Avaliação do efeito citotóxico da lectina da esponja marinha Cliona varians contra células de leucemia mielóide crônica

In this study, a BCR-ABL expressing human chronic myelogenous leukaemia cell line (K562) was used to investigate the antitumoral potential of a novel lectin (CvL) purified from the marine sponge Cliona varians. CvL inhibited the growth of K562 cells with an IC50 value of 70 g/ml, but was ineffective to normal human peripheral blood lymphocytes in the same range of concentrations tested (180 g/ml). Cell death occurred after 72 h of exposure to the lectin and with sign of apoptosis as analysed by DAPI staining. Investigation of the possible effectors of this process showed that cell death occurred in the presence of Bcl-2 and Bax expression, and involved a caspase-independent pathway. Confocal fluorescence microscopy indicated a major role for the lysosomal protease cathepsin B in mediating cell death. Accordingly, pre-incubation of K562 cells with the cathepsin inhibitor L-trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane (E-64) abolished the cytotoxic effect of CvL. Furthermore, we found upregulation of tumor necrosis factor receptor 1 (TNFR1) and down-modulation of p65 subunit of nuclear factor kappa B (NFB) expression in CvL-treated cells. These effects were accompanied by increased levels of p21 and downmodulation of pRb, suggesting that CvL is capable of cell cycle arrest. Collectively, these findings suggest that cathepsin B acts as death mediator in CvL-induced cytotoxicity possibly in a still uncharacterized connection with the membrane death receptor pathway

Caracterização Hematológica e Imunofenotípica em Pacientes com Leucemia Linfoblástica Aguda

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Função autonômica em pacientes portadores de lipodistrofia generalizada congênita - sindrome de berardinelli - SEIP

A Síndrome de Berardinelli-Seip ou Lipodistrofia Generalizada Congênita (LGC) é uma doença rara, com transmissão autossômica recessiva, caracterizada principalmente pela ausência quase total de tecido adiposo. Os pacientes afetados apresentam resistência a insulina, dislipidemia e hipertensão arterial. Estudos têm evidenciado que estas alterações metabólicas interferem na modulação autonômica para o nó sinusal. O principal objetivo deste estudo foi investigar a modulação autonômica em pacientes portadores de LGC, através da variabilidade de freqüência cardíaca (VFC), pelo método linear de domínio de tempo na Eletrocardiografia Dinâmica de 24 horas e estabelecer um critério relativamente simples, não invasivo, para diagnóstico de disfunção autonômica nestes pacientes. Participou voluntariamente deste estudo transversal, um grupo de pacientes portadores de LGC (n=18) na faixa etária de 9,3 a 39,8 anos (21,3 ± 8,3) cuja variabilidade de freqüência cardíaca foi comparada com um grupo de pacientes controles (n=19) com idade de 9,3 a 39,1 anos (21,4 ± 7,8). Todos os voluntários foram submetidos à avaliação clínica, laboratorial, antropométrica e análise de VFC no domínio de tempo através de eletrocardiografia dinâmica de 24 horas. Para análise dos dados relativos aos índices temporais de VFC foram utilizados o MeanRR, SSDN e rMSSD. Pacientes com LGC apresentavam aumento da pressão arterial comparados com indivíduos do grupo controle (sistólica, 131,1 vs 106,3 mmHg, p<0,05); diastólica, 85,0 vs 68,2 mmHg, p<0,05) e 10 tinham critérios para diagnóstico de Hipertensão Arterial e Hipertrofia do Ventrículo Esquerdo. Os níveis de glicose, triglicerídeos, colesterol e HOMA-R eram elevados e 12 pacientes tinham critérios para diabetes mellitus tipo 2. Comparado com os controles, pacientes com LGC tinham diminuição dos índices MeanRR (639,8 vs 780,5 ms, p<0,001), SDNN (79,2 vs 168,5 ms, p<0,001), e rMSSD (15,8 vs 59,6 ms, p<0,001). Em pacientes com LGC, a redução da VFC foi independente de distúrbios metabólicos e hemodinâmicos. Os resultados de nosso experimento indicam que pacientes com LGC apresentavam modulação autonômica anormal caracterizada pelo aumento da freqüência cardíaca e pronunciada redução da VFC, independente de distúrbios metabólicos e hemodinâmicos observados nesta síndrome. O caráter multidisciplinar desse estudo fica contemplado pela interação de profissionais de diversas áreas como: cardiologia, endocrinologia, metabolismo, neurologia, nutrição, etc

