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[PMID]:28454526
[Au] Autor:Lee W; Lee S; Bae H; Kim CY; Seong GJ
[Ad] Endereço:Department of Ophthalmology, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Republic of Korea.
[Ti] Título:Efficacy and tolerability of preservative-free 0.0015% tafluprost in glaucoma patients: a prospective crossover study.
[So] Source:BMC Ophthalmol;17(1):61, 2017 Apr 28.
[Is] ISSN:1471-2415
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aim of this work is to evaluate efficacy and tolerability of preservative containing 0.0015% tafluprost and preservative-free 0.0015% tafluprost using a prospective crossover study. METHODS: Primary open angle glaucoma (POAG) and normotensive glaucoma (NTG) patients were randomized enrolled. Group 1 ("NPT to PT") patients used preservative-free 0.0015% tafluprost (NPT) for 6 months and then changed to preservative containing 0.0015% tafluprost(PT) for 6 months. Group 2 ("PT to NPT") patients used preservative containing 0.0015% tafluprost for 6 months and changed to preservative-free 0.0015% tafluprost for 6 months. At 1, 3, 6, 7, 9, and 12 months, we measured intraocular pressure for efficacy and graded corneal erosion, tear break-up time (TBUT), and subjective discomfort. RESULTS: A total of 20 patients and 20 eyes were enrolled. In Group 1 and 2, intraocular pressure was well controlled to approximately 14 mmHg (9.38-18.46% decrease). Generally, subjective satisfaction was improved after changing from PT to NPT (p = 0.03) and TBUT using PT was numerically inferior to that using NPT (p = 0.06) but not when changing from NPT to PT. CONCLUSION: Both preservative containing and preservative-free 0.0015% tafluprost reduced intraocular pressure significantly. In addition, changing medication from PT to NPT might improve subjective satisfaction and tear break up time. TRIAL REGISTRATION: The trial registration number is NCT 03104621 (Apr/1/2017). Retrospectively registered.
[Mh] Termos MeSH primário: Tolerância a Medicamentos
Glaucoma/tratamento farmacológico
Pressão Intraocular/efeitos dos fármacos
Prostaglandinas F/administração & dosagem
[Mh] Termos MeSH secundário: Estudos Cross-Over
Relação Dose-Resposta a Droga
Feminino
Glaucoma/fisiopatologia
Seres Humanos
Masculino
Meia-Idade
Soluções Oftálmicas/administração & dosagem
Estudos Prospectivos
Tonometria Ocular
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Ophthalmic Solutions); 0 (Prostaglandins F); 1O6WQ6T7G3 (tafluprost)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180121
[Lr] Data última revisão:
180121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1186/s12886-017-0453-z


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[PMID]:29236784
[Au] Autor:Aizawa N; Kunikata H; Shiga Y; Tsuda S; Yokoyama Y; Omodaka K; Yasui T; Kato K; Kurashima H; Miyamoto E; Hashimoto M; Nakazawa T
[Ad] Endereço:Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan.
[Ti] Título:Preperimetric Glaucoma Prospective Observational Study (PPGPS): Design, baseline characteristics, and therapeutic effect of tafluprost in preperimetric glaucoma eye.
