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Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism:WLB-73502,an analgesic with improved efficacy and safety profile compared to strong opioids

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Acta Pharmaceutica Sinica B 2023年第1期13卷 82-99页

作者： Alba Vidal-Torres Begoña Fernández-pastor Mónica García Eva Ayet Anna Cabot Javier Burgueño Xavier Monroy Bertrand Aubel Xavier Codony Luz romero rosalía Pascual Maria Teresa Serafini Gregorio Encina Carmen Almansa Daniel Zamanillo Manuel Merlos JoséMiguel Vela WeLab Barcelona Parc Cientific de BarcelonaBarcelona 08028Spain

Opioids are the most effective painkillers,but their benefit-risk balance often hinder their therapeutic ***-73502 is a dual,bispecific compound that binds sigma-1(S1r)and mu-opioid(MOr)***-73502 is an antagonist at the *** behaved as a partial MOr agonist at the G-protein pathway and produced no/unsignificantβ-arrestin-2 recruitment,thus demonstrating low intrinsic efficacy on MOr at both signalling *** its partial MOr agonism,WLB-73502exerted full antinociceptive efficacy,with potency superior to morphine and similar to oxycodone against nociceptive,inflammatory and osteoarthritis pain,and superior to both morphine and oxycodone against neuropathic ***-73502 crosses the blood-brain barrier and binds brain S1r and MOr to an extent consistent with its antinociceptive *** to morphine and oxycodone,tolerance to its antinociceptive effect did not develop after repeated 4-week ***,contrary to opioid comparators,WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy,and it was devoid of proemetic effect(retching and vomiting)in ferrets at potentially effective ***-73502 benefits from its bivalent S1r antagonist and partial MOr agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

关键词： WLB-73502 Sigma-1 receptor Mu-opioid receptor Biased agonist Analgesic activity Chronic pain Neuropathic pain Safety

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泥石流泛滥区域数值模拟

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水利水电科技进展 2008年第6期28卷 1-4页

作者：李同春李杨杨章书成余斌 pastor M 河海大学水利水电工程学院江苏南京210098 中国科学院·水利部成都山地灾害与环境研究所四川成都610041 西班牙国家公共试验研究中心(CETA-CEDEX) 西班牙马德里28014

概述泥石流泛滥区域数值模拟的研究现状,介绍数值模拟Geoflow程序的基本方程、数值求解方法和定解条件。采用Geoflow程序对四川省境内某一较大泥石流沟遭遇20年一遇泥石流的泛滥区域进行数值模拟,得到的泛滥区域与采用经验公式法得到的... 详细信息

概述泥石流泛滥区域数值模拟的研究现状,介绍数值模拟Geoflow程序的基本方程、数值求解方法和定解条件。采用Geoflow程序对四川省境内某一较大泥石流沟遭遇20年一遇泥石流的泛滥区域进行数值模拟,得到的泛滥区域与采用经验公式法得到的结果基本一致,表明数值模拟的结果具有工程应用价值。由于该泥石流沟的重大威胁性,建议在堆积扇上修建的生产、生活设施应避让泛滥区域或采取适当的防护治理措施。

关键词：泥石流泛滥区域数值模拟 C,eoflow程序

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Modulation of faecal metagenome in Crohn's disease:role of microrNAs as biomarkers

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World Journal of Gastroenterology 2018年第46期24卷 5223-5233页

作者： María rojas-Feria Teresa romero-García Jose Angel Fernández Caballero-rico Helena pastor ramírez Marta Avilés-recio Manuel Castro-Fernandez Natalia Chueca Porcuna Manuel romero-Gomez Federico García Lourdes Grande JoséA Del Campo Department of Digestive Diseases Valme University HospitalUGC Digestive Disease and CIBERehdServicio Andaluz de SaludSeville E-41014Spain Complejo Hospitalario Universitario de Granada MicrobiologyGranada E-18016Spain Institute of Biomedicine of Seville Digestive DiseasesHospital Universitario Virgen del Rocío and CIBERehdSeville E-41013Spain Facultad de ciencias de la salud.Universidad Europea Miguel de Cervantes Madrid E-28280Spain

