Curcumin exerts anti-inflammatory and vasoprotective effects through amelioration of NFAT-dependent endothelin-1 production in mice with acute Chagas cardiomyopathy

BACKGROUND The anti-inflammatory and cardioprotective properties of curcumin (Cur), a natural polyphenolic flavonoid isolated from the rhizomes of Curcuma longa, are increasingly considered to have beneficial effects on the progression of Chagas heart disease, caused by the protozoan parasite Trypanosoma cruzi. OBJECTIVE To evaluate the effects of oral therapy with Cur on T. cruzi-mediated cardiovasculopathy in acutely infected mice and analyse the in vitro response of parasite-infected human microvascular endothelial cells treated with this phytochemical. METHODS Inflammation of heart vessels from Cur-treated and untreated infected mice were analysed by histology, with benznidazole (Bz) as the reference compound. Parasitaemia was monitored by the direct method. Capillary permeability was visualised by Evans-blue assay. Myocardial ET-1, IL-6, and TNF-α mRNA expressions were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Microvascular endothelial HMEC-1 cells were infected in vitro with or without addition of Cur or Bz. Induction of the Ca2+/NFAT pathway was assessed by fluorometry, immunoblotting, and reporter assay. FINDINGS Oral Cur therapy of recently infected mice reduced inflammatory cell infiltration of myocardial arteries without lowering parasite levels. Compared to that of the phosphate-buffered saline-receiving group, hearts from Cur-treated mice showed significantly decreased vessel inflammation scores (p < 0.001), vascular permeabilities (p < 0.001), and levels of IL-6/TNF-α (p < 0.01) and ET-1 (p < 0.05) mRNA. Moreover, Cur significantly (p < 0.05 for transcript; p < 0.01 for peptide) downregulated ET-1 secretion from infected HMEC-1 cells. Remarkably, Cur addition significantly (p < 0.05 at 27.0 μM) interfered with T. cruzi-dependent activation of the Ca2+/NFATc1 signalling pathway that promotes generation of inflammatory agents in HMEC-1 cells. CONCLUSIONS Oral treatment with Cur dampens cardiovasculopathy in acute Chagas mice. Cur impairs the Ca2+/NFATc1-regulated release of ET-1 from T. cruzi-infected vascular endothelium. These findings identify new perspectives for exploring the potential of Cur-based interventions to ameliorate Chagas heart disease.

Sífilis congénita en ecuador presente preocupante / Congenital syphilis in Ecuador present worrying

Introducción: La sífilis congénita (CS) se mantiene como un importante problema de salud pública. aún no se consigue satisfacer la atención prenatal, a pesar del aumento de cobertura, las acciones implementadas muestran baja efectividad en su prevención. La Organización Mundial de la Salud (OMS) estima que, globalmente, la mayoría de las infecciones de sífilis materna no se tratan y tienen un título suficientemente elevado (RPR ≥ 1: 8) como para causar una exposición fetal significativa a T. pallidum. Métodos: Es un estudio epidemiológico observacional y retrospectivo sobre la prevalencia, en el que se revisaron datos del Instituto Nacional de Censos y Estadísticas (INEC). Los datos se obtuvieron de los informes anuales de nacimiento, Se utilizó el programa SPSS 17.0 y Excel. Resultados: Se encontraron 2.210 casos de sífilis congénita en los últimos 16 años, con un incremento importante en los años 2003 y 2013 con 192 y 193 casos respectivamente. Discusión: La prevalencia de CS en el Ecuador igual que el resto de América se incrementa posiblemente la falta de control médico el sub diagnóstico y sub registro son factores importantes que impiden el control adecuado y por el contrario aumenten sistemáticamente. Los primeros años de registro (2000 a 2003) muestran casos tan altos como el final de la línea de base (2012 a 2016) este hecho podría deberse a la falta de prevención. Los registros presentados en el año 2008 tienen un pico que debe analizarse teniendo en cuenta la forma de registro. La presencia de falso positivo podría cuestionarse debido a nuevas técnicas de diagnóstico Conclusión: Los esfuerzos por disminuir la incidencia de sífilis congénita no han sido suficientes y según los datos obtenidos no se lograron cumplir las metas propuestas por la OMS y asumidas por el País, El desconocimiento por parte de los médicos que llevan el control prenatal y quienes reciben recién nacidos en los hospitales existiendo un alarmante sub registro y en otros casos un tratamiento poco eficiente y a destiempo. Sigue siendo la Sífilis congénita un problema médico social fácil de tratar si se diagnostica y trata oportunamente.

Introduction: Congenital syphilis (CS) remains an important public health problem. The prenatal care is still not achieved, despite the increase in coverage, the actions implemented show low effectiveness in its prevention. The World Health Organization (WHO) estimates that, overall, the majority of maternal syphilis infections are not treated and have a sufficiently high titer (RPR ≥ 1: 8) to cause significant fetal exposure to T. pallidum. Methods: This is an observational and retrospective epidemiological study on prevalence, in which data from the National Institute of Census and Statistics (INEC) were reviewed. The data was obtained from the annual birth reports. The SPSS 17.0 program and Excel were used. Results: We found 2,210 cases of congenital syphilis in the last 16 years, with a significant increase in the years 2003 and 2013 with 192 and 193 cases respectively. Discussion: The prevalence of CS in Ecuador, like the rest of the Americas, possibly increases the lack of medical control, the sub-diagnosis and sub-registration are important factors that prevent adequate control and, on the contrary, increase systematically. The first years of registration (2000 to 2003) show cases as high as the end of the baseline (2012 to 2016) this fact could be due to the lack of prevention. The records presented in 2008 have a peak that must be analyzed taking into account the registration form. The presence of false positive could be questioned due to new diagnostic techniques Conclusion: Efforts to reduce the incidence of congenital syphilis have not been sufficient and, according to the data obtained, the goals proposed by the WHO and assumed by the country were not achieved. The lack of knowledge on the part of the doctors who carry out prenatal care and they receive newborns in hospitals, there is an alarming sub-registry and in other cases an inefficient and untimely treatment. Congenital syphilis remains a social medical problem easy to treat if diagnosed and treated promptly