ABSTRACT INTRODUCTION: The development of monoclonal antibodies (mAbs) against Calcitonin Gene Related Peptide (CGRP) has determined a new therapeutic era in migraine prophylaxis, demonstrating its effectiveness in patients with episodic migraine (EM) and chronic migraine (CM), obtaining a response in naive patients and in those who are refractory to multiple medications. A 50% decrease in migraine attacks per month during the first 3 months of use is the approximate outcome in 50% of patients receiving this therapy. OBJECTIVE: This consensus from the Colombian Association of Neurology (ACN) has the objective of serving as a guide for the rational use of antiCGRP mAbs in patients with EM and CM. METHODS AND MATERIALS: The headache committee through the application of the Delphi methodology and discussions in subsequent meetings, develops this consensus, supported in the published literature and expert recommendations. RESULTS: Fourteen answers from headache experts were received regarding the use of drugs for migraine prophylaxis, analyzing their applicability in frequent clinical situations. DISCUSSION: AntiCGRP mAbs have proved their effectiveness with adequate pathophysiological support, but with a high price in a highly prevalent disease, there is then a need to select the patient who best benefits from this therapy. CONCLUSIONS: AntiCGRP mAbs are recommended in patients with EM and CM that have previously failed to other prophylactic drugs.

RESUMEN INTRODUCCIÓN: El desarrollo de anticuerpos monoclonales (mAbs) contra el péptido relacionado con el gen de la calcitonina (CGRP) ha determinado una nueva era terapéutica en la profilaxis de migraña, demostrando su efectividad en pacientes con migraña episódica (ME) y migraña crónica (MC), con respuesta desde pacientes naïve hasta refractarios a múltiples medicamentos. La disminución del 50% de los ataques de migraña al mes (DMM) durante los primeros 3 meses de uso es el desenlace aproximado en el 50% de los pacientes que reciben esta terapia. OBJETIVO: Este consenso de la Asociación Colombiana de Neurología (ACN) tiene el objetivo de guiar la selección y uso racional de los mAbs antiCGRP en pacientes con ME y MC. MATERIALES Y MÉTODOS: El comité de cefalea de la ACN mediante la aplicación de la metodología Delphi y discusiones en reuniones posteriores desarrolló un documento en formato de consenso soportado en literatura y recomendaciones de expertos. RESULTADOS: Se obtuvieron respuestas de 14 expertos en cefalea sobre moléculas utilizadas en profilaxis de migraña, analizando su aplicabilidad en situaciones clínicas frecuentes. DISCUSIÓN: Los mAbs antiCGRP han demostrado efectividad con adecuado soporte fisiopatológico, considerando que son moléculas de alto precio en una enfermedad de alta prevalencia, existe la necesidad de guíar la selección del paciente que mejor puede beneficiarse de su administración CONCLUSIONES: Los mAbs antiCGRP están recomendados en pacientes con ME y MC que presentan falla terapéutica a otras moléculas profilácticas.

ABSTRACT Purpose: Determine the sociodemographic and nutritional factors associated with anemia in children aged 1 to 5 years in Peru according to the Demographic and Health Survey (DHS). Methods: To determine the possible sociodemographic and nutritional factors associated with anemia, a sub-analysis of the DHS 2017 was carried out, taking into account a 95% confidence interval and considering the complexity of survey parameters. Relative frequencies were described in univariate analysis. For bivariate analysis, the chi-square test was used for categorical variables and Student t-test for continuous variables. For the multivariable analysis, a crude and an adjusted Poisson regression was done with backward method for variable selection. Main results: Independently associated factors were low wealth (aPR: 1.23; 95% CI: 1.0-1.4), no degree or primary education level of the mother (aPR: 1.25; 95%CI: 1.0-1.5), mother’s age under 19 years (aPR: 1.34; 95%CI: 1.1-1.7), not delivering in a health facility (aPR: 1.24; 95%CI: 1.1-1.5), no consumption of antiparasitic drugs (aPR: 1.13; 95%CI: 1.0-1.3) and living at greater than or equal to 4000 meters above sea level (aPR: 1.45; 95%CI: 1.2-1.8). Conclusions: The prevalence of anemia in children aged 1 to 5 years in 2017 was moderate. There are sociodemographic and nutritional factors associated with this condition.

