Evaluación de un curso online de educación sexual integral escolar de autoaprendizaje para público en general: curso MOOC / Evaluation of a comprehensive scholar sexual education course self-learning online to general population: MOOC course

Introducción: La educación sexual integral escolar es recomendada por la UNESCO, la OMS, la UNICEF y las NN.UU. Objetivo: Evaluación de un curso de educación sexual integral escolar on line de autoaprendizaje para público general, tipo MOOC (Massive Online Open Course), gratuito. Método: Constituido por 17 capítulos, 17 conferencias, 213 preguntas, 14 videos/talleres con 76 preguntas, curso en radio FM 102.5 UCH y 3 películas originales. Sin fecha de término. Resultados: Se inscribieron voluntariamente 230 estudiantes: el 88% provenientes de Chile, el 6% del extranjero y el 6% sin identificación. El 93% eran menores de 29 años, el 60% de sexo femenino y el 94% con educación media o universitaria. El tiempo de ejecución del curso fue menos de 50 días en el 6%, de 100 a 300 días en el 78,7%, y de 301 a 399 días en el 15%. De los 751 inscritos a diciembre de 2021, terminaron el primer módulo 230 (30,6%), el segundo 207 (28%), el tercero 199 (26%), el cuarto 184 (25%) y el quinto 177 (24%). De los 230 que iniciaron el primer módulo terminaron el curso 177 (77%). La evaluación final del cumplimiento de los objetivos de los cinco módulos del curso como bueno/excelente fue la siguiente: primero 89%, segundo 91%, tercero 92%, cuarto 93% y quinto 94%; para los cinco módulos fue 92% (intervalo de confianza del 95% [IC95%]: 90,9-92,7). La evaluación final de la calidad del desarrollo del curso como buena/excelente fue la siguiente: primero 92% (IC95%: 90,5-94,0) segundo 92% (IC95%: 90,1-93,9%), tercero 93% (IC95%: 91,2-94,9%), cuarto 94% (IC95%: 91,8-95,4%) y quinto 96% (IC95%: 92,0-98,4%); para los cinco módulos fue 93% (IC95%: 92,1-93,7%). Conclusiones: La evaluación de los participantes en el Cumplimiento de los Objetivos y en la Calidad del Desarrollo, en los 19 temas temas del curso alcanza un promedio de 92% y 93%, respectivamente.

Introduction: The comprehensive scholar sexual education is recommended by UNESCO, WHO, UNICEF and UN. Objective: Evaluation of comprehensive scholar sexual education course for general public, MOOC free. Method: On line course with 17 chapters, 17 conferences, 213 questions, 14 videos/workshops with 76 questions, course FM Radio 102.5 and 3 original films. Without date of term. Results: 230 free and voluntary student inscriptions: 88% were coming from Chile, 6% from other countries and 6% without identification. 93% were 29 years old or less, 60% were women and 94% with high school or university education. The periods of course execution were: 50 days or less in 6%, between 100 and 300 days in 78.7% and between 301 and 399 days in 15% on. From the 751 initial inscriptions at December/2021, 230 complete the first module (30,6%), 207 (28%) the second module, 199 (26%) the third module, 184 (25%) the fourth module and 177 (24%) the fifth module. From 230 initial of first module, finish 177 (77%). The final evaluation of the mastery of course objectives as good and excellent were: first module 89%, second module 91%, third module 92%, fourth module 93% and fifth module 94%; for the total course was 92% (95% confidence interval [95%CI]: 90.9-92.7). The course development quality were qualified as good and excellent in 92% (95%CI: 90.5-94.0) first module, 92% (95%CI: 90.1-93.9%) second module, 93% (95%CI: 91.2-94.9%) third module, 94% (95%CI:91.8-95.4%) fourth module and 96% (95%CI: 92.0-98.4%) fifth module; for the total course 93% (95%CI: 92.1-93.7%). Conclusions: The participants evaluation of the course, was 92% and 93% for the Mastery and Development Quality, respectively.

A2B Adenosine Receptor Enhances Chemoresistance of Glioblastoma Stem-Like Cells under Hypoxia: New Insights into MRP3 Transporter Function.

