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Intranasal delivery of nanostructured lipid carriers,solid lipid nanoparticles and nanoemulsions:A current overview of in vivo studies

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Acta Pharmaceutica Sinica B 2021年第4期11卷 925-940页

作者： Cláudia Pina Costa Joao Nuno Moreira josémanuel Sousa Lobo Ana Catarina silva UCIBIO/REQUIMTE MedtechLaboratory of Pharmaceutical TechnologyDepartment of Drug SciencesFaculty of PharmacyUniversity of PortoPorto 4050-313Portugal CNC-Center for Neuroscience and Cell Biology Center for Innovative Biomedicine and Biotechnology(CIBB)University of CoimbraFaculty of Medicine(Pólo I)Coimbra 3004-504Portugal UC-University of Coimbra CIBBFaculty of PharmacyPólo Das Ciências da SaúdeCoimbra 3000-548Portugal FP-ENAS(UFP Energy Environment and Health Research Unit)CEBIMED(Biomedical Research Centre)Faculty of Health SciencesUniversity Fernando PessoaPorto 4249-004Portugal

The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the *** the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising *** addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc *** review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain *** on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal *** results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried *** the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the *** systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.

关键词： Nose-to-brain delivery Intranasal administration Nanostructured lipid carriers NLC Solid lipid nanoparticles SLN Nanoemulsions In vivo studies Pharmacokinetic Pharmacodynamics

MEAT AND MEAT PRODUCTS

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Journal of Integrative Agriculture 2013年第11期12卷 1916-1918页

作者： josé M lorenzo Centro Tecnológico de la Carne de Galicia

In recent years, meat quality has assumed a greater consumer significance and public attention. There is growing awareness of the link between diet and health and this is reflected in the demand for more information a... 详细信息

关键词： MEAT AND MEAT PRODUCTS

Effect of the Inclusion of Chestnut in the Finishing Diet on Volatile Compounds of Dry-Cured Ham from Celta Pig Breed

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Journal of Integrative Agriculture 2013年第11期12卷 2002-2012页

作者： josé M lorenzo Javier Carballo Daniel Franco Centro Tecnológico de la Carne de Galicia Rúa Galicia No 4Parque Tecnológico de GaliciaSan Cibrán das Vias rea de Tecnología de los Alimentos Facultad de Ciencias de OurenseUniversidad de Vigo

The effect of the inclusion of chestnut in pigs ifnishing diet on volatile compounds of dry-cured Celta ham was studied. Twelve hams of each type （from three different pigs ifnishing diets：concentrate （CO）, mixed （MI） and chestnut （CH）） were used. Volatiles were extracted using a purge-and-trap method and analyzed by gas chromatography/mass spectrometry （GC/MS）. Thirty-nine volatile compounds were identified in dry-cured Celta ham samples. Most abundant volatiles in ham samples were aldehydes, which represented respectively, 53% （CO）, 51% （MI） and 46% （CH） of the total volatile composition. With the exception of 2-butenal, 2-methyl, all aldehydes were affected by feeding system. On the other hand, hydrocarbons n-alkanes were the second major group in the volatile proifle of dry-cured Celta hams and represented 28.9, 35.7 and 32.4%of the total volatile composition for CO, MI and CH groups, respectively. Ham samples from chestnut group showed a higher content of alcohols and this result could be related with the inclusion of chestnut in the ifnishing diet of pigs. Principal component analysis showed a good separation among groups. The discriminant analysis selected eight variables （butanoic acid, hexanal, octanal, nonenal （E）, decenal （E）, tetradecane, decane trimethyl and pyridine 2-methyl） and calculated two discriminating functions to predict if chestnut has been included in the ifnishing diet. Thus, it was possible to discriminate between groups fed with ifnishing diets containing chestnuts in their composition （mixed and chestnut group）.

