Diadenosine polyphosphates after laser in situ keratomileusis and photorefractive keratectomy refractive techniques

Purpose:  To study the concentrations of diadenosine polyphosphates in the ocular surface after PRK and LASIK. Methods:  Sixty-one patients (30 males and 31 females) with ages ranging from 20 to 63 (34.04 ± 9.13 years) were recruited in Balear Institute of Ophthalmology, Palma de Mallorca, Spain. LASIK was performed in 92 eyes of 46 patients and PRK in 25 eyes of 15 patients. Variations in the levels of diadenosine polyphosphate (Ap4A and Ap5A), Schirmer I (Jones test), TBUT, corneal staining together with the Dry Eye Questionnaire to evaluate discomfort and dryness were studied. All tests were performed at the preoperative visit and at 1-day, 2-week, 1-month and 3-month postoperative visits. Results:  Ap4A showed a 5 and 3.5 fold increase at the 1-day visit for LASIK and PRK, respectively. LASIK patients continued having higher statistically significant concentrations (p = 0.01) all over the follow-up. Ap5A showed no significant differences at any visit. Tear volume decreased during the 3 months in LASIK. The PRK cases had a normal volume at 1 month. TBUT in LASIK increased at the 1-day visit (p = 0,002) and decreased from the 2 weeks onwards and for the PRK, decreased by a 35% at the 1-day visit and kept reduced for a month. Discomfort only increased at the 1-day visit (p = 0.007). Dryness frequency was similar in all visits. Conclusions:  Ap4A levels only are increased in refractive surgery patients during the first day after the surgery. This increasing suggests that Ap4A may help accelerating the healing process.

Anthroponyms in health care interventions

Anthroponyms in Health Care Interventions. This research aims to examine the personal names used by health care professionals to refer to and speak with patients in medical consultations. To this end, a large corpus was created with anthroponyms used in this type of settings and extracted from a variety of sources. The data obtained were then analyzed, classified, described and explained. Our hypothesis is that personal names are relevant elements in the relationship between the health care provider and the patient; however, their use is decidedly complex. In the following pages we will discuss this designative complexity by way of an introduction, an analysis of anthroponymic studies and a conclusion.

Evaluación de la efectividad y coste efectividad del retinógrafo no midríatico y análisis coste-beneficio de las diferentes estrategias de cribado en el diagnóstico y seguimiento de la retinopatía diabética : modelo de aplicación y desarrollo del programa de cribado en la Comunidad Autónoma Canaria

Programa de doctorado: Avances en Medicina Interna. La fecha de publicación es la fecha de lectura

Programa de protección de madres adolescentes de niños hospitalizados “Cuidando a las cuidadoras”: Primeros dos años de experiencia

Introducción: “Cuidando a las cuidadoras” consiste en un programa interdisciplinario e intersectorial que brinda desde el año 2013 atención integral a las madres de niños hospitalizadas protegiendo sus derechos. Objetivos: describir un programa de protección de adolescentes que aproxima al sistema de salud a las madres de niños hospitalizados. Método: diseño: observacional, descriptivo. Período: 1 de marzo de 2013 al 1 de marzo de 2015. Criterios de inclusión: madres y/o cuidadoras menores de 19 años de los niños hospitalizados en cuidados moderados del CHPR. Se indagaron variables sociodemográficas, características del embarazo, conocimientos sobre el cuidado del hijo, hábitos de autocuidado. Resultados: se entrevistaron 208 madres y 2 cuidadoras hospitalizadas con sus niños. 195 no controladas en salud. Rango de edad: 14-19 años. Todas solteras y 11 conviviendo con su pareja. Nivel educativo: 150 terminaron primaria, 22 hasta tercer año de secundaria, abandono: 45 primaria, 128 secundaria. Se derivaron 180 cuidadoras al servicio de salud sexual y reproductiva. Las adolescentes decidieron iniciar medidas anticonceptivas en 110 casos. En 26 casos se logró la cobertura odontológica. En 21 se realizó consulta con oftalmología. En 26 se logró realizar conexión con programas socioeducativos logrando reinserción a nivel educativo. Todas las cuidadoras fueron controladas en salud, se les brindó el carnet de control de adolescentes y se realizó la contrarreferencia al primer nivel de atención. Discusión: ésta es la primera experiencia de abordaje de atención a la salud de cuidadoras de niños hospitalizados. Se detectó gran vulnerabilidad en las adolescentes incluidas, logrando un acercamiento a los servicios de salud y educativos.

