RESUMO
Chemical pollution is a global concern as contaminants are transported and reach even the remote regions of Antarctica. Seabirds serve as important sentinels of pollution due to their high trophic position and wide distribution. This study examines the influence of migration and trophic ecology on the exposure of two Antarctic seabirds, Wilson's storm petrel (Oceanites oceanicus - Ooc), and Cape petrel (Daption capense - Dca), to chemical elements and perfluoroalkyl substances (PFAS). Our methodology involved assessing the concentration of these pollutants in feather samples obtained from carcasses, offering a practical means for monitoring contamination. Trace and major element concentrations were comparable in both species, suggesting that migratory patterns have a minimal impact on exposure levels. However, Ooc had higher concentration of PFAS compared to Dca (mean, ng g-1dry weight, PFOA: Ooc:0.710, Dca:0.170; PFTrDA: Ooc:0.550, Dca:0.360, and PFTeDA: Ooc:1.01, Dca:0.190), indicating that migration to the more polluted Northern Hemisphere significantly affects PFAS exposure. Furthermore, while no strong associations were found between either trace elements or PFAS and the three stable isotopes (δ13C, δ15N, and δ34S), a negative association was observed between PFUnDA and δ15N, hinting at potential biodilution. The research concludes that the migratory patterns of these seabird species affect their PFAS exposure, underscoring the critical need for further exploration and understanding of these relationships to better inform conservation strategies.
Assuntos
Fluorocarbonos , Oligoelementos , Animais , Regiões Antárticas , Aves , Ecologia , Estado Nutricional , Fluorocarbonos/toxicidade , Monitoramento AmbientalRESUMO
The levels of eighteen trace elements (TEs) were evaluated in association with stable isotopes (δ15N, δ34S, and δ13C) in feathers and eggs of five migratory species breeding on the Antarctic Peninsula to test the factors that influence their exposure to contaminants. The feathers of seabirds migrating to the Northern Hemisphere (South polar skua) have concentrations (mean ± SD, µg. g-1) of Li (1.71 ± 2.08) and Mg (1169.5 ± 366.8) one order of magnitude higher than southern migrants, such as Snowy sheathbill Li (0.01 ± 0.005) and Mg (499.6 ± 111.9). Feathers had significantly higher concentrations for 11 of a total of 18 metals measured compared to eggs. South polar skua have higher concentrations of all TEs in eggs compared to antarctic tern. Therefore, the present study showed that migration and trophic ecology (δ15N, δ13C, and δ34S) influence Fe, Mn, Cu, and Se concentrations in feathers of Antarctic seabirds. The concentrations of Cu, Mn, Rb, Zn, Pb, Cd, Cr are higher than previously reported, which may be due to increased local and global human activities.
Assuntos
Charadriiformes , Poluentes Ambientais , Spheniscidae , Oligoelementos , Animais , Humanos , Oligoelementos/análise , Monitoramento Ambiental , Regiões Antárticas , Poluentes Ambientais/análise , Plumas/químicaRESUMO
Although naturally present in the environment, mercury (Hg) input is significantly amplified by anthropogenic activities on a global scale, leading to a growing concern about the recent increase in Hg levels observed in Antarctica. This study investigated total mercury (THg) concentrations in feathers and eggs of resident and migratory Antarctic seabirds. Stable isotope data (δ15N, δ13C, and δ34S) were employed to ascertain the key factors influencing the exposure of these species to Hg. We gathered feathers and eggs from three resident species - Adélie, Gentoo, and Chinstrap penguins, as well as five migratory species - Snowy Sheathbill, Antarctic Tern, Southern Giant Petrel, Kelp Gull, and South Polar Skua. These samples were collected from Admiralty Bay, King George Island, in the Antarctica Peninsula. For all species, THg concentrations were higher in feathers (mean ± SD: 2267 ± 2480 ng g-1 dw) than in eggs (906 ± 1461 ng g-1 dw). Species occupying higher trophic positions, such as the Southern Giant Petrel (5667 ± 1500 ng g-1 dw) and South Polar Skua (4216 ± 1101 ng. g-1 dw), exhibited higher THg levels in their feathers than those at lower positions, like Antarctic Tern (1254 ± 400 ng g-1 dw) and Chinstrap Penguin (910 ± 364 ng g-1 dw). The δ15N values, which serve as a proxy for the trophic position, significantly correlated with THg concentrations. These findings reveal that trophic position influences THg concentrations in Antarctic seabirds. Migration did not appear to significantly affect the exposure of seabirds to THg, contrary to initial expectations. This research highlights the importance of evaluating the impacts of THg contamination on the Antarctic ecosystem by considering a variety of species. This multi-species approach offers critical insights into the factors that may potentially influence the exposure of these species to contaminants.
