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        "resumen" => "<span class="elsevierStyleSectionTitle">Antecedentes</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El factor de necrosis tumoral alfa &#40;TNF-a&#41; se ha implicado en la p&#233;rdida de masa muscular en la enfermedad pulmonar obstructiva cr&#243;nica &#40;EPOC&#41; y otras enfermedades consumtivas&#46; Su producci&#243;n estar&#237;a en relaci&#243;n con la inflamaci&#243;n derivada de la propia enfermedad pulmonar o el h&#225;bito tab&#225;quico&#44; llegando al m&#250;sculo por el torrente sangu&#237;neo&#46; Sin embargo&#44; tambi&#233;n se ha sugerido que el TNF-&#945; podr&#237;a expresarse directamente en el tejido muscular&#46; Sea cual fuere el lugar de producci&#243;n&#44; la relaci&#243;n del TNF-&#945; con el da&#241;o muscular subsiguiente no es clara</p> <span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Hemos estudiado la expresi&#243;n del TNF-&#945; y una interleucina inhibidora de su producci&#243;n &#40;IL-10&#41; en los m&#250;sculos respiratorios principales y en un m&#250;sculo perif&#233;rico del perro</p> <span class="elsevierStyleSectionTitle">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se han incluido nueve animales machos&#44; adultos j&#243;venes de raza Beagle&#46; En todos ellos se tomaron biopsias del diafragma &#40;Df&#41;&#44; del intercostal externo &#40;IExt&#41; y de un m&#250;sculo de las extremidades &#40;vasto interno del cu&#225;driceps o VInt&#41;&#46; Se analiz&#243; la expresi&#243;n de los genes de TNF-&#945; e IL-10&#44; a trav&#233;s de la determinaci&#243;n de sus ARNm corres-pondientes&#44; utilizando la transcripci&#243;n reversa y reacci&#243;n en cadena de la polimerasa &#40;RT-PCR&#41;&#46; Tambi&#233;n se evalu&#243; el da&#241;o sarcol&#233;mico mediante detecci&#243;n de fibronectina intra-celular &#40;inmunohistoqu&#237;mica&#41;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Los valores de expresi&#243;n de ambas citocinas evidenciaron una amplia dispersi&#243;n interindividual&#46; Por un lado&#44; la expresi&#243;n de TNF-&#945; fue m&#237;nima en Df y IExt &#40;respectivamente&#44; 0&#44;02 &#177; 0&#44;03 y 0&#44;05 &#177; 0&#44;06 u&#46;a&#46;&#41;&#44; con valores relativamente elevados en VInt &#40;0&#44;14 &#177; 0&#44;08 u&#46;a&#46;&#41;&#46; A su vez&#44; la IL-10 evidenciaba valores bajos en DF &#40;0&#44;6 &#177; 0&#44;5 u&#46;a&#46;&#41;&#44; que eran algo superiores en IExt &#40;2&#44;7 &#177; 1&#44;9 u&#46;a&#46;&#59; p &#60; 0&#44;01&#41; y VInt &#40;1&#44;6 &#177; 1&#44;7 u&#46;a&#46;&#41;&#46; El da&#241;o sarcol&#233;mico era m&#237;nimo en los tres m&#250;sculos y se relacionaba con la expresi&#243;n de TNF-&#945; en el m&#250;sculo perif&#233;rico &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;682&#59; p &#60; 0&#44;05&#41;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">a&#41; TNF-&#945; e IL-10 parecen expresarse constitutivamente en el m&#250;sculo esquel&#233;tico canino&#59; b&#41; los valores basales de expresi&#243;n del TNF-&#945; son menores en los m&#250;sculos repiratorios que en los de las extremidades mos-trando relaci&#243;n en estos &#250;ltimos con el da&#241;o de membrana</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Tumor necrosis factor alpha &#40;TNF-&#945;&#41; has been implicated in loss of muscle mass in chronic obstructive pulmonary disease and other consumptive processes&#46; TNF-&#945; production would be related to inflammation arising from pulmonary disease itself or&#44; alternatively&#44; from smoking&#44; and would be carried to the muscle through the blood stream&#46; However&#44; it has also been suggested that TNF-&#945; may be expressed directly in muscle tissue&#46; Regardless the site of production of TNF-&#945;&#44; its relation to subsequent muscle damage is unclear</p> <span class="elsevierStyleSectionTitle">Objective</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">We studied the expression of TNF-&#945; and an interleukin inhibitor of its production &#40;IL-10&#41; in the main respiratory muscles and a peripheral muscle in the dog</p> <span class="elsevierStyleSectionTitle">Method</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nine young&#44; male Beagle dogs were included&#46; From all animals we obtained a biopsy of the diaphragm &#40;Dph&#41; and external intercostal &#40;ExtI&#41; muscles and a leg muscle &#40;internal vastus of the quadriceps&#44; IntV&#41;&#46; TNF-&#945; and IL-10 gene expressions were measured through the analysis of mes-senger RNA levels&#44; using reverse transcription and polymera-se chain reaction&#46; We also assessed sarcolemmal damage using intracellular fibronectin detection &#40;immunohistochemistry&#41;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The expression of both cytokines showed wide in-terindividual variability&#46; On the one hand&#44; TNF-&#945; &#40;was very low in Dph and ExtI &#40;0&#46;02 &#177; 0&#46;03 and 0&#46;05 &#177; 0&#46;06 a&#46;u&#46;&#44; respec-tively&#41;&#44; but relatively high in the IntV &#40;0&#46;14 &#177; 0&#46;08 a&#46;u&#46;&#41;&#46; IL-10 expression&#44; on the other hand was low in the Dph &#40;0&#46;06 &#177; 0&#46;05 a&#46;u&#46;&#41; and slightly higher in the ExtI &#40;2&#46;7 &#177; 1&#46;9 a&#46;u&#46;&#44; p &#60; 0&#46;01&#41; and IntV &#40;1&#46;6 &#177; 1&#46;7 a&#46;u&#46;&#41;&#46; Sarcolemmal damage was minimal in all three muscles and was related to TNF-&#945; expression in the peripheral muscle &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;682&#44; p &#60; 0&#46;05&#41;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">1&#41; TNF-&#945; and IL-10 appear to be constitutively expressed within the skeletal muscle in dogs&#46; 2&#41; Basal TNF-&#945; expression is lower in respiratory muscles than in peripheral muscles&#46; 3&#41; The expression in the latter is related to membrane damage</p>"
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                          "autores" => array:6 [
                            0 => "M&#46; Orozco-Levi"
                            1 => "J&#46; Gea"
                            2 => "J&#46; Lloreta"
                            3 => "M&#46;A&#46; Felez"
                            4 => "J&#46;L&#46; Minguella"
                            5 => "S&#46; Serrano"
                          ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
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                        "volumen" => "13"
                        "paginaInicial" => "371"
                        "paginaFinal" => "378"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10065684"
                            "web" => "Medline"
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              "identificador" => "bib0025"
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                      "titulo" => "Systemic effects of chronic obstructive pulmonary disease"
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                          "autores" => array:1 [
                            0 => "A&#46;G&#46; Agusti"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Novartis Found Symp"
                        "fecha" => "2001"
                        "volumen" => "234"
                        "paginaInicial" => "242"
                        "paginaFinal" => "254"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11199099"
                            "web" => "Medline"
