Avaliação de emergência de acessos de Passiflora cincinnata Mast, do banco de germoplasma de maracujá (BAG) da Embrapa Semi-Árido.

O objetivo deste trabalho foi avaliar a emergência de 32 acessos de P. cincinnata do BAG de maracujá da Embrapa Semi-Árido que se encontram armazenadas a 10º C e 40% de UR

Prognostic implications of the ID1 expression in acute myeloid leukemia patients treated in a resource-constrained setting

Introduction: The aberrant expression of the inhibitor of DNA binding (ID1) gene has been frequently associated with the leukemogenesis and prognostication acute myeloid leukemia (AML), although its clinical importance has never been investigated in patients treated outside well-controlled clinical trials. Methods: Using quantitative real-time polymerase chain reaction, we investigated the role of the ID1 expression in the clinical outcomes of non-selected patients with acute myeloid leukemia treated in a real-life setting. Results: Overall, 128 patients were enrolled. Patients with high ID1 expression had a lower 3-year overall survival (OS) rate of 9%, with the 95% confidence interval (95%CI) at 3 to 20%, compared to patients with a low ID1 expression (22%, 95%CI: 11 - 34%) (p = 0.037), although these findings did not retain significance after adjustment (hazard ratio (HR): 1.5, 95%CI: 0.98 - 2.28; p = 0.057). The ID1 expression had no impact on post-induction outcomes (disease-free survival, p = 0.648; cumulative incidence of relapse, p = 0.584). Conclusions: Although we are aware thar our data are confronted with many variables that cannot be fully controlled, including drug unavailability, risk-adapted treatment, comorbidities and the time from diagnosis to treatment initiation, we are firm believers that such an initiative can provide more realistic data on understudied populations, in particular those from low- and middle-income countries.</p

P2Y2 and P2Y6 receptor activation elicits intracellular calcium responses in human adipose-derived mesenchymal stromal cells

Adipose tissue contains self-renewing multipotent cells termed mesenchymal stromal cells. In situ, these cells serve to expand adipose tissue by adipogenesis, but their multipotency has gained interest for use in tissue regeneration. Little is known regarding the repertoire of receptors expressed by adipose-derived mesenchymal stromal cells (AD-MSCs). The purpose of this study was to undertake a comprehensive analysis of purinergic receptor expression. Mesenchymal stromal cells were isolated from human subcutaneous adipose tissue and confirmed by flow cytometry. The expression profile of purinergic receptors was determined by quantitative real-time PCR and immunocytochemistry. The molecular basis for adenine and uracil nucleotide-evoked intracellular calcium responses was determined using Fura-2 measurements. All the known subtypes of P2X and P2Y receptors, excluding P2X2, P2X3 and P2Y12 receptors, were detected at the mRNA and protein level. ATP, ADP and UTP elicited concentration-dependent calcium responses in mesenchymal cells (N = 7–9 donors), with a potency ranking ADP (EC50 1.3 ± 1.0 μM) > ATP (EC50 2.2 ± 1.1 μM) = UTP (3.2 ± 2.8 μM). Cells were unresponsive to UDP (< 30 μM) and UDP-glucose (< 30 μM). ATP responses were attenuated by selective P2Y2 receptor antagonism (AR-C118925XX; IC50 1.1 ± 0.8 μM, 73.0 ± 8.5% max inhibition; N = 7 donors), and UTP responses were abolished. ADP responses were attenuated by the selective P2Y6 receptor antagonist, MRS2587 (IC50 437 ± 133nM, 81.0 ± 8.4% max inhibition; N = 6 donors). These data demonstrate that adenine and uracil nucleotides elicit intracellular calcium responses in human AD-MSCs with a predominant role for P2Y2 and P2Y6 receptor activation. This study furthers understanding about how human adipose-derived mesenchymal stromal cells can respond to external signalling cues

Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis

We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis

Snake Venom Disintegrins and Cell Migration

Cell migration is a key process for the defense of pluricellular organisms against pathogens, and it involves a set of surface receptors acting in an ordered fashion to contribute directionality to the movement. Among these receptors are the integrins, which connect the cell cytoskeleton to the extracellular matrix components, thus playing a central role in cell migration. Integrin clustering at focal adhesions drives actin polymerization along the cell leading edge, resulting in polarity of cell movement. Therefore, small integrin-binding proteins such as the snake venom disintegrins that inhibit integrin-mediated cell adhesion are expected to inhibit cell migration. Here we review the current knowledge on disintegrin and disintegrin-like protein effects on cell migration and their potential use as pharmacological tools in anti-inflammatory therapy as well as in inhibition of metastatic invasion

Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

Background: To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D).Methods: This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups.Results: We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). the majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001).Conclusions: Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits.Farmanguinhos/Fundacao Oswaldo Cruz/National Health MinistryBrazilian Diabetes SocietyFundacao do Amparo a Pesquisa do Estado do Rio de JaneiroConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Estado Rio de Janeiro, Unit Diabet, BR-20551030 Rio de Janeiro, BrazilBaurus Diabet Assoc, São Paulo, BrazilFed Univ São Paulo State, Diabet Unit, São Paulo, BrazilFed Univ Hosp Porto Alegre, Porto Alegre, BrazilUniv Hosp São Paulo, Diabet Unit, São Paulo, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniv Fed Ceara, Fortaleza, Ceara, BrazilSanta Casa Misericordia, Belo Horizonte, MG, BrazilSanta Casa Misericordia São Paulo, São Paulo, BrazilUniv Fed Amazonas, Manaus, Amazonas, BrazilHosp Geral de Bonsucesso, Rio de Janeiro, BrazilHosp Univ Clementino Fraga Filho IPPMG, Rio de Janeiro, BrazilUniv Hosp São Paulo, São Paulo, BrazilFac Ciencias Med Santa Casa São Paulo, São Paulo, BrazilUniv São Paulo, Inst Crianca, Hosp Clin, São Paulo, BrazilUniv São Paulo, Fac Med Ribeirao Preto, Hosp Clin, Ribeirao Preto, BrazilAmbulatorio Fac Estadual Med Sao Jose Rio Preto, Ribeirao Preto, BrazilEscola Paulista Med, Ctr Diabet, Ribeirao Preto, BrazilClin Endocrinol Santa Casa Belo Horizonte, Belo Horizonte, MG, BrazilUniv Estadual Londrina, Londrina, BrazilUniv Fed Parana, Hosp Clin, Porto Alegre, RS, BrazilInst Crianca Com Diabet Rio Grande Sul, Rio Grande Do Sul, RS, BrazilGrp Hosp Conceicao, Inst Crianca Com Diabet, Porto Alegre, RS, BrazilHosp Univ Santa Catarina, Florianopolis, SC, BrazilInst Diabet Endocrinol Joinville, Joinville, BrazilHosp Reg Taguatinga, Brasilia, DF, BrazilHosp Geral Goiania, Goiania, Go, BrazilCtr Diabet & Endocrinol Estado Bahia, Goiania, Go, BrazilUniv Fed Maranhao, Sao Luis, BrazilCtr Integrado Diabet & Hipertensao Ceara, Fortaleza, Ceara, BrazilUniv Fed Sergipe, Aracaju, BrazilHosp Univ Alcides Carneiro, Campina Grande, BrazilHosp Univ Joao de Barros Barreto, Belem, Para, BrazilFed Univ São Paulo State, Diabet Unit, São Paulo, BrazilUniv Hosp São Paulo, Diabet Unit, São Paulo, BrazilUniv Hosp São Paulo, São Paulo, BrazilEscola Paulista Med, Ctr Diabet, Ribeirao Preto, BrazilWeb of Scienc