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Biomedical subjects

Mauricio Moreno

Publications and source records attributed to Mauricio Moreno.

9 recordsLinked to original sources

High resistance of atrioventricular node to cryoablation: a great safety margin targeting perinodal arrhythmic substrates.

BACKGROUND: Findings from animal studies and small series of patients support the greater safety of cryoenergy over radiofrequency in the ablation of arrhythmic substrates near the AV node. OBJECTIVES: The purpose of this study was to systematically evaluate the electrophysiologic effects of successive cryoenergy applications to the human AV node in order to better define the safety margin of cryothermal ablation. METHODS: In 15 patients referred for AV nodal ablation, 94 cryomapping and 105 cryoablation applications were delivered through a 6-mm-tip cryothermal ablation catheter (Freezor Xtra, CryoCath) at predefined sites of the triangle of Koch. RESULTS: Temporary effects on AV conduction were observed in 18 (19%) cryomapping and 38 (36%) cryoablation applications. Persistent effects were observed in 9 (9%) cryoablation applications. Persistent effects were associated with cryoablation at the superior third of the triangle of Koch (P = .05), nadir tip temperature < or = -79 degrees C (P = .007), and effect onset time < or =15 seconds (P = .03). Temperature and effect onset time remained statistically significant after multivariate adjustment (P = .01 and .02, respectively). Overall, persistent complete AV block was achieved with cryoenergy in only one patient. In two additional patients, AV conduction remained modified. In the remaining patients, persistent complete AV block was achieved with radiofrequency (median one application per patient). CONCLUSION: The low rate of persistent AV conduction impairment observed with attempts to cryoablate the AV node supports a great safety margin of perinodal cryothermal ablation.

Aged↗

Syndecan-4 regulates non-canonical Wnt signalling and is essential for convergent and extension movements in Xenopus embryos.

Early shaping of Xenopus laevis embryos occurs through convergent and extension movements, a process that is driven by intercalation of polarized dorsal mesodermal cells and regulated by non-canonical Wnt signalling. Here, we have identified Xenopus syndecan-4 (xSyn4), a cell-surface transmembrane heparan sulphate proteoglycan. At the gastrula stage, xSyn4 is expressed in the involuting dorsal mesoderm and the anterior neuroectoderm. Later, it is found in the pronephros, branchial arches, brain and tailbud. Both gain- and loss-of-function of xSyn4 impaired convergent extension movements in Xenopus embryos and in activin-treated ectodermal explants. xSyn4 interacts functionally and biochemically with the Wnt receptor Frizzled7 (xFz7) and its signal transducer Dishevelled (xDsh). Furthermore, xSyn4 is necessary and sufficient for translocation of xDsh to the plasma membrane - a landmark in the activation of non-canonical Wnt signalling. Our results suggest that the ability of xSyn4 to translocate xDsh is regulated by fibronectin, a component of the extracellular matrix required for proper convergent extension movements. We propose a model where xSyn4 and fibronectin cooperate with xFz7 and Wnt in the specific activation of the non-canonical Wnt pathway.

Adaptor Proteins, Signal Transducing↗

Biglycan is a new extracellular component of the Chordin-BMP4 signaling pathway.

The BMP4 signaling pathway plays key roles during early embryonic development and for maintenance of adult homeostasis. In the extracellular space, BMP4 activity is regulated by a group of interacting molecules including the BMP antagonist Chordin, the metalloproteinase Tolloid and Twisted gastrulation (Tsg). In this study, we identified Biglycan (Bgn), a member of the small leucine-rich proteoglycan family, as a new extracellular modulator of BMP4 signaling. Xenopus Bgn (xBgn) is expressed uniformly in the ectoderm and mesoderm and their derivatives during development. Microinjection of Bgn mRNA induced secondary axes, dorsalized the mesoderm and inhibited BMP4 activity in Xenopus embryos. Biochemical experiments showed that Bgn binds BMP4 and Chordin, interaction that increased binding of BMP4 to Chordin. Bgn was also able to improve the efficiency of Chordin-Tsg complexes to block BMP4 activity. Using antisense morpholinos, we demonstrated that Bgn required Chordin to induce double axes in Xenopus. This work unveiled a new function for Bgn, its ability to regulate BMP4 signaling through modulation of Chordin anti-BMP4 activity.

Animals↗

Pacemapping.

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Journal Article↗

Errors in pulmonary vein identification and ostia location in the absence of pulmonary vein imaging.

BACKGROUND: A key point in atrial fibrillation (AF) ablation is the ability to identify the pulmonary vein (PVs) and locate their ostia. OBJECTIVES: The purpose of this study was to assess the error margin of PV identification and ostia location in the absence of previous PV imaging. METHODS: This study was performed in patients referred for catheter ablation of AF. PVs were reconstructed before ablation using the CARTO system. The operator tagged the superior and inferior edges of the PV ostia before and after examining the corresponding PV angiograms. The distances between the tagged PV ostia were measured using CARTO software. RESULTS: A total of 105 location estimations of 54 PVs were analyzed. The location of PV ostia without angiography deviated from the angiographic PV ostia by a median of 13 mm (95% confidence interval = 11-14 mm; P < .0001). In 84 of the 105 estimations (80%), wrong tagging was performed inside the PV. A multiple logistic regression revealed that, at sites displaying PV potentials, the left atrial potential amplitude was an independent predictor of location at the angiographic PV ostium (odds ratio 24 [95% confidence interval = 3.7-227] per 1-mV increase). Receiver operator characteristic analysis set the optimal cutoff level at 0.7 mV. Use of this criterion improved the accuracy of PV ostium location by 4 mm (95% confidence interval = 1-6 mm; P = .005). CONCLUSION: Attempts at PV identification and ostia location in the absence of previous PV imaging are subject to a broad error margin.

