The Past, Present, and Future in the Diagnosis of a Neglected Sexually Transmitted Infection: Trichomoniasis.

More than one million curable sexually transmitted infections occur every day. Trichomonas vaginalis is one of the main infections responsible for these epidemiological data; however, the diagnosis of this protozoan is still mainly based on microscopic and culture identification. The commercialization of immunological tests and the development of molecular techniques have improved the sensitivity of classical methods. Nevertheless, the fact that trichomoniasis is a neglected parasitic infection hinders the development of novel techniques and their implementation in routine diagnosis. This review article shows the different methods developed to identify T. vaginalis in population and the difficulties in diagnosing male and asymptomatic patients. The importance of including this parasite in routine gynecological screening, especially in pregnant women, and the importance of considering T. vaginalis as an indicator of high-risk sexual behavior are also discussed.

Early warning systems and end-user decision-making: A risk formalism tool to aid communication and understanding.

In this work, we introduce a formalism to highlight the role of decision-making implicit in the setup of early warning systems (EWSs) and its consequences with respect to loss avoidance for end users. The formalism, a close relative of the cost/loss approach, combines EWS verification scores with traditional expressions of risk from the point of view of the user. This formalism articulates in mathematical format many well-known issues surrounding EWS usage, offering a conceptual anchor for concepts that otherwise may seem to wobble among the multidisciplinary perspectives participating in the EWS chain. This decision model is visually represented in a variation of the popular "performance diagram" used in forecast and warning verification. Our diagram adds to this the perspective of a generic user, in an effort to gain insight into how choices made regarding EWS settings may determine which users benefit from warnings and which do not. Although these results are based on a conceptual model, they are useful to better understand the actual benefits experienced by users and to highlight aspects that may temper unrealistic expectations on EWSs. The recent United Nations initiative to extend EWSs for natural hazards to all nations within 5 years will make EWSs more common and more public. The approach proposed here can be a tool to promote greater transparency and improve the necessary dialog between warning issuers and users in order to reduce loss.

Actualización en lesión renal aguda inducida por contraste en pediatría

Contexto: la lesión renal aguda inducida por contraste se ha convertido en un tema de gran interés en la comunidad médica a nivel mundial, siendo la tercera causa de lesión renal aguda adquirida en el hospital. Objetivo: el presente artículo presenta una revisión de la literatura con el fin de actualizar los conceptos de esta patología en el personal de la salud que está en contacto con la población pediátrica y que es sometida a procedimientos con medios de contraste. Metodología: en esta revisión narrativa de la literatura, presentamos la definición, los factores de riesgo, el enfoque clínico y las medidas preventivas de la nefropatía inducida por contraste en pediatría. Resultados: se define que hay un deterioro en la función renal aguda después de la administración del medio de contraste en donde se excluyen otras posibles etiologías y se establece una verdadera relación causal con la sustancia. Los factores de riesgo son múltiples, sin embargo, factores estrictamente relacionados en los niños no han sido establecidos en su totalidad. El abordaje de los pacientes que van a ser sometidos a estudios con medios de contraste inicia desde una historia clínica, un examen físico y unas medidas de laboratorio que permiten evaluar el estado basal de cada paciente para instaurar medidas preventivas. Por su parte, las estrategias de prevención de esta condición son múltiples, sin embargo, no existen guías basadas en la evidencia acerca de esta condición en el paciente pediátrico. Conclusiones: el artículo presenta una revisión de la literatura sobre lesión renal aguda para actualizar los conceptos de esta patología en el personal de la salud que está en contacto con la población pediátrica que se somete a procedimientos con medios de contraste.

