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Alves, Luiz Carlos
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[PMID]:29366735
[Au] Autor:Mariz Gomes da Silva LM; de Oliveira JF; Silva WL; da Silva AL; de Almeida Junior ASA; Barbosa Dos Santos VH; Alves LC; Brayner Dos Santos FA; Costa VMA; Aires AL; de Lima MDCA; Albuquerque MCPA
[Ad] Endereço:Keizo Asami Immunopathology Laboratory (LIKA), Federal University of Pernambuco, 50740-465, Recife, PE, Brazil.
[Ti] Título:New 1,3-benzodioxole derivatives: Synthesis, evaluation of in vitro schistosomicidal activity and ultrastructural analysis.
[So] Source:Chem Biol Interact;283:20-29, 2018 Mar 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Schistosomiasis is considered a serious public health problem in 78 countries and territories located in Africa, Asia and America and it is estimated in more than 249 million people infected by any of the species of Schistosoma. The exclusive use of praziquantel (PZQ), effective drug against all species of Schistosoma, has been the basis of the development of a possible resistance against the strains of this parasite. In addition, PZQ is not effective against young forms of worms. Thus, there is a need for the development of new drugs with schistosomicidal activity. The objective of this work was to synthesize and to evaluate the therapeutic potential of new benzodioxole derivatives (3-14) candidates for schistosomicidal drugs. All compounds synthesized showed in vitro schistosomicidal activity. The derivative 12 was considered the best compound, since it took 100% of worms to mortality in the first 72 h of exposure at the concentration of 100 µM and 83.3% at the concentration of 50 µM. Furthermore, male and female adult worms, incubated for 24 h with the compound 12 showed tegument damages characterized by extensive desquamation and edema, tuber destruction, bubble formation and exposure of the muscle layer. This compound has a restricted structure, where the thiazolidinone is attached to the 4-position of the 1,3-benzodioxol ring. The structural conformation of derivative 12 was probably responsible for the promising schistosomicidal activity, where the presence of an electron/conformational restriction of the thiazolidine ring, as well as the action of bromine as a bulk substitute, favored an increase in biological activity. In addition, tegumentary changes caused by derivative 12 may also have been responsible for the death of adult worms of Schistosoma mansoni. Therefore, we verified that the results obtained in this study make benzodioxole derivatives possible candidates for prototypes of new schistosomicidal drugs.
[Mh] Termos MeSH primário: Dioxóis/química
Dioxóis/farmacologia
Schistosoma mansoni/efeitos dos fármacos
Esquistossomicidas/síntese química
Esquistossomicidas/farmacologia
[Mh] Termos MeSH secundário: Animais
Sobrevivência Celular/efeitos dos fármacos
Dioxóis/uso terapêutico
Células HeLa
Seres Humanos
Microscopia Eletrônica de Varredura
Praziquantel/farmacologia
Praziquantel/uso terapêutico
Schistosoma mansoni/ultraestrutura
Esquistossomose/tratamento farmacológico
Esquistossomose/patologia
Esquistossomicidas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dioxoles); 0 (Schistosomicides); 6490C9U457 (Praziquantel); F0XLL582B8 (1,3-benzodioxole)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE


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[PMID]:29331278
[Au] Autor:Sobhy MMK; Mahmoud SS; El-Sayed SH; Rizk EMA; Raafat A; Negm MSI
[Ad] Endereço:Medical Parasitology Department, Kasr Al-Ainy School of Medicine, Cairo University, Egypt.
[Ti] Título:Impact of treatment with a Protein Tyrosine Kinase Inhibitor (Genistein) on acute and chronic experimental Schistosoma mansoni infection.