Glioblastoma is the most common and aggressive primary brain tumor, characterized by its high chemoresistance and the presence of a cell subpopulation that persists under hypoxic niches, called glioblastoma stem-like cells (GSCs). The chemoresistance of GSCs is mediated in part by adenosine signaling and ABC transporters, which extrude drugs outside the cell, such as the multidrug resistance-associated proteins (MRPs) subfamily. Adenosine promotes MRP1-dependent chemoresistance under normoxia. However, adenosine/MRPs-dependent chemoresistance under hypoxia has not been studied until now. Transcript and protein levels were determined by RT-qPCR and Western blot, respectively. MRP extrusion capacity was determined by intracellular 5 (6)-Carboxyfluorescein diacetate (CFDA) accumulation. Cell viability was measured by MTS assays. Cell cycle and apoptosis were determined by flow cytometry. Here, we show for the first time that MRP3 expression is induced under hypoxia through the A2B adenosine receptor. Hypoxia enhances MRP-dependent extrusion capacity and the chemoresistance of GSCs. Meanwhile, MRP3 knockdown decreases GSC viability under hypoxia. Downregulation of the A2B receptor decreases MRP3 expression and chemosensibilizes GSCs treated with teniposide under hypoxia. These data suggest that hypoxia-dependent activation of A2B adenosine receptor promotes survival of GSCs through MRP3 induction.

Global mental health research and practice: a decolonial approach.

The global health movement is having a paradigm crisis-a period characterised by a questioning of one's values, goals, and sense of identity. Despite important advances in population health worldwide, global health and global mental health often produce and reproduce power imbalances and patterns of oppression and exploitation that perpetuate the current modern world system (ie, Eurocentric, capitalist, and patriarchal) and its entangled global hierarchies (eg, gender, economic, epistemic, and linguistic). A consensus is emerging to decolonise global mental health, but it is not clear how to move from rhetoric to action. In this Personal View, we aim to share our experiences and the practices developed in the context of the COVID-19 health care workers (HEROES) Study. To do so, we present our HEROES decolonial team approach, which comprises three underlying principles: epistemic justice, pragmatic solidarity, and sovereign acts. We have developed decolonial team practices such as co-creating communication spaces to foster horizontal and equitable dialogue, locating and managing the study database in Chile, and ensuring local teams' rights and access to the data without barriers.

The impact of the COVID-19 pandemic on the mental health of healthcare workers: study protocol for the COVID-19 HEalth caRe wOrkErS (HEROES) study.

BACKGROUND: Preliminary country-specific reports suggest that the COVID-19 pandemic has a negative impact on the mental health of the healthcare workforce. In this paper, we summarize the protocol of the COVID-19 HEalth caRe wOrkErS (HEROES) study, an ongoing, global initiative, aimed to describe and track longitudinal trajectories of mental health symptoms and disorders among health care workers at different phases of the pandemic across a wide range of countries in Latin America, Europe, Africa, Middle-East, and Asia. METHODS: Participants from various settings, including primary care clinics, hospitals, nursing homes, and mental health facilities, are being enrolled. In 26 countries, we are using a similar study design with harmonized measures to capture data on COVID-19 related exposures and variables of interest during two years of follow-up. Exposures include potential stressors related to working in healthcare during the COVID-19 pandemic, as well as sociodemographic and clinical factors. Primary outcomes of interest include mental health variables such as psychological distress, depressive symptoms, and posttraumatic stress disorders. Other domains of interest include potentially mediating or moderating influences such as workplace conditions, trust in the government, and the country's income level. RESULTS: As of August 2021, ~ 34,000 health workers have been recruited. A general characterization of the recruited samples by sociodemographic and workplace variables is presented. Most participating countries have identified several health facilities where they can identify denominators and attain acceptable response rates. Of the 26 countries, 22 are collecting data and 2 plan to start shortly. CONCLUSIONS: This is one of the most extensive global studies on the mental health of healthcare workers during the COVID-19 pandemic, including a variety of countries with diverse economic realities and different levels of severity of pandemic and management. Moreover, unlike most previous studies, we included workers (clinical and non-clinical staff) in a wide range of settings.

