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Cancer Sci ; 112(11): 4641-4654, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510663


Screening custom-made libraries of inhibitors may reveal novel drugs for treating pancreatic cancer. In this manner, we identified ispinesib as a candidate and attempted to determine its clinical efficacy and the biological significance of its functional target Eg5 in pancreatic cancer. One hundred compounds in our library were screened for candidate drugs using cell cytotoxicity assays. Ispinesib was found to mediate effective antitumor effects in pancreatic cancer. The clinical significance of the expression of the ispinesib target Eg5 was investigated in 165 pancreatic cancer patients by immunohistochemical staining and in Eg5-positive pancreatic cancer patient-derived xenograft (PDX) mouse models. Patients with Eg5-positive tumors experienced significantly poorer clinical outcomes than those not expressing Eg5 (overall survival; P < .01, recurrence-free survival; P < .01). Ispinesib or Eg5 inhibition with specific siRNA significantly suppressed cell proliferation and induced apoptosis in pancreatic cancer cell lines. Mechanistically, ispinesib acted by inducing incomplete mitosis with nuclear disruption, resulting in multinucleated monoastral spindle cells. In the PDX mouse model, ispinesib dramatically reduced tumor growth relative to vehicle control (652.2 mm3 vs 18.1 mm3 in mean tumor volume, P < .01 by ANOVA; 545 mg vs 28 mg in tumor weight, P < .01, by ANOVA). Ispinesib, identified by inhibitor library screening, could be a promising novel therapeutic agent for pancreatic cancer. The expression of its target Eg5 is associated with poorer postoperative prognosis and is important for the clinical efficacy of ispinesib in pancreatic cancer.

Antineoplásicos/farmacologia , Benzamidas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Quinazolinas/farmacologia , Análise de Variância , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Intervalo Livre de Doença , Descoberta de Drogas , Feminino , Inativação Gênica , Humanos , /metabolismo , Bibliotecas Especializadas , Metáfase/efeitos dos fármacos , Camundongos , Camundongos Nus , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
Med Ref Serv Q ; 39(4): 334-343, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33085948


This report describes utilization of a librarian in a pharmacy laboratory course over two academic years. Library instruction evolved from a simple drug information review session to case-based, hands-on instruction, collaboratively taught with pharmacy faculty. Additionally, LibChat, an online chat service, was piloted in the pharmacy laboratory course so the librarian could be available to students at their point-of-need. Development of the drug information review sessions across both years, student utilization of LibChat, lessons learned, and ideas for improvement for future iterations of the course are described.

Currículo , Educação em Farmácia/organização & administração , Docentes de Farmácia , Colaboração Intersetorial , Bibliotecários , Bibliotecas Especializadas/organização & administração , Estudantes de Farmácia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
J Med Libr Assoc ; 108(2): 167-176, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32256228


Objective: The authors' objective was to document the effects of evolving veterinary accreditation standards on the development of currently existing accredited US and Canadian veterinary school libraries in the late nineteenth and twentieth centuries. Methods: We gathered historical standards that major veterinary accreditation agencies developed with respect to libraries and library services. Historical background on college libraries, their facilities, services, and personnel via surveys, literature searches, and archival documents was also collected. We then correlated the evolving standards with each library's development. Results: There was a marked correlation between the prevailing accreditation standards and library development, particularly during the post-World War II era and through the mid-1980s. These impacts-which included new and separate facilities, hiring of professional librarians, and additional open hours-affected not only the twenty new developing veterinary schools, but also the libraries of the preexisting colleges. Conclusions: Professional veterinary accrediting standards were an important influence on the evolution of veterinary school libraries, particularly during the years of major growth in the number of new veterinary colleges in the United States and Canada. In the 1990s and beyond, both libraries and accreditation standards continue to evolve in response to changes in technology, economics, publishing methods, and more. This latter is a story yet to be told.

Acreditação/história , Bibliotecas Especializadas/história , Faculdades de Medicina Veterinária/história , Canadá , História do Século XIX , História do Século XX , Bibliotecas Especializadas/organização & administração , Bibliotecas Especializadas/normas , Serviços de Biblioteca/história , Serviços de Biblioteca/organização & administração , Faculdades de Medicina Veterinária/normas , Estados Unidos
Hist Psychiatry ; 31(1): 3-20, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31564122


Leonhard Schwartz's importance in the history of psychology has probably not been fully appreciated, and this article is dedicated to the life and work of the Basel neurologist. It highlights the triangular relationship he maintained for 20 years with Pierre Janet, of whom he was a disciple, and Henri F. Ellenberger, to whom he passed on his passion for Janet's oeuvre.

