Francisco Valladares

Universidad de La Laguna

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Jesús Villar

St. Michael's Hospital

Carlos Flores

Instituto Tecnológico y de Energías Renovables

Arthur S. Slutsky

University of Toronto

Robert M. Kacmarek

Massachusetts General Hospital

Mercedes Muros

Hospital Universitario Nuestra Señora de Candelaria

Lucio Díaz‐Flores

Universidad de La Laguna

Delia Báez

Universidad de La Laguna

Aixa R. Bello

Hospital de Santa Cruz

Nuria E. Cabrera-Benítez

Instituto de Salud Carlos III

Teresa Almeida

Universidad de La Laguna

Cooperative Institutions

Universidad de La Laguna

Universidade de Brasília

Instituto de Salud Carlos III

Hospital Universitario de Canarias

Hospital Universitario de Gran Canaria Doctor Negrín

Hospital Universitario Nuestra Señora de Candelaria

Centro de Investigación Biomédica en Red

Canary Institute of Cancer Research

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias

St. Michael's Hospital

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury

Critical Care (2015)

Jesús Villar Nuria E. Cabrera-Benítez Francisco Valladares Sonia García-Hernández Ángela Ramos-Nuez

Abstract Introduction Most patients with sepsis and acute lung injury require mechanical ventilation to improve oxygenation and facilitate organ repair. Mast cells are important in response to infection and resolution of tissue injury. Since tryptase secreted from mast cells has been associated with tissue fibrosis, we hypothesized that tryptase would be involved in the early development of ventilator-induced pulmonary fibrosis in a clinically relevant model of sepsis-induced lung injury. Methods Prospective, randomized, controlled animal study using Sprague-Dawley rats. Sepsis was induced by cecal ligation and perforation. Animals were randomized to spontaneous breathing or two ventilatory strategies for 4 h: protective ventilation with tidal volume (VT) = 6 ml/kg plus 10 cmH 2 O positive end-expiratory pressure (PEEP) or injurious ventilation with VT = 20 ml/kg plus 2 cmH 2 O PEEP. Healthy, non-ventilated animals served as non-septic controls. We studied the following end points: histology, serum cytokine levels, hydroxyproline content, tryptase and proteinase-activated receptor-2 (PAR-2) protein level in lung homogenates, and tryptase and PAR-2 immunohistochemical localization in the lungs. Results All septic animals developed acute lung injury. Animals ventilated with high VT had a significant increase of pulmonary fibrosis, hydroxyproline content, tryptase and PAR-2 protein levels compared to septic controls ( P <0.0001). However, protective ventilation attenuated sepsis-induced lung injury and decreased lung tryptase and PAR-2 protein levels. Immunohistochemical staining confirmed the presence of tryptase and PAR-2 in the lungs. Conclusions Mechanical ventilation modified tryptase and PAR-2 in injured lungs. Increased levels of these proteins were associated with development of sepsis and ventilator-induced pulmonary fibrosis early in the course of sepsis-induced lung injury.

Tryptase

Diffuse alveolar damage

10.1186/s13054-015-0878-9

Cite

Citations (21)

Fixed Versus Removable Microdialysis Probes for In Vivo Neurochemical Analysis: Implications for Behavioral Studies

Journal of Neurochemistry (1994)