                          ]
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            5 => array:3 [
              "identificador" => "bib0030"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased resting energy expenditure is related to plasma TNF-alpha concentration in stable COPD patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;T&#46; Nguyen"
                            1 => "M&#46; Bedu"
                            2 => "D&#46; Caillaud"
                            3 => "B&#46; Beaufrere"
                            4 => "G&#46; Beaujon"
                            5 => "M&#46; Vasson"
                          ]
                        ]
                      ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1054/clnu.1999.0034"
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                        "tituloSerie" => "Clin Nutr"
                        "fecha" => "1999"
                        "volumen" => "18"
                        "paginaInicial" => "269"
                        "paginaFinal" => "274"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10601533"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
              ]
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            6 => array:3 [
              "identificador" => "bib0035"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tumor necrosis factor- alpha levels and weight loss in chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Di Francia"
                            1 => "D&#46; Barbier"
                            2 => "J&#46;L&#46; Mege"
                            3 => "J&#46; Orehek"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.150.5.7952575"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1994"
                        "volumen" => "150"
                        "paginaInicial" => "1453"
                        "paginaFinal" => "1455"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7952575"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cytokines and chemokines are both expressed by human myoblasts&#58; possible relevance for the immune pathogenesis of muscle inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; De Rossi"
                            1 => "P&#46; Bernasconi"
                            2 => "F&#46; Baggi"
                            3 => "R&#46; De Waal Malefyt"
                            4 => "R&#46; Mantegazza"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int Immunol"
                        "fecha" => "2000"
                        "volumen" => "12"
                        "paginaInicial" => "1329"
                        "paginaFinal" => "1335"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10967028"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            8 => array:3 [
              "identificador" => "bib0045"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diaphragm muscle fiber injury after inspiratory resistive breathing"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Zhu"
                            1 => "B&#46;J&#46; Petrof"
                            2 => "J&#46; Gea"
                            3 => "N&#46; Comtois"
                            4 => "A&#46;E&#46; Grassino"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.155.3.9116995"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1997"
                        "volumen" => "155"
                        "paginaInicial" => "1110"
                        "paginaFinal" => "1116"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9116995"
                            "web" => "Medline"
                          ]
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                      ]
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                ]
              ]
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            9 => array:3 [
              "identificador" => "bib0050"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Measurement of dog cytokines by reverse transcription-quantitative competitive polymerase chain reaction"
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                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Pinelli"
                            1 => "S&#46;Y&#46; Van der Kaaij"
                            2 => "C&#46;P&#46; Broeren"
                            3 => "E&#46;J&#46; Ruitenberg"
                            4 => "V&#46;P&#46; Rutten"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunogenetics"
                        "fecha" => "1999"
                        "volumen" => "49"
                        "paginaInicial" => "696"
                        "paginaFinal" => "699"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10369929"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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            10 => array:3 [
              "identificador" => "bib0055"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cloning and expression of canine interleukin-10"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "P&#46; Lu"
                            1 => "K&#46; Zucker"
                            2 => "L&#46; Fuller"
                            3 => "A&#46; Tzakis"
                            4 => "V&#46; Esquenazi"
                            5 => "J&#46; Miller"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1089/jir.1995.15.1103"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Interferon Cytokine Res"
                        "fecha" => "1995"
                        "volumen" => "15"
                        "paginaInicial" => "1103"
                        "paginaFinal" => "1109"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8746793"
                            "web" => "Medline"
                          ]
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                    ]
                  ]
                ]
              ]
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            11 => array:3 [
              "identificador" => "bib0060"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Evaluacion del dano de membrana en las fibras musculares&#58; marcadores biologicos frente a tecnicas estandar"
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                        0 => array:2 [
                          "etal" => false
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                            0 => "J&#46;B&#46; Galdiz"
                            1 => "J&#46; Palacio"
                            2 => "J&#46; Alvarez"
                            3 => "M&#46; Marinan"
                            4 => "M&#46; Orozco-Levi"
                            5 => "J&#46; Gea"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Bronconeumol"
                        "fecha" => "2001"
                        "volumen" => "37"
                        "numero" => "Supl 1"
                        "paginaInicial" => "16"
                        "paginaFinal" => "17"
                      ]
                    ]
                  ]
                ]
              ]
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            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:1 [
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                    0 => array:1 [
                      "LibroEditado" => array:2 [
                        "titulo" => "The cytokine handbook"
                        "serieFecha" => "1994"
