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Pharmacokinetics of sildenafil in children with pulmonary arterial hypertension

World Journal of Pediatrics 2017年第6期13卷 588-592页

作者： Hugo Juárez Olguín Hector Osnaya Martínez Carmen Flores Pérez blanca ramírez mendiola Liliana Rivera Espinosa Juan Luis Chávez Pacheco Janett Flores Pérez Ignacio Mora Maga(n)a Laboratory of Pharmacology National Institute of PediatricsMexico CityMexico Department of Pharmacology Faculty of MedicineNational Autonomous University of MexicoMexico CityMexico Service of Cardiology National Institute of PediatricsMexico CityMexico Laboratory of Pharmacology National Institute of PediatricsMexico CityMexico Subdirection of Teaching and Educational Programming National Institute of PediatricsMexico CityMexico

Background:Recently,sildenafil was introduced to treat pulmonary arterial hypertension (PAH);however,there are currently few studies on the pharmacokinetics of sildenalfil in ***,we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single ***:Twelve children diagnosed with PAH,consisting of with ten males and two females,were recruited for the study after obtaining written consent from their parents or *** samples were obtained predose and at 0.25,0.5,1,2,4,8 and 12 hours after the oral administration of 1 mg/kg of sildenafil using an extemporal pediatric formulation developed in our *** samples were analyzed using a previously validated high performance liquid chromatography ***:A pharmacokinetic analysis using the WinNonlin 3.1 program that considered the Akaike information criterion (AIC) for sdecting a more adjustable model was *** following pharmacokinetic parameters were obtained:maximal concentration (Cmax):366+179 ng/mL,time to maximal concentration:0.92±0.30 hours,elimination half-life (t1/2):2.41±1.18 hours,total clearance (CLto/F):5.85±2.81 L/hour,volume of distribution (Vd/F):20.13±14.5 L,absorption rate constants (Ka):0.343 hour-1,elimination rate (Ke):0.35 hour-1,area under curve from zero to infinity:2061±618 ng/mL/*** data of all patients adjusted to the model of one compartment were corroborated using ***:The parameters Ka,Ke and t1/2 were found to be similar to those reported in adults;however,the values of Cmax and Vd/F were significantly *** on these findings,we propose that treatment regimen of sildenafil be adjusted in children with PAH.

关键词： pharmacokinetics pulmonary arterial hypertension sildenafil

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Development and Validation of a Method to Quantify Midazolam in a New Oral Formulation for Pediatric Use

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American Journal of Analytical Chemistry 2012年第8期3卷 552-558页

作者： Carmen Flores Pérez Juan Luis Chávez Pacheco Janett Flores Pérez Hugo Juárez Olguín blanca ramírez mendiola Raquel García álvarez José Francisco González Zamora ángel Changin Guerra Chocolates Turínò S.A. de C.V. Departamento de Anestesia y Quirófano INP Laboratorio de Farmacología Instituto Nacional de Pediatría (INP)

Aim: To develop an HPLC method to quantify midazolam in a new oral formulation for pediatric use. Methods: The stability of the new formulation was evaluated at different storage conditions and a preliminary assay of relative bioavailability was carried out in healthy volunteers. Results: The method of quantification was linear in the range of 5 to 60 μg·mL-1. The midazolam amount in the formulation remained stable for 90 days at 4 and 40℃ (in the dark) while at 25℃ was stable only for 14 days (exposed to light). Discussion: The relative bioavailability assay suggests that our preparation of midazolam in white chocolate reaches plasma levels similar to those induced by the apple juice formulation. Conclusion: This new white chocolate formulation masks the unpleasing flavour and has a more attractive presentation to the paediatric patient, which may be useful for children sedation and to ease its management by health carers.

关键词： Children Liquid Chromatography Magistral Formulation Midazolam

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Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration

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Neural Regeneration Research 2024年第12期19卷 2626-2636页

作者： blanca Molins Andrea Rodríguez Víctor Llorenç Alfredo Adán Group of Ocular Inflammation:Clinical and Experimental Studies Institut d’Investigacions Biomèdiques AgustíPi I Sunyer(IDIBAPS)BarcelonaSpain Institut Clínic d’Oftalmologia(ICOF) Hospital Clínic BarcelonaSpain

Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the ***,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular *** in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying *** Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie *** the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of *** review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic ***,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.

