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[PMID]:28460126
[Au] Autor:Izevbekhai O; Adeagbo B; Olagunju A; Bolaji O
[Ad] Endereço:Department of Pharmaceutical Chemistry, Obafemi Awolowo University, Ile-Ife, Nigeria.
[Ti] Título:Quality of artemisinin-based antimalarial drugs marketed in Nigeria.
[So] Source:Trans R Soc Trop Med Hyg;111(2):90-96, 2017 02 01.
[Is] ISSN:1878-3503
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Artemisinin combination therapy is first-line therapy for treatment of malaria, which is one of the most significant public health problems in Nigeria. With the increasing level of use of these drugs coupled with the emergence of resistance, there is a need for regular post-market surveillance. Method: Twenty different brands of artesunate-containing antimalarial drugs and 10 brands of artemether-lumefantrine were multi-sourced in the south western part of Nigeria and were subjected to identification, weight uniformity test, and assay using United State pharmacopoeia and International Pharmacopoeia monographs. In vitro-dissolution test of the artemether tablets was also investigated. Results: All 10 brands (100%) of the artemether-lumefantrine tablets met the assay requirement for artemether and 8 (80%) met the assay requirement for lumefantrine, but only 4 brands (40%) met the requirement for artemether dissolution. One of these brands failed the weight uniformity test. Of the 20 brands of artesunate-containing brands included in this study, 15 (75%) met the standard assay requirement for artesunate and two failed the weight uniformity test. Conclusions: There is evidence of the presence of substandard artemisinin products in the Nigerian market.
[Mh] Termos MeSH primário: Antimaláricos/normas
Artemisininas/normas
[Mh] Termos MeSH secundário: Antimaláricos/análise
Antimaláricos/química
Artemisininas/análise
Artemisininas/química
Combinação de Medicamentos
Avaliação de Medicamentos
Controle de Medicamentos e Entorpecentes
Etanolaminas/análise
Etanolaminas/química
Etanolaminas/normas
Fluorenos/análise
Fluorenos/química
Fluorenos/normas
Seres Humanos
Malária Falciparum/tratamento farmacológico
Nigéria
Controle de Qualidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Drug Combinations); 0 (Ethanolamines); 0 (Fluorenes); 0 (artemether-lumefantrine combination); 60W3249T9M (artesunate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1093/trstmh/trx019


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[PMID]:28460112
[Au] Autor:Aponte S; Guerra ÁP; Álvarez-Larrotta C; Bernal SD; Restrepo C; González C; Yasnot MF; Knudson-Ospina A
[Ad] Endereço:Grupo de Bioquímica y Biología Celular, Instituto Nacional de Salud, Bogotá, D.C., Colombia.
[Ti] Título:Baseline in vivo, ex vivo and molecular responses of Plasmodium falciparum to artemether and lumefantrine in three endemic zones for malaria in Colombia.
[So] Source:Trans R Soc Trop Med Hyg;111(2):71-80, 2017 02 01.
[Is] ISSN:1878-3503
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Colombia began using artemisinin-based combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in 2006. It is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. The aim of this study was to establish a susceptibility baseline of P. falciparum to artemether-lumefantrine using three monitoring tools. Methods: Patients with uncomplicated malaria treated with artemether-lumefantrine underwent clinical and parasitological follow-up over 28 days. Ex vivo test was performed using the microtest technique for chloroquine, arthemeter, dihydroartemisinin and lumefantrine. Pfmdr1 copy number and polymorphisms in Pfk13, Pfatp6, Pfcrt and Pfmdr1 genes were analyzed. Results: From a total of 150 screened patients, 49 completed follow-up for 28 days. All treated patients had adequate clinical and parasitological responses. Parasitic clearance showed a drastic reduction of parasite biomass at 24 hours and complete elimination at 48 hours. One hundred eleven isolates were processed, all exhibited high susceptibility to artemisinins and a slight decrease in susceptibility to lumefantrine. No genetic polymorphisms associated with resistance to artemisinin were found. Conclusion: This study generated a susceptibility baseline in response to therapy with Coartem (artemether-lumefantrine) with numerical reference values, which will allow data comparison with future studies to systematically monitor changes in the parasite and to provide an early alert to the health authorities.
