Análise in vitro da atividade antifúngica e de toxicidade da anfotericina B pré-aquecida

The aim of this work was to evaluate how an aqueous micellar system containing Amphotericin B (AmB) and sodium deoxycholate (DOC) can be rebuilt after heating treatment. Also a review of the literature about the new physicochemical and biological properties of this new system was carried out. Afterwards, heated (AmB-DOC-H) and unheated (AmB-DOC) micelles were subsequently diluted at four different concentrations (50mg.L-1, 5mg.L-1, 0.5mg.L-1 and 0.05mg.L-1) to perform the physicochemical study and, then, the pharmacotoxicity assay, in which two cell models were used for the in vitro experiments, Red Blood Cells (RBC) from human donors and Candida parapisilosis (Cp). While potassium (K+) and hemoglobin leakage from RBC were the used parameters to evaluate the acute and chronic toxicity, respectively, the efficacy of AmB-DOC and AmB-DOC-H were assessed by K+ leakage and cell survival rate from Cp. The spectral study revealed a slight change on the aggregate peak from 327nm to 323nm for AmB-DOC-H compared to AmB-DOC. Concerning the toxicity, although AmB-DOC and AmB-DOC-H presented different behavior for hemoglobin leakage, AmB-DOC produced higher leakage than AmB-DOC-H at high concentrations (from 5mg.L-1) with values tending to zero. However, concerning K+ leakage, both AmB-DOC and AmB-DOC-H, showed similar profile for both cell models, RBC and Cp (p<0,05). AmB-DOC-H and AmB-DOC also revealed similar profile of activity against Cp with equivalent survival rate. In short, the AmB-DOC-H showed much less toxicity than AmB-DOC, but remained as active as the late one against fungal cell. Therefore, the results highlight the importance of this new procedure as a simple, inexpensive and safe alternative to produce a new kind of micelle system for treatment of systemic fungal infections

Alterações nas concentrações das SRAT, conteúdo de GSH e atividade da CAT em pacientes com esquistossomose aguda

Schistosomiasis is an ancient disease caused by helminth Schistosoma mansoni and is a public health problem in Brazil. The granulomatous lesion, typical of the disease, associates itself with increase in the oxidative damage through the generation of free radicals. The aim of this work was to evaluate the occurrence of changes in parameters oxidant / antioxidant that are part of the human defense system, and observe whether they would cause oxidative stress in subjects with schistosomiasis. Moreover, correlating with some biochemical and hematological parameters. Two groups were selected for study, consisting of individuals of both sexes, aged between 16 and 30 years. A control group, formed by individuals without schistosomiasis (n = 30) and a test group, formed by individuals with schistosomiasis (n = 30). The evaluation of lipid peroxidation in plasma was performed by determination of malondialdehyde and antioxidant defense by the quantification of reduced glutathione and catalase activity. For the parameters that assess oxidative stress, the results showed a decrease in the content of reduced glutathione and no change in the activity of catalase, with an increase in the value of malondialdehyde. Therefore, the data found suggest the occurrence of oxidative stress in subjects with schistosomiasis. Of the parameters that assess hepatic function, only levels of aspartate aminotransferase have been high, while there was a decrease of bilirubine. There was a significant change in the lipid profile (p <0.5), however with regard to the renal function of patients, there was a decrease in creatinine. The assessment hematological, made through hemogram and the quantification of hemoglobin, shows increase of eosinophils individuals in the group test, which can be related to the presence of the parasite. The amendments suggest the involvement of oxidative stress in the pathophysiology of this disease

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

Efeitos da administração aguda de quetamina sobre as oscilações eletrofisiológicas da região CA1 hipocampal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

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

Análise da toxicidade no açude Riacho da Cachoeira, Lajes Pintadas (RN): um desafio interdisciplinar

