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Potential of RP-UHPLC-DAD-MS for the qualitative and quantitative analysis of sofosbuvir in film coated tablets and profiling degradants

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Journal of Pharmaceutical Analysis 2017年第4期7卷 208-213页

作者： maría del mar contreras Aránzazu Morales-Soto Antonio Segura-Carretero Javier Valverde Department of Analytical Chemistry Faculty of SciencesUniversity of GranadaAvenida Fuentenueva s/n18071 GranadaSpain Research and Development Functional Food Centre (CIDAF) Bioregión BuildingHealth Science Technological ParkAvda. Del Conocimiento s/n18016 GranadaSpain

Sofosbuvir is one of the new direct-acting antiviral drugs against hepatitis C virus(HCV) infection. This drug has recently been launched into the market, and generic versions of the medication are expected to be produced by local drug producers in some countries. Therefore, new methods are required to control sofosbuvir in pharmaceuticals. In the present study, a new method based on reversed phase(RP)-ultra-high performance liquid chromatography(UHPLC) coupled to diode array detection(DAD) and mass spectrometry(MS) was developed to facilitate the qualitative and quantitative analysis of sofosbuvir in film coated tablets. A wavelength of 260 nm was selected to perform a cost-effective quantification and the method showed adequate linearity,with an R^2 value of 0.9998, and acceptable values of accuracy(75%–102%) and precision(residual standard deviation < 5%). The detection and quantification limits were 0.07 μg/mL and 0.36 μg/mL, ***, the use of high-resolution MS enabled us to ensure the specificity, check impurities and better sensitivity. Therefore, this methodology promises to be suitable not only for the routine analysis of sofosbuvir in pharmaceutical dosage forms, but also for potential degradants.

关键词： Film coated tablets Mass spectrometry RP-UHPLC Sofosbuvir

Powder metallurgy with space holder for porous titanium implants:A review

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Journal of Materials Science & Technology 2021年第17期76卷 129-149页

作者： Alejandra Rodriguez-contreras Miquel Punset JoséA.Calero Francisco Javier Gil Elisa Ruperez Josémaría Manero Biomaterials Biomechanics and Tissue Engineering Group(BBT)Department of Materials Science and EngineeringUniversitat Politecnica de Catalunya(UPC)Av.Edurad Maristany 1608019BarcelonaSpain Barcelona Research Centre in Multiscale Science and Engineering Technical University of Catalonia(UPC)Av.Eduard Maristany 10-1408019BarcelonaSpain UPC Innovation and Technology Center(CIT-UPC).Technical University of Catalonia(UPC) C.Jordi Girona 3-108034Barcelona.Spain AMES GROUP SA.Carretera Nacional 340 Pol.Ind."Les Fallulles"08620Sant Vicenc dels HortsBarcelonaSpain Bioengineering Institute for Technology Universitat Intemacional de Catalunyac/Josep Trueta s/n08195BarcelonaSpain

One of the biggest challenges in the biocompatibility of implantable metals is the prevention of the stress shielding effect,which is related to the coupling of the bone-metal mechanical *** stress shielding phenomenon provokes bone resorption and the consequent adverse effects on prosthesis ***,it can be inhibited by adapting the stiffness of the implant *** the use of titanium(Ti)porous structures is a great alternative not only to inhibit this effect but also to improve the osteointegration of orthopedic and dental implants,a brief description of the techniques used for their manufacturing and a review of the current commercialized implants produced from porous Ti assemblies are compiled in this *** powder metallurgy(PM)with space holder(SH)is a powerful technology used to produce porous Ti structures,it is here discussed its potential for the fabrication of medical devices from the perspectives of both design and *** most important parameters of the technique such as the size and shape of the initial metallic particles,the SH and binder type of materials,the compaction pressure of the green form,and in the sintering stage,the temperature,atmosphere,and time are reviewed according to the bibliography ***,the importance of the porosity and its types together with the influence of the mentioned parameters in the final porosity and,consequently,in the ultimate mechanical properties of the structure are ***,a few examples of the PM-SH application for the manufacturing of orthopedic implants are presented.

