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V Fernandez

Publications and source records attributed to V Fernandez.

At least 37 records · Page 2Linked to original sources
PubMed1999

Influence of copper-(II) on colloidal carbon-induced Kupffer cell-dependent oxygen uptake in rat liver: relation to hepatotoxicity.

Formation of reactive O2 species in biological systems can be accomplished by copper-(II) (Cu2+) catalysis, with the consequent cytotoxic response. We have evaluated the influence of Cu2+ on the respiratory activity of Kupffer cells in the perfused liver after colloidal carbon infusion. Studies were carried out in untreated rats and in animals pretreated with the Kupffer cell inactivator gadolinium chloride (GdCl3) or with the metallothionein (MT) inducing agent zinc sulphate, and results were correlated with changes in liver sinusoidal efflux of lactate dehydrogenase (LDH) as an index of hepatotoxicity. In the concentration range of 0.1-1 microM, Cu2+ did not modify carbon phagocytosis by Kupffer cells, whereas the carbon-induced liver O2 uptake showed a sigmoidal-type kinetics with a half-maximal concentration of 0.23 microM. Carbon-induced O2 uptake occurred concomitantly with an increased LDH efflux, effects that were significantly correlated and abolished by GdCl3 pretreatment or by MT induction. It is hypothesized that Cu2+ increases Kupffer cell-dependent O2 utilization by promotion of the free radical processes related to the respiratory burst of activated liver macrophages, which may contribute to the concomitant development of hepatocellular injury.

Animals↗
PubMed1999

Women relatives of Hispanic patients with type 2 diabetes are more prone to exhibit metabolic disturbances.

Hyperinsulinemia and impaired insulin action are familial and predictive of Type 2 diabetes onset. Since high levels of insulin are characteristic of our general (venezuelan)hispanic population, the purpose of this investigation was to identify early metabolic defects in a group of healthy first degree relatives of Type 2 diabetic patients. We studied 46 (29 women and 17 men; ages ranging 18-66 y) first degree relatives of Type 2 diabetic patients comparing them with 22 (12 women and 10 men; ages ranging 22-60 y) subjects who had no family history of diabetes. All subjects underwent resting blood pressure and anthropometric measurements; a 75 g oral glucose tolerance test with determination of glucose and insulin and a fasting lipid profile. The relatives of Type 2 diabetic patients had higher tricipital (TC) and subscapular (SC) skinfolds, and elevated DBP in relation to the control group. The skinfolds elevation was more evident in women, while in men the elevation in DBP predominates. None of the relatives had glucose intolerance, however, the glucose-stimulated insulin response was elevated at all points in men as well as in women. No difference was observed in the HOMA values for IR and beta cell function, or in the delta I30/delta G30 ratio. The lipid profile showed a marked elevation in TG levels in men as well as in women, with low HDL-C values in men. No other lipid abnormalities were observed. Correlation analysis revealed strong association between BMI and WHR with skinfolds and several parameters of the carbohydrate metabolism in women, but not in men. IR in women was possitively associated with skinfolds, SBP and lipid parameters and beta cell function with VLDL-C. Adult relatives of Type 2 diabetic venezuelan patients from hispanic origin had, early in their lives, several parameters of the metabolic syndrome as hyperinsulinemia, obesity, dyslipidemia and high blood pressure. These alterations were more prominent in women, group in which the association among BMI, WHR and IR were statistically significant respect to SBP, DBP, basal insulin, insulin/glucose ratio, TG and HDL-C.

Adult↗
PubMed1998

Developmental selection of var gene expression in Plasmodium falciparum.

The protozoan Plasmodium falciparum causes lethal malaria. Adhesion of erythrocytes infected with P. falciparum to vascular endothelium and to uninfected red blood cells (rosetting) may be involved in the pathogenesis of severe malaria. The binding is mediated by the antigenically variant erythrocyte-membrane-protein-1 (PfEMP-1), which is encoded by members of the P. falciparum var gene family. The control of expression and switching of var genes seems to lack resemblance to mechanisms operating in variant gene families of other microbial pathogens. Here we show that multiple, distinct var gene transcripts (about 24 or more) can be detected by reverse transcription and polymerase chain reaction in bulk cultures of the rosetting parasite FCR3S1.2, despite the adhesive homogeneity of the cultures. We also detected several var transcripts in single erythrocytes infected with a ring-stage parasite of FCR3S1.2, and found that different var genes are transcribed simultaneously from several chromosomes in the same cell. In contrast, we detected only one var transcript, FCR3S1.2 var-1, which encodes the rosetting PfEMP-1 protein, in individual rosette-adhesive trophozoite-infected cells, and we found only one PfEMP-1 type at the erythrocyte surface by labelling with 125iodine and immunoprecipitation. We conclude that a single P. falciparum parasite simultaneously transcribes multiple var genes but, through a developmentally regulated process, selects only one PfEMP-1 to reach the surface of the host cell.

