Cáncer de próstata, el problema del diagnóstico: ¿es la resonancia multiparamétrica de próstata la solución? / Prostate cancer, the problem of diagnosis: is multiparametric prostate magnetic resonance imaging the solution?

Junto con un aumento sostenido en la incidencia de cáncer de próstata en los países desarrollados ha habido un cambio en el enfrentamiento diagnóstico en estos pacientes. El diagnóstico tradicional basado en la medición del antígeno prostático específico y la biopsia randomizada ha mostrado tener muchas falencias ya que sobre-diagnostica cánceres no significativos y sub-diagnostica cánceres clínicamente significativos. La resonancia magnética de próstata multiparamétrica ha demostrado ser útil ya que disminuye este tipo de falencias. En este artículo se revisará la historia de la resonancia magnética de próstata y del PI-RADS, con el objeto de revisar el rendimiento de estos métodos y sus indicaciones actuales.

Along with a sustained increase in the incidence of prostate cancer in developed countries, there has been a change in the diagnostic approach in these patients. The traditional diagnosis based on the measurement of the specific prostate antigen and randomized biopsy has shown to have many shortcomings as it leads to overdiagnosis of non-significant cancers and underdiagnosis of clinically significant cancers. The multiparametric prostate magnetic resonance imaging has proven to be useful since it diminishes these shortcomings. In this article we will review part of the history of prostate magnetic resonance imaging and PI-RADS, in order to review the performance of these methods and their current indications.

De novo assembly of Vriesea carinata leaf transcriptome to identify candidate cysteine-proteases.

Vriesea carinata is an endemic bromeliad from the Brazilian Atlantic Forest. It has trichome and tank system in their leaves which allows to absorb water and nutrients. It belongs to Bromeliaceae family, which includes several species highly enriched of cysteine-proteases (CysPs). These proteolytic enzymes regulate processes as senescence, cell differentiation, pathogen-linked programmed cell death and mobilization of proteins. Although, their biological importance, there are not genomic resources in V. carinata that can help to identify and understand their molecular mechanisms involved in different biological processes. Thus high-throughput transcriptome sequencing of V. carinata is necessary to generate sequences for the purpose of gene discovery and functional genomic studies. In the present study, we sequenced and assembled the V. carinata transcriptome to the identification of CysPs. A total of 43,232 contigs were assembled for the leaf tissue. BLAST analysis indicated that 23,803 contigs exhibited similarity to non-redundant Viridiplantae proteins. 28.24% of the contigs were classified into the COG database, and gene ontology categorized them into 61 functional groups. A metabolic pathway analysis with KEGG revealed 9679 contigs assigned to 31 metabolic pathways. Among 16 full-length CysPs identified, 11 were evaluated in respect to their expression patterns in the leaf apex, base and inflorescence tissues. The results showed differential expression levels of legumain, metacaspase, pyroglutamyl and papain-like CysPs depending of the leaf region. These results provide a global overview of V. carinata gene functions and expression activities of CysPs in those tissues.

Estrongiloidiasis gastrointestinal en paciente inmunocompetente: a propósito de un caso / Gastrointestinal strongyloidosis in an immunocompetent patient: a case report

Intestinal parasitic infections cause a not insignificant number of chronic diarrhea in children, however, with the sociodemographic change that our country has experienced, the number of cases and new parasites (immigration from tropical endemic areas) could increase. We report the case of an immunocompetent patient who presents with chronic diarrhea associated with Strongyloides stercoralis infection. The patient migrated two years ago from an endemic area for this helminth. The diagnosis is challenging, and the chances of a successful outcome depend on the administration of the antiparasitic.

Las infecciones parasitarias intestinales provocan un número no despreciable de causas de diarrea crónica en niños, sin embargo, con el cambio sociodemográfico que ha vivido nuestro país se podría incrementar el número de casos y de nuevos parásitos (inmigración de áreas endémicas tropicales). Reportamos el caso de un paciente inmunocompetente, que presenta cuadro de diarrea crónica asociada a infección por Strongyloides stercoralis. El paciente habría migrado hace dos años desde zona endémica para este helminto. El diagnóstico es desafiante y las posibilidades de un resultado exitoso dependen de la administración del antiparasitario.