Correspondência como Assunto/história , Psicologia/história , Psicoterapia/história , História do Século XX , Humanos , Relações Interprofissionais , Bibliotecas Especializadas/história , Suíça
Rev. medica electron ; 41(6): 1341-1353, oct.-dic. 2019. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1094134


RESUMEN Introducción: los estudios actuales sobre la caracterización antropométrica de las vértebras, reviste importancia para las especialidades de Ortopedia y Neurocirugía por el interés quirúrgico que tiene este conocimiento. Objetivo: caracterizar las dimensiones antropométricas de las vértebras cervicales pertenecientes a la Osteoteca de la Universidad de Ciencias Médicas de Matanzas. Materiales y métodos: se realizó un estudio descriptivo, observacional. El universo de estudio estuvo integrado por 63 vértebras cervicales existentes en la Osteoteca. Se realizaron medidas del cuerpo, agujero vertebral, agujeros transversos y forma de los mismos. Resultados: los valores de las medidas del cuerpo vertebral mostraron un predominio de la media del diámetro transversal con 24,24 mm, sobre el anteroposterior de 15,57 mm. El diámetro transversal del agujero vertebral, midió 25,70 mm y el anteroposterior fue menor con 17,06 mm. Al estudiar la forma de los agujeros transversos, en total predominó el tipo redondo; mientras que al compararlos según lateralidad, en el lado izquierdo predominó el tipo redondo, mientras que en el derecho fue el tipo oval paralelo. Se observó en ambos agujeros transversos el predominio del diámetro transverso sobre el paralelo y comparando los agujeros entre sí, se oapreció una media mayor de ambos diámetros en los agujeros del lado izquierdo. Conclusiones: existió un predominio del diámetro transversal en el cuerpo y el agujero vertebral. Es más frecuente el tipo de agujero transverso redondo y los agujeros izquierdos presentaron mayores dimensiones (AU).

ABSTRACT Introduction: current studies on vertebras anthropometric characterization are of great importance for the specialties of Orthopedics and Neurosurgery due to the surgical interest of this knowledge. Objective: to characterize the anthropometric dimensions of the cervical vertebras belonging to the Osteotheque of the University of Medical Sciences of Matanzas. Materials and Methods: an observational, descriptive study was carried out. The universe of study was integrated by 63 cervical vertebras kept in the Osteotheque. Measures of the body, vertebral foramen and foramen transversarium were taken and their form was described. Results: the values of the vertebral body measures showed the predominance of the average transverse diameter with 24.24 mm, over the anterior-posterior one of 15.57 mm. The transverse diameter of the vertebral foramen was 25.70 mm, and the anterior-posterior one was 17.06 mm. When studying the form of the transverse foramens, in general the round kind predominated; at the comparison according to laterality, the round kind predominated in the left side while in the right the oval parallel one predominated. In both foramens transversaria the predominance of the transverse diameter over the parallel one was observed and when comparing both foramens, a higher diameter average was found in the left side foramens. Conclusions: there is a predominance of the transverse diameter in the body and vertebral foramen. The most frequent foramen was the round transverse one and left foramens had higher dimensions (AU).

Humanos , Coluna Vertebral/anatomia & histologia , Universidades , Vértebras Cervicais/anatomia & histologia , Antropometria , Bibliotecas Especializadas , Ortopedia , Especialidades Cirúrgicas , Epidemiologia Descritiva , Estudo Observacional , Medicina , Neurocirurgia
Rev. cub. inf. cienc. salud ; 30(3): e1413, jul.-set. 2019. tab
Artigo em Inglês | LILACS, CUMED | ID: biblio-1093076