Espesor macular medido con tomografía de coherencia óptica en ojos pseudoafáquicos con implante amarillo vs. transparente

Objetivo: Evaluar mediante tomografía de coherencia óptica (OCT) las variaciones de espesor macular producidas a lo largo del tiempo en ojos pseudoafáquicos implantados con una lente intraocular (LIO) transparente en comparación con sus respectivos ojos contralarerales implantados con LIO amarilla. Métodos: El espesor macular de 36 ojos de 18 sujetos fue evaluado mediante OCT. Los sujetos presentaban edades superiores a 65 años y habían sido intervenidos de cataratas en ambos ojos en 2 cirugías independientes. La principal característica de los individuos es que llevaban implantada una LIO con diferente absorción en cada ojo: transparente (absorbente de la radiación ultravioleta) y amarilla (con filtro adicional absorbente de las radiaciones violeta-azul del espectro visible). El espesor macular se evaluó en 2 sesiones separadas en el tiempo por un intervalo de tiempo de 5 años, mediante el sistema Stratus-OCT (protocolo fast macular thickness). Se analizaron estadísticamente las diferencias en la evolución del espesor macular entre ojos con diferente tipo de LIO. Resultados: Tras 5 años de seguimiento, se observó que los ojos implantados con LIO transparente manifestaban una reducción del espesor macular estadísticamente significativa, superior a la esperada por el aumento de la edad. Sin embargo, los ojos implantados con LIOs amarillas mantuvieron su espesor macular estable. La disminución del espesor macular promedio en ojos implantados con LIO transparente fue de 5 ± 8 μm (p = 0,02) y la reducción del espesor foveal fue de 10 ± 17 μm (p = 0,02). Conclusiones: Los cambios de espesor macular producidos en ojos implantados con una LIO amarilla difieren de los cambios manifestados en ojos con LIO transparente. Estas observaciones apuntan a un posible efecto protector de las LIOs amarillas contra los efectos dañinos de la luz en sujetos pseudoafáquicos. Sin embargo, estudios con un mayor tamaño muestral y mayor tiempo de seguimiento son necesarios para confirmar que la protección inducida por este tipo de LIO es clínicamente significativa.

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

Dinucleoside polyphosphates comprises a group of dinucleotides formed by two nucleosides linked by a variable number of phosphates, abbreviated NpnN (where n represents the number of phosphates). These compounds are naturally occurring substances present in tears, aqueous humour and in the retina. As the consequence of their presence, these dinucleotides contribute to many ocular physiological processes. On the ocular surface, dinucleoside polyphosphates can stimulate tear secretion, mucin release from goblet cells and they help epithelial wound healing by accelerating cell migration rate. These dinucleotides can also stimulate the presence of proteins known to protect the ocular surface against microorganisms, such as lysozyme and lactoferrin. One of the latest discoveries is the ability of some dinucleotides to facilitate the paracellular way on the cornea, therefore allowing the delivery of compounds, such as antiglaucomatous ones, more easily within the eye. The compound Ap4A has been described being abnormally elevated in patient's tears suffering of dry eye, Sjogren syndrome, congenital aniridia, or after refractive surgery, suggesting this molecule as biomarker for dry eye condition. At the intraocular level, some diadenosine polyphosphates are abnormally elevated in glaucoma patients, and this can be related to the stimulation of a P2Y2 receptor that increases the chloride efflux and water movement in the ciliary epithelium. In the retina, the dinucleotide dCp4U, has been proven to be useful to help in the recovery of retinal detachments. Altogether, dinucleoside polyphosphates are a group of compounds which present relevant physiological actions but which also can perform promising therapeutic benefits.

