covid
Buscar en
Endocrinología y Nutrición (English Edition)
Toda la web
Inicio Endocrinología y Nutrición (English Edition) Calcitriol-modulated human antibiotics: New pathophysiological aspects of vitami...
Journal Information

Statistics

Follow this link to access the full text of the article

Review article
Calcitriol-modulated human antibiotics: New pathophysiological aspects of vitamin D
Antibióticos humanos modulados por calcitriol: nuevos aspectos fisiopatológicos de la hipovitaminosis D
Carlos Antonio Amado Diagoa,
Corresponding author
camado@humv.es

Corresponding author.
, María Teresa García-Unzuetab, María del Carmen Fariñasc, Jose Antonio Amadod
a Servicio de Neumología, Hospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain
b Servicio de Bioquímica Clínica, Hospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain
c Servicio de Enfermedades Infecciosas, Hospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain
d Servicio de Endocrinología y Nutrición, Hospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain
Read
8508
Times
was read the article
1015
Total PDF
7493
Total HTML
Share statistics
 array:24 [
  "pii" => "S2173509316000246"
  "issn" => "21735093"
  "doi" => "10.1016/j.endoen.2016.02.003"
  "estado" => "S300"
  "fechaPublicacion" => "2016-02-01"
  "aid" => "741"
  "copyright" => "SEEN"
  "copyrightAnyo" => "2015"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "ssu"
  "cita" => "Endocrinol Nutr. 2016;63:87-94"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 2412
    "formatos" => array:3 [
      "EPUB" => 1
      "HTML" => 2123
      "PDF" => 288
    ]
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S1575092215002764"
      "issn" => "15750922"
      "doi" => "10.1016/j.endonu.2015.09.005"
      "estado" => "S300"
      "fechaPublicacion" => "2016-02-01"
      "aid" => "741"
      "copyright" => "SEEN"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "ssu"
      "cita" => "Endocrinol Nutr. 2016;63:87-94"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 3554
        "formatos" => array:3 [
          "EPUB" => 1
          "HTML" => 2888
          "PDF" => 665
        ]
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Revisi&#243;n</span>"
        "titulo" => "Antibi&#243;ticos humanos modulados por calcitriol&#58; nuevos aspectos fisiopatol&#243;gicos de la hipovitaminosis D"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "87"
            "paginaFinal" => "94"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Calcitriol-modulated human antibiotics&#58; New pathophysiological aspects of vitamin D"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Figura 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 1104
                "Ancho" => 1639
                "Tamanyo" => 92894
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Mecanismo por el que la vitamina D modula la secreci&#243;n de catelicidina y de beta 2 defensina&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La fijaci&#243;n de determinados ant&#237;genos microbianos &#40;Ag&#41; a los receptores toll-like &#40;TLR&#41; activa la 1 &#945; hidroxilasa de la 25 hidroxivitamina D &#40;CYP27b1&#41;&#44; de manera que&#44; en funci&#243;n de las concentraciones intracelulares existentes de 25 hidroxivitamina D&#44; se potencia la s&#237;ntesis local de 1&#44;25 dihidroxivitamina D&#46; Esta&#44; a su vez&#44; se fija a su receptor &#40;VDR&#41; y el complejo intranuclear hormona-receptor activa la transcripci&#243;n de los genes de la catelicidina y de la beta 2 defensina&#46; Las concentraciones intracelulares de 25 hidroxivitamina D dependen de las concentraciones plasm&#225;ticas de esta mol&#233;cula&#44; que es el indicador m&#225;s fiable del estado nutricional de esta vitamina&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Carlos Antonio Amado Diago, Mar&#237;a Teresa Garc&#237;a-Unzueta, Mar&#237;a del Carmen Fari&#241;as, Jose Antonio Amado"
            "autores" => array:4 [
              0 => array:2 [
                "nombre" => "Carlos Antonio"
                "apellidos" => "Amado Diago"
              ]
              1 => array:2 [
                "nombre" => "Mar&#237;a Teresa"
                "apellidos" => "Garc&#237;a-Unzueta"
              ]
              2 => array:2 [
                "nombre" => "Mar&#237;a del Carmen"
                "apellidos" => "Fari&#241;as"
              ]
              3 => array:2 [
                "nombre" => "Jose Antonio"
                "apellidos" => "Amado"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2173509316000246"
          "doi" => "10.1016/j.endoen.2016.02.003"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173509316000246?idApp=UINPBA00004N"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1575092215002764?idApp=UINPBA00004N"
      "url" => "/15750922/0000006300000002/v1_201601290049/S1575092215002764/v1_201601290049/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2173509316000295"
    "issn" => "21735093"
    "doi" => "10.1016/j.endoen.2015.11.016"
    "estado" => "S300"
    "fechaPublicacion" => "2016-02-01"
    "aid" => "747"
    "copyright" => "SEEN"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "crp"
    "cita" => "Endocrinol Nutr. 2016;63:95-6"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 2056
      "formatos" => array:2 [
        "HTML" => 1772
        "PDF" => 284
      ]
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>"
      "titulo" => "Hypothyroidism and protein-losing enteropathy&#58; A case report"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "95"
          "paginaFinal" => "96"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Hipotiroidismo y enteropat&#237;a pierde-prote&#237;nas&#58; a prop&#243;sito de un caso"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Irene Berges-Raso, Ismael Capel, Assumpta Caix&#224;s, Roser Trallero, Mercedes Rigla"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "Irene"
              "apellidos" => "Berges-Raso"
            ]
            1 => array:2 [
              "nombre" => "Ismael"
              "apellidos" => "Capel"
            ]
            2 => array:2 [
              "nombre" => "Assumpta"
              "apellidos" => "Caix&#224;s"
            ]
            3 => array:2 [
              "nombre" => "Roser"
              "apellidos" => "Trallero"
            ]
            4 => array:2 [
              "nombre" => "Mercedes"
              "apellidos" => "Rigla"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S1575092215003265"
        "doi" => "10.1016/j.endonu.2015.11.001"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1575092215003265?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173509316000295?idApp=UINPBA00004N"
    "url" => "/21735093/0000006300000002/v1_201603200109/S2173509316000295/v1_201603200109/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S217350931600026X"
    "issn" => "21735093"
    "doi" => "10.1016/j.endoen.2015.10.011"
    "estado" => "S300"
    "fechaPublicacion" => "2016-02-01"
    "aid" => "744"
    "copyright" => "SEEN"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Endocrinol Nutr. 2016;63:79-86"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 1089
      "formatos" => array:3 [
        "EPUB" => 3
        "HTML" => 837
        "PDF" => 249
      ]
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Differences in clinical and biological characteristics and prevalence of chronic complications related to aging in patients with type 2 diabetes"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "79"
          "paginaFinal" => "86"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Diferencias en las caracter&#237;sticas cl&#237;nico-biol&#243;gicas y prevalencia de complicaciones cr&#243;nicas en relaci&#243;n con el envejecimiento de pacientes con diabetes tipo 2"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Mar&#237;a Luisa Basanta-Alario, Jordi Ferri, Miguel Civera, Sergio Mart&#237;nez-Herv&#225;s, Juan Francisco Ascaso, Jos&#233; Tom&#225;s Real"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Mar&#237;a Luisa"
              "apellidos" => "Basanta-Alario"
            ]
            1 => array:2 [
              "nombre" => "Jordi"
              "apellidos" => "Ferri"
            ]
            2 => array:2 [
              "nombre" => "Miguel"
              "apellidos" => "Civera"
            ]
            3 => array:2 [
              "nombre" => "Sergio"
              "apellidos" => "Mart&#237;nez-Herv&#225;s"
            ]
            4 => array:2 [
              "nombre" => "Juan Francisco"
              "apellidos" => "Ascaso"
            ]
            5 => array:2 [
              "nombre" => "Jos&#233; Tom&#225;s"
              "apellidos" => "Real"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S157509221500279X"
        "doi" => "10.1016/j.endonu.2015.10.005"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157509221500279X?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217350931600026X?idApp=UINPBA00004N"
    "url" => "/21735093/0000006300000002/v1_201603200109/S217350931600026X/v1_201603200109/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>"
    "titulo" => "Calcitriol-modulated human antibiotics&#58; New pathophysiological aspects of vitamin D"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "87"
        "paginaFinal" => "94"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Carlos Antonio Amado Diago, Mar&#237;a Teresa Garc&#237;a-Unzueta, Mar&#237;a del Carmen Fari&#241;as, Jose Antonio Amado"
        "autores" => array:4 [
          0 => array:4 [
            "nombre" => "Carlos Antonio"
            "apellidos" => "Amado Diago"
            "email" => array:1 [
              0 => "camado&#64;humv&#46;es"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Mar&#237;a Teresa"
            "apellidos" => "Garc&#237;a-Unzueta"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Mar&#237;a del Carmen"
            "apellidos" => "Fari&#241;as"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Jose Antonio"
            "apellidos" => "Amado"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Servicio de Neumolog&#237;a&#44; Hospital Universitario Marqu&#233;s de Valdecilla&#44; IDIVAL&#44; Universidad de Cantabria&#44; Santander&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Bioqu&#237;mica Cl&#237;nica&#44; Hospital Universitario Marqu&#233;s de Valdecilla&#44; IDIVAL&#44; Universidad de Cantabria&#44; Santander&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Servicio de Enfermedades Infecciosas&#44; Hospital Universitario Marqu&#233;s de Valdecilla&#44; IDIVAL&#44; Universidad de Cantabria&#44; Santander&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Servicio de Endocrinolog&#237;a y Nutrici&#243;n&#44; Hospital Universitario Marqu&#233;s de Valdecilla&#44; IDIVAL&#44; Universidad de Cantabria&#44; Santander&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Antibi&#243;ticos humanos modulados por calcitriol&#58; nuevos aspectos fisiopatol&#243;gicos de la hipovitaminosis D"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1104
            "Ancho" => 1639
            "Tamanyo" => 92154