Metabolic and antioxidant effects of inoculation with arbuscular mycorrhizal fungi in crops of flesh-coloured Solanum tuberosum treated with fungicides.

BACKGROUND: Solanum tuberosum tubers have higher content of phenolic compounds such as hydroxycinnamic acid derivatives (HCAD) and anthocyanins in coloured genotypes. The use of fungicides for crops is common, but there are few studies regarding the interaction of fungicides and arbuscular mycorrhizal fungi (AMF). Here, the AMF-plant interactions and the metabolic responses of three potato genotypes with different tuber colorations (VR808, CB2011-509 and CB2011-104) inoculated with Claroideoglomus claroideum (CC), Claroideoglomus lamellosum (HMC26) or Funneliformis mosseae (HMC7) were studied together with the use of the fungicides MONCUT (M) and ReflectXtra (R). Mycorrhizal traits, phenolic compound profiles and antioxidant activity (AA) were evaluated. RESULTS: Despite only two HCADs being identified, with 5-caffeolquinic acid the most abundant, four anthocyanins were detected only in purple potato genotypes. The anthocyanin and HCAD profiles, as well as AA, showed that the CB2011-104 genotype had better characteristics than the other genotypes, while VR808 and CB509 showed similar responses. The responses were dependent on the specific combinations of genotype, fungicide and the AMF strain, and generally showed better responses when colonized by AMFs. CONCLUSION: The three potato genotypes had differential responses depending on the inoculated AMFs and the fungicide applied before sowing, where the optimal combinations for antioxidant response, mycorrhization degree and performance were HMC26/R for VR808, HMC7/M for CB2011-509 and HMC26/M for CB2011-104. Our results suggest the existence of functional compatibility that can be registered as beneficial effects even at the genotypic level of the host regarding a specific AMF strain. © 2021 Society of Chemical Industry.

Efectos del Entrenamiento de Marcha sobre la Habilidad para Caminar en Sujetos con Secuelas de Accidente Cerebrovascular Crónico / Effects of Gait Training on Walking Ability in Subjects with Sequelae of Chronic Stroke

Objetivo: Identificar los efectos de un programa de entrenamiento en los parámetros temporoespaciales de marcha en pacientes con secuelas de accidente cerebrovascular en etapa crónica. Métodos: Revisión sistemática de estudios randomizados controlados en la base de datos de PEDro, PubMed y ScienceDirect desde el año 2012 hasta el 2018 que su intervención consistiera en entrenamiento de marcha y midiera alguna de las variables de velocidad, balance y/o resistencia. Se valorizaron mediante la escala de PEDro y se analizó el riesgo de sesgos. Resultados: Se analizaron 12 artículos. Se encontraron mejoras en la velocidad de marcha, balance y en resistencia y cambios favorables en parámetros espaciotemporales. Conclusiones: Existió heterogeneidad en la muestra y en la forma del entrenamiento de marcha en cada uno de los artículos. Los sujetos con secuelas de accidente cerebrovascular crónico obtuvieron cambios favorables en la habilidad de marcha después de las intervenciones. Se requiere mayor uniformidad en criterios de intervención en el entrenamiento de marcha en pacientes con secuelas de accidente cerebrovascular para que así se actualice la evidencia a través de revisiones sistemáticas sobre el tratamiento a seguir en este tipo sujetos.No se puede determinar cuál es la dosificación más adecuada de entrenamiento para lograr mayores cambios en la habilidad para caminar en los sujetos con secuelas de accidente cerebrovascular crónico

Objective: Identify the effects of a training program on gait temporospatial parameters in patients with stroke in chronic stage. Methods: Systematic review of controlled randomized studies in the database of PEDro, PubMed and ScienceDirect from 2012 to 2018, whose intervention consisted of walking training and measure some of the variables speed, balance and / or resistance. The quality of the articles was assessed using the PEDro scale and the risk of bias in each of the selected articles was analyzed. Results: Twelve articles were analyzed. Improvements were found in gait speed, balance and resistance and favorable changes in parameters. Conclusions: There was heterogeneity in the sample and in the form of gait training in each of the articles. Subjects sequential to chronic stroke obtained favorable changes in gait ability after interventions Greater uniformity is required in intervention criteria in gait training in patients with sequelae of stroke so that the evidence is updated through reviews It is not possible to determine the most appropriate training dosage to achieve greater changes in walking ability in patients with sequelae of chronic cerebrovascular accident, regarding the treatment to be followed in this type of subjects.

