Polluted Air Exposure Compromises Corneal Immunity and Exacerbates Inflammation in Acute Herpes Simplex Keratitis.

Air pollution is a serious environmental issue worldwide in developing countries' megacities, affecting the population's health, including the ocular surface, by predisposing or exacerbating other ocular diseases. Herpes simplex keratitis (HSK) is caused by the herpes simplex virus type 1 (HSV-1). The primary or recurring infection in the ocular site causes progressive corneal scarring that may result in visual impairment. The present study was designed to study the immunopathological changes of acute HSK under urban polluted air, using the acute HSK model combined with an experimental urban polluted air exposure from Buenos Aires City. We evaluated the corneal clinical outcomes, viral DNA and pro-inflammatory cytokines by RT-PCR and ELISA assays, respectively. Then, we determined the innate and adaptive immune responses in both cornea and local lymph nodes after HSV-1 corneal by immunofluorescence staining and flow cytometry. Our results showed that mice exposed to polluted air develop a severe form of HSK with increased corneal opacity, neovascularization, HSV-1 DNA and production of TNF-α, IL-1ß, IFN-γ, and CCL2. A high number of corneal resident immune cells, including activated dendritic cells, was observed in mice exposed to polluted air; with a further significant influx of bone marrow-derived cells including GR1+ cells (neutrophils and inflammatory monocytes), CD11c+ cells (dendritic cells), and CD3+ (T cells) during acute corneal HSK. Moreover, mice exposed to polluted air showed a predominant Th1 type T cell response over Tregs in local lymph nodes during acute HSK with decreased corneal Tregs. These findings provide strong evidence that urban polluted air might trigger a local imbalance of innate and adaptive immune responses that exacerbate HSK severity. Taking this study into account, urban air pollution should be considered a key factor in developing ocular inflammatory diseases.

Effects of PUFAs in a Mouse Model of HSV-1 Chorioretinitis.

PURPOSE: To examine the effects of n-3 and n-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) in a murine model of herpetic chorioretinitis. METHODS: BALB/c mice were fed on three high fat diets, which contained: Menhaden oil (rich in n-3 PUFAs); Safflower oil (rich in n-6 PUFAs); or Corn oil (rich in saturated fatty acids) as control group, 14 days previously and until 12 days following anterior chamber (AC) HSV-1 inoculation. RESULTS: Mice fed on Menhaden oil present an early development of contralateral chorioretinitis by day 6 post-AC HSV-1 inoculation and also significant increase of RNA HSV-1 expression compared with Safflower and Corn oil groups. Furthermore, mice fed on Menhaden oil showed a significant decrease secretion of TNF-α, IFN-γ, IL-2 and IL-10 in splenic cells and both retinas. CONCLUSION: Our results showed that mice fed on Menhaden oil (n-3 PUFAs) presented an early development of contralateral chorioretinitis by day 6 post-AC HSV-1 inoculation and also a significant increase in RNA HSV-1 expression compared with animals fed on Safflower and Corn oils. This increase of HSV-1 could be associated with the higher development of chorioretinitis.

Nivel de conocimientos de los obstetras acerca del diagnóstico y tratamiento de la isoinmunización materna: Estudio de corte transversal en Bogotá (Colombia), 2012-2013 / Level of knowledge among obstetricians regarding diagnosis and treatment of maternal isoimmunization: Cross-sectional study in Bogotá (Colombia), 2012-2013

Objetivo: describir el nivel de conocimientos acerca del diagnóstico, tratamiento y pronóstico de la isoinmunización materna entre los especialistas de Ginecología y Obstetricia afiliados a la Asociación Bogotana de Perinatología (ABP). Materiales y métodos: estudio descriptivo de corte transversal. Entre noviembre de 2012 y marzo de 2013, se aplicó una encuesta elaborada por especialistas en Medicina Materno-Fetal (MMF). Se excluyeron los profesionales que ejercen su actividad fuera del territorio nacional, aquellos que no han practicado la obstetricia durante los últimos diez años y a quienes no suministraron la totalidad de la información requerida. El instrumento estuvo compuesto por 18 preguntas organizadas en tres dominios: características sociodemográficas, información sobre la práctica clínica y conocimientos. Se utilizó estadística descriptiva para el análisis en la materia. Resultados: el instrumento se aplicó a 220 profesionales de los cuales 127 (57,7 %) respondieron la encuesta en su totalidad y fueron incluidos en el análisis. El 32 % de los obstetras y el 45 % de los especialistas en MMF identificaron correctamente el punto de corte para el coombs indirecto. El 43 y 62 % de los obstetras y especialistas en MMF reconocieron el papel de la velocimetría de la arteria cerebral media para el diagnóstico de anemia fetal, y el 82 y 76 % respectivamente la utilizarían en el seguimiento del feto anémico. Tan solo el 76 % de los obstetras y el 66 % de los especialistas en MMF reconocen las indicaciones de culminar la gestación en caso de anemia fetal, en tanto que el 90 y 97 % (respectivamente) identificaron cuándo realizar cordocentesis y transfusión in utero. Finalmente, el 37 % de los obstetras y el 48 % de los especialistas en MMF no reconocen a la curva de Queenan-Liley como una alternativa cuando no hay acceso al Doppler fetal. Conclusión: existe una importante variabilidad con respecto al nivel de conocimientos de los obstetras y especialistas en MMF en cuanto al diagnóstico, tratamiento y seguimiento de las gestantes con isoinmunización. Se requieren más estudios que caractericen la variabilidad en la práctica clínica acerca del diagnóstico y tratamiento de la isoinmunización materna en Colombia.