[Mh] Termos MeSH primário: Antimaláricos/uso terapêutico
Artemisininas/uso terapêutico
Etanolaminas/uso terapêutico
Fluorenos/uso terapêutico
Malária/tratamento farmacológico
Plasmodium falciparum/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Antimaláricos/farmacologia
Artemisininas/farmacologia
Criança
Colômbia
Variações do Número de Cópias de DNA
Combinação de Medicamentos
Resistência a Medicamentos/efeitos dos fármacos
Resistência a Medicamentos/genética
Quimioterapia Combinada
Etanolaminas/farmacologia
Feminino
Fluorenos/farmacologia
Seres Humanos
Malária/parasitologia
Masculino
Meia-Idade
Parasitemia/tratamento farmacológico
Plasmodium falciparum/isolamento & purificação
Polimorfismo Genético
Proteínas de Protozoários/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Drug Combinations); 0 (Ethanolamines); 0 (Fluorenes); 0 (Protozoan Proteins); 0 (artemether-lumefantrine combination); C7D6T3H22J (artemether); F38R0JR742 (lumefantrine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1093/trstmh/trx021


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[PMID]:27776521
[Au] Autor:Denoeud-Ndam L; Dicko A; Baudin E; Guindo O; Grandesso F; Diawara H; Sissoko S; Sanogo K; Traoré S; Keita S; Barry A; de Smet M; Lasry E; Smit M; Wiesner L; Barnes KI; Djimde AA; Guerin PJ; Grais RF; Doumbo OK; Etard JF
[Ad] Endereço:Epicentre, Paris, France. lise.denoeud@epicentre.msf.org.
[Ti] Título:Efficacy of artemether-lumefantrine in relation to drug exposure in children with and without severe acute malnutrition: an open comparative intervention study in Mali and Niger.
[So] Source:BMC Med;14(1):167, 2016 10 24.
[Is] ISSN:1741-7015
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Severe acute malnutrition (SAM) affects almost all organs and has been associated with reduced intestinal absorption of medicines. However, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. We assessed artemether-lumefantrine (AL) clinical efficacy in children with SAM compared to those without. METHODS: Children under 5 years of age with uncomplicated P. falciparum malaria were enrolled between November 2013 and January 2015 in Mali and Niger, one third with uncomplicated SAM and two thirds without. AL was administered under direct observation with a fat intake consisting of ready-to-use therapeutic food (RUTF - Plumpy'Nut®) in SAM children, twice daily during 3 days. Children were followed for 42 days, with PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 as the primary outcome. Lumefantrine concentrations were assessed in a subset of participants at different time points, including systematic measurements on day 7. RESULTS: A total of 399 children (360 in Mali and 39 in Niger) were enrolled. Children with SAM were younger than their non-SAM counterparts (mean 17 vs. 28 months, P < 0.0001). PCR-corrected ACPR was 100 % (95 % CI, 96.8-100 %) in SAM at both day 28 and 42, versus 98.8 % (96.4-99.7 %) at day 28 and 98.3 % (95.6-99.4 %) at day 42 in non-SAM (P = 0.236 and 0.168, respectively). Compared to younger children, children older than 21 months experienced more reinfections and SAM was associated with a greater risk of reinfection until day 28 (adjusted hazard ratio = 2.10 (1.04-4.22), P = 0.038). Day 7 lumefantrine concentrations were significantly lower in SAM than non-SAM (median 251 vs. 365 ng/mL, P = 0.049). CONCLUSIONS: This study shows comparable therapeutic efficacy of AL in children without SAM and in those with SAM when given in combination with RUTF, but a higher risk of reinfection in older children suffering from SAM. This could be associated with poorer exposure to the antimalarials as documented by a lower lumefantrine concentration on day 7. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958905 , registration date: October 7, 2013.
