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1.
Mediators Inflamm ; 2013: 863036, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23766563

RESUMO

To test the hypothesis that brain-derived neurotrophic factor-(BDNF-) mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Retinopatia Diabética/sangue , Proteína HMGB1/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Western Blotting , Quimiocina CCL2/metabolismo , Retinopatia Diabética/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Feminino , Ácido Glicirrízico/uso terapêutico , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Adulto Jovem
2.
Ocul Immunol Inflamm ; 21(6): 468-74, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23734940

RESUMO

PURPOSE: To assess long-term efficacy and safety of infliximab for refractory Behçet disease (BD) uveitis and to evaluate the effect of withdrawal of infliximab after achieving long-term remission. METHODS: Retrospective study of 19 patients. RESULTS: Mean follow-up was 44.1 ± 36.5 months and mean number of infliximab infusions was 21.6 ± 14.6. At end of follow-up, there was significant improvement of visual acuity and reduction of central macular thickness. All patients achieved remission, 14 of whom were able to discontinue corticosteroids. Ten patients developed autoantibodies and 1 patient developed infusion reactions. Eight eyes underwent intraocular surgery without exacerbation of quiescent uveitis. After achieving complete remission, 5 patients discontinued infliximab and maintained remission during a mean of 24.6 ± 5.5 months. CONCLUSIONS: Infliximab is effective and safe for long-term treatment for refractory BD uveitis. Repeated infusions are required to maintain long-term remission, which may be sustained despite withdrawal of infliximab. Induction of autoantibodies is common.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Síndrome de Behçet/complicações , Uveíte Posterior/tratamento farmacológico , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Criança , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Infliximab , Infusões Intravenosas , Masculino , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte Posterior/diagnóstico , Uveíte Posterior/etiologia , Acuidade Visual , Adulto Jovem
3.
J Diabetes Res ; 2013: 539658, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23671874

RESUMO

This study was conducted to determine levels of angiogenic and endothelial progenitor cell mobilizing (vasculogenic) factors in vitreous fluid from proliferative diabetic retinopathy (PDR) patients and correlate their levels with clinical disease activity. Vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), stem cell factor (SCF), soluble c-kit (s-kit), endothelial nitric oxide synthase (eNOS), and prostaglandin E2 (PGE2) levels were measured by ELISA in vitreous samples from 34 PDR and 15 nondiabetic patients. eNOS was not detected. VEGF, sVEGFR-2, SCF, and s-kit levels were significantly higher in PDR with active neovascularization compared with quiescent PDR and nondiabetic patients (P < 0.001; 0.007; 0.001; <0.001, resp.). In contrast, PGE2 levels were significantly higher in nondiabetic patients compared with PDR patients (P < 0.001). There were significant correlations between levels of sVEGFR-2 versus SCF (r = 0.950, P < 0.001), sVEGFR-2 versus s-kit (r = 0.941, P < 0.001), and SCF versus s-kit (r = 0.970, P < 0.001). Our findings suggest that upregulation of VEGF, sVEGFR-2, SCF, and s-kit supports the contributions of angiogenesis and vasculogenesis in pathogenesis of PDR.

4.
Acta Ophthalmol ; 91(6): e486-93, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23575246

RESUMO

PURPOSE: To determine prognostic factors in patients with Vogt-Koyanagi-Harada (VKH) disease who were treated with high-dose corticosteroids. METHODS: Retrospective analysis of 87 patients (174 eyes). RESULTS: At presentation, there were 53 patients with initial-onset acute VKH disease and 34 patients with chronic recurrent VKH disease. Chronic recurrent presentation was significantly associated with more severe anterior segment inflammation at presentation as indicated by presence of mutton-fat keratic precipitates, anterior chamber reaction ≥2+, iris nodules and posterior synechiae (p < 0.001 for all comparisons), less exudative retinal detachment at presentation (p < 0.001), more complications during the follow-up period (p < 0.001) and a worse visual outcome (p < 0.001). The use of immunomodulatory therapy (cyclosporine and mycophenolate mofetil) as first-line therapy significantly reduced the development of complications in the whole study group (p = 0.006) and in initial-onset acute group (p = 0.024) and improved visual outcome in the whole study group (p = 0.004) and in chronic recurrent group (p = 0.024). In the whole study group, final visual acuity of 20/20 was significantly associated with good initial visual acuity of >20/200 [odds ratio = 4.25; 95% Confidence interval (CI) = 1.53-11.89] and age older than 16 years was significantly associated with the development of complications (odds ratio = 3.15; 95% CI = 1.04-9.48). CONCLUSIONS: Chronic recurrent VKH disease is significantly associated with more severe anterior segment inflammation and less exudative retinal detachment at presentation, more ocular complications and a worse visual outcome than initial-onset acute VKH disease. Use of immunomodulatory therapy significantly improved the clinical outcomes.


