Artículos (Fisiología Médica y Biofísica)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/11035

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Correction to: Differential effectiveness of tyrosine kinase inhibitors in 2D/3D culture according to cell differentiation, p53 status and mitochondrial respiration in liver cancer cells
(Springer Nature, 2024-08-20) Rodríguez Hernández, María A.; Chapresto Garzón, Raquel; Cadenas, Miryam; Navarro Villarán, Elena; Negrete, María; Gómez Bravo, Miguel Ángel; Victor, Victor M.; Padillo Ruiz, Francisco Javier; Muntané Relat, Jordi; Cirugía; Biología Celular; Fisiología Médica y Biofísica; CTS664: Cirugía Avanzada y Trasplantes. Terapia Celular y Bioingeniería Aplicada a la Cirugía; CTS1098: Mecanismos Moleculares del Hepatocarcinoma y Sus Estrategias Terapéuticas
In this article, the spheroid image obtained after 15 days of treatment of Hep3B with Cabozantinib was incorrectly duplicated from that obtained after 12 days. The new Fig. 1B shows the correct spheroid image at 15 days. The replacement does not change the results or conclusions of Fig. 1B. The authors apologize for the unexpected error in the preparation of Fig. 1B. (excerpt)
Targeting iysosomal acidification to restore microglial homeostasis and mitigate memory decline during male brain ageing
(Elsevier science; Elsevier BV, 2025-11-04) Barrella, Lorenzo; Ramírez-Ponce, María Pilar; Vázquez Román, María Victoria; Millán-Huang, Marta San; Maldonado y Aibar, María Dolores; Flores Cordero, Juan Antonio; Alés González de la Higuera, Eva María; Citología e Histología Normal y Patológica; Bioquímica Médica y Biología Molecular e Inmunología; Fisiología Médica y Biofísica; CTS439: Sistema Neuroendocrino Difuso; CTS160: Neuroinmunoendocrinología Molecular; CTS151: Bioquímica Medica; BIO236: Biofísica Celular
Lysosomal dysfunction lies at the nexus of inflammaging, microglial dystrophy and synaptic fragility, making it an attractive target for brain rejuvenation. Here we demonstrate that a five-month oral course of ketotifen, an approved H1-antihistamine and mast-cell stabiliser, re-acidifies lysosomes in aged C57BL/6J male mice, restoring the quinacrine signal of peripheral macrophages and SIM-A9 microglia. This proton rebound is coupled to broad anti-cytokine effects: ketotifen attenuates lipopolysaccharide-evoked release of TNF-α, IL-1β and IL-10 in vitro and ex vivo. In the brain, the drug restores a highly ramified, homeostatic microglial morphology throughout the cortex and hippocampus. Ketotifen robustly elevates cortical synaptophysin and PSD-95 above age-matched levels. Behaviourally, ketotifen enhances spatial learning and object-location memory without altering locomotor activity or anxiety-like behaviour. Collectively, these findings identify lysosomal re-acidification as the initiating trigger of a multifaceted rejuvenation cascade that dampens multi-cytokine signalling, restores microglial morphology and preserves synaptic integrity. Because ketotifen is inexpensive, brain-permeable and already licensed for human use, our work unveils an immediately actionable geroprotective strategy to forestall early cognitive decline.
Ketotifen reacidifies secretory lysosomes and normalises ageing phenotypes in mast cells
(Academic press inc jnl-comp subscriptions; Academic press inc elsevier science; Elsevier, 2025-10-29) Barrella, Lorenzo; Ramírez-Ponce, María Pilar; Vázquez Román, María Victoria; San Millán-Huang, Marta; Flores Cordero, Juan Antonio; Alés González de la Higuera, Eva María; Citología e Histología Normal y Patológica; Bioquímica Médica y Biología Molecular e Inmunología; Fisiología Médica y Biofísica; CTS439: Sistema Neuroendocrino Difuso; CTS151: Bioquímica Medica; BIO236: Biofísica Celular
Mast-cell (MC) granules are secretory lysosomes whose function depends on a highly acidic lumen. We asked whether lysosomal pH drifts with age and whether this alteration is reversible. Lysosomal acidification was assessed by quinacrine imaging of peritoneal MCs, which revealed very low fluorescence in MCs from 2-month-old mice, consistent with immature granules. As MCs matured, quinacrine signal increased, reflecting expansion of the secretory lysosome pool; however, from 15 to 17 months, fluorescence progressively declined, indicating gradual deacidification. Chronic ketotifen treatment restored and amplified the quinacrine signal, enlarged granules, and reduced late-life MC expansion. Acute pharmacological assays revealed that ketotifen's effect requires V-ATPase activity and dynamin-dependent endocytosis. FM1-43 uptake confirmed enhanced endocytic activity with ketotifen. In the brain, ageing led to hypertrophy of toluidine blue–positive MCs without major changes in cell number; five months of ketotifen treatment reversed these morphometric alterations toward a youthful profile. These findings identify lysosomal deacidification as a hallmark of ageing MCs and demonstrate that ketotifen reacidifies secretory lysosomes via V-ATPase and endocytosis-dependent mechanisms, highlighting lysosomal pH control as a tractable strategy to mitigate MC-driven components of inflammaging.
