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1.
FASEB J ; 34(6): 8749-8763, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32385915

RESUMEN

Leukotriene B4 receptor 1 (BLT1), a high-affinity G-protein-coupled receptor for leukotriene B4 (LTB4 ), is expressed on various inflammatory cells and plays critical roles in several inflammatory diseases. In myocardial infarction (MI), various inflammatory cells are known to be recruited to the infarcted area, but the function of BLT1 in MI is poorly understood. Here, we investigated the role of BLT1 in MI and the therapeutic effect of a BLT1 antagonist, ONO-4057, on MI. Mice with infarcted hearts showed increased BLT1 expression and LTB4 levels. BLT1-knockout mice with infarcted hearts exhibited attenuated leukocyte infiltration, proinflammatory cytokine production, and cell death, which led to reduced mortality and improved cardiac function after MI. Bone-marrow transplantation studies showed that BLT1 expressed on bone marrow-derived cells was responsible for the exacerbation of inflammation in infarcted hearts. Furthermore, ONO-4057 administration attenuated the inflammatory responses in hearts surgically treated for MI, which resulted in reduced mortality and improved cardiac function after MI. Our study demonstrated that BLT1 contributes to excessive inflammation after MI and could represent a new therapeutic target for MI.


Asunto(s)
Inflamación/metabolismo , Infarto del Miocardio/metabolismo , Receptores de Leucotrieno B4/metabolismo , Animales , Modelos Animales de Enfermedad , Leucotrieno B4/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal/fisiología
2.
Appl Opt ; 57(27): 7770-7777, 2018 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-30462040

RESUMEN

A flat-field grating spectrometer for tender x-ray emission spectroscopy has been developed. The grating has been coated with an aperiodic Ni/C multilayer that improves the diffraction efficiency in the range 1-3.5 keV at a constant angle of incidence. The aperiodic layer structure originates from the topmost bilayer with a larger thickness compared to other Ni/C bilayers. The performance of the spectrometer has been evaluated by measuring characteristic x rays such as the L series emitted from a Cu(In,Ga)Se2-based thin-film solar cell specimen. It is shown that the Lα1,2 x-ray emission spectra of Cu, In, Ga, and Se can be clearly simultaneously observed in the range from 0.9 to 3.3 keV, and the linewidths are 4.9, 26.1, 4.6, and 6.1 eV, respectively, corresponding to a spectral resolution of 100-300.

3.
J Clin Invest ; 127(1): 383-401, 2017 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-27918308

RESUMEN

Myocardial infarction (MI) results in the generation of dead cells in the infarcted area. These cells are swiftly removed by phagocytes to minimize inflammation and limit expansion of the damaged area. However, the types of cells and molecules responsible for the engulfment of dead cells in the infarcted area remain largely unknown. In this study, we demonstrated that cardiac myofibroblasts, which execute tissue fibrosis by producing extracellular matrix proteins, efficiently engulf dead cells. Furthermore, we identified a population of cardiac myofibroblasts that appears in the heart after MI in humans and mice. We found that these cardiac myofibroblasts secrete milk fat globule-epidermal growth factor 8 (MFG-E8), which promotes apoptotic engulfment, and determined that serum response factor is important for MFG-E8 production in myofibroblasts. Following MFG-E8-mediated engulfment of apoptotic cells, myofibroblasts acquired antiinflammatory properties. MFG-E8 deficiency in mice led to the accumulation of unengulfed dead cells after MI, resulting in exacerbated inflammatory responses and a substantial decrease in survival. Moreover, MFG-E8 administration into infarcted hearts restored cardiac function and morphology. MFG-E8-producing myofibroblasts mainly originated from resident cardiac fibroblasts and cells that underwent endothelial-mesenchymal transition in the heart. Together, our results reveal previously unrecognized roles of myofibroblasts in regulating apoptotic engulfment and a fundamental importance of these cells in recovery from MI.


