Multicentre, randomized, double-blind trial of intracoronary autologous mononuclear bone marrow cell injection in non-ischaemic dilated cardiomyopathy (the dilated cardiomyopathy arm of the MiHeart study).

AIMS: Pre-clinical and few clinical studies suggest that transplantation of autologous bone marrow mononuclear cells (BMNC) improves heart function in dilated cardiomyopathies. Our objective was to determine if intracoronary injection of autologous BMNC improves the left ventricular ejection fraction (LVEF) of patients with non-ischaemic dilated cardiomyopathy (NIDCM). METHODS AND RESULTS: This study was a multicentre, randomized, double-blind, placebo controlled trial with a follow-up of 12 months. Patients with NIDCM and LVEF <35% were recruited at heart failure ambulatories in specialized hospitals around Brazil. One hundred and sixty subjects were randomized to intracoronary injection of BMNC or placebo (1:1). The primary endpoint was the difference in change of LVEF between BMNC and placebo groups as determined by echocardiography. One hundred and fifteen patients completed the study. Left ventricular ejection fraction decreased from 24.0% (21.6-26.3) to 19.9% (15.4-24.4) in the BMNC group and from 24.3% (22.1-26.5) to 22.1% (17.4-26.8) in the placebo group. There were no significant differences in changes between cell and placebo groups for left ventricular systolic and diastolic volumes and ejection fraction. Mortality rate was 20.37% in placebo and 21.31% in BMNC. CONCLUSION: Intracoronary injection of autologous BMNC does not improve left ventricular function in patients with NIDCM. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00333827.

Predictors of all-cause 1-year mortality in implantable cardioverter defibrillator patients with chronic Chagas' cardiomyopathy.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) have been used in the treatment of either sustained ventricular tachycardia or ventricular fibrillation in patients with Chagas' cardiomyopathy. This study aimed at determining mortality rate and risk factors of all-cause 1-year mortality in primary and secondary ICD patients with Chagas' cardiomyopathy. METHODS: One hundred and forty-eight Chagas' patients with ICDs were included from the Medtronic ICD Registry Latin America. All patients were followed for 1 year. RESULTS: At implant, mean age was 60.1 ± 9.4 years and 72.9% were male. Mean left ventricular ejection fraction (LVEF) was 40.1 ± 11%. Mean follow-up was 12 ± 7 months. During the follow-up, 15 patients died (10.2%). Patients who died were older (64 ±10.8 years vs 59 ± 9.1; P = 0.04), had more atrial fibrillation (13.3% vs 3.8%; P = 0.02), had lower LVEF (33.4%± 9.8 vs 40.9%± 11.3; P = 0.01), and worse functional class (III/IV 40% vs 21.8%; P = 0.03). The multivariate analysis showed that two independent predictors of all-cause 1-year mortality remained statistically significant: age more than 65 (hazard ratio [HR] = 2.85, 95% confidence interval [CI] 1.77-3.92; P = 0.03) and LVEF less than 30% (HR = 2.68, 95% CI 1.57-3.79; P = 0.04). CONCLUSION: This analysis showed that patients older than 65 years of age and with LVEF less than 30% were independent predictors of all-cause 1-year mortality in patients with chronic Chagas' cardiomyopathy.

Conventional versus biventricular pacing in heart failure and bradyarrhythmia: the COMBAT study.

