Antecedentes de la formación de psicólogos en Mar del Plata / Pre-College Period of the Psychological Training in Mar del Plata

El Grupo de Investigación Historia , Enseñanza y Profesionalización de la Psicología en los países del Cono Sur de la UNMP desarrolla actualmente el proyecto Antecedentes de los estudios psicológicos en Mar del Plata y prospectiva en el marco de la psicología como profesión regulada, representando este trabajo un avance del mismo. En una primera etapa se atendió, especialmente, a indagar el período preuniversitario en el que se impartió en Mar del Plata, Argentina, formación psicológica en estudios sistemáticos. En tal sentido, se reconocen como antecedentes al Instituto de Pedagogía [ISP], uno de los cinco creados en 1949 en la Provincia de Buenos Aires bajo el gobierno peronista, y al Instituto Superior de Ciencias de la Educación [ISCE] que funcionó desde 1960 y hasta la creación del grado académico en la UPMP, en 1966. Estos Institutos formaban recursos humanos destinados al ámbito educativo, siendo el ISCE la institución otorgante de las primeras titulaciones específicas en Psicología. El presente trabajo se centra en esta última institución, e intenta indagar las razones que propiciaron el viraje del énfasis educativo al clínico en la formación de sus alumnos y posterior inserción laboral de sus egresados, incluyendo el análisis de testimonios orales de sus protagonistas.

Limited transgene immune response and long-term expression of human alpha-L-iduronidase in young adult mice with mucopolysaccharidosis type I by liver-directed gene therapy.

Mucopolysaccharidosis type I (MPS I) due to deficient alpha-L-iduronidase (IDUA) activity results in the accumulation of glycosaminoglycans (GAGs) in many of the cells of affected patients. Stable gene replacement by in vivo administration of lentiviral vectors (LVs) has therapeutic potential for metabolic disorders and other systemic diseases. We have previously shown in a murine model the therapeutic potential of lentiviral IDUA vector-mediated gene therapy, in which human IDUA cDNA was driven by the cytomegalovirus promoter. However, the major limitation of this approach was the induction of an immune response against the therapeutic protein, which limited the efficacy and long-term duration of treatment. In this study, we evaluate the potential of liver-directed gene therapy, that is, programming of murine hepatocytes to secrete the enzyme with mannose 6-phosphate (M6P), which can be taken up by distant cells. Eight- to 10-week-old mice were injected via the tail vein with a lentiviral vector expressing human IDUA cDNA driven by the albumin gene promoter selectively expressed in hepatocytes. One month after treatment, IDUA activity was present in the liver and spleen of treated mice; an expression level of 1% normal IDUA activity was sufficient to reduce the GAG level in liver, spleen, kidney, heart, and lung. Interestingly, 6 months after a single injection of this vector, IDUA activity was detectable in several murine tissues; the level of enzyme activity was low but sufficient to maintain the decrease in GAG levels in liver, spleen, kidney, heart, and lung. Also, the level of enzyme-specific antibodies reached at 6 months postinjection was nearly null, and real-time polymerase chain reaction analysis showed high levels of vector DNA content in liver and spleen. Thus, these results show that the use of LV with the albumin gene promoter selectively expressed in hepatocytes limited the immune response to the transgene and allowed stable and prolonged expression of the IDUA enzyme and a partial correction of the pathology.

Analysis of Sanfilippo A gene mutations in a large pedigree.

Mucopolysaccharidosis type IIIA, also known as Sanfilippo A disease, results from mutations in the sulfamidase gene. To date, a total of 62 mutations have been described underlying this lysosomal disorder. Expression studies on missense mutations have shown that each alteration was disease-causing and helped to clarify the genotype-phenotype correlation. In this report we describe a large pedigree where the mutations have been identified in two second cousins: one with severe disease (E369K/R433Q) and the other with a mild form of the illness (E369K/P128L). This study places R433Q as a severe mutation underlying Sanfilippo A disease.

Immobilised echistatin promotes platelet adhesion and protein tyrosine phosphorylation.

