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Objective: To evaluate the efficacy of 0.05% cyclosporine A eye drops combined with vitamin A palmitate eye gel in the treatment of dry eye associated with meibomian gland dysfunction (MGD). Methods: A single-center, prospective, randomized, parallel controlled trial design was used to include patients diagnosed with MGD-associated dry eye. The patients were randomly divided into three groups and administered with medications binocularly for 12 weeks. The CsA+VA group was given 0.05% cyclosporine A eye drops twice a day and vitamin A palmitate eye gel three times a day. The CsA+HA group was given 0.05% cyclosporine A eye drops twice a day and 0.1% sodium hyaluronate eye drops three times a day. The HA group was given 0.1% sodium hyaluronate eye drops 3 times a day. The OSDI score, tear meniscus height, fluorescein tear break-up time, Schirmer â test (without anesthesia), tear film lipid layer thickness, meibomian gland morphology and function examination, and corneal fluorescein sodium staining score were evaluated at baseline, 4, 8, and 12 weeks after the initiation of the treatment, respectively. Results: A total of 120 patients with MGD-related dry eye met the enrollment criteria, but 10 patients were lost to follow-up; 110 patients were finally included for observation, including 36 patients in the CsA+VA group, 38 in the CsA+HA group and 36 in the HA group. The OSDI score, tear meniscus height, fluorescein tear break-up time and meibomian gland secretion of the 3 groups were significantly improved. At the 12th week of the treatment, the differences of the CsA+VA group [25.45±15.11, (0.30±0.13) mm, (3.72±1.40) s, (5.03±2.52) points] and the CsA+HA group [26.98±16.89, (0.27±0.10) mm, (4.34±1.76) s, (5.11±2.39) points] from the HA group [24.57±11.26, (0.24±0.06) mm, (3.18±1.11) s, (9.11±3.34) points] were statistically significant (P<0.05). Compared with the CsA+HA group [(68.39±26.66) nm], the tear film lipid layer thickness in the CsA+VA group [(72.61±23.65) nm] was significantly increased (P<0.05). In the CsA+VA group, the meibomian gland secretion characters and discharge capacity among patients with severe abnormalities [(6.28±2.59) and (5.89±2.77) points at the 12th week of treatment], moderate abnormalities [(4.27±2.02) and (4.64±2.02) points at the 12th week of treatment] and mild abnormalities [(2.80±0.84) and (2.60±0.55) points at the 12th week of treatment] were significantly different (P<0.05). Conclusion: 0.05% cyclosporine A combined with vitamin A palmitate can significantly improve the symptoms and signs of patients with MGD-related dry eye, especially the tear film lipid layer thickness and the meibomian gland secretion characters and discharge capacity in severe cases.
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Diterpenos , Síndromes de Ojo Seco , Disfunción de la Glándula de Meibomio , Ésteres de Retinilo , Humanos , Ciclosporina/uso terapéutico , Estudios Prospectivos , Ácido Hialurónico , Glándulas Tarsales , Lágrimas , Síndromes de Ojo Seco/diagnóstico , Soluciones Oftálmicas/uso terapéutico , Lípidos , Fluoresceínas/uso terapéuticoRESUMEN
BACKGROUND: Endoscopic confocal laser endomicroscopy (eCLE) is an established technique that allows clinical evaluation of mucosal integrity by fluorescein leaking through the mucosa upon duodenal food challenge (DFC). Analysis of eCLE with DFC in eosinophilic esophagitis (EoE) would be interesting to evaluate epithelial barrier dysfunction also in other regions of the gastrointestinal tract and to characterize potential individual food allergens that trigger the esophageal inflammation. METHODS: In an observational and proof of concept study we evaluated 9 patients with histologically proven EoE by eCLE and DFC. Severity of symptoms were graduated according to the validated symptom-based EoE activity index. The endoscopic appearance of the esophagus was described according to the Endoscopic Reference Score System (ERERS). Spontaneous and food induced transfer of fluorescein into duodenal lumen were detected 10 minutes following intravenously application of fluorescein and 10 minutes after DFC. Food allergens were yeast, egg, soy, milk, and wheat, respectively. Local application of sodium chloride solution 10 % to the duodenal mucosa before DFC served as a control. Patients responding to DFC received a dietary exclusion therapy according to the results of DFC. RESULTS: We investigated 9 patients with EoE (8 men, 49.7±13.8, 36-76 years). Symptom-based EoE activity index was 79±27.4, 33-100. In all patients EoE was confirmed by histology with number of esophageal mucosal eosinophilic granulocytes > 15/HPF, (91.4±77.4, 42-263). Mean ERERS score was 4.5±1.3, 3-7. None of the patients was aware of any food intolerance. eCLE revealed one patient with spontaneous transfer of i. v. fluorescein into duodenal lumen before DFC ("leaky gut"). 40 DFC were performed in the remaining 8 patients of whom 5 patients (61 %) responded to DFC. Rank order of fluorescein leakage upon DFC was wheat and milk in 37.5 % each, soy in 25 %, and egg in 12.5 %. The patients were treated by PPI (n=9), esophageal bouginage (n=5) and/or local corticoid therapy (n=3). The 5 patients responding to DFC received an additional food exclusion dietary advice focussed on the results of DFC. All patients reported a reduction of their symptoms. EoE activity indexes of patients with positive DFC were 73.7+28.6, 33-100 before and 22.7+37.9, 0-79 four weeks after food exclusion. CONCLUSION: The findings of our proof of concept study suggest that eCLE with DFC may be an interesting tool to further evaluate patients with EoE. This technique has the potential to identify patients who may benefit from an additional individual dietary therapy.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Masculino , Humanos , Esofagitis Eosinofílica/diagnóstico , Fluoresceínas/uso terapéutico , Rayos LáserRESUMEN