BACKGrOUND The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16 S rrNA gene sequencing has shown that the microbiota in inflammatory bowel disease(IBD) is abnormal and characterized by reduced diversity. Micro rNAs(mirNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease(CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with mirNA profile from gut *** To investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with mirNA profile from gut *** Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of newonset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCr using primers directed to the 16 S bacterial rrNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MGrAST server with the database ribosomal Project was used. MirNA profile and their relative abundance were analyzed by quantitative *** Microbial community was characterized using 16 S rrNA gene sequencing in 29 samples(n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group(5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showe

关键词： Crohn’s disease Dysbiosis microrNAs Firmicutes Bacteroidetes

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Harmonic Analysis in Discrete Dynamical Systems

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International Journal of Modern Nonlinear Theory and Application 2012年第1期1卷 14-31页

作者： Gerardo pastor Miguel romera Amalia Beatriz Orue Agustin Martin Marius F. Danca Fausto Montoya Instituto de Seguridad de la Información CSIC Madrid Spain romanian Institute of Science and Technology Cluj-Napoca Romania

In this paper we review several contributions made in the field of discrete dynamical systems, inspired by harmonic analysis. Within discrete dynamical systems, we focus exclusively on quadratic maps, both one-dimensional (1D) and two-dimensional (2D), since these maps are the most widely used by experimental scientists. We first review the applications in 1D quadratic maps, in particular the harmonics and antiharmonics introduced by Metropolis, Stein and Stein (MSS). The MSS harmonics of a periodic orbit calculate the symbolic sequences of the period doubling cascade of the orbit. Based on MSS harmonics, pastor, romera and Montoya (PrM) introduced the PrM harmonics, which allow to calculate the structure of a 1D quadratic map. Likewise, we review the applications in 2D quadratic maps. In this case both MSS harmonics and PrM harmonics deal with external arguments instead of with symbolic sequences. Finally, we review pseudoharmonics and pseudoantiharmonics, which enable new interesting applications.

关键词： Harmonic Analysis Discrete Dynamical Systems MSS Harmonics PrM Harmonics Pseudoharmonics

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New network and synchronization approaches in focal epilepsy research and treatment

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Health 2013年第6期5卷 1-8页

作者： Jesús pastor rafael G. Sola Lorena Vega Zelaya Oscar Garnés Guillermo Ortega Clinical Neurophysiology Hospital Universitario de la Princesa Madrid Spain Instituto de Investigaciones Biomédicas Hospital de la Princesa Madrid Spain

Traditional approaches to focal epileptic surgery rely in the identification and resection of the epileptic zone. However, a significant minority of epileptic patients continue to experience seizures after surgery, a fact that shows how difficult it is to define this concept. In this work we will review some of the recent advances in the use of complex network theory and synchronization analysis in the study of neurophysiological epileptic records which shed new light on fragmented understanding of the epilepsy dynamic we have today. More important would be the potential treatments which could be implemented from the new information and change of perspective gathered by using this methodology, particularly the substitution of the traditional resective surgery in temporal lobe epilepsy patients.

关键词： Temporal Lobe Epilepsy Synchronization Complex Network Limbic Network Electroencephalography

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Excitation Transfer in Vertically Stacked in (Ga)As/GaAs Quantum rings

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Journal of Modern Physics 2012年第6期3卷 471-475页

作者： r. Naouari W. Ouerghui J. Martinez-pastor J. Gomis M. A. Maaref D. Granados J. M. Garcia Instituto de Ciencia de los Materials Universidad de Valencia Valencia Spain Instituto de Microelectrónica de Madrid Madrid Spain Unité de recherche des Physiques des Semiconducteurs et Capteurs Institut Préparatoire aux Etudes Scientifiques et Techniques Université Carthage Tunis Tunisia

Carrier tunnelling through GaAs barriers of different thicknesses is investigated in vertically InGaAs/GaAs quantum rings (Qr’s). Shorter PL decay time of the ground state emission of high-energy component in the sample with thicker spacer (1.5 nm) is ascribed to both tunnelling effect between the two Qr families and vertical coupling between layers in the stacks. We found that tunnelling time between Qr’s followed the Wentzel-Kramers-Brillouin (WKB) approximation. The non resonant tunnelling rate between Qr’s is found to be different by one order of magnitude from the rate in quantum dots (QD’s).

