Estudos imunopatológicos de biópsias de pacientes chagásicos crônicos ou com miocardiopatia dilatada idiopática

Foram estudadas biópsias de ventrículo direito de 30 pacientes, 15 com doença crônica de Chagas e 15 com miocardiopatia congestiva idiopática. Analisou-se também cinco fragmentos miocárdicos obtidos de pacientes chagásicos com menos de duas horas de óbito. Os Autores tentaram estabelecer, por meio de técnica de imunofluorescência direta, a presença de imunoglobulina G, A, e M, fibrinogênio e C3. Somente uma das 30 biópsias exibiu reação positiva para IgG que era de um paciente com miocardiopatia congestiva idiopática. Toods os fragmentos provenientes de pacientes chagásicos não apresentaram qualquer fluorescência com nenhum dos conjugados. Esses achados falam contra o conceito de que anticorpos antimiocárdio teriam importância patogenética na evolução das miocardiopatias chagásica ou dilatada idiopática.Right ventricular endomyocardial biopsies were studied in 30 patients, 15 with myocardiopathy from chronic Chagas'disease and 15 with idiopathic congestive myocardiopathy; five other myocardial samples were taken at necropsies of patients with chronic Chagas' disease. The authors tried to establish by means of direct immunofluorescence techniques whether there were immunoglobulins G, A and M, fibrinogen and C3 complement deposition in the myocardium; only one of these 30 patients exhibited a positive reaction to IgG, it was a patient with idiopathic congestive myocardiopathy. All fragments from patients with Chagas' disease showed no response to any of the fluorescent conjugates. These findings do not support the idea that anti-myoeardial antibodies have pathogenic importance in the evolution of dilated or chagasic myocardiopathies

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Diretriz da Sociedade Brasileira de Cardiologia sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas

This guideline aimed to update the concepts and formulate the standards of conduct and scientific evidence that support them, regarding the diagnosis and treatment of the Cardiomyopathy of Chagas disease, with special emphasis on the rationality base that supported it.&nbsp; Chagas disease in the 21st century maintains an epidemiological pattern of endemicity in 21 Latin American countries. Researchers and managers from endemic and non-endemic countries point to the need to adopt comprehensive public health policies to effectively control the interhuman transmission of T. cruzi infection, and to obtain an optimized level of care for already infected individuals, focusing on diagnostic and therapeutic opportunistic opportunities. &nbsp; Pathogenic and pathophysiological mechanisms of the Cardiomyopathy of Chagas disease were revisited after in-depth updating and the notion that necrosis and fibrosis are stimulated by tissue parasitic persistence and adverse immune reaction, as fundamental mechanisms, assisted by autonomic and microvascular disorders, was well established. Some of them have recently formed potential targets of therapies.&nbsp; The natural history of the acute and chronic phases was reviewed, with enhancement for oral transmission, indeterminate form and chronic syndromes. Recent meta-analyses of observational studies have estimated the risk of evolution from acute and indeterminate forms and mortality after chronic cardiomyopathy. Therapeutic approaches applicable to individuals with Indeterminate form of Chagas disease were specifically addressed. All methods to detect structural and/or functional alterations with various cardiac imaging techniques were also reviewed, with recommendations for use in various clinical scenarios. Mortality risk stratification based on the Rassi score, with recent studies of its application, was complemented by methods that detect myocardial fibrosis.&nbsp; The current methodology for etiological diagnosis and the consequent implications of trypanonomic treatment deserved a comprehensive and in-depth approach. Also the treatment of patients at risk or with heart failure, arrhythmias and thromboembolic events, based on pharmacological and complementary resources, received special attention. Additional chapters supported the conducts applicable to several special contexts, including t. cruzi/HIV co-infection, risk during surgeries, in pregnant women, in the reactivation of infection after heart transplantation, and others.&nbsp; &nbsp;&nbsp; Finally, two chapters of great social significance, addressing the structuring of specialized services to care for individuals with the Cardiomyopathy of Chagas disease, and reviewing the concepts of severe heart disease and its medical-labor implications completed this guideline.Esta diretriz teve como objetivo principal atualizar os conceitos e formular as normas de conduta e evidências científicas que as suportam, quanto ao diagnóstico e tratamento da CDC, com especial ênfase na base de racionalidade que a embasou. A DC no século XXI mantém padrão epidemiológico de endemicidade em 21 países da América Latina. Investigadores e gestores de países endêmicos e não endêmicos indigitam a necessidade de se adotarem políticas abrangentes, de saúde pública, para controle eficaz da transmissão inter-humanos da infecção pelo T. cruzi, e obter-se nível otimizado de atendimento aos indivíduos já infectados, com foco em oportunização diagnóstica e terapêutica. Mecanismos patogênicos e fisiopatológicos da CDC foram revisitados após atualização aprofundada e ficou bem consolidada a noção de que necrose e fibrose sejam estimuladas pela persistência parasitária tissular e reação imune adversa, como mecanismos fundamentais, coadjuvados por distúrbios autonômicos e microvasculares. Alguns deles recentemente constituíram alvos potenciais de terapêuticas. A história natural das fases aguda e crônica foi revista, com realce para a transmissão oral, a forma indeterminada e as síndromes crônicas. Metanálises recentes de estudos observacionais estimaram o risco de evolução a partir das formas aguda e indeterminada e de mortalidade após instalação da cardiomiopatia crônica. Condutas terapêuticas aplicáveis aos indivíduos com a FIDC foram abordadas especificamente. Todos os métodos para detectar alterações estruturais e/ou funcionais com variadas técnicas de imageamento cardíaco também foram revisados, com recomendações de uso nos vários cenários clínicos. Estratificação de risco de mortalidade fundamentada no escore de Rassi, com estudos recentes de sua aplicação, foi complementada por métodos que detectam fibrose miocárdica. A metodologia atual para diagnóstico etiológico e as consequentes implicações do tratamento tripanossomicida mereceram enfoque abrangente e aprofundado. Também o tratamento de pacientes em risco ou com insuficiência cardíaca, arritmias e eventos tromboembólicos, baseado em recursos farmacológicos e complementares, recebeu especial atenção. Capítulos suplementares subsidiaram as condutas aplicáveis a diversos contextos especiais, entre eles o da co-infecção por T. cruzi/HIV, risco durante cirurgias, em grávidas, na reativação da infecção após transplante cardíacos, e outros.&nbsp;&nbsp;&nbsp; Por fim, dois capítulos de grande significado social, abordando a estruturação de serviços especializados para atendimento aos indivíduos com a CDC, e revisando os conceitos de cardiopatia grave e suas implicações médico-trabalhistas completaram esta diretriz.&nbsp