Charmonium: comparison between potential models / Charmonio: comparación entre modelos potenciales

Abstract Heavy quark c c ¯ has been studied in the non relativistic framework using a quark-quark potential as a sum of power of the corresponding distance. The form of potential is based on phenomenological facts. The problem was solved numerically using a program written on C++. Mass spectra and the expectation value of the radius have been estimated for different quantum-mechanical states for c c ¯ system. The results have been compared with other similar and recent works. The mass spectra obtained is in acceptable agreement with the experimental data for c c ¯.

Resumen El sistema de quarks pesados c c ¯ ha sido estudiado en el marco no relativista usando un potencial quark-quark de la forma de la suma de potencias de la distancia entre las partículas. El problema se resolvió numéricamente usando un programa escrito en C++. Se estimaron el espectro de masa y el valor esperado del radio para diferentes estados de excitación. Los resultados fueron comparados con otros trabajos similares recientes. El espectro de masa obtenido concuerda de manera aceptable con los datos experimentales para el sistema c c ¯.

Study of light-particle multiplicities in p + non-fissionable nuclei events in the 0.5 - 2 GeV energy range / Estudio de la multiplicidad de partículas ligeras en proto-reacciones con núcleos no fisionables en el rango energético 0.5 - 2 GeV

Abstract In recent years, the investigation of spallation reactions have caught the attention of scientific community due to their application in the transmutation of nuclear waste by using the Accelerator Driven System (ADS) reactors. Due to the experimental difficulties that nuclear reactions researches face; the study of spallation reaction by using simulation codes is more suitable for generating more complete database for different energy ranges. This work aims to study spallation reactions induced by protons at intermediate energies 0.5 - 2 GeV on non-fissionable nuclei by using the Monte Carlo code: CRISP (Collaboration Rio-Ilhéus-São Paulo). The target nuclei studied were: 184 W, 197 Au and 208 Pb, focusing on the last one. Multiplicity of light particles obtained with CRISP was compared with the available experimental data and other Monte Carlo codes involved in the study of spallation reactions, resulting on a quite satisfactory agreement.

Resumen En años recientes la investigación de las reacciones nucleares de "espalación" han causado atención en la comunidad científica debido a su aplicación en la transmutación de los residuos nucleares usando reactores ADS (AcceleratorDriven System). Debido a las dificultades experimentales en el estudio de las reacciones nucleares, su estudio vía simulación es adecuado para generar una base de datos más completa en un amplio rango de energía. Este trabajo tiene como objetivo principal el estudio de reacciones nucleares inducidas por protones a energías intermedias, 0.5 - 2 GeV, en núcleos no fisionables, utilizando el código de Monte Carlo: CRISP (Collaboration Rio-Ilhéus-São Paulo). Los núcleos estudiados fueron: 184W, 197Au y 208Pb, con un enfoque en el último. La multiplicidad de partículas ligeras obtenida con el CRISPfue comparada con los datos experimentales disponibles y con otros códigos de Monte Carlo y se obtuvieron resultados satisfactorios.

Understanding the antimicrobial properties/activity of an 11-residue Lys homopeptide by alanine and proline scan.

