Biomedical subjects
Publications and source records attributed to Javier Moreno.
The different functions of skin dendritic cell subsets during Leishmania infection were recently reviewed by Ritter and Osterloh. In their article, they propose a new role for epidermal Langerhans cells and dermal dendritic cells to explain the events that take place after inoculation by Leishmania.
BACKGROUND: It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentrant. To test the hypothesis that functional reentry is involved in human AF maintenance, we determined the effects of adenosine infusion on local dominant frequency (DF) at different atrial sites. By increasing inward rectifier potassium channel conductance, adenosine would increase DF of reentrant drivers but decrease it in the case of a focal mechanism. METHODS AND RESULTS: Thirty-three patients were studied during AF (21 paroxysmal, 12 persistent) using recordings from each pulmonary vein-left atrial junction (PV-LAJ), high right atrium, and coronary sinus. DFs were determined during baseline and peak adenosine effect. In paroxysmal AF, adenosine increased maximal DF at each region compared with baseline (PV-LAJ, 8.03+/-2.2 versus 5.7+/-0.8; high right atrium, 7+/-2.2 versus 5.4+/-0.7; coronary sinus, 6.6+/-1.1 versus 5.3+/-0.7 Hz; P=0.001) and increased the left-to-right DF gradient (P=0.007). In contrast, in persistent AF, adenosine increased DF only in the high right atrium (8.33+/-1.1 versus 6.8+/-1.2 Hz; P=0.004). In 4 paroxysmal AF patients, real-time DF mapping of the left atrium identified the highest DF sites near the PV-LAJ, where adenosine induced an increase in DF (6.7+/-0.29 versus 4.96+/-0.26 Hz; P=0.008). Finally, simulations demonstrate that the frequency of reentrant drivers accelerates proportionally to the adenosine-modulated inward rectifier potassium current. CONCLUSIONS: Adenosine accelerates drivers and increases frequency differently in paroxysmal compared with persistent human AF. The results strongly suggest that AF is maintained by reentrant sources, most likely located at the PV-LAJ in paroxysmal AF, whereas non-PV locations are more likely in persistent AF.
The effects exerted by the new complex cis-dichloro-1,2-propylenediaminetetraacetato ruthenium (III), H[RuCl(2)(PDTA-H(2))] [1, RAP], on DNA and cultured tumor cells (ovarian carcinoma TG cell line) were studied. The comparative study of circular dichroism (CD) spectra obtained from DNA and RAP-DNA system evidences the interaction of the complex with DNA. Compound 1 also interacted with tumor TG cells to slow their proliferation rate. BrdU incorporation was enhanced in cells treated with compound 1, as evidenced by a single-cell electrophoresis method (comet assay), in accordance with RAP-induced DNA damage. DNA migration of compound 1-treated cells was similar to that induced by noxious agents other than cross-linking chemicals. The stability of [RuCl(2)(PDTA-H(2))]-DNA binding is suggested by the high degree of damage that persisted after removal of compound 1 from the culture medium.
One of the mechanisms plants have developed for chloroplast protection against oxidative damage involves a 2-Cys peroxiredoxin, which has been proposed to be reduced by ferredoxin and plastid thioredoxins, Trx x and CDSP32, the FTR/Trx pathway. We show that rice (Oryza sativa) chloroplast NADPH THIOREDOXIN REDUCTASE (NTRC), with a thioredoxin domain, uses NADPH to reduce the chloroplast 2-Cys peroxiredoxin BAS1, which then reduces hydrogen peroxide. The presence of both NTR and Trx-like domains in a single polypeptide is absolutely required for the high catalytic efficiency of NTRC. An Arabidopsis thaliana knockout mutant for NTRC shows irregular mesophyll cell shape, abnormal chloroplast structure, and unbalanced BAS1 redox state, resulting in impaired photosynthesis rate under low light. Constitutive expression of wild-type NTRC in mutant transgenic lines rescued this phenotype. Moreover, prolonged darkness followed by light/dark incubation produced an increase in hydrogen peroxide and lipid peroxidation in leaves and accelerated senescence of NTRC-deficient plants. We propose that NTRC constitutes an alternative system for chloroplast protection against oxidative damage, using NADPH as the source of reducing power. Since no light-driven reduced ferredoxin is produced at night, the NTRC-BAS1 pathway may be a key detoxification system during darkness, with NADPH produced by the oxidative pentose phosphate pathway as the source of reducing power.
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.
