Diana Margarita Márquez Fernández

[Clinical and laboratory profile of Plasmodium vivax malaria patients hospitalized in Apartadó, Colombia].

INTRODUCTION Malaria is a public health problem in the Urabá region recording rates of infection above those of the Antioquia department. The burden of vivax malaria is 78.7% and the profile of vivax malaria in this region has scarcely been studied. OBJECTIVES To analyze the clinical and laboratory characteristics of patients hospitalized for vivax malaria in Apartadó. MATERIALS AND METHODS We reviewed the medical records of patients with vivax malaria hospitalized in the Antonio Roldán Betancur hospital from 2004-2007. Results. Of 359 patients with vivax malaria who required hospitalization, 23.1% (83/359 patients) had the following complications: severe anemia, 51.8% (43/83); severe thrombocytopenia, 15.6% (13/83); hyperbilirubinemia, 7.2 % (6/83). Some patients met several criteria for complicated malaria simultaneously, including one case of acute respiratory distress syndrome. The most significant laboratory changes were decreases in the hemoglobin, hematocrit and platelet levels, with increased levels of transaminases and bilirubin. Only 4.82% (4/83) of patients with complicated malaria were treated with intravenous quinine, no one died. CONCLUSIONS The elevated frequency of complicated vivax malaria found in the Uraba region in this study is noteworthy, particularly in children under 5 years. The results highlight the need to strengthen, amongst the health staff, the knowledge of the guidelines for the clinical care of malaria patients, in order to make a correct clinical diagnosis and provide appropriate treatment.

In Vitro Susceptibility of Plasmodium vivax to Antimalarials in Colombia

ABSTRACT The in vitro susceptibilities of 30 isolates of Plasmodium vivax to a number of antimalarials (chloroquine [CQ], mefloquine, amodiaquine, quinine, and artesunate [AS]) were evaluated. The isolates came from the region of Urabá in Colombia, in which malaria is endemic, and were evaluated by the schizont maturation test. The 50% inhibitory concentration (IC50) was 0.6 nM (95% confidence interval [CI], 0.3 to 1.0 nM) for artesunate, 8.5 nM (95% CI, 5.6 to 13.0 nM) for amodiaquine, 23.3 nM (95% CI, 12.4 to 44.1 nM) for chloroquine, 55.6 nM (95% CI, 36.8 to 84.1 nM) for mefloquine, and 115.3 nM (95% CI, 57.7 to 230.5 nM) for quinine. The isolates were classified according to whether the initial parasites were mature or immature trophozoites (Tfz). It was found that the IC50s for chloroquine and artesunate were significantly different in the two aforementioned groups (P < 0.001). The IC50s of CQ and AS were higher in the isolates from mature Tfz (CQ, 39.3 nM versus 17 nM; AS, 1.4 nM versus 0.3 nM), and 10% of the isolates showed lower susceptibilities to one of the antimalarial drugs, 13.3% to two antimalarial drugs, and 3.3% to more than three antimalarial drugs. It should be highlighted that despite the extensive use of chloroquine in Colombia, P. vivax continues to be susceptible to antimalarials. This is the first report, to our knowledge, showing in vitro susceptibilities of P. vivax isolates to antimalarials in Colombia.

Synthesis and cytotoxic activity of tri-acyl ester derivatives of uridine in breast cancer cells

espanolObjetivos: Sintetizar derivados triesterificados de la uridina y evaluar su citotoxicidad sobre una linea celular de cancer de mama. Metodos: Se prepararon derivados triesterificados de la uridina mediante la esterificacion de Steglich para los acidos grasos y aromaticos, y con anhidrido acetico. Ademas se preparo el derivado acetonido mediante catalisis acida. Los compuestos se caracterizaron por espectroscopia de RMN (RMN ¹H y RMN 13C), y espectrometria de masas. Los derivados se evaluaron sobre lineas celulares de tumor de ovario de hamster chino (CHO) y de cancer de mama (MCF-7). Resultados: Se obtuvieron cinco derivados triesterificados de la uridina, uno con acido acetico, tres con acidos grasos (acido miristico, acido estearico y acido oleico) y uno con acido aromatico. Los derivados de uridina per-acetilada y acetonido se obtuvieron con rendimientos altos, sin embargo los derivados con acidos grasos y aromatico, se obtuvieron con rendimientos moderados y bajo, respectivamente. El acetonido y los compuestos 2 y 3, exhibieron inhibicion significativa de la viabilidad celular sobre ambas lineas a la concentracion mas alta evaluada. Conclusiones: El metodo de esterificacion con agentes de acoplamiento utilizado, permitio obtener derivados triesterificados de la uridina con acidos grasos y aromaticos. No se observo actividad citotoxica significativa (p EnglishAims: Synthesize tri-acyl ester derivatives of uridine, and evaluate its cytotoxicity against breast cancer cells line. Methods: The tri-esterified uridine derivatives were obtained through Steglich esterification reaction by fatty and aromatic acids, and with acetic anhydride. An acetonide derivative from uridine was prepared with acid catalysis. Compounds were characterized by NMR spectroscopy (¹H NMR and 13C NMR), and mass spectrometry. Derivatives were assessed in chinese hamster ovary (CHO-K1) and human breast cancer (MCF-7) cell lines. Results: Five tri-acyl ester derivatives of uridine were obtained one acetic acid, three fatty acids (myristic acid, stearic acid and oleic acid) with an aromatic acid. The uridine per-acetylated and uridine acetonide were obtained in high yields, however, the tri-acyl ester derivatives of uridine with fatty and aromatic acids were obtained in moderate and low yields, respectively. The acetonide and compounds 2 and 3 exhibited a cell viability inhibition significant on both cell lines to the higher concentration. Conclusions: Esterification method with coupling agents allowed obtained tri-acyl ester uridine derivatives with aliphatic and aromatic acids. However, significant cytotoxic activity (p

Synthesis and interaction of sterol-uridine conjugate with DMPC liposomes studied by differential scanning calorimetry

Differential scanning calorimetry (DSC) is a thermoanalytical technique which provides information on the interaction between drugs and models of cell membranes. Studies on the calorimetric behavior of hydrated phospholipids within liposomes are employed to shed light on the changes in the physico-chemical properties when interacting with drugs. In this report, new potential anti-cancer drugs such as uridine and uridine derivatives (acetonide and its succinate), 3β-5α,8α-endoperoxide-cholestan-6-en-3-ol (5,8-epidioxicholesterol) and conjugate (uridine acetonide-epidioxicholesterol succinate) have been synthesized. Steglich esterification method using coupling agents allowed to obtain the uridine acetonide-sterol conjugate. The study on the interaction between the drugs and dimiristoyl-phophatidilcholine (DMPC) liposomes has been conducted by the use of DSC. The analysis of the DSC curves indicated that the uridine and derivatives (acetonide and its succinate) present a very soft interaction with the DMPC liposomes, whereas the 5,8-epidioxicholesterol and the conjugate showed a strong effect on the thermotropic behavior. Our results suggested that the lipophilic character of uridine acetonide-sterol conjugate improves the affinity with the DMPC liposomes.