Navegando por Assunto "Cloroquina"

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Acesso aberto (Open Access)
Ação da hidroxicloroquina sobre neurônios da retina de embrião de galinha
(Universidade Federal do Pará, 2017-03-22) ROSÁRIO, Aldanete Santos; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
Hydroxychloroquine (HCQ) is currently used in the treatment of malaria and autoimmune diseases and others therapeutic purposes. However, this drug is known to cause side effects, including producing visual disturbances, which may be irreversible. The mechanisms that produce these visual disorders are not completely known. HCQ - related retinal toxicity may be due to high metabolic rate, being very susceptible to the action of xenobiotics and oxidative damages. Thus, this work aims to evaluate the effects of the HCQ on retinal cells, as well as their possible mechanisms of cytotoxicity. The model used in this work was of cultures of retina cells from chicken embryo. To evaluate cell viability, mitochondrial activity was measured by MTT. The lysosomal function was evaluated by the incorporation rate of the neutral red dye. The levels of reactive species of general oxygen and superoxide anion were evaluated by the CellROX probe and by Nitro Blue Tetrazolium (NBT) and total glutathione levels were quantified using the Ellman reagent. Viability was tested in mixed cultures (glia and neurons) or enriched cultures of neurons and glia after treatment with HCQ and compared with chloroquine (CQ). Cells were exposed to concentrations of 25μM, 50μM and 75μM for 24 hours. The results show that mixed cultures treated with CQ presented a reduction in viability of 36 and 61% at concentrations of 50μM and 75μM, respectively, whereas HCQ did not alter viability at any of the concentrations tested. However, when cultures enriched with glial cells were exposed to HCQ for 24 hours, the concentration of 75μM had a small reduction in cell viability, while that the reduction in neuronal cells was of 20, 33 and 56% at the concentrations of 25μM, 50μM and 75μM, respectively. Even a shorter treatment time (6 hours) there was loss of viability in retinal neurons. The incorporation of neutral red supravital dye was also altered in neuronal cultures treated with HCQ for 24 hours, with reduction of 19 and 32%, compared to the control for the concentrations of 50μM and 75μM, respectively. HCQ significantly reduced the levels of reactive oxygen species produced by the neuronal cells, mainly superoxide anion, 43, 52 and 61% for the concentrations of 25μM, 50μM and 75μM of HCQ in 24 hours of treatment, respectively. In concentrations of 50μM and 75μM of HCQ for 24 for hours, the levels of total glutathione in neuronal cells presented a reduction of 37 and 53%, respectively. When the glial cell conditioned medium was used in neuronal cells for 6 hours after treatment with HCQ, it completely reversed the drug-induced cytotoxicity. When total glutathione levels were measured in culture of glia treated with HCQ for 24 hours no changes were observed. These results suggest cytotoxic action of CQ in mixed culture of chicken embryo retina cells which is not observed in HCQ treatment. However, HCQ showed cytotoxic action when cells are cultured separately, mainly on neurons, which is reversed by some factor released by glial cells in the extracellular environment, and glutathione is a possible candidate to exert this neuroprotective function.
