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Objetivo: Determinar la efectividad del suero autólogo rico en factores de crecimiento en la reparación de lesiones de la superficie ocular de evolución incierta con el tratamiento convencional. Materiales y métodos: Se trataron 46 unidades oculares con afecciones de la superficie ocular agrupadas en queratopatías por exposición, queratopatías por síndrome de ojo seco / neurotróficas, y traumas oculares. Las partes oculares afectadas fueron: conjuntiva, cornea (epitelio, estroma) y esclera. Se evaluaron de manera anatómica y funcional con la prueba de Schirmer, tinción con Fluoresceína y tomografía de coherencia óptica (TCO) entre marzo y diciembre del 2020. Resultados: Los síntomas mejoraron en el siguiente orden: dolor ocular, sensación de cuerpo extraño, blefaroespasmo, hiperemia y lagrimeo. Las lesiones evolucionaron favorablemente de la siguiente manera: en primer lugar las conjuntivales y del epitelio corneal, luego las del estroma corneal y finalmente las lesiones en la esclera. Se obtuvo una media de 15 días para recuperación inmediata de la superficie y de 21 días para recuperación tardía. Las lesiones con adelgazamiento parcial profundo de esclera tomaron alrededor de 2 meses. Conclusiones: Los hallazgos relacionados al umbral del dolor, tiempo de recuperación, remodelación cicatrizal del tejido afectado y recuperación de la agudeza visual son prometedores e importantes. La utilización de suero autólogo rico en factores de crecimiento puede ser una alternativa terapéutica para las lesiones de difícil resolución con el tratamiento convencional.

Objective: To determine the effectiveness of autologous serum rich in growth factors to repair ocular surface lesions which have uncertain progression with conventional treatment. Materials and methods: AForty-six (46) eyes with ocular surface disorders such as exposure keratopathy, keratopathy caused by dry eye syndrome, neurotrophic keratopathy and blunt eye injury were treated. The affected areas were the conjunctiva, cornea (epithelium, stroma) and sclera. Anatomical and functional evaluations were performed between March and December 2020 using Schirmer's test, fluorescein eye stain and optical coherence tomography (OCT). Results: The symptoms improved in the following order: eye pain, foreign body sensation, blepharospasm, hyperemia and epiphora. Additionally, the lesions progressed favorably as follows: first, those of the conjunctiva and corneal epithelium; then, those of the corneal stroma; and, finally, those of the sclera. An average of 15 days was required for immediate ocular surface recovery and 21 days for late recovery. The lesions with total scleral thinning healed in about two months. Conclusions: The findings related to pain threshold, recovery time, scar tissue remodeling of the affected tissue and visual acuity improvement are promising and important. Using autologous serum rich in growth factors may be a therapeutic alternative for those lesions that are difficult to resolve with conventional treatment.

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RESUMEN Introducción: los avances científico-técnicos en el campo de la Biología celular y molecular han permitido restaurar y mejorar la función de órganos y tejidos lesionados por ciertas enfermedades y traumatismos. La Ingeniería de tejido se define como el uso de los principios y métodos de la Ingeniería, la Biología y la Bioquímica, los cuales están orientados a la comprensión de la estructura y la función de los tejidos normales y patológicos, y al consecuente desarrollo de sustitutos biológicos para restaurar, mantener o mejorar su función. Objetivo: realizar un acercamiento a algunos aspectos de la Biología celular y molecular vinculada con la Ingeniería tisular ósea. Métodos: se realizó una búsqueda bibliográfica en SciELO Cuba y en Google académico durante el período de 1 de marzo al 28 de abril de 2018. Se evaluaron 134 artículos y el estudio se circunscribió a los 25 artículos que se enfocaban en estas temáticas de manera integral. Conclusiones: se ofreció una visión general de los avances que se han obtenido en la Biología celular y molecular, y en particular a: la aplicación de los factores de crecimiento en la Ingeniería del tejido óseo, así como sus futuras perspectivas. Se concluyó que es fundamental consolidar una base apropiada de conocimientos sobre la Biología celular y molecular y el desarrollo actual de la Ingeniería del tejido óseo.