Effect of Melatonin and Analogues on Corneal Wound Healing: Involvement of Mt2 Melatonin Receptor

Purpose: We have investigated the effect of melatonin and its analogues on rabbit corneal epithelial wound healing. Methods: New Zealand rabbits were anaesthetised and wounds were made by placing Whatman paper discs soaked in n-heptanol on the cornea. Melatonin and analogues (all 10 nmol) were instilled. Wound diameter was measured every 2 hours by means of fluorescein application with a Topcon SL-8Z slit lamp. Melatonin antagonists (all 10 nmol) were applied 2 hours before the application of the n-heptanol-soaked disc and then every 6 hours together with melatonin. To confirm the presence of MT2 receptors in corneal epithelial cells immunohistochemistry, Western blot and RT-PCR assays in native tissue and in rabbit corneal epithelial cells were performed. The tear components were extracted then processed by HPLC to quantify melatonin in tears. Results: Migration assays revealed that melatonin and particularly the treatment with the MT2 agonist IIK7, accelerated the rate of healing (p < 0.001). The application of the non-selective melatonin receptor antagonist luzindole and the MT2 antagonist DH97 (but not prazosin), prevented the effect of melatonin on wound healing (both p < 0.001). Immunohistochemistry, Western blot and RT-PCR assays showed the presence of MT2 melatonin receptor in corneal epithelial cells. In addition, we have identified melatonin in tears and determined its daily variations. Conclusions: These data suggest that MT2 receptors are implicated in the effect of melatonin on corneal wound healing regulating migration rate. This suggests the potential use of melatonin and its analogues to enhance epithelial wound healing in ocular surface disease.

Signs and Symptoms of Dry Eye in Keratoconus Patients: A Pilot Study

Purpose: To compare signs and symptoms of dry eye in keratoconus (KC) patients versus healthy subjects. Methods: A total of 15 KC patients (KC group, n = 15 eyes) and 16 healthy subjects (control group, 16 eyes) were enrolled in this study. The Schirmer I test with no anesthetic, tear break-up time (TBUT), corneal staining characteristics, and ocular surface disease index (OSDI) scores were evaluated for both groups. Impression cytology, combined with/scanning laser confocal microscopy (LCM), was performed to evaluate goblet cell density, mucin cloud height (MCH), and goblet cell layer thickness (CLT). Finally, tear concentrations of di-adenosine tetraphosphate (Ap4A) were assessed. Results were statistically analyzed using Shapiro–Wilk and non-parametric Wilcoxon rank sum tests. Statistical significance was set at p < 0.05. Results: KC patients had lower tear volumes and greater corneal staining than did healthy subjects (p < 0.05). OSDI scores were 44.96 ± 8.65 and 17.78 ± 6.50 for the KC and control groups, respectively (p < 0.05). We found no statistically significant differences in TBUT between groups. Impression cytology revealed lower goblet cell densities in KC group patients versus control group subjects (84.88 ± 32.98 and 128.88 ± 50.60 cells/mm,2 respectively, p < 0.05). There was a statistically significant reduction in MCH and CLT in KC group patients compared with control group subjects. Ap4A tear concentrations were higher in KC group patients than in control group subjects (2.56 ± 1.10 and 0.15 ± 0.12 µM, respectively, p < 0.05). Conclusions: The parameters evaluated in this study indicate that KC patients suffer greater symptoms of dry eye and greater tear instability, primarily due to the decreased mucin production in their tears, than do healthy patients with no KC.

