Systemic immunological profile of children with B-cell acute lymphoblastic leukemia: performance of cell populations and soluble mediators as serum biomarkers.

Background: Children with B-cell acute lymphoblastic leukemia (B-ALL) have an immune imbalance that is marked by remodeling of the hematopoietic compartment, with effects on peripheral blood (PB). Although the bone marrow (BM) is the main maintenance site of malignancy, the frequency with which immune cells and molecules can be monitored is limited, thus the identification of biomarkers in PB becomes an alternative for monitoring the evolution of the disease. Methods: Here, we characterize the systemic immunological profile in children undergoing treatment for B-ALL, and evaluate the performance of cell populations, chemokines and cytokines as potential biomarkers during clinical follow-up. For this purpose, PB samples from 20 patients with B-ALL were collected on diagnosis (D0) and during induction therapy (days 8, 15 and 35). In addition, samples from 28 children were used as a control group (CG). The cellular profile (NK and NKT-cells, Treg, CD3+ T, CD4+ T and CD8+ T cells) and soluble immunological mediators (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-6, TNF, IFN-γ, IL-17A, IL- 4, IL-10 and IL-2) were evaluated via flow cytometry immunophenotyping and cytometric bead array assay. Results: On D0, B-ALL patients showed reduction in the frequency of cell populations, except for CD4+ T and CD8+ T cells, which together with CCL2, CXCL9, CXCL10, IL-6 and IL-10 were elevated in relation to the patients of the CG. On D8 and D15, the patients presented a transition in the immunological profile. While, on D35, they already presented an opposite profile to D0, with an increase in NKT, CD3+ T, CD4+ T and Treg cells, along with CCL5, and a decrease in the levels of CXCL9, CXCL10 and IL-10, thus demonstrating that B-ALL patients present a complex and dynamic immune network during induction therapy. Furthermore, we identified that many immunological mediators could be used to classify the therapeutic response based on currently used parameters. Conclusion: Finally, it is noted that the systemic immunological profile after remission induction still differs significantly when compared to the GC and that multiple immunological mediators performed well as serum biomarkers.

Bone Marrow Soluble Immunological Mediators as Clinical Prognosis Biomarkers in B-Cell Acute Lymphoblastic Leukemia Patients Undergoing Induction Therapy.

Different factors are used as predictors of unfavorable clinical outcomes in B-Cell Acute Lymphoblastic Leukemia (B-ALL) patients. However, new prognostic markers are needed in order to allow treatment to be more accurate, providing better results and an improved quality of life. In the present study, we have characterized the profile of bone marrow soluble mediators as possible biomarkers for risk group stratification and minimal residual disease (MRD) detection during induction therapy. The study featured 47 newly-diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients that were categorized into subgroups during induction therapy according to risk stratification at day 15 [Low Risk (LR), Low Risk increasing to High Risk (LR→HR) and High Risk (HR)] and the MRD detection on day 35 (MRD(-) and MRD(+)). Soluble immunological mediators (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1ß, IL-6, TNF, IFN-γ, IL-17A, IL-4, IL-5, IL-10 and IL-2) were quantified by cytometric bead array and ELISA. Our findings demonstrated that increased levels of CCL5, IFN-γ and IL-2 at baseline appeared as putative candidates of good prognosis in LR and MRD(-) subgroups, while CCL2 was identified as a consistent late biomarker associated with poor prognosis, which was observed on D35 in HR and MRD(+) subgroups. Furthermore, apparently controversial data regarding IL-17A and TNF did not allow the definition of these molecules as either positive or negative biomarkers. These results contribute to the search for novel prognostic indicators, and indicate the potential of bone marrow soluble mediators in prognosis and follow-up of B-ALL patients during induction therapy.

Imbalance of Chemokines and Cytokines in the Bone Marrow Microenvironment of Children with B-Cell Acute Lymphoblastic Leukemia.

