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Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage:Comparative analytical study of physicochemical quality attributes

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Journal of Pharmaceutical Analysis 2020年第6期10卷 532-545页

作者： Natalia Navas Jesús Hermosilla anabel torrente-lopez Jose Hernandez-Jimenez Jose Cabeza Raquel Perez-Roblesa Antonio Salmeron-García Department of Analytical Chemistry Science Faculty/Biomedical Research Institute ibs.GranadaUniversity of GranadaGranadaE-18071Spain UGC Farmacia Hospitalaria Biomedical Research Institute ibs.Granada.Hospital Universitario San Cecilio de GranadaGranadaE-18012Spain

COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest that cytokine storms(interleukins)may play an important role in severe cases of COVID-19.Neutralizing key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality rate.Tocilizumab(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS patients.Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical trials.This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug shortages.Here,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of TCZ.It is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.

关键词： COVID-19 Tocilizumab Critical quality attributes IV and SC medicines

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Environmental enrichment as a promising strategy for aiding multiple sclerosis treatment

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Neural Regeneration Research 2020年第9期15卷 1660-1661页

作者： Berenice anabel Silva Carina Cintia Ferrari Instituto de Medicina Translacional e Ingenieria Biomedica del Hospital italiano(IMTIB-CONICET) Leloir Institute Foundation Institute for Biochemical InvestigationsIIBBA-CONICETBuenos AiresArgentina

Multiple sclerosis(MS)is a complex chronic disease of the central nervous system(CNS)which includes three main anatomopathological characteristics:inflammation,demyelination,neurodegeneration.This pathology induces many clinical symptoms,depending on the site of the lesions,such as motor,sensitive,visual,urinary and cognitive manifestations.In addition,MS is a very heterogeneous disease that displays different clinical courses or phenotypes(relapsing/remitting MS,primary progressive MS(PPMS)and secondary progressive MS(SPMS).Both neurodegeneration and inflammation are present along the natural history of the disease.However,the balance of both phenomena varies according to the course of the disease.In relapsing/remitting MS form,the acute inflammation,mainly adaptive immunity,predominates over the neurodegeneration,being the main cause of the relapses.In SPMS and PPMS,the neurodegeneration predominates over the inflammation,which appears as chronic inflammation,being innate immunity(microglia and astroglia)the main feature in the neurodegenerative process.

关键词： inflammation immunity sclerosis

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Expression and function of renal and hepatic organic anion transporters in extrahepatic cholestasis

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World Journal of Gastroenterology 2012年第44期18卷 6387-6397页

作者： anabel Brandoni María Herminia Hazelhoff Romina Paula Bulacio Adriana Mónica Torres Pharmacology Unit Department of Physiological SciencesFaculty of Biochemical and Pharmaceutical SciencesNational University of Rosariothe National Scientific and Technical Research Council2000 RosarioArgentine

Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.

关键词：有机阴离子转运蛋白胆汁盐肝脏肾脏淤积非甾体类抗炎药抗病毒药物

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Role of inflammatory cytokines in peripheral nerve injury

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Neural Regeneration Research 2012年第29期7卷 2259-2266页

作者： Federica Fregnan Luisa Muratori anabel Rodriguez Simǒes Maria Giuseppina Giacobini-Robecchi Stefania Raimondo Department of Clinical and Biological Sciences University of TurinOrbassano 10043 TurinItaly Neuroscience Institute of the "Cavalieri Ottolenghi" Foundation Orbassano 10043TurinItaly

Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.

关键词： pro-inflammatory cytokines anti-inflammatory cytokines inflammatory reaction peripheral nervoussystem nerve injury wallerian degeneration Schwann cells macrophage axonal regeneration myelin neural regeneration

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Plant-herbivore assemblages under natural conditions are driven by plant size,not chemical defenses

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Journal of Plant Ecology 2017年第6期10卷 1012-1021页

作者： Eva Castells Maria Morante Sandra Saura-Mas anabel Blasco-Moreno Departament de Farmacologia Terapèutica i ToxicologiaUniversitat Autònoma de BarcelonaCerdanyola del Vallès 08193Spain CREAF Cerdanyola del Vallès 08193Spain Department de Biologia Animal Vegetal i EcologiaUniversitat Autònoma de BarcelonaCerdanyola del Vallès 08193Spain Servei d’Estadística Aplicada Universitat Autònoma de BarcelonaCerdanyola del Vallès 08193Spain

