9.