Comparison of Intraocular Pressure before and after Laser In Situ Keratomileusis Refractive Surgery Measured with Perkins Tonometry, Noncontact Tonometry, and Transpalpebral Tonometry

Purpose. To compare the intraocular pressure (IOP) before and after Laser In Situ Keratomileusis (LASIK), measured by Diaton, Perkins, and noncontact air pulse tonometers. Methods. Fifty-seven patients with a mean age of 34.88 were scheduled for myopia LASIK treatment. Spherical equivalent refraction (SER), corneal curvature (K), and central corneal thickness (CCT) and superior corneal thickness (SCT) were obtained before and after LASIK surgery. IOP values before and after surgery were measured using Diaton, Perkins, and noncontact air pulse tonometers. Results. The IOP values before and after LASIK surgery using Perkins tonometer and air tonometers were statistically significant (). However, no significant differences were found () for IOP values measured with Diaton tonometer. CCT decreases significantly after surgery () but no statistical differences were found in SCT (). Correlations between pre- and postsurgery were found for all tonometers used, with and for the air pulse tonometer, and for Perkins, and and for Diaton. Conclusion. Transpalpebral tonometry may be useful for measuring postsurgery IOP after myopic LASIK ablation because this technique is not influenced by the treatment.

Estudio morfológico y morfométrico del desarrollo del Ganglio de Scarpa en la rata blanca, en el gato y en el hombre

131 p.

Corneal Re-epithelialization Stimulated by Diadenosine Polyphosphates Recruits RhoA/ROCK and ERK1/2 Pathways

Purpose. To investigate the role of ERK1/2 and RhoA/ROCK intracellular pathways in the modification of corneal re-epithelialization when stimulated by the diadenosine polyphosphates Ap4A and Ap3A. Methods. In wounded confluent SIRC (Statens Seruminstitut rabbit cornea) cell monolayers and in the presence or absence of Ap4A or Ap3A 100 μM, a battery of P2 receptor antagonists and inhibitors of tyrosin kinases, MAPK, and cytoskeleton pathways (AG1478 100 μM, U0126 100 μM, Y27632 100 nM, and (−)-blebbistatin 10 μM; n = 8 each) were assayed. Also, the activation of ERK1/2 and ROCK-I was examined by Western blot assay after treatment with Ap4A and Ap3A (100 μM), with or without suramin, RB-2, U0126, and Y27632. The intracellular distribution of pERK and ROCK-I was examined in the presence of Ap4A or Ap3A (100 μM) with U0126 and Y27632 (100 nM). Results. In the presence of Ap4A, U0126, Y27632, AG1478, and (−)-blebbistatin, reduced the migration rate compared to the effect of Ap4A alone (P < 0.0001, P < 0.001, P < 0.01, and P < 0.1 versus Ap4A, respectively). In the presence of Ap3A 100 μM, U0126 and Y27632 accelerated the migration rate when compared with the effect of Ap3A alone, whereas AG1478 and (−)-blebbistatin (P < 0.0001 versus Ap3A) slowed the migration rate. Western blot assays demonstrated that both dinucleotides activated the ERK1/2 pathway but only Ap4A activated the ROCK-I pathway. The intracellular distribution of pERK1/2 and ROCK-I reflected cross-talk between these two pathways. Conclusions. The activation of the Ap4A/P2Y2 receptor, accelerates corneal epithelial cell migration during wound healing with the activation of MAPK and cytoskeleton pathways, whereas activation of the Ap3A/P2Y6 receptor signals only the MAPK pathway.