Assuntos
Charadriiformes , Mercúrio , Spheniscidae , Animais , Regiões Antárticas , Ecossistema , Efeitos AntropogênicosRESUMO
Zidovudine (3'-azido-3'-deoxythymidine; AZT) is a nucleoside analogue widely used for the treatment of acquired immune deficiency syndrome (AIDS). Medical guidelines recommend the use of AZT by pregnant women in order to reduce risk of HIV vertical transmission. Although it is efficacious, little is known about the side effects of AZT on embryonic development. In this sense, we used murine embryonic stem (mES) cells as a model to investigate the consequences of AZT exposure for embryogenesis. Firstly, mES colonies were incubated with AZT (50 or 100 µM) and cell cycle profile was evaluated. While 27.7 ± 5.43% of untreated mES cells were in G2/M phase, this percentage raised to 45.96 ± 4.18% after AZT exposure (100 µM). To identify whether accumulation of cells in G2/M phase could be related to chromosome missegregation with consequent cell cycle arrest, aneuploidy rate was evaluated after AZT treatment. Untreated colonies presented 39.6 ± 8.4% of cells aneuploid, while after AZT 100 µM treatment, the proportion of aneuploid cells raised to 67.8 ± 3.4% with prevalence of chromosome loss. This event was accompanied by micronuclei formation as AZT 100 µM treated mES cells presented a 2-fold increase compared to untreated ones. These data suggest that AZT exerts genotoxic effects and increases chromosome instability at early stages of embryonic development.
Assuntos
Aneuploidia , Fármacos Anti-HIV/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Células-Tronco Embrionárias/efeitos dos fármacos , Zidovudina/farmacologia , Animais , Células Cultivadas , Células-Tronco Embrionárias/citologia , Feminino , Camundongos , GravidezRESUMO
Recurrent haemarthroses leading to chronic synovitis and arthropathy remain a major cause of morbidity in patients with haemophilia. Radioactive synovectomy (RS) is considered the first choice of treatment for chronic haemophilic synovitis. The aim of this study was to evaluate the effect of RS with Yttrium(90) citrate (C-Y(90)) in the joints of patients with chronic haemophilic synovitis. From 2003 to 2007, 245 joints (118 knees, 76 elbows, 49 ankles and two shoulders) of 190 patients with haemophilia or von Willebrand disease were submitted to RS with C-Y(90) at Hemocentro de Mato Grosso, Brazil. Forty joints had radiographic Pettersson scores above 8. There were 36 joints of 22 patients with inhibitors to factor VIII. The procedure was safe with low occurrence of adverse events. The main effect was the overall reduction in joint bleeding frequency, from 19.8 to 2.6 per year post-RS. Similar results were obtained in cases with high radiographic scores and in inhibitor patients. Pain reduction was observed in most cases. Average range of motion was maintained or increased 1 year post-RS in most joints. Extension was stable or increased in 88.2% of the knees and 86.5% of the elbows. Ankle plantarflexion was stable or increased in 90.9%, whereas dorsiflexion was maintained or increased in 87.9%. Worsening of the range of motion, when present, ranged from 14 to 17 degrees. We concluded that RS with C-Y(90) represents an important resource for the treatment of chronic haemophilic synovitis, markedly reducing joint bleeding frequency and pain, irrespective of the radiographic stage and inhibitor status.
