Navegando por Assunto "Malária falciparum"
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Item Acesso aberto (Open Access) Avaliação dos níveis séricos de cortisol e de hidroepiandrosterona em pacientes com malária por Plasmodium falciparum não-complicada(Universidade Federal do Pará, 1997) LIBONATI, Rosana Maria Feio; MEDONÇA, Berenice Bilharinho de; http://lattes.cnpq.br/8356126875514076; SOUZA, José Maria de; http://lattes.cnpq.br/6459204248879587The main purpuse of our study was to determine the levels of both cortisol and dehydroepiandrosterone (DHEA) in serum samples from patients suffering from Plamodium falciparum malaria. Since cortisol is potentially immunesupressive, and, conversely, DHEA is inherently immunopotentiating, we sought to assess the possible association between serum levels of these steroids and patient's clinical conditions. We enrolled to participate in this study 24 patients aged 12 to 47 years, of whom 18 were male and 6 female, suffering from uncomplicated P. falciparum malaria. All patients lived in areas of the Amazon were malaria is endemic. Half of them were found to be primo-infected, whereas the others were being reinfected by P. falciparum when recruited for this investigation. Blood samples were obtained from each patients as follows: at 20-minutes intervals during the pre-treatment phase (i. e. on day 0, D0), 24 hours after starting drug therapy (D1) and at the 8th day of follow-up (D7), when patients were asymptomatic. All patients at D7 presented with negative parasitemia. Serum levels of cortisol and DHEA were measured on D0, Dl and D7 and D0 and D7, respectively. In addition, the determination of IgG antibodies to both P. falciparum and P. vivax was performed only on D0. Our results indicated that levels of cortisol in serum samples collected on D0 were significantly higher than those of D1 and D7. High levels of cortisol on D0/D1 and significant parasitemia on D1 led us to postulated that this corticosteroid may interfere with the initial response of P. falciparum-infected patients to treatment. The cortisol levels did not correlate with the intensity of fever, duration of illness and the levels of IgG antibories to P. falciparum. These findings suggest that temperature does not interfere with the cortisol levels, and these, on the other land, do not significantly ralate to either antibody response or the duration of illness. The DHEA levels were found to be significantly more elevated on D0 than on D7, even though patients were already symptomatic for more than one day when first serum samples was taken. The progressive decrease in the DHEA levels is therefore likely to be mediated by a continuous stimulus from the hypothalamic-pituitary-adrenal (HPA) axis. Similarly to cortisol, the DHEA levels on D0 correlated significantly with D1 parasitemia. Thus, it is suggested that in cortisol levels paralels that for DHEA. Of interest, the DHEA serum levels seem to inversely correlate with the duration of illness, in spite of high levels of this steroid detected at the pre-treatment phase. A not significant correlation has been noted if cortisol and DHEA serum levels are compared with temperature. This clinical parameter, however, was found to directly interfere with the correlation that exist between both cortisol and DHEA levels. It is known that fever reflects the occasion when erythrocytes disrupt from the schizogony, with release of cytokines , which act as an acute stimulating factor for the HPA axis. It would therefore be proposed that liberation of both hormones has a commom mechanism. The lack of significant interrelationships between DHEA levels and IgG antibodies indicates that this hormone does not seem to interfere with the production of antibodies by P. falciparum infected patients.Item Acesso aberto (Open Access) Correlação entre as concentrações sérica e eritrocitária de quinina no estado de equilíbrio em pacientes com malária por Plasmodium falciparum não complicada(Universidade Federal do Pará, 2007) GUIMARÃES, Erika Rodrigues; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098The correlation between the serum and red blood cells concentrations of quinine was studied in children and adults with falciparum malaria uncomplicated in Cachoeira of the Piriá, in the State of Pará. The patients had received the oral scheme of quinine (3 days) + doxycyclina (5 days) + primaquine (6º day). Quinine concentration in the serum and the red blood cells samples