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  1 / 1602 MEDLINE  
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[PMID]:29363364
[Au] Autor:Vlainic J; Kosalec I; Pavic K; Hadjipavlou-Litina D; Pontiki E; Zorc B
[Ad] Endereço:a Laboratory for Advanced Genomics, Division of Molecular Medicine , Rudjer Boskovic Institute , Zagreb , Croatia.
[Ti] Título:Insights into biological activity of ureidoamides with primaquine and amino acid moieties.
[So] Source:J Enzyme Inhib Med Chem;33(1):376-382, 2018 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Primaquine (PQ) ureidoamides 5a-f were screened for antimicrobial, biofilm eradication and antioxidative activities. Susceptibility of the tested microbial species towards tested compounds showed species- and compound-dependent activity. N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]-4-methylpentanamide (5a) and 2-(4-chlorophenyl)-N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]acetamide (5d) showed antibacterial activity against S. aureus strains (MIC = 6.5 µg/ml). Further, compounds 5c and 5d had weak antibacterial activity against Escherichia coli and Pseudomonas aeruginosa. None of the tested compounds showed a wide spectrum of antifungal activity. In contrast, most of the compounds exerted strong activity in a biofilm eradication assay against E. coli, P. aeruginosa and Candida albicans, comparable to or even higher than gentamycin, amphotericin B or parent PQ. The most active compounds were 5a and 5b. Tested compounds were inactive against biofilm formation by C. parapsylosis, Enterococcus faecalis, C. tropicalis and C. krusei. Compounds 5b-f significantly inhibited lipid peroxidation (80-99%), whereas compound 5c presented interesting LOX inhibition.
[Mh] Termos MeSH primário: Amidas/farmacologia
Aminoácidos/farmacologia
Antibacterianos/farmacologia
Antifúngicos/farmacologia
Antioxidantes/farmacologia
Primaquina/farmacologia
[Mh] Termos MeSH secundário: Amidas/química
Aminoácidos/química
Antibacterianos/química
Antifúngicos/química
Antioxidantes/química
Biofilmes/efeitos dos fármacos
Candida albicans/efeitos dos fármacos
Relação Dose-Resposta a Droga
Escherichia coli/efeitos dos fármacos
Seres Humanos
Peroxidação de Lipídeos/efeitos dos fármacos
Lipoxigenase/metabolismo
Inibidores de Lipoxigenase/química
Inibidores de Lipoxigenase/farmacologia
Testes de Sensibilidade Microbiana
Estrutura Molecular
Primaquina/química
Pseudomonas aeruginosa/efeitos dos fármacos
Feijão de Soja/enzimologia
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Amino Acids); 0 (Anti-Bacterial Agents); 0 (Antifungal Agents); 0 (Antioxidants); 0 (Lipoxygenase Inhibitors); EC 1.13.11.12 (Lipoxygenase); MVR3634GX1 (Primaquine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1423067


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[PMID]:29324864
[Au] Autor:Bastiaens GJH; Tiono AB; Okebe J; Pett HE; Coulibaly SA; Gonçalves BP; Affara M; Ouédraogo A; Bougouma EC; Sanou GS; Nébié I; Bradley J; Lanke KHW; Niemi M; Sirima SB; d'Alessandro U; Bousema T; Drakeley C
[Ad] Endereço:Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
[Ti] Título:Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males: Two open-label, randomized, safety trials.