Asunto(s)
Antígenos de Superficie/metabolismo , Apoptosis , Transición Epitelial-Mesenquimal , Proteínas de la Leche/metabolismo , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Miofibroblastos/metabolismo , Animales , Antígenos de Superficie/genética , Supervivencia Celular/genética , Masculino , Ratones , Ratones Noqueados , Proteínas de la Leche/genética , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Miocardio/patología , Miofibroblastos/patología
4.
Am J Case Rep ; 16: 728-32, 2015 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-26460101

RESUMEN

BACKGROUND: Visual disturbance caused by cancer metastasis from other organs is one of the largest challenges to cancer patients' quality of life (QOL). Lung cancer is the most frequent primary site of choroidal metastasis in men, but improvement of visual disturbance has not always been emphasized in lung cancers. Recently intravitreal bevacizumab is a newer modality being tried for local control of choroidal metastases. CASE REPORT: A 68-year-old man was admitted the hospital with complaint of visual disturbance in his left eye. He was diagnosed with lung adenocarcinoma cT2N0M1b (OSS, OTH) stage IV. The ophthalmologic evaluation showed exudative fluid, which caused retinal detachment under the retina. Fluorescence angiography showed granular hyperfluorescence with leakage consistent with a tumor. He received radiotherapy for bone metastasis and systematic chemotherapy with carboplatin, pemetrexed, and bevacizumab, as well as intravitreal injection of bevacizumab 1.25 mg to improve the visual disturbance. His visual symptom and retinal detachment improved until he died. An autopsy revealed that the metastatic lesion in his left eye was totally cured macroscopically and microscopically. CONCLUSIONS: We report a case of exudative retinal detachment secondary to a metastatic choroidal tumor from lung adenocarcinoma, which was treated with chemotherapy and intravitreal injection of bevacizumab. Although he finally died of lung cancer, he maintained his visual QOL and autopsy revealed complete cure of the choroidal metastasis.


Asunto(s)
Bevacizumab/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/secundario , Neoplasias de la Coroides/complicaciones , Neoplasias Pulmonares/patología , Desprendimiento de Retina/tratamiento farmacológico , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias de la Coroides/diagnóstico , Neoplasias de la Coroides/secundario , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Inyecciones Intravítreas , Neoplasias Pulmonares/complicaciones , Masculino , Tomografía de Emisión de Positrones , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/etiología , Tomografía Computarizada por Rayos X
5.
Nat Commun ; 4: 1532, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23443560

RESUMEN

Efficient engulfment of apoptotic cells is critical for maintaining tissue homoeostasis. When phagocytes recognize 'eat me' signals presented on the surface of apoptotic cells, this subsequently induces cytoskeletal rearrangement of phagocytes for the engulfment through Rac1 activation. However, the intracellular signalling cascades that result in Rac1 activation remain largely unknown. Here we show that G-protein-coupled receptor kinase 6 (GRK6) is involved in apoptotic cell clearance. GRK6 cooperates with GIT1 to activate Rac1, which promotes apoptotic engulfment independently from the two known DOCK180/ELMO/Rac1 and GULP1/Rac1 engulfment pathways. As a consequence, GRK6-deficient mice develop an autoimmune disease. GRK6-deficient mice also have increased iron stores in splenic red pulp in which F4/80(+) macrophages are responsible for senescent red blood cell clearance. Our results reveal previously unrecognized roles for GRK6 in regulating apoptotic engulfment and its fundamental importance in immune and iron homoeostasis.


Asunto(s)
Apoptosis , Enfermedades Autoinmunes/enzimología , Enfermedades Autoinmunes/patología , Quinasas de Receptores Acoplados a Proteína-G/deficiencia , Fagocitosis , Animales , Enfermedades Autoinmunes/sangre , Proteínas de Ciclo Celular/metabolismo , Senescencia Celular , Proteínas del Citoesqueleto/metabolismo , Electroforesis en Gel Bidimensional , Eritrocitos/metabolismo , Eritrocitos/patología , Femenino , Quinasas de Receptores Acoplados a Proteína-G/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Humanos , Macrófagos/metabolismo , Macrófagos/patología , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas de Microfilamentos/metabolismo , Células 3T3 NIH , Fosforilación , Transducción de Señal , Bazo/metabolismo , Bazo/patología , Proteínas de Unión al GTP rac/metabolismo
6.
Circ Res ; 112(2): 327-34, 2013 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-23212582