Objective: To evaluate the effectiveness and safety of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in treating severe dry eye associated with chronic graft-versus-host disease (cGVHD). Methods: This non-randomized concurrent control trial enrolled 83 eyes from 83 patients with cGVHD-associated severe dry eye. The treatment had two phases. During the initial shock treatment period (0-3 months), 44 patients received 0.05% cyclosporine A eye drops (4 times/day; group A) and 39 patients received 0.1% tacrolimus eye drops (twice/day; group B) alongside basic treatment. In the maintenance treatment period (3-6 months), both groups used 0.05% cyclosporine A eye drops (twice/day) and sodium hyaluronate. Examinations were conducted at 1, 3, and 6 months after treatment initiation, assessing the Ocular Surface Disease Index (OSDI), corneal fluorescein staining (CFS) score, and fluorescein tear break-up time (BUT) for efficacy. visual acuity and intraocular pressure (IOP) were evaluated for safety, and patients' post-medication irritation symptoms were recorded. Results: The study included 52 males and 31 females, aged (28.57±15.67) years. After 1 month of treatment, the CFS score in group A significantly decreased from 10.0 (6.0, 14.0) to 5.0 (3.0, 8.5) (P<0.001). in group B, the CFS score also significantly decreased from 10.0 (6.0, 15.0) to 6.0 (2.0, 10.0), and the BUT increased from 2.0 (1.0, 2.0) s to 2.0 (1.8, 3.3) s (P<0.001). No significant OSDI decrease was observed in either group. No significant differences were found in OSDI, CFS score, and BUT between the two groups. After 3 months, group A showed significant improvement in OSDI, CFS score, and BUT (P<0.05), while group B only demonstrated significant CFS score decrease (P<0.05). OSDI was significantly lower in group A than group B (P<0.05). No significant differences were noted in CFS score and BUT between groups. After 6 months, OSDI, CFS score, and BUT were 18.9 (9.3, 34.2), 7.0 (3.0, 8.5), and 2.0 (1.0, 3.0) s in group A, and 10.9 (3.6, 35.4), 5.5 (2.8, 10.0), and 2.0 (1.0, 10.0) s in group B. In both groups, CFS scores significantly decreased and BUT increased (P<0.05). Visual acuity improved significantly in group A at 1, 3, and 6 months (P<0.05), while no significant changes were seen in group B. Irritation symptoms were transient and self-resolving in both groups. Conclusions: Both 0.05% cyclosporine A and 0.1% tacrolimus eye drops, when combined with local glucocorticoids, exhibited significant anti-inflammatory effects, effectively and safely treating severe dry eye in cGVHD patients. Although the onset of 0.05% cyclosporine A was slower than 0.1% tacrolimus, it offered more stable long-term effects and better symptom improvement.
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Síndrome de Bronquiolitis Obliterante , Síndromes de Ojo Seco , Femenino , Humanos , Masculino , Ciclosporina/uso terapéutico , Síndromes de Ojo Seco/tratamiento farmacológico , Fluoresceínas/uso terapéutico , Soluciones Oftálmicas/uso terapéutico , Tacrolimus/uso terapéutico , LágrimasRESUMEN
Riboflavin/UV-A corneal cross-linking (CXL) has been applied to treat corneal ulcers in adult horses, but its use in critically ill neonatal foals has not been described. Five cases of hospitalized, critically ill neonatal foals that were in intensive care with corneal ulcers, the ophthalmic treatment, and their outcome up to 1 year are described. A single treatment of CXL phototherapy was performed in three of five foals (five eyes). The application of a riboflavin ophthalmic solution for 20 minutes was followed by the UV-A light irradiation at 30 mW/cm2 for 3 minutes. Topical antibiotic administration was withdrawn after CXL. Two other foals received standard treatment. Descriptions of ocular lesions, fluorescein staining, and photographic documentation were recorded. The visual outcome, corneal transparency, and aesthetics, as well as healing time were evaluated in the follow-up. The frequency of topical medication considerably decreased in cases treated with CXL. Corneal opacity and pain decreased within 3 days following CXL. In the foals treated with CXL, the ulcers healed (fluorescein stain negative) in 24, 28, and 35 days after the onset of clinical signs and 10, 15, and 21, after CXL. No fibrosis or corneal scars were found in the cases treated with CXL. The two standard treatment cases healed after 26 and 36 days respectively. Corneal cross-linking may be an additional or alternative treatment of corneal ulcers in critically ill neonatal foals and may reduce the use of antibiotics.