Blas Fumero Teresa Guadalupe Francisco Valladares Francisco Mora Robert O’Neill

Abstract: The levels of several neurochemicals, i.e., uric acid (UA), dopamine (DA), dihydroxyphenylacetic acid, and 5‐hydroxyindoleacetic acid, collected daily from the rat striatum with either fixed or removable microdialysis probes for 7 days after surgery were compared. The implantation of the fixed cannula was followed by a 10‐fold increase in the UA content in the dialysates collected from the first day after surgery onward and by a steady decrease in dihydroxyphenylacetic acid levels, whereas those of DA remained fairly stable. With the removable cannula system, only a smaller, transient increase in UA during the first 3 days after surgery was observed, with no change in DA or monoamine metabolites. The glial reaction around the cannula tracks was assessed by both quantitative histological techniques and measuring the glutamine levels in the dialysates collected at the time of surgery and 7 days later. Both the glial cell number and nuclear size, as well as the glutamine outflow, were considerably larger in the animals implanted with the fixed probes. It is, therefore, likely that the UA levels in the dialysate reflect the glial reaction to the probe. The suitability of the removable probe system for behavioral experiments involving repeated microdialysis sampling was illustrated in an experiment showing that the DA release in the nucleus accumbens of male rats assessed daily at postsurgery days 5–10 was virtually identical in three alternating sessions of sexual behavior as was the smaller release of this neurotransmitter detected during intervening nonsexual social interactions.

Microdialysis

Neurochemical

3,4-Dihydroxyphenylacetic acid

10.1046/j.1471-4159.1994.63041407.x

Cite

Citations (47)

Mechanical ventilation modulates Toll-like receptor signaling pathway in a sepsis-induced lung injury model

Intensive Care Medicine (2010)

Jesús Villar Nuria E. Cabrera Milena Casula Carlos Flores Francisco Valladares

Perforation

10.1007/s00134-010-1799-3

Cite

Citations (47)

Mercado laboral y situación económica en México en tiempos de pandemia

Editorial Uniagustiniana eBooks (2022)

Francisco Valladares

La situación de México ante la pandemia generada por el Covid-19 generó un conjunto de situaciones que hacen de esta época una de las más desalentadoras, para el mercado laboral y la prosperidad en los negocios. El efecto del coronavirus ha impactado fundamentalmente en tres áreas del tipo económico: 1) oferta, generada la interrupción de las actividades de diversos negocios y el trastorno de las cadenas de suministro; 2) demanda, al cambiar significativamente el comportamiento del consumidor; y 3) financiero, el cual muestra una secuela de los dos anteriores, principalmente, por modificación de las carteras de los inversionistas. El comportamiento de los indicadores macroeconómicos sugiere, en principio, una contracción significativa de la economía mexicana, lo cual se expresa debido a la suspensión de operaciones de la mayoría de armadoras, sobre todo de vehículos ligeros. Los indicadores de opinión empresarial muestran un deterioro en la percepción del sector empresarial, ya que particularmente los pedidos de manufactura cayeron a un nivel semejante al observado en la primera mitad del 2009. Los indicadores económicos utilizan conceptos y terminología no solo del campo de la economía y la estadística, y permiten tener una medición del comportamiento económico (Heath, 2012). Los puestos de trabajo afiliados al IMSS registraron una caída extraordinaria; el descenso comenzó a mediados del mes de marzo, cuando se iniciaron las medidas de confinamiento forzado, lo anterior señalado por el Gobierno federal.

10.28970/9789585498884.14

Cite

Citations (0)

Comparative Analysis of the ERα/ERβ Ratio and Neurotensin and its High-affinity Receptor in Myometrium, Uterine Leiomyoma, Atypical Leiomyoma, and Leiomyosarcoma

International Journal of Gynecological Pathology (2011)

Yurena Rodríguez Rodríguez Delia Báez Francisco Montes de Candelaria García Idaira Dorta