Previous work demonstrated that lysine homopeptides adopt a polyproline II (PPII) structure. Lysine homopeptides with odd number of residues, especially with 11 residues (K11), were capable of inhibiting the growth of a broader spectrum of bacteria than those with an even number. Confocal studies also determined that K11 was able to localize exclusively in the bacterial membrane, leading to cell death. In this work, the mechanism of action of this peptide was further analyzed focused on examining the structural changes in bacterial membrane induced by K11, and in K11 itself when interacting with bacterial membrane lipids. Moreover, alanine and proline scans were performed for K11 to identify relevant positions in structure conformation and antibacterial activity. To do so, circular dichroism spectroscopy (CD) was conducted in saline phosphate buffer (PBS) and in lipidic vesicles, using large unilamellar vesicles (LUV), composed of 2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) or bacterial membrane lipid. Antimicrobial activity of K11 and their analogs was evaluated in Gram-positive and Gram-negative bacterial strains. The scanning electron microscopy (SEM) micrographs of Staphylococcus aureus ATCC 25923 exposed to the Lys homopeptide at MIC concentration showed blisters and bubbles formed on the bacterial surface, suggesting that K11 exerts its action by destabilizing the bacterial membrane. CD analysis revealed a remarkably enhanced PPII structure of K11 when replacing some of its central residues by proline in PBS. However, when such peptide analogs were confronted with either DMPG-LUV or membrane lipid extract-LUV, the tendency to form PPII structure was severely weakened. On the contrary, K11 peptide showed a remarkably enhanced PPII structure in the presence of DMPG-LUV. Antibacterial tests revealed that K11 was able to inhibit all tested bacteria with an MIC value of 5 µM, while proline and alanine analogs have a reduced activity on Listeria monocytogenes. Besides, the activity against Vibrio parahaemolyticus was affected in most of the alanine-substituted analogs. However, lysine substitutions by alanine or proline at position 7 did not alter the activity against all tested bacterial strains, suggesting that this position can be screened to find a substitute amino acid yielding a peptide with increased antibacterial activity. These results also indicate that the PPII secondary structure of K11 is stabilized by the interaction of the peptide with negatively charged phospholipids in the bacterial membrane, though not being the sole determinant for its antimicrobial activity.

Antimicrobial activity of a new synthetic peptide loaded in polylactic acid or poly(lactic-co-glycolic) acid nanoparticles against Pseudomonas aeruginosa, Escherichia coli O157:H7 and methicillin resistant Staphylococcus aureus (MRSA).

Nanocarrier systems are currently being developed for peptide, protein and gene delivery to protect them in the blood circulation and in the gastrointestinal tract. Polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with a new antimicrobial GIBIM-P5S9K peptide were obtained by the double emulsion solvent extraction/evaporation method. PLA- and PLGA-NPs were spherical with sizes between 300 and 400 nm for PLA and 200 and 300 nm for PLGA and <0.3 polydispersity index as determined by dynamic light scattering and scanning electron microscopy), having the zeta potential of >20 mV. The peptide-loading efficiency of PLA-NP and PLGA-NPs was 75% and 55%, respectively. PLA- and PLGA-NPs released around 50% of this peptide over 8 h. In 10% human sera the size of peptide loaded PLA- and PLGA-NPs increased between 25.2% and 39.3%, the PDI changed from 3.2 to 5.1 and the surface charge from -7.15 to 14.6 mV. Both peptide loaded PLA- and PLGA-NPs at 0.5 µM peptide concentration inhibited the growth of Escherichia coli O157:H7 (E. coli O157:H7), methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. aeruginosa (P. aeruginosa). In contrast, free peptide inhibited at 10 µM but did not inhibit at 0.5 and 1 µM. These PLA- and PLGA-NPs presented <10% hemolysis indicating that they are hemocompatible and promising for delivery and protection system of GIBIM-P5S9K peptide.

Variations of B cell subpopulations in peripheral blood of healthy Mexican population according to age: Relevance for diagnosis of primary immunodeficiencies.

BACKGROUND: Peripheral blood B cells include lymphocytes at various stages of differentiation, each with a specific function in the immune response. All these stages show variations in percentage and absolute number throughout human life. The numbers and proportions of B subpopulation are influenced by factors such as gender, age, ethnicity, and lifestyle. This study establishes reference values according to age of peripheral blood B cell subtypes in healthy Mexican population. METHODS: Peripheral blood from healthy new-borns and adults were analysed for total B cell subpopulations, using surface markers such as CD19, IgM, IgD, CD21, CD24, CD27, and CD38, to identify naïve, memory with and without isotype switch, double-negative, transitional, and plasmablast cells. RESULTS: We observed a significant variation in terms of frequency and absolute counts between all groups analysed. Values from each B cell subpopulation show variations according to age. CONCLUSIONS: In order to attempt to elucidate reference values for B cell subpopulation, the present study evaluated a population sample of healthy blood donors from this region. Values reported here can also be used as a tool for diagnosis of diseases in which B cell maturation is affected.

