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PURPOSE: To investigate the distribution and clinical impact of glycogen accumulation on heart structure and function in individuals with GSD III. METHODS: We examined cardiac tissue and the clinical records of three individuals with GSD IIIa who died or underwent cardiac transplantation. Of the two patients that died, one was from infection and the other was from sudden cardiac death. The third patient required cardiac transplantation for end-stage heart failure with severe hypertrophic cardiomyopathy. RESULTS: Macro- and microscopic examination revealed cardiac fibrosis (n = 1), moderate to severe vacuolation of cardiac myocytes (n = 3), mild to severe glycogen accumulation in the atrioventricular (AV) node (n = 3), and glycogen accumulation in smooth muscle cells of intramyocardial arteries associated with smooth muscle hyperplasia and profoundly thickened vascular walls (n = 1). CONCLUSION: Our findings document diffuse though variable involvement of cardiac structures in GSD III patients. Furthermore, our results also show a potential for serious arrhythmia and symptomatic heart failure in some GSD III patients, and this should be considered when managing this patient population.
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AIM: To determine if recombinant tissue plasminogen activator (rtPA) injected into the vitreous cavity can penetrate the retinal vessels of porcine eyes with or without vascular occlusion. METHODS: Eight eyes (group I) of four pigs underwent clamping of the optic nerve flush with the globe for 90 minutes. One hour after reperfusion, one eye of each pig was injected with 75 microg of rtPA, and the fellow eye was injected with balanced salt solution (BSS). Eyes were processed for immunohistochemistry. Four additional eyes (group II) of two pigs were subjected to the same injections, but without optic nerve clamping. RESULTS: After reperfusion, the clinical picture was similar to that of a central retinal vein occlusion. Immunoperoxidase staining showed rtPA only in the retinal veins but not the retinal arteries in all eyes injected with rtPA in both groups I and II. Those eyes also showed intense rtPA staining at the level of the internal limiting membrane (ILM). No staining was seen at the level of the ILM or inside the retinal vessels in the BSS injected eyes. Immunofluorescence staining showed intense staining at the level of the ILM, but not inside the retinal vessels in the rtPA-injected eyes. CONCLUSIONS: rtPA may penetrate the retinal veins, but not the arteries of porcine eyes with and without vascular occlusion. The ILM may play a part in preventing rtPA penetration.
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Oclusión de la Vena Retiniana/metabolismo , Vena Retiniana/metabolismo , Activador de Tejido Plasminógeno/farmacocinética , Animales , Permeabilidad Capilar , Inmunohistoquímica/métodos , Inyecciones , Modelos Animales , Proteínas Recombinantes/análisis , Proteínas Recombinantes/farmacocinética , Porcinos , Activador de Tejido Plasminógeno/análisis , Cuerpo Vítreo/metabolismoRESUMEN
BACKGROUND: A full autopsy at our institution includes removal of the eyes for pathologic examination. To our knowledge, the rate of ophthalmic findings at autopsy has not been documented previously. DESIGN: We retrospectively reviewed 277 consecutive autopsies conducted between 1995 and 1999 in which the eyes were removed for examination. Ophthalmic findings were placed in the following categories: I, major findings included those that contributed to the patient's death, would have changed patient management, and/or may have important medical implications for close relatives; II, expected findings after ophthalmologic surgery and minor findings that may have eventually required treatment; and III, incidental findings. RESULTS: Major findings (category I) were found in 32% of autopsies. Minor findings (category II) and incidental findings (category III) were documented in 62% and 34% of autopsies, respectively. Only 14% of autopsies revealed no ophthalmologic diagnoses. CONCLUSION: In our series, postmortem ocular examination revealed a number of important findings, including several heritable and rare conditions. Eighty-six percent of autopsies disclosed at least one pathologic ophthalmologic finding, approximately one third of which demonstrated findings significant enough to have likely required management. Diabetic retinopathy was the most frequent major finding. Malignant melanoma of the choroid was the most commonly found intraocular neoplasm. Chronic uveitis was the most common minor finding. We conclude that important, often unexpected ophthalmic findings are frequently encountered at autopsy, underscoring the relevance of routine postmortem examination of the eyes.
