O aumento da prevalência da obesidade mórbida constitui um problema de saúde pública global. A obesidade mórbida pode ser definida por um índice de massa corpórea ( IMC ) superior a 35 Kg/ m²; vem acompanhada por diversas comorbidades e determina custos sócio-econômicos elevados. O único método efetivo a longo prazo no tratamento da obesidade mórbida, na atualidade, é a cirurgia bariátrica. Os procedimentos cirúrgicos para tratar a obesidade foram estimulados sobretudo pelo advento de técnicas videolaparoscópicas com menor morbidade pós-operatória e recuperação precoce. O sucesso operatório da cirurgia bariátrica representa perda de até 50% do excesso de peso dos pacientes em prazos variáveis de aproximadamente 24 meses. Após tal período, o processo de emagrecimento será refletido como excesso e flacidez cutânea generalizados e inicia-se a busca pela melhora da imagem corporal. A realização das cirurgias plásticas de contorno corporal exige ampla compreensão das peculiaridades clínicas desse paciente, e dos riscos de complicações, além de expectativas viáveis quanto aos resultados estéticos. Após as cirurgias de contorno corporal, passado o período pós-operatório recente, constata-se a manutenção de flacidez cutânea residual em graus variados. A obesidade interfere na qualidade dos componentes da pele humana. Entretanto, não há estudos específicos em relação à pele do paciente após perda ponderal maciça. Nesse estudo observacional histomorfométrico realizado entre 2006 e 2008, o autor avalia em biópsias de pele humana da região abdominal epigástrica e hipogástrica, o teor de colágeno e elastina em pacientes após perda ponderal maciça comparativamente a pacientes sem antecedentes de obesidade. Analisando a pele abdominal de mulheres não obesas ( controles epigástricos=15 e controles hipogástricos=25 ) e mulheres após tratamento dessa morbidade ( casos=40), verificou-se neste estudo com significância estatística aceita como p<0,05 que: a) na região epigástrica, o teor de colágeno foi superior no grupo controle em comparação ao grupo de casos; b) na região epigástrica, o teor de fibras elásticas foi superior nos casos; c) na região hipogástrica, não houve diferença estatisticamente significante no teor de colágeno entre os grupos estudados; d) na região hipogástrica, o teor de fibras elásticas foi superior no grupo controle / Morbid obesity is an increasing health problem and it is defined as a body mass index greater than 35 kg/m² with severe obesity related comorbidity or a body mass index greater than 40 kg/m² without comorbidity. The combined direct and indirect cost of obesity has been elevated. Bariatric surgery remains the only durable option for weight loss in the morbidly obese.Advanced laparoscopy procedures, as less invasive therapy, have contributed to fast recovery and acceptable perioperative morbidity. Results of bariatric surgery can reach about 50% of excess weight loss with a 2 year follow-up. As patients lose weight, they get laxity skin and their interest in body contouring surgery begins.Plastic surgery in massive weight loss patient demands attention to reduce risks and viable expectations concern to aesthetic results. However, after body contouring surgery, patients can keep up some laxity or folds of excess skin. Obesity changes the components of skin, but there arent definitive studies about skin in massive weight loss patients. In this histomorphometric comparative study, biopsies of human female abdominal skin were analysed in quantity of collagen and elastic fibers in controls (non obese patients, epigastric topography n=15 and hypogastric topography n=25 ) in comparison to massive weight loss patients (n=40). After statistical analyses with p<0,05 was demonstrated that: a)in epigastric topography, the quantity of collagen was higher in control group; b) in epigastric topography, the quantity of elastic fibers was higher in case group; c) in hypogastric topography, there werent diferences in the quantity of collagen between cases and controls; d) in hypogastric topography, the quantity of elastic fibers was higher in control group

