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Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system

neural Regeneration Research 2017年第8期12卷 1231-1240页

作者： Julia J.Segura-Uribe rodolfo pinto-almazán Angélica Coyoy-Salgado Claudia E.Fuentes-Venado Christian Guerra-Araiza Unidad de Investigacion Modica en Enfermedades neurologicas Hospital de Especialidades Centro Medico Nacional Siglo XXI Instituto Mexicano del Seguro Social Mexico City Mexico Seccion de Estudios de Posgrado e Investigacion Escuela Superior de Medicina Instituto Politecnico Nacional Mexico City Mexico Unidad de Investigacion Hospital Regional de Alta Especialidad Ixtapaluca Ixtapaluca Mexico Institute for the Developing Mind Children's Hospital Los Angeles Los Angeles CA USA Department of Pediatrics Keck School of Medicine University of Southern California Los Angeles CA USA Consejo nacional de Ciencia y Tecnologia Mexico City Mexico Clinica de Trastornos del Sueno Universidad Autonoma Metropolitana-Iztapalapa Mexico City Mexico Servicio de Medicina Fisica y Rehabilitacion Hospital General de Zona No. 197 Texcoco Mexico Unidad de Investigacion Modica en Farmacologla Hospital de Especialidades Centro Medico Nacional Siglo XXI Instituto Mexicano del Seguro Social Mexico City Mexico

Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（nF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.

关键词： estrogen receptor modulators selective estrogen receptor modulators microtubules neurofilaments tibolone tamoxifen raloxifene

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Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone

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neural Regeneration Research 2018年第3期13卷 440-448页

作者： rodolfo pinto-almazán Julia J. Segura-Uribe Marvin A. Soriano-Ursúa Eunice D. Farfán-García Juan M. Gallardo Christian Guerra-Araiza Unidad de Investigación Hospital Regional de Alta Especialidad Ixtapaluca Carretera Federal México-Puebla km 34.5 C.P. 56530. Ixtapaluca State of Mexico Mexico Institute for the Developing Mind Children's Hospital Los Angeles Los Angeles CA USA Department of Pediatrics Keck School of Medicine University of Southern California Los Angeles CA USA Unidad de Investigación Médica en Enfermedades neurológicas Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Av. Cuauhtémoc 330 Col. Doctores. C. P. 06720. Mexico City Mexico Escuela Superior de Medicina Instituto Politécnico Nacional Plan de San Luis y Diaz Mirón Col. Casco de Santo Tomis. C. P. 11340. Mexico City Mexico Unidad de Investigación Médica en Enfermedades nefrológicas Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Av. Cuauhtémoc 330 Col. Doctores. C. P. 06720. Mexico City Mexico Unidad de Investigación Médica en Farmacologia Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Av. Cuauhtémoc 330 Col. Doctores. C. P. 06720. Mexico City Mexico

Oxidative stress （OS） is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone （TIB）, a synthetic hormone used as a treatment for menopausal ymptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone （O3） exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β （GSK3β）, and the inactivation of Akt and phosphatases PP2A and PTEn induced by O3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups： control group （ozone-free air plus vehicle [C]）, control ＋ TIB group （ozone-free air plus TIB 1 mg/kg [C ＋ TIB]）; 7,15, 30, and 60 days of ozone exposure groups [O3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O3 ＋ TIB]. The effects of O3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2A, and PTEn proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods （Marklund and TBARS, respectively）. We observed that O3 exposure increases Tau phosphorylation, which is correlated with decreased PP2A and PTEn protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O3 exposure were prevented by the long-term treatment （over 15 days） with TIB. Malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O3 exposure. Our results

关键词： tibolone oxidative stress ozone exposure Tau GSK3 hippocampus neuroprotection

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Polyphenols as potential enhancers of stem cell therapy against neurodegeneration

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neural Regeneration Research 2022年第10期17卷 2093-2101页

