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Comparative Pharmacokinetic Study between Metformin Alone and Combined with Orlistat in Healthy Mexican Volunteers

Pharmacology & Pharmacy 2012年第3期3卷 300-306页

作者： Noemí Santos-Caballero francisco javier Flores-Murrieta Landsteiner Scientific S.A. de C.V. México D.F. Mexico Sección de Estudios de Posgrado e Investigación Escuela Superior de Medicina Instituto Politécnico Nacional México D.F. Mexico

Traditional treatment of type 2 diabetes mellitus (T2DM) has focused on correcting hyperglycemia. However, T2DM is almost always accompanied by other conditions and risk factors that affect its morbidity and mortality. Obesity represents one of the main risk factors associated in the T2DM and a modest weight loss around 5% is linked with significant reduction in the blood glucose levels. The objective of this study was to compare the pharmacokinetic parameters between two formulations of metformin, alone or combined with orlistat, in healthy volunteers. A single-blinded, single dose, two-period, two-sequence, crossover, randomized and balanced study design with a 7-day washout period was performed in 26 Mexican volunteers. Plasma samples were collected over a 24-hour period after administration of 500 mg metformin alone or combined with 60 mg orlistat in each period. A validated high-performance liquid chromatography coupled with a ultraviolet detector was used to analyze metformin concentration in plasma. Bioequivalence between metformin alone and metformin combined with orlistat was determined when the ratio for the 90% confidence intervals (CI) of area under the curve (AUC24h) and maximum concentration (Cmax) of the two formulations were within 80% and 125%. In the current study, the mean ± standard deviation (SD) of Cmax, AUC24h and AUC∞ of the formulation containing only metformin were 1.39 ± 0.44 μg/mL, 7.59 ± 3.17 μg h/mL and 8.48 ± 4.13 μg h/mL, respectively, while the mean ± SD of Cmax, AUC24h and AUC∞ of the formulation containing metformin and orlistat were 1.38 ± 0.48 μg/mL, 7.80 ± 2.83 μg h/mL and 9.13 ± 4.29 μg h/mL, respectively. The parametric 90% CI for Cmax and AUC24h were 87.5-109.3 and 88.7-124.7, respectively. These results suggest that both formulations are bioequivalent and there is not pharmacokinetic interaction between metformin and orlistat.

关键词： Metformin Orlistat Diabetes Obesity Bioequivalence Pharmacokinetic

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Indomethacin but not a selective cyclooxygenase-2 inhibitor inhibits esophageal adenocarcinogenesis in rats

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World Journal of Gastroenterology 2012年第35期18卷 4866-4874页

作者： Paula Esquivias Antonio Morandeira Alfredo Escartín Carmelo Cebrián Sonia Santander francisco Esteva María Asunción García-González javier Ortego Angel Lanas Elena Piazuelo CIBER Digestive and Hepatic Deseases Service of Surgery University Hospital "Lozano Blesa" Service of Pathology University Hospital "Lozano Blesa" Department of Medicine University of Zaragoza Service of Clinical Biochemistry University Hospital "Lozano Blesa" Aragon Health Science Institute Service of Gastroenterology University Hospital "Lozano Blesa"

AIM:To evaluate the effects of indomethacin [dual cyclooxygenase(COX)-1/COX-2 inhibitor] and 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl) phenyl)2-(5H)-furanone(MF-tricyclic)(COX-2 selective inhibitor) in a rat experimental model of Barrett's esophagus and esophageal ***:A total of 112 surviving post-surgery rats were randomly divided into three groups:the control group(n = 48),which did not receive any treatment;the indomethacin group(n = 32),which were given 2 mg/kg per day of the COX-1/COX-2 inhibitor;and the MF-tricyclic group(n = 32),which received 10 mg/kg per day of the selective COX-2 *** selected rats were killed either 8 wk or 16 wk after *** timing of the deaths was in accordance with a previous study performed in our *** rats that were killed at the times designated by the protocol were included in the *** then assessed the histology and prostaglandin E2(PGE2) expression levels in the rat *** additional group of eight animals that did not undergo esophagojejunostomy were included in order to obtain normal esophageal tissue as a ***:Compared to a control group with no treatment(vehicle-treated rats),indomethacin treatment was associated with decreases in ulcerated esophageal mucosa(16% vs 35% and 14% vs 17%,2 mo and 4 mo after surgery,respectively;P = 0.021),length of intestinal metaplasia in continuity with anastomosis(2 ± 1.17 mm vs 2.29 ± 0.75 mm and 1.25 ± 0.42 mm vs 3.5 ± 1.54 mm,2 mo and 4 mo after surgery,respectively;P = 0.007),presence of intestinal metaplasia beyond anastomosis(20% vs 71.4% and 0% vs 60%,2 mo and 4 mo after surgery,respectively;P = 0.009),severity of dysplasia(0% vs 71.4% and 20% vs 85.7% high-grade dysplasia,2 mo and 4 mo after surgery,respectively;P = 0.002),and adenocarcinoma incidence(0% vs 57.1% and 0% vs 60%,2 mo and 4 mo after surgery,respectively;P < 0.0001).Treatment with the selective COX-2 inhibitor,MF-tricyclic,did not prevent development of in