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Autopsia , Oftalmopatías/patología , Neoplasias del Ojo/patología , Ojo/patología , Nervio Óptico/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Oftalmopatías/clasificación , Neoplasias del Ojo/secundario , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Enfermedades del Nervio Óptico/patología , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate preoperative dendritic cell (DC) mobilization and tumor infiltration after administration of Flt3 ligand (Flt3L) to patients with metastatic colon cancer. PATIENTS AND METHODS: Twelve patients with colon cancer metastatic to the liver or lung received Flt3L (20 microg/kg/d subcutaneously for 14 days for one to three cycles at monthly intervals) before attempted metastasectomy. The number and phenotype of DCs mobilized into peripheral-blood mononuclear cells (PBMCs) were evaluated by flow cytometry. After surgical resection, metastatic tumor tissue was evaluated for DC infiltration. In vivo immune responses to recall antigens were measured. RESULTS: After Flt3L administration, on average, the total number of leukocytes in the peripheral blood increased from 5.9 +/- 1.0 x 10(3)/mm(3) to 11.2 +/- 3.8 x 10(3)/mm(3) (mean +/- SD, P: =. 0001). The percentage of CD11c(+)CD14(-) DCs in PBMCs increased from 2.4% +/- 1.8% to 8.8% +/- 4.7% (P: =.004). Delayed-type hypersensitivity (DTH) responses to recall antigens (CANDIDA:, mumps, and tetanus) showed marginally significant increases in reactivity after Flt3L administration (P: =.06, P: =.03, and P: =.08, respectively). An increase in the number of DCs was observed at the periphery of the tumors of patients who received Flt3L compared with those of patients who had not. CONCLUSION: Flt3L is capable of mobilizing DCs into the peripheral blood of patients with metastatic colon cancer and may be associated with increases in DC infiltration in the peritumoral regions. Flt3L mobilization is associated with a trend toward increased DTH responses to recall antigens in vivo. The use of Flt3L to increase circulating DCs for cancer immunotherapy should be considered.
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Adyuvantes Inmunológicos/uso terapéutico , Neoplasias del Colon/inmunología , Células Dendríticas/inmunología , Inmunoterapia Activa/métodos , Proteínas de la Membrana/inmunología , Antígenos/inmunología , Recuento de Células Sanguíneas , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/cirugía , Femenino , Humanos , Hipersensibilidad Tardía/inmunología , Inmunofenotipificación , Células Asesinas Naturales/inmunología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/secundario , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Proteínas de la Membrana/efectos adversos , Proteínas de la Membrana/uso terapéutico , Persona de Mediana Edad , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: We previously found that the inhibition of lipoxygenases resulted in delayed epithelial wound closure in organ-cultured rat corneas. The present study was undertaken to determine the lipoxygenase enzyme and metabolite(s) responsible for regulating reepithelialization and their mechanism of action. METHODS: The effects of esculetin--an established lipoxygenase inhibitor--on endogenous hydroxyeicosatetraenoic acids (HETEs) production, epithelial wound closure, filamentous-actin (F-actin) cytoskeleton, and mitotic rate were investigated using a cell-culture assay and an organ-culture assay of rat corneal epithelium. RESULTS: Lipoxygenase inhibition by esculetin, which resulted in the disruption of F-actin organization and a decrease in the mitotic rate, delayed wound closure in both cell- and organ-culture assays. Normal corneoscleral rims metabolized [3H]arachidonic acid to 12-HETE (major metabolite), 8-HETE, and 9-HETE. HETE synthesis was inhibited by esculetin in a dose-dependent fashion. Chiral-phase analysis revealed that they contained only (S)-enantiomers, which indicated that they were lipoxygenase metabolites. The inhibitory effects of esculetin on F-actin organization and epithelial wound closure in an organ-culture assay were totally reversed by exogenously added 8(S)-HETE, whereas 12- and 9-HETE had no effect. However, none of the HETEs reversed the decreased mitotic rate or achieved complete wound closure in the cell-culture assay. CONCLUSIONS: These results suggest that 8(S)-HETE is the key metabolite of arachidonic acid that regulates corneal epithelial cell migration during wound healing. The metabolite responsible for cell proliferation remains to be determined.
