Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Fil: Monsalvo, Ana Clara. Fundacion INFANT, Buenos Aires; Argentina.Fil: Batalle, Juan P. Fundacion INFANT, Buenos Aires; Argentina.Fil: Lopez, M Florencia. Fundacion INFANT, Buenos Aires; Argentina.Fil: Krause, Jens C. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Klemenc, Jennifer. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Hernandez, Johanna Zea. . Fundacion INFANT, Buenos Aires; Argentina.Fil: Maskin, Bernardo. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundacion INFANT, Buenos Aires; Argentina.Fil: Rubinstein, Carlos. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Aguilar, Leandro. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Dalurzo, Liliana. Hospital Italiano, Buenos Aires; Argentina.Fil: Libster, Romina. Fundacion INFANT, Buenos Aires; Argentina.Fil: Savy, Vilma. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Aguilar, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Font, Julia. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Solari, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Weller, Kevin P. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Johnson, Joyce. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Echavarria, Marcela. Department of Microbiology, CEMIC, Buenos Aires; Argentina.Fil: Edwards, Kathryn M. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Chappell, James D. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Crowe, James E. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Williams, John V. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Melendi, Guillermina A. Fundacion INFANT, Buenos Aires; Argentina.Fil: Polack, Fernando P. Fundacion INFANT, Buenos Aires; Argentina.Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Fil: Monsalvo, Ana Clara. Fundacion INFANT, Buenos Aires; Argentina.Fil: Batalle, Juan P. Fundacion INFANT, Buenos Aires; Argentina.Fil: Lopez, M Florencia. Fundacion INFANT, Buenos Aires; Argentina.Fil: Krause, Jens C. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Klemenc, Jennifer. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Hernandez, Johanna Zea. . Fundacion INFANT, Buenos Aires; Argentina.Fil: Maskin, Bernardo. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundacion INFANT, Buenos Aires; Argentina.Fil: Rubinstein, Carlos. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Aguilar, Leandro. Hospital Dr Federico Abete, Malvinas Argentinas, Buenos Aires; Argentina.Fil: Dalurzo, Liliana. Hospital Italiano, Buenos Aires; Argentina.Fil: Libster, Romina. Fundacion INFANT, Buenos Aires; Argentina.Fil: Savy, Vilma. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Aguilar, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Font, Julia. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Solari, Liliana. Hospital Nacional Prof. Alejandro Posadas, Buenos Aires; Argentina.Fil: Weller, Kevin P. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Johnson, Joyce. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Echavarria, Marcela. Department of Microbiology, CEMIC, Buenos Aires; Argentina.Fil: Edwards, Kathryn M. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Chappell, James D. Department of Pathology, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Crowe, James E. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Williams, John V. Department of Pediatrics, Vanderbilt University, Nashville, TN; Estados Unidos.Fil: Melendi, Guillermina A. Fundacion INFANT, Buenos Aires; Argentina.Fil: Polack, Fernando P. Fundacion INFANT, Buenos Aires; Argentina.Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics

Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1) in Argentina

Fil: Libster, Romina. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bugna, Jimena. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Coviello, Silvina. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Hijano, Diego R. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Dunaiewsky, Mariana. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Reynoso, Natalia. Hospital Municipal Materno Infantil de San Isidro; Argentina.Fil: Cavalieri, Maria L. Hospital Eva Perón, Benito Juárez, Buenos Aires; ArgentinaFil: Guglielmo, Maria C. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Areso, M. Soledad. Hospital Eva Perón, Benito Juárez, Buenos Aires; ArgentinaFil: Gilligan, Tomas. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Santucho, Fernanda. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Cabral, Graciela. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Gregorio, Gabriela L. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Moreno, Rina. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Lutz, Maria I. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Panigasi, Alicia L. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Saligari, Liliana. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Caballero, Mauricio T. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Egües Almeida, Rodrigo M. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Gutierrez Meyer, Maria E. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Neder, Maria D. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Davenport, Maria C. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Del Valle, Maria P. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Santidrian, Valeria S. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Mosca, Guillermina. Ministerio de Ciencia, Técnica e Innovación. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Alvarez, Liliana. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Landa, Patricia. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Pota, Ana. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Boloñati, Norma. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Dalamon, Ricardo. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Sanchez Mercol, Victoria I. Hospital Eva Perón, Benito Juárez, Buenos Aires; Argentina.Fil: Espinoza, Marco. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Peuchot, Juan Carlos. Hospital Eva Perón, Benito Juárez, Buenos Aires; Argentina.Fil: Karolinski, Ariel. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bruno, Miriam. Hospital General de Agudos Carlos G. Durand, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Borsa, Ana. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Ferrero, Fernando. Hospital General de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Bonina, Angel. Hospital De Niños Sor María Ludovica, La Plata; Argentina.Fil: Ramonet, Margarita. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Albano, Lidia C. Hospital Nacional Profesor Alejandro Posadas, El Palomar, Buenos Aires; Argentina.Fil: Luedicke, Nora. Ministerio de Ciencia, Técnica e Innovación. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Alterman, Elias. Fundación Infant, Ciudad Autónoma de Buenos Aires; Argentina.Fil: Savy, Vilma L. ANLIS Dr.C.G.Malbrán. Instituto de Enfermedades Infecciosas; Argentina.Fil: Baumeister, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Virosis Respiratoria; Argentina.Fil: Chappell, James D. Vanderbilt University. Pathology, Nashville, Tennessee; Estados Unidos.Fil: Edwards, Kathryn M. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Fil: Melendi, Guillermina A. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Fil: Polack, Fernando P. Vanderbilt University. Departments of Pediatrics, Nashville, Tennessee; Estados Unidos.Background: While the Northern Hemisphere experiences the effects of the 2009 pandemic influenza A (H1N1) virus, data from the recent influenza season in the Southern Hemisphere can provide important information on the burden of disease in children. Methods: We conducted a retrospective case series involving children with acute infection of the lower respiratory tract or fever in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay and who were admitted to one of six pediatric hospitals serving a catchment area of 1.2 million children. We compared rates of admission and death with those among age-matched children who had been infected with seasonal influenza strains in previous years. Results: Between May and July 2009, a total of 251 children were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double those for seasonal influenza in 2008. Of the children who were hospitalized, 47 (19%) were admitted to an intensive care unit, 42 (17%) required mechanical ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000 children, as compared with 0.1 per 100,000 children for seasonal influenza in 2007. (No pediatric deaths associated with seasonal influenza were reported in 2008.) Most deaths were caused by refractory hypoxemia in infants under 1 year of age (death rate, 7.6 per 100,000). Conclusions: Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years

Hábitos alimentares de crianças menores de 1 ano amamentadas e não-amamentadas Feeding habits of breastfed and non-breastfed children up to 1 year old

OBJETIVOS: Descrever os hábitos alimentares de crianças amamentadas e não-amamentadas através da análise dos alimentos consumidos pelas crianças menores de 1 ano de idade na cidade de Feira de Santana, BA, no ano de 2001. MÉTODOS: Foi realizado um estudo transversal, no qual foram aplicados questionários às mães das crianças menores de 1 ano no dia nacional de vacinação, presentes nas 44 (71%) unidades de vacinação, selecionadas por estratificação simples. Foram avaliadas 2.319 crianças, representando 24,3% da população estimada. As medidas de associação calculadas foram: razão de prevalência, com intervalo de confiança a 95%, e de significância estatística, através do teste do qui-quadrado com respectivo valor p. RESULTADOS: Nas crianças com idade igual ou inferior a 4 meses e não-amamentadas, foi observada uma chance 8,2 e 6,7 vezes maior de a criança ser alimentada, respectivamente, com a refeição da família (IC 95% 3,23-20,66) e com papas de legumes (IC 95% 3,84-11,78). Na mesma faixa etária, as prevalências de crianças não-amamentadas que receberam água, chás, sucos e papa de frutas foram significativamente maiores (70,7% versus 19,7%, 63,3% versus 26,7%, 33,3% versus 4,9% e 14,4% versus 1,4%, respectivamente). CONCLUSÕES: As crianças amamentadas, quando comparadas com as não-amamentadas, apresentaram melhores hábitos no que se refere à época de introdução dos alimentos complementares.<br>OBJECTIVE: To describe the eating habits of breastfed and non-breastfed children through the analysis of food intake by children younger than one year of age in Feira de Santana in 2001. METHODS: Cross-sectional study. The mothers of children younger than one year answered a questionnaire during the national vaccination day in 44 (71%) vaccination units selected by simple stratification. 2,319 children were evaluated, representing 24.3% of the estimated population. Prevalence ratio and 95% confidence interval were calculated. Statistical significance was determined using the chi-square test. RESULTS: Non-breastfed children aged four months or younger were 8.2 and 6.7 times more likely to receive the family food (95% CI: 3.23-20.66) or vegetable soup (95% CI: 3.84-11.78), respectively. In the same age group, the prevalence of non-breastfed children receiving water, juice, and fruit was significantly higher in relation to breastfed children (70.7 vs 19.7%, 63.3 vs 26.7%, 33.3 vs 4.9% and 14.4 vs 1.4%, respectively). CONCLUSION: Breastfed children had healthier habits than non-breastfed children in terms of the introduction of complementary foods

