Polydioxanone-Based Membranes for Bone Regeneration.

Resorbable synthetic and natural polymer-based membranes have been extensively studied for guided tissue regeneration. Alloplastic biomaterials are often used for tissue regeneration due to their lower immunoreactivity when compared with allogeneic and xenogeneic materials. Plenum® Guide is a synthetic membrane material based on polydioxanone (PDO), whose surface morphology closely mimics the extracellular matrix. In this study, Plenum® Guide was compared with collagen membranes as a barrier material for bone-tissue regeneration in terms of acute and subchronic systemic toxicity. Moreover, characterizations such as morphology, thermal analysis (Tm = 107.35 °C and crystallinity degree = 52.86 ± 2.97 %, final product), swelling (thickness: 0.25 mm ≅ 436% and 0.5 mm ≅ 425% within 24 h), and mechanical tests (E = 30.1 ± 6.25 MPa; σ = 3.92 ± 0.28 MPa; ε = 287.96 ± 34.68%, final product) were performed. The in vivo results revealed that the PDO membranes induced a slightly higher quantity of newly formed bone tissue than the control group (score: treated group = 15, control group = 13) without detectable systemic toxicity (clinical signs and evaluation of the membranes after necropsy did not result in differences between groups, i.e., non-reaction -> tissue-reaction index = 1.3), showing that these synthetic membranes have the essential characteristics for an effective tissue regeneration. Human adipose-derived stem cells (hASCs) were seeded on PDO membranes; results demonstrated efficient cell migration, adhesion, spread, and proliferation, such that there was a slightly better hASC osteogenic differentiation on PDO than on collagen membranes. Hence, Plenum® Guide membranes are a safe and efficient alternative for resorbable membranes for tissue regeneration.

HLA-A*31 como marcador de suscetibilidade genetica em sepse / HLA-A*31 as a marker of genetic susceptibility to sepsis

Objetivo: Haplótipos do HLA têm sido associados a muitas doenças autoimunes, mas não foi descrita qualquer associação na sepse. O objetivo desse estudo é investigar o sistema HLA como um possível marcador de suscetibilidade genética à sepse. Métodos: Estudo prospectivo de coorte, incluindo pacientes admitidos em unidade de terapia intensiva e controles-saudáveis obtidos em lista de doadores de transplante renal. Foram excluídos pacientes abaixo dos 18 anos de idade, gestantes ou HIV positivos, pacientes com doença maligna metastática ou sob quimioterapia, pacientes com hepatopatia avançada, com condições de fim de vida. O DNA foi extraído de sangue total, e a haplotipagem de HLA foi realizada com a tecnologia MiliPlex®. Resultados: Foram incluídos 1.121 pacientes (1.078 doadores de rim, 20 pacientes com sepse grave e 23 pacientes admitidos por choque séptico) entre outubro de 2010 e outubro de 2012. Os participantes positivos para HLA-A*31 tiveram risco aumentado de desenvolver sepse (OR: 2,36 IC95%: 1,26-5,35). Não foi identificada outra associação significativa, quando considerado como nível de significância o valor de p<0,01. Conclusão: A expressão de HLA-A*31 está associada ao risco de desenvolvimento de sepse. .

Objective: The HLA haplotype has been associated with many autoimmune diseases, but no associations have been described in sepsis. This study aims to investigate the HLA system as a possible marker of genetic sepsis susceptibility. Methods: This is a prospective cohort study including patients admitted to an intensive care unit and healthy controls from a list of renal transplant donors. Patients with less 18 years of age; pregnant or HIV positive patients; those with metastatic malignancies or receiving chemotherapy; or with advanced liver disease; or with end-of-life conditions were excluded. The DNA was extracted from the whole blood and HLA haplotypes determined using MiliPlex® technology. Results: From October 2010 to October 2012, 1,121 patients were included (1,078 kidney donors, 20 patients admitted with severe sepsis and 23 with septic shock). HLA-A*31 positive subjects had increased risk of developing sepsis (OR 2.36, 95%CI 1.26-5.35). Considering a p value <0.01, no other significant association was identified. Conclusion: HLA-A*31 expression is associated to risk of developing sepsis. .