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Ácido Araquidónico/metabolismo , Movimiento Celular/fisiología , Córnea/fisiología , Células Epiteliales/fisiología , Ácidos Hidroxieicosatetraenoicos/metabolismo , Lipooxigenasa/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Actinas/metabolismo , Animales , Células Cultivadas , Córnea/citología , Córnea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Femenino , Ácidos Hidroxieicosatetraenoicos/farmacología , Inhibidores de la Lipooxigenasa/farmacología , Índice Mitótico , Técnicas de Cultivo de Órganos , Ratas , Ratas Sprague-Dawley , Umbeliferonas/farmacología , Cicatrización de Heridas/fisiologíaRESUMEN
PURPOSE: To compare bovine pericardium (Periguard; Bio-Vascular, Inc., St. Paul, MN, U.S.A.) and homologous sclera as spacer graft analogs in a rabbit model. METHODS: A nonrandomized experimental animal study was conducted. Elliptical subconjunctival implants were placed in one lower eyelid each of 10 rabbits. Five rabbits received homologous sclera implants, and five received bovine pericardium implants. The rabbits were killed 7 weeks later, and the lower eyelids were examined clinically and histopathologically. RESULTS: Rabbit eyelids implanted with Periguard had a more marked inflammatory reaction and more significant collagen lamellar disruption than eyelids implanted with homologous sclera, although clinically they appeared quite similar. CONCLUSIONS: Although bovine pericardium elicited a more intense inflammatory response at the histopathologic level, both implants were similarly tolerated at the clinical level. These findings are consistent with animal and human investigations of bovine pericardium in other parts of the body, and warrant further studies into its potential use in the human eyelid.
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Párpados/cirugía , Pericardio/trasplante , Esclerótica/trasplante , Animales , Blefaritis/patología , Bovinos , Conjuntiva/cirugía , Párpados/patología , Pericardio/patología , Conejos , Esclerótica/patología , Trasplante Homólogo , Cicatrización de HeridasRESUMEN
Regulation of fatty acid beta-oxidation (FAO) represents an important mechanism for a sustained balance of energy production/utilization in kidney tissue. To examine the role of stimulated FAO during ischemia, Etomoxir (Eto), clofibrate, and WY-14,643 compounds were given 5 days prior to the induction of ischemia/reperfusion (I/R) injury. Compared with rats administered vehicle, Eto-, clofibrate-, and WY-treated rats had lower blood urea nitrogen and serum creatinines following I/R injury. Histological analysis confirmed a significant amelioration of acute tubular necrosis. I/R injury led to a threefold reduction of mRNA and protein levels of acyl CoA oxidase (AOX) and cytochrome P4A1, as well as twofold inhibition of their enzymatic activities. Eto treatment prevented the reduction of mRNA and protein levels and the inhibition of the enzymatic activities of these two peroxisome proliferator-activated receptor-alpha (PPARalpha) target genes during I/R injury. PPARalpha null mice subjected to I/R injury demonstrated significantly enhanced cortical necrosis and worse kidney function compared with wild-type controls. These results suggest that upregulation of PPARalpha-modulated FAO genes has an important role in the observed cytoprotection during I/R injury.