关键词： dry-cured ham chestnut volatile compound finishing diet discriminant analysis

sTWEAK is a marker of early haematoma growth and leukoaraiosis in intracerebral haemorrhage

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Stroke & Vascular Neurology 2021年第4期6卷 528-535,I0011,I0012页

作者： Andrés da silva-Candal Iria López-Dequidt manuel Rodriguez-Yañez PauloÁvila-Gómez josémanuel Pumar joséCastillo Tomás Sobrino Francisco Campos Ramón Iglesias-Rey Pablo Hervella Clinical Neurosciences Research Laboratory(LINC) Health Research Institute of Santiago de Compostela(IDIS)Santiago de CompostelaSpain Department of Neurology Hospital Clínico UniversitarioSantiago de CompostelaSpain Department of Neuroradiology Hospital Clínico UniversitarioSantiago de CompostelaSpain

Objective To study the association between early growth of haematoma with biomarkers of endothelial dysfunction such as leukoaraiosis(LA)and the soluble tumour necrosis factor-like weak inducer of apoptosis(sTWEAK)in patients with intracerebral haemorrhage(ICH).Methods This is a retrospective observational study of patients with nontraumatic *** and biochemical parameters were *** levels were measured by *** was analysed in the hemisphere without haemorrhage to avoid interference with the acute *** main endpoint was the haematoma growth evaluated by the difference in volume between the second and the initial *** functional outcome,defined as a modified Rankin Scale>2 at 3 months,was considered as secondary *** operating characteristic curve analysis was performed to stablish the best cut-off for sTWEAK levels associated with haematoma *** We included 653 patients with ICH in our analysis(71.1±11.9 years,44%women).Haematoma growth was observed in 188 patients(28.8%).sTWEAK levels≥5600 pg/mL predicted ICH growth with a sensitivity of 84%and a specificity of 87%.sTWEAK levels≥5600 pg/mL and the presence of LA were associated with haematoma growth(OR:42.46;(CI 95%22.67 to 79.52)and OR:2.73(CI 95%1.39 to 5.34),respectively).Also,the presence of LA(OR:4.31(CI 95%2.89 to 6.42))and the interaction between ICH growth and sTWEAK(OR:2.23(CI 95%1.40 to 3.55))were associated with poor functional outcome at 3 *** sTWEAKs,together with the presence and grade of LA,are biomarkers able to predict ICH growth and poor functional outcome in patients with ICH.

关键词： TWEAK intracerebral specificity

Predicting the aquatic risk of realistic pesticide mixtures to species assemblages in Portuguese river basins

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Journal of Environmental Sciences 2015年第5期27卷 12-20页

作者： Emília silva Michiel A.Daam Maria josé Cerejeira Centro de Engenharia dos Biossistemas (CEER) Instituto Superior de Agronomia (ISA) University of Lisbon (UL) Tapada da Ajuda1349-017 Lisbon Portugal

Although pesticide regulatory tools are mainly based on individual substances, aquatic ecosystems are usually exposed to multiple pesticides from their use on the variety of crops within the catchment of a river. This study estimated the impact of measured pesticide mixtures in surface waters from 2002 and 2008 within three important Portuguese river basins（＇Mondego＇, ＇Sado＇ and ＇Tejo＇） on primary producers, arthropods and fish by toxic pressure calculation. Species sensitivity distributions（SSDs）, in combination with mixture toxicity models, were applied. Considering the differences in the responses of the taxonomic groups as well as in the pesticide exposures that these organisms experience, variable acute multi-substance potentially affected fractions（ms PAFs） were obtained. The median msP AF for primary producers and arthropods in surface waters of all river basins exceeded 5%, the cut-off value used in the prospective SSD approach for deriving individual environmental quality standards. A ranking procedure identified various photosystem II inhibiting herbicides, with oxadiazon having the relatively largest toxic effects on primary producers, while the organophosphorus insecticides, chlorfenvinphos and chlorpyrifos, and the organochloride endosulfan had the largest effects on arthropods and fish, respectively. These results ensure compliance with European legislation with regard to ecological risk assessment and management of pesticides in surface waters.