Assuntos
Citratos/uso terapêutico , Hemofilia A/complicações , Hemofilia B/complicações , Compostos Organometálicos/uso terapêutico , Radioisótopos/uso terapêutico , Sinovite/radioterapia , Doenças de von Willebrand/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Fator VIII/antagonistas & inibidores , Feminino , Hemartrose/complicações , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Medição da Dor , Amplitude de Movimento Articular , Sinovite/etiologia , Adulto JovemRESUMO
Routine blood culture is used for the detection of bloodstream infections by aerobic and anaerobic bacteria and by common pathogenic yeasts. A retrospective study was conducted in a public hospital in Maceió-AL, by collecting data of all medical records with positive blood cultures. Out of the 2,107 blood cultures performed, 17% were positive with Staphylococcus coagulase negative (51.14%), followed by Staphylococcus aureus (11.21%) and Klebsiella pneumoniae (6.32%). Gram-positive bacteria predominated among positive blood cultures, highlighting the group of Staphylococcus coagulase-negative. While Gram-negative bacteria had a higher number of species among positive blood cultures.
Assuntos
Bactérias Gram-Negativas , Sepse , Brasil , Hospitais , Humanos , Estudos RetrospectivosRESUMO
Contaminant levels are lower in Antarctica than elsewhere in the world because of its low anthropogenic activities. However, the northern region of the Antarctic Peninsula, is close to South America and experiences the greatest anthropogenic pressure in Antarctica. Here, we investigated, in two Antarctic Peninsula islands, intra and interspecific factors that influence the concentrations of 17 trace elements (TEs) in blood and feathers of three penguin species breeding sympatrically in relation to their trophic ecology assessed via a stable isotopic approach (C, N and S). Geographical location, foraging zone (δ13C and δ34S) and diet influences the interspecific difference, and sex and maturity stage diet influence the intraspecific difference of Pygoscelis penguins. Penguins from Livingston showed higher values (mean, ng. g-1, dry weight - dw) of Zn (103), Mn (0.3), and Fe (95) than those from King George Island (Zn: 80, Mn: 1.9, and Fe: 11). Gender-related differences were observed, as males showed significantly higher values (mean, ng. g-1, dw) of Rb (3.4) and δ15N in blood of gentoo, and Ca (1344) in Adélie feathers. Chicks of gentoo and Adélie presented higher Zn, Mg, Ca, and Sr and lower 13C values in blood than adults. The highest concentrations (mean, ng. g-1, dw) of Cd (0.2) and Cu (26), and the lowest δ15N values were found in chinstrap. Geographical, intraspecific (i.e., ontogenetic and gender-related) and interspecific differences in feeding seemed to have influenced TE and stable isotope values in these animals. The TE bioaccumulation by penguins may have also been influenced by natural enrichment in environmental levels of these elements, which seems to be the case for Fe, Zn, and Mn. However, the high level of some of the TEs (Mn, Cd, and Cr) may reflect the increase of local and global human activities.