Les peptides élastiques (ELP, Elastin-like peptide) sont d'excellents exemples de polymères biomimétiques récemment proposés en médecine régénérative, en particulier dans le domaine de l'ingénierie tissulaire des tissus mous (peau, vaisseaux sanguins, poumons…) pour lesquels la modélisation est complexe car l'instruction correcte des cellules nécessite une élasticité fonctionnelle. L'ajustement précis de la structure primaire des ELP peut moduler voire améliorer les propriétés physico-chimiques, structurales et fonctionnelles de la protéine native. De plus, la capacité des ELP à ajuster leurs caractéristiques physico-chimiques en réponse à des stimuli externes (température, pH), les définit comme des polymères intelligents. Ces polymères bioactifs offrent ainsi une large gamme d'applications très prometteuses encore très peu explorées dans les technologies d'ingénierie tissulaire et les systèmes d'administration de médicaments. Dans ce travail de thèse, nous avons développé, caractérisé et évalué les potentiels thérapeutiques d'une protéine élastique synthétique, Elactiv', inspirée de la structure unique de la tropoélastine humaine, précurseur soluble de l'élastine. Elactiv' conserve les caractéristiques physico-chimiques (comportement thermosensible, propriétés d'autoassemblage) et les fonctions biologiques de la protéine native (prolifération, différenciation et survie des fibroblastes dermiques et kératinocytes humains, sensibilité à la dégradation enzymatique). De plus, Elactiv' possède la particularité in vitro de s'incorporer dans les fibres élastiques néo-synthétisées par des fibroblastes dermiques sains, et d'induire la synthèse de tropoélastine fibrillaire par des fibroblastes pathologiques, syndrome de Williams-Beuren, qui ne synthétisent pas ou très peu de fibres élastiques. Un hydrogel formé exclusivement d'Elactiv' a permis d'accéder aux propriétés mécaniques de l'ensemble et de vérifier sa biocompatibilité in vitro et son innocuité et sa résorption in vivo. Enfin, l'association de la protéine Elactiv' aux dendrigrafts de poly(L-lysine), polymères synthétiques hautement fonctionnalisables, a permis de faire évoluer l'architecture de l'hydrogel vers un biomatériau hybride dans le but d'augmenter ses propriétés mécaniques et biologiques. Ainsi, les potentiels biomimétiques et thérapeutiques de la protéine Elactiv' en font un candidat prometteur pour la régénération des tissus mous / Elastin-like peptides are excellent examples of biomimetic polymers recently proposed in regenerative medicine, particularly for soft tissue engineering (skin, blood vessels, lung ...) for which modeling is a complex task requiring functional elasticity to insctruct cells properelly. Fine-tuning of ELP’s primary structure can modulate or improve physicochemical, structural and functional properties of the native protein. In addition, the adjustment of ELP physicochemical characteristics through external stimuli (temperature, pH) defined them as intelligent polymers. These bioactive polymers thus provide a wide range of very promising applications in tissue engineering and drug delivery, although this has been under-explored until then. In this thesis, we have developed, characterized and evaluated therapeutic potentials of Elactiv', a synthetic elastic protein inspired by the unique structure of the human tropoelastin, the soluble precursor of elastin. Elactiv’ retains physicochemical characteristics (thermoresponsive behavior, self-assembly properties) and biological functions of the native protein (proliferation, differentiation and survival of human keratinocytes and dermal fibroblasts, susceptibility to enzymatic degradation). Besides, Elactiv’ is able to incorporate into neosynthesized elastic fibers by healthy dermal fibroblasts, and to induce fibrillar tropoelastin synthesis by pathological fibroblasts, Williams-Beuren syndrome, which do not synthesize or very few elastic fibres. A hydrogel formed exclusively of Elactiv’ allowed to access to mechanical properties of the scaffold and to verify its biocompatibility in vitro and its safety and resorption in vivo. Finally, the association of Elactiv' protein to poly(L-lysine) dendrigrafts, highly functionalizable synthetic polymers, enabled to evolve the hydrogel's architecture to a hybrid biomaterial in order to increase its mechanical and biological properties for skin tissue engineering. Taken together, biomimetic and therapeutic potentials of Elactiv' protein make it a promising candidate for soft tissue regeneration

L'élastine est la protéine matricielle responsable de l'élasticité des tissus retrouvée dans des tissus soumis à de fortes contraintes mécaniques tels que les poumons, les artères ou la peau. La dégradation de cette protéine lors de processus physiopathologiques produit des peptides bologiquement actifs nommés peptides d'élastine portant le motif GXXPG essentiel à leur activité. Ces peptides régulent diverses fonctions biologiques telles que le chimiotactisme, la synthèse de protéases, la prolifération. Tous ces effets dépendent de la fixation des peptides d'élastine au complexe récepteur de l'élastine. Ce complexe est composé de trois sous-unités : une protéine périphérique de 67 kDa, l'Elastin Binding Protein (EBP), et deux protéines