[So] Source:Exp Parasitol;185:115-123, 2018 Feb.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Schistosomiasis mansoni is considered one of the most common fibrotic diseases resulting from inflammation and deposition of fibrous tissue around parasitic eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge administration of it in endemic areas and its incompetence towards the immature stages have raised serious alarms against the development of drug resistance. Few drugs are directed to reverse schistosomal liver fibrosis, particularly at the chronic and advanced stages of the disease. Recently, protein tyrosine kinase (PTK) inhibitors have been identified as potent anti-schistosomal and anti-fibrotic drugs against schistosomes, that may suppress and reverse Schistosoma mansoni (S. mansoni) induced liver fibrosis. The present study was designed to assess the anti-schistosomal and antifibrotic activity of Genistein, a PTK inhibitor, in comparison to PZQ, on both acute and chronic S. mansoni-infected mice using different parasitological, histopathological and immunohistochemical studies. Genistein showed a significant reduction (P < .05) in total worm burden, tissue egg load, mean hepatic granulomas diameter and numbers, percentage of collagen and expression of transforming growth factor-beta 1 (TGF-ß 1) in the examined hepatocytes with elevation in percentage of degenerated ova, in comparison to the control groups, in both acute and chronic stages of infection. The best results were obtained when Genistein was combined with PZQ. Therefore, it was concluded that Genistein showed a promising anti-schistosomal and anti-fibrotic properties which could make it one of the new potential targets in chemotherapy against schistosomiasis.
[Mh] Termos MeSH primário: Genisteína/uso terapêutico
Inibidores de Proteínas Quinases/uso terapêutico
Proteínas Tirosina Quinases/antagonistas & inibidores
Esquistossomose mansoni/tratamento farmacológico
[Mh] Termos MeSH secundário: Doença Aguda
Animais
Anti-Helmínticos/farmacologia
Anti-Helmínticos/uso terapêutico
Biomphalaria
Doença Crônica
Colágeno/análise
Feminino
Genisteína/farmacologia
Granuloma/tratamento farmacológico
Granuloma/patologia
Processamento de Imagem Assistida por Computador
Imuno-Histoquímica/veterinária
Fígado/química
Fígado/parasitologia
Fígado/patologia
Cirrose Hepática/tratamento farmacológico
Cirrose Hepática/parasitologia
Cirrose Hepática/patologia
Masculino
Camundongos
Praziquantel/farmacologia
Praziquantel/uso terapêutico
Inibidores de Proteínas Quinases/farmacologia
Schistosoma mansoni/efeitos dos fármacos
Schistosoma mansoni/patogenicidade
Esquistossomose mansoni/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthelmintics); 0 (Protein Kinase Inhibitors); 6490C9U457 (Praziquantel); 9007-34-5 (Collagen); DH2M523P0H (Genistein); EC 2.7.10.1 (Protein-Tyrosine Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE


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[PMID]:28468637
[Au] Autor:Kigen G; Edwards G
[Ad] Endereço:Department of Pharmacology and Toxicology, Moi University School of Medicine, P.O. Box 4606, 30100, Eldoret, Kenya. kigengfk@gmail.com.
[Ti] Título:Drug-transporter mediated interactions between anthelminthic and antiretroviral drugs across the Caco-2 cell monolayers.
[So] Source:BMC Pharmacol Toxicol;18(1):20, 2017 May 04.
[Is] ISSN:2050-6511
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Drug interactions between antiretroviral drugs (ARVs) and anthelminthic drugs, ivermectin (IVM) and praziquantel (PZQ) were assessed by investigating their permeation through the Caco-2 cell monolayers in a transwell. The impact of anthelminthics on the transport of ARVs was determined by assessing the apical to basolateral (AP → BL) [passive] and basolateral to apical (BL → AP) [efflux] directions alone, and in presence of an anthelminthic. The reverse was conducted for the assessment of the influence of ARVs on anthelminthics. METHODS: Samples from the AP and BL compartments were taken at 60, 120, 180 and 240 min and quantified either by HPLC or radiolabeled assay using a liquid scintillating counter for the respective drugs. Transepithelial resistance (TEER) was used to assess the integrity of the monolayers. The amount of compound transported per second (apparent permeability, Papp) was calculated for both AP to BL (Papp ), and BL to AP (Papp ) movements. Samples collected after 60 min were used to determine the efflux ratio (ER), quotient of secretory permeability and absorptive permeability (PappBL-AP/PappAP-BL). The reverse, (PappAP-BL/PappBL-AP) constituted the uptake ratio. The impact of SQV, EFV and NVP on the transport of both IVM and PZQ were investigated. The effect of LPV on the transport of IVM was also determined. The influence of IVM on the transport of SQV, NVP, LPV and EFV; as well as the effect PZQ on the transport of SQV of was also investigated, and a two-tailed p value of <0.05 was considered significant. RESULTS: IVM significantly inhibited the efflux transport (BL → AP movement) of LPV (ER; 6.7 vs. 0.8, p = 0.0038) and SQV (ER; 3.1 vs. 1.2 p = 0.00328); and increased the efflux transport of EFV (ER; 0.7 vs. 0.9, p = 0.031) suggesting the possibility of drug transporter mediated interactions between the two drugs. NVP increased the efflux transport of IVM (ER; 0.8 vs. 1.8, p = 0.0094). CONCLUSIONS: The study provides in vitro evidence of potential interactions between IVM, an anthelminthic drug with antiretroviral drugs; LPV, SQV, NVP and EFV. Further investigations should be conducted to investigate the possibility of in vivo interactions.