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                    ]
                  ]
                ]
              ]
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            13 => array:3 [
              "identificador" => "bib0070"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Nicotine induces endothelial TNF-alpha expression&#44; which mediates growth retardation in vitro"
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                          "etal" => false
                          "autores" => array:6 [
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                            1 => "B&#46; Kann"
                            2 => "L&#46; Strande"
                            3 => "P&#46; Vemulapalli"
                            4 => "C&#46; Hewitt"
                            5 => "J&#46;B&#46; Alexander"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1006/jsre.2001.6215"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Surg Res"
                        "fecha" => "2001"
                        "volumen" => "99"
                        "paginaInicial" => "381"
                        "paginaFinal" => "384"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11469915"
                            "web" => "Medline"
                          ]
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                ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Skeletal muscle fibres express TNF-&#945; in mammals &#91;abstract&#93;"
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                          "etal" => true
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                            4 => "M&#46; Orozco-Levi"
                            5 => "P&#46; Martinez"
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2002"
                        "volumen" => "165"
                        "numero" => "Suppl"
                        "paginaInicial" => "A258"
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                    ]
                  ]
                ]
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            15 => array:3 [
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                    0 => array:2 [
                      "titulo" => "Effects of tumor necrosis factor-alpha on insulin action in cultured human muscle cells"
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                          "etal" => false
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                            0 => "R&#46; Halse"
                            1 => "S&#46;L&#46; Pearson"
                            2 => "J&#46;G&#46; McCormack"
                            3 => "S&#46;J&#46; Yeaman"
                            4 => "R&#46; Taylor"
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                    ]
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                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Diabetes"
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                        "paginaInicial" => "1102"
                        "paginaFinal" => "1109"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11334414"
                            "web" => "Medline"
                          ]
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                    0 => array:2 [
                      "titulo" => "Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients"
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                            2 => "A&#46;M&#46; Schols"
                            3 => "W&#46;A&#46; Buurman"
                            4 => "E&#46;F&#46; Wouters"
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                    0 => array:2 [
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                        "tituloSerie" => "J Clin Oncol"
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                        "volumen" => "13"
                        "paginaInicial" => "2600"
                        "paginaFinal" => "2605"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7595713"
                            "web" => "Medline"
                          ]
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                ]
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              "identificador" => "bib0090"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Circulating leptin in patients with chronic obstructive pulmonary disease"
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                            4 => "H&#46; Saito"
                            5 => "H&#46; Yuki"
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.159.4.9806134"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1999"
                        "volumen" => "159"
                        "paginaInicial" => "1215"
                        "paginaFinal" => "1219"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10194168"
                            "web" => "Medline"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease"
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                          "etal" => false
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                            1 => "W&#46;A&#46; Buurman"
                            2 => "A&#46;J&#46; Staal van den Brekel"
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                            4 => "E&#46;F&#46; Wouters"
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
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                        "tituloSerie" => "Thorax"
                        "fecha" => "1996"
                        "volumen" => "51"
                        "paginaInicial" => "819"
                        "paginaFinal" => "824"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8795671"
                            "web" => "Medline"
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              "identificador" => "bib0100"
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                    0 => array:2 [
                      "titulo" => "Cytokines and oxidative signalling in skeletal muscle"
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                          "etal" => false
                          "autores" => array:2 [
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1365-201x.2001.00824.x"
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                        "tituloSerie" => "Acta Physiol Scand"
                        "fecha" => "2001"
                        "volumen" => "171"
                        "paginaInicial" => "225"
                        "paginaFinal" => "232"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11412134"
                            "web" => "Medline"
                          ]
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                ]
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            20 => array:3 [
              "identificador" => "bib0105"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease- 1 from alveolar macrophages in cigarette smokers&#58; regulation by interleukin-10"
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                        0 => array:2 [
                          "etal" => false
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                            2 => "B&#46;G&#46; Oliver"
                            3 => "W&#46; Mattos"
                            4 => "P&#46;J&#46; Barnes"