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Mechanism through which vitamin D modulates the secretion of cathelicidin and beta-2-defensin&#46; Binding of some microbial antigens &#40;Ag&#41; to toll-like receptors &#40;TLRs&#41; activates 25-hydroxyvitamin D&#8211;1&#945;-hydroxylase &#40;CYP27b1&#41;&#44; so that&#44; depending on intracellular concentrations of 25-hydroxyvitamin D&#44; local synthesis of 1&#44;25-dihydroxyvitamin D is enhanced&#46; The latter in turn binds to its receptor &#40;VDR&#41;&#44; and the intranuclear hormone-receptor complex activates the transcription of the cathelicidin and beta-2-defensin genes&#46; Intracellular concentrations of 25-hydroxyvitamin D depend on plasma concentrations of this molecule&#44; which is the most reliable marker of the nutritional status of this vitamin&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Humans obtain vitamin D or calciferol from diet &#40;in a small proportion&#41; and&#44; primarily&#44; from endogenous synthesis in the epidermis through the effect of ultraviolet radiation&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">1</span></a> To be active&#44; calciferol should be hydroxylated twice&#44; first at position 25 and then at position 1&#945;&#44; to be converted into 1&#945;&#44;25-dihydroxycalciferol or calcitriol&#44; which behaves at systemic &#40;endocrine&#41; level as an essential hormone for phosphorus and calcium metabolism&#44; and at local &#40;autocrine or intracrine&#41; level as a substance regulating multiple cell functions independent of calcium metabolism&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Calciferol is initially hydroxylated in the liver through the effect of 25-hydroxylase of microsomal CYP2R1&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">2</span></a> This enzyme is poorly regulated&#44; and massive&#44; direct conversion of the calciferol that reaches the liver into 25-hydroxycalciferol therefore occurs&#46; This is bound to vitamin D binding protein and has a long half life&#46; Thus&#44; its plasma levels are the main indicator of the nutritional status of vitamin D&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The second hydroxylation may occur in the kidney &#40;classical hormonal pathway&#41; or in other cells unrelated to phosphorus and calcium metabolism &#40;nonclassical intracrine or paracrine pathways&#41;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">2</span></a> through 1&#945;-hydroxylase &#40;CYP27B1&#41; which generates the active metabolite&#46; This enzyme&#44; unlike 25-hydroxylase&#44; is strongly regulated&#44; but regulation at kidney level and at other cells is different&#46; PTH and other factors activate the enzyme in the kidney&#44; while phosphate and fibroblast growth factor 23 &#40;FGF23&#41; are negative regulators&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Calcitriol exerts its regulatory effects mainly&#44; but not only&#44; through activation of its receptor &#40;VDR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">3</span></a> VDR is a nuclear receptor which has both a carboxy-terminal portion that binds calcitriol&#44; and an amino-terminal portion that binds to DNA&#46; Calcitriol binding to VDR induces heterodimerization with the X receptor activated by retinoic acid&#46; This is bound to specific DNA sequence elements &#40;VDRE&#41; in the promoter region of genes that will respond to vitamin D&#46; Finally&#44; a molecular complex is assembled that induces or represses gene transcription&#44; thus modulating the synthesis of many proteins&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The presence of nonclassical effects &#40;independent of calcium and phosphorus metabolism&#41; of calcitriol is based on&#58; &#40;1&#41; a demonstration of 1&#945;-hydroxylase activity in multiple extrarenal cells&#44; regulated by their own mechanisms &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#59; &#40;2&#41; the presence of VDR in multiple cells &#40;it is estimated that up to 3&#37; of the human genome is modulated by calcitriol&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#59; and &#40;3&#41; the existence of specific effects mediated by VDR activation in these cells&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">4&#8211;6</span></a> This is a very primitive pathway from the evolutionary point of view&#44; prior to the hormone pathway&#46; The effect of vitamin D and its deficiency on calcitriol-modulated human antibiotics is reviewed below&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Antibacterial effects of vitamin D</span><p id="par0030" class="elsevierStylePara elsevierViewall">The association of rickets and infection has a long history&#46; In the 19th century&#44; the use of cod liver oil &#40;an excellent source of vitamins A and D&#41; was recommended not only for treating rickets&#44; but also for pulmonary tuberculosis&#44; and&#44; a little later&#44; sanatoriums specializing in heliotherapy under natural sunlight became fashionable&#46; In 1903&#44; Niels Finsen was awarded the Nobel Prize for Medicine for his work showing that ultraviolet light could cure tuberculosis of the skin&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In 1981&#44; Barbour et al&#46; showed extrarenal calcitriol production in sarcoidotic granulomas in an anephric patient with hypercalcemia&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">7</span></a> Calcitriol was later shown to promote the fusion of alveolar mouse macrophages&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">8</span></a> This was the first evidence of the effect of calcitriol on immune system cells&#46; In 1983&#44; Proveddini et al&#46; found VDR in human WBCs&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">9</span></a> In 1986&#44; vitamin D and interferon-&#947; were shown to be able to control the proliferation of Mycobacterium tuberculosis in human monocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Wang et al&#46; showed that calcitriol induced the expression of two human antimicrobial peptides&#44; cathelicidin and &#946;2-defensin&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">11</span></a> In 2006&#44; it was demonstrated that the recognition of Mycobacterium tuberculosis antigens by toll-like receptors &#40;TLRs&#41; in the membrane of monocytes&#44; or cells related to innate immunity &#40;skin&#44; respiratory and urinary epithelium&#44; etc&#46;&#41;&#44; induced the activation of 1&#945;-hydroxylase and VDR genes&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">12</span></a> which led in turn to the activation of cathelicidin and &#946;2-defensin genes&#46; Liu et al&#46; also showed that adequate release of the latter required normal 25-hydroxyvitamin D levels in the medium&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">12</span></a> which suggested that hypovitaminosis D restricted the production of such substances&#46; The gene promoter of both molecules contains at least one VDRE which&#44; interestingly&#44; in the case of cathelicidin is located in a small nuclear sequence that only occurs in humans and higher primates&#46; This suggests that regulation by vitamin D of this aspect of innate immunity is evolutionarily recent and occurs almost only in humans&#44; so that the results of some animal studies cannot necessarily be extrapolated to our species&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">13</span></a> The intracellular mediators through which the activation of TLRs 2&#47;1 stimulates the synthesis of calcitriol and its receptor are beginning to be known&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">14</span></a> On the other hand&#44; there are both stimulating cytokines &#40;interleukin-1&#44; interleukin-15&#44; interferon-&#947;&#41; and inhibitory cytokines &#40;interleukin-4&#44; interleukin-10&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">14</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Obviously&#44; vitamin D not only has the above mentioned immune and antimicrobial effects&#44; but also has an impact on many other areas of both innate and adaptive immunity&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">3&#8211;5</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Calcitriol-modulated human antibiotics</span><p id="par0050" class="elsevierStylePara elsevierViewall">These include cathelicidin or LL-37&#44; &#946;2-defensin and hepcidin&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Cathelicidin and defensins are part of a group of small&#44; multifunctional cationic polypeptides&#44; evolutionarily very primitive&#44; with potent antimicrobial effects &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">14&#8211;16</span></a> and resistant to proteolysis&#44; so that germs do not develop resistance to them&#46; Their production mechanism is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; They also have other functions&#44; as they modulate the initiation and activation of inflammatory response &#40;&#8220;alarmins&#8221;&#41; and the subsequent repair of damaged tissue&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">14&#8211;16</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Human cathelicidin or LL-37</span><p id="par0060" class="elsevierStylePara elsevierViewall">Human cathelicidin&#44; or LL-37&#44; a secretory protein generated enzymatically from human preprocathelicidine&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">14</span></a> has a signal peptide&#44; followed by a highly conserved cathelin domain &#40;hence the name of the molecule&#41; and a structurally very variable&#44; cationic carboxy-terminal peptide with broad antimicrobial effects&#46; In humans&#44; the molecule is encoded by a single gene&#44; called cathelicidin antimicrobial peptide&#46; Human cathelicidin is a 37-amino acid peptide that starts with the amino acids leucine-leucine&#44; hence its name of LL-37&#46; It is produced in many tissues &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#44; especially in cells involved in innate immunity&#44;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">15&#44;16</span></a> and may be measured in almost all human biological fluids&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Cathelicidin levels in the biological fluids of a healthy person are assumed to express the basal&#44; constitutive secretion of the peptide in the bone marrow&#44; neutrophils&#44; and other cells&#46; In patients with infection&#44; trauma&#44; and other conditions&#44; however&#44; levels are increased by the secretion induced through activation of the TLR 2&#47;1-VDR system in the innate immunity cells&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">17</span></a> It is generally accepted that&#44; assuming an equal antigen challenge&#44; <span class="elsevierStyleItalic">in vivo</span> response to cathelicidin is lower in patients with hypovitaminosis D&#44; although this has only been confirmed to date in <span class="elsevierStyleItalic">in vitro</span> studies&#46; However&#44; this is a simplification&#44; because cathelicidin secretion is influenced by multiple positive and negative factors<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">18</span></a> which do not all depend on calcitriol-VDR signaling&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Cathelicidin secretion is stimulated by TLR receptor agonists &#40;bacterial&#44; fungal&#44; or viral antigens&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">18</span></a> vitamin D receptor agonists &#40;e&#46;g&#46; paricalcitol&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">18</span></a> interferon-&#947;&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">18</span></a> interleukin-15&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">18</span></a> some bile acids &#40;lithocholic&#44; ursodeoxycholic&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">18</span></a> butyrate and its derivative 4-phenylbutyrate&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">18</span></a> agents causing endoplasmic reticulum stress that release sphingosine-1-phosphate&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">19</span></a> and some components of the diet &#40;curcumin&#44; resveratrol&#44; genistein&#44; etc&#46;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">20&#8211;22</span></a> Curcumin<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">20</span></a> and resveratrol<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">21</span></a> act through mechanisms independent of VDR and enhance the effects of calcitriol&#46; The activation of &#946;-estrogen receptors releases cathelicidin by a mechanism independent of VDR&#44; mediated by sphfingosine-1-phosphate&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">22</span></a> By contrast&#44; the release of LL-37 is inhibited by some endotoxins&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">18</span></a> Shigella&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">18</span></a> and FGF23&#44;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">23</span></a> amongst others&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">18</span></a> The response is tissue-specific &#40;it is not the same in the vaginal epithelium&#44; sensitive to estrogens&#44; as is it in the urothelium&#44; the bronchial epithelium&#44; or skin keratinocytes&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Tiosano et al&#46; found that monocytes from patients with rickets due to inactivating mutation in VDR&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">24</span></a> in whom signaling through VDR cannot occur&#44; expressed little &#40;but not zero&#41; basal cathelicidin&#44; and their response capacity in the presence of 25-OH vitamin D was much lower than that of monocytes from healthy subjects &#40;but not zero either&#41;&#46; This data emphasizes the role of VDR&#44; but also suggests that other stimuli may release cathelicidin&#44; because in the absence of signaling through VDR&#44; monocytes are able to produce it&#44; which suggests that while calcitriol is a potent positive modulator of cathelicidin secretion&#44; it is not the only