[Mh] Termos MeSH primário: Anti-Helmínticos/metabolismo
Antirretrovirais/metabolismo
Ivermectina/metabolismo
Praziquantel/metabolismo
[Mh] Termos MeSH secundário: Transporte Biológico Ativo
Células CACO-2
Interações Medicamentosas
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthelmintics); 0 (Anti-Retroviral Agents); 6490C9U457 (Praziquantel); 70288-86-7 (Ivermectin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1186/s40360-017-0129-6


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[PMID]:29240773
[Au] Autor:Sundaraneedi MK; Tedla BA; Eichenberger RM; Becker L; Pickering D; Smout MJ; Rajan S; Wangchuk P; Keene FR; Loukas A; Collins JG; Pearson MS
[Ad] Endereço:School of Physical, Environmental and Mathematical Sciences, UNSW Canberra, Canberra, Australian Capital Territory, Australia.
[Ti] Título:Polypyridylruthenium(II) complexes exert anti-schistosome activity and inhibit parasite acetylcholinesterases.
[So] Source:PLoS Negl Trop Dis;11(12):e0006134, 2017 12.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Schistosomiasis affects over 200 million people and there are concerns whether the current chemotherapeutic control strategy (periodic mass drug administration with praziquantel (PZQ)-the only licenced anti-schistosome compound) is sustainable, necessitating the development of new drugs. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the anti-schistosome efficacy of polypyridylruthenium(II) complexes and showed they were active against all intra-mammalian stages of S. mansoni. Two compounds, Rubb12-tri and Rubb7-tnl, which were among the most potent in their ability to kill schistosomula and adult worms and inhibit egg hatching in vitro, were assessed for their efficacy in a mouse model of schistosomiasis using 5 consecutive daily i.v. doses of 2 mg/kg (Rubb12-tri) and 10 mg/kg (Rubb7-tnl). Mice treated with Rubb12-tri showed an average 42% reduction (P = 0.009), over two independent trials, in adult worm burden. Liver egg burdens were not significantly decreased in either drug-treated group but ova from both of these groups showed significant decreases in hatching ability (Rubb12-tri-68%, Rubb7-tnl-56%) and were significantly morphologically altered (Rubb12-tri-62% abnormal, Rubb7-tnl-35% abnormal). We hypothesize that the drugs exerted their activity, at least partially, through inhibition of both neuronal and tegumental acetylcholinesterases (AChEs), as worms treated in vitro showed significant decreases in activity of these enzymes. Further, treated parasites exhibited a significantly decreased ability to uptake glucose, significantly depleted glycogen stores and withered tubercules (a site of glycogen storage), implying drug-mediated interference in this nutrient acquisition pathway. CONCLUSIONS/SIGNIFICANCE: Our data provide compelling evidence that ruthenium complexes are effective against all intra-mammalian stages of schistosomes, including schistosomula (refractory to PZQ) and eggs (agents of disease transmissibility). Further, the results of this study suggest that schistosome AChE is a target of ruthenium drugs, a finding that can inform modification of current compounds to identify analogues which are even more effective and selective against schistosomes.
[Mh] Termos MeSH primário: Acetilcolinesterase/efeitos dos fármacos
Inibidores da Colinesterase/farmacologia
Compostos Organometálicos/farmacologia
Rutênio/farmacologia
Schistosoma haematobium/efeitos dos fármacos
Schistosoma mansoni/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Transporte Biológico/efeitos dos fármacos
Modelos Animais de Doenças
Feminino
Glucose/metabolismo
Larva
Masculino
Camundongos
Praziquantel/uso terapêutico
Schistosoma haematobium/enzimologia
Schistosoma mansoni/enzimologia
Esquistossomose Urinária/tratamento farmacológico
Esquistossomose Urinária/parasitologia
Esquistossomose mansoni/tratamento farmacológico
Esquistossomose mansoni/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0 (Organometallic Compounds); 6490C9U457 (Praziquantel); 7UI0TKC3U5 (Ruthenium); EC 3.1.1.7 (Acetylcholinesterase); IY9XDZ35W2 (Glucose)
[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:171215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006134


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[PMID]:29220347
[Au] Autor:Phillips AE; Gazzinelli-Guimaraes PH; Aurelio HO; Ferro J; Nala R; Clements M; King CH; Fenwick A; Fleming FM; Dhanani N
[Ad] Endereço:Schistosomiasis Control Initiative, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
[Ti] Título:Assessing the benefits of five years of different approaches to treatment of urogenital schistosomiasis: A SCORE project in Northern Mozambique.