RESUMEN

RATIONALE: The clinical problem of loss of ß-adrenergic receptor (ß-AR) response, both in the pathogenesis of heart failure and during therapeutic application of ß-agonists, is attributable, at least in part, to desensitization, internalization, and downregulation of the receptors. In the regulation of ß-AR signaling, G protein-coupled receptor kinase 2 (GRK2) primarily phosphorylates agonist-occupied ß-ARs, and this modification promotes desensitization, internalization, and downregulation of ß-ARs. It has been demonstrated that GRK2 is inhibited by its S-nitrosylation. However, compounds that induce S-nitrosylation, such as S-nitrosoglutathione, simultaneously generate NO, which has been demonstrated to operate for cardiovascular protection. OBJECTIVE: We examine whether S-nitrosylation without NO generation inhibits desensitization of ß(2)-AR by GRK2. We thus aim to synthesize compounds that specifically induce S-nitrosylation. METHODS AND RESULTS: We have developed water-soluble N-nitrosamines that have S-nitrosylating activity but lack NO-generating activity. These compounds, at least partly, rescue ß-AR from desensitization in HEK 293 cells expressing FLAG-tagged human ß(2)-AR and in rat cardiac myocytes. They inhibit isoproterenol-dependent phosphorylation and internalization of ß(2)-AR. Indeed, they nitrosylate GRK2 in vitro and in cells, and their S-nitrosylation of GRK2 likely underlies their inhibition of ß(2)-AR desensitization. CONCLUSIONS: Compounds that induce S-nitrosylation without NO release inhibit GRK2 and attenuate ß(2)-AR desensitization. Developing water-soluble drugs that specifically induce S-nitrosylation may be a promising therapeutic strategy for heart failure.


Asunto(s)
Óxido Nítrico , Nitrosaminas/metabolismo , Nitrosaminas/farmacología , Receptores Adrenérgicos beta 2/metabolismo , Agua/fisiología , Animales , Células HEK293 , Humanos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Óxido Nítrico/metabolismo , Nitrosaminas/química , Ratas , Solubilidad/efectos de los fármacos , Agua/química
7.
Graefes Arch Clin Exp Ophthalmol ; 249(2): 273-80, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21038080

RESUMEN

BACKGROUND: Retinal function is transiently depressed after photodynamic therapy (PDT) alone. One of the reasons for this functional impairment is a reduction of choroidal circulation caused by the PDT. The purpose of this study was to determine whether PDT combined with intravitreal bevacizumab (PDT+IVB) can reduce or prevent the transient impaired macular function. In addition, we examined whether a significant correlation existed between the changes in the focal macular electroretinograms (FMERGs), optical coherence tomography (OCT)-determined morphology, and changes in choroidal circulation. METHODS: Thirty-eight eyes that were treated by full fluence PDT+IVB were studied. FMERGs, OCT, and indocyanine green angiography (ICGA) were performed before and after the PDT. The intensity of the diffuse fluorescence within the PDT site was measured by densitometry (I/N ratio). RESULTS: The macula was significantly thinner 1 week after PDT+IVB (P < 0.01). The mean a- and b-wave amplitudes of the FMERGs were not significantly decreased 1 week after PDT+IVB. The mean b-wave amplitudes 3 months after PDT+IVB were significantly increased (P < 0.01). The I/N ratio of ICGA 3 months after PDT+IVB was 0.88 ± 0.1. The correlation between the FMERGs and I/N ratio was not significant. CONCLUSION: The use of IVB with PDT mitigates the reduction of the FMERGs and reduces the macular thickness soon after PDT, regardless of the degree of impairment of choroidal circulation caused by PDT. Finally, the macular retinal function 3 months after PDT+IVB were better than that before the treatment.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Neovascularización Coroidal/tratamiento farmacológico , Degeneración Macular/tratamiento farmacológico , Fotoquimioterapia , Anciano , Anticuerpos Monoclonales Humanizados , Bevacizumab , Coroides/irrigación sanguínea , Neovascularización Coroidal/fisiopatología , Colorantes , Terapia Combinada , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Humanos , Verde de Indocianina , Inyecciones Intravítreas , Degeneración Macular/fisiopatología , Masculino , Flujo Sanguíneo Regional/fisiología , Retina/fisiología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
8.
Retina ; 30(3): 495-502, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19996828

