RESUMEN
We report our experience in the surgical technique of sutureless intrascleral posterior chamber intraocular lens (PC IOL) fixation in patients with insufficient capsular support using a uniquely designed, foldable, acrylic Carlevale IOL. It is specifically designed for sutureless scleral fixation and is equipped with a small plug attached to each of two haptics to anchor the lens to the sclera with a self-retaining mechanism. This surgery does not require creation of a scleral tunnel or transscleral exposure or excessive manipulation of the haptics. The harpoon-like plugs provide great stability to this implant, which can be injected through a 2.2mm incision. The characteristics of this IOL and the relative simplicity of this implantation technique makes it widely applicable in aphakic patients after previous complicated cataract surgery.
Asunto(s)
Implantación de Lentes Intraoculares , Lentes Intraoculares , Ojo Artificial , Humanos , Estudios Retrospectivos , Esclerótica/cirugía , Técnicas de SuturaAsunto(s)
Malformaciones Arteriovenosas/complicaciones , Ceguera/diagnóstico , Edema Macular/diagnóstico , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Arteria Retiniana/anomalías , Vena Retiniana/anomalías , Adulto , Malformaciones Arteriovenosas/diagnóstico , Ceguera/etiología , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Edema Macular/etiología , Imagen Multimodal , Embarazo , Complicaciones Cardiovasculares del Embarazo/etiología , Segundo Trimestre del Embarazo , Tomografía de Coherencia ÓpticaRESUMEN
The human body is colonized by a large number of microbes that are collectively referred to as the microbiota. They interact with the hosting organism and some do contribute to the physiological maintenance of the general good health thru regulation of some metabolic processes while some others are essential for the synthesis of vitamins and short-chain fatty acids. The abnormal variation, in the quality and/or quantity of individual bacterial species residing in the gastro-intestinal tract, is called dysmicrobism. The immune system of the host will respond to these changes at the intestinal mucosa level which could lead to Inflammatory Bowel Diseases (IBD). This inflammatory immune response could subsequently extend to other organs and systems outside the digestive tract such as the thyroid, culminating in thyroiditis. The goal of the present study is to review and analyze data reported in the literature about thyroiditis associated with inflammatory bowel diseases such as Ulcerative Colitis (UC) and Crohns Disease (CD). It was reported that similarities of some molecular bacterial components with molecular components of the host are considered among the factors causing IBD through an autoimmune reaction which could involve other non-immune cell types. The axis dysmicrobism-IBD-autoimmune reaction will be investigated as a possible etiopathogenic mechanism to Autoimmune Thyroiditis. If such is the case, then the employment of specific probiotic strains may represent a useful approach to moderate the immune system.
Asunto(s)
Tracto Gastrointestinal/microbiología , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/microbiología , Microbiota/fisiología , Tiroiditis Autoinmune/etiología , Animales , Traslocación Bacteriana/inmunología , Fermentación , Vida Libre de Gérmenes , Humanos , Enfermedades Inflamatorias del Intestino/terapia , Mucosa Intestinal/inmunología , Tejido Linfoide/inmunología , Ratones , Microbiota/inmunología , Imitación Molecular/inmunología , Probióticos/efectos adversos , Probióticos/uso terapéutico , Simbiosis , Deficiencia de Tiamina/etiología , Tiroiditis Autoinmune/inmunología , Tiroiditis Autoinmune/terapiaRESUMEN
Neuroblastoma (NB) is an aggressive pediatric tumor, responsible for 15% of cancer-related deaths in childhood, lacking an effective treatment in its advanced stages. The P2X7 receptor for extracellular ATP was associated to NB cell proliferation and recently emerged as a promoter of tumor engraftment, growth and vascularization. In an effort to identify new therapeutic options for neuroblastoma, we studied the role of P2X7 receptor in NB biology. We first analyzed the effect of P2X7 activation or down-modulation of the main biochemical ways involved in NB progression: the PI3K/Akt/GSK3ß/MYCN and the HIF1α/VEGF pathways. In ACN human NB cells, P2X7 stimulation enhanced PI3K/Akt, while decreasing GSK3ß activity. In the same model, P2X7 silencing or antagonist administration reduced the activity of PI3K/Akt and increased that of GSK3ß, leading to a decrease in cellular glycogen stores. Similarly, P2X7 downmodulation caused a reduction in HIF1α levels and vascular endothelial growth factor (VEGF) secretion. Systemic administration of two different P2X7 antagonists (AZ10606120 or A740003) in nude/nude mice reduced ACN-derived tumor growth. An even stronger effect of P2X7 blockade was obtained in a syngeneic immune-competent neuroblastoma model: Neuro2A cells injected in AlbinoJ mice. Together with tumor regression, treatment with P2X7 antagonists caused downmodulation of the Akt/HIF1α axis, leading to reduced VEGF content and decreased vessel formation. Interestingly, in both experimental models, P2X7 antagonists strongly reduced the expression of the probably best-accepted oncogene in NB: MYCN. Finally, we associated P2X7 overexpression with poor prognosis in advanced-stage NB patients. Taken together, our data suggest that P2X7 receptor is an upstream regulator of the main signaling pathways involved in NB growth, metabolic activity and angiogenesis, and a promising therapeutic target for neuroblastoma treatment.
Asunto(s)
Neuroblastoma/metabolismo , Receptores Purinérgicos P2X7/fisiología , Animales , Línea Celular Tumoral , Proliferación Celular , Femenino , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones Desnudos , Trasplante de Neoplasias , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Ability to adapt to conditions of limited nutrient supply requires a reorganization of the metabolic pathways to balance energy generation and production of biosynthetic intermediates. Several fast-growing cells overexpress the P2X7 receptor (P2X7R) for extracellular ATP. A feature of this receptor is to allow growth in the absence of serum. We show here that transfection of P2X7R allows proliferation of P2X7R-transfected HEK293 (HEK293-P2X7) cells not only in the absence of serum but also in low (4 mM) glucose, and increases lactate output compared with mock-transfected HEK293 (HEK293-mock) cells. In HEK293-P2X7, lactate output is further stimulated upon addition of exogenous ATP or the mitochondrial uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP). In the human neuroblastoma cell line ACN, lactate output is also dependent on P2X7R function. P2X7R-expressing cells upregulate (a) the glucose transporter Glut1, (b) the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase (G3PDH), (c) phosphofructokinase (PFK), (d) pyruvate kinase M2 (PKM2) and (e) pyruvate dehydrogenase kinase 1 (PDHK1); furthermore, P2X7R expression (a) inhibits pyruvate dehydrogenase (PDH) activity, (b) increases phosphorylated Akt/PKB and hypoxia-inducible factor 1α (HIF-1α) expression and (c) enhances intracellular glycogen stores. In HEK293-P2X7 cells, glucose deprivation increases lactate production, expression of glycolytic enzymes and ph-Akt/PKB level. These data show that the P2X7R has an intrinsic ability to reprogram cell metabolism to meet the needs imposed by adverse environmental conditions.