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Pesquisa : D03.383.742.698 [Categoria DeCS]
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Id: biblio-955116
Autor: Rogerio, Kamilla Rodrigues; Carvalho, Leonardo J M; Domingues, Luiza Helena Pinto; Neves, Bruno Junior; Moreira Filho, José Teófilo; Castro, Rosane Nora; Bianco Júnior, Cesare; Daniel-Ribeiro, Claudio Tadeu; Andrade, Carolina Horta; Graebin, Cedric Stephan.
Título: Synthesis and molecular modelling studies of pyrimidinones and pyrrolo[34-d]-pyrimidinodiones as new antiplasmodial compounds
Fonte: Mem. Inst. Oswaldo Cruz;113(8):e170452, 2018. tab, graf.
Idioma: en.
Resumo: BACKGROUND Malaria is responsible for 429,000 deaths per year worldwide, and more than 200 million cases were reported in 2015. Increasing parasite resistance has imposed restrictions to the currently available antimalarial drugs. Thus, the search for new, effective and safe antimalarial drugs is crucial. Heterocyclic compounds, such as dihydropyrimidinones (DHPM), synthesised via the Biginelli multicomponent reaction, as well as bicyclic compounds synthesised from DHPMs, have emerged as potential antimalarial candidates in the last few years. METHODS Thirty compounds were synthesised employing the Biginelli multicomponent reaction and subsequent one-pot substitution/cyclisation protocol; the compounds were then evaluated in vitro against chloroquine-resistant Plasmodium falciparum parasites (W2 strain). Drug cytotoxicity in baseline kidney African Green Monkey cells (BGM) was also evaluated. The most active in vitro compounds were evaluated against P. berghei parasites in mice. Additionally, we performed an in silico target fishing approach with the most active compounds, aiming to shed some light into the mechanism at a molecular level. RESULTS The synthetic route chosen was effective, leading to products with high purity and yields ranging from 10-84%. Three out of the 30 compounds tested were identified as active against the parasite and presented low toxicity. The in silico study suggested that among all the molecular targets identified by our target fishing approach, Protein Kinase 3 (PK5) and Glycogen Synthase Kinase 3β (GSK-3β) are the most likely molecular targets for the synthesised compounds. CONCLUSIONS We were able to easily obtain a collection of heterocyclic compounds with in vitro anti-P. falciparum activity that can be used as scaffolds for the design and development of new antiplasmodial drugs.
Descritores: Desenho de Drogas
Testes de Sensibilidade Parasitária
Antimaláricos/síntese química
Antimaláricos/farmacologia
-Pirimidinonas
Pirróis
Responsável: BR1.1 - BIREME


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Id: lil-610527
Autor: Wang, Yong-Zhong; Xiao, Jun-Hua; Liu, Long-Gen; Ye, Chun-Yan; Shen, Hong-Yu; Xu, Tian-Min; Zhu, Ke-Zhuan.
Título: Simultaneous detection of hepatitis B virus genotypes and mutations associated with resistance to lamivudine, adefovir, and telbivudine by the polymerase chain reaction-ligase detection reaction
Fonte: Braz. j. infect. dis;15(6):560-566, Nov.-Dec. 2011. ilus, tab.
Idioma: en.
Projeto: Social development fund.
Resumo: OBJECTIVES: Detection of mutations associated to nucleos(t)ide analogs and hepatitis B virus (HBV) genotyping are essential for monitoring treatment of HBV infection. We developed a multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) assay for the rapid detection of HBV genotypes and mutations associated with lamivudine, adefovir, and telbivudine resistance in HBV-infected patients. METHODS: HBV templates were amplified by PCR, followed by LDR and electrophoresis on a sequencer. The assay was evaluated using plasmids that contained wild-type or mutant HBV sequences and 216 clinical samples. RESULTS: The PCR-LDR assay and sequencing gave comparable results for 158 of the 216 samples (73.1 percent) with respect to mutation detection and genotyping. Complete agreement between the two methods was observed for all the samples (100 percent) at codon 180 and codon 204. Concordant results were observed for 99.4 percent of the 158 samples at codon 181 and 98.7 percent at codon 236. The genotyping results were completely concordant between the PCR-LDR assay and sequencing. The PCR-LDR assay could detect a proportion of 1 percent mutant plasmid in a background of wild-type plasmid. CONCLUSION: The PCR-LDR assay is sensitive and specific for detection of HBV genotypes and drug resistance mutations, and could be helpful for decision making in the treatment of HBV infection.
Descritores: Adenina/análogos & derivados
Antivirais/farmacologia
Farmacorresistência Viral Múltipla/genética
Vírus da Hepatite B/efeitos dos fármacos
Lamivudina/farmacologia
Mutação/genética
Nucleosídeos/farmacologia
Ácidos Fosforosos
Pirimidinonas/farmacologia
-Adenina/farmacologia
DNA Viral/genética
Genótipo
Vírus da Hepatite B/genética
Hepatite B/virologia
Reação em Cadeia da Ligase
Testes de Sensibilidade Microbiana
Reação em Cadeia da Polimerase Multiplex
Limites: Seres Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