one&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Cathelicidin concentrations in human fluids</span><p id="par0080" class="elsevierStylePara elsevierViewall">In 1997&#44; Sorensen et al&#46; published the first study that measured LL-37 in plasma&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">25</span></a> No sex or age differences were found in healthy individuals between plasma and serum&#46; Other authors found higher concentrations in patients with cystic fibrosis and bronchial infection than in patients with no infections&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">26</span></a> The results reported in severe sepsis are conflicting&#58; levels lower<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">27&#44;28</span></a> than or similar<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">29</span></a> to those in control subjects have been reported&#44; but the procedures used to measure LL-37 have differed&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Yamshchikov et al&#46; found hypovitaminosis D in 85&#37; of patients with tuberculosis&#46; The highest LL-37 levels were reported in those with positive sputum&#44; but no correlation was seen between LL-37 and 25 hydroxycalciferol levels&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">30</span></a> Another study also found no correlation between cathelicidin and 25-OH-vitamin D concentrations in healthy women before delivery or in their babies&#44; but a potent correlation existed between cathelicidin levels in maternal and umbilical cord blood&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">31</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Bhan et al&#46; reported that after administering vitamin D to healthy subjects&#44; those in the tertile with the highest 25-OH-vitamin D levels had a greater elevation in LL-37 values than those in the tertile with the lowest vitamin D levels&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">32</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Dixon et al&#46; showed a positive correlation between 25-OH vitamin D and cathelicidin concentrations in subjects with low levels of the nutritional marker of vitamin D&#44; but such a correlation was not seen in subjects with normal levels&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">33</span></a> Two previous studies by the same authors found no correlation between the levels of the vitamin D nutritional marker and cathelicidin in patients on dialysis&#44;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">34</span></a> or in patients who attended a clinic specializing in bone metabolic diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">35</span></a> Our group found higher cathelicidin levels in healthy elderly subjects with higher 25-OH vitamin D concentrations&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">36</span></a> Lehouck et al&#46; found no correlation between nutritional vitamin D status and LL-37 levels before or after high-dose supplementation with vitamin D in patients with chronic obstructive pulmonary disease&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">37</span></a> Similar subsequent studies in healthy subjects are available&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">38</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">To sum up&#44; cathelicidin levels in blood vary depending on the method used&#44; show a significant dispersion&#44; and have little or no correlation with concurrent 25-OH vitamin D levels in healthy subjects&#44; except possibly in those with hypovitaminosis D&#46; To interpret the results in patients&#44; the development stage of the process and treatment should also be taken into account&#44; because levels vary as the disease evolves&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">LL-37 has been shown to occur in sperm&#44; vaginal fluid&#44; sweat&#44; saliva&#44; tears&#44; nasal mucus&#44; sputum&#44; milk&#44; pleural fluid&#44; feces&#44; and urine&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">25</span></a> LL-37 is thought to exert in all these places a broad spectrum antibacterial effect&#44; acting as an early response when the barrier zones of the body detect pathogenic antigens&#46; In our research&#44; the highest cathelicidin concentrations were found in infected pleural fluid&#44; as compared to tumor transudates or exudates&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">39</span></a> In these patients&#44; a positive correlation was seen between serum cathelicidin and serum calcitriol&#44; but not 25-hydroxyvitamin D&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Antibacterial mechanisms of action of cathelicidin</span><p id="par0110" class="elsevierStylePara elsevierViewall">Most of the direct antimicrobial effects of LL-37 can be attributed to its &#945;-helical structure and its cationic and hydrophobic properties&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">40</span></a> The N-terminal helix is related to chemotaxis and resistance to proteolysis&#44; while the C-terminal helix is responsible for antimicrobial effects&#46; LL-37 reaches the microbial membrane&#44; covers its surface&#44; and perforates it&#44; forming in the membrane pores that eventually destroy the germ&#46; LL-37 essentially binds to cell membranes that contain lipopolysaccharides &#40;Gram-negative&#41; or teichoic acid &#40;Gram-positive&#41; with a negative charge&#44; different from the zwitterionic membranes of eukaryotes&#46; The antiviral action is also due to interaction with the membrane envelope and protein capsid&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The induction of autophagy in human monocytes&#47;macrophages is the mechanism which accounts for the capacity of this peptide to kill intracellular pathogens&#46; Autophagy is a very primitive biological process that serves to ensure cell cytoplasm homeostasis&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">41</span></a> When autophagy is activated&#44; some cytoplasm materials become trapped inside a dual membrane vacuole called an autophagosome which&#44; after merging with lysosomes&#44; becomes an autophagolysosome&#44; in which lysosomal enzymes degrade all trapped materials&#46; Autophagy was formerly thought to serve mainly for the recycling of nutrients from damaged molecules&#44; but it is now known that it is involved in a wide variety of processes&#44; including antimicrobial activity&#46;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">42&#44;43</span></a> Autophagy activates in response to cathelicidin production&#44; cell fasting&#44; or rapamycin treatment&#44; and is inhibited in response to nutrients&#44; hormones&#44; and some cytokines&#46; This mechanism makes possible normal cell function in changing metabolic conditions&#44; and activates the destruction of some intracellular germs such as the various mycobacteria&#44; which would otherwise remain alive indefinitely inside the cells&#46;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">41&#8211;43</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Cathelicidin is an essential mediator in the formation and function of autophagosomes and autophagolysosomes in human monocytes&#44;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">41&#8211;43</span></a> but it is not the only one&#44; as many other mechanisms inducing autophagy independent of the calcitriol-cathelicidin system have been discovered&#46; LL-37 induces the expression of two key factors for the development of autophagy&#44; beclin-1 and autophagin &#40;Atg&#41;-5&#46;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">41&#8211;44</span></a> These are essential for the maturation process of autophagy and for the merging of autophagosomes and lysosomes&#46; Autophagy mediated by curcumin&#44; cell fasting&#44; or rapamycin is not regulated by the calcitriol-cathelicidin system&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">44</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Cathelicidin has additional effects&#44; which may vary depending on the local concentration&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">44</span></a> It has been shown <span class="elsevierStyleItalic">in vitro</span>&#44; for example&#44; that at doses less than 1<span class="elsevierStyleHsp" style=""></span>&#956;mol&#44; cathelicidin induces neutrophil chemotaxis and survival&#44; and stimulates angiogenesis and fibroblast migration and proliferation &#40;beneficial effects on wound healing&#41;&#44; while very high concentrations&#44; usually beyond those reached in the usual response&#44; have cytotoxic and pro-inflammatory effects&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">44</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Defensins&#58; &#946;2-defensin or HBD2</span><p id="par0130" class="elsevierStylePara elsevierViewall">Defensins are other very primitive antimicrobial agents from the evolutionary point of view&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">45&#44;46</span></a> They contain six cysteine residues that form disulfide bonds&#46; Variations in the alignment of these bonds and molecular structures result in different families&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Humans have eight &#945;-defensins&#44; which are not modulated by vitamin D&#46; At least four different human HBDs are known&#44; of which HBD2 is modulated by VDR&#46; HBDs are expressed in various immune &#40;monocytes&#44; macrophages&#41; and epithelial cells&#46; HBD1 is constitutively expressed&#44; while the secretion of HBD2 is stimulated by some bacterial products &#40;lipopolysaccharides&#44; lipoteichoic acid&#41; and pro-inflammatory cytokines &#40;tumor necrosis factor-&#945;&#44; interleukin-1&#945;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">46</span></a> HBD2 is a small cationic peptide &#40;38 amino acids&#59; 4&#46;1<span class="elsevierStyleHsp" style=""></span>kDa&#41;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">47</span></a> expressed in the lung&#44; thymus&#44; skin&#44; bowel&#44; WBCs&#44; liver&#44; and trachea&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Wang et al&#46; showed that calcitriol causes the release of HBD2&#44; although in smaller amounts than cathelicidine&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">17</span></a> Full induction of the HBD2 gene requires the convergence of the interleukin-1&#946; and calcitriol pathways&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">48</span></a> On the other hand&#44; it has also been shown that the activation of nucleotide-binding oligomerization domain protein 2&#44; an intracellular receptor&#44; by its ligand&#44; muramyl dipeptide&#44; a derivative of lysosomal catabolism of bacterial peptidoglycans&#44; induces HBD2 gene expression&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">49</span></a> Calcitriol strongly induces the expression of the nucleotide-binding oligomerization domain protein 2 receptor in human barrier cells&#44; thus enhancing HBD2 expression&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">50</span></a> Other known mechanisms activating HBD2 include butyrate&#44; ceramide-1-phosphate released by endoplasmic reticulum stress&#44; or sulforaphane from cruciferous plants&#44; while retinoic acid inhibits HBD2 expression in normal keratinocytes&#44; and cigarette smoke blocks its production in the respiratory epithelium&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">15&#44;16&#44;45&#44;46</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Few studies measuring &#946;2-defensin levels are available&#46; Leow et al&#46; found that plasma HBD2 concentrations in patients with pneumonia did not correlate to 25-OH vitamin D levels or a 30-day mortality risk&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">51</span></a> In another model&#44; Lippross et al&#46; assessed changes in serum HBD2 levels over time in a group of patients with multiple trauma and compared them to other markers of inflammation and innate immunity&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">52</span></a> HBD2 levels at admission were seven-fold greater than normal and progressively decreased until they normalized at eight days&#44; while cathelicidin levels were 15 times higher at baseline and remained elevated during the 14 days of follow-up&#46; These data show that when tissue damage occurs&#44; there is an earlier and stronger response of cathelicidin as compared to &#946;2-defensin&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Hepcidin</span><p id="par0150" class="elsevierStylePara elsevierViewall">In 2001&#44; a small antimicrobial peptide produced in