RESUMEN Objetivo: Determinar los factores sociodemográficos y nutricionales asociados a la anemia en niños de 1 a 5 años de Perú según la Encuesta Nacional Demográfica y de Salud Familiar (DHS, por sus siglas en inglés Demographic and Health Survey). Metodología: Para determinar los posibles factores sociodemográficos y nutricionales asociados a la anemia, se hizo un subanálisis de la DHS 2017, tomando en cuenta un intervalo de confianza del 95% y considerando los parámetros de complejidad de la encuesta. Se describieron las frecuencias relativas en el análisis univariado. Para el análisis bivariado se empleó el test de chi cuadrado para las variables categóricas y t-Student para las variables continuas. Para el modelo de regresión múltiple, se realizó una regresión de Poisson cruda y ajustada con el método de selección de variables tipo backward. Principales resultados: La prevalencia de anemia fue de 38.5%. Los factores independientemente asociados fueron quintil de riqueza bajo (RP(a): 1,23; IC95%: 1,0-1,4), ningún grado de instrucción o grado de instrucción primaria de la madre (RP(a): 1,25; IC95%: 1,0-1,5), edad de la madre menor de 19 años (RP(a): 1,34; IC95%: 1,1-1,7), lugar del parto no institucionalizado (RP(a): 1,24; IC95%: 1,1-1,5), no consumo de antiparasitarios (RP(a): 1,13; IC95%:1,0-1,3) y altitud mayor o igual a 4000 msnm (RP(a): 1,45; IC95%: 1,2-1,8). Conclusiones: La prevalencia de anemia en niños de 1 a 5 años en el 2017 fue moderada. Existen factores sociodemográficos y nutricionales asociados a dicha condición.

Abstract Objectives: To determine the association between sociodemographic and reproductive factors with unwanted additional fertility (UAF) in Peru. Materials and methods: We carried out an observational, cross-sectional analytical study based on the 2018 Demographic and Family Health Survey (DHS) in Peru. The UAF variable was defined as the numerical difference between the general fertility rate and the total fertility rate. This variable was divided into 2 categories, UAF was considered when the numerical difference was positive. The Poisson regression was used, both crude and adjusted. Results: We analyzed data from 6,944 women with an average age of 44.3 years (range, 40 to 49). The prevalence of UAF was found to be 72.5% (95% CI: 70.4%-74.4%). In the adjusted model, patients in the top wealth quintile (aPR 0.80; 95% CI: 0.69-0.93) were found to have a lower probability of having unwanted pregnancies when compared to those in the middle quintile. On the other hand, patients from rural areas (aPR 1.07; 95% CI: 1.01-1.14) had a higher probability of having unwanted pregnancies when compared to those from urban áreas. Conclusions: The prevalence of UAF in Peruvian women between 40 and 49 years old who participated in the 2018 DHS is high. Patients from rural areas have a higher probability of having unwanted pregnancies, and those in the top wealth quintile have a lower probability.

Resumen Objetivos: Determinar la asociación entre los factores sociodemográficos y reproductivos con la fecundidad adicional no deseada (FAND) en el Perú. Materiales y métodos: Se realizó un estudio observacional, analítico transversal, a partir de la Encuesta Demográfica y de Salud Familiar (ENDES) 2018 en el Perú. La FAND es una variable que se creó a partir de la diferencia numérica entre la fecundidad obtenida y la fecundidad deseada. La variable FAND, se creó a partir de la diferencia numérica entre la fecundidad obtenida y la fecundidad deseada y se agrupó en dos categorías donde la diferencia numérica positiva correspondió a la presencia de FAND. Se realizó una regresión de Poisson, tanto cruda como ajustada. Resultados: Se analizaron los datos de 6944 mujeres entre 40 y 49 años, con una edad promedio de 44,3 años. Se halló una prevalencia de FAND de 72,5% (IC95%: 70,4%-74,4%). En el modelo ajustado, se observó que pertenecer al quintil superior de riqueza (RPa 0,80; IC95%: 0,69-0,93) disminuía la probabilidad de FAND con respecto al quintil intermedio. Por otro lado, provenir del ámbito rural (RPa 1,07; IC95%: 1,01-1,14), aumenta la probabilidad de FAND con respecto al provenir del ámbito urbano. Conclusiones: La prevalencia de FAND en mujeres peruanas de 40 a 49 años que participaron de la ENDES 2018 es alta. Provenir del área rural aumenta la probabilidad de FAND; y pertenecer al quintil superior de riqueza, la disminuye.

