Induction of pro-inflammatory response of the placental trophoblast by Plasmodium falciparum infected erythrocytes and TNF.

ABSTARCT: Plasmodium falciparum placental malaria is characterized by the sequestration of infected erythrocytes (IEs) in the placental intervillous space via adherence to chondroitin sulphate A (CSA), production of inflammatory molecules, and leukocytes infiltration. Previous reports suggest that the syncytiotrophoblast (ST) immunologically responds to IEs contact. This study explores the inflammatory response induced in BeWo cells by adherence of IEs and TNFstimulation. METHODS: A non-syncitialized BeWo cells (trophoblast model) were used to evaluate its response to CSA-adherents IEs (FCB1csa, FCB2csa, FCR3csa, 3D7csa) and TNF stimulation. Expression of membrane ICAM-1 (mICAM-1) receptor in BeWo cells was quantified by flow cytometry and the IL-8, IL-6 and soluble ICAM-1 (sICAM-1) concentrations were quantified by enzyme-linked immunosorbentassay (ELISA) in BeWo stimulated supernatants. RESULTS: BeWo cells stimulated with TNF and CSA-adherents IEs of FCB1csa and 3D7csa (strains with higher adhesion) increase the expression of ICAM-1 on the surface of cells and the secretion of immune factors IL-8, IL-6 and sICAM-1. This inflammatory response appears to be related to the level of adherence of IEs because less adherent strains do not induce significant changes. CONCLUSIONS: It was found that BeWo cells responds to CSA-IEs and to TNF favouring a placental pro-inflammatory environment, evidenced by increases in the expression of membrane mICAM-1 and release of soluble ICAM-1, as well as the IL-8 and IL-6 secretion. The expression of ICAM-1 in BeWo cells might be associated to an increase in leukocyte adhesion to the trophoblast barrier, promoting greater inflammation, while the sICAM-1 release could be a protection mechanism activated by trophoblastic cells, in order to regulate the local inflammatory response

Características clínicas y de laboratorio de la malaria por Plasmodium vivax, Colombia 2001

A descriptive study was carried out in 104 patients with Plasmodium vivax malaria, from the region of Turbo (Antioquia, Colombia). Clinical features and levels of hemoglobin, glycemia, serum bilirubin, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), creatinine and complete blood cell profile were established. 65% of the studied individuals were men and their mean age was 23. Of all individuals 59% had lived in the region for >; 1 year and 91% were resident in the rural area. 42% were farmers and 35% had a history of malaria. The mean parasitaemia was 5865 parasites/mm³. The evolution of the disease was short (average of 4.0 days). Fever, headache and chills were observed simultaneously in 91% of the cases while the most frequent signs were palmar pallor (46%), jaundice (15%), hepatomegaly (17%), and spleen enlargement (12%). Anemia was found in 39% of the women and in 51% of the men, 8% of individuals had thrombocytopaenia and 41% had hypoglycemia.Se realizó un estudio descriptivo con 104 enfermos de malaria por Plasmodium vivax, en Turbo (Antioquia, Colombia). Se evaluaron las características clínicas y los niveles de hemoglobina, glicemia, bilirrubina sérica, ALT, AST, creatinina y hemograma completo. Los hombres representaron el 65% del grupo, la edad promedio fue 23 años, el 59% tuvo más de un año de residir en el lugar, el 91% residían en zona rural, el 42% realizaba trabajos agrícolas y el 35% tenía antecedentes de malaria. La parasitemia promedio fue de 5865 parásitos/mm³. La evolución de la enfermedad fue corta (mediana de 4,0 días). Fiebre, cefalea y escalofrío estuvieron simultáneamente en 91% de los casos y los signos más frecuentes fueron palidez palmar (46%), ictericia (15%), hepatomegalia (17%) y esplenomegalia (12%). La anemia se encontró en el 39% de las mujeres y en el 51% de los hombres, y el 8% presentó trombocitopenia. Los niveles séricos de bilirrubinas directa e indirecta, de enzimas ALT y AST y de creatinina se encontraron, en general, normales. El 41% de los pacientes tuvo hipoglicemia

Simultaneous quantification of antimalarial steroids in solanum nudum extracts by high performance liquid chromatography (hplc)