was measured by High Performance Liquid Chromatography in the third day of treatment. The average of the serum concentration of the quinine in children with uncomplicated falciparum malaria was of 0,723 ± 0,6 μg/mL, and 0,537 ± 0,38 μg/mL for the red blood cells. And the relationship between the serum and red blood cells concentration was 1,89 ± 1,25 μg/mL, had not difference statistical significant between those concentrations. The average of the serum concentration of adult individuals was of 1,27 ± 1,12 μg/mL, and 0,63 ± 0,48 μg/mL for the red blood cells. The relationship between those concentration was of 2,27 ± 1,06 μg/mL. The results had shown that it did not have significant statistical difference between the averages of the relation of quinine levels in the serum and the red blood cells of the children and the adults.Item Acesso aberto (Open Access) Determinação de mefloquina e carboximefloquina em pacientes com malária por plasmodium falciparum no estado do Amapá(Universidade Federal do Pará, 2008) BORGES, Larissa Maria Guimarães; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098The determination of plasmatic and erythrocyte concentrations of mefloquine (MQ) and carboxymefloquine (CMQ) were studied in children and adults with malaria by Plasmodium falciparum not complicated in the Amapa state. The adult patients received oral outline of MQ 20 mg/kg divided in two days and artesunate 4 mg/kg/day for three days. For children the dose of MQ followed the schedule recommended by the manual of malaria therapy. Concentrations of MQ and CMQ in erythrocytes were quantified by high performance liquid chromatography on the third day of treatment (D3) and plasma levels were measured in the third and second fortieth day after the institution of therapy (D3 and D42). The average concentration of MQ and CMQ in plasma of children in D3 were 1.84 ± 0.83 μg/mL and 1.44 ± 0.70 μg/mL, and in erythrocytes 5.26 ± 1.46 μg/mL and 1.18 ± 0.65 μg/mL. In D42 the plasma concentrations were 0.45 ± 0.11 μg/mL and 0.51 ± 0.10 μg/mL, respectively. The relationship between plasma and erythrocytes concentrations of MQ and CMQ were 2.86 ± 1.27 and 0.75 ± 0.26. In adults, concentrations of MQ and CMQ in plasma were 2.43 ± 1.13 μg/mL and 1.10 ± 0.38 μg/mL, and in erythrocytes 5.51 ± 1.92 μg/mL and 1.08 ± 0.35 μg/mL, respectively. The plasma concentrations in D42 were 0.54 ± 0.15 μg/mL and 0.58 ± 0.93 μg/mL, respectively. The relationship erythrocyte:plasma for MQ was 3.03 ± 1.56 and 1.12 ± 0.29 to CMQ. The correlation coefficient between plasma and erythrocytes concentrations of MQ in children was 0.035 and adults 0.0436. For CMQ the correlation coefficient in children was 0.8722 and in adults 0.5155. The higher accumulation of MQ in the red blood cells allows us to emphasize the importance of the simple diffusion for the entry of the drug in the cell because of their physical and chemical characteristics.Item Acesso aberto (Open Access) Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum(Universidade Federal do Pará, 1997-12-04) SILVA, Rita do Socorro Uchôa; SOUZA, José Maria de; http://lattes.cnpq.br/6459204248879587The increasing resistance of P. falciparum strains to the current antimalarial drugs makes the searching of new drugs an urgent task. The compound Ro 42-1611 is an antimalarial drug that arises from a chinese herb Artabotrys uncinatus. Since its synthesis, Ro 42-1611 was used in three different clinical trials to treat falciparum malaria in Africa, but how it works in the South America malaria patients is obscure. Althouh being an effective antimalarial, a proper therapeutic dose to achieve the supressive cure of falciparum malaria has not been established yet. The purpose of this study is to evaluate the tolerance, the toxicity and the efficacy of 3 different dose schedules of Ro 42-1611 in the treatment of falciparum malaria. It was an open, prospective and randomized trial carried out in Maraba/Para State in male patients with maximum 80 kg bodyweight. All patients had fever or another constitutional malaria symptom and had a positive thick blood smear to P. falciparum (≥ 200 and ≤ 50,000 parasites/mm³). In a hospital, they were assigned into 3 groups according to drug administration time: Group I - 1,500 mg twice a day for 24 hours; Group II - 1,500 mg twice a day for 48 hours and Group III - 1,500 mg twice a day for 72 hours. Before treatment, the following procedures were recorded from all patients: personal data, height and weight, malarial signs and symptoms, history of simultaneous drug intake, body temperature, vital functions (respiratory rate, blood pressure), parasite count, haematology and blood chemistry assesments and electrocardiogram. Ouring the treatment, all those parameters were followed, including adverse reactions to Ro 42-1611. Statistical analysis (Friedman variance test) were performed on laboratory tests results. Sixteen patients were enrolled in the study: 5 patients in Group I; 6 in Group II and 5 patients in Group III. Among patients, age ranged from 17 to 41 years old (mean 266). body weight from 44 to 72 kg (mean 54.9). The assexual parasite count ranged from 200 to 40,000 parasites/mm³ . Regarding those variables, there were homogeneity in 3 groups. According to the protocol, clinical and laboratory data were evaluated, with the following results: the minimum and the maximum fever clearence time was 9 to 48 hours respectively. The mean assexual parasite clearence was 53.6 hours, without any statistical significance among the groups (p=0.7264). There were statistical significative difference (p=0.0046) in the hematocrit values before treatment (00), and the third (02) and the eighth (07) day of the follow-up. It was observed an increase in the leukocyte count between 02 and 07, also of statistical significance (p=0.0171), as well in the platelets of 00 and 07/02 and 07 (p=0.0001). Between DO and 07, statistical significative reduction ocurred in the values of total bilirrubin (p=0.0024), alkaline phosphatase (p=0.0195) and urea (p=0.0168). There were no statistical significative difference nor in the evalution of electrocardiogram results neither in the blood pressure. Short adverse reactions were mild to moderate. In the end of the treatment, 87,5% of patients were completely free of parasites, but just 2 achieved a radical cure (12,5%), both included in Group III. Any of the schedule treatment showed efficacy. Perhaps such efficacy might be attained using Ro 42-1611 in a superior dose, for a longer period of time or in association with other antimalarial in further studies.Item Acesso aberto (Open Access) Quinine levels in patients with uncomplicated falciparum malaria in the Amazon region of Brazil(2008-10) VIEIRA, José Luiz Fernandes; BORGES, Larissa Maria Guimarães; NASCIMENTO, Margareth Tavares Silva; GOMES, Andreza de Lourdes SouzaWe examined the plasmatic concentrations of quinine in patients with uncomplicated falciparum malaria in an endemic area of the Amazon region in Brazil in a prospective clinical trial, in which a standard three-day course of oral quinine plus doxycycline was used. We measured the quinine in the plasma samples on days 0 and 3by high performance liquid chromatography. The mean concentration of quinine was 6.04 ±2.21 µg/mL in male patients and 5.98 ±1.95 µg/mL in female patients. No significant differences in quinine concentration were observed between these two groups. All samples collected before starting treatment were negative for quinine. This information could help in the development of strategies for the rational use of antimalarial drugs in Brazil.Item Acesso aberto (Open Access) Relationship between plasma and red blood cell concentrations of quinine in Brazilian children with uncomplicated Plasmodium falciparummalaria on oral therapy(2009-04) VIEIRA, José Luiz Fernandes; GOMES, Andreza de Lourdes Souza; BORGES, Larissa Maria Guimarães; GUIMARÃES, Erika RodriguesWe determined the relationship between plasma and red blood cell concentrations of quinine in children with uncomplicated falciparum malaria from an endemic area of Amazonian region. Quinine was determined by high performance liquid chromatography with ultraviolet detection. In the steady state the ratio between plasma and red blood cell quinine concentration was 1.89 ± 1.25 ranging from 1.05 to 2.34. This result demonstrated that quinine do not concentrate in red blood cell of Brazilian children and characterize the absence of interracial difference in this relationship.Item Acesso aberto (Open Access) Validação de metodologia analítica para determinação de lumefantrina em plasma e sangue total adsorvido em papel de filtro por cromatografia líquida de alta eficiência (CLAE) em pacientes com malária por plasmodium falciparum(Universidade Federal do Pará, 2010-10-07) PINHEIRO, Priscila de Nazaré Quaresma; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098Among the tools to achieve