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Fernando Rodríguez

Publications and source records attributed to Fernando Rodríguez.

12 recordsLinked to original sources

A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome.

RATIONALE: Ventilation in the prone position for about 7 h/d in patients with acute respiratory distress syndrome (ARDS), acute lung injury, or acute respiratory failure does not decrease mortality. Whether it is beneficial to administer prone ventilation early, and for longer periods of time, is unknown. METHODS: We enrolled 136 patients within 48 h of tracheal intubation for severe ARDS, 60 randomized to supine and 76 to prone ventilation. Guidelines were established for ventilator settings and weaning. The prone group was targeted to receive continuous prone ventilation treatment for 20 h/d. RESULTS: The intensive care unit mortality was 58% (35/60) in the patients ventilated supine and 43% (33/76) in the patients ventilated prone (p = 0.12). The latter had a higher simplified acute physiology score II at inclusion. Multivariate analysis showed that simplified acute physiology score II at inclusion (odds ratio [OR], 1.07; p < 0.001), number of days elapsed between ARDS diagnosis and inclusion (OR, 2.83; p < 0.001), and randomization to supine position (OR, 2.53; p = 0.03) were independent risk factors for mortality. A total of 718 turning procedures were done, and prone position was applied for a mean of 17 h/d for a mean of 10 d. A total of 28 complications were reported, and most were rapidly reversible. CONCLUSION: Prone ventilation is feasible and safe, and may reduce mortality in patients with severe ARDS when it is initiated early and applied for most of the day.

APACHE↗

DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses.

Despite foot-and-mouth disease virus (FMDV) being responsible for one of the most devastating animal diseases, little is known about the cellular immune mechanisms involved in protection against this virus. In this work we have studied the potential of DNA vaccines based on viral minigenes corresponding to three major B and T-cell FMDV epitopes (isolate C-S8c1) originally identified in natural hosts. The BTT epitopes [VP1 (133-156)-3A (11-40)-VP4 (20-34)] were cloned into the plasmid pCMV, either alone or fused to ubiquitin, the lysosomal targeting signal from LIMPII, a soluble version of CTLA4 or a signal peptide from the human prion protein, to analyze the effect of processing through different antigenic presentation pathways on the immunogenicity of the FMDV epitopes. As a first step in the analysis of modulation exerted by these target signals, a FMDV infection inhibition assay in Swiss outbred mice was developed and used to analyze the protection conferred by the different BTT-expressing plasmids. Only one of the 37 mice immunized with minigene-bearing plasmids developed specific neutralizing antibodies prior to FMDV challenge. As expected, this single mouse that had been immunized with the BTT tandem epitopes fused to a signal peptide (pCMV-spBTT) was protected against FMDV infection. Interestingly, nine more of the animals immunized with BTT-expressing plasmids did not show viremia at 48 h post-infection (pi), even in the absence of anti-FMDV antibodies prior to challenge. The highest protection (50%, six out of 12 mice) was observed with the plasmid expressing BTT alone, indicating that the targeting strategies used did not result in an improvement of the protection conferred by BTT epitopes. Interestingly, peptide specific CD4+ T-cells were detected for some of the BTT-protected mice. Thus, a DNA vaccine based on single FMDV B and T cell epitopes can protect mice, in the absence of specific antibodies at the time of challenge. Further work must be done to elucidate the mechanisms involved in protection and to determine the protective potential of these vaccines in natural FMDV hosts.

Animals↗

A DNA vaccine expressing the E2 protein of classical swine fever virus elicits T cell responses that can prime for rapid antibody production and confer total protection upon viral challenge.