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Lesión Renal Aguda/enzimología , Enzimas/fisiología , Compuestos Epoxi/farmacología , Receptores Citoplasmáticos y Nucleares/fisiología , Factores de Transcripción/fisiología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/patología , Animales , Nitrógeno de la Urea Sanguínea , Carnitina O-Palmitoiltransferasa/antagonistas & inhibidores , Clofibrato/farmacología , Creatinina/sangre , Isquemia/patología , Isquemia/fisiopatología , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiopatología , Masculino , Ratones , Ratones Noqueados/genética , Necrosis , Pirimidinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptores Citoplasmáticos y Nucleares/genética , Circulación Renal , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Factores de Transcripción/genéticaRESUMEN
PURPOSE: Lack of adequate fibrovascular ingrowth has been implicated as a cause of exposure of hydroxyapatite (HA) implants in anophthalmic sockets. We investigated the vasculopathic effects of external beam irradiation, and the fibrovascular-enhancement effects of hyperbaric oxygen (HBO), on HA implant exposure and fibrovascular ingrowth in a rabbit model. METHODS: Eighteen rabbits underwent enucleation with implantation of a 12-mm HA sphere. Six rabbits received 20 Gy of external beam orbital irradiation prior to enucleation. Three irradiated and 6 nonirradiated rabbits received postoperative HBO. Three weeks postoperatively, all rabbits were evaluated clinically for evidence of implant exposure. Implants were then removed, and histopathologic analysis of fibrovascular ingrowth was performed. RESULTS: The amount of vascularization as measured by the depth of ingrowth was greater for nonirradiated (89% ingrowth) than for irradiated (71% ingrowth) animals. HA implant exposure occurred in 1 of 12 (8%) of the nonirradiated, and 4 of 6 (67%) of the irradiated rabbit orbits. HBO did not protect irradiated rabbits from exposure, but did enhance fibrovascular ingrowth in nonirradiated rabbits (100% ingrowth vs. 77% ingrowth). CONCLUSION: Impaired orbital vascularization from prior irradiation appears to retard fibrovascular ingrowth into HA implants, and is associated with an increased incidence of exposure. While HBO did not diminish the likelihood of exposure in irradiated sockets, HA fibrovascular ingrowth in normal orbits appeared to increase with HBO. This may have beneficial clinical application in cases of exposure in nonirradiated orbits.
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Durapatita , Oxigenoterapia Hiperbárica , Neovascularización Fisiológica/efectos de la radiación , Órbita/irrigación sanguínea , Implantes Orbitales , Complicaciones Posoperatorias/terapia , Animales , Enucleación del Ojo , Masculino , Órbita/patología , Órbita/efectos de la radiación , Complicaciones Posoperatorias/patología , ConejosRESUMEN
PURPOSE: We compared bovine pericardium and homologous sclera as wrapping materials for hydroxyapatite (HA) ocular implants in enucleated New Zealand white rabbits. METHODS: Eighteen rabbits were unilaterally enucleated and the sockets implanted with 10-mm HA spherical implants. Six implants were wrapped with homologous sclera, 6 with bovine pericardium, and 6 were not wrapped. The rabbits were killed 7 weeks later and the sockets were examined clinically for inflammation and implant exposure. Exenterated specimens were assessed histopathologically for inflammation and vascularization. RESULTS: No clinical evidence of implant exposure or extrusion was detected in rabbits receiving sclera or bovine pericardium wrapped implants. Histopathologically, the bovine pericardium displayed more inflammation in its outer portion, as well as more disruption of its lamellar arrangement than did the sclera. Fibrovascular in-growth was complete in all wrapped implants. CONCLUSION: Bovine pericardium behaves similar clinically to homologous sclera as a wrapping material for spherical HA ocular implants in a rabbit model, and may represent a reasonable alternative to sclera in such procedures in humans.
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Materiales Biocompatibles Revestidos , Durapatita , Implantes Orbitales , Pericardio/trasplante , Implantación de Prótesis/métodos , Esclerótica/trasplante , Animales , Bovinos , Pericardio/citología , Conejos , Esclerótica/citología , Trasplante HomólogoAsunto(s)
Carcinoma de Células Escamosas/secundario , Neoplasias de la Coroides/secundario , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas/terapia , Neoplasias de la Coroides/terapia , Neoplasias Esofágicas/terapia , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Cuidados PaliativosRESUMEN
Three patients are described in whom full-thickness glaucoma filtering procedures were complicated by marked extension of the bleb over the cornea, with subsequent symptoms that required surgical intervention. The surgical management in each case involved blunt dissection of the bleb from the cornea, with revision of the remaining portion of the bleb differing in each case according to the intraoperative findings. Light microscopic examination of one surgical specimen revealed a markedly attenuated epithelium covering hydropic corneal stroma. The authors postulate that the mechanism of formation involves aqueous humor dissection between corneal epithelium and stroma, leading to abnormal hydration of the superficial lamellae.