Echistatin, a 5000-Da disintegrin, is a strong competitive inhibitor of platelet alpha(IIb)beta(3) binding to fibrinogen. In addition to its antiplatelet activity, echistatin also exhibits activating properties by inducing a switch of alpha(IIb)beta(3) conformation towards an active state. However, soluble echistatin, which is a monomeric ligand, provides only receptor affinity modulation, but it is unable to activate integrin-dependent intracellular signals. Since proteins may exhibit a multivalent functionality as a result of their absorption to a substrate, in this study we evaluated whether immobilised echistatin is able to stimulate platelet adhesion and signalling. The immobilisation process led to an increase of echistatin affinity for integrin(s) expressed on resting platelets. Unlike the soluble form, immobilised echistatin bound at comparable extent either unstimulated or ADP-activated platelets. Furthermore, echistatin presented in this manner was effective in stimulating integrin-dependent protein tyrosine phosphorylation. Platelets adhering to immobilised echistatin showed a pattern of total tyrosine phosphorylated proteins resembling that of fibrinogen-attached platelets. In particular, solid-phase echistatin induced a strong phosphorylation of tyrosine kinases pp72(syk) and pp125(FAK). Inhibitors of platelet signalling, such as apyrase, prostaglandin E(1), cytochalasin D and bisindolylmaleimide, while not affecting platelet adhesion to immobilised echistatin, abolished pp125(FAK) phosphorylation. This suggests that signals activating protein kinase C function, dense granule secretion and cytoskeleton assembly might be involved in echistatin-induced pp125(FAK) phosphorylation.

H(2)O(2) activity on platelet adhesion to fibrinogen and protein tyrosine phosphorylation.

Platelets represent a target of reactive oxygen species produced under oxidative stress conditions. Controversial data on the effect of these species on platelet functions have been reported so far. In this study we evaluated the effect of a wide range of H(2)O(2) concentrations on platelet adhesion to immobilized fibrinogen and on pp72(syk) and pp125(FAK) tyrosine phosphorylation. Our results demonstrate that: (1) H(2)O(2) does not affect the adhesion of unstimulated or apyrase-treated platelets to immobilized fibrinogen; (2) H(2)O(2) does not affect pp72(syk) phosphorylation induced by platelet adhesion to fibrinogen-coated dishes; (3) H(2)O(2) reduces, in a dose-dependent fashion, pp125(FAK) phosphorylation of fibrinogen-adherent platelets; (4) concentrations of H(2)O(2) near to physiological values (10-12 microM) are able to strengthen the subthreshold activation of pp125(FAK) induced by epinephrine in apyrase-treated platelets; (5) H(2)O(2) doses higher than 0.1 mM inhibit ADP-induced platelet aggregation and dense granule secretion. The ability of H(2)O(2) to modulate pp125(FAK) phosphorylation suggests a role of this molecule in physiological hemostasis as well as in thrombus generation.

Molecular defects in the alpha-N-acetylglucosaminidase gene in Italian Sanfilippo type B patients.

Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is a rare autosomal recessive disorder characterized by the inability to degrade heparan sulfate because of a deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). We performed mutation screening in a group of 20 patients, identyifing 28 mutations, 14 of which were novel (L35F, 204delC, 221insGCGCG, G82D, W156C, 507delC, IVS3+1G-->A, E336X, V501G, R520W, S534Y, W649C, 1953insGCCA, 2185delAGA). Four of these mutations were found in homozygosity and only one was seen in two different patients, showing the remarkable molecular heterogeneity of the disease. Mutation IVS3+1G-->A produces aberrant RNA splicing: it represents a base substitution from G to A of the invariant GT dinucleotides at the splicing donor site of intron 3 resulting in the skipping of exon 3 and both exons 2 and 3. Transient transfection of COS cells, by DNA mutagenized with NAGLU mutations, produced enzymatic molecules without activity, demonstrating the deleterious nature of the defects. Metabolic labeling of transfected mutants suggested a normal synthesis of the involved polypeptide for missense alterations, whereas increased protein or mRNA instability was shown for nonsense and most of the frameshift mutations.

Effects of surfactants on the stabilization of the bovine lactoperoxidase activity.

Bovine lactoperoxidase (LPO) is taken as a model protein of mammalian peroxidases to investigate the activity and the stability of the enzyme in the presence of different surfactants. The cationic benzalkonium chloride (Bz) has proved efficient in preserving the enzymatic activity for over 10 days, while the native enzyme completely lost its activity within 3-4 days. The presence of Bz allows the enzyme to preserve its secondary structure for a long time, as shown in CD spectra, and creates a more hydrophobic environment for the enzyme, as indicated in fluorescence studies. Moreover, this surfactant at a concentration of 0.01% (0.3 mM) increases the lactoperoxidase activity in the first 2 h of incubation at 37 degrees C. Both hydrophobic and electrostatic interactions of the cationic surfactant seem to be responsible for the enzyme activation and stabilization, and this is a promising result in view of industrial applications of enzymes.

Metal-ion catalyzed oxidation affects fibrinogen activity on platelet aggregation and adhesion.