Assuntos
Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Síndrome Uveomeningoencefálica/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Angiofluoresceinografia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Prognóstico , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Síndrome Uveomeningoencefálica/diagnóstico , Acuidade Visual , Adulto Jovem
5.
Acta Diabetol ; 50(3): 363-71, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22864860

RESUMO

The proinflammatory lysophosphatidic acid (LPA) is a potent activator of several transcriptional factors and signaling pathways and a potent modulator of genes involved in inflammation, angiogenesis and fibrosis. This study was conducted to measure the levels of LPA and LPA-producing enzymes, autotaxin (ATX) and acylglycerol kinase (AGK) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the level of vascular endothelial growth factor (VEGF). In addition, we examined the expression of ATX, AGK and VEGF receptor-2 (VEGFR-2) in the retinas of diabetic rats. Vitreous samples from 42 PDR and 35 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blot analysis. VEGF, LPA and AGK levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p < 0.001 for all comparisons). ATX levels in PDR with active neovascularization and inactive PDR were significantly lower than those in nondiabetic patients (p = 0.045). Mean VEGF and AGK levels in PDR with active neovascularization were significantly higher than those in inactive PDR and nondiabetic patients (p < 0.001 for both comparisons). A significant correlation was observed between levels of VEGF and levels of AGK in PDR patients (r = 0.954; p < 0.001). Western blot analysis revealed a significant increase in the expression of AGK and VEGFR-2 in vitreous samples and the retinas of diabetic rats compared to nondiabetic controls, whereas ATX was significantly downregulated. Our findings suggest that ATX-AGK-LPA signaling axis might be an important player in the development and progression of diabetic retinopathy.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Lisofosfolipídeos/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Corpo Vítreo/metabolismo , Adulto Jovem
6.
Acta Diabetol ; 50(4): 545-51, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21947384

RESUMO

We determined the levels of the endogenous angiogenesis inhibitors soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), thrombospondin (TSP)-1 and TSP-2 in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and correlated their levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF). Vitreous samples from 30 PDR and 25 nondiabetic patients were studied by enzyme-linked immunosorbent assay. TSP-1 was not detected. VEGF and TSP-2 levels were significantly higher in PDR with active neovascularization compared with inactive PDR and nondiabetic patients (P < 0.001 for both comparisons). VEGF, sVEGFR-1 and TSP-2 levels were significantly higher in PDR with hemorrhage compared with PDR without hemorrhage and nondiabetic patients (P = 0.0063; 0.0144; <0.001, respectively). VEGF and sVEGFR-1 levels were significantly higher in PDR without traction retinal detachment (TRD) compared with PDR with TRD and nondiabetic patients (P = 0.038; 0.022, respectively). TSP-2 levels were significantly higher in PDR with TRD compared with PDR without TRD and nondiabetic patients (P < 0.001). There was a significant correlation between levels of VEGF and sVEGFR-1 (r = 0.427, P = 0.038). Our findings suggest that upregulation of sVEGFR-1 and TSP-2 may be a protective mechanism against progression of angiogenesis associated with PDR. TSP-2 might be associated with TRD.


