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1.
Exp Eye Res ; 221: 109121, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35605673

RESUMO

Validated biomarkers to be used as biological tools for managing ocular surface diseases (OSDs) are still an unmet need in daily clinical practice. Many studies have contributed to the already extensive list of candidate biomarkers for these disorders. Dry eye (DE) and ocular allergy (OA) are complex and multifactorial diseases, often coexisting and with overlapping symptoms. The purpose of this review is to present a comprehensive updated revision of the most relevant biomarkers of DE and OA, with an emphasis on quantitative analyses and correlations with clinical parameter data. Analysis of biomarkers common for these pathologies has highlighted an important physiological process. Namely, the interleukin proteins (IL-1α, IL-1ß and IL-17), tumour necrotic factor (TNFα) and interferon gamma (IFNγ; Th1-Th7 pathway) and IL-4, IL-5 and IL-13 (Th2 pathway) seem to represent similar inflammatory mechanisms. Moreover, changes in the levels of mucins (MUC1, MUC2, MUC4, MUC5 and MUC16) are common alterations in the tear film mucous layer. We also examine the current state of medical devices and the main limitations to their use in clinical practice. Translational research in biomarkers for clinical practice depends on a feasible transition from the laboratory to the point-of-care. This requires large-scale, coordinated clinical validation campaigns to select the biomarkers with the highest specificity and sensitivity and significant correlation with clinical parameters. Moreover, technical limitations of multiplexed quantitation systems must be overcome to detect and measure the levels of several biomarkers in very small samples. To ensure the future of biomarker research, significant progress is necessary in a number of fields. There is an urgent need for global unification of clinical classification and diagnostics criteria. Widespread integration of proteomic and transcriptomic data is paramount for performing meaningful analyses using appropriate bioinformatics tools and artificial intelligence systems.


Assuntos
Síndromes do Olho Seco , Oftalmopatias , Hipersensibilidade , Biomarcadores/análise , Biomarcadores/metabolismo , Túnica Conjuntiva/metabolismo , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/metabolismo , Oftalmopatias/diagnóstico , Oftalmopatias/metabolismo , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Interferon gama/metabolismo , Mucinas/metabolismo , Proteômica , Lágrimas/metabolismo
3.
Sci Rep ; 14(1): 9598, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671063

RESUMO

Allergic conjunctivitis (AC) is the most common form of allergic eye disease and an increasingly prevalent condition. Topical eye drop treatments are the usual approach for managing AC, although their impact on the ocular surface is not frequently investigated. The aim of this study was to perform a comparative physicochemical characterization, and in vitro biological evaluations in primary conjunctival and corneal epithelial cells of the new multidose preservative-free bilastine 0.6% and main commercially available eye drops. MTT assay was used to measure cell viability; oxidative stress was analyzed with a ROS-sensitive probe; and apoptosis was evaluated monitoring caspase 3/7 activation. Differences in pH value, osmolarity, viscosity and phosphate levels were identified. Among all formulations, bilastine exhibited pH, osmolarity and viscosity values closer to tear film (7.4, 300 mOsm/l and ~ 1.5-10 mPa·s, respectively), and was the only phosphates-free solution. Single-dose ketotifen did not induce ROS production, and single-dose azelastine and bilastine only induced a mild increase. Bilastine and single-dose ketotifen and azelastine showed high survival rates attributable to the absence of preservative in its formulation, not inducing caspase-3/7-mediated apoptosis after 24 h. Our findings support the use of the new bilastine 0.6% for treating patients with AC to preserve and maintain the integrity of the ocular surface.


Assuntos
Apoptose , Benzimidazóis , Caspase 3 , Sobrevivência Celular , Soluções Oftálmicas , Conservantes Farmacêuticos , Soluções Oftálmicas/farmacologia , Humanos , Conservantes Farmacêuticos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Benzimidazóis/farmacologia , Benzimidazóis/química , Caspase 3/metabolismo , Apoptose/efeitos dos fármacos , Piperidinas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Caspase 7/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/patologia , Conjuntivite Alérgica/metabolismo , Ftalazinas/farmacologia , Concentração Osmolar , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/metabolismo , Células Cultivadas , Viscosidade
4.
Antioxidants (Basel) ; 11(12)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36552707