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Úlcera de la Córnea , Enfermedades de los Caballos , Caballos , Animales , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/veterinaria , Reticulación Corneal/veterinaria , Fármacos Fotosensibilizantes/uso terapéutico , Úlcera/tratamiento farmacológico , Úlcera/veterinaria , Enfermedad Crítica/terapia , Riboflavina/uso terapéutico , Antibacterianos/uso terapéutico , Cuidados Críticos , Fluoresceínas/uso terapéutico , Enfermedades de los Caballos/tratamiento farmacológicoRESUMEN
Background: Reactive oxygen species (ROS) are powerful weapons for various anticancer therapies. However, high glutathione (GSH) levels in cancer cells can significantly reduce the efficacy of such therapies. Methods: In this study, pH-responsive fluorescein-encapsulated zeolitic imidazolate framework-8 nanoparticles were synthesized for ROS-mediated combination therapy. Results: Upon blue light activation, fluorescein displayed a high singlet oxygen photogeneration ability for photodynamic therapy. Concurrently, accumulated Zn2+ from degraded zeolitic imidazolate framework-8 stimulated simultaneous ROS generation and GSH depletion, thereby successfully inducing chemodynamic therapy. This triggered a cascade of photo-physical and chemical processes culminating in the localized generation of ROS, ultimately breaking the intracellular redox equilibrium. Conclusion: This nanoformulation can potentially be used for light-activated ROS-mediated therapy for the management of superficial tumors.
Highly reactive molecules called reactive oxygen species (ROS) are known to be present in excess in cancer cells. As a result, cancer cells are more susceptible to death by any further rise in levels of these species. In the current study, fluorescein-encapsulated zeolitic imidazolate nanoparticles were prepared for blue light-activated ROS-enhancing combination therapy. The nanoparticles displayed significant toxicity against a breast cancer cell line and simultaneously induced glutathione depletion, an antioxidant known to reduce the efficacy of various cancer therapies. Thus, this study reveals the potential of fluorescein-encapsulated zeolitic imidazolate nanoparticles for light-activated ROS-mediated therapy for the treatment of superficial tumors.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias/tratamiento farmacológico , Glutatión/metabolismo , Fluoresceínas/uso terapéutico , Línea Celular Tumoral , Peróxido de Hidrógeno/uso terapéutico , Microambiente TumoralRESUMEN
BACKGROUND: We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response. METHODS: Twenty-nine patients (15 with Crohn's disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4ß7 therapy. Biopsies were taken for fluorescein isothiocyanate-labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort. RESULTS: In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn's disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7). CONCLUSIONS: Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF-responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders.
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Productos Biológicos , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/genética , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Enfermedades Inflamatorias del Intestino/diagnóstico por imagen , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/genética , Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/genética , Factor de Necrosis Tumoral alfa/uso terapéutico , Terapia Biológica , Productos Biológicos/uso terapéutico , Expresión Génica , Fluoresceínas/uso terapéutico , Rayos Láser , Proteínas Adaptadoras Transductoras de Señales , Proteínas con Dominio LIMRESUMEN
BACKGROUND: Soft contact lens wearing increases the risk of an infectious keratitis. A patient present with a red painfull eye, in which case a corneal erosion (coloring with fluorescein) was seen by the general practitioner. It is possible that the clinical course worsens in a few days with a corneal perforation as a result. In these cases a timely referral is necessary. CASE: A fifteen year old soft contact lens wearing girl developed an infectious keratitis. Within a few days she developed a corneal perforation. As a result of an emergency transplantation within 24 hours the patient preserved her globe and her visual acuity recovered. CONCLUSION: Emergency transplantations usually have a complicated course with a high risk of re-transplantation and long-term pharmacological therapy. Such an emergency transplantation is primarily performed to preserve the globe. In the Netherlands a separate pool of emergency donor transplants is available, so that a transplantation can be performed within 24 hours.