Assuntos
Indutores da Angiogênese/metabolismo , Retinopatia Diabética/metabolismo , Corpo Vítreo/metabolismo , Indutores da Angiogênese/análise , Retinopatia Diabética/patologia , Humanos , Neovascularização Patológica , Trombospondina 1/análise , Trombospondina 1/metabolismo , Trombospondinas/análise , Trombospondinas/metabolismo , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/análise , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Corpo Vítreo/irrigação sanguínea , Corpo Vítreo/química
7.
Mediators Inflamm ; 2012: 697489, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23118492

RESUMO

The aim of this study was to measure the levels of high-mobility group box-1 (HMGB1) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate its levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF), the angiogenic cytokine granulocyte-colony-stimulating factor (G-CSF), the endothelial cell angiogenic markers soluble vascular endothelial-cadherin (sVE-cadherin), and soluble endoglin (sEng). Vitreous samples from 36 PDR and 21 nondiabetic patients were studied by enzyme-linked immunosorbent assay. HMGB1, VEGF, sVE-cadherin, and sEng levels were significantly higher in PDR patients than in nondiabetics (P = 0.008; <0.001; <0.001; 0.003, resp.). G-CSF was detected in only 3 PDR samples. In the whole study group, there was significant positive correlation between the levels of HMGB1, and sVE-cadherin (r = 0.378, P = 0.007). In PDR patients, there was significant negative correlation between the levels of sVE-cadherin and sEng (r = -0.517, P = 0.0005). Exploratory regression analysis identified significant associations between active PDR and high levels of VEGF (odds ratio = 76.4; 95% confidence interval = 6.32-923) and high levels of sEng (odds ratio = 6.01; 95% confidence interval = 1.25-29.0). Our findings suggest that HMGB1, VEGF, sVE-cadherin and sEng regulate the angiogenesis in PDR.


Assuntos
Retinopatia Diabética/metabolismo , Células Endoteliais/metabolismo , Proteína HMGB1/metabolismo , Corpo Vítreo/metabolismo , Antígenos CD/metabolismo , Biomarcadores , Caderinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Modelos Logísticos , Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Mediators Inflamm ; 2012: 493043, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23055574

RESUMO

The aim of this study was to determine the levels of the angiogenic and fibrogenic factors osteopontin (OPN), high-mobility group box-1 (HMGB1), and connective tissue growth factor (CTGF) and the antiangiogenic and antifibrogenic pigment epithelium-derived factor (PEDF) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and rhegmatogenous retinal detachment with no PVR (RD). Vitreous samples from 48 PDR, 17 PVR and 30 RD patients were studied by enzyme-linked immunosorbent assay. OPN, HMGB1, CTGF, and PEDF levels were significantly higher in PDR patients than in RD patients (P < 0.001; 0.002; <0.001; <0.001, resp.). CTGF and PEDF levels were significantly higher in PVR patients than in RD patients (P < 0.001; 0.004, resp.). Exploratory logistic regression analysis identified significant associations between PDR and high levels of HMGB1, CTGF and PEDF, between PDR with active neovascularization and high levels of CTGF and PEDF, and between PDR with traction retinal detachment and high levels of HMGB1. In patients with PDR, there were significant correlations between the levels of PEDF and the levels of OPN (r = 0.544, P = 0.001), HMGB1 (r = 0.719, P < 0.001), and CTGF (r = 0.715, P < 0.001). In patients with PVR, there were significant correlations between the levels of OPN and the levels of HMGB1 (r = 0.484, P = 0.049) and PEDF (r = 0.559, P = 0.02). Our findings suggest that OPN, HMGB1, and CTGF contribute to the pathogenesis of proliferative vitreoretinal disorders and that increased levels of PEDF may be a response to counterbalance the activity of angiogenic and fibrogenic factors in PDR and PVR.


Assuntos
Neovascularização Patológica/metabolismo , Osteopontina/metabolismo , Vitreorretinopatia Proliferativa/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Proteínas do Olho/metabolismo , Proteína HMGB1/metabolismo , Humanos , Fatores de Crescimento Neural/metabolismo , Serpinas/metabolismo , Corpo Vítreo/metabolismo
9.
Acta Ophthalmol ; 90(8): e603-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22971163

