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8 results on '"Cristina Sanabra"'

1. Using natural language processing to explore characteristics and management of patients with axial spondyloarthritis and psoriatic arthritis treated under real-world conditions in Spain: SpAINET study

Author

Diego Benavent, Santiago Muñoz-Fernández, Isabel De la Morena, Antonio Fernández-Nebro, Judith Marín-Corral, Eva Castillo Rosa, Miren Taberna, Cristina Sanabra, and Carlos Sastre

Subjects
Diseases of the musculoskeletal system, RC925-935
Abstract

Background: Spondyloarthritis (SpA) is a group of related but phenotypically distinct inflammatory disorders that include axial SpA (axSpA) and psoriatic arthritis (PsA). Information on the characteristics and management of these patients in the real world remains scarce. Objectives: To explore the characteristics and management [disease activity assessment and treatment with secukinumab (SEC) or other biologic disease-modifying antirheumatic drugs (bDMARDs)] of axSpA and PsA patients using natural language processing (NLP) in Electronic Health Records (EHRs). Design: National, multicenter, observational, and retrospective study. Methods: We analyzed free-text and structured clinical information from EHR at three hospitals. All adult patients with axSpA, PsA or non-classified SpA from 2018 to 2021 with minimum follow-up of three months were included when starting SEC or other bDMARDs. Clinical variables were extracted using EHRead ® technology based on Systemized Nomenclature of Medicine-Clinical Terms (SNOMED CT) terminology. Results: Out of 887,735 patients, 758 were included, of which 328 had axSpA [58.5% male; mean (SD) age of 50.7 (12.7) years], 365 PsA [54.8% female, 53.9 (12.4) years], and 65 non-classified SpA. Mean (SD) time since diagnosis was 36.8 (61.0) and 24.1 (35.2) months for axSpA and PsA, respectively. Only 116 axSpA patients (35.3%) had available Ankylosing Spondylitis Disease Activity Score (ASDAS) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at bDMARD onset, of which 61 presented active disease. Disease Activity in PSoriatic Arthritis (DAPSA) or Disease Assessment Score - 28 joints (DAS-28) values at bDMARD onset were available for only 61 PsA (16.7%) patients, with 23 of them having active disease. The number of patients with available tender joint count or swollen joint count assessment was 68 (20.7%) and 59 (18%) for axSpA, and 115 (31.5%) and 119 (32.6%) for PsA, respectively. SEC was used in 63 (19.2%) axSpA patients and in 63 (17.3%) PsA patients. Conclusion: Using NLP, the study showed that around one-third of axSpA and one-sixth of PsA patients have disease activity assessments with ASDAS/BASDAI or DAPSA/DAS-28, respectively, highlighting an area of improvement in these patients’ management.

Published
2023
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2. Disease activity indexes might not capture the same disease aspects in males and females with ankylosing spondylitis: A real-world nationwide analysis

Author

Cristina Fernández-Carballido, Vega Jovaní, Emma Beltrán Catalán, Manuel José Moreno-Ramos, Jesús Sanz Sanz, Adela Gallego, M. Luz García Vivar, José Manuel Rodríguez-Heredia, Cristina Sanabra, and Carlos Sastré

Subjects
gender, disease activity, ankylosing spondylitis (AS), health status, BASDAI, ASDAS-CRP, Medicine (General), R5-920
Abstract

BackgroundTo evaluate gender differences in disease activity and health status (HS) in patients with radiographic axial spondyloarthritis (r-axSpA)/ankylosing spondylitis (AS).MethodsAncillary analysis of the MIDAS study, an observational, non-interventional, cross-sectional and retrospective multicenter nationwide study to assess disease activity and its relationship with HS in clinical practice. Adult patients with AS diagnosis, fulfilling ASAS and modified New York criteria, treated for ≥3 months upon study inclusion according to clinical practice were included. The primary outcome was “disease control” assessed by the percentage of patients in remission and low disease activity (BASDAI and ASDAS-CRP scores). HS was evaluated using the ASAS health index (ASAS-HI). Patients' responses and characteristics were analyzed by gender.ResultsWe analyzed 313 patients with AS, 237 (75.7%) males and 76 (24.3%) females. A total of 202 (64.5%) patients had adequate disease control (BASDAI < 4); 69.2% of males [mean (SD) BASDAI 2.9 (2.1)] and 50.0% of females [mean (SD) BASDAI 3.8 (2.4); p = 0.01]. According to ASDAS-CRP, 57.5% of patients were adequately controlled (ASDAS-ID +ASDAS-LDA); 138 (58.2%) males and 42 (55.3%) females. The mean (SD) ASDAS-CRP was 1.9 (1.1); being 1.9 (1.0) in males and 2.0 (1.1) in females. Overall, the impact of AS on HS was low to moderate [mean (SD) ASAS-HI 5.8 (4.4)]; being 5.5 (4.4) for males and 6.8 (4.2) for females (p = 0.02).ConclusionThis study showed a higher proportion of females with AS and active disease using the BASDAI definition. When using the ASDAS-CRP definition these differences by gender were less pronounced. The impact of disease activity on HS appears to be higher in females than males.

