Resonancia magnética cardiaca: medidas lineales y volumétricas en adultos sanos

Introducción: La gran mayoría de las medidas de normalidad utilizadas para la interpretación de resonancia cardiaca son extrapoladas de las medidas de ecocardiografía. Los limitados registros de medidas de normalidad se encuentran ajustados en poblaciones extranjeras, no hay registros en latinoamericanos. Objetivo: Determinar las dimensiones cardiacas utilizando resonancia magnética en una población de personas sin antecedente médicos con repercusión cardiaca para lograr una muestra de valores que permitan ajustar las medidas de normalidad utilizadas por nuestro servicio. Materiales y métodos: se analizaron 45 sujetos sanos con edad comprendida entre los 21 y 45 años, las adquisiciones se realizaron utilizando un equipo de RM de 1,5 teslas, el análisis de las imágenes se realizó mediante el programa Cardiac Volume Vx. Se evaluaron múltiples parámetros morfofuncionales a través de análisis estadístico por medio del sistema SPSS versión 23. Resultados: Mediciones obtenidas de ventrículo izquierdo principales fueron volumen diastólico en mujeres de 62 ml +/- 7.1 y en hombres de 65 ml +/- 11.2 y fracción de eyección de 60 % +/- 5 en mujeres y de 62 % +/- 9 en hombres. En ventrículo derecho el volumen diastólico final se encontró 81.8 ml +/- 14.6 en mujeres y 100 ml +/- 24.8 en hombres y fracción de eyección de 53 % +/- 17 en mujeres y de 45 % +/- 12 en hombres. Volumen de fin de diástole de 50 +/- 12.7 ml en mujeres y de 49 ml +/- 19 ml en hombres y fracción de eyección de aurícula izquierda de 55 % +/- 0.08 en mujeres y de 50 % +/- 0.07 en hombres. Volumen de fin de diástole de 44.1 ml +/- 18.5 en mujeres y de 49.2 ml +/- 22.9 en hombres y fracción de eyección de aurícula derecha de 50 % +/- 11 en mujeres y de 45 % +/- 8 en hombres. Se obtuvieron otras medidas lineales y volumétricas adicionales de cavidades cardiacas y de grandes vasos supracardiacos. Conclusiones: se describen los valores de referencia de los parámetros morfofuncionales de las cavidades cardiacas y de vasos supracardiacos. El sexo fue tenido en cuenta como covariable relacionada con la modificación de los parámetros evaluados. Se sugieren variaciones en las medidas de cavidades cardiacas para la población estudiada relacionada con aclimatación crónica a la altitud de la ciudad de Bogotá.

Caracterización del trauma vascular periférico del hospital de Kennedy

Introducción: El trauma vascular en nuestro país es común, causando mortalidad en la población entre 15-44 años; como causa principal, las heridas por arma corto punzante en los miembros superiores lideran sobre las de arma de fuego y los miembros inferiores. En Colombia se cuenta con algunos registros de trauma vascular secundario a la guerra, por lo que con este trabajo buscamos describir la población afectada de la localidad octava como punto inicial para estudios analíticos. Metodología: revisión de la base de datos de los pacientes llevados a cirugía en el hospital de Kennedy, de los cuales se extrajeron aquellos con trauma vascular, recolección de las variables a estudiar y análisis de las mismas. Resultados: encontramos 1267 pacientes que consultaron por trauma, de ellos 32 cursaron con trauma vascular, llevados a cirugía(0,3%), el promedio de edad fue de 24 años, la mayoría de sexo masculino (84%); el 72% fueron heridas por arma blanca, 56% fueron heridas múltiples, afectando en el 41% a las extremidades superiores; las lesiones en cuello casi igualan a las heridas en miembros inferiores con un 28%, solo se presentó un caso de amputación y no se presentaron mortalidades. Discusión: en Colombia hacen falta estudios acerca de esta patología que aunque común esta subpublicada, este estudio es tan solo un paso que nos introduce en las características demográficas, y algunas característica clínicas interesantes en comparación a la literatura mundial consultada

Use of an artificial root to examine the influence of 8-hydroxyquinoline on soil microbial activity and bacterial community structure

