Characterization of the Effect of N-(2-Methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, Compound 8, against Leishmania mexicana and Its In Vivo Leishmanicidal Activity.

Chemotherapy currently available for leishmaniasis treatment has many adverse side effects and drug resistance. Therefore, the identification of new targets and the development of new drugs are urgently needed. Previously, we reported the synthesis of a N-(2-methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, named compound 8, with an IC50 value in the micromolar range against L. mexicana, it also inhibited 68.27% the activity of recombinant L. mexicana arginase. Herein, we report studies carried out to characterize the mechanism of action of compound 8, as well as its in vivo leishmanicidal activity. It was shown in our ultrastructural studies that compound 8 induces several changes, such as membrane blebbing, the presence of autophagosomes, membrane detachment and mitochondrial and kinetoplast disorganization, among others. Compound 8 triggers the production of ROS and parasite apoptosis. It reduced 71% of the parasite load of L. mexicana in an experimental model of cutaneous leishmaniasis in comparison with a control. Altogether, the data obtained suggest the potential use of compound 8 in the treatment of cutaneous leishmaniasis.

Eficacia de un programa de rehabilitación cardiaca en polideportivo municipal comparado con el programa hospitalario: ensayo controlado aleatorizado eCARCEX / Efficacy of a cardiac rehabilitation program in a municipal sports center compared to the hospital program: randomized controlled trial eCARCEX

Fundamento. El objetivo de este estudio es analizar los efectos de un programa de rehabilitación cardiaca (PRC) extrahospitalario en un centro municipal deportivo sobre la capacidad funcional y la adherencia al ejercicio físico, entre otras variables, en comparación con un modelo hospitalario. Métodos. Ensayo clínico aleatorizado con dos grupos paralelos de pacientes con síndrome coronario agudo que realizaron un PRC con ejercicio físico moderado interválico coordinado con educación en hábitos saludables en un centro deportivo municipal (GE) y en un hospital terciario (GC), entre septiembre de 2019 y junio de 2020. Se analizaron variables de adherencia, antropométricas, clínicas, psicológicas, de fuerza, de prevención secundaria (dieta, tabaco) y capacidad funcional en la prueba de ergoespirometría. Resultados. Veintidós pacientes completaron el PRC (GC=10, GE=12). Se observaron mejoras significativas pre-post en GC (colesterol, test de la silla, frecuencia cardiaca en VT1 y VT2, y vatios en VT1) y en GE (colesterol HDL, triglicéridos, test de la silla, y frecuencia cardiaca y vatios en VT1). Estas mejoras fueron mayores en el GC para la frecuencia cardiaca en VT2 (11,17 vs 2,88 lpm) y en el GE para el colesterol HDL (11,0 vs 0,63 mg/dL). Conclusiones. Este estudio no ha podido determinar la eficacia de los PRC extrahospitalarios por falta de potencia (abundantes abandonos debidos al confinamiento por COVID-19). A pesar de ello, en el GE se observó mayor aumento en colesterol HDL que en el GC, aunque la frecuencia cardiaca en VT2 fue mayor en el GC (AU)

Background. This study aimed to analyze the effects of an outpa-tient cardiac rehabilitation program in a municipal sports center on functional capacity and adherence to physical activity – among other variables – compared to an in-hospital program.Methods. Randomized clinical trial that included two parallel groups of acute coronary syndrome patients who performed a car-diac rehabilitation program that consisted of moderate physical ex-ercise intervals along with learning healthy habits in a municipal sports center (EG) and in a tertiary hospital (CG) between Septem-ber 2019 and June 2020. We collected the following data: compli-ance, anthropometrical, clinical, psychological variables, diet and tobacco habits, strength and functional capacity from ergospirom-etry. Results. Twenty-two patients completed the cardiac rehabilitation program (EG=12, CG=10). Significant improvement was observed for cholesterol, the sit-and-stand test, cardiac frequency in VT1 and VT2, and watts in VT1 in the CG, and for HDL-cholesterol, triglycerides, the sit-and-stand test, and frequency, and watts in VT1 in the EG. Better achievement was found in the CG for cardiac frequency in VT2 (11.17 vs 2.88 bpm) and in EG for HDL-cholesterol (11.0 vs 0.63 mg/dL).Conclusions. We are unable to determine the effectiveness of the out-of-hospital cardiac rehabilitation program due to a lack of power (high number of withdrawals caused by COVID-19 lockdown). How-ever, the EG achieved higher HDL-cholesterol levels, while cardiac frequency in VT2 was higher in the CG (AU)

Efficacy of a cardiac rehabilitation program in a municipal sports center compared to the hospital program: randomized controlled trial eCARCEX.

