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1.
Cells ; 13(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38920673

RESUMO

In the context of glaucoma, intraocular pressure (IOP) and age are recognized as the primary factors contributing to its onset and progression. However, significant reductions in IOP fail to completely halt its advancement. An emerging body of literature highlights the role of neuroinflammation in glaucoma. This study aimed to explore Bromfenac's anti-inflammatory properties in mitigating neuroinflammation associated with glaucoma using an ischemia-reperfusion (IR) glaucoma model. Bromfenac's impact on microglia and astrocytes under pressure was assessed via Western blotting and an enzyme-linked immunosorbent assay. Immunohistochemical staining was used to evaluate glial activation and changes in inflammatory marker expression in the IR model. Bromfenac led to the downregulation of inflammatory markers, which were elevated in the conditions of elevated pressure, and necroptosis markers were downregulated in astrocytes. In the IR model, elevated levels of GFAP and Iba-1 indicated glial activation. Following Bromfenac administration, levels of iNOS, COX-2, and PGE2-R were reduced, suggesting a decrease in neuroinflammation. Furthermore, Bromfenac administration in the IR model resulted in the improved survival of retinal ganglion cells (RGCs) and preservation of retinal function, as demonstrated by immunohistochemical staining and electroretinography. In summary, Bromfenac proved effective in diminishing neuroinflammation and resulted in enhanced RGC survival.


Assuntos
Astrócitos , Benzofenonas , Bromobenzenos , Modelos Animais de Doenças , Glaucoma , Traumatismo por Reperfusão , Bromobenzenos/farmacologia , Bromobenzenos/uso terapêutico , Animais , Benzofenonas/farmacologia , Benzofenonas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/complicações , Glaucoma/tratamento farmacológico , Glaucoma/patologia , Glaucoma/complicações , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Masculino , Pressão Intraocular/efeitos dos fármacos , Ratos
2.
Ocul Immunol Inflamm ; 29(4): 762-765, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-31418634

RESUMO

We present a case of a patient that experienced severe hemorrhagic occlusive retinal vasculitis secondary to injection of 1.0 mg/0.1 ml of intracameral vancomycin for endophthalmitis prophylaxis after an uneventful cataract surgery. The case is especially unique in that our patient ended up maintaining 20/25 vision with an ocular disease that is typically visually threatening. This may be due to the aggressive administration of periocular and oral steroids combined with scheduled anti-VEGF injections that were later transitioned into a treat and extend regimen.


Assuntos
Antibacterianos/efeitos adversos , Hemorragia Retiniana/tratamento farmacológico , Vasculite Retiniana/tratamento farmacológico , Vancomicina/efeitos adversos , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Extração de Catarata , Combinação de Medicamentos , Endoftalmite/microbiologia , Endoftalmite/prevenção & controle , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/prevenção & controle , Feminino , Angiofluoresceinografia , Glucocorticoides/uso terapêutico , Humanos , Prednisona/uso terapêutico , Hemorragia Retiniana/induzido quimicamente , Hemorragia Retiniana/diagnóstico , Vasculite Retiniana/induzido quimicamente , Vasculite Retiniana/diagnóstico , Tomografia de Coerência Óptica , Valaciclovir/uso terapêutico
3.
Adv Ther ; 37(7): 3223-3233, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32440977

RESUMO

PURPOSE: To evaluate, by laser photometry, the persistency of anterior chamber flare after uneventful phacoemulsification in asymptomatic patients with no signs of inflammation on slit lamp examination. METHOD: Seventy-five patients previously enrolled in a randomized clinical trial that evaluated inflammation after uneventful phacoemulsification in eyes treated with dexamethasone 0.1% ophthalmic suspension (group 1) or bromfenac 0.09% ophthalmic solution (group 2) for 2 weeks. Anterior chamber inflammation was investigated by laser flare photometry. At 30 days after surgery, laser flare showed persistently elevated values. For this reason, patients were further analyzed at 3 and 6 months. Additionally, optical coherence tomography was used to measure the central macular thickness (CMT) and to assess for postoperative pseudophakic macular edema. RESULTS: When compared to preoperative values, laser flare photometry demonstrated persistent ocular inflammation at postoperative days 90 and 180 in group 1, but not in group 2. Laser flare values showed a significant reduction in group 2 compared to group 1 throughout all the follow-up (p < 0.001). The increase in mean CMT at days 90 and 180 with respect to baseline was statistically significant in group 1 but not in group 2, in which it decreased to levels similar to preoperative value. Group 1 showed a higher increase in mean CMT compared to group 2 throughout all the follow-up (p < 0.001). The proportion of patients that developed pseudophakic cystoid macular edema (CME) was 14% (n = 5) and 0% (n = 0) in group 1 and group 2, respectively (p = 0.02). The bivariate analysis demonstrated a positive correlation between laser flare and CMT values in group 1 but not in group 2. CONCLUSION: Anterior chamber inflammation persists for more than 30 days in a significant proportion of patients after uncomplicated cataract surgery and may be responsible for late onset of cystoid macular edema cases. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03317847.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Extração de Catarata/efeitos adversos , Dexametasona/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Lasers , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Facoemulsificação/métodos , Fotometria/métodos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Tomografia de Coerência Óptica
4.
J Cataract Refract Surg ; 46(3): 350-354, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32142038