Context: Contrast-induced acute kidney injury has become a topic of great interest in the medical community worldwide, being the third cause of hospital-acquired acute kidney injury. Purpose: This article presents a review of the literature in order to update the concepts of this pathology in health personnel who are in contact with the pediatric population that undergoes procedures with contrast media. Methodology: In this narrative review of the literature, we present the definition, risk factors, clinical approach, and preventive measures of contrast-induced nephropathy in pediatrics. Results: It is defined as a deterioration in acute renal function after the administration of the contrast medium where other possible etiologies are excluded and a true causal relationship with the substance is established. The risk factors are multiple; nevertheless; Strictly related factors in children have not been fully established. The approach to patients who are going to undergo studies with contrast media begins with a clinical history, physical examination, and laboratory measurements that allow the baseline status of each patient to be evaluated in order to establish preventive measures. The prevention strategies of this condition are multiple; however, there are no evidence-based guidelines on this condition in pediatric patients. Conclusions: This article presents a review of the literature in order to update the concepts of acute kidney injury in health personnel who are in contact with the pediatric population that undergoes procedures with contrast media.

Multi-institutional expert update on the use of laparoscopic bile duct exploration in the management of choledocholithiasis: Lesson learned from 3950 procedures.

BACKGROUND: Recently there has been a growing interest in the laparoscopic management of common bile duct stones with gallbladder in situ (LBDE), which is favoring the expansion of this technique. Our study identified the standardization factors of LBDE and its implementation in the single-stage management of choledocholithiasis. METHODS: A retrospective multi-institutional study among 17 centers with proven experience in LBDE was performed. A cross-sectional survey consisting of a semi-structured pretested questionnaire was distributed covering the main aspects on the use of LBDE in the management of choledocholithiasis. RESULTS: A total of 3950 LBDEs were analyzed. The most frequent indication was jaundice (58.8%). LBDEs were performed after failed ERCP in 15.2%. The most common approach used was the transcystic (63.11%). The overall series failure rate of LBDE was 4% and the median rate for each center was 6% (IQR, 4.5-12.5). Median operative time ranged between 60-120 min (70.6%). Overall morbidity rate was 14.6%, with a postoperative bile leak and complications ≥3a rate of 4.5% and 2.5%, respectively. The operative time decreased with experience (P = .03) and length of hospital stay was longer in the presence of a biliary leak (P = .04). Current training of LBDE was defined as poor or very poor by 82.4%. CONCLUSION: Based on this multicenter survey, LBDE is a safe and effective approach when performed by experienced teams. The generalization of LBDE will be based on developing training programs.

Grafting Snake Melon [Cucumis melo L. subsp. melo Var. flexuosus (L.) Naudin] in Organic Farming: Effects on Agronomic Performance; Resistance to Pathogens; Sugar, Acid, and VOC Profiles; and Consumer Acceptance.

The performance of snake melon [Cucumis melo var. flexuosus (L.)] in organic farming was studied under high biotic and salt stress conditions. Soilborne diseases (mainly caused by Macrophomina phaseolina and Neocosmospora falciformis), combined with virus incidence [Watermelon mosaic virus (WMV), Zucchini yellow mosaic virus (ZYMV), and Tomato leaf curl New Delhi virus (ToLCNDV)] and Podosphaera xanthii attacks, reduced yield by more than 50%. Snake melon susceptibility to M. phaseolina and Monosporascus cannonballus was proved in pathogenicity tests, while it showed some degree of resistance to Neocosmospora keratoplastica and N. falciformis. On the contrary, salt stress had a minor impact, although a synergic effect was detected: yield losses caused by biotic stress increased dramatically when combined with salt stress. Under biotic stress, grafting onto the melon F1Pat81 and wild Cucumis rootstocks consistently reduced plant mortality in different agroecological conditions, with a better performance compared to classic Cucurbita commercial hybrids. Yield was even improved under saline conditions in grafted plants. A negative effect was detected, though, on consumer acceptability, especially with the use of Cucurbita rootstocks. Cucumis F1Pat81 rootstock minimized this side effect, which was probably related to changes in the profile of sugars, acids, and volatiles. Grafting affected sugars and organic acid contents, with this effect being more accentuated with the use of Cucurbita rootstocks than with Cucumis. In fact, the latter had a higher impact on the volatile organic compound profile than on sugar and acid profile, which may have resulted in a lower effect on consumer perception. The use of Cucumis rootstocks seems to be a strategy to enable organic farming production of snake melon targeted to high-quality markets in order to promote the cultivation of this neglected crop.