In the hematopoietic microenvironment, leukemic cells secrete factors that imbalanced chemokine and cytokine production. However, the network of soluble immunological molecules in the bone marrow microenvironment of acute lymphoblastic leukemia (ALL) remains underexplored. Herein, we evaluated the levels of the immunological molecules (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-6, TNF, IFN-γ, IL-17A, IL-4, IL-10, and IL-2) in the bone marrow plasma of 47 recently diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients during induction therapy using cytometric beads arrays. The results demonstrated that B-ALL patients showed high levels of CXCL9, CXCL10, IL-6, and IL-10 at the time of diagnosis, while at the end of induction therapy, a decrease in the levels of these immunological molecules and an increase in CCL5, IFN-γ, and IL-17A levels were observed. These findings indicate that B-ALL patients have an imbalance in chemokines and cytokines in the bone marrow microenvironment that contributes to suppressing the immune response. This immune imbalance may be associated with the presence of leukemic cells since, at the end of the induction therapy, with the elimination and reduction to residual cells, the proinflammatory profile is reestablished, characterized by an increase in the cytokines of the Th1 and Th17 profiles.

Application of Beauveria bassiana spore waste as adsorbent to uptake acid red 97 dye from aqueous medium.

The adsorption of acid red 97 dye (RED 97) by the waste of the filamentous fungus Beauveria bassiana was analyzed. The adsorbent was obtained as a waste of a fermentative process, and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffractometry (XRD), and specific surface area (BET). After the characterization, adsorption tests were carried out to determine the ideal conditions of pH, adsorbent mass, and contact time for the process. Adsorption isotherms, thermodynamic studies, and the treatment of textile effluent were also investigated. The adsorbent characterization allowed the visualization of its amorphous structure, with irregular and heterogeneous particles. The pore diameter was 51.9 nm and the surface area was 0.247 m2 g-1. 1.2 g L-1 of the adsorbent and pH of 2.0 were the ideal conditions for RED 97 adsorption. The pseudo-second-order kinetic model was the most appropriate to represent the experimental data, being the equilibrium reached in about 110 min. The Langmuir model was the most suitable to represent the equilibrium data, with maximum adsorption capacity of 194.1 mg g-1 at 45 °C. The adsorption processes was thermodynamically spontaneous, favorable, and exothermic. In the treatment of a real textile effluent, 5 g L-1 of the spores was capable to decolorize 70% of the solution. Therefore, spore wastes of Beauveria bassiana were promising for RED 97 adsorption.

Production of cutinase by solid-state fermentation and its use as adjuvant in bioherbicide formulation.

In the present study, it was presented a strategy to maximize the cutinase production by solid-state fermentation from different microorganisms and substrates. The best results were observed using Fusarium verticillioides, rice bran being the main substrate. Maximum yield of cutinase obtained by the strain was 16.22 U/g. For concentration, ethanol precipitation was used, and the purification factor was 2.4. The optimum temperature and pH for enzyme activity were 35 °C and 6.5, respectively. The enzyme was stable at a wide range of temperature and at all pH values tested. The concentrated cutinase was used as an adjuvant in a formulation containing cutinase + bioherbicide. The use of enzyme increased the efficiency of bioherbicide, since cutinase was responsible to remove/degrade the cutin that recovery the weed leaves and difficult the bioherbicide absorption. Cutinase showed to be a promising product to be used in formulation of bioherbicides.

Evaluation of meso-substituted cationic corroles as potential antibacterial agents.

Cationic derivatives of 5,10,15-tris[4-(pyridin-4-ylsulphanyl)-2,3,5,6-tetrafluorophenyl]-corrolategallium(III)pyridine and 5,10,15-tris[4-(pyridin-2-ylsulfanyl)-2,3,5,6-tetrafluorophenyl]-correlategallium(III)pyridine were synthesized and their photosensitizing properties against the naturally bioluminescent Gram-negative bacterium Allivibrio fischeri were evaluated. The cationic corrole derivatives exhibited antibacterial activity at micromolar concentrations against this Gram-negative bacterium strain.