Immunization of domestic pigs with a DNA vaccine expressing the complete E2 protein of classical swine fever virus (CSFV) conferred total protection against a severe viral challenge. Immunization with three doses of plasmid pcDNA3.1/E2 elicited a consistent and specific, MHC class II restricted T cell response in the three domestic pigs analyzed, in the absence of detectable anti-CSFV antibodies in serum. Upon challenge specific T cell responses were boosted in the three vaccinated pigs, and a rapid rise in the titers of CSFV neutralizing antibodies was noticed in two of them, which correlated with a total protection. In these two pigs, neither disease symptoms were observed nor was virus detected at any time after CSFV infection. Neutralizing antibody titers were lower in the third vaccine, which developed a mild and transient peak of pyrexia. As expected, similar analyses in three control pigs (injected with the empty vector or PBS) did not reveal the induction of specific T cells or viral antibodies and, upon challenge, animals developed severe symptoms of the disease, including high titers of viremia, hyperthermia and virus spread to different organs. Control pigs developed, also, a marked leucopenia, resulting in SWC3+ (myelomonocytic cells) being the major PBMC population, and a drastic decrease CD3+ T cells. This T cell depletion was prevented in animals immunized with pcDNA3.1/E2. The total protection achieved, in the absence of CSFV antibodies before challenge, supports the relevance in the antiviral response observed of specific T cell responses primed by pcDNA3.1/E2 vaccine, which, upon challenge, led to a rapid induction of neutralizing antibodies. The observation that CSFV antibodies could only be detected in protected animals after viral challenge opens the possibility of exploring the potential of the DNA vaccine approach used to develop marker vaccines against CSF.

Amino Acid Sequence↗

Protein kinase casein kinase 2 holoenzyme produced ectopically in human cells can be exported to the external side of the cellular membrane.

Ectokinases can phosphorylate extracellular proteins and external domains of membrane proteins influencing cell adhesion, movement, and cellular interactions. An ectokinase with the properties of casein kinase 2 (CK2) has been previously described, but little is known about the structural characteristics that allow this enzyme to be exported from the cell. Transfection of human embryonic kidney-293 cells with cDNAs coding for the catalytic (CK2alpha or CK2alpha') and regulatory (CK2beta) subunits with hemaglutinin tags allowed us to study the export of ectopically synthesized enzyme. When the catalytic (CK2alpha or CK2alpha') and the CK2beta regulatory subunits are cotransfected, the tetrameric enzyme composed of both subunits (holoenzyme) is detected outside the cell. This observation has been confirmed by assaying protein kinase activity in immunoprecipitates obtained with antihemaglutinin antibody by using a CK2-specific peptide substrate and by Western blots as well as by immunofluorescence of nonpermeabilized cells. Transfection with cDNA of catalytic or regulatory subunit alone does not result in export of these subunits. A study of the kinetics of appearance of the ectopically synthesized protein at different times after transfection indicates that a 5- to 7-h delay after the synthesis of the protein before it appears in the extracellular compartment. Using mutations of CK2alpha that eliminate phosphorylating activity [CK2alpha(Asp-156-Ala)] or that make it less sensitive to heparin inhibition [CK2alpha(Lys-75-Glu,Lys-76-Glu)] demonstrated that these mutations do not prevent the holoenzyme to be exported from the cells.

Blotting, Western↗

[Preoperative risk evaluation in beating-heart coronary artery bypass surgery].

INTRODUCTION AND OBJECTIVES: Operative risk stratification scales for use in cardiac surgery have been developed for patients who undergo procedures using extracorporeal circulation. The aims of the present study were to investigate the use of six preoperative risk stratification scales in patients undergoing beating-heart surgery and to identify risk factors for major complications and mortality in our group of patients who underwent revascularization using this approach. PATIENTS AND METHOD: Between January 1997 and December 2002, we performed 762 coronary artery bypass operations on the beating heart; 61 patients suffered major complications (8%) and 25 died (3.3%). Risk factors for major complications and death were identified using logistic regression analysis of prospectively collected data. The following risk scores were calculated for each patient: Parsonnet 95, Parsonnet 97, Euroscore, Cleveland, Ontario, and French. Receiver operating characteristic curves were used to compare the ability of each scale to predict mortality and major complications. RESULTS: In our patient group, the preoperative variables associated with increased risk were: need for cardiopulmonary resuscitation, renal dysfunction, peripheral vasculopathy, and the presence of severe left main coronary artery disease, three-vessel disease, or an impaired ejection fraction. CONCLUSIONS: Mortality and major complications were best predicted by the Parsonnet 95 and Euroscore scales.