RESUMO

PURPOSE: To determine the rate of postoperative cystoid macular edema (CME) in patients undergoing cataract surgery treated with intraoperative intracameral and postoperative topical nonsteroidal antiinflammatory drugs (NSAIDs) without steroids. SETTING: Academic outpatient surgery center Wake Forest Baptist Health in Bermuda Run, NC. DESIGN: Retrospective cohort study. METHODS: A retrospective chart review was performed. Patients were identified through a medical record search tool using criteria of the Current Procedural Terminology code (66984), a single surgeon, and a date range from January 1, 2016, through December 31, 2017. Medical records were reviewed to determine intraoperative and postoperative medication regimen, visual outcome, and development of postoperative CME. Patients with a history of uveitis, diabetic macular edema, retinal vein occlusions, epiretinal membranes, vitreomacular traction, or any prior macular edema were excluded. In addition, any patients with less than 6 weeks of postoperative follow-up were excluded. RESULTS: Overall, 824 patient records were reviewed, and the analysis included 504 eyes. Of these, 2 eyes developed postoperative CME (rate = 0.40%, 95% CI 0.0005 to 0.0143). CONCLUSIONS: The rate of CME in patients treated with intraoperative and postoperative NSAIDs without steroids was low and below the historical rates derived from a literature review of CME development with the use of steroids.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Edema Macular/epidemiologia , Facoemulsificação , Complicações Pós-Operatórias/epidemiologia , Pseudofacia/etiologia , Administração Oftálmica , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Feminino , Humanos , Cuidados Intraoperatórios , Cetorolaco/uso terapêutico , Edema Macular/prevenção & controle , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Fenilefrina/uso terapêutico , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Acuidade Visual
5.
Arq. bras. oftalmol ; 83(1): 55-61, Jan.-Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1088946

RESUMO

ABSTRACT Purpose: To evaluate the rate of cystoid macular edema development among cataract surgery patients on four different therapeutic regimens. Methods: The present study is a retrospective analysis of 5,380 eyes following uncomplicated phacoemulsification at Wake Forest University. The study period went from July 2007 to December 2012. Patients received one of four regimens, as follows: postoperative generic ketorolac 0.4% and prednisolone 1%, postoperative name-brand ketorolac 0.45% and prednisolone 1%, postoperative bromfenac 0.09% and prednisolone 1%, preoperative and postoperative bromfenac 0.09% alone. A statistical analysis was performed to assess the differences in rate of cystoid macular edema development among the four different therapeutic regimens. The diagnosis of cystoid macular edema required worsening of vision and evidence of increased macular thickness on optical coherence tomography. Results: The overall rate of cystoid macular edema was 0.82%. Treatment by postoperative generic ketorolac 0.45% and prednisolone 1% demonstrated the highest rate of cystoid macular edema development (2.20% of the cases). Postoperative name-brand ketorolac 0.45% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.90% of the cases). Postoperative administration of bromfenac 0.09% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.44% of the cases). Preoperative and postoperative bromfenac 0.09% alone resulted in the lowest rate of cystoid macular edema development (0.09% of the cases). The rate of cystoid macular edema was significantly lower when bromfenac was used alone vs. either regimen where ketorolac and prednisolone were used (OR 0.043, 95% CI 0.002 to 0.312; p<0.001). Conclusions: Post-cataract surgery cystoid macular edema developed less frequently following topical non-steroidal anti-inflammatory drugs regimen compared to the other therapies evaluated. Bromfenac, without corticosteroids, achieved lower rates of cystoid macular edema vs. various combinations of non-ste­roidal anti-inflammatory drugs with corticosteroids.