ABSTRACT Introduction: scientific and technical advances in the field of cellular and molecular biology have allowed restoring and improving the function of organs and tissues injured by certain diseases and trauma. Tissue engineering is defined as the use of the principles and methods of Engineering, Biology and Biochemistry, which are aimed at understanding the structure and function of normal and pathological tissues, and the consequent development of biological substitutes to restore, maintain or improve their function. Objective: to carry out an approach to some aspects of cellular and molecular biology related to bone tissue engineering. Methods: a bibliographic review was carried out in SciELO Cuba and Google Scholar from March 1 to April 28, 2018. A number of 134 articles were evaluated and the study was limited to 25 articles that focused on these topics in an integral way. Conclusions: an overview of the advances that have been obtained in cellular and molecular biology was offered, particularly to the application of growth factors in bone tissue engineering, as well as its future perspectives. We concluded that it is essential to consolidate an appropriate knowledge base on cellular and molecular biology and the current development of bone tissue engineering.

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ABSTRACT Objective: To identify evidence about the effects of growth factor application on venous ulcer healing. Method: Systematic review and meta-analysis, including Randomized Clinical Trials. Searches: Ovid MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, LILACS, Web of Science, Digital Library of Theses and Dissertations; Google Scholar and list of references. Results: 802 participants were recruited from the 10 included studies: 472 in the intervention group (growth factors) and 330 as control. The relative risk for the complete healing outcome was 1.06 [95% CI 0.92-1.22], p = 0.41. Participants who received Platelet-Rich Plasma and Epidermal Growth Factor showed a slight tendency to achieve complete healing, but without statistical relevance (p <0.05). Most of the studies were classified as moderate risk of bias. Conclusion: The effect of the application of growth factors for complete healing in venous ulcers is not clear, and clinical trials with methodological quality are required for more accurate recommendations.

RESUMEN Objetivo: Identificar evidencias acerca de los efectos de la aplicación de factores de crecimientoenlacicatrización de úlceras venosas. Método: Revisión sistemática y metanálisis, incluyendo Ensayos Clínicos aleatorizados. Búsquedas: Ovid MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, LILACS, Web of Science, Biblioteca Digital de Tesis y Disertaciones; Google Académico y lista de referencias Resultados: 802 participantes fueron reclutados por los 10 estudios incluidos: 472 en el grupo intervención (factores de crecimiento) y 330 como control. El riesgo relativo para el desenlace de cicatrización completa fue de 1,06 [IC95% 0,92-1,22], p = 0.41. Los participantes que recibieron Plasma Rico en Plaquetas y Factor de Crecimiento Epidérmico presentaron una ligera tendencia a alcanzar una cicatrización completa, pero sin relevancia estadística (p <0.05). La mayoría de los estudios se clasificaron como moderado riesgo de sesgo. Conclusión: El efecto de la aplicación de factores de crecimiento para cicatrización completa en úlceras venosas no está claro, siendo necesarios ensayos clínicos con calidad metodológica para recomendaciones más precisas.

RESUMO Objetivo: Identificar evidências acerca dos efeitos da aplicação de fatores de crescimento na cicatrização de úlceras venosas. Método: Revisão sistemática e metanálise, incluindo Ensaios Clínicos Randomizados. Buscas: Ovid MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL, LILACS, Web of Science, Biblioteca Digital de Teses e Dissertações; Google Acadêmico e lista de referências. Resultados: 802 participantes foram recrutados pelos 10 estudos incluídos: 472 no grupo intervenção (fatores de crescimento) e 330 como controle. O risco relativo para o desfecho de cicatrização completa foi de 1,06 [IC95% 0,92-1,22], p=0.41. Os participantes que receberam Plasma Rico em Plaquetas e Fator de Crescimento Epidérmico apresentaram uma ligeira tendência a alcançar cicatrização completa, porém sem relevância estatística (p<0.05). A maioria dos estudos foi classificada como moderado risco de viés. Conclusão: O efeito da aplicação de fatores de crescimento para cicatrização completa em úlceras venosas não está claro, sendo necessários ensaios clínicos com qualidade metodológica para recomendações mais precisas.

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Abstract Objective: To demonstrate the underlying mechanisms of aortic dissection compared to those of coronary artery disease in terms of the transforming growth factor-beta (TGF-β) signaling pathway. Methods: Twenty consecutive aortic dissection patients and 20 consecutive coronary artery disease patients undergoing a surgical treatment in this hospital were enrolled into this study. The aortic tissues were sampled and the TGF-β1 and its receptor TGF-β receptor I (TβRI) were detected by Western blotting assay. Results: TGF-β1 and TβRI were positively expressed in the aortic tissues in both groups by Western blotting assay. The expressions of the two proteins were significantly higher in the aortic tissue of patients with aortic dissection than in those with coronary artery disease. The quantitative analyses of the relative gray scales of the proteins disclosed close correlations between the expressions of TGF-β1 and TβRI in both the study and control group patients. Conclusions: The aortic remodeling of aortic dissection might differ from that of coronary artery atherosclerosis concerning the nature, mechanism, mode, and activities of TGF-β signaling pathway. The development of aortic dissection could be associated with a significantly enhanced function of TGF-β1/Smad signaling transduction as a result of aortic remodeling incorporating both vascular injury and repair.