关键词： Powder metallurgy Space holder method Porous titanium structures Medical devices Stress shielding effect Porous materials permeability Interconnected porosity Porous bone substitute materials Open-cell titanium foams Sintering-dissolution technique

Fuzzy Boundaries Between Post-Disaster Phases: The Case of L'Aquila, Italy

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International Journal of Disaster Risk Science 2016年第3期7卷 277-292页

作者： Diana contreras Department of Geoinformatics–Z_GIS University of Salzburg

A number of indices have been developed for measuring vulnerability to disasters, but little attention has been paid to recovery indices. Post-disaster periods are usually divided into four phases. The terms established by the United Nations Development Programme for post-disaster phases—relief, early recovery, recovery, and development—are used in this article. This research examines the hypothesis that the boundaries between post-disaster recovery phases are fuzzy and should be defined by the progress achieved in the recovery process, rather than by the amount of time elapsed since the event. The methodology employed involved four steps: fieldwork, mapping,identification of indicators, and assessment. The case study area was the city of L'Aquila in the Abruzzo region of central Italy, which was struck by an earthquake in April2009. For each phase of the recovery process in L'Aquila a score was calculated based on the progress observed in2016, 7 years after the earthquake. The highest score went to the early recovery phase(14 points), followed by the recovery phase(13 points), the development phase(12points), and the relief phase(4 points). The results demonstrate the possibility of defining post-disaster recovery phases in an affected area based on measuring achievements through indicators rather than defining recovery phases in terms of elapsed time after a disaster.

关键词： Disaster recovery Earthquakes Geographical information system (GIS) L’Aquila Post-disaster phases Spatial indicators

The Drivers of Child Mortality During the 2012–2016 Drought in La Guajira, Colombia

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International Journal of Disaster Risk Science 2020年第1期11卷 87-104页

作者： Diana contreras Alex Voets Jana Junghardt Srirama Bhamidipati Sandra contreras Research Center for Integrated Disaster Risk Management(CIGIDEN) Pontifical Catholic University of Chile7820436 MaculSantiagoChile School of Engineering Newcastle UniversityNewcastle upon TyneNorthumbria NE17RUUK Caritas Switzerland BogotaD.C.110231Colombia Caritas Switzerland 6002 Luzern LucernaSwitzerland Faculty of Technology Policy and ManagementDelft University of Technology2628 BX DelftThe Netherlands Communication and Language Pontifical Xavierian UniversityBogotaD.C.110231Colombia

During the 2012–2016 drought in La Guajira,Colombia, child mortality rates rose to 23.4 out of *** of these children belonged to the Wayuu indigenous community, the largest and one of the most vulnerable in Colombia. At the municipal level, this study found a significant positive correlation between the average child mortality rate and households with a monthly income of less than USD 100, the number of people without access to health insurance, being part of the indigenous population,being illiterate, lacking sewage systems, living in rural areas, and large households with members younger than5 years old and older than 65 years old. No correlation was found with households without access to a water *** stepwise regression analysis showed that households with a monthly income of less than USD 100, no members older than 65 years old, but several children younger than5 years old, account for 90.4% of the child mortality *** study concludes that, if inhabitants had had better incomes or assets, as well as an adequate infrastructure,they could have faced the drought without the observed increase in child mortality.

关键词： Child mortality Climate change Drought Socioeconomic vulnerability Water management Wayuu indigenous community

Role of quorum sensing in bacterial infections

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World Journal of Clinical Cases 2015年第7期3卷 575-598页