Deregulated steroids are involved in different hormone-dependent tumors, including benign and malignant uterine neoplasms. Leiomyomas (LM) are estrogen and progesterone-dependent benign tumors, whereas “bizarre or atypical LMs” (AL) are considered a subgroup of LM and clinically benign, although their malignant potential is suspect. Uterine leiomyosarcomas (LMS) are malignant smooth muscle tumors, and ovarian steroids may control their growth. Estrogen effects are mediated by 2 receptors, estrogen receptors (ER) α and β, and the ratio of both receptors seems to be a critical parameter in the estrogen-mediated carcinogenic process. Estradiol induces the expression of neurotensin (NTS), and the coupling of this peptide with its high-affinity receptor, NTS1, has been involved in the regulation of tumoral cell growth. Given the importance of these markers in tumor development, we aim to determine the status of ERα and ERβ in the myometrium and LM, AL, and LMS, concomitantly with the expression of NTS/NTS receptor 1 in these tumors. For that purpose, we use immunohistochemistry for all markers analyzed and in-situ hybridization to detect NTS mRNA. These data suggest that LMS are estrogen-dependent tumors, which may use NTS as an autocrine growth factor. In addition, the phenotype of AL with regard to ERα and ERβ status and NTS expression is closer to LMS than LM; thus, a potential malignization of this tumor is feasible.

Myometrium

Uterine Leiomyoma

10.1097/pgp.0b013e31820918cb

Cite

Citations (10)

Altered Profile of Circulating Endothelial-Derived Microparticles in Ventilator-Induced Lung Injury*

Critical Care Medicine (2015)

Nuria E. Cabrera-Benítez Francisco Valladares Sonia García-Hernández Ángela Ramos-Nuez José Luis Martín Barrasa

Objectives: Pulmonary endothelial cell injury is central to the pathophysiology of acute lung injury. Mechanical ventilation can cause endothelial disruption and injury, even in the absence of preexisting inflammation. Platelet-endothelial cell adhesion molecule-1 is a transmembrane protein connecting adjacent endothelial cells. We hypothesized that injurious mechanical ventilation will increase circulating lung endothelial-derived microparticles, defined as microparticles positive for platelet-endothelial cell adhesion molecule-1, which could serve as potential biomarkers and mediators of ventilator-induced lung injury. Design: Prospective randomized, controlled, animal investigation. Setting: A hospital preclinical animal laboratory. Subjects: Forty-eight Sprague-Dawley rats. Interventions: Animals were randomly allocated to one of the three following ventilatory protocols for 4 hours: spontaneous breathing (control group), mechanical ventilation with low tidal volume (6 mL/kg), and mechanical ventilation with high tidal volume (20 mL/kg). In both mechanical ventilation groups, positive end-expiratory pressure of 2 cm H2O was applied. Measurements and Main Results: We analyzed histologic lung damage, gas exchange, wet-to-dry lung weight ratio, serum cytokines levels, circulating endothelial-derived microparticles, platelet-endothelial cell adhesion molecule-1 lung protein content, and immunohistochemistry. When compared with low–tidal volume mechanical ventilation, high–tidal volume ventilation increased lung edema score and caused gas-exchange deterioration. These changes were associated with a marked increased of circulating endothelial-derived microparticles and a reduction of platelet-endothelial cell adhesion molecule-1 protein levels in the high–tidal volume lungs (p < 0.0001). Conclusions: There is an endothelial-derived microparticle profile associated with disease-specific features of ventilator-induced lung injury. This profile could serve both as a biomarker of acute lung injury and, potentially, as a mediator of systemic propagation of pulmonary inflammatory response.

Endothelial Dysfunction

Pathophysiology

10.1097/ccm.0000000000001280

Cite

Citations (28)

Mechanical stress induces lung fibrosis by epithelial–mesenchymal transition*

Critical Care Medicine (2011)

