Base de dados : MEDLINE
Pesquisa : D02.078.100 [Categoria DeCS]
Referências encontradas : 1037 [refinar]
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[PMID]:29223571
[Au] Autor:Perdigão GMC; Lopes MS; Marques LB; Prazeres PHDM; Gomes KS; de Oliveira RB; Pinto MCX; de Souza-Fagundes EM
[Ad] Endereço:Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
[Ti] Título:Novel nitroaromatic compound activates autophagy and apoptosis pathways in HL60 cells.
[So] Source:Chem Biol Interact;283:107-115, 2018 Mar 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:N-(2-butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (NBCN) is a nitroaromatic bioreducible compound with cytotoxic effects in cancer cell lines. The aim of this work was to investigate the molecular mechanisms involved in cell death promoted by NBCN in HL60 cells. We observed that NBCN treatment increased intracellular ROS and reduced mitochondria membrane potential (ΔΨm). NBCN treatment also induced morphological changes, phosphatidylserine exposure, cell cycle arrest in G2/M-phase, DNA condensation and fragmentation, but it did not show cytotoxic effects on normal human peripheral blood mononuclear cells (PBMCs). NBCN-induced caspase 3- and 9-dependent DNA fragmentation, which was blocked by pretreatment with the broad-spectrum caspase inhibitor, z-VAD-fmk. Flow cytometry analysis demonstrated that NBCN also increased of the number of autophagic vesicles in HL60 cells, which was not observed when cells were pre-treated with bafilomycin A1. Taken together, these results indicate that NBCN triggered the mitochondrial apoptotic pathway and led to the onset of autophagic cell death, which contributed to its cytotoxic effects.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Autofagia/efeitos dos fármacos
Benzamidinas/toxicidade
[Mh] Termos MeSH secundário: Clorometilcetonas de Aminoácidos/farmacologia
Benzamidinas/química
Inibidores de Caspase/farmacologia
Caspases/metabolismo
Células Cultivadas
Fragmentação do DNA/efeitos dos fármacos
Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos
Células HL-60
Seres Humanos
Leucócitos Mononucleares/citologia
Leucócitos Mononucleares/efeitos dos fármacos
Leucócitos Mononucleares/metabolismo
Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos
Macrolídeos/farmacologia
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acid Chloromethyl Ketones); 0 (Benzamidines); 0 (Caspase Inhibitors); 0 (Macrolides); 0 (Reactive Oxygen Species); 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone); 3459-99-2 (3-nitrobenzamidine); 88899-55-2 (bafilomycin A1); EC 3.4.22.- (Caspases)
[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:171211
[St] Status:MEDLINE


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[PMID]:29175302
[Au] Autor:Muñoz D; Serrano MK; Hernandez ME; Haller R; Swanson T; Slaton JW; Sinha AA; Wilson MJ
[Ad] Endereço:Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, Mexico; Centro de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, Mexico.
[Ti] Título:Matrix metalloproteinase and heparin-stimulated serine proteinase activities in post-prostate massage urine of men with prostate cancer.
[So] Source:Exp Mol Pathol;103(3):300-305, 2017 12.