Assuntos
Spheniscidae , Oligoelementos , Animais , Regiões Antárticas , Plumas/química , Humanos , Ilhas , Masculino , América do Sul , Oligoelementos/análiseRESUMO
Mangrove ecosystems are essential to society, providing ecological and economic services, and play a crucial role in the geochemical land-ocean interface as a sink for potentially toxic metals. This study assessed metals (Al, Ba, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Sr and Zn) and arsenic in sediments from three mangrove zones (Tidal Flat, Rhizophora mangle L. and Avicennia schaueriana Stapf & Leechman ex Moldenke forests) during two seasons: spring of 2015 and autumn of 2016, with the latter being a severe drought year. Overall results suggest that Fe/Mn oxyhydroxides and clay minerals control the distribution of metal and arsenic in the Tidal Flat zone. In the mangrove forest however, sulfur and organic matter dominate complexation, with Fe mainly present as insoluble sulfide, and As, Cd, Cu and Zn as metal sulfides or organometallic complexes. In the autumn of 2016, all elements except Cd and Pb had lower concentrations compared to the spring of 2015. Cd and Pb were probably transferred from sources other than mangrove sediments, due to increased saline water intrusion, a consequence of reduced riverine flow, and precipitated in the Rhizophora mangle and Avicennia schaueriana mangrove forests. This increase of Cd and Pb in the mangrove forest suggests potential storage of metal contaminants in the organic rich areas, a change in availability and potential toxicity to fauna and flora and a need for regulatory responses to sediment quality. These results indicate a change in sediment metal contaminant dynamics with the increasing occurrence of extreme weather events - an increased risk to the ecosystem.
RESUMO
Abstract Routine blood culture is used for the detection of bloodstream infections by aerobic and anaerobic bacteria and by common pathogenic yeasts. A retrospective study was conducted in a public hospital in Maceió-AL, by collecting data of all medical records with positive blood cultures. Out of the 2,107 blood cultures performed, 17% were positive with Staphylococcus coagulase negative (51.14%), followed by Staphylococcus aureus (11.21%) and Klebsiella pneumoniae (6.32%). Gram-positive bacteria predominated among positive blood cultures, highlighting the group of Staphylococcus coagulase-negative. While Gram-negative bacteria had a higher number of species among positive blood cultures.
Resumo A cultura sanguínea de rotina é usada para a detecção de infecções na corrente sanguínea por bactérias aeróbias e anaeróbias e por leveduras patogênicas comuns. Estudo retrospectivo realizado em hospital público de Maceió-AL, por meio da coleta de dados de todos os prontuários com culturas sanguíneas positivas. Das 2.107 culturas sanguíneas realizadas, 17% foram positivas com Staphylococcus coagulase negativo (51,14%), seguido por Staphylococcus aureus (11,21%) e Klebsiella pneumoniae (6,32%). As bactérias Gram-positiva predominaram entre as culturas de sangue positivas, destacando-se o grupo das Staphylococcus coagulase-negativo. Enquanto as bactérias Gram-negativas apresentaram um número maior de espécies entre as culturas de sangue positivas.
RESUMO
Abstract Routine blood culture is used for the detection of bloodstream infections by aerobic and anaerobic bacteria and by common pathogenic yeasts. A retrospective study was conducted in a public hospital in Maceió-AL, by collecting data of all medical records with positive blood cultures. Out of the 2,107 blood cultures performed, 17% were positive with Staphylococcus coagulase negative (51.14%), followed by Staphylococcus aureus (11.21%) and Klebsiella pneumoniae (6.32%). Gram-positive bacteria predominated among positive blood cultures, highlighting the group of Staphylococcus coagulase-negative. While Gram-negative bacteria had a higher number of species among positive blood cultures.
Resumo A cultura sanguínea de rotina é usada para a detecção de infecções na corrente sanguínea por bactérias aeróbias e anaeróbias e por leveduras patogênicas comuns. Estudo retrospectivo realizado em hospital público de Maceió-AL, por meio da coleta de dados de todos os prontuários com culturas sanguíneas positivas. Das 2.107 culturas sanguíneas realizadas, 17% foram positivas com Staphylococcus coagulase negativo (51,14%), seguido por Staphylococcus aureus (11,21%) e Klebsiella pneumoniae (6,32%). As bactérias Gram-positiva predominaram entre as culturas de sangue positivas, destacando-se o grupo das Staphylococcus coagulase-negativo. Enquanto as bactérias Gram-negativas apresentaram um número maior de espécies entre as culturas de sangue positivas.