                            5 => "J&#46;F&#46; Chung"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.162.4.9910097"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2000"
                        "volumen" => "162"
                        "paginaInicial" => "1355"
                        "paginaFinal" => "1360"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11029344"
                            "web" => "Medline"
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            21 => array:3 [
              "identificador" => "bib0110"
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                    0 => array:2 [
                      "titulo" => "Interleukin-10&#58; a novel stimulatory factor for mast cells and their progenitors"
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                          "etal" => false
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                            2 => "M&#46;W&#46; Bond"
                            3 => "T&#46;R&#46; Mosmann"
                            4 => "K&#46;W&#46; Moore"
                            5 => "D&#46;M&#46; Rennick"
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Exp Med"
                        "fecha" => "1991"
                        "volumen" => "173"
                        "paginaInicial" => "507"
                        "paginaFinal" => "510"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1899106"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "IL- 10&#44; a novel growth cofactor for mature and immature T cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "I&#46;A&#46; MacNeil"
                            1 => "T&#46; Suda"
                            2 => "K&#46;W&#46; Mootre"
                            3 => "T&#46;R&#46; Mosmann"
                            4 => "A&#46; Zlotnik"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "1990"
                        "volumen" => "145"
                        "paginaInicial" => "4167"
                        "paginaFinal" => "4173"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2124236"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleukin-10 level in sputum is reduced in bronchial asthma&#44; COPD and in smokers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Takanashi"
                            1 => "Y&#46; Hasegawa"
                            2 => "Y&#46; Kanehira"
                            3 => "K&#46; Yamamoto"
                            4 => "K&#46; Fujimoto"
                            5 => "K&#46; Satoh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "1999"
                        "volumen" => "14"
                        "paginaInicial" => "309"
                        "paginaFinal" => "314"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10515406"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleukin-10 regulation in normal subjects and patients with asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46; Borish"
                            1 => "A&#46; Aarons"
                            2 => "J&#46; Rumbyrt"
                            3 => "P&#46; Cvietusa"
                            4 => "J&#46; Negri"
                            5 => "S&#46; Wenzel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1996"
                        "volumen" => "97"
                        "paginaInicial" => "1288"
                        "paginaFinal" => "1296"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8648025"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased expression of the interleukin-10 gene by alveolar macrophages in interstitial lung disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;A&#46; Martinez"
                            1 => "T&#46;E&#46; J&#46;r&#46; King"
                            2 => "K&#46; Brown"
                            3 => "C&#46;A&#46; Jennings"
                            4 => "L&#46; Borish"
                            5 => "R&#46;L&#46; Mortenson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol"
                        "fecha" => "1997"
                        "volumen" => "273"
                        "paginaInicial" => "L676"
                        "paginaFinal" => "L683"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9316504"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1&#44; granulocyte-macrophage colonystimulating factor&#44; and interferon-&#947; release from alveolar macrophages in asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; John"
                            1 => "S&#46; Lim"
                            2 => "J&#46; Seybold"
                            3 => "P&#46; Jose"
                            4 => "A&#46; Rochibaud"
                            5 => "B&#46; O&#39;Connor"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.157.1.9703079"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1998"
                        "volumen" => "157"
                        "paginaInicial" => "256"
                        "paginaFinal" => "262"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9445307"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Expression of myosin heavy-chain isoforms in the respiratory muscles following inspiratory resistive breathing"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Gea"
                            1 => "Q&#46; Hamid"
                            2 => "G&#46; Czaika"
                            3 => "E&#46; Zhu"
                            4 => "V&#46; Mohan-ram"
                            5 => "G&#46; Goldspink"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.161.4.99040103"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2000"
                        "volumen" => "161"
                        "paginaInicial" => "1274"
                        "paginaFinal" => "1278"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10764323"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Morphological and functional recovery from diaphragm injury&#58; an in vivo rat diaphragm injury model"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Hayot"
                            1 => "E&#46; Barreiro"
                            2 => "A&#46; Perez"
                            3 => "G&#46; Czaika"
                            4 => "A&#46;S&#46; Comtois"
                            5 => "A&#46;E&#46; Grassino"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Appl Physiol"
                        "fecha" => "2001"
                        "volumen" => "90"
                        "paginaInicial" => "2269"
                        "paginaFinal" => "2278"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11356792"
                            "web" => "Medline"
                          ]
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                    ]
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                ]
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Vol. 38. Issue 7.
Pages 311-316 (July 2002)
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Vol. 38. Issue 7.
Pages 311-316 (July 2002)
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Expresión de los genes de la interleucina 10 (IL-10) y del factor de necrosis tumoral alfa (TNF-α) en músculos respiratorios y periféricos. Relación con el daño sarcolémico
Interleukin 10 and tumor necrosis factor alpha gene expression in respiratory and peripheral muscle. Relation to sarcolemmal damage
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J. Palacioa,
Corresponding author
jgea@imim.es