Decreased Equilibrative Nucleoside Transporter 1 (ENT1) Activity Contributes to the High Extracellular Adenosine Levels in Mesenchymal Glioblastoma Stem-Like Cells.

Glioblastoma multiforme is one of the most malignant types of cancer. This is mainly due to a cell subpopulation with an extremely aggressive potential, called glioblastoma stem-like cells (GSCs). These cells produce high levels of extracellular adenosine which has been associated with increased chemoresistance, migration, and invasion in glioblastoma. In this study, we attempted to elucidate the mechanisms that control extracellular adenosine levels in GSC subtypes. By using primary and U87MG-derived GSCs, we associated increased extracellular adenosine with the mesenchymal phenotype. [3H]-adenosine uptake occurred mainly through the equilibrative nucleoside transporters (ENTs) in GSCs, but mesenchymal GSCs have lower expression and ENT1-mediated uptake activity than proneural GSCs. By analyzing expression and enzymatic activity, we determined that ecto-5'-nucleotidase (CD73) is predominantly expressed in proneural GSCs, driving AMPase activity. While in mesenchymal GSCs, both CD73 and Prostatic Acid Phosphatase (PAP) contribute to the AMP (adenosine monophosphate) hydrolysis. We did not observe significant differences between the expression of proteins involved in the metabolization of adenosine among the GCSs subtypes. In conclusion, the lower expression and activity of the ENT1 transporter in mesenchymal GSCs contributes to the high level of extracellular adenosine that these GSCs present.

The TGF-ß profibrotic cascade targets ecto-5'-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease.

Progressive diabetic nephropathy (DN) and loss of renal function correlate with kidney fibrosis. Crosstalk between TGF-ß and adenosinergic signaling contributes to the phenotypic transition of cells and to renal fibrosis in DN models. We evaluated the role of TGF-ß on NT5E gene expression coding for the ecto-5`-nucleotidase CD73, the limiting enzyme in extracellular adenosine production. We showed that high d-glucose may predispose HK-2 cells towards active transcription of the proximal promoter region of the NT5E gene while additional TGF-ß results in full activation. The epigenetic landscape of the NT5E gene promoter was modified by concurrent TGF-ß with occupancy by the p300 co-activator and the phosphorylated forms of the Smad2/3 complex and RNA Pol II. Transcriptional induction at NT5E in response to TGF-ß was earlier compared to the classic responsiveness genes PAI-1 and Fn1. CD73 levels and AMPase activity were concomitantly increased by TGF-ß in HK-2 cells. Interestingly, we found increased CD73 content in urinary extracellular vesicles only in diabetic patients with renal repercussions. Further, CD73-mediated AMPase activity was increased in the urinary sediment of DN patients. We conclude that the NT5E gene is a target of the profibrotic TGF-ß cascade and is a traceable marker of progressive DN.

Author Correction: Deficient Insulin-mediated Upregulation of the Equilibrative Nucleoside Transporter 2 Contributes to Chronically Increased Adenosine in Diabetic Glomerulopathy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Glioma progression in diabesity.