Invasive plant species have been shown to alter the microbial community composition of the soils they invade and it is suggested that this below-ground perturbation of potential pathogens, decomposers or symbionts may feedback positively to allow invasive success. Whether these perturbations are mediated through specific components of root exudation are not understood. We focussed on 8-hydroxyquinoline, a putative allelochemical of Centaurea diffusa (diffuse knapweed) and used an artificial root system to differentiate the effects of 8-hydroxyquinoline against a background of total rhizodeposition as mimicked through supply of a synthetic exudate solution. In soil proximal (0-10 cm) to the artificial root, synthetic exudates had a highly significant (P < 0.001) influence on dehydrogenase, fluorescein diacetate hydrolysis and urease activity. in addition, 8-hydroxyquinoline was significant (p = 0.003) as a main effect on dehydrogenase activity and interacted with synthetic exudates to affect urease activity (p = 0.09). Hierarchical cluster analysis of 16S rDNA-based DGGE band patterns also identified a primary affect of synthetic exudates and a secondary affect of 8-hydroxyquinoline on bacterial community structure. Thus, we show that the artificial rhizosphere produced by the synthetic exudates was the predominant effect, but, that the influence of the 8-hydroxyquinoline signal on the activity and structure of soil microbial communities could also be detected. (C) 2009 Elsevier Ltd. All rights reserved.

Revisiting youden’s index as a useful measure of the misclassification error in meta-analysis of diagnostic studies

The paper considers meta-analysis of diagnostic studies that use a continuous score for classification of study participants into healthy or diseased groups. Classification is often done on the basis of a threshold or cut-off value, which might vary between studies. Consequently, conventional meta-analysis methodology focusing solely on separate analysis of sensitivity and specificity might be confounded by a potentially unknown variation of the cut-off value. To cope with this phenomena it is suggested to use, instead, an overall estimate of the misclassification error previously suggested and used as Youden’s index and; furthermore, it is argued that this index is less prone to between-study variation of cut-off values. A simple Mantel–Haenszel estimator as a summary measure of the overall misclassification error is suggested, which adjusts for a potential study effect. The measure of the misclassification error based on Youden’s index is advantageous in that it easily allows an extension to a likelihood approach, which is then able to cope with unobserved heterogeneity via a nonparametric mixture model. All methods are illustrated at hand of an example on a diagnostic meta-analysis on duplex doppler ultrasound, with angiography as the standard for stroke prevention.

Revisiting Youden's index as a useful measure of the misclassification error in meta-analysis of diagnostic studies

The paper considers meta-analysis of diagnostic studies that use a continuous Score for classification of study participants into healthy, or diseased groups. Classification is often done on the basis of a threshold or cut-off value, which might vary between Studies. Consequently, conventional meta-analysis methodology focusing solely on separate analysis of sensitivity and specificity might he confounded by a potentially unknown variation of the cut-off Value. To cope with this phenomena it is suggested to use, instead an overall estimate of the misclassification error previously suggested and used as Youden's index and; furthermore, it is argued that this index is less prone to between-study variation of cut-off values. A simple Mantel-Haenszel estimator as a summary measure of the overall misclassification error is suggested, which adjusts for a potential study effect. The measure of the misclassification error based on Youden's index is advantageous in that it easily allows an extension to a likelihood approach, which is then able to cope with unobserved heterogeneity via a nonparametric mixture model. All methods are illustrated at hand of an example on a diagnostic meta-analysis on duplex doppler ultrasound, with angiography as the standard for stroke prevention.

The effect of nicotine in vitro on the integrity of tight junctions in Caco-2 cell monolayers