associées à la membrane, la Protective Protein/Cathepsin A (PP/CA) et la Neuraminidase-1 (Neu-1) de 55 et 61 kDa respectivement. L'activité sialidase de Neu-1 est responsable de l'activation de ERK 1/2 après fixation des peptides d'élastine au complexe récepteur de l'élastine.Dans cette étude, nous démontrons que l'EBP et les radeaux lipidiques sont colocalisés à la membrane plasmique. Nous montrons, de plus, que la déstructuration de ces microdomaines aussi bien que leur déplétion en glycolipides bloque la signalisation du récepteur. L'utilisation d'un anticorps monoclonal bloquant dirigé contre le GM3 montre qu'il est essentiel à la signalisation. Après traitement par les peptides d'élastine, le contenu cellulaire en GM3 diminue alors que celui en lactosylcéramide augmente suggérant une conversion du GM3 en lactosylcéramide. L'utilisation de lactose ou de siRNA Neu-1 bloque cette conversion ce qui tend à démontrer que le complexe récepteur de l'élastine est impliqué dans ce mécanisme. Une analyse par cytométrie en flux confirme cette production de lactosylcéramide induite par les peptides d'élastine.L'analyse par spectrométrie de masse mettrait en évidence deux lactosylcéramides (C23:0 et C24:1) potentiellement bioactifs dont la synthèse chimique a été entreprise. La purification des radeaux lipidiques par ultracentrifugation différentielle en gradient de saccharose ainsi que leur identification par Dot-blot couplé à la fluorescence montre un changement de densité de ces microdomaines après stimulation par les peptides d'élastine.L'évaluation biologique in vitro de ces lactosylcéramides montre qu'ils miment les effets des peptides d'élastine sur l'activation de ERK 1/2, la prolifération et la synthèse de MMP-1. Enfin, l'évaluation ex vivo des lactosylcéramides démontre une réduction de la zone de tissu cardiaque nécrosé suggérant un rôle cardioprotecteur de ces molécules. Ce travail propose un mécanisme original de transduction du signal à la membrane plasmique et nous laisse envisager le complexe récepteur de l'élastine, les peptides d'élastine et le lactosylcéramide comme de nouveaux agents thérapeutiques potentiels. / Elastin is the matrix protein responsible for the elasticity of tissues where resilience is required such as lung, arteries or skin. Elastin degradation during physiopathological processes produces biologically active peptides named elastin peptides bearing the GXXPG pattern essential for their activity. These peptides regulate various biological functions such as chemotaxis, proteases synthesis and proliferation. These effects are dependent of elastin peptide binding to the elastin receptor complex (ERC). This complex is composed of three subunits: a peripheral protein of 67 kDa called elastin binding protein (EBP) and two membrane-associated proteins, protective protein/cathepsin A (PP/CA) and neuraminidase-1 (Neu-1) of 55 and 61 kDa, respectively. The sialidase activity of Neu-1 is responsible for ERK 1/2 pathway activation following binding of elastin peptide on the elastin receptor complex.In this study, we demonstrate that EBP and lipid rafts colocalize at the plasma membrane. We also show that the disruption of these microdomains and their depletion in glycolipids block the receptor signaling. The use of a monoclonal anti-GM3 blocking antibody shows that this glycosphingolipid is essential for signaling. Following elastin peptide treatment, cellular GM3 level decreases while the lactosylceramide one increases consistently with a GM3/LacCer conversion. The use of lactose or Neu-1 siRNA blocks this process suggesting that the elastin receptor complex is involved in this mechanism. Flow cytometry analysis confirms this elastin peptide-driven LacCer generation.Mass spectrometry analysis of elastin peptide-stimulated cell membrane extracts identified two potentially bioactive lactosylceramides (C23:0 and C24:1) and their synthesis has been realized. Lipid rafts purification by differencial ultracentrifugation in sucrose gradient shows a variation of the microdomains density as well as their identification by fluorescence linked-Dot-blot following elastin peptide stimulation.In vitro biological evaluation of these lactosylceramides shows that they mimic the elastin peptide effects on ERK 1/2 activation, proliferation and MMP-1 synthesis. Finally, ex vivo lactosylceramides evaluation demonstrates a decrease of cardiac tissue necrosis area suggesting that these molecules could be cardioprotective agents. This work proposes an original mechanism of signal transduction at the plasma membrane and let us foresees the elastin receptor complex, elastin peptides and lactosylceramide as new potential therapeutical targets.