Nuria E. Cabrera-Benítez Matteo Parotto Martin Post Bing Han Peter M. Spieth

In Brief Objectives: Many mechanically ventilated patients with acute respiratory distress syndrome develop pulmonary fibrosis. Stresses induced by mechanical ventilation may explain the development of fibrosis by a number of mechanisms (e.g., damage the alveolar epithelium, biotrauma). The objective of this study was t test the hypothesis that mechanical ventilation plays an important role in the pathogenesis of lung fibrosis. Methods: C57BL/6 mice were randomized into four groups: healthy controls; hydrochloric acid aspiration alone; vehicle control solution followed 24 hrs later by mechanical ventilation (peak inspiratory pressure 22 cm H2O and positive end-expiratory pressure 2 cm H2O for 2 hrs); and acid aspiration followed 24 hrs later by mechanical ventilation. The animals were monitored for up to 15 days after acid aspiration. To explore the direct effects of mechanical stress on lung fibrotic formation, human lung epithelial cells (BEAS-2B) were exposed to mechanical stretch for up to 48 hrs. Measurement and Main Results: Impaired lung mechanics after mechanical ventilation was associated with increased lung hydroxyproline content, and increased expression of transforming growth factor-β, β-catenin, and mesenchymal markers (α-smooth muscle actin and vimentin) at both the gene and protein levels. Expression of epithelial markers including cytokeratin-8, E-cadherin, and prosurfactant protein B decreased. Lung histology demonstrated fibrosis formation and potential epithelia–mesenchymal transition. In vitro direct mechanical stretch of BEAS-2B cells resulted in similar fibrotic and epithelia–mesenchymal transition formation. Conclusions: Mechanical stress induces lung fibrosis, and epithelia–mesenchymal transition may play an important role in mediating the ventilator-induced lung fibrosis. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ccmjournal.com).

Hydroxyproline

10.1097/ccm.0b013e31822f09d7

Cite

Citations (155)

Correction: Lung Transcriptomics during Protective Ventilatory Support in Sepsis-Induced Acute Lung Injury

PLoS ONE (2015)

Marialbert Acosta‐Herrera Fabián Lorenzo-Díaz Maria Pino‐Yanes Almudena Corrales Francisco Valladares

The accession number for the complete microarray data set deposited in ArrayExpress appears incorrectly throughout the article as E-MEXP-12345. The correct accession number should be E-MTAB-2673.

10.1371/journal.pone.0145696

Cite

Citations (6)

Intense vascular sprouting from rat femoral vein induced by prostaglandins E1 and E2

The Anatomical Record (1994)

Lucio Díaz‐Flores Ricardo Gutiérrez Francisco Valladares Hilda Varela M. A. Pérez

Abstract The formation of new capillaries from the rat femoral vein was specifically explored to assess whether venous vessels of this caliber may participate in the process of angiogenesis. Prostaglandins of the E series (PGE1 and PGE2) were administered into the soft connective tissue surrounding the rat femoral vessels as angiogenic inducers. In these conditions, between 2 and 7 days, a great number of new capillaries were observed in the media of the femoral vein, arising from the endothelial cells (EC) in the intima. The events of the capillary growth from the femoral vein included EC activation, local degradation of the basal membrane followed by migration and proliferation of EC, solid sprout formation with posterior canalization, development of a new basal membrane, and appearance of pericytes around the new capillary. Although numerous vascular buds were also observed arising from the small venules and capillaries in the periadventitial tissues, they were separated at first from those in the media of the femoral vein by the venous adventitia. Later, connections were observed between both newly formed microcirculations. The present study shows the capacity of PGE1 and PGE2 in the extravascular position of inducing capillary sprouting from veins. Furthermore, the observations provide greater evidence that vessels with characteristics similar to those of the rat femoral vein may contribute to angiogenesis, on occasion with an intense neovascularization. This fact may be of interest for the establishment of a functional circulation after angiogenesis by anastomoses of the new capillaries with those arising from pre‐existing vessels of greater caliber than the venules. © 1994 Wiley‐Liss, Inc.

Adventitia

Femoral vein

10.1002/ar.1092380109

Cite

Citations (56)

Role Of The Type 2 Alveolar Epithelial Cells In An Experimental Model Of Acute Lung Injury

Sonia García-Hernández Ricardo Gutiérrez Lucio Díaz‐Flores Jesús Villar Francisco Valladares

Diffuse alveolar damage

Alveolar Epithelium

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a6317

Cite

Citations (0)