Promising hit compounds against resistant trichomoniasis: Synthesis and antiparasitic activity of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles.

A series of 11 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles (2-12) has been prepared starting from 1-benzyl-5-nitroindazol-3-ol 13, and evaluated against sensitive and resistant isolates of the sexually transmitted protozoan Trichomonas vaginalis. Compounds 2, 3, 6, 9, 10 and 11 showed trichomonacidal profiles with IC50 < 20 µM against the metronidazole-sensitive isolate. Moreover, all these compounds submitted to cytotoxicity assays against mammalian cells exhibited low non-specific cytotoxic effects, except compounds 3 and 9 which displayed moderate cytotoxicity (CC50 = 74.7 and 59.1 µM, respectively). Those compounds with trichomonacidal effect were also evaluated against a metronidazole-resistant culture. Special mention deserve compounds 6 and 10, which displayed better IC50 values (1.3 and 0.5 µM respectively) than that of the reference drug (IC50 MTZ = 3.0 µM). The high activity of these compounds against the resistant isolate reinforces the absence of cross-resistance with the reference drug. The remarkable trichomonacidal results against resistant T. vaginalis isolates suggest the interest of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles to be considered as good prototypes to continue in the development of new drugs with enhanced trichomonacidal activity, aiming to increase the non-existent drugs to face clinical resistance efficiently for those patients in whom therapy with 5-nitroimidazoles is contraindicated.

Frequency of arterial hypertension, diabetes and dyslipidemia in children after kidney transplants. / Frecuencia de hipertensión arterial, diabetes y dislipidemia en niños con trasplante renal

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.

INTRODUCCIÓN: Los pacientes pediátricos con trasplante renal tienen un riesgo incrementado de desarrollar hipertensión arterial, dislipidemia, intolerancia a los hidratos de carbono y diabetes mellitus, factores de riesgo que se asocian con una mayor morbilidad y mortalidad cardiovascular. OBJETIVO: Evaluar la frecuencia de hipertensión arterial, dislipidemia y alteración en el metabolismo de los hidratos de carbono en una cohorte de pacientes pediátricos con trasplante renal durante 2006-2016 en el Hospital Pablo Tobon Uribe, en Colombia. MATERIAL Y MÉTODOS: Estudio descriptivo retrospectivo en el cual se utilizó estadística descriptiva. Adicionalmente se realizó análisis bivariado para comparar pacientes según el desenlace hipertensión arterial, dislipidemia y alteración en el metabolismo de los hidratos de carbono. RESULTADOS: De un total de 48 trasplantes renales pediátricos en el periodo estudiado, se obtuvo información completa de 43 pacientes al año de seguimiento. Se observó una frecuencia postrasplante de hipertensión arterial del 86%, de dislipidemia del 48%, de intolerancia a los hidratos de carbono del 14% y de diabetes del 2%. CONCLUSIONES: En la cohorte evaluada se encontró una alta frecuencia de hipertensión arterial y dislipidemia postrasplante renal. Se sugiere el desarrollo de guías de diagnóstico precoz y tratamiento que permitan disminuir el impacto de estas enfermedades asociadas a riesgo cardiovascular en la vida adulta.

Climate drives community-wide divergence within species over a limited spatial scale: evidence from an oceanic island.

Geographic isolation substantially contributes to species endemism on oceanic islands when speciation involves the colonisation of a new island. However, less is understood about the drivers of speciation within islands. What is lacking is a general understanding of the geographic scale of gene flow limitation within islands, and thus the spatial scale and drivers of geographical speciation within insular contexts. Using a community of beetle species, we show that when dispersal ability and climate tolerance are restricted, microclimatic variation over distances of only a few kilometres can maintain strong geographic isolation extending back several millions of years. Further to this, we demonstrate congruent diversification with gene flow across species, mediated by Quaternary climate oscillations that have facilitated a dynamic of isolation and secondary contact. The unprecedented scale of parallel species responses to a common environmental driver for evolutionary change has profound consequences for understanding past and future species responses to climate variation.