Acesso aberto (Open Access)
Avaliação da terapêutica da malária por Plasmodium vivax: perfil cinético da cloroquina e primaquina
(Universidade Federal do Pará, 2011) TEIXEIRA, José Ribamar Mesquita; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; SOUZA, José Maria de; http://lattes.cnpq.br/6459204248879587
Today search - new strategies for improving the treatment and control of malaria. The monitoring of plasma concentrations of drugs is an important tool that aims to provide more knowledge on the kinetics of several antimalarial drugs, aiming to achieve rapid therapeutic effect with reduced risk of toxicity. Thus, this study aimed to evaluate the therapeutic response to chloroquine and primaquine for vivax malaria patients, the plasma concentrations correlate with parasitemia, epidemiological data and evaluation of liver and kidney function, aiming at the optimization of various therapeutic regimens employed, evaluating if the responses are due to ineffective treatment of Plasmodium resistance to chloroquine or the presence of sub-therapeutic concentrations of drugs. Thus, we evaluated 40 patients with vivax malaria in the Program in Clinical Trials of Malaria Institute Evandro Chagas (Belém, Pará) in the period 2008 to 2010. Hemogram and other biochemical parameters were performed. The research of plasmodia in blood smear was performed and the parasitemia averaged 7187.5 ± 6732.7 parasitos/mm3. The prevalence of males with 67.5% of cases. The locations of malaria infection ranged from 14 municipalities in the state of Pará, most of which originates in the city of Anajás. For 42.5% of patients it was the first episode of the disease and 57.5% of applicants. In the evaluation of anemia by hemoglobin, there - if the levels below reference values in 60% of patients and hematological and biochemical parameters showed that the mean values of hematocrit and red blood cells showed highly significant difference between subgroups of patients and non-anemic anemic. The determination of chloroquine and primaquine in patients on D0, D2, D7, D14 and D30 were performed. The mean values of 0, 1102.1, 546.7, 185.8 and 98.6 ng / ml for chloroquine and 0, 210.2, 345.0, 91.7 and 0 ng/ml for primaquine.
Acesso aberto (Open Access)
Color vision loss in patients treated with chloroquine
(2003) VENTURA, Dora Selma Fix; SILVEIRA, Luiz Carlos de Lima; NISHI, Mauro; COSTA, Marcelo Fernandes da; GUALTIERI, Mirella; ALEXANDRE, Ruth Mayanna Araújo dos Santos; PINTO, Carolina Trindade; MOURA, Ana Laura de Araújo; RODRIGUES, Anderson Raiol; SAKURADA, Claudio; SAUMA, Maria de Fátima L. C.; SOUZA, John Manuel de
Patients that make use of chloroquine or hydroxychloroquine, drugs which are frequently administered for treatment of rheumatoid arthritis, lupus erithromatosus or malaria, may suffer alterations in color vision and in contrast sensitivity. The present work evaluates the visual function of these patients in a joint study of the University of São Paulo (USP), in São Paulo, and of the Federal University of Pará (UFPA), in Belém. Thirty two chloroquine user patients without alterations in the eye fundus exam were evaluated in São Paulo (n=10; aged 38 to 71 years; mean=55,8 years) and in Belém (n=22; aged 20 to 67; mean=40 years). The prescribed accumulated chloroquine dose was 45 to 430 g (mean=213 g; sd = 152 g) for the São Paulo group, and 36 to 540 g (mean=174 g; sd=183 g) for the Belém group. Tests were performed monocularly with corrected eye refractive state. Color discrimination was evaluated using the Cambridge Colour Test (CCT): the color discrimination threshold was measured first in the protan, deutan and tritan axes and, in succession, three MacAdam's ellipses were determined. The patient's color vision was also evaluated with color arrangement tests: the Farnsworth-Munsell 100 Hue (FM100), the Farnsworth-Munsell D15, and the Lanthony Desaturated (D15d) tests. We also measured the contrast sensitivity for black-and-white sine wave grating of twenty two patients. The results were compared with controls without ophthalmologic or neuro-ophthalmologic pathologies. Twenty four patients presented acquired dyschromatopsia. There were cases of selective loss (11 patients) and of diffuse loss (13 patients). Although losses were present in the FM100 there was no correlation between the FM100 error score and the ellipse area measured by the CCT. Moreover, three patients that scored normal in the FM100, failed to reach normal threshold in the CCT. The Lanthony test was less sensitive than the other two tests, since it failed to indicate loss in about half the patients, and the D15 was the least sensitive test, having failed to indicate loss in 9 out of 10 patients. Contrast sensitivity was within normal values for patients submitted to this test. The extent of losses in color discrimination was positively correlated with the accumulated dose. The CCT is recommended for follow up since it provides quantitative data that can be directly interpreted in CIE (Commission Internationalle d'Éclairage) color space.