The Use of Mucoadhesive Polymers to Enhance the Hypotensive Effect of a Melatonin Analogue, 5-MCA-NAT, in Rabbit Eyes

Purpose.: 5-Methoxy-carbonylamino-N-acetyltryptamine (5-MCA-NAT, a melatonin receptor agonist) produces a clear intraocular pressure (IOP) reduction in New Zealand White rabbits and glaucomatous monkeys. The goal of this study was to evaluate whether the hypotensive effect of 5-MCA-NAT was enhanced by the presence of cellulose derivatives, some of them with bioadhesive properties, as well as to determine whether these formulations were well tolerated by the ocular surface. Methods.: Formulations were prepared with propylene glycol (0.275%), carboxymethyl cellulose (CMC, 0.5% and 1.0%) of low and medium viscosity and hydroxypropylmethyl cellulose (0.3%). Quantification of 5-MCA-NAT (100 μM) was assessed by HPLC. In vitro tolerance was evaluated by the MTT method in human corneal-limbal epithelial cells and normal human conjunctival cells. In vivo tolerance was analyzed by biomicroscopy and specular microscopy in rabbit eyes. The ocular hypotensive effect was evaluated measuring IOP for 8 hours in rabbit eyes. Results.: All the formulations demonstrated good in vitro and in vivo tolerance. 5-MCA-NAT in CMC medium viscosity 0.5% was the most effective at reducing IOP (maximum IOP reduction, 30.27%), and its effect lasted approximately 7 hours. Conclusions.: The hypotensive effect of 5-MCA-NAT was increased by using bioadhesive polymers in formulations that are suitable for the ocular surface and also protective of the eye in long-term therapies. The use of 5-MCA-NAT combined with bioadhesive polymers is a good strategy in the treatment of ocular hypertension and glaucoma.

Radiotórax.es: una herramienta para la evaluación on-line de las capacidades interpretativas en radiografía de tórax.

Introducción La radiografía de tórax es una de las técnicas diagnósticas más importantes ya que aporta gran cantidad de información para el diagnóstico de enfermedades respiratorias y cardíacas. Es la prueba radiológica más usada en urgencias, ampliamente utilizada por especialistas de radiología, por médicos de familia y otras especialidades (intensivistas, neumólogos, anestesistas, internistas, pediatras y cardiólogos). Su correcta interpretación es fundamental, pues con frecuencia influye en la toma de decisión para el manejo del paciente. La autoevaluación, metodología poco explorada en nuestro entorno, es una parte del proceso educativo que fomenta la reflexión sobre las competencias adquiridas del individuo en formación, donde el alumno se evalúa para progresar en su formación y no para superar una nota, eliminar una materia o establecer un orden de prelación con sus compañeros. Justificación y objetivos Los objetivos de este trabajo son: 1) desarrollar una aplicación informática que permita autoevaluar las habilidades interpretativas de la radiografía de tórax emulando una sesión de trabajo de 20 casos; 2) evaluar el funcionamiento e introducir mejoras en fases preliminares, y 3) analizar los hábitos de uso y las posibilidades formativas de la misma. Material y métodos Radiotórax.es es una herramienta Web de libre acceso por toda la comunidad, ubicada en la URL www.radiotorax.es. El sistema pretende emular una sesión de trabajo, informando 20 casos radiológicos , seleccionados aleatoriamente de una base de datos de 400, con una o dos proyecciones de tórax que debe informar disponiendo de una hora. Los informes y resultados se archivan en una base de datos y el usuario dispone de un documento pdf detallado de cada ronda de evaluación que realice. Resultados Se analizan los resultados del global de usuarios registrados en la fase beta de desarrollo de la aplicación ( 30/05/2011 - 31/08/2011) y durante el período comprendido entre el 01/09/2011 hasta el 31/12/2013 de la fase definitiva de la aplicación, que sigue vigente en la actualidad. La autoevaluación en Radiotorax.es guarda correlación con el grado de experiencia y nivel de aprendizaje del usuario, obteniéndose mejores resultados los grupos con mayor experiencia y formación. Además el 75.7% de los usuarios mejoró en evaluaciones sucesivas. Conclusiones Radiotorax.es es un proyecto educativo de interés en pregrado y en la formación continuada de postgrado que persigue como objetivo facilitar la autoevaluación en habilidades interpretativas de radiología de tórax. Es una aplicación gratuita, de acceso libre, que se puede utilizar con cualquier sistema operativo y cualquier navegador Web y permite realizar autoevaluaciones sucesivas, modificando los casos y manteniendo la misma proporción de dificultad. Proporciona un documento pdf con toda la información de cada evaluación completada accesible por el usuario, lo que le permite controlar su evolución en el aprendizaje. Los estudios sobre la interpretación de radiografías de tórax por diferentes colectivos subrayan que la formación es esencial para disminuir el número de errores en la interpretación de radiografías de tórax y resaltan la necesidad de disponer de herramientas formativas de tipo práctico para mejorar la habilidad interpretando radiografías torácicas, como Radiotorax.es.