BACKGROUND: Worsening in clinical and cardiac status has been noted after chronic right ventricular pacing, but it is uncertain whether atriobiventricular (BiVP) is preferable to atrio-right ventricular pacing (RVP). Conventional versus Multisite Pacing for BradyArrhythmia Therapy study (COMBAT) sought to compare BiVP versus RVP in patients with symptomatic heart failure (HF) and atrioventricular (AV) block. METHODS AND RESULTS: COMBAT is a prospective multicenter randomized double blind crossover study. Patients with New York Heart Association functional class (FC) II-IV, left ventricular ejection fraction (LVEF) <40%, and AV block as an indication for pacing were enrolled. All patients underwent biventricular system implantation and then were randomized to receive successively (group A) RVP-BiVP-RVP, or (group B) BiVP-RVP-BiVP. At the end of each 3-month crossover period, patients were evaluated according to Quality of Life (QoL), FC, echocardiographic parameters, 6-Minute Walk Test (6MWT), and peak oxygen consumption (VO(2 max)). Sixty patients were enrolled, and the mean follow-up period was 17.5 +/- 10.7 months. There were significant improvements in QoL, FC, LVEF, and left ventricular end-systolic volume with BiVP compared with RVP. The effects of pacing mode on 6MWT and VO(2 max) were not significantly different. Death occurred more frequently with RVP. CONCLUSION: In patients with systolic HF and AV block requiring permanent ventricular pacing, BiVP is superior to RVP and should be considered the preferred pacing mode.

Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years.

BACKGROUND: Chronic obstructive pulmonary disease is a major inflammatory disease of the airways and an enormous therapeutic challenge. Within the spectrum of chronic obstructive pulmonary disease, pulmonary emphysema is characterized by the destruction of the alveolar walls with an increase in the air spaces distal to the terminal bronchioles but without significant pulmonary fibrosis. Therapeutic options are limited and palliative since they are unable to promote morphological and functional regeneration of the alveolar tissue. In this context, new therapeutic approaches, such as cell therapy with adult stem cells, are being evaluated. OBJECTIVE: This article aims to describe the follow-up of up to 3 years after the beginning of a phase I clinical trial and discuss the spirometry parameters achieved by patients with advanced pulmonary emphysema treated with bone marrow mononuclear cells. METHODS: Four patients with advanced pulmonary emphysema were submitted to autologous infusion of bone marrow mononuclear cells. Follow-ups were performed by spirometry up to 3 years after the procedure. RESULTS: The results showed that autologous cell therapy in patients having chronic obstructive pulmonary disease is a safe procedure and free of adverse effects. There was an improvement in laboratory parameters (spirometry) and a slowing down in the process of pathological degeneration. Also, patients reported improvements in the clinical condition and quality of life. CONCLUSIONS: Despite being in the initial stage and in spite of the small sample, the results of the clinical protocol of cell therapy in advanced pulmonary emphysema as proposed in this study, open new therapeutic perspectives in chronic obstructive pulmonary disease. It is worth emphasizing that this study corresponds to the first study in the literature that reports a change in the natural history of pulmonary emphysema after the use of cell therapy with a pool of bone marrow mononuclear cells.

Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema.

Within the chronic obstructive pulmonary disease (COPD) spectrum, lung emphysema presents, as a primarily histopathologic feature, the destruction of pulmonary parenchyma and, accordingly, an increase in the airflow obstruction distal to the terminal bronchiole. Notwithstanding the significant advances in prevention and treatment of symptoms, no effective or curative therapy has been accomplished. In this context, cellular therapy with stem cells (SCs) arises as a new therapeutic approach, with a wide application potential. The purpose of this study is to evaluate the safety of SCs infusion procedure in patients with advanced COPD (stage IV dyspnea). After selection, patients underwent clinical examination and received granulocyte colony-stimulating factor, immediately prior to the bone marrow harvest. The bone marrow mononuclear cells (BMMC) were isolated and infused into a peripheral vein. The 12-month follow-up showed a significant improvement in the quality of life, as well as a clinical stable condition, which suggest a change in the natural process of the disease. Therefore, the proposed methodology in this study for BMMC cell therapy in sufferers of advanced COPD was demonstrated to be free of significant adverse effects. Although a larger sample and a greater follow-up period are needed, it is possible to infer that BMMC cell therapy introduces an unprecedented change in the course or in the natural history of emphysema, inhibiting or slowing the progression of disease. This clinical trial was registered with ClinicalTrials.gov (NCT01110252) and was approved by the Brazilian National Committee of Ethics in Research (registration no. 14764, CONEP report 233/2009).

Journal impact factor: this editorial, academic and scientific influence.