[So] Source:PLoS One;13(1):e0190272, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. METHODS AND FINDINGS: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0.25 (n = 20) or 0.40 mg/kg (n = 20) dosage; G6PD-normal males received AL plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. In The Gambia, G6PDd adult males and boys received DP alone (n = 10) or with 0.25 mg/kg PQ (n = 20); G6PD-normal males received DP plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. The primary study endpoint was change in hemoglobin concentration during the 28-day follow-up. Cytochrome P-450 isoenzyme 2D6 (CYP2D6) metabolizer status, gametocyte carriage, haptoglobin, lactate dehydrogenase levels and reticulocyte counts were also determined. In Burkina Faso, the mean maximum absolute change in hemoglobin was -2.13 g/dL (95% confidence interval [CI], -2.78, -1.49) in G6PDd individuals randomized to 0.25 PQ mg/kg and -2.29 g/dL (95% CI, -2.79, -1.79) in those receiving 0.40 PQ mg/kg. In The Gambia, the mean maximum absolute change in hemoglobin concentration was -1.83 g/dL (95% CI, -2.19, -1.47) in G6PDd individuals receiving 0.25 PQ mg/kg. After adjustment for baseline concentrations, hemoglobin reductions in G6PDd individuals in Burkina Faso were more pronounced compared to those in G6PD-normal individuals receiving the same PQ doses (P = 0.062 and P = 0.022, respectively). Hemoglobin levels normalized during follow-up. Abnormal haptoglobin and lactate dehydrogenase levels provided additional evidence of mild transient hemolysis post-PQ. CONCLUSIONS: Single low-dose PQ in combination with AL and DP was associated with mild and transient reductions in hemoglobin. None of the study participants developed moderate or severe anemia; there were no severe adverse events. This indicates that single low-dose PQ is safe in G6PDd African males when used with artemisinin-based combination therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02174900 Clinicaltrials.gov NCT02654730.
[Mh] Termos MeSH primário: Antimaláricos/administração & dosagem
Glucosefosfato Desidrogenase/genética
Malária Falciparum/tratamento farmacológico
Primaquina/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Antimaláricos/efeitos adversos
Burkina Faso
Seres Humanos
Masculino
Primaquina/efeitos adversos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimalarials); EC 1.1.1.49 (Glucosephosphate Dehydrogenase); MVR3634GX1 (Primaquine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190272


  3 / 1602 MEDLINE  
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Romero, Gustavo Adolfo Sierra
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[PMID]:27770602
[Au] Autor:Peixoto HM; Brito MA; Romero GA; Monteiro WM; de Lacerda MV; de Oliveira MR
[Ad] Endereço:Centre for Tropical Medicine, University of Brasília, Brasília, Federal District, Brazil.
[Ti] Título:Rapid diagnostic test for G6PD deficiency in Plasmodium vivax-infected men: a budget impact analysis based in Brazilian Amazon.
[So] Source:Trop Med Int Health;22(1):21-31, 2017 01.
[Is] ISSN:1365-3156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The aim of this study was to estimate the incremental budget impact (IBI) of a rapid diagnostic test to detect G6PDd in male patients infected with Plasmodium vivax in the Brazilian Amazon, as compared with the routine protocol recommended in Brazil which does not include G6PDd testing. METHODS: The budget impact analysis was performed from the perspective of the Brazilian health system, in the Brazilian Amazon for the years 2013, 2014 and 2015. The analysis used a decision model to compare two scenarios: the first consisting of the routine recommended in Brazil which does not include prior diagnosis of dG6PD, and the second based on the use of RDT CareStart™ G6PD (CS-G6PD) in all male subjects diagnosed with vivax malaria. The expected implementation of the diagnostic test was 30% in the first year, 70% the second year and 100% in the third year. RESULTS: The analysis identified negative IBIs which were progressively smaller in the 3 years evaluated. The sensitivity analysis showed that the uncertainties associated with the analytical model did not significantly affect the results. CONCLUSION: A strategy based on the use of CS-G6PD would result in better use of public resources in the Brazilian Amazon.
[Mh] Termos MeSH primário: Técnicas e Procedimentos Diagnósticos/economia
Deficiência de Glucosefosfato Desidrogenase/diagnóstico
Deficiência de Glucosefosfato Desidrogenase/epidemiologia
Malária Vivax/epidemiologia
Programas de Rastreamento/economia
[Mh] Termos MeSH secundário: Antimaláricos/uso terapêutico
Brasil/epidemiologia
Orçamentos
Técnicas de Apoio para a Decisão
Seres Humanos
Malária Vivax/tratamento farmacológico
Masculino
Modelos Econométricos
Primaquina/uso terapêutico
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimalarials); MVR3634GX1 (Primaquine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE
[do] DOI:10.1111/tmi.12800


  4 / 1602 MEDLINE  
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[PMID]:29220797
[Au] Autor:Pavic K; Perkovic I; Pospísilová S; Machado M; Fontinha D; Prudêncio M; Jampilek J; Coffey A; Endersen L; Rimac H; Zorc B
[Ad] Endereço:University of Zagreb, Faculty of Pharmacy and Biochemistry, A. Kovacica 1, 10 000 Zagreb, Croatia.