Assuntos
Humanos , Sepse , Bactérias Gram-Negativas , Brasil , Estudos Retrospectivos , HospitaisRESUMO
Multiparameter flow cytometry has become an essential tool for monitoring response to therapy in hematological malignancies, including B-cell chronic lymphoproliferative disorders (B-CLPD). However, depending on the expertise of the operator minimal residual disease (MRD) can be misidentified, given that data analysis is based on the definition of expert-based bidimensional plots, where an operator selects the subpopulations of interest. Here, we propose and evaluate a probabilistic approach based on pattern classification tools and the Bayes theorem, for automated analysis of flow cytometry data from a group of 50 B-CLPD versus normal peripheral blood B-cells under MRD conditions, with the aim of reducing operator-associated subjectivity. The proposed approach provided a tool for MRD detection in B-CLPD by flow cytometry with a sensitivity of < or =8 x 10(-5) (median of < or =2 x 10(-7)). Furthermore, in 86% of B-CLPD cases tested, no events corresponding to normal B-cells were wrongly identified as belonging to the neoplastic B-cell population at a level of < or =10(-7). Thus, this approach based on the search for minimal numbers of neoplastic B-cells similar to those detected at diagnosis could potentially be applied with both a high sensitivity and specificity to investigate for the presence of MRD in virtually all B-CLPD. Further studies evaluating its efficiency in larger series of patients, where reactive conditions and non-neoplastic disorders are also included, are required to confirm these results.
Assuntos
Linfócitos B/metabolismo , Citometria de Fluxo/métodos , Imunofenotipagem/métodos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Neoplasia Residual/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/imunologia , Sensibilidade e EspecificidadeRESUMO
In order to determine the potential of Cerrado plants as sources of antimicrobial activity, the phytochemical screening of ethanol extracts from Virola surinamensis, Qualea grandiflora, Alchornea castaneifolia, Hancornia speciosa and Curatella americana traditionally used in folk medicine are reported.
Assuntos
Anti-Infecciosos/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Anti-Infecciosos/química , Apocynaceae/química , Brasil , Dilleniaceae/química , Lauraceae/química , Magnoliopsida/química , Testes de Sensibilidade Microbiana , Myristicaceae/química , Extratos Vegetais/química , Trichosporon/efeitos dos fármacosAssuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Criança , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão Oncogênica/genéticaRESUMO
Currently, multiparameter flow cytometry immunophenotyping is the selected method for the differential diagnostic screening between reactive lymphocytosis and neoplastic B-cell chronic lymphoproliferative disorders (B-CLPD). Despite this, current multiparameter flow cytometry data analysis approaches still remain subjective due to the need of experienced personnel for both data analysis and interpretation of the results. In this study, we describe and validate a new automated method based on vector quantization algorithms to analyze multiparameter flow cytometry immunophenotyping data in a series of 307 peripheral blood (PB) samples. Our results show that the automated method of analysis proposed compares well with currently used manual approach and significantly improves semiautomated approaches and, that by using it, a highly efficient discrimination with 100% specificity and 100% sensitivity can be made between normal/reactive PB samples and cases with B-CLPD based on the total B-cell number and/or the sIgkappa+/sIglambda+ B-cell ratio. In addition, the method proved to be able to detect the presence of pathologic neoplastic B-cells even when these are present at low frequencies (<5% of all lymphocytes in the sample) and in poor-quality samples enriched in 'noise' events.