Adult↗
PubMed1998

Polarization analysis in the 3-25 keV range at the ESRF magnetic scattering beamline.

The ESRF magnetic scattering beamline has been optimized for easy tunability of the polarization and energy in the 3-40 keV range. The linear horizontal polarization from the undulator reaches 99.9%, with a flux of approximately 10(12) photons s(-1) at the sample. The diffractometer can operate in horizontal and vertical geometries, with an energy or polarization analyser. The capabilities of this beamline in terms of flux, energy tunability and polarization, permitted polarization analysis of resonant magnetic scattering from antiferromagnetic UPd(2)Si(2) at both the L(2)- and M(4)-edges of uranium, to separate the contributions of the 5f and 6d electrons to the magnetism.

Journal Article↗
PubMed1998

Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum.

Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum-infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria. Here we report on the identification by single-cell reverse transcriptase PCR and cDNA cloning of the adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting PfEMP1 contains clusters of glycosaminoglycan-binding motifs. A recombinant fusion protein (Duffy binding-like 1-glutathione S transferase; Duffy binding-like-1-GST) was found to adhere directly to normal erythrocytes, disrupt naturally formed rosettes, block rosette reformation, and bind to a heparin-Sepharose matrix. The adhesive interactions could be inhibited with heparan sulfate or enzymes that remove heparan sulfate from the cell surface whereas other enzymes or similar glycosaminoglycans of a like negative charge did not affect the binding. PfEMP1 is suggested to be the rosetting ligand and heparan sulfate, or a heparan sulfate-like molecule, the receptor both for PfEMP1 binding and naturally formed erythrocyte rosettes.

Amino Acid Sequence↗
PubMed1998

Time course study of the influence of acute iron overload on Kupffer cell functioning and hepatotoxicity assessed in the isolated perfused rat liver.

This study tested the hypothesis that acute iron overload (500 mg/kg) alters Kupffer cell functioning by promoting free radical reactions associated with the respiratory burst of liver macrophages, assessed in the isolated perfused rat liver under conditions of Kupffer cell stimulation by carbon infusion and inactivation by gadolinium chloride pretreatment. Total serum and hepatic iron levels were markedly enhanced compared with control values 2 to 24 hours after iron treatment. Total liver O2 uptake progressively increased by iron overload reaching a maximum at 6 hours after treatment, an effect that was completely blocked by GdCl3. Concomitantly, carbon-induced GdCl3-sensitive liver O2 uptake was either enhanced by 119% at 2 hours after iron overload, diminished compared with control values at 4 hours, or abolished at 6 hours. Iron-overloaded rats showed a marked increase in liver sinusoidal lactate dehydrogenase efflux at 4 and 6 hours after treatment, an effect that is exacerbated by carbon infusion and reduced (69%-89%) by GdCl3 pretreatment. Both basal and carbon-induced lactate dehydrogenase effluxes returned to control values at 24 hours after iron overload concomitantly with depression of the basal O2 uptake, without development of iron-induced GdCl3-sensitive respiration or Kupffer cell activation by carbon infusion. It is concluded that iron overload induces a derangement in the Kupffer cell functional status represented by early increases in macrophage-dependent respiratory activity, which may contribute to the concomitant liver injury that developed and to the impairment of both hepatic respiration and the macrophage response to particle stimulation observed at later times after treatment.

Acute Disease↗
PubMed1998

Multiple adhesive phenotypes linked to rosetting binding of erythrocytes in Plasmodium falciparum malaria.

The cerebral form of severe malaria is associated with excessive intravascular sequestration of Plasmodium falciparum-infected erythrocytes (PRBC). Retention and accumulation of PRBC may lead to occlusion of brain microvessels and direct the triggering of acute pathologic changes. Here we report that by selection, cloning, and subcloning, we have identified rare P. falciparum parasites expressing a pan-adhesive phenotype linked to erythrocyte rosetting, a previously identified correlate of cerebral malaria. Rosetting PRBC not only bound uninfected erythrocytes but also formed autoagglutinates, adhered to endothelial cells, and bound to CD36, immunoglobulins, and the blood group A antigen. The linkage of rosetting, autoagglutination, and cytoadherence involved the coexpression on a single PRBC of ligands with multiple specificities and the binding to two or more receptors on erythrocytes and to at least two other cell adhesion molecules, including a new endothelial cell receptor for P. falciparum-infected erythrocytes. Limited proteolysis that differentially cleaved the rosetting ligand PfEMP1 from the PRBC surface abrogated all the binding phenotypes of these parasites, implicating the variant antigen PfEMP1 as a carrier of multiple ligand specificities. The results encourage the further study of pan-adhesion as a potentially important parasite phenotype in the pathogenesis of severe P. falciparum malaria.