Hemiparesia congênita e adquirida na criança: interrelação entre presença de crises epilépticas, os achados eletrencefalográficos e de neuroimagem por ressonância nuclear magnética

The purpose of this paper was to study patients with congenital and acquired hemiparesis, their clinical aspects, the presence or not of epileptic seizures, and electroencephalographic (EEG) and Magnetic Resonance Imaging (MRI) findings. We analyzed the interrelation between etiology, the presence and seriousness of epileptic seizures (ES) and the possible causes of refractoriness. This is a prospective study using the clinical diagnosis of a child neurologist, who attested to the presence of unilateral motor lesions. We compared the electroencephalographic findings in patients with or without epileptic seizures, and investigated if among the former, these seizures were controlled or not, their likely etiology and risks of refractoriness. EEG background activity on the lesion and contralateral side was analyzed, in addition to the presence of concomitant epileptiform activity. Encephalon MRIs of all the patients were studied to correlate etiology and the control or not of epileptic seizures. The disorganization of bilateral EEG activity correlated with the difficult-to-control epileptic seizures. Suitably organized background activity contralateral to the lesion is a good prognosis in relation to epileptic seizures. Focal epileptogenic activity does not necessarily predispose to epileptic manifestation. The MRI is more important in determining etiology than in prognosing epileptic seizures. This study used a multidisciplinary approach involving child neurologists, a physical therapist and a neuroradiologist. This meets the criteria of multidisciplinarity of the Postgraduate Program in Health Sciences

Intervenção dietoterápica em portadores de lipodistrofia generalizada congênita do Rio Grande do Norte

Congenital generalized lipodystrophy is a rare genetic disease with autosomal recessive inheritance characterized by the generalized absence of subcutaneous adipose tissue and insulin resistance. The aim of our study was to determine the profile of patients with congenital generalized lipodystrophy (Berardinelli-Seip syndrome) through their clinical history, eating habits, and socioeconomic and cultural aspects; assess food consumption and nutritional status of the study group; propose and evaluate a diet therapy model associated to oral supplementation with zinc to help in the control and prevention of metabolic complications associated to the pathology. Initial assessment of food consumption indicated a voracious appetite in all the patients studied. The introduction of zinc reduced appetite, contributing to patient adherence to the food plan proposed. It was also observed that the proposed diet contributed mainly to glycidic control, specifically with respect to HbA1c. The nutritional status of the patients investigated was adequate in terms of body mass index (BMI), arm muscle circumference (AMC), arm muscle area AMA, but triceps skinfold (TSF) indicated serious malnutrition. Our study is unique in the literature and provides important information to the field of nutrition and to individuals with this pathology. Furthermore, it contemplates the interdisciplinary and multidisciplinary requirements of the Postgraduate Program in Health Sciences of the Federal University of Rio Grande do Norte (UFRN), Natal, Brazil

Avaliação neuropsicológica de crianças com hemiparesia congênita e adquirida

A hemiparesia consiste no déficit da força muscular, com consequente debilidade na mão e no pé, afetando um dos lados do corpo. A literatura mostra poucos estudos enfocando detalhadamente as funções cognitivas e emocionais de crianças afetadas por essa condição neurológica. Este estudo teve como objetivo realizar avaliação neuropsicológica de 23 crianças e adolescentes, de ambos os gêneros, com idades entre 5 anos e 4 meses e 16 anos e 6 meses, com hemiparesia congênita e adquirida. Aplicou-se uma bateria de testes específica para avaliação de funções cognitivas superiores incluindo processos intelectuais, atenção, função perceptiva, função motora, praxias, gnosias, linguagem, memória e função visuomotora. Em relação aos aspectos emocionais, foi usado o teste do desenho da figura humana, visando-se a avaliação da percepção da imagem corporal dos pacientes. Os resultados mostraram que a hemiparesia da criança conduz a déficits em funções neuropsicológicas importantes, além de déficit motor e alterações na esfera emocional, mais precisamente aquelas relacionadas com a representação da imagem corporal. A abrangência multidisciplinar, envolvendo a neurologia pediátrica e a psicologia, engrandeceu o trabalho, referendando os resultados obtidos em todos os seus aspectos