  3 / 11 LILACS  
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Id: lil-589958
Autor: Peixoto, Mario Ferreira; Pilotto, José Henrique; Stoszek, Sonia Karolina; Kreitchmann, Regis; Mussi-Pinhata, Marisa Márcia; Melo, Victor Hugo; João, Esaú Custodio; Ceriotto, Mariana; Souza, Ricardo da Silva de; Read, Jennifer.
Título: Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities
Fonte: Braz. j. infect. dis;15(3):253-261, May-June 2011. tab.
Idioma: en.
Projeto: Eunice Kennedy Shriver. National Institute of Child Health and Human Development.
Resumo: OBJECTIVES: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r) dosing during the third trimester of pregnancy. METHODS: We evaluated data on pregnant women from NISDI cohorts (2002-2009) enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. RESULTS: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day) (Group 1)] and 70 increased dosing [(> 800/200 mg/day) (Group 2)]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts > 500 cells/mm³. Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. CONCLUSION: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants.
Descritores: Fármacos Anti-HIV/efeitos adversos
Infecções por HIV/tratamento farmacológico
Inibidores da Protease de HIV/efeitos adversos
Complicações Infecciosas na Gravidez/tratamento farmacológico
Pirimidinonas/efeitos adversos
Ritonavir/efeitos adversos
-Fármacos Anti-HIV/administração & dosagem
Estudos de Coortes
Infecções por HIV/sangue
Inibidores da Protease de HIV/administração & dosagem
Terceiro Trimestre da Gravidez
Complicações Infecciosas na Gravidez/sangue
Pirimidinonas/administração & dosagem
Fatores de Risco
Ritonavir/administração & dosagem
Limites: Feminino
Seres Humanos
Recém-Nascido
Masculino
Gravidez
Tipo de Publ: Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
Responsável: BR1.1 - BIREME


  4 / 11 LILACS  
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Id: lil-589953
Autor: Wiens, Astrid; Venson, Rafael; Correr, Cassyano Januário; Pontarolo, Roberto.
Título: Cost-effectiveness of telbivudine versus lamivudine for chronic hepatitis B
Fonte: Braz. j. infect. dis;15(3):225-230, May-June 2011. ilus, tab.
Idioma: en.
Resumo: BACKGROUND AND AIM: Chronic hepatitis B is a highly prevalent disease worldwide, leading to serious consequences if not properly treated. Six treatment options for chronic hepatitis B are currently provided by the Brazilian public health system. Telbivudine is a nucleoside analogue that is neither included in the Brazilian clinical protocol nor in the therapeutic guidelines for chronic hepatitis B. OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of telbivudine for the viewpoint of the Brazilian public system, comparing it to lamivudine. METHODS: A Markov model was used to project lifetime complications and costs of treatment with lamivudine or telbivudine for chronic hepatitis B in both HBeAg-positive and HBeAg-negative patients. To evaluate disease progression, probabilities and utilities of virologic response, virologic resistance, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, treatment, interruption of treatment, death and seroconversion were collected in systematic reviews. Costs were collected in DATASUS, ABC da Saúde and scientific literature. RESULTS: Higher rate of virologic response and seroconversion was obtained with telbivudine, and also higher values of quality adjusted life years. However lamivudine is associated with lower costs and also lower cost-effectiveness values. The incremental cost-effectiveness ratios for telbivudine, when compared with lamivudine, were US$ 30,575 and US$ 40,457, respectively for HBeAg-positive and HBeAg-negative patients. CONCLUSION: In chronic hepatitis B lamivudine is a more cost-effective or even cost-saving strategy when compared with telbivudine.
Descritores: Antivirais/uso terapêutico
Hepatite B Crônica/tratamento farmacológico
Lamivudina/uso terapêutico
Nucleosídeos/uso terapêutico
Pirimidinonas/uso terapêutico
Inibidores da Transcriptase Reversa/uso terapêutico
-Antivirais/economia
Análise Custo-Benefício
Hepatite B Crônica/economia
Lamivudina/economia
Nucleosídeos/economia
Pirimidinonas/economia
Inibidores da Transcriptase Reversa/economia
Limites: Seres Humanos
Tipo de Publ: Estudo Comparativo
Revisão
Responsável: BR1.1 - BIREME