Utilização de plasmas em pressão atmosférica para modificação de polímeros biocompatíveis

Neste trabalho foi desenvolvido um equipamento para produção de plasmas em pressão atmosférica. Empregando esse sistema, o polímero PLDLA (poli(L-Co,L ácido lático)) e sua blenda com o tri(carbonato de metileno) (poli(L-Co-D,L-Co TMC)) foram hidrofilizados em diferentes condições de tempo e potência de plasma. Seus ângulos de contato foram investigados anteriormente e após cada exposição ao plasma para se avaliar o efeito do tratamento. Espectroscopia de emissão óptica foi empregada para se caracterizar o plasma. A exposição por 10 segundos a um plasma excitado com 100 W, reduziu os ângulos de contato do PLDLA em 32,5% e da blenda PLDLA/TMC em 87%. No final do trabalho, apenas para ilustrar a capacidade de modificação de superfícies, diversas materiais como cobre, policloreto de vinila (PVC) acrílico, entre outros, foram tratados e seus ângulos de contato analisadosIn this work, an equipment to produce atmospheric pressure plasma was developed. With this system, polymer PLDLA (poli(L-Co-D, L latic acid)) and its blend with trimethylene carbonate (poli(L-Co_D,L-Co TMC) were hydrophilizated in different time conditions and plasma power. The contact angle were investigated before and after the plasma exposure to evaluate the treatment effect. Optical emission spectroscopy was used to characterize the plasma. Exposure for 10 seconds to a plasma excited with 100 W, reduced contact angles of PLDLA in 32,5% and the blend PLDLA/TMC at 87%. At the end of this work, just to illustrate the capacity of surface modification different kinds of materials as capper, Polyvinyl chloride (PVC), acrylic, and others, were treated and its contact angle were analyze

Cold plasma : fibroblast culture apoptosis modulation and its healing effect on rats skin wounds

