INTRODUÇÃO: A angiogênese muscular esquelética induzida pelo treinamento físico aeróbio (TF) é determinante na melhora da capacidade aeróbia. Entre os fatores envolvidos, as células progenitoras endoteliais (CPE) derivadas da medula óssea são descritas por promoverem o reparo vascular e a angiogênese. Embora o papel do TF sobre os parâmetros das CPE tenha sido investigado, pouco se conhece sobre os efeitos de diferentes volumes de TF sobre a função das CPE da medula óssea, alterações metabólicas e capilarização muscular. OBJETIVO: Testar a hipótese de que o TF melhore a função das CPE da medula óssea, acompanhada por maior capilarização e capacidade oxidativa muscular dependentes do aumento de volume de TF. MÉTODOS: Vinte e uma ratas Wistar foram divididas em três grupos: sedentário controle (SC), treinado protocolo 1 (P1), treinado protocolo 2 (P2). P1: o treinamento de natação consistiu de 60 min, 1x/dia, cinco dias/semana/10 semanas, com 5% de sobrecarga corporal. P2: o mesmo de P1 até a oitava semana, na nona semana os animais treinaram 2x/dia e na 10ª semana 3x/dia. RESULTADOS: O TF promoveu bradicardia de repouso, aumento da tolerância ao esforço, do consumo de oxigênio de pico e da atividade da enzima citrato sintase muscular no grupo P1, sendo estas adaptações mais exacerbadas no grupo P2, indicando que a condição aeróbia foi mais proeminente com este TF. O TF melhorou a função das CPE da medula óssea em P1, sendo ainda maior esta resposta no grupo P2. Em paralelo, observa-se também um aumento no número de capilares dependentes do volume de TF. CONCLUSÃO: Estes resultados sugerem que a medula óssea como o principal reservatório de CPE é influenciada por diferentes volumes de TF, sendo possivelmente responsável pelo maior rendimento físico observado mediante uma maior mobilização endógena de CPE, participantes ativas no processo de angiogênese muscular induzido pelo TF.

INTRODUCTION: Skeletal muscle angiogenesis induced by aerobic exercise training (ET) is crucial in the improvement of the aerobic capacity. The endothelial progenitor cells (EPC) derived from bone marrow have been described for promoting both the vascular repair and angiogenesis. Although the role of the ET on the parameters of the EPC has been investigated, the effect of different volumes of ET on the EPC function in bone marrow, skeletal muscle metabolic alterations and capilarization are unknown. OBJECTIVE: We hypothesized that ET improves the EPC function in bone marrow, accompanied by an increase of skeletal muscle oxidative capacity and angiogenesis dependents of the increase of volume of ET. METHODS: Twenty one Wistar rats were divided into 3 groups: sedentary control (SC), trained protocol 1 (T1) and trained protocol 2 (T2). T1: swimming training consisted of 60 min, 1x/day/10weeks, with 5% body weight load. T2 the same as T1 until 8th week, in the 9th week the rats trained 2x/day and in the 10th week 3x/day. RESULTS: ET promoted resting bradycardia, increase of exercise tolerance, peak oxygen uptake and citrate synthase enzyme activity in the T1 group, being these adaptative responses exacerbate in the P2 group, indicating that the aerobic condition was improved in this group. ET improved the EPC function of the bone marrow in T1, and the response was exacerbed in T2 group. In parallel, an increase in the number of capillaries dependent of ET volume was also observed. CONCLUSION: These findings suggest that the bone marrow as the main reservoir of EPC is influenced by different ET volume, possibly being responsible for the improvement of aerobic performance observed by higher endogenous EPC mobilization, active participants in the process of angiogenesis induced by ET.

Hereditary hemochromatosis (HH) is an autosomal recessive disorder classically related to HFE mutations. However, since 1996, it is known that HFE mutations explain about 80% of HH cases, with the remaining around 20% denominated non-HFE hemochromatosis. Nowadays, four main genes are implicated in the pathophysiology of clinical syndromes classified as non-HFE hemochromatosis: hemojuvelin (HJV, type 2Ajuvenile HH), hepcidin (HAMP, type 2B juvenile HH), transferrin receptor 2 (TFR2, type 3 HH) and ferroportin (SLC40A1, type 4 HH). The aim of this review is to explore molecular, clinical and management aspects of non-HFE hemochromatosis.

OBJETIVO: É descrita uma proposição cirúrgica para o tratamento de pacientes com doença arterial coronária (DAC) terminal, não mais passíveis de revascularização miocárdica convencional. Constitui-se na revascularização transmiocárdica com raios laser (RTML), associada ao emprego de células progenitoras hematopoiéticas autólogas (CPH). MÉTODOS: Nove pacientes (oito homens), 65±5 anos, com as características supracitadas foram submetidos ao procedimento combinado. Além da avaliação clínica, o protocolo incluiu o estudo da perfusão miocárdica através da ressonância cardíaca (RMC) sob estresse farmacológico, antes e seis meses após a intervenção cirúrgica. Procedeuse à RMTL através de minitoracotomia esquerda e utilização de laser de CO2, com média de 11±3 tiros por paciente. As CPH foram obtidas por punção medular, seguindo-se sua injeção direta (1,9±0,3x10(8) células/paciente) em múltiplas áreas do miocárdio isquêmico. RESULTADOS: Não ocorreram óbitos ou complicações imediatas decorrentes dos procedimentos. Um paciente faleceu no segundo ano de pós-operatório, de causa não cardíaca (choque séptico). O seguimento clínico pós-operatório desses pacientes revelou redução significativa da classe funcional de angina de 3,7±0,2 para 1,3±0,2 (p<0,0001). Também se verificou redução estatística do índice isquêmico do ventrículo esquerdo (VE) avaliado pela RMC de 1,64±0,10 para 0,88±0,09 (p=0,01). CONCLUSÃO: A associação da terapia celular com a RTML demonstrou-se segura nessa experiência inicial. Caso confirmado esse sinergismo em estudos mais abrangentes, com melhora da angina e redução documentada da isquemia miocárdica, passamos a contar com uma nova possibilidade de tratamento alternativo para esse grave grupo de pacientes.

