Biomedical subjects

J Bermúdez

Publications and source records attributed to J Bermúdez.

At least 19 recordsLinked to original sources

PubMed2005

Copolymers of poly-L-lysine with serine and tryptophan form stable DNA vectors: implications for receptor-mediated gene transfer.

Inefficient gene transfer and poor stability in physiological medium are important shortcomings for receptor-mediated gene transfer vectors. Here, we evaluate vectors formulated with random copolymers of L-lysine/L-serine (3:1) and L-lysine/L-tryptophan (4:1), focusing on both their biophysical and functional characterization. By means of dynamic light scattering (DLS) and transmission electron microscopy (TEM), we demonstrate that poly-L-lysine (pK), poly-L-lysine-L-tryptophan (pKW) and poly-L-lysine-L-serine (pKS) are able to form compacted, small particles when mixed with plasmid DNA in the absence of salt. Upon dilution in physiological medium, copolymers of both lys/ser and lys/trp do not aggregate, in contrast with poly-L-lysine DNA complexes as determined by scattering, DLS and TEM measurements. Tight packing, as demonstrated by resistance to heparin, SDS and trypsin treatments, is also featured in tryptophan-containing complexes. Successful receptor-mediated endocytosis gene transfer using galactosylated copolymers into cells expressing the asiagloglycoprotein receptor correlated with lack of aggregation. Particles obtained using galactosylated poly-L-lysine-L-tryptophan (Gal-pKW) copolymer demonstrated specific receptor-mediated gene transfer since reporter gene activity dropped in the presence of an excess ligand in the culture medium during transfection. Although copolymers of galactosylated poly-L-lysine-L-serine (Gal-pKS) do not aggregate in the presence of salt, they are not able to internalize in a specific receptor-mediated endocytosis fashion. The introduction of bulky aromatic/hydrophobic (tryptophan) or hydrophillic (serine) moieties into the positively charged vectors allows the compacted particles to disperse into salt-containing medium avoiding salt-induced aggregation. Moreover, tryptophan-containing particles are able to mediate specific gene transfer via receptor-mediated endocytosis.

Asialoglycoprotein Receptor↗

PubMed2005

[Quadrigeminal cistern and calcarine fissure lipoma: case report and review of the literature].

We report the case of a multiple intracranial lipoma in a 47 year-old patient presenting with headache dizziness and quadrantanopsia. MR imaging revealed the presence of 2 lipomas, one located within the quadrigeminal cistern and the other in the calcarine fissure. To our knowledge, this combination of this rare lesion has not been yet described. We review the current literature.

Brain Neoplasms↗

PubMed2000

Cells overexpressing fructose-2,6-bisphosphatase showed enhanced pentose phosphate pathway flux and resistance to oxidative stress.

Changes in the content of fructose-2,6-bisphosphate, a modulator of glycolytic flux, also affect other metabolic fluxes such as the non-oxidative pentose phosphate pathway. Since this is the main source of precursors for biosynthesis in proliferating cells, PFK-2/FBPase-2 has been proposed as a potential target for neoplastic treatments. Here we provide evidence that cells with a low content of fructose-2,6-bisphosphate have a lower energy status than controls, but they are also less sensitive to oxidative stress. This feature is related to the activation of the oxidative branch of the pentose phosphate pathway and the increased production of NADPH.

Animals↗

PubMed2000

MPP(+)-induced mitochondrial dysfunction is potentiated by dopamine.

MPP(+), the major metabolite of the Parkinsonism-inducing compound MPTP, responsible for the destruction of the nigrostriatal pathway in primates and rodents, has been assayed in isolated rat liver mitochondria in the presence of physiological concentrations of dopamine or analogous concentrations of melanin-dopamine. 5 microM MPP(+) in the presence of 70 microM dopamine or melanin-dopamine, but not alone, decreased the heat production and oxygen consumption of a mitochondrial suspension activated with succinate and ADP. Both dopamine and oxidized dopamine plus MPP(+) also decreased the mitochondrial reductive power measured with MTT. Mitochondrial swelling was observed, associated with an increase in membrane mitochondrial potential, as a synergistic effect between low concentrations of MPP(+) and dopamine. It is suggested that cytosolic dopamine, by itself or via its autooxidation products, may play a relevant role in the mitochondrial toxicity of MPP(+). A failure in the regulation of the storage/release of dopamine could aggravate a mitochondrial damage and trigger the neurodegenerative process underlying MPTP toxicity and Parkinson's disease.