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OBJECTIVE: To evaluate the neurotrophin mRNA expression and axon count in the median nerve of Wistar rats submitted to neural mobilization (NM) after nerve compression. METHODS: Eighteen animals were randomly divided into G1 (nerve compression only), G2 (NM for 1 min), and G3 (NM for 3 min). For NM, the animals were anesthetized and the right scapula received the mobilization, adapted as indicated for humans, on alternate days, from the third to the 13th postoperative (PO) day, totaling six days of therapy. On the 14th PO day, animals were anesthetized and euthanized. Fragments of the median nerve, distal to the compression procedure, were removed for histomorphometric analysis and expression of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) by RT-PCR. RESULTS: Histomorphometric analysis revealed differences in the number of axons in the injured side, which was significantly lower in the injured limb nerve compared to the control limb, whereas the RT-PCR analysis showed no significant differences in the expression of NGF or BDNF. CONCLUSION: NM treatment did not affect median nerve regeneration, which maintained normal recovery rates.

OBJETIVO: Avaliar a expressão de RNAm de neurotrofinas e a contagem de axônios no nervo mediano de ratos Wistar submetidos à mobilização neural (MN) após compressão nervosa. MÉTODOS: Foram divididos aleatoriamente 18 animais em G1 (apenas compressão nervosa), G2 (MN por 1 minuto) e G3 (MN por 3 minutos). Para a MN, os animais foram anestesiados e o membro escapular direito recebeu a mobilização, adaptada da forma indicada para humanos, em dias alternados, do terceiro ao 13° dia de pós-operatório (PO), em seis dias de terapia. No 14° dia PO, os animais foram anestesiados e eutanasiados. Fragmentos do nervo mediano, distais ao procedimento de compressão, foram retirados para análise histomorfométrica e de expressão das neutrotrofinas, fator de crescimento do nervo (NGF) e fator de crescimento derivado do cérebro (BNDF) por RT-PCR. RESULTADOS: A análise histomorfométrica evidenciou diferenças no número de axônios nos lados lesionados, que foi significativamente menor no nervo do membro lesado comparado com o membro controle; por sua vez, a análise por RT-PCR não apontou diferenças significativas na expressão de NGF e nem de BNDF. CONCLUSÃO: O tratamento de MN não afetou a regeneração do nervo mediano, que manteve índices normais de recuperação.

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ABSTRACT Objective: To evaluate the neurotrophin mRNA expression and axon count in the median nerve of Wistar rats submitted to neural mobilization (NM) after nerve compression. Methods: Eighteen animals were randomly divided into G1 (nerve compression only), G2 (NM for 1 min), and G3 (NM for 3 min). For NM, the animals were anesthetized and the right scapula received the mobilization, adapted as indicated for humans, on alternate days, from the third to the 13th postoperative (PO) day, totaling six days of therapy. On the 14th PO day, animals were anesthetized and euthanized. Fragments of the median nerve, distal to the compression procedure, were removed for histomorphometric analysis and expression of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) by RT-PCR. Results: Histomorphometric analysis revealed differences in the number of axons in the injured side, which was significantly lower in the injured limb nerve compared to the control limb, whereas the RT-PCR analysis showed no significant differences in the expression of NGF or BDNF. Conclusion: NM treatment did not affect median nerve regeneration, which maintained normal recovery rates.

RESUMO Objetivo: Avaliar a expressão de RNAm de neurotrofinas e a contagem de axônios no nervo mediano de ratos Wistar submetidos à mobilização neural (MN) após compressão nervosa. Métodos: Foram divididos aleatoriamente 18 animais em G1 (apenas compressão nervosa), G2 (MN por 1 minuto) e G3 (MN por 3 minutos). Para a MN, os animais foram anestesiados e o membro escapular direito recebeu a mobilização, adaptada da forma indicada para humanos, em dias alternados, do terceiro ao 13° dia de pós-operatório (PO), em seis dias de terapia. No 14° dia PO, os animais foram anestesiados e eutanasiados. Fragmentos do nervo mediano, distais ao procedimento de compressão, foram retirados para análise histomorfométrica e de expressão das neutrotrofinas, fator de crescimento do nervo (NGF) e fator de crescimento derivado do cérebro (BNDF) por RT-PCR. Resultados: A análise histomorfométrica evidenciou diferenças no número de axônios nos lados lesionados, que foi significativamente menor no nervo do membro lesado comparado com o membro controle; por sua vez, a análise por RT-PCR não apontou diferenças significativas na expressão de NGF e nem de BNDF. Conclusão: O tratamento de MN não afetou a regeneração do nervo mediano, que manteve índices normais de recuperação.