AIM: To analyze whether the presence of anti-HBs in liver transplant recipients is effective in preventing HBV infection. METHODS: Twenty-three patients receiving anti-HBc positive liver were studied. Nine recipients were anti-HBc positive as a result of previous HBV infection. Of them, one also received HBV vaccine during the pre-liver transplantation period. Fourteen recipients were anti-HBs positive due to HBV vaccine administered during the pre-transplant period. Liver biopsy was obtained in 10/14 anti-HBc negative/anti-HBs positive recipients and in 4/9 anti-HBc positive recipients. RESULTS: After a mean follow-up period of 46 months, 1 recipient with protective serum anti-HBs levels developed de novo HBV infection as a consequence of immune escape HBV mutants. Among the 14 vaccinated anti-HBc negative/anti-HBs positive recipients, 1/10 patients with available liver biopsy (10%) had liver HBV-DNA at 13 mo post-liver transplantation without serum viral markers and did not develop de novo HBV infection. The vaccinated anti-HBc positive recipient without HBV vaccine response was HBV-DNA positive in serum and liver, viral DNA was continuously negative in the following tests, so a spontaneous seroconversion was diagnosed. CONCLUSION: The presence of anti-HBs as a result of HBV vaccine or past HBV infection seems to be effective at protecting patients receiving livers from anti-HBc positive donors. However, the emergence of immune escape HBV mutants, which can evade the anti-HBs protection, should be considered as a risk of HBV infection.
The Sinorhizobium fredii HH103 rkp-1 region, which is involved in capsular polysaccharides (KPS) production, was isolated and sequenced. The organization of the S. fredii genes identified, rkpUAGHIJ and kpsF3, was identical to that described for S. meliloti 1021 but different from that of S. meliloti AK631. The long rkpA gene (7.5 kb) of S. fredii HH103 and S. meliloti 1021 appears as a fusion of six clustered AK631 genes, rkpABCDEF. S. fredii HH103-Rif(r) mutants affected in rkpH or rkpG were constructed. An exoA mutant unable to produce exopolysaccharide (EPS) and a double mutant exoA rkpH also were obtained. Glycine max (soybean) and Cajanus cajan (pigeon pea) plants inoculated with the rkpH, rkpG, and rkpH exoA derivatives of S. fredii HH103 showed reduced nodulation and severe symptoms of nitrogen starvation. The symbiotic capacity of the exoA mutant was not significantly altered. All these results indicate that KPS, but not EPS, is of crucial importance for the symbiotic capacity of S. fredii HH103-Rif(r). S. meliloti strains that produce only EPS or KPS are still effective with alfalfa. In S. fredii HH103, however, EPS and KPS are not equivalent, because mutants in rkp genes are symbiotically impaired regardless of whether or not EPS is produced.
INTRODUCTION: Atrial fibrillation (AF) may be triggered by ectopic beats originating in sleeves of atrial myocardium entering the pulmonary veins (PVs). PV isolation by means of circumferential ostial or atrial radiofrequency ablation is an effective but also a difficult and long procedure, requiring extensive applications that can have serious potential complications. Our objective was to examine pathological effects of PV beta-radiation, particularly the ability to destroy PV myocardial sleeves without inducing PV stenosis and other unwanted effects, in order to establish its potential feasibility for the treatment of AF. METHODS AND RESULTS: Ten minipigs were studied. A phosphorus-32 source wire centered within a 2.5-mm diameter balloon catheter (Galileo III Intravascular Radiotherapy System, Guidant, Santa Clara, CA, USA) was used to deliver beta-radiation to the superior wall of the right PV trunk. Pathological analysis was performed either immediately after ablation (2 pigs) or 81 +/- 27 days later (8 pigs). Acute effects of PV beta-radiation consisted of endothelial denudation covered by white thrombus, elastic lamina disruption, and PV sleeve necrosis. Late effects consisted of mild focal neointimal hyperplasia that reduced the PV luminal area by only 1.3 +/- 1.8%, elastic lamina thickening, and PV sleeve fibrosis. Four of these 8 PVs were completely re-endothelized. Lesions were transmural in 6 of 10 radiated PVs and segmental, involving 28 +/- 7% of the right PV perimeter. CONCLUSION: Intravascular beta-radiation can induce transmural necrosis and fibrosis of PV myocardial sleeves without PV stenosis and other unwanted effects, which supports a potential usefulness of this energy source in the treatment of AF.