Objective: To describe the level of knowledge regarding the diagnosis, treatment and prognosis of maternal isoimmunisation among Gynaecology and Obstetrics specialists, members of ABP (Asociación Bogotana de Perinatología). Materials and methods: Cross-sectional descriptive study. A questionnaire prepared by specialists in Maternal and Foetal Medicine (MFM) was administered between November 2012 and March 2013. Professionals practicing outside the national territory, those who had not practiced over the past ten years, and those who did not provide all the information required were excluded. The tool consisted of 18 questions organized in three domains: socio-demographic characteristics, information about clinical practice, and knowledge of the subject. A descriptive statistical analysis was used. Results: Of the 220 practitioners who were given the questionnaire, 127 (57.7%) completed the survey and were included in the analysis. The cut-off point for the indirect Coombs was correctly identified by 32% of the obstetricians and by 45% of the specialists in MFM. The role of middle cerebral artery velocimetry for the diagnosis of foetal anaemia was recognized by 43% and 62% of obstetricians and specialists in MFM, and 82% and 76%, respectively, would use it for the follow-up of foetuses with anaemia. Only 76% of obstetricians and 66% of MFM specialists recognized the indications for delivering the baby in cases of foetal anaemia, whereas 90% and 97%, respectively, identified the timing for cordocentesis and in utero transfusion. Finally, 37% of obstetricians and 48% of MFM specialists did not recognize the Queenan-Liley curve as an option in cases where there is no access to foetal Doppler. Conclusion: There is an important variability in the level of knowledge among obstetricians and MFM specialists regarding the diagnosis, treatment and follow-up of pregnant women with isoimmunisation. Additional studies are required to characterize the variability in clinical practice regarding the diagnosis and treatment of maternal isoimmunisation in Colombia.

Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study.

PURPOSE: Intravitreal melphalan is emerging as an effective treatment for refractory vitreous seeds in retinoblastoma, but there is limited understanding regarding its toxicity. This study evaluates the retinal and systemic toxicity of intravitreal melphalan in retinoblastoma patients, with preclinical validation in a rabbit model. DESIGN: Clinical and preclinical, prospective, cohort study. PARTICIPANTS: In the clinical study, 16 patient eyes received 107 intravitreal injections of 30 µg melphalan given weekly, a median of 6.5 times (range, 5-8). In the animal study, 12 New Zealand/Dutch Belt pigmented rabbits were given 3 weekly injections of 15 µg of intravitreal melphalan or vehicle to the right eye. METHODS: Electroretinogram (ERG) responses were recorded in both humans and rabbits. For the clinical study, ERG responses were recorded at baseline, immediately before each injection, and at each follow-up visit; 82 of these studies were deemed evaluable. Median follow-up time was 5.2 months (range, 1-11). Complete blood counts (CBCs) were obtained on the day of injection at 46 patient visits. In the animal study, ERG responses were obtained along with fluorescein angiography, CBCs, and melphalan plasma concentration. After humane killing, the histopathology of the eyes was evaluated. MAIN OUTCOME MEASURES: For the clinical study, we measured peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation with comparisons between ERG studies before and after intravitreal melphalan. For the animal study, we collected ERG parameters before and after intravitreal melphalan injections with histopathologic findings. RESULTS: By linear regression analysis, over the course of weekly intravitreal injections in retinoblastoma patients, for every additional injection, the ERG amplitude decreased by approximately 5.8 µV. The ERG remained stable once the treatment course was completed. In retinoblastoma patients, there were no grade 3 or 4 hematologic events. One week after the second injection in rabbits, the a- and b-wave amplitude declined significantly in the melphalan treated eyes compared with vehicle-treated eyes (P<0.05). Histopathology revealed severely atrophic retina. CONCLUSIONS: Weekly injections of 30 µg of melphalan can result in a decreased ERG response, which is indicative of retinal toxicity. These findings are confirmed at an equivalent dose in rabbit eyes by ERG measurements and by histopathologic evidence of severe retinal damage. Systemic toxicity with intravitreal melphalan at these doses in humans or rabbits was not detected.