RESUMEN El manejo del paciente con estado migrañoso en urgencias incluye un arsenal terapéutico multimodal en búsqueda de la mejoría del dolor y la reducción de la recurrencia. La mayoría de los pacientes responde al manejo inicial, pero en casos no despreciables este resultado no se obtiene con las medicaciones de primera línea y es necesario el uso de otros medicamentos y opciones terapéuticas que incluyen: bloqueos pericraneales, lidocaína, levetiracetam, propofol y, en casos seleccionados, el uso de opiodes. En este escrito se presenta un caso clínico de migraña que no mejora con el manejo inicial en urgencias y requiere el uso de otras opciones.

SUMMARY Management of the patient with status migrainosus in the emergency department includes a multimodal therapeutic arsenal seeking to improve pain and to reduce recurrence; the majority of patients respond to enhanced initial management, but in non-negligible cases this result is not obtained with first-line medications and the use of other medications and therapeutic options is necessary, including: pericranial blocks, lidocaine, levetiracetam, propofol and in selected cases the use of opioids. In this review we present a clinical case of migraine that does not improve in the initial management in the emergency department and requires the use of other options for management.

Abstract Objectives: To determine the association between sociodemographic and reproductive factors with unwanted additional fertility (UAF) in Peru. Materials and methods: We carried out an observational, cross-sectional analytical study based on the 2018 Demographic and Family Health Survey (DHS) in Peru. The UAF variable was defined as the numerical difference between the general fertility rate and the total fertility rate. This variable was divided into 2 categories, UAF was considered when the numerical difference was positive. The Poisson regression was used, both crude and adjusted. Results: We analyzed data from 6,944 women with an average age of 44.3 years (range, 40 to 49). The prevalence of UAF was found to be 72.5% (95% CI: 70.4%-74.4%). In the adjusted model, patients in the top wealth quintile (aPR 0.80; 95% CI: 0.69-0.93) were found to have a lower probability of having unwanted pregnancies when compared to those in the middle quintile. On the other hand, patients from rural areas (aPR 1.07; 95% CI: 1.01-1.14) had a higher probability of having unwanted pregnancies when compared to those from urban áreas. Conclusions: The prevalence of UAF in Peruvian women between 40 and 49 years old who participated in the 2018 DHS is high. Patients from rural areas have a higher probability of having unwanted pregnancies, and those in the top wealth quintile have a lower probability.

Resumen Objetivos: Determinar la asociación entre los factores sociodemográficos y reproductivos con la fecundidad adicional no deseada (FAND) en el Perú. Materiales y métodos: Se realizó un estudio observacional, analítico transversal, a partir de la Encuesta Demográfica y de Salud Familiar (ENDES) 2018 en el Perú. La FAND es una variable que se creó a partir de la diferencia numérica entre la fecundidad obtenida y la fecundidad deseada. La variable FAND, se creó a partir de la diferencia numérica entre la fecundidad obtenida y la fecundidad deseada y se agrupó en dos categorías donde la diferencia numérica positiva correspondió a la presencia de FAND. Se realizó una regresión de Poisson, tanto cruda como ajustada. Resultados: Se analizaron los datos de 6944 mujeres entre 40 y 49 años, con una edad promedio de 44,3 años. Se halló una prevalencia de FAND de 72,5% (IC95%: 70,4%-74,4%). En el modelo ajustado, se observó que pertenecer al quintil superior de riqueza (RPa 0,80; IC95%: 0,69-0,93) disminuía la probabilidad de FAND con respecto al quintil intermedio. Por otro lado, provenir del ámbito rural (RPa 1,07; IC95%: 1,01-1,14), aumenta la probabilidad de FAND con respecto al provenir del ámbito urbano. Conclusiones: La prevalencia de FAND en mujeres peruanas de 40 a 49 años que participaron de la ENDES 2018 es alta. Provenir del área rural aumenta la probabilidad de FAND; y pertenecer al quintil superior de riqueza, la disminuye.