[Mh] Termos MeSH primário: Antimaláricos/farmacocinética
Artemisininas/farmacocinética
Etanolaminas/farmacocinética
Fluorenos/farmacocinética
Malária Falciparum/tratamento farmacológico
Desnutrição Aguda Grave/metabolismo
[Mh] Termos MeSH secundário: Antimaláricos/administração & dosagem
Artemisininas/administração & dosagem
Pré-Escolar
Combinação de Medicamentos
Etanolaminas/administração & dosagem
Feminino
Fluorenos/administração & dosagem
Seres Humanos
Lactente
Malária Falciparum/metabolismo
Masculino
Mali
Níger
Desnutrição Aguda Grave/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Drug Combinations); 0 (Ethanolamines); 0 (Fluorenes); 0 (artemether-lumefantrine combination)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180127
[Lr] Data última revisão:
180127
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE


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[PMID]:29065172
[Au] Autor:Huang L; Carey V; Lindsey JC; Marzan F; Gingrich D; Graham B; Barlow-Mosha L; Ssemambo PK; Kamthunzi P; Nachman S; Parikh S; Aweeka FT; IMPAACT P1079 protocol team
[Ad] Endereço:Drug Research Unit, Department of Clinical Pharmacy, University of California, San Francisco, CA, United States of America.
[Ti] Título:Concomitant nevirapine impacts pharmacokinetic exposure to the antimalarial artemether-lumefantrine in African children.
[So] Source:PLoS One;12(10):e0186589, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The antiretroviral drug nevirapine and the antimalarial artemisinin-based combination therapy artemether-lumefantrine are commonly co-administered to treat malaria in the context of HIV. Nevirapine is a known inhibitor of cytochrome P450 3A4, which metabolizes artemether and lumefantrine. To address the concern that the antiretroviral nevirapine impacts the antimalarial artemether-lumefantrine pharmacokinetics, a prospective non-randomized controlled study in children presenting with uncomplicated malaria and HIV in sub-Saharan Africa was carried out. METHODS: Participants received artemether-lumefantrine (20/120 mg weight-based BID) for 3 days during nevirapine-based antiretroviral therapy (ART) co-administration (158-266 mg/m2 QD). HIV positive participants who were not yet on ART drugs were also enrolled as the control group. The target enrollment was children aged 3-12 years (n = 24 in each group). Intensive pharmacokinetics after the last artemether-lumefantrine dose was assessed for artemether, its active metabolite dihydroartemisinin, and lumefantrine. Pharmacokinetic parameters (area under the plasma concentration vs. time curve (AUC), maximum concentration and day 7 lumefantrine concentrations) were estimated using non-compartmental methods and compared to controls. RESULTS: Nineteen children (16 on nevirapine and three not on ART) enrolled. Fifteen of the 16 (aged 4 to 11 years) on nevirapine-based ART were included in the pharmacokinetic analysis. Due to evolving WHO HIV treatment guidelines, insufficient children were enrolled in the control group (n = 3), so the pharmacokinetic data were compared to a historical control group of 20 HIV-uninfected children 5-12 years of age who also presented with malaria and underwent identical study procedures. Decreases of pharmacokinetic exposure [as estimated by AUC (AUC0-8hr)] were marginally significant for artemether (by -46%, p = 0.08) and dihydroartemisinin (-22%, p = 0.06) in the children on nevirapine-based ART, compared to when artemether-lumefantrine was administered alone. Similarly, peak concentration was decreased by 50% (p = 0.07) for artemether and 36% (p = 0.01) for dihydroartemisinin. In contrast, exposure to lumefantrine increased significantly in the context of nevirapine [AUC0-120hr:123% (p<0.001); Cday7:116% (p<0.001), Cmax: 95% (p<0.001)]. CONCLUSIONS: Nevirapine-based ART increases the exposure to lumefantrine in pre-pubescent children with a trend toward diminished artemether and dihydroartemisinin exposure. These findings contrast with other studies indicating NVP reduces or results in no change in exposure of antimalarial drugs, and may be specific to this age group (4-12 years). Considering the excellent safety profile of artemether-lumefantrine, the increase in lumefantrine is not of concern. However, the reduction in artemisinin exposure may warrant further study, and suggests that dosage adjustment of artemether-lumefantrine with nevirapine-based ART in children is likely warranted.