Kolorektalcancer är den tredje vanligaste cancerformen hos både män och kvinnor i Sverige där storkärls invasion, venös invasion (VI), är en viktig prognostisk indikator. Noggrann bedömning av VI är särskilt viktigt för patienter med kolorektal cancer i stadium II eftersom det kan påverka beslutet att erbjuda adjuvant behandling. Histologisk bedömning av VI kan vara utmanande på rutinmässig Hematoxylin och Eosin färgning (H&amp;E). Elastinfärgning med syfte att identifiera elastinfibrer i kärlväggen kan underlätta bedömning av VI. I dagsläget finns inte någon bra elastinfärgning som kan användas rutinmässigt hos klinisk patologi i Värmland, Centralsjukhuset Karlstad, prover måste skickas till annat laboratorium vilket är tidskrävande. Denna studie ska finna den optimala färgningsmetoden för elastin genom att utvärdera tre olika färgningsmetoder för elastin fibrer. Färgningens resultat bedömdes rent histokemiskt av överläkare enlig kriterierna, frånvaro av avsedda kärl (skala 0–1), specifik infärgning (skala 0–1), specifik infärgnings intensitet (skala 1–3) och ospecifik infärgning (skala 0–1) och data samlades för respektive metod. Resultatet tyder på att rent histokemiskt är den manuella elastinfärgning metoden från Region Jönköpings län konsekvent och visade signifikant skillnad. Därför metoden är potentiellt användbar för den större frågeställningen om storkärlsinväxt i kolorektal cancer samt rekommenderas starkt som en rutinmässig elastinfärgning till klinisk patologi i Värmland, Centralsjukhuset Karlstad. / The third most common form of cancer in both men and women in Sweden is Colorectal cancer. Prognostic indicators of colorectal cancer include Large vessel invasion and venous invasion (VI). Careful assessment of VI is of particular interest especially with patients having stage II colorectal cancer. This is because it may influence decisions to offer adjuvant therapy. Accurate histological assessment of VI can be challenging on routine hematoxylin and eosin staining. But staining that can identify the elastin fibers in the vessel can enhance the assessment of VI. Currently, there is not any good Elastin staining that can be routinely used in clinical pathology in Värmland, Karlstad Central Hospital. Therefore, samples are required to be sent to other laboratories which in effect is time consuming. This study is aimed at finding an optimal elastin staining method through evaluations of three different staining methods for elastin fibers. Staining results were assessed histochemically by the chief physician according to the following criteria, absence of intended vessels (scale 0–1), specific staining (scale 0–1), specific staining intensity (scale 1–3) and nonspecific staining (scale 0–1), while different data were collected for each method. The results indicate that purely histochemically, elastin staining-manual method Region Jönköping County is consistent and significant. Therefore, the method is potentially useful for the detection of colorectal cancer and is strongly recommended as a routine elastin staining for clinical pathology in Värmland, Karlstad Central Hospital.