RESUMEN INTRODUCCIÓN: La cefalea crónica diaria es una entidad de alto impacto en la población general. Aunque la migraña crónica y la cefalea tipo tensión son las condiciones más frecuentes, es necesario considerar la hemicránea continua y la cefalea diaria persistente de novo como parte de los diagnósticos diferenciales para realizar un enfoque terapéutico correcto. OBJETIVO: Hacer recomendaciones para el tratamiento de la cefalea crónica diaria de origen primario METODOLOGÍA: La Asociación Colombiana de Neurología, mediante consenso y metodología GRADE (Grading of Reccomendations, Assesment, Development and Evaluation), presenta las recomendaciones para el tratamiento preventivo de cada una de las entidades del grupo de la cefalea crónica diaria de origen primario. RESULTADOS: Para el tratamiento de la migraña crónica, la Asociación Colombiana de Neurología recomienda onabotulinum toxina A, erenumab, galcanezumab, fremanezumab, topiramato, flunarizina, amitriptilina y naratriptan. En cefalea tipo tensional crónica las opciones terapéuticas recomendadas son amitriptilina, imipramina, venlafaxina y mirtazapina. Para el tratamiento de la hemicránea continua topiramato, melatonina y celecoxib. Las opciones para cefalea diaria persistente de novo incluyen gabapentin y doxiciclina. Se presentan adicionalmente las recomendaciones para el tratamiento intrahospitalario de los pacientes con cefalea crónica diaria y las justificaciones para la realización de bloqueos neurales como complemento terapéutico. CONCLUSIÓN: se presentan las recomendaciones terapéuticas para el tratamiento de la cefalea crónica diaria basado en metodología de consenso y sistema GRADE.

SUMMARY INTRODUCTION: Chronic daily headache is a high impact entity in the general population. Although chronic migraine and tension-type headache are the most frequent conditions, it is necessary to consider hemicrania continua and new daily persistent headache as part of the differential diagnoses to perform a correct therapeutic approach. OBJECTIVE: To make recommendations for the treatment of chronic daily headache of primary origin METHODOLOGY: The Colombian Association of Neurology, by consensus and Grade methodology (Grading of recommendations, assessment, development and evaluation), presents the recommendations for the preventive treatment of each of the entities of the daily chronic headache of primary origin group. RESULTS: For the treatment of chronic migraine, the Colombian Association of Neurology recommends onabotulinum toxin A, erenumab, topiramate, flunarizine, amitriptyline, and naratriptan. In chronic tension-type headache the recommended therapeutic options are amitriptyline, imipramine, venlafaxine and mirtazapine. Topiramate, melatonin, and celecoxib for the treatment of hemicrania continua. Options for new daily persistent headache include gabapentin and doxycycline. The recommendations for inpatient treatment of patients with chronic daily headache and the justifications for performing neural blockades as a therapeutic complement are also presented. CONCLUSION: The therapeutic recommendations for the treatment of chronic daily headache based on consensus methodology and Grade System are presented.

ABSTRACT Leprosy (Hansen’s disease) is a chronic granulomatous condition caused by Mycobacterium leprae, a microorganism that affects the skin and Schwann’s cells. Making a diagnosis of this condition is difficult in non-endemic areas because of low clinical suspicion. During the 2012-2019 time period, three cases of Hansen’s disease were diagnosed and treated in the ID service of Dos de Mayo Hospital. The average time history of the disease was 4 years. Patients started their condition with the appearance of pruriginous papular lesions affecting specific body regions, progressing to generalized nodular lesions. Paresthesia and tactile, thermal, pain, and vibratory hypoesthesia were found. These manifestations later progressed to anesthesia. Diagnosis was made through bacilloscopy in lymphatic fluid and skin node biopsy. Clinical features for each patient are also described. We emphasize the importance of clinical suspicion for diagnosing this unattended disease in non-endemic areas.

RESUMEN La lepra es una enfermedad crónica granulomatosa causada por el bacilo Mycobacterium Leprae que afecta piel y células de Schwann. En zonas no endémicas el diagnóstico de lepra suele ser dificultoso debido a la baja sospecha clínica. Durante el periodo de 2012 al 2019, se diagnosticaron y trataron tres casos de lepra en el servicio de infectología del Hospital Nacional Dos de Mayo. El tiempo de enfermedad promedio fue 4 años. Los pacientes iniciaron con pápulas pruriginosas en regiones corporales específicas, progresando a nódulos generalizados. Se constató parestesia e hipoestesia táctil, térmica, dolorosa y vibratoria; las cuales progresaron a anestesia. El diagnóstico se realizó mediante baciloscopía en secreción linfática y biopsia de nódulos cutáneos. Se describen las características clínicas de cada uno de los pacientes. Se remarca la importancia de la sospecha diagnóstica de esta entidad desatendida en áreas no endémicas.