Los esteroides con reconocida actividad antiplasmódica aislados de las hojas de Solanum nudum, fueron cuantificados en extractos de hexano, diclorometano, acetato de etilo y metanol mediante cromatografía liquida de alta eficiencia. Se verificaron algunos parámetros de validación con criterios de aceptación deseables tales como linealidad (r2= 0,9999), exactitud (R= 88,25- 102,82%), precisión (CV= 0,45 – 4,87 %), límites de detección y cuantificación (0,09

Amodiaquine failure associated with erythrocytic glutathione in Plasmodium falciparum malaria

OBJECTIVE: To establish the relationship between production of glutathione and the therapeutic response to amodiaquine (AQ) monotherapy in Plasmodium falciparum non-complicated malaria patients. METHODOLOGY: Therapeutic response to AQ was evaluated in 32 patients with falciparum malaria in two townships of Antioquia, Colombia, and followed-up for 28 days. For every patient, total glutathione and enzymatic activity (glutathione reductase, GR, and γ-glutamylcysteine synthetase, γ-GCS) were determined in parasitized erythrocytes, non-infected erythrocytes and free parasites, on the starting day (day zero, before ingestion of AQ) and on the day of failure (in case of occurrence). RESULTS: There was found an AQ failure of 31.25%. Independent of the therapeutic response, on the starting day and on the day of failure, lower total glutathione concentration and higher GR activities in parasitized erythrocytes were found, compared with non-infected erythrocytes (p < 0.003). In addition, only on the day of failure, γ-GCS activity of parasitized erythrocytes was higher, compared with that of healthy erythrocytes (p = 0.01). Parasitized and non-parasitized erythrocytes in therapeutic failure patients (TF) had higher total glutathione on the starting day compared with those of adequate clinical response (ACR) (p < 0.02). Parasitized erythrocytes of TF patients showed lower total glutathione on the failure day, compared with starting day (p = 0.017). No differences was seen in the GR and γ-GCS activities by compartment, neither between the two therapeutic response groups nor between the two treatment days. CONCLUSION: This study is a first approach to explaining P. falciparum therapeutic failure in humans through differences in glutathione metabolism in TF and ACR patients. These results suggest a role for glutathione in the therapeutic failure to antimalarials

La mitocondria en el género Plasmodium.

In eukaryotic cells, mitochondria are the ATP-producing and oxygen respiring organelles. In malaria cells, mitochondria adapts morphologically and physiologically to the metabolic conditions of the host. Therefore, in the mosquito, gametocytes have aerobic metabolism and a mitochondria of typical appearance, whereas in the vertebrate, sporozoites and merozoites respond to a microaerophilic metabolism and the mitochondria have cristae inner membranes and a low density matrix. Consequently, its electron transport chain and susceptibility to mitochondrial-inhibitors differ substantially. The influence of metabolic inhibitors on pyrimidine de novo synthesis has been of particular interest in malaria drug development. The current review briefly describes adaptations of Plasmodium mitochondria during development, biochemical aspects of mitochondrial function and the potential of mitochondria as antimalarial drug targets.La mitocondria en las células eucarióticas juega un papel central en el metabolismo energético. En Plasmodium, la mitocondria se adapta morfológica y fisiológicamente a las condiciones metabólicas de sus hospederos. Así, en el mosquito, los gametocitos tienen un metabolismo aerobio y una mitocondria de apariencia típica, mientras que en vertebrados, los esporozoítos y merozoitos responden a un metabolismo microaerofílico, su mitocondria tiene pocas crestas y matriz menos densa. Como consecuencia de estos cambios metabólicos, la cadena transportadora de electrones y la susceptibilidad a los inhibidores mitocondriales difiere sustancialmente. La dependencia de la síntesis de novo de pirimidinas a inhibidores metabólicos ha sido de particular interés en el desarrollo de drogas antimaláricas. El objeto de esta breve revisión es describir las adaptaciones de la mitocondria de Plasmodium durante su desarrollo y su potencial como blanco terapéutico. Se mencionan los aspectos bioquímicos importantes de la función mitocondrial en Plasmodium

Antiplasmodials soulattrolide derivatives from Calophyllum brasiliense and its mechanism of activity