Atherosclerosis is a macrophage-dominated nonresolving inflammatory disease of the arterial wall. Macrophage processes, including apoptosis, influence lesion development in atherosclerosis. Cannabinoids, compounds structurally related to Δ9-tetrahydrocannabinol (THC), the active ingredient in marijuana, exert their effects through cannabinoid receptors, CB1 and CB2. Cannabinoid treatment, THC or Win55,212-2, reduces atherosclerosis in ApoE-null mice by a mechanism thought to involve CB2. However, the exact role of CB2 in atherosclerosis remains unclear. We found that CB2-null macrophages are resistant to oxysterol/oxLDL-induced apoptosis leading us to hypothesize that CB2 may modulate macrophage apoptosis in atherosclerosis. To determine the functions of CB2 in atherosclerosis, we fed low density lipoprotein receptor-null (Ldlr-/-) and Ldlr-/- mice genetically deficient in CB2, an atherogenic diet for 8 and 12 weeks. CB2 deficiency did not significantly affect aortic root lesion area after 8 or 12 weeks; however, after 12 weeks, CB2-deficient lesions displayed increased lesional macrophage and smooth muscle cell (SMC) content and a ~2-fold reduction in lesional apoptosis. CB2-deficienct lesions also displayed reduced collagen content and elevated elastin fiber fragmentation that was associated with elevated levels of the extracellular matrix degrading enzyme, matrix metalloproteinase 9 (MMP9). These results demonstrate that although CB2 signaling does not affect atherosclerotic lesion size it does modulate lesional apoptosis, cellularity and ECM composition. Ldlr-/- and CB2-deficient Ldlr-/- mice were also subjected to daily treatments with Win55,212-2, a synthetic cannabinoid, over the last 2 weeks of an 8 week atherogenic diet to identify CB2-dependent and CB2-independent effects of cannabinoid receptor stimulation on atherosclerosis. Win55,212-2 did not affect hypercholesterolemia, aortic root lesion area, lesional macrophage infiltration, or ECM composition in either genotype but did significantly reduce total plasma triglyceride levels and lesional SMC content, independent of CB2. Surprisingly, lesional apoptosis was dose-dependently repressed by Win55,212-2 in Ldlr-/- mice by a CB2-dependent mechanism. All together, these results support the suggestion that CB2 may be a target for novel therapies aimed at modulating lesional apoptosis and cellularity to increase lesion stability and reduce the vulnerability to rupture.

No description available.

Introdução: A hiperidrose primária consiste em uma sudorese excessiva em regiões limitadas do corpo. A simpatectomia torácica videotoracoscópica é um dos tratamentos propostos para a hiperidrose primária palmar, aliando alto sucesso terapêutico com baixo risco. A fisiopatologia da hiperidrose primária ainda não está totalmente esclarecida. Objetivos: Analisar as características morfométricas dos gânglios simpáticos torácicos (G3), removidos cirurgicamente de pacientes portadores de hiperidrose palmar. Como controle foram utilizados os gânglios simpáticos, removidos no mesmo nível (G3), de pacientes doadores de órgãos por morte encefálica, sabidamente sem hiperidrose. Foram estudadas a estereologia e a apoptose celular e as fibras do sistema colágeno /elastina da matriz extracelular. Métodos: Estudo transversal, no qual foram incluídos 40 gânglios simpáticos torácicos (G3) removidos do hemitórax esquerdo, provenientes de pacientes com hiperidrose palmar (Grupo I), submetidos à simpatectomia videotoracoscópica, e 14 gânglios simpáticos de pacientes controle sabidamente sem hiperidrose (Grupo II), removidos por esternotomia mediana. Resultados: Em relação ao sexo, a proporção de mulheres e homens foi de 30:10, no Grupo I, e 7:7 no Grupo II, com p = 0,103. A idade no Grupo I, variou de 10 a 42 anos, com uma média de 23,73 (+ 7,51) e no Grupo II variou de 17 a 68 anos, com uma média de 37,57 (+ 16,65) , apresentando um p = 0,009. A média das células ganglionares nos pacientes do Grupo I foi de 14,25 (+ 3,81) e no Grupo II foi de 10,65 (+ 4,93) com p = 0,007. A média das células ganglionares coradas pela caspase (apoptose) no Grupo I foi de 2,37 (+ 0,79) e no Grupo II foi de 0,77 (+ 0,28) com p < 0,001. A mediana da área de colágeno corada pelo Picrosírius no Grupo I foi de 0,80 IQ (0,08-1,87) e no Grupo II foi de 2,36 IQ (0,49-5,98) com p = 0,061. Conclusões: Os pacientes portadores de hiperidrose primária palmar apresentam um maior número de células ganglionares no gânglio simpático, em relação aos do grupo controle. Há um número maior de células ganglionares simpáticas em apoptose na hiperidrose. Os pacientes portadores de hiperidrose apresentam menos colágeno no gânglio