Background: Chile is a low-endemic HBV country, but countries with the highest migratory flow to Chile have an intermediate-high endemicity. In order to avoid vertical transmission of HBV, immunoprophylaxis (IP) in the newborn (NB) is a key factor. Aim: To identify HBsAg prevalence in pregnant immigrants and Chilean pregnant women with risk behaviors (RB) and to asses IP use in the NB. Material and Methods: Prospective HBsAg screening cohort of immigrant and Chilean pregnant women with RB, between July 1, 2017 and June 30, 2018 in CABL. IP of all NB of reactive HBsAg mothers was assessed. Results: 1,415 HBsAg samples, 1,265 immigrants and 150 Chileans with RB. 37 reactive HBsAg. Two false positive. HBsAg prevalence in immigrant pregnant women was 2.7% and 0.66% in Chileans with RB (p < 0.05). 91.1% came from Haiti, with a prevalence of 3.5% in our region. All NB (36) received IP with a median of administration of 3:02 h. Conclusions: The prevalence in immigrant pregnant women was higher than that reported in the general population and in Chilean women with RB. We proposed the need for universal screening in pregnancy, especially in pregnant women from countries with intermediate-high endemicity.

Resumen Introducción: Chile es un país de baja endemia de virus de hepatitis B (VHB), pero los países de mayor flujo migratorio hacia Chile tienen una endemia intermediaalta. La inmunoprofilaxis (IP) en el recién nacido (RN) es fundamental para evitar la transmisión vertical de VHB. Objetivos: Determinar la prevalencia de HBsAg en mujeres embarazadas: inmigrantes, y chilenas con conductas de riesgo (CR), y evaluar el cumplimiento de la indicación de IP a los RN de madre con HBsAg reactivo. Material y Métodos: Cohorte prospectiva de cribado de HBsAg a mujeres embarazadas inmigrantes, y chilenas con CR, entre julio 2017 y junio 2018 en CABL. Los RN de madre con HBsAg reactivo se les administró IP adecuada (antes de 12 h de vida). Resultados: Se realizó un total de 1.415 HBsAg: 1.265 a inmigrantes y 150 a chilenas con CR. Se obtuvieron 37 pacientes con HBsAg reactivos. Dos falsos positivos. La prevalencia HBsAg en inmigrantes fue 2,7% y 0,66% en chilenas con CR (p < 0,05). El 91,1% provenía de Haití, con una prevalencia de 3,5% en nuestra área. Todos los RN (36) recibieron IP. La mediana de administración de IP fue 3:02 h. Conclusiones: La prevalencia de VHB en mujeres gestantes inmigrantes fue superior a lo reportado en la población general y en mujeres chilenas con CR. Planteamos la necesidad de implementar el cribado universal en el embarazo, y en especial, en mujeres embarazadas provenientes de países con endemia intermedia-alta.

This work performs an exploratory analysis of the sparkling wines from the state of Rio Grande do Sul, Brazil. Samples of traditional sparkling wine and Moscatel sparkling wine were analyzed and chemometrics tools were applied to physicochemical, gas chromatography and stable carbon isotope analysis. The carbon isotope ratio (δ13C-CO2) of the samples presents great heterogeneity and confirm that the isotopic signature of the CO2 could be derived from the fermentation of C4 sugar. The principal component analysis (PCA) was capable to discriminate and classify the samples in their respective groups and combined data approach was especially important to identify the correlation between the studied variables. With the increasing production of sparkling wines in Brazil, this work helps to evaluate the standards of the local sparkling wines.