Correspondencia: Dr. J. Gea. Servicio de Neumología. Hospital del Mar.P.° Marítim, 27. 08003 Barcelona
, J.B. Gáldizb, J.J. Bechc, M. Mariñánb, C. Casadevalla, P. Martínezc, J. Geaa
a Servicio de Neumología. Unidad de Investigación Respiratoria y Ambiental. Hospital del Mar. IMIM. Fisiopatología (CEXS). Universitat Pompeu Fabra. Barcelona
b Servicio de Neumología. Hospital de Cruces. Universidad del País Vasco. Bilbao
c Unidad de Inmunología.Instituto de Biotecnología y Biomedicina. Universitat Autònoma de Barcelona. Barcelona
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Antecedentes

El factor de necrosis tumoral alfa (TNF-a) se ha implicado en la pérdida de masa muscular en la enfermedad pulmonar obstructiva crónica (EPOC) y otras enfermedades consumtivas. Su producción estaría en relación con la inflamación derivada de la propia enfermedad pulmonar o el hábito tabáquico, llegando al músculo por el torrente sanguíneo. Sin embargo, también se ha sugerido que el TNF-α podría expresarse directamente en el tejido muscular. Sea cual fuere el lugar de producción, la relación del TNF-α con el daño muscular subsiguiente no es clara

