Carbohydrate-naphthalene diimide conjugates as potential antiparasitic drugs: Synthesis, evaluation and structure-activity studies.

The neglected tropical diseases Human African Trypanosomiasis and leishmaniasis are caused by infection with trypanosomatid parasites Trypanosoma brucei and Leishmania spp, respectively. The genomes of these organisms contain multiple putative G-quadruplex (G4) forming sequences which have recently been proposed to mediate processes relevant for parasite survival. Therefore, G4 could be considered as potential targets for a novel approach towards the development of antiparasitic drugs. Recently, we have demonstrated that G4 ligands such as carbohydrate naphthalene diimide conjugates (carb-NDIs) possess notable antiparasitic activity. Herein, we have synthesized a new family of carb-NDIs, characterized by significant structural variability, and evaluated their anti-parasitic activity, with special focus on T. brucei. The interaction with relevant G4 sequences was evaluated in vitro through independent biophysical methods (FRET melting assays under competing conditions with double stranded DNA, circular dichroism and fluorescence titrations). Finally, flow cytometry and confocal microscopy experiments demonstrated that the conjugates exhibit excellent uptake into T. brucei parasites, localizing in the nuclei and kinetoplasts. Promising antiparasitic activity and selectivity against control mammalian cells, together with their peculiar mechanism of action, render the carb-NDI conjugates as suitable candidates for the development of an innovative treatment of trypanosomiasis.

Doppler transcraneal, BIS y entropía como medición indirecta del flujo cerebral durante la anestesia total intravenosa en pacientes pediátricos / Transcranial Doppler ultrasound, bispectral index, and electroencephalographic monitoring of entropy during pediatric total intravenous anesthesia

OBJETIVOS: El Doppler transcraneal (DTC) es una técnica de monitorización no invasiva de la velocidad del flujo sanguíneo cerebral en las principales arterias intracraneales, especialmente las arterias del polígono de Willis. Nuestro propósito es analizar mediante Eco-Doppler pulsado, si durante la anestesia en pediatría, las alteraciones del flujo sanguíneo cerebral (FSC), se corresponden con modificaciones en los valores medidos de índice biespectral (BIS) y entropía [Estado (ES) y Respuesta (ER)]. MATERIAL Y MÉTODOS: Estudio observacional prospectivo y ciego, en 36 pacientes de 5 a 11 años, con anestesia general total intravenosa, para cirugía general menor. Se realizó inducción con propofol y fentanilo. Para el mantenimiento se utilizó propofol y remifentanilo en perfusión continua y cisatracurio. Se monitorizó el patrón hemodinámico y respiratorio, gases administrados, temperatura, patrón de hipnosis (BIS y entropía - ES y ER-), y patrón de FSC estimado (sonografía Doppler pulsada) en la arteria cerebral media. Se realizó un suavizamiento estadístico para el bruto de datos. Se obtuvieron los parámetros de índice de resistencia, índice de pulsatilidad, velocidad media y flujo sanguíneo estimado. Se determinaron correlaciones para los valores de BIS, ES, ER, índice de pulsatilidad, índice de resistencia, velocidad media, flujo sanguíneo estimado, CO2 espirado y temperatura obtenidos. Se determinó la existencia de modelos de regresión. RESULTADOS: La inducción presentó un patrón de alta resistencia (velocidades medias bajas, índices de pulsatilidad elevados) hasta obtener el valor más bajo de BIS y entropía ES (31 y 29). Durante el mantenimiento se presentó un patrón de sonografía más enlentecido (normalización de índice de pulsatilidad, índice de resistencia y velocidad media), existiendo correlación estadística y concordancia entre las modificaciones de flujo y los valores absolutos de Entropía y BIS (–Pearson– r >= ± 0,91. Concordancia Doppler-BIS de 95,6%); coincidentes con valores de BIS y ES de 35-45; y en el despertar, las velocidades de flujo se acercaron a cifras basales cuando los valores de BIS y ES ascendieron (90-98). Se detectaron modificaciones puntuales del FSC estimado coincidentes con elevación o descenso casi concomitante de BIS (r > 0,95), que presentó un ligero retraso no superior al minuto, y que no fueron detectadas de igual modo por entropía. CONCLUSIONES: Proporcionamos los patrones sonográficos durante la anestesia para propofol. Los sistemas de monitorización de hipnosis podrían ser considerados como sistemas indirectos de medición de flujo cerebral (siendo BIS el de mayor sensibilidad). El DTC permitiría objetivar modificaciones de flujo durante la anestesia relacionados con la profundidad de la hipnosis(AU)

