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Colorectal cancer mortality rate and highly altered proteins from the Wnt/β-catenin pathway increase the scientific community’s interest in finding alternatives for prevention and treatment. This study aims to determine the biological effect of chlorogenic acid (CGA) on two colorectal cancer cell lines, HT-29 and SW480, and its interactions with β-catenin and LRP6 to elucidate a possible modulatory mechanism on the Wnt/β-catenin pathway. These effects were determined by propidium iodide and DiOC6 for mitochondrial membrane permeability, MitoTracker Red for mitochondrial ROS production, DNA content for cell distribution on cell cycle phases, and molecular docking for protein–ligand interactions and binding affinity. Here, it was found that CGA at 2000 µM significantly affects cell viability and causes DNA fragmentation in SW480 cells rather than in HT-29 cells, but in both cell lines, it induces ROS production. Additionally, CGA has similar affinity and interactions for LRP6 as niclosamide but has a higher affinity for both β-catenin sites than C2 and iCRT14. These results suggest a possible modulatory role of CGA over the Wnt/β-catenin pathway in colorectal cancer.

TRPA1 channels are expressed in nociceptive neurons, where they detect noxious stimuli, and in the mammalian cochlea, where their function is unknown. Here we show that TRPA1 activation in the supporting non-sensory Hensen’s cells causes prolonged Ca2+responses, which propagate across the organ of Corti and cause long-lasting contractions of pillar and Deiters’ cells. Caged Ca2+experiments demonstrated that, similar to Deiters’ cells, pillar cells also possess Ca2+-dependent contractile machinery. TRPA1 channels are activated by endogenous products of oxidative stress and by extracellular ATP. Since both these stimuli are presentin vivoafter acoustic trauma, TRPA1 activation after noise may affect cochlear sensitivity through supporting cell contractions. Consistently, TRPA1 deficiency results in larger but less prolonged noise-induced temporary shift of hearing thresholds, accompanied by permanent changes of latency and shape of the auditory brainstem responses. We conclude that TRPA1 contributes to the regulation of cochlear sensitivity after acoustic trauma.

Introduction: Enough scientific evidence is available on the harmful effects of air pollution on the health of human beings, fauna, flora, and ecosystems in general. The mechanical and electronical monitoring networks are the first option for the air quality diagnosis, but they do not allow a direct and precise assessment of the impacts in living organisms that may result from the exposure to air pollutants. Objective:To evaluate the changes in the composition of corticulous lichen communities as a response to various stress factors in areas with different levels of air quality to diagnose the state of pollution or intervention in an area with a more complete option. Methods: Air quality contrasts and changes in richness and coverage of corticulous lichens in response to different stress factors, such as land use and distance to roads, in three different biomonitoring areas, were evaluate using GIS, and the data are presented in an easy-to-understand grey scale coded isoline map. Results:Indicators such as lichen coverage (R= -0.4) and richness (R= -0.7) are inverse correlated with PM2.5 concentrations in each area.A total of 110 lichen species were identified, being Phaeophyscia chloantha(Ach.) Moberg and Physcia poncinsii Huethe most frequent species (present in 38 and 33 % of the 86 sampled phorophytes, respectively). The intra-area relationships of lichen richness exhibit significant relationships with regards to the land use and distance to roads (with correlations coefficients greater than 0.5) and the Simpson index was higher than 0.9, in places with better conditions in terms of air quality and microenvironments, likewise the resistance factors calculated suggest that the most sensitive species can be found in environments with a lesser degree of disturbance. Conclusion:These evaluations represent more criteria elements for the diagnosis of the environmental health in the biomonitoring areas. Introducción: Existe suficiente evidencia científica de los efectos nocivos de la contaminación atmosférica sobre la salud de los seres humanos, fauna, flora y ecosistemas en general. La primera opción para el diagnóstico de la calidad del aire son las redes de monitoreo mecánicas o electrónicas, pero estas no permiten evaluar de forma directa y precisa el impacto en los organismos vivos como resultado de la exposición a contaminantes del aire. Objetivo:Evaluar los cambios en la composición de las comunidades de líquenes cortícolas como resultado a la exposición de factores de estrés ambiental en áreas con diferentes niveles de calidad del aire para diagnosticar el estado de contaminación o intervención en una zona de una manera más completa. Métodos: Se determinaron los contrastes y cambios en la calidad del aire, la riqueza y cobertura de líquenes cortícolas en respuesta a diferentes factores de estrés, como usos del suelo y distancia a carreteras, en tres diferentes áreas de biomonitoreo, las cuales fueron evaluadas usando GIS. Los datos se presentan en un mapa de isolíneas con códigos en escala de grises fácil de entender. Resultados:Indicadores como cobertura (R= -0.4) y riqueza (R= -0.7) de líquenes están inversamente correlacionados con las concentraciones de PM2.5en cada área. Se identificaron un total de 110 especies de líquenes, siendo Phaeophyscia chloantha(Ach.) Moberg y Physcia poncinsiiHue las especies más frecuentes (presentes en 38 y 33 % de los 86 forófitos muestreados, respectivamente). Las relaciones intra-área de riqueza de líquenes exhiben relaciones significativas con respecto al uso del suelo y distancia a carreteras (con coeficientes de correlación mayores a 0.5) y el índice de Simpson fue mayor a 0.9, en lugares con mejores condiciones en términos de calidad del aire y microambientes. Asimismo, los factores de resistencia calculados sugieren que las especies más sensibles se pueden encontrar en ambientes con menor grado de perturbación. Conclusión:Estas evaluaciones representan más elementos de criterio para el diagnóstico de la salud ambiental en las áreas de biomonitoreo.