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Abstract Periodontal regeneration is still a challenge in terms of predictability and magnitude of effect. In this study we assess the biological effects of combining chemical root conditioning and biological mediators on three relevant cell types for periodontal regeneration. Material and Methods: Bovine dentin slices were conditioned with 25% citric acid followed by topical application of basic fibroblast growth factor (bFGF, 10 and 50 ng). We used ELISA to assess the dynamics of bFGF release from the dentin surface and RT-qPCR to study the expression of Runx2, Col1a1, Bglap and fibronectin by periodontal ligament (PDL) fibroblasts, cementoblasts and bone marrow stromal cells (BMSC) grown onto these dentin slices. We also assessed the effects of topical application of bFGF on cell proliferation by quantification of genomic DNA. Results: Acid conditioning significantly increased the release of bFGF from dentin slices. Overall, bFGF application significantly (p<0.05) increased cell proliferation, except for BMSC grown on non-conditioned dentin slices. Dentin substrate discretely increased expression of Col1a1 in all cell types. Expression of Runx2, Col1a1 and Fn was either unaffected or inhibited by bFGF application in all cell types. We could not detect expression of the target genes on BMSC grown onto conditioned dentin. Conclusion: Acid conditioning of dentin improves the release of topically-applied bFGF. Topical application of bFGF had a stimulatory effect on proliferation of PDL fibroblasts, cementoblasts and BMSC, but did not affect expression of Runx2, Col1a1, Bglap and fibronectin by these cells.

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O PRF líquido pode facilitar o posicionamento e a escultura de enxertos ósseos particulados, além dos possíveis benefícios relacionados ao reparo ósseo e fibromucosa. Para tanto, é necessário que o profissional conheça os aspectos práticos e teóricos envolvidos no seu uso. Um paciente com 45 anos de idade, apresentava perda dos incisivos maxilares e de espessura da crista óssea na região, impossibilitando a colocação de implantes de diâmetro convencional. Para a regeneração óssea, foi utilizado enxerto com substituto ósseo associado a coágulos de PRF, PRF líquido e tela de titânio. Após o reparo ósseo, foram instalados dois implantes na região dos incisivos laterais como pilares de uma prótese parcial fixa de quatro elementos. O PRF líquido pode facilitar procedimentos de enxertia óssea e diminuir o risco de iatrogenia sem, contudo, aumentar significativamente o custo e o tempo do tratamento.

The liquid PRF can facilitate the positioning and carving of particulate bone grafts, in addition to possible benefi ts related to bone and soft tissue repair. Therefore, it is necessary that the professional knows the practical and theoretical aspects involved in its use. A 45-year-old patient presented loss of maxillary incisors and thickness of the bone crest in the region, making it impossible to place implants of conventional diameter. For bone regeneration, graft was used with bone substitute associated with PRF clots, liquid PRF and titanium mesh. After bone repair, two implants were installed in the region of the lateral incisors as pillars of a fixed partial denture of four elements. The liquid PRF can facilitate bone graft procedures and reduce the risk of iatrogenic, without, however, significantly increasing the cost and time of treatment.

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Abstract Myocardial infarction is the most significant manifestation of ischemic heart disease and is associated with high morbidity and mortality. Novel strategies targeting at regenerating the injured myocardium have been investigated, including gene therapy, cell therapy, and the use of growth factors. Growth factor therapy has aroused interest in cardiovascular medicine because of the regeneration mechanisms induced by these biomolecules, including angiogenesis, extracellular matrix remodeling, cardiomyocyte proliferation, stem-cell recruitment, and others. Together, these mechanisms promote myocardial repair and improvement of the cardiac function. This review aims to address the strategic role of growth factor therapy in cardiac regeneration, considering its innovative and multifactorial character in myocardial repair after ischemic injury. Different issues will be discussed, with emphasis on the regeneration mechanisms as a potential therapeutic resource mediated by growth factors, and the challenges to make these proteins therapeutically viable in the field of cardiology and regenerative medicine.