Afrostyrax lepidophyllus Mildbr. and Monodora myristica (Gaertn.) Dunal Extracts Decrease Doxorubicin Cytotoxicity on H9c2 Cardiomyoblasts

Ethnopharmacological Relevance. Doxorubicin (Dox) is an anthracycline antibiotic widely used in cancer treatment. Despite its antitumor efficacy, its clinical application is significantly limited because of its cardiotoxicity originated, among other factors, from pro-oxidant damage to cardiac mitochondria. Phytochemicals represent a potentially attractive strategy to mitigate Dox cardiotoxicity due to their antioxidant properties, with plant extracts used in traditional medicine often being ignored in terms of potential therapeutic uses. Aim of the Study. The present study aimed at investigating the protective effects of two native Cameroonian plants, Afrostyrax lepidophyllus Mildbr. (A. lepidophyllus) and Monodora myristica (Gaertn.) Dunal (M. myristica), against Dox-induced cytotoxicity on cultured H9c2 cardiomyoblast cells. Materials and Methods. Bark extracts of these plants (1 and 25 µg/mL) were added 3 hours before coincubating H9c2 cardiomyoblasts with Dox (0.5 and 1 µM) for 24 hours more. We measured cell mass and metabolic viability, mitochondrial transmembrane potential, superoxide anion content, and activity-like of caspase-3 and caspase-9 following treatment with the extracts and/or Dox. Also, selenium and vitamin C contents were measured in the plant extracts. Results. The results confirmed that Dox treatment decreased cell mass, mitochondrial membrane potential and metabolic viability, increased mitochondrial superoxide anion, and stimulated caspase-3 and caspase-9-like activities. Pretreatment of the cells with the plant extracts significantly inhibited Dox cytotoxicity, with more significant results at the higher concentration. Measurements of selenium and vitamin C in the extracts revealed higher concentration of both when compared with other Cameroonian spices. Conclusion. Both extracts of A. lepidophyllus and M. myristica were effective against Dox-induced cytotoxicity, most likely due to their content in antioxidants

Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection

Prions are composed of an isoform of a normal sialoglycoprotein called PrP(c), whose physiological role has been under investigation, with focus on the screening for ligands. Our group described a membrane 66 kDa PrP(c)-binding protein with the aid of antibodies against a peptide deduced by complementary hydropathy. Using these antibodies in western blots from two-dimensional protein gels followed by sequencing the specific spot, we have now identified the molecule as stress-inducible protein 1 (STI1). We show that this protein is also found at the cell membrane besides the cytoplasm. Both proteins interact in a specific and high affinity manner with a K(d) of 10(–7) M. The interaction sites were mapped to amino acids 113–128 from PrP(c) and 230–245 from STI1. Cell surface binding and pull-down experiments showed that recombinant PrP(c) binds to cellular STI1, and co-immunoprecipitation assays strongly suggest that both proteins are associated in vivo. Moreover, PrP(c) interaction with either STI1 or with the peptide we found that represents the binding domain in STI1 induce neuropro tective signals that rescue cells from apoptosis