Role of peripheral blood minimum residual disease at day 8 of induction therapy in high-risk pediatric patients with acute lymphocytic leukemia.

Risk stratification and treatment intensification, based on minimal residual disease (MRD) mensurement, changed the prognosis of pediatric patients with acute lymphocytic leukemia (ALL). The main aim of this study was to investigate whether peripheral blood (PB) MRD measurement at day 8 (D8) could predict the risk stratification category determined by bone marrow (BM) MRD at day 15 (D15). The study was performed prospectively, in a cohort of 40 children with B-lineage ALL, adopting the protocol of the Brazilian Cooperative Group of the Treatment Childhood Leukemia (GBTLI-2009). MRD was detected by flow cytometry (FC) using a simplifed panel that can reliably identify MRD at early phases of induction therapy. Upon diagnosis, the proportion of low and high-risk patients, was 24:16 (60%:40%). The main result of our study demonstrated the potential of D8 MRD in anticipating of week the risk stratification of high-risk patients as determined by D15 BM MRD. In these patients D8 MRD level of 1% was able to segregate high risk fast responders from high risk slow responders (p = 0.0097). This result could represent an opportunity for early treatment intensification, as already performed in some protocols.

Evaluation of biobutanol production by Clostridium beijerinckii NRRL B-592 using sweet sorghum as carbon source / Avaliação da produção de biobutanol por Clostridium beijerinckii NRRL B-592 usando sorgo sacarino como fonte de carbono

In this research it was evaluated the production of biobutanol by Clostridium beijerinckiiNRRL B-592 using sweet sorghum juice as carbon source. Operational variables, like pH and initial inoculum size, as well as supplementation of industrial media with yeast extract and tryptone, were evaluated. The maximum butanol obtained was 2.12g kg-1 using 12.5% of inoculum size, 0.05g 100mL-1 of tryptone and 0.1g 100mL-1 of yeast extract and initial pH of 5.5. The main contribution of this research was to show a systematic procedure for development of a low cost industrial media for biobutanol production from sweet sorghum.(AU)

Neste trabalho, foi avaliada a produção de biobutanol por Clostridium beijerinckiiNRRL B-592 usando o caldo de sorgo sacarino como fonte de carbono. Foram avaliadas as variáveis operacionais como pH e densidade de inóculo, bem como a suplementação de meios industriais com extrato de levedura e triptona. A máxima concentração de butanol obtida foi de 2,12g kg-1, utilizando 12,5% de inóculo, 0,05g 100mL-1 de triptona e 0,1g 100ml-1 de extrato de levedura e pH inicial de 5,5. A principal contribuição deste trabalho foi o de mostrar um procedimento sistemático para o desenvolvimento de um meio industrial de baixo custo para a produção de biobutanol a partir de sorgo sacarino.(AU)

Evaluation of biobutanol production by Clostridium beijerinckii NRRL B-592 using sweet sorghum as carbon source / Avaliação da produção de biobutanol por Clostridium beijerinckii NRRL B-592 usando sorgo sacarino como fonte de carbono

In this research it was evaluated the production of biobutanol by Clostridium beijerinckiiNRRL B-592 using sweet sorghum juice as carbon source. Operational variables, like pH and initial inoculum size, as well as supplementation of industrial media with yeast extract and tryptone, were evaluated. The maximum butanol obtained was 2.12g kg^-1 using 12.5% of inoculum size, 0.05g 100mL^-1 of tryptone and 0.1g 100mL^-1 of yeast extract and initial pH of 5.5. The main contribution of this research was to show a systematic procedure for development of a low cost industrial media for biobutanol production from sweet sorghum.