[So] Source:PLoS One;12(12):e0188692, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: There is no consensus on the diagnosis or treatment policy for Preperimetric Glaucoma (PPG) because the pathogenesis of PPG is not clear at this time. Preperimetric Glaucoma Prospective Observational Study (PPGPS) is a first multicenter, prospective, observational study to clarify the pathogenesis of PPG. This article indicates study design, patient baseline characteristics, and analysis focused on optic nerve head (ONH) blood flow in PPG, as well as the intraocular pressure (IOP) -lowering effect and ONH blood flow-improving effects of Tafluprost. METHOD: In this study, 122 eyes from 122 subjects (mean age: 53.1 ± 14.3) newly diagnosed as PPG were enrolled. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was evaluated with optical coherence tomography (OCT). The ONH blood flow was measured with laser speckle flowgraphy. The therapeutic effect of Tafluprost was evaluated at Month 0 (ONH blood flow-improving effect) and Month 4 (IOP-lowering effect). RESULTS: The untreated IOP, cpRNFLT, and baseline Mean deviation (MD) value was 16.4 ± 2.5 mmHg, 80.4 ± 8.2 µm, and -0.48 ± 1.29 dB, respectively. In the site-specific visual field evaluation using the sector map, there was no appreciable site-specific visual field defect in the eye with PPG. The inferior region of cpRNFLT in 4-quadrant OCT sector analysis and 6 o'clock region in 12-o'clock OCT sector analysis was the highest rate of abnormality in PPG eyes. Topical administration of Tafluprost significantly reduced IOP from 16.4 ± 2.5 mmHg at baseline to 14.5 ± 2.3 mmHg at Month 4 (P < 0.001, paired t-test). In the linear regression analysis, there was a significant relationship between the increase of ONH blood flow and baseline value. CONCLUSION: PPGPS is a first prospective study focusing on the pathology of PPG. This study is expected to elucidate the pathology of PPG, with evidence useful for determining a treatment strategy for PPG.
[Mh] Termos MeSH primário: Glaucoma/tratamento farmacológico
Prostaglandinas F/uso terapêutico
Testes de Campo Visual/métodos
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Glaucoma/fisiopatologia
Seres Humanos
Pressão Intraocular/efeitos dos fármacos
Masculino
Meia-Idade
Disco Óptico/irrigação sanguínea
Estudos Prospectivos
Prostaglandinas F/farmacologia
Tomografia de Coerência Óptica
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Prostaglandins F); 1O6WQ6T7G3 (tafluprost)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188692


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[PMID]:28768500
[Au] Autor:Rolle T; Spinetta R; Nuzzi R
[Ad] Endereço:Eye Clinic, Department of Surgical Sciences, University of Torino, Via Juvarra 19, 10122, Torino, Italy. teresa.rolle@unito.it.
[Ti] Título:Long term safety and tolerability of Tafluprost 0.0015% vs Timolol 0.1% preservative-free in ocular hypertensive and in primary open-angle glaucoma patients: a cross sectional study.
[So] Source:BMC Ophthalmol;17(1):136, 2017 Aug 03.
[Is] ISSN:1471-2415
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The effects of preservatives of antiglaucoma medications on corneal surface and tear function have been widely shown in literature; it's not the same as regards the active compounds themselves. The purpose of our study was to compare Ocular Surface Disease (OSD) signs and symptoms of Tafluprost 0.0015% versus preservative free (PF) Timolol 0.1% eyedrops in ocular hypertensive (OH) and in primary open-angle glaucoma (POAG) patients. METHODS: A cross-sectional study included patients in monotherapy for at least 36 months with Tafluprost 0.0015% (27) or PF Timolol 0.1% (24) and 20 healthy age and sex-matched volunteers. All subjects underwent clinical tests (Schirmer I and break-up time), in vivo confocal microscopy (IVCM) and were surveyed using Ocular Surface Disease Index (OSDI) and Glaucoma Symptoms Scale (GSS) questionnaires. The groups were compared with ANOVA, Kruskal-Wallis test, t-test, Mann-Whitney test and Bonferroni's adjustment of p-values. RESULTS: No significant differences were found in questionnaires scores, clinical tests, IVCM variables between therapy groups. Tafluprost 0.0015% group showed significantly higher OSDI score, basal epithelial cells density, stromal reflectivity, sub-basal nerves tortuosity (p = 0.0000, 0.037, 0.006, 0.0000) and less GSS score, number of sub-basal nerves (p = 0.0000, 0.037) than controls but similar clinical tests results (p > 0.05). PF Timolol group had significantly higher OSDI score, basal epithelial cells density, stromal reflectivity and sub-basal nerve tortuosity (p = 0.000, 0.014, 0.008, 0.002), less GSS score, BUT and number of sub-basal nerves (p = 0.0000, 0.026, 0.003) than controls. CONCLUSIONS: Compared to PF Timolol 0.1%, Tafluprost 0.0015% showed similar safety with regards to tear function and corneal status and a similar tolerability profile. Both therapy groups show some alterations in corneal microstructure but no side effects on tear function except for an increased tear instability in PF Timolol 0.1% group. Ophtalmologists should be aware that even PF formulations may lead to a mild ocular surface impairment.