Contamination by complex mixtures of various origins has been explored and studied for decades. Radon is a naturally occurring environmental contaminant that causes carcinogenic effects. These emissions can cause mutations in the lung tissue, which can initiate a carcinogenic process. Thus the dam Creek Falls, located in the municipality of Lajes Pintadas, was chosen for the development of this study, since cancer rates in the region reach 9% of the population annually, with this, the main objective of this study was evaluate the mutagenicity and toxicity of Riacho da Cachoeira damunder the influence of radon. The methodology ecotoxicological tests were performed with Ceriodaphinia dubia, as well as tests with Tradescantia pallida genotoxicologicos and Oreochromis niloticus. To understand how the population of Pintadas Slabs realizes the environment, we performed a study of environmental perception. The test results indicated that the reservoir water is toxic to test organimos exposed, found heavy metals, chloride, total and fecal coliforms as well as radon levels above the maximum allowed under Brazilian law. These results can be justified because it is so complex samples composed of different compounds that interact only with each other or causing synergistic effects. It was concluded that the dam Creek Waterfall, is contaminated with radon, as well as heavy metals, coliforms and chloride, causing toxic effects to the natural community. Thus, further studies should be performed with the human population of the region, to verify that the high rates of cancer in the population of the municipality may be linked to the presence of natural radiation. Thus, it is expected that the competent bodies that administer the municipality of Lajes Pintadas take reasonable steps to minimize risks and ensure the health of the community that still makes use of the weir

Avaliação do potencial de toxicidade de florações de cianobactérias como subsídio para ações de gestão ambiental em açudes do semiárido potiguar

Blooms negatively compromise the aquatic environment, plants, animals and human health.Some species are toxin-producing, such as the neurotoxin saxitoxin and the hepatotoxin microcystin, which may contaminate water reservoirs, as those existing in the semiarid region of Rio Grande do Norte (Brazil) which are used to supply the population, fishing, aquiculture and recreational activities, thereby providing the risk of human exposure through water intake, dermal contact and respiratory tract. Thus, it is recommended a constant monitoring of the density of cyanobacteria with the quantification of cyanotoxins. One goal with this work was the monitoring of water in four reservoirs in semiarid of RN through the identification and enumeration of cyanobacteria and through the identification and quantification of cyanotoxins by ELISA. Furthermore, we intended to assess the environmental perception of farmers and artisanal fishers in reservoirs of semiarid of RN through semi-structured interviews with questions mostly related to water and eutrophication. Through these objectives the aim was the development of management strategies for aquaculture and prevention of risks to public health. The results showed that the highest values of microcystins were found in the rainy season. Standards for drinking water, according to the guidelines of Ministry of Health 2914/2011 and CONAMA 357/05, setting the maximum values for raw water density of cyanobacteria: 50,000 cel.mL-1; microcystin: 1 μg. L-1 and saxitoxin: 3 μg. L-1. The values found for microcystin ranged between 0.00227 μg. L-1 and 24.1954 μg. L-1. From 128 samples analyzed, 27% were above the limit. There was no clear seasonal pattern for saxitoxins and their values ranged between 0.003 μg. L-1 and 0.766 μg. L-1 with none of the values above the limit. Furthermore, 76% of the densities of cyanobacteria values were above the limit. About environmental perception, 52 interviews were conducted and the results show that the respondents recognize the main uses of water of the rervoirs, recognize the importance and have a positive view about the reservoirs. They also realize that the water has a poor quality and can cause health problems. The results provide data showing the persistence of cyanobacteria and cyanotoxins, many times over the limit, reinforcing the importance of constant monitoring. The assessment of environmental perception gives foundation for later proposed environmental education linked to public health management into the context of this particular population, making it more effective

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.

Análise estrutural e avaliação do efeito condroitim sulfato extraído de tilápia (Oreochromis niloticus) em modelo de peritonite aguda

Chondroitin sulfate (CS) is a naturally glycosaminoglycan found in the extracellular matrix of connective tissues and it may be extracted and purified those tissues. CS is involved in various biological functions, which may be related to the having structural variability, despite the simplicity of the linear chain structure from this molecule. Researches in biotechnology and pharmaceutical field with wastes from aquaculture has been developed in Brazil. In recent decades, tilapia (Oreochromis niloticus), native fish from Africa, has been one of the most cultivated species in various regions of the world, including Brazil. The tilapia farming is a cost-effective activity, however, it generates large amount of wastes that are discarded by producers. It is understood that waste from tilapia can be used in research as a source of molecules with important biotechnological applications, which also helps in reducing environmental impacts and promote the development of an ecofriendly activity. Thus, nile tilapia viscera were subjected to proteolysis, then the glycosaminoglycans were complexed with ion exchange resin (Lewatit), it was fractionated with increasing volumes of acetone and purified by ion exchange chromatography DEAE-Sephacel. Further, the fraction was analyzed by agarose gel electrophoresis and nuclear magnetic resonance (NMR). The electrophoretic profile of the compound together the analysis of 1H NMR spectra and the HSQC correlation allow to affirm that the compound corresponds to a molecule like chondroitin sulfate. MTT assay was used to assess cell viability in the presence of CS tilapia isolated and showed that the compound is not cytotoxic to normal cells such as cells from the mouse embryo fibroblast (3T3). Then, this compound was tested for the ability to reduce the influx of leukocytes in model of acute peritonitis (in vivo) induced by sodium thioglycolate. In this context, it was done total and differential leukocytes counting in the blood and peritoneal fluid collected respectively from vena cava and the peritoneal cavity of the animals subjected to the experiment. The chondroitin sulfate for the first time isolated from tilapia (CST ) was able to reduce the migration of leukocytes to the peritoneal cavity of inflamed mice until 80.4 per cent at a dose 10µg/kg. The results also show that there was a significant reduction (p<0.001) of the population of polymorphonuclear leukocytes from peritoneal cavity in the three tested doses (0.1µg/kg; 1µg/kg and 10µg/kg) when it was compared to the positive control (just thioglycolate). Therefore, since the CST structure and mechanism of action has been completely elucidated, this compound may have potential for therapeutic use in inflammatory diseases