Adult↗

Gene flow among Anopheles albimanus populations in Central America, South America, and the Caribbean assessed by microsatellites and mitochondrial DNA.

Gene flow was examined among Anopheles albimanus populations from Cuba, Mexico, Guatemala, El Salvador, Nicaragua, Costa Rica, Panama, Colombia, and Venezuela by examining variation at four microsatellite (MS) loci and a mitochondrial DNA (mtDNA) marker. There was little variation among Central American populations and weak isolation by distance was only observed with the MS loci. There was moderate to large variation between Central and South American populations, suggesting a barrier to gene flow between Central and South America. However, Panamanian and Pacific Costa Rican populations differed with respect to western Central America, suggesting that there may be another barrier within Central America. There was small to moderate variation among Caribbean and continental populations. Phylogenetic and diversity analyses of mtDNA indicate that more ancestral and diverse haplotypes were present in the Caribbean population, suggesting that current continental An. albimanus populations may have originated from the Caribbean.

Animals↗

Synthesis, X-ray structure, polarized optical spectra and DFT theoretical calculations of two new organic-inorganic hybrid fluoromanganates(III): (bpaH2)[MnF4(H2O)2]2 and (bpeH2)[MnF4(H2O)2]2.

Two new fluoromanganates(III) of 1,2-bis(4-pyridyl)ethane (bpa) and trans-1,2-bis(4-pyridyl)ethylene (bpe), LH(2)[MnF(4)(H(2)O)(2)](2) (L = bpa or bpe), have been prepared and their structure have been solved by single-crystal X-ray diffraction. The [MnF(4)(H(2)O)(2)](-) anion displays an octahedral geometry with a strong Jahn-Teller tetragonal distortion along the H(2)O-Mn-OH(2) axis. The equatorial metal-ligand distances (Mn-F 1.827(1)-1.859(2) A) are shorter than the axial ones (Mn-O 2.203(2)-2.234(2) A). Three polarized absorption bands at 22,500, 18,300 and 14,500 cm(-1) are observed in the optical spectra of (bpaH(2))[MnF(4)(H(2)O)(2)](2). Finally, we present theoretical calculations on the equilibrium bond distances as well as the crystal-field electron structure using density functional methods. The calculated Mn-F bond distances (1.85 A) are in agreement with the experimental data but the obtained Mn-O distances (2.53-2.56 A) are higher than the experimental one as usually found in similar Jahn-Teller distorted systems. The calculated d-d transition energies are compared with experimental energies derived from the optical spectra. The variation of the HOMO energy and transition energies against the Mn-O distance is also shown.

Journal Article↗

Evolution of forebrain and spatial cognition in vertebrates: conservation across diversity.

Historically the dominant trend in comparative brain and behavior research has emphasized the differences in cognition and its neural basis among species. In fact, the vertebrate forebrain shows a remarkable range of diversity and specialized adaptations. Probably the major morphological variation is that observed in the telencephalon of the actinopterygian fish, which undergoes a process of eversion during embryonic development, relative to the telencephalon of non-actinopterygians (for instance, amniotes), which develops by a process of evagination. These different developmental processes produce notable variation, mainly two solid telencephalic hemispheres separated by a unique ventricle in the actinopterygian radiation that contrasts with the hemispheres with internal ventricles in other groups. However, an increasing amount of evidence reveals that the forebrain of vertebrates, whether everted or evaginated, presents a common pattern of basic organization that supports highly conserved cognitive functions. We analyze here recent data indicating a close functional similarity between spatial cognition mechanisms in different groups of vertebrates, mammals, birds, reptiles, and teleost fish, and we show in addition that they rely on homologous neural mechanisms. Thus, recent functional and behavioral comparative evidence is added to the developmental and neuroanatomical data suggesting that the evolution of cognitive capabilities and their neural basis in vertebrates could have been more conservative than previously realized.