A study of the association between chronic superficial keratitis and polymorphisms in the upstream regulatory regions of DLA-DRB1, DLA-DQB1 and DLA-DQA1.

Canine chronic superficial keratitis (CSK) is an inflammatory corneal disease that primarily occurs in German shepherd dogs (GSDs). Several studies support the hypothesis that CSK is an immune-mediated disease. To investigate the genetic factors associated with CSK development, the upstream regulatory regions (URRs) of the DLA-DRB, -DQA and -DQB genes were genotyped in 60 dogs, including 32 CSK animals. LD analysis identified two blocks (r(2)≤45), with two DLA-DRB1 and five DLA-DQB1 haplotypes. Analysis of DLA-URR alleles/haplotypes showed a significant association between DQB1*-154 [C/T] (p=0.016) and CSK, suggesting that the T variant may increase the risk for developing CSK disease (OR=3, 95% CI=1.25-7.68). When haplotype associations were performed, the URR-DQB*CATT haplotype was significantly associated with CSK (p=0.016), increasing the risk of develop this disease over two-fold (OR=3, 95%, CI=1.25-7.68). These results showed that dogs homozygous at DRB1*69 [C/T] had a risk for developing CSK disease that was over four times the risk for heterozygotes. This genetic association supports the previous clinical, histological and pharmacological studies that suggest that CSK is an immune-mediated disease, and this association could potentially be used to identify susceptible animals.

Topical use of rapamycin in herpetic stromal keratitis.

PURPOSE: To evaluate and compare the efficacy of rapamycin used topically in a mouse model of herpetic stromal keratitis. METHODS: The corneas were infected with herpes simplex virus type-1 strain KOS. Animals were divided into: control (CG), rapamycin (RAPA), cyclosporine (CsA), and dexamethasone (DEXA). The evolution of the disease was assessed clinically and histologically. RESULTS: On day 10 postinfection (pi), the RAPA group showed only a significantly lower angiogenic development than the CG. On day 14 pi, the treated groups had significantly lower scores for angiogenesis and necrosis than the CG. Also, on day 14 pi, the RAPA and DEXA groups showed significantly lower histopathological scores compared to the CG. CONCLUSIONS: The topical application of 0.05% rapamycin showed greater efficacy than 0.5% cyclosporine and similar efficacy to 0.1% dexamethasone to minimize the immuno-inflammatory process. Also, rapamycin showed early inhibition of the formation of new vessels.

Anti-VEGF monoclonal antibody-induced regression of corneal neovascularization and inflammation in a rabbit model of herpetic stromal keratitis.

BACKGROUND: To determine the efficacy of bevacizumab (Avastin), an anti-VEGF monoclonal antibody, administrated via subconjunctival injection as a corneal anti-angiogenic treatment. METHODS: Right corneas of rabbits were infected with herpes simplex virus type 1, KOS strain. On day 13 post-infection (p.i.), animals were treated subconjunctivally (sc) with a single 10-microl dose (25 microg/microl) of bevacizumab (group A) or with the same volume of an isotype monoclonal antibody, as negative control (group B). All animals were observed clinically on days 2, 5, 7, 14, 21, and 28 p.i., and two corneas each day were obtained for histological assessment and viral titration. RESULTS: Viral replication was observed no longer than 5 days after infection. By day 7 a dense neutrophil invasion of the cornea was detected, which significantly increased while herpetic stromal keratitis progressed in severity. Positive outcomes observed following the treatment with bevacizumab, compared to control, included: (1) Total involution of neovascularization, (2) reduction in disease severity, (3) improved corneal translucency, (4) absence of scarring, (5) preservation of corneal thickness, (6) no neutrophil infiltration of the cornea. CONCLUSIONS: Subconjunctival administration of bevacizumab induced involution of new vessels, abolished inflammatory response, and resulted in return of corneal function. Furthermore, bevacizumab is a novel approach for the treatment of herpetic stromal keratitis.

