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1.
Clin Interv Aging ; 12: 1313-1330, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28860733

RESUMO

BACKGROUND: Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. OBJECTIVE: The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. METHODS: An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. RESULTS: Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. CONCLUSION: Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease "wet AMD" into a more favorable outcome.


Assuntos
Degeneração Macular/tratamento farmacológico , Degeneração Macular/patologia , Fatores Etários , Idoso , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Comportamentos Relacionados com a Saúde , Humanos , Estilo de Vida , Degeneração Macular/diagnóstico , Anamnese , Qualidade de Vida , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/patologia , Zinco
2.
Oxid Med Cell Longev ; 2017: 9548767, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28243361

RESUMO

Purpose. To compare serum levels of malondialdehyde (MDA) in patients with wet age-related macular degeneration (wAMD), patients with dry AMD (dAMD), and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group), and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD.


Assuntos
Neovascularização de Coroide/dietoterapia , Suplementos Nutricionais , Degeneração Macular/dietoterapia , Malondialdeído/sangue , Degeneração Macular Exsudativa/dietoterapia , Idoso , Neovascularização de Coroide/sangue , Neovascularização de Coroide/patologia , Feminino , Humanos , Degeneração Macular/sangue , Degeneração Macular/patologia , Masculino , Degeneração Macular Exsudativa/sangue , Degeneração Macular Exsudativa/patologia
3.
Photochem Photobiol Sci ; 14(5): 972-81, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25793654

RESUMO

Photodynamic therapy (PDT) has been successfully implemented as a treatment for wet age-related macular degeneration (AMD), but very few photosensitizers have been developed for clinical use. Herein, we describe a novel formulation of liposomal hypocrellin B (LHB) that was prepared by high-pressure homogenization. The encapsulation efficiency and PDT efficacy in vitro of this new preparation were found to remain nearly constant over 1 year. Moreover, LHB is rapidly cleared from the blood, with a half-life of 2.319 ± 0.462 h and a very low serum concentration at 24 h after injection. Testing in a rat model of choroidal neovascularization (CNV) showed that leakage of blood vessels in CNV lesions was significantly reduced when LHB PDT was given at a dose of 1 mg kg(-1) along with yellow laser irradiation; the damage to the collateral retina and the retinal pigment epithelium was minimal. Skin phototoxicity assays showed that only two of the 200 mice given a 4 mg per kg dose of LHB experienced an inflammatory reaction in the auricle irradiated at 24 h after dosing. These data collectively indicate that LHB may be a safe and effective photosensitizer for vascular-targeted PDT of AMD.


Assuntos
Perileno/análogos & derivados , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Quinonas/administração & dosagem , Degeneração Macular Exsudativa/terapia , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Neovascularização de Coroide , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Orelha/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Células Endoteliais/efeitos da radiação , Feminino , Lipossomos/síntese química , Pulmão/irrigação sanguínea , Masculino , Camundongos , Microvasos/efeitos dos fármacos , Microvasos/fisiologia , Microvasos/efeitos da radiação , Tamanho do Órgão , Perileno/administração & dosagem , Perileno/síntese química , Perileno/farmacocinética , Perileno/toxicidade , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/toxicidade , Quinonas/síntese química , Quinonas/farmacocinética , Quinonas/toxicidade , Ratos , Retina/efeitos dos fármacos , Retina/patologia , Retina/efeitos da radiação , Pele/efeitos dos fármacos , Pele/patologia , Pele/efeitos da radiação , Degeneração Macular Exsudativa/patologia
4.
Klin Monbl Augenheilkd ; 230(3): 247-54, 2013 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-23508753

RESUMO

BACKGROUND: Multikinase inhibitors (MKI) interfere effectively at different levels of the neovascularisation cascade. Early clinical and experimental data suggest that MKIs represent a promising novel approach for the treatment of neovascular age-related macular degeneration (AMD). However, so far little is known about the biocompatibility of MKIs regarding human ocular cells. This in vitro study investigates and compares the biocompatibility of three MKIs, axitinib, pazopanib, and sorafenib regarding ocular cells of the anterior and posterior segments, as well as organ-cultured donor corneas. METHODS: Primary human optic nerve head astrocytes (ONHA), trabecular meshwork cells (TMC), and retinal pigment epithelium (RPE), human corneal endothelial and lens epithelial cells (CEC and LEC) were treated with different concentrations of axitinib, pazopanib, or sorafenib (0.1 to 100 µg/mL). To simulate oxidative stress, the cells were additionally co-incubated with 400 µM hydrogen peroxide. Induction of cell death and cellular viability were examined by live-dead assay and tetrazolium dye reduction assay (MTT). In addition, the influence of the three substances on human corneal endothelium was evaluated in seropositive donor corneas in organ culture by phase contrast microscopy. RESULTS: Up to a concentration of 7.5 mg/mL of the substances tested in any cell type examined, no toxic effects were found. Even after 10 days of incubation of organ-cultured donor corneas with 7.5 µg/mL, axitinib, pazopanib, or sorafenib, no evidence for endothelial toxicity was found. CONCLUSION: All three MKIs tested, axitinib, pazopanib, and sorafenib showed a good biocompatibility on the investigated ocular cells. Even under conditions of oxidative stress, there were no toxic effects up to a concentration of 7.5 µg/mL. Only at higher concentrations, there was a dose-dependent decrease in cellular viability and pronounced induction of cell death. These effects on cellular viability and induction of cell death appeared to be stronger with pazopanib, followed by sorafenib, than with axitinib.


Assuntos
Inibidores da Angiogênese/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Imidazóis/farmacologia , Indazóis/farmacologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/patologia , Inibidores da Angiogênese/efeitos adversos , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Axitinibe , Córnea/efeitos dos fármacos , Córnea/patologia , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Endotélio Corneano/efeitos dos fármacos , Endotélio Corneano/patologia , Humanos , Imidazóis/efeitos adversos , Indazóis/efeitos adversos , Cristalino/efeitos dos fármacos , Cristalino/patologia , Microscopia de Contraste de Fase , Niacinamida/efeitos adversos , Niacinamida/farmacologia , Disco Óptico/efeitos dos fármacos , Disco Óptico/patologia , Técnicas de Cultura de Órgãos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/patologia , Sorafenibe , Sulfonamidas/efeitos adversos , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/patologia
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