Study of Surface States on Cu(110) Using Optical Reflectance Anisotropy.
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Journal Article↗
Biomedical subjects
V Fernandez
Publications and source records attributed to V Fernandez.
Structure determination of an alkali metal-CO coadsorption phase: Ni(111)-K/CO.
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Journal Article↗
Adhesion of Plasmodium falciparum-infected erythrocytes to human cells and secretion of cytokines (IL-1-beta, IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF alpha, G-CSF, GM-CSF.
The scientific interest in the physical interaction of Plasmodium falciparum-infected erythrocytes with host cells stems from the suggestion that excessive binding in the microvasculature leads to severe malaria. The authors studied, therefore, two parasites for their ability to adhere to normal human cells and to induce cytokine production, one parasite lacking a binding capacity (DD2) and one which adhered to CD36+ transfected CHO cells (MCAMP). The MCAMP parasites readily bound to platelets and erythrocytes and to monocytes, polymorphonuclear granulocytes and EBV-transformed B cells as seen by light and electron microscopy. Platelets were frequently attached in large numbers to the infected erythrocyte surface and groups of infected erythrocytes were sometimes held together by several platelets. Nine out of 17 cytokines tested were found to be secreted into the culture supernatants after 35 h of co-cultures containing monocytes or unfractionated peripheral blood mononuclear cells (PBMC) and parasites (IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF alpha, G-CSF, IL-1-beta, and GM-CSF). Three additional cytokines were also present in low levels (< 200 pg/ml, IL-2, IL-4, IFN gamma) in the culture supernatants after incubation of the cells for 4 days. TNF alpha, IL-RA, and IL-8 were secreted from polymorphonuclear granulocytes, LGLs and T cells. Platelets and, to a lesser degree, monocytes and T cells secreted large amounts of TGF beta (10-30 ng/ml). Cytokines may participate in the pathogenesis but also the suppression of immune responses seen during acute malarial infections.
Animals↗
The therapeutic approach to the control of hypertension. Its impact on health policy.
The pharmacologic approach to the control of hypertension must consider both the clinical perspective and the Public Health approach policy in which social costs have to be balanced against benefits to the entire population. Cost-effectiveness analysis are at the core of decisions taken within this frame of reference. The issue of cost-effectiveness of preventive and therapeutic measures are crucial in the case of less developed countries. An analysis of studies undertaken in Mexico leads to the conclusion that, from a Public Health perspective, a program for the control of hypertension with a strong emphasis on drug therapy is likely to require a significant proportion of the health budget. Therefore, more emphasis must be placed on primary prevention based on modifications of life style.
Antihypertensive Agents↗
Rural campaign to diagnose and treat mucocutaneous leishmaniasis in Bolivia.
Mucocutaneous leishmaniasis (MCL) is endemic in the tropical Amazonian lowlands of Bolivia, an area that regularly receives influxes of migratory populations. In these new agricultural development areas, a campaign to diagnose and treat the disease was carried out between 1989 and 1992, in order to provide direct access to MCL treatment in the endemic areas at a standard equivalent to that offered in the urban centres in Bolivia. The campaign led to the creation of decentralized local centres for diagnosis and treatment of the disease. A campaign to inform the population about leishmaniasis was also undertaken and courses were run to educate medical and paramedical personnel. As a result of the campaign, 3285 cases of leishmaniasis were diagnosed, including 2152 cutaneous and 326 mucosal forms. Also, a total of 1888 cases were treated, 1677 of which cutaneous and 211, mucosal.
Bolivia↗
Cytokine synthesis analyzed at the single-cell level before and after revaccination with tetanus toxoid.
Tetanus toxoid (TT) is a potent immunogen which evokes strong antibody responses after immunization. Here, TT was used as a model antigen to study the production of cytokines at the single-cell level during the in vitro immune response to a specific recall antigen. Peripheral blood mononuclear cells were obtained from healthy volunteers before and 9 weeks after TT vaccination and were cultured with antigen in vitro. The kinetics of cytokine synthesis as well as frequencies of cytokine-producing cells were determined at the single-cell level by immunofluorescent intracellular staining of the cytokine protein. The phenotype of the producer cells was revealed by concomitant staining of surface markers. Two patterns of cytokine synthesis were induced by TT: (i) T lymphocytes expressed a number of lymphokines (interleukin (IL)-2, IL-3, IL-4, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-beta), each with distinct kinetics of synthesis. This cytokine expression was strictly dependent on the previous exposure of the donor to TT and positively correlated with the level of tetanus immunity, as judged by TT-specific Ab levels in plasma as well as lymphoproliferation. Cells producing IL-2, IFN-gamma and particularly TNF-beta dominated this in vitro response. After 96-120 h in culture, 1.0-1.3% of the cells produced TNF-beta, i.e. frequencies at least tenfold higher than for any of the other lymphokines assayed. The addition of IL-2 to the cultures caused a fourfold increase and a kinetics shift in the production of TNF-beta, which peaked already at 24 h. Exogenously added IL-2 also caused a five- to tenfold increase in the number of IL-2 and IFN-gamma producers but no apparent change in the kinetics of intracellular lymphokine appearance. (ii) The cytokines IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha were produced by monocytes. This inflammatory monokine response was independent of the TT-specific immune status of the donors, characterized by a rapid onset and was transient.