Secondary acute myeloid leukemia is a very rare complication in patients with solid organ transplantation. We report a 62 years old female who received a right single lung allograft for idiopathic pulmonary fibrosis. Her immunosuppression scheme consisted in prednisone, azathioprine, and tacrolimus. Two years after the transplantation, she presented with progressive pancytopenia. Bone marrow aspiration was informed as a M4 acute myeloid leukemia, confirmed by flow cytometry. Cytogenetic study was complex, including alterations in chromosome 5. A secondary acute myeloid leukemia was diagnosed. The patient developed nosocomial pneumonia and died a few days after the diagnosis, without specific treatment. The pathogenesis of acute myeloid leukemia is probably related to the intensive exposure to immunosuppressant, especially azathioprine, in these patients.

Background: Intensified treatment of Philadelphia chromosome negative acute lymphoblastic leukemia (Ph(-)ALL) in adolescents by pediatric teams, with fve years disease free survival (DFS) rate of 65%, encouraged the use of intensified protocols in patients between 15 and 30 years, improving the DFS from 45% to 60-80%. The protocol LLA 15-30 for patients between 15 and 30 years with Ph(-)ALL, based on the Children’s Oncology Group (COG) protocol AALL0232 resulting in a five years DFS of 78%, was started in 2007 by the PANDA national program. Aim: To report the results of the prospective cohort study evaluating the results of this protocol four years after its implementation. Patients and Methods: Between January 2007 and December 2010, 68 Ph(-) ALL patients, aged between 15-30 years (75% males) were incorporated. Survival was evaluated using Kaplan-Meier and log-rank tests. Results: Fifty percent of patients were of high risk. A complete response was achieved in 91%, early death occurred in 6% and induction failure in 3%. Median follow-up was 23 months. Overall survival, disease free survival and relapse rates at 35 months were 61.8, 67.5% and 31% respectively. Conclusions: LLA 15-30 protocol significantly improved three-year overall survival from 31 to 62%. The 20% difference observed with AALL0232 protocol is explained by the high rate of relapse. Improving provider and patient compliance with protocols may eliminate this gap.

En este artículo se presenta el caso clínico de un paciente de sexo masculino de 34 años que fue remitido al Instituto Neurológico de Colombia e internado en la unidad de cuidados intensivos neurológicos, por la sospecha inicial de un síndrome de Guillain-Barré. La presencia de alteraciones cognitivas durante su evolución, llevó a reconsiderar el diagnóstico presuntivo inicial por el de encefalitis de Bickerstaff. Se describen el tratamiento instaurado y la evolución del paciente, se hacen la revisión de la literatura y la discusión.

We describe the case of a 34-year-old male patient, who was referred to the Instituto Neurológico de Colombia with probable Guillain-Barré syndrome, requiring intensive care management. The presence of cognitive alterations during his evolution, lead the team to reconsider the initial diagnosis for the Bickerstaff´s brainstem encephalitis diagnosis. We aim to describe the patient´s treatment and evolution, as well as a brief review and discussion.

Background: Hematopoietic stem cell transplantation (HSCT) is an effective therapy for hematological diseases such as lymphoma and multiple myeloma. In 2004, the Cancer Unit of the Ministry of Health incorporated the HSCT to the National Cancer Program in Adults. Until 2008 we purchased services to private institutions while implementing the national center for HSCT of adults in the Hospital del Salvador. Aim: To report the first ten HSCT conducted in this center. Material and Methods: All cases were approved by a national commission for adult HSCT. The entire process was carried out based on evidence-based protocols. Results: Six patients with Hodgkin lymphoma, three with multiple myeloma and one with a diffuse large B cell lymphoma were transplanted. Age range was 19 to 48 years and five patients were male. An average of 2.2 aphereses per patient was required. The CD 34 stem cell collection was 5.06 x 10(6) x Kg. The conditioning regimes were BEAM (carmus-tine, etoposide, cytosine arabinoside, melphalan) and melphalan 200 according to the underlying disease. Seventy percent of the patients developed mild to moderate mucositis and 50% had febrile neutropenia, with good response to treatment. In two cases there was an association with influenza. The engraftment of neutrophils and platelets was achieved on day +10 and +11 respectively. At follow-up until day +100, there was no morbidity or mortality. Conclusions: These results confirm the quality standard that this intervention has achieved in our institution. The Chilean National Center for HSCT on Adults should be established as a public core care, teaching and research facility.