RESUMO Objetivo: Avaliar a taxa de desenvolvimento do edema macular cistóide em pacientes submetidos à cirurgia de catarata em quatro esquemas terapêuticos diferentes. Métodos: O presente estudo é uma análise retrospectiva de 5.380 olhos após facoemulsificação não complicada na Wake Forest University. O período do estudo foi entre julho de 2007 e dezembro de 2012. Os pacientes receberam um dos quatro esquemas: cetorolaco genérico pós-operatório 0,4% e prednisolona 1%, cetorolaco 0,45% pós-operatório e prednisolona 1%, bromfenac 0,09% e a prednisolona 1% pós-operatório, bromfenaco 0,09% no pré-operatório e isoladamente no pós-operatório. Uma análise estatística foi realizada para avaliar as diferenças na taxa de desenvolvimento do edema macular cistóide entre os quatro diferentes regimes terapêuticos. O diagnóstico de edema macular cistóide exigiu uma piora da visão e uma evidência de aumento da espessura macular na tomografia de coerência óptica. Resultados: A taxa global de edema macular cistóide foi de 0,82%. O tratamento com cetorolaco genérico pós-operatório 0,45% e prednisolona 1% demonstrou a maior taxa de desenvolvimento de edema macular cistóide (2,20% dos casos). O cetorolaco 0,45% e a prednisolona 1% no pós-operatório exibiram taxas intermediárias de desenvolvimento de edema macular cistóide (0,90% dos casos). A administração de bromofenac 0,09% e de prednisolona 1% no pós-operatório apresentou taxas interme­diárias de desenvolvimento de edema macular cistóide (0,44% dos casos). O bromfenac 0,09% no pré e pós-operatório isoladamente resultou na menor taxa de desenvolvimento de edema macular cistóide (0,09% dos casos). A taxa de edema macular cistóide foi significativamente menor quando o bromfenac foi utilizado isoladamente em relação ao esquema onde cetorolaco e a prednisolona foram usados (OR 0,043, 95% CI 0,002 a 0,312; p<0,001). Conclusões: O edema macular cistóide pós-cirurgia de catarata desenvolveu-se com menor frequência após o tratamento tópico de medicamentos anti-inflamatórios não esteroidais, comparado às outras terapias avaliadas. Bromfenac, sem corticosteróides, alcançou taxas mais baixas de edema macular cistóide vs. Várias combinações em comparação com as várias combinações de drogas anti-inflamatórias não esteroidais com corticosteróides.


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Prednisolona/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Edema Macular/prevenção & controle , Facoemulsificação/efeitos adversos , Catarata , Edema Macular/etiologia , Estudos Retrospectivos , Quimioterapia Combinada
6.
Arq Bras Oftalmol ; 83(1): 55-61, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31664337

RESUMO

PURPOSE: To evaluate the rate of cystoid macular edema development among cataract surgery patients on four different therapeutic regimens. METHODS: The present study is a retrospective analysis of 5,380 eyes following uncomplicated phacoemulsification at Wake Forest University. The study period went from July 2007 to December 2012. Patients received one of four regimens, as follows: postoperative generic ketorolac 0.4% and prednisolone 1%, postoperative name-brand ketorolac 0.45% and prednisolone 1%, postoperative bromfenac 0.09% and prednisolone 1%, preoperative and postoperative bromfenac 0.09% alone. A statistical analysis was performed to assess the differences in rate of cystoid macular edema development among the four different therapeutic regimens. The diagnosis of cystoid macular edema required worsening of vision and evidence of increased macular thickness on optical coherence tomography. RESULTS: The overall rate of cystoid macular edema was 0.82%. Treatment by postoperative generic ketorolac 0.45% and prednisolone 1% demonstrated the highest rate of cystoid macular edema development (2.20% of the cases). Postoperative name-brand ketorolac 0.45% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.90% of the cases). Postoperative administration of bromfenac 0.09% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.44% of the cases). Preoperative and postoperative bromfenac 0.09% alone resulted in the lowest rate of cystoid macular edema development (0.09% of the cases). The rate of cystoid macular edema was significantly lower when bromfenac was used alone vs. either regimen where ketorolac and prednisolone were used (OR 0.043, 95% CI 0.002 to 0.312; p<0.001). CONCLUSIONS: Post-cataract surgery cystoid macular edema developed less frequently following topical non-steroidal anti-inflammatory drugs regimen compared to the other therapies evaluated. Bromfenac, without corticosteroids, achieved lower rates of cystoid macular edema vs. various combinations of non-ste-roidal anti-inflammatory drugs with corticosteroids.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Edema Macular/prevenção & controle , Facoemulsificação/efeitos adversos , Prednisolona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Catarata , Quimioterapia Combinada , Feminino , Humanos , Edema Macular/etiologia , Masculino , Estudos Retrospectivos
7.
Adv Ther ; 36(10): 2712-2722, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31482510