关键词： COX-2抑制剂吲哚美辛食管大鼠 PGE2 前列腺素E2 二氟苯基实验模型

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Comparison of the impact of nesofilcon A hydrogel contact lens on the ocular surface and the comfort of presbyopic and non-presbyopic wearers

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International Journal of Ophthalmology(English edition) 2019年第4期12卷 640-646页

作者： Amalia Lorente-Velázquez María García-Montero francisco javier Gómez-Sanz Laura Rico del Viejo José Luis Hernández-Verdejo David Madrid-Costa Department of Optometry and Vision Faculty of Optics and Optometry Complutense University of Madrid

AIM: To assess and compare the impact of a daily disposable contact lens(CL) with high water content on the ocular surface and comfort of the presbyopic and nonpresbyopic population after one day of use. METHODS: Totally 20 presbyopes and 30 non-presbyopes non-contact wearers were fitted with nesofilcon A CLs. CL thickness was measured to assess material stability during daily wear, and ocular surface parameters were also assessed. Optical quality was analyzed for all cases. In addition, CL comfort was ***: No significant differences were found in CL thickness, tear film osmolarity, average tear break-up time, bulbar redness, central corneal thickness, corneal volume, root-mean-square of higher-order aberrations(RMS of HOAs) and vertical and horizontal coma, either as a function of the group or time of use. A significant decrease in tear meniscus height and first break-up of the tear film was found in the presbyopic group(P=0.038; P=0.007 respectively). A decrease in spherical aberration coefficient was found after CL insertion(P=0.031 monofocal CL; P=0.023 low addition multifocal CL; P=0.016 high addition multifocal CL). Multifocal CL were thicker than monofocal CL(P=0.045). Comparison between groups showed more discomfort in presbyopes than non-presbyopes(P=0.003).CONCLUSION: This study evidence that the behavior of the daily disposable CL with high water content seems to be stable during the day of use. Ocular parameters measured during wear show that CL behavior is the same for presbyopes and non-presbyopes, being more uncomfortable for presbyopes.

关键词： nesofilcon A hydrogel material ocular surface parameters presbyopia multifocal daily contact lenses

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Cucurbita ficifolia Bouché Regulates the Metabolism of Carbohydrates and Lipids in Liver by Activation of PPARα without Affectation on PPARγ in Vivo and in Vitro

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American Journal of Plant Sciences 2023年第7期14卷 763-781页

作者： Julio Cesar Almanza-Perez Vladimir Hernandez-Rosado Angeles Fortis-Barrera Gerardo Blancas-Flores Edgar Alarcon-Villaseñor Jose Luis Flores-Saenz Wendoline Rosiles-Alanis francisco javier Alarcon-Aguilar Pharmacology Laboratory Department of Health Sciences Division of Biological and Health Sciences Metropolitan Autonomous University Mexico City Mexico Adyderma Medical International Institute Mexico City Mexico

Diabetes mellitus control in Mexico is practiced by using antidiabetic agents and, by empirical way using medicinal plants. Cucurbita ficifolia (C. ficifolia) has been attributed with hypoglycemic, hypotriglyceridemic, and anti-inflam- matory effects, and D-chiro-inositol (DCI), 4-hydroxybenzoic acid, and β-sitosterol were proposed as active principles. The last two compounds were suggested as activators of two transcription factors, PPARα and PPARγ, in C2C12 myocytes, which participate in β-oxidation of fatty acids and insulin sensitivity. However, the involvement of the hepatocytic and adipocytic PPARs in the effects of C. ficifolia has not yet been explored. This research aimed to determine the effects of C. ficifolia on PPARα, PPARγ, and inflammatory cytokines in streptozotocin (STZ)-induced diabetes mice, HepG2 hepatocytes and 3T3-L1 adipocytes, implicating two additional cell types associated with metabolism of carbohydrates and lipids. STZ-induced diabetes mice received C. ficifolia (200 mg/kg/day) for 30 days, measuring serum cytokines (TNF-α and IL-6). RNA was extracted from liver. Besides, HepG2 and 3T3-L1 cells were incubated (24 h) with C. ficifolia (0.078 mM DCI), using pioglitazone or fenofibrate as controls. RNA was also extracted from cells and PCR in real-time was performed to determinate PPARα and PPARγ expression. In diabetic animals, C. ficifolia decreased glycemia and body weight, decreasing the expression level of TNF-α and IL-6. In addition, C. ficifolia increased PPARα expression in liver of diabetic animals, in HepG2 and 3T3-L1 cells;PPARγ expression only significantly increased in HepG2 cells. The data suggest that the effects on the glycemia and lipids of C. ficifolia and its anti-inflammatory effects imply, besides skeletal muscle cells, hepatic and adipocytic PPARα activation, without affectation on PPARγ. PPARs regulation by C. ficifolia may improve the metabolic dysfunctions associated with metabolic disease, controlling the intake, ac