Adult↗

[Percutaneous epicardial radiofrequency ablation of idiopathic ventricular tachycardia].

We describe 3 patients with ventricular tachycardia in whom epicardial ablation was done after prior attempts of endocardial ablation had failed. Clinical ventricular tachycardia originated at the right ventricular outflow tract in one patient and near the mitral annulus in another patient. In these two cases ventricular tachycardia was mapped and successfully ablated with a percutaneous subxiphoid approach to the pericardial space. In the remaining patient, ventricular tachycardia originated near the mitral annulus and was ablated via a coronary vein. The two patients who presented tachycardiomyopathy recovered normal left ventricular function after successful ablation. Failure of endocardial ablation may reflect a substrate of epicardial arrhythmia. Epicardial ablation is effective and provides an alternative therapy for patients with ventricular tachycardia, including those with no structural heart disease.

Adult↗

Hepatic overexpression of caveolins increases bile salt secretion in mice.

Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes, including cholesterol transport. Because hepatocytes express caveolin-1 and caveolin-2, these proteins might modulate hepatic lipid metabolism and biliary lipid secretion. Our aim was to investigate the potential physiologic role of caveolins in hepatic cholesterol and bile salt (BS) metabolism and transport using adenoviral gene transfer. C57BL/6 mice were infected with recombinant human caveolin-1 and caveolin-2 adenoviruses. Mice infected with adenovirus lacking the transgene were used as controls. Hepatic caveolin expression was evaluated by immunochemical methods. Reverse-transcription polymerase chain reaction (RT-PCR) and immunoblotting were used to assess messenger RNA (mRNA) levels and protein mass of BS transporters (sodium taurocholate cotransporting polypeptide [Ntcp] and bile salt export pump [Bsep]). Serum, liver, biliary, and fecal biochemical determinations and BS maximal secretory rate (SRm) were performed by standard methods. Ad.Cav-1- and Ad.Cav-2-infected mice exhibited a 10- and 7-fold increase in hepatic caveolin-1 and caveolin-2 protein expression, respectively. Caveolin-1-overexpressing mice had a significant increase in plasma high-density lipoprotein (HDL) cholesterol and hepatic free cholesterol content, whereas total plasma cholesterol and triglyceride levels remained unchanged. Hepatic caveolin-1 and/or caveolin-2 overexpression significantly increased bile flow and secretion of all biliary lipids. Caveolin-1-overexpressing mice showed a 2.5-fold increase in taurocholate (TC) SRm, indicating increased canalicular BS transport capacity. BS pool size and fecal BS excretion remained within the normal range in mice with Cav-1 overexpression. No changes were seen in the protein mass of BS transporters Ntcp and Bsep. In conclusion, our findings indicate that caveolins may play an important role in regulating hepatic BS and cholesterol metabolism.

Adenoviridae↗

TP53 abnormalities are frequent and early events in the sequential pathogenesis of gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) is a frequent neoplasm in Hispanic and native American populations. GBC is preceded by gallstones, chronic cholecystitis and dysplastic changes of the gallbladder epithelium. The knowledge of the molecular events involved in its pathogenesis is scarce. AIMS: We investigated the role of TP53 inactivation in the sequential pathogenesis of GBC. METHODS: Invasive tumor-, dysplastic- and histologically normal GB epithelial-cells were obtained from archival formalin-fixed tissues from GBC and GB from gallstone patients without GBC. Normal GB epithelia from 5 non-gallstone specimens were also studied. DNA extracted was examined for loss of heterozygosity (LOH) using 2 microsatellite markers and for TP53 mutations at exons 5 to 8. RESULTS: GBCs demonstrated a high frequency of LOH (81%) and mutation (67%), and both abnormalities indicating gene inactivation were detected in 52%. Similar frequency of TP53 abnormalities and gene inactivation (38%) were detected in their accompanying normal and dysplastic epithelia. Noteworthy, one third of normal and dysplastic epithelia obtained from GBs of gallstone patients without GBC demonstrated either TP53 allele loss or mutation, but gene inactivation was less frequent (11%). Most mutations affected exons 5 and 7, and they were more frequently missense point mutations. The same TP53 mutation was detected in only a subset (27%) of comparisons between non-malignant epithelia adjacent to GBCs, indicating that TP53 mutation occurs independently at several epithelial foci. CONCLUSIONS: These findings indicate that TP53 abnormalities are early and frequent events in the pathogenesis of GBC, starting from chronic cholecystitis.

Aged↗