Objetivo

Hemos estudiado la expresión del TNF-α y una interleucina inhibidora de su producción (IL-10) en los músculos respiratorios principales y en un músculo periférico del perro

Métodos

Se han incluido nueve animales machos, adultos jóvenes de raza Beagle. En todos ellos se tomaron biopsias del diafragma (Df), del intercostal externo (IExt) y de un músculo de las extremidades (vasto interno del cuádriceps o VInt). Se analizó la expresión de los genes de TNF-α e IL-10, a través de la determinación de sus ARNm corres-pondientes, utilizando la transcripción reversa y reacción en cadena de la polimerasa (RT-PCR). También se evaluó el daño sarcolémico mediante detección de fibronectina intra-celular (inmunohistoquímica)

Resultados

Los valores de expresión de ambas citocinas evidenciaron una amplia dispersión interindividual. Por un lado, la expresión de TNF-α fue mínima en Df y IExt (respectivamente, 0,02 ± 0,03 y 0,05 ± 0,06 u.a.), con valores relativamente elevados en VInt (0,14 ± 0,08 u.a.). A su vez, la IL-10 evidenciaba valores bajos en DF (0,6 ± 0,5 u.a.), que eran algo superiores en IExt (2,7 ± 1,9 u.a.; p < 0,01) y VInt (1,6 ± 1,7 u.a.). El daño sarcolémico era mínimo en los tres músculos y se relacionaba con la expresión de TNF-α en el músculo periférico (r=0,682; p < 0,05)

Conclusiones

a) TNF-α e IL-10 parecen expresarse constitutivamente en el músculo esquelético canino; b) los valores basales de expresión del TNF-α son menores en los músculos repiratorios que en los de las extremidades mos-trando relación en estos últimos con el daño de membrana

Palabras clave:
Músculos respiratorios
Músculos periféricos
Citocinas
Background

Tumor necrosis factor alpha (TNF-α) has been implicated in loss of muscle mass in chronic obstructive pulmonary disease and other consumptive processes. TNF-α production would be related to inflammation arising from pulmonary disease itself or, alternatively, from smoking, and would be carried to the muscle through the blood stream. However, it has also been suggested that TNF-α may be expressed directly in muscle tissue. Regardless the site of production of TNF-α, its relation to subsequent muscle damage is unclear

Objective

We studied the expression of TNF-α and an interleukin inhibitor of its production (IL-10) in the main respiratory muscles and a peripheral muscle in the dog

Method

Nine young, male Beagle dogs were included. From all animals we obtained a biopsy of the diaphragm (Dph) and external intercostal (ExtI) muscles and a leg muscle (internal vastus of the quadriceps, IntV). TNF-α and IL-10 gene expressions were measured through the analysis of mes-senger RNA levels, using reverse transcription and polymera-se chain reaction. We also assessed sarcolemmal damage using intracellular fibronectin detection (immunohistochemistry)