Reduced brain structural similarity is associated with maturation, neurobiological features, and clinical status in schizophrenia
(Springer Nature, 2025-10-01) García-San-Martín, Natalia; Bethlehem, Richard AI; Segura, Patricia; Mihalik, Agoston; Seidlitz, Jakob; Sebenius, Isaac; Ruiz Veguilla, Miguel; Crespo Facorro, Benedicto; Romero García, Rafael; Fisiología Médica y Biofísica; Psiquiatría; CTS1086: Psiquiatría Traslacional
Schizophrenia spectrum disorders (SSD) are characterized by atypical brain maturation, including alterations in structural similarity between regions. Using structural MRI data from 195 healthy controls (HC) and 352 individuals with SSD, we construct individual Morphometric INverse Divergence (MIND) networks. Compared to HC, individuals with SSD mainly exhibit reduced structural similarity in the temporal, cingulate, and insular lobes, being more pronounced in individuals exhibiting a ‘poor’ clinical status (more impaired cognitive functioning and more severe symptomatology). These alterations are associated with cortical hierarchy and maturational events, locating MIND reductions in higher-order association areas that mature later. Finally, we map 46 neurobiological features onto MIND networks, revealing a high presence of neurotransmitters and astrocytes, along with decreased metabolism and microstructure, in regions with reduced similarity in SSD. These findings provide evidence on the complex interplay between structural similarity, maturational events, and the underlying neurobiology in determining clinical status of individuals with SSD.
Advances in molecular research of oncogenes
(MDPI, 2023-04-13) Calvo Baltanás, Fernando; Santos, Eugenio; Fisiología Médica y Biofísica
Toll-like receptor agonists enhance HIV-specific T cell response mediated by plasmacytoid dendritic cells in diverse HIV-1 disease progression phenotypes
(Elsevier, 2023-04-03) Jiménez-León, María R.; Gasca-Capote, Carmen; Tarancón-Díez, Laura; Domínguez-Molina, Beatriz; López-Verdugo, Macarena; Ritraj, Ryan; Gallego Jiménez, Isabel; Rafii-El-Idrissi Benhnia, Mohammed; López Cortés, Luis Fernando; Ruiz-Mateos, Ezequiel; Fisiología Médica y Biofísica; Bioquímica Médica y Biología Molecular e Inmunología; Medicina; Instituto de Biomedicina de Sevilla (IBIS); Fondo Europeo de Desarrollo Regional (FEDER), (Instituto de Salud Carlos III); Red Temática de Investigación Cooperativa en SIDA; Consejo Superior de Investigaciones Científicas (CSIC)
Background: Plasmacytoid dendritic cells (pDCs) sense viral and bacterial products through Toll-like receptor (TLR)-7 and -9 and translate this sensing into Interferon-α (IFN-α) production and T-cell activation. The understanding of the mechanisms involved in pDCs stimulation may contribute to HIV-cure immunotherapeutic strategies. The objective of the present study was to characterize the immunomodulatory effects of TLR agonist stimulations in several HIV-1 disease progression phenotypes and in non HIV-1 infected donors. Methods: pDCs, CD4 and CD8 T-cells were isolated from 450 ml of whole blood from non HIV-1 infected donors, immune responders (IR), immune non responders (INR), viremic (VIR) and elite controller (EC) participants. pDCs were stimulated overnight with AT-2, CpG-A, CpG-C and GS-9620 or no stimuli. After that, pDCs were co-cultured with autologous CD4 or CD8 T-cells and with/without HIV-1 (Gag peptide pool) or SEB (Staphylococcal Enterotoxin B). Cytokine array, gene expression and deep immunophenotyping were assayed. Findings: pDCs showed an increase of activation markers levels, interferon related genes, HIV-1 restriction factors and cytokines levels after TLR stimulation in the different HIV-disease progression phenotypes. This pDC activation was prominent with CpG-C and GS-9620 and induced an increase of HIV-specific T-cell response even in VIR and INR comparable with EC. This HIV-1 specific T-cell response was associated with the upregulation of HIV-1 restriction factors and IFN-α production by pDC. Interpretation: These results shed light on the mechanisms associated with TLR-specific pDCs stimulation associated with the induction of a T-cell mediated antiviral response which is essential for HIV-1 eradication strategies. Funding: This work was supported by Gilead fellowship program, the Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, FEDER, "a way to make Europe") and the Red Temática de Investigación Cooperativa en SIDA and by the Spanish National Research Council (CSIC).