Pro-inflammatory caspase-1 activation during the immune response in cells from rainbow trout Oncorhynchus mykiss (Walbaum 1792) challenged with pathogen-associated molecular patterns.

In response to pathogens, the higher vertebrate innate immune system activates pro-inflammatory caspase-1 which is responsible for the processing and secretion of several important cytokines involved in the host's defence against infection. To date, caspase-1 has been described in few teleost fish, and its activity has been demonstrated through substrate cleavage and inhibition by pharmacological agents. In this study, the detection of the active form of caspase-1 during the immune response in salmonid fish is described, where two antibodies were produced. These antibodies differentially recognize the structural epitopes of the inactive pro-caspase-1 and the processed active form of the caspase. Firstly, caspase-1 activation was demonstrated in vitro by ELISA, Western blotting and immunocytochemistry in rainbow trout macrophages exposed to different pathogen-associated molecular patterns plus the pathogen Aeromonas hydrophila. This activity was clearly abrogated by a caspase inhibitor and seems to be unrelated to IL-1ß secretion. Caspase-1 activation was then validated in vivo in gill cells from fish challenged with Aeromonas salmonicida. These results represent the first demonstration of caspase-1 activation in salmonids, and the first evidence of the putative regulatory role which this protease plays in inflammatory response in this fish group, as described for some other teleosts and mammals.

Antimicrobial peptides: promising compounds against pathogenic microorganisms.

In the last decades, the indiscriminate use of conventional antibiotics has generated high rates of microbial resistance. This situation has increased the need for obtaining new antimicrobial compounds against infectious diseases. Among these, antimicrobial peptides (AMPs) constitute a promising alternative as therapeutic agents against various pathogenic microbes. These therapeutic agents can be isolated from different organisms, being widespread in nature and synthesized by microorganisms, plants and animals (both invertebrates and vertebrates). Additionally, AMPs are usually produced by a non-specific innate immune response. These peptides are involved in the inhibition of cell growth and in the killing of several microorganisms, such as bacteria, fungi, enveloped viruses, protozoans and other parasites. They have many interesting properties as potential antibiotics, such as relatively small sizes (below 25-30 kDa), amphipathic structures, cationic nature, and offer low probability for the generation of microbial resistance. In recent years, many novel AMPs, with very promising therapeutic properties, have been discovered. These peptides have been the base for the production of chemical analogs, which have been designed, chemically synthesized and tested in vitro for their antimicrobial activity. This review is focused on antibacterial (against Gram (-) and Gram (+) bacteria) and antifungal peptides, discussing action mode of AMPs, and recent advances in the study of the molecular basis of their anti-microbial activity. Finally, we emphasize on their current pharmacological development, future directions and applications of AMPs as promising antibiotics of therapeutic use for microbial infections.

Caracterización de enfermedad metastásica con PET/CT en cáncer de mama en etapificación y con recidiva postratamiento / Characterization of metastatic disease in recently diagnosed breast cancer and relapsed breast cancer (after treatment), with PET/CT

Objetivo: Describir la enfermedad metastásica detectada por PET/CT en cáncer de mama (CM) y estimar el aporte relativo del PET y del CT interpretados por separado. Pacientes y método. Se separaron dos grupos de pacientes con CM: 1) en etapificación 2) ya tratados con recidiva al PET/CT. Se describieron las lesiones encontradas exclusivamente con PET y exclusivamente con CT. Resultados. Los pacientes en etapificación (n=17) presentaron 88 por ciento adenopatías, 29 por ciento metástasis óseas (MO), 17 por ciento pulmonares, 17 por ciento hepáticas y 11 por ciento en otras localizaciones. Para los pacientes en seguimiento (n=35) estos porcentajes fueron de 54 por ciento, 62 por ciento, 34 por ciento, 31 por ciento y 28 por ciento, respectivamente. El CT detectó más nódulos pulmonares y MO escleróticas que el PET. El PET detectó más adenopatías, MO medulares y lesiones hepáticas. Se encontró cáncer sincrónico en 6 por ciento de los pacientes en etapificación y 11 por ciento en seguimiento. Conclusión. Las pacientes con CM presentaron principalmente metástasis ganglionares y óseas. El estudio híbrido PET/CT detectó más lesiones que el PET y el CT analizados por separado.