[Mh] Termos MeSH primário: Tolerância a Medicamentos
Glaucoma de Ângulo Aberto/tratamento farmacológico
Pressão Intraocular/efeitos dos fármacos
Hipertensão Ocular/tratamento farmacológico
Prostaglandinas F/administração & dosagem
Timolol/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Anti-Hipertensivos/administração & dosagem
Estudos Transversais
Relação Dose-Resposta a Droga
Feminino
Seguimentos
Glaucoma de Ângulo Aberto/fisiopatologia
Seres Humanos
Masculino
Microscopia Confocal
Meia-Idade
Hipertensão Ocular/fisiopatologia
Soluções Oftálmicas
Conservantes Farmacêuticos
Lágrimas/química
Fatores de Tempo
Tonometria Ocular
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Ophthalmic Solutions); 0 (Preservatives, Pharmaceutical); 0 (Prostaglandins F); 1O6WQ6T7G3 (tafluprost); 817W3C6175 (Timolol)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1186/s12886-017-0534-z


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[PMID]:28727804
[Au] Autor:Miki T; Naito T; Fujiwara M; Araki R; Kiyoi R; Shiode Y; Fujiwara A; Morizane Y; Shiraga F
[Ad] Endereço:Department of Ophthalmology, Okayama University Graduate School of Medicine, Okayama, Japan.
[Ti] Título:Effects of pre-surgical administration of prostaglandin analogs on the outcome of trabeculectomy.
[So] Source:PLoS One;12(7):e0181550, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:For primary open angle glaucoma (POAG), laser treatment or surgery is used when the target intraocular pressure (IOP) cannot be achieved by pharmacological agents, such as prostaglandin (PG) analogs; these drugs also have varied effects. We retrospectively reviewed the medical records of 74 POAG patients (74 eyes) whose IOP was inadequately controlled by PG analogs (bimatoprost [13 eyes], latanoprost [34 eyes], tafluprost [11 eyes], and travoprost [16 eyes]) and underwent primary trabeculectomy. The proportion of patients with no recurrent IOP elevation within 24 months post-trabeculectomy was significantly (P < 0.001) lower in the bimatoprost group (31.3%) than in the latanoprost (83.2%), tafluprost (45.5%), or travoprost groups (65.6%). Deepening of the upper eyelid sulcus (DUES) was observed before trabeculectomy in 18 of 74 eyes (24.3%) treated with bimatoprost (9 eyes; 50.0%), latanoprost (3 eyes; 16.7%), tafluprost (1 eye; 5.5%) and travoprost (5 eyes; 27.8%). The proportion of patients with no recurrent IOP elevation up to 24 months post-trabeculectomy was significantly (P < 0.0001) lower in the DUES(+) group (34.7%) than in the DUES(-) group (74.3%). Multivariate stepwise logistic regression analysis, with no recurrent IOP elevation used as dependent variable, and bimatoprost, latanoprost, travoprost, tafluprost, ß-blocker, carbonic anhydrase inhibitor, brimonidine, gender, age, preoperative IOP, mean deviation, duration of PG analog use before surgery, and the number of ophthalmic solutions used as independent variables, identified only bimatoprost as a significant independent factor (P = 0.0368). Thus, the outcome of trabeculectomy varied depending on the PG analog used preoperatively, and bimatoprost use was associated with a high risk of recurrent IOP elevation up to 2 years post-trabeculectomy. This may indicate that the incidence of DUES differed with the PG analog used. Patients with glaucoma who are treated with bimatoprost should be monitored for DUES, and when these patients undergo trabeculectomy, the postoperative course of IOP should be followed carefully.