[So] Source:PLoS Negl Trop Dis;11(12):e0006061, 2017 12.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In Mozambique, schistosomiasis is highly endemic across the whole country. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinates a five-year study that has been implemented in various African countries, including Mozambique. The overall goal of SCORE was to better understand how to best apply preventive chemotherapy with praziquantel (PZQ) for schistosomiasis control by evaluating the impact of alternative treatment approaches. METHODS: This was a cluster-randomised trial that compared the impact of different treatment strategies in study areas with prevalence among school children of ≥21% S. haematobium infection by urine dipstick. Each village was randomly allocated to one of six possible combinations of community-wide treatment (CWT), school-based treatment (SBT), and/or drug holidays over a period of four years, followed by final data collection in the fifth year. The most intense intervention arm involved four years of CWT, while the least intensive arm involved two years of SBT followed by two consecutive years of PZQ holiday. Each study arm included 25 villages randomly assigned to one of the six treatment arms. The primary outcome of interest was change in prevalence and intensity of S. haematobium among 100 children aged 9-to-12-years that were sampled each year in every village. In addition to children aged 9-to-12 years, 100 children aged 5-8 years in their first-year of school and 50 adults (aged 20-55 years) were tested in the first and final fifth year of the study. Prevalence and intensity of S. haematobium infection was evaluated by two filtrations, each of 10mL, from a single urine specimen. PRINCIPAL FINDINGS: In total, data was collected from 81,167 individuals across 149 villages in ten districts of Cabo Delgado province, Northern Mozambique. Overall PZQ treatment resulted in a significant reduction in the prevalence of S. haematobium infection from Year 1 to Year 5, where the average prevalence went from 60.5% to 38.8%, across all age groups and treatment arms. The proportion of those heavily infected also reduced from 17.6% to 11.9% over five years. There was a significantly higher likelihood of males being infected than females at baseline, but no significant difference between the sexes in their response to treatment. The only significant response based on a study arm was seen in both the 9-to-12-year-old and first-year cross sections, where two consecutive treatment holidays resulted in a significantly higher final prevalence of S. haematobium than no treatment holidays. When the arms were grouped together, four rounds of treatment (regardless of whether it was CWT or SBT), however, did result in a significantly greater reduction in S. haematobium prevalence than two rounds of treatment (i.e. with two intermittent or consecutive holiday years) over a five-year period. CONCLUSIONS: Although PC was successful in reducing the burden of active infection, even among those heavily infected, annual CWT did not have a significantly greater impact on disease prevalence or intensity than less intense treatment arms. This may be due to extremely high starting prevalence and intensity in the study area, with frequent exposure to reinfection, or related to challenges in achieving high treatment coverage More frequent treatment had a greater impact on prevalence and intensity of infection when arms were grouped by number of treatments, however, cost efficiency was greater in arms only receiving two treatments. Finally, a significant reduction in prevalence of S. haematobium was seen in adults even in the SBT arms implying the rate of transmission in the community had been decreased, even where only school children have been treated, which has significant logistical and cost-saving implications for a national control programme in justifying CWT.
[Mh] Termos MeSH primário: Anti-Helmínticos/uso terapêutico
Praziquantel/uso terapêutico
Schistosoma haematobium/efeitos dos fármacos
Esquistossomose Urinária/prevenção & controle
[Mh] Termos MeSH secundário: Adulto
Animais
Quimioprevenção
Criança
Pré-Escolar
Estudos Transversais
Doenças Endêmicas
Feminino
Seres Humanos
Masculino
Meia-Idade
Moçambique/epidemiologia
Pesquisa Operacional
Prevalência
Projetos de Pesquisa
Esquistossomose Urinária/tratamento farmacológico
Esquistossomose Urinária/epidemiologia
Instituições Acadêmicas
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anthelmintics); 6490C9U457 (Praziquantel)
[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:171209
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006061


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[PMID]:29329293
[Au] Autor:Ezeamama AE; Bustinduy AL; Nkwata AK; Martinez L; Pabalan N; Boivin MJ; King CH
[Ad] Endereço:Department of Psychiatry, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, United States of America.
