Niveles de sustancia P en sangre de cordón umbilical en neonatos a término

• Autores: Inmaculada Bueno Rodríguez
• Directores de la Tesis: Miguel Muñoz Sáez (dir. tes.), Antonio Pavón Delgado (dir. tes.), M. Rosso González (dir. tes.), Juan Carlos Crespo de la Rosa (tut. tes.)
• Lectura: En la Universidad de Sevilla ( España ) en 2014
• Idioma: español
• Tribunal Calificador de la Tesis: Antonio Ayala Gómez (presid.), María Mercedes Cano Rodríguez (secret.), José Bernabéu Wittel (voc.), Nieves Respaldiza (voc.), J. A. Soult Rubio (voc.)
• Materias:
  • Ciencias médicas
    • Ciencias clínicas
      • Pediatría
• Texto completo no disponible (Saber más ...)
• Resumen

  • INTRODUCCIÓN La SP se une a receptores específicos RNK-1 y desarrolla funciones proinflamatorias, por lo que es esperable que desempeñe un papel relevante en la corioamnionitis, en el síndrome inflamatorio fetal, en la inducción del parto prematuro, la hipertensión en el embarazo y consecuentemente en la morbimortalidad neonatal asociada.

    Para iniciar el estudio de la intervención de este neuropéptido en dichos procesos, nos encontramos con el desconocimiento actual de los valores ¿normales¿ o ¿fisiológicos¿ en la sangre de cordón de neonatos a término sanos. El conocer los valores de SP en sangre en recién nacidos sanos nos permitiría tener una referencia con la que compararlos en caso de patología. La evaluación de antagonistas de SP/RNK-1 como agentes terapéuticos y el uso como marcador de la SP para monitorizar los procesos inflamatorios enfatizan la necesidad de contar con métodos exactos en la medición de la SP en plasma o en suero con un alto nivel de precisión, sensibilidad y reproductibilidad (Campbell DE et al. 2006).

    Los niveles de SP en sangre de cordón podrían utilizarse con ventajas sobre los de IL-6 en el diagnóstico precoz de la corioamnionitis y el síndrome inflamatorio fetal, ya que la activación de la SP se produce antes que la de la referida IL-6.

    En nuestro conocimiento, aún no ha sido abordado el estudio de los valores normales de SP en sangre de cordón del neonato mediante la técnica de enzimoinmunoanálisis (ELISA).

    En esta ocasión pretendemos determinarlos mediante la técnica de ELISA y en una muestra representativa que permita la obtención de valores fiables definitivos a partir de los cuales basar futuras investigaciones.

    La disponibilidad de antagonistas selectivos de los RNK-1, del tipo no peptídico, abre la posibilidad de bloquear los efectos de la SP en la práctica clínica, si se llegara a probar que esta juega un papel relevante en los procesos referidos.

    DESARROLLO TEÓRICO OBJETIVOS Determinar los niveles normales de SP en sangre de cordón umbilical de recién nacidos a término sanos y sin aparentes malformaciones. Estudio observacional descriptivo.

    POBLACIÓN DE ESTUDIO Recién nacidos sanos y sin aparentes malformaciones cuyo parto haya ocurrido a término (entre las 37 y 41 semanas de gestación), descartando corioamnionitis de la placenta por anatomía patológica, con el consentimiento previo otorgado por sus representantes legales y cuyos criterios de exclusión son los mencionados en el apartado de material biológico.

    ASPECTOS ÉTICOS DE LA INVESTIGACIÓN Estudio sujeto a los principios adoptados por la 18ª Asamblea Médica Mundial (Helsinki, 1964) y posteriores revisiones. Se han seguido las normas de Buena Práctica Clínica dictadas por la Conferencia Internacional de Armonización de Directrices sobre Buena Práctica Clínica y los requisitos de las Autoridades Sanitarias Españolas establecidos en el Real Decreto 711/2002 de 19 de Julio. El consentimiento informado de los sujetos o representantes legales fueron obtenidos, tras haber sido informados tanto por escrito como oralmente de los objetivos del estudio, procedimientos a seguir, derechos y responsabilidades. Los sujetos del estudio se identificaron mediante código único de manera confidencial. Se ha cumplido lo estipulado por la Ley Orgánica 15/1999 de 13 de diciembre de Protección de Datos de Carácter Personal.

    RECOGIDA DE MUESTRAS Las muestras de sangre se recogen de la placenta, de la cara fetal, inmediatamente después de su alumbramiento. Se realiza mediante punción y aspiración con jeringa de 5 ml de venas placentarias.

    A continuación se transfieren a microtainers, sin EDTA y sin heparina de sodio, que contienen 500UI de aprotinina (agente hemostático que inhibe las proteasas) por cada ml de sangre de muestra fetal que se obtiene y posteriormente se centrifugan a 1500 rpm y 4ºC durante 15 minutos.

    Una vez obtenido el suero, se preparan en alícuotas de 250 ¿l en tubos de ependorff de 1,8 ml y tras su correcta identificación se mantienen congeladas a -80ºC hasta su procesamiento.

    MÉTODO DE PURIFICACIÓN DE LAS MUESTRAS DE SANGRE DE CORDÓN Acidificar las muestras Coger 250 ¿l de suero descongelado a temperatura ambiente y añadir ácido acético al 4% para diluirlo a ¿ consiguiendo un volumen total de 1000 ¿l, posteriormente homogeneizar la muestra vorteando durante un par de minutos e identificar la misma.

    Preparar, equilibrar, añadir y recoger las muestras a través de las columnas C 18 SPE 200 mg.

    Equilibrado de las columnas C18 SPE 200 mg Equilibrar las columnas C18 SPE 200 mg colocadas en la parte superior del Visiprep DL Disposable Liner Spe Vacuum Manifold además de los tubos de precipitado de cristal de 15 ml en la parte inferior del Visiprep. Hacer pasar a través de ellas 3 ml de acetonitrilo puro, seguido de 9 ml de ácido trifluoroacético al 1%. No dejar nunca secar las columnas C18 SPE 200 mg. Decantar el sobrenandante de los tubos de cristal de 15 ml y recolocarlos de nuevo en su mismo lugar.

    Verter la muestra previamente acidificada. Pasar lentamente los 1000 ¿l (volumen total) de la muestra ya acidificada por las C18 SPE 200 mg y añadir inmediatamente 3 ml de ácido Trifluoracético al 1% tres veces a través de las columnas sin dejarlas secar y dejar caer por gravedad, decantar nuevamente el sobrenadante de los tubos de cristal de 15 ml.

    Recogida del eluyente de las muestras. Cambiar los tubos de cristal de precipitado de 15 ml por criotubos de 3,6 ml en la parte inferior del Visiprep DL Disposable Liner Spe Vacuum Manifold para la recogida del eluyente de las columnas que se obtiene al pasar la mezcla de acetonitrilo y ácido trifluoracético al 1% (60/40), pasando de ml en ml hasta 2 ml en total.

    SECADO DE LAS MUESTRAS Las muestras ya eluidas en los criotubos de 3,6 ml pasan a ser secadas en el Evac-Orac system con flujo de nitrógeno a temperatura ambiente. Una vez secada la muestra se guarda a -80ºC hasta la elaboración del kit para SP por enzimoinmunoanálisis (ELISA).

    REALIZACIÓN DE ENZIMOINMUNOANÁLISIS (ELISA) Contenido del kit de elisa para determinación de SP - 1 vial para 100 determinaciones (dtn) de antisuero de SP.

    - 1 vial para 100 determinaciones de SP unida a acetilcolinesterasa.

    - 1 vial de SP en polvo para la curva estándar.

    - 2 viales de 10 ml de buffer para ELISA para concentración de 10X.

    - 1 vial de 5 ml de buffer de lavado de 400X.

    - 1 vial de 3 ml de Tween 20.

    - Placa de 96 pocillos cubiertos de anticuerpos Ig G contra conejo creado en ratón.

    - 1 cubre de placa de 96 pocillos.

    - 3 viales para 100 dtn de Reactivo Ellman¿s (sustrato de la acetilcolinesterasa).

    Descripción del enzimoinmunoanálisis de competición para la SP Este ensayo esta basado en un mecanismo de competición entre la SP libre y la SP marcada o conjugada con acetilcolinesterasa (SP AchE). Ambas compiten por el sitio de unión de los anticuerpos específicos contra la SP de conejo que se encuentran en los 96 pocillos.

    Mientras la concentración de SP conjugada se mantiene constante, la concentración de SP libre varia, la cantidad de SP conjugada que es capaz de unirse al antisuero de conejo, será inversamente proporcional a la concentración de SP libre que haya en el pocillo. El complejo antisuero de conejo-SP se une a los anticuerpos monoclonales de conejo hecho en ratón que se encuentran unido al fondo del pocillo. La placa es lavada para remover los reactivos no unidos y se añade el reactivo Ellman¿s (el cual contiene el sustrato de la acetilcolinesterasa) que es añadido al pocillo. El producto de esta reacción enzimática emite un color amarillo a una lectura de absorbancia de aproximadamente de 412 nm determinado espectrofotométricamente, la cuál es proporcional a la cantidad de SP conjugada con acetilcolinesterasa unida al pocillo e inversamente proporcional a la cantidad de SP libre presente en el pocillo (Ver figura 35).

    Absorbancia = Sustancia P conjugada con acetilcolinesterasa unida = 1/ sustancia P libre Preparación de los reactivos Preparación de la solución Buffer del ELISA. Diluir todo el contenido del vial del Buffer para conseguir una dilución a concentración 10X, añadiendo a dicho vial, 90 ml de agua ultrapura, homogenizar el vial y evitar que precipiten sales en el fondo del mismo.

    Preparación del Buffer de lavado. Diluir el vial de 5 ml de lavado a concentración 400X, hasta un total de 2 l con agua ultrapura y añadir 1 ml de Tween 20.

    Preparación del reactivo de Ellman. Reconstituirlo inmediatamente antes de su uso. Añadir 20 ml de agua ultrapura al vial del reactivo cantidad suficiente para los 96 pocillos.

    Preparación curva de SP estándar. Reconstituir la SP estándar con 2 ml de Buffer para ELISA. La concentración de esta disolución será de 5 ng/ml. Conservar esta solución a 4ºC y permanecerá estable durante 6 semanas. Para preparar la curva estándar hay que coger 8 tubos limpios y numerarlos del 1 al 8. Alicuotar 900 ¿l del buffer de ELISA para el tubo 1 y 500 ¿l para los tubos del 2 al 8. Transferir 100 ¿l del tubo matriz o madre al tubo 1 y mezclar enérgicamente, diluir seriadamente el estándar, coger 500 ¿l del tubo 1 y añadirlo al tubo 2 mezclar enérgicamente y repetir de nuevo el proceso cogiendo 500 ¿l del tubo 2 y añadirlo al tubo 3, mezclar enérgicamente y repetir este proceso hasta el tubo 8 (último de la curva estándar).

    Preparación de la SP conjugada con acetilcolinesterasa. Reconstituir con 6 ml de buffer para ELISA para placas de 96 pocillos.

    Preparación del antisuero SP para ELISA. Reconstituir con 6 ml de buffer para ELISA para placas de 96 pocillos Reconstituir las muestras con buffer para ELISA. Reconstituir con buffer para ELISA con un volumen igual al volumen de la muestra original, es decir, con 250 ¿l y vortear enérgicamente para homogenizar las muestras antes del montaje de la placa.

    DESCRIPCIÓN DEL MONTAJE DE LA PLACA Cada placa debe contener dos pocillos con blanco (blank), dos pocillos de unión no especifica (NSB), dos pocillos de máxima unión (B0), uno de total actividad (TA) y cada puntos de la curva estándar por duplicado (Std), dos controles internos, control 1(Ctrl 1) correspondiente al valor de SP del estándar 1 y el control 2 corresponde al valor de SP del estándar 3 según indicaciones del fabricante. Cada muestra analizada debe ser realizado doblemente y diluida al medio con el buffer del ensayo.

    ADICIÓN DE LOS REACTIVOS Y DE LAS MUESTRAS A LA PLACA Añadir 100 ¿l del buffer del ensayo a los pocillos de unión no especifica (NSB). Añadir 50 ¿l del mismo buffer a los pocillos de máxima unión (Bo). Añadir 50 ¿l del tubo 8 (el punto de mas baja concentración del estándar) comenzando por abajo de la placa y por duplicado (S8), según tabla del montaje mas arriba expuesto y repetir el proceso con cada punto del estándar.

    Usar la misma punta de pipeta para alicuotar todos los puntos del estándar en la placa, asegurándose en cada punto una adecuada calibración de la pipeta.

    Añadir 50 ¿l de cada muestra a analizar por pocillo realizándolo por duplicado y cada muestra debe ser ensayada con un mínimo de una dilución y cada dilución debe ser ensayada por duplicado.

    Añadir 50 ¿l de SP conjugada con colinesterasa a cada pocillo excepto al de total actividad (TA) y a los pocillos blancos (Blk). Añadir 50 ¿l de antisuero de SP excepto al de total actividad (TA), a los de la unión no especifica (NSB) y a los blancos (Blk).

    Cubrir la placa con tapa de plástico e incubar a 4ºC sobre una placa orbital toda la noche.

    Posteriormente vaciar los pocillos y enjuagarlos 5 veces con el buffer de lavado. Luego reconstituir el reactivo Ellman¿s inmediatamente antes de su uso con 20 ml de agua ultrapura y añadir 200 ¿l de este reactivo a cada pocillo con la pipeta multicanal (como se muestra en la figura 37) y 5 ¿l de SP conjugada al pocillo de total actividad (TA). Cubrir nuevamente la placa con el film de plástico e incubar en la oscuridad sobre una placa orbital durante 90-120 minutos y leer la absorbancia a 405-420 nm con un espectrofotómetro. La reacción será optima cuando la absorbancia de los pocillos de máxima unión (Bo) menos la absorbancia del blanco (Blank) esté entre 0,3-1 UA (unidades de absorbancia) y en ese momento debe ser leída.

    La SP es el mediador y desencadenante principal de la repuesta inflamatoria, por lo que al conocer los valores normales en sangre, podríamos tener una referencia para valorar si están alterados dichos valores y usarlo para el diagnóstico precoz de los procesos patológicos de la gestación y el tratamiento apropiado de esta patología con la utilización de antagonistas de los RNK-1.

    El diagnóstico de corioamnionitis podría realizarse más precozmente si se llegara a conocer la activación de los mediadores que intervienen en el inicio propiamente del proceso inflamatorio. Por estos motivos, es importante conocer los niveles sanguíneos de SP en RN sin patología y en RN a término para que sirvan de referencia para la patología fetal y perinatal, ya que se ha demostrado en repetidos estudios que la SP se halla elevada en los procesos inflamatorios de diversa causa.

    La asociación significativa de la corioamnionitis clínica o histológica con la parálisis cerebral, sugiere que las estrategias clínicas para prevenir o reducir la corioamnionitis daría lugar a una reducción de la parálisis cerebral (Shatrov JG et al. 2010) y una mejor comprensión de los mecanismos de la lesión cerebral perinatal permitirá descubrimientos de nuevos agentes neuroprotectores y mejores resultados tras el parto prematuro (Burd I et al. 2012).

    Muñoz y colaboradores (2010a, 2013b) demostraron la expresión y distribución de la SP y de su RNK-1 en tejido placentario humano a término mediante técnicas inmunohistoquímicas, por lo que se demuestra que tanto la SP como su RNK-1 podrían estar implicados en diversos procesos fisiopatológicos relacionados con la placenta, como la corioamnionitis o la preeclampsia con los riesgos que estas patologías conllevan para el desarrollo adecuado del feto.

    Nosotros proponemos a la SP como biomarcador en la inflamación ya que la SP estimula la producción de interleuquinas a través de distintas vías, como la IL-6 y regula los procesos inflamatorios. Es el mediador principal de la inflamación peptidérgica, es decir, la inflamación neurogénica y la no neurogénica. Dentro del interés que suscita la molécula como posible iniciador y mediador inflamatorio, habría que destacar la disponibilidad de diferentes antagonistas selectivos de los RNK-1, del tipo no peptídico, los cuales son candidatos idóneos para bloquear los efectos de la SP en la práctica clínica, si se llegara a demostrar más adelante que efectivamente ésta desempeña un papel importante en los procesos inflamatorios que llevan al desencadenamiento del parto.

    CONCLUSIONES 1- La SP está presente en todas las muestras estudiadas en sangre de cordón de RN a término.

    2- El método ELISA es fiable para la determinación de la SP ya que no hay diferencias significativas entre los valores de dos muestras del mismo individuo en cincuenta casos.

    3- Los niveles de SP en sangre de cordón de RN a término se hallan en concentraciones pg/ml. Oscilando entre 264,14 pg/ml ± 86,93 (196 pmol/L ± 64,50) y 256,88 pg/ml ± 84,25 (190,90 pmol/L ± 62,51).

    4- Los niveles normales de SP en sangre de cordón de RN a término establecen las bases para estudiar las posibles correlaciones de los mismos con las diferentes patologías del neonato.

    5- En base a las implicaciones fisiopatológicas de la SP, en un futuro se podrá utilizar la misma en la práctica clínica como un biomarcador precoz de inflamación e infección y cuadros hipertensivos y más concretamente en la patología del embarazo.

    6- El posible uso de la SP como biomarcador, incluiría la posibilidad del uso de los antagonistas de los RNK-1 como intervención terapéutica. Debido a que la SP al unirse al RNK-1 regula múltiples funciones fisiopatológicas, al contrario, los antagonistas de los RNK-1 bloquean dichas funciones fisiopatológicas. Por lo tanto, se amplia el concepto de biomarcador clásico pues también incluiría el uso de estos como dianas terapéuticas al poder actuar sobre la SP, sobre las enzimas que la degradan y sobre el receptor RNK-1.