[Is] ISSN:1096-0945
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Proteinases secreted by the prostate gland have a reproductive function in cleaving proteins in the ejaculate and in the female reproductive tract, but some may have a fundamental role in disease and pathological processes including cancer. The purpose of this study was to determine if there were differences in proteinase activities in urine samples collected following prostate massage of men positive (CaP) or negative (no evidence of malignancy, NEM) for biopsy determined prostate cancer. Matrix metalloproteinase (MMP) and serine proteinase activities were detected using protein substrate zymography. There were no differences in activities of MMP-2, proMMP-9, and MMP-9/NGAL (neutrophil gelatinase associated lipocalin) complex (gelatin substrate) in men with detected prostate cancer, although the latter two were somewhat diminished. A caseinolytic activity of about 75kDa inhibited by calcium did not differ between the NEM and CaP groups. Heparin stimulated calcium sensitive gelatinolytic activities of approximately 22, 42, and 60kDa, but did not affect activities of MMP-2, MMP-9, or the 75kDa caseinolytic activity. The 22, 42, and 60kDa activities appear to be serine proteinases since they were inhibited by benzamidine. There was a significant decrease in the 22kDa heparin-stimulated serine proteinase activity in urines of men with cancer. Proteinase expression and activities, perhaps in combination with other potential markers, may prove useful in urine for detection and evaluation of prostate cancer.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/urina
Metaloproteinase 2 da Matriz/urina
Metaloproteinase 9 da Matriz/urina
Neoplasias da Próstata/urina
Serina Proteases/urina
[Mh] Termos MeSH secundário: Idoso
Benzamidinas/administração & dosagem
Cálcio/metabolismo
Heparina/química
Seres Humanos
Lipocalina-2/urina
Masculino
Meia-Idade
Neoplasias da Próstata/enzimologia
Neoplasias da Próstata/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamidines); 0 (Biomarkers, Tumor); 0 (LCN2 protein, human); 0 (Lipocalin-2); 9005-49-6 (Heparin); EC 3.4.- (Serine Proteases); EC 3.4.24.24 (Matrix Metalloproteinase 2); EC 3.4.24.35 (MMP9 protein, human); EC 3.4.24.35 (Matrix Metalloproteinase 9); KUE3ZY3J1F (benzamidine); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171214
[Lr] Data última revisão:
171214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


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[PMID]:28582438
[Au] Autor:González ÀL; Konieczny P; Llamusi B; Delgado-Pinar E; Borrell JI; Teixidó J; García-España E; Pérez-Alonso M; Estrada-Tejedor R; Artero R
[Ad] Endereço:Grup d'Enginyeria Molecular (GEM), Institut Químic de Sarrià (IQS)-Universitat Ramon Llull (URL), Barcelona, Catalonia, Spain.
[Ti] Título:In silico discovery of substituted pyrido[2,3-d]pyrimidines and pentamidine-like compounds with biological activity in myotonic dystrophy models.
[So] Source:PLoS One;12(6):e0178931, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Myotonic dystrophy type 1 (DM1) is a rare multisystemic disorder associated with an expansion of CUG repeats in mutant DMPK (dystrophia myotonica protein kinase) transcripts; the main effect of these expansions is the induction of pre-mRNA splicing defects by sequestering muscleblind-like family proteins (e.g. MBNL1). Disruption of the CUG repeats and the MBNL1 protein complex has been established as the best therapeutic approach for DM1, hence two main strategies have been proposed: targeted degradation of mutant DMPK transcripts and the development of CUG-binding molecules that prevent MBNL1 sequestration. Herein, suitable CUG-binding small molecules were selected using in silico approaches such as scaffold analysis, similarity searching, and druggability analysis. We used polarization assays to confirm the CUG repeat binding in vitro for a number of candidate compounds, and went on to evaluate the biological activity of the two with the strongest affinity for CUG repeats (which we refer to as compounds 1-2 and 2-5) in DM1 mutant cells and Drosophila DM1 models with an impaired locomotion phenotype. In particular, 1-2 and 2-5 enhanced the levels of free MBNL1 in patient-derived myoblasts in vitro and greatly improved DM1 fly locomotion in climbing assays. This work provides new computational approaches for rational large-scale virtual screens of molecules that selectively recognize CUG structures. Moreover, it contributes valuable knowledge regarding two compounds with desirable biological activity in DM1 models.