  5 / 11 LILACS  
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Cherchiglia, Mariângela Leal
Acúrcio, Francisco de Assis
Texto completo
Id: lil-556013
Autor: Almeida, Alessandra Maciel; Ribeiro, Andréia Queiroz; Pádua, Cristiane Aparecida Menezes de; Brandão, Cristina Mariano Ruas; Andrade, Eli Iôla Gurgel; Cherchiglia, Mariângela Leal; Carmo, Ricardo Andrade; Acurcio, Francisco de Assis.
Título: Eficácia do adefovir dipivoxil, entecavir e telbivudina para o tratamento da hepatite crônica B: revisão sistemática / The efficacy of adefovir dipivoxil, entecavir and telbivudine for chronic hepatitis B treatment: a systematic review
Fonte: Rev. Soc. Bras. Med. Trop;43(4):440-451, jul.-ago. 2010. ilus, tab.
Idioma: pt.
Projeto: CNPq; . FAPEMIG.
Resumo: INTRODUÇÃO: A hepatite crônica B é uma das doenças infecciosas mais frequentes no mundo e constitui um grave problema de saúde pública MÉTODOS: Para avaliar a eficácia dos análogos de núcleosídeo/nucletídeo utilizados no seu tratamento (adefovir dipivoxil, entecavir e telbivudina) foi conduzida uma revisão sistemática de ensaios clínicos randomizados. Foram consultadas, dentre outras, as bases de dados PubMed e LILACS RESULTADOS: Foram selecionados 29 artigos entre os publicados de janeiro/1970 até dezembro/2009 CONCLUSÕES: Todos os análogos de núcleosídeo/nucletídeo apresentam eficácia superior ou similar à lamivudina. O entecavir pode ser indicado para o tratamento da hepatite B crônica como alternativa à lamivudina em pacientes HBeAg positivo e negativo virgens de tratamento, considerando seu baixo potencial de resistência viral. A adição de adefovir à lamivudina apresentou bons resultados em pacientes resistentes à lamivudina. O uso de entecavir e telbivudina nesses pacientes apresenta risco de resistência cruzada. Telbivudina é um dos mais recentes antivirais disponíveis, mas resistência antiviral já documentada representa limitação ao seu uso como opção terapêutica à lamivudina. Eventos adversos aos análogos de núcleosídeo/nucletídeo foram similares em características, gravidade e incidência quando comparados à lamivudina e placebo.

INTRODUCTION: Chronic hepatitis B is one of the most frequent infectious disease in the world and represents a serious problem of public health METHODS: A systematic review of randomized clinical trials was conducted to evaluate the efficacy of the nucleoside/nucleotide analogues (adefovir, entecavir and telbivudine) used for the treatment of chronic hepatitis B. The databases PubMed and LILACS were consulted, among others RESULTS: Twenty nine articles published between January/1970 to December/2009 were selected CONCLUSIONS: All nucleoside/nucleotide analogues demonstrate upper or similar efficacy to lamivudine. The entecavir can be appropriate for patients with chronic hepatitis B, HBeAg positive and negative treatment-naive as alternative to lamivudine, considering its low potential of viral resistance. The addition of adefovir to lamivudine presented good results in lamivudine resistant patients. The use of entecavir and telbivudine in those patients presents risk of crossed resistance. TBV is one of the most recent antivirals available, but antiviral resistance already documented represents limitation to its use as therapeutic option to LAM. Adverse events of nucleoside/nucleotide analogues were similar in characteristics, gravity and incidence when compared to the lamivudina and placebo.
Descritores: Adenina/análogos & derivados
Antivirais/uso terapêutico
Guanina/análogos & derivados
Hepatite B Crônica/tratamento farmacológico
Nucleosídeos/uso terapêutico
Ácidos Fosforosos
Pirimidinonas/uso terapêutico
-Adenina/uso terapêutico
Guanina/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
Resultado do Tratamento
Limites: Seres Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Revisão
Responsável: BR1.1 - BIREME