We assessed fluconazole susceptibility in 52 Candida tropicalis clinical strains using seven antifungal susceptibility methods, including broth microdilution (BMD) [standard M27 A3 (with neutral and acid pH), ATB Fungus 3, Vitek 2 system and flow cytometric analysis] and agar-based methods (disk diffusion and E-test). Trailing growth, detection of cell-associated secreted aspartic proteases (Saps) and morphological and ultrastructural traits of these clinical strains were also examined. The ranges of fluconazole 24 h-minimum inhibitory concentration (MIC) values were similar among all methods. The essential agreement among the methods used for MIC determinations was excellent and all methods categorised all strains as susceptible, except for one strain that showed a minor error. The presence of the trailing effect was assessed by six methods. Trailing positivity was observed for 86.5-100% of the strains. The exception was the BMD-Ac method where trailing growth was not observed. Morphological and ultrastructural alterations were detected in C. tropicalis trailing cells, including mitochondrial swelling and cell walls with irregular shapes. We tested the production of Saps in 13 C. tropicalis strains expressing trailing growth through flow cytometry. Our results showed that all of the C. tropicalis strains up-regulated surface Sap expression after 24 h or 48 h of exposure to fluconazole, which was not observed in untreated yeast strains. We concluded that C. tropicalis strains expressing trailing growth presented some particular features on both biological and ultrastructural levels.

Este trabalho apresenta a síntese de uma nova série de 2-[3-alquil (aril/heteroaril)-5-trialometil-5-hidróxi-4,5-diidro-1H-pirazol-1-il]-5-[3-alquil(aril/heteroaril)-5-trialometil-5-hidróxi-4,5-diidro-1H-pirazol-1-il-1-carbonil]piridinas, obtida a partir de reações de ciclocondensação de 4-alcóxi-4-alquil(aril/heteroaril)-1,1,1-trialo-3-alquen-2-onas [CX3C(O)CH=CR¹OR, onde R = Me, Et; R¹ = H, Me, Ph, 4-MeOPh, 4-NO2Ph, 4,4'-Bifenil, 1-Naftil, Fur-2-il e Tien-2-il e X = F, Cl] com hidrato de hidrazida 6-hidrazino-nicotínica. Os melhores rendimentos foram obtidos quando as reações foram executadas em etanol como solvente a 78 ºC por 4 horas (67-97%). Em sequência, são descritas as reações de desidratação de 2-(1H-pirazol-1-il)-5-(1H-pirazol- 1-il-1-carbonil)piridinas. Estas reações foram realizadas em meio piridina / benzeno, na presença de cloreto de tionila e levaram ao isolamento de uma série de 2-[3-alquil(aril/heteroaril)-5-trifluormetil-1H-pirazol-1-il]-5-[3-alquil(aril/heteroaril)-5-trifluormetil-1H-pirazol-1-il-1-carbonil]piridinas, com rendimentos de 64 a 86%.

This paper describes the synthesis of a new series of 2-[3-alkyl(aryl/heteroaryl)- 5-trifluoro(chloro)methyl-5-hydroxy-4,5-dihydro-1H-pyrazol-1-yl]-5-[3-alkyl(aryl/heteroaryl)-5-trifluoro(chloro)methyl-5-hydroxy-4,5-dihydro-1H-pyrazol-1-yl-1-carbonyl]pyridines by the cyclocondensation reaction of 4-alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1-trifluoro(chloro)-3-alken- 2-ones [CX3C(O)CH=CR¹OR, where R = Me, Et; R¹ = H, Me, Ph, 4-MeOPh, 4-NO2Ph, 4,4'-Biphenyl, 1-Naphthyl, Fur-2-yl, Thien-2-yl and X = F, Cl] with 6-hydrazinonicotinic hydrazide hydrate. Yields of 62 to 97% were obtained when the reactions were performed in ethanol as solvent at 78 ºC for 4 hours. In a subsequent step, the dehydration reactions of 2-(5-hydroxy-1H-pyrazol-1-yl)-5-(5-hydroxy-1H-pyrazol-1-yl-1-carbonyl)pyridines were carried out in pyridine/benzene in the presence of thionyl chloride and led to the isolation of a series of 2- [3-alkyl(aryl/heteroaryl)-5-trifluoro(chloro)methyl-1H-pyrazol-1-yl]-5-[3-alkyl(aryl/heteroaryl)-5-trifluoro(chloro)methyl-1H-pyrazol-1-yl-1-carbonyl]pyridines, in 64 to 86% yields.