Parasitic diseases such as malaria, leishmaniasis, trypanosomia-sis, and schistosomiasis are just one of the main causes of diseaseand death in the world today (WHO, 2016). In 2016, 91 countriesreported a total of 216 million cases of malaria, which representsan increase to 5 million cases in relation to the previous year, with15 countries holding 80% of the global burden of malaria. The totalnumber of deaths worldwide reached 445.000, similar to thatreported in 2015 (WHO, 2017; Chin, 2001; Newman et al., 2016),so there is an urgent need to discover new, safe and effective drugsfor the prophylaxis and treatment of malaria, mainly due to thedevelopment of resistance ofPlasmodium falciparum, the mostlethal Plasmodium species to chloroquine and other antimalarialdrugs. Few alternative drugs are in development and urgent mea-sures are needed to identify new types of antimalarial agents,many of which have originated from natural products (Olumese,2015; Leach, 2001).Clusiaceaeis one of the families of plants inwhich compounds with antimalarial activity have been found, suchas xanthones and derivatives of acylphloroglucinol. Since the genusCalophyllumis a potential source of secondary metabolites and itsspecies are little explored in the field of malaria, their explorationis justified as a phytotherapeutic alternative in the treatment ofmalaria (Hay et al., 2004; Chanphen et al., 1998; Pierson et al., 2010; Guillaume et al., 2009). This paper reports the isolation ofsoulattrolide (1) fromC. brasiliense. the preparation of eight newderivatives (2–9) by hemi-synthesis and the bioactivity studiesthereof

Diez años de eficacia terapéutica de la cloroquina en malaria no complicada por Plasmodium vivax, Turbo, Antioquia, años 2002 y 2011

Introduction: The therapeutic efficacy of antimalarial drugs should be monitored continuously because of the emergence of drug resistance. In Colombia, there are few studies evaluating the efficacy of chloroquine in uncomplicated malaria by Plasmodium vivax. This study evaluated the therapeutic efficacy of chloroquine at two different times, with an interval of ten years, in the same municipality.Objective: To evaluate the therapeutic response to chloroquine for the treatment of uncomplicated P.vivax malaria in Turbo, Antioquia, in 2002, and to compare these results with those observed in 2011 in the same municipality.Materials and methods: Two studies included 152 volunteers (50 in 2002 and 102 in 2011), older than 5 years old, with uncomplicated malaria according to the World Health Organization (WHO) criteria and simple infection with P. vivax. The efficacy of chloroquine, according to the current standard treatment of the Pan American Health Organization (PAHO) (1998) and WHO (2009), was monitored with 1,500 mg of chloroquine in 3 days and was followed clinically and parasitologically on days 0, 1, 2, 3, 7, 14 and 21 in 2002, and also on day 28 in 2011. At the end of the follow-up a dose of 0.25 mg/kg/day of primaquine was administered to each patient for 14 days.Results: A hundred percent of the volunteers had adequate clinical and parasitological response inboth studies.Conclusions: Chloroquine continues to be highly effective for the treatment of uncomplicated P. vivax malaria in Turbo, Antioquia, Colombia. doi: http://dx.doi.org/10.7705/biomedica.v33i3.1631Introducción. La eficacia terapéutica de los antipalúdicos debe ser vigilada permanentemente debido al problema de resistencia. En Colombia existen pocos estudios que evalúen la eficacia de la cloroquina en la malaria no complicada por Plasmodium vivax.Objetivo. Evaluar la respuesta terapéutica de la cloroquina en el tratamiento del paludismo no complicado por P. vivax en el año 2011 en Turbo, Antioquia, y comparar estos resultados con los del estudio realizado en el año 2002 en el mismo municipio.Materiales y métodos. Se llevaron a cabo dos estudios en los que se incluyeron 152 participantes (50 en el año 2002 y 102 en el año 2011), todos mayores de cinco años, con malaria no complicada e infección simple por P. vivax, según los criterios de la Organización Mundial de la Salud (OMS). Se evaluó la eficacia terapéutica de la cloroquina, según los protocolos vigentes de la Organización anamericana de la Salud (1998) y la OMS (2009); se dio tratamiento estándar supervisado con 1.500 mg de cloroquina en tres días y se hizo seguimiento clínico y parasitológico los días 0, 1, 2, 3, 7, 14 y 21 en el año 2002 y, además, el día 28 en el año 2011. Al finalizar el seguimiento se suministró primaquinaa una dosis diaria de 0,25 mg/kg durante 14 días en todos los participantes.Resultados. Los resultados clínico y parasitológicos fueron adecuados en el 100 % de los participantes de ambos estudios.Conclusiones. La cloroquina continúa siendo eficaz para el tratamiento de la malaria no complicada por P. vivax en Turbo, Antioquia. doi: http://dx.doi.org/10.7705/biomedica.v33i3.1631

Comparación de los métodos Optimal y gota gruesa para el diagnóstico de malaria en una zona endémica sin epidemia.