[Mh] Termos MeSH primário: Anabolizantes/farmacologia
Benzamidinas/farmacologia
Proteínas de Drosophila/antagonistas & inibidores
Distrofia Miotônica/tratamento farmacológico
Miotonina Proteína Quinase/antagonistas & inibidores
Pirimidinas/farmacologia
Bibliotecas de Moléculas Pequenas/farmacologia
[Mh] Termos MeSH secundário: Processamento Alternativo
Anabolizantes/química
Animais
Benzamidinas/química
Modelos Animais de Doenças
Proteínas de Drosophila/química
Proteínas de Drosophila/genética
Proteínas de Drosophila/metabolismo
Drosophila melanogaster
Descoberta de Drogas
Seres Humanos
Locomoção/efeitos dos fármacos
Simulação de Acoplamento Molecular
Mioblastos/efeitos dos fármacos
Mioblastos/metabolismo
Mioblastos/patologia
Distrofia Miotônica/genética
Distrofia Miotônica/metabolismo
Distrofia Miotônica/patologia
Miotonina Proteína Quinase/química
Miotonina Proteína Quinase/genética
Miotonina Proteína Quinase/metabolismo
Cultura Primária de Células
Pirimidinas/química
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Proteínas de Ligação a RNA/genética
Proteínas de Ligação a RNA/metabolismo
Transdução de Sinais
Bibliotecas de Moléculas Pequenas/química
Relação Estrutura-Atividade
Expansão das Repetições de Trinucleotídeos/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anabolic Agents); 0 (Benzamidines); 0 (DMPK protein, human); 0 (Drosophila Proteins); 0 (MBNL1 protein, human); 0 (Pyrimidines); 0 (RNA, Messenger); 0 (RNA-Binding Proteins); 0 (Small Molecule Libraries); EC 2.7.11.1 (Myotonin-Protein Kinase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178931


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[PMID]:28384032
[Au] Autor:Fernández-Ferreiro A; Santiago-Varela M; Gil-Martínez M; González-Barcia M; Luaces-Rodríguez A; Díaz-Tome V; Pardo M; Méndez JB; Piñeiro-Ces A; Rodríguez-Ares MT; Lamas MJ; Otero-Espinar FJ
[Ad] Endereço:1 Department Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC) , Santiago de Compostela, Spain .
[Ti] Título:In Vitro Evaluation of the Ophthalmic Toxicity Profile of Chlorhexidine and Propamidine Isethionate Eye Drops.
[So] Source:J Ocul Pharmacol Ther;33(3):202-209, 2017 Apr.
[Is] ISSN:1557-7732
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Acanthamoeba keratitis causes frequent epithelial lesions that fully expose the corneal stroma. The aim of this study was to determine the toxic profile of chlorhexidine and propamidine eye drops. METHODS: We used primary human keratocytes in cell culture in combination with a novel technology that evaluates dynamic real-time cytotoxicity through impedance analysis. Additional studies such as a classic cell viability test (WST-1 ), a bovine corneal opacity and permeability assay, and an irritation eye study (Hen's Egg Test [HET]) have been made. RESULTS: Both eye drop formulations showed a time- and concentration-dependent toxicity profile, in which long periods and high concentrations were more detrimental to cells. In prolonged times of exposure, propamidine is more harmful to cells than chlorhexidine. On the contrary, no irritation has been detected in using the HET-chorioallantoic membrane test and no alterations in the corneal transparency nor permeability was produced by the treatment with both eye drops. CONCLUSIONS: In culture assay, chlorhexidine eye drops have proven to be less cytotoxic than Brolene for a long contact period of time, but no signs of irritation or alterations in transparency or permeability have been observed in the cornea after both treatments.
[Mh] Termos MeSH primário: Benzamidinas/toxicidade
Clorexidina/toxicidade
Ceratócitos da Córnea/efeitos dos fármacos
Soluções Oftálmicas/toxicidade
[Mh] Termos MeSH secundário: Alternativas aos Testes com Animais
Animais
Benzamidinas/administração & dosagem
Bovinos
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Química Farmacêutica
Clorexidina/administração & dosagem
Córnea/efeitos dos fármacos
Relação Dose-Resposta a Droga
Olho/efeitos dos fármacos
Seres Humanos
Soluções Oftálmicas/administração & dosagem
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamidines); 0 (Ophthalmic Solutions); 7T9IJ84C42 (propamidine isethionate); R4KO0DY52L (Chlorhexidine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1089/jop.2016.0053


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[PMID]:28256222
[Au] Autor:Dickson A; Lotz SD
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan; Department of Computational Mathematics, Science, and Engineering, Michigan State University, East Lansing, Michigan. Electronic address: alexrd@msu.edu.
[Ti] Título:Multiple Ligand Unbinding Pathways and Ligand-Induced Destabilization Revealed by WExplore.
