Ensayo preclinico de la vacuna candid #1 producida en Argentina contra la fiebre hemorragica Argentina / Preclinical assay of candid #1 vaccine against argentine hemorrhagic fever made in Argentina

Se comparó en cobayos la seguridad, inmunogenicidad y eficácia protectora de um lote de vacuna Candid #1 (C#1) fabricada en Estados Unidos de América (EE.UU.) y distintos lotes de la misma vacuna fabricados en Argentina (Arg.). El lote TSI 5-1-92 (EE.UU) y los lotes Exp N3, 7A y 8A (Arg) fueron inoculados (0.5ml, IM) en cobayos de 250400g. Para cada ensayo diez animales recibieron solución fisiológica y sirvieron como control. Todos fueron desafiados con la cepa patógena P23790 de vírus Junin. Se registro: a) temperatura rectal, b) peso corporal , c) presencia de anticuerpos neutralizantes (AcNT) pré y post-vacunación, d) respuesta al desafio . Todos los animales vacunados desarrollaron AcNT anti vírus Junin (rango= 4081920 y sobrevivieron al desafio. En cada grupo control 810 animales murieron (dia 23.3+_ 5.4 post- desaportada y los diferentes lotes de C#1 producidos en Argentina.

Condition factor in nine species of fish of the Characidae family in the upper Paraná River floodplain, Brazil

The condition factor for nine species of tropical freshwater fish of the Characidae family in the upper Paraná River floodplain is described. Fish were caught over a period of 12 months (February 1993 to March 1994). Knowledge of the nine species is important for adequate management and maintenance of the biological equilibrium of the ecosystem

Prueba de neutralización del virus de la coriomeningitis linfocítica para diferenciar infecciones con dos arenavirus en Argentina / [Neutralization test for lymphocytic choriomeningitis virus for distinguishing between two arenavirus infections in Argentina]

The active coexistence of two pathogenic arenaviruses, Junin (JUNV) and lymphocytic choriomeningitis (LCMV), in the same region of Argentina, has been known since the early 70’s, and records of clinical and subclinical human infections by one and/or the other agent have been continuously produced for the last 25 years. Anti-LCMV antibody is currently searched only by indirect immunofluorescence, a test that shows cross reactions among a number of arenaviruses yielding, in the cases of LCMV and JUNV consecutive infections, a concomitant seroconversion for both viruses, as an inconclusive diagnostic result. In contrast, neutralization (NT) tests reveal arenavirus antibodies directed to unique epitopes on these virus envelopes, thus allowing to disclose the sequence in the cases of consecutive infections. In this paper, the characteristics of neutralization (NT) test for LCMV in cell cultures are described, as well as its performance in the field diagnosis of LCMV human infections. The native LCMV strain Cba An 13065 was inoculated on L-929 cell (ATCC CCL 1), and procedures were followed to perform a constant virus-variable serum NT test. Final points of sera titrations were expressed as the maximal serum dilution that yielded 75

of pfu inhibition. This NT test was assayed on paired serum samples of 36 patients with confirmed Argentine hemorrhagic fever (AHF) (a disease caused by JUNV), who had had a known previous contact with LCMV through IFI. The use of this one test led to confusing diagnosis of the disease due to concomitant seroconversion for JUNV and LCMV. By using NT test, it was shown that: some of them were possibly not infected by LCMV, and that 30/36 cases (83.3

) had a pre-existing level of LCMV antibody, with titers in the range of 5 to 640, remaining unchanged 60 days after the clinical AHF. This shows that NT antibodies to LCMV are not influenced by the outcome of the immune response to JUNV, thus confirming the efficiency of NT test as identificator among arenaviruses. To assess the performance of this NT test in individuals having only IFI antibodies to LCMV, 126 serum samples obtained through serological surveillance in a rural area of Argentina, were used. It was found that NT had improved coincidence with IFI as IFI titers increased. Interpretations were based on the pan-arenavirus antibody response obtained by using IFI as the only test. Results presented herein prove that the described NT test is a valuable tool for the detection of LCMV infections, particularly when a previous infection with LCMV has to be demonstrated during the acute phase of Argentine hemorrhagic fever.

Molecular characterization of attenuated Junin virus strains.

The Junin virus strain Candid #1 was developed as a live attenuated vaccine for Argentine haemorrhagic fever. In this paper we report the nucleotide sequences of S RNA of Candid #1 and its more virulent ancestors XJ#44 and XJ (prototype). Their relationship to Junin virus wild-type MC2 strain and other closely and distantly related arenaviruses was also examined. Comparisons of the nucleotide and amino acid sequences of N and GPC genes from Candid #1 and its progenitor strains revealed some changes that are unique to the vaccine strain. These changes could be provisionally associated with the attenuated phenotype.

Novel polyphosphazene/poly(lactide-co-glycolide) blends: miscibility and degradation studies.