关键词： Pesticides Mixtures Risk assessment Multi-substance potentially affected fraction Surface waters

Effectiveness of sacubitril-varsartan versus angiotensin converting enzyme inhibitors in patients hospitalized for acute heart failure:a retrospective cohort study of the RICA registry

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Journal of Geriatric Cardiology 2022年第11期19卷 802-810页

作者： Llanos Soler-Rangel manuel Méndez-Bailón joséPérez-Silvestre joséMaría Fernández-Rodríguez Beatriz Cuesta García Adrián Argüelles-Curto Álvaro González-Franco Alicia Conde-Martel Sara Carrascosa-García Marta Sánchez-Marteles josémanuel Cerqueiro-González Noel lorenzo-Villalba manuel Montero-Pérez-Barquero Llanos Soler-Rangel Servicio de Medicina InternaHospital Universitario Infanta SofíaFIIB HUIS HHENMadridSpain Servicio de Medicina Interna Hospital Clínico San CarlosInstituto de Investigación San Carlos(IdISSC)Spain Servicio de Medicina Interna Consorcio Hospital General Universitario de ValenciaSpain Servicio de Medicina Interna Hospital Carmen y Severo OchoaCangas del NarceaAsturiasSpain Servicio de Medicina Interna Hospital Universitario Central de AsturiasOviedoSpain Servicio de Medicina Interna Hospital Universitario de Gran Canaria Dr NegrínSpain Servicio de Medicina Interna Hospital Clínico Universitario Lozano Blesa de ZaragozaZaragozaSpain Hospital Universitario Lucus Augusti de Lugo LugoSpain Service de Médecine Interne Diabète et Maladies MétaboliquesHôpitaux Universitaires de StrasbourgFrance Servicio de Medicina Interna IMIBIC/Hospital Universitario Reina SofíaCórdobaSpain

BACKGROUND Sacubitril-valsartan has been shown to reduce hospitalizations and mortality in patients with heart failure(HF)and reduced ejection *** PIONEER-HF trial demonstrated that initiation of the drug during acute HF hospitalization reduced NT-proBNP levels and a post-hoc analysis of the trial found a reduction in HF hospitalizations and ***-life studies in the elderly population are *** aim of our study was to assess the effectiveness of sacubitril-valsartan versus angiotensin converting enzyme inhibitors(ACEI)in elderly patients who initiate this treatment during hospitalization for acute *** We conducted a retrospective cohort study using the Spanish acute heart failure registry(RICA)comparing rehospitalizations and deaths at 3 months and 1 year among patients aged 70 years or older who had initiated treatment with sacubitrilvalsartan during hospitalization for acute HF versus those treated with *** One hundred and ninety-nine patients hospitalized between October 2016 and November 2020 were included,with a median age of 82 years and high rate of *** these,107 were treated with sacubitril-valsartan and 92 with *** adjusted OR for readmission for HF at 3 months was 0.906(95%CI:0.241-3.404)and for the combined variable readmission for HF or death at 3 months was 0.696(95%CI:0.224-2.167).The adjusted OR for HF readmission at one year was 0.696(95%CI:0.224-2.167).and for the combined variable HF readmission or death at one year 0.724(95%CI:0.325-1.612).CONCLUSION Treatment with sacubitril-valsartan initiated early in hospitalization for HF in elderly patients with high comorbidity was associated with a trend towards a reduction in readmissions and death due to HF compared to treatment with ACEI,which did not reach statistical significance either at 3 months or 1 year of follow-up.