[Mh] Termos MeSH primário: Glaucoma/tratamento farmacológico
Glaucoma/cirurgia
Cuidados Pré-Operatórios
Prostaglandinas Sintéticas/administração & dosagem
Trabeculectomia
[Mh] Termos MeSH secundário: Idoso
Análise de Variância
Bimatoprost/administração & dosagem
Feminino
Glaucoma/fisiopatologia
Seres Humanos
Pressão Intraocular/efeitos dos fármacos
Modelos Logísticos
Masculino
Meia-Idade
Análise Multivariada
Prostaglandinas F/administração & dosagem
Prostaglandinas F Sintéticas/administração & dosagem
Recidiva
Estudos Retrospectivos
Travoprost/administração & dosagem
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Prostaglandins F); 0 (Prostaglandins F, Synthetic); 0 (Prostaglandins, Synthetic); 1O6WQ6T7G3 (tafluprost); 6Z5B6HVF6O (latanoprost); QXS94885MZ (Bimatoprost); WJ68R08KX9 (Travoprost)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181550


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[PMID]:28330896
[Au] Autor:Silva M; Fung RKF; Donnelly CB; Videira PA; Sackstein R
[Ad] Endereço:Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal.
[Ti] Título:Cell-Specific Variation in E-Selectin Ligand Expression among Human Peripheral Blood Mononuclear Cells: Implications for Immunosurveillance and Pathobiology.
[So] Source:J Immunol;198(9):3576-3587, 2017 May 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Both host defense and immunopathology are shaped by the ordered recruitment of circulating leukocytes to affected sites, a process initiated by binding of blood-borne cells to E-selectin displayed at target endothelial beds. Accordingly, knowledge of the expression and function of leukocyte E-selectin ligands is key to understanding the tempo and specificity of immunoreactivity. In this study, we performed E-selectin adherence assays under hemodynamic flow conditions coupled with flow cytometry and Western blot analysis to elucidate the function and structural biology of glycoprotein E-selectin ligands expressed on human PBMCs. Circulating monocytes uniformly express high levels of the canonical E-selectin binding determinant sialyl Lewis X (sLe ) and display markedly greater adhesive interactions with E-selectin than do circulating lymphocytes, which exhibit variable E-selectin binding among CD4 and CD8 T cells but no binding by B cells. Monocytes prominently present sLe decorations on an array of protein scaffolds, including P-selectin glycoprotein ligand-1, CD43, and CD44 (rendering the E-selectin ligands cutaneous lymphocyte Ag, CD43E, and hematopoietic cell E-selectin/L-selectin ligand, respectively), and B cells altogether lack E-selectin ligands. Quantitative PCR gene expression studies of glycosyltransferases that regulate display of sLe reveal high transcript levels among circulating monocytes and low levels among circulating B cells, and, commensurately, cell surface α(1,3)-fucosylation reveals that acceptor sialyllactosaminyl glycans convertible into sLe are abundantly expressed on human monocytes yet are relatively deficient on B cells. Collectively, these findings unveil distinct cell-specific patterns of E-selectin ligand expression among human PBMCs, indicating that circulating monocytes are specialized to engage E-selectin and providing key insights into the molecular effectors mediating recruitment of these cells at inflammatory sites.
[Mh] Termos MeSH primário: Selectina E/metabolismo
Células Endoteliais/fisiologia
Vigilância Imunológica
Leucócitos Mononucleares/imunologia
Oligossacarídeos/metabolismo
[Mh] Termos MeSH secundário: Adesão Celular
Regulação da Expressão Gênica
Glicosiltransferases/metabolismo
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Receptores de Hialuronatos
Leucossialina/metabolismo
Ligantes
Especificidade de Órgãos
Prostaglandinas F/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5-acetylneuraminyl-(2-3)-galactosyl-(1-4)-(fucopyranosyl-(1-3))-N-acetylglucosamine); 0 (E-Selectin); 0 (Hyaluronan Receptors); 0 (Leukosialin); 0 (Ligands); 0 (Oligosaccharides); 0 (Prostaglandins F); 0 (SELE protein, human); EC 2.4.- (Glycosyltransferases); WJ72O6860W (prostaglandin F1)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601636


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[PMID]:28146132
[Au] Autor:Krupa M; Chodynski M; Ostaszewska A; Cmoch P; Dams I
[Ad] Endereço:Chemistry Department, Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland. m.krupa@ifarm.eu.