In this report the authors present information on the bibliometric instruments and their importance in measuring the quality of scientific journals and researchers. They in particular the history and deployment of the impact factor of the existing Institute for Scientific Information since 1955. Are presented and discussed the criticism regarding the inadequacy of the impact factor for evaluation of scientific production, misuse and strategies editorial handling of the bibliometric index. It is presented to the new classification CAPES for the journals, based on various criteria and the impact factor and its influence on national scientific and academic life. The authors conclude that, despite all obstacles and discussions, the impact factor of the Institute for Scientific Information is still an useful tool and the only isolation available to assess the scientific and intellectual productivity.

Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years

BACKGROUND Chronic obstructive pulmonary disease is a major inflammatory disease of the airways and an enormous therapeutic challenge. Within the spectrum of chronic obstructive pulmonary disease, pulmonary emphysema is characterized by the destruction of the alveolar walls with an increase in the air spaces distal to the terminal bronchioles but without significant pulmonary fibrosis. Therapeutic options are limited and palliative since they are unable to promote morphological and functional regeneration of the alveolar tissue. In this context, new therapeutic approaches, such as cell therapy with adult stem cells, are being evaluated. OBJECTIVE This article aims to describe the follow-up of up to 3 years after the beginning of a phase I clinical trial and discuss the spirometry parameters achieved by patients with advanced pulmonary emphysema treated with bone marrow mononuclear cells. METHODS Four patients with advanced pulmonary emphysema were submitted to autologous infusion of bone marrow mononuclear cells. Follow-ups were performed by spirometry up to 3 years after the procedure. RESULTS The results showed that autologous cell therapy in patients having chronic obstructive pulmonary disease is a safe procedure and free of adverse effects. There was an improvement in laboratory parameters (spirometry) and a slowing down in the process of pathological degeneration. Also, patients reported improvements in the clinical condition and quality of life. CONCLUSIONS Despite being in the initial stage and in spite of the small sample, the results of the clinical protocol of cell therapy in advanced pulmonary emphysema as proposed in this study, open new therapeutic perspectives in chronic obstructive pulmonary disease. It is worth emphasizing that this study corresponds to the first study in the literature that reports a change in the natural history of pulmonary emphysema after the use of cell therapy with a pool of bone marrow mononuclear cells.

Labeled stem cells transplantation to the myocardium of a patient with Chagas' disease.

Stem cell transplantation is a new therapy applied to produce cardiac regeneration through differentiation or increase of heart myocytes or neovascular proliferation in patients in the end stage of congestive heart failure secondary to dilated cardiomyopathy, but the results are still unknown.

Sleep parameters in patients using pacemakers with sleep rate function on.

INTRODUCTION: The cardiovascular system (CVS) is heavily influenced by the autonomic nervous system. Additionally, there is a functional alteration during the various stages of sleep. In nonrapid eye movement (NREM), a state of cardiovascular relaxation occurs during stages three and four. A large amount of rapid ocular movements is concentrated in rapid eye movement (REM) sleep. During this phase, fluctuations in arterial pressure (AP) and heart rate (HR) can be readily noted. Sleep disordered breathing (SDB) has been associated with cardiac rhythm disorders. Recently, cardiac rhythm disorder treatment with pacemaker (PM) highlighted a reduction in abnormal respiratory events during sleep. OBJECTIVE: Comparison of sleep parameters of patients using PM with a sleep rate (SR) algorithm based on its rate-modulated capability during physical activity (Integrity PM with SR function on and off). METHODS: Twenty-two patients (14 women, 8 men), implanted with an Integrity PM (St. Jude Medical Cardiac Rhythm Management Division, Sylmar, CA) with SR function for standard clinical indications, were evaluated utilizing a double-blind protocol. The indication for pacing included sinus node disease (SND), atrium ventricular blockage (AVB), and atrial fibrillation (AF). Following randomization, half of our patients had SR function switched to "on" mode while the other half were on "off" mode. During the first stage of the protocol, all patients underwent two consecutive nights of polysomnographic sleep recordings (PSG). During the first night patients slept in the sleep lab only for adaptation purpose. PSG full recording was carried out in the subsequent night. At a later stage, the programing of SR functions was shifted to "on" or "off" modes. One week later, a third assessment was undertaken. RESULTS: Twelve patients (54%) showed sleep efficiency improvement (total sleeping time/recording time) with PM SR on. This group had the least effective sleep efficiency with PM off, if compared with the others who highlighted no change in this sleep parameter (72 +/- 12 vs 81 +/- 7%, P = 0.01, respectively). This first group displayed a lower latency for REM sleep than the last one (89 +/- 55 vs 174 +/- 107 minutes, P = 0.01, respectively). In 11 (50%) patients, the number per sleep hour of microarousals was reduced when PM SR was switched on. When we compared such findings to the group whose parameters had not changed, we noted that the first set of patients were sleepier (ESE: 9 +/- 4 vs 5 +/- 5, P = 0.04, respectively), and showed more microarousals with PM SR off (20 +/- 14 vs 7 +/- 5 microarousal/hour, P = 0.007). CONCLUSION: In PM patients with sleep-related issues, the SR function activation improved sleep both from a qualitative and quantitative perspective.