Emprego da citometria de fluxo na avaliação do perfil imunofenotípico de pacientes com leucemia linfocítica crônica

Chronic lymphocytic leukemia (B-CLL) is a clonal proliferation of mature B lymphocytes characterized by indolent clinical course. Biologically this clonallity is characterized by low expression of surface immunoglobulin (sIg) with restriction to a single immunoglobulin light chain associated with high expression of CD5 antigen and positivity to B cell antigens lymphocytes such as CD19, CD20 and CD23 and negativity to FMC7. The immunological profile and morphological analysis of lymphoid cells are the main means for the differential diagnosis of B-CLL from other chronic lymphoproliferative diseases. The aim of this study was to evaluate the expression pattern of a variety of membrane antigens in leukemic cells originating from patients with B-CLL. In this study, peripheral blood samples from 80 patients with B-CLL were analyzed by multiparametric flow cytometry in addition to routine hematologic exams, using a panel of monoclonal antibodies (MoAb): CD45/CD14, CD3/CD19/CD45, CD4/CD8 / CD3, CD20/CD5/CD3, CD3/CD16-56/CD45, CD2/CD7, FMC7/CD23, CD103/CD22/CD20, HLADR/CD38, CD10/CD19, CD1a, CD11b and also IgM/gD, kappa and lambda immunoglobulin light chains for the detection of surface immunoglobulin and clonal restriction for immunoglobulin light chain. The Hematological data were obtained from the hematological analyzer and cytomorphological analysis in blood film stained by Leishmann. The study samples consisted of 45 men and 35 women, ages ranging from 55 to 84 years (mean 65 years). Complete white blood count showed count ranging from 10.0 to 42.0 x 109/l. (mean 50.0 x 109/l) and lymphocytes count greater than 5.0 x 109/l in all cases. The neoplastic cells displayed B-CLL phenotype (CD5+/CD19+/CD20+/HLADR+/CD23+) in the vast majority of the cases, associated to failed to stain for T cell markers (CD1a, CD2, CD4, CD3, CD7, CD8), CD103, CD14 and FMC7. Leukemic cells of most patients also expressed low intensity of IgM and IgD with restricted kappa light chain, in most cases (59,7%). This observation highlights the importance of immunophenotyping for correct diagnosis of chronic lymphoproliferative syndromes and the panel of MoAb used was sufficient for diagnostic confirmation of B-CLL

Avaliação dos marcadores celulares por citometria de fluxo nos portadores de leucemia mieloide aguda atendidos no Hemocentro do Rio Grande do Norte-Hemonorte

The acute myeloid leukemia (AML) is a disease in which malignant myeloblasts expand, build up and suppress normal hematopoietic activity would represent a major diagnostic challenge. With the advent of immunophenotyping by flow cytometry, the diagnosis of these tumors have become more faithful, facilitating the treatment and monitoring of patients. The objectives of this study: diagnosis and classification of AML based on immunophenotyping by flow cytometry with a panel of AcMo specific for acute leukemias, set the frequency of AML in samples from patients with acute leukemias sent to the Department of Hematology Blood Center of Rio Grande do Norte - HEMONORTE, establish standards of antigen expression for different subtypes of acute leukemia and its correlation with the newly diagnosed cases refractory to treatment and recurrence of the disease, standardization of methods for detection and labeling of surface antigens by flow cytometry and intracytoplasmic flow, and observe the frequency of acute leukemia with aberrant phenotypes rare. During the study, 351 were diagnosed acute leukemia, and 179 (51%) classified as AML and 172 (49%) and ALL, which were excluded from the present work. Of the 179 AML, 92 (51.4%) were female and 87 (48.6%) were male, with ages ranging from 3 to 95 years of ag, with higher incidence in individuals in the age group of 41 to 65. Splenomegaly was the clinical finding more present, a total of 147 cases (82.1%), followed by hepatomegaly present in 132 cases (73.7%). The hemorrhagic events were observed in 55 cases (30.7%). Lymphadenopathy in turn was detected in 20 of 179 cases (11.2%). In order to classify subtypes of AML, we used a large panel of monoclonal antibodies, obtaining the following results: AML M0, 02 (1.1%) AML M1, 40 (22.3) AML M2, 60 (33.5) AML M3, 22 (12.3%) AML M4, 10 (5.6) AML M5, 13 (7.3%) AML M6 06 (3.4%) and AML M7 01 (0.6%). We observed some cases with aberrant expression of some antigens such as CD7, CD4, CD19, CD3, CD5 and TdT, CD 7 was present in 30 (16.8%), CD4 in 5 (2.8%), the CD 3 in 5 (2.8%), the CD19 in 3 (1.7%), the CD5 in 3 (1.7%) and TDT was in 7 (3.9%) cases of AML .the CD8 and CD79a was present in only a 1 case.

