Alfa 1 antitripsina y alfa 2 macroglobulina en esputo infectado y no infectado de pacientes con enfermedad pulmonar obstructiva cronica. Significacion fisiopatologica de ambas proteinas en el pulmon
Alpha 1-antitrypsin and alpha 2-macroglobulin in infected and non-infected sputum from patients with chronic obstructive pulmonary disease. Physiopathological significance of the two proteins in the lung
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Gomez Sebastian, J.A. Maestre Alcacer" "autores" => array:2 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Gomez Sebastian" ] 1 => array:2 [ "nombre" => "J.A." "apellidos" => "Maestre Alcacer" ] ] ] 1 => array:2 [ "autoresLista" => "L.L. Bernado, C. Leon" "autores" => array:2 [ 0 => array:2 [ "nombre" => "L.L." "apellidos" => "Bernado" ] 1 => array:2 [ "nombre" => "C." 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Plasencia Garcia, C.E. Gonzalez Reimers, F. Santolaria Fernandez, J.A. Jorge Hernandez, N. Batista Lopez, I. Gonzalez Martin, L. Hernandez Nieto" "autores" => array:7 [ 0 => array:2 [ "nombre" => "V." "apellidos" => "Plasencia Garcia" ] 1 => array:2 [ "nombre" => "C.E." "apellidos" => "Gonzalez Reimers" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Santolaria Fernandez" ] 3 => array:2 [ "nombre" => "J.A." "apellidos" => "Jorge Hernandez" ] 4 => array:2 [ "nombre" => "N." "apellidos" => "Batista Lopez" ] 5 => array:2 [ "nombre" => "I." "apellidos" => "Gonzalez Martin" ] 6 => array:2 [ "nombre" => "L." "apellidos" => "Hernandez Nieto" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289615322572?idApp=UINPBA00003Z" "url" => "/03002896/0000002000000002/v1_201509151130/S0300289615322572/v1_201509151130/es/main.assets" ] "es" => array:13 [ "idiomaDefecto" => true "titulo" => "Alfa 1 antitripsina y alfa 2 macroglobulina en esputo infectado y no infectado de pacientes con enfermedad pulmonar obstructiva cronica. Significacion fisiopatologica de ambas proteinas en el pulmon" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "60" "paginaFinal" => "69" ] ] "autores" => array:2 [ 0 => array:3 [ "autoresLista" => "L. Oteo Ochoa, M. Maties Prats, J.L. De La Cruz Rios, A. Izquierdo Del Amo, J.L. Cruz Ramos, C. Martin Serrano, J. Picher Nuñez, A. Sueiro Bendito" "autores" => array:8 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Oteo Ochoa" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Maties Prats" ] 2 => array:2 [ "nombre" => "J.L." "apellidos" => "De La Cruz Rios" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Izquierdo Del Amo" ] 4 => array:2 [ "nombre" => "J.L." "apellidos" => "Cruz Ramos" ] 5 => array:2 [ "nombre" => "C." "apellidos" => "Martin Serrano" ] 6 => array:2 [ "nombre" => "J." "apellidos" => "Picher Nuñez" ] 7 => array:2 [ "nombre" => "A." "apellidos" => "Sueiro Bendito" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Neumología. C.E. Ramón y Cajal de la S.S. Madrid" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "autoresLista" => "M. Diaz Enriquez" "autores" => array:1 [ 0 => array:3 [ "nombre" => "M." "apellidos" => "Diaz Enriquez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:3 [ "entidad" => "Servicio de Bioquímica. C.E. Ramón y Cajal de la S.S. Madrid" "etiqueta" => "*" "identificador" => "aff0010" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Alpha 1-antitrypsin and alpha 2-macroglobulin in infected and non-infected sputum from patients with chronic obstructive pulmonary disease. Physiopathological significance of the two proteins in the lung" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "1982-12-14" "fechaAceptado" => "1983-09-24" "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Alfa 1 antitripsina (α<span class="elsevierStyleInf">1</span> AT) y alfa 2 macroglobulina (α<span class="elsevierStyleInf">2</span> MG) son inhibidores enzimáticos con importantes funciones en la protección del tejido conectivo pulmonar.En el presente trabajo se determinaron ambas proteínas a nivel sérico y en fase sol de esputo en dos grupos de pacientes portadores de enfermedad pulmonar obstructiva crónica con y sin infección respiratoria del tracto inferior.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Durante los períodos de infección pulmonar, los niveles séricos de α<span class="elsevierStyleInf">1</span> AT aumentaron significativamente probablemente por incremento del metabolismo proteico, mientras que la concentración de α<span class="elsevierStyleInf">2</span> MG durante este mismo período decreció de forma significativa, sugiriendo bien un aumento del catabolismo proteico, una reducción de la capacidad de síntesis o la formación de complejos estables α<span class="elsevierStyleInf">2</span> MG-endopeptidasas bacterianas. Por otra parte, las tasas de α<span class="elsevierStyleInf">1</span> AT y α<span class="elsevierStyleInf">2</span> MG en esputo y su relación (esputo/suero) aumentaron significativamente en el transcurso de las infecciones pulmonares, evidenciando un importante aumento de la difusión pasiva proteica desde el plasma a la secreción bronquial. Cuando la relación esputo/suero de ambas macromoléculas fue corregida para la albúmina, no existieron diferencias significativas al comparar las distribuciones de ambaspoblaciones analizadas, sugiriendo un mecanismo de génesis común en los grupos con y sin infección pulmonar. La buena correlación existente entre α<span class="elsevierStyleInf">1</span>, AT y albúmina en presencia de infección respiratoria del tracto inferior confirma que la trasudación proteica es un mecanismo fisiopatológico preferencial.