Apnéia obstrutiva do sono e arritmias cardíacas: [revisão] / Obstructive sleep apnea and cardiac arrythmias: [review] / Apnea obstructiva del sueño y arritmias cardiacas: [revisión]

A síndrome da apnéia obstrutiva do sono (SAOS) é uma condição prevalente, frequentemente não diagnosticada, associada à elevação do risco cardiovascular, incluindo as arritmias. O reconhecimento da síndrome requer avaliação clínica detalhada, realizada por cardiologistas, e pode ser confirmada por meio da polissonografia. Arritmias que ocorrem durante o sono foram relatadas pela primeira vez em 1965, em pacientes com Síndrome de Pickwick. Desde então, diversos estudos foram realizados sobre incidência, fatores de risco, tratamentos, bem sobre sua importância clínica. Este artigo aborda a fisiopatologia e os aspectos clínicos das arritmias durante a apnéia do sono, por meio de uma revisão dos principais artigos sobre o assunto.

ABSTRACT: The syndrome of obstructive sleep apnea (OSA) is a prevailing condition in the population associated with increased cardiovascular risk, often undiagnosed, including arrhythmias. Therecognition of the syndrome requires a high degree of clinical suspicion, particularly by cardiologists, and it can be confirmed by polysomnography. Arrhythmias that occur during sleep have been reported since 1965 in patients with syndrome of Pickwick. Since then there have been several studies to analyze the frequency, risk factors, treatments, as well as the clinical importance. This article coversthe physiopathology and clinical aspects of arrhythmias during sleep apnea, through a review of the main articles on the subject.

RESUMEN: El síndrome de la apnea obstructiva del sueño (SAOS) es una condición prevalente en la población, asociada con el mayor riesgo cardiovascular, a menudo no diagnosticada, incluyéndose las arritmias. El reconocimiento del síndrome requiere alto grado de sospecha clínica, especialmentepor cardiólogos, y se la puede confirmar por medio de la polisonografia. Las arritmias que ocurren durante el sueño se relatan desde 1965 en pacientes con Síndrome de Pickwick. Desde esa época, se han llevado a cabo diversos estudios a fin de analizar su frecuencia, factores de riesgo, tratamientos, así como su importancia clínica. Este artículo aborda la fisiopatología y los aspectos clínicos de las arritmias durante la apnea del sueño, a través de una revisión de los principales artículos sobre el tema.

Estudo multicêntrico de pacientes submetidos a implante de cardioversor-desfibrilador implantável (CDI) na America Latina / Multi-center study of patients who underwent implants of implantable cardioverter-defibrillator (ICD) in Latin America / Estudio multicéntrico de pacientes sometidos a implante de cardioversor-desfibrilador implantable(CDI) en Latinoamérica

O ICD Register da Medtronic foi introduzido na América Latina com a finalidade de coletar dados relacionados à indicação de implantes de CDI para prevenção primária e secundária de morte súbita e ao acompanhamento de pacientes originários de Porto Rico, Caribe. México e América do Sul. Além dessa ampla variedade geográfica, também foram incluídos detalhes referentes aos cuidados de saúde recebidos como parte do tratamento. O presente estudo apresenta as características de desfecho de 910 portadores de cardiopatias tratados para prevenção primária, em comparação com aqueles nos quais o implante destinou-se à prevenção secundária.