作者： Diana Rodríguez-Vera Antonio Abad-García nancy Vargas-Mendoza rodolfo pinto-almazán Eunice D.Farfán-García José A.Morales-González Marvin A.Soriano-Ursúa Sección de Estudios de Posgrado e Investigación.Escuela Superior de Medicina Instituto Politécnico NacionalMéxico CityMéxico Unidad de Investigación Hospital Regional de Alta Especialidad IxtapalucaCarretera Federal México-Puebla km 34.5State of MéxicoMéxico

The potential of polyphenols for treating chronic-degenerative diseases(particularly neurodegenerative diseases)is ***,the selection of the best polyphenol for each treatment,the mechanisms by which they act,and their efficacy are frequently *** this review,the basics and the advances in the field,as well as suggestions for using natural and synthetic polyphenols alone or in a combinatorial strategy with stem cell assays,are compiled and ***,stem cells exhibit several responses when polyphenols are added to their environment,which could provide us with knowledge for advancing the elucidation of the origin of *** also,polyphenols are being included in the innovative strategies of novel therapies for treating neurodegenerative diseases as well as metabolic diseases related to *** this regard,flavonoid compounds are suggested as the best natural polyphenols due to their several mechanisms for acting in ameliorative effects;but increasing reports are involving other *** if some facts limiting bioactivity prevent them from conventional use,some natural polyphenols and derivatives hold the promise for being improved compounds,judged by their induced *** current results suggest polyphenols as enhancers of stem cell therapy against the targeted diseases.

关键词： Alzheimer’s disease chronic degenerative diseases combinatorial therapy metabolism neurodegenerative diseases neuronal damage neuroprotection Parkinson’s disease polyphenols stem cell assays

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nonlinear criterion for strength mobilization in brittle failure of rock and its extension to the tunnel scale

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International Journal of Mining Science and Technology 2022年第4期32卷 685-705页

作者： rodolfo Cabezas Javier Vallejos Faculty of Engineering and Technology Universidad San SebastianSantiagoChile Advanced Mining Technology Center Universidad de ChileSantiagoChile Department of Mining Engineering Universidad de ChileSantiagoChile

As underground excavations are getting deeper and field stresses increase, the behavior of intact rock blocks plays an increasingly important role in understanding and estimating the overall rock mass strength. To model the brittle behavior of intact rock blocks, the stress–strain curve is usually idealized considering a linear strength mobilization approach(cohesion-weakening-friction-strengthening, CWFS),however, it is well recognized that rock presents a nonlinear behavior in terms of the confining *** study extends the strength mobilization in brittle failure of rock using nonlinear criteria. To determine the model parameters, a standard statistical method that uses the complete laboratory stress–strain curves of the intact rock is employed. Several hypotheses of linear and nonlinear models are statistically compared for different types of rock and confining stress levels. Results demonstrate that the best approach to model the brittle failure of rock is to consider a nonlinear strength envelope, such as the Hoek-Brown criterion assuming a residual uniaxial compressive strength different from zero and a mi parameter that increases, both with simultaneous mobilization. This model helps to recreate highconfining conditions and a more realistic transition between peak and post-peak strength. The obtained parameters are discussed and compared with literature values to verify the validity and to develop guidelines for the estimation of parameters, providing an objective mobilization criterion. Finally, the nonlinear model was applied to a finite element code and extended to a tunnel scale in the brittle rock under high-stress conditions. A reasonable fit between the simulations and the in-situ overbreak measurements was found.

关键词： nonlinear strength Strength mobilization Brittle failure Intact rock Scaling

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Fortification Challenges and needs

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Biomedical and Environmental Sciences 2001年第1期14卷 98-103页

作者： rodolfo F. FLOREnTInO President Philippine Association of Nutrition Philippines

Experience in many parts of the developing world has shown that food fortification offers a cost_effective and sustainable solution to the problem of micronutrient malnutrition. Building on the advances in science and technology and backed by studies on the economic benefits of fortification programs, governments and industry are beginning to respond positively to the call of nutrition advocates to adopt fortification as a long_term strategy. On the other hand, formidable challenges still remain in many countries in Asia, constraining the widespread adoption of this strategy. The science and technology community needs to provide adequate scientific and technological information as basis for planning and decision making. The government faces the challenge of providing the enabling environment for all stakeholders to cooperate in the fortification effort. Industry faces the challenge of adapting its production system to the requirements of fortification in order that they can contribute to social objectives while pursuing their economic objectives. The international and bilateral aid agencies need to seek tried and innovative ways to support the multiple players of food fortification, as these players in turn face the challenges that confront them.