RESUMO

PURPOSE: To compare the efficacy of bromfenac 0.09% and dexamethasone 0.1% in the treatment of anterior chamber inflammation after uncomplicated cataract surgery. METHODS: Seventy-six patients with senile cataracts and no other ocular comorbidities who underwent uneventful phacoemulsification were randomized 1:1 to receive dexamethasone ophthalmic suspension 0.1% or bromfenac ophthalmic solution 0.09% for 2 weeks. All patients were examined on the day before surgery and postoperatively at day 1, 3, 7, 9, 11, 14 and 30. Laser flare photometry was used to quantify anterior chamber inflammation and optical coherence tomography to measure macular thickness. RESULTS: Bromfenac was as effective as dexamethasone in reducing inflammation in the anterior chamber of the eye. Laser flare increased the day after surgery and progressively decreased after starting the treatment with no statistically significant difference between dexamethasone and bromfenac at all time points. Visual acuity improved steadily after surgery in both groups. Mean macular thickness was similar in both the dexamethasone and bromfenac arms at 1 month. CONCLUSIONS: Short-term therapy with topical bromfenac alone is as effective as dexamethasone in low-risk cataract surgery patients. TRIAL REGISTRATION: ClinicalTrials.gov # NCT03317847; EudraCT # 2016-004358-14. FUNDING: Santa Maria Nuova Hospital IRCCS, Reggio Emilia, Italy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Extração de Catarata/efeitos adversos , Dexametasona/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Implante de Lente Intraocular/efeitos adversos , Soluções Oftálmicas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Câmara Anterior/fisiopatologia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Facoemulsificação/métodos , Complicações Pós-Operatórias/tratamento farmacológico
8.
Expert Opin Pharmacother ; 20(14): 1703-1709, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31343372

RESUMO

Introduction: Bromfenac is a topical ophthalmic non-steroidal anti-inflammatory drug (NSAID) used to reduce pain and treat post-operative inflammation after cataract surgery. Bromfenac 0.075% in the DuraSite™ vehicle is a newly-approved formulation which has been shown to be efficacious and safe for use in cataract surgery to reduce pain and treat inflammation. It has been shown to have a slightly better posterior segment ocular bioavailability compared to similar topical ophthalmic NSAIDs. However, there is a paucity of studies investigating its role in the prevention and treatment of post-operative pseudophakic cystoid macular edema. Areas covered: In this review, the authors provide an overview of similar products available, describe the novelty of bromfenac 0.075% in the DuraSite vehicle, and discuss the relevant clinical studies to determine if the formulation is safe and efficacious. Expert opinion: Bromfenac 0.075% in the DuraSite vehicle is a new topical ophthalmic medication which has been approved by the FDA for the prevention of pain and treatment of post-operative inflammation. It provides cataract surgeons with an additional medication for cataract surgery. However, no robust studies have been performed showing the effect that it has on the reduction or prevention of post-operative pseudophakic cystoid macular edema.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Catarata/patologia , Inflamação/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Benzofenonas/efeitos adversos , Benzofenonas/química , Bromobenzenos/efeitos adversos , Bromobenzenos/química , Extração de Catarata/efeitos adversos , Ensaios Clínicos como Assunto , Composição de Medicamentos , Humanos , Dor Pós-Operatória/etiologia , Resultado do Tratamento
9.
Biochem Pharmacol ; 168: 14-25, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31207212

RESUMO

Approximately 60% of melanoma have BRAF mutation which leads to the abnormal activation of MAPK signaling pathway. Therefore, targeting these signaling pathways is particularly important for melanoma therapy. Ribosomal S6 Kinase 2 (RSK2) is a downstream target of ERK1/2 in MAPK/ERK pathway and inhibition of RSK2 suppresses the tumorigenesis and metastasis of neoplasm. We investigated whether CX-F9, a novel RSK2 inhibitor predicted by computer, inhibits the malignant phenotype of melanoma cells. In this study, we found knockdown of RSK2 expression in melanoma cells induces autophagy and inhibits its proliferation, migration and invasion. CX-F9 directly binds to RSK2 and inhibits the kinase activity. CX-F9 significantly suppressed cell proliferation, induced autophagy, apoptosis and cycle arrest, as well as inhibited migration and invasion in SK-MEL-5 and SK-MEL-28 cells. Western blotting revealed that CX-F9 declined the activation of p-CREB. Moreover, CX-F9 inhibited tumor formation and metastasis in vivo. Furthermore, CX-F9 suppressed cell proliferation, migration, invasion in BRAF inhibitor resistant melanoma cells. These findings reveal a new RSK2 inhibitor CX-F9 could significantly suppressed malignant phenotype of melanoma in vitro and in vivo, which provide a novel strategy for melanoma treatment in clinic.


