Inhibition of lipopolysaccharide-induced macrophage IL-12 production by Leishmania mexicana amastigotes: the role of cysteine peptidases and the NF-kappaB signaling pathway.

Infection with lesion-derived Leishmania mexicana amastigotes inhibited LPS-induced IL-12 production by mouse bone marrow-derived macrophages. This effect was associated with expression of cysteine peptidase B (CPB) because amastigotes of CPB deletion mutants had limited ability to inhibit IL-12 production, whereas preincubation of cells with a CPB inhibitor, cathepsin inhibitor IV, was able to suppress the effect of wild-type amastigotes. Infection with wild-type amastigotes resulted in a time-dependent proteolytic degradation of IkappaBalpha and IkappaBbeta and the related protein NF-kappaB. This effect did not occur with amastigotes of CPB deletion mutants or wild-type promastigotes, which do not express detectable CPB. NF-kappaB DNA binding was also inhibited by amastigote infection, although nuclear translocation of cleaved fragments of p65 NF-kappaB was still observed. Cysteine peptidase inhibitors prevented IkappaBalpha, IkappaBbeta, and NF-kappaB degradation induced by amastigotes, and recombinant CPB2.8, an amastigote-specific isoenzyme of CPB, was shown to degrade GST-IkappaBalpha in vitro. LPS-mediated IkappaBalpha and IkappaBbeta degradation was not affected by these inhibitors, confirming that the site of degradation of IkappaBalpha, IkappaBbeta, and NF-kappaB by the amastigotes was not receptor-driven, proteosomal-mediated cleavage. Infection of bone marrow macrophages with amastigotes resulted in cleavage of JNK and ERK, but not p38 MAPK, whereas preincubation with a cysteine peptidase inhibitor prevented degradation of these proteins, but did not result in enhanced protein kinase activation. Collectively, our results suggest that the amastigote-specific cysteine peptidases of L. mexicana are central to the ability of the parasite to modulate signaling via NF-kappaB and consequently inhibit IL-12 production.

Human parvovirus infection in homozygous sickle cell disease

We studied the epidemiology of human parvovirus B19 infection in 308 children with homozygous sickle cell (SS) disease and 239 controls with a normal haemoglobin (AA) genotype followed from birth in a cohort study. Annual serum samples identified the time and frequency of B19 infection, which did not differ between SS and AA children, about 40 percent of each age group developing specific IgG by age 15. B19 infection followed an epidemic pattern similar to that observed for aplastic crises; accounted for all 91 aplastic crises that occurred; and was found in an additional 23 SS patients, of whom 10 showed mild haematological changes and 13 no changes. The magnitude or duration of IgG response did not differ between these groups. No patient had 2 attacks of aplasia and no patient nor control had 2 attacks of B19 infection. Following B19 infection, serial specific IgG concentrations remained high after 5 years in only 45 percent of SS patients, although the rarity of recurrent aplasia suggests lifelong immunity. B19 infection accounts for most if not all aplastic crises in SS disease, but at least 20 percent of infections do not result in aplasia. An effective vaccine against B19 might make an important contribution to the management of sickle cell disease (AU)

Nutrición materna y resultados del embarazo: evaluación, antropométrica / Maternal nutrition and pregnancy outcomes: anthropometric assessment