The capacity of Optimal to diagnose malaria was compared with the thick smear test in two representative samples, one with acute febrile syndrome (AFS) n = 107, and another diagnosed by thick smear test (AFS + M) n = 82. The samples were chosen from patients at the malaria diagnostic clinic in Turbo, Antioquia, Colombia, between June and August 2000. The study was designed to be descriptive, prospective, and cross-sectional. The two tests were applied simultaneously in the AFS group (parallel, double blind design), and in sequential form in the AFS + M group. The thick smear test was the standard test. Optimal tests were carried out according to the manufacturer's instructions. In the parallel design, Optimal showed, for Plasmodium falciparum, a sensitivity of 40% [95% CI: 18-67], a specificity of 98% (95% CI: 92-100) and positive and negative predictive values of 75% (95% CI: 36-96) and 91% (95% CI: 83-96%), respectively. For Plasmodium vivax, it showed a sensitivity of 97% (95% CI: 82-100), a specificity of 89% (95% CI: 80-95) and positive and negative predictive values of 79% (95% CI: 62-90) and 98% (95% CI: 91-100). With the sequential design, Optimal showed a sensitivity of 67% (95% CI: 52-79) and 97% (95% CI: 83-100) for P. falciparum and P. vivax, respectively. For P. falciparum, the sensitivity was directly proportional to the parasitemia, while the sensitivity for P. vivax was independent from the parasitemia. The diagnostic values and operative characteristics of the thick smear test surpassed the Optimal test in its sensitivity for P. falciparum; the specificities were similar. Both tests were nearly identical in their diagnostic capacity for P. vivax. These results recommend that the thick smear test be retained as a routine or reference test for malaria diagnosis, with Optimal used as an ancillary test.En Turbo, Antioquia, entre junio y agosto de 2000, se evaluó la capacidad diagnóstica de Optimal ® frente a la gota gruesa, en dos muestras representativas de las poblaciones de consultantes al puesto de diagnóstico de malaria: uno con síndrome febril agudo (SFA) n=107, y otro con malaria diagnosticada por gota gruesa (SFAM) n=82. Se usó un diseño descriptivo, prospectivo y transversal. Las dos pruebas se aplicaron en forma simultánea o paralela en el grupo (SFA) y en forma secuencial en el grupo (SFAM). La gota gruesa fue la prueba estándar. Optimal ® se usó según las instrucciones del fabricante. El grupo SFA se estudió con diseño ciego. Con diseño paralelo, Optimal ® tuvo para Plasmodium falciparum, una sensibilidad de 40% (intervalo de confianza del 95% (IC 95%: 18-67), especificidad de 98% (IC 95%: 92-100), valores predictivos positivo y negativo de 75% (IC 95%: 36-96) y 91% (IC 95%: 83-96%). Para Plasmodium vivax mostró sensibilidad de 97% (IC 95%: 82-100), especificidad de 89% (IC 95%: 80-95), valores predictivos positivo y negativo de 79% (IC 95%: 62-90) y 98% (IC 95%: 91- 100). Con diseño secuencial, Optimal ® tuvo sensibilidad de 67% (IC 95%: 52-79) para P. falciparum y 97% (IC 95%: 83-100) para P. vivax. Para P. falciparum, la sensibilidad fue directamente proporcional a la parasitemia, mientras que para P. vivax la sensibilidad fue independiente de la parasitemia. Por sus valores diagnósticos y sus características operativas, la gota gruesa supera ampliamente a Optimal ® en sensibilidad para P. falciparum, aunque fue similar en especificidad y ambas pruebas son iguales en diagnóstico de P. vivax. La gota gruesa debe conservarse como la prueba de rutina y de referencia para el diagnóstico de malaria y Optimal ® como una prueba auxiliar

Resting respiratory sinus arrhythmia and posttraumatic stress disorder: A meta-analysis

