Statistics

 array:21 [
  "pii" => "X2013251410050485"
  "issn" => "20132514"
  "doi" => "10.3265/Nefrologia.pre2010.Apr.10302"
  "estado" => "S300"
  "fechaPublicacion" => "2010-07-01"
  "documento" => "article"
  "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/"
  "subdocumento" => "fla"
  "cita" => "Nefrologia (English Version). 2010;30:413-9"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 4780
    "formatos" => array:3 [
      "EPUB" => 286
      "HTML" => 3939
      "PDF" => 555
    ]
  ]
  "Traduccion" => array:1 [
    "es" => array:17 [
      "pii" => "X0211699510050488"
      "issn" => "02116995"
      "doi" => "10.3265/Nefrologia.pre2010.Apr.10302"
      "estado" => "S300"
      "fechaPublicacion" => "2010-07-01"
      "documento" => "article"
      "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/"
      "subdocumento" => "fla"
      "cita" => "Nefrologia. 2010;30:413-9"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:2 [
        "total" => 8973
        "formatos" => array:3 [
          "EPUB" => 280
          "HTML" => 8089
          "PDF" => 604
        ]
      ]
      "es" => array:12 [
        "idiomaDefecto" => true
        "titulo" => "Dinámica in vitro de la secreción de hormona paratiroidea regulada por calcio y efecto sobre el ciclo celular: adenoma frente a hiperplasia paratiroidea"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "413"
            "paginaFinal" => "419"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "In vitro dynamics of parathyroid hormone secretion regulated by calcium and effects on the cell cycle: parathyroid hyperplasia versus adenoma"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:8 [
            "identificador" => "fig1"
            "etiqueta" => "Tab.  1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "copyright" => "Elsevier España"
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "10302_108_1839_es_10302_t1.jpg"
                "Alto" => 222
                "Ancho" => 1049
                "Tamanyo" => 43056
              ]
            ]
            "descripcion" => array:1 [
              "es" => "Características clínicas y hallazgos patológicos"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "C.E. Durán, J.V. Torregrosa, A. Canalejo, Y. Almadén, J.M. Campistol, M. Rodríguez Portillo"
            "autores" => array:6 [
              0 => array:2 [
                "Iniciales" => "C.E."
                "apellidos" => "Durán"
              ]
              1 => array:2 [
                "Iniciales" => "J.V."
                "apellidos" => "Torregrosa"
              ]
              2 => array:2 [
                "Iniciales" => "A."
                "apellidos" => "Canalejo"
              ]
              3 => array:2 [
                "Iniciales" => "Y."
                "apellidos" => "Almadén"
              ]
              4 => array:2 [
                "Iniciales" => "J.M."
                "apellidos" => "Campistol"
              ]
              5 => array:2 [
                "Iniciales" => "M."
                "apellidos" => "Rodríguez Portillo"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "X2013251410050485"
          "doi" => "10.3265/Nefrologia.pre2010.Apr.10302"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050485?idApp=UINPBA000064"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699510050488?idApp=UINPBA000064"
      "url" => "/02116995/0000003000000004/v0_201502091427/X0211699510050488/v0_201502091427/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:17 [
    "pii" => "X2013251410050477"
    "issn" => "20132514"
    "doi" => "10.3265/Nefrologia.pre2010.Jun.10456"
    "estado" => "S300"
    "fechaPublicacion" => "2010-07-01"
    "documento" => "article"
    "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/"
    "subdocumento" => "fla"
    "cita" => "Nefrologia (English Version). 2010;30:420-6"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 5468
      "formatos" => array:3 [
        "EPUB" => 270
        "HTML" => 3195
        "PDF" => 2003
      ]
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "titulo" => "Temporal evolution of renal involvement in a necropsy study of HIV patients from the pre and HAART eras"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "420"
          "paginaFinal" => "426"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Evolución temporal de la afectación renal en una serie necrópsica de pacientes VIH de las eras pre y TARGA"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig1"
          "etiqueta" => "Tab.  1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "copyright" => "Elsevier España"
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "10456_108_6694_en_10456en_t1.jpg"
              "Alto" => 471
              "Ancho" => 888
              "Tamanyo" => 61122
            ]
          ]
          "descripcion" => array:1 [
            "en" => "Sample characteristics"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "M.C. Nicolau Laparra, F. Martínez, V. Giner, C. Monteagudo, M.J. Galindo, F. Alcácer, V. Oliver, J. Guix, J. Redón"
          "autores" => array:9 [
            0 => array:2 [
              "Iniciales" => "M.C."
              "apellidos" => "Nicolau Laparra"
            ]
            1 => array:2 [
              "Iniciales" => "F."
              "apellidos" => "Martínez"
            ]
            2 => array:2 [
              "Iniciales" => "V."
              "apellidos" => "Giner"
            ]
            3 => array:2 [
              "Iniciales" => "C."
              "apellidos" => "Monteagudo"
            ]
            4 => array:2 [
              "Iniciales" => "M.J."
              "apellidos" => "Galindo"
            ]
            5 => array:2 [
              "Iniciales" => "F."
              "apellidos" => "Alcácer"
            ]
            6 => array:2 [
              "Iniciales" => "V."
              "apellidos" => "Oliver"
            ]
            7 => array:2 [
              "Iniciales" => "J."
              "apellidos" => "Guix"
            ]
            8 => array:2 [
              "Iniciales" => "J."