Acesso aberto (Open Access)
Concentrações plasmáticas de primaquina e metemoglobinemia em pacientes com malária por Plasmodium vivax
(Universidade Federal do Pará, 2010) FERREIRA, Michelli Erica Souza; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098
The vivax malaria is a disease that effects around 40% of the world, to treat it, chloroquine (150 mg) and primaquine (15 mg). This is an 8-aminoquinoline with tissue schizonticide action. Among the adverse effects enhance the capacity to hemoglobin oxidation, dose-dependent, which is exacerbated in individuals with glucose-6-phosphate dehydrogenase deficiency. When considering the lack of studies concerning the methemoglobin levels and its correlation with primaquine concentrations plasma in patients with vivax malaria, is justified this study using as tools to monitor the plasma primaquine concentrations and its correlation with methemoglobin levels. In this sense, it was followed up clinically and laboratory findings of 20 patients with vivax malaria before (D0) and after three (D3), seven (D7) and fourteen (D14) days starting the treatment, as well as validation of the method for primaquine determination by high performance liquid chromatography (HPLC). Methemoglobinemia was evaluated using the method of Hegesh et al. (1970) and glucose-6-phosphate dehydrogenase by colorimetric method of Brewer et al. (1962 ). The methodology validated was demonstrated efficient for primaquine determination, whose average levels at D3, D7 and D14 were 227 ± 106 ng / mL, 191 ± 97 ng / mL and 160 ± 128 ng/mL. In the analysis according to gender was not observed differences significant in the drug levels in several days of study. The average methemoglobin levels in D0, D3, D7 and D14 were 1.15 ± 0.9%, 4.1 ± 2%, 5.7 ± 2% and 3 ± 1.4%, respectively. There was an increase in the methemoglobin level after drug administration, without difference by gender. There was not significant correlation between the methemoglobin levels and primaquine concentrations plasma in both sexes. The coefficients of Pearson correlation for males and females were 0.8296 and 0.8137, respectively. We observed impaired expression of the enzyme glucose-6-phosphate dehydrogenase in six male patients without differences between the methemoglobin levels and primaquine concentrations plasma, compared with patients with expression normal of the enzyme.
Acesso aberto (Open Access)
Eletrorretinografia multifocal: desenvolvimento de método avaliativo e aplicação em pacientes com toxoplasmose ocular e investigação funcional da função retiniana em pacientes com malária, infectados pelo P. Vivax
(Universidade Federal do Pará, 2014-11-03) CARVALHO, Aline Correa de; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718; SILVEIRA, Luiz Carlos de Lima; http://lattes.cnpq.br/9383834641490219
The current thesis was composed by two studies performed in parallel. The first purpose was the development of a reliable method to classify the electroretinographic responses and to validate this method in ocular toxoplasmosis. The second purpose was to investigate the effect of the acute use of chloroquine in the retina of vivax malaria patients, which received the standard treatment of the Ministry of Health of Brazil. The experimental tool of both studies was the multifocal electroretinogram (mfERG). In the first study the Veris system was used to test 10 healthy subjects to calculate a signal to noise ratio analysis in order to find the best values to separate normal responses from impaired retinal responses. The final results of this analysis were applied in three patients with visual loss due ocular toxoplasmosis. The results showed an optimal signal to noise ratio of 0.47 to separate waveforms with and without signal. The signal to noise ratio of 0.47, 0.44, 0.48, 0.57, 0.78, 1.21 were optimal to separate normal responses from progressively attenuated responses. The application of the signal to noise ratio analysis into ocular toxoplasmosis patients was able to map the retinal area with no activity evoked by the light. The second study was performed using mfERG to evaluate 48 vivax malaria patients which received chloroquine-based treatment. Their data were compared to 37 healthy subjects. The results showed that number of infections ranged between from 01 to 18 times. During the treatment, the mean dosage of intaken chloroquine was 5429 ± 782.3 mg. The cumulative dosage normalized to the body mass ranged from 14.58 to 545.45 mg/kg. No difference was observed in the mfERG amplitude and implicit time obtained from malaria patients and control group at any concentric rings of the visual field. There was no significant correlation between the retinal activity with the chloroquine cumulative dosage. It was concluded that the signal to noise analysis developed in this thesis can be used as a reliable method to study impaired retinal function, including the mapping of ocular toxoplasmosis consequences; and the acute use of chloroquine for malaria treatment caused no impairments to retinal activity recorded by mfERG.