Aims Plant secondary metabolites have been traditionally recognized as key traits regulating plant-herbivore assemblages.However,the ecological relevance of secondary metabolites as resistance mecha-nisms in comparison to other plant attributes,including physical,morphological or ecological traits,has been recently questioned.We aim to evaluate the role of chemical defenses,plant size and the presence of insect competitors on driving the differences in her-bivory damage under natural conditions.Methods We performed a replicated field study on the herbivore commu-nity associated with four Senecio species(S.lividus,S.vulgaris,S.inaequidens and S.pterophorus)during a full-reproductive season in Montseny Natural Park(catalonia,NE Spain).Pyrrolizidine alka-loids(PAs),the most characteristic chemical defenses of Senecio due to their toxic effects on herbivores,were analyzed by gas chro-matography.Individual plant size was estimated by the number of flower heads produced over the entire reproductive season.We used linear mixed models to explore the relationships between total PA concentrations,plant size and herbivory levels.Important Findings PA concentrations were not related to the natural guild of herbivores within any plant species or insect type.Moreover,no significant interactions were found between insect species sharing the same host plants.In contrast,herbivore abundance was positively related to plant size in S.vulgaris,S.lividus and S.inaequidens.We found no evidence that PAs confer an increased plant resistance against herbivores in Senecio.Our study supports the hypothesis that plant chemical defenses have a secondary role in determining plant-her-bivore assemblages in comparison to other plant traits under the complexity of natural conditions.

关键词： Senecio herbivory chemical defenses pyrrolizidine alkaloids plant traits

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A Mean Curvature Regularized Based Model for Demodulating Phase Maps from Fringe Patterns

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Communications in Computational Physics 2018年第6期24卷 27-43页

作者： Carlos Brito-Loeza Ricardo Legarda-Saenz Arturo Espinosa-Romero anabel Martin-Gonzalez CLIR at Facultad de Matematicas Universidad Autonoma de YucatanMexico

We introduce a variationalmethod for demodulating phasemaps fromfringe patterns.This newmethod is based on themean curvature of the level sets of the phase surface that is used for regularization.The performance of th... 详细信息

关键词： Fringe analysis interferometry high-order regularization variational models

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Mainstreaming the nexus approach in climate services will enable coherent local and regional climate policies

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Advances in Climate Change Research 2021年第5期12卷 752-755页

作者： Nicu Constantin TUDOSE Roger CREMADES Annelies BROEKMAN anabel SANCHEZ-PLAZA Hermine MITTER Mirabela MARIN National Institute for Research and Development in Forestry“Marin Dracea”(INCDS) Ilfov County077190Romania Wageningen University and Research Leeuwenborch BuildingWageningenKN6706the Netherlands Climate Service Center Germany(GERICS) Hamburg20095Germany CREAF Centre de Recerca Ecològica i Aplicacions ForestalsCataloniaE08193Spain Institute for Sustainable Economic Development Department of Economics and Social SciencesUniversity of Natural Resources and Life SciencesVienna1180Austria Transilvania University of Brașov Brasov500036Romania

The current challenges that society faces call for actions fostering climate change adaptation and long-term sustainability grounded in effective policies. Consequently, to raise environmental resilience and sustain human wellbeing, we need to overhaul the policy-making process towards a ‘holistic approach’. The nexus approach has proven a valuable tool for identifying gaps and incoherencies in current policies, for understanding major interlinkages across sectors and scales, and for promoting the Sustainable Development Goals (SDGs). Nevertheless, a ‘silo approach’ to decision making currently prevails, thus achieving cross-sectoral and cross-scale harmonization still remains a challenge in policy-making. In response to this challenge, the next step in the science–policy–practice interface is to integrate the nexus approach in the ‘climate services’ arena, in order to support integrated policies. Climate services embody a bridge between researchers and stakeholders, and by supporting integrated policies they will ensure synergies between sectors and scales, reduce potential trade-offs, and enable co-benefits.

关键词： Stakeholders Nexus Climate services Cross-sectoral policies Climate resilience

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Research progress on protective coatings against molten nitrate salts for thermal energy storage in concentrating solar power plants

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Baosteel Technical Research 2023年第4期17卷 1-16页

作者： HOU Wenjie Maria Elena Navarro Rivero PAN Jin ZOU Boyang Benjamin Grégoire anabel Palacios DING Yulong Baowu Carbon Technology Co. Ltd.Shanghai 201999China Birmingham Centre for Energy Storage&School of Chemical Engineering University of BirminghamBirmingham B152TTUnited Kingdom

Concentrating solar power(CSP) has garnered considerable global attention as a reliable means of generating bulk electricity, effectively addressing the intermittent nature of solar resources.The integration of molten salt technology for thermal energy storage(TES) has further contributed to the growth of CSP plants;however, the corrosive nature of molten salts poses challenges to the durability of container materials, necessitating innovative corrosion mitigation strategies.This review summarizes scientific advancements in high-temperature anticorrosion coatings for molten nitrate salts, highlighting the key challenges and future trends.It also explores various coating types, including metallic, ceramic, and carbon-based coatings, and compares different coating deposition methods.This review emphasizes the need for durable coatings that meet long-term performance requirements and regulatory limitations, with an emphasis on carbon-based coatings and emerging nanomaterials.A combination of multiple coatings is required to achieve desirable anticorrosion properties while addressing material compatibility and cost considerations.The overall goal is to advance the manufacturing, assembly, and performance of CSP systems for increased efficiency, reliability, and durability in various applications.