              "apellidos" => "Redón"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "X021169951005047X"
        "doi" => "10.3265/Nefrologia.pre2010.Jun.10456"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X021169951005047X?idApp=UINPBA000064"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050477?idApp=UINPBA000064"
    "url" => "/20132514/0000003000000004/v0_201502091652/X2013251410050477/v0_201502091652/en/main.assets"
  ]
  "itemAnterior" => array:17 [
    "pii" => "X2013251410050493"
    "issn" => "20132514"
    "doi" => "10.3265/Nefrologia.pre2010.Jun.10264"
    "estado" => "S300"
    "fechaPublicacion" => "2010-07-01"
    "documento" => "article"
    "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/"
    "subdocumento" => "fla"
    "cita" => "Nefrologia (English Version). 2010;30:403-12"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 6692
      "formatos" => array:3 [
        "EPUB" => 294
        "HTML" => 5476
        "PDF" => 922
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "titulo" => "Economic evaluation of haemodialysis. Analysis of cost components based on patient-specific data"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "403"
          "paginaFinal" => "412"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Evaluación económica de la hemodiálisis. Análisis de los componentes del coste basado en datos individuales"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "V. Lorenzo, L. Perestelo, M. Barroso, A. Torres, J. Nazco"
          "autores" => array:5 [
            0 => array:2 [
              "Iniciales" => "V."
              "apellidos" => "Lorenzo"
            ]
            1 => array:2 [
              "Iniciales" => "L."
              "apellidos" => "Perestelo"
            ]
            2 => array:2 [
              "Iniciales" => "M."
              "apellidos" => "Barroso"
            ]
            3 => array:2 [
              "Iniciales" => "A."
              "apellidos" => "Torres"
            ]
            4 => array:2 [
              "Iniciales" => "J."
              "apellidos" => "Nazco"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "X0211699510050496"
        "doi" => "10.3265/Nefrologia.pre2010.Jun.10264"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699510050496?idApp=UINPBA000064"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050493?idApp=UINPBA000064"
    "url" => "/20132514/0000003000000004/v0_201502091652/X2013251410050493/v0_201502091652/en/main.assets"
  ]
  "en" => array:15 [
    "idiomaDefecto" => true
    "titulo" => "In vitro dynamics of parathyroid hormone secretion regulated by calcium and effects on the cell cycle: parathyroid hyperplasia versus adenoma"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "413"
        "paginaFinal" => "419"
      ]
    ]
    "autores" => array:1 [
      0 => array:3 [
        "autoresLista" => "C.E. Durán, J.V. Torregrosa, A. Canalejo, Y. Almadén, J.M. Campistol, M. Rodríguez Portillo"
        "autores" => array:6 [
          0 => array:4 [
            "Iniciales" => "C.E."
            "apellidos" => "Durán"
            "email" => array:1 [
              0 => "carlosed36@gmail.com"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "affa"
              ]
            ]
          ]
          1 => array:3 [
            "Iniciales" => "J.V."
            "apellidos" => "Torregrosa"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "affa"
              ]
            ]
          ]
          2 => array:3 [
            "Iniciales" => "A."
            "apellidos" => "Canalejo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "affb"
              ]
            ]
          ]
          3 => array:3 [
            "Iniciales" => "Y."
            "apellidos" => "Almad&#233;n"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "affb"
              ]
            ]
          ]
          4 => array:3 [
            "Iniciales" => "J.M."
            "apellidos" => "Campistol"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "affa"
              ]
            ]
          ]
          5 => array:3 [
            "Iniciales" => "M."
            "apellidos" => "Rodr&#237;guez Portillo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "affb"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "Unidad de Trasplante Renal, Hospital Clínic, Barcelona,   "
            "etiqueta" => "<span class="elsevierStyleSup">a</span>"
            "identificador" => "affa"
          ]
          1 => array:3 [
            "entidad" => "Unidad de Investigación, Hospital Reina Sofía, Córdoba,   "
            "etiqueta" => "<span class="elsevierStyleSup">b</span>"
            "identificador" => "affb"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Din&#225;mica in vitro de la secreci&#243;n de hormona paratiroidea regulada por calcio y efecto sobre el ciclo celular&#58; adenoma frente a hiperplasia paratiroidea"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig1"
        "etiqueta" => "Tab.  1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "copyright" => "Elsevier Espa&#241;a"
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "10302_108_6596_en_10302en_t1.jpg"
            "Alto" => 133
            "Ancho" => 455
            "Tamanyo" => 18456
          ]
        ]
        "descripcion" => array:1 [
          "en" => "Clinical characteristics and pathological findings"
        ]
      ]
    ]
    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">It has been known for some time that serum calcium is the main factor responsible for the stimulation and inhibition of parathyroid hormone &#40;PTH&#41; secretion and that there is an inverse sigmoidal relationship between the concentration of calcium and PTH&#46;<span class="elsevierStyleSup">1</span></p><p class="elsevierStylePara">The parathyroid gland is particularly sensitive to changes in serum calcium&#44; and thus&#44; small reductions in the concentration of calcium cause rapid increases in PTH secretions&#44; while small increases in serum calcium decrease PTH secretions&#46;</p><p class="elsevierStylePara">Some studies <span class="elsevierStyleItalic">in vivo </span>and <span class="elsevierStyleItalic">in vitro</span> have demonstrated that the PTH response to changes in calcium concentrations is abnormal in patients with primary hyperparathyroidism<span class="elsevierStyleSup">2&#44;3</span> and in uraemic patients with secondary hyperparathyroidism&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">At present&#44; it is known that calcium exerts its action through the specific calcium-sensing receptor of the parathyroid