A novel biodegradable polymer blend was developed for potential biomedical applications. A 50:50 poly(lactide-co-glycolide) (PLAGA) was blended in a 50:50 ratio with the followiing polyphosphazenes (PPHOS): poly[(25% ethyl glycinato)(75% p-methylphenoxy)phosphazene[, poly[(50% ethyl glycinato)(50% p-methylphenoxy)phosphazene], and poly[(75% ethyl glycinato)(25% p-methylphenoxy)phosphazene] to obtain Blends A, B, and C, respectively, using a mutual solvent technique. The miscibility of these blends was determined by measuring their glass transition temperature (Tg) using differential scanning calorimetry. After fabrication using a casting technique, the degradation of the matrices was examined. Differential scanning calorimetry showed one glass transition temperature for each blend which was between the Tg's of their respective parent polymers indicating miscibility of the blends. Surface analysis by scanning electron microscopy showed the matrices to have smooth uniform surfaces. Degradation studies showed near-zero order degradation kinetics for the blends with Blends A and B losing 10% of their mass after two weeks and Blend C degrading more rapidly (30% mass loss during the same period). These findings suggest that these novel biodegradable PLAGA/PPHOS blends may be useful for biomedical purposes.

Synthesis and characterization of pH-sensitive poly(organophosphazene) hydrogels.

A new class of pH-sensitive hydrogels has been designed and synthesized. These are novel polyphosphazenes that bear various ratios of sodium oxybenzoate and methoxyethoxyethoxy side groups. These water-soluble macromolecules were cross-linked by 60Co gamma irradiation and the products were allowed to absorb water to form hydrogels. The hydrogels had higher equilibrium degrees of swelling in basic than in acidic buffer solutions, and polymers with a higher loading of the ionic side group showed higher swellability than those with a lower loading of this side group. The effects of ionic strength, cation charge and radiation dose on the degree of swelling were also studied. A study of the diffusion of the dye Biebrich Scarlet from the hydrogels showed complete release of the dye in 4-12 h in pH 7.4 buffer solution but significantly lower release at pH 2 even after 48 h. The release rate also varied as the side-group ratios were changed. The prehydrogel polymers were synthesized via the macromolecular substitution reactions of poly(dichlorophosphazene) with sodium methoxyethoxyethoxide and the sodium salt of propyl 4-hydroxybenzoate, followed by ester hydrolysis to yield the sodium carboxylate. The hydrogels are of interest for possible use as pH-sensitive membranes and for a number of potential biomedical applications.

Transcript analysis of D category phenotypes predicts hybrid Rh D-CE-D proteins associated with alteration of D epitopes.

The RH blood group locus from RhD-positive donors is composed of two closely related genes, RHCE and RHD, encoding the Cc/Ee and D antigens, respectively. The major Rh antigen, D, is serologically defined as a mosaic of at least nine determinants (epD1 to epD9), and the lack of expression of some of these D epitopes at the surface of variant red blood cells defines the D category phenotypes. In this report, we have analyzed the Rh transcripts from reticulocytes of different D category phenotypes (DIVa, DIVb, DVa, and DFR). Although Southern blot analysis did not sow obvious deletions within the RHD gene, sequence analysis of the RhD transcripts indicated that, in all cases studied, the lack of D epitopes is associated with substitutions, in the deduced polypeptides, of amino acids specific of the RhD protein by those encoded at the equivalent position by the RHCE gene. These results strongly suggested that the D category phenotypes resulted from segmental DNA replacement between RHD-specific fragments and their equivalents in the RHCE gene. The regions involved in the DIVa, DIVb, DVa, and DFR phenotypes were shown to encompass all or part of the exons 3 and 7, exons 7 to 9, exon 5, and exon 4, respectively. All protein variants encoded by these rearranged RH genes represent new CE-D-CE hybrid molecules that retain only some of the nine D epitopes. Because segmental DNA replacements have been previously identified in other Rh variant genomes, we postulate that such genomic rearrangements between different regions of the RHCE and RHD genes should be one of the most frequent events involved in the extreme polymorphism of the RH blood group system.

Molecular analysis of the structure and expression of the RH locus in individuals with D--, Dc-, and DCw- gene complexes.

Rh blood group antigens of the D, C/c, and E/e series are carried by at least three red cell membrane polypeptides encoded by two highly related genes, RHD and RHCE. Homozygous individuals carrying the D--, Dc-, and DCw- gene complexes are characterized by a total or partial lack of expression of the RHCE-encoded antigens. Analysis of the molecular genetic basis of these rare conditions indicates that complete or partial expression defect of Cc/Ee antigens result from different alterations at the RH locus, but not from gross deletions. No rearrangement or mutation of the RHCE gene could be detected in donors homozygous for the D-- complex, suggesting that the lack of the Cc and Ee antigens might result from a reduced transcriptional activity of the RHCE gene. The Dc- and DCw- gene complexes, however, exhibited an important rearrangement of the RHCE gene. Instead of the normal RHCE gene, both variants carried a hybrid RHCE-D-CE gene in which exons 4 to 9 (Dc- complex) and 2 (or 3) to 9 (DCw- complex) of the RHCE gene, respectively, have been substituted by the equivalent region of the RHD gene. These gene conversion events provide an explanation for the well-described abnormal antigen profiles associated with the Dc- and DCw- complexes, like the increased expression of RhD, the reduced expression of RhC/c or RhCw, and the absence of RhE/e.

[Cold lymphocytotoxins in various pathological situations]. / Lymphocytotoxines froides dans diverses situations pathologiques

Cold lymphocytotoxins have been described extensively in many situations. In the present work, this kind of antibody has been found less frequently than previously in some diseases like infectious mononucleosis, rheumatoïd arthritis, or kidney transplanted patients. These discrepancies may be due to technical considerations. In contrast, cold lymphocytotoxins, in the present work, have been frequently detected in auto-immune hemolytic anemias with cold agglutinins, and in patients having immuno-deficiencies.