BACKGROUND AND OBJECTIVE: Transcranial Doppler ultrasound is a noninvasive technique for monitoring the velocity of blood flow in the main intracranial arteries, particularly those in the circle of Willis. Our aim was to assess whether changes in cerebral arterial blood flow in anesthetized pediatric patients detected by pulsed Doppler ultrasound correlate with changes in the bispectral (BIS) index and electroencephalographic state and response entropy (ES and ER, respectively). MATERIAL AND METHODS: Prospective, blinded observational study of 36 pediatric patients (age range, 5 to 11 years) under total intravenous anesthesia for minor surgical procedures. Propofol and fentanyl were used for induction; propofol and remifentanil in continuous perfusion and a single dose of cisatracurium were used for maintenance. In all patients we monitored hemodynamic and respiratory patterns, gases, temperature, and hypnosis (BIS, ES and ER) as well as cerebral blood flow estimated by pulsed Doppler ultrasound in the middle cerebral artery. Raw data were subjected to statistical smoothing. The resistance index, pulsatility index, mean velocity, and estimated baseline cerebral blood flow were calculated from the Doppler sonogram. We then studied the correlations between the Doppler-derived values and BIS, ES, ER, fraction of end-tidal carbon dioxide, and temperature. The variables were entered into logistic regression. RESULTS: The pattern at induction indicated high resistance (low mean velocities and high pulsatility indexes) until the lowest BIS and ES values of 31 and 29, respectively, were reached. During maintenance, the Doppler sonogram pattern was slower (normalization of the pulsatility index, the resistance index, and mean velocity). Changes in flow and absolute entropy and BIS values were statistically correlated (Pearson’s r values >= 0.91); there was 95.6% agreement between Doppler values and BIS and agreement between BIS and ES values of 35-45. On awakening, flow velocities approached baseline values when BIS and ES rose to between 90 and 98. The estimated cerebral blood flow underwent fluctuations coinciding with an approximately concomitant increase or decrease in BIS (r > 0.95); the response of BIS was slightly delayed by no more than a minute but there was no corresponding response of entropy measurements. CONCLUSIONS:We report Doppler ultrasound patterns during anesthesia with propofol. Systems for monitoring hypnosis could be considered indirect measurements of cerebral blood flow; BIS measurements are more sensitive to flow change. Transcranial Doppler ultrasound facilitates the observation of changes in blood flow that occur at different levels of hypnosis during anesthesia(AU)

[Transcranial Doppler ultrasound, bispectral index, and electroencephalographic monitoring of entropy during pediatric total intravenous anesthesia]. / Doppler transcraneal, BIS y entropía como medición indirecta del flujo cerebral durante la anestesia total intravenosa en pacientes pediátricos.

BACKGROUND AND OBJECTIVE: Transcranial Doppler ultrasound is a noninvasive technique for monitoring the velocity of blood flow in the main intracranial arteries, particularly those in the circle of Willis. Our aim was to assess whether changes in cerebral arterial blood flow in anesthetized pediatric patients detected by pulsed Doppler ultrasound correlate with changes in the bispectral (BIS) index and electroencephalographic state and response entropy (ES and ER, respectively). MATERIAL AND METHODS: Prospective, blinded observational study of 36 pediatric patients (age range, 5 to 11 years) under total intravenous anesthesia for minor surgical procedures. Propofol and fentanyl were used for induction; propofol and remifentanil in continuous perfusion and a single dose of cisatracurium were used for maintenance. In all patients we monitored hemodynamic and respiratory patterns, gases, temperature, and hypnosis (BIS, ES and ER) as well as cerebral blood flow estimated by pulsed Doppler ultrasound in the middle cerebral artery. Raw data were subjected to statistical smoothing. The resistance index, pulsatility index, mean velocity, and estimated baseline cerebral blood flow were calculated from the Doppler sonogram. We then studied the correlations between the Doppler-derived values and BIS, ES, ER, fraction of end-tidal carbon dioxide, and temperature. The variables were entered into logistic regression. RESULTS: The pattern at induction indicated high resistance (low mean velocities and high pulsatility indexes) until the lowest BIS and ES values of 31 and 29, respectively, were reached. During maintenance, the Doppler sonogram pattern was slower (normalization of the pulsatility index, the resistance index, and mean velocity). Changes in flow and absolute entropy and BIS values were statistically correlated (Pearson's r values > or = 0.91); there was 95.6% agreement between Doppler values and BIS and agreement between BIS and ES values of 35-45. On awakening, flow velocities approached baseline values when BIS and ES rose to between 90 and 98. The estimated cerebral blood flow underwent fluctuations coinciding with an approximately concomitant increase or decrease in BIS (r > 0.95); the response of BIS was slightly delayed by no more than a minute but there was no corresponding response of entropy measurements. CONCLUSIONS: We report Doppler ultrasound patterns during anesthesia with propofol. Systems for monitoring hypnosis could be considered indirect measurements of cerebral blood flow; BIS measurements are more sensitive to flow change. Transcranial Doppler ultrasound facilitates the observation of changes in blood flow that occur at different levels of hypnosis during anesthesia.