Resumo O infarto do miocárdio representa a manifestação mais significativa da cardiopatia isquêmica e está associado a elevada morbimortalidade. Novas estratégias vêm sendo investigadas com o intuito de regenerar o miocárdio lesionado, incluindo a terapia gênica, a terapia celular e a utilização de fatores de crescimento. A terapia com fatores de crescimento despertou interesse em medicina cardiovascular, devido aos mecanismos de regeneração induzidos por essas biomoléculas, incluindo angiogênese, remodelamento da matriz extracelular, proliferação de cardiomiócitos e recrutamento de células-tronco, dentre outros. Em conjunto, tais mecanismos promovem a reparação do miocárdio e a melhora da função cardíaca. Esta revisão pretende abordar o papel estratégico da terapia, com fatores de crescimento, para a regeneração cardíaca, considerando seu caráter inovador e multifatorial sobre o reparo do miocárdio após dano isquêmico. Diferentes questões serão discutidas, destacando-se os mecanismos de regeneração como recurso terapêutico potencial mediado por fatores de crescimento e os desafios para tornar essas proteínas terapeuticamente viáveis no âmbito da cardiologia e da medicina regenerativa.

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ABSTRACT Objective: To evaluate growth factors and cytokines in samples of platelet-rich plasma obtained by three different centrifugation methods. Methods: Peripheral blood of six individuals with no hematological diseases, aged 18 to 68 years, was drawn to obtain platelet-rich plasma, using the open method and commercial columns by Medtronic and Biomet. The products obtained with the different types of centrifugation were submitted to laboratory analysis, including pro-inflammatory cytokines and chemokines by flow cytometry assays, the concentration of fibroblast growth factors-2 (FGF-2) and transforming growth factor-beta1 (TGF-β1). Results: The diverse separation methods generated systematically different profiles regarding number of platelets and leukocytes. The Medtronic system yielded a product with the highest concentration of platelets, and the open method, with the lowest concentration of platelets. The results of cytokine analysis showed that the different types of centrifugation yielded products with high concentrations of interleukin 8, interleukin 1β. The open system resulted in a product with high levels of interleukin 6. Other cytokines and chemokines measured were similar between systems. The product obtained with the open method showed higher levels of TGF-β1 in relation to other systems and low FGF-2 levels. Conclusion: The formed elements, growth factors and cytokines in samples of platelet-rich plasma varied according to the centrifugation technique used.

RESUMO Objetivo: Avaliar fatores de crescimento e citocinas em amostras de plasma rico em plaquetas obtidas por três diferentes métodos de centrifugação. Métodos: Foi coletado sangue periférico de seis indivíduos, sem doença hematológica, com idades entre 18 e 68 anos, para obtenção de plasma rico em plaquetas, utilizando o método aberto e sistemas comerciais das empresas Medtronic e Biomet. Os produtos obtidos com os diferentes tipos de centrifugação foram submetidos às análises laboratoriais, incluindo citocinas próinflamatórias e quimiocinas, por meio de ensaios de citometria de fluxo, concentração do fator de crescimento fibroblástico-2 (FGF-2) e fator de crescimento transformador-beta1 (TGF-β1). Resultados: As diferentes centrifugações geraram perfis sistematicamente diferentes referentes ao número de plaquetas e de leucócitos. O sistema da Medtronic originou produto com a maior concentração de plaquetas, e o método aberto com a menor concentração de plaquetas. Os resultados da análise de citocinas demonstraram que os diferentes tipos de centrifugação originaram produtos com elevadas concentrações de interleucina 8 e interleucina 1β. O sistema aberto resultou em produto com elevados níveis de interleucina 6. As demais citocinas e quimiocinas mensuradas foram similares entre os sistemas. O produto obtido com o método aberto apresentou níveis superiores de TGF-β1 em relação aos demais sistemas e reduzidos níveis de FGF-2. Conclusão: Os elementos figurados, fatores de crescimento e citocinas, em amostras de plasma rico em plaquetas, variaram conforme a técnica de centrifugação utilizada.