Factores relacionados con el desarrollo de proyectos de investigación científica disciplinar por personal de enfermería / Factors related to the development of curricular scientific research projects made by the nursing staff

Introducción: es ineludible revisar la situación de la investigación en enfermería en relación con las condicionantes y dificultades que entraña esta actividad para los profesionales de enfermería. Objetivo: identificar los factores relacionados con el desarrollo de proyectos de investigación científica disciplinar por el personal de enfermería de un hospital de tercer nivel de atención del Instituto Mexicano del Seguro Social (IMSS). Métodos: estudio descriptivo transversal que incluyó una muestra aleatoria de 177 enfermeras. Se aplicó un cuestionario diseñado para el estudio y estructurado con 25 preguntas, con alfa de Cronbach de 0.772. Las variables cualitativas se analizaron con porcentajes y frecuencias, y las cuantitativas con medidas de tendencia central y de dispersión. El análisis de factores se hizo con chi cuadrada. Resultados: la media de edad fue de 41 ± 7.91 años. El nivel académico del personal fue técnico en 46.9% y de licenciatura en 46.3%. El 15.3% del personal ha hecho proyectos de investigación; no obstante que el 5.6% del personal opina que casi siempre dedica tiempo para hacer investigación, 4.5% cuenta con apoyo económico en su área laboral para realizarla y 4% ha publicado. Fue significativa la relación entre quien hace investigación con el tiempo para su desarrollo (p < 0.05), así como con la publicación de artículos (p < 0.05). Conclusión: el desarrollo de proyectos de investigación científica disciplinar por el personal de enfermería está relacionado con el tiempo que dedican para ello y la publicación de artículos.

Introduction: It is unavoidable to review the status of nursing research, concerning the conditions and difficulties that this activity entails for nursing professionals. Objective: To identify the factors related to the development of curricular scientific research projects by the nursing staff from a third level hospital of the Instituto Mexicano del Seguro Social (IMSS). Methods: Cross-sectional descriptive study which included a random sample of 177 nurses. A questionnaire designed for the study and structured with 25 questions was administered; it had a Cronbach's alpha of 0.772. Qualitative variables were analyzed with percentages and frequencies and quantitative variables with measures of central tendency and dispersion. The factor analysis was carried out with chi-square test. Results: Mean age was 41 ± 7.91 years. The school level of staff was technical in 46.9% and undergraduate in 46.3%. 15.3% has done research projects; despite the fact that 5.6% of staff believe that they almost always dedicate time to do research, 4.5% have financial support in their work area to carry it out and 4% have published. It was significant the relationship between those who carry out research with the time they take to develop it (p < 0.05), as well as with the publication of articles (p < 0.05). Conclusion: The development of curricular scientific research projects by nurses is related to the time they spend on it and the publication of articles.

Antichagasic, Leishmanicidal, and Trichomonacidal Activity of 2-Benzyl-5-nitroindazole-Derived Amines.

Three different series of new 5-nitroindazole derivatives-1-(ω-aminoalkyl)-2-benzylindazolin-3-ones (series A; ten compounds), 3-(ω-aminoalkoxy)-2-benzylindazoles (series B; four compounds) and 3-alkylamino-2-benzylindazoles (series C; five compounds)-have been synthesized and evaluated against the protozoan parasites Trypanosoma cruzi, Leishmania amazonensis, and Trichomonas vaginalis: etiological agents of Chagas disease, cutaneous leishmaniasis, and trichomoniasis, respectively. Many indazoles of series A, B, and C were efficient against T. cruzi. Some compounds in series A, after successfully passing the preliminary screening for epimastigotes, exhibited activity values against amastigotes of several T. cruzi strains that were better than or similar to those shown by the reference drug benznidazole and displayed low nonspecific toxicity against mammalian cells. On the other hand, preliminary studies against promastigotes of L. amazonensis showed high leishmanicidal activity for some derivatives of series A and C. With regard to activity against T. vaginalis, some indazoles of series B and C were rather efficient against trophozoites of a metronidazole-sensitive isolate and showed low nonspecific toxicities toward Vero cell cultures. Additionally, some of these compounds displayed similar activity against metronidazole-sensitive and resistant isolates, showing the absence of cross-resistance between these derivatives and the reference drug.