Neste trabalho, foi avaliada a produção de biobutanol por Clostridium beijerinckiiNRRL B-592 usando o caldo de sorgo sacarino como fonte de carbono. Foram avaliadas as variáveis operacionais como pH e densidade de inóculo, bem como a suplementação de meios industriais com extrato de levedura e triptona. A máxima concentração de butanol obtida foi de 2,12g kg^-1, utilizando 12,5% de inóculo, 0,05g 100mL^-1 de triptona e 0,1g 100ml^-1 de extrato de levedura e pH inicial de 5,5. A principal contribuição deste trabalho foi o de mostrar um procedimento sistemático para o desenvolvimento de um meio industrial de baixo custo para a produção de biobutanol a partir de sorgo sacarino.

Plasmodium falciparum, but not P. vivax, can induce erythrocytic apoptosis.

BACKGROUND: Apoptosis can occur in red blood cells (RBC) and seems to be involved in hematologic disorders related to many diseases. In malaria it is known that parasitized RBC (pRBC) is involved in the development of anemia and thrombosis; however, non-parasitized RBC (nRBC) apoptosis could amplify these malaria-associated hematologic events. In fact, in experimental malaria, increased levels of apoptosis were observed in nRBC during lethal Plasmodium yoelii 17XL infection, but in human malaria erythrocytic apoptosis has never been studied. The present study was performed to investigate if nRBC apoptosis also occurs in P. vivax and P. falciparum infections. FINDINGS: Apoptosis of nRBC was evaluated in blood samples of P. vivax malaria patients and clinically healthly individuals living in Manaus, Brazil, both ex vivo and after incubation of RBC for 24 h. Additionally, the capacity of plasma from P. vivax or P. falciparum patients was tested for induction of in vitro apoptosis of normal RBC from a clinically healthy individual living in a non-endemic malaria region. Apoptosis was detected by flow cytometry using annexin V staining. In contrast to experimental malaria that significantly increased the levels of apoptotic nRBC both ex-vivo and after 24 h of incubation, no significant alteration on apoptotic nRBC rates was detected in P. vivax infected patients when compared with non-infected control individuals. Similar results were observed when plasma of these P. vivax patients was incubated with normal RBC. Conversely, plasma from P. falciparum-infected subjects induced significant apoptosis of these cells. CONCLUSIONS: Apoptosis of normal RBC can be induced by plasma from individuals with P. falciparum (but not with P. vivax) malaria. This finding could reflect the existence of erythrocytic apoptosis during infection that could contribute to the pathogenesis of hematological and vascular complications associated with falciparum malaria.

Estudo dos antecedentes perinatais de mães adolescentes em Buenópolis/Minas Gerais / Study of perinatal antecedents of adolescent mothers in Buenópolis/Minas Gerais

Estudo descritivo exploratório de abordagem quantitativa que teve como objetivo estudar características das adolescentes grávidas acompanhadas pela atenção básica à saúde de Buenópolis/MG. Foram estudados a escolaridade, o estado civil, o perfil etário; o quantitativo de consultas de pré-natal; duração gestacional e tipo de parto. Para isso foram utilizados osdados secundários disponibilizados pelo Departamento de Informática do SUS (DATASUS), pelo Sistema de Informações sobre Nascidos Vivos (SINASC) e Sistema de Acompanhamento do Programa de Humanização no Pré-Natal e Nascimento (SISPRENATAL) no período de 2003 a 2012. O percentual de adolescentes grávidas ficou em torno de 24% no período. Apenas 45,2% das gestantes adolescentes fizeram entre sete ou mais consultas. Ocorreram 72,9% de partos vaginais e 27,1% cesáreos. Apenas 103 (38,1%) das 270 adolescentes analisadas no período realizaram a primeira consulta nos primeiros três meses. A prevalência de adolescentes que tiveram bebês prematuros no período estudado foi de 13,4%. 75,9% das adolescentes grávidas estavam solteiras quando tiveram seus filhos. Observou-se grande diferença escolar do grupo de adolescentes gestantes com ensino médio: do ano de 2003, 39,1%, para o grupo do ano de 2012, 100%. Acaracterização do perfil das adolescentes grávidas permite identificar as necessidades destas e assim direcionar as atividades educativas em saúde e a assistência pré e pós-parto para essa população. Perante os achados, ficou evidente a necessidade de: 1. ações educativas e intersetoriais que possam realmente transformar informações em comportamentos que previnam a gestação entre adolescentes, e 2. capacitação da Estratégia de Saúde da Família para realizar um pré- natal qualificado para as adolescentes gestantes e uma assistência que contemple oferta de métodos contraceptivos indicados para adolescentes em geral...