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Contextualização: Os fatores de crescimento atuam no reparo tecidual emitindo sinais modulatórios estimulando ou inibindo os processos celulares. Objetivo: Analisar a eficácia dos fatores de crescimento no processo cicatricial de úlceras venosas através da busca de evidência na literatura científica. Método: Revisão sistemática segundo as recomendações da Colaboração Cochrane. Critérios de inclusão: Ensaios clínicos randomizados sobre o uso dos fatores de crescimento no tratamento de úlceras venosas; abordando o número total de úlceras cicatrizadas, redução da área e/ou tempo de cicatrização. Exclusão: estudos em andamento, protocolos de pesquisa; artigos que associam fatores de crescimento ao enxerto de pele e estudos que incluíram úlceras de múltiplas etiologias sem análise por subgrupo. Bases de dados consultadas: Ovid MEDLINE(R); Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations; Ovid MEDLINE(R) Epub Ahead of Print; EMBASE; CINAHL Plus with Full Text, Cochrane CENTRAL, LILACS e Web of Science. Também foram consultados a Biblioteca Digital Brasileira de Teses e Dissertações e Google Acadêmico, além da busca manual através da lista de referências dos estudos incluídos. Não houve restrição temporal ou de idioma. A análise estatística foi realizada através do programa Review Manager 5.3 (Colaboração Cochrane). Para variáveis dicotômicas, foram calculados o risco relativo considerando um intervalo de confiança de 95%. A metanálise foi realizada utilizado o modelo de efeito fixo de Mantel-Haenszel quando I2 < 50% e modelo randômico para I2 > 50%. Resultados: A aplicação de fatores de crescimento para tratamento de úlceras venosas não acelerou o reparo tecidual comparado como tratamento padrão/placebo (RR 1,01 [IC 95%: 0,88-1,16]). Resultados semelhantes foram encontrados ao analisar os subgrupos PRP (RR 1,01 [IC 95%: 0,80-1,28]); KGF (RR 0,93 [IC 95%:0,78-1,11]); PDGF (RR 1,17 [IC 95%: 0,78-1,74]); EGF (RR 2,87 [IC 95%: 0,65-12,73; p=0,17]); TGF (RR 1,14 [IC 95%: 0,41-3,15]). Conclusão: Os resultados dessa revisão foram baseados em estudos classificados como moderado a alto risco de viés, portanto, precisam ser interpretados com cautela. Portanto, não há evidências para afirmar que os fatores de crescimento influenciam positivamente na cicatrização de úlceras venosas. Estudos mais robustos, com maior poder e melhor qualidade metodológica são necessários para de determinar melhores recomendações sobre o uso dos fatores de crescimento no tratamento de úlceras venosas. (Registro PROSPERO: CRD42016038390)

Background: Growth factors act in tissue repair by sending modulated signals stimulating or inhibiting cellular processes. Aim: To analyze the efficacy of growth factors in the healing process of venous ulcers by seeking evidence in the scientific literature. Method: Systematic review according to Cochrane Collaboration. Inclusion criteria: Randomized controlled trials using growth factors in the treatment of venous leg ulcers; approaching the total number of healed ulcers, wound area reduction and healing time. Exclusion: ongoing studies, research protocols; articles linking growth factors to the skin graft and studies that included ulcers of multiple etiologies without subgroup analysis. Databases consulted: Ovid MEDLINE (R); Ovid MEDLINE (R) In-Process & Other Non-Indexed Citations; Ovid MEDLINE (R) Epub Ahead of Print; EMBASE; CINAHL Plus with Full Text, Cochrane CENTRAL, LILACS and Web of Science. Also, the Brazilian Digital Library of Theses and Dissertations and Google Scholar were consulted, as well as hand search through the list of references of included studies. There was no time or language restrictions. Statistical analysis was performed using Review Manager 5.3 software (Cochrane Collaboration). For dichotomous variables, the relative risk was calculated considering a 95% confidence interval. The meta-analysis was performed using the fixed-effect model of Mantel-Haenszel when I2 <50% and a random model for I2> 50%. Results: The application of growth factors for the treatment of venous ulcers did not accelerate the healing process compared to standard treatment/placebo (RR 1.01 [95% CI: 0.88 to 1.16]). Similar results were found when analyzing the following subgroups: PRP (RR 1.01 [95% CI: 0.80 to 1.28]); KGF (RR 0.93 [95% CI: 0.78 to 1.11]); PDGF (RR 1.17 [95% CI: 0.78 to 1.74]); EGF (RR 2.87 [95% CI: 0.65 to 12.73, p = 0.17]); TGF (RR 1.14 [95% CI: 0.41 to 3.15]). Conclusion: The results of this review were based on studies classified as moderate to high risk of bias, therefore need to be interpreted with caution. So there is no evidence that the growth factors positively influence the healing of venous leg ulcers. More robust studies, more power and better methodological quality are needed to determine the best recommendations on the use of growth factors in the treatment of venous leg ulcers. (PROSPERO Registration: CRD42016038390)

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Autologous bone is reported by scientific literature as the gold standard for the replacement of the bone loss in maxillary atrophic area. Notwithstanding, this grafting type shows several disadvantages as: The procedure morbidity, limited size of the graft and longer recovering time. Recombinant human bone morphogenetic protein type 2 (rhBMP-2) has been used as bone substitute for the reconstruction of large bone defects. The aim of this case was to report a clinical case exhibiting the reconstruction of the atrophic maxilla through using rhBMP-2 as grafting material associated with absorbable collagen sponge (ACS). At 8 months of following-up, osseointegrated implants were placed. After 2 years and 5 months of following-up, it could be observed an appropriate aesthetical and functional rehabilitation.

