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1.
Adv Ther ; 40(9): 4074-4092, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37452961

RESUMO

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.


Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.


Assuntos
Glaucoma de Ângulo Aberto , Timolol , Humanos , Timolol/efeitos adversos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Estudos Cross-Over , Anti-Hipertensivos/efeitos adversos , Soluções Oftálmicas/uso terapêutico , Tartarato de Brimonidina/uso terapêutico , Pressão Intraocular , Prostaglandinas Sintéticas/uso terapêutico , Combinação de Medicamentos
2.
Biochem Biophys Res Commun ; 302(2): 226-32, 2003 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-12604335

RESUMO

This study shows that interleukin-6 (IL-6) combined with soluble interleukin-6 receptors (sIL-6R) modulates N-methyl-D-aspartate (NMDA)-induced retinal damage. Eyes pretreated with a combined injection of IL-6 and sIL-6R had NMDA administered into the vitreous cavity. Morphometric analysis and retrograde labeling analysis found that pretreatment with either IL-6 or sIL-6R alone did not bring about any neuroprotective effect. However, pretreatment with a combined administration of IL-6 and sIL-6R induced a significant neuroprotective effect against NMDA-induced retinal damage. Apoptotic changes in the retina were assessed by the TUNEL method. The results indicated that pretreatment with IL-6 combined with sIL-6R prevents NMDA-induced apoptosis. Western blotting studies demonstrated upregulation of gp130 expression in the NMDA-injected retina. Present studies suggest that IL-6 combined with sIL-6R provides a neuroprotective effect on NMDA-induced retinal damage.


Assuntos
Interleucina-6/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doenças Retinianas/prevenção & controle , Animais , Western Blotting , Contactinas , Modelos Animais de Doenças , Marcação In Situ das Extremidades Cortadas , Interleucina-6/administração & dosagem , Masculino , N-Metilaspartato , Moléculas de Adesão de Célula Nervosa/biossíntese , Moléculas de Adesão de Célula Nervosa/genética , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-6/administração & dosagem , Receptores de Interleucina-6/uso terapêutico , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/patologia
3.
Exp Eye Res ; 75(2): 135-42, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12137759

RESUMO

The role of myosin light chain kinase (MLCK) in regulating the intraocular pressure (IOP) and outflow facility in rabbit eyes were studied. The IOP and pupil diameter were determined before and after intracameral and intravitreal administration of ML-9, a specific MLCK inhibitor. Total outflow facility and uveoscleral outflow facility was determined 3hr after intracameral administration of ML-9. Immunoblotting was performed to identify MLCK and the 20-kDa light chain of myosin (MLC) isoforms in human trabecular meshwork (TM) cells. The phosphorylation status of MLC was examined following ML-9 treatment. The effects of ML-9 on the morphology and actin and vinculin distribution in cultured TM cells were also studied. In rabbit eyes, administration of ML-9 resulted in a dose-dependent decrease in IOP. An increase of the outflow facility was also observed. Immunoblot analysis revealed the presence of MLCK in human TM cells. Exposure to ML-9 dose-dependently inhibited MLC phosphorylation/activation. The inhibitor caused retraction and dissociation of cells, disruption of actin bundles and impairment of focal adhesion formation in TM cells. ML-9 induces a reduction in IOP and an increase in the outflow facility in rabbit eyes. The IOP-lowering effects may be related to alterations in TM cell shapes. Inhibitors of MLCK may potentially be developed into novel medications for glaucoma.


Assuntos
Azepinas/farmacologia , Inibidores Enzimáticos/farmacologia , Olho/enzimologia , Pressão Intraocular/efeitos dos fármacos , Actinas/metabolismo , Animais , Azepinas/metabolismo , Adesão Celular/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Olho/efeitos dos fármacos , Humanos , Immunoblotting , Microscopia de Contraste de Fase , Fosforilação , Pupila/efeitos dos fármacos , Coelhos , Malha Trabecular/efeitos dos fármacos
4.
Invest Ophthalmol Vis Sci ; 43(5): 1616-21, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11980882

RESUMO

PURPOSE: N-syndecan is a transmembrane heparan sulfate proteoglycan, that is highly expressed in neural tissues. In the current study, changes in N-syndecan expression during retinal development were examined. METHODS: Localization of N-syndecan in developing rat retina was examined by immunohistochemistry and in situ hybridization. The amount of the core protein was evaluated by immunoblot analysis, using retinal homogenates at various developmental stages. In addition, mRNA expression was semiquantified by reverse transcription-polymerase chain reaction (RT-PCR). To understand better the localization of N-syndecan in retinal neuronal cells, we performed immunocytochemistry using retinal ganglion cells in culture. RESULTS: N-syndecan is highly expressed in nerve fiber-rich layers of the retina at early postnatal stages (between postnatal day [P]0 and P14). In contrast, immunoreactivity was faint during embryonic stages and late postnatal stages. In addition, in retinal flatmounted sections, N-syndecan immunoreactivity was observed on the axons of retinal ganglion cells. Intense signals were observed in the ganglion cell layer during in situ hybridization. Immunoblot analyses demonstrated that the amount of N-syndecan core protein reached a peak at approximately P14. The RT-PCR analyses using N-syndecan primers showed that an intense amplified band was observed in the cDNA derived from P14 retinas, whereas only faint bands were detected in the embryonic day (E)16 and P42 retinas. In retinal ganglion cells in culture, N-syndecan was located on the long, extended neurites. CONCLUSIONS: The data show that N-syndecan is transiently expressed, primarily in retinal neural fibers, during retinal development, indicating that it may be involved in formation of the retinal neural network.


Assuntos
Proteínas do Olho/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteoglicanas/metabolismo , Retina/crescimento & desenvolvimento , Retina/metabolismo , Animais , Técnicas de Cultura de Células , Proteínas do Olho/genética , Técnica Indireta de Fluorescência para Anticorpo , Immunoblotting , Hibridização In Situ , Glicoproteínas de Membrana/genética , Microscopia Confocal , Fibras Nervosas/metabolismo , Neurônios/metabolismo , Proteoglicanas/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sindecana-3
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