关键词： Developing Countries Food Industry Food Fortified Asia Food Technology Humans nutrition Disorders Public Health

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Convergence in L^p-norm of Fourier Series on the Complete Product of Quaternion Groups with Bounded Orders

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Acta Mathematica Sinica,English Series 2014年第9期30卷 1566-1578页

作者： Gyrgy GAT rodolfo TOLEDO College of nyiregyhza Inst.of Math.and Comp.Sci.Nyiregyhza

A well-known result for Vilenkin systems is the fact that for all 1 〈 p 〈 oc the n-th partial sums of Fourier series of all functions in the space Lp converge to the function in LP-norm. This statement can not be generalized to any representative product system on the complete product of finite non-abelian groups, but even then it is true for the complete product of quaternion groups with bounded orders and monomial representative product system ordered in a specific way.

关键词： Fourier analysis Walsh-Paley system representative product systems complete product of quaternion groups convergence in norm

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Diffusion tensor imaging as a tool to detect presymptomatic axonal degeneration in a preclinical spinal cord model of amyotrophic lateral sclerosis

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neural Regeneration Research 2018年第3期13卷 425-426页

作者： rodolfo Gabriel Gatto Department of Anatomy and Cell Biology University of Illinois at Chicago

The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis （ALS）： ALS is a progressive neurological disease characterized primarily by the development of limb paralysis, which eventually leads to lack of control on muscles under voluntary control and death within 3–5 years. Genetic heterogeneity and environmental factors play a critical role in the rate of disease progression and patients display faster declines once the symptoms have manifested. Since its original discovery, ALS has been associated with pathological alterations in motor neurons located in the spinal cord （SC）, where neuronal loss by a mutation in the protein superoxide dismutase in parenthesis （mSOD1） and impairment in axonal connectivity, have been linked to early functional impairments. In addition,mechanisms of neuroinflammation, apoptosis, necroptosis and autophagy have been also implicated in the development of this disease. Among different animal models developed to study ALS, the transgenic G93A-SOD1 mouse has become recognized as a benchmark model for preclinical screening of ALS therapies. Furthermore, the progressive alterations in the locomotor phenotype expressed in this model closely resemble the progressive lower limb dysfunction of ALS patients. Among other imaging tools, MR diffusion tensor imaging （DTI） has emerged as a crucial, noninvasive and real time neuroimaging tool to gather information in ALS. One of the current concerns with the use of DTI is the lack of biological validation of the microstructural information given by this technique. Although clinical studies using DTI can provide a remarkable insight on the targets of neurodegeneration and disease course,they lack histological correlations. To address these shortcomings, preclinical models can be designed to validate the microstructural information unveiled by this particular MRI technique. Thus, the scope of this review is to describe how MRI diffusion and optical microscopy

关键词： ALS Diffusion tensor imaging as a tool to detect presymptomatic axonal degeneration in a preclinical spinal cord model of amyotrophic lateral sclerosis

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new technologies as a strategy to decrease medication errors: how do they affect adults and children differently?

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World Journal of Pediatrics 2016年第1期12卷 28-34页

作者： Margarita Ruano Elena Villamañán Ester Pérez Alicia Herrero rodolfo Álvarez-Sala Department of Pharmacy La Paz University HospitalMadridSpain Department of Pneumology La Paz University HospitalMadridSpain

Background:Medication error can occur throughout the drug treatment process,with special relevance in children given the risk of adverse effects resulting from a medication error is more prevalent than in *** significance of medication error in children is also greater because small error that would be tolerated in adults can cause significant damage in ***,the likelihood of injury is higher than in *** sources:Based on the data published,most medication errors take place in prescribing and administration stages in both *** in account that child's risk factors are different from those of adults,with some specific causes to pediatrics,we have reviewed available data about new technologies as a strategy to reduce pediatric medication ***:Even though there is a lack of standardized definitions and terminology that makes studies difficult to compare,we checked that new technologies have proven to be effectives in reducing medication errors,mainly computerized physician order entry(CPOE)and platforms to aid ***,we also observed that the use of these informatic tools can also generate new ***:Implementation of CPOE programs for pediatrics,communication improvement between healthcare professionals taking care of admitted children and the knowledge of these programs should be the mayor priorities for the safety of hospitalized children.