RESUMO

PURPOSE: To study the effectiveness of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. The outcomes in this group were compared with those of another group of patients with VKH disease who were treated with corticosteroid monotherapy or with delayed addition of immunomodulatory therapy. METHODS: This prospective study included 19 patients (38 eyes) diagnosed with acute uveitis associated with VKH disease. RESULTS: The mean follow-up period was 27.0 ± 11.1 months (range 16-54 months). Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering prednisone to 10 mg or less daily was 5.1 ± 1.2 months (range 3-7 months). Ten (53%) patients discontinued treatment without relapse of inflammation. The mean time observed of treatment was 17.3 ± 11.9 months (range 3-41.5 months). Visual acuity of 20/20 was achieved by 38% of the eyes in the corticosteroid group and by 74% in the corticosteroid + MMF group (p < 0.001). Recurrent inflammation of ≥3 times was reduced significantly (p = 0.0383) in the corticosteroid + MMF group (3%) as compared to corticosteroid group (18%). Development of all complications was significantly higher in the corticosteroid group (43%) compared with the corticosteroid + MMF group (8%) (p < 0.001). None of the eyes in the corticosteroid + MMF group developed 'sunset glow fundus'. CONCLUSIONS: Addition of MMF as first-line therapy to corticosteroids in patients with acute uveitis associated with VKH disease leads to significant reduction in recurrences of uveitis and development of late complications and significantly improves visual outcome.


Assuntos
Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Uveíte Posterior/tratamento farmacológico , Síndrome Uveomeningoencefálica/tratamento farmacológico , Doença Aguda , Administração Oral , Adolescente , Adulto , Criança , Corantes , Quimioterapia Combinada , Feminino , Angiofluoresceinografia , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Verde de Indocianina , Infusões Intravenosas , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Ácido Micofenólico/uso terapêutico , Oftalmoscopia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Estudos Prospectivos , Prevenção Secundária , Resultado do Tratamento , Uveíte Posterior/diagnóstico , Uveíte Posterior/etiologia , Síndrome Uveomeningoencefálica/complicações , Síndrome Uveomeningoencefálica/diagnóstico , Acuidade Visual/fisiologia , Adulto Jovem
10.
Cytokine ; 59(2): 377-81, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22583692

RESUMO

Aqueous humor (AH) samples from 14 patients with presumed tuberculous uveitis (PTU), and 30 control patients were assayed for the proinflammatory cytokines interleukin IL-4, IL-12, IL-15, IL-17, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, the immunosuppressive cytokine IL-10, and the chemokines GRO-α/CXCL1, IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and SDF-1/CXCL12 with the use of a multiplex assay. Among cytokines, IL-4 and IL-12 were not detected. IL-15, IL-17, IFN-γ, TNF-α and IL-10 levels in AH were significantly higher in patients than in controls (p<0.001; p=0.004; p<0.001; p<0.001; p<0.001, respectively). Among chemokines, SDF-1 levels did not differ significantly between patients and controls, whereas GRO-α, IL-8, MIG and IP-10 levels were significantly higher in patients than in controls (p=0.001; p<0.001; p<0.001; p<0.001, respectively). Mean GRO-α levels in AH of PTU patients were 6-fold higher than IL-8 levels and mean IP-10 levels were 15-fold higher than MIG levels. Clinical disease activity correlated significantly with the levels of IL-15, IFN-γ, TNF-α and IP-10. Logistic regression analysis demonstrated a significant positive association between PTU and high levels of IFN-γ, IL-8, MIG and IP-10. These data suggest that both T helper (Th) Th(1) and Th(17) cells are involved in PTU and that the cytokine profile is polarized toward a Th(1) response. GRO-α and IP-10 might be involved in neutrophil and activated T lymphocyte chemoattraction in PTU, respectively.


Assuntos
Humor Aquoso/imunologia , Quimiocinas CXC/metabolismo , Citocinas/metabolismo , Tuberculose/complicações , Tuberculose/imunologia , Uveíte/complicações , Uveíte/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Eur J Ophthalmol ; 22(3): 368-75, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21928252

RESUMO

PURPOSE: To evaluate the effect of immunosuppressive therapy on best-corrected visual acuity (BCVA), fixation stability, and central retinal sensitivity in patients with Vogt-Koyanagi-Harada (VKH) disease in the acute uveitic phase. Methods. In this prospective study, 14 patients (28 eyes) were evaluated. Best-corrected visual acuity and MP-1 microperimetric evaluation of retinal sensitivity in the central 12 degrees and fixation stability were assessed at baseline and at 1, 3, 6, 9, and 12 months after treatment. Results. At baseline, logarithm of the minimum angle of resolution (logMAR) BCVA, fixation stability, and mean retinal sensitivity levels were 0.685 ± 0.6 (Snellen equivalent, 20/100), 61.2% ± 29.0%, and 2.75 ± 3.8 dB, respectively. At 3 months, logMAR BCVA (0.11 ± 0.2, Snellen equivalent 20/25) and fixation stability (86.4% ± 13.4%) were almost maximum (p<0.001 for both comparisons), and thereafter remained almost unchanged. Mean retinal sensitivity continued to improve up to 12 months (12.0 ± 2.3 dB, p<0.001); however, it was still significantly decreased. There were significant correlations between logMAR BCVA and mean retinal sensitivity at all time points. The percentages of BCVA improvement were significantly higher than the percentages of mean retinal sensitivity improvement at all time points (p<0.001 for all comparisons). Conclusions. Compared with microperimetry, BCVA significantly underestimates macular dysfunction in VKH disease.