[Ti] Título:A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost.
[So] Source:Molecules;22(2), 2017 Jan 31.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to ß-blockers. A novel convergent synthesis of 5 was developed employing Julia-Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde ω-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF2α analogs 2-5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described.
[Mh] Termos MeSH primário: Anti-Hipertensivos/síntese química
Técnicas de Química Sintética
Prostaglandinas F/síntese química
[Mh] Termos MeSH secundário: Anti-Hipertensivos/farmacologia
Dinoprosta/química
Dinoprosta/farmacologia
Glaucoma/tratamento farmacológico
Estrutura Molecular
Hipertensão Ocular/tratamento farmacológico
Prostaglandinas F/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Prostaglandins F); 1O6WQ6T7G3 (tafluprost); B7IN85G1HY (Dinoprost)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170202
[St] Status:MEDLINE


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[PMID]:27913991
[Au] Autor:Konstas AG; Boboridis KG; Kapis P; Marinopoulos K; Voudouragkaki IC; Panayiotou D; Mikropoulos DG; Pagkalidou E; Haidich AB; Katsanos A; Quaranta L
[Ad] Endereço:1st University Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece. konstas@med.auth.gr.
[Ti] Título:24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.
[So] Source:Adv Ther;34(1):221-235, 2017 Jan.
[Is] ISSN:1865-8652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD). METHODS: Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period. RESULTS: Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001). CONCLUSIONS: In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02802137). FUNDING: Santen.
[Mh] Termos MeSH primário: Anti-Hipertensivos/uso terapêutico
Glaucoma de Ângulo Aberto/tratamento farmacológico
Prostaglandinas F/uso terapêutico
Sulfonamidas/uso terapêutico
Tiofenos/uso terapêutico
Timolol/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Anti-Hipertensivos/administração & dosagem
Anti-Hipertensivos/efeitos adversos
Estudos Cross-Over
Combinação de Medicamentos
Quimioterapia Combinada
Feminino
Seres Humanos
Pressão Intraocular
Masculino
Meia-Idade
Hipertensão Ocular/tratamento farmacológico
Conservantes Farmacêuticos
Estudos Prospectivos
Prostaglandinas F/administração & dosagem
Prostaglandinas F/efeitos adversos
Prostaglandinas F Sintéticas/uso terapêutico
Sulfonamidas/administração & dosagem
Sulfonamidas/efeitos adversos
Tiofenos/administração & dosagem
Tiofenos/efeitos adversos
Timolol/administração & dosagem
Timolol/efeitos adversos
Tonometria Ocular
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Drug Combinations); 0 (Preservatives, Pharmaceutical); 0 (Prostaglandins F); 0 (Prostaglandins F, Synthetic); 0 (Sulfonamides); 0 (Thiophenes); 0 (dorzolamide-timolol combination); 1O6WQ6T7G3 (tafluprost); 6Z5B6HVF6O (latanoprost); 817W3C6175 (Timolol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:T
[Da] Data de entrada para processamento:161204
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1007/s12325-016-0448-9


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[PMID]:27994439
[Au] Autor:Moschos MM; Nitoda E; Chatziralli IP; Panos GD; Demopoulos CA
[Ad] Endereço:1st Department of Ophthalmology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
[Ti] Título:Impact of prostaglandin glaucoma drops on platelet-activating factor action: an in vitro study.
[So] Source:Drug Des Devel Ther;10:3977-3981, 2016.