Assuntos
Autofagia/efeitos dos fármacos , Bromobenzenos/farmacologia , Bromobenzenos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Chalconas/farmacologia , Chalconas/uso terapêutico , Neoplasias Pulmonares/secundário , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Quinases S6 Ribossômicas 90-kDa/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Neoplasias Cutâneas/metabolismo , Transfecção , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Mol Cancer Ther ; 18(5): 873-885, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30824611

RESUMO

Treatment of advanced breast cancer remains challenging. Copper and some of the copper-dependent proteins are emerging therapeutic targets because they are essential for cell proliferation and survival, and have been shown to stimulate angiogenesis and metastasis. Here, we show that DCAC50, a recently developed small-molecule inhibitor of the intracellular copper chaperones, ATOX1 and CCS, reduces cell proliferation and elevates oxidative stress, triggering apoptosis in a panel of triple-negative breast cancer (TNBC) cells. Inhibition of ATOX1 activity with DCAC50 disrupts copper homeostasis, leading to increased copper levels, altered spatial copper redistribution, and accumulation of ATP7B to the cellular perinuclear region. The extent and impact of this disruption to copper homeostasis vary across cell lines and correlate with cellular baseline copper and glutathione levels. Ultimately, treatment with DCAC50 attenuates tumor growth and suppresses angiogenesis in a xenograft mouse model, and prevents endothelial cell network formation in vitro Co-treatment with paclitaxel and DCAC50 enhances cytotoxicity in TNBC and results in favorable dose reduction of both drugs. These data demonstrate that inhibition of intracellular copper transport targets tumor cells and the tumor microenvironment, and is a promising approach to treat breast cancer.


Assuntos
Benzotiazóis/farmacologia , Bromobenzenos/farmacologia , Proteínas de Transporte de Cobre/genética , ATPases Transportadoras de Cobre/genética , Fluorbenzenos/farmacologia , Chaperonas Moleculares/genética , Molibdênio/farmacologia , Neovascularização Patológica/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Benzotiazóis/uso terapêutico , Bromobenzenos/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cobre/metabolismo , Feminino , Fluorbenzenos/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Estresse Oxidativo/efeitos dos fármacos , Paclitaxel/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Mar Drugs ; 16(9)2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30134630

RESUMO

A marine natural product, pulmonarin B (1), and a series of related tacrine hybrid analogues were synthesized and evaluated as cholinesterase (ChE) inhibitors. The in vitro ChE assay results revealed that 1 showed moderate dual acetylcholinesterase (AChE)/ butyrylcholinesterase (BChE) inhibitory activity, while the hybrid 12j proved to be the most potent dual inhibitor among the designed derivatives, being almost as active as tacrine. Molecular modeling studies together with kinetic analysis suggested that 12j interacted with both the catalytic active site and peripheral anionic site of AChE. Compounds 1 and 12j could also inhibit self-induced and AChE-induced Aß aggregation. In addition, the cell-based assay against the human hepatoma cell line (HepG2) revealed that 1 and 12j did not show significant hepatotoxicity compared with tacrine and donepezil. Taken together, the present study confirmed that compound 1 was a potential anti-Alzheimer's disease (AD) hit, and 12j could be highlighted as a multifunctional lead compound for anti-AD drug development.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Bromobenzenos/farmacologia , Inibidores da Colinesterase/farmacologia , Agregação Patológica de Proteínas/tratamento farmacológico , Urocordados/química , Acetilcolinesterase/química , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Organismos Aquáticos/química , Bromo/química , Bromobenzenos/química , Bromobenzenos/uso terapêutico , Butirilcolinesterase/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/uso terapêutico , Donepezila/efeitos adversos , Descoberta de Drogas , Halogenação , Células Hep G2 , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Fenilacetatos/química , Agregação Patológica de Proteínas/patologia , Relação Estrutura-Atividade , Tacrina/química , Tacrina/farmacologia
13.
J Cataract Refract Surg ; 43(2): 183-188, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28366364