[So] Source:Biophys J;112(4):620-629, 2017 Feb 28.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We report simulations of full ligand exit pathways for the trypsin-benzamidine system, generated using the sampling technique WExplore. WExplore is able to observe millisecond-scale unbinding events using many nanosecond-scale trajectories that are run without introducing biasing forces. The algorithm generates rare events by dividing the coordinate space into regions, on-the-fly, and balancing computational effort between regions through cloning and merging steps, as in the weighted ensemble method. The averaged exit flux yields a ligand exit rate of 180 µs, which is within an order of magnitude of the experimental value. We obtain broad sampling of ligand exit pathways, and visualize our findings using conformation space networks. The analysis shows three distinct exit channels, two of which are formed through large, rare motions of the loop regions in trypsin. This broad set of ligand-bound poses is then used to investigate general properties of ligand binding: we observe both a direct stabilizing effect of ligand-protein interactions and an indirect destabilizing effect on intraprotein interactions that is induced by the ligand. Significantly, the crystallographic binding poses are distinguished not only because their ligands induce large stabilizing effects, but also because they induce relatively low indirect destabilizations.
[Mh] Termos MeSH primário: Benzamidinas/metabolismo
Benzamidinas/farmacologia
Tripsina/metabolismo
[Mh] Termos MeSH secundário: Estabilidade Enzimática/efeitos dos fármacos
Cinética
Ligantes
Simulação de Dinâmica Molecular
Ligação Proteica
Conformação Proteica
Tripsina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamidines); 0 (Ligands); EC 3.4.21.4 (Trypsin); KUE3ZY3J1F (benzamidine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE


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[PMID]:28043336
[Au] Autor:Wang Y; Sun Y; Zhang Y; Zhang Y; Han L; Zhang X; Feng J
[Ad] Endereço:Research and Development Center of Biorational Pesticides, Northwest A & F University, Yangling 712100, Shaanxi, China.
[Ti] Título:Sensitivity and biochemical characteristics of Sclerotinia sclerotiorum to propamidine.
[So] Source:Pestic Biochem Physiol;135:82-88, 2017 Jan.
[Is] ISSN:1095-9939
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Propamidine is an aromatic diamidine compound. In the current study, baseline sensitivity of Sclerotinia sclerotiorum to propamidine was determined using 78 strains collected from the oilseed rape fields without a previous history of propamidine usage. The median effective concentration (EC ) values for propamidine inhibiting mycelial growth ranged from 0.406 to 3.647µg/mL, with a mean of 1.616±0.217µg/mL. There was no correlation between sensitivity to propamidine and sensitivity to dimethachlon or carbendazim. After treated with propamidine, mycelia were thinner with irregular distortion and more branches; cell wall became thicker with uneven distribution of cytoplasm than untreated control. In addition, sclerotia production, cell membrane permeability and oxalic acid content significantly decreased. On detached oilseed rape leaves, propamidine exhibited better control efficacy than carbendazim at the same concentration whether the leaves were inoculated with carbendazim-sensitive or resistant strains. All the results showed that propamidine exhibited strong antifungal activity and potential application in controlling S. sclerotiorum. Importantly, these data will provide more information on understanding the mode of action of propamidine against S. sclerotiorum and should be valuable for development of new antifungal drugs.
[Mh] Termos MeSH primário: Ascomicetos/efeitos dos fármacos
Benzamidinas/toxicidade
Fungicidas Industriais/toxicidade
[Mh] Termos MeSH secundário: Ascomicetos/crescimento & desenvolvimento
Ascomicetos/metabolismo
Ascomicetos/ultraestrutura
Benzimidazóis/toxicidade
Brassica rapa/microbiologia
Carbamatos/toxicidade
Permeabilidade da Membrana Celular
Clorobenzenos/toxicidade
Resistência a Medicamentos
Microscopia Eletrônica de Varredura
Microscopia Eletrônica de Transmissão
Micélio/efeitos dos fármacos
Micélio/crescimento & desenvolvimento
Micélio/metabolismo
Micélio/ultraestrutura
Ácido Oxálico/metabolismo
Doenças das Plantas/microbiologia
Doenças das Plantas/prevenção & controle
Folhas de Planta/microbiologia
Succinimidas/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamidines); 0 (Benzimidazoles); 0 (Carbamates); 0 (Chlorobenzenes); 0 (Fungicides, Industrial); 0 (Succinimides); 0 (dimethachlon); 9E7R5L6H31 (Oxalic Acid); G20G12V769 (propamidine); H75J14AA89 (carbendazim)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170313
[Lr] Data última revisão:
170313
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170104
[St] Status:MEDLINE


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[PMID]:27951487
[Au] Autor:Ismail MA; Youssef MM; Arafa RK; Al-Shihry SS; El-Sayed WM
[Ad] Endereço:King Faisal University, College of Science, Department of Chemistry, Hofuf 31982, Saudi Arabia; Department of Chemistry, Faculty of Science, Mansoura University, Mansoura 35516, Egypt. Electronic address: ismail_158@yahoo.com.