Results

The expression of both cytokines showed wide in-terindividual variability. On the one hand, TNF-α (was very low in Dph and ExtI (0.02 ± 0.03 and 0.05 ± 0.06 a.u., respec-tively), but relatively high in the IntV (0.14 ± 0.08 a.u.). IL-10 expression, on the other hand was low in the Dph (0.06 ± 0.05 a.u.) and slightly higher in the ExtI (2.7 ± 1.9 a.u., p < 0.01) and IntV (1.6 ± 1.7 a.u.). Sarcolemmal damage was minimal in all three muscles and was related to TNF-α expression in the peripheral muscle (r=0.682, p < 0.05)

Conclusions

1) TNF-α and IL-10 appear to be constitutively expressed within the skeletal muscle in dogs. 2) Basal TNF-α expression is lower in respiratory muscles than in peripheral muscles. 3) The expression in the latter is related to membrane damage

Keywords:
Respiratory Muscles
Peripheral Muscles
Cytokines
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Bibliografía
[1.]
A.G.N. Agusti, J. Cotes, P.D. Wagner.
Responses to exercise in lung diseases. En: Wipp Roca J, editors. Clinical exercise testing.
Eur Respir Monograph, 6 (1997), pp. 32-50
[2.]
K.J. Killian, P. LeBlanc, D.H. Martin, E. Summers, N.L. Jones, E.J.M. Campbell.
Exercise capacity and ventilatory, circulatory, and symptom limitation in patients with chronic airflow limitation.
Am Rev Respir Dis, 146 (1992), pp. 935-940
[3.]
American Thoracic Society & European Respiratory Society.
Skeletal muscle dysfunction in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 159 (1999), pp. S1-S40
[4.]
M. Orozco-Levi, J. Gea, J. Lloreta, M.A. Felez, J.L. Minguella, S. Serrano, et al.
Subcellular adaptation of the human diaphragm in chronic obstructive pulmonary disease.
Eur Respir J, 13 (1999), pp. 371-378
[5.]
A.G. Agusti.
Systemic effects of chronic obstructive pulmonary disease.
Novartis Found Symp, 234 (2001), pp. 242-254
[6.]
L.T. Nguyen, M. Bedu, D. Caillaud, B. Beaufrere, G. Beaujon, M. Vasson, et al.
Increased resting energy expenditure is related to plasma TNF-alpha concentration in stable COPD patients.
Clin Nutr, 18 (1999), pp. 269-274
[7.]
M. Di Francia, D. Barbier, J.L. Mege, J. Orehek.
Tumor necrosis factor- alpha levels and weight loss in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 150 (1994), pp. 1453-1455
[8.]
M. De Rossi, P. Bernasconi, F. Baggi, R. De Waal Malefyt, R. Mantegazza.
Cytokines and chemokines are both expressed by human myoblasts: possible relevance for the immune pathogenesis of muscle inflammation.
Int Immunol, 12 (2000), pp. 1329-1335
[9.]
E. Zhu, B.J. Petrof, J. Gea, N. Comtois, A.E. Grassino.
Diaphragm muscle fiber injury after inspiratory resistive breathing.
Am J Respir Crit Care Med, 155 (1997), pp. 1110-1116
[10.]
E. Pinelli, S.Y. Van der Kaaij, C.P. Broeren, E.J. Ruitenberg, V.P. Rutten.
Measurement of dog cytokines by reverse transcription-quantitative competitive polymerase chain reaction.
Immunogenetics, 49 (1999), pp. 696-699
[11.]
P. Lu, K. Zucker, L. Fuller, A. Tzakis, V. Esquenazi, J. Miller.
Cloning and expression of canine interleukin-10.
J Interferon Cytokine Res, 15 (1995), pp. 1103-1109
[12.]
J.B. Galdiz, J. Palacio, J. Alvarez, M. Marinan, M. Orozco-Levi, J. Gea.
Evaluacion del dano de membrana en las fibras musculares: marcadores biologicos frente a tecnicas estandar.
Arch Bronconeumol, 37 (2001), pp. 16-17
[13.]
A.W. Thomson.
The cytokine handbook,