RESUMO

PURPOSE: To evaluate the safety, efficacy, and appropriate perioperative timing of the use of topical bromfenac ophthalmic solution 0.07% after femtosecond laser-assisted laser in situ keratomileusis (LASIK). SETTING: Keil LASIK Vision Center, Grand Rapids, Michigan, USA. DESIGN: Prospective case series. METHODS: Ocular discomfort was assessed 1, 2, and 5 hours postoperatively and the following morning using the Ocular Comfort Grading Assessment in patients treated with topical bromfenac 0.07% or artificial tears just before, just after, or before and after femtosecond laser-assisted LASIK. Visual outcomes and complications were noted up to 24 hours. RESULTS: The study enrolled 64 patients (120 eyes). Patients who were treated with bromfenac 0.07% just before or before and after femtosecond laser-assisted LASIK showed the greatest statistically significant decrease in several discomfort scores within the first few hours in comparison with the control group. Two hours after surgery, the majority of patients who were treated before and after LASIK were sleeping comfortably. There were no significant differences in visual acuity; 1 day postoperatively, the uncorrected distance visual acuity was 20/20 in 106 eyes (89%) and 20/25 or better in 116 eyes (97%). At 3 months, all patients had binocular distance visual acuity of 20/20 or better and 86% of patients had 20/15 or better. CONCLUSION: Ocular discomfort after femtosecond laser-assisted LASIK was reduced with a single dose of topical bromfenac 0.07% given immediately before surgery or given just before and after surgery and was typically minimal in all groups the morning after surgery.


Assuntos
Anti-Inflamatórios não Esteroides , Benzofenonas , Bromobenzenos , Ceratomileuse Assistida por Excimer Laser In Situ , Lasers de Excimer , Anti-Inflamatórios não Esteroides/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Humanos , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Lasers de Excimer/uso terapêutico , Miopia/cirurgia , Dor/tratamento farmacológico , Período Pós-Operatório , Visão Ocular
14.
Retina ; 37(2): 388-395, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27442130

RESUMO

PURPOSE: To evaluate the analgesic effect of bromfenac, a topically administered nonsteroidal antiinflammatory agent, in patients undergoing intravitreal injections (IVIs) of anti-vascular endothelial growth factor agents. METHODS: A single center, prospective, randomized, double-blind, placebo-controlled, cross over interventional study. Patients scheduled to undergo IVI of anti-vascular endothelial growth factor were randomized to receive topical bromfenac or placebo before IVI. Pain perception was assessed using the short form of the McGill Pain Questionnaire. Pain intensity was evaluated with the visual analog scale, the main component of the short form of the McGill Pain Questionnaire, and the Present Pain Intensity scores immediately and 6 hours postinjection. RESULTS: Sixty-five patients (65 eyes) were enrolled in the study. Immediately after IVI, pain perception was statistically significant lower in patients treated with bromfenac compared with placebo as assessed by the visual analog scale pain score and the main component of the short form of the McGill Pain Questionnaire (P = 0.002 and 0.001, respectively). At 6 hours postIVI, pain was statistically significant lower in patients treated with bromfenac, according to the visual analog scale pain score, the main component of the short form of the McGill Pain Questionnaire, and the Present Pain Intensity score (P < 0.001, <0.001, and P = 0.001, respectively). Multivariable regression analysis revealed that pain perception, as evaluated with the visual analog scale pain score immediately after IVI, was significantly lower in patients of older age, female patients and those with higher number of previous injections. Immediately after IVI, bromfenac seemed to be more effective in younger patients and in those who had already undergone an amount of injections. CONCLUSION: Topical instillation of bromfenac significantly reduced the IVI-related pain immediately after and 6 hours postinjection.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Dor Ocular/prevenção & controle , Injeções Intravítreas/efeitos adversos , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Estudos Prospectivos
15.
J Cataract Refract Surg ; 42(12): 1804-1813, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-28007113

