Infecciones por estreptococos del grupo S. anginosus en pediatría / S. anginosus group streptococcal infections in children

Los estreptococos del grupo Streptococcus anginosus (EGA), también llamados "Streptococcus milleri", fueron reconocidos como parte de los estreptococos del grupo viridans (EGV) desde principios del siglo XX. Su rol como patógenos humanos, sin embargo comenzó a destacarse recién en la década de 1970. En esta actualización se describen aspectos microbiológicos y clínicos de los EGA. Los métodos fenotípicos de identificacón e incluso algunos genotípicos carecen de precisión para reconocer las tres especies del grupo (Streptococcus anginosus, Streptococcus constellatus y Streptococcus intermedius) e incluso pueden fallar en su clasificación a nivel de grupo. La mayoría de ellos son sensibles a los antibióticos beta-lactámicos pero son considerables los porcentajes de resistencia a macrólidos, lincosamidas y tetraciclinas. Los EGA son colonizantes habituales de las mucosas orofaríngea, intestinal y genitourinaria, pero, cada vez más frecuentemente, son reconocidos como patógenos humanos. Es ampliamente conocida su capacidad de formar abscesos en órganos sólidos, especialmente abscesos cerebrales, pulmonares y hepáticos. También producen sinusitis, empiemas y colecciones en piel y tejidos blandos, hueso, articulaciones, etc. Se han encontrado asociados con exacerbaciones pulmonares en pacientes con fibrosis quística y con enfermedad pulmonar obstructiva crónica. Producen también infecciones posteriores a mordeduras humanas, infecciones diseminadas, bacteriemia sin foco aparente y, en menor medida, endocarditis infecciosa (AU)

Streptococci from the Streptococcus anginosus group (SAG), also termed "Streptococcus milleri", were recognized as members of the viridans group streptococci (VGS) in the early 20th century. Nevertheless, their role as human pathogens only became evident in the 1970s. In this update, microbiological and clinical aspects of the SAG are described. Phenotypic and even some genotypic identification methods lack accuracy in recognizing the three species of the group (Streptococcus anginosus, Streptococcus constellatus, and Streptococcus intermedius) and may fail to classify them at the group level. Most of them are sensitive to beta-lactam antibiotics but rates of resistance to macrolides, lincosamides, and tetracyclines are significant. SAGs are common colonizers of the oropharyngeal, intestinal, and genitourinary mucosa, but are increasingly recognized as human pathogens. Their ability to form abscesses in solid organs, especially brain, lung and liver, is widely known. They may produce sinusitis, empyemas, and collections in skin and soft tissues, bone, joints, etc. They have also been associated with pulmonary exacerbations in patients with cystic fibrosis and chronic obstructive pulmonary disease. In addition, they may cause infections following human bites, disseminated infections, bacteremia without apparent focus, and, to a lesser extent, infective endocarditis (AU)

Selection of CD271(+) cells and human AB serum allows a large expansion of mesenchymal stromal cells from human bone marrow.

BACKGROUND: Mesenchymal stromal cells (MSC) are promising candidates for cell therapy and tissue engineering and may be used to treat acute graft-versus-host disease (GvHD). However, major obstacles for their clinical use are the required cell dose and the biosafety and potential immunogenicity of fetal bovine serum (FBS), which is a crucial supplement of all media currently used for the culture of MSC. METHODS: In this study MSC were successfully expanded after selection of CD271 cells from human bone marrow (BM) mononuclear cells in medium supplemented with 10% pooled allogeneic human serum. RESULTS: We isolated MSC from 10 healthy donor BM by plastic adherence and immunomagnetic selection of the CD271(+) fraction and expanded MSC in medium supplemented with pooled human allogeneic serum and animal serum. We isolated a homogeneous multipotent population by CD271(+) selection with a proliferation rate that was higher than MSC isolated by plastic adherence, 6.8+/-1.57 compared with 2.07+/-1.40 logs. Similar to cells generated in animal serum medium, MSC from allogeneic human serum were positive for mesenchymal markers and negative for hematopoietic markers; moreover they expressed embryonic stem cell genes. A normal karyotype and differentiation capacity into adipogenic, osteogenic and chondrogenic lineages and neurosphere-like structures were preserved throughout long-term culture. DISCUSSION: Expansion of MSC is both feasible and large with a CD271-selected population in medium supplemented with 10% pooled allogeneic human serum, without loss of multipotent differentiation capacity or karyotype alterations.

Characterization and expansion of mesenchymal progenitor cells from first-trimester chorionic villi of human placenta.

BACKGROUND: Mesenchymal stromal cells (MSC) have been identified in a variety of fetal and adult tissues, including bone marrow (BM), fetal blood and liver. We report on the isolation, expansion and differentiation in vitro of MSC-like cells from chorionic villi (CV). METHODS: We evaluated 10 samples of CV collected at the first trimester (gestational age 11-13 weeks). We only used cells taken from back-up culture after a successful karyotype analysis. CV cells were characterized by morphologic, immunophenotypic and molecular analysis. The differentiation ability of mesenchymal and neural lineages was detected using specific culture conditions. Cell expansion was assessed after plating cells at different densities in different media, supplemented with animal and human serum. RESULTS: CV cells showed a homogeneous population of spindle-shaped cells after the first passage. Cells expressed CD90, CD105, CD73, CD44, CD29 and CD13 but not CD45, CD14, CD34 and CD117. They expressed Oct-4, Rex-1, GATA-4 and nestin, which characterize the undifferentiated stem cell state. They differentiated into osteocytes, adipocytes, chondrocytes and neuronal cells. Cell expansion was greater than that of adult BM-derived MSC, 9 logs with fetal bovine serum and 6 logs with human serum. Despite their high proliferative capacity, we did not observe any karyotypic abnormalities after culture. DISCUSSION: Our study shows that CV cells have better potential for expansion than adult stem cells. They can proliferate in a medium with human allogeneic serum and can differentiate into mesenchymal and neural lineages. CV cells may be an excellent cell source for therapeutic applications.

Humoral immune response against hepatitis C virus.

Antibodies are in several instances a reliable marker indicating vigorous immune response against infectious agents and in several viral diseases presence in the blood of specific anti-viral antibodies indicates an effective protection. However, this is not always true. For example, in the case of hepatitis C virus (HCV) an important human pathogen considered the causative agent of the nonA- nonB hepatitis, in spite of an intense antibody response there is no protection against a new infection and in the majority of infected individuals the virus overcomes host defences establishing a persistent infection. Here we describe how the dissection of the humoral immune response against HCV glycoprotein E2 of infected patients was useful for a better comprehension of the virus-host interplay. Cross-reactive antibodies directed against E2 are produced by the HCV-infected patient, but not all of them are protective, and some could even result to be detrimental for the patient. The cross-reactive anti-HCV/E2 humoral antibody response is complex and not necessarily completely beneficial to the host.

Heterogeneity of the humoral anti-HCV/E2 response in persistently infected patients as demonstrated by divergent patterns of inhibition of the binding of anti-HCV/E2 human monoclonal antibodies.

A complete understanding of the molecular features of humoral immune response could be of pivotal importance in the management of persistent viruses as HCV. In this study, 24 HCV-positive samples, characterized by classical virological parameters, are evaluated using a new assay for the quantitation of antibody subpopulations directed against discrete epitopes on surface glycoprotein E2, a key viral protein. The results, besides confirming the usefulness of this new approach, highlight the extreme heterogeneity of anti-HCV/E2 response as far as single epitopes are concerned. The specific epitopes under study are also demonstrated to be widely shared among different genotypes.