Investigação das alterações citogenéticas em pacientes pediátricos com leucemia linfóide aguda do Rio Grande do Norte

Leukemia is a heterogeneous group of hematologic malignancies that result from partial or total transformation of the blast cells. The Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in childhood, especially in male, Caucasian children younger than 14 years. Several criteria are adopted to classify ALL, including the cell morphology, cytochemistry, immunophenotyping and cytogenetic analysis. Cytogenetic studies allow a more detailed analysis to detect chromosomal abnormalities of leukemic cells. These modifications will determine the diagnosis, classification, stage characterization, remission assessment and prognosis. In this study were evaluated 30 patients, aged from four months to seventeen years, of both sexes and various ethnicities. The age distribution showed that 67% of patients had between one and ten years (with mean age of XX years old), the most prevalent ethnic was Caucasian (50%) and 57% were males. According to immunophenotype, 93% of patients had B-cells progenitor ALL and 7% early lineage T. Considering the total studied population, the most frequent medical findings were lymphadenopathy (37%), hepatomegaly (77%) and splenomegaly (70%), where one patient could present more than one of these medical findings. Regarding the CBC, the majority of patients had hemoglobin below 10 g / dl (73%), leukocyte count less than 10.000/μL (60%) and platelet count below 150.000/μL (83%). Chromosomal abnormalities were observed in 64% of all patients, where hyperdiploidy was the most common numerical change (67%), followed by hypodiploid (33%). All these data are in agreement with the literature. Moreover, complexes structural and/or number changes not yet described in literature were observed, which indicated poor prognosis. Finally, we concluded that this study demonstrated the importance of cytogenetic study in the diagnosis and identification of prognostic factors in pediatric patients with ALL in Rio Grande do Norte. The results obtained in this study are extremely useful and emphasizes that surveys of this nature must be conducted more frequently in our state

Função pulmonar de crianças com leucemia aguda

Introduction: The leukemias are the most common malignancy in children and adolescents. With the improvement in outcomes, there is a need to consider the morbidity to generate the protocols used in children under treatment. Aim: To evaluate pulmonary function in children with acute leukemia. Method: This study is an observational cross sectional. We evaluated 34 children distributed in groups A and B. Group A comprised 17 children with acute leukemia in the maintenance phase of chemotherapy treatment and group B with 17 healthy students from the public in the city of Natal / RN, matched for gender, age and height. The thoracic mobility was evaluated by thoracic expansion in the axillary and xiphoid levels. Spirometry was measured using a spirometer Microloop Viasys ® following the rules of the ATS and ERS. Maximal respiratory pressures were measured with digital manometer MVD300 (Globalmed ®). The maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured from residual volume and total lung capacity, respectively. The data were analyzed using the SPSS 17.0 software assigning the significance level of 5%. Descriptive analysis was expressed as mean and standard deviation. T'student test was used to compare unpaired values found in group A with group B values, as well as with the reference values used. To compare the respiratory coefficients in the axillary level with the xiphoid in each group, we used paired testing t student. Results: Group A was significantly decreased thoracic mobility and MIP compared to group B, and MIP compared to baseline. There was no significant difference between spirometric data from both groups and the values of group A with the reference values Mallozi (1995). There was no significant difference between the MIP and MEP values and lower limits of reference proposed by Borja (2011). Conclusion: Children with acute leukemia, myeloid or lymphoid, during maintenance phase of chemotherapy treatment have reduced thoracic mobility and MIP. However, to date, completion of clinical treatment, the spirometric variables and the strength of the expiratory muscles appear to remain preserved in children between five and ten years

