Short Antimicrobial Peptide Derived from the Venom Gland Transcriptome of Pamphobeteus verdolaga Increases Gentamicin Susceptibility of Multidrug-Resistant Klebsiella pneumoniae.

Infectious diseases account for nine percent of annual human deaths, and the widespread emergence of antimicrobial resistances threatens to significantly increase this number in the coming decades. The prospect of antimicrobial peptides (AMPs) derived from venomous animals presents an interesting alternative for developing novel active pharmaceutical ingredients (APIs). Small, cationic and amphiphilic peptides were predicted from the venom gland transcriptome of Pamphobeteus verdolaga using a custom database of the arthropod's AMPs. Ninety-four candidates were chemically synthesized and screened against ATCC® strains of Escherichia coli and Staphylococcus aureus. Among them, one AMP, named PvAMP66, showed broad-spectrum antimicrobial properties with selectivity towards Gram-negative bacteria. It also exhibited activity against Pseudomonas aeruginosa, as well as both an ATCC® and a clinically isolated multidrug-resistant (MDR) strain of K. pneumoniae. The scanning electron microscopy analysis revealed that PvAMP66 induced morphological changes of the MDR K. pneumoniae strain suggesting a potential "carpet model" mechanism of action. The isobologram analysis showed an additive interaction between PvAMP66 and gentamicin in inhibiting the growth of MDR K. pneumoniae, leading to a ten-fold reduction in gentamicin's effective concentration. A cytotoxicity against erythrocytes or peripheral blood mononuclear cells was observed at concentrations three to thirteen-fold higher than those exhibited against the evaluated bacterial strains. This evidence suggests that PvAMP66 can serve as a template for the development of AMPs with enhanced activity and deserves further pre-clinical studies as an API in combination therapy.

The limited knowledge of placental damage due to neglected infections: ongoing problems in Latin America.

The placenta works as a selective barrier, protecting the fetus from potential infections that may affect the maternal organism during pregnancy. In this review, we will discuss several challenging infections that are common within Latin American countries and that may affect the maternal-fetal interface and pose risks to fetal development. Specifically, we will focus on emerging infectious diseases including the arboviruses, malaria, leishmaniasis, and the bacterial foodborne disease caused by Shiga toxin-producing Escherichia coli. We will also highlight some topics of interest currently being studied by research groups that comprise an international effort aimed at filling the knowledge gaps in this field. These topics address the relationship between exposure to microorganisms and placental abnormalities, congenital anomalies, and complications of pregnancy. ABBREVIATIONS: ADE: antibody-dependent enhancement; CCL2: monocyte chemoattractant protein-1; CCL3: macrophage inflammatory protein-1 α; CCL5: chemokine (C-C motif) ligand 5; CHIKV: chikungunya virus; DCL: diffuse cutaneous leishmaniasis; DENV: dengue virus; Gb3: glycolipid globotriaosylceramyde; HIF: hypoxia-inducible factor; HUS: hemolytic uremic syndrome; IFN: interferon; Ig: immunoglobulins; IL: interleukin; IUGR: intrauterine growth restriction; LCL: localized cutaneous leishmaniasis; LPS: lipopolysaccharid; MCL: mucocutaneous leishmaniasis; NO: nitric oxide; PCR: polymerase chain reaction; PGF: placental growth factor; PM: placental malaria; RIVATREM: Red Iberoamericana de Alteraciones Vasculares em transtornos del Embarazo; sVEGFR: soluble vascular endothelial growth factor receptor; STEC: shiga toxin-producing Escherichia coli; stx: shiga toxin protein; TNF: tumor necrosis factor; TOAS: T cell original antigenic sin; Var2CSA: variant surface antigen 2-CSA; VEGF: vascular endothelial growth factor; VL: visceral leishmaniasis; WHO: world health organization; YFV: yellow fever virus; ZIKV: Zika virus.

Vascular Dysfunction in Mother and Offspring During Preeclampsia: Contributions from Latin-American Countries.