The aim of this study was to investigate the status and ranking of job motivational factors using Herzberg Two-factor Theory. This is a descriptive-analytical survey, and researcher-made questionnaire was used for data collection with reliability of 0.92 based on Cronbach Alpha. The statistical population included librarians of 7 special libraries of Ahvaz city, Iran, out of which 53 responded to the questionnaire. Data analysis was done using SPSS and descriptive and statistical statistics. The results indicate that according to librarians' viewpoint, from hygiene or extrinsic factors of job motivation, three components of qualified supervisor, proper management of affairs and desirable working condition, and from intrinsic or subjective factors, three components of success, assignment of responsibilities, and sense of achievement are in the first to third ranks, respectively. On the other hand, appreciation and salary components are in the lowest ranks among other factors. Therefore, it can be concluded that the status of hygiene (extrinsic) factors and motivational (intrinsic) factors is satisfactory in the studied population. However, it is required to plan for improving the current condition and compensating weaknesses(AU)

El objetivo principal del presente estudio fue estudiar el estado y la clasificación de los factores de motivación laboral basados ​​en la teoría de los dos factores de Herzberg. El estudio consistió en una encuesta descriptiva-analítica, la cual se utilizó para recopilar datos. Este cuestionario fue realizado por investigadores y su confiabilidad se calculó 0,92 utilizando el coeficiente alfa de Cronbach. La población estadística incluyó bibliotecarios de bibliotecas especializadas de Ahvaz, 53 de los cuales respondieron el cuestionario. Los datos fueron analizados por el software SPSS utilizando estadísticas descriptivas y estadísticas inferenciales. Los resultados mostraron que desde la perspectiva de los bibliotecarios de las bibliotecas especializadas de salud (externos) o de la motivación laboral, tres componentes del supervisor competente, la gestión adecuada de los asuntos y las condiciones de trabajo óptimas, y entre los factores de trabajo internos (subjetivos), la motivación, tres componentes del éxito, la asignación de responsabilidad y el progreso están en buenas condiciones. También, en función de los resultados de la investigación, en términos de clasificación del estado de los factores motivacionales, los componentes de las condiciones de trabajo óptimas, la gestión adecuada de los asuntos y el supervisor competente se clasifican de primero a tercero, respectivamente. Por otro lado, los componentes de apreciación y salario tienen el rango más bajo entre otros factores. En general, según los hallazgos del estudio, se puede concluir que el estado de salud (externo) y los factores de motivación laboral (interno) en la población estudiada fueron prometedores. Sin embargo, se necesita una planificación principal para mejorar la situación actual y eliminar las debilidades existentes(AU)

Humanos , Condições de Trabalho , Planejamento , Bibliotecas Especializadas , Análise de Dados
Multimedia | Recursos Multimídia | ID: multimedia-3135


Pôster apresentado no CRICS10, no eixo temático de Gestão da Informação .Apresenta conceitos de Biblioteca Especializada na área da Saúde, demonstrando a necessidade da sua organização e representação por um profissional especializado da Biblioteconomia.

Bibliotecas Especializadas
Multimedia | Recursos Multimídia | ID: multimedia-3103


Pôster apresentado no CRICS10, no eixo temático de Gestão da Informação. Apresenta o trabalho elaborado na Biblioteca Virtual em Saúde, Prevenção e Controle de Câncer visando fortalecer a rede de conteúdos, ampliar a promoção da comunicação técnico-científica no âmbito das BVS, incrementar um modelo de gestão com critérios para a normalização e padronização de informações e elaborar um modelo de organização voltado para a informação em formato eletrônico.

Bibliotecas Digitais , Gestão da Informação , Bibliotecas Especializadas
J Med Libr Assoc ; 107(1): 98-102, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30598654


Librarians have ever-expanding teaching responsibilities in many academic disciplines. Assessment of learning outcomes requires longitudinal evaluation to measure true retention of skills and knowledge. This is especially important in the health sciences, including pharmacy, where librarians take an active role in teaching students to help prepare them for a profession in which solid information literacy skills are required to safely and effectively provide evidence-based care to patients. In this commentary, I reflect on a year of teaching in a pharmacy program and consider the outcomes of my instruction, areas for improvement, student retention of learning, assessment challenges, faculty-librarian collaboration, and continued support for library instruction in the pharmacy curriculum.