Background Pediatric kidney transplant patients have an increased risk of developing arterial hypertension, dyslipidemia, carbohydrate intolerance and diabetes mellitus, risk factors associated with increased cardiovascular morbidity and mortality. Objective This study evaluates the frequency of arterial hypertension, dyslipidemia and alteration in carbohydrate metabolism in a cohort of pediatric kidney transplant patients during 2006-2016 at the Pablo Tobon Uribe Hospital, in Colombia. Material and methods Retrospective descriptive study in which descriptive statistics were used. Additionally, a bivariate analysis was performed to compare patients according to the outcome of arterial hypertension, dyslipidemia and alteration in carbohydrate metabolism. Results From a total of 48 pediatric kidney transplants in the period studied, complete information was obtained from 43 patients at one year of follow-up. There was a post-transplant frequency of hypertension of 86%, dyslipidemia 48%, carbohydrate intolerance 14% and diabetes of 2%. Conclusions In the evaluated cohort a high frequency of arterial hypertension and dyslipidemia was found after kidney transplantation. The development of early diagnosis and treatment guidelines is suggested to reduce the impact of these diseases associated with cardiovascular risk in adult life.

Despite all recent achievements in identification of the molecules that are essential for the structure and mechanosensory function of stereocilia bundles in the auditory hair cells of mammalian species, we still have only a rudimentary understanding of the mechanisms of stereocilia formation, maintenance, and repair. Important molecular differences distinguishing mammalian auditory hair cells from hair cells of other types and species have been recently revealed. In addition, we are beginning to solve the puzzle of the apparent life-long stability of the stereocilia bundles in these cells. New data link the stability of the cytoskeleton in the mammalian auditory stereocilia with the normal activity of mechanotransduction channels. These data suggest new ideas on how a terminally-differentiated non-regenerating hair cell in the mammalian cochlea may repair and tune its stereocilia bundle throughout the life span of the organism.

Presented in this paper is an investigation on wire-length dependence of transient hot-wire calorimetry, a technique generally used to measure the thermal conductivity of materials. In particular, a measurement protocol that includes the use of a calibration fluid that was designed for wires of reduced lengths; so as to reliably apply the transient hot-wire method to materials exhibiting a solid-liquid phase transition as a function of temperature. An experimental study of the onset of convection was also carried out, including a comparison between measurements performed in the liquid and solid phases. For the purpose of validation, presented are experimental measurements of the thermal conductivity of water Ih-ice at 0.1 MPa, within a temperature range of 259–266 K, and that of n-eicosane within the range of 259–348 K, which encompasses its melting point.

Inner ear hair cells detect sound-induced displacements and transduce these stimuli into electrical signals in a hair bundle that consists of stereocilia that are arranged in rows of increasing height. When stereocilia are deflected, they tug on tiny (~5 nm in diameter) extracellular tip links interconnecting stereocilia, which convey forces to the mechanosensitive transduction channels. Although mechanotransduction has been studied in live hair cells for decades, the functionally important ultrastructural details of the mechanotransduction machinery at the tips of stereocilia (such as tip link dynamics or transduction-dependent stereocilia remodeling) can still be studied only in dead cells with electron microscopy. Theoretically, scanning probe techniques, such as atomic force microscopy, have enough resolution to visualize the surface of stereocilia. However, independent of imaging mode, even the slightest contact of the atomic force microscopy probe with the stereocilia bundle usually damages the bundle. Here we present a detailed protocol for the hopping probe ion conductance microscopy (HPICM) imaging of live rodent auditory hair cells. This non-contact scanning probe technique allows time lapse imaging of the surface of live cells with a complex topography, like hair cells, with single nanometers resolution and without making physical contact with the sample. The HPICM uses an electrical current passing through the glass nanopipette to detect the cell surface in close vicinity to the pipette, while a 3D-positioning piezoelectric system scans the surface and generates its image. With HPICM, we were able to image stereocilia bundles and the links interconnecting stereocilia in live auditory hair cells for several hours without noticeable damage. We anticipate that the use of HPICM will allow direct exploration of ultrastructural changes in the stereocilia of live hair cells for better understanding of their function.

Objetivo: describir la experiencia del curso virtual Bioseguridad en odontología en tiempos de la COVID-19, dirigido a odontólogos. Métodos: se diseñó e implementó un curso virtual en la plataforma Moodle, de CES Virtual, con cuatro cohortes. El curso fue autogestionable, constó de tres módulos, cada uno evaluable, y emitió certificación en el área de bioseguridad para la atención odontológica. Resultados: se inscribieron 472 personas entre odontólogos, higienistas, auxiliares de consultorio y estudiantes de odontología. Del total de inscritos en las cuatro cohortes, el 96,18% recibió su certificación y el 48,8% respondió la encuesta de satisfacción, en donde valoraron el curso de manera positiva; con base en sus opiniones se definió un plan de mejoramiento para las siguientes cohortes. Conclusiones: las personas expresaron su satisfacción con el curso, teniendo en cuenta la facilidad para explorar los contenidos de forma autogestionable, la actualidad del tema, las presentaciones del expositor y la didáctica empleada para su desarrollo. Además, el diseño intuitivo del entorno virtual favoreció el autoaprendizaje y autogestión del conocimiento.