Orientador: Maria Beatriz PuzziTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Plasmas de pressão atmosférica e de temperatura ambiente contém uma mistura de diferentes radicais de base oxigenada e nitrogenada, espécies eletricamente carregadas como íons positivos e elétrons, sendo recentemente descobertas diversas aplicações biomédicas. Portanto, investigar como plasmas interagem com meio biológico foi o tema proposto por este trabalho. O estudo se iniciou na tentativa de compreender a morte celular expondo cultura de fibroblasto ex vivo a diferentes tempos (doses) de plasma: 0 segundos, 30, 60 e 300 segundos. Para isto foi avaliado desde contagem da população das células durante 7 dias após a exposição ao feixe de plasmas, assim como a viabilidade celular, taxa de apoptose e expressão gênica de dois genes associados à apoptose, BAX (pró apoptótico) e BCL2 (anti apoptótico). Compreendido o efeito de cada dose em células uma segunda etapa do estudo foi proposta com objetivo de avaliar os efeitos terapeuticos do plasma diretamente em lesões de pele em ratos. Em um primeiro estudo foram realizadas lesões no dorso por punch em 48 ratos Wistar para estudar a velocidade de cicatrização e histologia quanto à quantidade de filtrado inflamatório comparando grupos tratados com 0, 30 e 60 segundos. Como foi observado menor inflamação no último dia da cicatrização no grupo tratado com 60 segundos um segundo estudo pré clínico com esta dose de plasma foi realizado investigando além da velocidade de cicatrização, também foram quantificados o infiltrado inflamatório, angiogênese, fibroplasia e colagênese. Este trabalho identificou que é possível modular as taxas de apoptose celular de acordo com o tempo de exposição, sendo que 30 segundos não apresentou diferenças significativas em relação ao controle e uma dose 10 vezes maior, 300 segundos, apresentou-se tóxica às células. Para a avaliação pré clínica, foi possível destacar uma ação inflamatória intensa no 2º dia de lesão e controlada nos dias subsequentes acompanhada de uma angiogênese estimulada no início da cicatrização e também atenuada nos dias posteriores. Não foi observada uma fibroblasia exagerada, entretanto foi constatado uma colagênese expressiva. Concluindo que o plasma ativa o recrutamento de macrófagos e neutrófilos para a região lesionada e estimula a angiongênese neste período para suprir a demanada de nutrientes necessária no desbridamento bioquímico, seguida pela colagênese que servirá de suporte estrutural para a proliferação celular. Desta forma, o plasma mostrou-se uma potencial ferramenta terapêutica para auxiliar em processos de cicatrização quando em doses moderadas ou como fonte de indutora de apoptose, especialmente interessante para controle de crescimento anormal de células como em câncerAbstract: Atmospheric pressure and room temperature plasmas has a mixture of different radicals based on oxygen and nitrogen, charged species as positive ions and electrons, that recently found various biomedical applications. Thus, investigate how plasmas interacts with biological media was the theme of this work. The study initiated trying to understand the cellular death exposing ex vivo fibroblast culture to different exposure time (doses) of plasma: 0, 30, 60 and 300 seconds. Was evaluated since the population cells counting during 7 days after the exposure to the plasma beam, and the cells viability, apoptosis rate and genic expression of two apoptosis associated gen, BAX (pro apoptotic) and BCL2 (anti apoptotic). Investigated the effect of each dose in cells, a second step of the study was proposed with the objective to evaluate the plasma's therapeutic effects directly on rats skin wounds. In a preliminary study, wounds were performed in the back of 48 Wistar rats to understand the healing speed and histology of the qualiy the inflammatory infiltrate in comparison treated groups with 0, 30 and 60 seconds of plasma. As observed a lower inflammation in the last healing day in the 60 seconds group, a second pre-clinical study with this dose was performed and the healing speed as quantification for inflammatory infiltrate, angiogenesis, fibroplasia and collagenesis. This work identified that is possible to modulate the apoptosis rate according the plasma exposition time, and 30 seconds did not showed significant difference comparing with the control group and a 10 times higher dose, 300 seconds, showed be toxic to cells. To the pre-clinical evaluation, was possible to observe an intense inflammatory effect in the 2nd day of wound and controlled in the day after followed by an stimulated angiogenesis in the beginning and also attenuated in the past days. It was not observed a exaggerated fibroplasia, however was detected an expressive and controlled collagenesis. The work concluded that plasma activate the migration of macrophages and neutrophils to the wound region and stimulates the angiogenesis in this period to feed with necessary nutrients run the biochemical debridement, followed by collagenesis that will form the structural matrix to the cells proliferation. In this way, plasma showed be a potential therapeutic tool to enhance wound healing process with moderate doses or as apoptosis induction source, especially interesting to control abnormal cell multiplication as in cancersDoutoradoClinica MedicaDoutor em Clínica MédicaCNP

Controlled fluorination of a-C:F:H films by PECVD of ethylene-hexafluorobenzene mixtures

Highly fluorinated plasma polymers are chemically inert,acid resistant and have low friction coefficients, thereby being useful in chemical laboratories and for tribological applications. Here we report the plasma polymerization of ethylene-hexafluorobenzene mixtures by PECVD. The principal parameter of interest is the proportion of C(6)F(6) in the feed, R(F). Films were analyzed using near-normal and grazing-angle Infrared Reflection Absorption Spectroscopy (IRRAS), the latter being particularly useful for detecting modes not usually observed at near-normal incidence. The presence of CH and CF(x) (x=1 to 2) groups was thus confirmed in films deposited with R(F)>= 40%. Depending on R(F) IRRAS also revealed the presence of -CH(x) (x=1 to 3) -C=C, -C=O and phenyl rings. Deconvolution of C is spectra obtained by X-ray Photoelectron Spectroscopy (XPS) confirmed the presence of CH, CF and CF(2) groups in films deposited with R(F)>= 40%. Atomic ratios of F:C calculated from the XPS spectral data show that the degree of fluorination rises with increasing RF Some unbound fluorine is present in the films. Post-deposition reactions account for the presence of oxygen (similar to 5%) in the films. Surface energies, determined from contact angle measurements, fall with increasing R(F). (C) 2008 Elsevier B.V. All rights reserved