Assuntos
Imunossupressores/uso terapêutico , Retina/fisiopatologia , Síndrome Uveomeningoencefálica/tratamento farmacológico , Síndrome Uveomeningoencefálica/fisiopatologia , Acuidade Visual/fisiologia , Testes de Campo Visual , Adolescente , Adulto , Criança , Quimioterapia Combinada , Feminino , Fixação Ocular/fisiologia , Angiofluoresceinografia , Humanos , Verde de Indocianina , Masculino , Metilprednisolona/uso terapêutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Estudos Prospectivos , Tomografia de Coerência Óptica , Adulto Jovem
12.
Mol Vis ; 17: 1829-38, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21850157

RESUMO

PURPOSE: To measure levels of high-mobility group box -1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the levels of the inflammatory biomarkers monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-1ß (IL-1ß), and granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, we examined the expression of HMGB1 in the retinas of diabetic mice. METHODS: Vitreous samples from 29 PDR and 17 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Retinas of mice were examined by immunofluorescence analysis and western blotting. RESULTS: HMGB1 was detected in all vitreous samples and sRAGE was detected in 5 PDR samples. IL-1ß was detected in 3PDR samples and GM-CSF was not detected. Mean HMGB1 levels in PDR with active neovascularization were twofold and threefold higher than that in inactive PDR and nondiabetic patients, respectively. Mean HMGB1 levels in PDR patients with hemorrhage were significantly higher than those in PDR patients without hemorrhage and nondiabetic patients (p=0.0111). There were significant correlations between levels of HMGB1 and levels of MCP-1 (r=0.333, p=0.025) and sICAM-1 (r=0.548, p<0.001). HMGB1 expression was also upregulated in the retinas of diabetic mice. CONCLUSIONS: Subclinical chronic inflammation might contribute to the progression of PDR.


Assuntos
Biomarcadores/análise , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Retinopatia Diabética/metabolismo , Inflamação/metabolismo , Retina/metabolismo , Neovascularização Retiniana/metabolismo , Vitreorretinopatia Proliferativa/metabolismo , Corpo Vítreo/metabolismo , Adulto , Idoso , Animais , Western Blotting , Quimiocina CCL2/análise , Quimiocina CCL2/biossíntese , Complicações do Diabetes/patologia , Complicações do Diabetes/cirurgia , Diabetes Mellitus/patologia , Diabetes Mellitus/cirurgia , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Retinopatia Diabética/cirurgia , Ensaio de Imunoadsorção Enzimática , Feminino , Proteína HMGB1/análise , Proteína HMGB1/biossíntese , Humanos , Molécula 1 de Adesão Intercelular/análise , Molécula 1 de Adesão Intercelular/biossíntese , Interleucina-1beta/análise , Interleucina-1beta/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/análise , Receptores Imunológicos/biossíntese , Retina/patologia , Neovascularização Retiniana/etiologia , Neovascularização Retiniana/patologia , Neovascularização Retiniana/cirurgia , Vitrectomia , Vitreorretinopatia Proliferativa/etiologia , Vitreorretinopatia Proliferativa/patologia , Vitreorretinopatia Proliferativa/cirurgia , Corpo Vítreo/patologia , Corpo Vítreo/cirurgia
13.
Immunobiology ; 216(9): 1004-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21531038