HLA-A*31 as a marker of genetic susceptibility to sepsis.

OBJECTIVE: The HLA haplotype has been associated with many autoimmune diseases, but no associations have been described in sepsis. This study aims to investigate the HLA system as a possible marker of genetic sepsis susceptibility. METHODS: This is a prospective cohort study including patients admitted to an intensive care unit and healthy controls from a list of renal transplant donors. Patients with less 18 years of age; pregnant or HIV positive patients; those with metastatic malignancies or receiving chemotherapy; or with advanced liver disease; or with end-of-life conditions were excluded. The DNA was extracted from the whole blood and HLA haplotypes determined using MiliPlex® technology. RESULTS: From October 2010 to October 2012, 1,121 patients were included (1,078 kidney donors, 20 patients admitted with severe sepsis and 23 with septic shock). HLA-A*31 positive subjects had increased risk of developing sepsis (OR 2.36, 95%CI 1.26-5.35). Considering a p value <0.01, no other significant association was identified. CONCLUSION: HLA-A*31 expression is associated to risk of developing sepsis.

A termodinâmica como princípio motriz do sistema imune / Thermodynamics as the driving principle behind the immune system

Nos últimos 120 anos, poucas coisas contribuíram tanto para a compreensão do funcionamento do sistema imune quanto o estudo de seu comportamento na relação hospedeiro/parasita. Apesar do avanço, algumas questões permanecem sem resposta clara, como, por exemplo: qual o objetivo do sistema imune? Qual o princípio de sua atuação? Se perguntarmos aleatoriamente, a maioria imediatamente responderá: "defender o organismo contra invasores externos", mas exatamente do que nos defendemos? Como esses invasores nos prejudicam? Quais critérios determinam o que é um invasor? Por outro lado, se o sistema imune existe para nos defender de invasores externos, como qualificar sua atuação contra processos "internos", como as neoplasias? Por que morremos de câncer? Ou de infecção? Ou mesmo: por que morremos? Essas perguntas aparentemente óbvias não são simples nem triviais e a dificuldade em respondê-las revela a complexa realidade que o sistema imune administra. O objetivo deste artigo foi articular, para o leitor, algo que ele instintivamente já sabe: que as decisões do sistema imune são tomadas segundo princípios termodinâmicos. Adicionalmente, discutiremos como esta aparente mudança de paradigma altera conceitos como saúde, doença e terapêutica.

Over the last 120 years, few things contributed more to our understanding of immune system than the study of its behavior in the host/parasite relationship. Despite the advances though, a few questions remain, such as what drives the immune system? What are its guiding principles? If we ask these questions randomly, most will immediately answer "defend the body from external threats," but what exactly do we defend ourselves from? How do these threats harm us? What criteria define what constitutes a threat? On the other hand, if the immune system evolved to defend us against external threats, how does its action against "internal" processes, such as neoplasms, qualify? Why do we die from cancer? Or from infection? Or even, why do we die at all? These apparently obvious questions are nor simple neither trivial, and the difficulty answering them reveals the complex reality that the immune system handles. The objective of this article is to articulate for the reader something that he instinctively already knows: that the decisions of the immune system are thermodynamically driven. Additionally, we will discuss how this apparent change in paradigm alters concepts such as health, disease, and therapeutics.

Thermodynamics as the driving principle behind the immune system.