simpático / Introduction: Primary hyperhidrosis consists of excessive sweating in small areas of the body. The video-assisted thoracic sympathectomy is one of the suggested treatments for primary palmar hyperhidrosis, which combines high therapeutic success with low risk. The pathophysiology of primary hyperhidrosis is not fully understood yet. Objectives: Analyzing the morphometric characteristics of the thoracic sympathetic ganglion (G3) surgically removed from patients with palmar hyperhidrosis. The sympathetic ganglion removed at the same level (G3) from patients who are organ donors after brain death and who did not have hyperhidrosis were used as control. Stereology and cellular apoptosis, as well as the fibers of the collagen/elastin system of the extracellular matrix were subjected to scrutiny. Methods: Cross-sectional study, which included 40 thoracic sympathetic ganglion (G3) removed from the left hemithorax of patients who have palmar hyperhidrosis (Group I) and underwent video-assisted thoracoscopic sympathectomy, and also 14 sympathetic ganglion from control patients who did not have hyperhidrosis (Group II), which were removed with median sternotomy. Results: In regards to gender , the proportion of women to men was 30:10 in Group I and 7:7 in Group II, with p = 0.103. The age Group I ranged from 10 to 42 years, with an average of 23.73 (+ 7.51) years and in Group II, from to 17 to 68 years, with an average of 37.57 (+ 16.65) years, with p = 0.009. The average of ganglion cells in Group I was 14.25 (+ 3.81) and in Group II, 10.65 (+ 4.93) with p = 0.007. The average ganglion cells stained by Caspase (apoptosis) in Group I was 2.37 (+0.79) and in Group II, 0.77 (+ 0.28) with p = 0.001. The median collagen area by Picrosirius in Group I was 0.80 IQ (0.08-1.87) and in Group II, 2.36 IQ (0.49-5.98) with p = 0.061. Conclusions: Patients with primary palmar hyperhidrosis have an increased number of ganglion cells in the sympathetic ganglion in comparison to the control group. There are a higher number of sympathetic ganglion cells in apoptosis in hyperhidrosis. Patients with hyperhidrosis have less collagen in sympathetic ganglion

Introdução: A síndrome de Williams-Beuren (SWB) consiste de uma deleção no cromossomo 7q11.23, região responsável pela codificação de 28 genes, estando o gene codificador da elastina situado aproximadamente no ponto médio dos extremos da deleção; a mutação no gene da elastina leva a alterações fenotípicas no paciente, com prejuízo do desenvolvimento neuropsicomotor de graus variados, fáscies características, anormalidades cardiovasculares, hipercalcemia, disfunções urológicas e osteoarticulares. O presente estudo avaliou a prevalência de escoliose em pacientes com diagnóstico de SWB, bem como sua relação com o padrão das curvas nos portadores de escoliose. Métodos: Foram incluídos 41 pacientes com diagnóstico de SWB através da realização de anamnese, exame físico e investigação radiográfica, sendo 25 do sexo masculino. Realizou-se a interpretação das radiografias e obtenção do ângulo de Cobb. Resultados: Observou-se que 14 pacientes eram portadores de escoliose, sendo 10 do sexo masculino. O padrão da deformidade apresentou-se, nos pacientes mais jovens, através de curvas simples e flexíveis, e, apesar de adultos apresentarem ocorrência de duplas curvas e triplas curvas, a análise estatística não evidenciou relação entre escoliose e idade ou sexo dos pacientes. Conclusões: O estudo evidenciou prevalência de escoliose em portadores de SWB: 34,1%; entretanto, as variáveis idade e sexo não apresentaram relação com a ocorrência de escoliose, assim como a gravidade das curvas apresentadas / Introduction: Williams-Beuren syndrome (WBS) consists of a chromosome 7q11.23 deletion in the region responsible for encoding 28 genes, with the elastin encoding gene situated approximately at the midpoint of the extremes of deletion; mutation of the elastin gene leads to phenotypic changes in patients with neurodevelopment impairment of varying degrees, characteristic facies, cardiovascular abnormalities, hypercalcemia, and urological and bone and joint dysfunctions. This study assessed the prevalence of scoliosis in patients with WBS, and the relationship with the pattern of scoliotic curves. Methods: A total of 41 patients diagnosed with SWB were included in the study, 25 males, through anamnesis, physical examination and radiographic investigation. Radiographic imaging was interpreted and the Cobb angle was calculated. Results: It was observed that 14 patients had scoliosis, and 10 of them were male. The pattern of the deformity in younger patients was of flexible and simple curves, and although adults presented double and triple curves, statistical analysis showed no relationship between scoliosis and age or sex. Conclusion: The study revealed a prevalence of scoliosis in patients with SWB of 34.1%; however, the variables age and sex had were not significantly associated with scoliosis, nor with the severity of the curves