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Introdução: Os distúrbios minerais e ósseos da doença renal crônica (DMO-DRC) são influenciados por vários fatores, como idade, etiologia da DRC, toxinas urêmicas e modalidade dialítica. Os DMO-DRC são bem descritos em pacientes tratados com hemodiálise (HD). No entanto, na diálise peritoneal (DP) os estudos são escassos e, na maioria deles, não há dados de histologia óssea. Objetivos: caracterizar os DMO-DRC em uma coorte de pacientes em DP; comparar os resultados com aqueles obtidos da HD; e analisar o desempenho de marcadores séricos para o diagnóstico das doenças de alto e baixo remodelamento ósseo. Métodos: quarenta e um pacientes tratados com DP submeteram-se a avaliação clínica, bioquímica e biópsia óssea. Resultados: a doença óssea adinâmica (DOA) foi o tipo de osteodistrofia renal (OR) predominante, correspondendo a 49% da amostra. Ao se analisar separadamente diabéticos e não diabéticos, a prevalência de DOA foi de 77,7% no primeiro grupo e 26% no segundo (p=0,001). Na comparação entre DP e HD, observou-se que os pacientes do primeiro grupo apresentavam 25(OH) vitamina D mais baixa, mineralização óssea mais comprometida e melhor volume ósseo. A fosfatase alcalina óssea (FAO) apresentou a melhor sensibilidade e especificidade tanto para o diagnóstico de alto, quanto de baixo remodelamento ósseo. Conclusões: a DOA é o tipo de OR mais prevalente na DP. No entanto, a influência do diabetes como fator de risco parece ser maior do que a própria modalidade dialítica.

Introduction: Chronic kidney disease - mineral bone disorder (CKD-MBD) is a complex syndrome influenced by various factors, such as age, CKD etiology, uremic toxins and dialysis modality. CKD-MBD has been extensively studied in hemodialysis (HD) patients. However, for peritoneal dialysis (PD), only a few, older studies exist, most of which contain no bone biopsy data. The present study sought to: characterize CKD-MBD in a cohort of prevalent PD patients; compare the results with that obtained from HD patients; and analyse performance of bone turnover serum markers to make the diagnosis of high or low bone turnover disease in PD patients. Methods: Forty-one PD patients underwent to a clinical evaluation, biochemical analysis and bone biopsy. Results: The most prevalent pattern of renal osteodystrophy (ROD) was adynamic bone disease (ABD), comprising 49% of the sample population. When we separately analyzed diabetic and non-diabetic patients, the ABD prevalence was 77.7% in the former group and 26% in the latter group (p=0.001). The comparison between DP and HD patients revealed low 25(OH) vitamin D level, worst bone mineralization and better bone volume parameters in the former group. Bone alkaline phosphatase (BAP) demonstrated the best sensitivity and specificity values to detect both high and low turnover disease. Conclusion: ABD is the most frequent type of ROD. However, the effect of diabetes on the development of ABD is more important than the dialysis modality itself.

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Platelet Rich Plasma (PRP) is used in musculoskeletal lesion surgery, including muscle, bone, tendons and ligaments. PRP might accelerate the healing process and the integration of the graft, allowing an earlier return to sports activities of patients. PRP is obtained from autologous blood, which is centrifuged, obtaining platelet and supposedly growth factor concentrations three to five times higher than those of regular blood. The clinical results of studies performed in Chile and elsewhere on PRP use in knee anterior cruciate ligament (ACL) reconstruction have been variable. Therefore, there is not enough evidence to support or deny the usefulness of PRP in ACL reconstructions.