Ulcerative colitis is characterised by impairment of the epithelial barrier and tight junction alterations resulting in increased intestinal permeability. UC is less common in smokers with smoking reported to decrease paracellular permeability. The aim of this study was thus to determine the effect of nicotine, the major constituent in cigarettes and its metabolites on the integrity of tight junctions in Caco-2 cell monolayers. The integrity of Caco-2 tight junctions was analysed by measuring the transepithelial electrical resistance (TER) and by tracing the flux of the fluorescent marker fluorescein, after treatment with various concentrations of nicotine or nicotine metabolites over 48 h. TER was significantly higher compared to the control for all concentrations of nicotine 0.01-10 M at 48 h (p < 0.001), and for 0.01 mu M (p < 0.001) and 0.1 mu M and 10 M nicotine (p < 0.01) at 12 and 24 h. The fluorescein flux results supported those of the TER assay. TER readings for all nicotine metabolites tested were also higher at 24 and 48 h only (p <= 0.01). Western blot analysis demonstrated that nicotine up-regulated the expression of the tight junction proteins occludin and claudin-l (p < 0.01). Overall, it appears that nicotine and its metabolites, at concentrations corresponding to those reported in the blood of smokers, can significantly improve tight junction integrity, and thus, decrease epithelial gut permeability. We have shown that in vitro, nicotine appears more potent than its metabolites in decreasing epithelial gut permeability. We speculate that this enhanced gut barrier may be the result of increased expression of claudin-l and occludin proteins, which are associated with the formation of tight junctions. These findings may help explain the mechanism of action of nicotine treatment and indeed smoking in reducing epithelial gut permeability. (c) 2007 Elsevier Ltd. All rights reserved.

An exploratory study into the putative prebiotic activity of fructans isolated from Agave angustifolia and the associated anticancer activity

Linear Inulin type fructan (ITF) prebiotics have a putative role in the prevention of colorectal cancer, whereas relatively little is known about branched fructans. This study aims to investigate the fermentation properties and potential prebiotic activity of branched fructans derived from Agave angustifolia Haw, using the Simulator of Human Intestinal Microbial Ecosystem (SHIME) model. The proximal, transverse and distal vessels were used to investigate fructan fermentation throughout the colon and to assess the alterations of the microbial composition and fermentation metabolites (short chain fatty acids and ammonia). The influence on bioactivity of the fermentation supernatant was assessed by MTT, Comet and transepithelial electrical resistance (TER), respectively. Addition of Agave fructan to the SHIME model significantly increased (P<0.05), bifidobacteria populations (proximal and transverse), SCFA concentrations (proximal, transverse and distal) and decreased ammonia concentrations in the distal vessel. Furthermore, the fermentation supernatant significantly (P<0.05) increased the TER of a Caco-2 cell monolayer (%) and decreased fluorescein-based paracellular flux, suggesting enhanced barrier function and reduced epithelial barrier permeability (proximal and distal vessel). While cytotoxicity and genotoxicity remained unaltered in response to the presence of Agave fructans. To conclude, branched Agave fructans show indications of prebiotic activity, particularly in relation to colon health by exerting a positive influence on gut barrier function, an important aspect of colon carcinogenesis.

Synthesis of thiolated and acrylated nanoparticles using thiol-ene click chemistry: towards novel mucoadhesive materials for drug delivery

Thiol- and acrylate-functionalized nanoparticles have been synthesized from pentaerythritol tetrakis(3-mercapto-propionate) and pentaerythritol tetraacrylate using thiol-ene click chemistry. Using Raman and 1H NMR spectroscopy as well as Ellman's assay, it was demonstrated that excess pentaerythritol tetraacrylate in the feed mixture led to nanoparticles with free acrylate groups on their surface, whereas nanoparticles with thiolated surfaces could be synthesized using feed mixtures with excess pentaerythritol tetrakis(3-mercapto-propionate). The possibility of fluorescent labelling of thiolated nanoparticles has been demonstrated through their reaction with fluorescein-5-maleimide. The thiolated nanoparticles were found to be mucoadhesive and exhibited retention on mucosal surface of porcine urinary bladder.

Platelet endothelial cell adhesion molecule-1 inhibits platelet response to thrombin and von Willebrand factor by regulating the internalization of glycoprotein Ib via AKT/glycogen synthase kinase-3/dynamin and integrin αIIbβ3