Assuntos
Citometria de Fluxo/métodos , Citometria de Fluxo/normas , Imunofenotipagem/métodos , Imunofenotipagem/normas , Leucemia de Células B/diagnóstico , Linfocitose/diagnóstico , Artefatos , Diagnóstico Precoce , Citometria de Fluxo/estatística & dados numéricos , Humanos , Imunofenotipagem/estatística & dados numéricos , Leucemia de Células B/sangue , Subpopulações de Linfócitos , Linfocitose/sangue , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Programas de Rastreamento/estatística & dados numéricos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Chemotherapy is essential for the cancer treatment. Usually, in the preparation process of the chemotherapy, part of the medication must be discarded to achieve the dose prescribed by the doctor. The dose of medication discarded results in toxic waste production. The objective is to analyze the chemotherapy waste in the preparation process of the drug. METHODS: It has been conducted a cross-sectional observational study. The study data were obtained from chemotherapy's requests by oncologists linked to a health insurance plan. It has been calculated the dose of chemotherapy waste in each application, considering the dose prescribed by the doctor and the drug dosage form. RESULTS: It were analyzed 1,289 prescriptions for intravenous chemotherapy of 106 users with cancer. There were a total of 63,824mg of chemotherapy residue produced, with an average of 602mg by user and 49mg by application. The average percentage of chemotherapy waste was 11.96%, between 0 to 50%. CONCLUSION: The number of applications and the dose used in the treatment protocol, the commercial dosage forms and the no use of dose rounding of medication to the nearest vial size were factors related to increased production of chemotherapy waste.
RESUMO
We evaluated oil and powder formulations of Melia azedarach for controlling larvae of Diabrotica speciosa (Germar) in corn and plant enhancement. Five concentrations of each formulation were evaluated and compared to fipronil (negative control) and distilled water (positive control). After treatment, the number of surviving insects (larvae, pupae, and adults), the adult body weight, the sex ratio, and the longevity were recorded, while the height, dry weight of aerial part and roots, and number of leaves of plants were measured. The oil formulation at 4.0 mL reduced the larvae population of D. speciosa similarly to the insecticide fipronil, which resulted in greater height, dry weight of the root system, and number of leaves. Powder formulation at concentrations of 40, 80, and 160 mg caused larval mortality above 80%; however, these concentrations did not prevent reduction of plant height and dry weight of aerial part. Further studies assessing the residual period of M. azedarach control against D. speciosa larvae and its phytotoxicity, which are common traits associated with azadirachtin application, are necessary to subsidize the next steps of this alternative control strategy.
Assuntos
Besouros/efeitos dos fármacos , Besouros/fisiologia , Controle de Insetos/métodos , Larva/efeitos dos fármacos , Melia azedarach , Extratos Vegetais/farmacologia , Zea mays/parasitologia , Animais , Composição de Medicamentos , Feminino , MasculinoRESUMO
Crotoxin (CTX) is the main neurotoxic component of Crotalus durissus terrificus snake venom. It inhibits tumour growth and modulates the function of macrophages, which are essential cells in the tumour microenvironment. The present study investigated the effect of CTX on the secretory activity of monocultured macrophages and macrophages co-cultivated with LLC-WRC 256 cells. The effect of the macrophage secretory activities on tumour cell proliferation was also evaluated. Macrophages pre-treated with CTX (0.3 µg/mL) for 2 h were co-cultivated with LLC-WRC 256 cells, and the secretory activity of the macrophages was determined after 12, 24 and 48 h. The co-cultivation of CTX-treated macrophages with the tumour cells caused a 20% reduction in tumour cell proliferation. The production of both H2O2 and NO was increased by 41% and 29% after 24 or 48 h of co-cultivation, respectively, compared to the values for the co-cultures of macrophages of control. The level of secreted IL-1ß increased by 3.7- and 3.2-fold after 12 h and 24 h of co-cultivation, respectively. Moreover, an increased level of LXA4 (25%) was observed after 24 h of co-cultivation, and a 2.3- and 2.1-fold increased level of 15-epi-LXA4 was observed after 24 h and 48 h, respectively. Boc-2, a selective antagonist of formyl peptide receptors, blocked both the stimulatory effect of CTX on the macrophage secretory activity and the inhibitory effect of these cells on tumour cell proliferation. Taken together, these results indicate that CTX enhanced the secretory activity of macrophages, which may contribute to the antitumour activity of these cells, and that activation of formyl peptide receptors appears to play a major role in this effect.