The ICD Register was introduced to Latin America to collect data related to implant indication of ICD for the prevention of primary and secondary deaths and for the follow-up of patients from Puerto Rico, the Caribbean, Mexico and South America. In addition to this vast geographic variety, information related to the health care as part of the treatment has also been included. This study shows the characteristics of the outcome of 910 cardiopathy patients treated for primary prevention, incomparison to those whose implants were meant for secondary prevention.

El ICD Register de Medtronic fue introducido en América Latina a fin de recoger datos relacionados a la indicación de implantes de CDI para la prevención primaria y secundaria de muerte súbita y a la remisión de pacientes provenientes de Puerto Rico, Caribe, México y Sudamérica. Ademásde esa amplia variedad geográfica, también se incluyeron detalles referentes a los cuidados de saludrecibidos como parte del tratamiento. El presente estudio presenta las características de solución de 910 portadores de cardiopatías tratados para la prevención primaria, en comparación con aquellos cuyo implante se destinó a la prevención secundaria.

Bloqueio atrioventricular total pós- correção cirúrgica de defeito do septo atrioventricular parcial em paciente com associação charge / Total atrioventricular block after septum defect correction surgery partial atrioventricular in patients with charge association / Bloqueo aurículoventricular total post-corrección quirúrgica de defecto del septo aurículoventricular parcial en paciente con asociación charge

Descreveremos o caso de uma paciente com uma síndrome rara (Associação Charge), que evoluiu para uma complicação bastante temida, o bloqueio atrioventricular total, no pós-operatório de correção do defeito do septo atrioventricular parcial.

We will describe a woman’s case with a rare syndrome (Charge Association) with a quite feared complication evolution, the total atrioventricular block, in the postoperative of partialatrioventricular defect correction.

Describiremos el caso de una paciente con un síndrome raro (Asociación Charge), que evolucionó hacia una complicación bastante temida, el bloqueo aurículoventricular total, en el postoperatorio de corrección del defecto del septo aurículoventricular parcial.

Taquicardia mediada por marcapasso ou por reentrada eletrônica - uma revisão / Pacemaker mediated tachycadia - a revision / Taquicardia mediada por marcapasos o por reentrada electrónica - una revisión

A estimulação cardíaca artificial constitui-se em um dos grandes avanços tecnológicos na área da cardiologia para o tratamento das bradiarritmias, contudo não está livre de complicações. A implantação de marcapassos bicamerais trouxe uma nova e importante condição: a Taquicardia Mediada por Marcapasso ou também denominada Taquicardia por Reentrada Eletrônica. Nesse artigo, procuramos atualizar o estado da arte sobre essa condição, suas causas e possíveis formas de prevenção.

The artificial cardiac stimulation constitutes one of the great advances thechnological in the cardiology for the treatment of bradyarrhythmias. However it is not free of complications. The implantation of bicameral pacemakers brought a new and important condition, the Pacemaker Mediated Tachycrdia. In this article, we look for to bring up to date the state of the art on this condition, its causesand possible forms of prevention.

La estimulación cardiaca artificial se constituye en uno de los grandes avances tecnológicos en el área de la cardiología para el tratamiento de las bradiarritmias, sin embargo no estálibre de complicaciones. La implantación de marcapasos bicamerales trajo una nueva e importante condición: la Taquicardia Mediada por Marcapasos o también denominada Taquicardia por Reentrada Electrónica. En este artículo, tratamos de actualizar el estado del arte sobre esa condición, sus causasy posibles formas de prevención.

Long-term experience with a contractility (autonomic nervous system) driven pacemaker sensor in patients with chronic chagasic cardiomyopathy.