Pregnancy is a physiologically stressful condition that generates a series of functional adaptations by the cardiovascular system. The impact of pregnancy on this system persists from conception beyond birth. Recent evidence suggests that vascular changes associated with pregnancy complications, such as preeclampsia, affect the function of the maternal and offspring vascular systems, after delivery and into adult life. Since the vascular system contributes to systemic homeostasis, defective development or function of blood vessels predisposes both mother and infant to future risk for chronic disease. These alterations in later life range from fertility problems to alterations in the central nervous system or immune system, among others. It is important to note that rates of morbi-mortality due to pregnancy complications including preeclampsia, as well as cardiovascular diseases, have a higher incidence in Latin-American countries than in more developed countries. Nonetheless, there is a lack both in the amount and impact of research conducted in Latin America. An impact, although smaller, can be seen when research in vascular disorders related to problems during pregnancy is analyzed. Therefore, in this review, information about preeclampsia and endothelial dysfunction generated from research groups based in Latin-American countries will be highlighted. We relate the need, as present in many other countries in the world, for increased effective regional and international collaboration to generate new data specific to our region on this topic.

Screening of anthocyanins in single red grapes using a non-destructive method based on the near infrared hyperspectral technology and chemometrics.

BACKGROUND: Anthocyanins are the main compounds responsible for the colour of red wines and therefore it may be important to evaluate the content of the aforesaid secondary metabolites during grape ripening due to the crucial importance to determine wine colour. Nowadays, there is a growing demand of rapid and non-destructive analytical tools for analysing grapes, such as the emerging hyperspectral analysis. RESULTS: The hyperspectral images of intact grapes (Vitis vinifera L. cv. Tempranillo, Graciano, Garnacha and Mazuelo red grape from vineyards located in the D.O.Ca. Rioja at two different developmental stages) were recorded using a near infrared hyperspectral imaging device (900-1700 nm). Reference values of anthocyanins were obtained by HPLC-DAD. Calibrations were performed by modified partial least squares regression and present a good potential (coefficient of determination of 0.72 and standard error of cross-validation values of 0.78 and 0.70 mg per grape for total and non-acylated anthocyanins respectively). CONCLUSION: The procedure reported here presents a good potential for a fast and reasonably inexpensive screening of these compounds in intact single berries. Moreover, the heterogeneity of anthocyanins within the same ripeness stage could be evaluated using this non-detructive tool.

High IFN-gamma and TNF production by peripheral NK cells of Colombian patients with different clinical presentation of Plasmodium falciparum.

BACKGROUND: In Colombia, Plasmodium falciparum infection rarely results in severe disease or mortality compared to infections in African populations. During natural infection NK cells exhibit a cytolytic effect and regulate dendritic cells, macrophages, neutrophils as well as affect antigen specific T and B cell responses. To characterize the NK cells in P. falciparum infected patients of a highly endemic region of Colombia, the degree of NK proliferation and production of IFN gamma and TNF production in these cells were explored. METHODS: Seventeen patients with acute and three with severe P. falciparum malaria patients from the Northwest region of the country were recruited in the study. In addition, 20 healthy controls were included: 10 from Medellin (no-transmission area) and 10 from the Uraba region (a malaria endemic area). Immunophenotypic analysis of peripheral mononuclear cells was performed by FACS to detect total number of NK cells, subtypes and intracellular IFNγ and TNF production by NK cells in the different patient groups. RESULTS: The total mean CD56(+)/CD3(-) NK cell proportions in acute and severe malaria subjects were 9.14% (7.15%CD56(dim), 2.01%CD56(bright)) and 19.62% (16.05%CD56(dim), 3.58%CD56(bright)), respectively, in contrast to healthy controls from endemic (total mean CD56(+)/CD3(-)1.2%) and non-endemic area (total mean CD56(+)/CD3(-) 0.67%). Analysis of basal IFNγ and TNF levels confirmed the CD56(bright) NK population as the main cytokine producer (p < 0.0001) in the groups affected with malaria, with the CD56(dim) NK cell exhibiting the highest potential of TNF production after stimulus in the acute malaria group. CONCLUSIONS: The results confirm the important role of not only CD56(bright) but also of CD56(dim) NK cell populations as producers of the two cytokines in malaria patients in Colombia.

Preeclamptic sera directly induce slit-diaphragm protein redistribution and alter podocyte barrier-forming capacity.