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Lentes de Contacto Hidrofílicos , Perforación Corneal , Trasplante de Córnea , Queratitis , Femenino , Humanos , Adolescente , Quimioterapia Combinada , Queratitis/etiología , Fluoresceínas/uso terapéuticoRESUMEN
Purpose: There remains a high unmet need for therapies with new mechanisms of action to achieve reperfusion of ischemic retina in diabetic retinopathy. We examined whether a novel frizzled class receptor 4 (FZD4) agonist could promote regeneration of functional blood vessels in animal models of retinopathy. Methods: We developed a novel Norrin mimetic (SZN-413-p) targeting FZD4 and low-density lipoprotein receptor-related protein 5 (LRP5) and examined its effect on retinal and brain endothelial cells in vitro. SZN-413-p was subsequently humanized, resulting in the therapeutic candidate SZN-413, and was examined in animal models of retinopathy. In an oxygen-induced retinopathy mouse model, avascular and neovascularization areas were measured. Furthermore, in a vascular endothelial growth factor (VEGF)-induced retinal vascular leakage rabbit model, the impact on vascular leakage by SZN-413 was examined by measuring fluorescein leakage. Results: SZN-413-p induced Wnt/ß-catenin signaling and upregulated blood-brain barrier/blood-retina barrier gene expressions in endothelial cells. In the oxygen-induced retinopathy mouse model, SZN-413-p and SZN-413 significantly reduced the neovascularization area size (P < 0.001) to a level comparable to, or better than the positive control aflibercept. Both agonists also showed a reduction in avascular area size compared to vehicle (P < 0.001) and aflibercept groups (P < 0.05 and P < 0.01 for SZN-413-p and SZN-413, respectively). In the VEGF-induced retinal vascular leakage rabbit model, SZN-413 reduced retinal vascular leakage by â¼80%, compared to the vehicle-treated group (P < 0.01). Conclusions: Reduction of neovascular tufts and avascular areas and of VEGF-driven retinal vascular leakage suggests that SZN-413 can simultaneously address retinal non-perfusion and vascular leakage. Translational Relevance: FZD4 signaling modulation by SZN-413 is a novel mechanism of action that can offer a new therapeutic strategy for diabetic retinopathy.
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Diabetes Mellitus , Retinopatía Diabética , Animales , Retinopatía Diabética/tratamiento farmacológico , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Fluoresceínas/uso terapéutico , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad , Ratones , Neovascularización Patológica , Oxígeno/uso terapéutico , Conejos , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , beta Catenina/metabolismo , beta Catenina/uso terapéuticoRESUMEN
This study aimed at investigating the clinical effect of ranibizumab combined with panretinal photocoagulation in the treatment of macular edema in diabetic retinopathy (DR) patients. A parametric deformation model was constructed, and based on this, it was evaluated using optical coherence tomography (OCT) combined with fluorescein fundus angiography (FFA). 56 DR patients (80 eyes) who needed surgery were selected for OCT and FFA scanning, and 0.5 mg ranibizumab was administered intravitreal injection before surgery. It should observe the OCT and FFA image characteristics of patients. In addition, the vision correction status before the surgery, 1 month, 3 months, and 6 months after the surgery, the thickness of the macular retina, operation time, the number of intraoperative electrocoagulation, and complications of patients were recorded. It was found that 82.85% of patients had improved visual acuity after surgery. Compared with preoperative, the average logarithm of the minimum angle of resolution (logMAR) of patients at 6 months after surgery increased significantly (P < 0.01). With the increase of the grade of fibrosis and the grade of hemorrhage, the logMAR visual acuity recovery at 6 months after the surgery became worse; the macular retinal thickness at 6 months after the surgery decreased significantly (P < 0.01). With the increase of the grade of fibrous proliferation and the grade of bleeding, the operation time, the number of electrocoagulation, and the possibility of iatrogenic holes of patient would increase. It can be known that ranibizumab combined with panretinal photocoagulation surgery could not only reduce the macular edema but also effectively reduce the intraoperative bleeding, simplify the removal of proliferative membranes, decrease the number of electrocoagulation, and shorten the operation time, enhancing the visual function of patients.