Mammalian hair cells develop their mechanosensory bundles through consecutive phases of stereocilia elongation, thickening, and retraction of supernumerary stereocilia. Many molecules involved in stereocilia elongation have been identified, including myosin-XVa. Significantly less is known about molecular mechanisms of stereocilia thickening and retraction. Here, we used scanning electron microscopy (SEM) to quantify postnatal changes in number and diameters of the auditory hair cell stereocilia in shaker-2 mice (Myo15(sh2)) that lack both “long” and “short” isoforms of myosin-XVa, and in mice lacking only the “long” myosin-XVa isoform (Myo15(∆N)). Previously, we observed large mechanotransduction current in young postnatal inner (IHC) and outer (OHC) hair cells of both these strains. Stereocilia counts showed nearly identical developmental retraction of supernumerary stereocilia in control heterozygous, Myo15(sh2/sh2), and Myo15(∆N/∆N) mice, suggesting that this retraction is largely unaffected by myosin-XVa deficiency. However, myosin-XVa deficiency does affect stereocilia diameters. In control, the first (tallest) and second row stereocilia grow in diameter simultaneously. However, the third row stereocilia in IHCs grow only until postnatal day 1–2 and then become thinner. In OHCs, they also grow slower than taller stereocilia, forming a stereocilia diameter gradation within a hair bundle. The sh2 mutation disrupts this gradation and makes all stereocilia nearly identical in thickness in both IHCs and OHCs, with only subtle residual diameter differences. All Myo15(sh2/sh2) stereocilia grow postnatally including the third row, which is not a part of normal development. Serial sections with focused ion beam (FIB)-SEM confirmed that diameter changes of Myo15(sh2/sh2) IHC and OHC stereocilia resulted from corresponding changes of their actin cores. In contrast to Myo15(sh2/sh2), Myo15(∆N/∆N) hair cells develop prominent stereocilia diameter gradation. Thus, besides building the staircase, the short isoform of myosin-XVa is essential for controlling the diameter of the third row stereocilia and formation of the stereocilia diameter gradation in a hair bundle.

RESUMEN: El trasplante renal pediátrico es el tratamiento de elección en los niños con enfermedad renal crónica terminal. Muchos agentes se utilizan en dos regímenes de terapia inmunosupresora, primero en una fase de inducción y posteriormente para el mantenimiento. Existen dos estrategias para disminuir el riesgo de rechazo del injerto renal: la primera consiste en suministrar altas dosis de los inmunosupresores convencionales, y la segunda, en la utilización en la fase de inducción de anticuerpos monoclonales o policlonales contra antígenos de los linfocitos T. Los dos anticuerpos policlonales más usados son las globulinas antitimocito de caballo (ATGAM) y de conejo (rATG). Los anticuerpos monoclonales más usados son aquellos contra el receptor de IL-2 (basiliximab y daclizumab) y el dirigido contra el antígeno CD52 (alemtuzumab). La terapia de mantenimiento consiste en un esquema que combina el uso de tres drogas inmunosupresoras convencionales: glucocorticoides, inhibidores de la calcineurina, inhibidores de mTOR y antiproliferativos. Entre las principales complicaciones del trasplante renal pediátrico están: rechazo agudo del injerto, infecciones virales (por poliomavirus-BK y citomegalovirus) y aparición del trastorno linfoproliferativo postrasplante (PTLD, por la sigla en inglés de Post-transplant lymphoproliferative disorder). ABSTRACT: Pediatric renal transplantation is the treatment of choice in children with chronic kidney disease. Many agents are available for immunosuppressive therapy, which are used in two different regimes: first for the induction phase, and then for maintenance. There are two strategies for reducing the risk of renal graft rejection: the first is the use of high doses of conventional immunosuppressive agents, and the second is the use in the induction phase of monoclonal or polyclonal antibodies against antigens of T cells. The two most frequently used polyclonal antibodies are horse and rabbit anti-thymocyte globulins, ATGAM and rATG, respectively. The most frequently used monoclonal antibodies are those against IL-2 receptor (basiliximab and daclizumab) and the one against antigen CD52 (alemtuzumab). Maintenance therapy is a scheme that combines the use of three conventional immunosuppressive drugs: glucocorticoids, calcineurin inhibitors, mTOR inhibitors and antiproliferatives. The following are among the major complications of renal transplantation: acute graft rejection, viral infection (cytomegalovirus and BK polyomavirus) and appearance of PTLD (posttransplant lymphoproliferative disorder).