关键词： Cucurbita ficifolia Diabetes Mellitus Hypoglycemic Plants Anti-Inflammatory Plants PPARs PPARα

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Ophiolite hosted chromitite formed by supra-subduction zone peridotite–plume interaction

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Geoscience Frontiers 2020年第6期11卷 2083-2102页

作者： Júlia Farré-de-Pablo Joaquín A.Proenza JoséMaría González-Jiménez Thomas Aiglsperger Antonio Garcia-Casco javier Escuder-Viruete Vanessa Colás francisco Longo Departament de Mineralogia Petrologia i Geologia AplicadaUniversitat de BarcelonaC/Martíi Franquess/n08028BarcelonaSpain Departamento de Mineraloga y Petrologa Universidad de GranadaFacultad de CienciasFuentenueva s/n18002GranadaSpain Department of Civil Engineering and Natural Resources LuleåUniversity of TechnologySE 97187LuleåSweden Instituto Andaluz de Ciencias de la Tierra(CSIC-UGR) Avda.de las Palmeras 4E-18100ArmillaGranadaSpain Instituto Geologico y Minero de Espana C/La Calera 1Tres Cantos28760MadridSpain Instituto de Geología Universidad Nacional Autonoma de MéxicoCiudad Universitaria04510Ciudad de MéxicoMexico Facultad de Ingeniería Universidad Catòlica de CibaoLa VegaDominican Republic

Chromitite bodies hosted in peridotites typical of suboceanic mantle(***)are found in the northern and central part of the Loma Caribe peridotite,in the Cordillera Central of the Dominican *** chromitites are massive pods of small size(less than a few meters across)and veins that intrude both dunite and ***,they are high-Cr chromitites[Cr#=Cr/(Cr+Al)atomic ratio=0.71-0.83]singularly enriched in TiO2(up to 1.25 wt.%),Fe2 O3(2.77-9.16 wt.%)as well as some trace elements(Ga,V,Co,Mn,and Zn)and PGE(up to 4548 ppb in whole-rock).This geochemical signature is unknown for chromitites hosted in oceanic upper mantle but akin to those chromites crystallized from mantle plume derived ***,the melt estimated to be in equilibrium with such chromite from the Loma Caribe chromitites is similar to basalts derived from different source regions of a heterogeneous Caribbean mantle *** mantle plume is responsible for the formation of the Caribbean Large Igneous Province(CLIP).Dolerite dykes with back-arc basin basalt(BABB)and enriched mid-ocean ridge basalt(E-MORB)affinities commonly intrude the Loma Caribe peridotite,and are interpreted as evidence of the impact that the Caribbean plume had in the off-axis magmatism of the back-arc basin,developed after the Caribbean island-arc extension in the Late *** propose a model in which chromitites were formed in the shallow portion of the back-arc mantle as a result of the metasomatic reaction between the supra-subduction zone(SSZ)peridotites and upwelling plume-related melts.

关键词： Chromitite Ophiolite Plume Mantle Back-arc basin Dominican Republic

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Characterization of a Collection of Brassica carinata Genotypes for in vitro Culture Response and Mode of Shoot Regeneration

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American Journal of Plant Sciences 2011年第1期2卷 27-34页