Purpose: To describe metastatic disease detected by PET/CT in breast cancer (BC), and to evaluate the relative contribution of PET and CT analyzed separately. Patients and Method. We defined two groups of patients with BC: 1) recently diagnosed with no treatment, 2) with relapse after treatment. We described findings which are visible exclusively with CT and exclusively with PET. Results. In recently diagnosed patients (n=17) 88 percent show lymphadenopathies, 29 percent bone metastases (BM), 17 percent lung metastases, 17 percent hepatic metastases, and 11 percent other localizations. For relapsed patients (n=35) these percentages were 54 percent, 62 percent, 34 percent, 31 percent and 28 percent, respectively. CT detected more lung nodules and sclerotic bone lesions than PET. PET detected more lymphadenopathies, medullary bone and hepatic lesions than CT. There were synchronous cancers in 6 percent of recently diagnosed patients and in 11 percent of relapsed patients. Conclusion. BC patients show mainly lymph nodal and bone metastasis. The PET/CT hybrid study detected more lesions than PET and CT analyzed separately.

Development of a new antibody for detecting natural killer enhancing factor (NKEF)-like protein in infected salmonids.

The main cellular responses of innate immunity are phagocytic activity and the respiratory burst, which produces a high amount of reactive oxygen species. Natural killer enhancing factor (NKEF) belongs to the peroxiredoxin family that has an antioxidant function and enhances cytotoxic cell activity. This molecule may play a key role in macrophage and cytotoxic cell communication during the innate immune response of fish against pathogens. In fish, the NKEF gene has been characterized in some species as showing an up-regulation in infected fish, suggesting a trigger effect upon NK-like cells. To detect and localize this molecule in salmonids at protein level, a monospecific polyclonal antibody was generated. A probable NKEF-like protein epitope region was identified and characterized using bioinformatic tools, and the sequence was chemically synthesized using Fmoc strategy, analysed by RP-HPLC and its molecular weight confirmed by mass spectrometry. The synthetic peptide was immunized and antibodies from ascitic fluid were obtained. The resulting antibody is a versatile tool for detecting NKEF by different immune techniques such as ELISA, Western blotting and immunohistochemistry. Analysis of NKEF-like protein is a useful method for characterizing immune properties of this molecule in fish during response to pathogens.

Identification of two immunoreactive peptides useful for the detection of porcine astrovirus.

Porcine astroviruses (PAstVs) are small RNA viruses associated with gastroenteritis. The capsid polyprotein of PAstVs, human (HAstVs) and feline (FAstVs) AstVs has a high similarity at the N-terminus before residue 415. Previous results showed the cross-detection of PAstVs and HAstVs from diarrheal samples using a commercial ELISA test that uses a monoclonal antibody to capture HAstVs, suggesting the existence of common immunoreactive epitopes between these two virus types. In this study, we seeked immunoreactive peptides located in the PAstV capsid that may be potentially used for their specific detection. The variability and hydrophobicity of a short fragment of 132 amino acids were analyzed using several capsid sequences of PAstVs and HAstVs. Peptides TATL, SLNP and IDIV were selected, synthesized and inoculated into rabbits. Pre- and hyperimmune sera were collected and their reactivity was examined by immunoassay and immunofluorescence against two wild-type strains of PAstV adapted to grow in cell culture, observing reactivity in two of the sera. Finally, the possible cross-reactivity of the sera against HAstVs was partially ruled out using HAstV8. Our data suggest that TATLGTIGSNSSGKTELEAC and IDIVVGKAATFNLKASDLSGP peptides represent immunoreactive regions useful for the specific detection of PAstVs.