Animals↗
PubMed1997

PECAM-1/CD31, an endothelial receptor for binding Plasmodium falciparum-infected erythrocytes.

Excessive binding of Plasmodium falciparum-infected red blood cells (pRBCs) to the vascular endothelium (cytoadherence) and to uninfected erythrocytes (rosetting) may lead to occlusion of the microvasculature and thereby contribute directly to the acute pathology of severe human malaria. A number of endothelial receptors have been identified as targets for the pRBCs, including CD36, intercellular adhesion molecule-1 (ICAM-1) and chondroitin-4-sulfate (CSA). In vitro, CD36 is the most frequent target of strains from patients with mild as well as severe P. falciparum malaria, but is expressed at low levels on the cerebral microvasculature and therefore seems unlikely to be involved in the evolution of cerebral disease. Strains of P. falciparum that form rosettes are associated both with the occurrence of cerebral malaria and severe anemia. Here we report that malaria-infected RBCs adhere to platelet/endothelial cell adhesion molecule-1 (PECAM-1/CD31) on the vascular endothelium. pRBCs bind to endothelial cells, to PECAM-1/CD31 transfected cells, and directly to recombinant PECAM-1/CD31 absorbed onto plastic. Soluble PECAM-1/CD31 and monoclonal antibodies specific for the amino-terminal segment of PECAM-1/CD31 (domains 1-4) blocked the binding. Interferon-gamma (IFN-gamma)-essential for the development of cerebral malaria in the mouse-was found to augment adhesion of human pRBCs to PECAM-1/CD31 on endothelial cell monolayers. Our results suggest that PECAM-1/CD31 is a virulence-associated endothelial receptor of P. falciparum-infected RBCs.

Animals↗
PubMed1997

Improved triglyceride control with low glycaemic index-high carbohydrate modified-lipid diet in a hypertriglyceridaemic child.

This study reports a 7-y-old boy with severe hypertriglyceridaemia who was successfully treated for 6 y with a low glycaemic index-high carbohydrate modified-lipid diet that produced beneficial changes in triglyceride and total cholesterol levels. It is suggested that a selection of a complex digestible carbohydrate and an adequate ratio between polyunsaturated and monounsaturated fat may, in the long term, favourably improve the lipid profile.

Child↗
PubMed1997

Immunoglobulin E, a pathogenic factor in Plasmodium falciparum malaria.

Most children and adults living in areas where the endemicity of Plasmodium falciparum malaria is high have significantly elevated levels of both total immunoglobulin E (IgE) and IgE antimalarial antibodies in blood. This elevation is highest in patients with cerebral malaria, suggesting a pathogenic role for this immunoglobulin isotype. In this study, we show that IgE elevation may also be seen in severe malaria without cerebral involvement and parallels an elevation of tumor necrosis factor alpha (TNF). IgE-containing serum from malaria immune donors was added to tissue culture plates coated with rabbit anti-human IgE antibodies or with P. falciparum antigen. IgE-anti-IgE complexes as well as antigen-binding IgE antibodies induced TNF release from peripheral blood mononuclear cells (PBMC). Nonmalaria control sera with no IgE elevation induced significantly less of this cytokine, and the TNF-inducing capacity of malaria sera was also strongly reduced by passing them over anti-IgE Sepharose columns. The cells giving rise to TNF were adherent PBMC. The release of this cytokine probably reflects cross-linking of their low-affinity receptors for IgE (CD23) by IgE-containing immune complexes known to give rise to monocyte activation via the NO transduction pathway. In line with this, adherent monocytic cells exposed to IgE complexes displayed increased expression of CD23. As the malaria sera contained IgG anti-IgE antibodies, such complexes probably also play a role in the induction of TNF in vivo. Overproduction of TNF is considered a major pathogenic mechanism responsible for fever and tissue lesions in P. falciparum malaria. This overproduction is generally assumed to reflect a direct stimulation of effector cells by certain parasite-derived toxins. Our results suggest that IgE elevation constitutes yet another important mechanism involved in excessive TNF induction in this disease.