关键词： age-related macular degeneration Bruch's membrane decellularization retinal pigment epithelium scaffold

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Latest developments in early diagnosis and specific treatment of severe influenza infection

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Journal of Intensive Medicine 2024年第2期4卷 160-174页

作者： Francisco Valenzuela-Sánchez blanca Valenzuela-Méndez Juan Francisco Rodríguez-Gutiérrez Ángel Estella Intensive Care Unit University Hospital of JerezRonda de Circunvalación s/nJerez de la FronteraSpain Haematology Department University Hospital of JerezRonda de Circunvalación s/nJerez de la FronteraSpain Centro de Investigación Biomédica en Red Enfermedades respiratoriasCIBERESInstituto de Salud Carlos IIIAv.de Monforte de LemosMadridSpain Department of Oncological Surgery Institut du Cancer de Montpellier(ICM)Parc Euromédecine208 Av.des ApothicairesMontpellierFrance Department of Medicine Faculty of MedicineUniversity of CádizCalle Doctor MarañónCádizSpain Instituto de Investigación e Innovación Biomédica de Cádiz(INIBiCA) Avenida Ana de Viya 21CádizSpain

Influenza pandemics are unpredictable recurrent events with global health,economic,and social *** objective of this review is to provide an update on the latest developments in early diagnosis and specific treatment of the disease and its complications,particularly with regard to respiratory organ *** advances in treatment,the rate of mortality in the intensive care unit remains approximately 30%.Therefore,early identification of potentially severe viral pneumonia is extremely important to optimize treatment in these *** pathogenesis of influenza virus infection depends on viral virulence and host ***,in some patients,it is associated with an excessive systemic response mediated by an authentic cytokine *** process leads to severe primary pneumonia and acute respiratory distress *** prognostication in the emergency department based on comorbidities,vital signs,and biomarkers(e.g.,procalcitonin,ferritin,human leukocyte antigen-DR,mid-regional proadrenomedullin,and lactate)is *** of these biomarkers on admission may facilitate clinical decision-making to determine early admission to the hospital or the intensive care *** decisions are reached considering pathophysiological circumstances that are associated with a poor prognosis(e.g.,bacterial co-infection,hyperinflammation,immune paralysis,severe endothelial damage,organ dysfunction,and septic shock).Moreover,early implementation is important to increase treatment *** on a limited level of evidence,all current guidelines recommend using oseltamivir in this *** possibility of drug resistance should also be *** options include other antiviral drugs and combination therapies with monoclonal ***,it is not recommended to use corticosteroids in the initial treatment of these ***,the implementation of supportive measures for respiratory failure is ***

关键词： Influenza Pandemic Respiratory failure Acute respiratory distress syndrome Intensive care unit admission

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Obstructive uropathy: Overview of the pathogenesis, etiology and management of a prevalent cause of acute kidney injury

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World Journal of Nephrology 2024年第2期13卷 5-15页

作者： Xabier Pérez-Aizpurua ramiro Cabello Benavente Gonzalo Bueno Serrano JoséMaría Alcázar Peral blanca Gómez-Jordana Mañas Jaime Tufet i Jaumot Joaquín Ruiz de Castroviejo Blanco Felipe Osorio Ospina Carmen Gonzalez-Enguita Department of Urology Hospital Universitario Fundación Jiménez DíazMadrid 28015MadridSpain