Avaliação clínica e microbiológica da mucosa oral de crianças com leucemia linfoblástica aguda, submetidas à ação profilática do gluconato de clorexidina A 0,12%

Regarding the morbidity potential of oral complications in patients with leukemia, it evaluated the clínical and microbiologic changes of oral mucosal in children with LLA, with age range of O to 15 years old, undergone the chemotherapy antineoplastic and for the use prophylactic of chlorhexidine gluconate 0,12% during ten days, that was utilized in each chemotherapy treatment stage. The collect for rnicrobiological study was obtained preferentiality in intensification stage at the end prophylatic treatment. The study grouup had 20 children, where it observed clinically decrease in frequency of mucositis, with 8 cases (40%) only. In microbiological examination observed one reduced incidence of pathogenic microorganisms with Staphylococcus coagulase- negative (40%), Klebsiella pneumoniae (5%), Escherichia coZi enteropathogenic (15%), Stenotrophomonas maltophilia (5%) e Candida albicans (35%). The findings obtained in the present trial suggest that the use of chlorhexidine gluconate 0,12% can be responsible for incidence reduced of mucositis, but it wasn t possible to make correlation between isolated pathogenic microorganisms and mucositis development

Investigação do funcionamento cognitivo de pacientes pediátricos diagnosticados com leucemia linfóide aguda - LLA

The present work investigated the cognitive operation of children diagnosed with acute lymphoblastic leukaemia (ALL), accompanied at pediatric oncologic institutions at the city of Natal/RN. Had participated in this study twenty children, of both sexes, between six and twelve years old, with the ALL diagnostic, who were in treatment (n=10) and out of treatment for at least one year (n=10) and were submitted exclusively to chemotherapy as CNS prophylaxis. The utilized protocol of neuropsychological evaluation covered the following cognitive abilities: intellective capability, attentional and memory systems, and executive functions. Data was analyzed through descriptive and inferential measures, with the support of the Mann-Whitney U Test and T-test, considering the influence of the variables sex, age at diagnostic and the past time since the beginning of the treatment over children s performance. The intellective capability evaluation showed low score to the out-of-treatment groups, female and children under five years old to the diagnostic. In concern of attentional systems, groups showed the expected performance. In a relevant way, in the evaluation of executive functions, were found reduced scores within all groups, especially inside the in-treatment group. Memory evaluation pointed to reduced performance in items concerning to learning evolution and spontaneous evocation after interference to the several groups. It can be concluded, reffer to the occurrence of transitory and permanent impact associated to the intrusion of chemotherapic components during the maturational course of the CNS. It s expected that the present investigation and the development of similar studies enable major comprehension about the mode, extension and repercussion of these damages subsidizing the development of strategies which may minimize them and provide better xxiii life quality to this clinical subgroup

Avaliação das habilidades neurocognitivas em crianças e adolescentes sobreviventes da Leucemia Linfoide Aguda - LLA

The present study investigated the impact of the treatment modalities of Acute Lymphoblastic Leukemia on neurocognitive abilities of children and adolescents survivors, aged between 6 and 16 years of age, accompanied in pediatric oncology sectors of public health services in the cities of Campina Grande-PB and Natal-RN. The study included 52 children, 13 of these being children and adolescents diagnosed with leukemia and 39 healthy children matched in relation to the study group considering gender, age, school type and level of maternal education. Later the group of children with leukemia was subdivided into two subgroups depending on treatment modality which were submitted: Group 1A (only chemotherapy) and 1B (chemotherapy and radiotherapy). All participants were subjected to a battery of neuropsychological tests that investigated the following neurocognitive abilities: intellectual ability, memory system, attention, visuospatiality and visuoconstruction, processing speed and executive functions. Data were analyzed using descriptive and inferential measurements with the aid of the U test of Mann-Whitney and T test, considering the influence of the variables: sex, age at diagnosis, time since completion of treatment and level of schooling mothers, on the performance of children. Overall, it is concluded that the illness and the treatment of acute lymphoblastic leukemia significantly favors the emergence of cognitive deficits, particularly in terms of visuospatial skills, and executive skills visoconstrutivas. In turn, the treatment modality of radiotherapy is associated with the presence of more severe deficits, highlighting the significant impact on the speed of information processing. It is hoped that the results presented here will contribute to a better understanding of the nature and extent of neurocognitive effects arising ALL treatment