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A radiographic and histomorphometric study was conducted on the influence of autologous plasma rich in growth factors (PRGF) upon bone healing in surgically created defects in rabbits. Radiographically, bone regeneration was significantly greater with the use of PRGF after one month (p = 0.005), though no differences were recorded after the second month. In the histomorphometric analysis one month after surgery, the defects filled with autologous bone plus PRGF showed a greater percentage of neoformed bone (35.01 ± 5.31) than the control defects (22.90 ± 12.23), though the differences were not significant. Two months after surgery, the defects filled with autologous bone showed greater regeneration (46.04 ± 10.36 percent) than the control defects (30.59 ± 5.69 percent), though the differences were not significant. The application of PRGF in the bone defects produced in New Zealand rabbits exerted a limited effect on local bone formation.

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We review the growth factor receptor-mediated cell signaling events that induce the responses required for the maintenance of corneal epithelial health. Our focus is to show how such responses contribute to sustaining corneal transparency and deturgescence, so basic to the pathogenesis of corneal diseases. Furthermore, we point out how alterations of receptor-mediated control of these responses account for losses in corneal transparency. In particular, the roles of growth factors in the mediation of normal corneal function, including epithelial cell proliferation, prevention of compromise of the barrier function of the cornea, and maintenance of normal renewal processes are discussed in relation to clinical entities involving the cornea.

Revimos os eventos de sinalização celular mediados por receptores de fatores de crescimento, usados para manter a saúde do epitélio da córnea. O objetivo é mostrar como essas respostas contribuem para manter a transparência e a deturgescência da córnea, críticos na patogênese das doenças da córnea. Mais ainda, enfatizamos como alterações no controle mediado por receptor dessas respostas contribuem na transparência da córnea. Especificamente, o papel dos fatores de crescimento na mediação do controle funcional normal da córnea, incluindo proliferação epitelial, prevenção da quebra da função de barreira, manutenção do processo de renovação são discutidos em relação às entidades clínicas envolvidas na córnea.

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Introdução: O objetivo foi avaliar a expressão de algumas proteínas no endométrio durante a fase lútea do ciclo menstrual de mulheres férteis e inférteis, por meio imunoistoquímica de micro-arranjos teciduais (TMA). Métodos: Analisou-se a expressão de dez proteínas em 52 amostras de endométrio obtidas nas fases lútea inicial, intermediária (janela de implantação) e final. Resultados: As proteínas, fator inibidor de leucemia (LIF), fator de crescimento insulinóide tipo 1 (IGF-1), receptor de progesterona (PR), claudina-4, receptor de fator de crescimento vascular endotelial 3 (VEGFR-3) e citoqueratina 7 (CK-7) mostraram-se expressas no endométrio nas fases lútea inicial, intermediária e final. A proteína morfogenética óssea 4 (BMP-4) expressou-se no endométrio nas fases lútea inicial e intermediária. As proteínas citoqueratina 17 (CK-17), substância solúvel 100 (S100) e calretinina não se expressaram no endométrio durante os três períodos avaliados. Houve correlação entre as expressões protéicas de LIF, IGF-1 e PR. As proteínas LIF e BMP-4 foram diferencialmente expressos no endométrio nas fases lútea inicial, intermediária e final. As proteínas claudina-4 e PR não se expressam simultâneamente no endométrio durante a fase lútea. Conclusão: Baseados nos resultados deste estudo podemos sugerir que a presença das proteínas LIF, IGF-1 e PR durante a janela implantacional teria relevância como preditor do adequado desenvolvimento do endométrio.

Introduction: The objective of this study was to evaluate endometrial protein expressions from fertile and infertile women during the luteal phase of the menstrual cycle by immunohistochemistry in tissue microarrays (TMA). Method: The expression of ten proteins obtained from 52 endometrial samples in the initial, mid (window of implantation) and late (premenstrual) phases of the menstrual cycle were evaluated. Results: The proteins leukemia inhibitory factor (LIF), insulin like growth factor 1 (IGF-1), progesterone receptor (PR), claudin-4, vascular endothelial growth factor receptor 3 (VEGFR-3), and cytokeratin 7 (CK-7) were expressed in the endometrium in the three intervals of the luteal phase. Endometrial expression of the morphogenetic bone protein 4 (BMP-4) occurred during the initial and mid luteal phases. Cytokeratin 17, substance 100 and calretinin were not expressed in the luteal phase. There were positive correlations among endometrial expressions of LIF, IGF- 1, and PR. LIF and BMP-4 were differently expressed in the initial, mid and late phases of the luteal phase. Claudin-4 and PR did not express simultaneously during the different intervals of the luteal phase. Conclusion: These findings suggest that positively correlated endometrial expressions of LIF, IGF-1 and PR at the window of implantation could characterize an adequately developed and receptive endometrium.

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