Evaluación y tratamiento del niño con síntomas del tracto urinario inferior (LUTS) / Evaluation and management of children with lower urinary tract symptoms (LUTS)

RESUMEN La disfunción miccional es un trastorno del llenado o vaciado de la vejiga en niños sin alteraciones neurológicas o anatómicas. Los síntomas del tracto urinario inferior (LUTS, por la sigla en inglés de Lower urinary tract symptoms) son un motivo frecuente de consulta con el pediatra, el nefrólogo o el urólogo pediatra, e incluso con el neurólogo y el psicólogo infantil. Se le considera una enfermedad relativamente benigna lo que en ocasiones genera desinterés entre médicos y familiares y lleva a consultas tardías e interpretación inadecuada de los síntomas. Manifestaciones como urgencia, incontinencia, enuresis, goteo posmiccional, infecciones urinarias, vulvovaginitis recurrente y constipación, en un niño sin enfermedad neurológica, deben hacer pensar al médico en disfunción miccional para enfocar oportunamente el diagnóstico, restablecer la calidad de vida del paciente, evitar las infecciones urinarias y el daño renal subsecuente e irreversible secundario a un diagnóstico tardío. Las recomendaciones actuales hacen énfasis en un enfoque menos invasivo, tratamiento conservador, manejo de la constipación y reentrenamiento vesical. Este artículo discute la evaluación, el diagnóstico y el tratamiento correctos de niños con LUTS.

SUMMARY Voiding dysfunction is a disorder of the bladder filling or emptying in children without neurological or anatomical disorders. Lower urinary tract symptoms (LUTS) are a frequent reason for consulting the pediatrician, nephrologist or pediatric urologist, and even the neurologist and child psychologist. It is considered a relatively benign disease that sometimes generates disinterest among doctors and families, leading to late consultation and inadequate interpretation of symptoms. Urgency, incontinence, enuresis, post-void dribbling, urinary tract infections, recurrent vulvovaginitis and constipation in children without neurological disease should lead to consider the possibility of voiding dysfunction, in order to recognize it timely, restore the quality of life, prevent urinary tract infection and the irreversible kidney damage secondary to delayed diagnosis. Current recommendations emphasize on a less invasive approach, conservative treatment, management of constipation and bladder retraining. This article discusses the correct assessment, diagnosis and management of children with LUTS.

Neutrophil gelatinase-associated lipocalin as an early predictor of delayed graft function.

INTRODUCTION: Delayed graft function occurs in about 20 to 50 percent of kidney transplants.  OBJECTIVE: 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.  MATERIALS AND METHODS: 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.  RESULTS: 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.  CONCLUSIONS: 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.

Plasmaféresis en rechazo agudo del injerto renal mediado por anticuerpos. Estudio realizado en el Hospital Pablo Tobón Uribe, Medellín, Colombia. Año 2005-2015 / Plasmapheresis in antibody-mediated renal allograft rejection. Experience of Pablo Tobon Uribe, Medellin, Colombia. Year 2005-2015

