Melatonin as a preventive treatment of tongue mucosa alterations in an animal model of orofacial radiation

Objective: To evaluate the effect of melatonin as a protective treatment for the tongue in irradiated rats. Materials and Methods: Male Sprague Dawley rats were subjected to a single session of 50 Gy radiation and treated with melatonin 30 minutes before and after the radiotherapy session. A clinical evaluation was carried out a week and a half, third- and sixth-week post-treatment; finally, a tongue biopsy was taken for a histopathological study in the third and sixth weeks after radiation. Results: Clinical evaluation shows a clear trend, that preventive administration of melatonin could facilitate the recovery of mucosal tissue after radiation. Additionally, cellular infiltrate was 40% fewer in the melatonin-treated group compared to the control, as well as the number of the congested vessel were fewer. Conclusion: These findings showed for the first time the preventive role of melatonin in the tongue mucosa reducing the changes associated with mucositis, inflammatory infiltrate, and congestive blood vessels.

Melatonin, minocycline and ascorbic acid reduce oxidative stress and viral titers and increase survival rate in experimental Venezuelan equine encephalitis.

Venezuelan equine encephalitis (VEE) virus causes an acute central nervous system infection in human and animals. Melatonin (MLT), minocycline (MIN) and ascorbic acid (AA) have been shown to have antiviral activities in experimental infections; however, the mechanisms involved are poorly studied. Therefore, the aim of this study was to determine the effects of those compounds on the viral titers, NO production and lipid peroxidation in the brain of mice and neuroblastoma cultures infected by VEE virus. Infected mouse (10 LD50) were treated with MLT (500 µg/kg bw), MIN (50mg/kg bw) or AA (50mg/kg bw). Infected neuroblastoma cultures (MOI: 1); MLT: 0.5, 1, 5mM, MIN: 0.1, 0.2, 2 µM or AA: 25, 50, 75 µM. Brains were obtained at days 1, 3 and 5. In addition, survival rate of infected treated mice was also analyzed. Viral replication was determined by the plaque formation technique. NO and lipid peroxidation were measured by Griess׳ reaction and thiobarbituric acid assay respectively. Increased viral replication, NO production and lipid peroxidation were observed in both, infected brain and neuroblastoma cell cultures compared with uninfected controls. Those effects were diminished by the studied treatments. In addition, increased survival rate (50%) in treated infected animals compared with untreated infected mice (0%) was found. MLT, MIN and AA have an antiviral effect involving their anti-oxidant properties, and suggesting a potential use of these compounds for human VEE virus infection.

[Methotrexate as inducer of proinflammatory cytokines by epithelial cells]. / Metotrexate como inductor en la producci6n de citocinas proinflamatorias en células epiteliales.

Methotrexate (MTX), a drug commonly used in childhood cancer, has also been indicated as a cytotoxic agent of the oral mucosa, which can trigger the inflammatory process and increase the vascularity of epithelial tissues during the early stages of oral mucositis. The aim of this study was to determine the production of proinflammatory cytokines IL-1beta, IL-6 y TNF-alpha in epithelial cell cultures treated with MTX. Epithelial cells of human larynx, obtained from the cell line Hep-2, were cultured with different doses of MTX during different incubation times. The drug cytotoxicity was analyzed by means of the colorimetric test, which is based on the metabolic reduction of the bromide of 3-(4, 5-dimetiltiazol-2-ilo)-2,5-difeniltetrazol (MTT); and the proinflammatory cytokines production by the test enzyme-linked immunosorbent assay (ELISA). Cultures of HEp-2 cells showed increased production of proinflammatory cytokines at 72 hours with 0.32 microM of MTX. These results suggest that depending on the dose and exposure time, MTX alters the physiology of human epithelial cells, which may play an important role during the phases of initiation and development of oral mucositis.

Metotrexate como inductor en la producción de citocinas proinflamatorias en células epiteliales / Methotrexate as inducer of proinflammatory cytokines by epithelial cells