cell<span class="elsevierStyleSup">5&#44;6</span> and it has been suggested that a decrease in its density could be responsible for the decreased response to changes in calcium concentrations in the hypertrophic parathyroid glands and the adenomatous glands&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara">So far&#44; the <span class="elsevierStyleItalic">in vitro </span>comparison of the calcium-regulated PTH response of adenomas from patients with primary hyperparathyroidism versus hyperplastic glands from patients with secondary hyperparathyroidism has not been fully studied&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">Additionally&#44; it is known that different concentrations of calcium can stimulate or halt the proliferation of parathyroid cells&#44;<span class="elsevierStyleSup">9</span> but the relationship between the cell cycle and the calcium concentration of parathyroid adenomas and glandular hyperplasia has also not been studied thoroughly&#46;</p><p class="elsevierStylePara">The aim of this study was to compare the dynamic of calcium-regulated PTH secretion <span class="elsevierStyleItalic">in vitro</span> in adenomas versus hyperplastic glands and to assess the relationship between the parathyroid cell cycle and the calcium-regulated PTH secretion in these glands&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Patients</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The study included glands from eight patients with primary hyperparathyroidism and seven from patients with chronic kidney disease with secondary hyperparathyroidism&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Parathyroid tissue</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">A total of 31 parathyroid glands were included in the study&#44; along with 8 adenomas and 23 glands with diffuse hyperplasia&#44; which were processed in the following manner&#58; immediately after resection&#44; both the adenomatous and the hyperplastic glands were separated in several aliquots and incubated at 4&#176;C in RPMI with calcium concentrations of 1&#46;5mM for 16-18 hours until an <span class="elsevierStyleItalic">in vitro</span> study was carried out&#46;</p><p class="elsevierStylePara">One of the incubated aliquots of each gland was used to evaluate PTH secretion <span class="elsevierStyleItalic">in vitro </span>and another was used to study the cell cycle&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Evaluation of </span></span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">calcium-regulated parathyroid hormone secretion </span></span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">in vitro</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Incubation medium</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The parathyroid tissue aliquot was cut into pieces of approximately 1mm<span class="elsevierStyleSup">3</span> that were then separated into individual nylon wells&#44; each in 2ml of an incubation medium at 37&#176; C &#40;AOS-0&#44; SBS Instruments S&#46;A&#46;&#44; Badalona&#44; Spain&#41;&#46; The incubation medium was a buffered solution &#40;pH&#61; 7&#46;4&#41; containing in mM&#44; NaCl 125&#44; KCl 5&#46;9&#44; MgCl<span class="elsevierStyleInf">2</span> 0&#46;5&#44; NaH<span class="elsevierStyleInf">2</span>PO<span class="elsevierStyleInf">4</span> and Na<span class="elsevierStyleInf">2</span>HPO<span class="elsevierStyleInf">4</span> &#40;1&#58;2&#41; 1&#44; Na-pyruvate 1&#44; glutamine 4&#44; glucose 12&#44; Hepes 25 with quick insulin 0&#46;1 U&#47;ml&#44; 0&#46;1&#37; bovine serum albumin&#44; penicillin G 100 U&#47;ml&#44; streptomycin 100&#956;g&#47;ml and CaCl<span class="elsevierStyleInf">2</span> ranging from 0&#46;4 to 1&#46;5&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Calcium-regulated parathyroid hormone secretion</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">After five hours of incubation&#44; the parathyroid tissue was sequentially transferred in hourly intervals to other wells containing solutions with varying concentrations of calcium&#58; 0&#46;4&#44; 0&#46;6&#44; 0&#46;8&#44; 1&#46;0&#44; 1&#46;25 and 1&#46;35 or 1&#46;5mM&#46; Calcium concentrations were confirmed for each experiment employing the measurement of ionised calcium using a selective electrode &#40;model 634&#44; Ciba Corning&#44; Essex&#44; United Kingdom&#41;&#46; The ionised calcium in the medium was kept constant during the incubation period&#46; PTHi concentration in the incubation medium was measured using the human PTHi IRMA assay &#40;Nichols Institute&#44; San Juan Capistrano&#44; CA&#44; USA&#41; with an intra-assay and inter-assay coefficient of variation of 4&#46;3&#37; and 4&#46;7&#37;&#44; respectively&#46; The serum ionised calcium was measured with a calcium-selective electrode &#40;Ciba Corning c-634&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Terminology</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The following terms were used&#58; <span class="elsevierStyleItalic">1&#41;</span> Baseline PTH&#44; the PTH value before induction of hypocalcaemia or hypercalcaemia&#59; <span class="elsevierStyleItalic">2&#41;</span> Peak PTH&#44; the highest PTH value observed in response to hypocalcaemia and whose value could not be increased by a reduction in serum calcium concentration&#59; <span class="elsevierStyleItalic">3&#41;</span> Minimum PTH&#44; the lowest PTH level during the supression by hypercalcaemia and whose value could not be lowered by later increases in serum calcium&#59; <span class="elsevierStyleItalic">4&#41;</span> the set point<span class="elsevierStyleItalic"> </span>of PTH secretion was calculated in two ways&#58; one as the serum calcium concentration that reduced the maximum PTH secretion by 50&#37; and the other as the calcium concentration that reduced the PTH secretion by half between the maximum and minimum secretion&#46;<span class="elsevierStyleSup">10</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Parathyroid cell cycle analysis</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Parathyroid cells were isolated without the use of enzymes&#46; Small parathyroid tissue fragments were squashed using DuPont forceps under an inverted microscope &#40;x10&#41; followed by gentle pipetting&#46; To maintain a high cellular concentration&#44; all of these manipulations were performed with low volumes of PBS &#40;50&#956;l&#41;&#46;</p><p class="elsevierStylePara">The parathyroid cell cycle was analysed using the method described by Vindelov and Christensen&#46;<span class="elsevierStyleSup">11</span> Briefly&#44; the