OBJECTIVE: Platelet endothelial cell adhesion molecule-1 (PECAM-1) regulates platelet response to multiple agonists. How this immunoreceptor tyrosine-based inhibitory motif-containing receptor inhibits G protein-coupled receptor-mediated thrombin-induced activation of platelets is unknown. APPROACH AND RESULTS: Here, we show that the activation of PECAM-1 inhibits fibrinogen binding to integrin αIIbβ3 and P-selectin surface expression in response to thrombin (0.1-3 U/mL) but not thrombin receptor-activating peptides SFLLRN (3×10(-7)-1×10(-5) mol/L) and GYPGQV (3×10(-6)-1×10(-4) mol/L). We hypothesized a role for PECAM-1 in reducing the tethering of thrombin to glycoprotein Ibα (GPIbα) on the platelet surface. We show that PECAM-1 signaling regulates the binding of fluorescein isothiocyanate-labeled thrombin to the platelet surface and reduces the levels of cell surface GPIbα by promoting its internalization, while concomitantly reducing the binding of platelets to von Willebrand factor under flow in vitro. PECAM-1-mediated internalization of GPIbα was reduced in the presence of both EGTA and cytochalasin D or latrunculin, but not either individually, and was reduced in mice in which tyrosines 747 and 759 of the cytoplasmic tail of β3 integrin were mutated to phenylalanine. Furthermore, PECAM-1 cross-linking led to a significant reduction in the phosphorylation of glycogen synthase kinase-3β Ser(9), but interestingly an increase in glycogen synthase kinase-3α pSer(21). PECAM-1-mediated internalization of GPIbα was reduced by inhibitors of dynamin (Dynasore) and glycogen synthase kinase-3 (CHIR99021), an effect that was enhanced in the presence of EGTA. CONCLUSIONS: PECAM-1 mediates internalization of GPIbα in platelets through dual AKT/protein kinase B/glycogen synthase kinase-3/dynamin-dependent and αIIbβ3-dependent mechanisms. These findings expand our understanding of how PECAM-1 regulates nonimmunoreceptor signaling pathways and helps to explains how PECAM-1 regulates thrombosis.

A self-assembling fluorescent dipeptide conjugate for cell labelling

Derivatives of fluorophore FITC (fluorescein isothiocyanate) are widely used in bioassays to label proteins and cells. An N-terminal leucine dipeptide is attached to FITC, and we show that this simple conjugate molecule is cytocompatible and is uptaken by cells (human dermal and corneal fibroblasts) in contrast to FITC itself. Co-localisation shows that FITC-LL segregates in peri-nuclear and intracellular vesicle regions. Above a critical aggregation concentration, the conjugate is shown to self-assemble into beta-sheet nanostructures comprising molecular bilayers.

Right coronary artery fistula to the coronary sinus and right atrium associated with giant right coronary enlargement detected by transthoracic echocardiography

We present the case of a 54-year-old female with a previous history of lung fibrosis secondary to methotrexate used for rheumatoid arthritis who was referred to cardiology evaluation due to precordial pain. Echocardiography showed biatrial enlargement with an enlarged coronary sinus and tubular image posterior to the heart. On the coronary angiogram, the right coronary artery was enlarged, and a distal fistula was identified. The patient underwent a contrast enhanced cardiac computed tomography which demonstrated an aneurysmatic right coronary artery with a distal fistula to the right atrium and coronary sinus. As the chest pain did not recur and there was a high risk of the intervention to correct coronary fistula, the patient remained on conservative treatment.

Vitellin-binding proteins in the nematode Oscheius tipulae (Nematoda, Rhabditida)

We describe the first application of a non-radioactive ligand-blotting technique to the characterization of proteins interacting with nematode vitellins. Chromatographically purified vitellins from the free-living nematode Oscheius tipulae were labeled with fluorescein in vitro. Ligand-blotting assays with horseradish peroxidase-conjugated anti-fluorescein antibodies showed that labeled vitellins reacted specifically with a polypeptide of approximately 100 kDa, which we named P100. This polypeptide is a specific worm`s vitellin-binding protein that is present only in adult worms. Blots containing purified O. tipulae vitellin preparations showed no detectable signal in the 100 kDa region, ruling out any possibility of yolk polypeptides self-assembling under the conditions used in our assay. Experiments done in the presence of alpha-methyl mannoside ruled out the possibility of vitellins binding to P100 through mannose residues. Triton X-114 fractionation of whole worm extracts showed that P100 is either a membrane protein or has highly hydrophobic regions. (C) 2008 Elsevier Inc. All rights reserved.