BACKGROUND: This study aimed to analyze the effects of an outpatient cardiac rehabilitation program in a municipal sports center on functional capacity and adherence to physical exercise - among other variables - compared to an in-hospital program. METHODS: Randomized clinical trial that included two parallel groups of acute coronary syndrome patients who performed a cardiac rehabilitation program that consisted of moderate physical exercise intervals along with learning healthy habits in a municipal sports center (experimental group) and in a tertiary hospital (control group) between September 2019 and June 2020. We collected the following data: compliance, anthropometrical, clinical, psychological variables, diet and tobacco habits, strength and functional capacity from ergospirometry. RESULTS: Twenty-two patients completed the cardiac rehabilitation program (experimental group=12, control group=10). Significant improvement was observed for cholesterol, the sit-and-stand test, cardiac frequency in VT1 and VT2, and watts in VT1 in the control group, and for HDL-cholesterol, triglycerides, the sit-and-stand test, and frequency, and watts in VT1 in the experimental group. Better achievement was found in the control group for cardiac frequency in VT2 (11.17 vs 2.88 bpm) and in EG for HDL-cholesterol (11.0 vs 0.63 mg/dL). CONCLUSIONS: We are unable to determine the effectiveness of the out-of-hospital cardiac rehabilitation program due to a lack of power (high number of withdrawals caused by COVID-19 lockdown). However, the experimented group achieved higher HDL-cholesterol levels, while cardiac frequency in VT2 was higher in the control group.

Treatment With Adalimumab 80 mg Every Other Week in Inflammatory Bowel Disease: Results of Treatment Intensification in Clinical Practice.

Background: Loss of response to anti-tumor necrosis factor drugs in patients with inflammatory bowel disease (IBD) is frequent and, in case of low drug levels, treatment intensification is recommended. In addition, in cases in which clinical response without attainment of remission (clinical, endoscopic, or radiological), intensification could be justified since higher drug levels are associated with better outcomes. For adalimumab (ADA), the standard intensification regimen is 40 mg every week (ew). Availability of ADA 80 mg prefilled pens has enabled every other week (eow) intensification. We assessed the clinical efficacy of intensification with ADA 80 mg eow. Methods: This retrospective study was conducted at a tertiary hospital in Spain. Patients with IBD receiving maintenance ADA 80 mg eow with clinical, biomarker, and drug-level assessments were included. Demographics and clinical, biological, and endoscopic evaluation of the disease before and after ADA intensification, and pharmacokinetic assessments, were collected. Results: Eighty-seven patients (72 Crohn's disease, 15 ulcerative colitis; average age 50 years) were included. Reasons for ADA intensification were: low ADA levels-<5 µg mL-1-(17%), low ADA levels-<5 µg mL-1-without clinical response (63%), clinical response without clinical remission (15%) and active disease on objective evaluation (including colonoscopy, magnetic resonance imaging, capsule endoscopy, and/or intestinal ultrasound; 5%). Following treatment intensification to ADA 80 mg eow, 75 patients (86%) were in clinical remission and 69 (79.3%) were in biologic remission (clinical remission and normalization of biomarkers). After a median follow-up of 19 months (interquartile range 13-25), 63 patients (72%) remained on treatment and in clinical remission. There were no serious infections, hospitalizations, or deaths. Drug costs did not increase with the 80 mg eow regimen versus a standard intensification regimen. Conclusions: ADA intensification to 80 mg eow was safe, effective, and did not increase drug costs versus standard intensification to 40 mg ew in our experience.

A systematic review and meta-analysis of randomized controlled trials evaluating pharmacologic therapies for acute and recurrent pericarditis.