Exposure of fibrinogen to the Fe3+/ascorbate oxidative system resulted in structural modifications and altered functionality of the glycoprotein. The overnight treatment of fibrinogen by oxidants caused a 20-fold increase of carbonyl content with respect to the native protein. Formation of dityrosines as well as loss of tryptophan following fibrinogen oxidation were observed. The occurrence of conformational changes of the fibrinogen molecule as a consequence of the oxidative treatment was also established. Oxidized fibrinogen showed a distinct capability from the native molecule to mediate platelet aggregation and adhesion. The percentage of ADP-induced platelet aggregation decreased as a function of fibrinogen oxidative damage. Further, both unstimulated platelets and ADP-activated platelets showed a reduced ability to adhere to oxidized fibrinogen than to the native protein. These results suggest that oxidative treatment alters fibrinogen domains involved in the recognition and the binding of this molecule by the platelet receptor GP IIb/IIIa.

Saporin production from in vitro cultures of the soapwort Saponaria officinalis L.

We report here the successful establishment of callus, cell and root cultures from explants of in-vitro-grown plantlets of the soapwort Saponaria officinalis L. The production of saporin in the different tissue systems was evaluated by determining the capability of crude extracts to inactivate protein synthesis and by Western blotting analysis. Protein synthesis inhibition varied in callus and derived cell suspensions and in cultured roots, the latter, in particular, showing the lowest specific activity. The ribosome-inactivating principle from root cultures was purified to homogeneity by cation exchange chromatography.

Echistatin inhibits pp72syk and pp125FAK phosphorylation in fibrinogen-adherent platelets.

The adhesion of ADP-stimulated platelets to immobilized fibrinogen induces the tyrosine phosphorylation of multiple proteins which include pp72syk and pp125FAK. The phosphorylation of these two proteins increases as function of time of platelet adhesion to fibrinogen; however, pp72syk results strongly phosphorylated already after 15 min, whereas pp125FAK reaches high levels of phosphorylation after 1 h of platelet adhesion. Phosphorylation of both proteins is only slightly detectable when platelets are held in suspension or when platelets are allowed to adhere to bovine serum albumin, a non-specific substrate. Echistatin, an Arg-Gly-Asp (RGD)-containing snake-venom protein, affects protein tyrosine phosphorylation promoted by platelet adhesion to fibrinogen, by causing an approximately 44% and 39% decrease of pp72syk and pp125FAK phosphorylation, respectively. The interaction of echistatin with fibrinogen receptor glycoprotein IIb-IIIa on platelet surface might be responsible for the block of integrin-mediated signaling cascade, including pp72syk and pp125FAK inactivation.

[Current status and perspectives of bioethics in Argentina]. / Estado actual y perspectivas de la bioética en la Argentina.

The study of bioethics in Argentina owes much to the efforts of José Alberto Mainetti, who in 1972 founded the Institute of Medical Humanities, devoted to researching, teaching, and publicizing the discipline. Because of growing interest in the field of bioethics, a Bioethics Center was created in the Institute in 1987 and it has stimulated the organization of several groups in various provinces in the country. One of the most important of them, located at the National University of Mar del Plata, is responsible for designing a graduate-level specialization in bioethics and for organizing the First Mar del Plata Bioethics Workshop. This interdisciplinary group examines the bioethical implications of concrete scientific and professional activities as well as legislative measures and decisions affecting the public.

Present status and prospects of bioethics in Argentina.

Most developments supporting the study of bioethics in Argentina are of relatively recent vintage. This article is dedicated to describing those developments--including creation of Argentina's Institute of Medical Humanities, formation of a bioethics working group at the National University of Mar del Plata, initiation of a two-year graduate bioethics course at the same university, and the holding of an international symposium and workshop on bioethics at Mar del Plata in 1988. Particular attention is devoted to the graduate course, the detailed design of which is outlined in Annex 1.

Production and reproduction. Women and breastfeeding: some Nigerian examples.

Breastfeeding is of crucial importance in the developing world, not only to the health of the mother and her infant, but to the community in general. The importance of breastfeeding of infants lies not only in its nutritional and hygienic properties, but also because of its immunological effects and its influence in the control of fertility. The literature review is combined with a discussion of aspects of research undertaken by the authors under the headings of length of breastfeeding, bottlefeeding and breastfeeding and fertility. Most of the examples come from Nigeria, but the problems discussed are common to much of the developing world. Under a discussion of social and policy implications, the need for governments in the developing countries to adopt the recent World Health Organisation's code of practice to curtail the sale of artificial infant milks, is stressed. It is suggested that health agencies in countries like Nigeria should go to the rural areas now, to instruct the women and men in the dangers of bottle feeding and the benefits of breastfeeding, before the 'modernisation' of infant feeding, so evident in the towns, spreads to the rural areas.