RESUMO

In diabetes, chronic hyperglycemia, dyslipidemia, inflammation and oxidative stress contribute to the progression of macro/microvascular complications. Recently, benefits of the use of flavonoids in these conditions have been established. This study investigates, in two different mouse models of diabetes, the vasculoprotective effects of the synthetic flavonoid hidrosmin on endothelial dysfunction and atherogenesis. In a type 2 diabetes model of leptin-receptor-deficient (db/db) mice, orally administered hidrosmin (600 mg/kg/day) for 16 weeks markedly improved vascular function in aorta and mesenteric arteries without affecting vascular structural properties, as assessed by wire and pressure myography. In streptozotocin-induced type 1 diabetic apolipoprotein E-deficient mice, hidrosmin treatment for 7 weeks reduced atherosclerotic plaque size and lipid content; increased markers of plaque stability; and decreased markers of inflammation, senescence and oxidative stress in aorta. Hidrosmin showed cardiovascular safety, as neither functional nor structural abnormalities were noted in diabetic hearts. Ex vivo, hidrosmin induced vascular relaxation that was blocked by nitric oxide synthase (NOS) inhibition. In vitro, hidrosmin stimulated endothelial NOS activity and NO production and downregulated hyperglycemia-induced inflammatory and oxidant genes in vascular smooth muscle cells. Our results highlight hidrosmin as a potential add-on therapy in the treatment of macrovascular complications of diabetes.

5.
Antioxidants (Basel) ; 10(12)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34943023

RESUMO

Diabetes mellitus (DM) is a high-impact disease commonly characterized by hyperglycemia, inflammation, and oxidative stress. Diabetic nephropathy (DN) is a common diabetic microvascular complication and the leading cause of chronic kidney disease worldwide. This study investigates the protective effects of the synthetic flavonoid hidrosmin (5-O-(beta-hydroxyethyl) diosmin) in experimental DN induced by streptozotocin injection in apolipoprotein E deficient mice. Oral administration of hidrosmin (300 mg/kg/day, n = 11) to diabetic mice for 7 weeks markedly reduced albuminuria (albumin-to-creatinine ratio: 47 ± 11% vs. control) and ameliorated renal pathological damage and expression of kidney injury markers. Kidneys of hidrosmin-treated mice exhibited lower content of macrophages and T cells, reduced expression of cytokines and chemokines, and attenuated inflammatory signaling pathways. Hidrosmin treatment improved the redox balance by reducing prooxidant enzymes and enhancing antioxidant genes, and also decreased senescence markers in diabetic kidneys. In vitro, hidrosmin dose-dependently reduced the expression of inflammatory and oxidative genes in tubuloepithelial cells exposed to either high-glucose or cytokines, with no evidence of cytotoxicity at effective concentrations. In conclusion, the synthetic flavonoid hidrosmin exerts a beneficial effect against DN by reducing inflammation, oxidative stress, and senescence pathways. Hidrosmin could have a potential role as a coadjutant therapy for the chronic complications of DM.

6.
Cornea ; 35(3): 336-41, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26785302

RESUMO

PURPOSE: To assess the effects of autologous serum eye drops on conjunctival expression of the mucin gene MUC5AC by means of quantitative reverse transcription polymerase chain reaction (RT-qPCR). METHODS: A prospective and comparative interventional case series study of 38 eyes of 19 patients with different ocular surface disorders was performed before and 6 weeks after the treatment with autologous serum eye drops. All patients underwent a complete ophthalmic assessment, including evaluation of the tear film, ocular surface exploration, conjunctival impression cytology (IC), and MUC5AC detection by reverse transcription polymerase chain reaction. RESULTS: A total of 34 eyes were studied by IC and MUC5AC quantitative reverse transcription polymerase chain reaction before and after treatment with autologous serum. This treatment improved breakup time, conjunctival squamous metaplasia, goblet cell density, and subjective perception in 76.2%, 70.6%, 55.9% and 73.5% of eyes, respectively. Treatment with autologous serum enhanced conjunctival expression of MUC5AC (P = 0.001), although these differences were not statistically significant if data are analyzed patient by patient (P = 0.09). In 13 of 34 eyes (38.2%), we found increased expression of MUC5AC; in 12 eyes (35.3%), no significant changes were found; and in 9 eyes (26.5%), a decreased expression was found. The MUC5AC gene upregulation was related to the conjunctival involvement before treatment and with the improvement in the degree of squamous metaplasia and the increase in the number of goblet cells in IC after treatment (P = 0.001). CONCLUSIONS: Treatment with autologous serum enhances the conjunctival expression of MUC5AC by increasing the density of goblet cells, mainly in patients with severe conjunctival involvement.