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Cirugía Filtrante/efectos adversos , Glaucoma de Ángulo Abierto/cirugía , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/cirugía , Anciano , Estudios de Seguimiento , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Reoperación , Colgajos Quirúrgicos , Agudeza VisualRESUMEN
We report the development of cytomegalovirus (CMV) keratitis in the penetrating keratoplasty of a 59-year-old human immunodeficiency virus-negative woman after uncomplicated corneal transplantation. Immunosuppression with topical cyclosporine A 2% in corn oil and topical prednisolone acetate 1% suspension was used postoperatively. The 15-month postoperative course was complicated by multiple episodes of endothelial rejection, medically controlled elevated intraocular pressure, polymicrobial bacterial (coagulase-negative staphlococcus and alpha-hemolytic streptococcus) keratitis, and endothelial plaque formation with associated hypopyon and epithelial defect. The graft failed and penetrating keratoplasty was repeated. Cytomegalovirus infection of superficial keratocytes in a region of scarring was identified in histological sections stained with hematoxylin and eosin and confirmed using mouse monoclonal anti-cytomegalovirus antibodies. Excision of the diseased corneal button with no additional treatment appears to have been curative. Low-grade keratitis was the only manifestation of the CMV infection, and it has not recurred 6 months postoperatively.
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Infecciones por Citomegalovirus/etiología , Infecciones Virales del Ojo/etiología , Queratitis/virología , Queratoplastia Penetrante/efectos adversos , Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales , Antígenos Virales/análisis , Córnea/patología , Córnea/cirugía , Córnea/virología , Sustancia Propia/patología , Sustancia Propia/virología , Ciclosporina/administración & dosificación , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/patología , Infecciones Virales del Ojo/patología , Femenino , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Humanos , Técnicas para Inmunoenzimas , Inmunosupresores/administración & dosificación , Queratitis/patología , Persona de Mediana Edad , Soluciones Oftálmicas , Prednisolona/administración & dosificación , ReoperaciónRESUMEN
We used subtractive screening of a cDNA library prepared from corneoscleral rims after cauterizing rat corneas. We identified 76 clones whose corresponding mRNA increased during the wound healing process in an in vivo model of injury which damages the corneal epithelium, stroma, and endothelium. Of these clones, 31 sequences encode known proteins. Another 45 clones are novel sequences based on comparison with the GenBank/EMBL databases. Changes in the level of expression of the novel genes, and a selected number of the known genes, were examined by in situ hybridization 22 and 72 hr after corneal injury. The majority produced a 'wound pattern' of expression such that the mRNAs were highly induced in all cell types adjacent to the wound site at 22 hr post injury. This signal decreased in intensity with distance from the wound site. In a subset of corneoslceral rims examined by in situ hybridization, the mRNAs for these genes were also highly induced in the limbal epithelium, where the progenitor corneal epithelial stem cells reside. By 72 hr, when acute tissue damage had been repaired, the induced mRNA was only faintly present in the thickened epithelium. Our results provide a useful framework for further studies defining the pathophysiological roles of the known and novel proteins encoded by the isolated cDNA clones.
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Lesiones de la Cornea , Regulación de la Expresión Génica , Cicatrización de Heridas/genética , Animales , Córnea/química , Cristalinas/genética , ADN Complementario/análisis , Endotelio/química , Endotelio/citología , Femenino , Expresión Génica , Hibridación in Situ , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Fosfolipasas de Tipo C/genéticaRESUMEN
BACKGROUND: The morphologic features and clinical consequences of removing residual optic disc stalks during vitrectomy for complications of diabetic retinopathy have not been described. METHODS: Twenty-four residual optic disc stalks that were surgically removed from eyes with proliferative diabetic retinopathy and dense nonclearing vitreous hemorrhage and/or traction retinal detachment were studied histologically using conventional hematoxylin and eosin staining as well as a modified Glees staining technique. RESULTS: Histologic examination demonstrated that 79% of the specimens consisted of vascularized glial tissue with an infiltrate of mononuclear cells and 21% consisted of glial membranes devoid of vasculature. Axons were identified in 33% of all tissues studied. Intra-operative hemorrhage occurred in three eyes with strongly adherent optic disc stalks and was controlled with transient elevation of the intraocular pressure. The presence of axons in the removed optic disc stalks was not correlated with a decreased final postoperative visual acuity (median time to follow-up 21 months). CONCLUSIONS: Residual optic disc stalks removed during vitrectomy for proliferative diabetic retinopathy frequently contained axons. The presence of axons does not portend an unfavorable postoperative visual outcome.