Diabetes mellitus, obesity, and cancer are diseases that in recent years have caused a large number of deaths worldwide, so have been in the front line of biomedical research. On the other hand, obesity is a risk factor for several types of cancer and type 2 diabetes mellitus. The metabolic disorder and global inflammatory environment seen in obese patients is also critical for the treatment of both diabetes mellitus and gliomas. Several molecules are increased in patients with obesity and are considered risk factors in the failure of multimodal therapies for diabetes mellitus and gliomas. These molecules include adenosine, insulin, adenosine deaminases, adenosine kinase, lipids, as well as adenosine receptors, adenosine membrane transporters, and the immune response. The role of adenosine will be explained in depth since it is a nucleoside aberrantly increased in patients with these diseases, is one of the main causes of diabetes mellitus progression and the failure of glioma therapies. In addition, the role of type 2 diabetes mellitus/obesity, i.e., diabesity, and its implication in glioma treatment is discussed.

Deficient Insulin-mediated Upregulation of the Equilibrative Nucleoside Transporter 2 Contributes to Chronically Increased Adenosine in Diabetic Glomerulopathy.

Deficient insulin signaling is a key event mediating diabetic glomerulopathy. Additionally, diabetic kidney disease has been related to increased levels of adenosine. Therefore, we tested a link between insulin deficiency and dysregulated activity of the equilibrative nucleoside transporters (ENTs) responsible for controlling extracellular levels of adenosine. In ex vivo glomeruli, high D-glucose decreased nucleoside uptake mediated by ENT1 and ENT2 transporters, resulting in augmented extracellular levels of adenosine. This condition was reversed by exposure to insulin. Particularly, insulin through insulin receptor/PI3K pathway markedly upregulated ENT2 uptake activity to restores the extracellular basal level of adenosine. Using primary cultured rat podocytes as a cellular model, we found insulin was able to increase ENT2 maximal velocity of transport. Also, PI3K activity was necessary to maintain ENT2 protein levels in the long term. In glomeruli of streptozotocin-induced diabetic rats, insulin deficiency leads to decreased activity of ENT2 and chronically increased extracellular levels of adenosine. Treatment of diabetic rats with adenosine deaminase attenuated both the glomerular loss of nephrin and proteinuria. In conclusion, we evidenced ENT2 as a target of insulin signaling and sensitive to dysregulation in diabetes, leading to chronically increased extracellular adenosine levels and thereby setting conditions conducive to kidney injury.

Adenosine contribution to normal renal physiology and chronic kidney disease.

Adenosine is a nucleoside that is particularly interesting to many scientific and clinical communities as it has important physiological and pathophysiological roles in the kidney. The distribution of adenosine receptors has only recently been elucidated; therefore it is likely that more biological roles of this nucleoside will be unveiled in the near future. Since the discovery of the involvement of adenosine in renal vasoconstriction and regulation of local renin production, further evidence has shown that adenosine signaling is also involved in the tubuloglomerular feedback mechanism, sodium reabsorption and the adaptive response to acute insults, such as ischemia. However, the most interesting finding was the increased adenosine levels in chronic kidney diseases such as diabetic nephropathy and also in non-diabetic animal models of renal fibrosis. When adenosine is chronically increased its signaling via the adenosine receptors may change, switching to a state that induces renal damage and produces phenotypic changes in resident cells. This review discusses the physiological and pathophysiological roles of adenosine and pays special attention to the mechanisms associated with switching homeostatic nucleoside levels to increased adenosine production in kidneys affected by CKD.

The cellular and signalling alterations conducted by TGF-ß contributing to renal fibrosis.

Renal fibrosis is a common irreversible process of chronic kidney disease (CKD) characterized by uncontrolled deposits of extracellular matrix, replacement of cellular parenchyma and progressive loss of renal function. Recent evidence suggests that a series of phenotypic transformations of resident renal cells are responsible for the formation of interstitial myofibroblasts, cells that play a key role in the fibrotic process. In the renal glomerulus transformation of mesangial cells to myofibroblasts is an event that orchestrates glomerulosclerosis and the participation of other cells types has also been suggested. Recent findings clarify the role of tubular epithelium in mediating the generation of ECM producing cells in the tubule interstitium. Also, crosstalk between injured cells and myofibroblasts for amplification of the fibrogenic cascade in CKD occurs. The crucial conductor of these changes in the kidney is the transforming growth factor-ß (TGF-ß). Thus, this review focuses on the control of this cytokines signaling mechanisms and their dysregulation in CKD. Further, some of the promising interventional alternatives targeting TGF-ß are also discussed.

