RESUMO
The immune mechanisms underlying the pathogenesis of severe pneumonia associated with the A/H1N1 virus are not well known. The objective of this study was to determine whether severe A/H1N1-associated pneumonia can be explained by the emergence of particular T-cell subsets and the cytokines/chemokines they produced, as well as distinct responses to infection. T-cell subset distribution and cytokine/chemokine levels in peripheral blood and bronchoalveolar lavage (BAL) were determined in patients with severe A/H1N1 infection, asymptomatic household contacts, and healthy controls. Cytokine and chemokine production was also evaluated after in vitro infection with seasonal H1N1 and pandemic A/H1N1 strains. We found an increase in the frequency of peripheral Th2 and Tc2 cells in A/H1N1 patients. A trend toward increased Tc1 cells was observed in household contacts. Elevated serum levels of IL-6, CXCL8, and CCL2 were found in patients and a similar cytokine/chemokine profile was observed in BAL, in which CCL5 was also increased. Infection assays revealed that both strains induce the production of several cytokines/chemokines at 24 and 72 h, however, IL-6, CCL3, and CXCL8 were strongly up-regulated in 72-h cultures in presence of the A/H1N1 virus. Several inflammatory mediators are up-regulated in peripheral and lung samples from A/H1N1-infected patients who developed severe pneumonia. In addition, the A/H1N1 strain induces higher levels of pro-inflammatory cytokines and chemokines than the seasonal H1N1 strain. These findings suggest that it is possible to identify biomarkers of severe pneumonia and also suggest the therapeutic use of immunomodulatory drugs in patients with severe pneumonia associated with A/H1N1 infection.
Assuntos
Surtos de Doenças , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/complicações , Pneumonia Viral/virologia , Adulto , Anticorpos Antivirais/sangue , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/análise , Feminino , Hispânico ou Latino , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/virologia , Masculino , México , Pneumonia Viral/imunologia , RNA Viral/química , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologia , Linfócitos T/imunologia , Linfócitos T/virologiaRESUMO
In Mexico informed consent is a legal requirement that ensures that patients who are invited to participate in clinical trials are provided with all the information needed to decide whether to participate, or not, in a research protocol. To improve our understanding of the problems physicians in developing countries encounter, when obtaining informed consent (IC), we examined their opinion on the importance of IC in clinical research, the quantity and quality of the information provided to the participant, and the conditions in which the IC is obtained. Investigators considered that IC was useful to the patients, providing information that helped the patient to make a decision about his/her participation. Nevertheless, they felt that for some aspects of the research, like drug development in general, the use of placebos, and the randomization process, many of the patients were not capable of fully understanding the information provided, referring to the complexity of the information and illiteracy as the main reasons. Many investigators were not acquainted with some of the guidelines established in the Mexican General Law of Health,(1) 36% of them admitting to not having completed their IC letters. Most investigators gave only minutes to the patient to make a decision and 20% of ICs were obtained while the patient was hospitalized. Except for one investigator, all of them considered that specific training in medical ethics would be useful for the daily clinical work.
Assuntos
Atitude , Ensaios Clínicos como Assunto , Consentimento Livre e Esclarecido , Pesquisadores/psicologia , Ensaios Clínicos como Assunto/ética , Ensaios Clínicos como Assunto/normas , Compreensão , Revelação/ética , Revelação/normas , Ética Médica/educação , Humanos , Consentimento Livre e Esclarecido/psicologia , Consentimento Livre e Esclarecido/estatística & dados numéricos , México , Relações Médico-Paciente , Projetos de Pesquisa , Sujeitos da Pesquisa , Medição de RiscoRESUMO
Genetic variability among Taenia solium isolates was studied in 160 cysticerci from 6 pigs, 4 from Mexico, 1 from Honduras, and 1 from Tanzania. Random amplified polymorphic DNA (RAPD) analysis performed with 4 commercial primers showed 88% polymorphic loci and an average heterozygosity of 0.077; however, several alleles were fixed within each isolate. Linkage disequilibrium analysis indicated that 3 of the 6 isolates had a random association of alleles, whereas the other 3 had a clonal structure. These results suggest the existence of local lineages in T. solium, with events of genetic recombination within them.