Effect of a calcium-channel blocker (verapamil) on the morphology, cytoskeleton and collagenase activity of human skin fibroblasts

The effects of verapamil modulating collagen biosynthesis have prompted us to study the role of this drug in cultured fibroblasts. In this article, we describe the effects of verapamil on fibroblast behaviour, with special emphasis to phenotypic modifications, reorganisation of actin filaments and secretion of MMP1. Human dermal fibroblasts treated with 50-mu M verapamil changed their normal spindle-shaped morphology to stellate. Treated cells showed discrete reorganisation of actin filaments, as revealed by fluorescein isothiocyanate (FITC)-phalloidin staining and confocal microscopy. We hypothesised that these effects would be associated to lower levels of cytosolic Ca(2+). Indeed, short time loading with calcium green confirmed that verapamil-treated fibroblasts exhibited lower intracellular calcium levels compared to controls. We also observed that verapamil increases the secretion of MMP1 in cultured fibroblasts, as demonstrated by zymography, specific substrate assays and immunoblot. The morphological alterations induced by verapamil are neither cytotoxic nor associated with other dramatic cytoskeleton alterations. Thus we may conclude that this drug enhances collagenase secretion and does not disrupt the major tracks necessary to deliver these enzymes in the extracellular space. The present results suggested that verapamil could be used at physiological levels to enhance collagen I breakdown, and maybe considered a potential candidate for intralesional therapy of wound healing and fibrocontractive diseases. (C) 2010 Elsevier Ltd and ISBI. All rights reserved.

A non-parametric vessel detection method for complex vascular structures

Modern medical imaging techniques enable the acquisition of in vivo high resolution images of the vascular system. Most common methods for the detection of vessels in these images, such as multiscale Hessian-based operators and matched filters, rely on the assumption that at each voxel there is a single cylinder. Such an assumption is clearly violated at the multitude of branching points that are easily observed in all, but the Most focused vascular image studies. In this paper, we propose a novel method for detecting vessels in medical images that relaxes this single cylinder assumption. We directly exploit local neighborhood intensities and extract characteristics of the local intensity profile (in a spherical polar coordinate system) which we term as the polar neighborhood intensity profile. We present a new method to capture the common properties shared by polar neighborhood intensity profiles for all the types of vascular points belonging to the vascular system. The new method enables us to detect vessels even near complex extreme points, including branching points. Our method demonstrates improved performance over standard methods on both 2D synthetic images and 3D animal and clinical vascular images, particularly close to vessel branching regions. (C) 2008 Elsevier B.V. All rights reserved.

1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation

The alpha-aminoketone 1,4-diamino-2-butanone (DAB), a putrescine analogue, is highly toxic to various microorganisms, including Trypanosoma cruzi. However, little is known about the molecular mechanisms underlying DAB`s cytotoxic properties. We report here that DAB (pK(a) 7.5 and 9.5) undergoes aerobic oxidation in phosphate buffer, pH 7.4, at 37 degrees C, catalyzed by Fe(II) and Cu(II) ions yielding NH(4)(+) ion, H(2)O(2), and 4-amino-2-oxobutanal (oxoDAB). OxoDAB, like methylglyoxal and other alpha-oxoaldehydes, is expected to cause protein aggregation and nucleobase lesions. Propagation of DAB oxidation by superoxide radical was confirmed by the inhibitory effect of added SOD (50 U ml(-1)) and stimulatory effect of xanthine/xanthine oxidase, a source of superoxide radical. EPR spin trapping studies with 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) revealed an adduct attributable to DMPO-HO(center dot), and those with alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone or 3,5-dibromo-4-nitrosobenzenesulfonic acid, a six-line adduct assignable to a DAB(center dot) resonant enoyl radical adduct. Added horse spleen ferritin (HoSF) and bovine apo-transferrin underwent oxidative changes in tryptophan residues in the presence of 1.0-10 mM DAB. Iron release from HoSF was observed as well. Assays performed with fluorescein-encapsulated liposomes of cardiolipin and phosphatidylcholine (20:80) incubated with DAB resulted in extensive lipid peroxidation and consequent vesicle permeabilization. DAB (0-10 mM) administration to cultured LLC-MK2 epithelial cells caused a decline in cell viability, which was inhibited by preaddition of either catalase (4.5 mu M) or aminoguanidine (25 mM). Our findings support the hypothesis that DAB toxicity to several pathogenic microorganisms previously described may involve not only reported inhibition of polyamine metabolism but also DAB pro-oxidant activity. (C) 2011 Elsevier Inc. All rights reserved.