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Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Algoritmos , Inhibidores de la Angiogénesis/uso terapéutico , Angiografía , Diabetes Mellitus/terapia , Retinopatía Diabética/diagnóstico por imagen , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/cirugía , Fluoresceínas/uso terapéutico , Humanos , Coagulación con Láser/métodos , Edema Macular/diagnóstico por imagen , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Ranibizumab/uso terapéutico , Retina/diagnóstico por imagen , Retina/cirugía , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
IMPORTANCE: Antibiotics are commonly used to treat and prevent urinary tract infection (UTI), but resistance is growing. Nonantibiotic prophylaxis such as methenamine hippurate (MH) shows clinical promise, but its impact on bladder factors influencing recurrent UTIs (rUTIs) is not well described. OBJECTIVE: The aim of the study was to examine the effect of MH on bladder inflammation and barrier function in aged mice and women with rUTI. STUDY DESIGN: This study included urine samples from an experimental study involving aged female mice with and without methenamine treatment as well as women with rUTI who received either no prophylaxis, MH alone, vaginal estrogen therapy and/or d-mannose alone, or MH in addition to vaginal estrogen therapy and/or d-mannose. We performed a comprehensive cytopathological analysis, which included enzyme-linked immunosorbent assay for immunoglobulin A (IgA), interleukin 6 (in human samples), and fluorescein isothiocyanate-conjugated-dextran permeability assay (in mice) to assess for urothelial permeability. RESULTS: In the aged mice model, there was a decreased urothelial permeability (as seen by retention of fluorescein isothiocyanate-conjugated-dextran fluorescence in superficial cells) and increased urinary IgA in mice treated with MH compared with controls. There was no significant difference in urothelial shedding (P > 0.05). In human samples, there was significantly increased urinary IgA in those taking MH alone compared with no prophylaxis (830.1 vs 540.1 ng/mL, P = 0.04), but no significant difference in interleukin 6. CONCLUSIONS: Methenamine hippurate seems to enhance barrier function as evidenced by decreased urothelial permeability and increased urinary IgA levels, without worsening inflammation. This may reflect another beneficial mechanism by which MH helps prevent rUTI.
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Cistitis , Infecciones Urinarias , Animales , Cistitis/tratamiento farmacológico , Dextranos/uso terapéutico , Estrógenos , Femenino , Fluoresceínas/uso terapéutico , Hipuratos , Humanos , Inmunoglobulina A/uso terapéutico , Interleucina-6/uso terapéutico , Isotiocianatos/uso terapéutico , Manosa/uso terapéutico , Metenamina/análogos & derivados , Metenamina/uso terapéutico , Ratones , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/prevención & controlRESUMEN
METHOD: We report a case of bilateral panuveitis and its resolution based on multimodal retinal images after she was administered the first dose of a viral vector-based vaccine against SARS-CoV-2. CASE REPORT: A 72-year-old woman complained of bilateral blurred vision with headache, neck stiffness, and tinnitus 3 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. Initial examination revealed anterior chamber reactions, left optic disc hyperemia, and bilateral chorioretinal folds with choroidal thickening. Fluorescein and indocyanine green angiography revealed bilateral choroiditis and papillitis. Systemic steroid therapy dramatically alleviated panuveitis and meningeal signs. No recurrence was noted until 3 months after discontinuation of steroids. CONCLUSIONS: Bilateral panuveitis mimicking Vogt-Koyanagi-Harada disease can develop shortly after the first dose of the ChAdOx1 nCoV-19 vaccine. Ophthalmologists should consider bilateral panuveitis as a presumed post-vaccination adverse event. Systemic steroid therapy may be effective for the nCoV-19 vaccine-associated panuveitis.
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Vacunas contra la COVID-19 , COVID-19 , Panuveítis , Síndrome Uveomeningoencefálico , Anciano , Femenino , Humanos , ChAdOx1 nCoV-19 , Vacunas contra la COVID-19/efectos adversos , Angiografía con Fluoresceína/métodos , Fluoresceínas/uso terapéutico , Verde de Indocianina , Panuveítis/inducido químicamente , Panuveítis/diagnóstico , Panuveítis/tratamiento farmacológico , SARS-CoV-2 , Síndrome Uveomeningoencefálico/diagnóstico , Síndrome Uveomeningoencefálico/tratamiento farmacológicoRESUMEN
PURPOSE: The purpose of the study was to clarify the clinical and imaging features of sympathetic ophthalmia (SO) and evaluate the efficacy of the current therapy. METHODS: The databases PubMed, EMBASE and Ovid up to January 2021 were searched to identify relevant studies. R software version 3.6.3 was used to perform the statistical analyses. RESULTS: Thirty-two studies involving 1067 patients were finally included. Our study found SO was male-dominated, and more than half of SO patients aged 16 to 60 years old. Ocular trauma, surgical interventions and unknown events were estimated to be inciting events in 63%, 36% and 4% of SO patients. About 35% of the patients underwent baseline enucleation, and 45% took compelled enucleation during follow-up. The most common symptoms at the first presentation were decreased vision, followed by pain and redness. The most common signs were anterior chamber cells/flare, followed by vitritis, exudative retinal detachment and Dalen-Fuch nodules. Choroidal thickening was detected in 81% of SO patients by ocular ultrasound. The most common fluorescein fundus angiography signs were disc leakage. After corticosteroid therapy became the mainstay for SO, about 76% of SO patients could get inflammation well-controlled, while 24% of them might have recurrent inflammation. Around 72% of SO patients could achieve visual improvement, and more than half of them might have a best-corrected visual acuity of 20/50 or better. CONCLUSION: SO is a complicated ocular disease with diverse clinical manifestations and imaging features. After proper anti-inflammation therapy, SO might not necessarily result in a poor prognosis.