关键词： Quantum rings Vertical Stack Time resolved Photoluminescence

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Comparative effects of idazoxan, efaroxan, and BU 224 on insulin secretion in the rabbit: Not only interaction with pancreatic imidazoline I2 binding sites

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Health 2010年第2期2卷 112-123页

作者： María José García-Barrado María Francisca pastor María Carmen Iglesias-Osma Christian Carpéné Julio Moratinos 不详

The nature of the binding site(s) involved in the insulin secretory activity of imidazoline compo- unds remains unclear. An imidazoline I2 binding site (I2BS) has been neglected since the classic I2 ligand, idazoxan, does not release insulin. Using the rabbit as an appropriate model for the study of this type of binding sites, we have tried to re-evaluate the effects of idazoxan, the selective I2 compound BU 224, and efaroxan on insulin secretion. Mimicking efaroxan, idazoxan and BU 224 potentiated insulin release from perifused islets in the presence of 8 mM glucose. In static incubation, insulin secretion induced by idazoxan and BU 224 exhibited both dose and glucose dependencies. ATP-sensitive K+ (KATP) channel blockade, though at a different site from the SUr1 receptor, with subsequent Ca2+ entry, mediates the insulin releasing effect of the three ligands. However, additional MAO independent intracellular steps in stimulus- secretion coupling linked to PKA and PKC activation are only involved in the effect of BU 224. Therefore, both an I2 related binding site at the channel level shared by the three ligands and a putative I3-intracellularly located binding site stimulated by BU 224 would be mediating insulin release by these compounds. In vivo experiments reassess the abilities of idazoxan and BU 224 to enhance glucose-induced insulin secretion and to elicit a modest blood glucose lowering response.

关键词： BU 224 Efaroxan Idazoxan Imidazoline Ligands Insulin Secretion IVGTT (Intravenous Glucose Tolerance Test) KATP Channel PK Activity rabbit Pancreatic Islets

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果蝇基底膜的生物研究:释放,装配以及在组织生长中的作用（英文）

果蝇基底膜的生物研究:释放,装配以及在组织生长中的作用（英文）

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中国生理学会基质生物学专业委员会第二次全国基质生物学学术会议

作者： Jose Carlos pastor-Pareja School of Life sciences Tsinghua University

Basement membranes(BMs)are polymers of ECM proteins underlying epithelia and surrounding organs in all *** my laboratory,we are working to understand the biology of BMs using the fruitfly Drosophila melanogaster as a model organism,mostly through genetics and cell biology *** my talk,I will present our findings regarding the secretion of Collagen IV,the hierarchy of assembly of BM components and the

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用于检测非注猪瘟两种ELSA抗原的比较

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国外兽医学（畜禽传染病） 1991年第4期11卷 41-42页

作者： M.J.pastor

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驱动多个固态继电器的单个振荡器

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电子设计技术 EDN CHINA 2006年第6期13卷 112-112,114页

作者： Juan ram ón Vadillo pastor SOr Internacional SA Saint Quirze Del Valles Barcelona Spain

普通的机电式继电器具有低成本和低导通电阻的优点，经常用于大负载电流的通断切换，以及不需要按比例控制负载电流或电压的情况。低成本和低导通电阻是它们在工业中获得广泛应用的主要原因。另外，一只继电器可以用于低电压电子控制下... 详细信息

普通的机电式继电器具有低成本和低导通电阻的优点，经常用于大负载电流的通断切换，以及不需要按比例控制负载电流或电压的情况。低成本和低导通电阻是它们在工业中获得广泛应用的主要原因。另外，一只继电器可以用于低电压电子控制下交流大电压的切换，因为控制电路和负载电路之间具有高度的隔离能力。

关键词：固态继电器振荡器低导通电阻负载电流低电压比例控制电子控制负载电路控制电路

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