the liver was identified and called hepcidin &#40;from <span class="elsevierStyleItalic">hep-</span> &#8220;liver&#8221;&#44; and <span class="elsevierStyleItalic">-cidin</span> from &#8220;microbicidal&#8221;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">53</span></a> Hepcidin is cationic&#44; amphipathic&#44; and rich in cysteines&#44; which generate four intramolecular disulfide bonds and stabilize the molecule in a folding structure &#946;&#46; Hepcidin is active against Gram-positive bacteria&#44; but also inhibits the development of some fungi and Gram-negative bacteria with an antibacterial spectrum similar to that of &#946;1-defensin&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">54</span></a> Nemeth et al&#46; showed hepcidin production in response to interleukin-6&#46; Other inflammatory cytokines also induced its synthesis&#44; but to a lesser extent&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">55</span></a> Hepcidin is the main regulator of iron homeostasis&#44; because it binds to ferroportin&#44; the only known iron transporter to the outside of the cell&#46; Hepcidin binding to ferroportin induces the internalization and degradation of ferroportin&#44; which blocks the exit of iron from the cells&#46; The cells mainly affected by this interaction include enterocytes &#40;which block iron absorption in the bowel&#41; and macrophages &#40;which prevent iron release into blood&#41;&#46; The consequence is the occurrence of the so-called &#8220;anemia of chronic diseases&#8221;&#44; due to decreased circulating iron concentrations&#46; Low serum iron levels restrict iron availability to extracellular bacteria&#44; which are deprived of an essential nutrient and are therefore easier to kill&#46; Paradoxically&#44; however&#44; intracellular pathogens &#40;Salmonella&#44; Mycobacteria&#44; Candida&#44; etc&#46;&#41; have greater amounts of iron available and may thus more easily develop inside macrophages&#44; which therefore increase the local production of hepcidin to kill the germs&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Calcitriol has also been shown to modulate the iron&#8211;hepcidin&#8211;ferroportin axis&#46; Bachetta et al&#46; showed that the calcitriol-VDR complex may directly inhibit hepcidin expression by binding to a VDRE at the hepcidin promoter&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">56</span></a> On the other hand&#44; calcitriol decreases interleukin-6 production in response to the lipopolysaccharide&#44; and thus indirectly decreases IL-6 secretion&#46; In healthy subjects and patients with kidney failure&#44; it has been shown that when 25-OH vitamin D levels increase&#44; hepcidin decreases and anemia improves&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">56</span></a> Interestingly&#44; a Spanish group had already shown that the intravenous administration of calcitriol to patients on hemodialysis improves anemia and reduces the need for erythropoietin&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">57</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Final discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">Calcitriol is significantly involved in the metabolism of different antimicrobial peptides which act upon external microbiological agents through different pathways&#46; The optimization of vitamin D levels may promote the formation of these molecules&#44; thus improving the immune status of patients and their resistance to infection&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:13 [
        0 => array:3 [
          "identificador" => "xres618610"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec632633"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres618609"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec632634"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Antibacterial effects of vitamin D"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Calcitriol-modulated human antibiotics"
        ]
        7 => array:3 [
          "identificador" => "sec0020"
          "titulo" => "Human cathelicidin or LL-37"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Cathelicidin concentrations in human fluids"
            ]
            1 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Antibacterial mechanisms of action of cathelicidin"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Defensins&#58; &#946;2-defensin or HBD2"
        ]
        9 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Hepcidin"
        ]
        10 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Final discussion"
        ]
        11 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Conflicts of interest"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2015-05-20"
    "fechaAceptado" => "2015-09-07"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec632633"
          "palabras" => array:5 [
            0 => "Cathelicidin"
            1 => "Defensin"
            2 => "Hepcidin"
            3 => "Calcitriol"
            4 => "Vitamin D"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec632634"
          "palabras" => array:5 [
            0 => "Catelicidina"
            1 => "Defensina"
            2 => "Hepcidina"
            3 => "Calcitriol"
            4 => "Vitamina D"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Traditionally&#44; calcitriol has been considered a calcium and phosphate regulating hormone&#44; but has recently been shown to play a pivotal role in innate immunity&#46; Many barrier and immune cells have membrane and intracellular receptors that recognize different microbial antigens&#46; Activation of these receptors induces synthesis of 1&#945;-hydroxylase&#44; which acts on 25 hydroxyvitamin D to generate intracellular calcitriol&#46; Calcitriol activates its receptor and enhances the synthesis of important human antibiotics like cathelicidin and &#946;2-defensin while inhibiting hepcidin&#46; These pluripotent peptides have an important role in innate immunity&#44; and their regulation is abnormal in hypovitaminosis D&#46; The literature on their secretion mechanisms&#44; levels in different organic fluids&#44; mechanism of action&#44; and relationship with vitamin D is reviewed here&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El calcitriol ha sido considerado durante a&#241;os exclusivamente como una hormona reguladora del metabolismo fosfoc&#225;lcico&#44; pero &#250;ltimamente se ha demostrado que numerosas c&#233;lulas implicadas en la inmunidad innata &#40;epitelios de barrera&#44; monocitos&#47;macr&#243;fagos&#44; etc&#46;&#41; son capaces de reconocer determinadas mol&#233;culas repetitivas caracter&#237;sticas de diversos g&#233;rmenes pat&#243;genos mediante receptores de membrana o intranucleares&#46; La activaci&#243;n de estos receptores induce la s&#237;ntesis de la 1&#945;-hidroxilasa&#44; con lo que dichas c&#233;lulas son capaces de sintetizar calcitriol a partir de la 25 hidroxivitamina D circulante&#46; El calcitriol&#44; a trav&#233;s del receptor la vitamina D&#44; modula la expresi&#243;n de determinados p&#233;ptidos antimicrobianos&#44; como la catelicidina&#44; la &#946;2-defensina o la hepcidina&#46; Estos p&#233;ptidos representan un mecanismo vers&#225;til de la lucha antibacteriana innata y su producci&#243;n se ve alterada en la hipovitaminosis D&#46; Se realiza un an&#225;lisis de la literatura sobre sus mecanismos de secreci&#243;n&#44; las concentraciones en diversos l&#237;quidos org&#225;nicos&#44; y los mecanismos de acci&#243;n y su relaci&#243;n con la vitamina D&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Amado Diago CA&#44; Garc&#237;a-Unzueta MT&#44; Fari&#241;as MC&#44; Amado JA&#46; Antibi&#243;ticos humanos modulados por calcitriol&#58; nuevos aspectos fisiopatol&#243;gicos de la hipovitaminosis D&#46; Endocrinol Nutr&#46; 2016&#59;63&#58;87&#8211;94&#46;</p>"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1104
            "Ancho" => 1639
            "Tamanyo" => 92154
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Mechanism through which vitamin D modulates the secretion of cathelicidin and beta-2-defensin&#46; Binding of some microbial antigens &#40;Ag&#41; to toll-like receptors &#40;TLRs&#41; activates 25-hydroxyvitamin D&#8211;1&#945;-hydroxylase &#40;CYP27b1&#41;&#44; so that&#44; depending on intracellular concentrations of 25-hydroxyvitamin D&#44; local synthesis of 1&#44;25-dihydroxyvitamin D is enhanced&#46; The latter in turn binds to its receptor &#40;VDR&#41;&#44; and the intranuclear hormone-receptor complex activates the transcription of the cathelicidin and beta-2-defensin genes&#46; Intracellular concentrations of 25-hydroxyvitamin D depend on plasma concentrations of this molecule&#44; which is the most reliable marker of the nutritional status of this vitamin&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Monocytes&#47;macrophages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dendritic cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Endothelial cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bronchial epithelium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pleural mesothelial cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Brain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Breast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pancreatic islets&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Parathyroid glands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Skin &#40;keratinocytes&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prostate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Myoblasts&#44; regenerating skeletal muscle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Placenta &#40;fetal trophoblasts&#44; maternal decidual cells&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1012707.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Tissues with extrarenal expression of 1&#945;-hydroxylase and calcitriol production&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Musculoskeletal system&#58; osteoblasts&#44; bone marrow&#44; chondrocytes&#44; striated muscle&#44; smooth muscle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Circulatory system&#58; atrial myoendocrine cells&#44; cardiomyocytes&#44; endothelial cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gastrointestinal tract&#58; parotid&#44; epithelial cells of the mouth&#44; stomach&#44; enterocytes&#44; colonic cells&#44; hepatocytes&#44; gallbladder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kidney and urinary tract&#58; tubular epithelial cells &#40;proximal and distal&#41;&#44; urothelium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immune system&#58; activated T- and B-cells&#44; monocytes&#44; macrophages&#44; dendritic cells&#44; neutrophils&#44; spleen&#44; thymus&#44; and lymph node cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Reproductive system&#58; amnion&#44; chorioallantoic membrane&#44; alveolar and ductal breast cells&#44; ovary&#44; oviduct&#44; uterus&#44; placenta&#44; epididymis&#44; Sertoli and Leydig cells of testis&#44; prostate&#44; eggshell gland &#40;hen&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Skin&#58; epidermis&#44; fibroblasts&#44; hair follicles&#44; keratinocytes&#44; melanocytes&#44; sebocytes&#44; sebaceous glands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nervous system&#58; encephalon &#40;hippocampus&#44; cerebellar Purkinje and granular cells&#44; stria terminalis&#44; central nucleus of the amygdala&#41;&#44; sensory ganglia&#44; spinal cord&#44; choroid plexuses&#44; lacrimal glands&#44; retina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Endocrine system&#58; adipose tissue&#44; adrenal gland &#40;cortex and medulla&#41;&#44; &#946; cells of pancreas&#44; pituitary gland&#44; thyroid gland &#40;follicular cells&#44; C cells&#41;&#44; parathyroid glands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tumor cells&#58; melanoma&#44; myeloid leukemia&#44; B-cell lymphoma&#44; breast&#44; prostate&#44; stomach&#44; colon&#44; squamous cell carcinoma&#44; endometrial carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Respiratory tract&#58; lung&#44; respiratory tract epithelium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1012709.