[Ti] Título:Cognitive deficits and educational loss in children with schistosome infection-A systematic review and meta-analysis.
[So] Source:PLoS Negl Trop Dis;12(1):e0005524, 2018 01.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. METHODOLOGY/PRINCIPAL FINDINGS: This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in scholastic achievement was sensitive to ROB. Schistosoma infection-related deficits in learning and memory tests were invariant by ROB and study design. CONCLUSION/SIGNIFICANCE: Schistosoma infection/non-treatment was significantly associated with educational, learning, and memory deficits in SAC. Early treatment of children in Schistosoma-endemic regions could potentially mitigate these deficits. TRIAL REGISTRATION: ClinicalTrials.gov CRD42016040052.
[Mh] Termos MeSH primário: Disfunção Cognitiva/parasitologia
Transtornos de Aprendizagem/parasitologia
Transtornos da Memória/parasitologia
Esquistossomose/complicações
[Mh] Termos MeSH secundário: Adolescente
Animais
Anti-Helmínticos/uso terapêutico
Criança
Pré-Escolar
Cognição/fisiologia
Seres Humanos
Inteligência/fisiologia
Memória/fisiologia
Testes de Memória e Aprendizagem
Praziquantel/uso terapêutico
Tempo de Reação/fisiologia
Schistosoma/patogenicidade
Esquistossomose/tratamento farmacológico
Esquistossomose/psicologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Anthelmintics); 6490C9U457 (Praziquantel)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180210
[Lr] Data última revisão:
180210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005524


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[PMID]:29235368
[Au] Autor:Lago EM; Xavier RP; Teixeira TR; Silva LM; da Silva Filho AA; de Moraes J
[Ad] Endereço:Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Universus Veritas (UNIVERITAS UNG), Praça Tereza Cristina, 229, Centro, Guarulhos 07023-070, SP, Brazil.
[Ti] Título:Antischistosomal agents: state of art and perspectives.
[So] Source:Future Med Chem;10(1):89-120, 2018 Jan.
[Is] ISSN:1756-8927
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Praziquantel has remained the drug of choice for schistosomiasis chemotherapy for almost 40 years. The pressing need to develop a new antischistosomal drug may necessitate exploring and filtering chemotherapeutic history to search for the most promising ones. In this context, this review attempts to summarize all progress made in schistosomiasis chemotherapy from the early 20th century (mid-1910s) to 2016. We gathered almost 100 compounds providing information on therapeutic action, specifically covering at least first in vivo studies in animal model and in vitro. Pharmacokinetic and toxicity profiles of antischistosomal agents were also described. Preclinical studies indicate a handful of promising future candidates.
[Mh] Termos MeSH primário: Anti-Helmínticos/farmacologia
Praziquantel/farmacologia
Schistosoma/efeitos dos fármacos
Esquistossomose/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Testes de Sensibilidade Parasitária
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anthelmintics); 6490C9U457 (Praziquantel)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171225
[Lr] Data última revisão:
171225
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.4155/fmc-2017-0112


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[PMID]:29190292
[Au] Autor:Mahanty S; Orrego MA; Cangalaya C; Adrianzen MP; Arroyo G; Calcina J; Gonzalez AE; García HH; Guerra-Giraldez C; Nash TE; Cysticercosis Working Group in Peru
[Ad] Endereço:Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
[Ti] Título:TNF-α blockade suppresses pericystic inflammation following anthelmintic treatment in porcine neurocysticercosis.