[Ti] Título:Primaquine hybrids as promising antimycobacterial and antimalarial agents.
[So] Source:Eur J Med Chem;143:769-779, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Four series of primaquine (PQ) derivatives were screened for antitubercular and antiplasmodial activity: amides 1a-k, ureas 2a-s, semicarbazides 3a-c and bis-ureas 4a-u. Antimycobacterial activity of PQ derivatives against Mycobacterium tuberculosis (MTB), M. avium complex (MAC) and M. avium subsp. paratuberculosis (MAP) were evaluated in vitro and compared with PQ and the standard antitubercular drugs. In general, the PQ derivatives showed higher potency than the parent compound. Most of the compounds of series 1 and 2 showed high activity against MAP, comparable or even higher than the relevant drug ciprofloxacin, and weak or no activity against MTB and MAC. bis-Trifluoromethylated cinnamamide 1k showed low cytotoxicity and high activity against all three Mycobacterium species and their activities were comparable or slightly higher than those of the reference drugs. PQ urea derivatives with hydroxyl, halogen and trifluoromethyl substituents on benzene ring 2f-p exerted very strong antimycobacterial activity towards all tested mycobacteria, stronger than PQ and the relevant standard drug(s). Unfortunately, these compounds had relatively high cytotoxicity, except bromo 2l and trifluoromethyl 2m, 2n derivatives. In general, meta-substituted derivatives were more active than analogues para-derivatives. Phenyl ureas were also more active than cycloalkyl or hydroxyalkyl ureas. Semicarbazide 3a showed similar activity as PQ, while the other two semicarbazides were inactive. Bis-urea derivatives 4 were generally less active than the urea derivatives sharing the same scaffold, differing only in the spacer type. Out of 21 evaluated bis-urea derivatives, only p-Cl/m-CF phenyl derivative 4p, benzhydryl derivatives 4t and 4u and bis-PQ derivative 4s showed high activity, higher than all three reference drugs. After comparison of activity and cytotoxicity, urea 2m and bis-urea 4u could be considered as the most promising agents. Antimalarial potential of PQ derivatives in vitro against the liver stage of P. berghei was evaluated as well. 3-(4-Chlorophenyl)-1-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]urea (4l) was the most active compound (IC = 42 nM; cytotoxicity/activity ratio >2000). Our results bring new insights into development of novel anti-TB and antimalarial compounds.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Antimaláricos/farmacologia
Mycobacterium/efeitos dos fármacos
Plasmodium berghei/efeitos dos fármacos
Primaquina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antibacterianos/síntese química
Antibacterianos/química
Antimaláricos/síntese química
Antimaláricos/química
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Testes de Sensibilidade Microbiana
Estrutura Molecular
Mycobacterium/crescimento & desenvolvimento
Plasmodium berghei/crescimento & desenvolvimento
Primaquina/síntese química
Primaquina/química
Ratos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antimalarials); MVR3634GX1 (Primaquine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


  5 / 1602 MEDLINE  
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[PMID]:28939120
[Au] Autor:McQueen A; Blake LD; Azhari A; Kemp MT; McGaha TW; Namelikonda N; Larsen RW; Manetsch R; Kyle DE
[Ad] Endereço:Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
[Ti] Título:Synthesis, characterization, and cellular localization of a fluorescent probe of the antimalarial 8-aminoquinoline primaquine.
[So] Source:Bioorg Med Chem Lett;27(20):4597-4600, 2017 10 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Primaquine (PQ) is the only commercially available drug that clears dormant liver stages of malaria and blocks transmission to mosquito vectors. Although an old drug, much remains to be known about the mechanism(s) of action. Herein we develop a fluorescent tagged PQ to discover cellular localization in the human malaria parasite, Plasmodium falciparum. Successful synthesis and characterization of a primaquine-coumarin fluorescent probe (PQCP) demonstrated potency equivalent to the parent drug and the probe was not cytotoxic to HepG2 carcinoma cells. Cellular localization was found primarily in the cytosol of the asexual erythrocytic and gametocyte stages of parasite development.