Adult↗
PubMed1997

Overweight and hypertension: data from the 1992-1993 Mexican survey.

Data of the 1992-1993 Mexican Survey of Chronic Diseases in the Urban Adult Population were analyzed to investigate the effects of age and sex on the association between overweight and hypertension. Blood pressure, body weight, and height were measured in a group of 13,945 Mexicans aged 20 to 69 years living in towns and cities larger than 15,000 people. Hypertension was defined following the recommendations of the Joint National Committee for Detection, Evaluation, and Treatment of High Blood Pressure-V. Overweight was defined following the recommendations of the National Institutes of Health Consensus on Health and Obesity. The prevalence of types of hypertension was higher in men than in women, particularly in the groups of 20 to 39 years of age. Cross-classification of subjects according to the presence of hypertension and overweight confirmed the association between both variables. The odds ratio and 95% confidence intervals indicated that overweight was associated with systolic and diastolic hypertension and with isolated diastolic hypertension in women and, to a lesser extent, in men. This association was not found in the 60- to 69-year group in both sexes. Overweight did not show significant association with isolated systolic hypertension in both sexes. Results of a multiple logistic regression analysis of overweight on hypertension, controlling for age and sex, were consistent with these findings. It is suggested that other factors, independent of overweight, explain the observed gender-specific differences in the prevalence of hypertension in younger age groups. The hormonal environment of young women is one of the mentioned factors modifying the prevalence of hypertension in this group of the Mexican urban adult population.

Adult↗
PubMed1996

Influence of body mass index and slimming habits on menstrual pain and cycle irregularity.

Using a cross-sectional sample of 1147 urban adolescents, aged between 14 and 20 years, the variability of some menstrual cycle indicators was related to weight loss. Nearly 40% of the adolescents tried to lose weight and the results showed that attempting to lose weight is significantly associated with increased prevalence of menstrual irregularity and menstrual pain. This finding is independent of body mass index.

Adolescent↗
PubMed1996

HLA DR and DQ polymorphism in Ashkenazi and non-Ashkenazi Jews: comparison with other Mediterraneans.

HLA-DR and DQ alleles have been detected by DNA typing in Ashkenazi and non-Ashkenazi Jews from Israel. Allele frequencies, characteristic DR/DQ linkage disequilibria, population distances and their corresponding dendrogram by using the Neighbor-Joining method were used to study relatedness between Jewish and other Mediterranean and non Mediterranean populations. Closest relatedness is observed between Ashkenazi and non-Ashkenazi Jews, and, in decreasing order, also with Algerians, Spaniards (including Spanish-Basques), French and Italians. Also, particular characteristic Central European alleles are observed in Ashkenazi Jews and Mediterranean/African alleles in non-Ashkenazi Jews. This is consistent with historical data, Jews being an ancient Mediterranean population, who have had a certain degree of admixture with their 2000-3000 years old neighbors in spite of cultural and religious traditions which have preserved identity outside Israel.

Algeria↗
PubMed1996

Enzyme therapy of xeroderma pigmentosum: safety and efficacy testing of T4N5 liposome lotion containing a prokaryotic DNA repair enzyme.

Xeroderma pigmentosum (XP) is a rare genetic disease in which patients are defective in DNA repair and are extremely sensitive to solar UV radiation exposure. A new treatment approach was tested in these patients, in which a prokaryotic DNA repair enzyme specific for UV-induced DNA damage was delivered into the skin by means of topically applied liposomes to supplement the deficient activity. Acute and chronic safety testing in both mice and humans showed neither adverse reactions nor significant changes in serum chemistry or in skin histology. The skin of XP patients treated with the DNA repair liposomes had fewer cyclobutylpyrimidine dimers in DNA and showed less erythema than did control sites. The results encourage further clinical testing of this new enzyme therapy approach.

Adolescent↗
PubMed1996

Biochemical aspects of cellular antioxidant systems.

Aerobic life is characterized by a steady generation of reactive oxygen species balanced by a similar rate of their consumption by antioxidants. To maintain homeostasis, there is a requirement for the continuous regeneration of antioxidant capacity, and if this is not met, oxidative stress occurs, resulting in pathophysiological events. Cellular protection against oxidative stress is organized at multiple levels. Defense strategies include prevention, interception, replacement, and repair. These mechanisms are coupled to the intermediary metabolism for a continuous supply of energy, reducing equivalents, and precursors, and depend on the dietary supply of metabolic fuels and essential molecules to allow an optimal cellular functioning.

Antioxidants↗