NMDA-Mediated Regulation of DSCAM Dendritic Local Translation Is Lost in a Mouse Model of Down's Syndrome
(Ed. Society for Neuroscience, 2010-10-06) Alves-Sampaio, Alexandra; Troca-Marín, José Antonio; Montesinos Gutiérrez, María Luz; Fisiología Médica y Biofísica; Fondation Jerome Lejeune (France); Fundacion Ramon Areces (Spain); Junta de Andalucía; Ministerio de Ciencia e Innovación (MICIN). España
Down's syndrome cell adhesion molecule (DSCAM) belongs to the Down's syndrome critical region of human chromosome 21, and it encodes a cell adhesion molecule involved in dendrite morphology and neuronal wiring. Although the function of DSCAM in the adult brain is unknown, its expression pattern suggests a role in synaptic plasticity. Local mRNA translation is a key process in axonal growth, dendritogenesis, and synaptogenesis during development, and in synaptic plasticity in adulthood. Here, we report the dendritic localization of DSCAM mRNA in the adult mouse hippocampus, where it associates with CPEB1 [cytoplasmic polyadenylation element (CPE) binding protein 1], an important regulator of mRNA transport and local translation. We identified five DSCAM isoforms produced by alternative polyadenylation bearing different combinations of regulatory CPE motifs. Overexpression of DSCAM in hippocampal neurons inhibited dendritic branching. Interestingly, dendritic levels of DSCAM mRNA and protein were increased in hippocampal neurons from Ts1Cje mice, a model of Down's syndrome. Most importantly, DSCAM dendritic translation was rapidly induced by NMDA in wild-type, but not in Ts1Cje neurons. We propose that impairment of the NMDA-mediated regulation of DSCAM translation may contribute to the alterations in dendritic morphology and/or synaptic plasticity in Down's syndrome.
Nitric oxide and cancer
(Baishideng Publishing Group, 2010-09-27) Muntané Relat, Jordi; Mata-García, Manuel De La; Fisiología Médica y Biofísica
Nitric oxide (NO) is a lipophilic, highly diffusible and short-lived physiological messenger which regulates a variety of important physiological responses including vasodilation, respiration, cell migration, immune response and apoptosis. NO is synthesized by three differentially gene-encoded NO synthase (NOS) in mammals: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2) and endothelial NOS (eNOS or NOS-3). All isoforms of NOS catalyze the reaction of L-arginine, NADPH and oxygen to NO, L-citrulline and NADP. NO may exert its cellular action by cGMP-dependent as well as by cGMP-independent pathways including postranslational modifications in cysteine (S-nitrosylation or S-nitrosation) and tyrosine (nitration) residues, mixed disulfide formation (S-nitrosoglutathione or GSNO) or promoting further oxidation protein stages which have been related to altered protein function and gene transcription, genotoxic lesions, alteration of cell-cycle check points, apoptosis and DNA repair. NO sensitizes tumor cells to chemotherapeutic compounds. The expression of NOS-2 and NOS-3 has been found to be increased in a variety of human cancers. The multiple actions of NO in the tumor environment is related to heterogeneous cell responses with particular attention in the regulation of the stress response mediated by the hypoxia inducible factor-1 and p53 generally leading to growth arrest, apoptosis or adaptation.
Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3
(Rockefeller University Press, 2010) Xu, Yunling; Yuan, Li; Mak, Judy; Pardanaud, Luc; Caunt, Maresa; Kasman, Ian; Toro Estévez, Raquel del; Bagri, Anil; Fisiología Médica y Biofísica; Agence Nationale de la Recherche (Neuroscience, blanc); European Community (EC); Institut de France (Cino del Duca); Institut National de la Sante et de la Recherche Medicale; Institut National du Cancer; Medical Research Council
Vascular sprouting is a key process-driving development of the vascular system. In this study, we show that neuropilin-2 (Nrp2), a transmembrane receptor for the lymphangiogenic vascular endothelial growth factor C (VEGF-C), plays an important role in lymphatic vessel sprouting. Blocking VEGF-C binding to Nrp2 using antibodies specifically inhibits sprouting of developing lymphatic endothelial tip cells in vivo. In vitro analyses show that Nrp2 modulates lymphatic endothelial tip cell extension and prevents tip cell stalling and retraction during vascular sprout formation. Genetic deletion of Nrp2 reproduces the sprouting defects seen after antibody treatment. To investigate whether this defect depends on Nrp2 interaction with VEGF receptor 2 (VEGFR2) and/or 3, we intercrossed heterozygous mice lacking one allele of these receptors. Double-heterozygous nrp2vegfr2 mice develop normally without detectable lymphatic sprouting defects. In contrast, double-heterozygote nrp2vegfr3 mice show a reduction of lymphatic vessel sprouting and decreased lymph vessel branching in adult organs. Thus, interaction between Nrp2 and VEGFR3 mediates proper lymphatic vessel sprouting in response to VEGF-C.
Kisspeptin Signaling Is Required for Peripheral But Not Central Stimulation of Gonadotropin-Releasing Hormone Neurons by NMDA
(Oxford University Press, 2010-06-23) D'Anglemont De Tassigny, Xavier; Ackroyd, Karen J.; Chatzidaki, Emmanouella E.; Colledge, William H.; Fisiología Médica y Biofísica
NMDA and kisspeptins can stimulate gonadotropin-releasing hormone (GnRH) release after peripheral or central administration in mice. To determine whether these agonists act independently or through a common pathway, we have examined their ability to stimulate GnRH/luteinizing hormone (LH) release after peripheral or central administration in Kiss1- or Gpr54 (Kiss1r)-null mutant mice. Peripheral injection of NMDA failed to stimulate GnRH/LH release in prepubertal or gonadally intact mutant male mice. Dual-labeling experiments indicated a direct activation of Kiss1-expressing neurons in the arcuate nucleus. In contrast, central injection of NMDA into the lateral ventricle increased plasma LH levels in both Kiss1 and Gpr54 mutant male mice similar to the responses in wild-type mice. Central injection of NMDA stimulated c-Fos expression throughout the hypothalamus but not in GnRH neurons, suggesting an action at the nerve terminals only. In contrast, kisspeptin-10 stimulated LH release after both central and peripheral injection but induced c-Fos expression in GnRH neurons only after central administration. Finally, central injection of NMDA induces c-Fos expression in catecholamine- and nitric oxide-producing neurons in the hypothalamus of mutant mice, indicating a possible kisspeptin-independent GnRH/LH release by NMDA through activation of these neurons. Thus, NMDA may act at both GnRH cell bodies (kisspeptin-independent) and nerve terminals (kisspeptin-dependent) in a dual way to participate in the GnRH/LH secretion in the male mouse.
Inhibition of Glioblastoma Growth by the Thiadiazolidinone Compound TDZD-8
(Public Library of Science, 2010-11-08) Aguilar Morante, Diana; Morales-García, José Angel; Sanz-SanCristóbal, Marina; García-Cabezas, Miguel Angel; Santos, Angel; Pérez-Castillo, Ana; Fisiología Médica y Biofísica; Ministerio de Educación. España; Ministerio de Ciencia e Innovación; CIBERNED; Instituto de Salud Carlos III
Background Thiadiazolidinones (TDZD) are small heterocyclic compounds first described as non-ATP competitive inhibitors of glycogen synthase kinase 3β (GSK-3β). In this study, we analyzed the effects of 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), on murine GL261 cells growth in vitro and on the growth of established intracerebral murine gliomas in vivo. Methodology/Principal Findings Our data show that TDZD-8 decreased proliferation and induced apoptosis of GL261 glioblastoma cells in vitro, delayed tumor growth in vivo, and augmented animal survival. These effects were associated with an early activation of extracellular signal-regulated kinase (ERK) pathway and increased expression of EGR-1 and p21 genes. Also, we observed a sustained activation of the ERK pathway, a concomitant phosphorylation and activation of ribosomal S6 kinase (p90RSK) and an inactivation of GSK-3β by phosphorylation at Ser 9. Finally, treatment of glioblastoma stem cells with TDZD-8 resulted in an inhibition of proliferation and self-renewal of these cells. Conclusions/Significance Our results suggest that TDZD-8 uses a novel mechanism to target glioblastoma cells, and that malignant progenitor population could be a target of this compound.