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Oftalmía Simpática , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Angiografía con Fluoresceína , Fluoresceínas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Oftalmía Simpática/diagnóstico , Oftalmía Simpática/tratamiento farmacológico , Oftalmía Simpática/etiología , Agudeza Visual , Adulto JovenRESUMEN
BACKGROUND/AIM: To evaluate relationships between subretinal fluid (SRF), macular atrophy (MA) and visual outcomes in ranibizumab-treated neovascular age-related macular degeneration (nAMD). METHODS: This post hoc HARBOR trial (NCT00891735) analysis included ranibizumab-treated (0.5 or 2.0 mg, monthly or as-needed, all treatment arms pooled) eyes with nAMD and baseline (screening, baseline and week 1) SRF. SRF presence, SRF thickness (0, >0-50, >50-100 and >100 µm) and subretinal fluid volume (SRFV) were determined by spectral domain optical coherence tomography (SD-OCT). Best-corrected visual acuity (BCVA) was assessed. MA was identified using fluorescein angiograms and colour fundus photographs, as well as SD-OCT. RESULTS: Seven hundred eighty-five of 1097 eyes met analysis criteria. In eyes without baseline MA, residual versus no SRF at month (M) 3 was associated with lower MA rates at M12 (5.1% vs 22.1%) and M24 (13.3% vs 31.2%) (both p<0.0001); MA percentages at M12/M24 were similar among patients with residual SRF at M6. Higher baseline SRFV was associated with a lower MA rate. Greater mean BCVA was observed with residual SRF of any thickness (>0-50 µm, 71.2 letters; >50-100 µm, 71.3 letters; >100 µm, 69.2 letters) versus no SRF (63.6 letters), but the change in BCVA from baseline to M12 or M24 was the same for eyes with or without treatment-resistant subretinal fluid (TR-SRF) at M3 or M6. CONCLUSION: TR-SRF was not detrimental to vision outcomes over 2 years, regardless of thickness. MA rates were significantly higher without TR-SRF.
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Degeneración Macular , Líquido Subretiniano , Humanos , Ranibizumab/uso terapéutico , Inyecciones Intravítreas , Agudeza Visual , Factor A de Crecimiento Endotelial Vascular , Estudios Prospectivos , Inhibidores de la Angiogénesis/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Factores de Crecimiento Endotelial Vascular , Atrofia , Fluoresceínas/uso terapéuticoRESUMEN
The functionalization of liposomes with monoclonal antibodies is a potential strategy to increase the specificity of liposomes and reduce the side-effects associated with chemotherapeutic agents. The active targeting of the Human Epidermal growth factor Receptor 2 (HER2), which is overexpressed in HER2 positive breast cancer cells, can be achieved by coating liposomes with an anti-HER2 monoclonal antibody. In this study, we synthesized calcein and Doxorubicin-loaded immunoliposomes functionalized with the monoclonal antibody Trastuzumab (TRA). Both liposomes were characterized for their size, phospholipid content and antibody conjugation. Exposing the liposomes to low-frequency ultrasound (LFUS) triggered drug release which increased with the increase in power density. Trastuzumab conjugation resulted in enhancing the sensitivity of the liposomes to LFUS. Compared to the control liposomes, TRA-liposomes showed higher cellular toxicity and higher drug uptake by the HER2 + cell line (SKBR3) which was further improved following sonication with LFUS. Combining immunoliposomes with LFUS is a promising technique in the field of targeted drug delivery that can enhance efficiency and reduce the cytotoxicity of antineoplastic drugs.
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Sistemas de Liberación de Medicamentos/métodos , Liposomas/uso terapéutico , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Liberación de Fármacos , Femenino , Fluoresceínas/administración & dosificación , Fluoresceínas/uso terapéutico , Humanos , Inmunoconjugados/metabolismo , Receptor ErbB-2/inmunología , Trastuzumab/administración & dosificación , Trastuzumab/uso terapéutico , Terapia por Ultrasonido/métodosRESUMEN
Because of the physiological and anatomical constraints of the eye, ophthalmic drug delivery is challenging. When applied topically, less than 1% of administered ophthalmic drugs reach the aqueous humor. The delivery of a drug within an efficient therapeutic concentration, to the required site of action, for an extended period of time, is complicated. Herein, a novel type of contact lens device, with embedded microtubes as drug containers, is reported. This device can provide a simple, noninvasive, extended drug release up to 45 days with higher bioavailability and lower risk for adverse effects. Another unique feature of the device is the release of drug triggered by stretching of the contact lens, indicating the possibility for achieving a self-adaptive drug release device for treating glaucoma patients.