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Organs and tissues thought to express calcitriol receptors&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mycobacterium tuberculosis&#44; leprae&#44; bovis&#44; smegmatis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Borrelia spp&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Staphylococcus aureus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Streptococcus pneumoniae&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Propionibacterium acnes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nocardia sp&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Micrococcus luteus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Listeria monocytogenes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lactobacillus casei&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Enterococcus fecalis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bacillus anthracis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Achromobacter xylosoxidans&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acinetobacter baumannii&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Capnocytophaga spp&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aggregatibacter actinomycetumcomitans&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Brucella suis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Burkholderia pseudomallei&#44; cepacia&#44; thailandensis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clostridium difficile&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Escherichia coli&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Franciscella novicida&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fusobacterium nucleatum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Haemophilus influenzae&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Helicobacter pylori&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Klebsiella pneumoniae&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Leptospira interrogans&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mannheimia haemolytica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pasteurella multocida&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Shigella sp&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Porphyromonas gingivalis&#44; circumdentaria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Salmonella sp&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prevotella intermedia&#44; loescheii&#44; melanogenica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pseudomonas aeruginosa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stenotrophomonas maltophilia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tannerella forsythia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treponema pallidum&#44; denticola&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Malassezia furfur&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Yersinia pestis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Candida albicans&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Trichophyton rubrum&#44; mentagrophytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Adenovirus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cytomegalovirus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Human immunodeficiency virus-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Papillomavirus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Influenza virus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vaccinia virus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Herpes simplex virus-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Varicella-zoster virus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1012708.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Biological agents sensitive to the effect of the vitamin D-vitamin D-dependent antibiotics&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bone marrow&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Granulocytes &#40;storage&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Monocytes&#47;macrophages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mast cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Placenta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Skin &#40;keratinocytes&#44; sweat gland cells&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Epithelial cells&#58; eye&#44; lacrimal glands&#44; nose&#44; oral cavity&#44; gingival cells&#44; salivary glands&#44; gastrointestinal tract&#44; Paneth cells&#44; genitourinary tract&#44; respiratory tract&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Breast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cancer cells &#40;melanoma&#44; myeloid leukemia&#44; B-cell lymphoma&#44; breast&#44; prostate&#44; stomach&#44; colon&#44; squamous cell carcinoma&#44; endometrium&#44; ovary&#44; breast&#44; lung&#41; &#40;varies depending on cell lines&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1012710.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Cells and tissues producing cathelicidin&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:57 [
            0 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation of vitamin D metabolism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "H&#46;L&#46; Henry"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Best Pract Res Clin Endocr Metab"
                        "fecha" => "2011"
                        "volumen" => "25"
                        "paginaInicial" => "531"
                        "paginaFinal" => "541"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cytochrome P-450-mediated metabolism of vitamin D"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G&#46; Jones"
                            1 => "D&#46;E&#46; Prosser"
                            2 => "M&#46; Kaufmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Lipid Res"
                        "fecha" => "2014"
                        "volumen" => "51"
                        "paginaInicial" => "13"
                        "paginaFinal" => "31"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Molecular mechanisms of vitamin D action"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;R&#46; Haussler"
                            1 => "G&#46;K&#46; Whitfield"
                            2 => "I&#46; Kaneko"
                            3 => "C&#46;A&#46; Haussler"
                            4 => "D&#46; Hsieh"
                            5 => "J&#46;C&#46; Hsieh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00223-012-9619-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Calcif Tissue Int"
                        "fecha" => "2013"
                        "volumen" => "92"
                        "paginaInicial" => "77"
                        "paginaFinal" => "98"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22782502"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D&#58; beyond bone"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Christakos"
                            1 => "M&#46; Hewison"
                            2 => "D&#46;G&#46; Gardner"
                            3 => "C&#46;L&#46; Wagner"
                            4 => "I&#46;N&#46; Sergeev"
                            5 => "E&#46; Rutten"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/nyas.12129"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann N Y Acad Sci"
                        "fecha" => "2013"
                        "volumen" => "1287"
                        "paginaInicial" => "45"
                        "paginaFinal" => "58"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23682710"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An update of vitamin D and human immunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46; Hewison"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2265.2011.04261.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Endocr"
                        "fecha" => "2012"
                        "volumen" => "76"
                        "paginaInicial" => "315"
                        "paginaFinal" => "325"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21995874"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Where is the vitamin D receptor&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Y&#46; Wang"
                            1 => "Z&#46; Zhu"
                            2 => "H&#46;F&#46; DeLuca"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.abb.2012.04.001"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arch Biochem Biophys"
                        "fecha" => "2012"
                        "volumen" => "523"
                        "paginaInicial" => "123"
                        "paginaFinal" => "133"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22503810"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S021348531100226X"
                          "estado" => "S300"
                          "issn" => "02134853"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypercalcemia in an anephric patient with sarcoidosis&#58; evidence for extrarenal generation of 1&#44;25-dihydroxyvitamin D"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "G&#46;L&#46; Barbour"
                            1 => "J&#46;W&#46; Coburn"
                            2 => "E&#46; Slatopolsky"
                            3 => "A&#46;W&#46; Norman"
                            4 => "R&#46;L&#46; Horst"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM198108203050807"
                      "Revista" => array:6 [
                        "tituloSerie" => "New Engl J Med"
                        "fecha" => "1981"
                        "volumen" => "305"
                        "paginaInicial" => "440"
                        "paginaFinal" => "443"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6894783"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "1&#945;&#44;25 dihydroxy-vitamin D3 promotes fusion of mouse alveolar macrophages both by a direct mechanism and by a spleen cell-mediated indirect mechanism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Abe"
                            1 => "C&#46; Miyaura"
                            2 => "H&#46; Tanaka"
                            3 => "Y&#46; Shiina"
                            4 => "T&#46; Kuribayashi"
                            5 => "S&#46; Suda"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci U S A"
                        "fecha" => "1983"
                        "volumen" => "80"
                        "paginaInicial" => "5583"
                        "paginaFinal" => "5587"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6577445"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "1&#44;25-dihydroxyvitamin D3 receptors in human leukocytes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46;M&#46; Proveddini"
                            1 => "C&#46;D&#46; Tsoukas"
                            2 => "L&#46;J&#46; Deftos"
                            3 => "S&#46;C&#46; Manolagas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "1983"
                        "volumen" => "221"
                        "paginaInicial" => "1181"
                        "paginaFinal" => "1183"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6310748"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D<span class="elsevierStyleInf">3</span>&#44; &#947;-interferon and control of proliferation of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> by human monocytes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;A&#46; Rook"
                            1 => "L&#46; Steele"
                            2 => "S&#46; Fraher"
                            3 => "R&#46; Barker"
                            4 => "J&#46; Karmali"
                            5 => "J&#46; O&#8217;Riordan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunology"
                        "fecha" => "1986"
                        "volumen" => "57"
                        "paginaInicial" => "159"
                        "paginaFinal" => "163"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3002968"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cutting edge&#58; 1&#44;25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;T&#46; Wang"
                            1 => "F&#46;P&#46; Nestel"
                            2 => "V&#46; Bourdeau"
                            3 => "Y&#46; Nagai"
                            4 => "Q&#46; Wang"
                            5 => "J&#46; Liao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2004"
                        "volumen" => "173"
                        "paginaInicial" => "2909"
                        "paginaFinal" => "2912"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15322146"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;T&#46; Liu"
                            1 => "S&#46; Stenger"
                            2 => "H&#46; Li"
                            3 => "L&#46; Wenzel"
                            4 => "B&#46;H&#46; Tan"
                            5 => "S&#46;R&#46; Krutzik"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.1123933"