Leishmania-HIV co-infection has been globally controlled in Southern Europe since 1997 because of highly active anti retroviral therapy (HAART), but it appears to be an increasing problem in other countries such as Ethopia, Sudan, Brazil or India where both infections are becoming more and more prevalent. Most of the scientific background on Leishmania/HIV co-infection has been dropped from the Mediterranean experience and although the situations among countries are not fully comparable, it is of high importance to take advantage of this knowledge. In this review several aspects of the Leishmania/HIV co-infection are emphasized viz., epidemiological features, new ways of transmission, pathogenesis, clinical outcome, diagnosis, treatment and secondary prohylaxis. An extensive review of the literature on Leishmania/HIV co-infection has allowed the inclusion of a comprehensive and updated list of bibliographical references.
INTRODUCTION AND OBJECTIVES: The identification and ablation of atrial ectopic foci could complement the conventional empirical pulmonary vein approach and may increase the success rate of atrial fibrillation ablation. Although both adenosine and isoproterenol infusion have been reported to induce ectopics, no clear findings on their use during ablation have been published. Our aim was to investigate the utility of these two pharmacologic maneuvers in patients referred for atrial fibrillation ablation. METHODS: The effects of adenosine infusion, isoproterenol infusion, or both were evaluated in 53 patients with refractory atrial fibrillation referred for ablation. Patients were in sinus rhythm during evaluation. RESULTS: Administration of adenosine or isoproterenol induced atrial arrhythmias in 46 patients (87%). Arrhythmia inducibility was similar in those with paroxysmal and those with persistent atrial fibrillation (87% and 86%, respectively). Atrial ectopics alone were induced in 31 patients (65%), atrial tachycardia in four (8%), and atrial fibrillation in 13 (27%). In 10 patients (19%), ectopic foci were located outside the pulmonary veins and subsequently underwent ablation. In 32 of the 46 patients with inducible arrhythmias, only the induced ectopic foci were ablated (mean 1.4 [0.6] targets per patient). The long-term success rate of first procedures was 66%. CONCLUSION: Adenosine and isoproterenol infusion induced atrial ectopics in most patients with drug-refractory atrial fibrillation while they were in sinus rhythm. In almost 20%, the ectopic foci were located outside the pulmonary veins. The effectiveness of induced ectopic-guided ablation observed in our patient series supports the clinical utility of this approach.
A 1,963-bp cDNA was isolated from an Anisakis simplex cDNA library by immunoscreening with a hyperimmune rabbit serum raised against a crude extract of A. simplex L3 larvae. The open reading frame encodes a putative protein of 436 amino acid residues, which exhibits high similarity (70-80%) to enolase molecules from various other organisms, including helminth parasites. After subcloning and expression of the A. simplex cDNA in PGEX-4T-3, the resulting glutathione S-transferase fusion protein, purified by glutathione-Sepharose-4B chromatography, showed functional enolase activity. The immunogenicity of the recombinant A. simplex enolase was analyzed by immunoblotting using sera obtained from (a) mice immunized with crude extracts (CE) of A. simplex, or other nematode species, (b) mice immunized with excretory-secretory (ES) antigens from A. simplex, or (c) mice infected with L3 larvae by the intraperitoneal route. In addition, we used ELISA, to investigate the presence of IgG1 and IgE antibodies against this molecule in sera from patients infected with A. simplex. Mouse sera obtained after infection with L3 or raised against CE antigens, but not sera raised against ES antigens, showed strong reactivity with the recombinant A. simplex enolase. We also obtained good reactivity in Western blotting with sera from mice immunized with CE antigens from Ascaris suum and Toxocara canis, but not with sera from mice immunized with CE antigens from Trichuris muris, Trichinella spiralis or Hysterothylacium aduncum. In contrast to the experimental infections/immunizations in mice, we were unable to detect anti-enolase IgE antibodies in sera from human patients infected with A.simplex (15 sera), and the levels of anti-enolase IgG1 antibodies in these sera were low and apparently nonspecific. These results seem to indicate that, during natural infection in humans, A. simplex larvae do not offer sufficient antigenic stimulus to induce anti-enolase antibodies.