RESUMO

Aqueous humor (AH) samples from patients with Behçet's disease (BD) (n=29), Vogt-Koyanagi-Harada (VKH) disease (n=21), and HLA-B27-associated uveitis (n=8), and 42 control patients were assayed for the neutrophil chemoattractants CXCL1/GRO-α and CXCL8/IL-8 and the lymphocyte chemoattractants CXCL9/MIG, CXCL10/IP-10 and CXCL12/SDF-1 with the use of a multiplex chemokine assay. Chemokine levels except SDF-1 were significantly higher in the 3 disease groups than in normal controls. Considering all patients, mean GRO-α levels were 15-fold higher than IL-8 levels and mean IP-10 levels were 22-fold higher than MIG levels. In patients with the same disease activity, AH levels of GRO-α and IP-10 were significantly higher in patients with BD than in patients with VKH disease and HLA-B27-associated uveitis (p=0.0474; p<0.001, respectively). These data suggest that GRO-α and IP-10 are the predominant CXC chemokines involved in neutrophil and activated T lymphocyte chemoattraction in endogenous uveitis, particularly in BD.


Assuntos
Humor Aquoso/metabolismo , Síndrome de Behçet/metabolismo , Quimiocina CXCL10/biossíntese , Quimiocina CXCL1/biossíntese , Quimiocina CXCL9/biossíntese , Uveíte/metabolismo , Síndrome Uveomeningoencefálica/metabolismo , Adolescente , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Humor Aquoso/imunologia , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/imunologia , Biomarcadores/análise , Estudos de Casos e Controles , Quimiocina CXCL1/imunologia , Quimiocina CXCL10/imunologia , Quimiocina CXCL9/imunologia , Feminino , Expressão Gênica , Antígeno HLA-B27/análise , Antígeno HLA-B27/imunologia , Humanos , Imunoensaio , Ativação Linfocitária/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/metabolismo , Uveíte/tratamento farmacológico , Uveíte/imunologia , Síndrome Uveomeningoencefálica/tratamento farmacológico , Síndrome Uveomeningoencefálica/imunologia
14.
Clin Immunol ; 139(2): 177-84, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21334264

RESUMO

We assayed aqueous humor (AH) samples from patients with Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, and HLA-B27-associated uveitis and control patients for the proinflammatory cytokines IL-15, IL-17, interferon-γ and tumor necrosis factor-α and the immunosuppressive cytokine IL-10. Cytokine levels were significantly higher in the three disease groups than in controls. In patients with similar disease activity, levels of IL-15 and IFN-γ were significantly higher in BD patients than in VKH and HLA-B27-associated uveitis groups. Logistic regression identified a significant negative correlation between BD and high levels of IL-10 and a significant positive correlation between VKH disease and high levels of IL-10. The proinflammatory cytokines versus IL-10 ratios were significantly higher in BD compared with other groups. These data suggest that both T helper (Th) 1 and Th17 cells are involved in endogenous uveitis immunopathogenesis. BD is characterized by extensive Th1 polarization, severe proinflammatory conditions and a low immunosuppressive status.


Assuntos
Humor Aquoso/metabolismo , Citocinas/metabolismo , Uveíte/metabolismo , Adolescente , Corticosteroides/administração & dosagem , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Adulto , Humor Aquoso/efeitos dos fármacos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/imunologia , Síndrome de Behçet/metabolismo , Ciclosporina/administração & dosagem , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Feminino , Antígeno HLA-B27/genética , Humanos , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-15/metabolismo , Interleucina-17/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/genética , Uveíte/imunologia , Síndrome Uveomeningoencefálica/diagnóstico , Síndrome Uveomeningoencefálica/imunologia , Síndrome Uveomeningoencefálica/metabolismo , Adulto Jovem
16.
Eur J Ophthalmol ; 20(5): 852-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20815096