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "2006"
                        "volumen" => "311"
                        "paginaInicial" => "1770"
                        "paginaFinal" => "1773"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16497887"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;F&#46; Gombart"
                            1 => "T&#46; Saito"
                            2 => "H&#46;P&#46; Koeffler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2164-10-321"
                      "Revista" => array:6 [
                        "tituloSerie" => "BMC Genomics"
                        "fecha" => "2009"
                        "volumen" => "10"
                        "paginaInicial" => "321"
                        "paginaFinal" => "332"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19607716"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A comprehensive summary of LL-37&#44; the factotum human cathelicidin peptide"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46; Vandamme"
                            1 => "B&#46; Landuyt"
                            2 => "W&#46; Luyten"
                            3 => "L&#46; Schoofs"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cellimm.2012.11.009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Immunol"
                        "fecha" => "2012"
                        "volumen" => "280"
                        "paginaInicial" => "22"
                        "paginaFinal" => "35"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23246832"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D and immune function"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "B&#46; Prietl"
                            1 => "G&#46; Treiber"
                            2 => "T&#46;R&#46; Pieber"
                            3 => "K&#46; Amrein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Nutrients"
                        "fecha" => "2013"
                        "volumen" => "250"
                        "paginaInicial" => "2502"
                        "paginaFinal" => "2521"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antimicrobial peptides&#58; clinical relevance and therapeutic implications"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46; Pinheiro da Silva"
                            1 => "M&#46;C&#46;C&#46; Machado"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.peptides.2012.05.014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Peptides"
                        "fecha" => "2012"
                        "volumen" => "36"
                        "paginaInicial" => "308"
                        "paginaFinal" => "314"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22659161"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation of the human cathelicidin antimicrobial peptide gene by 1&#945;-25 dihydroxyvitamin D3 in primary immune cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;B&#46; Lowry"
                            1 => "C&#46; Guo"
                            2 => "N&#46; Borregaard"
                            3 => "A&#46;F&#46; Gombart"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jsbmb.2014.02.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Steroid Biochem Mol Biol"
                        "fecha" => "2014"
                        "volumen" => "143"
                        "paginaInicial" => "183"
                        "paginaFinal" => "191"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24565560"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation of antimicrobial peptide gene expression by nutrients and by-products of microbial metabolism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Y&#46; Campbell"
                            1 => "M&#46;L&#46; Fantacone"
                            2 => "A&#46;F&#46; Gombart"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00394-012-0415-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Nutr"
                        "fecha" => "2012"
                        "volumen" => "51"
                        "paginaInicial" => "899"
                        "paginaFinal" => "907"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22797470"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A novel role of a lipid species&#44; sphingosine-1-phosphate&#44; in epithelial innate immunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Park"
                            1 => "P&#46;M&#46; Elias"
                            2 => "K&#46;O&#46; Shin"
                            3 => "Y&#46;M&#46; Lee"
                            4 => "M&#46; Hupe"
                            5 => "A&#46;W&#46; Borkowski"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/MCB.01103-12"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Cell Biol"
                        "fecha" => "2013"
                        "volumen" => "33"
                        "paginaInicial" => "752"
                        "paginaFinal" => "762"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23230267"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Curcumin induces human cathelicidin antimicrobial peptide gene expression through a vitamin D receptor-independent pathway"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46; Guo"
                            1 => "E&#46; Rosoha"
                            2 => "M&#46;B&#46; Lowry"
                            3 => "N&#46; Borregaard"
                            4 => "A&#46;F&#46; Gombart"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jnutbio.2012.04.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Nutr Biochem"
                        "fecha" => "2013"
                        "volumen" => "24"
                        "paginaInicial" => "754"
                        "paginaFinal" => "759"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22841393"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46; Guo"
                            1 => "B&#46; Sinnott Niu"
                            2 => "M&#46;B&#46; Lowry"
                            3 => "M&#46;L&#46; Fantacone"
                            4 => "A&#46;F&#46; Gombart"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/mnfr.201300266"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Nutr Food Res"
                        "fecha" => "2014"
                        "volumen" => "58"
                        "paginaInicial" => "528"
                        "paginaFinal" => "536"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24039193"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The dietary ingredient&#44; genistein&#44; stimulates cathelicidin antimicrobial peptide expression through a novel S1P dependent mechanism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Park"
                            1 => "Y&#46; Kim"
                            2 => "K&#46;O&#46; Shin"
                            3 => "H&#46;S&#46; Seo"
                            4 => "J&#46;Y&#46; Kim"
                            5 => "T&#46; Mann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jnutbio.2014.03.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Nutr Biochem"
                        "fecha" => "2014"
                        "volumen" => "25"
                        "paginaInicial" => "734"
                        "paginaFinal" => "740"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24768661"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibroblast growth factor 23 inhibits extrarenal synthesis of 1&#44;25 dihydroxyvitamin D in human monocytes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Bachetta"
                            1 => "J&#46;L&#46; Sea"
                            2 => "R&#46;F&#46; Chun"
                            3 => "T&#46;S&#46; Lisse"
                            4 => "K&#46; Wesseling-Perry"
                            5 => "B&#46; Gales"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jbmr.1740"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bone Miner Res"
                        "fecha" => "2013"
                        "volumen" => "28"
                        "paginaInicial" => "46"
                        "paginaFinal" => "55"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22886720"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of vitamin D receptor in innate and adaptive immunity&#58; a study in hereditary vitamin D-resistant rickets patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Tiosano"
                            1 => "G&#46; Wildbaum"
                            2 => "V&#46; Gepstein"
                            3 => "O&#46; Verbitsky"
                            4 => "Y&#46; Weisman"
                            5 => "N&#46; Karin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Endocrin Metab"
                        "fecha" => "2013"
                        "volumen" => "98"
                        "paginaInicial" => "1685"
                        "paginaFinal" => "1693"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An ELISA for hCAP-18&#44; the cathelicidin present in human neutrophils and plasma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "O&#46; Sorensen"
                            1 => "J&#46;B&#46; Cowland"
                            2 => "J&#46; Askaa"
                            3 => "N&#46; Borregaard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Immunol Methods"
                        "fecha" => "1997"
                        "volumen" => "206"
                        "paginaInicial" => "53"
                        "paginaFinal" => "55"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9328568"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0033833810002249"
                          "estado" => "S300"
                          "issn" => "00338338"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sputum cathelicidin&#44; urokinase plasminogen activation system components&#44; and cytokines discriminate cystic fibrosis&#44; COPD&#44; and asthma inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "W&#46; Xiao"
                            1 => "Y&#46;P&#46; Hsu"
                            2 => "A&#46; Ishizaka"
                            3 => "T&#46; Kirikae"
                            4 => "R&#46;B&#46; Moss"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.128.4.2316"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2005"
                        "volumen" => "128"
                        "paginaInicial" => "2316"
                        "paginaFinal" => "2326"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16236890"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Jeng"
                            1 => "A&#46;V&#46; Yamshchikov"
                            2 => "S&#46;E&#46; Judd"
                            3 => "H&#46;M&#46; Blumberg"
                            4 => "G&#46;S&#46; Martin"
                            5 => "T&#46;R&#46; Ziegler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1479-5876-7-28"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Transl Med"
                        "fecha" => "2009"
                        "volumen" => "7"
                        "paginaInicial" => "28"
                        "paginaFinal" => "36"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19389235"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cathelicidin LL-37 bloodstream surveillance is down regulated during septic shock"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;F&#46; Barbeiro"
                            1 => "H&#46;V&#46; Barbeiro"
                            2 => "F&#46;G&#46; Zampieri"
                            3 => "M&#46;C&#46; Cesar Machado"
                            4 => "F&#46; Torggler Filho"
                            5 => "D&#46;M&#46; Gomes Cunha"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.micinf.2013.01.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Microbes Infect"
                        "fecha" => "2013"
                        "volumen" => "15"
                        "paginaInicial" => "342"
                        "paginaFinal" => "346"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23328115"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Elevated plasma levels of antimicrobial polypeptides in patients with severe sepsis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "I&#46; Berkestedt"
                            1 => "H&#46; Herwald"
                            2 => "L&#46; Ljunggren"
                            3 => "A&#46; Nelson"
                            4 => "M&#46; Bodelsson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000317036"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Innate Immun"