作者： Israel Castillo-Juárez Toshinari Maeda Edna Ayerim Mandujano-Tinoco maría Tomás Berenice Pérez-Eretza Silvia Julieta García-contreras Thomas K Wood Rodolfo García-contreras Colegio de Postgraduados Campus Montecillo Department of Biological Functions and Engineering Kyushu Institute of Technology Epigenetics of Cancer Laboratory Division of Basic ResearchNational Institute of Genomic Medicine Department of Microbiology Instituto de Investigación Biomédica de A Coruña(INIBIC)Complexo Hospitalario Universitario de A Coruña(CHUAC)SergasUniversidade da Coruña(UDC)15006 A CoruñaSpain Departamento de Microbiología y Parasitología Facultad de MedicinaUniversidad Nacional Autónoma de México Centro Médico Coyoacán Department of Chemical Engineering Pennsylvania State UniversityUniversity Park Department of Biochemistry and Molecular Biology Pennsylvania State UniversityUniversity Park

Quorum sensing(QS) is cell communication that is widely used by bacterial pathogens to coordinate the expression of several collective traits, including the production of multiple virulence factors, biofilm formation, and swarming motility once a population threshold is reached. Several lines of evidence indicate that QS enhances virulence of bacterial pathogens in animal models as well as in human infections; however, its relative importance for bacterial pathogenesis is still incomplete. In this review, we discuss the present evidence from in vitro and in vivo experiments in animal models, as well as from clinical studies, that link QS systems with human infections. We focus on two major QS bacterial models, the opportunistic Gram negative bacteria Pseudomonas aeruginosa and the Gram positive Staphylococcus aureus, which are also two of the main agents responsible of nosocomial and wound infections. In addition, QS communication systems in other bacterial, eukaryotic pathogens, and even immune and cancer cells are also reviewed, and finally, the new approaches proposed to combat bacterial infections by the attenuation of their QS communication systems and virulence are also discussed.

关键词： Quorum sensing Virulence Infections Pseudomonas aeruginosa Staphylococcus aureus Animal models

Endotoxin-induced alterations of adipose tissue function:a pathway to bovine metabolic stress

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1391-1407页

作者： Miguel Chirivi G.Andres contreras Department of Large Animal Clinical Sciences Michigan State UniversityEast LansingMIUSA

During the periparturient period, dairy cows exhibit negative energy balance due to limited appetite and increased energy requirements for lactogenesis. The delicate equilibrium between energy availability and expenditure puts cows in a state of metabolic stress characterized by excessive lipolysis in white adipose tissues(AT), increased production of reactive oxygen species, and immune cell dysfunction. Metabolic stress, especially in AT, increases the risk for metabolic and inflammatory diseases. Around parturition, cows are also susceptible to endotoxemia. Bacterial-derived toxins cause endotoxemia by promoting inflammatory processes and immune cell infiltration in different organs and systems while impacting metabolic function by altering lipolysis, mitochondrial activity, and insulin sensitivity. In dairy cows, endotoxins enter the bloodstream after overcoming the defense mechanisms of the epithelial barriers, particularly during common periparturient conditions such as mastitis, metritis, and pneumonia, or after abrupt changes in the gut microbiome. In the bovine AT, endotoxins induce a pro-inflammatory response and stimulate lipolysis in AT, leading to the release of free fatty acids into the bloodstream. When excessive and protracted, endotoxin-induced lipolysis can impair adipocyte's insulin signaling pathways and lipid synthesis. Endotoxin exposure can also induce oxidative stress in AT through the production of reactive oxygen species by inflammatory cells and other cellular components. This review provides insights into endotoxins' impact on AT function, highlighting the gaps in our knowledge of the mechanisms underlying AT dysfunction, its connection with periparturient cows' disease risk, and the need to develop effective interventions to prevent and treat endotoxemia-related inflammatory conditions in dairy cattle.

关键词： Adipose tissue dysfunction Endotoxin Inflammation Insulin resistance

Slope reliability and back analysis of failure with geotechnical parameters estimated using Bayesian inference

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Journal of Rock Mechanics and Geotechnical Engineering 2019年第3期11卷 628-643页

作者： Luis-Fernando contreras Edwin T.Brown The University of Queensland St Lucia Campus