Eco-doppler transcraneal. Utilización en anestesiología / Transcranial doppler ultrasonography. Use in anesthesilogy

El efecto Doppler ha sido utilizado en numerosas parcelas científicas, incluida la anestesiología. La información que muestra la ecografía Doppler transcraneal relativa a los índices de pulsatilidad y resistencia, derivadas del estudio de la velocidad de flujo sanguíneo intracerebral, supone un avance en el estudio del comportamiento de los distintos fármacos y técnicas anestésicas. Se muestra aquí una breve descripción de los fundamentos de uso en anestesiología y la utilidad que puede presentar como sistema de monitorización compleja aunque no invasiva, en el conocimiento de los patrones específicos de comportamiento que presentan los fármacos más utilizados actualmente respecto de la velocidad de flujo intracranial (AU)

The Doppler effect is used in many scientific fields, even anaesthesiology. The inform data showed by the transcranial Doppler ultrasound, regarding to pulsatility or resistance index, derived from the study of the behaviour of the different drugs and anaesthetic techniques. We present here a brief description of the use basis in anaesthesiology and the utility that can present like a complex although non-invasive monitoring system in knowledge of the specific pattern behaviour that the more actually utilized drugs present respect to the cerebral blood flow velocity(AU)

Antiinflammatory investigation of some species of Mikania.

Mikania laevigata Schultz Bip. ex Baker, M. involucrata Hook. et Arn. and M. hirsutissima DC. (Asteraceae), commonly occurring in the southern Brazilian State of Rio Grande do Sul, were submitted to biological tests to evaluate their potential antiinflammatory activity. Decoctions from the leaves and stems were analysed by the induced rat paw oedema and pleurisy models. The animals were treated orally with different decoction doses. In the induced rat paw oedema test, the animals treated with leaf decoctions from M. laevigata (200 mg/ kg) and M. involucrata (50 mg/ kg) presented an oedema inhibition of 81.56% and 81.67%, respectively, 3 h after the administration of the phlogistic agent. Leaf decoctions from M. hirsutissima (400 mg/ kg) did not show such an activity. Stem decoctions displayed lower antiinflammatory activity when compared with the same doses and response time of the leaf decoctions for all analysed species. In the pleurisy assay, leaf decoctions from M. laevigata (400 mg/ kg) and M. involucrata (200 mg/ kg) inhibited leukocyte migration to the pleural exudate by 28.26% and 54.35%, respectively.

[Medical training in the information society. Preparing legislation for health care revolution]. / Capacitación médica en la sociedad de la información. Preparando la legislación para una revolución asistencial.

The information society is continuously pushing to a rapid change und updating of laws and training and qualification programs from which medicine is not excluded. This paper summarises the norms and laws applicable to telemedicine with three basic principles involved: medical practice, data management, and communication technologies. Following the subsidiary principle, the applicable legislative levels are: European Union, National, Autonomous Community, Medical Professional Colleges, and Local Medical Colleges. Contradictory and little innovative issues appear in the results and discussion sections of the deontologic codes, the pressing demand on doctors' awareness and to provide them with technical skills. An exhortation follows to work out an informative-ethic code for the telemedicine practice.

Capacitación médica en la sociedad de la información. Preparando la legislación para una revolución asistencial / Medical training in the information society

La sociedad de la información obliga a un rápido cambio y adecuación de leyes y programas de formación y capacitación, de los cuales la medicina no está exenta. Este trabajo resume las leyes y normativas aplicables a la telemedicina que afectan a 3 principios: práctica médica, manejo de datos y tecnologías de la comunicación.Siguiendo el principio de subsidiariedad, los niveles legislativos aplicables son: Unión Europea, nacional, Comunidades Autónomas, Organización Médica Colegial (OMC) y colegios de médicos.En los resultados y discusión aparecen aspectos contradictorios o poco innovadores de los códigos deontológicos, la urgente necesidad de concienciar y capacitar a los médicos en las nuevas tecnologías y se exhorta a elaborar un código infoético para la práctica de la telemedicina (AU)

[Health Councils: assessment after 1 year of functioning]. / Los Consejos de Salud: balance de un año de funcionamiento.

OBJECTIVE: Analysis of the experience from creating and developing Health Committees in the areas of Santa Maria de Gracia and La Nora (Murcia) throughout more than one year in operation (1989-90), as bodies for community participation. DESIGN: Participative research which has meant the transformation of existing reality, and which in the process has been a source of knowledge. LOCATION: Clinic Centres, at community level, in two basic health areas, one rural and one urban. PARTICIPANTS: E.A.P., education officers, pharmacists, various associations, mayors, the Government, Department of Socio-health Sciences of the Faculty of Medicine, and the community in general. INTERVENTIONS: The analysis of developing the participative dynamics. MAIN RESULTS: The content of the Minutes of the meetings were analysed in order to give an objective, systematic and quantitative view of what has occurred, 22 variables were identified which were grouped and cross grouped. CONCLUSIONS: Everyone is invited to the Committees and the large majority attend. Citizens and professionals speak and express their views. The meetings are democratic and agreements are reached, objectives established, health problems are resolved and the only instrument used being participation. This has all been stable throughout the year of operation.