                        "fecha" => "2010"
                        "volumen" => "2"
                        "paginaInicial" => "478"
                        "paginaFinal" => "482"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20571257"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0033833810003449"
                          "estado" => "S300"
                          "issn" => "00338338"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D status and antimicrobial peptide cathelicidin &#40;LL-37&#41; concentrations in patients with active pulmonary tuberculosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;V&#46; Yamshchikov"
                            1 => "E&#46;V&#46; Kurbatova"
                            2 => "M&#46; Kumari"
                            3 => "H&#46;M&#46; Blumberg"
                            4 => "T&#46;R&#46; Ziegler"
                            5 => "S&#46;M&#46; Ray"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3945/ajcn.2010.29411"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Clin Nutr"
                        "fecha" => "2010"
                        "volumen" => "92"
                        "paginaInicial" => "603"
                        "paginaFinal" => "611"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20610636"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maternal plasma level of antimicrobial peptide LL37 is a major determinant factor of neonatal plasma LL37 level"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;M&#46; Havelka"
                            1 => "E&#46; Yektaei-Karin"
                            2 => "K&#46; Hultenby"
                            3 => "O&#46;E&#46; Sorensen"
                            4 => "J&#46; Lundahl"
                            5 => "V&#46; Berggren"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1651-2227.2010.01726.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Paediatr"
                        "fecha" => "2010"
                        "volumen" => "99"
                        "paginaInicial" => "836"
                        "paginaFinal" => "841"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20178514"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Circulating levels of 25-hydroxyvitamin D and human cathelicidin in healthy adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Bhan"
                            1 => "C&#46;A&#46; Camargo Jr&#46;"
                            2 => "J&#46; Wenger"
                            3 => "C&#46; Ricciardi"
                            4 => "J&#46; Ye"
                            5 => "N&#46; Borregaard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2010.12.1097"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2011"
                        "volumen" => "127"
                        "paginaInicial" => "1302"
                        "paginaFinal" => "1304"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21310475"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Positive correlation between circulating cathelicidin antimicrobial peptide &#40;hCAP18&#47;LL-37&#41; and 25-hydroxyvitamin D levels in healthy adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;M&#46; Dixon"
                            1 => "T&#46; Barker"
                            2 => "T&#46; McKinnon"
                            3 => "J&#46; Cuomo"
                            4 => "B&#46; Frei"
                            5 => "N&#46; Borregaard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1756-0500-5-575"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Res Notes"
                        "fecha" => "2012"
                        "volumen" => "5"
                        "paginaInicial" => "575"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23095332"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low plasma level of cathelicidin antimicrobial peptide &#40;hCAP18&#41; predicts increased infectious disease mortality in patients undergoing hemodialysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;F&#46; Gombart"
                            1 => "I&#46; Bhan"
                            2 => "N&#46; Borregaard"
                            3 => "H&#46; Tamez"
                            4 => "C&#46;A&#46; Camargo Jr&#46;"
                            5 => "H&#46;P&#46; Koeffler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/596314"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "2009"
                        "volumen" => "48"
                        "paginaInicial" => "418"
                        "paginaFinal" => "424"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19133797"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S014067360208649X"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D-directed rheostatic regulation of monocyte antibacterial responses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;S&#46; Adams"
                            1 => "S&#46; Ren"
                            2 => "P&#46;T&#46; Liu"
                            3 => "R&#46;F&#46; Chun"
                            4 => "V&#46; Lagishetty"
                            5 => "A&#46;F&#46; Gombart"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4049/jimmunol.0803736"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2009"
                        "volumen" => "182"
                        "paginaInicial" => "4289"
                        "paginaFinal" => "4295"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19299728"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0959804908000087"
                          "estado" => "S300"
                          "issn" => "09598049"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Age and low levels of circulating vitamin D are associated with impaired innate immune function"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46; Alvarez-Rodriguez"
                            1 => "M&#46; L&#243;pez-Hoyos"
                            2 => "M&#46;T&#46; Garc&#237;a-Unzueta"
                            3 => "J&#46;A&#46; Amado"
                            4 => "P&#46;M&#46; Cacho"
                            5 => "V&#46;M&#46; Mart&#237;nez-Taboada"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1189/jlb.1011523"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Leukoc Biol"
                        "fecha" => "2012"
                        "volumen" => "91"
                        "paginaInicial" => "829"
                        "paginaFinal" => "838"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22345707"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease&#46; A randomized trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Lehouck"
                            1 => "C&#46; Mathieu"
                            2 => "C&#46; Carremans"
                            3 => "F&#46; Baeke"
                            4 => "J&#46; Verhaegen"
                            5 => "J&#46; van Eldere"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/0003-4819-156-2-201201170-00004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2012"
                        "volumen" => "156"
                        "paginaInicial" => "105"
                        "paginaFinal" => "114"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22250141"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of vitamin D supplementation on cathelicidin&#44; IFN-&#947;&#44; interleuquina-4&#44; and Th1&#47;Th2 transcription factors in young healthy females"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Das"
                            1 => "N&#46; Tomar"
                            2 => "V&#46; Screenivas"
                            3 => "N&#46; Gupta"
                            4 => "R&#46; Groswami"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ejcn.2013.268"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Clin Nutr"
                        "fecha" => "2014"
                        "volumen" => "68"
                        "paginaInicial" => "338"
                        "paginaFinal" => "343"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24398649"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "LL-37 is produced intrapleurally in infectious pleural effusion"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;A&#46; Amado"
                            1 => "J&#46; Villuela"
                            2 => "M&#46;T&#46; Garc&#237;a-Unzueta"
                            3 => "J&#46;J&#46; Ruiz-Cubillan"
                            4 => "A&#46; Daly"
                            5 => "B&#46; Abascal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2012"
                        "volumen" => "40"
                        "numero" => "Suppl 56"
                        "paginaInicial" => "2520"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The chemistry and biology of LL-37"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;F&#46; Burton"
                            1 => "P&#46;G&#46; Steel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1039/b912533g"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Prod Rep"
                        "fecha" => "2009"
                        "volumen" => "26"
                        "paginaInicial" => "1572"
                        "paginaFinal" => "1584"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19936387"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunologic manifestations of autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "V&#46; Deretic"
                            1 => "T&#46; Kimura"
                            2 => "G&#46; Timmins"
                            3 => "P&#46; Moseley"
                            4 => "S&#46; Chauhan"
                            5 => "M&#46; Mandell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI73945"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2015"
                        "volumen" => "125"
                        "paginaInicial" => "75"
                        "paginaFinal" => "84"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25654553"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D3 induces autophagy in human monocytes&#47;macrophages via cathelicidin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Yuk"
                            1 => "D&#46;M&#46; Shin"
                            2 => "H&#46;M&#46; Lee"
                            3 => "C&#46;S&#46; Yang"
                            4 => "H&#46;S&#46; Jin"
                            5 => "K&#46;K&#46; Kim"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.chom.2009.08.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Host Microbe"
                        "fecha" => "2009"
                        "volumen" => "6"
                        "paginaInicial" => "231"
                        "paginaFinal" => "243"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19748465"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of autophagy in host defence against Mycobacterium tuberculosis infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Songane"
                            1 => "J&#46; Kleinnjehnuis"
                            2 => "M&#46;G&#46; Netea"
                            3 => "R&#46; van Crevel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.tube.2012.05.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Tuberculosis"
                        "fecha" => "2012"
                        "volumen" => "92"
                        "paginaInicial" => "388"
                        "paginaFinal" => "396"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22683183"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The human cathelicidin antimicrobial peptide LL-37 as a potential treatment for polymicrobial infected wounds"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;J&#46; Duplantier"
                            1 => "M&#46;L&#46; van Hoek"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fimmu.2013.00014"
                      "Revista" => array:5 [
                        "tituloSerie" => "Front Immunol"
                        "fecha" => "2013"
                        "volumen" => "4"
                        "paginaInicial" => "14"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23386852"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antimicrobial peptides important in innate immunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Cederlund"
                            1 => "G&#46;H&#46; Gudmundsson"
                            2 => "B&#46; Agerberth"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1742-4658.2009.07122.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "FEBS J"
                        "fecha" => "2011"
                        "volumen" => "276"