We analyzed performance of a ventricle-paced, ventricle-sensed, inhibited, rate-responsive (VVIR) pacemaker driven by autonomic nervous system activity sensor in chagasic patients with cardiac conduction system disturbances. Forty-seven chagasic patients were studied (28 male, 19 female; age, 24-68 years). Thirty-six patients had complete atrioventricular (AV) block, eight had second-degree AV block, and the remaining three patients had sinus node disease. Patients were divided into two groups according to their heart rate (HR) at rest: group 1 had an HR more than 65 bpm; group 2, HR less than 65 bpm. A comparative study that extended over the first 12 months after pacemaker implantation evaluated: HR at rest and during various types of stress tests, arterial blood pressure at rest and during exercise, and performance of the TIR-60 UP leads in conjunction with the sensor function as compared with the performance of other leads. Patients from group 1 had a higher HR at rest and a smaller HR variation during stress test than did patients from group 2. This indicates that with this type of rate-adaptive system it is possible to control each patient individually. The blood pressure at rest and during stress tests did not differ between the two patient groups. With respect to the sensor function, the TIR-60 UP leads offered the same performance as others leads. The VVIR pacemaker equipped with the sensor of autonomic nervous system activity allowed chagasic patients to restore their physiologic mechanisms. Seventy-four percent of the patients had the New York Heart Association Functional Class improved by 1 or 2 steps, after the pacemaker implantation.

Fator de impacto: importância e influência no meio editorial, acadêmico e científico / Journal impact factor: this editorial, academic and scientific influence

Neste relato, os autores apresentam informações sobre os instrumentos bibliométricos e a sua importância na aferição da qualidade dos periódicos científicos, pesquisadores e docentes. Apresentam em particular a história e a implantação do fator de impacto do Institute for Scientific Information existente desde 1955. São apresentadas e discutidas as críticas referentes à inadequação do fator de impacto para avaliação da produção científica, uso indevido e estratégias editoriais de manipulação deste índice bibliométrico. É apresentada a nova classificação CAPES para os periódicos, baseada em vários critérios e no Fator de impacto, em especial, e a sua influência na vida acadêmica e científica nacional. Conclui que, apesar de todos os óbices e discussões, o Fator de Impacto do Institute for Scientific Information ainda é uma ferramenta útil e, isoladamente, a única existente para avaliar os periódicos científicos e a produtividade intelectual

In this report the authors present information on the bibliometric instruments and their importance in measuring the quality of scientific journals and researchers. They in particular the history and deployment of the impact factor of the existing Institute for Scientific Information since 1955. Are presented and discussed the criticism regarding the inadequacy of the impact factor for evaluation of scientific production, misuse and strategies editorial handling of the bibliometric index. It is presented to the new classification CAPES for the journals, based on various criteria and the impact factor and its influence on national scientific and academic life. The authors conclude that, despite all obstacles and discussions, the impact factor of the Institute for Scientific Information is still an useful tool and the only isolation available to assess the scientific and intellectual productivity

Fator de impacto: importância e influência no meio editorial, acadêmico e científico / Journal impact factor: its editorial, academic and scientific importance

Neste relato os autores apresentam informações sobre os instrumentos bibliométricos e a sua importância na aferição da qualidade dos periódicos científicos, pesquisadores e docentes. Apresentam em particular a história e a implantação do fator de impacto do Institute for Scientific Information, existente desde 1955. São apresentados e discutidos as críticas referentes à inadequação do fator de impacto para avaliação da produção científica, uso indevido e estratégias editoriais de manipulação deste índice bibliométrico.É apresentada a nova classificação Capes para os periódicos, baseada em vários critérios e no Fator de Impacto, em especial, e a sua influência na vida acadêmica e científica nacional. Conclui que, apesar de todos os óbices e discussões, o Fator de Impacto do Institute for Scientific Information ainda é uma ferramenta útil e, isoladamente, a única existente para avaliar os periódicos científicos e a produtividade intelectual.