[Is] ISSN:1177-8881
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:AIM: The aim of this study was to investigate the effect of different prostaglandin analogs on platelet-activating factor (PAF) levels. METHODS: Three prostaglandin analogs were selected: bimatoprost 0.3 mg/mL, latanoprost 50 µg/mL, and tafluprost 15 µg/mL. Each drug sample was tested for its ability to cause platelet aggregation, which was measured as PAF-induced aggregation, before and after the addition of various concentrations of the examined sample, creating a linear curve of percentage inhibition (ranging from 0% to 100%) versus different concentrations of the sample. The concentration of the sample that inhibited 50% PAF-induced aggregation was calculated based on this curve, and this value was defined as IC50. In addition, the effect of eye drops on PAF metabolism was examined, through an in vitro analysis on PAF basic metabolic enzymes (PAF-cholinephosphotransferase, PAF-acetyl-CoA:1-O-alkyl-sn-glycero-3-phosphocholine acetyltransferase, and PAF-acetylhydrolase). RESULTS: The IC50 values for Lumigan UD (bimatoprost 0.3 mg/mL), Monoprost (latanoprost 50 µg/mL), and Saflutan (tafluprost 15 µg/mL) were 8.7, 0.28, and 1.4 µg/mL, respectively. DISCUSSION: All three prostaglandin analogs suspended PAF, but bimatoprost induced the most potent inhibition, compared to tafluprost and to the weak effect of latanoprost.
[Mh] Termos MeSH primário: Bimatoprost/farmacologia
Plaquetas/efeitos dos fármacos
Glaucoma/tratamento farmacológico
Fator de Ativação de Plaquetas/metabolismo
Inibidores da Agregação de Plaquetas/farmacologia
Agregação Plaquetária/efeitos dos fármacos
Prostaglandinas F Sintéticas/farmacologia
Prostaglandinas F/farmacologia
[Mh] Termos MeSH secundário: Administração Oftálmica
Bimatoprost/administração & dosagem
Bimatoprost/química
Plaquetas/metabolismo
Relação Dose-Resposta a Droga
Composição de Medicamentos
Seres Humanos
Soluções Oftálmicas
Inibidores da Agregação de Plaquetas/administração & dosagem
Inibidores da Agregação de Plaquetas/química
Prostaglandinas F/administração & dosagem
Prostaglandinas F/química
Prostaglandinas F Sintéticas/administração & dosagem
Prostaglandinas F Sintéticas/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ophthalmic Solutions); 0 (Platelet Activating Factor); 0 (Platelet Aggregation Inhibitors); 0 (Prostaglandins F); 0 (Prostaglandins F, Synthetic); 1O6WQ6T7G3 (tafluprost); 6Z5B6HVF6O (latanoprost); QXS94885MZ (Bimatoprost)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170328
[Lr] Data última revisão:
170328
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161221
[St] Status:MEDLINE


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[PMID]:27401285
[Au] Autor:Wang MM; Xue M; Miao Y; Kou N; Xu YG; Yang L; Zhang Y; Shi DZ
[Ad] Endereço:Center for Cardiovascular Disease, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
[Ti] Título:Panax quinquefolium saponin combined with dual antiplatelet drugs inhibits platelet adhesion to injured HUVECs via PI3K/AKT and COX pathways.
[So] Source:J Ethnopharmacol;192:10-19, 2016 Nov 04.