clean cell nuclei were isolated by the combined action of the nonionic detergent Nonidet-P40 and trypsin&#44; followed by treatment with trypsin inhibitor &#40;type II-0&#41; to stop the reaction of trypsin&#44; and with RNase&#44; to prevent the dye from joining with the double-stranded RNA&#46; In the final step&#44; the isolated nuclei were strained with propidium iodide and stabilised with spermine&#46;</p><p class="elsevierStylePara">The nuclei were acquired by flow cytometry &#40;FACScan&#44; Beckton-Dickinson&#44; CA&#44; USA&#41; and analysed using CELLFIT software &#40;Beckton-Dickinson&#41;&#46;</p><p class="elsevierStylePara">Cell viability was evaluated by flow cytometry&#46; The cells were stained with green fluorodiacetate &#40;15min at 37&#176;C in darkness&#41;&#44; which stains living cells&#44; and red propidium iodide &#40;5min at 37&#176;C in darkness&#41;&#44; which marks dead cells&#46; Subsequently&#44; the cells were introduced into the flow cytometer and analysed with Lysis II software &#40;Beckton-Dickinson&#41;&#46;<span class="elsevierStyleSup"> 12</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Reactants</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The RPMI was purchased from Biowhittaker&#44; Vervier&#44; Belgium&#59; the PBS from Oxoid&#44; Hampshire&#44; United Kingdom&#59; and all other reagants from Sigma&#44; St&#46; Louis&#44; MO&#44; USA&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical analysis</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Values are expressed as mean &#177; SD&#46; We used ANOVA and Duncan&#8217;s test for comparing multiple averages&#46; The unpaired t-test was used to evaluate differences between group averages&#46; The correlation between two variables was evaluated by linear regression analysis&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The changes in calcium-regulated PTH secretion <span class="elsevierStyleItalic">in vitro</span> in the 23 hyperplastic parathyroid glands and the 8 adenomas described earlier are shown in Figure 1&#46; The increase in extracellular calcium in the parathyroid tissues of the hyperplastic glands decreased the secretion of PTH manifested in calcium values of 0&#46;8mM and a maximum inhibition of PTH secretion in a calcium value of 1&#46;25mM&#46; In contrast&#44; the parathyroid adenoma tissues required Ca concentrations of 1&#46;2mM to cause a slight decrease in PTH secretion&#44; achieving inhibition of secretion with an increase in Ca concentration&#46;</p><p class="elsevierStylePara">The cell cycle analysis showed that the percentage of G0&#47;G1-phase parathyroid cells in parathyroid adenomas varied from 13&#37; to 97&#37;&#44; with a mean of 64&#37;&#177;12&#37;&#46; These values contrast with those observed in secondary hyperplastic glands&#44; which were always greater than 74&#37; with a mean of 89&#37;&#177;3&#37; &#40;Figure 2&#41;&#46; Similarly&#44; the precentage of S-phase cells was less than 10&#37; in hyperplastic parathyroid glands while 3 of the 8 parathyroid adenomas had more than 11&#37; S-phase cells &#40;Figure 3&#41;&#46;</p><p class="elsevierStylePara">There were no significant differences between the values of the mean percentages of G0&#47;G1-phase or S-phase cells of the adenomas with respect to the hyperplastic glands&#46;</p><p class="elsevierStylePara">To evaluate a possible association between the severity of hyperparathyroidism and the percentage of cells at rest &#40;G0&#47;S1 phase&#41;&#44; the minimum and maximum basal PTH values were correlated with the percentage of G0&#47;G1-phase cells&#46;</p><p class="elsevierStylePara">There was no significant correlation in the adenomas&#46;</p><p class="elsevierStylePara">There was no significant correlation in the hyperplastic glands between the minimum and maximum basal PTH concentrations and the percentage of cells in G0&#47;G1 phase &#40;r values &#61; 0&#46;525&#44; 0&#46;0821 and 0&#46;709&#44; respectively&#41;&#46; However&#44; there was a significant correlation between the percentage of G0&#47;G1 phase cells with the calcium set point<span class="elsevierStyleItalic"> </span>&#40;r&#61; 0&#46;914&#44; p&#60; 0&#46;005&#41; &#40;Figure 4&#41; and the basal serum calcium concentration &#40;r&#61; 0&#46;862&#59; p &#60;0&#46;02&#41; &#40;Figure 5&#41;&#44; in other words&#44; the greater the calcium concentration&#44; the lesser the proliferation&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Previous studies have shown that the regulation of PTH secretion <span class="elsevierStyleItalic">in vivo</span> in response to changes in calcium concentration is altered both in primary and secondary hyperparathyroidism&#46;<span class="elsevierStyleSup">6-8&#44;13</span> Other studies have shown that the set point<span class="elsevierStyleItalic"> </span>of Ca&#44; both <span class="elsevierStyleItalic">in vivo </span>and <span class="elsevierStyleItalic">in vitro</span>&#44; and the non-suppresive PTH secretion is greater in patients with hyperparathyroidism than in healthy subjects&#46;<span class="elsevierStyleSup">14-16</span></p><p class="elsevierStylePara">In a recent study<span class="elsevierStyleSup">10</span> using hyperplastic tissue&#44; it was observed that although there are differences between the set point<span class="elsevierStyleItalic"> </span>of calcium <span class="elsevierStyleItalic">in vivo </span>and <span class="elsevierStyleItalic">in vitro&#44; </span>the maximum degree of PTH inhibition and the dynamic of calcium-regulated PTH secretion are similar in both circumstances&#44; which means we can extrapolate that the results obtained <span class="elsevierStyleItalic">in vitro</span> with intact tissue are similar to those produced <span class="elsevierStyleItalic">in vivo</span>&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic">In vitro </span>studies using isolated parathyroid cells from adenomatous and hyperplastic glands have shown that the set point<span class="elsevierStyleItalic"> </span>of PTH secretion was greater than in normal parathyroid tissue&#44; suggesting abnormal regulation of PTH secretion by calcium&#46;<span class="elsevierStyleSup">6-8&#44;14</span></p><p class="elsevierStylePara">In our study&#44; unlike previous ones&#44; calcium-regulated PTH secretion <span class="elsevierStyleItalic">in vitro</span> was assessed in parathyroid adenomas and in secondary parathyroid hyperplasia using small quantities of intact parathyroid tissue&#46; This study shows that calcium-regulated PTH secretion is clearly different between