Diadenosine Polyphosphates in Tears of Sjögren Syndrome Patients

Purpose.: To analyze the levels of diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) in tears of subjects with Sjögren syndrome and to compare them with those in a control group. Methods.: Twelve subjects with a diagnosis of Sjögren syndrome and 20 healthy control subjects were invited to participate in the present study. Schirmer strips were used to measure tear secretion (Schirmer I test) and to collect tears. Ap4A and Ap5A were measured by high-pressure liquid chromatography (HPLC), and a dry eye questionnaire (DEQ) was used to evaluate dry eye symptomatology. Results.: The mean concentrations of Ap4A and Ap5A in the Sjögren syndrome group were 2.54 ± 1.02 and 26.13 ± 6.95 μM, respectively. This group of patients was divided in two subgroups: four patients with normal tear production and eight patients with low tear production. Concentrations of Ap4A, and Ap5A in patients with normal tear production (Schirmer test result, 12.3 ± 1.2 mm) were 0.47 ± 0.20 and 8.03 ± 3.27 μM, respectively. In the patients with low tear production (Schirmer test result, 1.0 ± 0.3 mm), the concentrations were 4.09 ± 1.36 and 39.51 ± 8.46 μM, respectively and in the control group, 0.13 ± 0.03 and 0.04 ± 0.02 μM, respectively. Conclusions.: Patients with Sjögren syndrome have abnormally elevated concentrations of diadenosine polyphosphates, indicating that these compounds could be used in the diagnosis of this disease.

Dual Roles of Diadenosine Polyphosphates in Corneal Epithelial Cell Migration

Purpose. To investigate the influence of diadenosine polyphosphates on the rate of corneal epithelial cell migration. Methods. Primary corneal epithelial cell cultures were obtained from New Zealand White rabbits. Immunocytochemical experiments were performed by fixing the cells with 4% paraformaldehyde (PFA) and incubated with cytokeratin 3 primary antibody, which was subsequently incubated with a secondary IgG mouse labeled with FITC, and the cells were observed under confocal microscopy. Migration studies were performed by taking confluent monolayers that were wounded with a pipette tip and challenged with different di- and mononucleotides with or without P2 antagonist (n = 8 each treatment). For concentration–response analysis, compounds were tested in doses ranging from 10−8 to 10−3 M (n = 8). The stability of the dinucleotides was assayed by HPLC, with an isocratic method (n = 4). Results. Cells under study were verified as corneal epithelial cells via the immunocytochemical analysis. Cell migration experiments showed that Ap4A, UTP, and ATP accelerated the rate of healing (5, 2.75, and 3 hours, respectively; P < 0.05; P < 0.001), whereas Ap3A, Ap5A, and UDP delayed it (6.5, 10, and 2 hours, respectively; P < 0.05). ADP did not modify the rate of migration. Antagonists demonstrated that Ap4A and Ap3A did activate different P2Y receptors mediating corneal wound-healing acceleration and delay. Concerning the possible degradation of the dinucleotides, it was almost impossible to detect any products resulting from their cleavage. Conclusions. Based on the pharmacological profile of all the compounds tested, the two main P2Y receptors that exist in these corneal cells are a P2Y2 receptor accelerating the rate of healing and a P2Y6 receptor that delays this process.