  6 / 11 LILACS  
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Id: lil-454677
Autor: Machado, Daisy Maria; Gouvêa, Aída de Fátima Barbosa; Cardoso, Maria Regina; Beltrão, Suênia Vasconcelos; Cunegundes, Kelly Simone; Bononi, Fabiana; Almeida, Fernanda; Cavalheiro, Kaline; Angelis, Daniela Souza Araújo de; Succi, Regina Célia de Menezes.
Título: Factors associated with clinical, immunological and virological responses in protease-inhibitor-experienced brazilian children receiving highly active antiretroviral therapy containing Lopinavir-Ritonavir
Fonte: Braz. j. infect. dis;11(1):16-19, Feb. 2007. tab.
Idioma: en.
Resumo: This study evaluates clinical, virological and immunological responses to antiretroviral (ARV) therapy based on Lopinavir/ritonovir (LPV/r) in previously protease -inhibitor-experienced children. The study included 29 Brazilian children (median age = 5.91 years) who had failed previous ARV therapy and had begun a regimen based on LPV/r. At 12 months follow-up, a good virological response to LPV/r therapy was defined as achieving an undetectable viral load or as a decrease in plasma HIV RNA levels to > 1 log. A good immunological response was defined as an increase in CD4+ cell count from baseline sufficient to attain a better CDC immune stage classification. The number of infectious episodes 12 months before and 12 months after beginning LPV/r was assessed. Sixteen (55.2 percent) and 19 (65.5 percent) of 29 patients exhibited good virological and immunological responses, respectively. Baseline CD4+ values (>500) predicted both virological and immunological responses (p<0.05). Older children were less likely to develop an immunological response (p<0.001) than younger children. Nine children receiving 3 ARV drugs plus LPV/r showed an immunological response (100 percent) compared to 10/20 (50 percent) children receiving 2 drugs plus LPV/r (p=0.01). A lower number (n<5) of infectious episodes was noted after 12 months follow-up in children using the LPV/r regimen (p=0.006). There was a positive correlation between children whose baseline CD4+ values were greater than 500 cells/mm³ and virological responses. Although virological responses to therapy were seen in about half the children (55.2 percent), the use of HAART containing LPV/r provided clinical and immmunological benefits.
Descritores: Terapia Antirretroviral de Alta Atividade
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico
Inibidores da Protease de HIV/uso terapêutico
Pirimidinonas/uso terapêutico
Ritonavir/uso terapêutico
-Síndrome de Imunodeficiência Adquirida/imunologia
Síndrome de Imunodeficiência Adquirida/virologia
CDABBREVIATIONS AS TOPIC LYMPHOCYTE COUNT
Seguimentos
Estudos Longitudinais
RNA Viral
Resultado do Tratamento
Carga Viral
Limites: Criança
Pré-Escolar
Seres Humanos
Responsável: BR1.1 - BIREME


  7 / 11 LILACS  
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Id: lil-439442
Autor: Vallejos Campos, Maysie.
Título: I. Sección medicamentos: Lopinavir: Ritonavir / I. Section medicines: Lopinavir: Ritonavir
Fonte: Bol. inf. medicam. (Santiago de Chile);22(1/2):10-17, sept. 2005. ilus.
Idioma: es.
Descritores: Pirimidinonas/administração & dosagem
Pirimidinonas
Pirimidinonas/efeitos adversos
Ritonavir/análogos & derivados
Ritonavir
Ritonavir/efeitos adversos
-Overdose de Drogas
Inibidores da Protease de HIV
Responsável: CL1.1 - Biblioteca Central