Acute idiopathic pericarditis (AIP) is a benign inflammatory condition associated with high recurrence rates. Non-steroidal anti-inflammatory drug (NSAIDs) and colchicine are the recommended therapies. Our objective was to systematically assess effects of pharmacological therapies on recurrences or treatment failure in patients with first and subsequent AIP episodes. PubMed, BioMedCentral, Cochrane, Clinicaltrials.gov, Google Scholar and EMBASE (Ovid) were searched up to April 2020 for randomized controlled trials (RCT) evaluating NSAIDs, indomethacin, colchicine, steroids, intravenous immunoglobulins, immunomodulators, or interleukin receptor antagonists in adult patients with acute episode of idiopathic pericarditis. Mantel-Haenzel random effects models were used for meta-analyses, and effects were reported as odds ratios (ORs) and their 95% confidence intervals (CI). Six RCTs of colchicine plus NSAIDs (n=914 patients) and one RCT of anakinra (n=21) were found. No RCTs testing NSAIDs or corticosteroids were identified. Colchicine plus NSAIDs and anakinra significantly reduced recurrence (OR 0.37; 95%CI 0.27-0.51; and OR 0.02; 95%CI, 0.00-0.32, respectively). Colchicine plus NSAIDs also reduced treatment failure (OR 0.29; 95%CI 0.21-0.41). No differences in adverse events between colchicine and placebo were found (OR 1.16; 95%CI 0.72 to 1.86). In conclusion, Colchicine plus NSAIDS and anakinra are efficacious for preventing AIP recurrences. Colchicine reduces treatment failure as well. Although its use is supported by clinical experience, no solid evidence is currently available for the role of NSAIDs or steroids in the treatment of AIP.

In vitro activity of new N-benzyl-1H-benzimidazol-2-amine derivatives against cutaneous, mucocutaneous and visceral Leishmania species.

The identification of specific therapeutic targets and the development of new drugs against leishmaniasis are urgently needed, since chemotherapy currently available for its treatment has several problems including many adverse side effects. In an effort to develop new antileishmanial drugs, in the present study a series of 28 N-benzyl-1H-benzimidazol-2-amine derivatives was synthesized and evaluated in vitro against Leishmania mexicana promastigotes. Compounds 7 and 8 with the highest antileishmanial activity (micromolar) and lower cytotoxicity than miltefosine and amphotericin B were selected to evaluate their activity against L. braziliensis 9and L. donovani, species causative of mucocutaneous and visceral leishmaniasis, respectively. Compound 7 showed significantly higher activity against L. braziliensis promastigotes than compound 8 and slightly lower than miltefosine. Compounds 7 and 8 had IC50 values in the micromolar range against the amastigote of L. mexicana and L. braziliensis. However, both compounds did not show better activity against L. donovani than miltefosine. Compound 8 showed the highest SI against both parasite stages of L. mexicana. In addition, compound 8 inhibited 68.27% the activity of recombinant L. mexicana arginase (LmARG), a therapeutic target for the treatment of leishmaniasis. Docking studies were also performed in order to establish the possible mechanism of action by which this compound exerts its inhibitory effect. Compound 8 shows promising potential for the development of more potent antileishmanial benzimidazole derivatives.

Synthesis and biological evaluation of 2-methyl-1H-benzimidazole-5-carbohydrazides derivatives as modifiers of redox homeostasis of Trypanosoma cruzi.

Twelve novel benzimidazole derivatives were synthesized and their in vitro activities against epimastigotes of Trypanosoma cruzi were evaluated. Two derivatives (6 and 7), which have 4-hydroxy-3-methoxyphenyl moiety in their structures, proved to be the most active in inhibiting the parasite growth. Compound 6 showed a trypanocidal activity higher than benznidazole (IC50=5µM and 7.5µM, respectively) and less than nifurtimox (IC50=3.6µM). In addition, the ability of 6 and 7 to modify the redox homeostasis in T cruzi epimastigote was studied; cysteine and glutathione increased in parasites exposed to both compounds, whereas trypanothione only increased with 7 treatment. These results suggest that the decrease in viability of T. cruzi may be attributed to the change in cellular redox balance caused by compound 6 or 7. Furthermore, compounds 6 and 7 showed CC50 values of 160.64 and 160.66µM when tested in mouse macrophage cell line J774 and selectivity indexes (macrophage/parasite) of 32 and 20.1, respectively.