Obstructive uropathy is defined as the structural or functional interruption of urinary outflow at any level in the urinary *** is regarded as one of the most prevalent causes of acute kidney injury(AKI),accounting for 5%–10%of *** severe obstruction of the urinary tract is a potentially threatening situation for the kidneys and therefore requires prompt identification and management to relieve *** aim of the present article is to review and synthesize available evidence on obstructive uropathy,providing a clinical guideline for clinicians.A literature review on obstructive uropathy in the context of AKI was performed,focusing on the least clarified aspects regarding diagnosis and *** literature searching was conducted in English and top-level evidence articles including systematic reviews,metanalyses and large series were *** obstruction of the urinary tract is a diagnostic and therapeutical challenge that may lead to important clinical complications together with direct structural and hemodynamic damage to the *** recognition of the leading cause and its exact location is essential to ensure prompt urinary drainage together with the most suitable drainage technique selection.A multidisciplinary approach,including urologists,nephrologists,and other medical specialties,is best suited to correctly manage concomitant hemodynamic changes,fluid and electrolyte imbalances,and other related *** uropathy is one of the leading causes of *** of patients suitable for early diversion and feasibility or adequate selection of the indicated technique is sometimes challeng-ing.A thorough understanding of the physiopathology behind the development of urinary obstruction is vital for correct diagnosis and management.

关键词： Obstructive uropathy Urinary tract obstruction Obstruction of the urinary tract Acute kidney injury Urinary diversion Renal recovery

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Multi-omic study to unmask genes involved in prostate cancer development in amulti-case family

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Cancer Communications 2024年第3期44卷 443-447页

作者： Lucia Chica-Redecillas Sergio Cuenca-Lopez Eduardo Andres-Leon Laura Carmen Terron-Camero blanca Cano-Gutierrez Jose Manuel Cozar Jose Antonio Lorente Fernando Vazquez-Alonso Luis Javier Martinez-Gonzalez Maria Jesus Alvarez-Cubero GENYO Centre for Genomics and Oncological ResearchPfizerUniversity of GranadaAndalusian Regional GovernmentPTS GranadaGranadaGranadaSpain Department of Biochemistry Molecular Biology III and ImmunologyFaculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Bioinformatics Unit Institute of Parasitology and Biomedicine“López-Neyra”Spanish National Research CouncilGranadaGranadaSpain Nursery Service.University Hospital Clínico San Cecilio GranadaGranadaSpain Urology Department University Hospital Virgen de las NievesGranadaGranadaSpain Legal Medicine and Toxicology Department Faculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Ibs Biosanitary Research InstituteGranadaGranadaSpain

Dear Editor,Hereditary prostate cancer(PC)comprises 5%-10%of all PC *** increased risk of PC in menwith a family his-tory of the disease is well known and is commonly caused by germline mutations,leading to clinical guidelines men-tioning various genes for identifying high-risk ***,the complex inheritance patterns involvingmul-tiple single nucleotide polymorphisms(SNPs)make it a genetically heterogeneous disease,with genetic testing still in its early stages.

关键词： cancer clinical cases

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Organ Abscission in Plants: With Special Emphasis on Bell Pepper

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1467-1484页

作者： ramiro Reyes-Castro Héctor G.Núñez-Palenius Juan I.Valiente-Banuet María E.Sosa-Morales blanca E.Orosco-Alcalá Rafael Guzmán-Mendoza Graciela M.L.Ruiz-Aguilar Rogelio Costilla-Salazar Life Sciences Division Universidad de GuanajuatoIrapuato36500México School of Engineering and Sciences Tecnologico de MonterreyQuerétaro76130México

Bell pepper(Capsicum annuum L.),along with potato and tomato,is one of the three most cultivated vegetables in the *** pepper is worldwide accepted due to its characteristics of color,smell,ﬂavor,and *** pepper is also considered a nutritious food due to its vitamin and antioxidant *** Mexico,bell pepper production has a high value because it is grown for the international markets,particularly the United States of ***,the abscission ofﬂowers and fruits is a factor that limits the yield,hinders the planning of activities,and causes a variation in the prices of *** to the importance of this process,in this work we did a bibliometric analysis and literature review of scientiﬁc advances for the understanding of the abscission pro-cess in plants,and in particular for the bell ***,we introduce new perspectives that would help direct future research about organ abscission in ***,the lack of research that would further clarify abscis-sion process in the bell pepper plant is discussed.