[14.]
G. Albaugh, B. Kann, L. Strande, P. Vemulapalli, C. Hewitt, J.B. Alexander.
Nicotine induces endothelial TNF-alpha expression, which mediates growth retardation in vitro.
J Surg Res, 99 (2001), pp. 381-384
[15.]
J. Palacio, J.B. Galdiz, C. Casadevall, M. Marinan, M. Orozco-Levi, P. Martinez, et al.
Skeletal muscle fibres express TNF-α in mammals [abstract].
Am J Respir Crit Care Med, 165 (2002), pp. A258
[16.]
R. Halse, S.L. Pearson, J.G. McCormack, S.J. Yeaman, R. Taylor.
Effects of tumor necrosis factor-alpha on insulin action in cultured human muscle cells.
Diabetes, 50 (2001), pp. 1102-1109
[17.]
A.J. Staal-van den Brekel, M.A. Dentener, A.M. Schols, W.A. Buurman, E.F. Wouters.
Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients.
J Clin Oncol, 13 (1995), pp. 2600-2605
[18.]
N. Takabatake, H. Nakamura, S. Abe, T. Hino, H. Saito, H. Yuki, et al.
Circulating leptin in patients with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 159 (1999), pp. 1215-1219
[19.]
A.M. Schols, W.A. Buurman, A.J. Staal van den Brekel, M.A. Dentener, E.F. Wouters.
Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease.
Thorax, 51 (1996), pp. 819-824
[20.]
M.B. Reid, Y.P. Li.
Cytokines and oxidative signalling in skeletal muscle.
Acta Physiol Scand, 171 (2001), pp. 225-232
[21.]
S. Lim, N. Roche, B.G. Oliver, W. Mattos, P.J. Barnes, J.F. Chung.
Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease- 1 from alveolar macrophages in cigarette smokers: regulation by interleukin-10.
Am J Respir Crit Care Med, 162 (2000), pp. 1355-1360
[22.]
L. Thompson-Snipes, V. Dhar, M.W. Bond, T.R. Mosmann, K.W. Moore, D.M. Rennick.
Interleukin-10: a novel stimulatory factor for mast cells and their progenitors.
J Exp Med, 173 (1991), pp. 507-510
[23.]
I.A. MacNeil, T. Suda, K.W. Mootre, T.R. Mosmann, A. Zlotnik.
IL- 10, a novel growth cofactor for mature and immature T cells.
J Immunol, 145 (1990), pp. 4167-4173
[24.]
S. Takanashi, Y. Hasegawa, Y. Kanehira, K. Yamamoto, K. Fujimoto, K. Satoh, et al.
Interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers.
Eur Respir J, 14 (1999), pp. 309-314
[25.]
L. Borish, A. Aarons, J. Rumbyrt, P. Cvietusa, J. Negri, S. Wenzel.
Interleukin-10 regulation in normal subjects and patients with asthma.
J Allergy Clin Immunol, 97 (1996), pp. 1288-1296
[26.]
J.A. Martinez, T.E. J.r. King, K. Brown, C.A. Jennings, L. Borish, R.L. Mortenson, et al.
Increased expression of the interleukin-10 gene by alveolar macrophages in interstitial lung disease.
Am J Physiol, 273 (1997), pp. L676-L683
[27.]
M. John, S. Lim, J. Seybold, P. Jose, A. Rochibaud, B. O'Connor, et al.
Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1, granulocyte-macrophage colonystimulating factor, and interferon-γ release from alveolar macrophages in asthma.
Am J Respir Crit Care Med, 157 (1998), pp. 256-262
[28.]
J. Gea, Q. Hamid, G. Czaika, E. Zhu, V. Mohan-ram, G. Goldspink, et al.
Expression of myosin heavy-chain isoforms in the respiratory muscles following inspiratory resistive breathing.
Am J Respir Crit Care Med, 161 (2000), pp. 1274-1278
[29.]
M. Hayot, E. Barreiro, A. Perez, G. Czaika, A.S. Comtois, A.E. Grassino.
Morphological and functional recovery from diaphragm injury: an in vivo rat diaphragm injury model.
J Appl Physiol, 90 (2001), pp. 2269-2278
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