Hiperexcitabilidad nerviosa en el síndrome de Michaelis-Manz / Nerve hyperexcitability in Michaelis-Manz syndrome

No disponible

Synthesis and trypanocidal activity of novel benzimidazole derivatives.

The present work reports the synthesis and biological activity of a series of 14 benzimidazole derivatives designed to act on the enzyme triosephosphate isomerase of Trypanosoma cruzi (TcTIM). This enzyme is involved in the metabolism of glucose, the only source of energy for the parasite. In this study, we found four compounds that inhibit TcTIM moderately and lack inhibitory activity against human TIM (HsTIM). In vitro studies against T. cruzi epimastigotes showed two compounds that were more active than the reference drug nifurtimox, and these presented a low cytotoxic effect in mouse macrophages (J744 cell line).

¿Cómo mejorar la eficacia de los equipos a través de los procesos grupales? Un ejemplo en la industria automotriz / How to improve team effectiveness through group processess: An example in the automotive industry

Incrementar la efectividad de los grupos y equipos de trabajo es fundamental en cualquier organización, y más, durante los periodos de crisis económica. Para diseñar un equipo, formar un grupo u optimizar su trabajo, es preciso considerar las tareas, los procesos y los resultados. Siendo los equipos una herramienta clave en la competitividad del sector de la automoción, en este artículo nos enfocaremos en cómo mejorar el desempeño y la efectividad de los equipos de producción de este sector en las industrias españolas, a través de tres procesos, desarrollo grupal, identificación con el grupo y potencia del equipo. Los resultados indican que estos procesos predicen el 57% del desempeño grupal y especialmente dos de los criterios de efectividad utilizados en el sector (absentismo y orden e higiene en el lugar de trabajo). Discutiremos la utilidad de estos resultados para gerentes y lideres de equipos, con el objetivo de favorecer la efectividad de los equipos de producción del sector

Increasing group and team effectiveness is fundamental for any organisation, especially during periods of economic crisis. In order to build or design a team or to optimise its work, it is necessary to consider tasks, processes and results. Given that teams are a key tool for competitiveness in the automotive sector, this paper focuses on how to improve the performance and the effectiveness of production teams in Spain's automotive industry through three processes: group development, group identification, and team potency. The results show that these processes predict 57% of group performance, and in particular two of the effectiveness criteria used in this sector: absenteeism and order and hygiene in the workplace. We discuss the usefulness of these results for managers and team leaders in order to improve team performance and effectiveness in the automotive sector

What distinguish teams from social aggregates? A tool to assess the group development / ¿Qué distingue a los equipos de los agregados sociales? Un instrumento para evaluar el desarrollo del grupo

This research uses the construct of group development (GD) to distinguish highly developed workgroups and teams from mere social aggregates. The aims were to develop a scale capable of measuring this basic emergent process and to study the scale’s reliability and construct validity (content, factorial, convergent and criteria). Data concerning the GD, other related processes (entitativity and group identification) and team outputs (group performance and team effectiveness) were gathered from four successive studies (4099 participants belonging to 521 workgroups in 13 organizations). All the studies were carried out using a cross-sectional and correlational design. The results revealed an one-dimensional solution for the proposed measurement scale, which showed adequate reliability and validity. The scale is not only practical (quick and easy to apply) but also useful for group managers and leaders, since it provides them with a tool for determining the extent to which their groups are actually functioning as highly developed groups

Esta investigación utiliza el constructor de desarrollo del grupo (GD) para distinguir grupos de trabajo y equipos altamente desarrollados de los meros agregados sociales. Los objetivos fueron desarrollar una escala capaz de medir este proceso emergente básico y estudiar la fiabilidad y validez de constructo de la escala (de contenido, factorial, convergente y orientada al criterio). Los datos relativos al GD y otros procesos relacionados (entitatividad e identificación del grupo) y resultados del equipo (desempe- ño y efectividad del grupo) se obtuvieron de cuatro estudios sucesivos (4099 participantes pertenecientes a 559 grupos de trabajo de 12 organizaciones). Todos los estudios se llevaron a cabo utilizando un diseño transversal y correlacional. Los resultados revelaron una solución unidimensional de la escala propuesta, que demostró validez y fiabilidad adecuadas. La escala no sólo es práctica (rápida y fácil de aplicar), sino que también es útil para los gestores y líderes de grupos ya que les proporciona una herramienta para determinar el grado en que sus grupos funcionan en realidad como equipos altamente desarrollados

Design, synthesis and biological evaluation of quinazoline derivatives as anti-trypanosomatid and anti-plasmodial agents.