RESUMO

PURPOSE: To assess the changes in clear corneal incision (CCI) healing resulting from the postoperative administration of nonsteroidal antiinflammatory drugs (NSAIDs) or steroids using anterior segment optical coherence tomography (AS-OCT). SETTING: Institute of Vision Research, Department of Ophthalmology, Yonsei University, Seoul, South Korea. DESIGN: Prospective randomized comparative study. METHODS: Eyes having cataract surgery were randomly given an NSAID (bromfenac 0.1% [Bronuck]) or a steroid (prednisolone acetate 1.0% [Pred Forte]). Using AS-OCT, structural changes of CCIs were examined 1 day and 1, 3.5, and 23 weeks postoperatively. The incidence and size of 5 wound deformities (endothelial gape, Descemet membrane detachment, epithelial detachment or defect, posterior misalignment, loss of coaptation) were analyzed. The correlation between the mean total wound deformity scores (wound instability) and surgically induced astigmatism (SIA) was evaluated. RESULTS: The bromfenac group comprised 29 eyes and the prednisolone group, 30 eyes. During the 6-month follow-up, the overall changes in wound instability were not significantly different between groups, although epithelial detachment or a larger defect was more frequent in the bromfenac group between 1 week and 3.5 weeks postoperatively. The SIA at 1 week was positively correlated with wound instability and wound instability at 1 day was positively correlated with cataract grading in both groups. CONCLUSIONS: No significant difference in the conformational changes of cataract wounds (aside from increased epithelial detachment or defect in bromfenac group) was observed between NSAIDs and steroids administered postoperatively. In the early postoperative period, high wound instability was associated with SIA, possibly contributing to worse visual outcomes. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Extração de Catarata , Prednisolona/análogos & derivados , Cicatrização , Catarata , Córnea , Humanos , Implante de Lente Intraocular , Prednisolona/uso terapêutico , Estudos Prospectivos
16.
Dev Ophthalmol ; 55: 212-20, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26502088

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important class of drugs in medicine and ophthalmology. Several NSAIDs have been commercially available for many years: diclofenac, flurbiprofen, indomethacin, ketorolac and suprofen. The purpose of this chapter is to review the clinical use of earlier and newer pharmacologic agents of the NSAID class. NSAIDs may have a modulating effect on ocular inflammation and pain through the prevention of prostaglandin synthesis via cyclooxygenase inhibition. Newer-generation NSAIDs have emerged in recent years for the treatment of ocular pain and inflammation. Nepafenac ophthalmic suspension 0.1% is a new topical NSAID prodrug that has been approved by the Food and Drug Administration for the treatment of pain and inflammation after cataract surgery. Preliminary data suggest nepafenac may also provide unique efficacy in the posterior segment, since its corneal permeability characteristics are superior to those of other NSAIDs. Nevanac, diclofenac, ketorolac and bromfenac are some notable NSAID candidates which should be investigated intravitreally or topically for retinal pharmacotherapy. In addition, for intraocular surgery, NSAIDs can help to prevent intraoperative miosis, reduce ocular pain, decrease postoperative inflammation and prevent cystoid macular edema. Retinal, choroidal and vitreous diseases may be the target of future nepafenac studies, either as monotherapy or as combination treatments.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Doenças Retinianas/tratamento farmacológico , Benzenoacetamidas/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Diclofenaco/uso terapêutico , Humanos , Cetorolaco/uso terapêutico , Fenilacetatos/uso terapêutico
17.
J Glaucoma ; 25(3): e204-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25642812

RESUMO

PURPOSE: It is reported that nonsteroidal anti-inflammatory drug (NSAID) ophthalmic solution affected the therapeutic efficacy of prostaglandin (PG) analog by inhibiting endogenous PG production. However, whether NSAID ophthalmic solution interferes with its conjunctival hyperemia is unknown. We investigated the effect of NSAID ophthalmic solution on its hyperemia. MATERIALS AND METHODS: This was a prospective, randomized, double-blind, placebo-controlled 1-month trial. Benzalkonium chloride-free travoprost 0.004% was used as a PG analog and administered once daily (08:00) in both eyes. Bromfenac sodium hydrate was assigned randomly to 1 eye twice daily (08:00 and 20:00) (the NSAID side), whereas flavin adenine dinucleotide sodium was applied to the fellow eye of each patient twice daily (08:00 and 20:00) (the control side). Conjunctival photographs of both eyes were taken 3 times (08:00, 14:00, 20:00) on days 1, 2, 7, and 28, and hyperemia was scored from 0 to 5 (H-score). We compared H-scores on the NSAID and control sides. RESULTS: Twenty-eight Japanese normal subjects completed the study. The H-score on the NSAID side was significantly lower than that on the control side on day 1 at 14:00 (P=0.016, paired t test) and day 2 at 14:00 (P=0.016). But there were no differences at 20:00 on each day and after that time. CONCLUSIONS: The use of NSAID ophthalmic solution had almost no impact on PG analog-related conjunctival hyperemia. This partly suggests that the action mechanism of endogenous PG after administrating PG analog might be no correlation with conjunctival hyperemia.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Túnica Conjuntiva/irrigação sanguínea , Doenças da Túnica Conjuntiva/tratamento farmacológico , Hiperemia/tratamento farmacológico , Travoprost/efeitos adversos , Adulto , Doenças da Túnica Conjuntiva/induzido quimicamente , Doenças da Túnica Conjuntiva/diagnóstico , Método Duplo-Cego , Feminino , Humanos , Hiperemia/induzido quimicamente , Hiperemia/diagnóstico , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Estudos Prospectivos , Fatores de Tempo , Adulto Jovem
18.
Klin Oczna ; 118(3): 197-200, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-30088383