La nutrición de la mujer, antes y durante el embarazo, es crítica para la salud y supervivencia tanto de ella como de su hijo. Las mediciones utilizadas en la evaluación del estado nutricional materno (indicadores antropométricos) son esenciales para identificar mujeres a riesgo de complicaciones gestacionales y de dar a luz infantes con retraso del crecimiento intrauterino. En abril de 1990, la USAID (Agencia Internacional para el Desarrollo), MotherCare y la Organización Panamericana de la Salud/Organización Mundial de la Salud patrocinaron el primer foro internacional que examinó específicamente la evaluación antropométrica del estado nutricional materno en los países. Este libro expone los resultados de dicha reunión, enfocando cinco indicadores: aumento de peso en el embarazo, peso pregestacional, talla, circunferencia braquial y peso-para-talla, así como el índice de masa corporal. Las editoras presentan una revisión comprensiva de los conocimientos actuales sobre el valor de dichos indicadores para predecir resultados del embarazo en diferentes circunstancias y en diferentes períodos de la vida reproductiva de la mujer. Las recomendaciones aquí planteadas sobre la idoinedad de ciertos instrumentos de medición a aplicarse en países en desarrollo y áreas prioritarias de investigación constituirán un tesoro tanto para investigadores como par personal de campo

Folato sérico y eritrocitario en el lactante: influencia de la nutrición de hierro / Serum and erythrocyte folate in infancy: effect of iron nutrition

Se midieron, en un grupo de lactantes de término, concentraciones de folato sérico y eritrocitario, hemoglobina, capacidad total de combinación de hierro, protoporfirina libre eritrocitaria y ferritina sérica a los 9 meses (n = 215) y 15 meses de edad (n = 198). Los lactantes anémicos ferroprivos presentaron un promedio de folato eritrocitario significativamente más alto (p < 0,005) que los sujetos normales. No se apreciaron diferencias en las concentraciones de folato sérico. Estos resultados sugieren que, a igual aporte de ácido fólico, las reservas de folato dependen de la adecuación de la nutrición de hierro. Una eritropoyesis deficiente en hierro determinaría menor utilización de los depósitos de ácido fólico

Folato serico y eritrocitario en el lactante. / Serum and erythrocyte folate in the infant

Se siguio longitudinalmente un grupo de 149 lactantes de termino de baja condicion socieconomica, provenientes de las Areas Sur y Oriente de Santiago. En una submuestra se determinaron los niveles de folato serico y eritrocitario a los 3,9 y 15 meses de vida. A los 3 meses se constataron concentraciones elevadas de folato serico y eritrocitario, las que descendieron a los 9 meses para recuperarse parcialmente a los 15 meses.A todas las edades estudiadas, los lactantes presentaron valores de folato mas altos que los de un grupo de adultos normales.En los ninos estudiados se encontro una baja prevalencia de valores subnormales de acido folico

The development and use of an antibody capture radioimmunoassay for specific IgM to a human parvovirus-like agent

An IgM-antibody capture radioimmunoassay (MACRIA) was developed for detection of IgM antibody specific for the human parvovirus-like agent B19. Diagnosis of infection with this agent by either antigen detection or antibody seroconversion had been made by counter-current immunoelectrophoresis (CIE) in 18 cases of aplastic crisis occurring in children with homozygous sickle-cell desease. The MACRIA described here gave positive results in 17 of 18 cases; in the remaining case only an acute specimen taken from the patient during viraemia and late convalescent specimens taken 184 and 247 days after onset of illness were avaliable. The test was used to investigate 20 further cases of aplastic crisis in which neither viral antigen nor antibody seroconversion could be detected by CIE. Detection of virus-specific IgM permitted diagnosis of infection with this parvovirus-like agent in 17 of these cases. In the remaining three cases only single serum specimens taken late in convalescence, 82, days or more after the onset of symptoms, were available. In addition to these 34 cases of aplastic crisis in which primary infection with this agent was diagnosed by MACRIA, seven cases of apparent 'silent' infection detected by CIE were investigated. The test permitted the discrimination between primary infection and re-exposure to the virus in six of these patients. The use of this assay has added a considerable weight of evidence implicating primary infection with this parvovirus-like agent as an important cause of aplasic crisis in children with sickle-cell disease. Furthermore, MACRIA permits diagnosis of infection when only single serum specimens taken up to ten weeks after infection are available. Thus the use of this test will significantly facilitate the investigation of other clinical syndromes of presumptive infective infectious aetiology (AU)