    7- Los niveles normales de SP en sangre de cordón ayuda a la comprensión de los fenómenos fisiológicos donde se halla implicada la SP. Y establece las bases para un futuro abordaje de la fisiopatología en los que está involucrada la SP.

    BIBLIOGRAFÍA Abele-Horn M, Peters J, Genzel-Boroviczény O, Wolff C, Zimmermann A, Gottschling W.

    Vaginal Ureaplasma urealyticum colonization: influence on pregnancy outcome and neonatal morbidity. Infection 1997;25:286-91.

    Advenier C, Joos G, Molimard M, Lagente V and Pauwels R. Role of tachykinins as contractile agonists of human airways in asthma. Clin Exp Allergy 1999;29(5):579-584.

    Afan AM, Broome CS, Nicholls SE, Whetton AD, Miyan J A. Bone marrow innervation regulates cellular retention in the murine haemopoietic system. Br J Haematol 1997;98:569- 577.

    Agrawal V and E. Hirsch, ¿Intrauterine infection and preterm labor,¿ Seminars in Fetal and Neonatal Medicine;2012;17:12-19.

    Akazawa T, Kwatra SG, Goldsmith LE, Richardson MD, Cox EA, Sampom JH, Kwatra MM.

    A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor-mediated apoptosis in gioblastomas. J neuro chem 2009;109:1079-1086.

    Alexander JM, Gilstrap LC, Cox SM, McIntire DM, Leveno KJ. Clinical chorionamnionitis and the prognosis for very low birth weight infants. Obstet Gynecol 1988;91:725-729.

    Alexander JM, McIntire DM, Leveno KJ. Chorioamnionitis and the prognosis for term infants. Obstet Gynecol 1999;94:274.

    Aliakbari J, Sreedharan SP, Turck CW, Goetzl EJ. Selective localization of vasoactive intestinal peptide and substance P in human eosinophils. Biochem Biophys Res Commun 1987;148:1440-5.

    Allen JM, Hoyle NR, Yeats JC, Ghatei MA, Thomas DG and Bloom SR. Neuropeptides in neurological tumours. J Neuro-Oncol 1985;3:197-202.

    Almeida TA, Rojo J, Nieto PM, Pinto FM, Hernández M, Martín JD, Cándenas ML.

    Tachykinins and Tachykinins Receptors: Structure and Activity Relationships. Current Medicinal Chemistry 2004;11:763-771.

    Álvaro Iglesias E, Fernando Fernández Calvo, Verónica Recio Pascual. Patología Umbilical Frecuente. Protocolos de aeped 2008;41:398-404.

    An H, Nishimaki S, Ohyama M, Haruki A, Naruto T, Kobayashi N et al. Interleukin-6, interleukin-8, and soluble tumor necrosis factor receptor-I in the cord blood as predictors of chronic lung disease in premature infants. Am J Obstet Gynecol 2004;191:1649-1654.

    Andrews WW, Hauth JC, Goldenberg RL. Infection and preterm birth. Am J Perinatol 2000;17:357-365.

    Andrews T, Zhang P, Bhat NR. TNF¿ potentiates IFN¿-induced cell death in oligodendrocyte progenitors. J Neurosci Res 1998;54:574-83.

    Andrews WW, Cliver SP, Biasini F, Peralta-Carcelen AM, Rector R, Alriksson-Schmidt AI, Faye-Petersen O, Carlo W, Goldenberg R, Hauth JC. Early preterm birth: association between in utero exposure to acute inflammation and severe neurodevelopmental disability at 6 years of age. Am J Obstet Gynecol 2008;198:466.

    Anichini M, Cesaretti S, Lepori M, Maddali Bongi S, Maresca M, Zoppi M. Substance P in the serum of patients with rheumatoid arthritis. Rev Rhum Engl Ed 1997; 64:18-21.

    Ansel JC, Brown JR, Payan DG, Brown MA. Substance P selectively activates TNF-alpha gene expression in murine mast cells. J Immunol 1993;150:4478-4485.

    Annunziata P, Cioni C, Toneatto S, Paccagnini E. HIV-1 gp120 increases the permeability of rat brain endothelium cultures by a mechanism involving substance P. AIDS 1998;12:2377- 2385.

    Arck PC, Meralis FS, Stanisz AM, Stead RH, Chaouat G, Manuel J, Clark DA. Stress-induced murine abortion associated with substance P-dependend alteration in cytokines in maternal uterine decidua. Biol Reprod 1995;53:814-819.

    Arck PC, Troutt AB, Clark DA. Soluble receptors neutralizing TNF¿ and IL-1 block stresstriggered murine abortion. Am J Reprod Immunol 1997;37:262¿266.

    Aristoteles Metafísica de Aristóteles. Libro I.

    Ashina M, Bendtsen L, Jensen R, Ekman R, Olesen J. Plasma levels of substance P, neuropeptide Y and vasoactive intestinal polypeptide y patients with chronic tention -type headache. Pain 1999;83:541-547.

    Awardekar KP. Changing spectrum of neonatal omphalitis. Pediatr Infect Dis J 2004;23:22-6.

    Azzari C, Rossi ME, Resti M, Caldini AL, Lega, L, Galli L, Fico E, Vierucci A. Changed levels of substance P and somatostatin in HIVpositive children. Pediatr Med Chir 1992;14:577-581.

    Azzolina A, Bongiovanni A and Lampiasi N. ¿Substance P induces TNF-¿ and IL-6 production through NF¿B in peritoneal mast cells,¿ Biochimica et Biophysica Acta 2003; 1643:75-83.

    Baergen RN. Ed. B. Berde, Springer Velag. New York. Manual of Benirschke and Kaufmann¿s Pathology of the Human Placenta 2005.

    Bandari PS, Qian J, Yehia G, Seegopaul H P, Harrison J S, Gascon, P., . . Rameshwar P.

    Differences in the expression of neurokinin receptor in neural and bone marrow mesenchymal cells: implications for neuronal expansion from bone marrow cells. Neuropeptides 2002;36:13-21.

    Bang R, Sass G, Kiemer AK, Vollmar AM, Neuhuber WL, Tiegs G. Neurokinin-1 receptor antagonists CP-96,345 and L-733,060 protect mice from cytokine-mediated liver injury. J Pharmacol Exp Ther 2003;305:31-39.

    Bang R, Biburger M, Neuhuber WL, Tiegs G. Neurokinin-1 receptor antagonists protect mice from CD95- and tumor necrosis factor-alphamediated apoptotic liver damage. J Pharmacol Exp Ther 2004;308:1174-1180.

    Bargmann W.. Ed. B. Berde, Springer Velag. New York. Neurohypophysal hormone and similar polypeptides 1968.

    Barker R. Substance P and neurodegenerative disorders: a speculative review. Neuropeptides 1991;20:73-78.

    Bashiri A, Burstein E, Mazor M. Cerebral palsy and fetal inflammatory response syndrome: a review. Journal of Perinatal Medicine 2006;34:5-12.

    Bailey BA, Byrom AR. Factors predicting birth weight in a low-risk sample: the role of modifiable pregnancy health behaviors. Matern Child Health J 2007;11:173-9.

    Beal M F., & Mazurek MF. (1987). Substance P-like immunoreactivity is reduced in Alzheimer's disease cerebral cortex. Neurology 1987;37(7):1205-1209.

    Beartschi AJ, Zingg HH, Dreifuss JJ. Enkephalins, substance P, bradykinin and angiotensin II: differential sites of action on the hypothalamo-neurohypoohyseal system. Brain Res 1981; 220:107-119.

    Bejar R, Wozniak P, Allard M et al. Antenatal origin of neurologic damage in newborn infants. Am J Obstet Gynecol 1988;159:357-363.

    Belady PH, Farkouh LJ, Gibbs RS. Intaamniotic infection and premature rupture of the membranes. Clinics in Perinatology 1997;24:3-57.

    Benshop RJ, Nieuwenhuis ES, Tromp EA, Godaert GL, Ballieux RE, Doormen LJ. Effects of ß-adrenergic blockade on immunologic and cardiovascular changes induced by mental stress.

    Circulation 1994;89:762-769.

    Betancur C, Azzi M, Rostene W. Nonpeptide antagonists of neuropeptide receptors: tools for research and therapy. Trends Physiol Sci 1997;18:372-386.

    Bjorklund H, Eriksdotter-Nilsson M, Dahl D, Rose G, Hoffer B, Olson L. Image analysis of GFA-positive astrocytes from adolescence to senescence. Exp Brain Res 1985;58: 163-170.

    Bigioni M, Benzo A, Irrissuto C, Maggi CA, Goso C. Role of NK-1 and NK-2 tachykinin receptor antagonism on the growth of human breast carcinoma cell line MDA-MB-231.

    Anticancer Drugs 2005;16:1083-1089 Blanc W. Pathology of the placenta and cord in ascending and hematogenous infections. En: ¿Perinatal Infections, CIBA Foundation Symposium 77¿. Marshall W. London: Excerpta Medica 1980;17-38.

    Blalock JE. Harnessing a neural-immune circuit to control inflammation andshock. Exp Med 2002;195:25-28.

    Blanco Martínez B (2012). La SP y el RNK1 en la esclerosis mesial temporal. Tesis de doctorado para la obtenención del título de doctor en medicina,Facultad de medicina, Universidad de Sevilla, Sevilla 2012.

    Bloom FE. Neuropeptides. Scientific American 1981;124-144.

    Bobryshev YV. Subset of cells immunopositive for neurokinin-1 receptor identified as arterial interstitial cells of Cajal in human large arteries. Cell Tissue Res 2005;321:45-55.

    Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 2002;8:136-142.

    Bost KL, Breeding SA, Pascual DW. Modulation of the mRNAs encoding substance P and its receptor in rat macrophages by LPS. Reg Immunol 1992;4:105-112.

    Bountra C, Bunce K, Dale T, Garner C, Jordan C, Twissell D, Ward P. Anti-emetic profile of a non-peptide neurokinin NK1 receptor antagonist, CP-99,994 in ferret. Eur J Pharmacol 1993; 249:R3-R4.

    Botella J, Clavero JA. Fisiología de la Placenta. En: ¿Tratado de Ginecología¿. Díaz de Santos. España 1993;213-235.

    Brener S, Gonzalez-Moles MA, Tostes D, Esteban F, Gil-Montoya JA, Ruiz-Avila I, Munoz M. A role for the substance P/NK-1 receptor complex in cell proliferation in oral squamous cell carcinoma. Anticancer Res 2009;29: 2323-2329.

    Brogden KA, Guthmiller JM, Salzet M, Zasloff M. The nervoussystem and innate immunity: the neuropeptide connection. Nat Immunol 2005;6:558-564.

    Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M, et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 2004;61:774-80.

    Brown ER, Roth KA, Krause JE. Sexually dimorphic distribution of substance P in specific anterior pituitary cell populations. Proc Natl Acad Sci USA 1991;88:1222¿1226.

    Brownbill P, Bell NJ, Woods RJ, Lowry PJ, Page NM, Sibley CP. Neurokinin B is a paracrine vasodilator in the human fetal placental circulation. J Clin Endocrinol Metab 2003;88:2164- 2170.

    Bruce M, Arbor A. Placenta and Extraembryonic Membranes. En: ¿Human Embryology and Developmental Biology ¿. Elsevier. Philadelphia, PA Mosby 2004; 356-382.

    Buck SH, Burcher E. The tachykinins: a family of peptides with a brood of receptors. Trends Pharmacol Sci 1986;7:65-68.

    Buntinx M, Moreels M, Vandenabeele F, Lambrichts I, Raus J, Steels P, et al. Cytokineinduced cell death in human oligodendroglial cell lines: I. Synergistic effects of IFN¿ and TNF¿ on apoptosis. J Neurosci Res 2004;76:834-45.

    Burd I, Balakrishnan B, Kannan S. Models of fetal brain injury, intrauterine inflammation, and preterm birth. Am J Reprod Immunol 2012;67:287-94.

    Bustamante, E. Cáp. 6. Las células nerviosas. En: ¿El Sistema Nervioso: desde las neuronas hasta el cerebro.¿ Universidad de Antioquia 2007;6:91-99.

    Caberlotto L, Hurd YL, Murdock P, Wahlin JP, Melotto S, Corsi M, Carletti R. Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain. Eur J Neurosci 2003;17:1736-1746.

    Cahill CM, Coderre TJ. Attenuation of hyperalgesia in a rat model of neuropathic pain after intrathecal pre- or post-treatment with a neurokinin-1 antagonist. Pain 2002;95:277-285.

    Calzado MA, Bacher S, Schmitz ML. ¿NF-¿B inhibitors for the treatment of inflammatory diseases and cancer,¿ Current Medicinal Chemistry 2007;14:367-376.

    Calvo CF, Chavanel G, Senik A. Substance P enhances IL-2 expression in activated human T cells. J Immunol 1992;148:3498-3504.

    Costa JC and Tomaz C. Posttraining administration of substance P and its N-terminal fragment block the amnestic effects of diazepam. Neurobiol Learn Mem 1998;69:65-70.

    Camras CB, Bito LZ. The patophysiological effects of nitrogen mustard on the rabbit eyes II.

    The inhibition of the initial hypertensive phase by capsaicin and the apparent role of substance P. Invest Ophtalmol Vis Sci 1980;19:423-428.

    Campbell Donald E, Nancy Raftery, Richard Tustin III, Nancy B. Tustin, Michelle L.

    DeSilvio, Avital Cnaan, Pyone Pyone Aye, Andrew A. Lackner, and Steven D. Douglas.

    Measurement of Plasma-Derived Substance P: Biological, Methodological, and Statistical Considerations. Clin Vaccine Immunol 2006;13:1197-1203.

    Campbell DE, Bruckner P, Tustin NB, Tustin R III and Douglas SD. Novel Method for Determination of Substance P Levels in Unextracted Human Plasma by Using Acidification.

    Clin Vaccine Immunol 2009;16:594-6.

    Candenas ML, Magraner J, Armesto CP, Anselmi E, Nieto M, Martin JD, Advenier C, Pinto FM. Changes in the expression of tachykinin receptors in the rat uterus during the course of pregnancy. Biol Reprod 2001;65:538-543.

    Cao YQ, Mantyh PW, Carlson EJ, Gillespie AM, Epstein CJ, Basbaum AI. Primary afferent tachykinins are required to experience moderate to intense pain. Nature 1998;392: 390-394.

    . Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor. J Immunol 2010;185:1248-1257.

    Cascieri MA, Huang RR, Fong TM, Cheung AH, Sadowski S, Ber E et al. Determination of the aminoacid residues in substance P conferring selectivity and specificity for the rat neurokinin receptors. Mol Pharmacol 1992;41:1096-1099.

    Castagliuolo I, Riegler M, Pasha A, Nikulasson S, Lu B, Gerard C, Gerard NP, Pothoulakis C.

    Neurokinin-1 (NK-1) receptor is required in Clostridium difficile-induced enteritis. J Clin Invest 1998;101:1547-1550.

    Castagliuolo I, Keates AC, Qiu B, Kelly CP, Nikulasson S, Leeman SE, Pothoulakis C.

    Increased substance P responses in dorsal root gangliaand intestinal macrophages during Clostridium difficile toxin A enteritis in rats. Proc Natl Acad Sci 1997; 94:4788-4793.

    Castellanos González CH. Onfalitis. Infectología neonatal. In: González N, editor.. 2 ed.

    México DF.: McGrawHill interamericana 2006;336-9.

    Castro-Obregón S, del Río G, Chen SF, Swanson RA, Frankowski H. A ligand-receptor pair that triggers a non-apoptotic form of programmed cell death. Cell Death Differ 2002;9807- 817.

    Cayman`s Substance P EIA Kits.Item No. 583751. Cayman Chemical Company,Ann Arbor, MI. 08/31/2011.www.caymanchem.com Chahl LA, Ladd RJ. Local oedema and general excitation of cutaneous sensory receptors produced by electrical stimulation of the saphenous nerve in the rat. Pain 1976;2:25-34.

    Chan-Palay V, Jonsson E and Palay SL. Serotonin and substance P coexist in neurons of the rat¿s central nervous system. Proc Natl Acad Sci 1978;75:1582-86.

    Chang MM, Leeman SE and Niall HD. Amino acid sequence of substance P. Nature New Biol 1971;232:86-87.

    Chapman RW, Hey JA, McLeod R, Minnicozzi M, Rizzo C. Tachykinins in the lungs. Drug News Perspect 1998;11:480-489.

    Chavolla-Calderon M, Bayer MK and Fontan JJ. Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation. J Clin Invest2003;111:973-980.

    Chernova I, Lai JP, Li H et al. ¿Substance P (SP) enhances CCL5-induced chemotaxis and intracellular signaling in human monocytes, which express the truncated neurokinin- 1 receptor (NK1R),¿ Journal of Leukocyte Biology 2009;85:154-164.

    Chiwakata C, Brackmann B, Hunt N, Davidoff M, Schulze W, Ivell R. Tachykinin (Substance-P) gene expression in Leydig cells of the human and mouse testis. Endocrinology 1991;128:2441-2448.

    Cho KJ, Trzaska KA, Greco SJ, McArdle J, Wang FS, Ye JH, Rameshwar P. Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1 alpha. Stem Cells 2005;23:383-391.

    Cirillo R, Astolfi M, Conte B, Lopez G, Parlani M, Terracciano R. Pharmacology of the peptidomimetic, MEN 11,149, a new potent, selective and orally effective tachykinin NK1 receptor antagonist. Eur J Pharmacol 1998;341:201-209.

    Cook GA, Elliott D, Metwali A, Blu AM, Sandor M, Lynch R, Weinstock JV. Molecular evidence that granuloma T lymphocytes in murine Schistosomiasis mansoni express an authentic SP (NK1) receptor. J Immunology 1994;152:1830-1835.

    Corbally N, Powell D, Tipton KF. The binding of endogenous and exogenous substance-P in human plasma. Biochem. Pharmacol 1990;39:1161-1166.

    Costa E. The present status of neurohumoral transmission. En ¿Neural regulatory mechanisms during aging¿. Alan R Liss Inc 1980;1-23.

    Crome SQ, Wang AY, Levings MK. Translational mini-review series on Th17 cells: function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 2010;159:109-119.

    Crum CP, Kumar V, Abbas AK, Fausto N. Elsevier. España Tracto Genital Femenino. En: Patología Estructural y Funcional 2005;22:1063-1112.

    Cui QL, Yung WH, Chen L. Effects of substance P on neuronal firing of pallidal neurons in parkinsonian rats. Neurosci Res 2008;60:162-169.

    Cunin P, Caillon A, Corvaisier M, Garo E, Scotet M, Blanchard S, Jeannin P. The tachykinins substance P and hemokinin-1 favor the generation of human memory Th17 cells by inducing IL-1beta, IL-23, and TNF-like1 A expression by monocytes. J Immunol 2011;186:4175-4182.

    Curran MP, Robinson DM. Aprepitant: a review of its use in the prevention of nausea and vomiting. Drugs 2009;69:1853-78.

    D'Agati VD, Kaskel FJ, Falk R. Substance P on lymphocyte proliferation in HIV infection.

    Clin Exp Immunol 1994;96:384-388.

    Dale H. Pharmacology and Nerve-endings (Walter Ernest Dixon Memorial Lecture): (Section of Therapeutics and Pharmacology). Proc R Soc Med 1935;28:319-332.

    Dalsgaard CJ, Jonsson CE, Hijkfelt T, and Cuello AC. Localization of substance Pinmunoreactive nerve fibers in the human digital skin. Experientia Base1 1983;39:1018-1020.

    Dam TV.; Quirion R. Pharmacological characterization and autoradiographic characterization of substance P receptors in guinea-pig brain. Peptides 1986;7:855-864.

    D'Anna R, Baviera G, Corrado F, Crisafulli A, Ientile R, Buemi M, Squadrito F. Neurokinin B and nitric oxide plasma levels in pre-eclampsia and isolated intrauterine growth restriction.

    BJOG 2004;111:1046-1050.

    Dean JM, Farrag D, Zahkouk SA, El Zawahry EY, Hagberg H, Kjellmer I, et al. Cerebellar white matter injury following systemic endotoxemia in preterm fetal sheep. Neuroscience 2009;160:606-615.

    De Biasi S, Rustioni A. Glutamate and substance P coexist in primaryafferent terminals in the superficial laminae of spinal cord. Proc Natl Acad Sci 1988;85:7820-7824.

    De Felice C, Toti P, Laurini R, Stumpo M, Picciolini E, Todros T et al. Early neonatal brain injury and histologic chorioamnionitis. J Pediat 2001;138:101-104.

    De Felipe C, Herrero F, O'Brien JA, Palmer JA, Doyle CA, Smith AJ, Laird JM, Belmonte C, Cervero F, Hunt SP. Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. Nature 1998;392:394-397.

    De Moura RS; Withrington PG. Vascular actions of VIP, substance P and neurotension the isolated perfused human fetal placenta. Contrib Gynecol Obstet 1985;13:174-175.

    Dempsey E, Chen MF., Kokottis T et al. Outcome of neonates less than 30 weeks gestation with histologic chorioamnionitis. Am J Perinatol 2005;22:155-159.

    De Vane CL. Substance P: a new era, a new role. Pharmacotherap 2001;21:1061-1069.

    Di Salvo D. The correlation between placental pathology and intraventricular hemorrhage in the preterm infant. The Developmental Epidemiology Network Investigators. Pediatr Res 1998;43:15-19.

    Döllner H, Vatten L, Halgunset J, Rahimipoor S, Austgulen R. Histologic chorioamnionitis and umbilical serum levels of pro-inflammatory cytokines and cytokine inhibitors. Br J Obstet Gynaecol 2002;109:534-539.

    Donaldson LF, Haskell CA, Hanley MR. Messenger RNA localization and further characterisation of the putative tachykinin receptor NK4 (NK3B). Receptors Channels 2001;7:259-72.

    Douglas SD, Ho WZ, Gettes DR, Cnaan A, Zhao H, Leserman J, Petitto JM, Golden RN, and Evans DL. Elevated substance P levels in HIV-infected men. AIDS 2001;15:2043-2045.

    Dunzendorfer S, Meierhofer C, Wiedermann CJ. Signaling in neuropeptide induced migration of human eosinophils. J Leukocyte Biol 1998;64:828-834.

    Ebner K, Rupniak NM, Saria A, Singewald N. Substance P in themedial amygdala: emotional stress-sensitive release and modulation of anxiety-related behavior in rats. Proc Natl Acad Sci 2004;10:4280-4285.

    Ebner K, Singewald GM, Whittle N, Ferraguti F, Singewald N. Neurokinin 1 receptor antagonism promotes active stress coping via enhanced septal 5-HT transmission.

    Neuropsychopharmacology 2008a;33:1929-1941.

    Ebner K, Muigg P, Singewald G, Singewald N. Substance P in stress and anxiety: NK-1 receptor antagonism interacts with key brain areas of the stress circuitry. Ann NY Acad Sci 2008b;1144:61-73.

    Ebner K, Singewald N. Stress-induced release of substance P in the locus coeruleus modulates cortical noradrenaline release. Naunyn Schmiedebergs Arch Pharmacol 2007;376: 73-78.

    Edwards RK, Duff P. Single additional dose postpartum therapy for women with chorioamniotis. Obstet Gynecol 2003;102:957.

    Eistetter HR, Mills A, Brewster R, Alouani S, Rambosson C, Kawashima E. Functional characterization of neurokinin-1 receptors on human U373MG astrocytoma cells. Glia 1992;6:89-95.

    Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES.The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 2000;52:595- 638.

    Elovitz MA, Brown AG, Breen K, Anton L, Maubert M, Burd I. Intrauterine inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury. Int J Dev neurosci 2011;29:663-71.

    Entschladen F, Lang K, Drell TL, Joseph J, Zaenker KS. Neurotransmitters are regulators for the migration of tumor cells and leukocytes. Cancer Immunol Immunother 2002;51:467-482.

    Erspamer V. The tachykinin peptide family. Trends Neuroscience 1981;4:267-269.

    Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI.Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology 2006;105:660- 664.

    Fackler OT, Grosse R. Cell motility through plasma membrane blebbing. J Cell Biol 2008; 181:879-884.

    Fan TP, Hu DE, Guard S, Gresham GA, Watling KJ. Stimulation of angiogenesis by substance P and interleukin-1 in the rat and its inhibition by NK1 or interleukin-1 receptor antagonists.

    Br J Pharmacol 1993;110:43-49.

    Farooqi Aijaz, Bruno Hägglöf, Gunnar Sedin and Fredrik Serenius Impact at Age 11 Years of Major Neonatal Morbidities in Children Born Extremely Preterm. Pediatrics 2011;127:1247- 1257.

    Fehder WP, Ho WZ, Campbell DE, Tourtellotte WW, Michaels L, Cutilli JR, Uvaydova M, and Douglas SD. Development and evaluation of a chromatographic procedure for partial purification of substance P with quantitation by an enzyme immunoassay. Clin Diagn Lab Immunol 1998;5:303-307.

    Fehder WP, Sachs J, Uvaydova M and Douglas SD. Substance P as an immune modulator of anxiety. Neuroimmunomodulation 1997;4:42-48.

    Feistritzer C, Clausen J, Sturn DH, Djanani A, Gunsilius E, Wiedermann CJ, Kahler CM.

    Natural killer cell functions mediated by the neuropeptide substance P. Regul Pep 2003;116: 119-126.

    Fernandez-Rodriguez CM, Prieto J, Quiroga J, Zozoya JM, Andrade A, Nunez M, Sangro B and Penas J. Plasma levels of substance P in liver cirrhosis: relationship to the activation of vasopressor systems and urinary sodium excretion. Hepatology 1995;21:35-40.

    Ferrante RJ, Kowall NW, Richardson EP. Jr., Bird ED., & Martin J B. Topography of enkephalin, substance P and acetylcholinesterase staining in Huntington's disease striatum.

    Neurosci Lett 1986;71(3):283-288.

    Fest S, Zenclussen AC, Joachim R, Hagen E, Demuth HU, Hoffmann T. Stress and Substance P but not the Substance P-metabolite SP5-11 trigger murine abortion by augmenting TNF-¿ levels at the feto¿maternal interface. Scandinavian Journal of Immunology 2006;63:42-49.

    Fiebich BL, Schleicher S, Butcher RD, Craig A, Lieb K. The neuropeptide substance P activates p38 mitogen-activated protein kinase resulting in IL-6 expression independently from NF-kappa B. J Immunol 2000;165:5606-5611.

    Flageole H, Senterman M, Trudel JM. Substance P increases in vitro lymphokine-activetedkiller (LAK) cell cytotoxicity against fresh colorectal cancer cells. J Surg Res 1992;53:445- 449.

    Flórez J y Martínez Lage JM. EUNSA. Neurofarmacología fundamental y clínica 1983.

    Pamplona 1983.

    Fowler CJ, Brannstrom G. Substance P enhances forskolin-stimulated cyclic AMP production in human UC11MG astrocytoma cells. Methods Find Exp Clin Pharmacol 1994;16:21-28.

    Fraser N, Davies BW, Cusack J. Neonatal omphalitis: A review of its serious complications.

    Acta pediátrica 2006;95:519-22.

    Fras C, Kravetz P, Mody DR, Heggeness MH. Substance P-containing nerves within the human vertebral body. an immunohistochemical study of the basivertebral nerve. Spine J 2003;3:63-67.

    Frerichs Valerie A, Herrmann Jennifer K, Aguirre Alfredo, Colon Luis A. Trace level determination of substance P using capillary electrophoresis and laser-induced fluorescence.

    Microchemical Journal 2004;78:135-142 Friedman SA. Preeclampsia: a review of the role of prostaglandins. Obstet Gynecol 1988;71: 122-137.

    Friess H, Zhu Z, Liard V et al. Neurokinin-1 receptor expression and its potential effects on tumour growth in human pancreatic cancer. Lab Invest 2003;83:731-742.

    Fuigueras AJ, Álvarez Miró R. El ombligo del recién nacido. Jano 1997;52:1214-33.

    Furness JB, Costa M. The Enteric Nervous System. Churchill Livingstone. New York. 1987.

    Furness JB, Papka RE, Della NG, Costa M, Eskay RL. Substance P-like immunoreactivity in nerves associated with the vascular system of guinea-pigs. Neuroscience 1982;7:447-459.

    Gai WP, Halliday GM., Blumbergs PC, Geffen LB, & Blessing WW. Substance Pcontaining neurons in the mesopontine tegmentum are severely affected in Parkinson's disease. Brain1991;114( Pt 5):2253-2267.

    Gallagher PG, Shah SS. Omphalitis. http://www emedicine com/ped/topic1641 htm 2006 August 18 [cited 2007 Dec 15]; (Springer, Shelley C.) Available from: URL: http://www.emedicine.com/ped/topic1641.htm ] Gallicchio M, Rosa AC, Benetti E, Collino M, Dianzani C, Fantozzi R. Substance P-induced cyclooxygenase-2 expression in human umbilical vein endothelial cells. Br J Pharmacol 2006;147:681-9.

    Garland AM, Grady EF, Payan DG, Vigna SR, Bunnett NW. Agonist induced internalization of the substance P (NK1) receptor expressed in epithelial cells. Biochem J 1994;303:177-186.

    Gavilanes AW, Gantert M, Strackx E, Zimmermann LJ, Seeldrayers S, Vles JS et al.

    Increased EEG delta frequency corresponds to chorioamnionitis-related brain injury. Front Biosci (Schol Ed) 2010;2:432-8.

    Geissbuehler V, Moser R, Zimmermann K, Hillermann R, Czarniecki J, Gebhardt SG, Eberhard J: Altered plasma neurokinin B levels in patients with pre-eclampsia. Arch Gynecol Obstet 2007;276:151-157.

    George DT, Gilman J, Hersh J, et al. Neurokinin 1 receptor antagonism as a possible therapy for alcoholism. Science 2008;319:1536-9 Gerard NP, Garraway LA, Eddy RL, Jr, Shows TB, Iijima H, Paquet JL, Gerard C. Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones. Biochemistry 1991;30:10640-10646.

    Gether U, Johansen TE, Snider RM, Lowe AJ, Nakanishi S, Schwartz TW. Different binding epitope for substance P and the non-peptide antagonist, CP 96,345 on the NK1 receptor.

    Nature 1993;362:345-348.

    Giardina GAM, Gagliardi S and Martinelli M. Antagonists at the neurokinin receptors. Recent patent literature. Drugs 2003;6:758-772.

    Gibran N S, Jang YC, Isik FF, Greenhalgh DG, Muffley LA, Underwood RA, Olerud JE.

    Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus. J Surg Res 2002;108:122-128.

    Gidron Y, Perry H, Glennie M. Does the vagus nerve inform the brain about preclinical tumours and modulate them? . Lancet Oncol 2005;6:245-248.

    Gibbs RS, Duff P. Progress in pathogenesis and management of clinical intraamniotic infection. Am J Obstet Gynecol 1991;164:1317-1326.

    Gillberg PG, Aquilonius SM, Eckernas SA, Lundqvist G and Winblad B. Choline acetyltransferase and substance P-like immuno-reactivity in the human spinal cord: changes in amyotrophic lateral sclerosis. Brain Res 1982;250(2):394-397.

    Gitter BD, Regoli D, Howbert JJ, Glasebrook AL, Waters DC. Interleukin-6 secretion from human astrocytoma cells induced by substance P. J Neuroimmunol 1994;51:101-108.

    Goldemberg RL, Hauth J, Andrews W. Intrauterine infection and preterm delivery. N Engl J Med 2000;342:1500-1507.

    Goldenberg RL, Andrews WW, Hauth JC. Choriodecidual infection and preterm birth. Nutr Rev 2002;60:19-25.

    Goldenberg RL, Culhene JF. Infection as a cause of preterm birth. Clin Perinat 2003;30:677- 700.

    Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth.

    Lancet 2008;371:75-84.

    Gómez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflamatory response síndrome. Am J Obstet Gynecol 1998;179:194-202.

    Gomez R, Ghezzi F, Romero R, Munoz H. Premature labor and intra-amniotic infection.

    Clinical aspects and role of the cytokines in diagnosis and pathophysiology. Clin Perinatol 1995;22:281.

    Gómez R, Romero R, Nien JK. Idiopathic vaginal bleeding during pregnancy as the only clinical manifestation of intrauterine infection. J Matern Fetal Neonat Med 2005;18:31-7.

    González¿Merlo J. y González E. Cáp. 6. Desarrollo y estructura de la Placenta. En ¿Obstetricia¿. Elsevier. España. 2006;6,84-86.

    González Moles MA, Esteban F, Ruiz-Avila I, Gil Montoya JA, Brener S, Bascones-Martinez A, Muñoz M. A role for the substance P/NK-1 receptor complex in cell proliferation and apoptosis in oral lichen planus. Oral Dis 2009;15:162-169.

    González Moles MA, Mosqueda-Taylor A, Esteban F, Gil-Montoya JA, Diaz-Franco MA, Delgado M, Muñoz M. Cell proliferation associated with actions of the substance P/NK-1 receptor complex in keratocystic odontogenic tumours. Oral Oncol 2008;44:1127-1133.

    González Saldaña N, Chacón Sánchez JDC, Aguilar Ituarte F. Infecciones piógenas de la piel.

    In: Gonzalez N, editor. Infectologia Neonatal. 2 ed. México DF: McGrawHill interamericana.; 2006;96-9.

    Gonzalez-Rey E, Chorny A, Delgado M. Regulation of immune tolerance by antiinflammatory neuropeptides. Nat Rev Immunol 2007;7:52-63.

    Gonsalves S, Watson J, Ashton C. Broad spectrum antiemetic effects of CP-122,721, a tachykinin NK1 receptor antagonist, in ferrets. Eur J Pharmacol 1996;305:181-185.

    Gotsch F, Romero R, Kusanovic JP, Mazaki-Tovi S, Pineles BL, Erez O, Espinoza J, Hassan SS. The fetal inflammatory response syndrome. Clin Obstet Gynecol 2007;50:652-83.

    Grady EF, Garland AM, Gamp PD, Lovett M, Payan DG, Bunnett NW. Delineation of the endocytic pathway of substance P and its seven transmembrane domains NK1 receptor. Mol Biol Cell 1995;6:509-524.

    Graf AH, Hütter W, Hacker GW, Steiner H, Anderson V, Staudach A, Dietze O. Localitation and distribution of vasoactive neuropeptides in the human placenta. Placenta 1996;17:413- 421.

    Graham GJ, Stevens JM, Page NM, Grant AD, Brain SD, Lowry PJ, Gibbins JM. Tachykinins regulate the function of platelets. Blood 2004;104:1058-1065.

    Grant AD, Akhtar R, Gerard NP, & Brain SD. Neurokinin B induces oedema formation in mouse lung via tachykinin receptor-independent mechanisms. J Physiol 2002;543(Pt 3):1007- 1014.

    Green SA, Alon A, Ianus J et al. Efficacy and safety of a neurokinin-1 receptor antagonist in postmenopausal women with overactive bladder with urge urinary incontinence. J Urol 2006;176:2535-40.

    Grossmman JH. Infecctions affecting the placenta. En: ¿The Placenta¿. Rockville M.D., Labery JP. (Eds.) Aspen Publishing. 1987;131-134.

    Guo CJ, Lai JP, Luo HM, Douglas SD, HoWZ. ¿Substance P up-regulates macrophage inflammatory protein-1ß expression in human T lymphocytes,¿ Journal of Neuroimmunology 2002;131:160-167.

    Guha S, Eibl G, Kisfalvi K, Fan RS, Burdick M, Reber H, Hines OJ, Strieter R, Rozengurt E.

    Broad-spectrum G protein¿coupled receptor antagonist, [D-Arg1,DTrp5,7,9,Leu11]SP: a dual inhibitor of growth and angiogenesis in pancreatic cancer. Cancer Res 2005;65:2738-2745.

    Guillomot M, Flechon J and Leroy F. Blastocyst development and implantation. En: ¿Reproduction in mammals and Man¿. Thibault C., Levasseur M. and Hunter R.H.F (Eds.) Ellipses. Paris. 1993;6:435-459.

    Güvenc H, Aygün A, Yasar F, Soylu F, Guvenc M, Kocabay K. Omphalitis in term and preterm appropiate for gestational age and small for gestational age infants. J Trop Pediatr 1997;43:368-72.

    Hagermark O, Hokfelt T, Pernow B. Flare and itch induced by substance P in human skin. J Invest Dermatol 1978;71: 233-235.

    Hall V. When the womb is no longer safe: chorioamnionitis. Midwifery Today Int Midwife.

    2011;99:20-1 Harmar AJ, Hyde V, Chapman K. Identification and cDNA secuence of deltapreprotachykinin, a four splicing variant of the rat substance P precursor. FEBS Lett 1990; 275:22-24.

    Hasen V, Maigaard S, Allen J, Forman A. Effects of vasoactive intestinal polypeptide and substance P on human intramyometrial arteries and stem villous arteries in term pregnancy.

    Placenta 1988;9:501-506.

    Harrison T, Williams BJ, Swain CJ, Ball RG. Piperidine-ether based hNK1 antagonists 1: determination of the relative and absolute stereochemical requirements. Biomed Chem Lett 1994;4:2545-2550.

    Harrison S, Geppetti P. Substance P. Int J Biochem Cell Biol 2001;33:555-576.

    Harrowe Greg, Masato Mitsuhashi and Donald G. Payan. Measles Virus-Substance P Receptor Interactions Possible Novel Mechanism of Viral Fusion J Clin Invest 1990;85: 1324- 1327.

    Hartung HP, Toyka KV. Substance P, the immune system and inflammation. Int Rev Immunol 1989;4:229-249.

    Hashimoto M, Hayashi K, Murai M, Fujii T, Nishikawa M, Kiyoto S, Imanaka H. WS9326A, a novel tachykinin antagonist isolated from Streptomyces violaceusniger no. 9326. II.

    Biological and pharmacological properties of WS9326A and tetrahydro-WS9326A (FK224).

    J Antibiot 1992;45:1064-1070.

    Heep A, Behrendt D, Nitsch P, Fimmers R, Bartmann P, Dembinski J. Increased serum levels of interleukin-6 are associated with severe intraventricular haemorrhage in extremely premature infants. Arch Dis Child Fetal Neonatal Ed 2003;88:501-4.

    Hegde A, Zhang H, Moochhala SM and Bhatia M. ¿Neurokinin-1 receptor antagonist treatment protects mice against lung injury in polymicrobial sepsis.¿ Journal of Leukocyte Biology 2007;82:678-685.

    Hegde A, Koh YH, Moochhala SM, Bhatia M. Neurokinin-1 receptor antagonist treatment in polymicrobial sepsis: molecular insights. Int J Inflam 2010;20:2010-601098.

    Hennig IM, Laissue JA, Horisberger U, Reubi JC. Substance P receptors in human primary neoplasm: tumoral and vascular localization. Int J Cancer 1995;61:786-792.

    Henry JL. Participation of substance P in spinal physiological responses to peripheral aversive stimulation. Regul Pept 1993;46:138-143.

    Hernandez Gonzalez N, Salas Hernandez S, Garcia-Alix A, Rodríguez herrero C, Perez Rodríguez J, Omeñaca Teres F, Quero Jiménez J. Morbilidad a los 2 años de edad en niños con peso al nacimento menor de 1500 gramos. An Pediatr 2005;62:320-327.

    Hershey AD, Dykema PE, Krause JE. Organization, structure, and expression of the gene encoding the rat substance P receptor. J Biol Chem 1991;226:4366-4374.

    Hillier SL, Martius J, Krohn M, Kiviat N, Holmes KK, Eschenbach DA. A case-control study of chorioamniotic infection and histologic chorioamnionitis in prematurity. N Engl J Med 1988;319:972-978.

    Hirayama A, Okoshi Y, Hachiya Y, Ozawa Y, Ito M, Kida Y, et al. Early immunohistochemical detection of axonal damage and glial activation in extremely immature brains with periventricular leukomalacia. Clin Neuropathol 2001;20:87-91.

    Ho WZ, Kaufman D, Uvaydova M, Douglas SD. Substance P augments interleukin-10 and tumor necrosis factor-alpha release by human cord blood monocytes and macrophages. J Neuroimmunol 1996;71:73-80.

    Ho WZ, Cnaan A, Li YH, Zhao H, Lee HR, Song L, Douglas SD. Substance P modulates human immunodeficiency virus replication in human peripheral blood monocyte-derived macrophages. AIDS Res. Hum. Retroviruses 1996;12:195-198.

    Ho WZ, Lai JP, Zhu XH, Uvaydova M, Douglas SD. Human monocytes and macrophages express substance P and neurokinin-1 receptor. J Immunol 1997; 159:5654-5660.

    Ho WZ, and Douglas SD. Substance P and neurokinin-1 receptor modulation of HIV.

    Neuroimmunology 2004;157:48-55.

    Hökfelt T, Kellerth JO, Nilsson G and Pernow B. Substance P: Localization in the central nervous system and in some primary sensory neurons. Science 1975;190:889-890.

    Hokfelt T, Johansson O, Kellerth JO, Ljungdahl A, Nilsson G, Nygards A, Pernow B.

    Immunohistochemical distribution of substance P. En: ¿Substance P¿. Von Euler U.S. and Pernow B. (Eds.) Raven Press, New York 1977; 117-145.

    Hókfelt T, Lundberg JM, Schultzberg M, Johansson O, Ljungdahl A, Rehfeld JF. Coexistence of peptides and putative transmitters in neurons. Adv Biochem Phychopharmacol 1980a;22: 1- 23.

    Hókfelt T, Johansson O, Ljungdahl A, Lundberg JM, Schultzberg M. Peptidergic neurons.

    Nature 1980b;284:515-521.

    Hökfelt T, Vincent S, Dalsgaard CJ, Skirboll L, Johansson O, Schultzberg M, Lundberg JM, Rosell S, Pernow B, Jancso G. Distribution of substance P in brain and periphery and its possible role as a co-transmitter. Ciba Found Symp 1982;91:84-106.

    Hokfelt T, Kellerth JO, Nilsson G, Pernow B. Substance P: localization in the central nervous system and in some primary sensory neurons. Science 1985;190:889-890.

    Hökfelt T, Pernow B, Wahren J. Substance P: a pioneer amongst neuropeptides. J Intern Med 2001;249:27-40.

    Holzer P. Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience 1988; 24:739-768.

    Holzer P, Holzer-Petsche U. Tachykinins in the gut. Part I. Expresión, release and motor function. Pharmacol Ther 1997;73:173-217.

    Holzer P, Holzer-Petsche U. Tachykinins in the gut. Part II Roles in neural excitación, secretion and inflamation. Pharmacol Ther 1997;73:219-263.

    Hofstater C, Dubiel M, Gudmundsson S. Two types of umbilical venous pulsations and outcome of high-risk pregnancy. Early Hum Develop 2001;61:111-117.

    Hopkins B, Powell SJ, Danks P, Briggs I, Graham A. Isolation and characterisation of the human lung NK-1 receptor cDNA. Biochem Biophys Res Commun 1991;180:1110-1117.

    Hoskins L, Smaill F. Antibiotic regimens for management of intraamniotic infection.

    Cochrane Database Syst Rev 2002: CD003254. [PubMed: 12137684] Horton AL, Barroilhet L, Wolfe HM. Perinatal outcomes in isolated single umbilical artery.

    Am J Perinatol 2010;27:321-4.

    Horvath B, Grasselly M, Bodecs T, Boncz I, Bodis J. Histological chorioamnionitis is associated with cerebral palsy in preterm neonates. Eur J Obstet Gynecol Reprod 2012;163:160-4.

    Hughes SR, Williams TJ, Brain SD. Evidence that endogenous nitric oxide modulates edema formation induced by substance P. Eur J Pharmacol 1990;191:481-484.

    Hwang L, Leichter R, Okamoto A, Payan D, Collins SM, Bunnett N W. Downregulation of neutral endopeptidase (EC 3.4.24.11) in the inflamed rat intestine. Am J Physiol 1993;264 :G735-743.

    Ikegami T, Tsuda A, Karube A, Kodama H, Hirano H, Tanaka T. Efectos de la IL-6 e IL-8 intrauterinas sobre la expresión del ARNm de apoproteínas del surfactante en pulmón fetal de rata. European Journal of Obstetrics and Gynecology and Reroductive Bioloy 2001;1:202- 208.

    Janelsins BM, Mathers AR, Tkacheva OA, Erdos G, Shufesky WJ, Morelli AE, Larregina AT.

    Proinflammatory tachykinins that signal through the neurokinin 1 receptor promote survival of dendritic cells and potent cellular immunity. Blood 2009;113:3017-3026.

    Jessell TM. Substance P release from the rat substantia nigra. Brain Res 1978;151:469-478.

    Jessell TM, Iversen LL. Opiate analgesics inhibit substance P release from the rat trigeminal nucleus. Nature 1977;268: 549-551.

    Jiang Z, Dun NJ, Karczmar AG. Substance P: a putative sensory transmitter in mammalian autonomic ganglia. Science 1982; 217:739-741.

    Joachim RA, Hildebrndt M, Oder J, Klapp BF, Arck PC. Murine stress-triggered abortion is mediated by increase of CD-8+TNF-alpha+decidual cells via substance P. Am J Reprod Immunol 2001;45:303-309.

    Jones EG. The Neuron Doctrine 1891. J Hist Neurosci 1994;3:3-20.

    Jones S, Tucker KL, Sage T, Kaiser WJ, Barrett NE, Lowry PJ, Zimmer A, Hunt SP, Emerson M, Gibbins JM: Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation. Blood 2008;111:605-612.

    Joos G.F., Germonpre P.R., Pauwels R.A. Role of tachykinins in asthma. Allergy 2000;55: 321-37.

    Junqueira LC, Carneiro J, Kelley RO. Histología Básica, 5ª ed. Masson, Barcelona. 2000; 452-458.

    Kage R, McGregor GP, Thim L. Neuropeptide-¿. A peptide isolated from rabbit intestine that is derived from ¿-Preprotachykinin. J Neurochem 1988;50:1412-1417.

    Kalinichev M, Bradford A, Bison S, et al. Potentiation of the anticonvulsant efficacy of sodium channel inhibitors by an NK-1 receptor antagonist in the rat. Epilepsia 2010;51:1543- 51.

    Kang HS, Trzaska KA, Corcoran K, Chang VT, Rameshwar P. Neurokinin receptors: relevance to the emerging immune system. [Research Support, U.S. Gov't, P.H.S. Review].

    Arch Immunol Ther Exp 2004;52:338-347.

    Kangawa K, Minamino N, Fukuda A, Matsuo H. Neuromedin K: a novel mammalian tachykinin identified in porcine spinal cord. Biochem Biophys Res Commun 1983;114:533- 540.

    Kant V, Gopal A, Kumar D, Bag S, Kurade NP, Kumar A, Tandan SK, Kumar D. Topically applied substance P enhanced healing of open excision wound in rats. Eur J Pharmacol 2013;715:345-53.

    Karagiannides I, Kokkotou E, Tansky M et al. ¿Induction of colitis causes inflammatory responses in fat depots: evidence for substance P pathways in human mesenteric preadipocytes,¿ Proceedings of the National Academy of Sciences of the United States of America 2006;103:5207:5212.

    Kavelaars A, Broeke D, Jeurissen F, Kardux J, Meijer A, Franklin R, Gelfand EW, Heijnen CJ. Activation of human monocytes via a non-neurokinin substance P receptor that is coupled to Gi protein, calcium, phospholipase D, MAP kinase, and IL-6 production. J Immunol 1994; 153:3691-3699.

    Kawaguchi Y, Hoshimaru M, Nawa H, Nakanishi S. Secuence analysis of cloned cDNA for rat substance P precursor: existence of a third substance P precursor. Biochem Biophys Res Commun 1986;139:1040-1046.

    Kawada H, Takizawa S, Takanashi T, Morita Y, Fujita J, Fukuda K, Takagi S, Okano H, Ando K, Hotta T. Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells. Circulation 2006;113:701-710.

    Kaukola T, Herva R, Perhomaa M, Pääkkö E, Kingsmore S, Vainionpää L et al.

    Chorioamnionitis and cord serum proinflammatory cytokines: lack of association with brain damage and neurologic outcome in very preterm infants. Pediatr Res 2005;58:1-6.

    Kaukola T, Herva R, Perhomaa M, Pääkkö E, Kingsmore S, Vainionpää L, et al. Population cohort associating chorioamnionitis, cord inflammatory cytokines and neurologic outcome in very preterm, extremely low birth weight infants. Pediatr Res 2006;59:478-483.

    Keller M, Montgomery S, Ball W, Morrison M, Snavely D, Liu G, Hargreaves R, Hietala J, Lines C, Beebe K, Reines S. Lack of efficacy of the substance P (neurokinin-1 receptor) antagonist aprepitant in the treatment of major depressive disorder. Biol Psychiatry 2006;59: 216-223.

    Kessler JA, Black IB. Regulation of substance P in adult rat sympathetic ganglia. Brain Res 1982;234;182-187.

    Keogh MJ, Bennet L, Drury PP, Booth LC, Mathai S, Naylor AS, et al. Subclinical exposure to low-dose endotoxin impairs EEG maturation in preterm fetal sheep. Am J Physiol Regul Integr Comp Physiol 2012;303:270-8.

    Kerdelhue B, Williams RF, Lenoir V, Fardin V, Kolm P, Hodgen GD, Jones HW, Jr. Variations in plasma levels of substance P and effects of a specific substance P antagonist of the NK(1) receptor on preovulatory LH and FSH surges and progesterone secretion in the cycling cynomolgus monkey. Neuroendocrinology 2000;71:228-236.

    Kerdelhue B, Lenoir V, Scholler R, Jones HW, Jr. Substance P plasma concentration during the LH preovulatory surge of the menstrual cycle in the human. Neuro Endocrinol Lett 2006;27:359-364.

    Kimball ES, Fisher MC. Potentiation of IL-1-induced BALB/3T3 fibroblast proliferation by substance P. Ann N Y Acad Sci 1988;540:681-683.

    Kimura S, Okada M, Sugita Y, Kanazawa I, Munekata E. Novel neuropeptides: neurokinin ¿ and ß, isolated from porcine spinal cord. Proc Jpn Acad 1983;59:101-104.

    Kincy-Cain T, Bost KL. Substance P-induced IL-12 production by murine macrophages. J.

    Immunol 1997;158:2334-2339.

    King KA, Hu C, Rodriguez MM, Romaguera R, Jiang X, Piedimonte G. Exaggerated neurogenic inflammation and substance P receptor upregulation in RSV-infected eanling rats.

    Am J Respir Cell Mol Biol 2001;24:101-107.

    Khong TY, De Wolf , Robertson WB, Brosens I. Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br J Obstet Gynaecol 1986; 93:1049-1059.

    Koon H-W, Zhao D, Zhan Y, Simeonidis S, Moyer MP, Pothoulakis C. ¿Substance Pstimulated interleukin-8 expression in human colonic epithelial cells involves protein kinase C¿ activation,¿ Journal of Pharmacology and Experimental Therapeutics 2005;314:1393- 1400.

    Kowall NW, Quigley BJ, Jr., Krause JE, Lu F, Kosofsky BE, & Ferrante R J. Substance P and substance P receptor histochemistry in human neurodegenerative diseases. Regul Pept 1993;46(1-2):174-185.

    Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-Knowles E, Hale JJ, Mills SG, MacCoss M, Swain CJ, Harrison T, Hill RJ, Hefti F, Scolnick EM, Cascieri MA, Chicchi GG, Sadowski S, Williams AR,Hewson L, Smith D, Carlson EJ, Hargreaves RJ and Rupniak NMJ. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 1998;281:1640-1645.

    Kraus FT, Redline RW, Gersell DJ et al. Placental Pathology.Washington DC. AFIP, 2004.

    Krause JE, Takeda Y, Hershey AD. Structure, functions and mechanisms of Substance P receptor action. J Invest Dermatol 1992;98:2-7.

    Kulka M, Sheen CH, Tancowny BP, Grammer LC and Schleimer RP. ¿Neuropeptides activate human mast cell degranulation and chemokine production¿. Immunology 2008;123:398:410.

    Kurtz MM, Wamg R, Clements M, Cascieri M, Austin C, Cunnighan B, Chicchi G, Liu Q.

    Identification, localization and receptor characterization of novel mammalian substance P-like peptides. Gene 2002;296:205-212.

    Kuypers Elke, Daan Ophelders, Reint K. Jellema, Steffen Kunzmann Antonio W. Gavilanes, Boris W. Kramer. White matter injury following fetal inflammatory response syndrome induced by chorioamnionitis and fetal sepsis: Lessons from experimental ovine models. Early Human Development 2012;88:931-936.

    Lai J-P, Douglas SD, Rappaport E, Wu JM, Ho WZ. Identification of a delta isoform of preprotachykinin mRNA in human mononuclear phagocytes and lymphocytes. J.

    Neuroimmunol 1998;91:121-128.

    Lai J-P, Douglas SD, Wang Y-J and Ho W-Z. Real-Time Reverse Transcription-PCR Quantitation of Substance P Receptor (NK-1R) mRNA. Clinical and Diagnostic Laboratory Immunology 2005;12:537-541.

    Lai J-P, Lai S, Tuluc F et al. ¿Differences in the length of the carboxyl terminus mediate functional properties of neurokinin-1 receptor,¿ Proceedings of the National Academy of Sciences of the United States of America 2008;105:12605-12610.

    Laliberte C, DiMarzo L, Morrish DW, Kaufman S. Neurokinin B causes concentrationdependent relaxation of isolated human placental resistance vessels. Regul Pept 2004;117: 123-126.

    Lambrecht BN, Germonpre PR, Everaert EG, Carro-Muino I, De Veerman M, de Felipe C, Hunt SP, Thielemans K, Joos GF, Pauwels RA. Endogenously produced substance P contributes to lymphocyte proliferation induced by dendritic cells and direct TCR ligation.

    Eur J Immunol 1999;29:3815-3825.

    Lambrecht BN. Immunologists getting nervous: neuropeptides, dendritic cells and T cell activation. Respir Res 2001;2:133-138.

    Langdon S, Sethi T, Richie A, Muir M, Smyth J, Rozengurt E. Broad spectrum neuropeptide antagonists inhibit the growth of small cell lung cancer in vivo. Cancer Res 1992;52:4554-7.

    Langman Embriología médica 11 edición TW Sadler. Editorial panamericana.

    Lang S, Sperk G. Neurochemical characterization of preprotachykinin B (50-79) immunoreactivity in the rat. Regul Pept 1995;57:183-192.

    Lang K, Drell TL, Niggemann B, Zanker KS, Entschladen F. Neurotransmitters regulate the migration and cytotoxicity in natural killer cells. Immunol Lett 2003;90:165-172.

    Lang K, Drell TL, Lindecke A, Niggemann B, Kaltschmidt C, Zaenker KS, Entschladen F.

    Induction of a metastatogenic tumor cell type by neurotransmitters and its pharmacological inhibition by established drugs. Int J Cancer 2004;112:231-238.

    Lasaga M, Debeljuk L. Tachykinins and the hypothalamo-pituitary-gonadal axis: An update.

    Peptides 2011;32:1972-1978.

    Lazure C, Seidah NG, Pelaprat D, Chretien M. Proteases and posttranslational processing of prohormones: a review. Can J Biochem Cell Biol 1983;61:501-515.

    Lecci A, Maggi CA. Peripheral tachykinin receptors as potential therapeutic targets in visceral diseases. Expert Opin Ther Targets 2003;7:343-362.

    Lechpammer M, Manning SM, Samonte F, Nelligan J, Sabo E, Talos DM, et al. Minocycline treatment following hypoxic/ischaemic injury attenuates white matter injury in a rodent model of periventricular leucomalacia. Neuropathol Appl Neurobiol 2008;34:379-93.

    Lee CM, Iversen LL, Hanley MR, Sandbreg BEB. The posible existence of multiple receptors for substance P. Naunyn-Schmiedebrg¿s Arch Pharmacol 1982;318:281-287.

    Lee SE, Romero R, Jung H, Park CW, Park JS, Yoon BH. The intensity of the fetal inflammatory response in intraamniotic inflammation with and without microbial invasion of the amniotic cavity. Am J Obstet Gynecol 2007;197:294.

    Lefkowitz R.J. The superfamily of heptahelical receptors. Nature Cell Biology 2000;2:133- 136.

    Lembeck F. Zur frage der zentrale ubertragung afferent impulse, III. Mitteilung. Naunyn- Schmiedeberg¿s Arch exp pathol Pharmacol 1953;219:197-213.

    Lembeck F, Holzer P. Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn-Schmiedeberg¿s Arch Pharmacol 1979;310:175- 183.

    Lembeck F. The 1988 Ulf Euler Lecture. Substance P: from extract to excitement. Acta Physiol Scand 1988;133:435-454.

    Lembeck F, Donnerer J, Tsuchiya M, Nagahisa A. The non-peptide tachykinin antagonist, CP- 96,345, is a potent inhibitor of neurogenic inflammation. Br J Pharmacol 1992;105:527-530.

    Lerner-Natoli M. Inflammation, angiogénesis and epilepsy. Biol Aujourdhui 2001;205:33-41.

    Lehtonen L, Rautava L, Korvenranta E et al. Perfect preterm infant study. Ann Med.

    2011;43:S47-53.

    Leviton A, Paneth N, Reuss ML, Susser M, Allred EN, Damman O et al. Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants.

    Developmental Epidemiology Network Investigators. Pediatr Res 1999;46:566-575.

    Leviton A. Preterm birth and cerebral palsy: is tumor necrosis factor the Messing link? Dev Med Child Neurol 1993;95:553-8.

    Levy M, Koeppen B, Stanton B, Berne R. Reproducción Femenina. Elsevier. España. En: ¿Berne y Levy Fisiología¿ 2006;737-743.

    Li Y, Douglas SD and Ho W, ¿Human stem cells express substance P gene and its receptor.,¿ Journal of hematotherapy and stem cell research 2000;9:445-452.

    Lieb K, Ahlvers K, Dancker K, Strohbusch S, Reincke M, Feige B,Voderholzer U. Effects of the neuropeptide substance P on sleep, mood, and neuroendocrine measures in healthy young men. Neuropsychopharmacology 2002;27:1041-1049.

    Lieb K, Fiebich BL, Berger M, Bauer J, Schulze-Osthoff K. The neuropeptide substance P activates transcription factor NF-kB and kB-dependent gene expression in human astrocitoma cells. The Journal of Inmunology 1997;159:4952-4958.

    Ljungdahl A, Hokfelt T, Nilsson G. Distribution of substance P-like immunoreactivity in the central nervous system of the rat--I. Cell bodies and nerve terminals. Neuroscience 1978; 3:861-943.

    Limosin F, Rouillon F, Payan C, Cohen JM, Strub N. Prenatal exposure to influenza as a risk factor for adult schizophrenia. Acta Psychiatr Scand 2003;107:331-5.

    Limperopoulos C, Bassan H, Sullivan NR, Soul JS, Robertson RL, Moore M, et al. Positive screening for autism in ex-preterm infants: prevalence and risk factors. Pediatrics 2008;121:758-65.

    Linnik MD, Moskowitz MA. Identification of immunoreactive substance P in human and other mammalian endothelial cells. Peptides 1989;10:957-962.

    Liu H, Mazarati AM, Katsumor H, Sankar R, Wasterlain C G. Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus. Proc Natl Acad Sci U S A 1999;96:5286-5291.

    Locksmith GJ, Chin A, Vu T, et al. High compared with standard gentamicin dosing for chorioamnionitis: a comparison of maternal and fetal serum drug levels. Obstet Gynecol 2005;105:473.

    Loonam TM, Noailles PA, Yu J, Zhu JP, Angulo JA. Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum. Life Sci 2003; 73:727-739.

    Lotz M, Carson DA, Vaughan JH. Substance P activation of rheumatoid synoviocytes: neural pathway in pathogenesis of arthritis. Science 1987; 235:893-5.

    Lotz M, Vaughan JH, Carson DA. Effect of neuropeptides on production of inflammatory cytokines by human monocytes. Science 1988;241:1218-1221.

    Lundberg JM, Brodin E, Hua X, Saria A. Vascular permeability changes and smooth muscle contraction in relation to capsaicin-sensitive substance P afferents in the guinea-pig. Acta Physiol Scand 1984;120:217-227.

    Luo W, Sharif TR, Sharif M. Substance P-induced mitogenesis in human astrocytoma cells correlates with activation of the mitogen-activated protein kinase signaling pathway. Cancer Res 1996;56:4983-4991.

    MacDonald SG, Boyd ND. Regulation of substance P receptor affinity by guanine nucleotide binding proteins. J Neurochem 1989;53:264-272.

    MacDonald SG, Dumas JJ, Boyd ND. Chemical cross-linking of the substance P (NK-1) receptor to the alpha subunits of the G proteins Gq and G11. Biochemistry 1996;35:2909- 2916.

    MacLeod AM, Merchant KJ, Brookfield F, Kelleher F, Stevenson G, Owens AP, Swain CJ, Cascieri MA, Sadowski S, Ber E, Strader CD, Fong TM. Identification of L-tryptophan derivatives with potent and selective antagonist activity at the NK1 receptor. J Med Chem 1994;37:1269-1274.

    Maggi CA, Meli A. The sensory-efferent function of capsaicin-sensitive sensory neurons. Gen Pharmacol 1988;19:l-43.

    Maggi CA, Patacchini R, Rovero P, Giachetti A. Tachykinin receptors and tachykinin receptor antagonists. J Auton Pharmacol 1993;13:23-93.

    Maggi CA. The effects of tachykinins on inflammatory and immune cells. Regul Pept 1997; 70:75-90.

    Maggi C A. The mammalian tachykinin receptors. Gen Pharmacol 1995;26:911-944.

    Maggi CA. Principles of tachykininergic co-transmission in the peripheral and enteric nervous system. Regul Pept 2000;93:53-64.

    Maggi CA, Giachetti A, Dey R D, Said SI. Neuropeptides as regulators of airway function: vasoactive intestinal peptide and the tachykinins. Physiol Rev 1995;75:277-322.

    Maggi CA, Giuliani S, Santicioli P, Regoli D, Meli A. Peripheraleffects of neurokinins: functional evidence for the existence of multiple receptors. J Auton Pharmacol 1987;7:11-32.

    Maggi CA, Meli A. The sensory-efferent function of capsaicin-sensitive sensory neurons. Gen Pharmacol 1988;19:1-43.

    Maggi CA, Santicioli P, Giulian S, Regoli D, Meli A. Activation of micturition reflex by substance P and substance K: indirect evidence for the existence of multiple tachykinin receptors in the rat urinary bladder. J Pharmacol Exp Ther1986;238:259-266.

    Maggi CA, Schwartz T W. The dual nature of the tachykinin NK1 receptor. [Review]. Trends Pharmacol Sci 1997;18:351-355.

    Maggio JE. ¿Kassinin" in mammals: the newest tachykinins. Peptides 1985;6:237-243.

    Maggio JE. Tachykininis. Annu Rev Neurosci 1988;11:13-28.

    Maintz L, Wardelmann E, Walgenbach K, Fimmers R, Bieber T, Raap U, and Novak N.

    Neuropeptide blood levels correlate with mast cell load in patients with mastocytosis. Allergy 2011;66(7):862-869.

    Makhortova NR, Askovich P, Patterson CE, Gechman LA, Gerard NP, Rall GF. Neurokinin-1 enables measles virus trans-synaptic spread in neurons. Virology 2007;362:235-244.

    Manak MM, Moshkoff DA, Nguyen LT, et al. Anti-HIV-1 activity of the neurokinin-1 receptor antagonist aprepitant and synergistic interactions with other antiretrovirals. AIDS 2010;24:2789-96.

    Manotas Cabarcas R. Infecciones bacterianas en el neonato. Neonatología. 1 ed. Medellín.: Editorial Universidad de Antioquia 1994;629-31.

    Manotas Cabarcas R. Infecciones perinatales. In: Gómez J, Gómez L, editors. Pautas de tratamiento en Pediatría. 3 ed. Medellín: 2000;47-57.

    Mantyh PW, Hunt SP, Maggio JE. Substance P receptors: localization by light microscopic autoradiography in rat brain using [3H] SP as the radioligand. Brain Research 1984;307:147- 165.

    Mantyh PW. Substance P and the inflammatory and immune response. Ann NY Acad Sci 1991;632:263-271.

    Mantyh PW, Allen CJ, Ghilardi JR, Rogers SD, Mantyh CR, Liu H et al. Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo. Proc Natl Acad Sci USA 1995;92:2622-2626.

    Marcket UR, Arck PC, McBey BA, Manuel JS, Croy BA, Marshall JS, ChaouatG, Clark DA.

    Stress triggered abortions are associated with alterations of granulated cells into the decidua.

    Am J Reprod Immunol 1997;37:94-100.

    Marriott I, Mason MJ, Elhofy A, Bost KL. Substance P activates NFkappaB independent of elevations in intracellular calcium in murine macrophages and dendritic cells. J.

    Neuroimmunol 2000;102:163-171.

    Marshall KW, Chiu B, Inman RD. Substance P and arthritis: analysis of plasma and synovial fluid levels. Arthr Rheumat 1990;33:87-90.

    Martin FC, Charles AC, Sanderson MJ, Merill JE. Substance P stimulates IL-1 production by astrocytes via intracellular calcium. Brain Research 1992;599:13-18.

    Martin FC, Anton PA, Gornbein JA, Shanahan F, merrill JE. Production of interleukin-1 by microglia in response to substance P: role for a non-classical NK-1 receptor. J Neuroimmunol 1993;42;53-60.

    Martinelli P, Sarno L, Maruotti GM, Paludetto R. Chorioamnionitis and prematurity: a critical review. J Matern Fetal Neonatal Med 2012;25:29-31.

    Marx L, Arck P, Kieslich C, Mitterlenchner S, Kapp M, Dietl J. Decidual mast cells might be involved in the onset of human first-trimester abortion. Am J Reprod Immunol 1999;41:13-18.

    Marzioni D, Fiore G, Giordano A, Nabissi M, Florio P, Verdenelli F, Petraglia F, Castellucci M. Placental expression of substance P and vasoactive intestinal peptide: evidence for a local effect on hormone release. J Clin Endocrinol Metab 2005;90:2378-2383.

    Matsuishi T, Nagamitsu S, Shoji H, Itoh M, Takashima S, Iwaki T., . . . Kato H. Increased cerebrospinal fluid levels of substance P in patients with amyotrophic lateral sclerosis. Short communication. J Neural Transm 1999;106(9-10):943-948.

    Matsuishi T, Sakai T, Nagamitsu S, Shoji H, Ueda N, Kaneko S, . . . Kato H. Decreased cerebrospinal fluid levels of substance P in Machado-Joseph disease. J Neurol Sci 1996;142(1-2):107-110.

    Mauborgne A, Javoy-Agid F, Legrand JC, Agid Y, & Cesselin F. Decrease of substance P-like immunoreactivity in the substantia nigra and pallidum of parkinsonian brains. Brain Res 1983;268(1):167-170.

    McElrath TF, Hecht JL, Dammann O et al.; ELGAN Study Investigators. Pregnancy disorders that lead to delivery before the 28th week of gestation: an epidemiologic approach to classification. Am J Epidemiol 2008;168:980-9.

    McGillis JP, Organist ML, Scriven KH, Payan DG. Purification of the 33,000-dalton ligand binding-protein constituent of the lymphoblast substance P receptor. J Neurosci Res 1987a; 18:190-194 McGillis JP, Organist ML, Payan DG. Immunoaffinity purification of membrane protein constituents of the IM-9 lymphoblast receptor for substance P. Anal Biochem 1987b;164:502- 513.

    McGillis JP, Mitsuhashi M, Payan DG. Immunomodulation by tachykinin neuropeptides. Ann NY Acad Sci 1990;594:85-94.

    Meshki J, Douglas SD, Lai JP, Schwartz L, Kilpatrick LE, Tuluc F. Neurokinin 1 receptor mediates membrane blebbing in HEK293 cells through a Rho/Rho-associated coiled-coil kinase-dependent mechanism. J Biol Chem 2009;284:9280-9289.

    Metwali A, Blum AM, Elliott DE, Setiawan T, Weinstock JV. Cutting edge: hemokinin has substance P-like function and expression in inflammation. J Immunol 2004;172:6528-6532.

    Michaels Lisa A, Kwaku Ohene-Frempong, Zhao H and Douglas SD. Serum Levels of Substance P Are Elevated in Patients With Sickle Cell Disease and Increase Further During Vaso-Occlusive Crisis. Blood 1998;92:3148-3151.

    Milner P, Kirkpatrick KA, Ralevic V, Toothill V, Pearson J, Burnstock G. Endothelial Cells cultured from human umbilical vein release ATP, substance P and acetylcholine in response to increased flow. Proc Biol Sci 1990;22:245-248.

    Minkes RK. Disorders of the Umbilicus. http://www emedicine com/ped/topic2948 htm 2006 April 27 [cited 2007 Dec 15]; Available from:http://www.emedicine.com/ped/topic2948.htm Mitchell BS, Ahmed E. An immunohistochemical study of the catecholamine synthesizing enzymes and neuropeptides in the female guinea-pig uterus and vagina. Histochem J 1992; 24:361-7.

    Mitsuhashi M, Ohashi Y, Schichijo S, Christian C, Sudduth-Klinger J, Harrowe G, Payan DG.

    Multiple intracellular signalling pathways of the neuropeptide SP receptor. J Neurosci Res 1992;32:437-443.

    Mirzaie F, Mohammah-Alizadeh S. Contributing factors of preterm delivery in parturient in a University Hospital in Iran. Saudi Med J 2007;28:400-4.

    Mittendorf R, Covert R, Montag AG, elMasri W, Muraskas J, Lee KS, et al. Special relationships between fetal inflammatory response syndrome and bronchopulmonary dyplasia in neonates. J Perinat med. 2005;33:428-434.

    Mochizuki-Oda N, Nakajima Y, Nakanishi S, Ito S. Characterization of the SP receptormediated Ca influx in cDNA transfected CHO cells. J Biol Chem 1994;269:9651-9658.

    Monaco-Shawver L, Schwartz L, Tuluc F, Guo CJ, Lai JP, Gunnam SM, Orange JS.

    Substance P inhibits natural killer cell cytotoxicity through the neurokinin-1 receptor. J Leukoc Biol 2011;89:113-125.

    Moore KL, Persaud VN, Martínez C. Placenta y Membranas Fetales. En: ¿Embriología Clínica: el Desarrollo del Ser Humano¿. Cáp. 7. Elsevier. España. 2004;7,119-153.

    Moussaoui SM, Le Prado N, Bonici B, Faucher DC, Cuine F, Laduron PM et al. Distribution of neurokinin B in rat spinal cord and peripherical tisúes: comparison with neurokinin A and substance P and effects of neonatal capsaicin treatment. Neuroscience 1992;48:969-978.

    Mravec B, Gidron Y, Kukanova B, Bizik J, Kiss A, Hulin I. Neuralendocrine-immune complex in the central modulation of tumorigenesis: facts, assumptions, and hypotheses. J Neuroimmunol 2006;180:104-116.

    Mueller-Heubach E, Rubinstein D.N., Schwarz S.S. Histologic chorioamnionitis and preterm delivery in different patient populations. Obstet Gynecol 1990; 75: 622-626.

    Mullany LC, Darmstadt GL, Katz J, Khatry SK, Leclerq SC, Adhikari RK, et al. Risk Factors for Umbilical Cord Infections among Newborns of Southern Nepal. American Journal of Epidemiology 2007;165:203-11.

    Muñoz M, Perez A, Coveñas R, Rosso M, Castro E. Antitumoural action of L-733,060 on neuroblastoma and glioma cell lines. Arch Ital Biol 2004a;142:105-112.

    Muñoz M, Perez A, Rosso M, Zamarriego C, Rosso R. Antitumoral action of the neurokinin- 1 receptor antagonist L-733, 060 on human melanoma cell lines. Melanoma Res 2004b;14: 183-188.

    Muñoz M, Rosso M, Perez A, Coveñas , Rosso R., Zamarriego C. and Piruat J. The NK1 receptor is involved in the antitumoral action of L-733,060 and the mitogenic action of substance P on neuroblastoma and glioma cell lines. Neuropeptides 2005a;39:427-432.

    Muñoz M, Rosso M, Perez A, Coveñas R, Rosso R, Zamarriego C, Soult JA., Montero I.

    Antitumoral action of the neurokinin-1-receptor antagonist L-733,060 and mitogenic action of substance P on human retinoblastoma cell lines. Invest Ophthalmol Vis Sci 2005b;46:2567- 2570.

    Muñoz M; Rosso M; Coveñas R. The NK-1 receptor is involved in the antitumoural action of L-733,060 and in the mitogenic action of substance P on human pancreatic cancer cell lines.

    Lett. Drug Des. Discovery 2006;3:323-329.

    Muñoz M, Rosso M, Coveñas R. In: Focus on Neuroblastoma Research, Fernandes, Ed.; Nova Science Publishers: New York 2007a;31-56.

    Muñoz M, Rosso M, Coveñas R, Montero I, González-Moles MA, Robles MJ. Neurokinin-1 receptors located in human retinoblastoma cell lines: antitumor action of its antagonist, L- 732,138. Invest Ophthalmol Vis Sci 2007b;48: 2775-2781.

    Muñoz M, Rosso M, Aguilar FJ, González-Moles MA, Redondo M, Esteban F. NK-1 receptor antagonists induce apoptosis and counteract substance P-related mitogenesis in human laryngeal cancer cell line HEp-2. Invest New Drugs 2008;26:111-118.

    Muñoz M, Rosso M, Casinello F, Coveñas R. Paravertebral anesthesia: how substance P and the NK-1 receptor could be involved in regional block and breast cancer recurrence. Breast Cancer Res Treat 2010g;122:601-603.

    Muñoz M, Rosso M, Coveñas R. A new frontier in the treatment of cancer: NK-1 receptor antagonists. Curr Med Chem 2010c;17:504-516.

    Muñoz M, Pavón A, Rosso M, Salinas MV, Pérez A, Carranza A, González-Ortega A.

    Immunolocalization of NK-1 receptor and Substance P in human normal placenta. Placenta 2010a;31:649-651.

    Muñoz M, Rosso M. The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug. Invest New Drugs 2010d;28:187-193.

    Muñoz M, Rosso M, González A, Saénz J, Coveñas R. The broad spectrum antitumor action of cyclosporin A is due to its tachykinin receptor antagonist pharmacological profile. Peptides 2010b;31:643-1648.

    Muñoz M, Rosso M, Robles-Frias MJ, Salinas-Martin MV, Rosso R,González-Ortega A, Coveñas R. The NK-1 receptor is expressed in human melanoma and is involved in the antitumor action of the NK-1 receptor antagonist aprepitant on melanoma cell lines. Lab Invest 2010f;90:1259-1269.

    Muñoz M, y Coveñas R. Neurokinin-1 receptor: a new promising target in the treatment of cancer. Discov Med 2010e;10:305-313.

    Muñoz M, y Coveñas R. NK-1 receptor antagonists: a new paradigm in pharmacological therapy. Curr Med Chem 2011a;18:11820-1831.

    Muñoz M, Rosso M, Coveñas R. The NK-1 receptor: a new target in cancer therapy. Curr Drug Targets 2011b;12:909-921.

    Muñoz M, Bernabeu-Wittel J, Coveñas R. RNK-1 as a melanoma target. Expert opinion on therapeutic targets 2011c;15:889-97.

    Muñoz M y Coveñas R. NK-1 receptor antagonists: a new generation of anticancer drugs.

    Mini Rev Med Chem 2012a;12:593-599.

    Muñoz M, González-Ortega A, Coveñas R. The NK-1 receptor is expressed in human leukemia and is involved in the antitumor action of aprepitant and other NK-1 receptor antagonists on acute lymphoblastic leukemia cell lines. Investigational new drugs 2012b;30:529-40.

    Muñoz M, Gónzalez-Ortega A, Rosso M, Robles-Frias MJ, Carranza A, Salinas- Martin MV, Coveñas R. The substance P/neurokinin-1 receptor system in lung cancer: Focus on the antitumor action of neurokinin-1 receptor antagonists. Peptides 2012c;38:318-25.

    Muñoz M, Martinez-Armesto J, Coveñas R. NK-1 receptor antagonists as antitumor drugs: a survey of the literature from 2000 to 2011. Expert Opin Ther Pat 2012d;22:735-746.

    Muñoz M, Coveñas R. Involvement of substance P and the NK-1 receptor in cancer progression Review Article Peptides 2013b;48:1-9.

    Muñoz M, Berger B, Rosso M, Gonzalez-Ortega A, Carranza A, Coveñas R. Antitumor activity of neurokinin-1 receptor antagonists in MG-63 human osteosarcoma xenografts.

    International Journal of Oncology 2014; DOI:10.3892/ijo.2013.2164. PubMed.

    Muñoz M, Coveñas R. Safety of neurokinin-1 receptor antagonists. Expert Opinion on Drug Safety 2013c;12:673-85.

    Muñoz M, Andrés Carranza, Antonio Pavón, George Anderson y Rafael Coveñas.

    Immunolocalization of Substance P and NK-1 Receptor in Hofbauer Cells in Human Normal Placenta. Microscopy Research and Technique 2013a;76:1310-1313.

    Nakajima Y, Tsuchida K, Negishi M, Ito S, Nakanishi S. Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cAMP cascades in transfected chinese hamster ovary cells. J Biol Chem 1992;267:2437-2442.

    Nakanishi S. Substance P precursor and kininogen: their structures, gene organizations and regulation. Physiol Rev 1987;67:1117-1142.

    Nakanishi S. Mammalian tachykinin receptors. Annu Rev Neuroscience 1991;14:123-136.

    Nakata Y, Hiraoka C, Segawa T. Apparent molecular w..eight of the substance P binding site in rat brain. Eur J Pharmacol 1988;152:171-174.

    Nakagawa N, Sano H, Iwamoto I. Substance P induces the expression of intercellular adhesion molecule-1 on vascular endothelial cells and enhances neutrophil transendothelial migration. Peptides 1995;16:721-725.

    Nápoles Méndez C. Danilo. Consideraciones sobre el síndrome de respuesta inflamatoria fetal. Considerations on fetal inflammatory response syndrome. Artículo de revisión. Medisan 2012;16:1761.

    Nasef N, Shabaan AE, Schurr P, Iaboni D, Choudhury J, Church P, Dunn MS.Z Geburtshilfe.

    Intrauterine inflammation and its sequelae: does chorioamnionitis really matter for outcome of very low birth weight infants?. Neonatol 2012;216:173-6.

    Nasef N, Shabaan AE, Schurr P, Iaboni D, Choudhury J, Church P, Dunn MS. Effect of clinical and histological chorioamnionitis on the outcome of preterm infants. Am J Perinatol.

    2013;30:59-68.

    Navari RM, Reinhart RR, Gralla RJ, Hesketh P, Khojasteh A, Kindler H. Grote TH, Pendergrass K, Grunberg SM, Carides AD, Gertz BJ. Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. N Engl J Med 1999;340:190-195.

    Nawa H, Doteuchi M, Igano K, Inouye K, Nakanishi S. Substance K: a novel mammalian tachykinin that differs from substance P in its pharmacological profile. Life Sci 1984;34: 1153-1160.

    Nawa H, Kotani H, Nakanishi S. Tissue-specific generation of two preprotachykinin mRNAs from one gene by alternative RNA splicing. Nature 1985;312:729-734.

    Nazer H, Jarpa C , Cifuentes L. Incidencia y asociaciones de arteria umbilical única en recién nacidos. Maternidad del Hospital Clínico de la Universidad de Chile, 1998-2010. Rev chilena de Obstet Ginecología 2011;76: 21-25.

    Ness RB, Grisso JA, Hirschinger N, Marcovic N, Shaw LM, Day NL, Kline J. Cocaine and tobacco use and the risk of spontaneous abortion. N Engl J Med 1999;340:333-9.

    Nio DA, Moylan RN, Roche JK. Modulation of T lymphocyte function by neuropeptides.

    Evidence for their role as local immunoregulatory elements. J Immunol 1993;150:5281-5288.

    Newton ER. Chorioamnionitis and intraamniotic infection. Clin Obstet Gynecol 1993;36:795.

    Newton ER, Piper J, Peairs W. Bacterial vaginosis and intraamniotic infection. Am J Obstet Gynecol 1997;176:672¿7.

    Nilsson G, Dahlberg K, Brodin E, Sundler F, Strandberg K. Distribution and constrictor effect o substance P in guinea pig tracheobronchial tissue. En: ¿Substance P (Nobel Symposium 37)¿ By U.S. von Euler U.S. and B. Pernow B. (Eds.). Raven Press 1977;75-81.

    Nilsson J, von Euler AM, Dalsgaard CJ. Stimulation of connective tissue cell growth by substance P and substance K. Nature 1985;315:61-63.

    Nimmo AJ, Cernak I, Heath DL, Hu X, Bennett CJ, & Vink R. Neurogenic inflammation is associated with development of edema and functional deficits following traumatic brain injury in rats. Neuropeptides 2004;38(1):40-47.

    Nitsos I, Rees SM, Duncan J, Kramer BW, Harding R, Newnham JP, et al. Chronic exposure to intra-amniotic lipopolysaccharide affects the ovine fetal brain. J Soc Gynecol Investig 2006;13:239-47.

    O¿Connor TM, O¿Connell J, O¿Brien DI, Goode T, Verdin CP, Sanan F. The role of substance P in inflammatory disease. J Cell Physiol 2004;201:167-180.

    O¿Harte F, Burcher E, Lovas S, Smith DD, Vaudry H, Conlon JM. Ranakinin: a novel NK1 tachykinin receptor agonist isolated with neurokinin B from the brain of the frog Rana ridibunda. J Neurochem 1991;57:2086¿2.

    Onuoha GN, Alpar EK. Calcitonin gene-related peptide and other neuropeptides in the plasma of patients with soft tissue injury. Life Sci 1999;65:1351-8.

    Ortega HH, Salvetti NR, Baravalle C, Lorente JA, Mira GA. Oestradiol induced inhibition of neuroendocrine marker expression in Leydig cells of 191 adult rats. Reprod Domest Anim 2006;41:204-209.

    Ozo D, Segura JJ, Jiménez-Rubio A, García-Pergañeda A, Bettahi I, Guerrero JM, Calvo JR.

    Identification of G-protein coupled receptor subunits in normal human dental pulp. J Endod 2000;26:16-19.

    Pacora P, Chaiworapongsa T, Maymon E et al. Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome. J Matern Fetal Neonatal Med 2002;11:18-25.

    Page NM, Woods RJ, Gardiner SM, Lomthaisong K, Gladwell RT, Butlin DJ, Mayonda IT, Lowry PJ. Excessive placental secretion of neurokinin B during the third trimester causes preeclampsia.

    Nature 2000;405:797-800.

    Page NM, Woods RJ, Lowry PJ. A regulatory role for neurokinin B in placental physiology and pre-eclampsia. Regul Pept 2001;98:97-104.

    Page NM, Nicola J. Bell. The human tachykinin NK1 (short form) and tachykinin NK4 receptor: a reappraisal. European Journal of Pharmacology 2002;437:27:30.

    Page NM, Bell NJ, Gardiner SM, Manyonda IT, Brayley KJ., Strange PG et al.

    Characterization of the endokinins: human tachykinins with cardiovascular activity. Proc Natl Acad Sci 2003;100: 6245-6250.

    Page NM. Hemokinins and endokinins. Cell Mol Life Sci 2004;61:1652-1663.

    Page NM. New challenges in the study of the mammalian tachykinins. Peptides 2005;26:1356-1358.

    Page NM, Dakour J, Morrish DW. Gene regulation of neurokinin B and its receptor NK3 in late pregnancy and pre-eclampsia. Molecular Human Reproduction 2006;12:427-433.

    Page NM. Neurokinin B and pre-eclampsia: a decade of discovery. Biology and Endocrinology 2010;8:4.

    Palma C, Goso C. Manzini S. Neurosci Letters 1994;171:221-224.

    Palma C, Nardelli F, Manzini S, Maggi CA. Substance P activates responses correlated with tumor growth in human glioma cells line bearing tachykinin NK1 receptors. Br J Cancer 1999;79:236-43.

    Palma C, Bigioni M, Irrissuto C, Nardelli F, Maggi CA, Manzini S. Antitumour activity of tachykinin NK1 receptor antagonists on human glioma U373 MG xenograft. Br J Cancer 2000; 82:480-487.

    Pascual DW, Xu-Amano JC, Kiyono H, McGhee JR, Bost KL. Substance P acts directly upon cloned B lymphoma cells to enhance IgA and IgM production. J Immunol 1991;146:2130- 2136.

    Pascual DW, Bost KL. Substance P production by P388D1 macrophages:a possible autocrine function for this neuropeptide. Immunology 1990;71:52-56.

    Park SW, Yan YP, Satriotomo I, Vemuganti R, Dempsey RJ. Substance P is a promoter of adult neural progenitor cell proliferation under normal and ischemic conditions. J Neurosurg 2007;107: 593-599.

    Patacchini R, Lecci A, Holzer P, Maggi CA. New discovered tachykinins raise new questions about their peripheral roles and the tachykinin nomenclature. Trends Pharmacol Sci 2004;25:1-3.

    Patak E, Candenas ML, Pennefather JN, Ziccone S, Lilley A, Martín JD, Flores C, Mantecón AG., Story ME, Pinto FM. Tachykinins and tachykinins receptors in human uterus. Br J Pharmacol 2003;139:523-532.

    Patak E, Pinto FM, Story ME, Pintado CO, Fleming A, Page NM, Pennefather JN, Candenas ML. Functional and molecular characterization of tachykinins and tachykinins receptors in the mouse uterus. Biol Reprod 2005;72:1125-1133.

    Patel L, Lindley C. Aprepitant, a novel NK1-receptor antagonist. Expert Opin Pharmacother 2003;4:2279-2296.

    Patrick LA, Gaudet LM, Farley AE, Rossiter JP, Tomalty LL, Smith GN. Development of a guinea pig model of chorioamnionitis and fetal brain injury. Am J Obstet Gynecol 2004;191:1205-1211.

    Payan DG, Brewster DR, Goetzl EJ. Specific stimulation of human T linphocytes by substance P. J Immunol 1983;131:1613-1615.

    Payan DG, McGillis JP, Organist ML. Binding characteristics and affinity labelling of protein constituents of the human IM-9 lymphoblast receptor for substance P. J Biol Chem 1986;261: 14321-14329.

    Pawelczyk E et al. Spontaneous preterm labor is associated with an increase in the proinflammatory signal transducer TLR4 receptor on maternal blood monocytes. BMC Pregnancy and Childbirth 2010;10:66.

    Pearse AGE. Common cytochemical and ultrastructural characteristics of cells producing polypeptide hormones (the APUD series) and their relevance to thyroid cells and ultimobranchial C cells and calcitonin. Proceedings of the Royal Society of London B 1968;170:71-80.

    Pearse AGE. The cytochemistry and ultrastructure of polypeptide hormone-producing cells at the APUD series and the embryologic, physiologic and pathologic implications of the concept. The Journal of Histochemistry and Cytochemistry 1969;17:303-317.

    Pennefather JN, Zeng XP, Gould D, Hall S, Burcher E. Mammalian tachykinins stimulate rat uterus by activating NK-2 receptors. Peptides 1993;14:169-174.

    Perlman JM, Risser R, Broyles S. Bilateral cystic periventricular leukomalacia in the preterm infant: associated risk factors. Pediatrics 1996;97:822-827.

    Pernow B. Substance P. Pharmacol Rev 1983;35: 85-141.

    Persson-Sjogren S, Lejon K, Holmberg D, Forsgren S. Expression of the NK-1 receptor on islet cells and invading immune cells in the non-obese diabetic mouse. J Autoimmun 2005;24:269-279.

    Peters KL, Rosychuk RJ, Hendson L, Cote¿ JJ, McPherson C, Tyebkhan JM. Improvement of shortand long-term outcomes for very low birth weight infants: Edmonton NIDCAP Trial.

    Pediatrics 2009;124:1009-1020.

    Petraglia F, Florio P, Nappi C, Genazzani AR. Peptide signaling in human placenta and membranes: autocrine, paracrine and endocrine mechanisms. Endocrine Reviews 1996;17:156-186.

    Pinelli J, Zwaigenbaum L. Chorioamnionitis, gestational age, male sex, birth weight, and illness severity predicted positive autism screening scores in very-low-birth-weight preterm infants. Evid Based Nurs 2008;11:122.

    Pintado CO, Pinto FM, Pennefather JN, Hidalgo A, Baamonde A, Sanchez T, Candenas ML.

    A role for tachykinins in female mouse and rat reproductive function. Biol Reprod 2003;69:940-946.

    Pinto FM, Almeida TA, Hernández M, Devillier P, Advenier C, Candenas ML. mRNA expression of tachykinins and tachykinin receptors in different human tissues. Eur J Pharmacol 2004;494: 233-239.

    Pinto FM, Cintado CG, Devillier P, Candenas ML. Expression of preprotachykinin-B, the gene that encodes neurokinin B, in the rat uterus. Eur J Pharmaco 2001;425:R1-2.

    Pinto FM, Ravina CG, Subiran N, Cejudo-Román A, Fernández-Sánchez M, Irazusta J, Garrido N, Candenas L. Autocrine regulation of human sperm motility by tachykinins.

    Reprod biol endocrinol 2010;26:104.

    Piper JM, Newton ER, Berkus MD, Peairs WA. Meconium: A marker for peripartum infection. Obstet Gynecol 1998;91:741-5.

    Polam S, Koons A, Anwar M, Shen-Schwarz S, Hegyi T. Effect of chorioamnionitis on neurodevelopmental outcome in preterm infants. Arch Pediatr Adolesc Med 2005;159:1032-5.

    Polak JM, Bloom SR. The neuroendocrine design of the gut. Clin Endocrinol Metab 1979;8:313-330.

    Potharst ES, van Wassenaer AG, Houtzager BA, van Hus JW, Last BF, Kok JH. High incidence of multi-domain disabilities in very preterm children at five years of age. J Pediatric 2011;159:79-85.

    Quartara L, Maggi CA. The tachykinin NK1 receptor. Part I: ligands and mechanisms of cellular activation. Neuropeptides 1997;31:537-563.

    Quartara L, Maggi CA. The tachykinin NK1 receptor. Part II: distribution and pathophysiological roles. Neuropeptides 1998;32:1-49.

    Quinlan KL, Song IS, Bunnett NW, Letran E, Steinhoff M, Harten B, et al. Neuropeptide regulation of human dermal microvascular endothelial cell ICAM-1 expression and function.

    Am J Physiol 1998; 275:C1580-C1590.

    Radhakrishnan V, Henry JL. Electrophysiology of neuropeptides in the sensory spinal cord.

    Prog Brain Res 1995;104:175-195.

    Radhakrishnan V, Henry JL. Novel substance P antagonist, CP-99,345, blocks responses of cat spinal dorsal horn neurones to noxious cutaneous stimulation and to substance P. Neurosci Lett 1991;132:39-43.

    Rameshwar P, Ganea D, Gascon P. In vitro stimulatory effect of substance P on hematopoiesis. Blood 1993;81:391-398.

    Rameshwar P, Gascon P, Ganea D. Stimulation of IL-2 production inmurine lymphocytes by substance P and related tachykinins. J Immunol 1993;151:2484-2496.

    Rameshwar P, Gascon P. Substance P (SP) mediates production of stem cell factor and interleukin-1 in bone marrow stroma: potential autoregulatory role for these cytokines in SP receptor expression and induction. Blood 1995;86:482-490.

    Rameshwar P, Gascon P. Hematopoietic modulation by the tachykinins. Acta Haematol 1997;98:59-64.

    Ramón y Cajal, S. El nuevo concepto de la histología de los centros nerviosos. Revista de Ciencias Médicas 1982;18:457-476.

    Ravina CG, Seda M, Pinto FM, Orea A, Fernandez-Sanchez M, Pintado CO, Candenas ML. A role for tachykinins in the regulation of human spermmotility. Hum Reprod 2007;22:1617- 1625.

    Redline R. Placental inflammation. Semin Neonatol 2004;9:265-274.

    Reeve, J.G.; Bleehen, N.M. [D-Arg1-D-Phe5, D-Trp7, 9, Leu11] Substance P induces apoptosis in lung cancer cell lines in vitro. Biochem Bioph Res Com 1994;199:1313-1319.

    Regoli D, Drapeau G, Dion S, D¿Orleans-Juste P. Receptors for substance P and related neurokinins. Pharmacology 1989;38:1-15.

    Regoli D, Boudon A, Fauchere J. Receptors and antagonists for substance P and related peptides. Pharmacol Rev 1994;46:551-599.

    Reid MS, Herrera-Marschitz M, Kehr J, Ungerstedt U. Striatal dopamine and glutamate release: effects of intranigral injections of substance P. Acta Physiol Scand 1990;140:527-537.

    Reid MS, Herrera-Marschitz M, Hökfelt T, Ohlin M, Valentino KL, Ungerstedt U. Effects of intranigral substance P and neurokinin A on striatal dopamine release ¿ I. Interactions with substance P antagonists. Neuroscience 1990;36:643-658.

    Reiman M, Kujari H, Ekholm E, Lapinleimu H, Lehtonen L, Haataja L. Interleukin-6 polymorphism is associated with chorioamnionitis and neonatal infections in preterm infants.

    Journal of Pediatrics 2008;153:19-24.

    Reinke E, Fabry Z. Breaking or making immunological privilege in the central nervous system: the regulation of immunity by neuropeptides. Immunol Lett 2006;104:102-109.

    Reinke EK, Johnson MJ, Ling C, Karman J, Lee J, Weinstock JV, Fabry Z. Substance P receptor mediated maintenance of chronic inflammation in EAE. J Neuroimmunol 2006;180:117-125.

    Resch B, Müller WD. Interleukin-6-174 CC polymorphism is associated with clinical chorioamnionitis and cerebral palsy. Ann neurol 2010;68:768-9.

    Richfield EK., Vonsattel JP, MacDonald ME, Sun Z, Deng YP., & Reiner A. Selective loss of striatal preprotachykinin neurons in a phenocopy of Huntington's disease. Mov Disord 2002;17(2):327-332.

    Rickert VI, Wiemann CM, Hankins GD, McKee JM, Berenson AB. Prevalence and risk factors of chorioamnionitis among adolescents. Obstet Gynecol 1998;92:254-7.

    Rincón Ricote MI , Fernando Magdaleno Dans , Sancha Naranjo M, Omeñaca Teres F, González González A. Corioamnionitis histológica y morbimortalidad neonatal: aproximación al síndrome de respuesta inflamatoria fetal. Rev Chil Obstet Ginecol 2010;75:172-178 Rissler K. Sample preparation, high-performance liquid chromatographic separation and determination of substance P-related peptides. J Chromatogr 1995; B 665:233¿270.

    Robinson P, Garza A, Moore J, Eckols TK, Parti S, Balaji V, Vallejo J, Tweardy DJ. Substance P is required for the pathogenesis of EMCV infection in mice. Int J Clin Exp Med 2009;2:76- 86.

    Robinson JN, Muhamad AZ. Anomalías de la pared abdominal y del cordón umbilical. Clin Perinatol 2000;4:987-8.

    Rollandy I, Dreux C, Imhoff V, Rossignol B. Importance of the presence of the N-terminal tripeptide of substance P for the stimulation of phosphatidylinositol metabolism in rat parotide gland: a possible activation of phospholipases C and D. Neuropeptides 1989;13:175-185.

    Romero R, Chaiworapongsa T, Espinoza J. Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J Nutr 2003;133:1668S-1673S.

    Romero R, Espinoza J, Gonçalves LF, Kusanovic JP, Friel L, Hassan S. The role of inflammation and infection in preterm birth. Semin Reprod Med 2007;25:21-39.

    Rosenberg ZF, Fauci A.S. Immunopathogenic mechanisms of HIV infection: cytokine induction of HIV expression. Immunol. Today 1990;11:176-180.

    Rosenberg, ZF.; Fauci AS. Immunopathogenesis of HIV infection. FASEB J 1991;5:2382- 2390.

    Rosler N, Wichart I, & Jellinger KA. Clinical significance of neurobiochemical profiles in the lumbar cerebrospinal fluid of Alzheimer's diseasepatients. J Neural Transm 2001;108(2):231- 246.

    Rosso M, Robles-Frías MJ, Coveñas R, Salinas-Martín MV, Muñoz M. The NK-1 Receptor Is Expressed in Human Primary Gastric and Colon Adenocarcinomas and Is Involved in the Antitumor Action of L-733,060 and the Mitogenic Action of Substance P on Human Gastrointestinal Cancer Cell Lines. Tumor Biol 2008;29:245-254.

    Rosso M, Muñoz M, Berger M. The role of neurokinin-1 receptor in the microenvironment of inflammation and cancer. Scientific World Journal 2012;2012:381434.

    Rouse DJ, Landon M, Leveno KJ, et al. The Maternal-Fetal Medicine Units cesarean registry: chorioamnionitis at term and its duration-relationship to outcomes. Am J Obstet Gynecol 2004;191:211-6.

    Rudd JA, Jordan CC, Naylor RJ. The action of the NK1 tachykinin receptor antagonist CP- 99,994 in antagonizing the acute and delayed emesis induced by cisplatin in the ferret. Br J Pharmacol 1996;119:931-936.

    Rupniak NM, Carlson E, Boyce S, Webb JK, Hill RG. Enantioselective inhibition of the formalin paw late phase by the NK1 receptor antagonist L-733,060 in gerbils. Pain 1996;67:189-195.

    Rupniak NM and Kramer MS. Discovery of the antidepressant and anti-emetic efficacy of substance P receptor (NK1) antagonists. Trens Pharmacol Sci 1999;20:485-490.

    Rupniak NM, Carlson EC, Harrison T, Oates B, Seward E, Owen S, de Felipe C, Hunt S, Wheeldon A. Pharmacological blockade or genetic deletion of substance P (NK1) receptors attenuates neonatal vocalisation in guinea-pigs and mice. Neuropharmacology 2000;39:1413- 1421.

    Rupniak NM, Carlson EJ, Webb JK, Harrison T, Porsolt RD, Roux S, de Felipe C, Hunt SP, Oates B, Wheeldon A. Comparison of the phenotype of NK1R-/- mice with pharmacological blockade of the substance P (NK1 ) receptor in assays for antidepressant and anxiolytic drugs.

    Behav Pharmacol 2001;12:497-508.

    Russell P. Inflammatory lesions of the human placenta. Clinical significance of acute chorioamninitis. Am J Diag Gynecol Obstet 1979;1:127-137.

    Ruff MR, Wahl SM, Pert CB. Substance P receptor-mediated chemotaxis of human monocytes Peptides 1985;6:107-111.

    Sadler TW. Langman Embriología Médica. Quinta edición. Editorial Panamericana SA.

    Capítulo 7, pag 99-115.

    Saffroy M, Torrens Y, Glowinski J, Beaujouan JC. Presence of NK2 binding sites in the rat brain. J Neurochem 2001;79:985-996.

    Salvador L, Sabanes F, Bueno JA. Mensajeros neuronales y transmisión sináptica. Medicine 1986; 67:2777-2790.

    Samsam M, Coveñas R, Ahangari R, Yajeya J, Narváez JA, Tramu G. Simultaneous depletion of neurokinin A, substance P and calcitonin gene-related peptide from the caudal trigeminal nucleus of the rat during electrical stimulation of the trigeminal ganglion. Pain 2000;84:389- 95.

    Samsam M, Coveñas R, Csillik B, Ahangari R.; Yajeya J, Riquelme R, Narváez JA, Tramu G.

    Depletion of substance P, neurokinin A and calcitonin gene-related peptide from the contralateral and ipsilateral caudal trigeminal nucleus following unilateral electrical stimulation of the trigeminal ganglion: a possible neurophysiological and neuroanatomical link to generalized head pain. J Chem Neuroanat 2001;21:161-169.

    Sanchez-Castellanos M, Sandoval-Tress C, Hernández-Torres M. Persistencia del conducto onfalomesentérico. Diagnóstico diferencial de granuloma umbilical en la infancia. Actas de Dermosifiliogr 2006;97:404-5.

    Sasai Y., Nakanishi S. Molecular characterization of rat substance K receptor and its mRNAs.

    Biochem Biophys Res Commun 1990;165:699-702.

    Sastry BV, Tayeb OS, Barnwell SL, Janson VE. Owens L.K. peptides from human placenta: methionine, enkephalin and substance P. Placenta Suppl 1981;3:327-337.

    Sastry BV, Janson VE, Owens LK. Significance of substance P- and enkephalin-peptide systems in the male genital tract. Ann N Y Acad Sci 1991;632:339-53.

    Sawardekar KP. Changing spectrum of neonatal omphalitis. Pediatr Infect Dis J 2004;23:22- 6.

    Scharrer E, Scharrer B. Neurosecretion. Physiol Rev 1945;25:171-181.

    Schwartz JP, Costa E. Hybridization approaches to the study of neuropeptides. Annu Rev Neurosci 1986;9:277-304.

    Scholzen T, Armstrong CA, Bunnett NW, Luger TA, Olerud JE, Ansel JC. Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems. Exp Dermatol 1998; 7:81-96.

    Scholle S, Glaser S, Zwacka G, Scheidt B. Plasma levels of beta-endorphin and substance P in the first year of life in full-term and preterm infants. Acta Paediatr Scand 1990;79:1237-9.

    Schmidt B, Asztalos EV, Roberts RS, et al.Impact of bronchopulmonary dysplasia,brain injury, and severe retinopathy on the outcome of extremely low-birth weight infantsat 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA 2003;289:1124- 11297.

    Schratzberger P, Reinisch N, Prodinger WM, Kahler CM, Sitte BA, Bellmann R, Fischer- Colbrie R, Winkler H, Wiedermann CJ. Differential chemotactic activities of sensory neuropeptides for human peripheral blood mononuclear cells. J Immunol 1997;158:3895- 3901.

    Schreck R, Rieber P, Baeuerle PA. Reactive oxygen intermediates as apparently widely use messengers in the activation f te NF-kB transcription factor and HIV 1. EMBO J 1991;10:2247.

    Schwartz L, Spitsin SV, Meshki J, Tuluc F, Douglas S D, & Wolfe JH. Substance P enhances HIV-1 infection in human fetal brain cell cultures expressing full-length neurokinin-1 receptor. J Neurovirol 2013;19:219-27.

    Schwarcz R, Diverges A, Díaz A, Fescina R. Embarazo patológico. Anomalía de las membranas fetoovulares. En: ¿Obstetricia¿. Buenos Aires. El Ateneo. 1992;190-192.

    Scicchitano R, Biennenstock J, Stanisz AM. In vivo immunomodulation by the neuropeptide substance P. Immunology 1988;63:733-735.

    Seabrook GR, Fong TM. Thapsigargin blocks the mobilization of intracellular Ca caused by activation of human NK1 (long) receptors expressed in CHO cells. Neurosci Lett 1993;152:9- 12.

    Seaward PG, Hannah ME, Myhr TL, Farine D, Ohlsson A, Wang EE, Haque K, Weston JA, Hewson SA, Ohel G, Hodnett ED. International Multicentre Term Prelabor Rupture of Membranes Study: evaluation of predictors of clinical chorioamnionitis and postpartum fever in patients with prelabor rupture of membranes at term. Am J Obstet Gynecol 1997;177:1024- 9.

    Seckl MJ, Higgins T, Wildmer F, Rozengurt E. [D-Arg1, D-Trp5,7, 9, Leu11] Substance P: A novel potent inhibitor of signal transduction and growth in vitro and in vivo in small cell lung cancer cells. Cancer Res 1997;57:51-4.

    Seegers HC, Hood VC, Kidd BL, Cruwys SC, Walsh DA. Enhancement of angiogenesis by endogenous substance P release and neurokinin-1 receptors during neurogenic inflammation.

    J Pharmacol Exp Ther 2003;306:8-12.

    Seong HS, Lee SE, Kang JH, Romero R, Yoon BH. The frequency of microbial invasion of the amniotic cavity and histologic chorioamnionitis in women at term with intact membranes in the presence or absence of labor. Am J Obstet Gynecol 2008;199:375.

    Seidah, N. G., & Chretien, M. Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res 1999; 848:45-62.

    Severini C, Improta G,Falconieri-Erspamer G, Salvadori S, Erspamer E. The tachykinin peptide family. Pharmacol Rev 2002;54:285-322.

    Severini C, Salvadori S, Guerrini R, Falconieri-Erspamer G, Mignogna G, Erspamer V.

    Parallel bioassay of 39 tachykinins on 11 smooth muscle preparations. Structure and receptor selectivity/affinity relationship. Peptides 2000;21:1587-1595.

    Sharif TR, Luo W, Houghron PJ, Sharif M. Substance K peptide induces mitogenesis by activating the mitogen-activated protein kinase signalling pathway through the substance P receptor (NK-1 subtype) in human astrocytoma. Cell Pharmacol 1996;3:441-449.

    Shatrov JG, Birch SC, Lam LT, Quinlivan JA, McIntyre S, Mendz GL Chorioamnionitis and cerebral palsy: a meta-analysis. Obstet Gynecol 2010;116.387-92.

    Shen XZ y Bernstein KE. The peptide network regulated by angiotensin converting enzyme (ACE) in hematopoiesis. Cell Cycle 2011;10:1363-1369.

    Shepherd, Gordon M. Neuroanatomy; Neurons; History 1991;6:338p. Book (ISBN 0195064917).

    Sherrington C.The integrative action of the central nervous system. London. Constable Co.

    1906.

    Shigemoto R, Yokota Y., Tsuchida K., Nakanishi S. Cloning and expression of a rat neuromedin K receptor cDNA. J Biol Chem 1990;265:623-628.

    Shibata K, Haverstick DM, Bannon MJ. Tachykinin gene expression in rat limbic nuclei: modulation by dopamine antagonists. J Pharmacol Exp Ther 1990;255:388-392.

    Shibata H, Mio M, Tasaka K. Analysis of the mechanism of histamine release induced by substance P. Biochem. Biophys Acta 1985;846:1-7.

    Shirayama Y, Mitsushio H, Takashima M, Ichinawa H, Takahashi, K. Reduction of substance P after chronic antidepressants treatment in the striatum, substantia nigra and amygdala of the rat. Brain Res 1996;739:70-78.

    Simon NP, Simon MW. Changes in Newborn Bathing Practices May Increase the Risk for Omphalitis. Clin pediatr 2004;43:763-7.

    Singh D, Joshi DD, Hameed M, Qian J, Gascon P, Maloof PB, Mosenthal A, Rameshwar P.

    Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: implications for bone marrow metastasis. Proc Natl Acad Sci USA 2000;97:388-393.

    Sitohy B, El Salhy M. Changes in the colonic enteric nervous system in rat witn chemically induced colon dysplasia and carcinoma. Acta Oncol 2002;41:543-549.

    Sivam SP, & Krause JE. (Tachykinin systems in the spinal cord and basal ganglia: influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA. J Neuroche 1992;59(6):2278-2284.

    Skinner DC. Rethinking the stalk effect: A new hypothesis explaining suprasellar tumorinduced hyperprolactinemia. Medical Hypotheses 2009;72:309-310.

    Skrabanek P, Balfe A, McDonald D, McKaigney J, Powell D. Substance P in human cord blood and its degradation by placenta in vitro. Eur J Obstet Gynecol Reprod Biol 1980;11:157-161.

    Smith V, Ferrés E, Montesinos M. Anidación y Placentación. En: ¿Manual de Embriología y Anatomía General¿. Universitat de Valencia. España. 1992;85-96.

    Snider RM, Constantine JW, Lowwe IJ. A potent nonpeptide antagonist of the substance P (NK1) receptor. Science 1991;251:435-437.

    Snyder C. Current management of umbilical abnormalities and related anomalies. Seminars in pediatric surgery 2007;16:41-9.

    Somogyi P, Prietsley J, Cuello AC, Smith AD, Bolam JP. Synaptic connections of substance P-immunoreactive nerve terminals in the substantia nigra of the rat. Cell Tissue Res 1982;223:469-486.

    Sonomura T, Nakamura K, Furuta T, Hioki H, Nishi A, Yamanaka A., . . .Kaneko T. (2007).

    Expression of D1 but not D2 dopamine receptors in striatal neurons producing neurokinin B in rats. Eur J Neurosci2007;26(11) :3093-3103.

    Soper DE, Mayhall CG, Dalton HP. Risk factors for intraamniotic infection: a prospective epidemiologic study. Am J Obstet Gynecol 1989;161:562-6.

    Soper DE, Mayhall CG, Froggatt JW. Characterization and control of intraamniotic infection in an urban teaching hospital. Am J Obstet Gynecol 1996;175:304-9.

    Soraisham AS, Trevenen C, Wood S, Singhal N, Sauve R. Histological chorioamnionitis and neurodevelopmental outcome in preterm infants. J Perinatol 2013;33:70-5.

    Southwell BR, Seybold VS, Woodman HL, Jenkinson KM, Furness JB. Quantitation of neurokinin 1 receptor internalization and recycling in guinea-pig myenteric neurons.

    Neuroscience 1998;87: 925-931.

    Ständer S, Siepmann D, Herrgott I,et al. Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One 2010;5(6):e10968.

    Stead RH, Bienenstock J. Cellular interactions between the immune and peripheral nervous system. A normal role for mast cells?. En: ¿Cell to Cell Interaction¿. Basel, Karger.

    1990;170-187.

    Steinman L. Elaborate interactions between the immune and nervous systems. Nat Immunol 2004; 5:575-581.

    Strader CD, Fong TM, Tota MR, Underwood D, Dixon RF et al. Structure and function of G protein-coupled receptors. Annu Rev Biochem 1994;63:101-132.

    Studer RO, Trzeciak H and Lergier W. Isolierung and Aminosäuresequenz von Substanz P aus Pferdedarm. Helv Cchim Acta 1973;56:860-866.

    Takeda Y, Blount P, Sachais BS, Hershey AD, Raddatz R, Krause JE. Ligand binding kinetics of substance P and neurokinin A receptors stably expressed in CHO cells and evidence for differential stimulation of inositol 1, 4, 5-triphosphate and camp second messenger responses.

    J Neurochem 1992;59:740-745.

    Takemoto K, Lundberg JM, Jörnvall H. Neuropeptide K: isolation, structure and biological activities of a novel brain tachykinin. Biochem Biophys Res Comm 1985;128:947-953.

    Tasci Y, Dilbaz B, Onal BU, Caliskan E, Dilbaz S, Doganci L et al. The value of cord blood interleukin-6 levels for predicting chorioamnionitis, funisitis and neonatal infection in term premature rupture of membranes. Eur J Obstet Gynecol Reprod Biol 2006;128:34-39.

    Tattersall FD, Rycroft W, Hargreaves RJ, Hill RG. The tachykinin NK-1 receptor antagonist CP-99,994 attenuates cisplatin induced emesis in the ferret. Eur J Pharmacol 1993;250:R5-6.

    Tauscher MK, Berg D, Brockmann M, Seidenspinner S, Speer CP. Association of histologic chorioamnionitis, increased levels of cord blood cytokines, and intracerebral hemorrhage in preterm neonates. Biol Neonate 2003;83:166-70.

    Teichberg VI, Cohen S, Blumbreg S. Distinct classes of substance P receptors for substance P.

    Receptors revealed by a comparison of the activities of substance P and some of its esgments.

    Regul Pept 1981;1:327-333.

    Teixeira RM, Santos AR, Ribeiro SJ, Calixto JB, Rae GA, De Lima TC. Effects of central administration of tachykinin receptor agonists and antagonists on plus-maze behavior in mice.

    Eur J Pharmacol 1996;311:7-14.

    Thomas W, Speer CP. Chorioamnionitis: important risk factor or innocent bystander for neonatal outcome? Neonatology 2011;99:177-87.

    Thomas W, Speer CP. Intrauterine inflammation and its sequelae: does chorioamnionitis really matter for outcome of very low birth weight infants?. Z Geburtshilfe Neonatol 2012;216:173-6.

    Tomettem M, Klapp BF, Joachim R, Fest S, Zenclussen AC, Peters EM, Hertwig K, Arck PC.

    Nerve growth factor and its functional receptor TrkA are up-regulated in murine decidual tissue of stress-triggered and substance P-mediated abortion. Am J Reprod Immunol 2004;51:86-93.

    Toneatto, S.; Finco, O.; van der Putten, H.; Abrignani, S.; Annunziata, P. Evidence of bloodbrain barrier alteration and activation in HIV-1 gp120 transgenic mice. AIDS 1999;13:2343- 2348 Tran SH, Caughey AB, Musci TJ. Meconium-stained amniotic fluid is associated with puerperal infections. Am J Obstet Gynecol 2003;189:746-50.

    Treager GW, Niall HD, Potts JT, Leeman SE, Chang MM. Synthesis of substance P. Nature New Biol 1971;232:87-89.

    Tsuchida K, Shigemoto R, Yokota Y, Nakanishi S. Tissue distribution and quantitation of the mRNAs for three rat tachykinin receptors. Eur J Biochem 1990;193:751-757.

    Tucker J, McGuire W, Epidemiology of preterm birth . BMJ 2004;329:675-678 Van Ginkel FW, Pascual DW. Recognition of neurokinin 1 receptor (NK1-R): an antibody to a peptide sequence from the third extracellular region binds to brain NK1-R. J Neuroimmunol 1996; 67:49-58.

    Varty, G.B.; Morgan, C.A.; Cohen-Williams, M.E.; Coffin, V.L.; Carey, G.J. The gerbil elevated plus-maze I: behavioral characterization and pharmacological validation.

    Neuropsychopharmacology 2002;27:357-370.

    Vedovato S, Zanardo V. Chorioamnionitis and inflammatory disease in the premature newborn infant. Review. Italian. Minerva Pediatr 2010;62:155-6.

    Vergani P, Patanè L, Doria P, Borroni C, Cappellini A, Pezzullo JCet a l. Risk factors for neonatal intraventricular haemorrhage in spontaneous prematurity at 32 weeks gestation or less. Placenta 2000;21:402-407.

    Verma U, Tejani N, Klein S, Reale MR, Beneck D, Figueroa R et al. Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate.

    Am J Obstet Gynecol 1995;176:275-281.

    Verma U, Tejani N, Klein S, Reale M, Beneck D, Figueroa D, et al. Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate.

    Am J Obstet Gynecol 1997;176:275-81.

    Vermeij-Keers C, Hartwig NG, van der Werff JF. Embryonic development of the ventral body wall and its congenital malformations. Semin Pediatr Surg 1996;5:82-9.

    Vink R, Donkin JJ, Cruz MI., Nimmo AJ, & Cernak I. A substance P antagonist increases brain intracellular free magnesium concentration after diffuse traumatic brain injury in rats. J Am Coll Nutr 2004;23(5):538S-540S.

    Villablanca AC and MR Hanley. 17 beta-estradiol stimulates substance P receptor gene expression. Mol Cell Endocrinol 1997;135:109-117.

    Volpe G, Volpe P, Boscia FM, Volpe N, Buonadonna AL, Gentile L. ¿Isolated¿ single umblical artery: incidence, cytogenetic abnormalities, malformation and perinatal outcome.

    Minerva Ginecol 2005;57:189-198.

    Von Euler US, Gaddum JH. An unidentified depressor substance in certain tissue extracts. J Physiol 1931;72:74-87.

    Wallace-Boone TL, Newton AE, Wright RN, Lodge NJ, McElroy JF. Behavioral and pharmacological validation of the gerbil forced-swim test: effects of neurokinin-1 receptor antagonists. Neuropsychopharmacology 2008;33:1919-1928.

    Walsh DT, Weg VB, Williams TJ, Nourshargh S. Substance P induced inflammatory responses in guinea-pig skin: the effect of specific NK1 receptor antagonists and the role of endogenous mediators. Br J Pharmacol 1995;114:1343-1350.

    Walsh DA, Hu EE, Mapp PI, Polar JM, Blake DR, Fan TP. Innervation and neurokinin receptors during angiogenesis in the rat sponge granuloma. Histochem J 1996;28:759-769.

    Wang X, Hagberg H, Zhu C, Jacobsson B, Mallard C. Effects of intrauterine inflammation on the developing mouse brain. Brain Res 2007;1144:180-5.

    Watterberg KL, Demers LM, Scott SM et al. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996;97:210-215.

    Weeks JW, Reynolds L, Taylor D, Lewis J, Wan T, Gall SA. Umbilical cord blood interleukin- 6 levels and neonatal morbidity. Obstet Gynecol 1997;90:815-818.

    Weiner GP. The clinical spectrum of preeclampsia. Am J Kidney Dis 1987;9:312-316.

    Weinstock JV, Blum A, Walder J, Walder R. Eosinophils from granulomas in murine schistosomiasis mansoni produce substance P. J Immunol 1988;141:961-966.

    Weinstock JV, Blum A, Metwali A, Elliott D and Arsenescu R. IL-18 and IL-12 signal through the NF-kappa B pathway to induce NK-1R expression on T cells. J. Immunol 2003;170:5003- 5007.

    Werge TM. Identification of an Epitope in the Substance P Receptor Important for Recognition of the Common Carboxyl-terminal Tachykinin Sequence. J Biol Chem 1994;269:22054-22058.

    Wiegand S, McKenna DS, Croom C, Ventolini G, Jonek JD, Neiger R. Serial sonographic growth assessment in pregnancies complicated by an isolated single umbilical artery. Am J Perinatol 2008;25:149-52.

    Williams R, Zou X and Hoyle GW, ¿Tachykinin-1 receptor stimulates proinflammatory gene expression in lung epithelial cells through activation of NF-¿B via a Gq-dependent pathway,¿American Journal of Physiologyy 2007;292:L430¿L437.

    Wilson MI, Goodwin TM, Pan VI, Ingles SA. Molecular epidemiology of preeclampsia.

    Obstet Gynecol Survey 2003;58:39-66.

    Wimalasundera RC, Thom SA, Regan L, Hughes AD. Effects of vasoactive agents on intracellular calcium and force in myometrial and subcutaneous resistance arteries isolated from preeclamptic, pregnant, and nonpregnant woman. Am J Obstet Gynecol 2005;192:625- 32.

    Woll PJ, Rozengurt E. [D-Arg1-D-Phe5, D-Trp7, 9, Leu11] Substance P, a potent bombesin antagonist in murine Swiss 3T3 cells, inhibits the growth of human small cell lung cancer cells in vitro. Proc Natl Acad Sci USA 1988;35:1859-1863.

    Wooding F, Flint A. Placentation in Lamming G.E. Chapman and Hall. London. Marshall's Physiology of Reproduction 1985;3:233-460.

    Wong Simon S, Nina N, Sun R, Lantz C and Mark L. Witten Substance P and neutral endopeptidase in development of acute respiratory distress syndrome following fire smoke inhalation Am J Physiol Lung Cell Mol Physiol 2004; 287:859-866.

    Wong CM, Boyle EM, Stephen RI, Smith J, Stenson BJ, McIntosh N and Laing IA.

    Normative values of substance P and neurokinin A in neonates. Ann Clin Biochem 2010;47:331-335.

    Wu YW, Colford JM. Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis.

    JAMA 2000;284:1417-1424.

    Xie GX, Myyajima A, Goldstein A. Expression cloning of cDNA encoding a seven-helix receptor from human placenta with affinity for opioid ligands. Proc Natl Acad Sci USA 1992;89:4124-4128.

    Xu Junyang, Fadi Xu, Yong Lin. Cigarette smoke synergizes lipopolysaccharide-induced interleukin-1ß and tumor necrosis factor-¿ secretion from macrophages via substance Pmediated nuclear factor-¿B activation. American Journal of Respiratory Cell and Molecular Biology 2010; 44:302-8.

    Yancey MK, Duff P, Clark P, Kurtzer T, Frentzen BH, Kubilis P. Peripartum infection associated with vaginal group B streptococcal colonization. Obstet Gynecol 1994;84:816-9.

    Yoon BH, Romero R, Yang SH, Jun JK. Interleukin 6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesion associated with periventricular leukomalacia. Am J Obstet Gynecol 1996;174:1.433-40.

    Yoon BH, Jun JK, Romero R, Park KH, Gomez R, Choi JH et al. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol 1997;177:19-26.

    Yoon BH, Romero R, Jun JK et al. Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-¿, interleukin-1ß, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1997;177:825-830.

    Yoon BH, Romero R, Kim CJ, et al. High expression of tumor necrosis factor-alpha and interleukin-6 in periventricular leukomalacia. Am J Obstet Gynecol 1997;177:406-11.

    Yoon BH, Romero R, Moon JB, Shim SS, Kim M, Kim G, Jun JK. Clinical significance of intra- amniotic inflammation in patients with preterm labor and intact membranes. Am J Obstet Gynecol 2001;185:1130¿6.

    Yoon BH, Park CW, Chaiworapongsa T. Intrauterine infection and the development of cerebral palsy. Br J Obstet Gynaecol 2003;110:124-7.

    Young B, Heath JW, Wheater PR. Aparato Genital Femenino. En: ¿Wheater's histologia funcional¿.

    Elsevier, España. 2000; 341-370.

    Yu J, Cadet JL, Angulo JA. Neurokinin-1 (NK-1) receptor antagonists abrogate methamphetamine-induced striatal dopaminergic neurotoxicity in the murine brain. J Neurochem 2002;83:613-622.

    Yu Z, Cheng G, Huang X, Li K, Cao X. Neurokinin-1 receptor antagonist SR-140,333: a novel type of drug to treat cerebral ischemia. Neuroreport 1997;8:2117-2119.

    Yuan M, Wen-Xia Z, Jun-Ping C, Yong-Xiang Z. Age related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse. Reprod Fertil Dev 2005;17: 507-512.

    Zachrisson O, Lindefors N, Brene S. A tachykinin NK1 receptor antagonist, CP-122,721-1, attenuates kainic acid-induced seizure activity. Brain Res Mol Brain Res 1998;60:291-295.

    Zhang Y, Lu L, Furlonger C, Wu GE, Paige CJ. Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis. Nat Immunol 2000;1:392-397.

    Zhang Y, Berger A, Milne CD, Paige CJ. Tachykinins in the inmune system. Curr Drug Targets 2006;7:1011-1020.

    Zhou Q, Nyberg F. Injection of substance P (SP) N-terminal fragment SP(1-7) into the ventral tegmental area modulates the levels of nucleus accumbens dopamine and dihydroxyphenylacetic acid in male rats during morphine withdrawal. Neurosci Lett 2002;320:117-120.

    Zhou L, Chong MM, Littman DR. Plasticity of CD4+ T cell lineage differentiation. Immunity 2009;30:646-655.

    Ziche M, Morbidelli L, Pacini M, Geppetti P, Alessandri G, Maggi CA. Substance P stimulates neovascularization in vivo and proliferation of cultured endothelial cells.

    Microvasc Res 1990;40: 264-278.

    Ziche M, Morbidelli L, Masini E, Amerini S, Granger HJ, Maggi CA, Geppetti P, and Ledda F. Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Invest 1994;94:2036-2044.

    .

    .