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Lentes de Contacto Hidrofílicos , Sistemas de Liberación de Medicamentos , Fluoresceínas/uso terapéutico , Glaucoma/tratamiento farmacológico , Soluciones Oftálmicas/uso terapéutico , Timolol/uso terapéutico , Difusión , Liberación de Fármacos , Fluoresceínas/administración & dosificación , Humanos , Hipertensión Intracraneal/tratamiento farmacológico , Microtúbulos/química , Soluciones Oftálmicas/administración & dosificación , Imagen Óptica , Tamaño de la Partícula , Propiedades de Superficie , Timolol/administración & dosificaciónRESUMEN
OBJECTIVE: To study the fluorescein angiography (FA) features post-intravitreal bevacizumab (post-IVB) monotherapy for retinopathy of prematurity (ROP) that may pose risk for late sight-threatening ROP and support rescue laser to the avascular retina. METHODS: A retrospective review of 26 infants (47 eyes) with type 1 ROP treated with IVB monotherapy. RESULTS: All infants had RetCam and FA performed at an average of 68 weeks postmenstrual age (PMA), 19 at an average 98 weeks PMA, and 10 at an average of 120 weeks PMA. Average gestational age at birth and birth weight were 24.8 weeks (standard deviation [SD] 1.91 weeks) and 683 g (SD 158.85 g), respectively. Average PMA at first IVB was 37 weeks. Eight eyes of 6 infants received repeat IVB for recurrent stage 3 at an average of 46.6 weeks PMA. All infants had inhibited retinal vasculature in zone 2, and 25 of 26 had conventional FA features, which included peripheral leakage, shunts, abnormal branching, and tangles with no late reactivation of ROP until age 3 years. Only 1 infant showed diffuse hyperfluorescence along the regressed proliferation site with a late proliferation necessitating laser to preserve vision. CONCLUSIONS: Conventional FA features seen in 98% post-IVB monotherapy showed no late complications without rescue laser photocoagulation to the avascular retina.
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Retinopatía de la Prematuridad , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Preescolar , Angiografía con Fluoresceína , Fluoresceínas/uso terapéutico , Edad Gestacional , Humanos , Lactante , Recién Nacido , Inyecciones Intravítreas , Coagulación con Láser , Retina , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/cirugía , Estudios RetrospectivosRESUMEN
Chemokines and chemokine receptors play important roles in the immune response. We previously reported the pathogenic role of C-C chemokine receptor type 4 (CCR4) in experimental autoimmune encephalomyelitis (EAE). Here, we examined whether CCR4 antagonism modulates the disease course of EAE. Wild-type and CCR4-knockout mice were induced EAE and were administered Compound 22, an antagonist of CCR4. Compound 22 significantly ameliorated the severity of EAE in wild-type mice, but not in the CCR4-knockout mice. Compound 22 inhibited Th1 and Th17 polarization of antigen-induced T-cell responses. Therefore, CCR4 antagonists might be potential therapeutic agents for multiple sclerosis.
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Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Fluoresceínas/uso terapéutico , Receptores CCR4/antagonistas & inhibidores , Animales , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Encefalomielitis Autoinmune Experimental/inducido químicamente , Encefalomielitis Autoinmune Experimental/genética , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Glicoproteína Mielina-Oligodendrócito/inmunología , Glicoproteína Mielina-Oligodendrócito/toxicidad , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/toxicidad , Receptores CCR4/deficiencia , Receptores CCR4/genética , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Factores de TiempoRESUMEN
PURPOSE: Levetiracetam has been reported to be well tolerated and effective in status epilepticus (SE) refractory to benzodiazepine. Because of little preclinical or clinical data concerning the outcomes of LEV in SE-induced neuronal death and vasogenic edema, we investigated the effect of LEV on SE-induced injury in comparison to diazepam (DZP), and valproate (VPA). METHODS: Two hours after pilocarpine-induced SE, rats were given one of the following drugs; (1) DZP, (2) LEV, (3) VPA, (4) DZP+LEV, (5) DZP+VPA, and (6) DZP+oxiracetam. Three-four days after SE, neuronal damage and vasogenic edema were evaluated by Fluoro-Jade B (FJB) staining and serum-protein extravasation, respectively. RESULTS: LEV (≥50 mg/kg) was effective to protect neuronal damage from SE in comparison to DZP and VPA. LEV as an add-on drug with DZP could not alleviate neuronal damage as compared to LEV alone. VPA (≥100 mg/kg) was effective to protect neuronal damage from SE, as compared to DZP. VPA as an add-on drug with DZP reduced neuronal damage, as compared to DZP alone. CONCLUSION: These findings suggest that LEV may negatively interact with DZP, and be more effective to prevent SE-induced neuronal death as a first line drug than as a second line therapy after BDZ treatment.