Reduced Adenosine Uptake and Its Contribution to Signaling that Mediates Profibrotic Activation in Renal Tubular Epithelial Cells: Implication in Diabetic Nephropathy.

Altered nucleoside levels may be linked to pathogenic signaling through adenosine receptors. We hypothesized that adenosine dysregulation contributes to fibrosis in diabetic kidney disease. Our findings indicate that high glucose levels and experimental diabetes decreased uptake activity through the equilibrative nucleoside transporter 1 (ENT1) in proximal tubule cells. In addition, a correlation between increased plasma content of adenosine and a marker of renal fibrosis in diabetic rats was evidenced. At the cellular level, exposure of HK2 cells to high glucose, TGF-ß and the general adenosine receptor agonist NECA, induced the expression of profibrotic cell activation markers α-SMA and fibronectin. These effects can be avoided by using a selective antagonist of the adenosine A3 receptor subtype in vitro. Furthermore, induction of fibrosis marker α-SMA was prevented by the A3 receptor antagonist in diabetic rat kidneys. In conclusion, we evidenced the contribution of purinergic signaling to renal fibrosis in experimental diabetic nephropathy.

Estudio comparativo entre sondajes lacrimonasales de primera intención con y sin control endoscópico / Comparative study of primary intention lacrimal probing with and without nasal endoscopy

Objetivo: Comparar los resultados de dos series de sondajes de primera intención, sin y con endoscopia nasal, acompañados en este segundo caso de luxación de cornete inferior y corrección de enfermedad del meato inferior si la hubiera, en casos de obstrucción nasolagrimal congénita. Métodos: Se practica un estudio de cohortes retrospectivos con 36 sondajes simples (grupo 1) frente a 36 sondajes con endoscopia (grupo 2), entre enero de 2011 y enero de 2013, en 2 grupos de población parecidos sin intervenciones previas. El rango de edad fue entre 8 y 27 meses en el grupo 1 y entre 7 y 30 meses en el grupo 2. Resultados: El 50% de cirugías lagrimales fueron realizadas con éxito en el grupo de los sondajes sin endoscopia, frente al 97,22% en el grupo guiado por endoscopia. En el grupo 2 se diagnosticó y corrigió intraoperatoriamente un 16,67% de vías lagrimales con aposición del cornete inferior en su porción distal y un 11,11% de falsas vías o trayectos submucosos. En un 30,56% de los sondajes practicados con endoscopia se observó más de una anomalía nasolagrimal, tanto a nivel del canal como en el meato inferior, que influía negativamente en su funcionamiento. Conclusión: Aunque clásicamente se ha reservado la endoscopia para fracasos quirúrgicos en reintervenciones, su utilización de primera intención mejora significativamente los éxitos. En nuestra serie un 97,22% tuvieron resolución completa de los síntomas, evitando un segundo paso por quirófano y la utilización de materiales y técnicas más costosas. Nos ayuda a la visualización y compresión de esta enfermedad y es el único método para confirmar directamente un correcto sondaje en tiempo real (AU)

Objective: Our objective was to compare the results of probing with and without endoscopy in cases of congenital nasolacrimal duct obstruction without prior probing. Methods: This was a retrospective analysis on 2 non-randomized cohorts, 36 simple soundings (group 1) and 36 soundings with endoscope (group 2), between January 2011 and January 2013. Both groups were similar in age and had no previous surgery. The age of the patients studied ranged between 8 and 27 months in the first group and between 7 and 30 months in the second group. Results: The procedure was successful in 50% of the conventional probing group and in 97.22% in the endoscopy probing group. In this group 16.67% of patients with tight inferior turbinate and 11.11% of those where the probe passed into the submucosal space were diagnosed and corrected intraoperatively. Some anomaly was observed in 30.56% of patients undergoing endoscopy. Conclusion: Although nasal endoscopy is classically reserved for unsuccessful probing, its use in primary intention increases the success rate of the procedure. In our study, 97.22% of eyes had complete resolution of symptoms, avoiding a second surgery and the use of more expensive materials and techniques. Nasal endoscopy helps intraoperative visualisation, understanding and management of congenital nasolacrimal duct obstruction and is the only method that confirms the correct anatomic position of the catheterisation in real time (AU)

Comparative study of primary intention lacrimal probing with and without nasal endoscopy.