[So] Source:PLoS Negl Trop Dis;11(11):e0006059, 2017 Nov.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Neurocysticercosis (NCC) is an infection of the brain with the larval cyst of the tapeworm, Taenia solium. Cysticidal treatment induces parasite killing resulting in a post inflammatory response and seizures, which generally requires corticosteroid treatment to control inflammation. The nature of this response and how to best control it is unclear. We investigated the anti-inflammatory effects of pretreatment with etanercept (ETN), an anti-tumor necrosis factor agent, or dexamethasone (DEX), a high potency corticosteroid, on the post treatment inflammatory response in naturally infected pigs with neurocysticercosis after a single dose of the cysticidal drug praziquantel (PZQ). METHODOLOGY/PRINCIPAL FINDINGS: We followed the methods from a previously developed treatment model of NCC in naturally infected swine. The four study groups of infected pigs included 3 groups treated with PZQ on day 0: PZQ-treated alone (100 mg/kg PO; n = 9), pretreated with dexamethasone (DEX, 0.2 mg/kg IM administered on days -1, +1 and +3; n = 6), and pretreated with etanercept (ETN, 25 mg IM per animal on days -7 and 0; n = 6). The fourth group remained untreated (n = 3). As measured by quantitative RT-PCR, ETN pretreatment depressed transcription of a wide range of proinflammatory, regulatory and matrix protease encoding genes at 120 hr post PZQ treatment in capsules of cysts that demonstrated extravasated Evans Blue (EB) (a measure of blood brain barrier dysfunction) compared to animals not receiving ETN. Transcription was significantly depressed for the proinflammatory genes tumor necrosis factor (TNF)-α, and interferon (IFN)-γ; the inflammation regulating genes cytotoxic T-lymphocyte-associated protein (CTLA)4, interleukin (IL)-13 and transforming growth factor (TGF)-ß; the tissue remodeling genes matrix metalloprotease (MMP)1 and 9, tissue inhibitors of metalloproteases (TIMP)1 and 2, and the genes regulating endothelial function vascular endothelial growth factor (VEGF)1, angiopoietin (Ang)1, Ang 2, and platelet endothelial cell adhesion molecule (PECAM)-1. In contrast, transcription was only modestly decreased in the DEX pretreated pigs compared to PZQ alone, and only for TNF-α, IL-6, IFN-γ, TGF-ß and Ang1. IL-10 was not affected by either ETN or DEX pretreatments. The degree of inflammation, assessed by semi-quantitative inflammatory scores, was modestly decreased in both ETN and DEX pretreated animals compared to PZQ treated pigs whereas cyst damage scores were moderately decreased only in cysts from DEX pretreated pigs. However, the proportion of cysts with EB extravasation was not significantly changed in ETN and DEX pretreated groups. CONCLUSIONS/SIGNIFICANCE: Overall, TNF-α blockade using ETN treatment modulated expression of a large variety of genes that play a role in induction and control of inflammation and structural changes. In contrast the number of inflammatory cells was only moderately decreased suggesting weaker effects on cell migration into the inflammatory capsules surrounding cysts than on release of modulatory molecules. Taken together, these data suggest that TNF-α blockade may provide a viable strategy to manage post-treatment pericystic inflammation that follows antiparasitic therapy for neurocysticercosis.
[Mh] Termos MeSH primário: Etanercepte/administração & dosagem
Imunossupressores/administração & dosagem
Inflamação/prevenção & controle
Neurocisticercose/veterinária
Doenças dos Suínos/tratamento farmacológico
Fator de Necrose Tumoral alfa/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Anticestoides/uso terapêutico
Antiparasitários/efeitos adversos
Antiparasitários/uso terapêutico
Barreira Hematoencefálica/efeitos dos fármacos
Encéfalo/parasitologia
Citocinas/genética
Citocinas/imunologia
Dexametasona/administração & dosagem
Dexametasona/efeitos adversos
Etanercepte/efeitos adversos
Imunossupressores/efeitos adversos
Interferon gama/genética
Interferon gama/imunologia
Neurocisticercose/complicações
Neurocisticercose/tratamento farmacológico
Neurocisticercose/imunologia
Praziquantel/administração & dosagem
Praziquantel/efeitos adversos
Praziquantel/uso terapêutico
Suínos
Doenças dos Suínos/imunologia
Taenia solium/efeitos dos fármacos
Fator de Necrose Tumoral alfa/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticestodal Agents); 0 (Antiparasitic Agents); 0 (Cytokines); 0 (Immunosuppressive Agents); 0 (Tumor Necrosis Factor-alpha); 6490C9U457 (Praziquantel); 7S5I7G3JQL (Dexamethasone); 82115-62-6 (Interferon-gamma); OP401G7OJC (Etanercept)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006059


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[PMID]:29218962
[Ti] Título:Schistosomiasis and soil-transmitted helminthiases: number of people treated in 2016.