Lichens have been widely used worldwide as bioindicators of air quality and also integrated into national programs and protocols in several countries. The Index of Atmospheric Purity (IAP) has been a commonly used tool for the diagnosis of air quality using corticulous lichens. However, its implementation is recommended when phorophytes with similar characteristics of the bark are used. Therefore, many studies are restricted to the use of a single supporting phorophyte. This criterion makes it difficult to implement this index in areas with limited number of individuals and species of phorophytes. This research evaluates the functionality of this index without differentiating among carrier phorophytes for the classification of areas with differences in air quality. For this, the lichens were mapped and collected, along with bark samples to determine the pH bark of phorophytes close to air quality monitoring stations located in Medellin City. A total of 148 lichen species were identified, belonging to 26 families and 52 genera. In addition, indicators such as thallus heterogeneity, richness (with correlations coefficients r = 0.52 with no phorophyte differentiation and for the tree species F. uhdei and T. rosea, r = 0.578 and r = 0.777; respectively) and total coverage of corticulous lichens (r = 0.76) vary in response to air pollution levels, no matter if their evaluation is carried out on a single phorophyte or in a diversity of phorophytes. This research also revealed that the evaluation of IAP in the biomonitoring zones is functional, resulting in positive correlations between the IAP and the air quality classification when this index is evaluated without differentiation of phorophytes (r = 0.78) and for T. rosea (r = 0.94) and F. uhdei (r = 0.99). In this sense, the uniformity criterion in the selection of the phorophyte use for the application of this index can be complemented taking into account the possibility of using a heterogeneous sample of phorophytes.

The thermal properties including the thermal conductivity ( λ ), the specific heat ( c p ), the melting and crystallization temperatures together with their corresponding transition heat enthalpies of the odd-numbered linear alkane hydrocarbons n-pentadecane, n-heptadecane and n-nonadecane were measured in both the solid and liquid phases using the transient hot wire and the differential scanning calorimetry (DSC) techniques. The obtained results were compared with available literature data. Discussions were based also on the X-ray diffraction spectra of the three n-alkanes carried out at different temperatures and including both solid and liquid phases. A discontinuity of λ is observed at the solid - liquid phase transition of the three n-alkane hydrocarbons.

The thermal conductivity (λ) and thermal diffusivity (aT) of the solid/liquid phase change linear n-alkanes were measured simultaneously by the transient multi-current hot wire technique at atmospheric pressure in the range 258–348 K. The same set-up was used to measure λ and aT of the liquid and the solid states at different electrical currents. Three n-alkanes, n-hexadecane (C16H34), n-octadecane (C18H38) and n-eicosane (C20H42) were studied. Differential scanning calorimetry was applied at the temperature range 248–348 K to determine the melting/crystallization temperature, the heat of melting/crystallization and the specific heat of both the solid and liquid phases. Some results were compared with available literature data. The density of the n-alkanes at liquid state was also measured at different temperatures and their thermal diffusivity was estimated and compared to that obtained by the hot wire technique. The cumulative energy stored was estimated over a definite range of temperature for the three n-alkanes and this was found to be higher for eicosane.

Background Histoplasmosis is an uncommon systemic fungal infection, but it is potentially fatal in immunosuppressed populations. In Latin America, which is considered an endemic area for this mycosis, there have been no published reports regarding the incidence, clinical presentation, morbidity, and mortality of histoplasmosis in renal transplant patients. The objective of this study was to describe cases of histoplasmosis in renal transplant patients treated at the Pablo Tobon Uribe Hospital (Medellin, Colombia) between 2006 and 2013. Methods This is a descriptive, retrospective study. Results The incidence of histoplasmosis in our renal transplant population was 1.1%. The ages of the 9 patients (4 men and 5 women) ranged between 27 and 59 years. In 2 of these patients, histoplasmosis appeared during the first year after transplantation. At the time of transplantation, 66% of patients received induction with alemtuzumab; 88% had a prior rejection episode and required increased immunosuppressive medication; 88% had renal graft dysfunction with creatinine levels >1.5 mg/dL; and the primary clinical presentation was disseminated histoplasmosis followed by the pulmonary form of the disease. Diagnoses were performed by histology in 6 patients, blood culture in 2 patients, and antigenuria in 1 patient. Three patients required treatment with amphotericin B for the severity of their infection, and 2 of these patients died before receiving the cumulative dose of amphotericin B. The 7 remaining patients received itraconazole for 12 months and had a successful treatment response. Regarding complications, 2 patients had hemophagocytic syndrome. At the 1-year follow-up appointment, renal function remained stable in all patients, and no patients had acute rejection or required renal replacement therapy. Thus, the overall mortality rate observed was 22.2%. Conclusions In this series, histoplasmosis in renal transplant patients presented as an aggressive opportunistic infection with a higher incidence than that previously reported in the literature. The following risk factors have been associated with histoplasmosis: renal graft dysfunction, previous acute rejection, immunosuppression with tacrolimus-mycophenolate, and induction with alemtuzumab. The clinical presentation of histoplasmosis was nonspecific, which complicated disease diagnosis, and the treatment regimens were highly toxic and associated with significant morbidity and mortality rates.