关键词： electronic prescribing new technologies pediatric medication errors

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Preliminary examination of early neuroconnectivity features in the R6/1 mouse model of Huntington's disease by ultra-high field diffusion MRI

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neural Regeneration Research 2022年第5期17卷 983-986页

作者： rodolfo G.Gatto Carina Weissmann Department of Bioengineering the University of Illinois at ChicagoChicagoILUSA Instituto de Fisiología Biología Molecular y neurociencias-IFIBYnECOnICET Universidad de Buenos AiresBuenos AiresArgentina

During the last decades,advances in the understanding of genetic,cellular,and microstructural alterations associated to Huntington's disease(HD)have improved the understanding of this progressive and fatal ***,events related to early neuropathological events,neuroinflammation,deterioration of neuronal connectivity and compensatory mechanisms still remain vastly ***-high field diffusion MRI(UHFD-MRI)techniques can contribute to a more comprehensive analysis of the early microstructural changes observed in *** addition,it is possible to evaluate if early imaging microstructural parameters might be linked to histological ***,qualitative studies analyzing histological complexity in brain areas susceptible to neurodegeneration could provide information on inflammatory events,compensatory increase of neuroconnectivity and mechanisms of brain repair and *** application of ultra-high field diffusion-MRI technology in animal models,particularly the R6/1 mice(a common preclinical mammalian model of HD),provide the opportunity to analyze alterations in a physiologically intact model of the *** some disparities in volumetric changes across different brain structures between preclinical and clinical models has been documented,further application of different diffusion MRI techniques used in combination like diffusion tensor imaging,and neurite orientation dispersion and density imaging have proved effective in characterizing early parameters associated to alteration in water diffusion exchange within intracellular and extracellular compartments in brain white and grey ***,the combination of diffusion MRI imaging techniques and more complex neuropathological analysis could accelerate the discovery of new imaging biomarkers and the early diagnosis and neuromonitoring of patients affected with HD.

关键词： brain repair diffusion tensor imaging Huntington's disease neurite orientation dispersion and density imaging neuroconnectivity neuroinflammation neuroplasticity neuroregeneration R6/1 mice ultra-high field diffusion MRI

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The impact of different corona models on FD algorithms for the solution of multiconductor transmission lines equations

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High Voltage 2021年第5期6卷 822-835页

作者： Erika Stracqualursi rodolfo Araneo Amedeo Andreotti DIAEE-Electrical Engineering Division University of Rome“La Sapienza”RomeItaly Electrical Engineering Department University Federico II of NapoliNapoliItaly

In this study,the implementation of different corona discharge models in a transient program for overhead multiconductor lines based on the implicit Crank‐nicolson Finite Difference Time Domain method is *** different corona models available in the literature,two empirical models(Gary's and Suliciu's models)and a physics‐based model(Malik's model)are discussed,which are broadly used in EMT programs,and their predictions under fast‐front lightning surges and slow‐front switching impulses are *** authors critically review the dynamic capacitance approach in terms of numerical accuracy,when dealing with slowly varying voltages,and applicability,regarding dispersive models assuming a non‐instantaneous charge‐voltage *** alternative voltage‐controlled generator approach is proposed,which is successfully included in the implicit Crank‐nicolson *** of the objectives of this study is to show how different corona models may predict overvoltages with huge discrepancies,depending on the transient waveform and the propagation distance,despite the similarity of the q‐v hysteresis *** evident discrepancies between models under fast‐front voltage waves are reported,rather than for switching *** consistency of these results in terms of the models'features and q‐v curves is analysed,highlighting the necessity for new engineering tools for corona simulation of general predictive capability.

关键词： conductor transient dealing

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