RESUMEN

PURPOSE: Choroidal hypofluorescence has been reported beneath the photodynamic therapy (PDT) site in clinical studies. We evaluated the choroidal hypofluorescence after combined PDT with posterior subtenon injection of triamcinolone acetonide or PDT with an intravitreal injection of bevacizumab for age-related macular degeneration. METHODS: Two hundred and forty-two eyes with a subfoveal choroidal neovascularization caused by age-related macular degeneration were studied. Ninety-two eyes underwent PDT alone, 90 eyes underwent PDT with sub-Tenon injection of triamcinolone acetonide, and 60 eyes underwent PDT with intravitreal injection of bevacizumab. Verteporfin-induced choroidal hypoperfusion was determined by indocyanine green angiograms. The intensity of the diffuse fluorescence within the PDT site away from the choroidal neovascularization lesion and from the normal retina just peripheral to the optic disk was measured by densitometry (Topcon IMAGEnet computer system, Topcon, Tokyo, Japan) in the indocyanine green angiogram images obtained at 10 minutes 3 months after the PDT. The ratio of the average brightness of the retina within the PDT area to that of the retina peripheral to the optic disk (irradiated/nonirradiated retinal brightness ratio) was calculated for each angiogram. RESULTS: The irradiated/nonirradiated retinal brightness ratio of the angiograms was 0.96 in the PDT-alone group, 0.85 in the sub-Tenon injection of triamcinolone acetonide-PDT group, and 0.89 in the intravitreal injection of bevacizumab-PDT group (Kruskal-Wallis H test, P < 0.05). CONCLUSION: The degree of choroidal hypofluorescence in the indocyanine green angiogram images 3 months after PDT in the sub-Tenon injection of triamcinolone acetonide and intravitreal injection of bevacizumab group was higher than that of PDT-alone group. Sub-Tenon injection of triamcinolone acetonide and intravitreal injection of bevacizumab can prolong the duration of the choroidal hypofluorescence after PDT.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Coroides/irrigación sanguínea , Neovascularización Coroidal/fisiopatología , Verde de Indocianina , Degeneración Macular/tratamiento farmacológico , Fotoquimioterapia , Triamcinolona Acetonida/administración & dosificación , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales Humanizados , Bevacizumab , Neovascularización Coroidal/etiología , Colorantes , Quimioterapia Combinada , Femenino , Angiografía con Fluoresceína , Glucocorticoides/administración & dosificación , Humanos , Inyecciones , Degeneración Macular/complicaciones , Masculino , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo , Agudeza Visual/fisiología , Cuerpo Vítreo
9.
Retina ; 29(6): 793-802, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19516119

RESUMEN

PURPOSE: To evaluate the differences in the optical coherence tomographically determined macular morphology in eyes with polypoidal choroidal vasculopathy (PCV) from eyes with exudative age-related macular degeneration (AMD) quantitatively. METHODS: The medical records of 208 eyes of 203 Japanese patients with PCV or exudative AMD who were newly treated for choroidal neovascularization were reviewed. The six linear, low-resolution, high-speed scans of 6 mm were analyzed using a manually assisted computer algorithm, which allowed us to manually draw spline lines arbitrarily on the images so that the subretinal fluid and neurosensory retina could be segmented. The thickness of the neurosensory retina and height of the serous retinal detachment (SRD) within the central 3-mm and 6-mm areas were calculated. RESULTS: SRDs were observed in 53% (63/119) of the eyes with exudative AMD and in 78% (69/89) of the eyes with PCV (P < 0.001). The height of the SRD was 21.9 +/- 3.7 microm (+/-SEMs) in eyes with exudative AMD and 56.3 +/- 7.4 microm in eyes with PCV (P < 0.001). The thickness of the neurosensory retina was 300.0 +/- 5.2 microm in eyes with exudative AMD and 275.8 +/- 4.7 microm in eyes with PCV (P < 0.001). CONCLUSION: Eyes with PCV are characterized by a higher incidence of SRDs, greater SRD height, and less intraretinal edema than eyes with exudative AMD.


Asunto(s)
Coroides/irrigación sanguínea , Mácula Lútea/patología , Degeneración Macular/diagnóstico , Enfermedades Vasculares Periféricas/diagnóstico , Desprendimiento de Retina/diagnóstico , Tomografía de Coherencia Óptica/métodos , Anciano , Exudados y Transudados , Femenino , Humanos , Incidencia , Masculino , Agudeza Visual
10.
Retina ; 29(6): 803-10, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19262429

RESUMEN

PURPOSE: Retinal function is commonly depressed transiently after photodynamic therapy (PDT). Additional treatment may prevent this impaired retinal function. The purpose of this study was to determine the changes in the focal macular electroretinograms (FMERGs) after PDT combined with TA for age-related macular degeneration. METHODS: Thirty-four eyes that were successfully treated by PDT with a posterior juxtascleral injection of TA were studied. FMERGs, optical coherence tomography, and indocyanine green angiography were performed before and after the PDT. RESULTS: The mean amplitudes of the FMERGs were not significantly decreased 1 week after PDT with TA (P > 0.05). The mean ratio of the FMERG b-wave 1 week after PDT to that before PDT was 1.09, with an indistinct hypofluorescence at the site of the PDT (18 eyes), and the ratio was 0.91 in the eyes with a distinct hypofluorescence border (16 eyes; P < 0.05). CONCLUSION: The combined use of TA with PDT mitigated the depression of retinal function soon after PDT. However, there were cases of severe choroidal hypoperfusion corresponding to the site of the laser spot that impaired retinal function in comparison to cases with mild hypoperfusion. Even with severe choroidal hypoperfusion, the deterioration in retinal function was relatively mild, with the b-wave FMERG reduced by only 10%.


