Profiling of Flavonol Derivatives for the Development of Antitrypanosomatidic Drugs

Flavonoids represent a potential source of new antitrypanosomatidic leads. Starting from a library of natural products, we combined target-based screening on pteridine reductase 1 with phenotypic screening on Trypanosoma brucei for hit identification. Flavonols were identified as hits, and a library of 16 derivatives was synthesized. Twelve compounds showed EC50 values against T. brucei below 10 \u3bcM. Four X-ray crystal structures and docking studies explained the observed structure-activity relationships. Compound 2 (3,6-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one) was selected for pharmacokinetic studies. Encapsulation of compound 2 in PLGA nanoparticles or cyclodextrins resulted in lower in vitro toxicity when compared to the free compound. Combination studies with methotrexate revealed that compound 13 (3-hydroxy-6-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one) has the highest synergistic effect at concentration of 1.3 \u3bcM, 11.7-fold dose reduction index and no toxicity toward host cells. Our results provide the basis for further chemical modifications aimed at identifying novel antitrypanosomatidic agents showing higher potency toward PTR1 and increased metabolic stability

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Book Reviews N°24

JAMES, Daniel; Doña María. Historia de vida, memoria e identidad política, Manantial, Buenos Aires, 2004, 291 pp. CALVEIRO, Pilar. Política y/o violencia. Una aproximación a la guerrilla de los años 70. Norma, Buenos Aires, 2005. 192 p. RONIGER, Luis y SNAJDER, Mario; El legado de las violaciones de los derechos humanos en el Cono Sur. Buenos Aires, ediciones Al Margen, 2005. GODOY, Cristina y LABORANTI, María Inés (compiladoras), Historia & Ficción, Rosario, UNR Editora - Universidad Nacional de Rosario, 2005, 214 p. TEOBALDO, Mirta Elena; GARCÍA, Amelia Beatriz; NICOLETTI, María Andrea y BEL, Rolando Bel y ROMERO, Teresa Romero (colaboradores); Hoy nos visita el Inspector. Historia e historias de la Inspección y Supervisión escolar en Río Negro y Neuquén. 1884 - 1992; Centro de Estudios Patagónicos (CEP). Facultad de Ciencias de la Educación. Universidad Nacional del Comahue. Departamento de Publicaciones de la Facultad de Derecho y Ciencias Sociales. Universidad Nacional del Comahue, General Roca, Río Negro. 2005. BRIEGER, Pedro; Qué es Al Qaeda. Terrorismo y violencia política; Capital Intelectual, Buenos Aires, 2006, 112 pp. BARRIERA, Darío G.; Conquista y colonización hispánica. Santa Fe la Vieja (1573-1660), Nueva Historia de Santa Fe, Tomo 2, La Capital/Prohistoria, Rosario, 2006, 216 pp.Fil: Apellido, Nombre. Universidad 1. Universidad 2; Argentina.Cerio, Débora. CEHO. UNR; Argentina.Pasquali, Laura. UNR. Conicet. ISP 3; Argentina.Luciani, Laura. CEHO. UNR; Argentina.Nicastro Mauri, Roxana C. UNR; ArgentinaPierini, María de los Milagros. Universidad Nacional de la Patagonia Austral; Argentina.González, Juan Aníbal Edgardo. ISP 3; Argentina.De los Ríos, Evangelina. UNR; Argentina

Cervical cancer prevention in El Salvador (CAPE)—An HPV testing-based demonstration project: Changing the secondary prevention paradigm in a lower middle-income country

Highlights • CareHPV tests were used to compare screen-and-treat and colposcopy management. • Screen-and-treat strategy with HPV testing was found to be very cost-effective. • CAPE has screened > 25,000 women in the Paracentral region. • Over 70% of screen-positive women received recommended treatment within six months. • CAPE is an example of public-private partnership resulting in paradigm change