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Retinopatía Diabética/cirugía , Disco Óptico/cirugía , Vitrectomía , Vitreorretinopatía Proliferativa/cirugía , Adulto , Anciano , Axones/patología , Retinopatía Diabética/complicaciones , Retinopatía Diabética/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroglía/patología , Disco Óptico/patología , Vitreorretinopatía Proliferativa/complicaciones , Vitreorretinopatía Proliferativa/patologíaRESUMEN
A pyogenic granuloma of the cornea developed on the vascularized cornea of a 79-year-old woman after "snake oil" accidentally dripped in her eye. The snake oil was being used to relieve forehead pain, which may have been referred. The five previously reported examples of corneal pyogenic granuloma are similar to this case in that trauma preceded development of the lesion. However, the chemical trauma induced by the snake oil appears to be a unique mechanism of injury.
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Enfermedades de la Córnea/inducido químicamente , Granuloma Piogénico/inducido químicamente , Materia Medica/efectos adversos , Anciano , Animales , Córnea/efectos de los fármacos , Córnea/patología , Enfermedades de la Córnea/patología , Dolor Facial/tratamiento farmacológico , Femenino , Granuloma Piogénico/patología , Humanos , Linimentos , Aceites/efectos adversos , SerpientesRESUMEN
Folkman and coworkers have described angiostatic steroids that markedly inhibit neovascularization of the rabbit cornea when given topically with beta-cyclodextrin tetradecasulfate (beta-CD), yet have minimal or no glucocorticoid or mineralocorticoid activity. Our objective was to extend these observations to another species, the rat. We induced neovascularization by cauterizing rat corneas with silver nitrate/potassium nitrate; drugs were applied topically four times per day for 4 days in most experiments. Submicron sized emulsions of lipid-soluble dexamethasone and the angiostatic steroids 17 alpha-hydroxyprogesterone (1 or 10 mg ml-1) and cortexolone (1 or 10 mg ml-1) were prepared by lecithin encapsulation of drug microcrystals. The vehicle for water-soluble hydrocortisone 21-phosphate (HCP) +/- beta-CD (Molecusol; Pharmatec, Inc) was 10% Tween 20 in Tris-buffered 0.9% saline. Angiogenesis was significantly inhibited only by 1 mg ml-1 dexamethasone (-63.2% when compared with controls), 0.5 mg ml-1 HCP + 1 mg ml-1 beta-CD (-33.4%), and 1 mg ml-1 HCP (-40.2%). HCP (0.5 mg ml-1) or beta-CD (1 or 2 mg ml-1) alone had no significant effect on neovascularization; the inhibition by 1.0 mg ml-1 HCP was not potentiated by 2 mg ml-1 beta-CD. We also tested HCP and tetrahydro-S (TH-S) using 1.5% hydroxypropyl methylcellulose vehicle and beta-CD from Takeda Chemical Industries, Ltd., to simulate the procedure of Folkman and coworkers.(ABSTRACT TRUNCATED AT 250 WORDS)
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Córnea/irrigación sanguínea , Ciclodextrinas/uso terapéutico , Neovascularización Patológica/prevención & control , Esteroides/uso terapéutico , beta-Ciclodextrinas , 17-alfa-Hidroxiprogesterona , Animales , Cortodoxona/análogos & derivados , Cortodoxona/uso terapéutico , Dexametasona/uso terapéutico , Quimioterapia Combinada , Femenino , Hidrocortisona/análogos & derivados , Hidrocortisona/uso terapéutico , Hidroxiprogesteronas/uso terapéutico , Masculino , Neovascularización Patológica/inducido químicamente , Nitratos , Compuestos de Potasio , Ratas , Ratas Sprague-Dawley , Nitrato de PlataRESUMEN
We examined the ability of inhibitors of arachidonic acid metabolism to influence the rate of healing of organ-cultured rat corneas with 3-mm diameter central epithelial abrasions. In control corneas, and in the presence of the cyclooxygenase inhibitors indomethacin (1 microM), or flurbiprofen (1 microM), the defect was completely reepithelialized by 25 hr. In contrast, corneas cultured with the lipoxygenase inhibitors quercetin (100 microM), esculetin (100 microM), or baicalein (10 microM) or the dual cyclooxygenase/lipoxygenase inhibitors BW 775C (100 microM) or BW A540C (100 microM) had significantly delayed epithelial healing rates when compared with the controls; complete healing of the epithelial defects required 32.5-40 