1-Methyl-4-phenylpyridinium↗

PubMed2000

Chemical degradation of liposomes by serum components detected by NMR.

Interaction between serum components and liposomes is an oxygen-dependent exothermic process. We studied the interaction of 100 nm extruded liposomes (bearing positive, negative or no charge) with foetal calf serum by 1H NMR and 13C NMR, in order to further our understanding of these reactions. Studies of aqueous or organic extracts obtained after 2 h, 1 day or 1 week, showed hydrolysis to be a degradation process concomitant with the interaction with serum. Oxidation was identified as additional to hydrolysis in the process of degradation. Oxidation produced aldehydes, acids and alcohols, although aldehydes and alcohols were prone to further decomposition and only appeared transiently. Alkenes and other oxidized compounds predominated in those products derived from oxidation. In stearylamine-containing liposomes some aldehydes and a nitroderivative were found as degradation products. Such metabolites are apolar and their presence might explain the intrinsic toxicity of this kind of liposome in cell cultures. The work described in the present study revealed the chemical degradation of liposomes in the serum used. In all cases the results obtained were compared with liposomes not incubated with serum.

Aldehydes↗

PubMed2000

Angiogenesis in neuroblastoma: relationship to survival and other prognostic factors in a cohort of neuroblastoma patients.

PURPOSE: To study angiogenesis in neuroblastoma, using morphometric and computerized image analysis, and correlate the results with survival and other prognostic factors. PATIENTS AND METHODS: Sixty-nine patients from the Spanish Cooperative Study for Neuroblastoma were studied. Tumoral angiogenesis was studied using an avidin-biotin immunoperoxidase technique with an anti-CD34 antibody. Vascular parameters (VPs) were analyzed by a computerized system. Statistical analysis was also performed. RESULTS: Sixty-six samples had adequate tumoral tissue, and their tumoral vessels were counted. Endothelial cells were more prominent in pure neuroblastomas than in maturing and more mature tumors. VPs showed no statistical difference between the groups of patients as defined by the levels of the other prognostic factors in neuroblastoma: age, stage, histopathology, TRK-A, P-glycoprotein expression, or MYCN copy number. In patients who relapsed, tumors did not show statistically significant difference in VPs when compared with tumors from patients who did not relapse. There was also no difference in VPs in tumors from living patients when compared with tumors from deceased patients. Overall survival was 75%, and event-free survival was 55% at 50 months. CONCLUSION: VPs could be adequately determined by a computerized system in neuroblastoma; however, VPs were not predictive of survival for our patients. In our patients, neither disseminated nor local relapses were influenced by the angiogenic characteristics of the tumors.

Adolescent↗

PubMed1999

Na(+)-K(+) pump and metabolic activities of trout erythrocytes during anoxia.

Metabolic activity in the red blood cells of brown trout was monitored under conditions of oxygen depletion and chemically induced anoxia. Although metabolic activity was reduced during anoxia to one-third of the normoxic value, these cells maintained their ATP contents stable and were viable for hours in the absence of oxygen. In addition, Na(+)-K(+) pump activity was not down-regulated when metabolic activity was reduced during anoxia. The compatibility of this finding with energy equilibrium and ion homeostasis was investigated.

Adenosine Triphosphate↗

PubMed1997

Serum-liposome interaction is an oxygen-dependent process.

Measurements of heat dissipation, oxygen concentration and average vesicle size were correlated to study the effect of serum components on different types of liposome. The results indicate that the interaction between serum components and liposomes is exothermic and oxygen dependent, and leads to disruption of vesicles. The dependence of this effect on serum concentration, vesicle surface charge and type of liposome was also evaluated. Serum components did not produce any effect on conventional liposomes in the absence of oxygen. Moreover, in hypoxic conditions the serum-liposome interaction was delayed. Both results suggest that this interaction is an oxygen-dependent event. Finally, we confirmed that sterically stabilised liposomes remain unalterated in the presence of serum.

Animals↗

PubMed1997

Anxiety and attention: is there an attentional bias for positive emotional stimuli?

Empirical research has shown that anxiety is associated with a systematic bias in the cognitive system. Anxious individuals (clinically anxious patients and normal individuals with high-trait anxiety) are characterized by a pattern of selective processing that favors the encoding of threatening information. Is this attentional bias specific to threat-related information, or does it operate for positive emotional stimuli? The research directly connected with the existence of an attentional bias for threat in anxiety was examined.

Anxiety↗

PubMed1997

Exogenous fructose 1,6-bisphosphate reduces K+ permeability in isolated rat hepatocytes.