Asunto(s)
Glucocorticoides/uso terapéutico , Mácula Lútea/fisiopatología , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/fisiopatología , Fotoquimioterapia , Triamcinolona Acetonida/uso terapéutico , Anciano , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/fisiopatología , Colorantes , Terapia Combinada , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Humanos , Verde de Indocianina , Inyecciones , Masculino , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/uso terapéutico , Esclerótica , Tomografía de Coherencia Óptica , Verteporfina
11.
Jpn J Ophthalmol ; 52(3): 182-189, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18661268

RESUMEN

PURPOSE: To determine whether an algorithm we have developed can be used to measure the retinal thickness on optical coherence tomography (OCT) images. METHODS: Six radial linear scans of 6 mm were made with the OCT instrument. The retinal thickness and volume determined with the built-in algorithm for the OCT instrument for 50 eyes of 50 control subjects with normal retinal boundaries were compared to the values obtained with our algorithm. The macular volume was also measured in 26 eyes of 25 subjects before and after photodynamic therapy (PDT). RESULTS: The values obtained by the two algorithms in normal retinas were strongly correlated (R=0.99). Bland-Altman plots of the mean differences between the two algorithm measurement values showed excellent agreement. The mean macular volume determined before and 1 week after PDT with the built-in algorithm was significantly larger than that measured with our algorithm (P=0.035 pre-PDT; P=0.004 1 week after PDT). CONCLUSIONS: Our algorithm can be used to obtain a valid measurement of retinal thickness in normal retinas. The macular volume before and 1 week after PDT obtained with the built-in algorithm was larger than those measurements obtained with our algorithm.


Asunto(s)
Algoritmos , Retina/patología , Tomografía de Coherencia Óptica/métodos , Anciano , Coroides/irrigación sanguínea , Enfermedades de la Coroides/tratamiento farmacológico , Femenino , Humanos , Degeneración Macular/tratamiento farmacológico , Masculino , Enfermedades Vasculares Periféricas/tratamiento farmacológico , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/uso terapéutico , Verteporfina
12.
Invest Ophthalmol Vis Sci ; 49(7): 3121-5, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18408182

RESUMEN

PURPOSE: To study the properties of the focal macular electroretinograms (fmERGs) in eyes with untreated wet-type age-related macular degeneration (AMD). METHODS: fmERGs were recorded from 157 eyes of 157 consecutive patients with untreated wet-type AMD (113 men, 44 women; age, 71.3 +/- 8.0 years). The fmERGs were recorded under direct fundus observation using a modified infrared fundus camera and a 15 degrees stimulus spot. Amplitudes and implicit times of the fmERGs recorded from the AMD patients were compared with those from 21 age-similar healthy controls. RESULTS: The amplitudes of fmERGs in the AMD patients were significantly smaller (P < 0.001) and the implicit times were significantly longer (P < 0.001) than the corresponding values in the control eyes. There was a significant correlation between amplitude and implicit time of the fmERG and visual acuity (logMAR), but the degree of correlation was weak. The difference in the b/a amplitude ratio between the AMD patients and healthy controls was not significant. CONCLUSIONS: The significant reduction in amplitude and the severe delay in implicit times of a- and b-waves of the fmERGs indicated significant functional alterations in the inner and the outer retinal layers of the macular area of eyes with wet-type AMD.


Asunto(s)
Electrorretinografía , Mácula Lútea/fisiopatología , Degeneración Macular/clasificación , Degeneración Macular/diagnóstico , Anciano , Femenino , Fondo de Ojo , Humanos , Rayos Infrarrojos , Degeneración Macular/fisiopatología , Masculino , Persona de Mediana Edad , Retina/fisiopatología , Factores de Tiempo , Agudeza Visual
13.
Ophthalmology ; 114(9): 1722-7, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17400294