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Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Piracetam/análogos & derivados , Estado Epiléptico/tratamiento farmacológico , Animales , Conducta Animal/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Diazepam/uso terapéutico , Modelos Animales de Enfermedad , Quimioterapia Combinada/métodos , Fluoresceínas/uso terapéutico , Levetiracetam , Pilocarpina/uso terapéutico , Piracetam/uso terapéutico , Ratas , Ratas Sprague-Dawley , Estado Epiléptico/inducido químicamente , Estado Epiléptico/patología , Ácido Valproico/uso terapéuticoRESUMEN
The cGMP-dependent protein kinase type I (PKG I) is an essential regulator of cellular function in blood vessels throughout the body. DT-2, a peptidic inhibitor of PKG, has played a central role in determining the molecular mechanisms of vascular control involving PKG and its signaling partners. Here, we report the development of (d)-amino acid DT-2 derivatives, namely the retro-inverso ri-(d)-DT-2 and the all (d)-amino acid analog, (d)-DT-2. Both peptide analogs were potent PKG Ialpha inhibitors with K(i) values of 5.5 nM (ri-(d)-DT-2) and 0.8 nM ((d)-DT-2) as determined using a hyperbolic mixed-type inhibition model. Also, both analogs were proteolytically stable in vivo, showed elevated selectivity, and displayed enhanced membrane translocation properties. Studies on isolated arteries from the resistance vasculature demonstrated that intraluminally perfused (d)-DT-2 significantly inhibited vasodilation induced by 8-Br-cGMP. Furthermore, in vivo application of (d)-DT-2 established a uniform translocation pattern in the resistance vasculature, with exception of the brain. Thus, (d)-DT-2 caused significant increases in mean arterial blood pressure in unrestrained, awake mice. Further, mesenteric arteries isolated from (d)-DT-2 treated animals showed a markedly reduced dilator response to 8-Br-cGMP in vitro. Our results clearly demonstrate that (d)-DT-2 is a superior inhibitor of PKG Ialpha and its application in vivo leads to sustained inhibition of PKG in vascular smooth muscle cells. The discovery of (d)-DT-2 may help our understanding of how blood vessels constrict and dilate and may also aid the development of new strategies and therapeutic agents targeted to the prevention and treatment of vascular disorders such as hypertension, stroke and coronary artery disease.
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Proteínas Quinasas Dependientes de GMP Cíclico/antagonistas & inhibidores , Fluoresceínas/farmacología , Fragmentos de Péptidos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Vasodilatación/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Línea Celular , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/enzimología , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacología , Proteína Quinasa Dependiente de GMP Cíclico Tipo I , Proteínas Quinasas Dependientes de GMP Cíclico/química , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Fluoresceínas/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/enzimología , Masculino , Arterias Mesentéricas/enzimología , Ratones , Modelos Biológicos , Músculo Liso Vascular/enzimología , Miocitos del Músculo Liso/enzimología , Fragmentos de Péptidos/uso terapéutico , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/uso terapéutico , Spodoptera , Vasoconstricción/efectos de los fármacosRESUMEN
Multiple myeloma (MM) is an incurable B-cell cancer characterised by the monoclonal proliferation of tumour cells in the bone marrow (BM). It has been described that matrix metalloproteinases (MMPs) and especially MMP-9 is secreted by MM cells. In this study, we investigated the possibility to exploit MMP-9 activity to activate prodrugs and to target MM cells as a new tumour-specific therapy. Cleavage of the prodrug EV1-FITC by MMP-9 resulted in release of fluorescence which can be used as a measure of prodrug activation. The 5T33MM mouse model was used in this proof-of-principle study. The prodrug was activated in a higher amount by addition to MMP-9-producing 5T33MMvv cells, homogenates from tumour-bearing organs (BM, spleen) and isolated 5T33MM-diseased BM and spleen cells compared to non-MMP-9-producing 5T33MMvt cells and homogenates/cells from non-tumour-bearing organs/mice, as measured by fluorescence release. This fluorescence release could be inhibited by the MMP-2/MMP-9-specific inhibitor, CTT. Activation of the prodrug in the 5T33MM spleen and BM homogenates was confirmed by chromatography. EV1-fluorescein isothiocyanate injection into 5T33MM-diseased animals resulted in a higher fluorescence release by the isolated BM and spleen cells compared to injection into healthy animals. In conclusion, MMP-9 activity can be used to activate prodrugs that target MM.