Frequência e significado clínico da expressão da glicoproteína P e da proteína relacionada a resistência a múltiplas drogas na leucemia mielóide aguda

Despite the advances in the cure rate for acute myeloid leukemia, a considerable number of patients die from their disease due to the occurrence of multidrug resistance (MDR). Overexpression of the transporter proteins P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) confer resistance to the treatment these leukemias. OBJECTIVE: To analyze the expression of the Gpp and MRP1 in patients with AML by flow cytometry (FC) and to determine the correlation between expression and demographic and also clinical and laboratorial variables. METHODS: Bone marrow and peripheral blood samples from 346 patients with a diagnosis of AML were assessed for the expression of Pgp and MRP1 by FC. RESULTS: The expression of Pgp and MRP1 was found in 111 (32.1%) and 133 (38.4%) patients, respectively, with greater prevalence in older patients and lower in adolescents, observing also a high incidence in patients with refractory disease, recurrence and secondary in comparison with the cases of de novo AML. Regarding the laboratory findings, we observed a higher correlation statistically significant between the expression of Pgp and MRP1 in AML CD34+ and FAB AML M7, M5A and M2 and lower the M3 subtype, not observed statistically significant correlation between the phenotype MDR and other laboratory data such with hemoglobin, leukocyte count, platelet count, aberrant expression of lymphoid antigens (CD2, CD7 and CD19) and clinical signs related to the disease. CONCLUSIONS: The results showed that the detection of MDR phenotype by flow cytometry can be a molecular marker for prognosis independent patients diagnosed with AML.

Avaliação do desenvolvimento infantil e a influência dos fatores biopsicossociais em crianças com cardiopatia congênita

Child development is the result of the interaction of biological, psychological and social factors. Hostile environment, income, offered stimuli, as well as the presence of a chronic illness are issues that may interfere significantly. Considering the chronic diseases, we can identify congenital heart disease (CHD) is characterized by anatomical heart defects and functional and currently has presented an incidence of up to 1% of the population of live births. This research aimed to evaluate child development and verify an association with the commitment by biopsychosocial factors of children with and without CHD. Study participants were children from zero to six years, divided into three groups: Group1- 29 children pre-surgical congenital heart disease, Group2- 43 children post-surgical cardiac patients and Group3- 56 healthy children. The instruments used were a biopsychosocial questionnaire and the Screening Test Denver II. Of the total of 128 children evaluated, 66 (51.56%) are girls, and ages ranged from two months to six years (median 24.5 months). In G1 and G2 predominated acyanotic heart disease (55.2% and 58.1%). Regarding the Denver II reviews, children with heart disease had more development ratings "suspicious" and "suspect/abnormal", and 41.9% of children who have gone through surgery had characterized its development as "suspect/abnormal" . In the group of healthy children 53.6% were classified as developmental profile "normal" (p = ˂0,0001). On the areas of Denver II, among children with heart disease was greatest change in motor areas (p = 0.016, p = ˂0,001). The biopsychosocial variables that were related to a possible developmental delay were gender (p = 0.042), child's age (p = 0.0001) and income per capita (p = 0.019). There were no associations between the variables related to the treatment of disease, information, understanding of the disease and the way parents treat their children. In the group of healthy children showed that children who underwent hospitalization rates were more changes in development (p = 0.025) and the higher the number of admissions over these changes have intensified (p = 0.023). The results suggest that children with congenital heart disease have likely delayed development. It was also observed that there is a significant difference between the children who have gone through surgery, those who are still waiting for surgery only doing clinical follow-up. Changes in the development are more connected motor areas can be explained by the characteristic features of the disease and treatment, such as dyspnea, fatigue, care and limitations in daily activities. The gender and age appear to be decisive in the development as well as healthy children go through hospitalization experience. Already in children with heart disease, it was realized that social variables involved in the disease and the treatment did not affect the development. This question can be understood by means of protective factors and resiliency, as this population receives family and social support.