Educação em Farmácia/organização & administração , Docentes/psicologia , Competência em Informação , Bibliotecários/psicologia , Bibliotecas Especializadas/organização & administração , Estudantes de Farmácia , Ensino/psicologia , Adulto , Currículo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pennsylvania , Adulto Jovem
J Deaf Stud Deaf Educ ; 24(2): 74-83, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30597103


In today's public libraries, children's librarians are challenged to provide inclusive programming that welcomes all individuals, including deaf and hard-of-hearing children at risk for delayed reading and literacy development. This study, using quantitative survey data and qualitative interview methods, investigated the programs and accommodations public libraries provide for deaf and hard-of-hearing children, the impetus for providing these programs, and the training required. Nearly 500 public libraries in the United States with service areas greater than 100,000 patrons were invited to participate in an online survey. Fifty-nine librarians completed the survey and 11 participated in an additional telephone interview. Results indicated less than half of the libraries surveyed provided services for deaf and hard-of-hearing children. Nearly all of the programs offered were inclusive; among the accommodations provided were books with sign language and sign language interpreters. Training was the most common limitation facing librarians in their role as community partners in the literacy development of deaf and hard-of-hearing children.

Educação de Pessoas com Deficiência Auditiva/organização & administração , Criança , Humanos , Bibliotecas Especializadas , Logradouros Públicos , Inquéritos e Questionários , Estados Unidos
Rev. pesqui. cuid. fundam. (Online) ; 10(3): 599-604, jul.-set. 2018. ilus
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-906040


Objetivo: Mostrar os resultados do projeto de digitalização e publicação on-line dos acervos da Coleção Memória da Enfermagem (BSEN). Método: Foi realizada pesquisa do material bibliográfico existente no acervo, com as etapas de seleção, preparação dos itens, digitalização e publicação no catálogo on-line. Resultados: Criação da biblioteca digital da Coleção Memória da Enfermagem da UNIRIO. Conclusão: A digitalização dos acervos especiais é processo indispensável para a preservação da memória e disseminação da informação histórica

Objective: The study's goal has been to show the results of the digitization project and online publishing of Collection of Nursing Memory (BSEN). Methods: It is a research of existing bibliographical material that was held in the collection, with the stages of selection, preparation of items, digitization and publication in the catalog. Results: The creation of the digital library collection Memory Nursing - UNIRIO. Conclusion: The digitization of special collections is an essential process for the preservation of memory and dissemination of historical information

Objetivo: Mostrar los resultados de las colecciones de diseño y publicación en línea de escaneo de la colección Memoria de Enfermería (BSEN). Método: Investigación del material bibliográfico existente con las etapas de selección, preparación de artículos, la digitalización y publicación en el catálogo. Resultados: La creación de la biblioteca digital de la Colección Memoria de la Enfermería - UNIRIO. Conclusión: La digitalización de las colecciones especiales es un proceso esencial para la preservación de la memoria y la difusión de información histórica

Humanos , Masculino , Feminino , História da Enfermagem , Bibliotecas Digitais/tendências , Bibliotecas de Enfermagem/história , Catálogos de Bibliotecas , Bibliotecas Especializadas , Desenvolvimento de Coleções em Bibliotecas
E-Cienc. inf ; 8(1): 151-171, ene.-jun. 2018. tab, graf
Artigo em Espanhol | LILACS, SaludCR | ID: biblio-1089842


Resumen Se expone, en detalle, el proceso de implementación de dos servicios de referencia en la Biblioteca de la Corte Interamericana de Derechos Humanos, mediante el uso de dispositivos y aplicaciones móviles. Los servicios implementados son la atención de consultas por mensaje de texto (SMS) y el envío de alertas informativas a través de Whatsapp. Se abordan detalles de la instalación, las pruebas del servicio y las políticas de implementación. Se concluye que las nuevas tecnologías móviles están brindando a las bibliotecas modernas posibilidades de ofertar sus servicios, dando al usuario la capacidad de utilizar los recursos de la unidad de información sin desplazarse físicamente al edificio; estas posibilidades no necesariamente requieren de una alta inversión presupuestaria para llevarlas a cabo.

Abstract The process of implementation of two reference services in the Library of the Inter-American Court of Human Rights is presented in detail through the use of mobile devices and applications. The services implemented are the attention of queries by text message (SMS) and the sending of informational alerts through Whatsapp. Installation details, service testing and implementation policies are addressed. It is concluded that new mobile technologies are giving libraries new possibilities to offer their services, giving the user the ability to use the resources of the information unit without moving physically to the building. These new possibilities do not necessarily require a high budget investment to carry them out.