El metotrexate (MTX) es uno de los medicamentos frecuentemente utilizados en el cáncer infantil señalándose además, como agente citotóxico de la mucosa bucal, que puede desencadenar el proceso inflamatorio e incremento de la vascularidad en los tejidos epiteliales durante las fases iniciales de la mucositis oral. El presente trabajo tiene como objetivo determinar la producción de citocinas proinflamatorias IL-1b, IL-6 y TNF-a en cultivos de células epiteliales tratadas con MTX. Se realizaron cultivos de células epiteliales de laringe humana obtenidas de la línea celular Hep-2, con diferentes dosis de MTX en distintos tiempos de incubación, y a su vez se analizó la citotoxicidad del fármaco mediante el ensayo colorimétrico, el cual se basa en la reducción metabólica del bromuro de 3-(4,5- dimetiltiazol-2-ilo)-2,5-difeniltetrazol (MTT), y la producción de citocinas proinflamatorias mediante el ensayo inmuno enzimático indirecto (ELISA). En cuanto a los resultados se observó, que los cultivos de células Hep-2 presentaron aumento en la producción de las citocinas proinflamatorias a las 72 horas al utilizar las dosis de 0.32µM MTX. Estos resultados sugieren que la dosis y el tiempo de exposición del MTX alteran la fisiología de las células epiteliales humanas, lo cual podrían desempeñar un papel importante durante las fases de iniciación y de desarrollo de la mucositis oral.

Methotrexate (MTX), a drug commonly used in childhood cancer, has also been indicated as a cytotoxic agent of the oral mucosa, which can trigger the inflammatory process and increase the vascularity of epithelial tissues during the early stages of oral mucositis. The aim of this study was to determine the production of proinflammatory cytokines IL-1b, IL-6 y TNF-a in epithelial cell cultures treated with MTX. Epithelial cells of human larynx, obtained from the cell line Hep-2, were cultured with different doses of MTX during different incubation times. The drug cytotoxicity was analyzed by means of the colorimetric test, which is based on the metabolic reduction of the bromide of 3-(4, 5-dimetiltiazol-2-ilo)-2,5-difeniltetrazol (MTT); and the proinflammatory cytokines production by the test enzyme-linked immunosorbent assay (ELISA). Cultures of HEp-2 cells showed increased production of proinflammatory cytokines at 72 hours with 0.32µM of MTX. These results suggest that depending on the dose and exposure time, MTX alters the physiology of human epithelial cells, which may play an important role during the phases of initiation and development of oral mucositis.

[Frequency of gastrointestinal signs and symptoms of dengue. Analysis of a cohort of 1484 patients]. / Frecuencia de signos y síntomas gastrointestinales del dengue. Análisis de una cohorte de 1484 pacientes.

Dengue is characterized by fever, headache, arthralgia and myalgia. The presence of gastrointestinal signs and symptoms (GISS) is considered a sign of alarm in dengue; however, little information exists regarding the occurrence of these events. The aim of this study was to determine the frequency of gastrointestinal signs and symptoms in a cohort of patients with dengue. A total of 1484 medical records of patients with confirmed dengue were reviewed and classified as: dengue without warning signs (DNWS) (n = 700), dengue with warning signs (DWWS) (n = 700) and severe dengue (SD) (n = 84). Of the studied records, 65.71% of patients with DNWS, 92.59% with DWWS and 100% of patients with SD had GISS. In patients with DNWS, nausea / vomiting were the most common symptoms in 319/700 cases (45.57%), followed by abdominal pain in 142/700 (20.29%) and diarrhea in 125/700 (17.86%). There were no cases with melena, hepatomegaly or hematemesis. While in DWWS nausea/vomiting were present in 529/700 (75.57%), abdominal pain in 439/700 (62.71%) and diarrhea in 198/700 (28.28%),(p <0.0001). Melena, hematemesis and hepatomegaly ranged from 0.57% to 1.86% of cases. In SD, nausea/vomiting were registered in 100% of the cases, abdominal pain in 82/84 (97.62%), diarrhea in 65/84 (77.38%), melena in 32/84 (38.10%), hepatomegaly in 28/84 (33.33%) and hematemesis in 26/84 (30.95%). It was evident the high frequency of GISS in cases of DWWS and SD, in contrast to DNWS, in which the frequency of GISS was significantly lower. This suggests a relationship of GISS with the severity of dengue, and their presence should be considered by the decision-making health team for appropriate patient management.

