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)

Distracción ósea: tratamiento de la apnea obstructiva en neonatos con micrognatia / Mandibular distraction: treatment of obstructive apnea in neonates with micrognathia

Las malformaciones craneofaciales (secuencia de Pierre Robin, síndrome de Threacher-Collins, síndrome de Nager, etc.) con frecuencia van asociadas a hipoplasia mandibular grave, que puede causar obstrucción de la vía aérea superior por retroposición de la base de la lengua dentro del espacio faríngeo posterior. La mayoría de los pacientes responden al tratamiento postural, en decúbito prono, puede ser necesario controlar la saturación de oxígeno, insertar un tubo nasofaríngeo e incluso intratraqueal. En casos más graves con pausas prolongadas y frecuentes de apnea, la traqueostomía puede ser necesaria, pero se asocia a una alta morbilidad y, ocasionalmente, mortalidad. En los últimos 2 años, en la Unidad Multidisciplinaria de Labio y Fisura Palatina del Hospital Virgen de las Nieves de Granada, se ha tratado a 4 niños con apnea obstructiva grave secundaria a hipoplasia mandibular grave mediante distracción mandibular osteogénica, y este procedimiento se ha mostrado eficaz en la resolución del problema. Ha evitado la traqueostomía y se ha elongado la mandíbula en el plazo de 3-4 semanas. En este tiempo han desaparecido los problemas respiratorios obstructivos, así como también de la deglución, y los resultados estéticos obtenidos han resultado excelentes y las complicaciones, por el momento, mínimas(AU)

Craniofacial malformations (Pierre-Robin sequence, Treacher-Collins syndrome, Nager syndrome, etc.) are frequently accompanied by severe mandibular hypoplasia, which can cause upper airway obstruction due to retroposition of the base of the tongue in the posterior pharyngeal space. The majority of patients respond to postural treatment in decubitus prono. It may be necessary to monitor oxygen saturation and insert a nasopharyngeal or even an endotracheal tube. Tracheostomy may be necessary in more serious cases with long and frequent apnea pauses, but it is associated with high morbidity and occasional mortality. In the last two years, four children with severe obstructive apnea secondary to mandibular hypoplasia were treated by means of "osteogenic mandibular distraction" in the multidisciplinary Cleft Palate Department of Virgin de las Nieves Hospital (Granada, Spain). This procedure effectively resolved the problem, making tracheostomy unnecessary and lengthening the jaw within 3-4 weeks; in this period, obstructive respiratory problems and swallowing difficulties disappeared. The aesthetic results were excellent and the complications so far have been minimal. Objective: To present the results of a patient series with several types of POP treated using the same approach and operation(AU)