In this paper, the design, synthesis and biological evaluation of a set of quinazoline-2,4,6-triamine derivatives (1-9) as trypanocidal, antileishmanial and antiplasmodial agents are explained. The compounds were rationalized basing on docking studies of the dihydrofolate reductase (DHFR from Trypanosoma cruzi, Leishmania major and Plasmodium vivax) and pteridin reductase (PTR from T. cruzi and L. major) structures. All compounds were in vitro screened against both bloodstream trypomastigotes of T. cruzi (NINOA and INC-5 strains) and promatigotes of Leishmania mexicana (MHOM/BZ/61/M379 strain), and also for cytotoxicity using Vero cell line. Against T. cruzi, three compounds (5, 6 and 8) were the most effective showing a better activity profile than nifurtimox and benznidazole (reference drugs). Against L. mexicana, four compounds (5, 6, 8, and 9) exhibited the highest activity, even than glucantime (reference drug). In the cytotoxicity assay, protozoa were more susceptible than Vero cells. In vivo Plasmodium berghei assay (ANKA strain), the compounds 1, 5, 6 and 8 showed a more comparable activity than chloroquine and pyrimethamine (reference drugs) when they were administrated by the oral route. The antiprotozoal activity of these substances, endowed with redox properties, represented a good starting point for a medicinal chemistry program aiming for chemotherapy of Chagas' disease, leishmaniosis and malaria.

In vitro and in vivo trypanocidal activity of some benzimidazole derivatives against two strains of Trypanosoma cruzi.

The trypanocidal effect of five benzimidazole derivatives (1-5) was determined in vitro and in vivo assays against two strains of Trypanosoma cruzi (NINOA and INC5). The in vitro trypanocidal activity was evaluated by measuring the percentage of lysis of bloodstream trypomastigotes of T. cruzi. Results point to 5-chloro-1H-benzimidazole-2-thiol (1) as the best activity profile compound with a 50% lytic concentration (LC(50)) of 0.014 mM (NINOA strain) and 0.32 mM (INC5 strain). Reference drugs were nifurtimox (Nfx) and benznidazole (Bnz), which on NINOA strain displayed a LC(50)=0.60 mM and LC(50)=0.78 mM, respectively; while on INC5 strain they exhibited LC(50) values of 0.31 mM and 0.69 mM, respectively. The in vivo trypanocidal activity of 1-5 on parasitemia in a murine model acute Chagas' disease indicated that 1 and Nfx showed similar activity on INC5 strain, while 5-chloro-1-methyl-1H-benzimidazole-2-thiol (2) and its regioisomer, 6-chloro-1-methyl-1H-benzimidazole-2-thiol (3), displayed better activity than Nfx and Bnz on NINOA strain. All compounds showed low cytotoxicity against Vero cells, with selective index 38-3000 times higher to the parasite.

Grupos en las organizaciones: Herramienta básica para gestionar la incertidumbre y ambigüedad crecientes / No disponible

El mundo del trabajo y de las organizaciones ha sufrido una transformación fundamental en los últimos años: hay mucha más incertidumbre. La respuesta organizativa a dicha incertidumbre ha sido la de diseñar organizaciones más complejas fundamentadas en el trabajo en equipo. Pero no todas las tareas requieren del trabajo en equipo ni todos los grupos de trabajo son auténticos equipos. En este trabajo repasaremos las investigaciones que venimos realizando para clarificar cómo entender operativamente la incertidumbre de las tareas que ha de hacer el equipo, el nivel de desarrollo que pueden alcanzar los equipos de trabajo y cómo el ajuste entre uno y otro (a mayor incertidumbre en las tareas más necesario su abordaje en equipos) es determinante en la efectividad que dichos equipos consiguen. Ofrecemos también guías para la intervención profesional si el objetivo es diseñar y dirigir equipos de trabajo eficaces (AU)

The world of work and organizations has undergone a radical transformation in recent years: nowadays there are much more uncertainty. The organizational response has been to design more sophisticated organization based on teams. But not all the tasks require teamwork and not all workgroups are really teams. In this paper, we review the research we have been doing to clarify how to understand the tasks group uncertainty, the level of group development that can meet the teams and how the fit between each other (the larger tasks uncertainty can be approached better in teams) is central to the team effectiveness. We also offer guidelines for professional intervention in order to design and manage effective work teams (AU)

[Narcolepsy: update on etiology, clinical features and treatment]. / Narcolepsia: actualización en etiología, manifestaciones clínicas y tratamiento.