[Is] ISSN:1872-7573
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:ETHNOPHARMACOLOGICAL RELEVANCE: Panax quinquefolium saponin (PQS) is the active component extracted from traditional Chinese medicine Panax quinquefolius L. and has been widely used as a supplement to dual antiplatelet drugs (DA) for treatment of coronary artery disease (CAD) for two decades; however, the efficacy of PQS combined with DA against platelet adhesion to endothelial cells (ECs), an essential step in thrombosis, remains unclear. AIM OF THE STUDY: To compare PQS combined with DA and DA alone in inhibiting platelet adhesion to injured human umbilical vein endothelial cells (HUVECs) and to explore the possible mechanisms focusing on PI3K/AKT, COX-2/6-keto-PGF , and COX-1/TXB pathways. METHODS: HUVECs injured by oxidized low-density lipoprotein (ox-LDL) were randomly allocated into control, model, DA, PQS+DA (P+DA), LY294002 (a PI3K inhibitor)+DA (L+DA), and LY294002+PQS+DA (LP+DA) groups. HUVEC apoptosis, platelet adhesion to injured HUVECs, and platelet CD62p expression were assayed by fluorescence activated cell sorting (FACS). The concentrations of 6-keto-PGF and TXB in the supernatant were measured by radioimmunoassay. Protein expression of phosphorylated-PI3K, PI3K, phosphorylated-AKT, AKT, COX-1, and COX-2 in both platelets and HUVECs was evaluated by western blot. RESULTS: Compared to DA alone, PQS combined with DA reduced platelet adhesion to HUVECs and HUVEC apoptosis more potently, increased the concentration of supernatant 6-keto-PGF and up-regulated phospho-AKT protein in HUVECs. LY294002 mitigated the effects of PQS on HUVEC apoptosis and platelet adhesion. CONCLUSIONS: These findings show that PQS as a powerful supplement to DA, attenuated HUVEC apoptosis and improved the DA-mediated reduction of platelet adhesion to injured HUVECs and the underlying mechanisms may be associated with PI3K/AKT and COX pathways in HUVECs and platelets. PQS might provide a new complementary approach to improve the prognosis of thrombotic diseases in future.
[Mh] Termos MeSH primário: Aspirina/farmacologia
Plaquetas/efeitos dos fármacos
Ciclo-Oxigenase 1/metabolismo
Ciclo-Oxigenase 2/metabolismo
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Fosfatidilinositol 3-Quinase/metabolismo
Adesividade Plaquetária/efeitos dos fármacos
Inibidores da Agregação de Plaquetas/farmacologia
Proteínas Proto-Oncogênicas c-akt/metabolismo
Saponinas/farmacologia
Ticlopidina/análogos & derivados
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Plaquetas/enzimologia
Células Cultivadas
Cromonas/farmacologia
Quimioterapia Combinada
Células Endoteliais da Veia Umbilical Humana/enzimologia
Células Endoteliais da Veia Umbilical Humana/patologia
Seres Humanos
Lipoproteínas LDL/toxicidade
Morfolinas/farmacologia
Selectina-P/metabolismo
Fosfatidilinositol 3-Quinase/antagonistas & inibidores
Fosforilação
Fitoterapia
Plantas Medicinais
Inibidores da Agregação de Plaquetas/isolamento & purificação
Prostaglandinas F/metabolismo
Inibidores de Proteínas Quinases/farmacologia
Saponinas/isolamento & purificação
Transdução de Sinais/efeitos dos fármacos
Tromboxano B2/metabolismo
Ticlopidina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromones); 0 (Lipoproteins, LDL); 0 (Morpholines); 0 (P-Selectin); 0 (Panax quinquefolium saponin); 0 (Platelet Aggregation Inhibitors); 0 (Prostaglandins F); 0 (Protein Kinase Inhibitors); 0 (SELP protein, human); 0 (Saponins); 0 (oxidized low density lipoprotein); 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one); 54397-85-2 (Thromboxane B2); A74586SNO7 (clopidogrel); EC 1.14.99.1 (Cyclooxygenase 1); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.14.99.1 (PTGS1 protein, human); EC 1.14.99.1 (PTGS2 protein, human); EC 2.7.1.137 (Phosphatidylinositol 3-Kinase); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); OM90ZUW7M1 (Ticlopidine); R16CO5Y76E (Aspirin); WJ72O6860W (prostaglandin F1)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160713
[St] Status:MEDLINE


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Texto completo
[PMID]:27383260
[Au] Autor:Fuwa M; Ueda K; Akaishi T; Yamashita N; Kirihara T; Shimazaki A; Mano H; Kawazu K
[Ad] Endereço:Global Research and Development, Santen Pharmaceutical Co., Ltd., Ikoma-shi, Nara, Japan.
[Ti] Título:Advantages of Efficacy and Safety of Fixed-Dose Tafluprost/Timolol Combination Over Fixed-Dose Latanoprost/Timolol Combination.