[Ti] Título:Synthesis and antiproliferative activity of monocationic arylthiophene derivatives.
[So] Source:Eur J Med Chem;126:789-798, 2017 Jan 27.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Eleven compounds of substituted 4-(5-arylthiophen-2-yl)benzamidines 4a-k were synthesized from their corresponding mononitriles via treatment with lithium trimethylsilylamide and subsequent de-protection with ethanol/hydrogen chloride. In vitro antiproliferative activities of the new monocationic arylthiophenes were evaluated against 60 human cell lines at NCI, USA. This class of compounds displayed promising submicromolar antiproliferative activities with the most potent compound being 4i (GI and TGI of 0.20 and 0.37 µM, respectively). On the other hand, most of the tested compounds exhibited LC at concentrations much higher than those they had GI at; ∼10× (for 4b) up to 228× (for 4e) which indicates lower lethality and efficient growth inhibition. Cancer cell lines, HCC-2998 colon, SNB-75 CNS, MDA-MB-435 melanoma, and MCF-7 breast cancer were the most responsive, with GI of 0.156, 0.165, 0.163, and 0.168 µM, respectively. The p-chlorophenyl derivatives 4e and 4i discerned themselves with GI values at 0.36 and 0.20 µM, respectively, and LC values at ∼83 and 36 µM, respectively, but safe to RBCs at 1000 µM. The cytotoxic activity data of these compounds in two normal cell lines; WI38 and WISH proved that they are very safe on normal cells. The plausible mechanism of action of the tested monocations was examined by evaluating their antioxidant power, nuclease-like DNA degradation aptitude and tyrosine kinase (TK) inhibition activities. The tested monocations showed potent activity in all assays. Compounds 4e and 4i caused 88 and 98%, respectively, inhibition in TK activity at 1 µM and the IC for 4i was 13 nM. The tested monocations have selective anticancer activity without insulting normal cells most probably due to inhibition of the key enzyme TK at nanomolar concentrations.
[Mh] Termos MeSH primário: Antineoplásicos/síntese química
Proliferação Celular/efeitos dos fármacos
Tiofenos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Antioxidantes
Benzamidinas/química
Morte Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Fragmentação do DNA/efeitos dos fármacos
Relação Dose-Resposta a Droga
Seres Humanos
Proteínas Tirosina Quinases/antagonistas & inibidores
Sensibilidade e Especificidade
Tiofenos/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antioxidants); 0 (Benzamidines); 0 (Thiophenes); EC 2.7.10.1 (Protein-Tyrosine Kinases)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170221
[Lr] Data última revisão:
170221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161213
[St] Status:MEDLINE


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[PMID]:27874294
[Au] Autor:Sengor T; Yuzbasioglu E; Aydin Kurna S; Irkec M; Altun A; Kökcen K; Yalcin NG
[Ad] Endereço:a Department of Ophthalmology , Bilim University, Florence Nightingale Hospital , Istanbul , Turkey.
[Ti] Título:Dacryoadenitis and extraocular muscle inflammation associated with contact lens-related Acanthamoeba keratitis: A case report and review of the literature.
[So] Source:Orbit;36(1):43-47, 2017 Feb.