[Ti] Título:Schistosomiase et géohelminthiases: nombre de personnes traitées en 2016..
[So] Source:Wkly Epidemiol Rec;92(49):749-60, 2017 Dec 08.
[Is] ISSN:0049-8114
[Cp] País de publicação:Switzerland
[La] Idioma:eng; fre
[Mh] Termos MeSH primário: Anti-Helmínticos/uso terapêutico
Helmintíase/tratamento farmacológico
Helmintíase/epidemiologia
Mebendazol/uso terapêutico
Esquistossomose/tratamento farmacológico
Esquistossomose/epidemiologia
Solo/parasitologia
[Mh] Termos MeSH secundário: Adulto
África/epidemiologia
Albendazol/uso terapêutico
Américas/epidemiologia
Ásia/epidemiologia
Criança
Pré-Escolar
Feminino
Helmintíase/transmissão
Seres Humanos
Lactente
Masculino
Região do Mediterrâneo/epidemiologia
Praziquantel/uso terapêutico
Esquistossomose/transmissão
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthelmintics); 0 (Soil); 6490C9U457 (Praziquantel); 81G6I5V05I (Mebendazole); F4216019LN (Albendazole)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171208
[Lr] Data última revisão:
171208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


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[PMID]:29077723
[Au] Autor:Burnim M; Ivy JA; King CH
[Ad] Endereço:Center for Global Health and Diseases and WHO Collaborating Centre for Research and Training for Schistosomiasis Elimination, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
[Ti] Título:Systematic review of community-based, school-based, and combined delivery modes for reaching school-aged children in mass drug administration programs for schistosomiasis.
[So] Source:PLoS Negl Trop Dis;11(10):e0006043, 2017 Oct.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The mainstay of current schistosomiasis control programs is mass preventive chemotherapy of school-aged children with praziquantel. This treatment is delivered through school-based, community-based, or combined school- and community-based systems. Attaining very high coverage rates for children is essential in mass schistosomiasis treatment programs, as is ensuring that there are no persistently untreated subpopulations, a potential challenge for school-based programs in areas with low school enrollment. This review sought to compare the different treatment delivery methods based both on their coverage of school-aged children overall and on their coverage specifically of non-enrolled children. In addition, qualitative community or programmatic factors associated with high or low coverage rates were identified, with suggestions for overall coverage improvement. METHODOLOGY/PRINCIPAL FINDINGS: This review was registered prospectively with PROSPERO (CRD 42015017656). Five hundred forty-nine publication of potential relevance were identified through database searches, reference lists, and personal communications. Eligible studies included those published before October 2015, written in English or French, containing quantitative or qualitative data about coverage rates for MDA of school-aged children with praziquantel. Among the 22 selected studies, combined community- and school-based programs achieved the highest median coverage rates (89%), followed by community-based programs (72%). School-based programs had both the lowest median coverage of children overall (49%) and the lowest coverage of the non-enrolled subpopulation of children. Qualitatively, major factors affecting program success included fear of side effects, inadequate education about schistosomiasis, lack of incentives for drug distributors, and inequitable distribution to minority groups. CONCLUSIONS/SIGNIFICANCE: This review provides an evidence-based framework for the development of future schistosomiasis control programs. Based on our results, a combined community and school-based delivery system should maximize coverage for both in- and out-of-school children, especially when combined with interventions such as snacks for treated children, educational campaigns, incentives for drug distributors, and active inclusion of marginalized groups. TRIAL REGISTRATION: ClinicalTrials.gov CRD42015017656.
[Mh] Termos MeSH primário: Quimioprevenção/métodos
Serviços de Saúde Comunitária
Esquistossomose/prevenção & controle
Esquistossomicidas/uso terapêutico
Instituições Acadêmicas
[Mh] Termos MeSH secundário: Quimioprevenção/estatística & dados numéricos
Criança
Ensaios Clínicos como Assunto
Assistência à Saúde
Transmissão de Doença Infecciosa/prevenção & controle
Esquema de Medicação
Seres Humanos
Praziquantel/uso terapêutico
Esquistossomose/parasitologia
Esquistossomose/transmissão
Esquistossomicidas/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Schistosomicides); 6490C9U457 (Praziquantel)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171119
[Lr] Data última revisão:
171119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171028
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006043



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