[Mh] Termos MeSH primário: Antimaláricos/farmacocinética
Artemisininas/farmacocinética
Etanolaminas/farmacocinética
Fluorenos/farmacocinética
Nevirapina/uso terapêutico
[Mh] Termos MeSH secundário: África ao Sul do Saara
Artemisininas/administração & dosagem
Criança
Pré-Escolar
Etanolaminas/administração & dosagem
Feminino
Fluorenos/administração & dosagem
Seres Humanos
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Ethanolamines); 0 (Fluorenes); 99DK7FVK1H (Nevirapine); C7D6T3H22J (artemether); F38R0JR742 (lumefantrine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186589


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[PMID]:28954820
[Au] Autor:Couch DG; Tasker C; Theophilidou E; Lund JN; O'Sullivan SE
[Ad] Endereço:School of Medicine, Royal Derby Hospital, University of Nottingham, Derby DE22 3DT, U.K. Couch27@gmail.com.
[Ti] Título:Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon.
[So] Source:Clin Sci (Lond);131(21):2611-2626, 2017 Nov 01.
[Is] ISSN:1470-8736
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. DESIGN: Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex. Inflammatory cytokine secretion was determined using ELISA. Receptor mechanisms were investigated using antagonists for CB , CB , PPARα, PPARγ, TRPV1 and GPR55. RESULTS: IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants. Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants. CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB antagonist AM630 and TRPV1 antagonist SB366791. PEA effects were blocked by the PPARα antagonist GW6471. PEA and CBD were anti-inflammatory in IBD and appendicitis explants. CONCLUSION: PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy.
[Mh] Termos MeSH primário: Amidas/química
Anti-Inflamatórios/farmacologia
Canabidiol/farmacologia
Colo/efeitos dos fármacos
Etanolaminas/farmacologia
Doenças Inflamatórias Intestinais/tratamento farmacológico
Ácidos Palmíticos/farmacologia
[Mh] Termos MeSH secundário: Doença Aguda
Células CACO-2/efeitos dos fármacos
Citocinas/metabolismo
Seres Humanos
Doenças Inflamatórias Intestinais/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amides); 0 (Anti-Inflammatory Agents); 0 (Cytokines); 0 (Ethanolamines); 0 (Palmitic Acids); 0 (TNF protein, human); 0 (Tumor Necrosis Factor-alpha); 19GBJ60SN5 (Cannabidiol); 6R8T1UDM3V (palmidrol)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170929
[St] Status:MEDLINE
[do] DOI:10.1042/CS20171288


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[PMID]:28874446
[Au] Autor:Harper M; Wright A; St Michael F; Li J; Deveson Lucas D; Ford M; Adler B; Cox AD; Boyce JD
[Ad] Endereço:Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, VIC, Australia marina.harper@monash.edu.
[Ti] Título:Characterization of Two Novel Lipopolysaccharide Phosphoethanolamine Transferases in Pasteurella multocida and Their Role in Resistance to Cathelicidin-2.
[So] Source:Infect Immun;85(11), 2017 Nov.
[Is] ISSN:1098-5522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The lipopolysaccharide (LPS) produced by the Gram-negative bacterial pathogen has phosphoethanolamine (PEtn) residues attached to lipid A, 3-deoxy-d-manno-octulosonic acid (Kdo), heptose, and galactose. In this report, we show that PEtn is transferred to lipid A by the EptA homologue, PetL, and is transferred to galactose by a novel PEtn transferase that is unique to called PetG. Transcriptomic analyses indicated that expression was positively regulated by the global regulator Fis and negatively regulated by an Hfq-dependent small RNA. Importantly, we have identified a novel PEtn transferase called PetK that is responsible for PEtn addition to the single Kdo molecule (Kdo ), directly linked to lipid A in the glycoform A LPS. assays showed that the presence of a functional and , and therefore the presence of PEtn on lipid A and Kdo , was essential for resistance to the cationic, antimicrobial peptide cathelicidin-2. The importance of PEtn on Kdo and the identification of the transferase responsible for this addition have not previously been shown. Phylogenetic analysis revealed that PetK is the first representative of a new family of predicted PEtn transferases. The PetK family consists of uncharacterized proteins from a range of Gram-negative bacteria that produce LPS glycoforms with only one Kdo molecule, including pathogenic species within the genera , , and We predict that many of these bacteria will require the addition of PEtn to Kdo for maximum protection against host antimicrobial peptides.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Proteínas Sanguíneas/toxicidade