  8 / 11 LILACS  
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Id: lil-419504
Autor: Cunha, André Marquez.
Título: Açao da associação lopinavir/ritonavir sobre a prenhez da rata albuna: aspectos microscópicos e bioquímicos / The effect of associated lopinavir/ritonavir on albino rat pregnancy: microscopical and biochemical aspects.
Fonte: São Paulo; s.n; 2005. [50] p.
Idioma: pt.
Tese: Apresentada a Universidade Federal de São Paulo. Escola Paulista de Medicina. Curso de Obstetrícia para obtenção do grau de Doutor.
Resumo: Objetivo: Avaliar a associação lopinavir/ritonavir quanto aos seus efeitos sobre bioquímica e histologia de fígado e rins de ratas prenhes. Métodos: A associação foi administrada a 4 grupos de 10 ratas, durante toda a prenhez, diariamente, nas doses de 13,3mg lopinavir/3,3mg ritonavir por kg (dose equivalente à de humanos)(Expert1); 39,9mg/9,9mg por kg (Exper2); 119,7mg/29,9mg por kg (Exper3); 2ml propilenoglicol(veículo) para grupo controle (Contr). Resultados: Histologia de Exper1 foi normal. Fígados maternos de Exper2 apresentaram hepatócitos menores, citoplasma eosinófilo e núcleos pequenos além de vasodilatação; em Exper3, alterações foram semelhantes, pouco mais intensas. Rins maternos de Exper2 apresentaram alguns tubulos contorcidos com áreas eosinófilas e núcleos hipercromáticos além de vasodilatação; em Exper3 foram semelhantes, porém mais intensas. Órgãos fetais apresentaram apenas vasodilatação, em Exper3. ANOVA mostrou que apenas Transminase Glutâmica Pirúvica não se alterou (p = 0,293). Nas comparações múltiplas dos demais exames, comparados a Contr, grupos experimentais mostraram: Transaminase Glutâmica Oxalacética aumentada em Exper2 (p=0,007) e Exper3 (p=0,001); uréia diminuída em Exper1 (p=0,023) e Exper3 (p=0,114) assim como a creatinina em Exper1 (p<0,001), Exper2 (p=0,32) e Exper3 (p=0,048). Conclusões: Doses superiores à preconizada em humanos causaram alterações focais na histologia hepática e renal sem aumento nas provas funcionais que pudessem refletir destes órgãos. A maior dose causou vasodilatação nos órgãos fetais
Descritores: Gravidez
Pirimidinonas
Ratos
Ritonavir
Responsável: BR1.2 - Biblioteca Central
BR1.2; 9155


  9 / 11 LILACS  
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Texto completo SciELO Chile
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Id: lil-274637
Autor: Gallardo E., Jorge; Rubio L., Betzabé; Ahumada O., Mónica; Cortés A., Claudio.
Título: Eficacia de gemcitabina en cáncer de vesícula biliar: experiencia inicial en 4 casos / Efficacy of gemcitabine in gallbladder cancer: report of 4 cases
Fonte: Rev. méd. Chile;128(9):1025-30, sept. 2000. ilus.
Idioma: es.
Resumo: Surgery continues to be the only curative therapy for gallbladder cancer, but useful in very few patients. Mean survival of patients with gallbladder cancer, that are out of the reach of surgery, is 3 months. The few clinical trials of chemotherapy for this disease, report very low success rates. We report four patients with advanced gallbladder cancer, treated with gemcitabine in an intravenous dose of 1000 mg/m2, given in 30 min, once a week during three consecutive weeks, every 28 days. There was a partial response that lasted 40,3 23,2 weeks with a mean survival of 59,75 17 weeks. One patient survives without evidences of disease after 17 months of the diagnosis of an advanced cancer. In all patients, symptoms were alleviated, functional status and quality of life improved. Toxicity was mild and did not require reduction in doses or delay in therapy. Therefore, this medication deserves further investigation for the treatment of gallbladder cancer
Descritores: Antimetabólitos Antineoplásicos/uso terapêutico
Neoplasias da Vesícula Biliar/tratamento farmacológico
-Quimioterapia Adjuvante
Intervalo Livre de Doença
Metástase Neoplásica/tratamento farmacológico
Pirimidinonas/administração & dosagem
Pirimidinonas/farmacologia
Resultado do Tratamento
Limites: Seres Humanos
Feminino
Masculino
Adulto
Meia-Idade
Tipo de Publ: Relatos de Casos
Responsável: CL1.1 - Biblioteca Central


  10 / 11 LILACS  
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Colussi, V. C
Id: lil-186409
Autor: Colussi, V. C; Nicola, E. M. D; Nicola, J. H.
Título: Fototerapia, fotoquimioterapia e alguns fotossensibilizadores / Phototherapy, photochemotherapy and some photosensitizers
Fonte: Rev. Assoc. Med. Bras. (1992);42(4):229-36, out.-dez. 1996. graf.
Idioma: pt.
Descritores: Fotoquimioterapia
Fármacos Fotossensibilizantes/uso terapêutico
Fototerapia
-Corantes Fluorescentes/uso terapêutico
Pirimidinonas/uso terapêutico
Rodaminas/uso terapêutico
Limites: Animais
Seres Humanos
Tipo de Publ: Revisão
Responsável: BR1.1 - BIREME



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