Avaliação da toxicidade subcrônica e reprodutiva do extrato seco de pericarpo de passiflora edulis variedade flavicarpa degener em ratos

The pericarp of Passiflora edulis var. flavicarpa Degener is now being investigated for medicine purposes. There are no reports about it toxicity. The aim of the present study was investigate the sub chronic toxicity in male rats and reproductive toxicity in pregnant rats and exposed fetuses of an extract obtained by infusion of the pericarp in water (1:3 m/v;100o C, 10 min). The extract composition was evaluated by tube reactions and thin lawyer chromatography (TLC). Adult male rats (n=8) were treated with 300 mg/kg of the extract, by gavage, during 30 days and pregnant rats (n=7) from gestation day 0 to day 20. Control received tap water (1 mL). Water and food intakes and body weight gain were recorded. At day 29 of treatment the sexual behavior of the males was analyzed and then half of males from each group received cyclophosphamide (50 mg/kg, i.p.) to (anti)genotoxic assessment in bone marrow. At day 30, males were anesthesized for parameters collection. At day 20 of gestation, the dams were anesthesized for reproductive performance evaluation. The fetal analysis was conducted by visceral and skeletal. Phytochemical analysis revealed the presence of flavonoids, unspecific alkaloids, phenols and triterpenic compounds. Statistical analysis revealed absence of significant differences between experimental and control. This study suggest that the aqueous extract obtained from pericarp of P. edulis var. flavicarpa Degener was not able to promote toxic effects in rats. Cytotoxicity was evaluated with the PCE/NCE ratio (NCE=normochromatic erythrocytes). Statistical analysis (mean ± SEM) revealed absence of changes in the frequency of MNPCE (negative control: 3.26±0.42; positive control: 11.72±1.02; negative experimental: 4.02±0.13; positive experimental: 10.47±0.87) or cytotoxicity (negative control: 0.37±0.08; positive control: 0.23±0.05; negative experimental: 0.37±0.07; positive experimental: 0.23±0.02). This study suggests that the extracts showed no (anti)genotoxic and no cytotoxic activities under the experimental conditions.

miRNAS circulantes como biomarcadores para fibrilação atrial aguda

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Some non-coding RNAs (miRNAs) have been involved in regulatory activity in arrhythmogenesis, targeting genes that contribute to the development of AF. The present study aimed to evaluate the expression of candidate miRNAs in plasma from patients with AF and new-onset AF and its application as future markers for diagnosis and monitoring of disease. miR-21, miR-133a, miR-133b, miR-150, miR-328 and miR-499 were selected as targets in this study through a prior literature review. They were isolated from plas-ma of individuals aged from 20 to 85 years old with AF (n = 17), new-onset AF (n = 5) and without AF (n = 15), where the latter was the control group. The results were ana-lyzed by Real-Time PCR (RT-PCR) with miScript SYBR Green PCR. We observed that miR-21, miR-133b, miR-328 and miR-499 had different levels of expression be-tween the three groups (p <0.05). Increased expression of miR-21 (0.6-fold), miR-133b (1.4-fold), miR-328 (2.0-fold) and miR-499 (2.3-fold) in patients with new-onset AF when compared to AF and control subjects. The miR-133a and miR-150 expression did not differ among the groups. miR-21, miR-133b, miR-328 and miR-499 may be potential biomarkers for AF as well as for new-onset AF, for monitoring and for the di-agnosis. These findings may contribute to the understanding of the process that trig-gers AF and suggest application these molecules as future biomarkers for AF.