Genetic Structure of the Spanish Population
(BioMed Central, 2010-05-25) Gayán, Javier; Galan, José J.; González-Pérez, Antonio; Sáez, María Eugenia; Martínez-Larrad, María Teresa; Zabena, Carina; Ramírez Lorca, Reposo; Real Navarrete, Luis Miguel; Serrano-Ríos, Manuel; Fisiología Médica y Biofísica; Junta de Andalucía; Corporación Tecnológica de Andalucía; Ministerio de Educación y Ciencia (MEC). España; Ministerio de Ciencia e Innovación; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
Background Genetic admixture is a common caveat for genetic association analysis. Therefore, it is important to characterize the genetic structure of the population under study to control for this kind of potential bias. Results In this study we have sampled over 800 unrelated individuals from the population of Spain, and have genotyped them with a genome-wide coverage. We have carried out linkage disequilibrium, haplotype, population structure and copy-number variation (CNV) analyses, and have compared these estimates of the Spanish population with existing data from similar efforts. Conclusions In general, the Spanish population is similar to the Western and Northern Europeans, but has a more diverse haplotypic structure. Moreover, the Spanish population is also largely homogeneous within itself, although patterns of micro-structure may be able to predict locations of origin from distant regions. Finally, we also present the first characterization of a CNV map of the Spanish population. These results and original data are made available to the scientific community.
Association Analysis of Urotensin II Gene (UTS2) and Flanking Regions with Biochemical Parameters Related to Insulin Resistance
(Association Analysis of Urotensin II Gene (UTS2) and Flanking Regions with Biochemical Parameters Related to Insulin Resistance, 2011-04-29) Sáez, María E.; Smani Hajami, Tarik; Ramírez Lorca, Reposo; Díaz, Ignacio; Ruiz, Agustín; Ruiz, Agustín; Ordóñez Fernández, José Antonio; Fisiología Médica y Biofísica; Centro para el Desarrollo Tecnologico Industrial (CDTI); CIBER of Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM); Instituto de Salud Carlos III; Junta de Andalucía; Ministerio de Ciencia e Innovación; Red RECAVA
Background Urotensin II (UII) is a potent vasoconstrictor peptide, which signals through a G-protein coupled receptor (GPCR) known as GPR14 or urotensin receptor (UTR). UII exerts a broad spectrum of actions in several systems such as vascular cell, heart muscle or pancreas, where it inhibits insulin release. Objective Given the reported role of UII in insulin secretion, we have performed a genetic association analysis of the UTS2 gene and flanking regions with biochemical parameters related to insulin resistance (fasting glucose, glucose 2 hours after a glucose overload, fasting insulin and insulin resistance estimated as HOMA). Results and Conclusions We have identified several polymorphisms associated with the analysed clinical traits, not only at the UTS2 gene, but also in thePER3 gene, located upstream from UTS2. Our results are compatible with a role for UII in glucose homeostasis and diabetes although we cannot rule out the possibility that PER3 gene may underlie the reported associations.