The relationship between the protective effect of fructose 1,6-bisphosphate (F-1,6-P2) against cell injury and the modifications produced in the metabolic fluxes and in the membrane permeability to K+ was studied in isolated rat hepatocytes. Incubation of these cells in the presence of F-1,6-P2 reduced metabolic activity without affecting the ATP content, which suggests a downregulation of the ATP turnover. Using 86Rb+ as a tracer, we analyzed the relationship between these metabolic changes and alterations in K+ fluxes. In the presence of F-1,6-P2 the passive and the active K+ fluxes in hepatocytes decreased. However, the Na(+)-K+ pump from semipurified membranes was not directly affected by F-1,6-P2, which suggests a secondarily induced reduction of Na(+)-K+ pump activity. Moreover, galactosamine-treated cells showed a marked increase in permeability to K+ that was abolished by the presence of F-1,6-P2. This protective effect may be related to the prevention of K+ efflux. The results reported here strongly suggest the induction of channel arrest, and the associated metabolic downregulation, as the primary protective effect of F-1,6-P2, as has been shown in the prevention of galactosamine-induced hepatotoxicity.

Animals↗

PubMed1996

Early effects of basic fibroblast growth factor on foetal rat mesencephalic cell suspensions.

Mesencephalic cell suspensions are used, experimentally but also clinically, to compensate for neurological deficiencies, by implantation into the striatum. Here, we have studied the metabolism of mesencephalic cell suspensions obtained from rat embryos by measuring heat dissipation, oxygen consumption, ATP and lactate production. The effect of basic fibroblast growth factor (bFGF) at a 50 ng/ml concentration on these parameters was studied in order to assess the effect of in vitro exposure of cell suspensions to this trophic factor. Heat production and oxygen consumption were low, as could be expected from an immature nervous tissue, and they further decreased after addition of bFGF. This trophic factor decreased the total ATP concentration and increased the lactate production. The viability of the cell suspensions was reduced by nearly a half, 2 h after the addition of bFGF, and numerous fragmented nuclei were observed. It seems that, in contrast to the neuroprotective effect of bFGF on mesencephalic cultures and nigrostriatal neurons, this factor could have an initial sorting effect in the development of mesencephalic structures.

Acridine Orange↗

PubMed1996

Effects of taxol on isolated rat hepatocyte metabolism.

Taxol is a natural product, isolated from Taxus brevifolia, with increasing clinical applications because of its potent antitumor activity. Although it is mainly metabolized in the liver, its effect on hepatocyte metabolism has been scarcely investigated. In this study, the response of isolated rat hepatocytes to taxol was evaluated by correlating the changes observed in global indexes such as viability and heat dissipation with those produced in oxygen consumption and intracellular metabolites (ATP, fructose 2,6-bisphosphate, and lactate). The results indicate that taxol reduces aerobic metabolism, which induces an insufficient increase of the ATP via anaerobic glycolysis. Moreover, incubations of isolated mitochondria with taxol indicate that the respiratory chain is directly affected by this drug.

Animals↗

PubMed1995

Microcalorimetric evaluation of the effect of combined chemotherapeutic drugs.

A study of the effect of combined antineoplastic drugs in vitro was carried out by microcalorimetric monitoring of the metabolic activity of treated cells. Power-time curves of growing T-lymphoma cell suspensions, treated with single or combined drugs, were recorded. The extent of the effect was evaluated by changes in the slopes of the microcalorimetric curves and the kinetics of the drug action were interpreted from the time at which these changes reached their maximum value. The method was validated using two well-established drug combinations, the potentiatory effect of dipyridamole on methotrexate cytotoxicity, and the synergism between methotrexate and 6-thioguanine. In the first case, where one drug is not toxic, the modulation may be evaluated by comparing the inhibition produced by the toxic drug alone and in combination with its modulator. Otherwise, when both drugs are toxic, the combined effect must be evaluated by means of their combination index. The measurement procedure is simple, the electric signal is well suited to automation of data acquisition and the response may be evaluated within 5 to 6 h of drug administration. Moreover, we demonstrate that microcalorimetry is a reliable method for the detection of modulatory effects in combination chemotherapy.

Antineoplastic Agents↗

PubMed1995

Neuroticism, mood, and retrieval of negative personal memories.

Most studies of the effects of neuroticism on memory investigate the recall of self-related material learned during the course of the experimental session. The present study was designed to examine the effects of neuroticism on more complex personal events in real life. High levels of neuroticism were associated with a tendency toward fewer happy thoughts and memories. The results also suggest that neuroticism increased retrieval of negative personal memories independent of depressed mood. These findings are discussed in relation to cognitive vulnerability to depression.