Respiratory sinus arrhythmia (RSA) has been examined as a psychophysiological marker of stress vulnerability. Research indicates that low resting RSA is associated with physical and mental health problems, including posttraumatic stress disorder (PTSD). Some research suggests that people diagnosed with PTSD have lower RSA than people without PTSD, but findings have been mixed and the overall magnitude of this effect is unknown, indicating the need for a comprehensive meta-analysis. This meta-analysis examined the association between PTSD and baseline RSA in 55 studies, including 12 unpublished studies, with a total sample size of 6689. Studies were included if they used a PTSD measure, a baseline measure of RSA, and involved humans. Studies were excluded if they were not available in English, did not present quantitative data, presented duplicate data, were a case series, or did not provide results required for computing an effect size. The meta-analysis indicated there is a small but significant association between PTSD and RSA (g = -0.26; 95% CI = -0.35, -0.16) with moderate heterogeneity. Moderator analyses suggested that effects are larger for adults than for children and for DSM-5 PTSD measures than for non-DSM referenced measures. We found some evidence for publication bias among the meta-analysis findings. Overall, there is a small but reliable association between PTSD and lower resting RSA, providing support for further research examining the complex relationship between parasympathetic activity and PTSD

Malaria por Plasmodium vivax: curación del ataque agudo con tres dosis diferentes de primaquina y dosis fija de cloroquina. Antioquia, Colombia, 2003-2004

Introduction. Chloroquine (CQ) and primaquine (PQ) are used in Colombia for treatment of uncomplicated vivax malaria but there are few efficacy studies of this scheme. Objectives. a) to investigate the clinical picture of vivax malaria in adult patients; b) to evaluate the antimalarial treatment response to the standard scheme CQ-PQ; c) to compare the efficacy of the standard scheme and two alternative schemes with equal dose of CQ and different PQ dose; d) to identify the adverse effects of CQ-PQ treatment.Materials and methods. Randomized, nonblind design; three groups, defined according to total dose of PQ: 45, 105 and 210 mg. All patients received CQ (1500 mg, in 48 hours), which was followed by PQ. Patients were recruited in Turbo and El Bagre. The follow-up period was 28 days. Antimalarial treatment response was classified according to the WHO-2001 protocol (early failure, late failure, adequate response).Results. In total 228 patients were recruited, 18 were lost between days 4 and 27; the antimalarial treatment response was evaluated in 210. The clinical findings were similar to those described by other authors. Parasitaemia clearance was confirmed during the first 24 hours of CQ treatment in 11% of patients. At 48 hours 66% and at 72 hours 97% of patients were negative. All patients (210) displayed adequate treatment response to the CQ-PQ treatment. The different doses of PQ did not affect this response.Conclusions. CQ-PQ should be conserved as the first treatment choice and should be evaluated in other areas. Simultaneous administration of CQ and PQ is proposed.Introducción. Cloroquina (CQ) y primaquina (PQ) se usan en Colombia para tratar la malaria vivax no complicada, pero son escasas las evaluaciones de su eficacia. Objetivos. a) investigar la clínica de la malaria vivax en dos zonas con muy diferente nivel endémico; b) evaluar la respuesta terapéutica antimalárica obtenida con el tratamiento estándar CQ-PQ tomadas simultáneamente; c) comparar la eficacia del tratamiento estándar y la de otros dos esquemas que conservan la dosis total de CQ pero varían la de PQ; d) identificar los efectos adversos ocurridos durante el tratamiento CQ-PQ.Materiales y métodos. Diseño aleatorio, controlado, no ciego; tres grupos definidos según dosis total de PQ: 45, 105 y 210 mg. Todos recibieron CQ (1500 mg, en 48 horas) y simultáneamente PQ. Pacientes captados consecutivamente, en Turbo y El Bagre. Seguimiento durante 28 días. La respuesta terapéutica antimalárica clasificada en falla precoz, falla tardía y respuesta adecuada.Resultados. Se trataron 228 pacientes y la respuesta terapéutica antimalárica se evaluó en 210. El cuadro clínico encontrado es similar al descrito por otros autores. En todos los tres grupos, la parasitemia se eliminó en 24 horas de tratamiento con CQ en 11% de los pacientes, en 48 horas en 66% y en 72 horas en 97%. Todos los 210 pacientes respondieron adecuadamente al tratamiento CQ-PQ. La dosis variable de PQ no afectó esta respuesta.Conclusiones. CQ-PQ debe conservarse como la primera opción terapéutica y debe evaluarse en otras áreas. Se propone la administración concomitante de CQ y PQ