Incarcerated Spigelian hernia: Diagnosis by computed tomography
(Garsi, 2012-12) Cruz, Adolfo; Lerma, Rocío; Sánchez-Ganfornina, Francisco; Muntané Relat, Jordi; Padillo Ruiz, Francisco Javier; Fisiología Médica y Biofísica
Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype
(Springer Science and Business Media LLC, 2025-08-13) Miquel-Rio Luis; Jericó-Escolar, Judith; Sarriés-Serrano, Unai; Yanes-Castilla, Claudia; Torres López, María; Argibay, Uxia; Bortolozzi, Analia; Fisiología Médica y Biofísica; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Gobierno de España; Ministerio de Ciencia e Innovación (MICIN). España
Anxiety and depression are common in Parkinson’s disease (PD), affecting quality of life. Aggregates of α-synuclein (α-Syn) are found in serotonergic (5-HT) raphe nuclei early in the disease, but their relationship to brain changes is unclear. We investigated synaptic plasticity, neuronal activity, and functional magnetic resonance imaging (fMRI)-based brain connectivity in a PD-like mouse model with depressive phenotype. AAV-induced human α-Syn accumulation in raphe 5-HT neurons causes progressive synaptic pathology in interconnected brain regions. This is marked by lower MAP-2, PSD95 and higher SV2A, VAMP2, which are key to synaptic structure and function, as confirmed in human brain tissue samples. Abnormalities in Egr-1-dependent neuronal activity and region-specific differences in resting-state functional brain activity were also detected eight weeks post-AAV infusion, before neurodegeneration. This provides evidence for synaptic and fMRI markers associated with α-Syn pathology in emotional brain circuits, and has translational importance for identifying PD patients at risk for depression.
Spanish Consensus Statement: Clinical Management and Treatment of Tendinopathies in Sport
(Sage Publications Inc, 2017-08-30) Fernandez-Jaén, Tomas; Rey, Guillermo Álvarez; Angulo, Francisco; Cuesta, Jordi Ardevol; Loureda, Rafael Arriaza; España, Fernando Ávila; Spanish Group for Tendon Consensus; Ribas Serna, Juan; García, Pedro Guillen; Fisiología Médica y Biofísica
On October 15, 2016, experts met at Clínica CEMTRO in Madrid, Spain, under the patronage of the Spanish Society for Sports Traumatology (SETRADE), the Spanish Society of Sports Medicine (SEMED), the Spanish Association of Medical Services for Football Clubs (AEMEF), the Spanish Association of Medical Services for Basketball Clubs (AEMB), F.C. Barcelona, and Clínica CEMTRO. The purpose was to consider the most appropriate clinical management and treatment of tendinopathies in sports, based on proven scientific data described in the medical literature as well as on each expert’s experience. Prior to the meeting, each expert received a questionnaire regarding clinical management and treatment of tendinopathies in sports. The present consensus document summarizes the answers to the questionnaire and the resulting discussion and consensus regarding current concepts on tendinopathies in sports.
Simulation-based training during medical degree for diagnosis of mitral stenosis. Clinics, images and decision making
(Elsevier BV, 2017-11) Juvin-Bouvier, Charles E.; Tena-Santana, Gonzalo; Torrejón-Domínguez, José M.; Aumesquet-Contreras, Ángel; Gutiérrez Carretero, Encarnación; Álvarez de Toledo Naranjo, Guillermo; Fisiología Médica y Biofísica
Dada la importancia del conocimiento de la estenosis mitral, se desarrollan simulaciones para el entrenamiento de su diagnóstico durante el grado. Se preparan varios supuestos clínicos de alta fidelidad y diferentes niveles de dificultad y se adaptan a maniquí SimMan, incluyendo información de anamnesis, signos e imágenes reales anonimizadas. Una vez probados los casos, son utilizados en sesiones teórico-prácticas para reforzar lo aprendido en clase. Los alumnos presentan dificultades para reconocer la patología basándose en la clínica y la información recabada durante la anamnesis. No obstante, mantienen alto grado de sospecha clínica que no confirman hasta la visualización de las imágenes. El alumnado es capaz de reconocer el cuadro gracias a las imágenes complementarias, pero no de elaborar un juicio clínico previo. Creemos que se debe reforzar el reconocimiento de signos, haciendo hincapié en que las pruebas complementarias sirven para confirmar una presunción clínica que previamente han debido de elaborar ellos mismos.
Outlook on the neuroprotective effect of estrogen
(Editorial Board of Neural Regeneration Research, 2017-11) D'Anglemont De Tassigny, Xavier; Fisiología Médica y Biofísica
Epidemiologic studies often consider gender differences in a particular pathology, and constantly observe variations between men and women. Indeed, a remarkable sexual dimorphism exists in the epidemiology of neurological conditions and brain diseases. Physiologically, males and females differ by their levels of circulating hormones that drive sexual behavioral, as well as endocrine functions. Estrogen is the primary female sex hormonal group that enwraps estradiol, estrone and estriol, and which are the major naturally occurring hormones prevalent in women. Their role in the reproductive function has long been established, although the ubiquitous expression of its receptors (alpha, beta and G protein-coupled, GPR30) presumes a broader spectrum of action. This short review will summarize the current knowledge in estrogen therapy with particular focus on some of the recent work that might lead to new neuroprotective treatments.