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The dog is the main reservoir of Leishmania infantum, the parasite responsible for visceral leishmaniasis in Mediterranean countries. The infection in dogs shows different clinical presentations, from subclinical/asymptomatic to a fully developed disease, depending on the host's immune responses. The Th1/Th2 dichotomy is not clear in the different forms of canine leishmaniasis, since the data available from studies of immunity response in canine leishmaniasis are scarce and fragmented. The present work describes the cytokine expression in peripheral blood mononuclear cells (PBMC) obtained from asymptomatic dogs experimentally infected with L. infantum that present a cellular protective immune response. The results obtained from freshly isolated PBMC showed expressions of TNF-alpha, IL-2, IFN-gamma, IL-10 and IL-18 mRNA, similar to those from non-infected dogs. However, there was almost no expression of IL-4 mRNA detected in the asymptomatic infected dogs compared to the control dogs. Unspecific stimulation with ConA promoted the expression in a greater or lower degree of all the cytokines studied. In vitro stimulation of PBMC with soluble leishmanial antigen (SLA) promoted the expression of IL-2, IFN-gamma, TNF-alpha, IL-18, IL-4, IL-6 and IL-10 mRNA, with the two first being specifically induced. Although both Th1 and Th2 cytokines are produced, cell mediated immunity observed in these L. infantum-infected asymptomatic dogs depended on the preferential expression of Th1 cytokines.
OBJECTIVE: The dynamics of ventricular fibrillation (VF) in the presence of heart failure (HF) are different from those in the normal heart. This has been attributed solely to HF-induced electrophysiologic remodelling. We hypothesized that acute stretch and ischaemia, which are normally present during VF, might contribute significantly to the altered VF dynamics in HF. METHODS: HF was induced in eight sheep by rapid ventricular pacing for 4-6 weeks. Eight sheep served as controls. Optical mapping of isolated hearts was performed during VF at low intraventricular pressure (0-5 mm Hg), high pressure (25-30 mm Hg, in six HF and six controls), and at low pressure after 5 min of global ischaemia (six HF, five controls). Maximum dominant frequency (DF(max)), singularity point (SP) density and number of SP lasting more than one revolution (rotors) were analyzed. Possible statistical interactions between HF and ischaemia (HF x ischaemia) or stretch (HF x stretch) were evaluated. RESULTS: At low pressure, VF in HF was slower (13% reduction in DF(max)) and more organized than in control: 33% less SPs and 74% less rotors with 20% longer life spans. Acute stretch did not affect DF(max) but increased SP and rotors density similarly in both groups (no interaction HF x stretch). In controls, ischaemia caused a marked decrease in DF(max), SP density and incidence of rotors. However, in HF animals, the ischaemia-induced decrease in SP density was virtually abolished, indicating a significant interaction HF x ischaemia (p<0.005). CONCLUSIONS: HF remodelling decreases VF rate and increases VF organization. Acute stretch partially reverses these effects by a mechanism that is independent of remodelling. The effects of acute ischaemia on VF dynamics are significantly attenuated in HF compared to normal hearts.
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.
BACKGROUND AND AIMS: Partial splenic embolization (PSE) is a non-surgical alternative for the treatment of hypersplenism. Thrombocytopenia precludes the use of pegylated interferon (peg-IFN) and ribavirin in cirrhotic patients with hepatitis C virus (HCV). We aimed to evaluate the role of PSE as a procedure allowing combined HCV therapy in this setting. METHODS: A retrospective analysis of the safety and rate of sustained virological response (SVR) after a full-dose course of peg-IFN plus ribavirin in eight HCV cirrhotic patients with severe hypersplenism undergoing PSE at a tertiary centre in Madrid, Spain, from May 2002 to August 2004. RESULTS: Six patients (75%) were in Child-Pugh class B (median score 7). PSE significantly improved the mean platelet (P = 0.012), leucocyte (P = 0.017) and haemoglobin (P = 0.035) levels, and prothrombin activity (P = 0.012). After a mean of 20 weeks after PSE all patients started weight-adjusted ribavirin plus peg-IFN-alpha2b (n = 6) or 180 microg/week of peg-IFN-alpha2a (n = 2). Six subjects (75%) completed therapy with no peg-IFN dose reductions; the dose of ribavirin was reduced in two patients reaching haemoglobin levels of less than 10 g/dl (one also received erythropoietin and granulocyte colony-stimulating factor because of neutrophil counts < 300 cells/microl). Three patients (38%) achieved SVR. Portal vein thrombosis was observed in 50% of patients, but did not preclude antiviral therapy. The pathogenic mechanism was multifactorial. It was successfully managed with anticoagulant therapy in two cases. CONCLUSIONS: PSE allowed the safe use of peg-IFN plus ribavirin in HCV cirrhotic patients with severe cytopenias who otherwise would never have been treated. The rate of SVR was 38%.
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.
Prosthetic valves may make ventricular access difficult in radiofrequency catheter ablation. This case report describes an optimized atrial transseptal approach to access the ventricle in a patient with left ventricular tachycardia and a mechanical prosthetic aortic valve.