关键词： patients initiated admission

Miscibility of Poly(hydroxybutyrate)/Poly(vinyl alcohol)Melt Blends Plasticized With Glycerol

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Journal of Renewable Materials 2019年第4期7卷 325-333页

作者： Deliane da silva Cabral Antonio joséFelix Carvalho Department of Materials Engineering São Carlos School of EngineeringUniversity of São PauloAv.João Dagnone110013563-120São Carlos-SP-Brazil

Poly(hydroxybutyrate)/poly(vinyl alcohol)(PHB/PVA)blends plasticized with glycerol were prepared by melt blending of PHB and glycerol plasticized *** PHB/PVA-glycerol compositions were 90:10,75:25 and 50:50 w/w,being the concentration of glycerol in the PVA mixture of 10 wt%.The blends were characterized by infrared spectroscopy,dynamic-mechanical thermal analysis,and scanning electron microscope of the fragile fractured *** results showed one single phase blend,indicating miscibility corroborated by the presence of a single glass transition *** blending method proved to be an efficient way to tune PHB properties keeping its biodegradable nature since both PVA and glycerol are fully biodegradable materials.

关键词： Blend miscibility melt processing poly(hydroxybutyrate) poly(vinyl alcohol)

Microstructural Morphologies and Experimental Growth Laws during Solidification of Monotectic and Hypermonotectic Al-Pb Alloys

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Journal of Materials Science & Technology 2014年第4期30卷 401-407页

作者： Adrina P.silva Amauri Garcia josé E.Spinelli Department of Materials Engineering University of Campinas-UNICAMP Department of Materials Engineering Federal University of Sao Carlos-UFSCar

AI-Pb alloys with monotectic and hypermonotectic compositions were directionally solidified under unsteady- state heat flow conditions. The cooling curves recorded during solidification allowed solidification thermal parameters such as the cooling rate （T）, growth rate （v） and thermal gradient （G） to be experimentally determined. Different microstructural patterns have been associated with the alloy solute content, i.e., AI-1.2 and 2.1 wt% Pb. A sequence of morphologies from the bottom to the top of the A1-1.2 wt% Pb alloy casting （monotectic） can be observed： Pb-rich droplets in the aluminum-rich matrix, followed by a region of microstructural transition formed by droplets and fibers and finally by a mixture of fibers and strings of pearls. A completely fibrous structure （without transition） has been observed along the entire AI-2.1 wt% Pb alloy casting （hypermonotectic）. The interphase spacing （λ） was measured along the casting length, and experimental correlations between λand experimental solidification thermal parameters have been established. Power laws with a -2.2 exponent expressing λ as a function of the growth rate, v, were found to better represent the fibrous growth of both AI-Pb alloys. Moreover, a single experimental law expressing λ as a function of both G and v was found to describe the fibrous growth of both the monotectic and the hypermonotectic alloys experimentally examined.

关键词： Aluminum alloys Casting Phase transformation

Performance of masonry enclosure walls:lessons learned from recent earthquakes

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Earthquake Engineering and Engineering Vibration 2012年第1期11卷 23-34页

作者： Romeu silva Vicente Hugo Rodrigues Humberto Varum Aníbal Costa jos António Raimundo Mendes da silva University of Aveiro Civil Engineering Department Campus Universitario de SantiagoAveiroPT3810-193Portugal University of Coimbra Civil Engineering Pinhal de MarrocosPolo ⅡCoimbraPT3030Portugal

This paper discusses the issue of performance requirements and construction criteria for masonry enclosure and infill walls. Vertical building enclosures in European countries are very often constituted by non-load-bearing masonry walls, using horizontally perforated clay bricks. These walls are generally supported and confined by a reinforced concrete frame structure of columns and beams/slabs. Since these walls are commonly considered to be nonstructural elements and their influence on the structural response is ignored, their consideration in the design of structures as well as their connection to the adjacent structural elements is frequently negligent or insufficiently detailed. As a consequence, nonstructural elements, as for wall enclosures, are relatively sensitive to drift and acceleration demands when buildings are subjected to seismic actions. Many international standards and technical documents stress the need for design acceptability criteria for nonstructural elements, however they do not specifically indicate how to prevent collapse and severe cracking, and how to enhance the overall stability in the case of moderate to high seismic loading. Furthermore, a review of appropriate measures to improve enclosure wall performance and both in-plane and out-of-plane integrity under seismic actions is addressed.

关键词： RC structures masonry enclosure walls infill walls in-plane out-of-plane cracking performanceimprovement