RESUMEN

PURPOSE: To determine the relationship between systemic C-reactive protein (CRP) levels and polypoidal choroidal vasculopathy (PCV) and advanced neovascular age-related macular degeneration (AMD) in Japanese patients. DESIGN: Case-control study. PARTICIPANTS: Ninety-seven patients with PCV, 176 with advanced neovascular AMD, and 262 control subjects without any macular abnormality were studied. METHODS: Color fundus photographs of the macular area were taken from both eyes in all subjects. Indocyanine green angiography and fluorescein angiography were performed for diagnosis. The CRP level was measured by a high-sensitivity assay using a latex aggregation immunoassay, and the levels in patients with PCV and neovascular AMD were compared with that in the control group using the Kruskal-Wallis test. Associations between CRP and PCV or neovascular AMD were compared using logistic regression analysis by computing the odds ratios (ORs) and 95% confidence intervals (CIs) after the study populations were divided into quartiles. MAIN OUTCOME MEASURES: The CRP levels in patients with PCV, patients with neovascular AMD, and control subjects. Standard univariate and multivariate analyses between groups. RESULTS: Median CRP levels were significantly higher in cases with PCV (0.94 mg/l) or with advanced neovascular AMD (0.95 mg/l) than in control subjects (0.43 mg/l) (P<0.001 for Kruskal-Wallis test). After adjusting for baseline characteristics such as age, gender, smoking status, alcohol use, body mass index, history, and use of antiinflammatory drugs, the increase in risk was significant for the highest quartile of CRP for both PCV (OR, 3.53; 95% CI, 1.49-8.40) and neovascular AMD (OR, 4.08; 95% CI, 1.94-8.56), and for the third quartile of CRP for neovascular AMD (OR, 2.29; 95% CI, 1.07-4.91). The trends for an increase in risk of disease with increase in CRP were statistically significant for both PCV (P = 0.001) and neovascular AMD (P<0.001). CONCLUSIONS: The significant associations between elevated serum CRP levels and PCV or neovascular AMD in the Japanese strongly suggest that inflammatory processes are involved in the pathogenesis of PCV and neovascular AMD.


Asunto(s)
Proteína C-Reactiva/metabolismo , Enfermedades de la Coroides/sangre , Coroides/irrigación sanguínea , Neovascularización Coroidal/sangre , Degeneración Macular/sangre , Enfermedades Vasculares Periféricas/sangre , Anciano , Anciano de 80 o más Años , Enfermedades de la Coroides/diagnóstico , Neovascularización Coroidal/diagnóstico , Colorantes , Intervalos de Confianza , Femenino , Angiografía con Fluoresceína , Humanos , Verde de Indocianina , Pruebas de Fijación de Látex , Degeneración Macular/diagnóstico , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedades Vasculares Periféricas/diagnóstico , Encuestas y Cuestionarios
14.
Invest Ophthalmol Vis Sci ; 48(5): 2254-9, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17460288

RESUMEN

PURPOSE: It is known that the amplitudes of the multifocal electroretinograms are generally reduced soon after photodynamic therapy (PDT). The purpose of this study was to determine whether this amplitude reduction correlates with the changes in macular thickness or with changes in choroidal circulation. METHODS: Thirty-seven eyes that were successfully treated by PDT were studied. Focal macular electroretinograms (fmERGs) and optical coherence tomography were performed before and 1 week, 1 month, and 3 months after PDT. Indocyanine green angiography was performed before and 3 months after PDT. The indocyanine green angiographic findings were classified into two groups: group A, with indistinct hypofluorescence at the site of the PDT, and group B, with well-defined hypofluorescence borders coinciding with the site of the PDT. RESULTS: The mean amplitudes of the fmERGs were significantly reduced at 1 week after PDT (P < 0.05). The correlations between the changes in the amplitude of the fmERG and the changes in macular thickness were not significant. Sixteen (43%) of the study eyes were classified into group A and 21 (57%) into group B by indocyanine green angiography. The mean ratio of the fmERG b-wave 1 week after PDT to that before PDT was 1.14 +/- 0.62 in group A and 0.65 +/- 0.29 in group B. This difference was statistically significant (P < 0.01). CONCLUSIONS: One of the possibilities that could explain the reduction in the amplitude of the fmERGs soon after PDT is the reduction in choroidal circulation caused by the PDT.


Asunto(s)
Coroides/irrigación sanguínea , Electrorretinografía , Angiografía con Fluoresceína , Fotoquimioterapia , Retina/fisiología , Anciano , Circulación Sanguínea , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/etiología , Femenino , Humanos , Verde de Indocianina , Degeneración Macular/complicaciones , Degeneración Macular/tratamiento farmacológico , Masculino , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual
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