Introducción: el rechazo agudo mediado por anticuerpos es una complicación que se presenta luego del trasplante renal y es una causa importante de pérdida del injerto. La plasmaféresis es una de las terapias utilizadas para su tratamiento, algunos estudios sugieren mejor supervivencia del injerto renal con el uso de plasmaféresis; sin embargo su evidencia es débil. Objetivo: este estudio tiene como objetivo describir la experiencia del uso de plasmaféresis en el rechazo agudo mediado por anticuerpos. Materiales y Métodos: estudio descriptivo retrospectivo realizado en el Hospital Pablo Tobón Uribe entre agosto de 2005 y junio de 2015 en pacientes con diagnóstico de rechazo agudo mediado por anticuerpos, quienes recibieron entre tres y nueve sesiones de plasmaféresis. Resultados: se realizaron un total de 769 trasplantes renales; de los cuales 26 pacientes presentaron rechazo agudo mediado por anticuerpos y recibieron plasmaféresis como parte del tratamiento. Todos los pacientes recibieron terapia de inducción al momento del trasplante y en el 80,8% la terapia de mantenimiento utilizada fue tacrolimus-micofenolato-prednisolona. El rechazo mediado por anticuerpos se presentó en forma temprana en el 61,5% de los pacientes. A seis y doce meses el 44% y 53,8% de los pacientes respectivamente presentaron pérdida del injerto renal; las complicaciones se presentaron en el 53,8% de los pacientes, las cuales fueron hipocalcemia, hipotensión y anafilaxia. Conclusión: en esta cohorte el uso de plasmaféresis en el rechazo agudo mediado por anticuerpos no logró evitar la pérdida del injerto renal en el 50% de los pacientes; se sugiere adicionar a esta terapia otras alternativas de tratamiento entre ellas, la inmunoglobulinas intravenosas, rituximab, eculizumab y bortezomib. MÉD.UIS. 2016;29(2):41-8.

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 Tobón 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. MÉD.UIS. 2016;29(2):41-8.

La lipocalina asociada con la gelatinasa de neutrófilos como factor temprano de predicción de la función retardada del injerto renal / Neutrophil gelatinase-associated lipocalin as an early predictor of delayed graft function

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.

Introduction: Delayed graft function occurs in about 20 to 50 percent of kidney transplants. Objective: 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. Materials and methods: 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. Results: 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. Conclusions: 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.

Antichagasic and trichomonacidal activity of 1-substituted 2-benzyl-5-nitroindazolin-3-ones and 3-alkoxy-2-benzyl-5-nitro-2H-indazoles.

Two series of new 5-nitroindazole derivatives, 1-substituted 2-benzylindazolin-3-ones (6-29, series A) and 3-alkoxy-2-benzyl-2H-indazoles (30-37, series B), containing differently functionalized chains at position 1 and 3, respectively, have been synthesized starting from 2-benzyl-5-nitroindazolin-3-one 5, and evaluated against the protozoan parasites Trypanosoma cruzi and Trichomonas vaginalis, etiological agents of Chagas disease and trichomonosis, respectively. Many indazolinones of series A were efficient against different morphological forms of T. cruzi CL Brener strain (compounds 6, 7, 9, 10 and 19-21: IC50 = 1.58-4.19 µM for epimastigotes; compounds 6, 19-21 and 24: IC50 = 0.22-0.54 µM for amastigotes) being as potent as the reference drug benznidazole. SAR analysis suggests that electron-donating groups at position 1 of indazolinone ring are associated with an improved antichagasic activity. Moreover, compounds of series A displayed low unspecific toxicities against an in vitro model of mammalian cells (fibroblasts), which were reflected in high values of the selectivity indexes (SI). Compound 20 was also very efficient against amastigotes from Tulahuen and Y strains of T. cruzi (IC50 = 0.81 and 0.60 µM, respectively), showing low toxicity towards cardiac cells (LC50 > 100 µM). In what concerns compounds of series B, some of them displayed moderate activity against trophozoites of a metronidazole-sensitive isolate of T. vaginalis (35 and 36: IC50 = 9.82 and 7.25 µM, respectively), with low unspecific toxicity towards Vero cells. Compound 36 was also active against a metronidazole-resistant isolate (IC50 = 9.11 µM) and can thus be considered a good prototype for the development of drugs directed to T. vaginalis resistant to 5-nitroimidazoles.