RESUMO

Aim: To assess macular thickness and volume using optical coherence tomography in patients treated with different anti-inflammatory agents after uneventful phacoemulsification. Material and methods: We analysed macular parameters using optical coherence tomography in 50 consecutive patients (mean age 70.5 years) who underwent uneventful phacoemulsification cataract surgery at the Ophthalmology Department, Medical University of Warsaw between March 2012 and January 2013. Patients were divided into 3 groups, according to 3 different anti- -inflammatory agents used during the postoperative period: group T receiving dexamethasone 0.1% (n=17), group Y receiving bromfenac sodium 0.09% (n=16) and group D receiving diclofenac sodium (n=17). We evaluated macular scans obtained the day before surgery and on days 1., 7., 30. and 90. postoperatively. Central subfield thickness, cube volume and cube average thickness were measured during the optical coherent tomography. The data was analysed statistically using the SAS 9.2 software. The graphs were prepared using the STATISTICA 12 software. Results: A significant increase in central subfield thickness was observed on day 30. postoperatively. However, there were no statistically significant differences in macular thickness between the study groups. Conclusions: Central retinal thickness increases after uneventful phacoemulsification despite active anti-inflammatory treatment and irrespective of the drug class used.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Benzofenonas/uso terapêutico , Bromobenzenos/uso terapêutico , Implante de Lente Intraocular/efeitos adversos , Facoemulsificação/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Idoso , Dexametasona/uso terapêutico , Diclofenaco/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Facoemulsificação/métodos , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório , Tomografia de Coerência Óptica/métodos , Acuidade Visual/efeitos dos fármacos
20.
J Cataract Refract Surg ; 41(10): 2043-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26703278

RESUMO

PURPOSE: To study the effect of topical ketorolac 0.4% (Acular LS), bromfenac 0.09% (Megabrom), and nepafenac 0.1% (Nevanac) on postoperative inflammation using laser flare photometry in patients having phacoemulsification with posterior chamber intraocular lens (PC IOL) implantation. SETTING: Tertiary care center, Chandigarh, India. DESIGN: Prospective randomized case series. METHODS: Patients with age-related cataract having phacoemulsification with PC IOL implantation were randomized into 4 groups receiving topical ketorolac 0.4% (Group A), bromfenac 0.09% (Group B), nepafenac 0.1% (Group C), or no nonsteroidal antiinflammatory drugs (NSAIDs) (Group D, control). The topical NSAIDs were started 1 day prior to the surgery and continued for 6 weeks postoperatively. All patients received a standard regimen of moxifloxacin 0.5% (Vigamox) and prednisolone acetate 1.0% (Pred Forte) eyedrops in tapering doses postoperatively. Visual acuity, intraocular pressure (IOP), laser flare photometry, and fundus examination were done preoperatively and postoperatively at 1 day and 1, 2, 4, and 8 weeks. RESULTS: The study comprised 120 patients (120 eyes) (Group A = 33 patients, Group B = 30 patients, Group C = 31 patients, and Group D = 26 patients). The laser flare photometry values at the end of 4 weeks and 8 weeks were minimal in the nepafenac group compared with the other NSAID groups and the no-NSAID group (P = .032 at 4 weeks and P = .252 at 8 weeks). CONCLUSIONS: The topical NSAIDs ketorolac 0.4%, bromfenac 0.09%, and nepafenac 0.1% were effective for the reduction of postoperative inflammation following phacoemulsification. Compared with ketorolac tromethamine, bromfenac, and the control, nepafenac was significantly effective 1 month postoperatively in reducing anterior chamber flare, as evidenced by decreased laser flare photometry. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Endoftalmite/tratamento farmacológico , Facoemulsificação , Complicações Pós-Operatórias/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Benzenoacetamidas/administração & dosagem , Benzenoacetamidas/uso terapêutico , Benzofenonas/administração & dosagem , Benzofenonas/uso terapêutico , Bromobenzenos/administração & dosagem , Bromobenzenos/uso terapêutico , Endoftalmite/etiologia , Endoftalmite/fisiopatologia , Feminino , Humanos , Pressão Intraocular/fisiologia , Cetorolaco/administração & dosagem , Cetorolaco/uso terapêutico , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Fenilacetatos/administração & dosagem , Fenilacetatos/uso terapêutico , Fotometria/métodos , Estudos Prospectivos , Acuidade Visual/fisiologia
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