作者： javier Gil-Humanes Antonio Martín francisco Barro 不详

Brassica carinata, a natural alloploid formed between B. oleracea and B. nigra, is a potential oil crop for the Mediterranean area in which genetic transformation could help to breeding. In vitro culture and shoot regeneration are key factors in developing an efficient transformation method in the genus Brassica. However, the studies for in vitro culture and shoot regeneration in B. carinata are limited to only a few genotypes. The aim of this study was to evaluate the in vitro culture response and shoot regeneration in a collection of B. carinata accessions to identify promising genotypes with high shoot regeneration for genetic transformation experiments. Cotyledonary explants from 51 genotypes were cultured in vitro and callus formation and swelling as well as the mode of shoot regeneration evaluated. A highly positive response to in vitro culture, i.e. callus formation or swelling, was observed in all the genotypes tested. Tissue blackening occurred only in eleven genotypes. Parameters like callus formation and swelling, and number of shoots per explant were highly variable among genotypes. Fourteen genotypes regenerated only via callus formation, whereas only one regenerated only via swelling. Most genotypes showed a higher percentage of callus formation than swelling. The average number of shoots regenerating per explant among genotypes was the most variable factor measured. Six genotypes regenerated more than 6 shoots per explant via callus phase. These genotypes have been identified as having a high regeneration potential and can be used in genetic transformation via Agrobacterium.

关键词： Mustard Tissue Culture Genotype Cotyledons Swelling Callus

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Huge metastable axial strain in ultrathin heteroepitaxial vertically aligned nanowires

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Nano Research 2015年第6期8卷 1964-1974页

作者： Vivien Schuler francisco javier Bonilia Dominique Demaille Alessandro Coati Alina Vlad Yves Garreau Michele Sauvage-Simkin Anastasiia Novikova Emiliano Fonda Sarah Hidki Victor Etgens Franck Vidal Yunlin Zheng Sorbonne Universites UPMC Institut des NonoSciences de Paris 4 place Jussieu Paris 75005 France CNRS UMR7588 Institut des NanoSciences de Paris 4 place Jussieu Paris 75005 France Synchrotron Soleil L'Orme des Merisiers Saint-Aubin BP 48 91192 Gif-sur-Yvette Cedex France Universite Paris Diderot Sorbonne Paris Cite MPO UMR 7162 CNRS Batiment Condorcet Case courrier 7021 75205 Paris Cedex 13 France Universite de Versailles Saint-Quentin en Yvelines 55 Av. de Paris Versailles 78035 France

紧张工程是一个强大的工具定制协调地在取向附生的 heterostructure 叠的材料的物理性质。如此的一条途径，适用于平面 heteroepitaxy 的成熟领域，产出许多新现象和设备。最近， heteroepitaxial 垂直地排列了 nanocomposites 作为平... 详细信息

紧张工程是一个强大的工具定制协调地在取向附生的 heterostructure 叠的材料的物理性质。如此的一条途径，适用于平面 heteroepitaxy 的成熟领域，产出许多新现象和设备。最近， heteroepitaxial 垂直地排列了 nanocomposites 作为平面结构的选择出现了。由于如此的 nanoarchitectures 的古怪几何学，有效种类控制能被完成，打开到新奇功能的路。在这份报纸，我们在在一个氧化物矩阵嵌入的取向附生的转变金属 nanowires 报导一个很大的张力的轴的种类。我们证明超过 1.5% 罐头的轴的种类在有 ultrasmall 直径(36 nm ) 的取向附生的 nanowires 在大厚度(一些百纳米) 上被支撑。轴的种类取决于 nanowires 的直径，反映它的取向附生的性质和接口和有弹性的精力的平衡。而且，如此的种类是亚稳的，这试验性地被显示出，与在 Frenkel-Kontorova 模型的框架执行的计算一致。直径依赖和 metastability 提供有效方法控制种类，为功能的 nanoarchitectures 的设计的一个呼吁的特征。

关键词：异质结构材料金属纳米线轴向应变垂直排列 Frenkel-Kontorova模型超薄纳米复合材料超小直径

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不同医院内外科病房护理工作量的测算与比较研究

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International Journal of Nursing Sciences 2022年第4期9卷 460-466,I0002页

作者： María Fuensanta Hellín Gil Marzena Mikla Ana Myriam Seva Llor María Dolores Roldán Valcárcel francisco javier Ibáñez-López María JoséLópez Montesinos University of Murcia MurciaSpain Biomedical Research Institute of Murcia(IMIB) MurciaSpain

目的旨在应用护理工作量测量统计表对不同医院内外科成人住院病房的护理工作量进行估算。方法采用多中心、观察性、描述性研究方法。应用护理工作量测量统计表对4所医院内外科住院病房进行调查,该统计表中将护理工作按功能分为4种(患者... 详细信息