关键词： Capsicum annuum abscission zone plant growth regulators environmental factors

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Characterisation of the Bacteria and Archaea Community Associated with Wild Oysters, At Three Possible Restoration Sites in the North Sea

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Open Journal of Marine Science 2024年第2期14卷 19-40页

作者： Natacha M. S. Juste-Poinapen Yang Lu blanca Bolaños De Hoyos George C. Birch Camille Saurel Oyster Heaven Rotterdam Netherlands Nucleus Rotterdam Netherlands Microbial Ecology and Wastewater Microbiology Queensland University of Technology Brisbane Australia National Institute of Aquatic Resources Technical University of Denmark Lyngby Denmark

With 85% of the global oyster reefs destroyed, there is an urgent need for large scale restoration to benefit from the ecosystem services provided by biogenic oyster reefs and their associated biodiversity, including microorganisms that drive marine biogeochemical cycles. This experiment established a baseline for the monitoring of the bacterial and archaeal community associated with wild oysters, using samples from their immediate environment of the Voordelta, with cohabiting Crassostrea gigas and Ostrea edulis, Duikplaats with only C. gigas attached to rocks, and the Dansk Skaldyrcentre, with no onsite oysters. The microbial profiling was carried out through DNA analysis of samples collected from the surfaces of oyster shells and their substrate, the sediment and seawater. Following 16S rRNA amplicon sequencing and bioinformatics, alpha indices implied high species abundance and diversity in sediment but low abundance in seawater. As expected, Proteobacteria, Bacteroidetes, Firmicutes and Thaumarchaeota dominated the top 20 OTUs. In the Voordelta, OTUs related to Colwellia, Shewanella and Psychrobium differentiated the oysters collected from a reef with those attached to rocks. Duikplaats were distinct for sulfur-oxidizers Sulfurimonas and sulfate-reducers from the Sva 0081 sediment group. Archaea were found mainly in sediments and the oyster associated microbiome, with greater abundance at the reef site, consisting mostly of Thaumarchaeota from the family Nitrosopumilaceae. The oyster free site displayed archaea in sediments only, and algal bloom indicator microorganisms from the Rhodobacteraceae, Flavobacteriaceae family and genus [Polaribacter] huanghezhanensis, in addition to the ascidian symbiotic partner, Synechococcus. This study suggests site specific microbiome shifts, influenced by the presence of oysters and the type of substrate.

关键词： Oyster Reefs Microbiome Marine Bacteria Marine Archaea Restoration

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Conifer establishment after the eruption of the Paricutin volcano in central Mexico

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Forest Ecosystems 2022年第1期9卷 71-82页

作者： Jesús Eduardo Sáenz-Ceja blanca Lizeth Sáenz-Ceja J.Trinidad Sáenz-Reyes Diego Rafael Pérez-Salicrup Instituto de Investigaciones en Ecosistemas y Sustentabilidad Universidad Nacional Autéonoma de MéxicoAntigua Carretera a Patzcuaro 8701 Col.Ex hacienda San Joséde la Huerta58190MoreliaMexico Escuela Nacional de Estudios Superiores Unidad Morelia Universidad Nacional Autónoma de MéxicoAntigua Carretera a Patzcuaro 8701 Col.Ex hacienda San Joséde la Huerta58190MoreliaMexico Instituto Nacional de Investigaciones Forestales Agrícolas y PecuariasCampo Experimental UruapanAv.Latinoamericana 1101Col.Revolución60500UruapanMexico