Acesso aberto (Open Access)
Estimativas da dose e dos parâmetros farmacocinéticos da cloroquina em pacientes com malária por Plasmodium vivax na amazônia brasileira
(Universidade Federal do Pará, 2019-10-07) FERREIRA, Michelle Valéria Dias; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; https://orcid.org/0000-0003-4842-8762
Malaria caused by Plasmodium vivax is still an important public health issue in the Brazilian Amazon basin, with 169,000 cases recorded in 2018. The treatment is based on the concurrent administration of chloroquine and primaquine. Despite the efficacy and tolerability over 60 years of use, there are several issues related to chloroquine uses that should be elucidated in the Brazilian Amazon. The aims of the present study were to estimate the doses administered and to assess the pharmacokinetics parameters of chloroquine by a no-compartmental approach associating with patients age and gender. A prospective study of cases was carried out in the municipality of Anajas, PA, with 161 patients diagnosed with malaria caused by P. vivax, 81 children and 80 adults. The geometric mean of parasites at admission were 2,644 in children and 1,210 per mm3 of blood in adults. Parasites were cleared from the peripheral blood within 28 days. The doses of chloroquine administered ranged from 20,2 to 28,9 mg/kg in children and 16,3 to 34,09 mg/kg in adults. The proportions of patients with chloroquine doses below 25 mg/kg ranged from 29,4% to 63,6% in children and 59% in adults. The required doses were lower than the given doses in ages ranges of 4-8 years (U=64; p=0,007), 9-11 years (U=32; p<0,001) and 12-14 years (U=18; p<0,0001). Blood chloroquine concentrations in 168h in ng/ml ranged from 107 to 440 in children and 201 to 582 in adults. Blood levels of desethylchloroquine ranged from 167 to 412 in children and 178 to 482 in adults. The pharmacokinetics parameters derived from no-compartmental approach were elimination rate constant, area under the curve at day 28, extrapolated to infinite, maximum concentration, total clearance, elimination half-life, volume of distribution and meantime of residence. Overall, the data were similar to those found in other population groups and confirmed the high elimination half-life and a large volume of distribution of the drug. There was no significant influence of gender, but the age decreased significantly the clearance and the volume of distribution. The results permit to conclude that chloroquine is yet effective in the research area. Most of the patients received sub-doses of chloroquine. The pharmacokinetics parameters were not influenced by gender, but the age promoted a significant decrease in the volume of distribution and in the clearance, with the lower values in children.