In this report, the authors present information on bibliometric instruments and their importance in measuring the quality of scientific journals and researchers. They present the history and deployment of the impact factor by the Institute for Scientific Information that exists since 1955. Criticism regarding the inadequacy of the impact factor in the evaluation of scientific publications, its misuse and editorial handling strategies of this bibliometric index are presented and discussed. The new Capes classification for journals, based on various criteria and in particular the impact factor, is presented as is its influence on national scientific and academic life. The authors conclude that, despite all obstacles and discussions, the impact factor of the Institute for Scientific Information is still a useful tool and is the only one available to assess, in isolation, scientific and intellectual productivity.

Importância e influência do fator de impacto nos meios editorial, acadêmico e científico / Impact factor confirms nature is top research journal

Os autores descrevem os instrumentos bibliométricos utilizados atualmente para aferir a qualidade de periódicos científicos, pesquisadores e docentes. apresentam a história de criação do fator de impcto (FI) do Institute for Scientific Information (ISI), existente desde 1955. Discutem as críticas referentes ao instrumento, entre elas sua inadequação para avaliação da produção científica, seu uso indevido e as estratégias editoriais de manipulação desse índice. Apresentam a nova classificação CAPES para periódicos científicos, baseada no FI em outros critérios, destacando sua influência na vida acadêmica e científica nacional. Concluem que, apesar de seus limites, o FI ainda é uma ferramenta útil para avaliar os periódicos científicos e a produtividade intelectual.

O G-CSF na terapia do acidente vascular cerebral / The potential role of G-CSF in stroke

O fator estimulador de colônias granulocitárias (G-CSF) é uma glicoproteína descrita há mais de vinte anos, e é largamente utilizada para tratamento de estados neutropênicos e no transplante de medula óssea. O G-CSF estimula células-tronco hematopoéticas e regula crucialmente a sobrevivência de neutrófilos maduros, pós-mitóticos, através da inibição da apoptose. Além do efeito sistêmico, mais recentemente tem-se demonstrado uma surpreendente atividade do G-CSF no sistema nervoso central. A administração de G-CSF mobiliza células-tronco e progenitoras da medula óssea para o sangue periférico, que, por sua vez, atravessa a barreira hemato-encefálica (BHE) e se dirige à área acometida do cérebro. A atividade do G-CSF no sistema nervoso central tem sido caracterizada como multimodal, pois, além do efeito mobilizador de células da medula óssea, demonstrou uma ação direta neuroprotetora através de diferentes mecanismos, tais como a atividade antiapoptótica em neurônios, regeneração da vascularização, efeito anti-inflamatório e estimulação da neurogênese endógena. Este relato sumariza a ação do G-CSF no sistema nervoso central e aborda seu potencial para o emprego no acidente vascular cerebral.

The granulocyte colony-stimulating-factor (G-CSF) is a glycoproteina which has been described for decades, and it is commonly utilized in the treatment of neutropenic states and bone marrow transplants. G-CSF stimulates hematopoietic stem-cels e crucially regulates the survival of mature neutrophils through a mechanism of apoptosis inhibition. Beyond its systemic effect, recently it has been shown its surprising activity in the central nervous system (CNS). G-CSF administration mobilizes bone marrow stem cells para systemic blood, and those cells cross the blood-brain-barrier e target brain's damaged area. G-CSF's activity in the CNS has been defined as multimodal, because additionally it has been demonstrated a direct neuroprotective action through different mechanisms such as antiapoptotic activity, angiogenesis, anti-inflamatory effect, and stimulation of endogenous neurogenesis. This paper sumarizes G-CSF action in the CNS and approaches its potential para use in stroke.