Narcolepsy is a disease that involves an alteration in the generation and organisation of sleep. The main symptoms are excessive daytime sleepiness and cataplexy, followed by hypnagogic hallucinations, sleep paralysis and disrupted nocturnal sleep. The prevalence of typical narcolepsy oscillates between 25-50: 100.000 in general. Recently there has been a peak incidence in patients born in the month of March. According to the new classification, the Multiple Sleep Latency Test (MSLT) is mandatory for diagnosing narcolepsy without cataplexy, and advisable for diagnosing narcolepsy with cataplexy. Until now, the attempt has been made to control each symptom by its own specific treatment. At present, new American and European treatment guidelines propose new drugs that act on all the symptoms. The application of new criteria of diagnosis and treatment has improved the diagnosis, giving better options of treatment.

Virucidal activity of Colombian Lippia essential oils on dengue virus replication in vitro.

The inhibitory effect of Lippia alba and Lippia citriodora essential oils on dengue virus serotypes replication in vitro was investigated. The cytotoxicity (CC50) was evaluated by the MTT assay and the mode of viral inhibitory effect was investigated with a plaque reduction assay. The virus was treated with the essential oil for 2 h at 37 masculineC before cell adsorption and experiments were conducted to evaluate inhibition of untreated-virus replication in the presence of oil. Antiviral activity was defined as the concentration of essential oil that caused 50% reduction of the virus plaque number (IC50). L. alba oil resulted in less cytotoxicity than L. citriodora oil (CC50: 139.5 vs. 57.6 microg/mL). Virus plaque reduction for all four dengue serotypes was observed by treatment of the virus before adsorption on cell. The IC50 values for L. alba oil were between 0.4-32.6 microg/mL and between 1.9-33.7 microg/mL for L. citriodora oil. No viral inhibitory effect was observed by addition of the essential oil after virus adsorption. The inhibitory effect of the essential oil seems to cause direct virus inactivation before adsorption on host cell.

Virucidal activity of Colombian Lippia essential oils on dengue virus replication in vitro

The inhibitory effect of Lippia alba and Lippia citriodora essential oils on dengue virus serotypes replication in vitro was investigated. The cytotoxicity (CC50) was evaluated by the MTT assay and the mode of viral inhibitory effect was investigated with a plaque reduction assay. The virus was treated with the essential oil for 2 h at 37ºC before cell adsorption and experiments were conducted to evaluate inhibition of untreated-virus replication in the presence of oil. Antiviral activity was defined as the concentration of essential oil that caused 50 percent reduction of the virus plaque number (IC50). L. alba oil resulted in less cytotoxicity than L. citriodora oil (CC50: 139.5 vs. 57.6 μg/mL). Virus plaque reduction for all four dengue serotypes was observed by treatment of the virus before adsorption on cell. The IC50 values for L. alba oil were between 0.4-32.6 μg/mL and between 1.9-33.7 μg/mL for L. citriodora oil. No viral inhibitory effect was observed by addition of the essential oil after virus adsorption. The inhibitory effect of the essential oil seems to cause direct virus inactivation before adsorption on host cell.

Aceites esenciales de plantas colombianas inactivan el virus del dengue y el virus de la fiebre amarilla / Essential oils from colombian plants inactive dengue virus and yellow fever virus