Over the last 120 years, few things contributed more to our understanding of immune system than the study of its behavior in the host/parasite relationship. Despite the advances though, a few questions remain, such as what drives the immune system? What are its guiding principles? If we ask these questions randomly, most will immediately answer "defend the body from external threats," but what exactly do we defend ourselves from? How do these threats harm us? What criteria define what constitutes a threat? On the other hand, if the immune system evolved to defend us against external threats, how does its action against "internal" processes, such as neoplasms, qualify? Why do we die from cancer? Or from infection? Or even, why do we die at all? These apparently obvious questions are nor simple neither trivial, and the difficulty answering them reveals the complex reality that the immune system handles. The objective of this article is to articulate for the reader something that he instinctively already knows: that the decisions of the immune system are thermodynamically driven. Additionally, we will discuss how this apparent change in paradigm alters concepts such as health, disease, and therapeutics.

A imunofisiopatologia da autoimunidade / Immunophysiopathology of autoimmunity

Este artigo visa explicar conceitos básicos de imunologia de forma clara e sucinta para expor a fisiopatologia das síndromes autoimunes através de exemplos clínicos e/ou experimentais. Esperamos assim esclarecer pontos-chaves que contribuem para a instalação destas patologias.

The development of erythema elevatum diutinum in a patient with juvenile idiopathic arthritis under treatment with abatacept.

In this case report, we present the first report of erythema elevatum diutinum after treatment of juvenile idiopathic arthritis with abatacept. Although it could also be coincidental, in our case, the appearance of vasculitis was not blocked by the simultaneous administration of a stimulation inhibitor, and alerts to the fact that as effective as a abatacept may be to control of the inflammatory articular symptoms, this might not translate into control of the disease.

Ganciclovir-resistant, cytomegalic interstitial lung disease in a patient with systemic lupus erythematosus.

A patient with systemic lupus erythematosus developed interstitial lung disease initially felt to be a manifestation of the disease but that, on further workup, proved to be a manifestation of cytomegalic disease resistant to ganciclovir. Treatment with foscarnet was associated with prompt improvement.

Rituximab (Mabthera), uma nova abordagem para tratamento da artrite reumatóide. Uma revisãosistemática / Rituximab (Mabthera), a new approach for the treatment of rheumatoid arthritis. A systematic review

Rituximab é um anticorpo monoclonal quimérico capaz de reduziro repertório de linfócitos B que expressam CD20. Estudos clínicosrealizados em pacientes com diagnóstico definido de artrite reumatóideativa confirmaram que um ciclo único de rituximab aplicado por meiode duas infusões no intervalo de uma semana, associado a um regimesemanal de metotrexato, produz resposta clínica duradoura comparávelàquela observada com o bloqueio do TNF e pode reduzir a velocidadede dano estrutural nas articulações. Rituximab foi recentementeaprovado para tratamento de artrite reumatóide ativa não-responsivaao tratamento com agentes inibidores do TNF e apresenta um bom histórico de segurança, mas sua infusão pode gerar reações comfreqüência e gravidade variáveis que, na maior parte dos casos,podem ser evitadas com a administração intravenosa de corticóides eanti-histamínicos antes da infusão. O perfil de segurança do rituximaba longo prazo, a julgar pelo acompanhamento de pacientes tratadosem decorrência de linfomas não-Hodgkin, é favorável e motivador. Asdúvidas atuais sobre o uso do rituximab na artrite reumatóide são: a)como tratar falhas de resposta ao rituximab e b) falta de marcadoresconfiáveis para indicar de forma racional a melhor opção de agentebiológico a ser utilizado.

Silicone breast implants, auto antibodies and rheumatic diseases

Objective: Systematic prospective study in six hundred and nineteen symptomatic woman with breast implants. Methods: To evaluate the symptoms and laboratory findings of patients with silicone breast implants. Results: The majority of the patients in our study presented with the atypical rheumatic syndrome (74,9 percent). A few with so called silicone disease. Various auto antibodies were found sometimes more than one in close to ten percent of the patients analysed. Conclusions: A systemic disease characterized by fatigue, cognitive dysfunction, muscle skeletal pain and the presence of auto antibodies in certain patients were observed in symptomatic brazilian woman with silicone breast implants.