Background:Volcanic eruptions have large effects on forest ecosystems and create new substrates,triggering primary succession *** Paricutín volcano,born in central-western Mexico,erupted between 1943 and *** the cessation of the eruptive activity,plant colonization began on the lava flows and tephra deposits,including the conifer species that dominate the surrounding mature *** study aims to reconstruct the history of the establishment of conifer trees on the substrates created by the Paricutín ***:16 sampling plots were established along three transects with northern,southern,and south-western aspects,located every 250 m from the preserved forest to the volcanic *** cores from 400 conifer trees were extracted and their age was determined by cross-dating annual tree *** order of the species colonization and the tree establishment,abundance,and dominance patterns were ***,the influence of the distance from the mature forests and the inter-annual climatic conditions on the temporal tree establishment pattern was ***:Eight pine and one fir species have been established since 1970,only 18 years after the end of the eruptive ***,tree establishment increased by 12.9%annually after 1995,with the youngest tree in our sample getting established in *** did not find a well-defined temporal and spatial pattern of species arrival,which suggests that colonization occurred randomly,although the four pine species that were established early became the most abundant and *** establishment was not influenced by the distance from the mature forest,and wet inter-annual conditions did not enhance pulses of tree recruitment,exhibiting a continuous tree establishment ***:Conifer species have shown a great capacity for colonizing volcanic substrates created by the Paricutín eruption,which suggests that tropical montane conifers can regenerate rapidly under high-magni

关键词： Age structure Dendrochronology Lava flow Primary succession Tropical montane forest

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Cognitive disorder and dementia in type 2 diabetes mellitus

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World Journal of Diabetes 2022年第4期13卷 319-337页

作者： Genaro G Ortiz Miguel Huerta Héctor A González-Usigli Erandis D Torres-Sánchez Daniela LC Delgado-Lara Fermín P Pacheco-Moisés Mario A Mireles-ramírez blanca MG Torres-Mendoza Roxana I Moreno-Cih Irma E Velázquez-Brizuela Department of Philosophical and Methodological Disciplines University Health Sciences CenterUniversity of GuadalajaraGuadalajara 44340JaliscoMexico Department of Neurology Movement Disorders ClinicSub-Specialty Medical UnitNational Western Medical CenterMexican Social Security Institute(IMSS)Guadalajara 44340JaliscoMexico University Biomedical Research Center University of ColimaColima 28040Mexico Department of Medical and Life Sciences University Center of‘La Ciénega’University of GuadalajaraOcotlán 47810JaliscoMexico Department of Chemistry University Center of Exact Sciences and EngineeringUniversity of GuadalajaraGuadalajara 44340JaliscoMexico Division of Neurosciences Western Biomedical Research CenterMexican Social Security Institute(IMSS)Guadalajara 44340JaliscoMexico Gerontology Postgraduate Program Public Health DepartmentUniversity Health Sciences CenterUniversity of GuadalajaraGuadalajara 44340JaliscoMexico

Insulin,a key pleiotropic hormone,regulates metabolism through several signaling pathways in target tissues including skeletal muscle,liver,and *** the brain,insulin modulates learning and memory,and impaired insulin signaling is associated with metabolic dysregulation and neurodegenerative *** the receptor level,in aging and Alzheimer’s disease(AD)models,the amount of insulin receptors and their functions are *** and animal model studies suggest that memory improvements are due to changes in insulin ***,diabetes mellitus(DM)and insulin resistance are associated with age-related cognitive decline,increased levels ofβ-amyloid peptide,phosphorylation of tau protein;oxidative stress,pro-inflammatory cytokine production and dyslipidemia. Recent evidence shows that deleting brain insulin receptors leads to mildobesity and insulin resistance without influencing brain size and apoptosis ***, deleting insulin-like growth factor 1 receptor (IGF-1R) affects brain size anddevelopment, and contributes to behavior changes. Insulin is synthesized locally in the brain andis released from the neurons. Here, we reviewed proposed pathophysiological hypotheses toexplain increased risk of dementia in the presence of DM. Regardless of the exact sequence ofevents leading to neurodegeneration, there is strong evidence that mitochondrial dysfunctionplays a key role in AD and DM. A triple transgenic mouse model of AD showed mitochondrialdysfunction, oxidative stress, and loss of synaptic integrity. These alterations are comparable tothose induced in wild-type mice treated with sucrose, which is consistent with the proposal thatmitochondrial alterations are associated with DM and contribute to AD development. Alterationsin insulin/IGF-1 signaling in DM could lead to mitochondrial dysfunction and low antioxidantcapacity of the cell. Thus, insulin/IGF-1 signaling is important for increased neural processing andsystemic metabolism, a

关键词： Alzheimer´s disease Diabetes mellitus Insulin Vascular dementia Cognitive decline

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