O transplante de células-tronco hematopoéticas como opção no tratamento de doenças não hematológicas: [revisão] / Hematopoietic stem cell transplant: a therapeutic option for non-hematologic diseases: [review]

Nesta revisão são abordadas as doenças em que existem dados e perspectivas do uso de transplante de células-tronco hematopoéticas em suas diversas modalidades. São apresentados também os aspectos referentes aos regimes de condicionamento empregados, e sua relação com toxicidade e taxa de mortalidade ligadas ao transplante. São apresentadas as doenças autoimunes e particularizados dados específicos do lúpus eritematoso sistêmico, esclerose sistêmica e esclerose múltipla e diabetes mellitus tipo 1. A base do procedimento nas doenças autoimunes é a reprogramação imunológica. Aparentemente o procedimento tem sua indicação nas doenças em que os tratamentos convencionais de imunossupressão tenham falhado, e o dano orgânico não tenha sido definitivo, mas tenha chance de ocorrer caso não seja realizado o transplante. A modalidade aparentemente indicada no momento deve ser o transplante de células-tronco autogênico com regimes de condicionamento não mieloablativo para se obter sobrevivência estimada em mais de 50 por cento em todas as doenças, com baixa toxicidade e com mortalidade nula ligada ao transplante. São apresentados também os resultados nos tumores sólidos, que são discutíveis, e particularidades no câncer de mama. A aparente indicação para os tumores sólidos é transplante de células-tronco alogênico e se baseia no tratamento intensivo com doses mieloablativas com a finalidade de se induzir o efeito enxerto contra o tumor. Os regimes não mieloablativos são preconizados com a finalidade de redução da toxicidade e indução de imunossupressão, sendo os dados insuficientes e discutíveis, o que obriga a introdução de novas estratégias terapêuticas baseadas na terapia imune e celular.

In this report we discuss data and perspectives of hematopoietic stem cell transplantation in non-hematologic diseases. Aspects related to the conditioning regimen and its relationship with toxicity and mortality are also presented. Specific autoimmune diseases are discussed, in particular systemic lupus erythematosus, systemic sclerosis, multiple sclerosis and type 1 diabetes mellitus. The aim of the procedure in autoimmune diseases is immune reprogramming. Apparently this procedure has indications for diseases in which conventional treatments have failed when organ damage is not definitive, but likely to occur if transplantation is not performed. The most promising method appears to be autologous stem cell transplantation with non-myeloablative conditioning regimens to obtain survival that is estimated at more than 50 percent for all autoimmune diseases, with low toxicity and no mortality related to transplantation. The controversial results of solid tumor treatment and particularities of breast cancer are also presented. Hematopoietic stem cell transplantation is the apparent indication for solid tumors based on intensive treatment with myeloablative doses in order to induce the graft versus tumor effect. The myeloablative conditioning regimens are introduced with the purpose of reducing the toxicity and inducing immunosuppression but the data are insufficient and questionable requiring the introduction of new therapeutic strategies based on cellular and immune therapy.

Células-tronco de medula óssea em isquemia crítica de membros / Bone marrow stem cells in critical limb ischemia

Os autores discutem aspectos clínicos e de tratamento convencional da isquemia critica dos membros inferiores e consideram a possibilidade de tratamento com células-tronco autógenas de medula óssea para os pacientes que já esgotaram, sem sucesso, todos os meios de tratamento conhecidos. Comentam sobre o histórico, as fontes, as experiências animais e clínicas e, finalmente, apresentam sua experiência inicial com seis pacientes, todos com indicação de amputação maior ou menor. Em apenas um paciente não foi possível evitar a amputação. Além de ótimos resultados, quanto à supressão da dor e cicatrização de lesões isquêmicas, pode-se notar a ausência de quaisquer efeitos colaterais deletérios, sugerindo que a terapia celular é eficiente e segura, demandando, porém, mais pesquisas e estudos randomizados para se tornar uma terapia de uso corrente.

The authors discuss clinical aspects and conventional treatment of lower limb critical ischemia and the alternative of therapy with autogenous bone marrow stem cells in patients who have exhausted, without success, all the current means of treatment. They comment on the historical aspects, the sources, animal experiments, clinical research and, finally, their initial experience with six patients, all of whom had previous indication of major or minor amputation. For only one patient amputation could not be avoided. In addition to excellent results in pain relief and healing of ischemic ulcers, no deleterious side effects were noted suggesting that this type of cell therapy is safe and efficient although further research and randomized studies are needed to make this a standard therapy.