parathyroid adenomatous and hyperplastic glands&#44; with PTH secretion being minimally inhibited by calcium in adenomas and progressively reduced in hyperplastic glands despite involving patients with significantly higher basal PTH levels than those with adenomas&#46;</p><p class="elsevierStylePara">The concentration of extracellular calcium required to reduce PTH secretion was significantly greater in adenomas than in hyperplastic glands&#46; These results indicate that the suppressibility of PTH secretion in adenomas is reduced when compared with hyperplastic glands&#46; These findings are similar to others reported in the scientific literature and in those studies that used isolated parathyroid cells&#46;<span class="elsevierStyleSup">7</span> In our case&#44; the difference between adenomatous and hyperplastic tissue appears magnified&#44; which could be attributed to the fact that we used intact tissue&#44; which may be more comparable to the <span class="elsevierStyleItalic">in vivo </span>situation&#46; A change in the calcium-sensing receptor in the parathyroid cells could explain this difference&#46; Some studies have shown that the protein and messenger RNA of the calcium-sensing receptor are decreased in both parathyroid adenomas and in hyperplastic glands&#44; although more so in adenomas&#46;<span class="elsevierStyleSup">17-19</span> Nevertheles&#44; in a similar study&#44; the calcium-sensing receptor protein determined by immunohistochemistry did not differ between adenomas and hyperplasia&#46;<span class="elsevierStyleSup">20</span> Other studies have shown considerable variation in the number of cells with calcium receptor deficit in parathyroids adenomas&#44; but in any case&#44; there is always a significant reduction in the expression of the Ca receptor&#46;<span class="elsevierStyleSup">21</span></p><p class="elsevierStylePara">Regarding parathyroid adenomas&#44; there was a wide range in the percentage of cells in the G0&#47;G1 phase &#40;from 13&#37; to 97&#37;&#41;&#44; in contrast to secondary hyperplasia that had more than 74&#37; of cells in the G0&#47;G1 phase&#46; These findings are similar to those reported by other work groups showing that the percentage of cells in G0&#47;G1 phase in parathyroid adenomas was between 10&#37; and 90&#37;&#44; while in secondary hyperplasia all glands had more than 70&#37; of the cells in the G0&#47;G1 phase&#46;<span class="elsevierStyleSup">22-24</span> These data suggest a different pathological growth stimulant for parathyroid adenomas with respect to hyperplastic glands&#46; There were no statistical differences between the mean average of cells in the G0&#47;G1 phase in adenomas versus those in secondary hyperplasia&#44; perhaps because of the high dispersion of the values in the group of adenomas&#46;</p><p class="elsevierStylePara">It is known that cells in the hyperplastic parathyroid glands show moderate proliferative activity&#46; In order to proliferate&#44; a cell must enter the cell cycle phase where DNA synthesis and subsequent mitosis occurs&#44; and follow an organised process&#46;<span class="elsevierStyleSup">25&#44;26</span> The progression through the cell cycle ensures that DNA replication is complete before mitosis occurs&#46; During the transition through the cell cycle&#44; a cell can remain at rest at a number of specific checkpoints that prevent the completion of the cell cycle and thereby proliferation&#46;</p><p class="elsevierStylePara">An interesting observation from our study was the good correlation between the set point of PTH secretion and basal calcium with the percentage of cells in the G0&#47;G1 phase&#46; In fact&#44; the high calcium concentrations were associated with a low percentage of proliferating cells&#46; These results show that in the hyperplastic glands&#44; parathyroid cells are not always in a proliferation phase&#44; as expected&#46;</p><p class="elsevierStylePara">Additionally&#44; hypocalcaemia is considered an important factor in the generation and development of secondary hyperparathyroidism due to the effect on the stimulation of parathyroid proliferation&#46;<span class="elsevierStyleSup">22</span> Our findings indicate that control of parathyroid cell proliferation by calcium is maintained even in advanced stages of secondary hyperparathyrodism&#46;</p><p class="elsevierStylePara">In conclusion&#44; the regulation of PTH secretion by extracellular calcium <span class="elsevierStyleItalic">in vitro</span> is less sensitive in parathyroid adenomas than in parathyroid hyperplastic glands&#46; Also&#44; cell proliferation in parathyroid hyperplasia by secondary hyperparathyroidism seems to be regulated by the concentration of extracellular calcium&#59; in other words&#44; the higher the calcaemia the lower the proliferation&#46;</p><p class="elsevierStylePara">From all of this we can deduce that a certain degree of hypercalcaemia&#44; or perhaps more importantly&#44; treatment with calcimimetics&#44; may slow cell proliferation in secondary hyperparathyroidism&#46; With this we could theoretically prevent monoclonal growth and the formation of adenomas&#44; which are much more difficult to control&#46;</p><p class="elsevierStylePara"><a href="grande&#47;10302&#95;108&#95;6596&#95;en&#95;10302en&#95;t1&#46;jpg" class="elsevierStyleCrossRefs"><img src="10302_108_6596_en_10302en_t1.jpg" alt="Clinical characteristics and pathological findings"></img></a></p><p class="elsevierStylePara">Table 1&#46; Clinical characteristics and pathological findings</p><p class="elsevierStylePara"><a href="grande&#47;10302&#95;108&#95;6597&#95;en&#95;10302en&#95;f1&#46;jpg" class="elsevierStyleCrossRefs"><img src="10302_108_6597_en_10302en_f1.jpg" alt="Changes in calcium-regulated PTH secretion in vitro&#58; adenoma versus parathyroid hyperplasia "></img></a></p><p class="elsevierStylePara">Figure 1&#46; Changes in calcium-regulated PTH secretion in vitro&#58; adenoma versus parathyroid hyperplasia </p><p class="elsevierStylePara"><a href="grande&#47;10302&#95;108&#95;6603&#95;en&#95;10302en&#95;f2&#46;jpg" class="elsevierStyleCrossRefs"><img src="10302_108_6603_en_10302en_f2.jpg" alt="Percentage of cells in G0-G1 phase &#40;&#37;&#41; "></img></a></p><p class="elsevierStylePara">Figure 2&#46; Percentage of cells in G0-G1 phase &#40;&#37;&#41; </p><p class="elsevierStylePara"><a href="grande&#47;10302&#95;108&#95;6604&#95;en&#95;10302en&#95;f3&#46;jpg" class="elsevierStyleCrossRefs"><img src="10302_108_6604_en_10302en_f3.jpg" alt="Percentage of cells in S phase &#40;&#37;&#41; "></img></a></p><p class="elsevierStylePara">Figure 3&#46; Percentage of cells in S phase &#40;&#37;&#41; </p><p class="elsevierStylePara"><a href="grande&#47;10302&#95;108&#95;6605&#95;en&#95;10302en&#95;f4&#46;jpg" class="elsevierStyleCrossRefs"><img src="10302_108_6605_en_10302en_f4.jpg" alt="Correlation between percentage of cells in G0&#47;G1 phase with the set point of calcium "></img></a></p><p class="elsevierStylePara">Figure 4&#46; Correlation between percentage of cells in G0&#47;G1 phase with the set point of calcium </p><p class="elsevierStylePara"><a href="grande&#47;10302&#95;108&#95;6606&#95;en&#95;10302en&#95;f5&#46;jpg" class="elsevierStyleCrossRefs"><img src="10302_108_6606_en_10302en_f5.jpg" alt="Correlation between percentage of cells in G0&#47;G1 phase with the &#91;Ca&#93;"></img></a></p><p class="elsevierStylePara">Figure 5&#46; Correlation between percentage of cells in G0&#47;G1 phase with the &#91;Ca&#93;</p>"