Assuntos
Túnica Conjuntiva/metabolismo , Doenças da Túnica Conjuntiva/terapia , Mucina-5AC/metabolismo , Soluções Oftálmicas/uso terapêutico , Soro , Adulto , Idoso , Túnica Conjuntiva/efeitos dos fármacos , Doenças da Túnica Conjuntiva/metabolismo , Doenças da Túnica Conjuntiva/patologia , Feminino , Células Caliciformes/efeitos dos fármacos , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Soluções Oftálmicas/farmacologia , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Lágrimas/efeitos dos fármacos , Lágrimas/metabolismo
7.
Invest Ophthalmol Vis Sci ; 54(8): 5227-35, 2013 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-23800769

RESUMO

PURPOSE: To investigate the effect of poly (lactic-co-glycolic acid) (PLGA) implants loaded with mitomycin C (MMC) and with different adjuvant treatments after glaucoma filtration surgery (GFS), in comparison to standard treatments. METHODS: Forty-two New Zealand White rabbits underwent bilateral GFS and received different treatments: topical MMC (group 1); topical 5-fluorouracil (5-FU; group 2); PLGA implant (group 3); MMC-loaded and -coated PLGA implant (group 4); MMC-loaded and 5-FU-coated PLGA implant (group 5); subconjunctival bevacizumab (group 6); MMC-loaded PLGA implant and subconjunctival bevacizumab (group 7); and no treatment (right eye of all animals; control group). Intraocular pressure (IOP) and filtering bleb were evaluated on different days after GFS. Histology was performed to examine the conjunctiva, sclerotomy, filtering bleb, and persistence of the implant. RESULTS: The best hypotensive results were achieved in the MMC-loaded and -coated PLGA implant group, which presented the lowest IOP values on days 1, 5, 7, 14, and 28 after GFS. Excluding the implant groups, in which the bleb could not be properly measured, bleb survival was superior to controls in groups 1, 2 and lower in group 6. Group 7 presented greater extension, height, and vascularization of the bleb. Epithelial thinning and lymphoplasmacytic infiltrate were observed in groups 1, 2, 4, 5, and 7. The rates of closure of the sclerotomy and bleb were 100% and 76%, respectively, and implant persistence was 95%. CONCLUSIONS: MMC-loaded and -coated implants have optimal surgical results, followed by topical MMC application. In this experimental model, bevacizumab could interact with MMC.


Assuntos
Antimitóticos/administração & dosagem , Túnica Conjuntiva/cirurgia , Glaucoma/cirurgia , Ácido Láctico , Ácido Poliglicólico , Complicações Pós-Operatórias/tratamento farmacológico , Próteses e Implantes , Trabeculectomia/métodos , Animais , Materiais Revestidos Biocompatíveis , Modelos Animais de Doenças , Portadores de Fármacos , Feminino , Glaucoma/fisiopatologia , Pressão Intraocular , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Resultado do Tratamento
8.
Invest Ophthalmol Vis Sci ; 54(8): 5643-52, 2013 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-23882697

RESUMO

PURPOSE: To evaluate the sensitivity and specificity of a PCR-strip system based on reverse dot blot for detection of MUC5AC mRNA in corneal epithelium samples from patients with limbal stem cell deficiency (LSCD), and to determine the correlation with clinical diagnosis. METHODS: We obtained 87 corneal impression cytology (IC) samples from 55 subjects (37 patients clinically diagnosed with LSCD and 18 control subjects). Total RNA was extracted from each IC sample and retrotranscribed to cDNA. MUC5AC mRNA transcript was amplified by a customized RT-PCR assay and detected in PCR strips based on reverse dot blot hybridization and in agarose gels. Conjunctival IC samples were used as positive controls. RESULTS: Forty-four of 45 corneal IC samples obtained from patients clinically diagnosed with LSCD were positive for MUC5AC, whereas 34 of 42 corneal ICs from healthy subjects were negative for MUC5AC. Four healthy corneas were found MUC5AC positive, and four rendered inconclusive results. A correlation of 91.4% (P < 0.001) between molecular testing and clinical diagnosis was found. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the PCR-strip system were 98%, 89%, 92%, and 97%, respectively. CONCLUSIONS: Corneal epithelium MUC5AC transcript detection by reverse dot blot PCR-strip is a highly sensitive technique for LSCD diagnosis. The test results strongly correlate with clinical diagnosis of characterized LSCD cases. The PCR-strip system may be used for early detection, and for the detection of mild cases of LSCD, and constitutes an objective clinical tool for the monitoring of treatments and surgical decisions.


Assuntos
Doenças da Córnea/diagnóstico , Epitélio Corneano/patologia , Limbo da Córnea/patologia , Mucina-5AC/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Células-Tronco/patologia , Adulto , Doenças da Córnea/genética , Técnicas de Diagnóstico Oftalmológico , Epitélio Corneano/fisiologia , Feminino , Testes Genéticos/métodos , Testes Genéticos/normas , Humanos , Limbo da Córnea/fisiologia , Masculino , RNA Mensageiro/genética , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Sensibilidade e Especificidade , Células-Tronco/fisiologia
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