Alpha-tocopherol protects against oxidative damage to lipids of the rod outer segments of the equine retina.

Oxidative stress is a possible risk factor for eye diseases. Lipid peroxidation is one of the major events induced by oxidative stress and is particularly active in polyunsaturated fatty acid (PUFA)-rich biomembranes. This work evaluated endogenous lipid antioxidants, in vitro non-enzymatic lipid peroxidation of rod outer segment membranes (ROS), the fatty acid composition during oxidative damage of total lipids from equine retina and ROS, and the protective action of alpha-tocopherol (alpha-Toc). The major lipid soluble antioxidant was alpha-Toc followed by retinoids and carotenoids. The retina contained a high percentage of PUFAs, mainly docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6). Lipid peroxidation of the equine ROS, induced by Fe(2+)-ascorbate, was monitored using chemiluminescence (CL) with or without pre-treatment with alpha-Toc. With alpha-Toc pre-treatment, CL values were significantly decreased. The most abundant fatty acid was 22:6n-3. After 3h incubation, 95% of total PUFAs were destroyed by peroxidation, whereas in alpha-Toc pre-treated ROS the percentage was significantly decreased. The results show that the retina has an endogenous lipid soluble antioxidant system. ROS were highly sensitive to oxidative damage, since their fatty acid composition was markedly modified during the lipid peroxidation process. The protective role of alpha-Toc as an antioxidant was evident and it could be used in the treatment of equine ocular diseases in which free radicals are involved.

Tear urea nitrogen and creatinine levels in horse and their correlation with serum values.

The objective of this paper was to determine the physiological values of urea nitrogen and creatinine in tears, and to compare the results with those obtained from serum. Thirty healthy thoroughbred horses were included in the study. Tear fluid samples were obtained using a glass capillary tube placed in lower conjunctival cul-de-sac. Blood samples were taken from the jugular vein. Tear and serum urea nitrogen and creatinine levels were quantitatively analyzed by an enzymatic colorimetric method. Urea nitrogen values were 4.22+/-1.84 mmol/l in tears and 4.44+/-1.78 mmol/l in serum, whereas creatinine values in tears were 14.14+/-7.74 micromol/l and in serum 147.63+/-12.17 micromol/l. Statistical analysis confirmed a significant correlation between serum and tear urea levels (P<0001). However, there was no significant correlation between blood and tear creatinine values. Mean value of creatinine obtained from tears was 9.6% of the mean value from serum. Urea nitrogen and creatinine levels can be measured in tears. A significant correlation was found between serum and tears urea levels. This finding may permit development of a new alternative laboratory diagnosis of uremia based on the content of urea in tears.

La comunicación no verbal en el nado sincronizado / The not verbal communication in synchronized swim

En la comunicación especializada del deporte y la música instrumental, la comunicación no verbal constituye un aspecto de vital importancia en elintercambio de información, másaún si se tiene en cuenta que en lacomunicación general humana este tipo de comportamiento constituye cerca del 65% del proceso (Pei, 1949), Y es un tema al cual los estudios língüísticos y sobre todo los terminológicos le han prestado relativamente poca atención. A partir del estudio sistematizado de la comunicación no verbal en una área del conocimiento proponemos una definición, representación dinámica y posterior almacenamiento de los conceptos específicos que allí se generan.

In sports specialized communication and in instrumental music, non-verbalcommunication constitutes an aspect of vital importance in the exchange of information, especial1y if ir is considered that in general human eommunicationthis type of behavior constitutes nearly 65% of the process (Pei, 1949), moreover, it is an aspeet that has reeeived relatively Hule attention by linguistic studies and mainly by terminological studies.Starting with a systematized study of a non-verbal eommunication in a determined area of knowledge, we propase a definition, dynamic representation and further storage of the specific coneepts thereupon generated.