In vitro trichomonacidal activity and preliminary in silico chemometric studies of 5-nitroindazolin-3-one and 3-alkoxy-5-nitroindazole derivatives.

A selection of 1,2-disubstituted 5-nitroindazolin-3-ones (1-19) and 3-alkoxy-5-nitroindazoles substituted at positions 1 (20-24) or 2 (25-39) from our in-house compound library were screened in vitro against the most common curable sexually transmitted pathogen, Trichomonas vaginalis. A total of 41% of the studied molecules (16/39) achieved a significant activity of more than 85% growth inhibition at the highest concentration assayed (100 µg mL(-1)). Among these compounds, 3-alkoxy-5-nitroindazole derivatives 23, 24, 25 and 27 inhibited parasite growth by more than 50% at 10 µg mL(-1). In addition, the first two compounds (23, 24) still showed remarkable activity at the lowest dose tested (1 µg mL(-1)), inhibiting parasite growth by nearly 40%. Their specific activity towards the parasite was corroborated by the determination of their non-specific cytotoxicity against mammalian cells. The four mentioned compounds exhibited non-cytotoxic profiles at all of the concentrations assayed, showing a fair antiparasitic selectivity index (SI > 7·5). In silico studies were performed to predict pharmacokinetic properties, toxicity and drug-score using Molinspiration and OSIRIS computational tools. The current in vitro results supported by the virtual screening suggest 2-substituted and, especially, 1-substituted 3-alkoxy-5-nitroindazoles as promising starting scaffolds for further development of novel chemical compounds with the main aim of promoting highly selective trichomonacidal lead-like drugs with adequate pharmacokinetic and toxicological profiles.

Hallazgos nefro-urológicos postnatales de pacientes con diagnóstico prenatal de hidronefrosis evaluados en un hospital de cuarto nivel de complejidad / Postnatal nephro-urology findings of patients with prenatal diagnosis of hydronephrosis

No es clara la repercusión clínica de la hidronefrosis. Este estudio busca determinar las características de las imágenes diagnósticas de los pacientes con hidronefrosis prenatal y determinar si el valor del diámetro anteroposterior de la pelvis renal puede identificar la presencia de malformaciones urológicas posnatales y la necesidad de cirugía. Materiales y métodos: estudio transversal en el que se revisaron las historias clínicas de todos los pacientes con edades entre 0 y 5 años de edad, con diagnóstico prenatal de hidronefrosis, quienes consultaron a un hospital de cuarto nivel de complejidad en la ciudad de Medellín - Colombia. Cada unidad renal se evaluó en forma independiente. Resultados: en total se estudiaron 135 unidades renales de 97 pacientes. No se encontró hidronefrosis posnatal en el 17,8 %. Al seguimiento, el 85 % de los pacientes con estenosis pieloureteral y 90 % de los pacientes con valvas de uretra posterior fueron clasificados prenatalmente como hidronefrosis moderada a grave. Por el contrario, el 41,4 % de los riñones con diagnóstico de reflujo vesico-ureteral fueron clasificados como hidronefrosis leve, 34,5 % moderada y 24,1 % grave. El 56,3 % de los riñones necesitaron algún tipo de cirugía. El 26 % de las hidronefrosis clasificadas como leves necesitaron algún procedimiento quirúrgico. Un diámetro anteroposterior de la pelvis renal de 10,5 mm tuvo una sensibilidad de 67 % y una especificidad de 71,2 % para la detección de malformaciones nefro-urológicas. Conclusión: la hidronefrosis prenatal, independiente de su grado, puede ser indicativa de malformaciones del tracto genitourinario. Se recomienda un seguimiento estricto en los pacientes con hidronefrosis, incluso en los casos leves, para así detectar tempranamente la presencia o no de malformaciones nefro-urológicas que requieran algún tipo de intervención.