Adolescent↗

PubMed1995

[Hereditary diseases and congenital malformations at the Unit of Medical Genetics of the University of Zulia. Years: 1983-1992].

The Medical Genetics Unit at Universidad del Zulia (UGM-LUZ) gives counsel to patients with partial and total genetic diseases. Counseling is available for patients of both sexes and all ages, from public and private health centers and several medical specialities. In the present study an analysis of 4617 clinical records from families referred for genetic counseling to the UGM-LUZ is given. The study spans from January 1983 to December 1992. Fifty four (1.2%) of these histories correspond to pre-nuptial counseling, 773 (16.7%) pre-conceptional, 316 (6.8%) pre-natal and 3474 (75.3%) for diagnosis. A computerized system was developed, based on relational data base manager, that permits access with interactive Dbase type applications. A total of 5433 diagnoses were made. The most frequent causes of genetic diseases were chromosomal abnormalities (12.32%), mainly Down and Turner syndromes. Mendelian diseases occupied 14.45% of all cases, with Marfan and Noonan syndrome, Osteogenesis imperfecta. Duchenne-Becker muscular dystrophy and Incontinentia Pigmenti as the most frequent syndromes. Diseases that involve multifactorial inheritance, such as neural tube defects, accounted for 7.36% of all diagnosis. Effects of teratogenic agents such as german measles, radiations and others were detected in 3.96% of all cases. In 8.5% of the patients a hereditary factor was suspected. No definitive diagnosis was reached in 32.45% of all cases and 20.96% of the patients were normal. The need for data from other medical genetic centers is stressed. In this way the regional and national genetic diseases on morbidity can be known.

Adolescent↗

PubMed1994

Fructose 1,6-bisphosphate protects against D-galactosamine toxicity in isolated rat hepatocytes.

Incubation of hepatocytes with D-galactosamine (GalN) produced a dose-dependent alteration in cell viability and a fall in ATP and fructose 2,6-bisphosphate (Fru-2,6-P2) levels. The reduction in Fru-2,6-P2 can be explained by changes in the substrates or modulators of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, because neither the adenosine 3',5'-cyclic monophosphate level nor the activity ratio of the enzyme was modified. Microcalorimetric measurements showed that GalN produced an exothermic peak followed by a progressive decrease in heat dissipation. Simultaneous administration of GalN and fructose 1,6-bisphosphate (Fru-1,6-P2) significantly increased cell viability, and concentrations of ATP and Fru-2,6-P2 and led to stable heat production. In the presence of Fru-1,6-P2 alone, hepatocytes kept ATP and Fru-2,6-P2 levels constant, whereas they increased the oxygen uptake-to-heat output ratio. Our results suggest that GalN initiates the hepatotoxic effect by means of an energy-dissipating interaction, produced before its metabolism and presumably at the membrane level, whereas Fru-1,6-P2 protects the cells against this injury in a way that prevents the initial interaction and increases the metabolic efficiency of the cell.

Adenosine Triphosphate↗

PubMed1989

On the analysis of microbiological processes by Monte Carlo simulation techniques.

The Barcelonagram is a Monte Carlo simulator recently designed in order to take account of the behaviour of living systems. In this paper we apply this technique to real bacterial growth in different and significant experimental conditions, namely (i) the growth of the Serratia marcescens in a minimal glucose-limited medium, (ii) the temperature effect on the anaerobic growth of the same strain, (iii) the growth of the Escherichia coli in a minimal medium and (iv) the normal specific growth rate of bacterial populations against the available substrate concentration. In the context of these different cases we discuss the diverse contributions of these simulated results to the understanding of the microbiological processes and the general reliability of the simulation considered as a third alternative besides both (and together with!) experience and mathematical modelling.

Bacteria↗

PubMed1988

Discriminant analysis of microcalorimetric data of bacterial growth.

In this work a bacterial classification method based on the discriminant analysis of the microcalorimetric data provided by the growth power-time (p-t) curves is developed. This method is applied to classify several species of Enterobacteria of different origins, and the results are compared with those obtained by conventional techniques. The proposed analysis allows us to classify bacteria into species and discriminate among strains of the same species. The classification is carried out using one run of each isolate after standardization of inocula and growth conditions. The discrimination power of available microcalorimetric data is also discussed, and the most discriminant set of data is proposed as the input variables of the analysis. Finally, the advantages of microcalorimetry as a taxonomical technique are discussed.

Calorimetry↗