Animals↗

Incorporation of Ahc into model dipeptides as an inducer of a beta-turn with a distorted amide bond. Conformational analysis.

The proline residue of dipeptides Ser-Pro and Pro-Ser has been replaced by 7-azabicyclo[2.2.1]heptane-1-carboxylic acid (Ahc), a conformationally restricted analogue of proline that is capable of mimicking distorted amides. The conformational analysis of the new peptides in the solid state revealed that the Ahc-Ser sequence displays a type I beta-turn, which includes a distorted amide bond. In contrast, the Ser-Ahc sequence exists in a nonfolded structure.

Bridged Bicyclo Compounds, Heterocyclic↗

Conservation of spatial memory function in the pallial forebrain of reptiles and ray-finned fishes.

The hippocampus of mammals and birds is critical for spatial memory. Neuroanatomical evidence indicates that the medial cortex (MC) of reptiles and the lateral pallium (LP) of ray-finned fishes could be homologous to the hippocampus of mammals and birds. In this work, we studied the effects of lesions to the MC of turtles and to the LP of goldfish in spatial memory. Lesioned animals were trained in place, and cue maze tasks and crucial probe and transfer tests were performed. In experiment 1, MC-lesioned turtles in the place task failed to locate the goal during trials in which new start positions were used, whereas sham animals navigated directly to the goal independently of start location. In contrast, no deficit was observed in cue learning. In experiment 2, LP lesion produced a dramatic impairment in goldfish trained in the place task, whereas medial and dorsal pallium lesions did not decrease accuracy. In addition, none of these pallial lesions produced deficits in cue learning. These results indicate that lesions to the MC of turtles and to the LP of goldfish, like hippocampal lesions in mammals and birds, selectively impair map-like memory representations of the environmental space. Thus, the forebrain structures of reptiles and teleost fish neuroanatomically equivalent to the mammalian and avian hippocampus also share a central role in spatial cognition. Present results suggest that the presence of a hippocampus-dependent spatial memory system is a primitive feature of the vertebrate forebrain that has been conserved through evolution.

Animals↗

Off-pump total arterial revascularization: our experience.

BACKGROUND AND AIM: Off-pump coronary artery bypass grafting with both the internal thoracic arteries, such as the Tector technique, can reduce the morbidity associated with extracorporeal circulation and aortic cross-clamp. The aim of the present study is to describe our experience and the results obtained. METHODS: From April 1998 to December 2003, the off-pump Tector technique was performed on 743 patients, of whom 621 were male (83.5%), with a mean age of 65.3 +/- 9.5 years (23-90). Preoperative risk factors were diabetes mellitus in 29.5% and peripheral vasculopathy in 14.7% of the patients. Angiography showed left main disease in 25.6% and triple-vessel disease in 50.3% of the patients, with a mean ejection fraction of 60%+/- 13% (23-88). Both the internal thoracic arteries were harvested using the skeletonization technique and were anastomosed as "Y" or "T" grafts. Intraoperative graft patency was checked using a Doppler flowmeter. RESULTS: A total of 2028 distal anastomoses were performed, the average being 2.7 (1 to 5) per patient. At least three distal anastomoses were undertaken in 62% of the patients. Postoperative complications included atrial fibrillation in 40 patients (5.4%), myocardial infarction in 24 (3.2%), mediastinitis and reoperation for bleeding in 7 (0.9%) and stroke in 3 (0.4%). Twenty-four patients (3.2%) died in the first month postoperatively. CONCLUSIONS: The off-pump Tector technique appears to be safe, showing a low surgical morbidity.

Adult↗