BACKGROUND/AIMS: Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the slit diaphragm. We hypothesized that disturbances of podocyte biology contribute to proteinuria in women with preeclampsia (PE). METHODS: A human podocyte cell line was stimulated with serum from women with PE (patients) and healthy pregnant women (controls); the main changes in 3 important podocyte proteins: podocin, CD2AP and actin were established by immunofluorescence and Western blot; we also searched for changes in cell plasticity by measuring the resistance of cultured podocytes. RESULTS: Different distributions of CD2AP, podocin and actin were observed in the podocytes stimulated with patient sera compared to podocytes stimulated with control sera. We also found that the mean resistance value of podocytes cultured with serum from women with PE was significantly lower than podocytes cultured with serum from controls. There was no difference in the protein expression level of podocin and CD2AP between patients and controls. CONCLUSIONS: We present evidence that there are differences in podocytes when stimulated with sera from women with PE compared to those stimulated with healthy pregnancy sera. This is the first time that podocyte alterations have been directly related to PE; these descriptive findings could be considered as an interesting beginning for further studies relating podocytes and PE.

Metabolismo del triptofano: ¿Un elemento más en el enigma de la tolerancia materna al feto? / Triptophan metabilism in the regulation of inmune system

Este es un artículo de revisión donde se hace énfasis en el papel del metabolismo del triptófano en la regulación del sistema inmune principalmente por inhibición de la proliferación de los linfocitos T, tanto en la respuesta inmune sistémica como en la de la interfase maternofetal. El triptófano es metabolizado por dos vías: la vía de la serotonina y la vía de la quinurenina, participando en esta última las enzimas triptófano 2-3 dioxigenasa (TDO) y la indolamina 2-3 dioxigenasa (IDO). El interferón gama estimula la producción de IDO por una subpoblación de macrófagos diferenciados por el factor estimulante de colonias 1 y por las células dendríticas. Otros activadores del sistema inmune como las interleuquinas 1 y 2, el lipopolisacárido bacteriano y el virus de la inmunodeficiencia humana, pueden aumentar los niveles de IDO. En el caso particular de la gestación, se ha planteado que la IDO expresada por el sincitiotrofoblasto disminuye el triptófano disponible para la proliferación de los linfocitos T en la interfase materno fetal que serían los mediadores del rechazo del aloinjerto fetal. La inhibición de la IDO con el 1-metil-triptófano, competidor específico de la enzima, disminuye la reabsorción embrionaria. En nuestro grupo estamos planteando que los macrófagos deciduales expresan IDO en respuesta al IFN-g producido por las células NK, y que ésta al metabolizar el triptófano, modula la activación de las células NK

Citoquinas en reproduccion / Cytokines in reproductive events

Se presenta una revisión de la literatura sobre el papel de las citoquinas en diferentes eventos de la reproducción como la ovulación, la luteinización, la menstruación y la implantación. Se hace particular énfasis en las interacciones neuroinmunoendocrinas a través del eje hipotálamo-hipófisis-ovario y la interacción recíproca de las hormonas y las citoquinas. Además se resalta la importancia de los factores de crecimiento en el desarrollo de la unidad fetoplacentaria

Experiencia del uso del desfibrilador cardioverter automático implantable / The automatic implantable cardioverter desfibrillator. cuban experience

Por primera vez en Cuba a 10 pacientes con arritmias ventricualares malignas, muerte súbita y/o taquicardias ventriculares sincopales les ha sido implatntado un desfibrilador automático implantable, con marcapasos incorporado, después de estimulación eléctrica programada seriada. Esto permitió caracterizar sus arritmias y evaluar la respuesta a diferentes fármacos. Los pacintes fueron 9 hombres con edad media de 48 (23-70) añosy FE 32% (18-62): 7 portadores de infarto antiguo y 3 con miocardiopatía dilatada. En el seguimiento (entre 2 y 25 mese), 4 pacientes han recibido choques apropiados y efectivos precedidos de palpitaciones rápidas y pre-sincopales. No se han detectado choques erróneos. Dos pacientes fallecieron, uno por TV incesante y otro por causa no aatribuíble a fallo del equipo. Se concluye que el Guardian 4201 y 4202 ofrece un alto grado de efectividad en la prevención de muerte súbita para pacientes de alto riesgo de tal complicación