Currently, we do know the clinical repercussions of prenatal hydronephrosis. This study aims to assess the imaging features of hydronephrosis patients and to determine whether the renal pelvis value in the prenatal ultrasound correlates with the presence of urologic malformations and the need for surgery. Materials and methods: Cross sectional study. We evaluated the medical records of all patients almost 5 years old with prenatal hydronephrosis who had consulted during 2006-2010. Results: we analyzed 97 patients, for a total of 135 kidneys. 17.8 % had not hydronephosis; 85.1 % of the patients with pyeloureteral junction stenosis and 90 % of those with posterior urethral valves had been prenatally classified as having mild to severe hydronephrosis. Conversely, 41.4 % of kidneys with vesicouretral reflux were classified as having mild hydronephrosis, 34.5 % moderate and 24.14 % severe. Furthermore, 56.3 % of the evaluated kidneys needed some type of surgery. It is also worth mentioning that it was necessary to perform surgical procedures on 26 % of the kidneys with mild hydronephrosis. Finally, the analysis of the ROC curve made it possible to find that, when the pelvis has an anteroposterior diameter of 10.5 mm, the sensitivity for the detection of nephro-urologic malformations is 67 % and the specificity 71.2 %. Conclusion: prenatal hydronephrosis, regardless of its degree, may be an indication of malformations in the urinary tract. We recommend performing strict follow-ups on the patients to determine the presence of nephro-urologic malformations requiring some kind of intervention.

Sequestration of host-CD59 as potential immune evasion strategy of Trichomonas vaginalis.

Trichomonas vaginalis is known to evade complement-mediated lysis. Because the genome of T. vaginalis does not possess DNA sequence with homology to human protectin (CD59), a complement lysis restricting factor, we tested the hypothesis that host CD59 acquisition by T. vaginalis organisms mediates resistance to complement killing. This hypothesis was based on the fact that trichomonads are known to associate with host proteins. No CD59 was detected on the surface of T. vaginalis grown in serum-based medium using as probe anti-CD59 monoclonal antibody (MAb). We, therefore, infected mice intraperitoneally with live T. vaginalis, and trichomonads harvested from ascites were tested for binding of CD59. Immunofluorescence showed that parasites had surface CD59. Furthermore, as mouse erythrocytes (RBCs) possess membrane-associated CD59, and trichomonads use RBCs as a nutrient source, organisms were co-cultured with murine RBCs for one week. Parasites were shown to have detectable surface CD59. Importantly, live T. vaginalis with bound CD59 were compared with batch-grown parasites without surface-associated CD59 for sensitivity to complement in human serum. Trichomonads without surface-bound CD59 had a higher level of killing by complement than did parasites with surface CD59. These data show that host CD59 acquired onto the surface by live T. vaginalis may be an alternative mechanism for complement evasion. We describe a novel strategy by T. vaginalis consistent with host protein procurement by this parasite to evade the lytic action of complement.

Synthesis and in vitro and in vivo biological evaluation of substituted nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents.

Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3-diones with diverse substituents at positions 1 and 4 were synthesized and evaluated against the sexually transmitted parasite Trichomonas vaginalis. Furthermore, diverse molecular and drug-likeness properties were analyzed to predict the oral bioavailability following the Lipinski's "rule of five". 7-Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both kinds of compounds did not show cytotoxic effects in mammalian cells. 7-Nitro-4-(3-piperidinopropyl)quinoxalin-2-one 9 achieved the highest trichomonacidal activity (IC50 = 18.26 µM) and was subsequently assayed in vivo in a murine model of trichomonosis. A 46.13% and a 50.70% reduction of pathogenic injuries were observed in the experimental groups treated orally during 7 days with 50 mg/kg and 100 mg/kg doses. The results obtained in the biological assays against T. vaginalis indicate that compounds with ω-(dialkylamino)alkyl substituents and a keto group at positions 4 and 2 of quinoxaline ring, respectively, provide interesting structural cores to develop novel prototypes to enhance the nitroquinoxalinones activity as trichomonacidal agents with interesting ADME properties according to virtual screening analysis.