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Las bajas concentraciones detectadas de α<span class="elsevierStyleInf">1</span> AT y α<span class="elsevierStyleInf">2</span> MG en la secreción bronquial en el grupo de sujetos sin infección pulmonar, son indicativas de su limitada contribución antiproteasa en este medio biológico. Durante la infección pulmonar la proteína α<span class="elsevierStyleInf">2</span> MG aumentó significativamente en esputo por efecto de la difusión pasiva desde el plasma y quizá por estimulación inespecífica de la producción local, pudiendo en esta circunstancia desarrollar una importante función inhibidora de la actividad enzimática libre. Sin embargo, a pesar de la contribución de α<span class="elsevierStyleInf">2</span> MG a la corrección del disbalance entre proteasas neutras e inhibidores, los sujetos portadores de EPOC con infección pulmonar intercurrente mantienen un estado de desequilibrio enzimático con elevado riesgo para la integridad del tejido conectivo pulmonar.</p></span>" ] "en" => array:1 [ "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Both proteins were determined in this study in the serum and in a colloidal solution of sputum in two groups of patients with chronic obstructive lung disease (COLD) with infection and without lower respiratory infection.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The serum levels of α<span class="elsevierStyleInf">1</span> AT augmented significantly during pulmonary infection probably due to protein metabolism, while α<span class="elsevierStyleInf">2</span> MG concentration decreased significantly during the same period suggesting either an increase in the protein catabolism, a reduction of the synthetic capacity, or the formation of stable complexes of α<span class="elsevierStyleInf">2</span> MG-bacterial endopeptidases. On the other hand, the levels of α<span class="elsevierStyleInf">1</span> AT and α<span class="elsevierStyleInf">2</span> MG in sputum and their ratio (sputum/serum) augmented markedly during pulmonary infection, demonstrating a significant increase in the protein passive diffusion from the plasma to the bronchial secretions. There were no significant differences in the</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">ratio sputum/serum of both macromolecules when comparing the 2 groups analyze after correcting for the albumin. This suggests a common original mechanism in the groups with and without pulmonary infection. The strong correlation between α<span class="elsevierStyleInf">1</span> AT and albumin with lower respiratory infection confirms that protein transudate is a preferential physiopathological mechanism.</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The low concentrations of α<span class="elsevierStyleInf">1</span> AT and α<span class="elsevierStyleInf">2</span> detected in bronchial secretions of patients without pulmonary infection indicate their limited contribution to antiprotease activity in this biological medium. α<span class="elsevierStyleInf">2</span> MG protein increased in the sputum significantly during pulmonary infection due to the passive diffusion from the plasma and perhaps too to the nonspecific stimulation of local production. An important inhibitory function of the free enzyme activity could be developed in this case. Nevertheless, patients with COLD and recurrent pulmonary infections mantain a State of enzymatic disequilibrium in spite of the contribution of α<span class="elsevierStyleInf">2</span> MG in the correction of the disequilibrium between neutral proteases and inhibitors. This constitutes an important risk for the integrity of the pulmonary connective tissue.</p></span>" ] ] "bibliografia" => array:2 [ "titulo" => "Bibliografia" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:50 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of elastases in the development of emphysema" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Kuhn" 1 => "R.M. Senior" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lung" "fecha" => "1978" "volumen" => "155" "paginaInicial" => "185" "paginaFinal" => "197" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/703379" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung injury by leukocytic protease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Janoff" 1 => "R.K. White" 2 => "H. Carp" 3 => "S. Harel" 4 => "R. Deering" 5 => "D. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Pathol" "fecha" => "1979" "volumen" => "97" "paginaInicial" => "111" "paginaFinal" => "135" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/495691" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relation of smoking and age to emphysema. Whole lung study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "O. Auerbach" 1 => "E.C. Hammond" 2 => "L. Garfinkel" 3 => "C. Benante" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM197204202861601" "Revista" => array:6 [ "tituloSerie" => "New Engl J Med" "fecha" => "1972" "volumen" => "286" "paginaInicial" => "853" "paginaFinal" => "857" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5061068" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Granulocyte collagenase, elastase and plasma protease inhibitors in purulent sputum" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K. Ohlsson" 1 => "H. Tegner" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Europ J Clin Invest" "fecha" => "1975" "volumen" => "5" "paginaInicial" => "221" "paginaFinal" => "227" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/50236" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Polymorphonuclear leukocyte collagenasa" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "K. Ohlsson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:4 [ "titulo" => "En: Collagenase in normal pathological connective tissues" "paginaInicial" => "209" "paginaFinal" => "222" "serieFecha" => "1980" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human leukocyte granule elastase: rapid isolation and characterization" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.M.J. Baugh" 1 => "J. Travis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Biochemistry" "fecha" => "1976" "volumen" => "15" "paginaInicial" => "836" "paginaFinal" => "841" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1082346" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Elastase release from human alveolar macrophages; comparison between smokers and non-smokers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.J. Rodríguez" 1 => "R.R. White" 2 => "R.M. Senior" 3 => "E.A. Levine" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "1977" "volumen" => "198" "paginaInicial" => "313" "paginaFinal" => "314" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/910131" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The interactions of 2-macroglobulin with proteinases. Characteristics and specifity of the reaction and a hypotesis concerning its molecular mechanism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.J. Barret" 1 => "P.M. Starkey" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Biochem J" "fecha" => "1973" "volumen" => "133" "paginaInicial" => "709" "paginaFinal" => "724" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4201304" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Activation of human leukocyte elastase by human 2-macroglobulin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D.Y. Twumasi" 1 => "I.E. Liener" 2 => "M. Galdston" 3 => "V. Levytska" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "1977" "volumen" => "267" "paginaInicial" => "61" "paginaFinal" => "63" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/67568" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Granulocyte collagenase and elastase and their interactions with alpha 1 antitrypsin and alpha 2 macroglobulin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "K. Ohlsson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:4 [ "titulo" => "En: Proteases biological control" "paginaInicial" => "591" "paginaFinal" => "602" "serieFecha" => "1975" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Studies in alpha 1 antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. Eriksson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Acta Med Scand" "fecha" => "1965" "volumen" => "177" "numero" => "suppl" "paginaInicial" => "1" "paginaFinal" => "85" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14251847" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The pathogenesis of pulmonary emphysema" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Editorial" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(13)70145-0" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1980" "volumen" => "1" "paginaInicial" => "743" "paginaFinal" => "745" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24429277" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of the protease-anti-protease theory of human destructive lung disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.E. Gadek" 1 => "G.W. Hunninghake" 2 => "G.A. Fells" 3 => "R.L. Zimmerman" 4 => "B.A. Keogh" 5 => "R.G. Crystal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Bull Europ Physiopath Resp" "fecha" => "1980" "volumen" => "16" "numero" => "suppl" "paginaInicial" => "27" "paginaFinal" => "40" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulmonary emphysema and alpha 1 antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. Eriksson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Acta Med