[Mh] Termos MeSH primário: Antimaláricos/química
Corantes Fluorescentes/química
Plasmodium falciparum/metabolismo
Primaquina/química
[Mh] Termos MeSH secundário: Aminoquinolinas/química
Antimaláricos/metabolismo
Antimaláricos/farmacologia
Antimaláricos/uso terapêutico
Eritrócitos/parasitologia
Células Hep G2
Seres Humanos
Estágios do Ciclo de Vida
Malária Falciparum/tratamento farmacológico
Microscopia de Fluorescência
Plasmodium falciparum/química
Plasmodium falciparum/efeitos dos fármacos
Primaquina/metabolismo
Primaquina/farmacologia
Primaquina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aminoquinolines); 0 (Antimalarials); 0 (Fluorescent Dyes); MVR3634GX1 (Primaquine); U34EAV21TG (8-aminoquinoline)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170924
[St] Status:MEDLINE


  6 / 1602 MEDLINE  
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[PMID]:28931236
[Au] Autor:Stone W; Sawa P; Lanke K; Rijpma S; Oriango R; Nyaurah M; Osodo P; Osoti V; Mahamar A; Diawara H; Woestenenk R; Graumans W; van de Vegte-Bolmer M; Bradley J; Chen I; Brown J; Siciliano G; Alano P; Gosling R; Dicko A; Drakeley C; Bousema T
[Ad] Endereço:Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
[Ti] Título:A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance.
[So] Source:J Infect Dis;216(4):457-467, 2017 Aug 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Single low-dose primaquine (PQ) reduces Plasmodium falciparum infectivity before it impacts gametocyte density. Here, we examined the effect of PQ on gametocyte sex ratio as a possible explanation for this early sterilizing effect. Methods: Quantitative reverse-transcription polymerase chain reaction assays were developed to quantify female gametocytes (targeting Pfs25 messenger RNA [mRNA]) and male gametocytes (targeting Pf3D7_1469900 mRNA) in 2 randomized trials in Kenya and Mali, comparing dihydroartemisinin-piperaquine (DP) alone to DP with PQ. Gametocyte sex ratio was examined in relation to time since treatment and infectivity to mosquitoes. Results: In Kenya, the median proportion of male gametocytes was 0.33 at baseline. Seven days after treatment, gametocyte density was significantly reduced in the DP-PQ arm relative to the DP arm (females: 0.05% [interquartile range {IQR}, 0.0-0.7%] of baseline; males: 3.4% [IQR, 0.4%-32.9%] of baseline; P < .001). Twenty-four hours after treatment, gametocyte sex ratio became male-biased and was not significantly different between the DP and DP-PQ groups. In Mali, there was no significant difference in sex ratio between the DP and DP-PQ groups (>0.125 mg/kg) 48 hours after treatment, and gametocyte sex ratio was not associated with mosquito infection rates. Conclusions: The early sterilizing effects of PQ may not be explained by the preferential clearance of male gametocytes and may be due to an effect on gametocyte fitness.
[Mh] Termos MeSH primário: Antimaláricos/uso terapêutico
Células Germinativas/efeitos dos fármacos
Primaquina/uso terapêutico
Proteínas de Protozoários/genética
[Mh] Termos MeSH secundário: Adolescente
Artemisininas/uso terapêutico
Criança
Pré-Escolar
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Quênia
Masculino
Mali
Plasmodium falciparum
Proteínas de Protozoários/metabolismo
Quinolinas/uso terapêutico
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Tamanho da Amostra
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Pfs25 protein, Plasmodium falciparum); 0 (Protozoan Proteins); 0 (Quinolines); 0 (RNA, Messenger); 6A9O50735X (dihydroartemisinin); A0HV2Q956Y (piperaquine); MVR3634GX1 (Primaquine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix237


  7 / 1602 MEDLINE  
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[PMID]:28898049
[Au] Autor:Hassett MR; Riegel BE; Callaghan PS; Roepe PD
[Ad] Endereço:Departments of Chemistry and of Biochemistry & Cellular & Molecular Biology, Georgetown University , 37th and O Streets NW, Washington, D.C. 20057, United States.
[Ti] Título:Analysis of Plasmodium vivax Chloroquine Resistance Transporter Mutant Isoforms.