Published
2022
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5. Critical role for PDE4 subfamilies in the development of experimental autoimmune encephalomyelitis

Author

Guadalupe Mengod, Cristina Sanabra, and Emily M. Johansson

Subjects
Encephalomyelitis, Autoimmune, Experimental, Encephalomyelitis, medicine.medical_treatment, Enzyme-Linked Immunosorbent Assay, Real-Time Polymerase Chain Reaction, Myelin oligodendrocyte glycoprotein, Mice, Cellular and Molecular Neuroscience, medicine, Animals, In Situ Hybridization, Neuroinflammation, Mice, Knockout, biology, Microglia, Reverse Transcriptase Polymerase Chain Reaction, Experimental autoimmune encephalomyelitis, FOXP3, Transforming growth factor beta, medicine.disease, Immunohistochemistry, Cyclic Nucleotide Phosphodiesterases, Type 4, Isoenzymes, Mice, Inbred C57BL, medicine.anatomical_structure, Cytokine, Immunology, biology.protein, Female
Abstract

El pdf del artículo es la versión post-print., Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis exhibiting neuroinflammation, axonal damage and demyelination, further characterized by T- and B-cell responses to myelin oligodendrocyte glycoprotein. Pharmacological manipulation of phosphodiesterases (PDEs) provokes profound anti-inflammatory responses through modulation of cAMP levels. The PDE4B subfamily has been related to the inflammatory immune response in mice and PDE4 inhibition produces amelioration of the clinical signs and delayed onset in the EAE model. Analyses of the expression of the mRNA coding for PDE4B splice variants revealed an upregulation of PDE4B2 in the brainstem and spinal cord of EAE mice which correlated with forkhead box P3 (FoxP3) and transforming growth factor beta (TGF-β) mRNAs expression in a score-dependent manner. The increase observed for the PDE4B protein was mainly found in antigen-presenting cells (APCs) such as dendritic cells and microglia/macrophages, in areas with high cellular infiltration. Unexpectedly, PDE4B-/- mice showed an earlier onset of the disease compared to wildtype mice. The results point to a possible role of the PDE4B enzyme and in particular the PDE4B2 splice variant during EAE pathogenesis, probably by modulating cAMP levels in APCs, consequently influencing the cytokine environment important for T-cell differentiation. © 2013 Elsevier B.V., This work was supported by grants awarded by the Ministerio de Ciencia e Innovación (SAF2006-10243; SAF2009-11052; PI-10/01874), FEDER Funds and by the Generalitat de Catalunya (SGR2009/220).

Published
2013

6. Sex-related differences of cAMP-specific PDE4B3 mRNA in oligodendrocytes following systemic inflammation

Author

Guadalupe Mengod, Emily M. Johansson, Cristina Sanabra, Ministerio de Educación y Ciencia (España), Ministerio de Ciencia e Innovación (España), and Generalitat de Catalunya

Subjects
Male, medicine.medical_specialty, LPS, education, Inflammation, In situ hybridization, Biology, Systemic inflammation, neuroinflammation, Multiple sclerosis, Mice, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Myelin, Downregulation and upregulation, Internal medicine, Cyclic AMP, medicine, Animals, Cyclic adenosine monophosphate, RNA, Messenger, health care economics and organizations, Neuroinflammation, Sex Characteristics, ICER, medicine.disease, Systemic Inflammatory Response Syndrome, Cyclic Nucleotide Phosphodiesterases, Type 4, Mice, Inbred C57BL, Oligodendroglia, Endocrinology, medicine.anatomical_structure, Neurology, chemistry, Female, in situ hybridization, medicine.symptom
Abstract

Sex-related differences have been observed in the incidence and severity of several neurological diseases and in sepsis in humans. Cyclic adenosine monophosphate (cAMP) has been shown to play an important role in modulating the inflammatory environment during neuroinflammation and importantly in protecting myelin from excitotoxic cell death. Considering the sexual dimorphism in the functional properties of oligodendrocytes and the importance of a systemic inflammation in the progression of multiple sclerosis, we focused on identifying possible sex-related differences in the alterations previously reported for the two phosphodiesterase4B (PDE4B) splice-variants (PDE4B2 and PDE4B3) mRNA expression during innate neuroinflammation. PDE4A, PDE4B, and PDE4D are present in oligodendrocytes and we have previously reported that PDE4B3 mRNA is readily expressed in both oligodendrocytes and neurons. In this study, we analyzed the influence of an intraperitoneal lipopolysaccharide injection on the distribution pattern and expression levels of the PDE4B mRNA splicing variants in both male and female mice brains. Clear differences were observed in PDE4B2 and PDE4B3 mRNA expression levels in males compared with females in a time-dependent manner. Furthermore, we observed that the clear downregulation of PDE4B3 mRNA was reflected in a lower percentage of oligodendrocytes positive for this transcript which correlated with a decrease in inducible cAMP early repressor expression in female corpus callosum. © 2012 Wiley Periodicals, Inc., Grant sponsor: Spanish Ministerio de Educación y Ciencia; Grant number: SAF2006-10243; Grant sponsor: Ministerio de Ciencia e Innovación; Grant numbers: SAF 2009-11052, PI-10/01874; Grant sponsor: Generalitat de Catalunya; Grant number: SGR2009/220; Grant sponsor: FEDER Funds (European Union).