Adult↗
Comparison of chagasic and non-chagasic myocardiopathies by ELISA and immunoblotting with antigens of Trypanosoma cruzi and Trypanosoma rangeli.
Trypanosoma cruzi associated myocardiopathy, or Chagas disease, continues to be a serious problem in Venezuela, for which there is neither a vaccine nor a cure. In order to learn more about the humoral immune response to trypanosomal antigens, and to try to identify dominant antigens, we used ELISA and immunoblotting to study the reactivity of sera from patients with chagasic and non-chagasic myocardiopathies, against surface and secreted proteins from T. cruzi and T. rangeli. Both species are found in the same insect vector, but only T. cruzi is thought to be pathogenic in vertebrates. The ELISA results fell into three patterns: (1) high reactivity values with both T. cruzi and T. rangeli surface and secreted proteins; (2) high values to T. cruzi but low values with T. rangeli; and (3) high values to T. rangeli and low values with T. cruzi. This finding that some chagasic sera react more strongly against T. rangeli than against T. cruzi is intriguing, and warrants further investigation. When chagasic sera were tested on Western blots of total extracts of T. cruzi and T. rangeli, the pattern of reactive bands was similar against both parasites, but no two sera showed an identical pattern. Furthermore, there was no correlation between a particular immunoblotting pattern and either the antibody titer, or the severity of the disease. Several T. cruzi and T. rangeli antigens were recognized by sera from healthy controls as well as from patients with other tropical diseases endemic in Venezuela. Overall, our results suggest that the humoral immune response to trypanosomal antigens is complex, and no single antigen may be the determining factor in the pathogenesis of chagasic myocardiopathy.
Adult↗
Rosetting.
Why do some individuals get severe falciparum malaria while others don't? Rosetting (the binding of uninfected erythrocytes to Plasmodium falciparum-infected erythrocytes), together with endothelial cytoadherence, has been shown to play a crucial role in the obstruction of the microvosculoture in P. falciparum malaria. Here, Mats Wahlgren, Victor Fernandez, Carin Scholonder and Johan Carlson review the literature surrounding rosetting.
Journal Article↗
Influence of thyroid hormone administration on hepatic glutathione content and basolateral gamma-glutamyltransferase ectoactivity in the isolated perfused rat liver.
The effect of thyroid hormone administration on liver glutathione (GSH) content and gamma-glutamyltransferase activity in the isolated perfused liver was studied for a period of 1-7 days in fed rats following a single dose of 0.1 mg 3,5,3'-L-triiodothyronine (T3)/kg. T3 elicited an early and transient calorigenic response, together with GSH depletion at 1 day after treatment. Recovery of hepatic GSH content and enhancement in total basolateral gamma-glutamyltransferase activity occurred in parallel 2-3 days after T3 treatment, parameters that were normalized in the 4- to 7-day time interval studied. The increase in total basolateral gamma-glutamyltransferase activity by T3 at early times after treatment was due mainly to increments in its transpeptidation mechanism, and was characterized by increments in the apparent maximum velocities without changes in the apparent Michaelis constant (Km) for the substrate gamma-glutamyl-p-nitroanilide. Data presented suggest that the elevation in sinusoidal gamma-glutamyltransferase activity could be related to the recovery of hepatic GSH content after depletion by T3 treatment, by supplying the precursors for intracellular GSH synthesis, an effect that seems to be mediated by enhanced synthesis of the enzyme.
Animals↗
Radiation-induced lung injury: a hypersensitivity pneumonitis?