    "pdfFichero" => "P1-E501-S2436-A10302-EN.pdf"
    "tienePdf" => true
    "PalabrasClave" => array:2 [
      "es" => array:3 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec441727"
          "palabras" => array:1 [
            0 => "Ciclo celular"
          ]
        ]
        1 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec441729"
          "palabras" => array:1 [
            0 => "Hiperparatiroidismo secundario"
          ]
        ]
        2 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec441731"
          "palabras" => array:1 [
            0 => "Set-point de calcio"
          ]
        ]
      ]
      "en" => array:3 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec441728"
          "palabras" => array:1 [
            0 => "Cellular cycle"
          ]
        ]
        1 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec441730"
          "palabras" => array:1 [
            0 => "Secondary hyperparathyroidism"
          ]
        ]
        2 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec441732"
          "palabras" => array:1 [
            0 => "Set-point of Ca"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "es" => array:1 [
        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Objetivo&#58;</span> Comparar <span class="elsevierStyleItalic">in vitro</span> la din&#225;mica de la secreci&#243;n de hormona paratiroidea &#40;PTH&#41; regulada por calcio y su relaci&#243;n con el ciclo celular en adenomas frente a&#160;hiperplasia de paratiroides&#46; <span class="elsevierStyleBold">Material y m&#233;todos&#58; </span>Ocho adenomas de paratiroides y 23 gl&#225;ndulas hiperpl&#225;sicas procedentes de 8 pacientes con hiperparatiroidismo primario y 7 pacientes con hiperparatiroidismo secundario&#44; respectivamente&#46; Para el estudio de la din&#225;mica de secreci&#243;n&#44; peque&#241;os&#160;fragmentos de tejido paratiroideo se transfirieron secuencialmente a intervalos de una hora a pocillos con concentraciones variables de calcio&#58; 0&#44;4&#44; 0&#44;6&#44; 0&#44;8&#44; 1&#44;0&#44; 1&#44;25&#44; y 1&#44;35 o 1&#44;5 mM&#46; Se determinaron las concentraciones de iPTH en el medio&#46; C&#233;lulas paratiroides se aislaron sin el uso de enzimas y el ciclo celular paratiroideo se analiz&#243; por el m&#233;todo de Vindelov&#46; El n&#250;cleo se adquiri&#243; por citometr&#237;a de flujo y se analiz&#243; usando un <span class="elsevierStyleItalic">software</span> CELLFIT&#46; <span class="elsevierStyleBold">Resultados&#58;</span> En los tejidos paratiroideos de las gl&#225;ndulas hiperpl&#225;sicas&#44; el aumento del calcio extracelular produjo una disminuci&#243;n de la secreci&#243;n de PTH manifestada con valores de calcio de 0&#44;8 mM y una inhibici&#243;n m&#225;xima de secreci&#243;n de PTH con un calcio de 1&#44;25 mM&#46; Por el contrario&#44; en los tejidos de los adenomas de paratiroides se requirieron concentraciones de Ca de 1&#44;2 mM para provocar una m&#237;nima disminuci&#243;n de la secreci&#243;n de PTH&#46; En los adenomas no hubo correlaci&#243;n entre las fases del ciclo celular y la calcemia o el <span class="elsevierStyleItalic">set point</span>&#44; en las hiperplasias hubo una correlaci&#243;n significativa entre el porcentaje de c&#233;lulas en fase G0&#47;G1 con el <span class="elsevierStyleItalic">set point</span> &#40;r &#61; 0&#44;914&#59; p &#60;0&#44;005&#41; y el calcio s&#233;rico basal &#40;r &#61; 0&#44;862&#59; p &#60;0&#44;02&#41;&#46; <span class="elsevierStyleBold">Conclusiones&#58;</span> La regulaci&#243;n de la secreci&#243;n de PTH por el calcio extracelular <span class="elsevierStyleItalic">in vitro</span> es menos sensible en adenomas que en gl&#225;ndulas hiperpl&#225;sicas paratiroideas&#46; En hiperplasia paratiroidea la proliferaci&#243;n celular parece estar regulada por la concentraci&#243;n de calcio extracelular &#40;a mayor calcemia menor proliferaci&#243;n&#41;&#46;</p>"
      ]
      "en" => array:1 [
        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">Aim&#58;</span> To compare the dynamics of calcium-regulated PTH secretion</span> in vitro <span class="elsevierStyleItalic">from adenomatous versus hyperplastic glands and to investigate the relationship between the parathyroid cell cycle and the calcium-regulated PTH secretion in these glands&#46; <span class="elsevierStyleBold">Materials and methods&#58;</span> A total of 31 parathyroid glands &#40;8 adenomatous and 23 hyperplastic&#41; from 8 patients with primary hyperparathyroidism and 7 with secondary hyperparathyroidism respectively were studied&#46; For the evaluation of calcium-regulated PTH secretion&#44; small parathyroid pieces of 1 mm were sequentially transferred to wells with varying Ca concentrations&#58; 0&#46;4&#44; 0&#46;6&#44; 0&#46;8&#44; 1&#44; 1&#46;25 and 1&#46;35 or 1&#46;5 mM&#46; PTH concentrations were determined in the medium&#46; For the parathyroid cell cycle studies&#44; parathyroid cells were isolated without the use of enzymes and cell cycle was analyzed using the method described by Vindelov&#46; The nuclei were acquired by flow cytometer and analyzed using the CELLFIT software&#46; <span class="elsevierStyleBold">Results&#58;</span> In parathyroid tissues from hyperplastic glands&#44; the increase in extracellular calcium produced a decrease in PTH secretion which was apparent with a calcium level as low as 0&#46;8 mM and the maximal inhibition of PTH secretion was obtained with a calcium of 1&#46;25 mM&#44; by the contrary&#44; adenomatous glands required a calcium of 1&#46;2 mM to produce a minimal decrease in PTH secretion&#46; In hyperplastic parathyroid glands but not in parathyroid adenomas there was a significant correlation between the percentage of cells in G0&#47;G1 phase with the set point &#40;r &#61; 0&#46;914&#59; P &#60;0&#46;005&#41; and the basal serum Ca &#40;r &#61; 0&#46;862&#59; P &#60;0&#46;02&#41;&#46; <span class="elsevierStyleBold">Conclusions&#58;</span> The control of the extracellular calcium-PTH release</span> in vitro <span class="elsevierStyleItalic">is less sensitive in parathyroid adenomas than hyperplasic parathyroid glands&#46; In parathyroid hyperplasia the cell proliferation may be regulated by the extracellular calcium concentration &#40;higher calcemia less proliferation&#41;&#46;</span></p>"
      ]
    ]
    "multimedia" => array:6 [
      0 => array:8 [
        "identificador" => "fig1"
        "etiqueta" => "Tab.  1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "copyright" => "Elsevier Espa&#241;a"
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "10302_108_6596_en_10302en_t1.jpg"
            "Alto" => 133
            "Ancho" => 455
            "Tamanyo" => 18456
          ]
        ]
        "descripcion" => array:1 [
          "en" => "Clinical characteristics and pathological findings"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig2"
        "etiqueta" => "Fig. 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "copyright" => "Elsevier Espa&#241;a"
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "10302_108_6597_en_10302en_f1.jpg"
            "Alto" => 579
            "Ancho" => 738
            "Tamanyo" => 34676
          ]
        ]
        "descripcion" => array:1 [
          "en" => "Changes in calcium-regulated PTH secretion in vitro&#58; adenoma versus parathyroid hyperplasia"
        ]
      ]
      2 => array:8 [
        "identificador" => "fig3"
        "etiqueta" => "Fig. 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "copyright" => "Elsevier Espa&#241;a"
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "10302_108_6603_en_10302en_f2.jpg"
            "Alto" => 537
            "Ancho" => 379
            "Tamanyo" => 15094
          ]
        ]
        "descripcion" => array:1 [
          "en" => "Percentage of cells in G0-G1 phase &#40;&#37;&#41;"
        ]
      ]
      3 => array:8 [
        "identificador" => "fig4"
        "etiqueta" => "Fig. 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "copyright" => "Elsevier Espa&#241;a"
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "10302_108_6604_en_10302en_f3.jpg"
            "Alto" => 537
            "Ancho" => 399
            "Tamanyo" => 14764
          ]
        ]
        "descripcion" => array:1 [
          "en" => "Percentage of cells in S phase &#40;&#37;&#41;"
        ]
      ]
      4 => array:8 [
        "identificador" => "fig5"
        "etiqueta" => "Fig. 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "copyright" => "Elsevier Espa&#241;a"
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "10302_108_6605_en_10302en_f4.jpg"
            "Alto" => 525
            "Ancho" => 687
            "Tamanyo" => 26111
          ]
        ]
        "descripcion" => array:1 [
          "en" => "Correlation between percentage of cells in G0&#47;G1 phase with the set point of calcium"
        ]
      ]
      5 => array:8 [
        "identificador" => "fig6"
        "etiqueta" => "Fig. 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "copyright" => "Elsevier Espa&#241;a"
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "10302_108_6606_en_10302en_f5.jpg"
            "Alto" => 540
            "Ancho" => 717
            "Tamanyo" => 27670
          ]
        ]
        "descripcion" => array:1 [
          "en" => "Correlation between percentage of cells in G0&#47;G1 phase with the &#91;Ca&#93;"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Bibliography"
      "seccion" => array:1 [
        0 => array:1 [
          "bibliografiaReferencia" => array:26 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Mater GP, Hurst JG. The sigmoidal relationship between parathyroid hormona secretion rate and plasma calcium concentrations in calves. Endocrinology 1978;102:1036-39."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Brown EM, Gardner DG, Brennan MF, et al. Calcium-regulated parathyroid hormone released in primary hyperparathyroidism. Am J Med 1979;66:923-31.\u{A0} <a href="http://www.ncbi.nlm.nih.gov/pubmed/453225" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib3"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Gardin JP, Patron P, Fouqueray B, et al. Maximal PTH secretory rate and set point for calcium in normal subjects and patients with primary hyperparathyroidism. Min Elect Metab 1988;14:221-8."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109708032348"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib4"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Rudberg C, Akerstrom G, Ljunghall S, et al. Regulation of parathyroid hormone release in primary and secondary hyperparathyroidism-studies in vivo and in vitro. Acta Endocrinol 1982; 101: 408-13. <a href="http://www.ncbi.nlm.nih.gov/pubmed/7148339" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib5"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Brown EM, Gamba G, Riccardi D, et al. Cloning and characterization of an extracellular Ca2 -sensing receptor from bovine parathyroid. Nature 1993;366:575-80. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8255296" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib6"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Chattopadhyay N, Mothal A, Brown EM. The calcium-sensing receptor: Window into the physiology and pathophysiology of mineral ion metabolism. Endocr Rev 1996;17:289-307. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8854047" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109707029026"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib7"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Felsenfeld AJ, Llach F. Parathyroid gland function in chronic renal failure. Kidney Int 1993;43:1722-5."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109708026090"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Felsenfeld AJ, Rodríguez M, Aguilera-Tejero E. Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism. Clin J Am Soc Nephrol 2007;2:1283-305.\u{A0} <a href="http://www.ncbi.nlm.nih.gov/pubmed/17942777" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Wallfelt C, Gylfe E, Larsson R, et al. Relationship between external and cytoplasmic calcium concentrations, parathyroid hormone release and weight of parathyroid glands in human hyperparathyroidism. J Endocr 1988;116:457-64. <a href="http://www.ncbi.nlm.nih.gov/pubmed/3351432" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib10"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Durán CE, Torregrosa JV, Almadén Y, Canalejo A, Campistol JM, Rodríguez Portillo M. Dynamics of calcium-regulated PTH secretion in secondary hyperparahtyroidism: comparison between ¿in vivo¿ versus ¿in vitro¿ responses. Nefrologia\u{A0}2010;30(1):54-63.\u{A0}"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109707020608"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib11"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Vindelov LL, Christensen IJ. Detergent and proteolytic enzyme-based techniques for nuclear isolation and DNA content analysis. In: Darzynkiewicz Z, Robinson JP, Crissman HA, eds. Methods in Cell Biology, vol 41 Flow Cytometry, 2nd De. New York: Academic Press;1994:219-29."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib12"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Burton K. A study of the conditions and mechanisms of the diphenylamine reaction for the colorimetric estimation of the desoxyribonucleic acid. Biochem J\u{A0}1956;62:315-23. <a href="http://www.ncbi.nlm.nih.gov/pubmed/13293190" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib13"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Malberti F, Farina M, Imbasciati E. the PTH-calcium curve and the set poin of calcium in primary and secondary hyperparathyroidism. Nephrol Dial Transplant 1999;14:2398-2406.\u{A0} <a href="http://www.ncbi.nlm.nih.gov/pubmed/10528664" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Brown EM, Wilson RE, Eastmen RC, Pallotta J, Marinick S. Abnormal regulation of parathyroid hormone release by calcium in secondary hyperparathyroidism due to chronic renal failure. J Clin Endocrinol Metab 1982;54:172-9.\u{A0} <a href="http://www.ncbi.nlm.nih.gov/pubmed/7054214" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Brown EM. Four-parameter model of the sigmoidal relationship between parathyroid hormone release and extracellular calcium concentration in normal and abnormal parathyroid tissue. J Clin Endocrinol Metab 1983;56:572-81. <a href="http://www.ncbi.nlm.nih.gov/pubmed/6822654" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib16"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Khosla S, Ebeling PR, Firek AF, Burrit MM, Kao PC, Heath H. Calcium infusion suggest a ¿set point¿ abnormality of parathyroid gland function in familial benign hypercalcemia andmore complex disturbances in primary hyperparathyroidism. J Clin Endocrinol Metab 1993;76:715-20. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8445032" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib17"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Mithal A, Kifor I, et al. The reduced responsiveness of cultured bovine parathyroid cells to extracellular Ca2 is associated with marked reduction in the expression of extracellular Ca2 -sensing receptor mRNA and protein. Endocrinology 1995;136:3087-92. <a href="http://www.ncbi.nlm.nih.gov/pubmed/7789335" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109711017037"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib18"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Hosokawa Y, Pollak MR, Brown EM, Arnold A. Mutational analysis of the extracellular Ca2 -sensing receptor gene in human parathyroid tumors. J Clin Endocrinol Metab 1995;80:3107-10. <a href="http://www.ncbi.nlm.nih.gov/pubmed/7593409" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:1 [
                        "itemHostRev" => array:3 [
                          "pii" => "S0735109706010564"
                          "estado" => "S300"
                          "issn" => "07351097"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Gogusev J, Duchambon P, Hory J, et al. Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 1997;51:328-36. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8995751" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Kifor O, Moo FD, Wang P, et al. Reduced immunostaining for the extracellular Ca2 -sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab 1996;81:1598-606.\u{A0} <a href="http://www.ncbi.nlm.nih.gov/pubmed/8636374" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Kaneco C, Mizunashi K, Tanaka M, Uzuki M, Kikuchi M, Sawai T, Goto MM. Relationship between Ca-dependent change of serum PTH and extracellular Ca¿ sensing receptor expresión in parathyroid adenoma. Calcif Tissue Int 1999;64:271-2. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10024390" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib22"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Naveh-Many T, Rahamimov R, Livni N, et al. Parathyroid cell proliferation in normal and chronic renal failure rats: the effect of calcium, phosphate and vitamin D. J Clin Invest 1995;96:327-33.\u{A0}"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib23"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Shenton BK, Ellis H, Johnston ID, Farndon JR. DNA analysis and parathyroid pathology. World J Surg 1990;14:296-302.\u{A0}"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib24"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Arnold A, Brown MF, Ureña P, et al. Monoclonality of parathyroid tumors in chronic renal failure and in primary parathyroid hyperplasia. J Clin Invest 1995;95:1047-53. <a href="http://www.ncbi.nlm.nih.gov/pubmed/7883952" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib25"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Pardee AB. G1 Events and regulation of cell proliferation. Science 1989;246:603-8.\u{A0} <a href="http://www.ncbi.nlm.nih.gov/pubmed/2683075" target="_blank">[Pubmed]</a>"
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib26"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:3 [
                  "referenciaCompleta" => "Morgan DO. Principles of CDK regulation. Nature 1995;374:131-4."
                  "contribucion" => array:1 [
                    0 => null
                  ]
                  "host" => array:1 [
                    0 => null
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/20132514/0000003000000004/v0_201502091652/X2013251410050485/v0_201502091652/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "35441"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Originals"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003000000004/v0_201502091652/X2013251410050485/v0_201502091652/en/P1-E501-S2436-A10302-EN.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050485?idApp=UINPBA000064"
]