Mechanotransducer channels at the tips of sensory stereocilia of inner ear hair cells are gated by the tension of 'tip links' interconnecting stereocilia. To ensure maximal sensitivity, tip links are tensioned at rest, resulting in a continuous influx of Ca2+ into the cell. Here, we show that this constitutive Ca2+ influx, usually considered as potentially deleterious for hair cells, is in fact essential for stereocilia stability. In the auditory hair cells of young postnatal mice and rats, a reduction in mechanotransducer current, via pharmacological channel blockers or disruption of tip links, leads to stereocilia shape changes and shortening. These effects occur only in stereocilia that harbor mechanotransducer channels, recover upon blocker washout or tip link regeneration and can be replicated by manipulations of extracellular Ca2+ or intracellular Ca2+ buffering. Thus, our data provide the first experimental evidence for the dynamic control of stereocilia morphology by the mechanotransduction current. DOI: http://dx.doi.org/10.7554/eLife.24661.001, eLife digest Our sense of hearing depends on cells known as hair cells that line the inner ear. Each hair cell has tiny projections called stereocilia, which are arranged in a bundle with rows of increasing height like a staircase and are connected to each other by tiny filaments called tip-links. When sound waves hit the stereocilia, the tension on the tip-links increases, which opens “mechanotransduction” channels on the shorter stereocilia that allow calcium ions to flow into the cells. To ensure that the ears can detect even the softest sounds, the tip-links always have a small amount of tension which allows a small, but continuous flow of calcium ions into the cell. Scientists generally consider this continuous flow of calcium ions as a potentially harmful byproduct of sensitive hearing. Vélez-Ortega et al. isolated inner ear tissues from young mice and rats and exposed them to drugs that either block the flow of calcium ions through the mechanotransduction channels or break the tip-links on stereocilia. Surprisingly, these drugs made profound changes in the shape of individual stereocilia and the staircase architecture of the stereocilia bundle. When the drugs were rinsed out of the hair cells, the stereocilia went back to their normal shape. Sequestering of free calcium ions inside the hair cells had a similar effect on the shape of stereocilia. These findings show that the flow of calcium ions into the sterocilia via mechanotransduction channels controls the exquisite staircase-like architecture of the stereocilia bundle. More research is needed to identify which structural proteins cause the stereocilia shape changes and to work out exactly how calcium ions are involved. DOI: http://dx.doi.org/10.7554/eLife.24661.002

INTODUCTION: Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA) is one of the treatments used in such situations. OBJECTIVE: To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS) and to assess the therapeutic response to MA. METHODS: This was a retrospective and descriptive study. RESULTS: 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS). The immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75: 3.25) after using this medication (p = 0.08). Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62) mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day (p < 0.001), in 8 patients prednisolone was stopped. CONCLUSION: In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage. INTRODUÇÃO: A síndrome nefrótica é uma das mais frequentes doenças glomerulares em crianças e o tratamento com corticosteróides ainda é o tratamento de escolha. Apesar disso, 10 a 15% dos pacientes são resistentes a corticosteróides, e o melhor tratamento para tais casos ainda não foi definido. O ácido micofenólico (AM) é um dos tratamentos usados em tais situações. OBJETIVO: Descrever o comportamento clínico de crianças diagnosticadas com síndrome nefrótica resistente a corticosteróide (SNRC) e avaliar a resposta terapêutica ao AM. MÉTODOS: Esse foi um estudo retrospectivo e descritivo. RESULTADOS: 26 registros de pacientes com SNRC; 70% homens e 30% mulheres. Todos os pacientes foram submetidos a biópsias renais, o que mostrou predominância de glomeruloesclerose segmentar focal (GESF). Os medicamentos imunossupressores utilizados foram: Mofetil Micofenolato (MMF) 100%; Ciclosporina 69,2%; Ciclosfosfamida 23,1%; e Rituximabe 23%. Um mês após início do tratamento com MMF, 61,5% tiveram remissão. A mediana das recidivas por ano para os pacientes foi de 3 (p25: 2,75 - p75: 4). Essa mediana se tornou 1 (p25: 1 - p75: 3,25) após o uso da medicação (p = 0,08). Além disso, antes do início do tratamento com MMF, a mediana da dose de corticosteróide foi de 1 (p25: 0.5 - p75: 1.62) mg/k/ dia. Após a utilização do MMF, essa mediana se tornou 0,07 (p25: 0 - p75: 0,55) mg/k/dia (p < 0,001), em 8 pacientes a prednisolona foi interrompida. CONCLUSÃO: em nossa casuística, o tratamento com MMF mostrou resultados positivos, tais como a redução na frequência de recidivas, menos proteinúria, e redução da dose de corticosteróide administrada sem deterioração nas taxas de filtração glomerular. Entretanto, mais estudos são necessários para se avaliar a eficácia, segurança e otimização da dosagem.

Introduction. A dysregulation of regulatory T cells (Tregs) could play a major role in the pathogenesis of bronchial asthma. Sex-dependent differences as well as the impact of hormonal changes in the incidence and severity of asthma are widely recognized. Emerging evidence suggests that asthma symptoms are alleviated in female patients taking hormone oral contraceptives (OCs). The impact of OCs on the generation of induced Tregs (iTregs) was assessed in a cohort of female patients with asthma. Methods. Thirteen patients were included in this pilot study. During three distinct phases of their menstrual cycles, we measured exhaled nitric oxide (eNO) levels, forced expiratory volume at 1 second (FEV1s), asthma control test (ACT) score, sex steroid hormone levels in serum, natural Tregs in peripheral blood, and the ability of CD4(+) T cells to generate iTregs ex vivo. Results. The luteal serum levels of estradiol and progesterone negatively correlated with the proportion of iTregs generated ex vivo in patients not taking OCs. In addition, physiological doses of estradiol and progesterone prevented the acquisition of a suppressor T cell phenotype in vitro. Interestingly, patients taking OCs had reduced serum sex hormone levels associated with higher iTreg induction, a better ACT score, and a tendency toward lower eNO levels. Conclusions. Our results identify an impact of sex hormones on the capacity of T cells to polarize towards a regulatory phenotype and suggest the regulation of peripheral T cell lineage plasticity as a potential mechanism underlying the beneficial effects of OCs in women with asthma.

Background : antibody-mediated renal allograft rejection is a complication after kidney transplantation, and it has poor prognosis for graft survival. Plasmapheresis has been used with controversial results; few trials indicate a trend towards superior graft survival in patients receiving this treatment; however, the evidence remains weak. Objetive: the aim of this study was to describe the experience in treating Antibody-mediated renal allograft rejection with plasmapheresis in kidney transplant recipients. Methods: retrospective and descriptive study of the patients that underwent three to nine session of plasmapheresis as a treatment of severe Antibody-mediated renal allograft rejection in Pablo Tobon Uribe Hospital. Results: between August 2005 and June 2015, 769 patients underwent kidney transplantation at our institution; 26 patients received plasmapheresis as part of the treatment for Antibody-mediated renal allograft rejection. All patients received induction therapy. Maintenance therapy used was tacrolimus, mycophenolic acid and steroids in 80,8% of the patients and cyclosporine, micophenolic acid and steroids in 19,2%. Antibody mediated rejection had an early onset in 61,5% of the cases. At six and 12 months after therapy, 44% and 53,8% patients respectively were back on dialysis. Complications were reported in 53,8% of the patients (hypocalcaemia, hypotension and anaphylaxis). Conclusion: in this cohort, 50% of patients who received Plasmapheresis as therapy for severe Antibody-mediated renal allograft rejection presented loss graft after one year of follow up. It is necessary adding to this therapy new treatment alternatives, among them intravenous immunoglobulin, rituximab, eculizumab and bortezomib. MED.UIS. 2016;29(2):41-8. Keywords: Plasmapheresis. Graft rejection. Graft Survival. Kidney transplantation.

The mechanosensory apparatus that detects sound-induced vibrations in the cochlea is located on the apex of the auditory sensory hair cells and it is made up of actin-filled projections, called stereocilia. In young rodents, stereocilia bundles of auditory hair cells consist of 3-4 rows of stereocilia of decreasing height and varying thickness. Morphological studies of the auditory stereocilia bundles in live hair cells have been challenging because the diameter of each stereocilium is near or below the resolution limit of optical microscopy. In theory, scanning probe microscopy techniques, such as atomic force microscopy, could visualize the surface of a living cell at a nanoscale resolution. However, their implementations for hair cell imaging have been largely unsuccessful because the probe usually damages the bundle and disrupts the bundle cohesiveness during imaging. We overcome these limitations by using hopping probe ion conductance microscopy (HPICM), a non-contact scanning probe technique that is ideally suited for the imaging of live cells with a complex topography. Organ of Corti explants are placed in a physiological solution and then a glass nanopipette-which is connected to a 3D-positioning piezoelectric system and to a patch clamp amplifier-is used to scan the surface of the live hair cells at nanometer resolution without ever touching the cell surface.Here, we provide a detailed protocol for the imaging of mouse or rat stereocilia bundles in live auditory hair cells using HPICM. We provide information about the fabrication of the nanopipettes, the calibration of the HPICM setup, the parameters we have optimized for the imaging of live stereocilia bundles and, lastly, a few basic image post-processing manipulations.

Peripherally induced Tregs (iTregs) are being recognized as a functional and physiologically relevant T-cell subset. Understanding the molecular basis of their development is a necessary step before the therapeutic potential of iTreg manipulation can be exploited. In this study, we report that the differentiation of primary human T cells to suppressor iTregs involves the relocation of key proximal TCR signaling elements to the highly active IL-2-Receptor (IL-2-R) pathway. In addition to the recruitment of lymphocyte-specific protein tyrosine kinase (Lck) to the IL-2-R complex, we identified the dissociation of the voltage-gated K(+) channel Kv1.3 from the TCR pathway and its functional coupling to the IL-2-R. The regulatory switch of Kv1.3 activity in iTregs may constitute an important contributing factor in the signaling rewiring associated with the development of peripheral human iTregs and sheds new light upon the reciprocal crosstalk between the TCR and the IL-2-R pathways.

Delayed graft function occurs in about 20 to 50 percent of kidney transplants. To describe the behavior of urinary neutrophil gelatinase-associated lipocalin (NGALu) in deceased-donor renal transplant recipients and to compare this indicator with the percentage of creatinine decrease (PdC) for the early detection of delayed graft function. NGALu levels were evaluated in a prospective cohort in the first, 12th, 24th and 48th hours after kidney transplant, and compared with the daily PdC until day 5. We included 79 patients in the study. Delayed graft function occurred in 13 patients (16.5%), and five patients (6.3%) required dialysis in the first week. NGALu levels at all cut-off points were higher in patients with delayed graft function (p=0.526, p=0.049, p=0.032, and p=0.001). NGALu levels above 120 ng/ml at 48 hours predicted delayed graft function with a sensitivity of 75% and a specificity of 71%. A PdC of 59.5% best discriminated the delayed graft function, with a sensitivity of 92% and a specificity of 83% at 48 hours. Using logistic regression for the adjusted delayed graft function, the only significant values to predict it were those of PdC. NGALu levels measured at 48 hours after renal transplantation predicted delayed graft function, including the need for dialysis; however, this marker was not superior to the PdC for early detection.

