Leishmanicidal Activity of Isoselenocyanate Derivatives.

Conventional chemotherapy against leishmaniasis includes agents exhibiting considerable toxicity. In addition, reports of drug resistance are not uncommon. Thus, safe and effective therapies are urgently needed. Isoselenocyanate compounds have recently been identified with potential antitumor activity. It is well known that some antitumor agents demonstrate effects against Leishmania In this study, the in vitro leishmanicidal activities of several organo-selenium and organo-sulfur compounds were tested against Leishmania major and Leishmania amazonensis parasites, using promastigotes and intracellular amastigote forms. The cytotoxicity of these agents was measured in murine peritoneal macrophages and their selectivity indexes were calculated. One of the tested compounds, the isoselenocyanate derivative NISC-6, showed selectivity indexes 2- and 10-fold higher than those of the reference drug amphotericin B when evaluated in L. amazonensis and L. major, respectively. The American strain (L. amazonensis) was less sensitive to NISC-6 than L. major, showing a trend similar to that observed previously for amphotericin B. In addition, we also observed that NISC-6 significantly reduced the number of amastigotes per infected macrophage. On the other hand, we showed that NISC-6 decreases expression levels of Leishmania genes involved in the cell cycle, such as topoisomerase-2 (TOP-2), PCNA, and MCM4, therefore contributing to its leishmanicidal activity. The effect of this compound on cell cycle progression was confirmed by flow cytometry. We observed a significant increase of cells in the G1 phase and a dramatic reduction of cells in the S phase compared to untreated cells. Altogether, our data suggest that the isoselenocyanate NISC-6 may be a promising candidate for new drug development against leishmaniasis.

Comportamiento de comorbilidades en la mortalidad de pacientes con insuficiencia cardiaca crónica / Behavior of comorbidities in mortality of patients with chronic heart failure

Introducción: La insuficiencia cardíaca constituye un problema a nivel mundial y aumentará en los próximos años a consecuencia del envejecimiento poblacional. Se asocia a múltiples comorbilidades que pueden estar implicadas en su desarrollo, contribuir a la progresión de la enfermedad o empeorar el pronóstico. Objetivo: Evaluar la influencia de comorbilidades en la mortalidad de pacientes con insuficiencia cardíaca crónica. Métodos: Se realizó un estudio de cohorte retrospectivo en 242 pacientes, con diagnóstico de insuficiencia cardíaca crónica y una media de seguimiento de 5 años en la consulta de protocolo de insuficiencia cardíaca del Hospital Clínico Quirúrgico Hermanos Ameijeiras. Se determinó la magnitud de la asociación de la presencia de comorbilidades y la mortalidad a través del empleo de regresión logística. Resultados: El promedio de la edad fue mayor en los pacientes fallecidos 72,12 ± 12,088 años (p = 0,003). La presencia aislada de comorbilidades no mostró asociación con la mortalidad pero sí cuando coexistían más de dos comorbilidades. (OR: 2,91. IC: .991-8,61). Se encontró asociación lineal entre el número de comorbilidades y la mortalidad (p = 0,044). Conclusión: Las comorbilidades estudiadas no presentaron una asociación independiente con la mortalidad, pero la suma de ellas sí aumentó el riesgo de muerte en los pacientes con insuficiencia cardiaca(AU)

Introduction: Heart failure is a worldwide problem and will increase in the coming years as a result of population aging. It is associated with multiple comorbidities that may be involved in its development, contribute to the progression of the disease, or worsen the prognosis. Objective: To assess the influence of comorbidities on the mortality of patients with chronic heart failure. Methods: A retrospective cohort study was carried out in 242 patients with a diagnosis of chronic heart failure and a mean follow-up of 5 years in the heart failure protocol consultation at Hermanos Ameijeiras Surgical Clinical Hospital. The magnitude of the association between the presence of comorbidities and mortality was determined through the use of logistic regression. Results: The mean age was higher in deceased patients 72.12 ± 12.088 years (p = 0.003). The isolated presence of comorbidities did not show an association with mortality, but it did when more than two comorbidities coexisted. (OR: 2.91. CI: .991-8.61). A linear association was found between the number of comorbidities and mortality (p = 0.044). Conclusion: The studied comorbidities did not show an independent association with mortality, but the sum of them did increase the risk of death in patients with heart failure(AU)