[So] Source:Biochemistry;56(41):5615-5622, 2017 Oct 17.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum malaria is widespread and has limited the use of CQ in many regions of the globe. Malaria caused by the related human parasite P. vivax is as widespread as is P. falciparum malaria and has been treated with CQ as extensively as has P. falciparum, suggesting that P. vivax parasites have been selected with CQ as profoundly as have P. falciparum parasites. Indeed, a growing number of clinical reports have presented data suggesting increased P. vivax CQR. Cytostatic (growth inhibitory) CQR for P. falciparum is caused by Plasmodium falciparum chloroquine resistance transporter (PfCRT) mutations, and it has been proposed that mutations in the PvCRT orthologue may simliarly cause P. vivax CQR via increasing CQ transport from the P. vivax digestive vacuole. Here we report the first quantitative analysis of drug transport mediated by all known mutant isoforms of Plasmodium vivax chloroquine resistance transporter (PvCRT) in order to test the protein's potential link to growing P. vivax CQR phenomena. Small, but statistically significant, differences in the transport of CQ and other quinoline antimalarial drugs were found for multiple PvCRT isoforms, relative to wild type PvCRT, suggesting that mutations in PvCRT can contribute to P. vivax CQR and other examples of quinoline antimalarial drug resistance.
[Mh] Termos MeSH primário: Antimaláricos/metabolismo
Cloroquina/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
Modelos Moleculares
Mutação
Plasmodium vivax/metabolismo
Proteínas de Protozoários/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Antimaláricos/farmacologia
Transporte Biológico
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Cloroquina/farmacologia
Contagem de Colônia Microbiana
Resistência a Medicamentos
Seres Humanos
Malária Vivax/tratamento farmacológico
Malária Vivax/parasitologia
Proteínas de Membrana Transportadoras/química
Proteínas de Membrana Transportadoras/genética
Mutagênese Sítio-Dirigida
Plasmodium vivax/efeitos dos fármacos
Plasmodium vivax/crescimento & desenvolvimento
Plasmodium vivax/isolamento & purificação
Primaquina/metabolismo
Primaquina/farmacologia
Conformação Proteica
Isoformas de Proteínas/química
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Proteínas de Protozoários/química
Proteínas de Protozoários/genética
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Saccharomyces cerevisiae/efeitos dos fármacos
Saccharomyces cerevisiae/crescimento & desenvolvimento
Saccharomyces cerevisiae/metabolismo
Trítio
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); 0 (Crt-o protein, Plasmodium vivax); 0 (Membrane Transport Proteins); 0 (Protein Isoforms); 0 (Protozoan Proteins); 0 (Recombinant Proteins); 10028-17-8 (Tritium); 886U3H6UFF (Chloroquine); MVR3634GX1 (Primaquine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00749


  8 / 1602 MEDLINE  
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[PMID]:28850568
[Au] Autor:Douglas NM; Poespoprodjo JR; Patriani D; Malloy MJ; Kenangalem E; Sugiarto P; Simpson JA; Soenarto Y; Anstey NM; Price RN
[Ad] Endereço:Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
[Ti] Título:Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study.
[So] Source:PLoS Med;14(8):e1002379, 2017 Aug.