Farmacorresistência Bacteriana/genética
Etanolaminofosfotransferase/genética
Regulação Bacteriana da Expressão Gênica
Pasteurella multocida/genética
Pasteurella multocida/patogenicidade
Precursores de Proteínas/toxicidade
[Mh] Termos MeSH secundário: Animais
Proteínas de Bactérias/metabolismo
Galinhas
Biologia Computacional
Etanolaminofosfotransferase/metabolismo
Etanolaminas/química
Etanolaminas/metabolismo
Fator Proteico para Inversão de Estimulação/genética
Fator Proteico para Inversão de Estimulação/metabolismo
Galactose/química
Galactose/metabolismo
Perfilação da Expressão Gênica
Heptoses/química
Heptoses/metabolismo
Isoenzimas
Lipídeo A/química
Lipídeo A/metabolismo
Mutação
Proteínas Nucleares/genética
Proteínas Nucleares/metabolismo
Infecções por Pasteurella/microbiologia
Infecções por Pasteurella/patologia
Pasteurella multocida/classificação
Pasteurella multocida/efeitos dos fármacos
Filogenia
Açúcares Ácidos/química
Açúcares Ácidos/metabolismo
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Blood Proteins); 0 (Ethanolamines); 0 (Factor For Inversion Stimulation Protein); 0 (Heptoses); 0 (Isoenzymes); 0 (Lipid A); 0 (Nuclear Proteins); 0 (Protein Precursors); 0 (Sugar Acids); 0 (cathelicidin 2 protein, mammal); 1069-03-0 (2-keto-3-deoxyoctonate); 78A2BX7AEU (phosphorylethanolamine); EC 2.7.8.1 (Ethanolaminephosphotransferase); X2RN3Q8DNE (Galactose)
[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:170907
[St] Status:MEDLINE


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[PMID]:28829723
[Au] Autor:Mwaiswelo R; Ngasala B; Gil JP; Malmberg M; Jovel I; Xu W; Premji Z; Mmbando BP; Björkman A; Mårtensson A
[Ad] Endereço:Department of Parasitology and Medical Entomology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
[Ti] Título:Sustained High Cure Rate of Artemether-Lumefantrine against Uncomplicated Malaria after 8 Years of Its Wide-Scale Use in Bagamoyo District, Tanzania.
[So] Source:Am J Trop Med Hyg;97(2):526-532, 2017 Aug.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We assessed the temporal trend of artemether-lumefantrine (AL) cure rate after 8 years of its wide-scale use for treatment of uncomplicated malaria from 2006 to 2014 in Bagamoyo district, Tanzania. Trend analysis was performed for four studies conducted in 2006, 2007-2008, 2012-2013, and 2014. Patients with acute uncomplicated malaria were enrolled, treated with standard AL regimen and followed-up for 3 (2006), 28 (2014), 42 (2012-2013), or 56 (2007-2008) days for clinical and laboratory evaluation. Primary outcome was day 28 polymerase chain reaction (PCR)-adjusted cure rate across years from 2007 to 2014. Parasite clearance was slower for the 2006 and 2007-2008 cohorts with less than 50% of patients cleared of parasitemia on day 1, but was rapid for the 2012-2013 and 2014 cohorts. Day 28 PCR-adjusted cure rate was 168/170 (98.8%) (95% confidence interval [CI], 97.2-100), 122/127 (96.1%) (95% CI, 92.6-99.5), and 206/207 (99.5%) (95% CI, 98.6-100) in 2007-2008, 2012-2013, and 2014, respectively. There was no significant change in the trend of cure rate between 2007 and 2014 (χ test = 0.06, = 0.90). Pretreatment multidrug-resistant gene 1 ( ) N86 prevalence increased significantly across years from 13/48 (27.1%) in 2006 to 183/213 (85.9%) in 2014 ( < 0.001), and chloroquine resistance transporter gene ( ) K76 prevalence increased significantly from 24/47 (51.1%) in 2006 to 198/205 (96.6%) in 2014 ( < 0.001). The AL cure rate remained high after 8 years of its wide-scale use in Bagamoyo district for the treatment of uncomplicated malaria despite an increase in prevalence of pretreatment N86 and K76 between 2006 and 2014.