Radiation pneumonitis occurs 6 to 12 weeks after thoracic irradiation, and is thought to be due to direct radiation-induced lung injury. Four patients who developed pneumonitis after unilateral thoracic irradiation for carcinoma of the breast were studied with bronchoalveolar lavage, gallium scan of the lung, and respiratory function tests. On the irradiated side of the chest, all four patients showed an increase in total cells recovered from the lavage fluid and a marked increase in the percentage of lymphocytes. When results for the unirradiated lung were compared with results for the irradiated lung, there was a comparable increase in total cells and percentage of lymphocytes. Gallium scans showed increases for both irradiated and unirradiated lungs. Prompt improvement was seen after corticosteroid therapy in all patients. The fact that abnormal findings occur equally in irradiated and unirradiated lung is inconsistent with simple direct radiation-induced injury and suggests an immunologically mediated mechanism such as a hypersensitivity pneumonitis.
Aged↗
Age-dependent changes in in vivo ethanol metabolism and in the activity of hepatic enzymes involved in ethanol oxidation and microsomal functions.
The study of the influence of the age of the animals (13 to 53 weeks) on the rate of ethanol metabolism in vivo and the total activity of liver alcohol dehydrogenase and microsomal ethanol oxidizing system showed a progressive decline with age. These effects were observed concomitantly with a diminution in the content of cytochrome P-450 and microsomal functions related to oxidative and free-radical mediated reactions, namely, NADPH oxidase activity, NADPH-dependent oxygen uptake and NADPH-or t-butyl hydroperoxide-induced chemiluminescence. It is concluded that ageing is accompanied by a diminution in the total oxidative activity of the liver tissue, which would explain the depression in basal and ethanol-induced lipid peroxidation found in the oldest group of rats studied.
Aging↗
Microlymphatic bypass in obstructive lymphoedema.
A small series of patients with obstructive or secondary lymphoedema treated by microlymphatic bypass is presented. The procedures in the lower and upper limbs are described. Preoperative assessment by lymphangiography and lymphoscintigraphy are required to assess suitability for the procedure. Postoperatively, patent lymph collectors can be demonstrated by lymphoscintigraphy. Microlymphatic bypass must be carried out before the peripheral lymph collectors have been destroyed or permanently damaged by increasing back pressure and recurrent infection. Factors influencing a successful result are enumerated. Other microsurgical techniques and treatment are reviewed.
Anastomosis, Surgical↗
Alpha 2-agonists block ADH action in toad bladder and this inhibition is not modified by indomethacin.
To identify the type of alpha-adrenoceptors involved in the inhibition of the hydrosmotic effect of antidiuretic hormone (ADH) on the toad bladder, we studied the effect of different alpha-adrenergic agonists and antagonists on ADH-induced water transport. Serosal addition of epinephrine (10(-6) M) and norepinephrine (10(-6) M) in the presence of 10(-4) M propranolol significantly inhibited the hydrosmotic effect of ADH (arginine vasopressin). This inhibitory effect of the catecholamines was completely reversed by 10(-5) M yohimbine but not by prazosin. Clonidine did not block ADH-induced water transport, but guanabenz, another alpha 2-agonist, inhibited water transport in response to ADH. In bladders pretreated with indomethacin to block prostaglandin synthesis, basal water permeability was increased, and even in this condition epinephrine inhibited ADH-induced water transport. These studies indicate that alpha 2-adrenergic receptors are involved in the inhibitory effect of catecholamines on ADH-mediated water permeability in the toad bladder. However, this effect was not mimicked by clonidine, as in the case of rabbit cortical collecting tubule. The inhibitory effect of epinephrine appears to be exerted independently of prostaglandin synthesis.
Adrenergic alpha-Agonists↗
Chemiluminescent and respiratory responses related to thyroid hormone-induced liver oxidative stress.
Chemiluminescent and respiratory responses were studied in the liver of rats treated with 0.1 mg of triiodothyronine (T3)/kg for 1 to 7 days. Hyperthyroidism resulted in significant increments in the spontaneous chemiluminescence of the in situ liver in animals exhibiting a calorigenic response. Microsomal NADPH-dependent oxygen uptake was enhanced by T3 treatment for 2 days, an effect that was completely abolished by the antioxidant cyanidanol. A similar microsomal antioxidant-sensitive respiratory component was observed in this situation after the addition of t-butyl hydroperoxide (t-BHP). However, basal rates of microsomal oxygen uptake and light emission in liver homogenates and microsomes were decreased by t-BHP, probably related to thyroid hormone-induced diminution in the content of cytochrome P-450 (Fernández et al.) In addition, liver superoxide dismutase and catalase activities as well as the total content of glutathione were depressed by T3. These results indicate that the calorigenic response in the hyperthyroid state is accompanied by the development of an hepatic oxidative stress characterized by enhanced spontaneous chemiluminescence, enhanced NADPH-dependent microsomal respiration and a decreased antioxidant cellular activity.
Animals↗
Age-dependent changes in rat liver lipid peroxidation and glutathione content induced by acute ethanol ingestion.