Characterize the role of Hydrogen Sulfide (H2S) in the brain
(Universidad Pablo de Olavide, 2022-03-17) Benítez, Aida Estefanía Rosa; Espadas, Isabel; Fisiología Médica y Biofísica
Motivation: The deregulation of H2S levels in the brain seems to be involved in the origin of several neurodegenerative diseases. However, its precise functions as a gasotransmiter in the central nervous system remains unknown. For this reason, the main objective of this study is to characterize the role of hydrogen sulfide (H2S) as a key element in neurotransmission supporting synaptic plasticity processes in the brain. Methods:We used both, in vitro (primary neuronal cultures) and in vivo (mouse brain tissue) to characterize the synthesis of H2S in the brain by immunofluorescence using the specific antibody for the enzyme cystathionine gamma-lyase (CTH). Results:CTH enzyme has been detected for the first time in primary cortical neuronal cultures and confirmed by immunofluorescence in adult males and females mice cortex. In addition, we also observe a specific pattern of expression in striatum, substantia nigra and hippocampus. Surprisingly, we identified a specific expression in the mossy fiber pathway. Their unmyelinated axons projecting from granulosa cells in the dentate gyrus that terminate in mossy hilar modulator cells and in Cornu Ammonis area 3 (CA3), a region involved in encoding short-term memory. Conclusions: The presence of H2S-producing enzyme CTH in CA3 and Hilus in the hippocampus suggest that H2S has a critical role in memory consolidation. Understanding the regulation of the H2S production and the specific stimuli that induce their release will provide new insights into the biology of H2S and the development of novel therapies for neurodegenerative diseases.
Functional Vascular Smooth Muscle-like Cells Derived from Adult Mouse Uterine Mesothelial Cells
(Public Library of Science, 2013-02-06) Lachaud, Christian Claude; Pezzolla, Daniela; Domínguez-Rodríguez, Alejandro; Smani Hajami, Tarik; Soria, Bernat; Hmadcha, Abdelkrim; Fisiología Médica y Biofísica; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Instituto de Salud Carlos III; Ministerio de Sanidad y Política Social. España
In mammalian visceral organs, vascular smooth muscle cells (VSMCs) originate from an epithelial-to-mesenchymal transition (EMT) of embryonic mesothelial cells (MCs). The ability of adult MCs to recapitulate EMT and to acquire smooth muscle (SM) markers upon provasculogenic culture suggested they might retain embryonic vasculogenic differentiation potential. However, it remains unknown whether adult MCs-derived SM-like cells may acquire specific vascular SM lineage markers and the functionality of differentiated contractile VSMCs. Here, we describe how a gentle trypsinization of adult mouse uterine cords could selectively detach their outermost uterine mesothelial layer cells. As other MCs; uterine MCs (UtMCs) uniformly expressed the epithelial markers β-catenin, ZO-1, E-cadherin, CD54, CD29, and CK18. When cultured in a modified SM differentiation media (SMDM) UtMCs initiated a loss of epithelial characteristics and gained markers expression of EMT (Twist, Snail, and Slug), stem and progenitor (Nanog, Sox2, C-kit, Gata-4, Isl-1, and nestin), SM (α-SMA, calponin, caldesmon, SM22α, desmin, SM-MHC, and smoothelin-B) and cardiac (BMP2, BMP4, ACTC1, sACTN, cTnI, cTnT, ANF, Cx43, and MLC2a). UtMCs repeatedly subcultured in SMDM acquired differentiated VSM-like characteristics and expressed smoothelin-B in the typical stress-fiber pattern expression of contractile VSMCs. Relevantly, UtMCs-derived VSM-like cells could generate “mechanical force” to compact collagen lattices and displayed in diverse degree voltage (K+) and receptor (endothelin-1, oxytocin, norepinephrine, carbachol and vasopressin)-induced [Ca2+]i rises and contraction. Thus, we show for the first time that UtMCs could recapitulate in vitro differentiative events of early cardiovascular differentiation and transdifferentiate in cells exhibiting molecular and functional characteristics of VSMCs.

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