Pacientes submetidos ao tratamento cirúrgico da obesidade mórbida apresentam perda ponderal acentuada e dismorfismo corporal e, com frequência, solicitam cirurgias plásticas visando um contorno corporal mais adequado. Os resultados dessas cirurgias plásticas são, em parte, limitados pela qualidade da pele resultante do grande emagrecimento. O presente estudo observacional teve como objetivo comparar fragmentos de pele da região epigástrica de 20 pacientes após perda ponderal acentuada consequente à cirurgia bariátrica com 20 pacientes portadores de obesidade mórbida, no sentido de analisar as alterações estruturais da pele como consequência do emagrecimento. A análise histomorfométrica foi realizada sobre o sistema colagênico através da metodologia Picrossírius/luz polarizada, e sobre o sistema elástico através da metodologia resorcinafucsina de Weigert. Foram observados, a redução das fibras colagênicas grossas (p=0,048); o aumento das fibras colagênicas finas (p=0,0085); e o aumento da densidade das fibras elásticas (p=0,0000009033) no grupo de pacientes emagrecidas. Não houve diferença entre os grupos quanto à média de idades (p=0,917) e quantidade total de fibras colágenas (p=0,3619). Os resultados evidenciaram as alterações estruturais da derme decorrentes do emagrecimento acentuado, demonstradas por meio do remodelamento colagênico, com a consequente redução das fibras espessas, organizadas, estruturadas e direcionadas em prol do aumento de fibras finas, desalinhadas e frouxamente dispostas, isso em associação ao aumento da elasticidade da pele. Isto explica cientificamente a já estabelecida percepção clínica das alterações cutâneas dos pacientes emagrecidos após cirurgias bariátricas, apresentando menor resistência e maior flacidez, quando comparadas ao período anterior ao emagrecimento / Post-bariatric patients develop body contour deformities and need plastic surgery procedures for reduction of excess skin and subcutaneous tissue. The results of these contouring procedures are typically limited by the poor quality of the skin. This observational study compared the epigastric skin of 20 post-bariatric with massive weight loss women with 20 women with morbid obesity through histomorphometric analysis of collagen fibers (picrosiriuspolarization) and elastic fibers (Weigert\'s resorcin-fuchsin). A reduction of thick collagen fibers (p=0.048), increase of thin collagen fibers (p=0.0085) and increase of the density of elastic fibers (p=0.0000009) were observed in the group of post-bariatric patients. There was no difference between the groups for mean age (p=0.917) and the total amount of collagen fibers (p=0.3619). These results represent structural changes in the dermis due to the massive weight loss once it demonstrates collagen modifications with reduction of thickness, organized and structured fibers, increase of thin, misaligned and disarranged fibers, and augmentation of the density of elastic fibers. This brings the scientific explanation for the established clinical perception that the skins of post-bariatric patients are less resistant and with more laxity when compared with what they were before the bariatric surgery

A doença pulmonar obstrutiva crônica (DPOC) é uma das principais causas de morbidade crônica e mortalidade em todo o mundo e tem como principal manifestação o enfisema pulmonar, caracterizado pelo contínuo e progressivo remodelamento dos componentes da matriz extracelular (MEC). De acordo com estudos experimentais e clínicos esse remodelamento pode ser atribuído à ação proteolítica das metaloproteases de matriz (MMPs), especialmente da MMP-12, sobre os componentes da MEC, sendo a elastina considerada, até recentemente, a principal fibra alvo da proteólise. Dessa forma, só recentemente tem sido esclarecida a importância de outros componentes da MEC e outras MMPs, como as colagenases, no remodelamento da MEC. Sendo assim, o objetivo deste trabalho foi analisar a progressão do remodelamento das fibras no parênquima pulmonar e a expressão gênica das MMPs no início do desenvolvimento do enfisema. Para isso camundongos C57BL/6 receberam instilação intranasal de elastase pancreática suína (PPE 0,667 UI / Grupos ELA: n=40) ou o mesmo tratamento com solução salina (NaCl 0,9% / Grupos controle SAL: n=40). Os animais foram anestesiados, eutanasiados e separados em sub-grupos