Introducción: Un antiviral contra el virus del dengue (VDEN) y el virus de la fiebre amarilla (VFA) para tratamiento de los enfermos no está disponible en el mercado, a pesar de numerosas investigaciones con compuestos sintéticos. Objetivo: Evaluar el efecto inhibitorio in vitro sobre el VDEN y el VFA del aceite esencial obtenido de plantas cultivadas en Colombia. Materiales y métodos: Los virus se incubaron con el aceite esencial (100 µg/mL) 2 h a 37oC antes de la adsorción a la célula y el efecto inhibitorio fue determinado por el método de reducción de placa. Resultados: El aceite esencial obtenido de 10 y 8 plantas redujo desde 74 hasta 100% placas del VDEN y del VFA, respectivamente. Los aceites de Lippia citriodora (verbena) y Pimenta racemosa (laurel) fueron más activos contra ambos virus reduciendo 100% las placas. La magnitud del efecto inhibitorio se relacionó con el método de extracción del aceite y la parte de la planta seleccionada. Conclusión: El aceite esencial de las plantas colombianas puede inhibir la replicación in vitro del VDEN y VFA. Se requieren más estudios para determinar la concentración mínima inhibitoria y el índice de selectividad para considerar estas plantas como fuente de compuestos antivirales.

Background: Products obtained from plants can inhibit in vitro viruses that cause human diseases. An antiviral drug against dengue virus (DENV) and yellow fever virus (YFV) does not exist despite extensive research exploring synthetic compounds. Objective: To evaluate the inhibitory effect on DENV and YFV of essential oils obtained from Colombian plants. Materials and methods: Viruses were incubated with essential oil (100 µg/mL) 2 h at 37oC before cell adsorption and the inhibitory effect was determined by plaque reduction assay. Results: The essential oil obtained from 10 and 8 plants reduced from 74 to 100% DENV and YFV plaques, respectively. Essential oils from Lippia citriodora and Pimenta racemosa were the most active against both viruses causing 100% reduction of plaques. The magnitude of the inhibitory effect was related to the method of oil extraction and part of plant used. Conclusion: Essential oils from Colombian plants can inhibit the replication in vitro of DENV and YFV. Further studies determining the minimal inhibitory concentrations and selectivity index are needed in order to consider these plants as a source of antiviral compounds.

Inhibitory effect of essential oils obtained from plants grown in Colombia on yellow fever virus replication in vitro.

BACKGROUND: An antiviral drug is needed for the treatment of patients suffering from yellow fever. Several compounds present in plants can inactive in vitro a wide spectrum of animal viruses. AIM: In the present study the inhibitory effect of essential oils of Lippia alba, Lippia origanoides, Oreganum vulgare and Artemisia vulgaris on yellow fever virus (YFV) replication was investigated. METHODS: The cytotoxicity (CC(50)) on Vero cells was evaluated by the MTT reduction method. The minimum concentration of the essential oil that inhibited virus titer by more than 50% (MIC) was determined by virus yield reduction assay. YFV was incubated 24 h at 4 degrees C with essential oil before adsorption on Vero cell, and viral replication was carried out in the absence or presence of essential oil. Vero cells were exposed to essential oil 24 h at 37 degrees C before the adsorption of untreated-virus. RESULTS: The CC(50) values were less than 100 microg/mL and the MIC values were 3.7 and 11.1 microg/mL. The CC(50)/MIC ratio was of 22.9, 26.4, 26.5 and 8.8 for L. alba, L origanoides, O. vulgare and A. vulgaris, respectively. The presence of essential oil in the culture medium enhances the antiviral effect: L. origanoides oil at 11.1 microg/mL produced a 100% reduction of virus yield, and the same result was observed with L. alba, O. vulgare and A. vulgaris oils at 100 microg/mL. No reduction of virus yield was observed when Vero cells were treated with essential oil before the adsorption of untreated-virus. CONCLUSION: The essential oils evaluated in the study showed antiviral activities against YFV. The mode of action seems to be direct virus inactivation.

[Transition from prostacyclin to bosentan in five patients with severe pulmonary hypertension: the switch is possible]. / Transición de prostaciclina a bosentán en 5 pacientes con hipertensión pulmonar severa: el cambio es posible.

Prostacyclin improves symptoms, exercise tolerance, and survival in patients with pulmonary arterial hypertension. However, the difficulty of administration (whether intravenous, subcutaneous, or by inhalation) often causes side effects that can reduce the patient's quality of life and which may sometimes be serious. Bosentan, an orally active endothelin receptor antagonist, improves functional class and exercise tolerance in these patients. We describe the successful transition from prostacyclin to bosentan in five patients with severe pulmonary arterial hypertension who suffered serious side effects with prostacyclin treatment.