OBJECTIVE: We tested the hypothesis that TMLR combined with intramyocardial injection of BMC is safe, and may help increase the functional capacity of patient with refractory angina. METHODS: Nine patients (eight men), 65±5 years old, with refractory angina for multivessel disease and previous myocardial revascularization procedures (CABG/PCI), not candidates for another procedure due to the extension of the disease were enrolled. TMLR (11±3 laser drills) was performed via a limited thoracotomy using a CO2 Heart Laser System. BMC were obtained immediately prior to surgery, and the lymphomonocytic fraction separated by density gradient centrifugation. During surgery, 5mL containing approximately 1.9±0.3x10(8) BMC were delivered by multiple injections in the ischemic myocardium. Before (B) and 6 months (6M) after the procedure, patient underwent clinical evaluation and myocardial perfusion assessment by cardiac magnetic resonance imaging (MRI) during pharmacological stress with dypiridamole. RESULTS: No major complications or deaths occurred during the procedure. One patient died after 2 years (non cardiac cause).There was a reduction in the ischemic score as assessed by MRI from 1.64±0.10 (B) to 0.88±0.09 (6M) (P=0.01). Clinically, there was a reduction in functional class of angina from 3.7±0.2 (B) to 1.3±0.2 (6M) (P<0.0001). CONCLUSIONS: In this initial experience, the combined strategy of TMLR plus cell therapy appeared to be safe, and may have synergistically acted to reduce myocardial ischemia, with clinically relevant improvement in functional capacity. Provided these data are confirmed in a larger, randomized, controlled trial with longer follow-up, this strategy could be used as a novel therapeutic option for treating pt with refractory angina.

OBJECTIVES: To determine the safety of intramyocardial injection of autologous bone marrow cells in patients undergoing surgical myocardial revascularization (CABG) for severe coronary artery disease. INTRODUCTION: There is little data available regarding the safety profile of autologous bone marrow cells injected during surgical myocardial revascularization. Potential risks include arrythmias, fibrosis in the injected sites and growth of non-cardiac tissues. METHODS: Ten patients (eight men) were enrolled; they were 59±5 years old with limiting angina and were non-optimal candidates for complete CABG. Bone marrow cells (1.3±0.3x10(8)) were obtained prior to surgery, and the lymphomonocytic fraction (CD34+=1.8±0.3%) was separated by density gradient centrifugation. During surgery, bone marrow cells were injected in non-grafted areas of ischemic myocardium. During the first year after surgery, the patients underwent laboratory tests, cardiac imaging, and 24-hour ECG monitoring. RESULTS: Injected segments: inferior (n=7), anterior (n=2), septal (n=1), apical (n=1), and lateral (n=1) walls. Except for a transient elevation of C-reactive protein at one month post-surgery (P=0.01), laboratory tests results were within normal ranges; neither complex arrhythmias nor structural abnormalities were detected during follow-up. There was a reduction in functional class of angina from 3.6±0.8 (baseline) to 1.2±0.4 (one year) (P<0.0001). Also, patients had a significant decrease in the ischemic score assessed by magnetic resonance, not only globally from 0.65±0.14 (baseline) to 0.17±0.05 (one year) (P=0.002), but also in the injected areas from 1.11±0.20 (baseline) to 0.34±0.13 (one year) (P=0.0009). CONCLUSIONS: Intramyocardial injection of bone marrow cells combined with CABG appears to be safe. Theoretical concerns with arrhythmias and/or structural abnormalities after cell therapy were not confirmed in this safety trial.

A síndrome hemofagocítica (SH) caracteriza-se por um quadro clínico de febre, hepatoesplenomegalia, linfonodomegalia e pancitopenia periférica. A fagocitose de elementos hematopoiéticos por macrófagos, morfologicamente normais, está na origem da síndrome. A SH é considerada rara, manifestando-se como uma doença primária, ou associada a vírus, a neoplasias ou a doenças auto-imunes. O tratamento é controverso e a sua evolução, muitas vezes é fatal. A avaliação anátomo-patológica, apresenta o fenômeno da hemofagocitose em diversos órgãos, incluindo, principalmente, os hematopoéticos. Apresentamos os vários contextos clínicos no qual esta síndrome aparece, a importância do seu diagnóstico e o estudo da interação entre as citoquinas, as células imunorreguladoras e a terapêutica imunossupressora. Exemplificamos a síndrome hemofagocítica através de um caso clínico, com seus dados complementares, incluindo os necroscópicos.

The hemophagocytic syndrome (HS) is characterized by a clinical picture of fever, hepatosplenomegaly, lymphadenopathy and peripheral pancytopenia. The morphologic hallmark of this syndrome is the phagocytosis of hematopoietic elements by morphologically normal macrophages. HS is considered rare and may be a primary disease or associated to viral, infection, neoplasias or autoimmune diseases. Treatment is controversial and its evolution is often fatal. Anatomo-pathological evaluation shows the phenomenon of hemophagocytosis in several organs, especially the hematopoietic tissues. We describe a case of HS, discuss its possible causes, its clinical and pathologic features, its pathophysiology and therapeutic possibilities.