关键词： anticorrosive coating high temperature molten salt concentrated solar power thermal energy storage

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Expression of renal Oat5 and NaDC1 transporters in rats with acute biliary obstruction

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World Journal of Gastroenterology 2015年第29期21卷 8817-8825页

作者： anabel Brandoni Adriana Mónica Torres Pharmacology Department of Physiological Sciences Faculty of Biochemical and Pharmaceutical Sciences National University of Rosario

AIM: To examine renal expression of organic anion transporter 5(Oat5) and sodium-dicarboxylate cotransporter 1(Na DC1), and excretion of citrate in rats with acute extrahepatic cholestasis.METHODS: Obstructive jaundice was induced in rats by double ligation and division of the common bile duct(BDL group). Controls underwent sham operation that consisted of exposure, but not ligation, of the common bile duct(Sham group). Studies were performed 21 h after surgery. During this period, animals were maintained in metabolic cages in order to collect urine. The urinary volume was determined by gravimetry. The day of the experiment, blood samples were withdrawn and used to measure total and direct bilirubin as indicative parameters of hepatic function. Serum and urine samples were used for biochemical determinations. Immunoblotting for Oat5 and Na DC1 were performed in renal homogenates and brush border membranes from Sham and BDL rats. Immunohistochemistry studies were performed in kidneys from both experimental groups. Total RNA was extracted from rat renal tissue in order to perform reverse transcription polymerase chain reaction. Another set of experimental animals were used toevaluate medullar renal blood flow(m RBF) using fluorescent microspheres.RESULTS: Total and direct bilirubin levels were significantly higher in BDL animals, attesting to the adequacy of biliary obstruction. An important increase in m RBF was determined in BDL group(Sham: 0.53 ± 0.12 m L/min per 100 g body weight vs BDL: 1.58 ± 0.24 m L/min per 100 g body weight, P < 0.05). An increase in the urinary volume was observed in BDL animals. An important decrease in urinary levels of citrate was seen in BDL group. Besides, a decrease in urinary citrate excretion(Sham: 0.53 ± 0.11 g/g creatinine vs BDL: 0.07 ± 0.02 g/g creatinine, P < 0.05) and an increase in urinary excretion of H+(Sham: 0.082 ± 0.03 μmol/g creatinine vs BDL: 0.21 ± 0.04 μmol/g creatinine, P < 0.05) were observed in BDL animals. We found upregulations of both proteins Oat5 and Na DC1

关键词： Cholestasis Kidney Transporters Organicanions

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Gamma Irradiation Effect on Nylon 6-12 Modification under Argon Atmosphere

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材料科学与工程（中英文B版） 2012年第4期2卷 247-254页

作者： Carmina Menchaca Griselda Demesa anabel Santiaguillo Gonzalo Martinez-Barrera Hetor lopez-Valdivia Hetor Carrasco Jorge Uruchurtu Centro de Investigacion en Ingenieria y Ciencias Aplicadas （CIICAp） Universidad Aut6noma del Estado de Morelos Cuernavaca Morelos Mexico Laboratorio de Investigacion y Desarrollo de Materiales Avanzados （LIDMA） Facultad de Quimica Universidad Aut6noma del Estado de Mexico Edo. de Mexico Mexico Sintesis y Caracterizacion de Materiales Instituto Nacional de lnvestigaciones Nucleares Edo. de Mexico Mexico

Nylon is an important industrial material, and gamma irradiation is used for material modification. In this work, different gamma radiation dose were applied to crystalline fibres of nylon 6-12 at room temperature under argon atmosphere. Post-radiation effect was also studied, to know the effects of time. Some physical properties were measured obtaining the degree of modification with respect to the applied dose. X-ray values showed increment on the crystallinity and crystal size with dose increase up to 300 kGy. Brill Transition can be appreciated as a result of the in-situ X-ray with temperature study. Thermal analyses and AFM roughness measurements corroborate the modifying mechanisms in terms of the applied dose. For 15 and 50 kGy re-polymerization and crosslinking are the main mechanisms. Increment in the melting point at 15 kGy occurs, returning at 50 kGy to the original value. For 100 to 300 kGy the chain scission is the dominant mechanism because the melting point is lower than the original one. Both mechanisms take place in the amorphous zone.

关键词：改性尼龙辐射效应氩气保护伽玛辐射剂量原子力显微镜 γ射线辐照粗糙度测量

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