                        "paginaInicial" => "3942"
                        "paginaFinal" => "3951"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19583765"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Defensins&#58; natural component of human innate immunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Jarczak"
                            1 => "E&#46;M&#46; Kosciuczuk"
                            2 => "P&#46; Lisowski"
                            3 => "N&#46; Strzalkowska"
                            4 => "A&#46; J&#243;zwik"
                            5 => "J&#46; Horbanczuk"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Hum Immun"
                        "fecha" => "2013"
                        "volumen" => "64"
                        "paginaInicial" => "1069"
                        "paginaFinal" => "1079"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human &#946;-defensin-2 is a salt-sensitive peptide antibiotic expressed in human lung"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Bals"
                            1 => "X&#46; Wang"
                            2 => "Z&#46; Wu"
                            3 => "T&#46; Freeman"
                            4 => "V&#46; Bafna"
                            5 => "M&#46; Zasloff"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI2410"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "1998"
                        "volumen" => "102"
                        "paginaInicial" => "874"
                        "paginaFinal" => "880"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9727055"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0212656709001863"
                          "estado" => "S300"
                          "issn" => "02126567"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Convergence of interleuquina-1&#946; and VDR activation pathways in human TLR2&#47;1-induced antimicrobial responses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;T&#46; Liu"
                            1 => "M&#46; Schenck"
                            2 => "V&#46;P&#46; Walker"
                            3 => "P&#46;W&#46; Dempsey"
                            4 => "M&#46; Kanchanapoomi"
                            5 => "M&#46; Wheelwright"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0005810"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2009"
                        "volumen" => "4"
                        "paginaInicial" => "e5810"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19503839"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "NOD2&#47;CARD15 mediates induction of the antimicrobial peptide human &#946;-defensin-2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E&#46; Voss"
                            1 => "J&#46; Whekamp"
                            2 => "K&#46; Whekamp"
                            3 => "E&#46;F&#46; Stange"
                            4 => "J&#46;M&#46; Schroder"
                            5 => "J&#46; Harder"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.M511044200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2006"
                        "volumen" => "281"
                        "paginaInicial" => "2005"
                        "paginaFinal" => "2011"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16319062"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0535"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Direct and indirect induction by 1&#44;25-dihydroxyvitamin D3 of the NOD2&#47;CARD15-defensin &#946;2 innate immune pathway defective in Crohn disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;T&#46; Wang"
                            1 => "B&#46; Dabbas"
                            2 => "D&#46; Laperriere"
                            3 => "A&#46;I&#46; Bitton"
                            4 => "H&#46; Soualhine"
                            5 => "L&#46;E&#46; Tavera-Mendoza"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.C109.071225"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2010"
                        "volumen" => "285"
                        "paginaInicial" => "2227"
                        "paginaFinal" => "2231"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19948723"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0540"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D&#44; innate immunity and outcomes in community acquired pneumonia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "L&#46; Leow"
                            1 => "T&#46; Simpson"
                            2 => "R&#46; Cursons"
                            3 => "N&#46; Karalus"
                            4 => "R&#46;J&#46; Hancox"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1440-1843.2011.01924.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Respirology"
                        "fecha" => "2011"
                        "volumen" => "16"
                        "paginaInicial" => "611"
                        "paginaFinal" => "616"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21244571"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0545"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multiple trauma induces serum production of host defence peptides"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Lippross"
                            1 => "T&#46; Klueter"
                            2 => "N&#46; Steubesand"
                            3 => "S&#46; Oestern"
                            4 => "R&#46; Mentlein"
                            5 => "F&#46; Hildebrandt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.injury.2011.03.044"
                      "Revista" => array:6 [
                        "tituloSerie" => "Injury"
                        "fecha" => "2011"
                        "volumen" => "43"
                        "paginaInicial" => "137"
                        "paginaFinal" => "142"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21561617"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepcidin a urinary antimicrobial peptide synthesized in the liver"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46;H&#46; Park"
                            1 => "E&#46;V&#46; Valore"
                            2 => "A&#46;J&#46; Waring"
                            3 => "T&#46; Ganz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.M008922200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2001"
                        "volumen" => "276"
                        "paginaInicial" => "7806"
                        "paginaFinal" => "7810"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11113131"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0555"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antimicrobial activity of human hepcidin 20 and 25 against clinically relevant bacterial strains&#58; effect of copper and acidic pH"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Maisetta"
                            1 => "R&#46; Petruzzelli"
                            2 => "F&#46;L&#46; Brancatisano"
                            3 => "S&#46; Esin"
                            4 => "A&#46; Vitali"
                            5 => "M&#46; Campa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.peptides.2010.08.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Peptides"
                        "fecha" => "2010"
                        "volumen" => "31"
                        "paginaInicial" => "1995"
                        "paginaFinal" => "2002"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20713108"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0560"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleuquina-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Nemeth"
                            1 => "M&#46;S&#46; Tuttle"
                            2 => "J&#46; Poelson"
                            3 => "M&#46;B&#46; Vaughn"
                            4 => "A&#46; Doniovan"
                            5 => "D&#46;M&#46; Ward"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI20945"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2004"
                        "volumen" => "113"
                        "paginaInicial" => "1271"
                        "paginaFinal" => "1276"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15124018"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0565"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Suppression of iron-regulatory hepcidin by vitamin D"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Bacchetta"
                            1 => "J&#46;J&#46; Zaritsky"
                            2 => "J&#46;L&#46; Sea"
                            3 => "R&#46;F&#46; Chun"
                            4 => "T&#46;S&#46; Lisse"
                            5 => "K&#46; Zavala"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2013040355"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2014"
                        "volumen" => "25"
                        "paginaInicial" => "564"
                        "paginaFinal" => "572"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24204002"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0570"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intravenous calcitriol improves anaemia and reduces the need for erthropoyetin in haemodialysis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Goicoechea"
                            1 => "M&#46;I&#46; Vazquez"
                            2 => "M&#46;A&#46; Ruiz"
                            3 => "F&#46; Gomez-Campdera"
                            4 => "R&#46; Perez-Garcia"
                            5 => "F&#46; Valderrabano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephron"
                        "fecha" => "1998"
                        "volumen" => "78"
                        "paginaInicial" => "23"
                        "paginaFinal" => "27"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9453399"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/21735093/0000006300000002/v1_201603200109/S2173509316000246/v1_201603200109/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "8670"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/21735093/0000006300000002/v1_201603200109/S2173509316000246/v1_201603200109/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173509316000246?idApp=UINPBA00004N"
]
Article information
ISSN: 21735093
Original language: English
The statistics are updated each day
Year/Month Html Pdf Total
2024 November 3 0 3
2024 October 96 11 107
2024 September 234 5 239
2024 August 94 2 96
2024 July 117 29 146
2024 June 90 6 96
2024 May 112 11 123
2024 April 95 3 98
2024 March 174 6 180
2024 February 161 11 172
2024 January 137 13 150
2023 December 149 12 161
2023 November 175 24 199
2023 October 178 17 195
2023 September 105 10 115
2023 August 82 6 88
2023 July 143 5 148
2023 June 100 16 116
2023 May 162 19 181
2023 April 109 9 118
2023 March 102 6 108
2023 February 111 7 118
2023 January 99 13 112
2022 December 61 10 71
2022 November 72 6 78
2022 October 65 11 76
2022 September 67 12 79
2022 August 66 21 87
2022 July 40 10 50
2022 June 44 7 51
2022 May 36 7 43
2022 April 77 12 89
2022 March 87 6 93
2022 February 68 4 72
2022 January 104 16 120
2021 December 86 18 104
2021 November 64 10 74
2021 October 83 18 101
2021 September 74 14 88
2021 August 66 11 77
2021 July 77 12 89
2021 June 63 12 75
2021 May 75 19 94
2021 April 163 34 197
2021 March 177 17 194
2021 February 60 19 79
2021 January 83 17 100
2020 December 68 15 83
2020 November 77 15 92
2020 October 37 12 49
2020 September 49 17 66
2020 August 75 15 90
2020 July 83 16 99
2020 June 83 20 103
2020 May 113 23 136
2020 April 31 16 47
2020 March 53 12 65
2020 February 38 7 45
2020 January 42 6 48
2019 December 58 11 69
2019 November 19 27 46
2019 October 33 8 41
2019 September 38 17 55
2019 August 21 3 24
2019 July 31 23 54
2019 June 76 26 102
2019 May 200 39 239
2019 April 115 8 123
2019 March 40 6 46
2019 February 65 3 68
2019 January 50 8 58
2018 December 59 4 63
2018 November 66 9 75
2018 October 63 3 66
2018 September 46 6 52
2018 August 39 2 41
2018 July 36 8 44
2018 June 21 0 21
2018 May 28 2 30
2018 April 59 2 61
2018 March 28 4 32
2018 February 141 0 141
2018 January 76 1 77
2017 December 149 3 152
2017 November 78 4 82
2017 October 21 2 23
2017 September 18 1 19
2017 August 26 2 28
2017 July 13 1 14
2017 June 21 1 22
2017 May 36 3 39
2017 April 28 1 29
2017 March 26 1 27
2017 February 72 8 80
2017 January 21 1 22
2016 December 23 3 26
2016 November 36 5 41
2016 October 38 9 47
2016 September 18 7 25
2016 August 26 4 30
2016 May 0 1 1
Show all

Follow this link to access the full text of the article

es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos