Sara Gonzalez | Independent Researcher (original) (raw)

Books by Sara Gonzalez

Research paper thumbnail of Congreso Nacional de Historia 2021 Independencia tomo I libro

La divergencia en la fecha que consignan los estudiosos se debe a las repetidas declaraciones de ... more La divergencia en la fecha que consignan los estudiosos se debe a las repetidas declaraciones de Mariano Lechuga y los momentos que se produjeron

Research paper thumbnail of Jo é A t o i o B e n i t Ro d í∫u e

Research paper thumbnail of Jo é A t o i o B e n i t Ro d í∫u e

Research paper thumbnail of Templos virreinales - AGOSTO (1)

Las numerosas iglesias de doctrina que sobreviven en la sierra de las provincias de Oyón y Huaura... more Las numerosas iglesias de doctrina que sobreviven en la sierra de las provincias de Oyón y Huaura (zona que pertenecía a los antiguos corregimientos de Cajatambo y Chancay, respectivamente) se construyeron entre fines del siglo XVI y principios del XVII, con posteriores reformas y ampliaciones. Cuentan entre los edificiños religiosos virreinales más originales del Perú, pero a pesar de sus pinturas murales, altares barrocos y techos decorados, no se conocen fuera de la zona y, por consiguiente, están expuestas a desastres naturales, abandono, robo y vandalismo. Tampoco existe mucha información o bibliografía sobre ellas, salvo por los trabajos puntuales de dos autores: uno es el brevísimo texto "Iglesias en el área de Oyón y Cajatambo" de Antonio San Cristóbal Sebastián 1 , concebido como prólogo a unas investigaciones del profesor César Maguiña y que más bien es una reflexión general sobre arquitectura rural andina sin mencionar ninguna iglesia específica del área que nos ocupa; el otro son apuntes sobre los murales de San Cristóbal de Rapaz de Pablo Macera 2. Otros historiadores de la arquitectura virreinal peruana, como Jorge Bernales Ballesteros,

Research paper thumbnail of Templos virreinales de la sierra de Oyón y Huaura: estudio artístico e iconográfico

Research paper thumbnail of Catálogo de Estadística Parroquial del Archivo del Obispado de Huacho (Perú)

Research paper thumbnail of Las efigies de los Incas en el Ms. 1551 de la Biblioteca Angelica (Roma)

Research paper thumbnail of Certificado para el Curso Iniciacion a la Mariologia 1

Research paper thumbnail of Creación de la parroquia de Huaral

El pueblo de Huaral tuvo obviamente su propio templo, dedicado a San Juan Bautista, desde el mome... more El pueblo de Huaral tuvo obviamente su propio templo, dedicado a San Juan Bautista, desde el momento de su fundación en 1551. En principio sería una construcción sencilla y modesta, pero en 1775 tenía de fábrica 16 pesos al año en un solar. 1

Research paper thumbnail of Writing Pre-Hispanic History in Viceregal Peru: The Dynastic Iconography of the Inca Kings

(Note: figure 2 is NOT at the Church of Our Lady of Copacabana in Lima. This is an editors' mista... more (Note: figure 2 is NOT at the Church of Our Lady of Copacabana in Lima. This is an editors' mistake, not mine)

Research paper thumbnail of Chapter 8 of The Musical Iconography of Power in Seventeenth-Century Spain and Her Territories

Research paper thumbnail of Chapter 7 of The Musical Iconography of Power in Seventeenth-Century Spain and Her Territories (Word document)

Research paper thumbnail of The Musical Iconography of Power in Seventeenth-Century Spain and Her Territories

Summnary la (bis paper. wc uy a svnthesís of~vhatwe know írorn ancicnt Greek literar sources abou... more Summnary la (bis paper. wc uy a svnthesís of~vhatwe know írorn ancicnt Greek literar sources about Orpheus the musician, We also establisb sorne linlcs bctween the rnyth and Greek cultural bistorv. First of alí, 've examine tbe technical devices of Orpbeus' art (tbe Is re, tbe song. also the language itselfl Reicrenees to ihe power of spcecb niake us reniember be irnportant pbenonienon of tbc approach between tbe poet-musícians figure and [be sopbists one: botb of [bern enabodíed [be educator's functíon. ni successíse stages of Grcek historv. Thercaftcr. "e deal aboní tbe relationslsíp of Orpheus 'llusic ;viIl, noiihuman nature, with hunían societv and with [be gods. AH powers of his Inusie belong lo a magical-an¡m¡stic view of (be unixerse: Orpheus is capable (o listen to ¡be uni'crse libere are sorne píeces ofciidencc abaul Isis leaáning ofnsusic lrom birds arofaslrologv frorn tbe bannony of (be spheres as he reproduced it with bis lvre>. So, he can also chana and order tbe world and [be gods. as well as sorne of [ben, are bid en,bodiments of elemenís of naturc: about flades and Persepbone, a relalion wi[h orph>c ri[uals is suggeslcd. And be is capable to transniit tbat knowledge. bs íneans of musie. to human beings, and wc diseuss aneient exidenee of allegoristie ínterpretatíon of Orpbeus cbarming (he ssíld bcasts -a metapbortoreisiIi~ing theínankind. Fina»~, Iegendr about tbesue-vnal of Orpbeus' art are exarníned: thcv are coberent wíth the ebaracter of Orpbeus nr -a transgressing and eivili.zing bero.

Teaching Documents by Sara Gonzalez

Research paper thumbnail of Introducción a la Historia del Arte e iconografía

Research paper thumbnail of Idolatrica: Idolatría e Inquisición en los Andes, España y Portugal

Exhibitions by Sara Gonzalez

Research paper thumbnail of L'Inca et le conquistador

Drafts by Sara Gonzalez

Research paper thumbnail of La Virgen de la Candelaria de Cayma (Arequipa): historia del culto y Coronación Pontificia

Research paper thumbnail of TEMPLOS VIRREINALES DE LOS ANDES CENTRALES DEL PERÚ VISITADOS POR SANTO TORIBIO (OYÓN, HUAURA Y CAJATAMBO

Research paper thumbnail of APUNTES SOBRE LA PARTICIPACIÓN DEL CLERO RURAL EN EL PROCESO DE INDEPENDENCIA DEL PERÚ: DOS CASOS INÉDITOS DE LA SIERRA DE LIMA: NAVÁN Y ANDAJES (PROVINCIA OYÓN) Y MANGAS (PROVINCIA BOLOGNESI

Introducción Cuando se iniciaron los procesos de independencia americanos, la Iglesia del Perú co... more Introducción Cuando se iniciaron los procesos de independencia americanos, la Iglesia del Perú contaba con un Arzobispado capitalino en Lima y cuatro Obispados provinciales en Cusco, Arequipa, Trujillo y Huamanga. Era una institución poderosa y respetada pero social e ideológicamente heterogénea, cuyos miembros colaboraron con ambas facciones, realista y patriótica, de acuerdo con sus convicciones políticas o con sus intereses pastorales o comunitarios. Para dificultar más las cosas, en aquella época muchos obispos y sacerdotes eran no sólo súbditos de España, sino además peninsulares, de modo que les resultaba difícil someterse al nuevo poder ejecutivo sin plantearse que de alguna manera traicionaban a la madre patria. El término "súbditos de España", independientemente del lugar de nacimiento de cada prelado, se refería a la vinculación y dependencia en que la Iglesia peruana se hallaba respecto de la autoridad real española por razón del Patronato regio, es decir, el ejercicio por parte de la monarquía de todas o la mayoría de facultades atribuidas a la Iglesia en el gobierno de los fieles, lo que convertía a los reyes de España en la máxima autoridad eclesiástica en los territorios bajo su gobierno.1 Ese poder les fue otorgado por las llamadas Bulas alejandrinas del Papa Alejandro VI y confirmado por la bula Universalis Ecclesiae de Julio II, fechada el 28 de julio de 1508.2 La Corona española tenía poder sobre los asuntos misionales de Indias y en el siglo XVII lo consiguió sobre la Congregación de Propaganda Fidei. A sus titulares correspondía, pues, la difusión de la fe, la distribución y delimitación de las sedes episcopales y la sustentación y administración económica de las misiones, facultades no concedidas hasta entonces a ningún otro príncipe de la Cristiandad y que hasta fines del siglo XV eran de la exclusiva incumbencia de la Santa Sede y de las Órdenes religiosas.3 Las reformas de Carlos III hicieron migrar la idea del Patronato Regio al Regio Vicariato, que implicaba que el monarca español tenía también la facultad de ser vicario por la naturaleza de su propio poder real, y no sólo como una concesión otorgada por el Papa.

Research paper thumbnail of THE MUSICAL ICONOGRAPHY OF POWER IN SEVENTEENTH-CENTURY SPAIN AND HER TERRITORIES Uncorrected Proof Copy Copyright Material – Do Not Distribute

Research paper thumbnail of Congreso Nacional de Historia 2021 Independencia tomo I libro

La divergencia en la fecha que consignan los estudiosos se debe a las repetidas declaraciones de ... more La divergencia en la fecha que consignan los estudiosos se debe a las repetidas declaraciones de Mariano Lechuga y los momentos que se produjeron

Research paper thumbnail of Jo é A t o i o B e n i t Ro d í∫u e

Research paper thumbnail of Jo é A t o i o B e n i t Ro d í∫u e

Research paper thumbnail of Templos virreinales - AGOSTO (1)

Las numerosas iglesias de doctrina que sobreviven en la sierra de las provincias de Oyón y Huaura... more Las numerosas iglesias de doctrina que sobreviven en la sierra de las provincias de Oyón y Huaura (zona que pertenecía a los antiguos corregimientos de Cajatambo y Chancay, respectivamente) se construyeron entre fines del siglo XVI y principios del XVII, con posteriores reformas y ampliaciones. Cuentan entre los edificiños religiosos virreinales más originales del Perú, pero a pesar de sus pinturas murales, altares barrocos y techos decorados, no se conocen fuera de la zona y, por consiguiente, están expuestas a desastres naturales, abandono, robo y vandalismo. Tampoco existe mucha información o bibliografía sobre ellas, salvo por los trabajos puntuales de dos autores: uno es el brevísimo texto "Iglesias en el área de Oyón y Cajatambo" de Antonio San Cristóbal Sebastián 1 , concebido como prólogo a unas investigaciones del profesor César Maguiña y que más bien es una reflexión general sobre arquitectura rural andina sin mencionar ninguna iglesia específica del área que nos ocupa; el otro son apuntes sobre los murales de San Cristóbal de Rapaz de Pablo Macera 2. Otros historiadores de la arquitectura virreinal peruana, como Jorge Bernales Ballesteros,

Research paper thumbnail of Templos virreinales de la sierra de Oyón y Huaura: estudio artístico e iconográfico

Research paper thumbnail of Catálogo de Estadística Parroquial del Archivo del Obispado de Huacho (Perú)

Research paper thumbnail of Las efigies de los Incas en el Ms. 1551 de la Biblioteca Angelica (Roma)

Research paper thumbnail of Certificado para el Curso Iniciacion a la Mariologia 1

Research paper thumbnail of Creación de la parroquia de Huaral

El pueblo de Huaral tuvo obviamente su propio templo, dedicado a San Juan Bautista, desde el mome... more El pueblo de Huaral tuvo obviamente su propio templo, dedicado a San Juan Bautista, desde el momento de su fundación en 1551. En principio sería una construcción sencilla y modesta, pero en 1775 tenía de fábrica 16 pesos al año en un solar. 1

Research paper thumbnail of Writing Pre-Hispanic History in Viceregal Peru: The Dynastic Iconography of the Inca Kings

(Note: figure 2 is NOT at the Church of Our Lady of Copacabana in Lima. This is an editors' mista... more (Note: figure 2 is NOT at the Church of Our Lady of Copacabana in Lima. This is an editors' mistake, not mine)

Research paper thumbnail of Chapter 8 of The Musical Iconography of Power in Seventeenth-Century Spain and Her Territories

Research paper thumbnail of Chapter 7 of The Musical Iconography of Power in Seventeenth-Century Spain and Her Territories (Word document)

Research paper thumbnail of The Musical Iconography of Power in Seventeenth-Century Spain and Her Territories

Summnary la (bis paper. wc uy a svnthesís of~vhatwe know írorn ancicnt Greek literar sources abou... more Summnary la (bis paper. wc uy a svnthesís of~vhatwe know írorn ancicnt Greek literar sources about Orpheus the musician, We also establisb sorne linlcs bctween the rnyth and Greek cultural bistorv. First of alí, 've examine tbe technical devices of Orpbeus' art (tbe Is re, tbe song. also the language itselfl Reicrenees to ihe power of spcecb niake us reniember be irnportant pbenonienon of tbc approach between tbe poet-musícians figure and [be sopbists one: botb of [bern enabodíed [be educator's functíon. ni successíse stages of Grcek historv. Thercaftcr. "e deal aboní tbe relationslsíp of Orpheus 'llusic ;viIl, noiihuman nature, with hunían societv and with [be gods. AH powers of his Inusie belong lo a magical-an¡m¡stic view of (be unixerse: Orpheus is capable (o listen to ¡be uni'crse libere are sorne píeces ofciidencc abaul Isis leaáning ofnsusic lrom birds arofaslrologv frorn tbe bannony of (be spheres as he reproduced it with bis lvre>. So, he can also chana and order tbe world and [be gods. as well as sorne of [ben, are bid en,bodiments of elemenís of naturc: about flades and Persepbone, a relalion wi[h orph>c ri[uals is suggeslcd. And be is capable to transniit tbat knowledge. bs íneans of musie. to human beings, and wc diseuss aneient exidenee of allegoristie ínterpretatíon of Orpbeus cbarming (he ssíld bcasts -a metapbortoreisiIi~ing theínankind. Fina»~, Iegendr about tbesue-vnal of Orpbeus' art are exarníned: thcv are coberent wíth the ebaracter of Orpbeus nr -a transgressing and eivili.zing bero.

Research paper thumbnail of Introducción a la Historia del Arte e iconografía

Research paper thumbnail of Idolatrica: Idolatría e Inquisición en los Andes, España y Portugal

Research paper thumbnail of L'Inca et le conquistador

Research paper thumbnail of La Virgen de la Candelaria de Cayma (Arequipa): historia del culto y Coronación Pontificia

Research paper thumbnail of TEMPLOS VIRREINALES DE LOS ANDES CENTRALES DEL PERÚ VISITADOS POR SANTO TORIBIO (OYÓN, HUAURA Y CAJATAMBO

Research paper thumbnail of APUNTES SOBRE LA PARTICIPACIÓN DEL CLERO RURAL EN EL PROCESO DE INDEPENDENCIA DEL PERÚ: DOS CASOS INÉDITOS DE LA SIERRA DE LIMA: NAVÁN Y ANDAJES (PROVINCIA OYÓN) Y MANGAS (PROVINCIA BOLOGNESI

Introducción Cuando se iniciaron los procesos de independencia americanos, la Iglesia del Perú co... more Introducción Cuando se iniciaron los procesos de independencia americanos, la Iglesia del Perú contaba con un Arzobispado capitalino en Lima y cuatro Obispados provinciales en Cusco, Arequipa, Trujillo y Huamanga. Era una institución poderosa y respetada pero social e ideológicamente heterogénea, cuyos miembros colaboraron con ambas facciones, realista y patriótica, de acuerdo con sus convicciones políticas o con sus intereses pastorales o comunitarios. Para dificultar más las cosas, en aquella época muchos obispos y sacerdotes eran no sólo súbditos de España, sino además peninsulares, de modo que les resultaba difícil someterse al nuevo poder ejecutivo sin plantearse que de alguna manera traicionaban a la madre patria. El término "súbditos de España", independientemente del lugar de nacimiento de cada prelado, se refería a la vinculación y dependencia en que la Iglesia peruana se hallaba respecto de la autoridad real española por razón del Patronato regio, es decir, el ejercicio por parte de la monarquía de todas o la mayoría de facultades atribuidas a la Iglesia en el gobierno de los fieles, lo que convertía a los reyes de España en la máxima autoridad eclesiástica en los territorios bajo su gobierno.1 Ese poder les fue otorgado por las llamadas Bulas alejandrinas del Papa Alejandro VI y confirmado por la bula Universalis Ecclesiae de Julio II, fechada el 28 de julio de 1508.2 La Corona española tenía poder sobre los asuntos misionales de Indias y en el siglo XVII lo consiguió sobre la Congregación de Propaganda Fidei. A sus titulares correspondía, pues, la difusión de la fe, la distribución y delimitación de las sedes episcopales y la sustentación y administración económica de las misiones, facultades no concedidas hasta entonces a ningún otro príncipe de la Cristiandad y que hasta fines del siglo XV eran de la exclusiva incumbencia de la Santa Sede y de las Órdenes religiosas.3 Las reformas de Carlos III hicieron migrar la idea del Patronato Regio al Regio Vicariato, que implicaba que el monarca español tenía también la facultad de ser vicario por la naturaleza de su propio poder real, y no sólo como una concesión otorgada por el Papa.

Research paper thumbnail of THE MUSICAL ICONOGRAPHY OF POWER IN SEVENTEENTH-CENTURY SPAIN AND HER TERRITORIES Uncorrected Proof Copy Copyright Material – Do Not Distribute

Research paper thumbnail of Las iglesias virreinales de los valles de los ríos Huaura y Checras: patrimonio religioso y turismo en la sierra de Lima

Turismo y Patrimonio, 2018

Este es un artículo Open Access bajo la licencia Creative Commons Atribución-NoComercial-Comparti... more Este es un artículo Open Access bajo la licencia Creative Commons Atribución-NoComercial-CompartirIgual 4.0

Research paper thumbnail of Writing Pre-Hispanic History in Viceregal Peru: the Dynastic Iconography of the Inca Kings

This essay discusses the ways in which the indigenous elites of viceregal Peru fabricated Inca hi... more This essay discusses the ways in which the indigenous elites of viceregal Peru fabricated Inca history through visual representations of their kings, giving shape to an Andean identity that adapted to the ideological demands of the colonial society while at the same time defying them. Images of the Inca dynasty were an essential part of the indigenous Peruvians’ attempt to challenge, intellectually and socially, the definition of Andeans as “Indians,” a colonial legal concept that signified cultural inferiority. In this process the indigenous noblemen, especially those living in Lima, who presented themselves as representatives of a united “Andean front” refashioned the official iconography of the Inca dynasty. This had been created in the 1570s under the auspices of Viceroy Francisco de Toledo who portrayed the Incas as devil-worshipping, tyrannical sovereigns in order to legitimize the Spanish conquest. Audacious neo-Incan effigies were created with specific references to Christia...

Research paper thumbnail of Incidencia de complicaciones arteriales y biliares en pacientes trasplantados de hígado en Uruguay y utilidad de la ecografía Doppler para el diagnóstico de las mismas

Dres. Elbio Kuster, Eduardo Ferencz y colaboradores Revista Médica del Uruguay 84 Rev Med Urug 20... more Dres. Elbio Kuster, Eduardo Ferencz y colaboradores Revista Médica del Uruguay 84 Rev Med Urug 2007; 23: 84-91 ARTÍCULO ORIGINAL Incidencia de complicaciones arteriales y biliares en pacientes trasplantados de hígado en Uruguay y utilidad de la ecografía Doppler para el diagnóstico de las mismas Resumen Introducción: el trasplante hepático constituye actualmente el tratamiento de elección de las hepatopatías crónicas en fase terminal. Este trabajo constituye el primer reporte sobre el tema a nivel nacional. Objetivos: evaluar la incidencia de complicaciones arteriales y biliares en pacientes trasplantados de hígado en Uruguay y determinar el rendimiento de la ecografía Doppler para el diagnóstico de las mismas. Material y método: se estudiaron retrospectivamente 13 trasplantes de hígado llevados a cabo en 12 pacientes entre marzo de 1998 y noviembre de 2001. En todos ellos se realizó ecografía Doppler.

Research paper thumbnail of ChemInform Abstract: Design, Synthesis and Biological Evaluation of Novel Arachidonic Acid Derivatives as Highly Potent and Selective Endocannabinoid Transporter Inhibitors

Research paper thumbnail of Multiagent systems and self-organizative virtual organizations, a step ahead in adaptive MAS

2011 11th International Conference on Intelligent Systems Design and Applications, 2011

Organizations needs to be supported by a coordinated effort that explicitly determines how the ag... more Organizations needs to be supported by a coordinated effort that explicitly determines how the agents should be organized and carry out the actions and tasks assigned to them. The interactions of a multi-agent system cannot be only related to the agent and the communication skills, but also to the concepts of organizational engineering. Moreover, nowadays there is a clear trend towards using methods and tools that can help to develop and simulate virtual organizations by means of multiagent systems (MAS). Simulation is used for several purposes ranging from work flow to system's procedures representation. The contribution from agent based computing to the field of computer simulation mediated by ABS (Agent Based Simulation) is a new paradigm for the simulation of complex systems that require a high level of interaction between the entities of the system. The main goal of this work is a new global coordination model for an agent organization in a simulation context. The innovation of this work consists of the dynamic and adaptive planning capability to distribute tasks among the agent of the organization. The middleware used for simulation makes it possible to visualize the emergent agent behaviour and the entity agent.

Research paper thumbnail of ChemInform Abstract: Design, Synthesis and Biological Evaluation of Novel Arachidonic Acid Derivatives as Highly Potent and Selective Endocannabinoid Transporter Inhibitors

Research paper thumbnail of Receptores implicados en la inducción de citoquinas promovida por la LDL electronegativa en monocitos

Clínica e Investigación en Arteriosclerosis, 2010

Recibido el 22 de marzo de 2010; aceptado el 8 de abril de 2010 Disponible en Internet el 8 de ju... more Recibido el 22 de marzo de 2010; aceptado el 8 de abril de 2010 Disponible en Internet el 8 de junio de 2010 PALABRAS CLAVE LDL electronegative; Monocytes; Cytokines; Toll-like receptors; CD14

Research paper thumbnail of Cannabinoids in neurodegeneration and neuroprotection

Milestones in Drug Therapy MDT, 2005

Cannabinoids as Therapeutics Edited by R. Mechoulam © 2005 Birkhäuser Verlag/Switzerland 82 J. Fe... more Cannabinoids as Therapeutics Edited by R. Mechoulam © 2005 Birkhäuser Verlag/Switzerland 82 J. Fernández-Ruiz et al.

Research paper thumbnail of <title>Dynamic infrared imaging for biological and medical applications in Boron neutron capture therapy</title>

Thermosense: Thermal Infrared Applications XXXIII, 2011

Boron Neutron Capture Therapy (BNCT) is a treatment modality, currently focused on the treatment ... more Boron Neutron Capture Therapy (BNCT) is a treatment modality, currently focused on the treatment of cancer, which involves a tumor selective 10B compound and a specially tuned neutron beam to produce a lethal nuclear reaction. BNCT kills target cells with microscopic selectivity while sparing normal tissues from potentially lethal doses of radiation. In the context of the Argentine clinical and research BNCT projects at the National Atomic Energy Commission and in a strong collaboration with INVAP SE, we successfully implemented Dynamic Infrared Imaging (DIRI) in the clinical setting for the observation of cutaneous melanoma patients and included DIRI as a non invasive methodology in several research protocols involving small animals. We were able to characterize melanoma lesions in terms of temperature and temperature rate-of-recovery after applying a mild cold thermal stress, distinguishing melanoma from other skin pigmented lesions. We observed a spatial and temporal correlation between skin acute reactions after irradiation, the temperature pattern and the dose distribution. We studied temperature distribution as a function of tumor growth in mouse xenografts, observing a significant correlation between tumor temperature and drug uptake; we investigated temperature evolution in the limbs of Wistar rats for a protocol of induced rheumatoid arthritis (RA), DIRI being especially sensitive to RA induction even before the development of clinical signs and studied surface characteristics of tumors, precancerous and normal tissues in a model of oral cancer in the hamster cheek pouch.

Research paper thumbnail of The Photon-Isoeffective Dose in Boron Neutron Capture Therapy

Radiation Research, 2012

With the aim to relate the effects observed in a clinical boron neutron capture therapy protocol ... more With the aim to relate the effects observed in a clinical boron neutron capture therapy protocol to the corresponding outcomes in a standard photon radiation therapy, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;RBE-weighted&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; doses are customarily calculated by adding the contributions of the different radiations, each one weighted by a fixed (dose and dose rate independent) relative biological effectiveness factor. In this study, the use of fixed factors is shown to have a formal inconsistency, which in practice leads to unrealistically high tumor doses. We then introduce a more realistic approach that essentially exploits all the experimental information available from survival experiments. The proposed formalism also includes first-order repair of sublethal lesions by means of the generalized Lea-Catcheside factor in the modified linear-quadratic model, and considers synergistic interactions between different radiations. This formalism is of sufficient simplicity therefore to be directly included in all BNCT treatment planning systems. In light of this formalism, the photon-isoeffective doses for two BNCT clinical targets were computed and compared with the standard dose calculation procedure. For the case of brain tumors and clinically relevant absorbed doses, the proposed approach derives isoeffective doses that are much lower than the fixed RBE method, regardless of considering synergism. Thus, for a tumor that receives a mean total absorbed dose of 15 Gy (value achievable with 50 ppm of boron concentration and typical beams used in the clinic), the photon-isoeffective doses are 28 Gy (IsoE) and 30 Gy (IsoE) (without and with synergism, respectively), in contrast to 51 Gy (RBE) for the fixed RBE method. When the clinical outcome of the Argentine cutaneous melanoma treatments is assessed with regard to the doses derived from the standard procedure, it follows that the fixed RBE approach is not suitable to understand the observed clinical results in terms of the photon radiotherapy data. Moreover, even though the assumed (10)B concentration in tumors is lowered to reduce the obtained doses with the standard procedure, the fixed RBE approach is still unsuitable to explain the observed outcomes (the model is always rejected with P values of virtually zero). Additionally, the numbers of controlled tumors predicted by the proposed approach are statistically consistent with observed outcomes. As a by-product of this work, a dose-response clinical reference for single-fraction melanoma treatments is developed.

Research paper thumbnail of Cannabinoid tolerance and dependence: A review of studies in laboratory animals

Pharmacology Biochemistry and Behavior, 2005

Two are the issues on cannabis addiction that provoke more controversy from a research perspectiv... more Two are the issues on cannabis addiction that provoke more controversy from a research perspective. The first one is related to the development of tolerance phenomena and, in particular, of a dependence state after chronic cannabinoid consumption, with appearance of withdrawal signs when this is interrupted, that would be (or not) comparable to those observed for other drugs. A second controversial issue is related to the possibility that chronic cannabinoid consumption may increase the risk to consume other drugs of greater addictive power. Since the discovery in the 1990s of the endocannabinoid signaling system as the target for the action of plant-derived cannabinoids, many studies have addressed these two questions in laboratory animals and, although the results have resulted controversial in various aspects, the following conclusions seem evident: (i) prolonged exposure to plant-derived, synthetic or endogenous cannabinoid agonists in laboratory animals is currently associated with the development of tolerance for most of their pharmacological effects, (ii) tolerance is essentially due to adaptative phenomena consisting in pharmacodynamic events (down-regulation/desensitization of cannabinoid receptors), although some evidence exist on additional pharmacokinetic responses, (iii) the discontinuation of chronic cannabinoid treatment does not elicit abstinence responses spontaneously in most of the cases, presumably because the pharmacokinetic characteristics of cannabinoids, but these responses may be elicited after the blockade of cannabinoid CB1 receptors in cannabinoid-tolerant animals, (iv) these abstinent responses include mainly somatic signs and changes in various molecular processes affected during the abstinence to other drugs although the magnitude of these changes was currently lower in the case of cannabinoids, and (v) cannabinoid-tolerant animals do not appear to be more vulnerable to reinforcing properties of morphine, although the manipulation of the endocannabinoid signaling might serve to treat cannabis addiction and, in particular, the addiction to other drugs such as alcohol, nicotine or opioids. The present review article will address all these aspects trying to establish the bases for future research.

Research paper thumbnail of Identification of Endocannabinoids and Cannabinoid CB<sub>1</sub> Receptor mRNA in the Pituitary Gland

Neuroendocrinology, 1999

Most data on effects of natural and synthetic cannabinoids on anterior pituitary hormone secretio... more Most data on effects of natural and synthetic cannabinoids on anterior pituitary hormone secretion point out to a primary impact on the hypothalamus. There is also some evidence, however, of possible direct actions of these compounds on the anterior pituitary, although the presence of cannabinoid receptors in the pituitary has not been documented as yet. In the present study, we evaluated the presence of cannabinoid CB(1) receptor-mRNA transcripts in the pituitary gland by in situ hybridization. We observed CB(1) receptor-mRNA transcripts in the anterior pituitary and to a lesser extent in the intermediate lobe whereas they were absent in the neural lobe. We then examined whether CB(1) receptor-mRNA levels in both pituitary lobes responded to chronic activation by a specific agonist, as did receptors located in adjacent hypothalamic nuclei and in other brain regions. Daily administration of CP-55,940 for 18 days produced a small, but statistically significant paradoxical increase in CB(1) receptor-mRNA levels in the anterior pituitary, with no changes in the intermediate lobe, in contrast to reduced CB(1) receptor-mRNA levels observed in the ventromedial hypothalamic nucleus (VMN), and to decreased CB(1) receptor binding in the VMN and the arcuate nucleus. The time-course of up-regulation of CB(1) receptor-mRNA transcripts in the anterior lobe was biphasic; daily administration of Delta(9)-tetrahydrocannabinol produced an early and marked decrease in CB(1) receptor-mRNA levels after 1 and 3 days, followed by normalization after 7 days and by a small increase after 14 days. We also checked whether endogenous cannabinoid ligands are present in the anterior pituitary and the hypothalamus. Although anandamide itself was detected only in trace amounts, concentrations of its precursor N-arachidonoyl-phosphatidyl-ethanolamine and of 2-arachidonoyl-glycerol were found in both tissues, suggesting that endocannabinoids may be synthetized in the anterior pituitary. In summary, CB(1) receptors and corresponding ligands seem to be expressed in cells of the anterior and intermediate lobes of the pituitary, but the response of CB(1) receptor-mRNA transcripts in the anterior lobe to chronic agonist activation is different than the desensitization observed in hypothalamic nuclei.

Research paper thumbnail of The hypothalamic levels of the endocannabinoid, anandamide, peak immediately before the onset of puberty in female rats

Life Sciences, 2002

Several data suggest that the endogenous cannabinoid system plays a role in neuroendocrine regula... more Several data suggest that the endogenous cannabinoid system plays a role in neuroendocrine regulation in adult individuals, although the information on its involvement in peri-pubertal processes is scarce. In the present study, we have examined the ontogeny (from postnatal day [PND] 5 up to adulthood) of hypothalamic and anterior pituitary contents of anandamide (arachidonyl-ethanolamide, AEA). We observed that the content of AEA in the hypothalamus was low at PND5, PND15 and PND25, but it markedly increased (approximately 3-fold) immediately before the puberty (on the day of 1st proestrus), to return to intermediate values immediately after the vaginal opening (day of 2nd proestrus) and, eventually, adulthood. By contrast, no consistent differences were observed in AEA levels in the anterior pituitary. These results demonstrate the occurrence of a parallelism between the peri-pubertal events and a rise in the hypothalamic content of AEA immediately before the puberty, which might indicate that this endocannabinoid may be involved in the onset of puberty in rats.

Research paper thumbnail of Cannabinoid CB1 Receptors Are Expressed by Parietal Cells of the Human Gastric Mucosa

Journal of Histochemistry and Cytochemistry, 2008

S U M M A R Y Experimental data suggest that the endogenous cannabinoid system is involved in gas... more S U M M A R Y Experimental data suggest that the endogenous cannabinoid system is involved in gastric function in different animal species. In most of them, CB 1 receptors have been localized on vagal terminals innervating the external wall of the stomach. We aimed at studying the putative presence and distribution of these receptors in the human gastric mucosa. To this end, we first performed Western blotting, RT-PCR, in situ hybridization, and immunohistochemical analysis of CB 1 protein distribution in biopsy samples of healthy individuals.

Research paper thumbnail of Design, Synthesis and Biological Evaluation of Novel Arachidonic Acid Derivatives as Highly Potent and Selective Endocannabinoid Transporter Inhibitors

Journal of Medicinal Chemistry, 2001

Research paper thumbnail of Cannabinoid CB 2 receptor agonists protect the striatum against malonate toxicity: Relevance for Huntington's disease

Glia, 2009

Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, ... more Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington's disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB 2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB 2 receptor agonists are neuroprotective was confirmed by using the selective CB 2 receptor antagonist, SR144528, and by the observation that mice deficient in CB 2 receptor were more sensitive to malonate than wild-type animals. CB 2 receptors are scarce in the striatum in healthy conditions but they are markedly up-regulated after the lesion with malonate. Studies of double immunostaining revealed a significant presence of CB 2 receptors in cells labelled with the marker of reactive microglia OX-42, and also in cells labelled with GFAP (a marker of astrocytes). We further showed that the activation of CB 2 receptors significantly reduced the levels of tumor necrosis factor-α (TNF-α) that had been increased by the lesion with malonate. In summary, our results demonstrate that stimulation of CB 2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB 2 receptors would be upregulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-α. Altogether our results support the hypothesis that CB 2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD.

Research paper thumbnail of Tu1136 Pilot Study of Hypoallergenic Formula With Lactobacillus GG: Impact on Crying Time, Inflammatory Biomarkers and Microbiota in Infants With Colic

Research paper thumbnail of Large-scale shrimp farming in coastal wetlands of Venezuela, South America: Causes and consequences of land-use conflicts

Environmental Management, 1994

In Venezuela, large-scale shrimp farming began in the 1980s. By 1987, the Ministry of Environment... more In Venezuela, large-scale shrimp farming began in the 1980s. By 1987, the Ministry of Environment and Natural Resources (MARNR) had received 14 proposals for approval. A developer illegally started the construction of ponds at the Piritu Lagoon in the State of Anzo~tegui before the authorization process was completed. This action triggered a land-use conflict. This study identifies the causes for public protest and determines the consequences of this conflict for land-use management. The results show that public protest was based on the impacts of the partial construction of ponds. These impacts were related to direct removal of wetlands, interruption of natural patterns of surface flows, and alteration of feeding grounds of some bird species with migratory status. Consequences were identified in relation to the role that nongovernmental organizations (NGOs) play in land-use conflicts and the actions that MARNR could take in the future to prevent and solve similar situations.

Research paper thumbnail of Chronic exposure to morphine, cocaine or ethanol in rats produced different effects in brain cannabinoid CB1 receptor binding and mRNA levels

Drug and Alcohol Dependence, 2002

Recent evidence suggest that the endocannabinoid system might be a component of the brain reward ... more Recent evidence suggest that the endocannabinoid system might be a component of the brain reward system and, then, play a role, not only in cannabinoid tolerance/dependence, but also in dependence/withdrawal to other drugs of abuse. However, there are not many studies that compare the changes in endocannabinoid ligands and/or receptors in brain regions (particularly in those areas related to reinforcement processes) during dependence to opiates, cocaine or alcohol. The present study addressed this objective, by examining the changes in CB 1 receptor binding (measured by [ 3 H]-CP55,940 autoradiography) and its mRNA levels (measured by in situ hybridization) in different brain regions of animals chronically exposed to morphine, cocaine or ethanol. The results showed that these three drugs produced different changes in CB 1 receptor binding and mRNA levels, a finding that precludes the existence of a common alteration of the endocannabinoid system during dependence states to these habit-foming drugs. Thus, chronic ethanol exposure was usually uneffective in altering both CB 1 receptor binding and mRNA levels in all regions examined. In contrast, chronic cocaine exposure produced significant changes only at the level of CB 1 receptor mRNA, with decreases of the transcript levels in the ventromedial hypothalamic nucleus and the superficial and deep layers of the cerebral cortex, but no changes in the hippocampal, motor and limbic structures. Finally, chronic morphine exposure increased the density of CB 1 receptors in the medial caudate-putamen, but decreased their mRNA levels in this region and also in the lateral caudate-putamen and the cerebellum. In limbic structures, chronic morphine exposure increased both binding and mRNA levels for CB 1 receptors in the septum nuclei. Binding was also increased in the nucleus accumbens, but reduced in the basolateral amygdala. In hippocampal structures, chronic morphine exposure reduced CB 1 receptor binding in the dentate gyrus, although mRNA levels were unaffected in this region, but increased in the CA2 subfield of the Ammon's horn. The results indicate that mechanisms of dependence for alcohol, cocaine and morphine are different in terms of their impact on the endocannabinoid system. Alcohol did not produce any effects on CB 1 receptor binding and mRNA levels, whereas cocaine only affected transcript levels in selected regions and morphine produced divergent and region-dependent effects.

Research paper thumbnail of Behavioral and molecular changes elicited by acute administration of SR141716 to Δ9-tetrahydrocannabinol-tolerant rats: an experimental model of cannabinoid abstinence

Drug and Alcohol Dependence, 2004

Whether chronic cannabinoid consumption produces a dependent state comparable to that occurring w... more Whether chronic cannabinoid consumption produces a dependent state comparable to that occurring with other drugs (e.g. the appearance of withdrawal signs when consumption is interrupted), and whether chronic cannabinoid consumption increases the risk of consuming other drugs of greater addictive power, are probably the two questions relating to cannabinoid addiction that provoke the most controversy. The present study was designed to further explore these two questions in laboratory animals. Firstly, we examined the effects of an acute challenge with SR141716 (an antagonist for the cannabinoid CB 1 receptor) in 9 -tetrahydrocannabinol ( 9 -THC)-tolerant rats. This antagonist has been reported to precipitate a cannabinoid withdrawal syndrome. Thus, the administration of SR141716 to 9 -THC-tolerant rats reduced inactivity in the open-field test and enhanced responses as tremor, turning and retropulsion-these responses that were only slightly enhanced in control rats. The administration of SR141716 increased the plasma prolactin and the corticosterone concentration in controls, but these increases were much lesser in 9 -THC-tolerant rats. In addition, CRF-mRNA levels in the paraventricular hypothalamic nucleus, while reduced in SR141716-treated controls, were significantly increased in 9 -THC-tolerant rats. The analysis of endocannabinoids also revealed that the administration of SR141716, which was mostly inactive in control rats, was able to reverse the changes in anandamide or 2-arachidonoylglycerol concentrations found in 9 -THC-tolerant rats, in the striatum, limbic forebrain, diencephalon, cerebellum and brainstem, but not in the midbrain and hippocampus. As a second objective, we evaluated whether 9 -THC-tolerant rats were more vulnerable to morphine in a self-administration paradigm. The 9 -THC-tolerant and control rats self-administered morphine to a similar extent, in concordance with the similar values of dopaminergic activity in limbic and motor regions. In summary, our data indicate that 9 -THC-tolerant rats were not more vulnerable to the reinforcing properties of morphine. However, they responded to the blockade of CB 1 receptors by exhibiting slightly but possibly relevant differences in behavioral, endocrine and molecular parameters compared to the response in non-tolerant rats. This is indicative of the existence of a withdrawal syndrome in cannabinoid-tolerant rats that is mild compared with abstinence in opioid-dependent rats.