Assuntos
Crotoxina/toxicidade , Macrófagos/efeitos dos fármacos , Receptores de Formil Peptídeo/metabolismo , Venenos de Serpentes/isolamento & purificação , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Crotalus , Peróxido de Hidrogênio/metabolismo , Lipoxinas/metabolismo , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Receptores de Formil Peptídeo/genética , Venenos de Serpentes/químicaRESUMO
Chronic myeloid leukemia (CML) is rare in the pediatric population, accounting for 2-3% of childhood leukemia cases, with an annual incidence of one case per million children. The low toxicity profile of imatinib mesylate has led to its approval as a front-line therapy in children for whom interferon treatment has failed or who have relapsed after allogeneic transplantation. We describe the positive responses of 2 children (case 1 - from a 7-year-old male since May 2005; case 2 - from a 5-year-old female since June 2006) with Philadelphia-positive chromosome CML treated with imatinib (300 mg/day, orally) for up to 28 months, as evaluated by morphological, cytogenetic, and molecular approaches. Our patients are alive, are in the chronic phase, and are in continuous morphological complete remission.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Benzamidas , Criança , Pré-Escolar , Feminino , Humanos , Mesilato de Imatinib , Masculino , Neoplasia Residual , Resultado do TratamentoRESUMO
Immunophenotypic characterization of B-cell chronic lymphoproliferative disorders (B-CLPD) is becoming increasingly complex due to usage of progressively larger panels of reagents and a high number of World Health Organization (WHO) entities. Typically, data analysis is performed separately for each stained aliquot of a sample; subsequently, an expert interprets the overall immunophenotypic profile (IP) of neoplastic B-cells and assigns it to specific diagnostic categories. We constructed a principal component analysis (PCA)-based tool to guide immunophenotypic classification of B-CLPD. Three reference groups of immunophenotypic data files-B-cell chronic lymphocytic leukemias (B-CLL; n = 10), mantle cell (MCL; n = 10) and follicular lymphomas (FL; n = 10)--were built. Subsequently, each of the 175 cases studied was evaluated and assigned to either one of the three reference groups or to none of them (other B-CLPD). Most cases (89%) were correctly assigned to their corresponding WHO diagnostic group with overall positive and negative predictive values of 89 and 96%, respectively. The efficiency of the PCA-based approach was particularly high among typical B-CLL, MCL and FL vs other B-CLPD cases. In summary, PCA-guided immunophenotypic classification of B-CLPD is a promising tool for standardized interpretation of tumor IP, their classification into well-defined entities and comprehensive evaluation of antibody panels.
Assuntos
Linfócitos B/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/imunologia , Automação , Linfócitos B/patologia , Feminino , Citometria de Fluxo/métodos , Humanos , Imunoglobulina A/imunologia , Imunofenotipagem/métodos , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma/imunologia , Linfoma/patologia , Linfoma Folicular/imunologia , Linfoma Folicular/patologia , Linfoma de Célula do Manto/imunologia , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common malignancy in children. The Wnt signaling pathway has been found to be extensively involved in cancer onset and progression but its role in BCP-ALL remains controversial. We evaluate the role of the Wnt pathway in maintenance of BCP-ALL cells and resistance to chemotherapy. Gene expression profile revealed that BCP-ALL cells are potentially sensitive to modulation of Wnt pathway. Nalm-16 and Nalm-6 cell lines displayed low levels of canonical activation, as reflected by the virtually complete absence of total beta-catenin in Nalm-6 and the beta-catenin cell membrane distribution in Nalm-16 cell line. Canonical activation with Wnt3a induced nuclear beta-catenin translocation and led to BCP-ALL cell death. Lithium chloride (LiCl) also induced a cytotoxic effect on leukemic cells. In contrast, both Wnt5a and Dkk-1 increased Nalm-16 cell survival. Also, Wnt3a enhanced the in vitro sensitivity of Nalm-16 to etoposide (VP-16) while treatment with canonical antagonists protected leukemic cells from chemotherapy-induced cell death. Overall, our results suggest that canonical activation of the Wnt pathway may exerts a tumor suppressive effect, thus its inhibition may support BCP-ALL cell survival.