the optimal treatment for malaria, it highlights the concentration monitoring of antimalarials in biological fluids. Considering that Coartem ® is used in first-line therapy for treatment of falciparum malaria, it is appropriate that this study aims to validate an analytical methodology for determination of lumefantrine in whole blood samples, adsorbed on filter paper, and in plasma by high performance liquid chromatography (HPLC) in patients with falciparum malaria uncomplicated, using liquid-liquid extraction. Were carried out studies of selectivity, linearity, calibration curve, limits of detection and quantification, recovery, intra and inter assay precision, stability and robustness. The samples for study of applicability of the proposed method, were collected from patients with falciparum malaria using Coartem ® (artemether-20mg + lumefantrine-120mg) on D3. The optimized chromatographic conditions were: wavelength 335nm, flow 1.2 mL / min. and a mobile phase consisting of acetonitrile-water (60:40, v / v) pH = 3,5. The liquid-liquid extraction can be efficient, because the average recovery was 101.3% for plasma and 84.3% for whole blood. The method was selective and linear in the concentration range of 160 to 1760ng/mL. The limits of detection and quantitation was 32ng/mL and 160ng/mL. The average coefficient of variation intra assay, plasma and whole blood, respectively, were 10.88 and 8.38% and inter assay of 13.21 and 11.78%. The compound proved to be stable in whole blood absorbed onto filter paper for 70 days. Modification of pH, flow and mobile phase composition did not significantly alter the resolution of the analytes, suggesting an adequate strength. The method proved effective in quantifying lumefantrine in whole blood samples from patients with falciparum malaria and the validation parameters are consistent with the recommendations of regulatory agencies in Brazil.Item Acesso aberto (Open Access) Validação de metodologia analítica por cromatografia liquida de alta eficiencia (CLAE), para determinação de mefloquina e carboximefloquina em amostras de sangue total adsorvidas em papel de filtro, em pacientes com malária por Plasmodium falciparum(Universidade Federal do Pará, 2010) ATAIDE, Patrícia Marques de; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098Among the main challenges for malaria control in Brazil and in the world, the advent of resistance to the Plasmodium, particularly Plasmodium falciparum, is presented as the most relevant. Mefloquine is a drug of first line for the treatment of falciparum malaria, and the availability of sensitive methods and low cost for monitoring of blood concentrations of the drug and carboxymefloquine assists in the optimization of drug regimens. In this sense, analytical methodology was validated in accordance with the parameters suggested by official regulatory agency for determination of mefloquine and its carboxylated derivative on the whole blood sample adsorbed on filter paper. The method was employed using High Performance Liquid Chromatography after liquid-liquid extraction of the analytes. The detection was performed at 222nm. No interference was observed in other antimalarials commonly used. The method was linear in concentration range from 0.25 to 2.5 μg/mL for mefloquine and its carboxylated derivative. The detection and quantification limits were 35 ng/mL and 70 ng/mL for mefloquine and carboxymefloquine, respectively. The average intra assay precision was 31±4% for mefloquine and 21±5% for carboxymefloquine. The average inter assay precision was 38±4% for mefloquine and 25±7% for carboxymefloquine. The average of recovery for concentrations of mefloquine ranging from 0.25 to 2.5μg/mL was 83±14% and carboxymefloquine varying from 0.375 to 3740 μg/mL was 88±11%. The drug was stable in samples adsorbed on filter paper for a period of a month. . The method showed to be robust for small changes on pH of the mobile phase. To evaluate the applicability of the method was performed determination of analytes in blood samples adsorbed on filter paper from patients with falciparum malaria. The average concentration of mefloquine was 0.861±0.723 μg/mL and carboxymefloquine 0.472±0.086 μg/mL. The validation parameters of the analytical methodology followed the recommendations proposed by the official agencies and the method showed to be appropriate for determination of mefloquine and carboxymefloquine in whole blood samples adsorbed on filter paper.