This is a descriptive exploratory study with a quantitative approach that aimed to study characteristics of pregnantteenagers accompanied by primary care of Buenópolis/MG. We studied education, marital status, age profile, the amount of prenatal consultations, gestational duration and type of delivery. For this we used the secondary data provided by the Department of SUS (DATASUS), the Information System on Live Births (SINASC) and System Monitoring Program for Humanization of Prenatal and Birth (SISPRENATAL) in the period 2003 to 2012. The percentage of pregnant teens was around 24% in the period. Only 45.2% of pregnant teenagers had 7 or more appointments. There were 72.9% vaginal deliveries and 27.1% cesarean sections. Only 103 (38.1%) of the 270 adolescents had their first appointment during the first trimester. The prevalence of adolescents who delivered premature babies during the study period was 13.4%. 75.9% of pregnant adolescents were unmarried when they had their children. There was a significant difference between thegroups of pregnant adolescents regarding having graduated from high school: in 2003, 39.1%; for group of the year 2012, 100%. The characterization of the profile of pregnant adolescents can identify their needs and thus direct health education activities and prenatal and postnatal care for this population. Given the findings, what became evident was the need for: 1.Educational and intersectoral actions that can really transform information into behaviors that prevent pregnancy among adolescents, and 2. Training professionals who work in Family Health to conduct qualified prenatal care for pregnant adolescents, and give assistance that includes a supply of contraceptive indicated for adolescents in general...

Estudio exploratorio descriptivo de abordaje cuantitativo que tuvo como objetivo estudiar las características de las adolescentes embarazadas acompañadas por la atención primaria de Buenópolis/MG. Se estudiaron la escolaridad, estado civil, el perfil etario, la cantidad de consultas prenatales; duración de la gestación y el tipo de parto. Se utilizaron los datos secundarios suministrados por el Departamento del SUS (DATASUL), por el sistema de información SINASC yPrograma de Monitoreo para la Humanización del Prenatal y Nacimiento (SISPRENATAL) en el período de 2003 a 2012. El porcentaje de adolescentes embarazadas fue de alrededor de 24% en el período. Sólo el 45,2% de las adolescentes embarazadas hizo entre 7 o más visitas. Hubo 72,9% de los partos vaginales y el 27,1% por cesárea. Sólo 103 (38,1%) de las 270 adolescentes analizadas en el período hizo la primera consulta en los tres primeros meses. La prevalencia deadolescentes que han tenido bebés prematuros durante el período de estudio fue de 13,4%. 75,9% de las adolescentes embarazadas estaban solteras cuando tuvieron a sus hijos. Se ha observado una gran diferencia escolar del grupo deadolescentes embarazadas con enseñanza secundaria: del año 2003, el 39,1% para el grupo del año 2012, el 100%. La caracterización del perfil de las adolescentes embarazadas permite identificar sus necesidades y así dirigir las actividades de educación en salud y la atención pre y postparto en esta población. Dados los resultados, se hizo evidente la necesidad de: 1. acciones educativas e intersectoriales que pueden realmente transformar las informaciones en conductas que previenen el embarazo entre las adolescentes, y 2. Formación de la Estrategia Salud de la Familia para lograr una atención prenatal calificada para adolescentes embarazadas y una atención que cubra la oferta de métodosanticonceptivos adecuados para los adolescentes en general...