OBJECTIVE: Our objective was to compare the results of probing with and without endoscopy in cases of congenital nasolacrimal duct obstruction without prior probing. METHODS: This was a retrospective analysis on 2 non-randomized cohorts, 36 simple soundings (group 1) and 36 soundings with endoscope (group 2), between January 2011 and January 2013. Both groups were similar in age and had no previous surgery. The age of the patients studied ranged between 8 and 27 months in the first group and between 7 and 30 months in the second group. RESULTS: The procedure was successful in 50% of the conventional probing group and in 97.22% in the endoscopy probing group. In this group 16.67% of patients with tight inferior turbinate and 11.11% of those where the probe passed into the submucosal space were diagnosed and corrected intraoperatively. Some anomaly was observed in 30.56% of patients undergoing endoscopy. CONCLUSION: Although nasal endoscopy is classically reserved for unsuccessful probing, its use in primary intention increases the success rate of the procedure. In our study, 97.22% of eyes had complete resolution of symptoms, avoiding a second surgery and the use of more expensive materials and techniques. Nasal endoscopy helps intraoperative visualisation, understanding and management of congenital nasolacrimal duct obstruction and is the only method that confirms the correct anatomic position of the catheterisation in real time.

Targeting adenosine signaling to treatment of diabetic nephropathy.

Diabetic nephropathy (DN) continues being the primary cause of chronic hemodialysis and terminal renal disease worldwide. At tissue levels the DN occurs with glomerulopathy affecting the integrity of the filtration barrier and with an extensive glomerular and tubule-interstitial fibrosis. Current available therapeutic approaches have only demonstrated a modest effect on progression of kidney injury. Therefore, more research concerning the pathomechanisms and possible interventions are needed. Interestingly, in the last years it has been documented that DN progresses with growing levels of the nucleoside adenosine. This finding increased the interest in the events controlling the extracellular levels of the nucleoside. While the metabolism of extracellular ATP and cyclic AMP are well recognized sources, evidences regarding the role of the equilibrative nucleoside transporters in controlling adenosine availability and promoting diabetic glomerulopathy have recently acquired a pivotal role. The physiological effects of nucleoside are mediated by the P1 family of adenosine receptors. It has been shown in vivo that the use of an antagonist of the A2B receptor subtype can block the most remarkable early alterations seen in diabetic glomerulopathy. Furthermore, using models of chronic kidney injury it was demonstrated that fibrosis can also be blocked using treatment with the antagonist of A2B receptor subtype. This review highlights these findings that correlate the activity of a low affinity adenosine receptor with an increase in the ligand availability in the pathological state. In addition, we discuss the possible therapeutic interventions of adenosine signaling with regards to DN treatment.

Increased expression of the multidrug resistance-associated protein 1 (MRP1) in kidney glomeruli of streptozotocin-induced diabetic rats.

Oxidative stress has been linked to the podocytopathy, mesangial expansion and progression of diabetic nephropathy. The major cell defence mechanism against oxidative stress is reduced glutathione (GSH). Some ABC transporters have been shown to extrude GSH, oxidised glutathione or their conjugates out of the cell, thus implying a role for these transporters in GSH homeostasis. We found a remarkable expression of mRNA for multidrug resistance-associated proteins (MRP/ABCC) 1, 3, 4 and 5 in rat glomeruli. Three weeks after induction of diabetes in glomeruli of streptozotocin-treated rats, we observed a decline in reduced GSH levels and an increase in the expression and activity of MRP1 (ABCC1). These lower GSH levels were improved by ex vivo treatment with pharmacological inhibitors of MRP1 activity (MK571). We conclude that increased activity of MRP1 in diabetic glomeruli is correlated with an inadequate adaptive response to oxidative stress.