ABSTRACT
Curcumin (CUR) has gained much attention for its widely reported anticancer effect; however, its clinical use is restricted due to its low water solubility and, consequently, its poor bioavailability. Here, we report on the use of a nanoformulation of CUR with cationic nanogels for colon cancer therapy. Cationic stimuli-sensitive nanogels were prepared using a scale-up polymerization methodology based on surfactant-free emulsion polymerization of N,N'-diethylaminoethyl methacrylate (DEAEM) and poly(ethyleneglycol) methacrylate (PEGMA). The obtained nanogels showed a homogeneous size distribution (from 51 to 162 nm, polydispersity index (PDI) < 0.138) and exhibited a spherical form and core-shell morphology as confirmed by dynamic light scattering and electron microscopy, respectively. Nanogels were responsive to and degradable by variations of pH, temperature, or the redox environment, depending on the cross-linker used in the synthesis. Nanogels cross-linked with bis(acryloyl)cystamine incubated in a buffer (pH 7.4) containing 3 mM glutathione degraded in 60 min, while nanogels cross-linked with a divinylacetal cross-linker degraded in 10 min (pH ≤ 6). Nanoformulations of nanogels with CUR were stable as tested up to 30 days at physiological conditions. In vitro studies of the human colon cancer cell line (HCT-116) showed a synergistic effect of CUR and the degradable nanogels. Further, in vivo acute cytotoxicity tests of empty nanogels in mice demonstrate their potential as CUR nanocarriers for colon-anticancer therapies.
ABSTRACT
The study of the effector mechanisms of T helper cells has revealed different phenotypic characteristics that can be manipulated for designing new therapeutic schemes in different pathological scenarios. Ion channels are significant targets in T lymphocyte modulation since they are closely related to their effector activity. Remarkably, some toxins produced by scorpions specifically affect the function of these membrane proteins. For that reason, these toxins are important candidates in the search for new immunomodulators. Here, the effect of two venom fractions of the scorpion Centruroides limpidus was assessed on T lymphocyte proliferation and cytokine production. The venom fractions ClF8 and ClF9 were separated by reversed-phase high-performance liquid chromatography (RP-HPLC) and cultured at 25 and 35 µg/ml with murine T lymphocytes. The results indicate that the fraction ClF8 increased both production and secretion levels of IFN-γ, IL-4, IL-17A and IL-10 by CD4+ T cells at 24 h. In contrast, fraction ClF9 only promoted the secretion of IL-17A and IL-10 at its highest concentration (35 µg/ml). Both fractions did not show any effect on T cell proliferation. Subsequent analyses by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed seventeen toxins in the fraction ClF8 and five toxins in the fraction ClF9, most of them with voltage-gated sodium (NaScTx) and potassium (KScTx) channels as molecular targets. These toxins might probably interact with ion channels involved in T lymphocyte activity. Our findings suggest that the difference in composition between the two fractions could be related to the observed effects, and the components identified could be isolated to search for possible immunomodulatory molecules.
Subject(s)
Cytokines/immunology , Scorpion Venoms/chemistry , Scorpion Venoms/toxicity , T-Lymphocytes, Helper-Inducer/drug effects , Animals , Cell Proliferation/drug effects , Cells, Cultured , Chromatography, Liquid , Male , Mice, Inbred BALB C , Scorpions , T-Lymphocytes, Helper-Inducer/immunology , Tandem Mass SpectrometryABSTRACT
Introducción: Se presenta el caso de un paciente de 10 años de edad a quien se le realizó el diagnóstico de meduloepitelioma de cuerpo ciliar con posterior enucleación. Objetivo: Presentar las principales características clínicas, abordaje diagnostico y terapéutico de un paciente con meduloepitelioma de cuerpo cilar, realizando una revisión de la literatura existente de esta patología. Diseño del estudio: Reporte de caso. Resumen del caso: Paciente masculino de 10 años de edad que presentó perdida de agudeza visual asociada a dolor ocular, al examen oftalmológico se encontró masa en cámara anterior. Se realizó biopsia de lesión iridiana diagnosticándose meduloepitelioma de cuerpo ciliar con posterior enucleación. Conclusión: Se presentó el caso de un niño con meduloepitelioma de cuerpo ciliar, exponiéndose las manifestaciones clínicas, su diagnóstico y tratamiento, así como la revisión de la literatura existente.