Steroids are the cornerstone of therapy for nephrotic syndrome (NS) with a remission rate as high as 90%. In patients who do not respond to them or are steroid dependent, other immunosuppressive drugs have been used. Although rituximab use in NS is off-label, many authors have published their experience with it. Objective and methods: To describe retrospectively a group of seven children with nephrotic syndrome, either steroid-dependent (SDNS) or steroid-resistant (SRNS), treated with rituximab and mycophenolate, at Pablo Tobón Uribe Hospital, in Medellín, Colombia. Results: Two patients with SDNS and five with SRNS were evaluated; median age at diagnosis was 2 years (p25-75: 1-5); six months after treatment with rituximab there was reduction in proteinuria (93%), in the steroid dose (100%) and in the relapse episodes. However, proteinuria reappeared 12 months after treatment. Conclusion: During the first year after rituximab treatment of NS there is reduction in proteinuria and in the steroid dose, but thereafter there is relapse. It is suggested to carry out another study using a second dose of rituximab one year after the first one. RESUMEN: Los esteroides son el tratamiento de elección del síndrome nefrótico con tasas de éxito hasta del 90%. En pacientes que no responden adecuadamente a ellos, se han usado diferentes esquemas de inmunosupresión. Objetivo y métodos: describir la respuesta terapéutica en un grupo de siete niños con síndrome nefrótico córtico-dependiente (SNCD) o córtico-resistente (SNCR) que recibieron tratamiento con rituximab y micofenolato mofetil en un hospital universitario de la ciudad de Medellín durante los años 2010-2012. Resultados: dos pacientes tenían SNCD y cinco, SNCR; la mediana de edad en el momento del diagnóstico fue de 2 años (p25-75: 1-5); seis meses después de la aplicación del rituximab se encontró disminución de la proteinuria en el 93% de los pacientes; los esteroides se lograron suspender en el 100%; además, disminuyó el número de recaídas; sin embargo, la proteinuria reapareció un año después de dicho tratamiento. Conclusión: con el rituximab disminuyen la proteinuria y la dosis de esteroides, pero la enfermedad recurre 12 meses después de usarlo. Se sugiere hacer otro estudio evaluando el efecto de una segunda dosis de rituximab al año de la primera. COL0058784

Common variable immunodeficiency is a heterogeneous syndrome characterized by recurrent infections, hypogammaglobulinemia and defective production of specific antibodies. Abnormalities in peripheral blood lymphocyte subpopulations, in particular of B lymphocytes, allow the classification of patients into homogeneous groups.To perform a clinical and immunological characterization and to evaluate lymphocyte subpopulations of twelve Colombian patients with common variable immunodeficiency in order to define homogeneous groups.We reviewed medical records and evaluated serum immunoglobulins (Ig), lymphoproliferation, delayed hypersensitivity and used flow cytometry to quantify peripheral blood total lymphocyte and B cell populations.All patients had recurrent respiratory and/or gastrointestinal infections, while some also had infections affecting other systems. All patients had abnormally low serum IgG levels, while IgA and IgM levels were reduced in nine and ten patients, respectively. Lymphoproliferation to mitogen was lower in patients than in healthy controls but lymphoproliferation to specific antigen was normal in all. Flow cytometry revealed high numbers of T cells in three patients, while seven had a low CD4+/CD8+ ratio and four had reduced NK cells . Eleven patients had normal B cell counts, and eight of them also showed decreased memory B lymphocytes, and four had increased transitional or CD21 low B lymphocytes.Lymphocyte typing allowed assigning all but one patient to homogeneous groups according to international classification schemes, indicating the necessity of including more criteria until an ideal classification is achieved. This study will lead to a better medical monitoring of common variable immunodeficiency patients in groups at high risk of developing clinical complications.