[Mh] Termos MeSH primário: Antimaláricos/uso terapêutico
Artemisininas/uso terapêutico
Quimioterapia Combinada
Etanolaminas/uso terapêutico
Fluorenos/uso terapêutico
Malária Falciparum/tratamento farmacológico
Malária Falciparum/epidemiologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seres Humanos
Masculino
Meia-Idade
Prevalência
Tanzânia/epidemiologia
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Ethanolamines); 0 (Fluorenes); C7D6T3H22J (artemether); F38R0JR742 (lumefantrine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.16-0780


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[PMID]:28822205
[Au] Autor:Sondo P; Derra K; Nakanabo SD; Tarnagda Z; Kazienga A; Valea I; Sorgho H; Ouédraogo JB; Guiguemdé TR; Tinto H
[Ad] Endereço:Institut de Recherche en Science de la Santé- Unité de Recherche Clinique de Nanoro (IRSS-URCN) BP 218 Ouagadougou CMS11, Nanoro, Burkina Faso
[Ti] Título:Comparison of effectiveness of two different artemisinin-based combination therapies in an area with high seasonal transmission of malaria in Burkina Faso
[So] Source:Ann Parasitol;63(2):127-131, 2017.
[Is] ISSN:2299-0631
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:In Sahelian countries such as Burkina Faso, malaria transmission is seasonal with a high incidence of transmission during the rainy season. This study aimed to compare the effectiveness of the two recommended treatments (Artemether-Lumefantrine and Artesunate-Amodiaquine) for uncomplicated malaria in Burkina Faso regarding this seasonal variation of malaria transmission. This is part of a randomized open label trial comparing the effectiveness and safety of Artemether-Lumefantrine versus Artesunate-Amodiaquine according to routine practice in Nanoro. Patients with uncomplicated falciparum malaria were recruited all year round and followed-up for 28 days. To distinguish recrudescences from new infections, dried blood spots from day 0 and day of recurrent parasitaemia were used for nested-PCR genotyping of the polymorphic loci of the merozoite surface proteins 1 and 2. Seasonal influence was investigated by assessing the treatment outcomes according to the recruitment period of the patients. Two main groups (dry season versus rainy season) were defined following the seasonal characteristics of the study area. In Artemether-Lumefantrine group, the uncorrected cure rate was 76.5% in dry season versus 37.9% in rainy season. In Artesunate-Amodiaquine group, this was 93.3% and 57.1% during dry and rainy seasons, respectively. After PCR adjustment, the cure rate decreased from 85.9% in dry season to 75.0% in rainy season in Artemether-Lumefantrine group. InA rtesunate-Amodiaquine group, it was 93.3% in dry season and 80.7% during the rainy season. During the rainy season around 50% of patients had a new malaria episode by Day 28. The cure rate of both Artemether-Lumefantrine and Artesunate-Amodiaquine treatments was higher in dry season compared to rainy season due to high incidence of reinfections during the rainy season. For this reason, in addition to the curative effect, the post-treatment prophylactic effect should be taken into account in the choice of antimalarial regimens.
[Mh] Termos MeSH primário: Amodiaquina/uso terapêutico
Artemisininas/uso terapêutico
Etanolaminas/uso terapêutico
Fluorenos/uso terapêutico
Malária Falciparum/tratamento farmacológico
Estações do Ano
[Mh] Termos MeSH secundário: Artemisininas/administração & dosagem
Burkina Faso/epidemiologia
Pré-Escolar
Combinação de Medicamentos
Quimioterapia Combinada
Etanolaminas/administração & dosagem
Fluorenos/administração & dosagem
Seres Humanos
Lactente
Malária Falciparum/epidemiologia
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Artemisinins); 0 (Drug Combinations); 0 (Ethanolamines); 0 (Fluorenes); 0 (amodiaquine, artesunate drug combination); 220236ED28 (Amodiaquine); C7D6T3H22J (artemether); F38R0JR742 (lumefantrine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170820
[St] Status:MEDLINE
[do] DOI:10.17420/ap6302.96


  9 / 10399 MEDLINE  
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[PMID]:28796890
[Au] Autor:Uyama T; Tsuboi K; Ueda N
[Ad] Endereço:Department of Biochemistry, Kagawa University School of Medicine, Japan.