RESUMO

PURPOSE: To compare central corneal thickness (CCT) measurements obtained using the Pentacam Scheimpflug system with those obtained using DGH ultrasound pachymetry (UP) in post-laser in situ keratomileusis (LASIK) eyes for myopia. METHODS: In a prospective study, measurement agreement was assessed in 143 eyes of 72 post-LASIK patients using both the Pentacam and UP at the Eye Consultants Center in Riyadh, Saudi Arabia. RESULTS: The mean CCT was 522 +/- 42.2 microm with the Oculus Pentacam and 516.2 +/- 40.6 microm with UP. The Bland-Altman plot showed that the mean +/- SD for the differences between the 2 devices was 5.8 +/- 13.6 microm, with 95% confidence interval limits ranging from -20.9 microm to 32.6 microm. A test of statistical significance indicated that the mean differences of 5.8 +/- 13.6 microm differed significantly from zero (p<0.001; Wilcoxon signed-rank test), thus indicating that the Pentacam measurements tended to overestimate CCT compared with UP. Analysis of regression showed a high correlation between the values obtained with both devices (r=0.947, p<0.001). CONCLUSIONS: In post-LASIK myopic eyes, although a high correlation has been shown between Pentacam and UP measurements, Pentacam tends to overestimate CCT compared to UP. Pentacam probably cannot be used interchangeably with UP in post-LASIK eyes for myopia.


Assuntos
Córnea/patologia , Técnicas de Diagnóstico Oftalmológico/instrumentação , Ceratomileuse Assistida por Excimer Laser In Situ , Miopia/cirurgia , Pesos e Medidas Corporais , Humanos , Microscopia Acústica/métodos , Fotografação/métodos , Período Pós-Operatório , Estudos Prospectivos
17.
Ocul Immunol Inflamm ; 18(6): 424-31, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20735294

RESUMO

PURPOSE: To analyze clinical patterns, causes, and systemic disease associations among patients with uveitis admitted to King Abdulaziz University Hospital. METHODS: The authors retrospectively reviewed the medical records of 351 patients (600 eyes). RESULTS: The study subjects consisted of 183 (52.1%) males and 168 (47.9%) females, with a mean age of 39.9 ± 14.2 years at presentation. The most common anatomic diagnosis was panuveitis (68.6%), followed by posterior uveitis (12.7%), anterior uveitis (12.7%), and intermediate uveitis (6.0%). The most common identifiable specific diagnoses were presumed tuberculous uveitis (PTU) (28.2%), Vogt-Koyanagi-Harada (VKH) disease (19.4%), Behçet disease (BD) (12.5%), and toxoplasmosis (8.2%). After a mean follow-up period of 29.5 ± 22.1 months, 63.5% of the eyes achieved visual acuity of 20/40 or better. Eyes from patients with PTU had the worst final visual outcome. CONCLUSIONS: The most common anatomic diagnosis was panuveitis. PTU, VKH disease, BD, and toxoplasmosis were the most frequent specific diagnoses.


Assuntos
Hospitalização , Hospitais Universitários , Uveíte/epidemiologia , Uveíte/etiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Síndrome de Behçet/complicações , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pan-Uveíte/epidemiologia , Pan-Uveíte/etiologia , Prevalência , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Distribuição por Sexo , Toxoplasmose Ocular , Tuberculose Ocular , Uveíte/microbiologia , Uveíte/parasitologia , Uveíte Anterior/epidemiologia , Uveíte Anterior/etiologia , Uveíte Intermediária/epidemiologia , Uveíte Intermediária/etiologia , Uveíte Posterior/epidemiologia , Uveíte Posterior/etiologia , Síndrome Uveomeningoencefálica/complicações , Adulto Jovem
18.
Ocul Immunol Inflamm ; 18(2): 121-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20370342

RESUMO

PURPOSE: To identify the microbiological spectrum and visual outcome of bleb-associated endophthalmitis. METHODS: The medical records of patients treated for bleb-associated endophthalmitis were reviewed. RESULTS: Seventy-five patients were identified. Vitreous cultures were positive in 48 (64%) patients. The most common isolates were Streptococcus species in 24 (50%) eyes, gram-negative bacteria in 10 (20.8%) eyes, and Staphylococcus epidermidis in 7 (14.6%) eyes. Good visual outcome was achieved in 33 (44%) patients. On univariate analysis, shorter interval from onset of symptoms and treatment (p = .005), better initial visual acuity (p = .004), clear cornea at presentation (p = .048), isolation of less virulent organisms (p < .001), and absence of diabetes mellitus (p = .048) were significant positive predictors for good visual outcome. CONCLUSIONS: Bleb-associated endophthalmitis is associated with severe visual impairment. Clinical features associated with better visual outcome include early presentation, better presenting visual acuity, clear cornea at presentation, culture of a less virulent organism, and absence of diabetes mellitus.


