Evaluation of the immunomodulatory activity of thalidomide on tumor-associated macrophages in the 4T1 murine metastatic breast cancer model / [Avaliação do efeito imunomodulador da talidomida em macrófagos associados a tumores no modelo murino de câncer de mama metastático 4T1]

The present work evaluated the immunomodulatory effect of thalidomide (Thal) at different doses on tumor-associated macrophages (TAMs) using a mouse model of human breast cancer. Mice were inoculated with 4T1 cells in the left flank and treated with Thal once a day at concentrations of 50, 100, and 150mg/kg body weight from the 5th day until the 28th day of tumor inoculation. The tumors were sized, proliferation index and TAMs count were evaluated in primary tumors and metastatic lungs. In addition, the metastasis rate was evaluated in the lungs. Thal at 150mg/kg significantly decreased tumor growth, proliferation index, and TAMs infiltration in primary tumors. Conversely, a higher number of TAMs and lower proliferation index were observed in metastatic lungs in mice treated with 150mg/kg of Thal. Furthermore, Thal at 150mg/kg significantly decreased the metastatic nodules in the lungs. Our findings demonstrated that Thal treatment considerably decreased the primary tumor and lung metastasis in mice associated with different TAM infiltration effects in these sites.(AU)

No presente trabalho, foi avaliado o efeito imunomodulador de diferentes doses de talidomida em macrófagos associados ao tumor (TAMs), em um modelo murino de câncer de mama. Camundongos foram inoculados com células 4T1, na região do flanco esquerdo, e tratados com talidomida, uma vez ao dia, nas doses de 50, 100 e 150mg/k, por massa corporal, do quinto dia ao 28º dia de inoculação tumoral. Os tumores foram medidos, o índice de proliferação celular e a contagem de TAMs foram avaliados nos tumores primários e nos pulmões com metástases. Além disso, a taxa de metástases pulmonares também foi avaliada. A talidomida na dose de 150mg/kg diminuiu significativamente o crescimento tumoral, o índice de proliferação celular e a infiltração de TAMs nos tumores primários. Por outro lado, maior número de TAMs e menor índice de proliferação celular foram observados nos pulmões metastáticos, em camundongos tratados com 150mg/kg de talidomida. Ademais, a talidomida na dose de 150mg/kg diminuiu significativamente os nódulos metastáticos nos pulmões. Os resultados demonstraram que o tratamento com talidomida diminuiu o crescimento tumoral e as metástases pulmonares em camundongos, associado com diferentes efeitos na infiltração de TAMs nesses locais.(AU)

Steroidal saponins from the roots of Solanum sisymbriifolium Lam. (Solanaceae) have inhibitory activity against dengue virus and yellow fever virus

Dengue is the most important arthropod-borne viral disease worldwide. Infection with any of the four dengue virus (DENV) serotypes can be asymptomatic or lead to disease with clinical symptoms ranging from undifferentiated and self-limiting fever to severe dengue disease, which can be fatal in some cases. Currently, no specific antiviral compound is available for treating DENV. The aim of this study was to identify compounds in plants from Paraguayan folk medicine with inhibitory effects against DENV. We found high virucidal activity (50% maximal effective concentration (EC50) value of 24.97 µg/mL) against DENV-2 in the ethanolic extract of the roots of Solanum sisymbriifolium Lam. (Solanaceae) without an evident cytotoxic effect on Vero E6 cells. Three saponins isolated from the root extract showed virucidal effects (EC50 values ranging from 24.9 to 35.1 µg/mL) against DENV-2. Additionally, the saponins showed inhibitory activity against yellow fever virus (EC50 values ranging from 126 to 302.6 µg/mL), the prototype virus of the Flavivirus genus, suggesting that they may also be effective against other members of this genus. Consequently, these saponins may be lead compounds for the development of antiviral agents.

Sawtooth waves during REM sleep after administration of haloperidol combined with total sleep deprivation in healthy young subjects

We sought to examine the possible participation of dopaminergic receptors in the phasic events that occur during rapid eye movement (REM) sleep, known as sawtooth waves (STW). These phasic phenomena of REM sleep exhibit a unique morphology and, although they represent a characteristic feature of REM sleep, little is known about the mechanisms which generate them and which are apparently different from rapid eye movements. STW behavior was studied in 10 male volunteers aged 20 to 35 years, who were submitted to polysomnographic monitoring (PSG). On the adaptation night they were submitted to the first PSG and on the second night, to the basal PSG. On the third night the volunteers received placebo or haloperidol and spent the whole night awake. On the fourth night they were submitted to the third PSG. After a 15-day rest period, the volunteers returned to the sleep laboratory and, according to a double-blind crossover randomized design, received haloperidol or placebo and spent the whole night awake, after which they were submitted to the fourth PSG. The volunteers who were given haloperidol combined with sleep deprivation exhibited an elevation of the duration and density of the STW, without significant alterations of the other REM sleep phasic phenomena such as rapid eye movement. These findings suggest that sawtooth waves must have their own generating mechanisms and that the dopaminergic receptors must exert a modulating role since REM sleep deprivation, as well as administration of neuroleptics, produces supersensitivity of dopaminergic receptors

Alteraciones de la función pulmonar en pacientes con lupus eritematoso sitémico juvenil / Alterations of pulmonary function in patients with systemic lupus erithematosus

El Lupus Eritematoso Sistémico (LES) es una enfermedad multiorgánica con frecuente afectación pulmonar. Se ha descripto la presencia de alteraciones funcionales, aún sin evidencia clínica de compromiso respiratorio. Objetivos: evaluar la incidencia de alteraciones de la función pulmonar en pacientes con LES y correlacionarlas con la presencia de síntomas respiratorios y signos radiológicos. Se analizó un grupo no seleccionado de 35 pacientes con LES con enfermedad estable. Treinta y tres mujeres, edad x 13.8 años (9-22). Se consignaron síntomas respiratorios (disnea ante medianos esfuerzos, tos crónica), actividad de la enfermedad según parámetros clínicos y bioquimicos, radiografía de tórax y pruebas de función pulmonar (PFP): espirometría, difusión de CO (DLCO), pletismografía. Resultados: de los 35 pacientes 8 (23 por ciento) presentaron sintomatología respiratoria, 10 (28.6 por ciento) alteraciones radiológicas y 20 (57 por ciento) alteraciones de la funció pulmonar. La alteración funcional más frecuente fue la disminución de la DLCO en 16/20 pacientes, aislada en 9 y asociada en 7 casos a incapacidad ventilatoria restrictiva 4/20 pacientes sólo presentaron incapacidad ventilatoria restrictiva. La pletismografía mostró disminución de la capacidad pulmonar total en 5/9 pacientes con espirometría restrictiva. Los 20 pacientes con alteraciones en PFP no presentaron diferencias significativas con los pacientes con PFP normales en los parámetros clínicos y bioquiímicos de actividad de la enfermedad. De 27 pacientes asintomáticos 12 (44,4 por ciento) presentaron alteraciones de la función pulmonar, asociadas a signos radiológicos. Los 8 pacientes con síntoma respiratorios presentaron altraciones de la funcion pulmonar, asociadas en 7 a radiografía patológica. Conclusiones: el compromiso pulmonar en LES es muy frecuente; 44,4 por ciento de pacientes sin síntomas respiratorios presentaron alteraciones de la función pulmonar.