Scand" "fecha" => "1964" "volumen" => "177" "paginaInicial" => "175" "paginaFinal" => "179" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14279499" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inherited differences in alpha 1 antitrypsin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F. Kueppers" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:4 [ "titulo" => "En: Genetic determinants of pulmonary disease" "paginaInicial" => "23" "paginaFinal" => "74" "serieFecha" => "1978" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Experimental emphysema induced with purified human neutrophil elastase. Tissue localization of the instilled protease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "A. Janoff" 1 => "B. Sloan" 2 => "G. Weinbaum" 3 => "V. Damiano" 4 => "R.A. Sandhaus" 5 => "J. Elias" 6 => "P. Kimbel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1977.115.3.461" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1977" "volumen" => "115" "paginaInicial" => "461" "paginaFinal" => "478" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/842956" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The induction of pulmonary emphysema with human leukocyte elastase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R.M. Senior" 1 => "H. Tegner" 2 => "C. Kuhn" 3 => "K. Ohlsson" 4 => "B.C. Starcher" 5 => "J.A. Pierce" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1977.116.3.469" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1977" "volumen" => "116" "paginaInicial" => "469" "paginaFinal" => "475" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/900634" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Elastase, collagenase, emphysema and alpha 1 antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Lieberman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "1976" "volumen" => "70" "paginaInicial" => "62" "paginaFinal" => "67" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/179761" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changes in pulmonary connective tissue after a single intatracheal instillation of papain in the rat" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "V. Kobrle" 1 => "J. Hurych" 2 => "R. Holuva" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1982.125.2.239" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1982" "volumen" => "125" "paginaInicial" => "239" "paginaFinal" => "243" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7065529" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The induction of emphysema with elastase. II Changes in conective tissue" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C. Kuhn" 1 => "S.-Y. Yu" 2 => "M. Chraplyvy" 3 => "H.E. Linder" 4 => "R.M. Senior" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lab Invest" "fecha" => "1976" "volumen" => "34" "paginaInicial" => "372" "paginaFinal" => "380" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/177809" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "State of the art. Animal models of emphysema" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.B. Karlinsky" 1 => "G.L. Sinder" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1978.117.6.1109" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1978" "volumen" => "117" "paginaInicial" => "1109" "paginaFinal" => "1133" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/352207" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Experimental emphysema: its production with papain in normal and silicotic rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Gross" 1 => "E.Z. Pfitzer" 2 => "E. Tolker" 3 => "N.A. Babyak" 4 => "M. Kaschak" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arch Environ Hlth" "fecha" => "1965" "volumen" => "11" "paginaInicial" => "50" "paginaFinal" => "58" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The induction of emphysema with elastase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P.D. Kaplan" 1 => "C. Kuhn" 2 => "J.A. Pierce" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Lab Clin Med" "fecha" => "1973" "volumen" => "82" "paginaInicial" => "349" "paginaFinal" => "365" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4728287" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Introduction of experimental emphysema in dogs using leukocyte homogenates" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "V. Marco" 1 => "B. Mass" 2 => "D.R. Meranze" 3 => "G. Weinbaum" 4 => "P. Kimbel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1971.104.4.595" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1971" "volumen" => "104" "paginaInicial" => "595" "paginaFinal" => "598" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5094060" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Collagenase in the lower respiratory tract of patients with idiophatic pulmonary fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "J.E. Gadek" 1 => "J.A. Kelman" 2 => "S.E. Weinberger" 3 => "A.L. Horwitz" 4 => "H.Y. Reynolds" 5 => "J.D. Fulmer" 6 => "R.G. Crystal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM197910043011401" "Revista" => array:6 [ "tituloSerie" => "New Engl J Med" "fecha" => "1979" "volumen" => "301" "paginaInicial" => "737" "paginaFinal" => "742" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/225666" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Granulocite collagenase: selective digestion of type 1 over type 111 collagen" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.L. Horwitz" 1 => "A.J. Hance" 2 => "R.G. Crystal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Proc Nat Acad Sci Wash" "fecha" => "1977" "volumen" => "74" "paginaInicial" => "897" "paginaFinal" => "901" ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Degradaron if a cartilage proteoglican by human leukocyte granule neutral proteases a model of joint injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Janoff" 1 => "G. Feinstein" 2 => "C.J. Malemud" 3 => "J.M. Elias" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI108317" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "1976" "volumen" => "57" "paginaInicial" => "615" "paginaFinal" => "624" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/129482" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung elastin content in normal and emphysematous lungs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G.M. Turino" 1 => "S. Keller" 2 => "P. Chrzanowski" 3 => "M. Osman" 4 => "J. Cerreta" 5 => "I. Mandl" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Bull Europ Physiopath Resp" "fecha" => "1980" "volumen" => "16" "numero" => "suppl" "paginaInicial" => "43" "paginaFinal" => "56" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The conective tissue of the lung" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.J. Hance" 1 => "R.G. Crystal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1975.112.5.657" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1975" "volumen" => "112" "paginaInicial" => "657" "paginaFinal" => "711" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1103668" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aetiology of emphysema" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.S. Dunnill" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Bull Europ Physiopath Resp" "fecha" => "1979" "volumen" => "15" "paginaInicial" => "1015" "paginaFinal" => "1029" ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulmonary emphysema and 1-antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.C.S. Hutchinson" 1 => "P.J.L. Cook" 2 => "C.E. Barter" 3 => "H. Harris" 4 => "P. Hugh-Jones" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Brit Med J" "fecha" => "1971" "volumen" => "1" "paginaInicial" => "689" "paginaFinal" => "694" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/435740" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comparative study of the severity of emphysema in necropsy populations in three different countries" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "W.M. Thurlbeck" 1 => "R.C. Ryder" 2 => "N. Sternby" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1974.109.2.239" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1974" "volumen" => "109" "paginaInicial" => "239" "paginaFinal" => "248" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4811778" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Possible mechanisms of emphysema in smokers. Cigarrette smoke condensate suppresses protease inhibition in vitro" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Janoff" 1 => "H. Carp" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1977.116.1.65" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1977" "volumen" => "116" "paginaInicial" => "65" "paginaFinal" => "72" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/301725" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Possible mechanisms of emphysema smokers. In vitro suppression of serum elastase inhibitory capacity by antioxidants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F. Carp" 1 => "A. Janoff" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1978.118.3.617" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1978" "volumen" => "118" "paginaInicial" => "617" "paginaFinal" => "621" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/101105" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Synthesis and secretion of alpha 2 macroglobulin by cultured adherent lung cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.F. Mosher" 1 => "O. Saksela" 2 => "A. Valeri" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI108854" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "1978" "volumen" => "60" "paginaInicial" => "1036" "paginaFinal" => "1045" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/71307" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Secretion of alpha 2 macroglobulin by human alveolar macrophages" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.R. White" 1 => "A. Janoff" 2 => "H.P. Godfrey" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1980" "volumen" => "121" "numero" => "suppl" "paginaInicial" => "418 (A)" ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Syntesis and secretion of alpha 2 macroglobulin by cultured human fibroblast" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.F. Mosher" 1 => "D.A. Wing" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Exp Med" "fecha" => "1976" "volumen" => "143" "paginaInicial" => "462" "paginaFinal" => "467" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/55456" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proteinase (elastase) inhibitor from the ciliated membranes of the human respiratory tract" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "K. Hochstrasser" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Methods Enzymol" "fecha" => "1976" "volumen" => "45" "paginaInicial" => "869" "paginaFinal" => "872" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1012039" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biochemical analyses of bronchoalveolar lavage fluids of healthy human volunteer smokers and non smokers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.B. Low" 1 => "G.S. Davis" 2 => "M.S. Giancola" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1978.118.5.863" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1978" "volumen" => "118" "paginaInicial" => "863" "paginaFinal" => "875" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/736357" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Studies on the structure of elastin and the mechanims of action of elastolytic enzymes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Robert" 1 => "L. Robert" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:6 [ "editores" => "E.A.Balazs" "paginaInicial" => "665" "paginaFinal" => "670" "serieVolumen" => "vol 1" "serieTitulo" => "Chemistry molecular biology of the intercellular matrix" "serieFecha" => "1970" ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of elastase from granulocytes by the low molecular weight bronchial protease inhibitor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K. Ohlsson" 1 => "H. Tegner" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Scand J Clin Lab Invest" "fecha" => "1976" "volumen" => "36" "paginaInicial" => "437" "paginaFinal" => "445" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/185683" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interactions between granulocyte elastase and collagenase and the plasma proteinase inhibitors in vitro and in vivo" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K. Ohlsson" 1 => "M. Delshammar" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:4 [ "titulo" => "En: Dynamics of conective tissue macromolecules" "paginaInicial" => "259" "paginaFinal" => "275" "serieFecha" => "1975" ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proteases and antiproteases in bronchoalveolar lavage" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Hayem" 1 => "A. Scharfman" 2 => "A. Laine" 3 => "J.J. Lafitte" 4 => "B. Sablonniére" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Bull Europ Physiopath Resp" "fecha" => "1980" "volumen" => "16" "numero" => "suppl" "paginaInicial" => "247" "paginaFinal" => "258" ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Definition and classification of chronic bronchitis" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Medical Research Council" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1965" "volumen" => "1" "paginaInicial" => "775" "paginaFinal" => "799" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2895308" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunochemical quantitation of antigens by single radial immunodiffusion" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Mancini" 1 => "A.D. Carbonara" 2 => "J.F. Heremans" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Immunochemistry" "fecha" => "1965" "volumen" => "2" "paginaInicial" => "235" "paginaFinal" => "254" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4956917" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alpha 1 antitrypsin and alpha 2 macroglobulin, interactions with human neutrophil collagenase and elastase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "K. Olhsson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann NY Acad Sci" "fecha" => "1975" "volumen" => "256" "paginaInicial" => "409" "paginaFinal" => "419" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/51604" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A study of plasma proteins in the sol phase of sputum from patients with chronic bronchitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.A. Stokley" 1 => "M. Mistry" 2 => "A.R. Bradwell" 3 => "D. Burnett" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "1979" "volumen" => "34" "paginaInicial" => "777" "paginaFinal" => "782" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/542918" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interrelationships between the human alveolar macrophage and alpha 1 antitrypsin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A.B. Cohen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI107475" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "1973" "volumen" => "52" "paginaInicial" => "2793" "paginaFinal" => "2799" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4201266" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "49." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum and sputum alpha 2 macroglobulin in patients with chronic obstrucive airways disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. Burnett" 1 => "R.A. Stokley" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "1981" "volumen" => "36" "paginaInicial" => "512" "paginaFinal" => "516" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6171904" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0250" "etiqueta" => "50." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protease inhibitors in chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T.B. Barnett" 1 => "D. Gottovi" 2 => "M.A. Johnson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/arrd.1975.111.5.587" "Revista" => array:6 [ "tituloSerie" => "Am Rev Respir Dis" "fecha" => "1975" "volumen" => "111" "paginaInicial" => "587" "paginaFinal" => "593" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1079422" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "es" "url" => "/03002896/0000002000000002/v1_201509151130/S0300289615322584/v1_201509151130/es/main.assets" "Apartado" => array:4 [ "identificador" => "9277" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Originales" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03002896/0000002000000002/v1_201509151130/S0300289615322584/v1_201509151130/es/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289615322584?idApp=UINPBA00003Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 2 | 7 |
| 2024 October | 31 | 16 | 47 |
| 2024 September | 26 | 13 | 39 |
| 2024 August | 43 | 32 | 75 |
| 2024 July | 34 | 24 | 58 |
| 2024 June | 48 | 27 | 75 |
| 2024 May | 48 | 41 | 89 |
| 2024 April | 21 | 20 | 41 |
| 2024 March | 36 | 32 | 68 |
| 2024 February | 32 | 30 | 62 |
| 2024 January | 0 | 3 | 3 |
| 2023 November | 0 | 2 | 2 |
| 2023 October | 3 | 10 | 13 |
| 2023 September | 4 | 8 | 12 |
| 2023 August | 7 | 16 | 23 |
| 2023 July | 2 | 17 | 19 |
| 2023 June | 0 | 2 | 2 |
| 2023 May | 0 | 5 | 5 |
| 2023 April | 0 | 1 | 1 |
| 2023 March | 6 | 0 | 6 |
| 2023 February | 24 | 16 | 40 |
| 2023 January | 29 | 31 | 60 |
| 2022 December | 30 | 18 | 48 |
| 2022 November | 42 | 20 | 62 |
| 2022 October | 36 | 41 | 77 |
| 2022 September | 31 | 16 | 47 |
| 2022 August | 25 | 30 | 55 |
| 2022 July | 33 | 43 | 76 |
| 2022 June | 34 | 31 | 65 |
| 2022 May | 29 | 25 | 54 |
| 2022 April | 38 | 26 | 64 |
| 2022 March | 34 | 27 | 61 |
| 2022 February | 39 | 21 | 60 |
| 2022 January | 33 | 33 | 66 |
| 2021 December | 18 | 29 | 47 |
| 2021 November | 21 | 36 | 57 |
| 2021 October | 23 | 43 | 66 |
| 2021 September | 14 | 30 | 44 |
| 2021 August | 13 | 19 | 32 |
| 2021 July | 41 | 26 | 67 |
| 2021 June | 25 | 16 | 41 |
| 2021 May | 30 | 19 | 49 |
| 2021 April | 27 | 43 | 70 |
| 2021 March | 39 | 23 | 62 |
| 2021 February | 17 | 12 | 29 |
| 2021 January | 18 | 22 | 40 |
| 2020 December | 16 | 10 | 26 |
| 2020 November | 15 | 5 | 20 |
| 2020 October | 2 | 4 | 6 |
| 2020 September | 17 | 6 | 23 |
| 2020 August | 23 | 15 | 38 |
| 2020 July | 17 | 20 | 37 |
| 2020 June | 11 | 6 | 17 |
| 2020 May | 15 | 12 | 27 |
| 2020 April | 16 | 10 | 26 |
| 2020 March | 33 | 37 | 70 |
| 2020 February | 14 | 21 | 35 |
| 2020 January | 34 | 19 | 53 |
| 2019 December | 30 | 38 | 68 |
| 2019 November | 30 | 24 | 54 |
| 2019 October | 11 | 31 | 42 |
| 2019 September | 19 | 31 | 50 |
| 2019 August | 10 | 18 | 28 |
| 2019 July | 8 | 27 | 35 |
| 2019 June | 22 | 24 | 46 |
| 2019 May | 17 | 28 | 45 |
| 2019 April | 47 | 76 | 123 |
| 2019 March | 13 | 30 | 43 |
| 2019 February | 9 | 12 | 21 |
| 2019 January | 11 | 4 | 15 |
| 2018 December | 22 | 9 | 31 |
| 2018 November | 16 | 30 | 46 |
| 2018 October | 14 | 27 | 41 |
| 2018 September | 16 | 52 | 68 |
| 2018 May | 5 | 1 | 6 |
| 2018 April | 5 | 2 | 7 |
| 2018 March | 13 | 9 | 22 |
| 2018 February | 5 | 12 | 17 |
| 2018 January | 3 | 8 | 11 |
| 2017 December | 10 | 23 | 33 |
| 2017 November | 9 | 40 | 49 |
| 2017 October | 7 | 69 | 76 |
| 2017 September | 14 | 55 | 69 |
| 2017 August | 7 | 45 | 52 |
| 2017 July | 4 | 44 | 48 |
| 2017 June | 12 | 58 | 70 |
| 2017 May | 13 | 70 | 83 |
| 2017 April | 32 | 69 | 101 |
| 2017 March | 5 | 67 | 72 |
| 2017 February | 9 | 71 | 80 |
| 2017 January | 6 | 36 | 42 |
| 2016 December | 6 | 32 | 38 |
| 2016 November | 18 | 64 | 82 |
| 2016 October | 17 | 85 | 102 |
| 2016 September | 26 | 99 | 125 |
| 2016 August | 65 | 57 | 122 |
| 2016 July | 36 | 24 | 60 |
| 2016 June | 45 | 38 | 83 |
| 2016 May | 16 | 11 | 27 |
| 2016 April | 8 | 0 | 8 |
| 2016 March | 12 | 0 | 12 |
| 2016 February | 10 | 1 | 11 |
| 2016 January | 23 | 13 | 36 |
| 2015 December | 22 | 14 | 36 |
| 2015 November | 27 | 13 | 40 |
| 2015 October | 7 | 1 | 8 |
| 2015 September | 2 | 0 | 2 |
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