[Is] ISSN:1549-1676
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Primaquine is the only licensed drug for eradicating Plasmodium vivax hypnozoites and, therefore, preventing relapses of vivax malaria. It is a vital component of global malaria elimination efforts. Primaquine is efficacious when supervised in clinical trials, but its effectiveness in real-world settings is unknown. We aimed to determine whether unsupervised primaquine was effective for preventing re-presentation to hospital with vivax malaria in southern Papua, Indonesia. METHODS AND FINDINGS: Routinely-collected hospital surveillance data were used to undertake a pragmatic comparison of the risk of re-presentation to hospital with vivax malaria in patients prescribed dihydroartemisinin-piperaquine (DHP) combined with primaquine versus those patients prescribed DHP alone. The omission of primaquine was predominantly due to 3 stock outages. Individual clinical, pharmacy, and laboratory data were merged using individual hospital identification numbers and the date of presentation to hospital. Between April 2004 and December 2013, there were 86,797 documented episodes of vivax malaria, of which 62,492 (72.0%) were included in the analysis. The risk of re-presentation with vivax malaria within 1 year was 33.8% (95% confidence Interval [CI] 33.1%-34.5%) after initial monoinfection with P. vivax and 29.2% (95% CI 28.1%-30.4%) after mixed-species infection. The risk of re-presentation with P. vivax malaria was higher in children 1 to <5 years of age (49.6% [95% CI 48.4%-50.9%]) compared to patients 15 years of age or older (24.2% [95% CI 23.4-24.9%]); Adjusted Hazard Ratio (AHR) = 2.23 (95% CI 2.15-2.31), p < 0.001. Overall, the risk of re-presentation was 37.2% (95% CI 35.6%-38.8%) in patients who were prescribed no primaquine compared to 31.6% (95% CI 30.9%-32.3%) in those prescribed either a low (≥1.5 mg/kg and <5 mg/kg) or high (≥5 mg/kg) dose of primaquine (AHR = 0.90 [95% CI 0.86-0.95, p < 0.001]). Limiting the comparison to high dose versus no primaquine in the period during and 12 months before and after a large stock outage resulted in minimal change in the estimated clinical effectiveness of primaquine (AHR 0.91, 95% CI 0.85-0.97, p = 0.003). Our pragmatic study avoided the clinical influences associated with prospective study involvement but was subject to attrition bias caused by passive follow-up. CONCLUSIONS: Unsupervised primaquine for vivax malaria, prescribed according to the current World Health Organization guidelines, was associated with a minimal reduction in the risk of clinical recurrence within 1 year in Papua, Indonesia. New strategies for the effective radical cure of vivax malaria are needed in resource-poor settings.
[Mh] Termos MeSH primário: Antimaláricos/uso terapêutico
Artemisininas/uso terapêutico
Malária Vivax/tratamento farmacológico
Primaquina/uso terapêutico
Quinolinas/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Criança
Pré-Escolar
Estudos de Coortes
Quimioterapia Combinada
Feminino
Seres Humanos
Indonésia
Lactente
Malária Vivax/prevenção & controle
Masculino
Meia-Idade
Recidiva
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Quinolines); 6A9O50735X (dihydroartemisinin); A0HV2Q956Y (piperaquine); MVR3634GX1 (Primaquine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170917
[Lr] Data última revisão:
170917
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pmed.1002379


  9 / 1602 MEDLINE  
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[PMID]:28820691
[Au] Autor:Weppelmann TA; von Fricken ME; Wilfong TD; Aguenza E; Philippe TT; Okech BA
[Ad] Endereço:Herbert Wertheim College of Medicine, Florida International University, Miami, Florida.
[Ti] Título:Field Trial of the CareStart Biosensor Analyzer for the Determination of Glucose-6-Phosphate Dehydrogenase Activity in Haiti.
[So] Source:Am J Trop Med Hyg;97(4):1262-1270, 2017 Oct.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Throughout many developing and tropical countries around the world, malaria remains a significant threat to human health. One barrier to malaria elimination is the ability to safely administer primaquine chemotherapy for the radical cure of malaria infections in populations with a high prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency. In the current study, a field trial of the world's first quantitative, point-of-care assay for measuring G6PD activity was conducted in Haiti. The performance of the CareStart Biosensor Analyzer was compared with the gold standard spectrophotometric assay and genotyping of the allele in schoolchildren ( = 343) from the Ouest Department of Haiti. In this population, 19.5% of participants (67/343) had some form of G6PD deficiency (< 60% residual activity) and 9.9% (34/343) had moderate-to-severe G6PD deficiency (< 30% residual activity). Overall, 18.95% of participants had the presence of the A-allele (65/343) with 7.87% (27/343) considered at high risk for drug-induced hemolysis (hemizygous males and homozygous females). Compared with the spectrophotometric assay, the sensitivity and specificity to determine participants with < 60% residual activity were 53.7% and 94.6%, respectively; for participants with 30% residual activity, the sensitivity and specificity were 5.9% and 99.7%, respectively. The biosensor overestimated the activity in deficient individuals and underestimated it in participants with normal G6PD activity, indicating the potential for a systematic measurement error. Thus, we suggest that the current version of the biosensor lacks adequate sensitivity and should be improved prior to its use as a point-of-care diagnostic for G6PD deficiency.