[Ti] Título:An involvement of phospholipase A/acyltransferase family proteins in peroxisome regulation and plasmalogen metabolism.
[So] Source:FEBS Lett;591(18):2745-2760, 2017 Sep.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The H-Ras-like suppressor (HRASLS) is a protein family consisting of five members in humans. Despite their discovery as tumor suppressors, we demonstrated that all these proteins are phospholipid-metabolizing enzymes, such as phospholipase (PL) A /A and acyltransferase. We thus proposed to rename HRASLS1-5 as PLA/acyltransferase (PLAAT)-1-5. Notably, PLAATs exhibit N-acyltransferase activity to biosynthesize N-acylated ethanolamine phospholipids, including N-acyl-plasmalogen, which serve as precursors of bioactive N-acylethanolamines. Furthermore, the overexpression of PLAAT-3 in animal cells causes disappearance of peroxisomes and a remarkable reduction in plasmalogen levels. This finding might be related to the inhibitory effect of PLAAT-3 on the chaperone activity of the peroxin PEX19. In this article, we will review our recent findings about PLAAT proteins, with special reference to their roles in peroxisome biogenesis and plasmalogen metabolism.
[Mh] Termos MeSH primário: Peroxissomos/metabolismo
Plasmalogênios/metabolismo
[Mh] Termos MeSH secundário: Animais
Diacilglicerol O-Aciltransferase/metabolismo
Etanolaminas/metabolismo
Seres Humanos
Proteínas de Membrana/metabolismo
Fosfolipases A1/metabolismo
Fosfolipases A2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Ethanolamines); 0 (Membrane Proteins); 0 (N-acylethanolamines); 0 (Plasmalogens); EC 2.3.1.20 (Diacylglycerol O-Acyltransferase); EC 3.1.1.32 (Phospholipases A1); EC 3.1.1.4 (Phospholipases A2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12787


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[PMID]:28772225
[Au] Autor:Suh JH; Makarova AM; Gomez JM; Paul LA; Saba JD
[Ad] Endereço:Children's Hospital Oakland Research Institute, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
[Ti] Título:An LC/MS/MS method for quantitation of chemopreventive sphingadienes in food products and biological samples.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1061-1062:292-299, 2017 Sep 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Colorectal cancer (CRC) is a leading cause of cancer mortality. Diet has a significant influence on colon cancer risk. Identifying chemopreventive agents, dietary constituents, practices and/or diet supplements that promote gut health and reduce the incidence of intestinal neoplasias and CRC could significantly impact public health. Sphingadienes (SDs) are dietary sphingolipids found in plant-based food products. SDs are cytotoxic to colon cancer cells and exhibit chemopreventive properties. The aim of the present study was to develop a sensitive and robust ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for quantifying SDs in food products and biological samples. The assay was linear over a concentration range of 80nM to 50µM and was sensitive to a detection limit of 3.3nM. Post-extraction stability was 100% at 24h. SD content in soy oils was approximately 10nM. SDs were detected transiently in the plasma of adult mice 10min after gavage delivery of a 25mg/kg bolus and declined to baseline by 1h. SD uptake in the gut was maximal in the duodenum and peaked 1h after gavage delivery. Disappearance of SDs in the lower gastrointestinal tract suggests either rapid metabolism to yet unidentified products or potentially luminal export.
[Mh] Termos MeSH primário: Cromatografia Líquida/métodos
Etanolaminas/análise
Análise de Alimentos/métodos
Esfingolipídeos/análise
[Mh] Termos MeSH secundário: Animais
Etanolaminas/farmacocinética
Absorção Intestinal
Limite de Detecção
Modelos Lineares
Camundongos
Reprodutibilidade dos Testes
Alimentos de Soja/análise
Esfingolipídeos/farmacocinética
Espectrometria de Massas em Tandem/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ethanolamines); 0 (Sphingolipids); 25696-03-1 (sphingadienine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE



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