[Is] ISSN:1744-5108
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The present report discusses a new case of dacryoadenitis with extraocular muscle inflammation associated with Acanthamoeba keratitis (AK) in a contact lens wearer. A 41-year-old male, who has worn silicone hydrogel contact lenses on an extended basis for about 10 years, attended with the complaints of vision disturbance, hyperemia, and pain in his right eye. His history revealed that 1.5 month ago, he had been diagnosed with allergic conjunctivitis and had used steroid eye drops. Biomicroscopic examination revealed eyelid edema, chemosis, and ring infiltration, radial keratoneuritis and an epithelial defect in the cornea. Magnetic resonance imaging demonstrated enlarged lacrimal gland with edematous changes consistent with inflammation due to dacryoadenitis. There were also thickening and edema of the right superior oblique and lateral rectus muscle. The treatment protocol for AK was applied with no specific treatment for dacryoadenitis. After 4 months of the treatment, dacryoadenitis and keratitis regressed. Dacryoadenitis and extraocular muscle inflammation may accompany AK more frequently than expected and previously known. The evaluation of the lacrimal gland and extraocular muscles in presence of AK might be beneficial for understanding better the exact clinical picture and course of the keratitis.
[Mh] Termos MeSH primário: Ceratite por Acanthamoeba/parasitologia
Lentes de Contato/parasitologia
Dacriocistite/parasitologia
Infecções Oculares Parasitárias/parasitologia
Músculos Oculomotores/parasitologia
Miosite Orbital/parasitologia
[Mh] Termos MeSH secundário: Ceratite por Acanthamoeba/diagnóstico
Ceratite por Acanthamoeba/tratamento farmacológico
Adulto
Antibacterianos/uso terapêutico
Antiprotozoários/uso terapêutico
Benzamidinas/uso terapêutico
Biguanidas/uso terapêutico
Dacriocistite/diagnóstico
Dacriocistite/tratamento farmacológico
Quimioterapia Combinada
Infecções Oculares Parasitárias/diagnóstico
Infecções Oculares Parasitárias/tratamento farmacológico
Fluoroquinolonas/uso terapêutico
Gentamicinas/uso terapêutico
Seres Humanos
Imagem por Ressonância Magnética
Masculino
Microscopia Confocal
Miosite Orbital/diagnóstico
Miosite Orbital/tratamento farmacológico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antiprotozoal Agents); 0 (Benzamidines); 0 (Biguanides); 0 (Fluoroquinolones); 0 (Gentamicins); 322U039GMF (polihexanide); 7T9IJ84C42 (propamidine isethionate); U188XYD42P (moxifloxacin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161123
[St] Status:MEDLINE
[do] DOI:10.1080/01676830.2016.1243132


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[PMID]:27870779
[Au] Autor:Kwok PW; Kam KW; Jhanji V; Young AL
[Ad] Endereço:*MRCSEd(Ophth), MBBS †MD ‡FRCS, MMedSc(Hons) Department of Ophthalmology & Visual Sciences, Prince of Wales Hospital and Alice Ho Miu Ling Nethersole Hospital, Shatin, New Territory, Hong Kong, SAR (PWRK, KWK, VJ, ALY); and Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Shatin, New Territory, Hong Kong, SAR (VJ, ALY).
[Ti] Título:Painless Acanthamoeba Keratitis with Normal Vision.
[So] Source:Optom Vis Sci;94(3):432-435, 2017 Mar.
[Is] ISSN:1538-9235
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To report an atypical case of contact lens-related Acanthamoeba keratitis. CASE REPORT: A 15-year-old secondary school female student with a history of soft contact lens wear was referred to our hospital by a private general practitioner for management of right eye redness and discomfort for 2 weeks. Upon examination, the best-corrected visual acuity was 20/20 and 20/16 for her right and left eyes, respectively. There was diffuse radial keratoneuritis noted in the cornea of her right eye without any associated epithelial defect. Corneal scraping was performed to induce epithelial defect over the keratoneuritis area, and it was positive for Acanthamoeba trophozoites. She was treated with amoebicidal therapy consisting of propamidine isethionate 0.1% and polyhexamethylene biguanide 0.02%, for 6 months. The patient did not complain of any ocular pain in the entire course of her disease. She attained a final visual acuity of 20/13 in the affected eye with residual peripheral radial perineuritic scar. CONCLUSIONS: Atypical presentation of Acanthamoeba infection is uncommon. This case should arouse the awareness of an indolent presentation of this potentially sight-threatening disease. Clinicians should have a high level of suspicion in contact lens users who present with corneal abnormalities despite an absence of pain. Microbiological work-up and prompt treatment led to a complete resolution of Acanthamoeba infection in our patient.