Background: We present the case of a 10-year-old patient who underwent a diagnosis of ciliary body medulloepithelioma with subsequent enucleation. Objective: To present the main clinical characteristics, diagnostic and therapeutic aproach of a patient with a ciliary body medulloepithelioma, carrying out a review of the existing literature of this pathology. Study design: Case report. Case summary: A 10-year-old male patient presented with loss of visual acuity associated with ocular pain. Ophthalmological examination revealed a mass in the anterior chamber. A biopsy of an iris lesion was made, diagnosing a ciliary body medulloepithelioma with subsequent enucleation. Conclusion: The case of a child with ciliary body medulloepithelioma was presented, exposing the clinical manifestations, their diagnosis and treatment, as well as the review of the existing literature.
Subject(s)
Neuroectodermal Tumors, Primitive/diagnosis , Ciliary Body/pathology , Neuroectodermal Tumors, Primitive/therapy , Eye NeoplasmsABSTRACT
Objetivo: describir los factores que infuyen en la aparición del rechazo al trasplante en los pacientes operados de queratoplastia penetrante óptica, en el 1er. año de evolución. Métodos: se realizó un estudio descriptivo, retrospectivo, cuyo universo estuvo constituido por todos los pacientes operados de queratoplastia penetrante óptica en el período comprendido de enero del año 2010 a enero de 2014, quienes fueron sometidos a esta cirugía y que presentaron rechazo al trasplante en el primer año después de operados. Se determinaron los factores pre y transoperatorios, el tiempo de presentación del rechazo, las manifestaciones clínicas y la remisión con tratamiento médico. Resultados: la edad media de presentación fue de 57,34 años, predominio del sexo masculino y procedencia rural. La vascularización en el receptor tuvo mayor porcentaje de presentación, seguido por rechazo previo, afaquia, glaucoma y la utilización de trépanos > 8 mm. Los factores transoperatorios fueron la vitrectomía anterior y la pupiloplastia. La queratopatía bullosa y el leucoma posúlcera fueron los diagnósticos preoperatorios más frecuentes en los casos con rechazo. El tiempo de aparición de este varió entre 7,1 y 10,9 meses. Las manifestaciones clínicas fueron la pérdida de la agudeza visual y el dolor. La remisión del rechazo fue del 87,50 por ciento con diagnóstico preoperatorio de queratocono; 81,82 por ciento con queratopatía bullosa y 80,00 por ciento con leucoma postrauma. Conclusiones: los factores oculares más relevantes en pacientes con rechazo al trasplante fueron la vascularización corneal, el rechazo previo, la afaquia y el glaucoma entre los factores preoperatorios, y la vitrectomía anterior y la pupiloplastia entre los factores transoperatorios(AU)
Objective: describe the factors influencing the appearance of graft rejection in patients undergoing penetrating keratoplasty during the first year of evolution. Methods: a retrospective descriptive study was conducted whose universe was composed of all the patients undergoing penetrating keratoplasty from January 2010 to January 2014 who developed graft rejection within the first year after surgery. Determination was made of pre- and perioperative factors, time of appearance of the rejection, clinical manifestations and remission with medical treatment. Results: mean age at presentation was 57.34 years, with a predominance of the male sex and rural origin. Vascularization in recipients exhibited a higher percentage of presentation, followed by previous rejection, aphakia, glaucoma and the use of trephines > 8 mm. The perioperative factors were anterior vitrectomy and pupilloplasty. Bullous keratopathy and post-ulcer leucoma were the most common preoperative diagnoses in rejection cases. The time of appearance of rejection ranged from 7.1 to 10.9 months. The clinical manifestations were visual acuity loss and pain. Rejection remission was 87.50 percent with a preoperative diagnosis of keratoconus, 81.82 percent bullous keratopathy and 80.00 percent post-traumatic leucoma. Conclusions: the most relevant preoperative factors in patients with graft rejection were corneal vascularization, previous rejection, aphakia and glaucoma. The most relevant perioperative factors were anterior vitrectomy and pupilloplasty(AU)