Enhanced survival from CLP-induced sepsis following late administration of low doses of anti-IFNγ F(ab')2 antibody fragments.

OBJECTIVE: To assess the impact of different doses of anti-interferon gamma (anti-IFNγ) F(ab')2 fragments, administered prophylactically, on survival and on serum concentration of cytokines in a murine model of sepsis induced by cecal ligation and puncture (CLP). We further explore the impact of therapeutic administration of the most protective dose on survival. SUBJECTS AND TREATMENT: Balb/c mice were prophylactically treated by the intraperitoneal route with anti-IFNγ initiated 2 h before CLP and every 24 h for a total of five times in each of the following doses: 0.01, 0.1, or 1 mg/kg. Sham and control groups received sterile saline solution in a similar scheme. METHODS: Serum tumor necrosis factor (TNF), interleukin (IL)-1ß, IL-6, IL-10 and IFNγ were measured at 3, 24 and 48 h after CLP by ELISA. Survival curves were compared using a Mantel-Haenzel method. RESULTS: Significant prophylactic protection was found only with 0.01 mg/kg, in association with regulation of IL-1ß and IL-10 concentrations. As therapy, anti-IFNγ fragments were protective only when initiated 24 h after CLP. CONCLUSIONS: Delicate modulation of IFNγ at the correct timing, even when the septic process has begun, is an exciting alternative to explore in the treatment of sepsis.

Amino acid domains 280-297 of VP6 and 531-554 of VP4 are implicated in heat shock cognate protein hsc70-mediated rotavirus infection.

The rotavirus infection mechanism seems to be a multi-step process which is still not fully understood. The heat shock cognate protein hsc70 has been proposed as being a co-receptor molecule for rotavirus entry into susceptible cells. In this work, an attempt was made to determine the existence of possible domains for VP4 and VP6 binding to hsc70. We selected amino acid sequences 531-554 from VP4 and 280-297 from VP6 on the basis of already recognized sequences for binding to hsc70. This study determined that DLPs and synthetic peptides from VP6 (aa 280-297) and VP4 (aa 531-554), individually or in combination, inhibited rotavirus RRV, YM and WA entry into MA104 and Caco-2 cells in an additive and dose-dependent manner. Hyperimmune sera against these synthetic peptides blocked infection by infectious TLPs. Capture ELISA results showed that DLPs interact with hsc70, probably through VP6 as the specific interaction between hcs70 and DLPs was disrupted by a VP6 peptide. These results suggest that VP6 takes part during rotavirus cell entry by binding to hsc70. This, as well as previous work, provides insight concerning the function of hsc70 within a multi-step model of rotavirus entry.

Localization of sweet potato chlorotic stunt virus (SPCSV) in synergic infection with potyviruses in sweet potato

Among diseases reported worldwidely for sweet potato (Ipomoea batatas (L) Lam) crop, one of the most frequent is the Sweet potato virus disease (SPVD), caused by sweet potato chlorotic stunt virus (SPCSV) and sweet potato feathery mottle virus (SPFMV) co-infection. In Argentina, there exists the sweet potato chlorotic dwarf (SPCD), a sweet potato disease caused by triple co-infection with SPCSV, SPFMV and sweet potato mild speckling virus (SPMSV). Both diseases cause a synergism between the potyviruses (SPFMV and SPMSV) and the crinivirus (SPCSV). Up to date, studies carried out on the interaction among these three viruses have not described their localization in the infected tissues. In single infections, virions of the crinivirus genus are limited to the phloem while potyviral virions are found in most tissues of the infected plant. The purpose of this work was to localize the heat shock protein 70 homolog (HSP70h), a movement protein for genus crinivirus, of an Argentinean SPCSV isolate in its single infection and in its double and triple co-infection with SPFMV and SPMSV. The localization was made by in situ hybridization (ISH) for electron microscopy (EM) on ultrathin sections of sweet potato cv. Morada INTA infected tissues. The results demonstrated that viral RNA coding HSP70h is restricted to phloem cells during crinivirus single infection, while it was detected outside the phloem in infections combined with the potyviruses involved in chlorotic dwarf disease.