Software , Produtos e Serviços de Informação , Aplicativos Móveis , Bibliotecas Especializadas/organização & administração , Acesso à Internet , Jurisprudência
J Proteome Res ; 17(3): 1309-1313, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29400473


The recent establishment of cloud computing, high-throughput networking, and more versatile web standards and browsers has led to a renewed interest in web-based applications. While traditionally big data has been the domain of optimized desktop and server applications, it is now possible to store vast amounts of data and perform the necessary calculations offsite in cloud storage and computing providers, with the results visualized in a high-quality cross-platform interface via a web browser. There are number of emerging platforms for cloud-based mass spectrometry data analysis; however, there is limited pre-existing code accessible to web developers, especially for those that are constrained to a shared hosting environment where Java and C applications are often forbidden from use by the hosting provider. To remedy this, we provide an open-source mass spectrometry library for one of the most commonly used web development languages, PHP. Our new library, phpMs, provides objects for storing and manipulating spectra and identification data as well as utilities for file reading, file writing, calculations, peptide fragmentation, and protein digestion as well as a software interface for controlling search engines. We provide a working demonstration of some of the capabilities at .

Disseminação de Informação/métodos , Bibliotecas Especializadas/estatística & dados numéricos , Espectrometria de Massas/estatística & dados numéricos , Bibliotecas de Moléculas Pequenas/provisão & distribuição , Software , Bases de Dados de Proteínas , Humanos , Armazenamento e Recuperação da Informação/estatística & dados numéricos , Internet , Espectrometria de Massas/métodos , Proteômica/métodos , Proteômica/estatística & dados numéricos
J Proteome Res ; 17(2): 846-857, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29281288


Spectral library searching (SLS) is an attractive alternative to sequence database searching (SDS) for peptide identification due to its speed, sensitivity, and ability to include any selected mass spectra. While decoy methods for SLS have been developed for low mass accuracy peptide spectral libraries, it is not clear that they are optimal or directly applicable to high mass accuracy spectra. Therefore, we report the development and validation of methods for high mass accuracy decoy libraries. Two types of decoy libraries were found to be suitable for this purpose. The first, referred to as Reverse, constructs spectra by reversing a library's peptide sequences except for the C-terminal residue. The second, termed Random, randomly replaces all non-C-terminal residues and either retains the original C-terminal residue or replaces it based on the amino-acid frequency of the library's C-terminus. In both cases the m/z values of fragment ions are shifted accordingly. Determination of FDR is performed in a manner equivalent to SDS, concatenating a library with its decoy prior to a search. The utility of Reverse and Random libraries for target-decoy SLS in estimating false-positives and FDRs was demonstrated using spectra derived from a recently published synthetic human proteome project (Zolg, D. P.; et al. Nat. Methods 2017, 14, 259-262). For data sets from two large-scale label-free and iTRAQ experiments, these decoy building methods yielded highly similar score thresholds and spectral identifications at 1% FDR. The results were also found to be equivalent to those of using the decoy-free PeptideProphet algorithm. Using these new methods for FDR estimation, MSPepSearch, which is freely available search software, led to 18% more identifications at 1% FDR and 23% more at 0.1% FDR when compared with other widely used SDS engines coupled to postprocessing approaches such as Percolator. An application of these methods for FDR estimation for the recently reported "hybrid" library search (Burke, M. C.; et al. J. Proteome Res. 2017, 16, 1924-1935) method is also made. The application of decoy methods for high mass accuracy SLS permits the merging of these results with those of SDS, thereby increasing the assignment of more peptides, leading to deeper proteome coverage.

Algoritmos , Aminoácidos/química , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Bibliotecas Especializadas/métodos , Biblioteca de Peptídeos , Peptídeos/análise , Sequência de Aminoácidos , Humanos , Peptídeos/química , Software , Espectrometria de Massas em Tandem
Cult. cuid ; 21(47): 69-82, ene.-abr. 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-163342


La prensa profesional enfermera y de sus antecedentes profesiones auxiliares, constituye una fuente valiosa para el estudio de la evolución que desarrollaron y su interrelación entre las diferentes disciplinas sanitarias. Conocer y estudiar las publicaciones seriadas de este sector nos permite acercarnos a la realidad e identidad profesional, formativa y de actualidad por la que atravesaban. En el presente artículo se propone una guía metodológica para la búsqueda de este tipo de fuente de información historiográfica y un modelo para el estudio histórico de la prensa profesional enfermera basado a los últimos avances en la metodología historiográfica; apoyado en el análisis por separado de la estructura de la prensa mediante los preceptos de Jaques Kayser y de su contenido por ejes temáticos a través los métodos heurístico, hermenéutico e histórico en la interpretación de textos (AU)