Published
2012

7. Lipopolysaccharide administration in vivo induces differential expression of cAMP-specific phosphodiesterase 4B mRNA splice variants in the mouse brain

Author

M. Teresa Vilaró, Roser Cortés, Guadalupe Mengod, Cristina Sanabra, and Emily M. Johansson

Subjects
Lipopolysaccharides, Male, Messenger RNA, Lipopolysaccharide, Phosphodiesterase, Brain, In situ hybridization, Biology, Molecular biology, Cyclic Nucleotide Phosphodiesterases, Type 4, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Mice, PDE4B, Downregulation and upregulation, chemistry, Lectins, Animals, Protein Isoforms, RNA, Messenger, Neuroinflammation, Cellular localization
Abstract

El pdf del artículo es la versión pre-print., Many inflammatory processes involve cAMP. Pharmacological manipulation of cAMP levels using specific phosphodiesterase (PDE) inhibitors provokes an antiinflammatory response. The aim of this study was to investigate changes in the pattern and levels of expression of mRNAs coding for the cAMP-specific PDE4 family and subfamilies in mouse brain during the immediate acute immune response provoked by an intraperitoneal injection of lipopolysaccharide (LPS). PDE4B, and furthermore the splice variants PDE4B2 and PDE4B3, were the only mRNAs that showed altered expression. Whereas PDE4B2 presented increased expression at both 3 and 8 hr postinjection, PDE4B3 mRNA showed decreased expression that reached a minimum 8 hr postinjection. PDE4B2 mRNA upregulation was observed mainly in endothelial and macrophage/neutrophil cell populations in the leptomeninges, and the downregulation of PDE4B3 was observed mainly in oligodendrocytes throughout the brain. Our results clearly illustrate the distinctive anatomical distribution and cellular localization of the PDE4Bs during neuroinflammation and emphasize the importance of PDE4B splice-variant-specific inhibitors as therapeutic tools. © 2011 Wiley-Liss, Inc., This work was supported by grants awarded by the Spanish Ministerio de Educación y Ciencia and FEDER Funds (SAF2006-10243; SAF2009-11052). Emily Johansson was a recipient of a fellowship from the Ministerio de Educación y Ciencia and Cristina Sanabra was a recipient of a fellowship from the IDIBAPS.

Published
2011

8. Neuroanatomical distribution and neurochemical characterization of cells expressing adenylyl cyclase isoforms in mouse and rat brain

Author

Guadalupe Mengod and Cristina Sanabra

Subjects
Male, Cerebellum, Hippocampus, Glutamic Acid, In situ hybridization, Biology, Basal Ganglia, Adenylyl cyclase, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Glutamatergic, Mice, Species Specificity, medicine, Animals, Rats, Wistar, Cellular localization, In Situ Hybridization, gamma-Aminobutyric Acid, Neurons, Brain, Olfactory Pathways, Rats, Isoenzymes, Mice, Inbred C57BL, medicine.anatomical_structure, chemistry, Cholinergic Fibers, Organ Specificity, Synaptic plasticity, Cholinergic, Neuroscience, Adenylyl Cyclases
Abstract

El pdf del artículo es el manuscrito de autor., Transmembrane adenylyl cyclases (Adcy) are involved in the regulation of multiple brain processes such as synaptic plasticity, learning and memory. They synthesize intracellular cyclic adenosine monophosphate (cAMP) following activation by G-protein coupled receptors. We examined the neuroanatomical distribution of the nine Adcy isoforms in rat and mouse brain by in situ hybridization, as well as their location in glutamatergic, GABAergic and cholinergic neurons in several mouse brain areas by double in situ hybridization. The Adcys are widely distributed throughout the brain in both rat and mouse, being especially abundant in cortex, hippocampus, thalamic nuclei, the olfactory system and the granular layer of the cerebellum. Double-labeling experiments showed that Adcy isoforms are differently expressed in glutamatergic, GABAergic and cholinergic neuronal cell populations. We report the neuroanatomical distribution of the nine known Adcy isoforms in rat and mouse brain and their cellular localization. © 2010 Elsevier B.V., This work was supported by grants awarded by the Spanish Ministerio de Educación y Ciencia and FEDER Funds (SAF2006-10243, SAF 2009-11052).

Published
2010

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