hr. Dose-response studies with esculetin and BW 755C demonstrated that the concentrations for 50% inhibition of reepithelialization (65.3 microM for esculetin, 39.6 microM for BW 755 C) were significantly greater than those for inhibition of 12-lipoxygenase activity (16.6 microM for esculetin, 21.1 microM for BW 755C), the major lipoxygenase activity in normal rat cornea. Addition of 12(S)-5,8,10,14- hydroxyeicosatetraenoic acid [12(S)-HETE, 0.01-10 microM], the main 12-lipoxygenase metabolite of arachidonic acid in normal rat cornea, to the organ cultures did not influence the rate of epithelial wound healing in the absence of presence of 100 microM esculetin. Our results suggest that lipoxygenase activity is an important factor in regulating corneal epithelial wound healing in the rat, presumably by influencing epithelial cell migration. The lipoxygenase enzyme and metabolite(s) responsible for regulating reepithelialization, and the mechanism of action, remain to be determined.
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Ácido Araquidónico/antagonistas & inhibidores , Ácido Araquidónico/metabolismo , Córnea/fisiología , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores de la Lipooxigenasa/farmacología , Cicatrización de Heridas/fisiología , Animales , Araquidonato 12-Lipooxigenasa/metabolismo , Córnea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Epitelio/efectos de los fármacos , Epitelio/fisiología , Masculino , Técnicas de Cultivo de Órganos , Prostaglandina-Endoperóxido Sintasas/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND METHODS: The authors report the clinical and ocular histopathologic findings in three patients with longstanding unilateral post-traumatic blindness. After one or more decades, acute pain associated with conjunctival hyperemia and apparent keratoprecipitates or a hypopyon developed in the affected eye of each individual. Phacoanaphylaxis was diagnosed preoperatively in two patients. RESULTS: Calcified granular lens fragments were dispersed throughout all three eyes. The anterior chamber in all patients contained extracellular calcified lens particles, but only one eye contained conspicuous macrophages. Two eyes showed elevated intraocular pressure (IOP), and in one patient calcified particles extended into a glaucomatous optic nerve head. CONCLUSION: To the authors' knowledge, this is the first report describing a rare condition involving the intraocular dispersal of calcified lens particles after disruption of the lens capsule. The authors have designated this entity as calcific phacolysis.
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Calcinosis/patología , Enfermedades del Cristalino/patología , Ceguera/patología , Cuerpos Extraños en el Ojo/patología , Lesiones Oculares Penetrantes/patología , Humanos , Presión Intraocular , Cápsula del Cristalino/patología , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To examine the ability of protein kinase C (PKC) inhibitors and activators to influence the rate of corneal re-epithelialization in the rat. METHOD: Rat corneas with 3 mm diameter central epithelial abrasions were organ-cultured in control medium or in medium with inhibitors or activators of PKC. RESULTS: In control corneas, the defect was completely re-epithelialized by 25 hr. In the presence of the PKC inhibitors staurosporine (100 nM), sphinganine (50 mumol/l), or H-7 (100 mumol/l) there were significantly larger epithelial defects than in controls after 5-25 hr of incubation. Re-epithelialization rates were similar to control corneas when the incubation medium contained HA1004 (100 mumol/l), an analogue of H-7 that is a potent inhibitor of cyclic adenosine monophosphate- and cyclic guanosine monophosphate-dependent protein kinases and a weak inhibitor of PKC. Two PKC activators, 1-oleoyl-2-acetyl-sn-glycerol (OAG) and phorbol 12-myristate 13-acetate (PMA), were unable to enhance the rate of epithelial wound healing. CONCLUSIONS: Our results suggest that PKC activity is an important factor in regulating corneal epithelial wound healing, presumably by influencing cell migration. Moreover, the results with OAG and PMA suggest that PKC is maximally activated during re-epithelialization in this organ-culture assay.