目的旨在应用护理工作量测量统计表对不同医院内外科成人住院病房的护理工作量进行估算。方法采用多中心、观察性、描述性研究方法。应用护理工作量测量统计表对4所医院内外科住院病房进行调查,该统计表中将护理工作按功能分为4种(患者护理、教学、管理和研究),共21个项目。每个项目都包含1个或多个护理干预分类(Nursing Interventions Classification,NIC)中的护理干预措施,并在将执行每项干预措施所需的实际时间与北美护理诊断协会(the North American Nursing Diagnosis Association,NANDA)的标准化时间进行比较后,为每一项干预措施确定具体时间。在2020年的9个月期间,每个月测量两天,对指定病房当天护理人员3个班次(早班、下午班及晚班)护理工作量进行统计(涉及当天入院所有患者)。结果共完成11756份统计表单(外科5695份,内科6061份)。早班护理工作量较大(外科总计227034 min,内科总计261835 min),特别是自我护理、药物治疗、常见侵入性操作、液体治疗和患者与家庭支持项目;不同病房不同班次管理方面的工作量则较为相近,各班次合计在57348到62901 min之间。对不同班次及不同医院护理工作量进行比较,总工作量和4类护理功能工作量的差异均具有统计学意义(P<0.001)。结论采用经过验证的、基于标准化护理功能术语、适用于病房的统计表单,可提供关于护理工作量的客观数据,用于调整护理人力安排,以适应不同医院和科室的实际情况,从而提高护理质量和患者安全。

关键词：护理人员,医院护理管理研究工作量测量

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Development and postnatal neurogenesis in the retina: a comparison between altricial and precocial bird species

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Neural Regeneration Research 2021年第1期16卷 16-20页

作者： Guadalupe Álvarez-Hernán José Antonio de Mera-Rodríguez Yolanda Gañán Jorge Solana-Fajardo Gervasio Martín-Partido Joaquín Rodríguez-León javier francisco-Morcillo Área de Biología Celular Departamento de AnatomíaBiología Celular y ZoologíaFacultad de CienciasUniversidad de ExtremaduraBadajozSpain Área de Anatomía Humana Departamento de AnatomíaBiología Celular y ZoologíaFacultad de MedicinaUniversidad de ExtremaduraBadajozSpain Servicio de Oftalmología Complejo Hospitalario Universitario de BadajozBadajozSpain

The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in *** vertebrate phylogeny,the retina has two kinds of specialized niches of constitutive neurogenesis:the retinal progenitors located in the circumferential marginal zone and Müller *** proliferative activity in the retinal progenitors located in the circumferential marginal zone in precocial birds such as the chicken,the commonest bird model used in developmental and regenerative studies,is very *** region adds only a few retinal cells to the peripheral edge of the retina during several months after hatching,but does not seem to be involved in retinal regeneration.Müller cells in the chicken retina are not proliferative under physiological conditions,but after acute damage some of them undergo a reprogramming event,dedifferentiating into retinal stem cells and generating new retinal ***,regenerative response after injury occurs with low efficiency in the precocial avian *** contrast,it has recently been shown that neurogenesis is intense in the retina of altricial birds at *** particular,abundant proliferative activity is detected both in the circumferential marginal zone and in the outer half of the inner nuclear ***,stem cell niches are very active in the retina of altricial *** more extensive research is needed to assess the potential of proliferating cells in the adult retina of altricial birds,it emerges as an attractive model for studying different aspects of neurogenesis and neural regeneration in vertebrates.

关键词： altricial birds circumferential marginal zone Müller glia postnatal neurogenesis precocial regeneration retinogenesis

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Gender Differences in the Pharmacokinetics of Oral Drugs

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Pharmacology & Pharmacy 2011年第1期2卷 31-41页

作者： Miriam del Carmen Carrasco-Portugal francisco javier Flores-Murrieta 不详

Establishment of rational dosage regimens requires the knowledge of pharmacokinetics and pharmacodynamics in the target population. It has been established that side effects produced by drugs are more frequent in women than in men. This may be due to two possibilities, one is that normalized dose received by women is higher than men and the other is that anatomical and physiological characteristics are a quite different. In this review, some aspects that may play a role in the generation of such differences are analyzed, including the impact on absorption, distribution, metabolism and excretion of drugs. Most of the changes can be explained by differences in volume of distribution and systemic clear- ance, however, presystemic clearance also seems to play a role in such dissimilarities. The final result, in general, is that women have higher plasma levels of drugs and usually these differences are reduced or abolished when data are normalized by the body weight, since both, volume of distribution and systemic clearance are influenced by it;however, there are some cases in which differences remain. Further research oriented to establish the role of each of the ana- tomical and physiological differences in the oral pharmacokinetics of drugs is warranted.

关键词： Gender-Related Differences Oral Pharmacokinetics Sex Differences

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