iguais (n=8) de acordo com o tempo após a instilação de PPE (1, 3, 6 horas, 3 e 21 dias) para remoção dos seus pulmões. Foram medidos o intercepto linear médio (Lm) e as proporções do volume de colágeno tipo I e tipo III, elastina e fibrilina. A expressão gênica para metaloproteinases (MMP-1a, MMP-1b, MMP-8, MMP-12 e MMP-13) no parênquima pulmonar foi avaliada por RT-PCR em tempo real. Os resultados demonstraram que o Lm aumentou desde 3 horas após a instilação de PPE, atingindo os maiores aumentos no 3º e 21º dias, sugerindo uma progressão no alargamento alveolar. Em comparação com o grupo SAL, os grupos ELA apresentaram uma diminuição no colágeno tipo I (no 3º dia) e colágeno tipo III (a partir de 6 horas até 3 dias) em tempos posteriores ao aumento da expressão gênica para MMP-8 (a partir de 3 até 6 horas) e - 13 (a partir de 1 até 6 horas). Após 21 dias, o colágeno tipo III apresentou aumento e o colágeno tipo I retornou a valores semelhantes aos do seu respectivo grupo controle. A expressão gênica para MMP-12 aumentou nos grupos ELA em tempos anteriores (3 e 6 horas) aos que constatamos a redução na proporção de elastina no pulmão (3º dia), reforçando a importância já estabelecida da MMP-12 na quebra deste componente da MEC. A proporção de volume de elastina aumentou no grupo ELA em relação ao respectivo grupo SAL no 21º dia. Não houve aumento na expressão gênica da MMP-1b em nenhum momento e a MMP-1a não teve expressão mensurável em nenhum dos grupos. Não foram observadas diferenças entre os grupos experimentais na avaliação da fibrilina. Nossos resultados serão úteis para melhor elucidar as alterações dinâmicas nos componentes da MEC e a importância, não só da metaloelastase, mas também das colagenases em estágios iniciais do enfisema, fornecendo novas ferramentas para futuros estudos sobre possíveis alvos terapêuticos / Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide and has as the major manifestation pulmonary emphysema in which the components of the extracellular matrix (ECM) are in a continuous process of remodeling. According to experimental and clinical studies that remodeling can be attributed to proteolytic action of matrix metalloproteinases (MMPs), particularly MMP-12, on the ECM components, with elastin being considered until recently, the primary target fiber of proteolysis. Therefore, only recently has been clarified the importance of other components of the ECM and other MMPs such as collagenases on ECM remodeling. Thus, the objective of this study was to analyze the progression of lung parenchymal fibers remodeling and the gene expression of MMPs in the early development of emphysema. For this C57BL/6 mice were given intranasal instillation of porcine pancreatic elastase (PPE 0,667 IU / ELA groups: n=40) or the same treatment with saline (0.9% NaCl / SAL Control groups: n=40). The animals were anesthetized and euthanized divided into equal sub-groups (n=8) according to time after PPE instillation (1, 3, 6 hours, 3 and 21 days) to remove their lungs. The mean linear intercept (Lm) and the volume proportions of type I and type III collagen, elastin and fibrillin were measured. Gene expression of metalloproteinases (MMP-1a, 1b-MMP, MMP-8, MMP-12 and MMP-13) in the lung parenchyma was evaluated by Real Time RT-PCR. The results demonstrated that the Lm has increased from 3 hours after PPE instillation, with the highest increases reached at 3rd and 21th day, suggesting a progression in the alveolar enlargement. Compared to SAL group, ELA group showed a decrease in type I collagen (3rd day) and collagen type III (from 6 hours to 3 days) on later times to the increase in MMP-8 gene expression (from 3 to 6 hours) and - 13 (from 1 to 6 hours). After 21 days, type III collagen showed an increase and collagen type I returned to values similar to those of their respective control group. Gene expression for MMP-12 increased on PPE groups in earlier times (3 and 6 hours) at which we detected reduction in elastin proportion in the lung (3rd day), reinforcing the importance already established of MMP-12 in the breakage of this ECM component. The elastin volume proportion increased in PPE group compared to respective SAL group at 21st day. There was no increase in MMP-1b gene expression at any time and MMP-1a shows no measurable expression in either group. There were no differences between the experimental groups in the evaluation of fibrillin. Our results will be useful to better elucidate the dynamic changes in ECM components and the importance not only of metalloelastase but also of collagenases in the early stages of emphysema, providing new tools for future studies of potential therapeutic targets