Acesso aberto (Open Access)
Utilização do DELI-teste para avaliação da sensibilidade in vitro do Plasmodium vivax à Cloroquina em condições de campo no município de Tucuruí, Pará
(Universidade Federal do Pará, 2007) AMÉRICO, Ana Paula Larêdo; CARVALHO, Leonardo José Moura; http://lattes.cnpq.br/2705233211612041; SOUZA, José Maria de; http://lattes.cnpq.br/6459204248879587
The State of Para is responsible for a large amount of malaria notifications in the Brazilian Amazon region. Plasmodium vivax is the most prevalent specie and the evaluation of its in vitro sensitivity to chloroquine is essential to verify if this drug keeps its efficacy. However, this kind of evaluation was not feasible due to unavailability of methodologies for short-term in vitro culture and for evaluation of growth/maturation of this parasite. Recently, a method for shortterm in vitro culture of P. vivax was introduced, as well as a reliable methodology (DELI-test) for measurement of this parasite’s growth/maturation, based on the detection of the parasite enzyme Lactate Dehydrogenase (pLDH), allowing studies of sensitivity of this plasmodial specie to antimalarials. The aim of this study was then to evaluate the chemosensitivity of P. vivax to chloroquine under field conditions in the municipality of Tucurui, State of Para, Brazil. A total of 45 patients with vivax malaria were enrolled in the study, after microscopic diagnosis by thick smear, and 5mL of blood were withdrawn from each patient. An erythrocyte suspension was prepared for each patient’s blood, using a special culture medium (mixing of RPMI and Waymouth media, AB+ serum, 1.8% hematocrit), and put in short-term (48 hours) culture at 37°C and low tension of oxygen, under a range of concentrations (2,34-600ng/mL) of chloroquine. Plates were then frozen and, later, parasites were lysed by freezing-thawing, releasing the pLDH, which was measured by a sandwich-ELISA (DELI-test), using for capture the monoclonal antibody (MAb) 6C9 (anti-Plasmodium pLDH) e 11D (anti-P. vivax pLDH) and for detection the MAb19G (anti-Plasmodium pLDH). The optical density values allowed in most cases the drawing of curves of sensitivity to the drug and calculation of the 50% inhibitory concentration (IC50). Nearly half (53.8%) of the samples showed better curves with the MAb 11D. Out of the 44 samples, 26 (59.2%) allowed the drawing of interpretable curves of sensitivity for chloroquine. The parasite growth performance of 59% of the samples can be considered satisfactory, taking into account the known difficulty in culturing P. vivax in vitro, and the poor laboratory conditions for carrying out the cultures. Thirteen (46.2%) of the 26 interpretable samples showed an IC50 above the threshold of 100nM of chloroquine, being considered resistants. This high frequency of samples with low sensitivity to chloroquine is of concern and indicates that this kind of evaluation should be continued and extended to other localities in order to have a more clear picture of the situation. The DELI-test is currently the only able to evaluate in vitro resistance of P. vivax and its use in fild conditions can contribute for helping definitions in the malaria therapeutic strategies in Brazil.
Acesso aberto (Open Access)
Validação de método para determinação de cloroquina e desetilcloroquina em amostras de sangue adsorvidas em papel de filtro por cromatografia líquida de alta eficiência com detector de UV
(Universidade Federal do Pará, 2008) NASCIMENTO, Margareth Tavares Silva; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098
The determination of the antimalarial blood concentrations employing by fast simple and sensitive methods represents important tool for the optimization of therapeutic regimens currently used in Brazil. In this sense, this paper describes the validation of an analytical methodology by high performance liquid chromatography with ultraviolet detection for the determination of chloroquine in blood samples adsorbed on filter paper, from patients with vivax malaria. It was evaluated: precision intra and inter assay, recovery, limits of detection and quantification, robustness, stability, linearity and selectivity. The results showed that the coefficients of variation of intra assay, at concentrations of 100 to 1000 ng/ml ranged from 6 to 10% for both chloroquine and desethylchloroquine. The coefficient of variation inter assay, at concentrations of 100 to 1000 ng/ml ranged from 5 to 10% and 4 to 10% for chloroquine and desethylchloroq uine, respectively. The limits of detection were 62.5 ng/mL for chloroquine and 50.0 ng/mL f or desethylchloroquine and limits of quantificatio n were 100 ng/mL for both analytes. The recovery in the concentration from 100 to 1000 ng/ml ranged from 90 to 105 % and 95% to 105 for chloroquine and desethylchloroquine, respectively. The method was linear in the range of concentration of 100 to 2000 ng/ml for chl oroquine and 100 to 800 ng/ml for desethylchloroquine. The method showed to be robust for small changes in flow, pH of the mobile phase and composition of the organic phase. It was not observed interferents in the validated procedure among those drugs used to treat malaria. The determination of chloroquine and desethylchloroquine in patients with vivax malar ia whose average values were 1266±455 ng/mL and 357±165 ng/mL, characterized the applicabilityof the validated procedure for the determination of antimalarial drugs in these patients.