[Mh] Termos MeSH primário: Técnicas Biossensoriais
Glucosefosfato Desidrogenase/metabolismo
Malária/diagnóstico
Malária/epidemiologia
[Mh] Termos MeSH secundário: Alelos
Antimaláricos/administração & dosagem
Antimaláricos/efeitos adversos
Criança
Feminino
Genótipo
Glucosefosfato Desidrogenase/genética
Haiti
Seres Humanos
Masculino
Sistemas Automatizados de Assistência Junto ao Leito
Primaquina/administração & dosagem
Primaquina/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); EC 1.1.1.49 (Glucosephosphate Dehydrogenase); MVR3634GX1 (Primaquine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.16-0714


  10 / 1602 MEDLINE  
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[PMID]:28732068
[Au] Autor:Wampfler R; Hofmann NE; Karl S; Betuela I; Kinboro B; Lorry L; Silkey M; Robinson LJ; Mueller I; Felger I
[Ad] Endereço:Swiss Tropical and Public Health Institute, Basel, Switzerland.
[Ti] Título:Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum.
[So] Source:PLoS Negl Trop Dis;11(7):e0005753, 2017 Jul.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Primaquine (PQ) is the only currently licensed antimalarial that prevents Plasmodium vivax (Pv) relapses. It also clears mature P. falciparum (Pf) gametocytes, thereby reducing post-treatment transmission. Randomized PQ treatment in a treatment-to-reinfection cohort in Papua New Guinean children permitted the study of Pv and Pf gametocyte carriage after radical cure and to investigate the contribution of Pv relapses. METHODS: Children received radical cure with Chloroquine, Artemether-Lumefantrine plus either PQ or placebo. Blood samples were subsequently collected in 2-to 4-weekly intervals over 8 months. Gametocytes were detected by quantitative reverse transcription-PCR targeting pvs25 and pfs25. RESULTS: PQ treatment reduced the incidence of Pv gametocytes by 73%, which was comparable to the effect of PQ on incidence of blood-stage infections. 92% of Pv and 79% of Pf gametocyte-positive infections were asymptomatic. Pv and to a lesser extent Pf gametocyte positivity and density were associated with high blood-stage parasite densities. Multivariate analysis revealed that the odds of gametocytes were significantly reduced in mixed-species infections compared to single-species infections for both species (ORPv = 0.39 [95% CI 0.25-0.62], ORPf = 0.33 [95% CI 0.18-0.60], p<0.001). No difference between the PQ and placebo treatment arms was observed in density of Pv gametocytes or in the proportion of Pv infections that carried gametocytes. First infections after blood-stage and placebo treatment, likely caused by a relapsing hypnozoite, were equally likely to carry gametocytes than first infections after PQ treatment, likely caused by an infective mosquito bite. CONCLUSION: Pv relapses and new infections are associated with similar levels of gametocytaemia. Relapses thus contribute considerably to the Pv reservoir highlighting the importance of effective anti-hypnozoite treatment for efficient control of Pv. TRIAL REGISTRATION: ClinicalTrials.gov NCT02143934.
[Mh] Termos MeSH primário: Antimaláricos/uso terapêutico
Malária Falciparum/tratamento farmacológico
Malária Vivax/tratamento farmacológico
Plasmodium falciparum/efeitos dos fármacos
Plasmodium vivax/efeitos dos fármacos
Primaquina/uso terapêutico
[Mh] Termos MeSH secundário: Artemisininas/uso terapêutico
Sangue/parasitologia
Criança
Pré-Escolar
Cloroquina/uso terapêutico
Método Duplo-Cego
Combinação de Medicamentos
Etanolaminas/uso terapêutico
Feminino
Fluorenos/uso terapêutico
Seres Humanos
Fígado/efeitos dos fármacos
Fígado/parasitologia
Masculino
Análise Multivariada
Papua Nova Guiné
Recidiva
Análise de Regressão
Fatores de Risco
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE IV; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Drug Combinations); 0 (Ethanolamines); 0 (Fluorenes); 0 (artemether-lumefantrine combination); 886U3H6UFF (Chloroquine); MVR3634GX1 (Primaquine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170813
[Lr] Data última revisão:
170813
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005753



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