Frecuencia de signos y síntomas gastrointestinales del dengue: Análisis de una cohorte de 1484 pacientes / Frequency of gastrointestinal signs and symptoms of dengue: Analysis of a cohort of 1484 patients

El dengue se caracteriza por fiebre, cefalea, artralgia y mialgia. La presencia de signos y síntomas gastrointestinales (SSGI), se considera señal de alarma en dengue; sin embargo, existe poca información respecto a la ocurrencia de estas manifestaciones. El objetivo de este estudio fue determinar la frecuencia de signos y síntomas gastrointestinales en una cohorte de pacientes con dengue. Se revisaron 1484 fichas clínicas de pacientes con diagnóstico confirmado de dengue, clasificados como: dengue con signos de alarma (DCSA) (n=700); sin signos de alarma (DSSA) (n=700) y dengue grave (DG) (n=84). El 65,71% de los pacientes con DSSA, el 92,59% DCSA y el 100% de los pacientes con DG presentaron SSGI. En los pacientes con DSSA, las náuseas/vómitos fue el síntoma más frecuente 319/700 (45,57%), seguido de dolor abdominal 142/700 (20,29%) y diarrea 125/700 (17,86%). No se registraron casos con melena, hepatomegalia y/o hematemesis. Mientras que en DCSA las náuseas/vómitos estuvieron en 529/700 (75,57%), dolor abdominal 439/700 (62,71%) y diarrea 198/700 (28,28%), fueron los más frecuentes (p<0,0001). Melena, hematemesis y hepatomegalia variaron de 0,57% a 1,86%. En DG, las náuseas/vómitos se registraron en el 100%, dolor abdominal 82/84 (97,62%), diarrea 65/84 (77,38%), melena 32/84 (38,10%), hepatomegalia 28/84 (33,33%) y hematemesis 26/84 (30,95%). Se evidencia alta frecuencia de SSGI en los casos de DCSA y DG a diferencia de DSSA, en los cuales fue significativamente menor. Se sugiere relación de los SSGI con la severidad del dengue y su presencia debe considerarse en la toma de decisiones del equipo de salud para el manejo adecuado del paciente.

Dengue is characterized by fever, headache, arthralgia and myalgia. The presence of gastrointestinal signs and symptoms (GISS) is considered a sign of alarm in dengue; however, little information exists regarding the occurrence of these events. The aim of this study was to determine the frequency of gastrointestinal signs and symptoms in a cohort of patients with dengue. A total of 1484 medical records of patients with confirmed dengue were reviewed and classified as: dengue without warning signs (DNWS) (n = 700), dengue with warning signs (DWWS) (n = 700) and severe dengue (SD) (n = 84). Of the studied records, 65.71% of patients with DNWS, 92.59% with DWWS and 100% of patients with SD had GISS. In patients with DNWS, nausea / vomiting were the most common symptoms in 319/700 cases (45.57%), followed by abdominal pain in 142/700 (20.29%) and diarrhea in 125/700 (17.86%). There were no cases with melena, hepatomegaly or hematemesis. While in DWWS nausea/vomiting were present in 529/700 (75.57%), abdominal pain in 439/700 (62.71%) and diarrhea in 198/700 (28.28%),(p <0.0001). Melena, hematemesis and hepatomegaly ranged from 0.57% to 1.86% of cases. In SD, nausea/vomiting were registered in 100% of the cases, abdominal pain in 82/84 (97.62%), diarrhea in 65/84 (77.38%), melena in 32/84 (38.10%), hepatomegaly in 28/84 (33.33%) and hematemesis in 26/84 (30.95%). It was evident the high frequency of GISS in cases of DWWS and SD, in contrast to DNWS, in which the frequency of GISS was significantly lower. This suggests a relationship of GISS with the severity of dengue, and their presence should be considered by the decision-making health team for appropriate patient management.

Dengue nonstructural protein-1 status is not associated to circulating levels of interleukin-17, C-reactive protein and complement in children with acute dengue.

BACKGROUND: During dengue infection increase in plasma level of various substances have been reported. Some of those molecules are related to the virus biology and others result of the interaction virus-host. Nonstructural protein-1 (NS1) secreted by dengue virus has been reported to have a role in dengue pathogenesis. NS1 is capable of interacting with complement to evade viral clearance. However, there is little information about the presence of serum NS1 and the levels of other molecules related to dengue pathogenesis. OBJECTIVES: The aim of this study was to determine the association of the NS1 status and the circulating levels of interleukin-17 (IL-17), C-reactive protein (CRP), C3 and C4 in acute dengue. STUDY DESIGN: In this study the serum presence of NS1, IL-17, CRP, C3 and C4 was determined in children with acute dengue. IL-17, CRP, anti dengue-IgG content was measured by ELISA, C3 and C4 levels by an immunoturbidimetric assay and NS1 by an immunochromatographic assay. RESULTS: All patients were positive for dengue infection as shown by antibodies anti-dengue and/or virus isolation. Increased levels of IL-17, CRP and C4 no related to the presence of NS1 were found in the patients. Values of C3 remained similar to controls. CONCLUSIONS: These findings suggest that NS1 does not module the production of studied molecules during dengue infection.