Assuntos
Bactérias/classificação , Vesícula/microbiologia , Endoftalmite/microbiologia , Infecções Oculares Bacterianas/microbiologia , Acuidade Visual , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Vesícula/tratamento farmacológico , Vesícula/fisiopatologia , Criança , Pré-Escolar , Endoftalmite/tratamento farmacológico , Endoftalmite/fisiopatologia , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/fisiopatologia , Feminino , Glaucoma/cirurgia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Arábia Saudita , Resultado do Tratamento , Adulto Jovem
19.
Eur J Ophthalmol ; 20(1): 201-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19882538

RESUMO

PURPOSE: To identify risk factors for the development of culture-positive endophthalmitis after repair of open globe injuries. METHODS: We retrospectively reviewed the medical records of 629 consecutive patients with open globe injuries admitted to King Abdulaziz University Hospital between May 1996 and January 2008. RESULTS: Endophthalmitis developed in 12 (1.9%) patients. The following factors were significantly associated with endophthalmitis by univariate analysis: delayed presentation (>24 hours) (p=0.008), rural address (p=0.013), and dirty wound (p=0.012). Logistic regression analysis identified dirty wound to be associated with the development of endophthalmitis (odds ratio = 11.6; 95% confidence interval [CI] = 2.67-50.6). On logistic regression analysis, presence of retained intraocular foreign body (IOFB) in association with rural address (odds ratio = 11.0; 95% CI = 1.44-83.3) or dirty wound (odds ratio = 9.2; 95% CI = 1.22-69.1) was associated with development of endophthalmitis. Endophthalmitis was a significant negative predictor for final good visual outcome (p=0.00261) and was significantly associated with hypotony (p=0.033). CONCLUSIONS: Delayed presentation, rural address, and dirty wound were associated with development of endophthalmitis. Retained IOFB in association with rural address or dirty wound was associated with a particularly high risk of endophthalmitis.


Assuntos
Endoftalmite/etiologia , Infecções Oculares Bacterianas/etiologia , Ferimentos Oculares Penetrantes/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Criança , Pré-Escolar , Endoftalmite/epidemiologia , Infecções Oculares Bacterianas/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , População Rural/estatística & dados numéricos , Arábia Saudita , Fatores de Tempo , População Urbana/estatística & dados numéricos
20.
J Cataract Refract Surg ; 35(4): 643-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19304084

RESUMO

PURPOSE: To estimate the incidence of acute-onset endophthalmitis after cataract surgery and to report its clinical features, microbiology, and final visual outcomes. SETTING: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. METHODS: This was a retrospective observational case series. RESULTS: The 10-year incidence of acute-onset endophthalmitis after cataract surgery was 0.068%: 0.049% for extracapsular cataract extraction (ECCE) and 0.085% for clear corneal phacoemulsification (P = .268). The incidence of endophthalmitis was 0.053% during the first 5 years of the study and 0.08% during the next 5 years. The most common presenting features were pain and poor red reflex. Of the 20 cases, 18 were culture positive. The culture isolates showed Staphylococcus species in 7 eyes (35%), Streptococcus species in 7 eyes (35%), polymicrobial or mixed infections in 3 eyes (15%), and Propionibacterium acnes in 1 eye (5%). Two patients (10%) achieved a final visual acuity of 20/40 or better, 5 (25%) had worse than 20/40 to better than 20/200, and 8 (40%) had worse than 20/200; 5 eyes (25%) were eviscerated. Visual outcomes were good in endophthalmitis cases after phacoemulsification and in cases caused by Staphylococcus epidermidis and worse in cases that had Streptococcus species endophthalmitis. CONCLUSIONS: Clear corneal phacoemulsification had a 1.73-fold higher risk for acute endophthalmitis than ECCE. Although the incidence of endophthalmitis after ECCE was lower than after phacoemulsification, the outcome was much worse in post-ECCE endophthalmitis cases. Poor visual outcomes were associated with more virulent organisms and delayed presentation.


Assuntos
Bactérias/isolamento & purificação , Extração de Catarata , Infecção Hospitalar/microbiologia , Endoftalmite/microbiologia , Infecções Oculares Bacterianas/microbiologia , Acuidade Visual/fisiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Endoftalmite/diagnóstico , Endoftalmite/tratamento farmacológico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Feminino , Humanos , Incidência , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos
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