[So] Source:PLoS One;11(7):e0158797, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To compare the safety and efficacy of fixed-dose tafluprost/timolol combination (Taf/T-FDC) with those of fixed-dose latanoprost/timolol combination (Lat/T-FDC) by measuring the intraocular pressure (IOP)-lowering effect, ocular pharmacokinetics, and ocular surface toxicity. METHODS: The IOP-lowering effect of Taf/T-FDC and Lat/T-FDC in ocular normotensive monkeys was evaluated at 4 and 8 h after instillation in study A, at 12, 14, 16, and 18 h after instillation in study B, and at 24, 26, 28, and 30 h after instillation in study C. Drug penetration into the eye was evaluated by measuring the concentrations of timolol, tafluprost acid (active metabolic form of tafluprost), and latanoprost acid (active metabolic form of latanoprost) using liquid chromatography coupled with tandem mass spectrometry after single instillation of Taf/T-FDC or Lat/T-FDC to Sprague Dawley rats. Cytotoxicity following 1-30 min exposure of SV40-transformed human corneal epithelial cells to Taf/T-FDC or Lat/T-FDC was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays. Undiluted and 10-fold diluted solutions of each FDC were evaluated. RESULTS: The IOP-lowering effect of Taf/T-FDC was almost equivalent to that of Lat/T-FDC at 4-8 h after instillation. The peak IOP reduction of Taf/T-FDC and Lat/T-FDC was observed at 8 h after instillation, and there is no difference between the two. The difference between them was observed at 24-30 h after instillation, and Taf/T-FDC demonstrated a significantly greater IOP-lowering effect than Lat/T-FDC at 24-30 h after instillation. The IOP-lowering effect of Taf/T-FDC was sustained up to 30 h after instillation, while that of Lat/T-FDC had almost disappeared at 28 h after instillation. Timolol concentrations in aqueous humor after Taf/T-FDC instillation were higher than those after Lat/T-FDC instillation (Cmax, 3870 ng/mL vs 1330 ng/mL; AUCinf, 3970 ng·h/mL vs 1250 ng·h/mL). The concentrations of tafluprost acid and latanoprost acid in aqueous humor after instillation of Taf/T-FDC and Lat/T-FDC, respectively, were similar to those after instillation of mono-preparations of tafluprost and latanoprost, respectively. The cytotoxic effect of Taf/T-FDC to the human corneal epithelial cells was significantly lower than that of Lat/T-FDC at all evaluated time points in both undiluted and 10-fold diluted FDCs. CONCLUSION: Taf/T-FDC provides increased IOP-lowering effect duration and lower potential ocular surface toxicity than Lat/T-FDC.
[Mh] Termos MeSH primário: Pressão Intraocular/efeitos dos fármacos
Prostaglandinas F Sintéticas/farmacologia
Prostaglandinas F/farmacologia
Timolol/farmacologia
[Mh] Termos MeSH secundário: Animais
Anti-Hipertensivos/farmacocinética
Anti-Hipertensivos/farmacologia
Área Sob a Curva
Linhagem Celular
Cromatografia Líquida
Modelos Animais de Doenças
Combinação de Medicamentos
Feminino
Glaucoma/tratamento farmacológico
Glaucoma/metabolismo
Glaucoma/fisiopatologia
Seres Humanos
Pressão Intraocular/fisiologia
Macaca fascicularis
Masculino
Taxa de Depuração Metabólica
Hipertensão Ocular/tratamento farmacológico
Hipertensão Ocular/metabolismo
Hipertensão Ocular/fisiopatologia
Prostaglandinas F/farmacocinética
Prostaglandinas F Sintéticas/farmacocinética
Ratos Sprague-Dawley
Espectrometria de Massas em Tandem
Fatores de Tempo
Timolol/farmacocinética
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Drug Combinations); 0 (Prostaglandins F); 0 (Prostaglandins F, Synthetic); 1O6WQ6T7G3 (tafluprost); 6Z5B6HVF6O (latanoprost); 817W3C6175 (Timolol)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160708
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0158797



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