A imprensa profissional enfermeiro e suas profissões antecedentes de saúde é uma fonte valiosa para o estudo da evolução que desenvolveu e sua inter-relação entre as diferentes disciplinas da saúde. Conhecer e estudar folhetins nesse setor nos permite abordar a realidade e identidade profissional, educacional e tópica que atingiu. Neste artigo tenciona um guia metodológico para encontrar este tipo de fonte de informação historiográfica e um modelo para o estudo histórico da imprensa profissional enfermeiro com base nos mais recentes desenvolvimentos na metodologia historiográfica; suportado pela análise separada da estructura da imprensa os preceitos de Jaques Kayser e seu conteúdo por temas através de heurística, hermenêutica e método histórico na interpretação de textos (AU)

The nurse and previous auxiliary professions press, is a valuable source for the study of evolution developed and its interrelationship between different health disciplines. Knowing and studying serials publications in this sector allow us to approach reality and professional identity, educational and current which hit. In this article is proposed a metodological guide for finding this kind of source of historiographical information and a model for the historical study of the nurse professional press based on the latest developments in the historiographical methodology; supported on separate analysis of the structure of the press by the precepts of Jaques Kayser and its contents by themes through heuristic, hermeneutic and historical methods in the interpretation of texts (AU)

Humanos , História da Enfermagem , Publicações Periódicas como Assunto/história , Tocologia/história , Assistentes de Enfermagem/história , Bibliotecas Especializadas
Medizinhist J ; 52(1): 41-55, 2017.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-30549771


Are marginal notes marginal? Backed by a book from the private library of Emil von Behring the paper reflects whether annotations are peripheral sources or whether they can give some hints concerning biographical details. Behring's traces of reading are exposed and discussed by using the example of Otto Rot's Arzneimittel der heutigen Medicin (1877). The marginal notes demonstrate Behring's intensive work on hypnotics, sedativs, and analgetics which were possibly used for the therapy of others or himself. The findings will be compared to other sources of Behring's personal papers.

Analgésicos/história , Livros/história , Hipnóticos e Sedativos/história , Bibliotecas Especializadas/história , Redação/história , História do Século XIX , História do Século XX , Prússia
J Alzheimers Dis ; 53(4): 1499-516, 2016 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-27392852


The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins, and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer's disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC®1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76-4.56 µM. Of these 7 drugs, 5 were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Aß in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron, and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD.

Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/toxicidade , Barreira Hematoencefálica/efeitos dos fármacos , Reposicionamento de Medicamentos/métodos , Células Endoteliais/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Encéfalo/citologia , Linhagem Celular Transformada , Claudina-5/metabolismo , Técnicas de Cocultura , Técnicas In Vitro , Bibliotecas Especializadas , Camundongos , Modelos Biológicos , Fragmentos de Peptídeos , Permeabilidade/efeitos dos fármacos
J Hist Biol ; 49(1): 191-230, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26242744


This paper focuses on the geography of the botanical community in Paris, under the July Monarchy (1830-1848). At that time, the Muséum d'Histoire naturelle (MHN) was at its institutional acme and, under the impulse of François Guizot, its budget was increasing dramatically. However, closer attention to manuscript sources (correspondence, travel diaries) reveals that the botanists of the time favoured other private institutions, located both on the Right and Left Banks of the Seine. The MHN was prestigious for its collections and professors but it was relatively remote from the centre of Paris, and its plant samples were sometimes difficult to access. Several other first-class private herbaria granted liberal access to botanists: those of Jacques Gay, Phillip Barker Webb, and Benjamin Delessert. Thanks to their wealth, these plant amateurs had ownership of historical herbaria consisting of species types alongside rich botanical libraries. Botanists visiting Paris from foreign countries or other provinces of France also spent some time studying less general plant collections, like those of Count Jaubert, or specialized collections, like Montagne's or Léveillé's on cryptogams. Other botanists also enjoyed renown at the time, although they published little, if anything (like Maire). Living in crammed apartments, literally in the middle of their plant samples, these botanists were key nodes in botanical networks, although they had no relation with the prestigious MHN.

Botânica/história , Museus/história , Agricultura/história , Geografia/história , História do Século XIX , Bibliotecas Especializadas/história , Paris , Plantas