Estudio genético en embarazadas / Genetic studies in pregnancies

Introducción: con base en el impacto que genera el hallazg de un feto o recién nacido con alguna alteración cromosómica, desde el punto de vista familiar, social y para las entidades de salud, se analizan los resultados de los estudios genéticos realizados por el Servicio de Perinatología de la Clínica Rafael Uribe Uribe del Instituto de los Seguros Sociales en la ciudad de Cali, durante los últimos seis años. Objetivo: describir la frecuencia de las alteraciones cromosómicas encontradas en la Clínica Rafael Uribe Uribe de Cali durante los estudios genéticos realizados por el Servicio de Perinatología, desde enero 1 de 1997 hasta diciembre 31 de 2002. Materiales y métodos: se realizó un estudio retrospectivo, en el cual se revisaron las historias clínicas de todos los procedimientos genéticos practicados a las gestantes que aceptaron amniocentesis o cordocentesis, según la indicación. Resultados: se encontraron 615 procedimientos de diagnóstico prenatal: 604 amniocentesis (98,21 por ciento) y once cordocentesis (1,79 por ciento). Se evidenciaron 19 estudios anormales (3,09 por ciento); de ellos, 17 correspondieron a aneuploidías (89,47 por ciento): seis trisomías 21 (31,57 por ciento), cuatro trisomías 18 (21,05 por ciento), dos trisomías 13 (10,52 por ciento), dos síndromes de Klinefelter (10,52 por ciento) y tres monosomías 45XO (15,78 por ciento); se presentaron dos alteraciones estructurales (10,53), de las cuales una correspondió a una translocación recíproca (46XX, t (6,15) der 15) (5,26 por ciento) y una delección (46XX, 9 q (-)) (5,26 por ciento). Las indicaciones más frecuentes del estudio genético fueron: edad materna(>35 años), hallazgos ecográficos, deseo de la pareja. Conclusiones: los resultados obtenidos no distan de los publicados en la literatura mundial; la alteración cromosómica más frecuente fue la trisomía 21. Puesto que para diagnosticar una alteración cromosómica se requirieron 12 estudios de diagnóstico prenatal, debemos afinar (con la ayuda de las directivas de la institución) en la determinación de marcadores ecográficos y bioquímicos con el propósito de someter al menor número de pacientes al riesgo que implican los procedimientos invasivos.

Examen clínico objetivamente estructurado en la rotación de neumología de los estudiantes de 4to. año de medicina: Instituto Nacional del Tórax, 2002 / Clinical examination objetively structured in the rotation of neumology of the students of 4§ year of medicine, Instituto Nacional del Torax, 2002

El presente trabajo de investigación motiva el interés pormejorar uno de los componentes dinámicos estructurales del Proceso Docente Educativo, la evalación porque actualmente se enfrenta dificultades para evaluar en forma integral a los alumnos del rote de Neumología de la Facultad de Medicina de la Universidad Mayor de San Andrés. El objetivo es contar con un sistema de evalaución que responda a los enunciados de validez, confiabilidad, factivilidad, objetividad, justeza y que permita valorar el grado de cumplimiento de los objetivos educativos e instructivos de la rotación de Neumología El presente trabjo se realizó en el Departamento de Neumología del Instituto Nacional del Tórax durante los meses de Febrero a Julio del 2002. Las estaciones en número seis fueron las siguientes: Estación I Micro historia clínica, Estación II Interrogatorio, examen semiológico, Estación III Toracocentesis, Estación IV Toxicidad medicamentosa. Estación V. Diagnóstico macroscópico del líquido pleural. Estación VI Parones radiográficos de la tuberculosis y su correlación con los síndromes físicos. La muestra poblacional fue de 149 alumnos regulares del cuarto año. La presente investigación comprendió dos modalidades, una exploratoria y otra descriptiva con la implementación del Examen Objetivamente Estructurado previa encuesta a los alumnos y profesores. La tuberculosis ha sido considerada en el presente trabjo, por ser una de las enfermedades más prevalentes en el medio. Las variables para cada estación han sido consideradas como la mediana, promedio, desviación promedio, desviación estaándar, error estándar, tanto en varones como en mujeres. El examen Clínico Objetivamente Esructurado se implementó en la fase final de la evaluación de cada rote de Neumología sumadas a las frecuentes evaluaciones teórico prácticas. Este trabjo muestra la eficaciá y valides del procedimiento evaluatorio del Examen Clínico Objetivamente Estructurado, para certificar las habilidades teórica y práctica en las estaciones examinadas.

Tumor de células gigantes en hueso: analisis de 4 casos tratados con rección en bloque del tumor y artrodesis / Paraarticular giant cell tumos of bone

Se hizo una revisión de 4 casos de tumor de células gigantes del hueso, los cuales ameritaron resección segmentaria y artrodesis: 2 a nivel de la rodilla, 1 a nivel del tobillo y 1 a nivel del hombro

Tumor de células gigantes: um problema difícil, reporte de um caso / Giant cell tumor: a difficult problem, report of a case

Se reporta sobre un caso de tumor de células gigantes de tibia distal que si bien se pudo tratar satisfactoriamente desde el punto de vista ortopédico se complicó con metástasis pulmonares demostradas en biopsia