Sequencing of the bicistronic genome segments S7 and S9 of Mal de Río Cuarto virus (Fijivirus, Reoviridae) completes the genome of this virus.

The nucleotide sequences of genomic segments S7 and S9 of Mal de Río Cuarto virus (MRCV, Fijivirus group II) have been determined, thus completing the entire genome sequence of the virus. These segments showed a non-overlapping bicistronic structure, as in other members of the genus. MRCV S7 ORF-1 had a length of 1086 bp and encoded a 41.5 kDa putative polypeptide, whereas MRCV S7 ORF-2 had a length of 930 bp and encoded a 36.8 kDa putative polypeptide. Proteins of 39 and 20.5 kDa were predicted for the 1014 bp long MRCV S9 ORF-1 and the 537 bp long MRCV S9 ORF-2, respectively. The terminal 5' and 3' sequences of both segments were 5'AAGUUUUU3' and 5'CAGCUnnnGUC3', respectively. Specific imperfect inverted repeats of each segment were identified. Comparison of the predicted proteins with those of related virus genome segments counterparts in maize rough dwarf virus (MRDV) and rice black streaked dwarf virus (RBSDV), showed 64.5-44.3% identities. These values are lower than those resulting from comparisons between MRDV and RBSDV. The topology of the trees obtained using the complete nucleotide and amino acid sequences of MRCV S7 and MRCV S9 was consistent with the analysis of the other MRCV segments previously published.

In vitro effects of gamma radiation from 60Co and 137Cs on plasmid DNA.

The effects of gamma radiation from (60)Co and (137)Cs on DNA in aqueous solution are studied experimentally. Using an improved plasmid purification protocol and improved electrophoretic gel analysis techniques provided results with relatively small uncertainties. The results are compared with both theoretical and experimental results. In particular, the results obtained here are discussed in the light of recent discussion on supposed differences of the effects induced by gamma radiation from (60)Co and (137)Cs. We find that the effects of both types of gamma radiation are similar.

Anti-tumor necrosis factor alpha F(ab')2 antibody fragments protect in murine polymicrobial sepsis: concentration and early intervention are fundamental to the outcome.

BACKGROUND: Negative results are frequent using anti-TNFalpha antibodies in sepsis models and clinical trials. METHODS AND RESULTS: Different prophylactic doses of anti-TNFalpha F(ab')2 antibody fragments were compared for the prevention of death by sepsis induced by cecal ligation and puncture (CLP) in mice. High (10 mg/kg) and very low (0.01 and 0.1 mg/kg) concentrations of anti-TNFalpha antibody fragments were not the most adequate for treating polymicrobial sepsis, since they did not significantly improve survival. To the contrary, intermediate doses (1 mg/kg) significantly protected the challenged animals. Protective activity was also observed when administration of the antibody fragments was initiated early (up to 30 min) after CLP. CONCLUSIONS: These results suggest that in processes where excessive production of cytokines is involved, the aim should be to return them to their physiologically acting range but not to inhibit their production. The timing of initiating therapy should also be considered in order to maximize the possible benefits.

Long-term accumulation and microdistribution of uranium in the bone and marrow of beagle dog.

The accumulation and microdistribution of uranium in the bone and marrow of Beagle dogs were determined by both neutron activation and neutron-fission analysis. The experiment started immediately after the weaning period, lasting till maturity. Two animal groups were fed daily with uranyl nitrate at concentrations of 20 and 100 microg g(-1) food. Of the two measuring techniques, uranium accumulated along the marrow as much as in the bone, contrary to the results obtained with single, acute doses. The role played by this finding for the evaluation of radiobiological long-term risks is discussed. It was demonstrated, by means of a biokinetical approach, that the long-term accumulation of uranium in bone and marrow could be described by a piling up of single dose daily incorporation.