Nephrotic syndrome (NS) is a glomerular disease that frequently affects children. There have been few studies on it in Colombia. Objective: To describe the clinical and epidemiological features of children with SN treated at HUSVP between 1960 and 2009. Methodology: Retrospective and descriptive study. Results: Steroid-sensitive nephrotic syndrome was diagnosed in 87.9% of the patients, and between 1.7%-5.4% turned steroid-resistant. Biopsies revealed disease with minimal changes in 43.6% and focal segmental glomerulosclerosis in 37.3%. Additional immunosuppressive therapy was required by 40% of the patients; in 88.8% of these, cyclophosphamide was used, and remission was achieved in 85.7%. In 56% of the cases there were complications that were infectious in 52%. Nine percent of the patients progressed to end-stage renal disease. Mortality rate was 5.7%. Discussion: The large number of patients with nephrotic syndrome studied in this series and the long period of follow-up (up to 35 years) provide valuable information about the clinical behavior of this syndrome in Colombia and on its response to immunosuppressive therapy. RESUMEN: El síndrome nefrótico (SN) es una de las enfermedades glomerulares más frecuentes en la infancia y son pocos los estudios realizados en Colombia sobre esta enfermedad. Objetivo: describir las características clínicas y epidemiológicas de los niños con SN atendidos en el Hospital Universitario San Vicente de Paúl, de Medellín, Colombia, entre los años 1960-2009. Metodología: estudio descriptivo retrospectivo. Resultados: el 87,9% de los pacientes fueron corticosensibles, entre 1,7%-5,4% se tornaron corticorresistentes. La histopatología predominante fue la del síndrome nefrótico con cambios mínimos (43,6%) seguida por la glomeruloesclerosis focal y segmentaria (37,3%). El 40% requirieron inmunosupresión adicional; en 88,8% de estos se utilizó ciclofosfamida con remisión en 85,7%. Se presentaron complicaciones en 56% y 52% de ellas fueron infecciosas. El 9% de los pacientes llegaron a la insuficiencia renal crónica. La tasa de mortalidad fue del 5,7%. Discusión: esta es una de las series más grandes de pacientes con SN reportadas hasta el momento y con un período de seguimiento de hasta 35 años, lo que aporta información valiosa sobre el comportamiento local de la enfermedad y la respuesta al tratamiento inmunosupresor, El seguimiento a largo plazo de estos pacientes es fundamental para ofrecer el mejor tratamiento disponible y nos plantea nuevos interrogantes sobre la evolución del SN en nuestra población.

Introducción: una de las principales infecciones bacterianas en la población pediátrica es la infección urinaria (ITU). Factores asociados como reflujo vesicoureteral (RVU), valvas de la uretra posterior, vejiga neurogénica y otras malformaciones anatómicas aumentan la probabilidad de desarrollar cicatrices renales y displasia/hipoplasia, lo que a su vez eleva el riesgo de hipertensión arterial (HTA), proteinuria y enfermedad renal crónica (ERC) a largo plazo. Objetivo: describir las malformaciones asociadas a ITU y la frecuencia de desarrollo de ERC en pacientes pediátricos que consultaron al Hospital Universitario San Vicente de Paúl entre 1960 y 2010. Metodología: estudio descriptivo, retrospectivo, en el que se evaluaron 4.476 registros de pacientes con diagnóstico de ITU. Resultados: los pacientes con anomalías de las vías urinarias correspondieron al 78,3% (con predominio de mujeres: 52,8%). Se encontró RVU primario en 29,9%; de estos 5,1% evolucionaron a ERC. La vejiga neurogénica se diagnosticó en 8,1%, de los cuales 70,8% fueron secundarios a mielomeningocele y 4,9% desarrollaron ERC. Las valvas de la uretra posterior se presentaron en 3,5% de la muestra total, de los cuales el 28,5% llegaron a ERC. Conclusión: la ITU en la población pediátrica es un marcador de malformación de la vía urinaria y su pronóstico está determinado por la presencia de RVU, anomalías obstructivas y/o displasia renal que favorecen la aparición de cicatrices renales y aumentan el riesgo de HTA, proteinuria y ERC. Un enfoque diagnóstico adecuado permitiría establecer estrategias de manejo con el objetivo de evitar el deterioro de la función renal.

Introducción. La función retardada del injerto renal se presenta en 20 a 50 % de los trasplantes renales.Objetivo. Describir el comportamiento de la lipocalina urinaria asociada a la gelatinasa de neutrófilos en receptores de trasplante renal de donante fallecido y compararlo con el porcentaje de descenso de la creatinina sérica para detectar tempranamente la función retardada del injerto renal.Materiales y métodos. Se evaluaron los niveles de lipocalina urinaria asociada a la gelatinasa de neutrófilos en una cohorte prospectiva 1, 12, 24 y 48 horas después del trasplante renal, y se compararon diariamente con los de la creatinina sérica hasta el quinto día del trasplante.Resultados. Se incluyeron en el estudio 79 pacientes con trasplante renal de donante fallecido. La función retardada del injerto renal se presentó en 13 pacientes (16,5 %) y cinco de ellos (6,3 %) necesitaron diálisis en la primera semana. Los valores de lipocalina urinaria asociada a la gelatinasa de neutrófilos en todos los puntos de corte fueron mayores en los pacientes con función retardada del injerto renal (p=0,526, p=0,049, p=0,032 y p=0,001, respectivamente). Se estableció un valor de más de 120 ng/ml a las 48 horas como factor de predicción de la función retardada del injerto, con una sensibilidad de 75 % y una especificidad de 71 %; el valor de creatinina sérica que mejor discriminó la función retardada se presentó a las 48 horas (59,5 %), con una sensibilidad de 92 % y una especificidad de 83 %. En la regresión logística los únicos valores significativos para predecir la función retardada del injerto renal fueron los de la creatinina serica.Conclusión. Los niveles de lipocalina urinaria asociada a la gelatinasa de neutrófilos a las 48 horas del trasplante renal predijeron la función retardada, incluida la necesidad de diálisis, pero no fueron superiores a los de la creatinina sérica para la detección temprana.