The study of the influence of the age of animals (13 to 53 weeks) on total liver thiobarbituric acid reactive substances (TBAR) content showed an increase which is maximal in rats of 39 weeks of age compared to young animals (13 weeks), followed by a dimunition in the 53 weeks old group. In this situation, the content of hepatic GSH and total GSH equivalents as well as the GSH/GSSG ratio were decreased with ageing, while GSSG levels were enhanced in the oldest group studied. Acute ethanol intoxication resulted in a marked increase in liver TBAR content in young animals, together with a decline in GSH, total GSH equivalents and GSH/GSSG ratio, and an enhancement in GSSG. These changes elicited by ethanol intake were reduced with ageing. It is concluded that ethanol-induced oxidative stress in the liver is diminished during ageing, despite the progressive decrease in the glutathione content of the tissue observed in control animals.
Aging↗
Hepatic and biliary levels of glutathione and lipid peroxides following iron overload in the rat: effect of simultaneous ethanol administration.
The administration of 125 mg of iron/kg (iron-dextran-Imferon) to fed rats was followed by an increase in the non-hem iron content in plasma and liver over a period of 22 hr, reaching a peak value after 6 hr. Plasma and hepatic iron levels were not modified by ethanol ingestion (5 g/kg). Iron and ethanol treatments enhanced liver lipid peroxidation (malondialdehyde (MDA) formation) by 70 and 35%, respectively, at 6 hr. Since the hepatic MDA formation increased by 92% after the joint iron-ethanol treatment, an additive effect in lipid peroxidation was suggested to occur in this condition. Both iron and ethanol treatments increased biliary levels and release of MDA, in the absence of changes in bile flow. These parameters were further enhanced by the joint iron-ethanol exposure, in that hepatic MDA levels and biliary MDA release were significantly correlated (r = 0.86; p less than 0.05). Plasma MDA levels also increased after iron, ethanol, and iron-ethanol treatments, but they did not reflect the changes in MDA levels in liver. Iron exposure resulted in 26 to 33% decreases in hepatic GSH content at the 6-hr treatment, associated with the peak effect on lipid peroxidation. In this situation, glutathione disulfide (GSSG) levels in liver were not changed, but its biliary release increased by 76%. Hepatic reduced glutathione (GSH) levels were recovered by 18 hr and increased by 23% after 22 hr of iron ingestion. Acute ethanol intake diminished liver GSH content by 30% and enhanced that of GSSG by 73%, thus eliciting a net decrease of 20% in total GSH equivalents (GSH + 2GSSG). Biliary release of total GSH was reduced in this condition. The combined administration of iron and ethanol further influenced the decrease in hepatic GSH and the increase in GSSG levels elicited by the separate treatments, but no alterations in the biliary content and release of total GSH were observed in this situation. These data indicate that iron exposure accentuates the changes in lipid peroxidation and in the glutathione status of the liver cell induced by acute ethanol intoxication.
Animals↗
On the organization of the retino-tecto-thalamo-telencephalic pathways in a Chilean rodent; the Octodon degus.
After performing eye enucleations or restricted lesions in the superior colliculus or the pulvinar nucleus, the degeneration patterns provoked by these procedures were analyzed by means of the Nissl and the Fink-Heimer methods in 30 specimens of Octodon degus. The pulvinar or lateroposterior nucleus can be subdivided into 3 regions (rostrolateral, rostromedial and caudal), on the basis of cytoarchitecture, tectofugal afferent and efferent connections to the cerebral cortex. In addition, this nucleus projects to the ipsilateral tail of the caudate nucleus and the nucleus lateralis dorsalis of the thalamus, which has been shown to project over the cingulate cortex in this animal 43. These findings support the possibility that the pulvinar may have an important role visuo-limbic interactions, by way of its connections with the nucleus lateralis dorsalis. Another highly interesting finding from the phylogenetic point of view is that the organization of the pulvinar in the Octodon degus is remarkably similar to that of the inferior pulvinar described for the owl monkey 46. Furthermore, the fact that the organization of the retino-tecto-thalamo-cortical pathways described in the grey squirrel 54 and in the tree shrew 33 is strikingly similar to those found in the Octodon degus, a semi-fossorial South American rodent that has evolved in isolation from the two former species for about 40 million years, makes it impossible to explain the organization of this pathway by advocating convergent evolution, due to environmental pressures determined by arboreal life, as postulated by kaas et al 39.
Animals↗
Effect of acute ethanol intoxication on the content of reduced glutathione of the liver in relation to its lipoperoxidative capacity in the rat.
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Alcohol Drinking↗