[Mh] Termos MeSH primário: Ceratite por Acanthamoeba/parasitologia
Lentes de Contato Hidrofílicas/parasitologia
Acuidade Visual/fisiologia
[Mh] Termos MeSH secundário: Acanthamoeba
Ceratite por Acanthamoeba/diagnóstico
Ceratite por Acanthamoeba/tratamento farmacológico
Adolescente
Antiprotozoários/uso terapêutico
Benzamidinas/uso terapêutico
Biguanidas/uso terapêutico
Córnea/parasitologia
Desinfetantes/uso terapêutico
Quimioterapia Combinada
Dor Ocular/diagnóstico
Dor Ocular/tratamento farmacológico
Dor Ocular/etiologia
Feminino
Seres Humanos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Benzamidines); 0 (Biguanides); 0 (Disinfectants); 322U039GMF (polihexanide); 7T9IJ84C42 (propamidine isethionate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170804
[Lr] Data última revisão:
170804
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161122
[St] Status:MEDLINE
[do] DOI:10.1097/OPX.0000000000001023


  10 / 1037 MEDLINE  
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[PMID]:27527618
[Au] Autor:Mendez-Cuesta CA; Herrera-Rueda MA; Hidalgo-Figueroa S; Tlahuext H; Moo-Puc R; Chale-Dzul JB; Chan-Bacab M; Ortega-Morales BO; Hernandez-Nunez E; Mendez-Lucio O; Medina-Franco JL; Navarrete-Vazquez G
[Ti] Título:Synthesis, Screening and in silico Simulations of Anti-Parasitic Propamidine/Benzimidazole Derivatives.
[So] Source:Med Chem;13(2):137-148, 2017.
[Is] ISSN:1875-6638
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: We designed hybrid molecules between propamidine and benzimidazole in order to retain the antiprotozoal action, but decreasing the toxic effect of the molecule. OBJECTIVE: Design and prepare 12 hybrids for testing their antiparasitic effect over three protozoa: Giardia intestinalis, Trichomonas vaginalis and Leishmania mexicana, as well as conduct several in silico simulations such as toxicological profile, molecular docking and molecular dynamics in order to understand their potential mode of action. METHODS: Hybrids 1-3, 6-9 and 12 were obtained using a chemical pathway previously reported. Compounds 4, 5, 10 and 11 were prepared using a one-pot reduction-cyclization reaction. The in vitro antiparasitic and cytotoxic activities of these compounds were conducted. It was calculated several properties such as toxicity, PK behavior, as well as docking studies and molecular dynamics of the most active compound performed in a DNA sequence dodecamer in comparison with propamidine. RESULTS: Compound 2 was 183, 127 and 202 times more active against G. intestinalis than metronidazole, pentamidine and propamidine. It was eleven times more active than pentamidine against L. mexicana. This compound showed low in vitro mammalian cytotoxicity. Molecular simulations showed a stable complex 2-DNA that occurred in the minor groove, analogous to propamidine-DNA complex. CONCLUSION: Compound 2, exhibited the higher bioactivity, especially towards G. intestinalis and L. mexicana. This study demonstrated that the replacement of benzimidazole scaffold instead of toxic amidine group in propamidine, results in an enhancement of antiprotozoal bioactivity. The preliminary molecular dynamics simulation suggests that the ligand-DNA complex is stable.
[Mh] Termos MeSH primário: Antiparasitários/síntese química
Antiparasitários/farmacologia
Benzamidinas/química
Benzimidazóis/síntese química
Benzimidazóis/farmacologia
Simulação por Computador
[Mh] Termos MeSH secundário: Animais
Antiparasitários/química
Antiparasitários/toxicidade
Benzimidazóis/química
Benzimidazóis/toxicidade
Cercopithecus aethiops
Técnicas de Química Sintética
DNA/química
DNA/metabolismo
Avaliação Pré-Clínica de Medicamentos
Concentração Inibidora 50
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
Conformação de Ácido Nucleico
Relação Estrutura-Atividade
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiparasitic Agents); 0 (Benzamidines); 0 (Benzimidazoles); 9007-49-2 (DNA); G20G12V769 (propamidine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160817
[St] Status:MEDLINE
[do] DOI:10.2174/1573406412666160811112408



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