A Bayesian approach is proposed for the inference of the geotechnical parameters used in slope *** methodology involves the construction of posterior probability distributions that combine prior information on the parameter values with typical data from laboratory tests and site investigations used in *** posterior distributions are often complex,multidimensional functions whose analysis requires the use of markov chain Monte Carlo(MCMC)*** procedures are used to draw representative samples of the parameters investigated,providing information on their best estimate values,variability and *** paper describes the methodology to define the posterior distributions of the input parameters for slope design and the use of these results for evaluation of the reliability of a slope with the first order reliability method(FORM).The reliability analysis corresponds to a forward stability analysis of the slope where the factor of safety(FS)is calculated with a surrogate model from the more likely values of the input *** Bayesian model is also used to update the estimation of the input parameters based on the back analysis of slope *** this case,the condition FS?1 is treated as a data point that is compared with the model prediction of *** analysis requires a sufficient number of observations of failure to outbalance the effect of the initial input *** parameters are updated according to their uncertainty,which is determined by the amount of data supporting *** methodology is illustrated with an example of a rock slope characterised with a Hoek-Brown rock mass *** example is used to highlight the advantages of using Bayesian methods for the slope reliability analysis and to show the effects of data support on the results of the updating process from back analysis of failure.

关键词： Bayesian analysis Hoek-Brown criterion Slope reliability Back analysis of failure

Oligo-carrageenan kappa increases C, N and S assimilation, auxin and gibberellin contents, and growth in Pinus radiata trees

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Journal of Forestry Research 2015年第3期26卷 635-640页

作者： Silvia Saucedo Rodrigo A. contreras Alejandra Moenne University of Santiago of Chile Santiago Chile Facultad de Ciencias Agrarias Universidad Te'cnica Estatal de Quevedo 63 Quevedo Ecuador

Oligo-carrageenans （OCs） obtained from pure carrageenans extracted from marine red algae stimulate growth by enhancing photosynthesis and basal metabolism in tobacco plants and Eucalyptus trees. In addition, OCs stimulate secondary metabolism, increasing the level of metabolites involved in defense against pathogens. In this work, we analyzed the effect of OC kappa on the increase in height, in activities of basal metabolism enzymes in- volved in carbon, nitrogen and sulphur assimilation, ribu- lose 1,5 biphosphate carboxylase/oxygenase （rubisco）, glutamate dehydrogenase （GDH） and O-acetylserine thiol- lyase （OASTL）, and in the level of growth-promoting hormones, the auxin indole acetic acid （IAA） and the gibberellin GA3, in pine （Pinus radiata） trees treated with OC kappa at concentrations of 1 and 5 mg mL-1 and cultivated for 9 months without additional treatment. Pines treated with OC kappa at 1 mg mL-1 showed a similar increase in height but displayed a higher increased in total chlorophyll, activities of rubisco, GDH and OASTL and level of IAA and GA3 than those treated with OC kappa at 5 mg mL-1. Thus, OC kappa stimulates growth and basal metabolism and increases the level of growth-promoting hormones in pine trees, mainly at 1 mg mL-1.

关键词： Auxin Basal metabolism C, N and Sassimilation Gibberellin Oligo-carrageenan kappaPinus radiata

Extracellular vesicles in Alzheimer’s disease:from pathology to therapeutic approaches

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Neural Regeneration Research 2023年第1期18卷 18-22页

作者： marta Garcia-contreras Avnesh S.Thakor Interventional Regenerative Medicine and Imaging Laboratory Department of RadiologyStanford UniversityPalo AltoCAUSA

Alzheimer’s disease is a progressive and fatal neurodegenerative disorder that starts many years before the onset of cognitive *** novel biomarkers for Alzheimer’s disease has the potential for patient risk stratification,early diagnosis,and disease monitoring in response to therapy.A novel class of biomarkers is extracellular vesicles given their sensitivity and specificity to specific *** addition,extracellular vesicles can be used as novel biological therapeutics given their ability to efficiently and functionally deliver therapeutic *** is critical given the huge unmet need for novel treatment strategies for Alzheimer’s *** review summarizes and discusses the most recent findings in this field.

关键词： Alzheimer’s disease brain diagnostic extracellular vesicles isolation methods microglia neurodegenerative diseases neuroinflammation neurons therapy