Utilidad de una estrategia de cribado de hipertensión ocular y glaucoma en atención primaria

ObjetivosEvaluar la utilidad de una estrategia de cribado de glaucoma e hipertensión ocular (HTO) medida como número de casos detectados. Evaluar la aceptabilidad de la toma de presión intraocular (PIO) y la aparición de efectos secundarios.DiseñoEstudio descriptivo transversal.EmplazamientoCentro de salud urbano y consulta de oftalmología del hospital de referencia.ParticipantesEn total, 2.044 pacientes mayores de 40 años, seleccionados por muestreo consecutivo entre los que consultaron en el centro de salud durante 9 meses. Se excluyeron los sujetos diagnosticados de glaucoma, HTO, conjuntivitis o enfermedad corneal.IntervencionesToma de PIO con Tonopen XL en atención primaria. Se remitió a oftalmología a los sujetos con una PIO≥21 mmHg. En éstos se midió la PIO con la prueba de Goldmann y, en los que se confirmó la HTO, se realizaron una oftalmoscopia y una campimetría.Mediciones principalesPorcentaje de sujetos con glaucoma, sospecha de glaucoma e HTO confirmada en oftalmología. Valor predictivo positivo (VPP) para HTO.ResultadosSe detectaron 100 sujetos con HTO (4,89%; intervalo de confianza [IC] del 95%, 3,93-5,85%), de los que 21 fueron diagnosticados de glaucoma (1,04%; IC del 95%, 0,57-1,49%) y 10 de sospecha de glaucoma (0,49%; IC del 95%, 0,16-0,82). El VPP para HTO fue del 44,27%. La aceptabilidad de la prueba fue del 98,09%. Ningún paciente presentó efectos secundarios tras la toma de la PIO.ConclusionesLa estrategia evaluada es útil en cuanto al porcentaje de sujetos con glaucoma e HTO detectados. La aceptabilidad de la toma de la PIO con Tonopen XL es alta.ObjectivesTo evaluate the usefulness of a glaucoma and intraocular hypertension screening strategy for new cases detected. To evaluate the acceptability of taking intraocular pressure (IOP) and the appearance of side effects.DesignCross-sectional, descriptive study.SettingAn urban health centre and the ophthalmology clinic of its main hospital.ParticipantsA total of 2044 patients aged over 40, 63.5% women and 36.5% men, with a mean age of 61.23 (SD, 11.42). They were selected by consecutive sampling from patients who visited the health centre over a 9-month period. Subjects diagnosed with glaucoma, ocular hypertension (OH), conjunctivitis, or corneal pathology were excluded.InterventionsTaking of IOP with Tonopen XL in primary care. Subjects with IOP ≥21 mm Hg were referred to ophthalmology. In these patients, IOP was measured with Goldmann, and patients with confirmed OH received ophthalmoscopy and campimetry.Main measurementsPercentage of subjects with glaucoma, suspected glaucoma, and OH confirmed in ophthalmology. Positive predictive value (PPV) for OH.ResultsOne hundred subjects with OH were detected (4.89%; 95% CI, 3.93%-5.85%), of whom 21 were diagnosed with glaucoma (1.04%; 95% CI, 0.57-1.49) and 10 with suspected glaucoma (0.49%; 95% CI, 0.16-0.82). The PPV for OH was 44.27%. The acceptability of the test was 98.09%. No patients presented with side-effects following the taking of their IOP.ConclusionsThe strategy evaluated is useful in terms of the number of subjects with glaucoma and OH detected. The acceptability of taking IOP with Tonopen XL was high

Rac2 GTPase activation by angiotensin II is modulated by Ca2+/calcineurin and mitogen-activated protein kinases in human neutrophils

Angiotensin II (Ang II) highly stimulates superoxide anion production by neutrophils. The G-protein Rac2 modulates the activity of NADPH oxidase in response to various stimuli. Here, we describe that Ang II induced both Rac2 translocation from the cytosol to the plasma membrane and Rac2 GTP-binding activity. Furthermore, Clostridium difficile toxin A, an inhibitor of the Rho-GTPases family Rho, Rac and Cdc42, prevented Ang II-elicited O2/ROS production, phosphorylation of the mitogen-activated protein kinases (MAPKs) p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2, and Rac2 activation. Rac2 GTPase inhibition by C. difficile toxin A was accompanied by a robust reduction of the cytosolic Ca2+ elevation induced by Ang II in human neutrophils. Furthermore, SB203580 and PD098059 act as inhibitors of p38MAPK and ERK1/2 respectively, wortmannin, an inhibitor of phosphatidylinositol-3-kinase, and cyclosporin A, a calcineurin inhibitor, hindered both translocation of Rac2 from the cytosol to the plasma membrane and enhancement of Rac2 GTP-binding elicited by Ang II. These results provide evidence that the activation of Rac2 by Ang II is exerted through multiple signalling pathways, involving Ca2+/calcineurin and protein kinases, the elucidation of which should be insightful in the design of new therapies aimed at reversing the inflammation of vessel walls found in a number of cardiovascular diseases.This work was financed by grants from the Ministerio de Educación y Ciencia (BFU2006-13802), and the Consejería de Innovación, Ciencia y Empresa (P06-CTS-1936), Junta de Andalucía, Spain, awarded to F S

Estudio de la dinámica del humor acuoso mediante fluorofotometría en el glaucoma de ángulo abierto

Tesis Univ. Complutense de Madrid, 1991, Facultad de Medicina, Departamento de OftalmologíaDepto. de Inmunología, Oftalmología y ORLFac. de MedicinaTRUEpu

Expression of the transcription factor NFAT2 in human neutrophils: IgE-dependent, Ca2+- and calcineurin-mediated NFAT2 activation

NFAT (nuclear factors of activated T cells) proteins constitute a family of transcription factors involved in mediating signal transduction. The presence of NFAT isoforms has been described in all cell types of the immune system, with the exception of neutrophils. In the present work we report for the first time the expression in human neutrophils of NFAT2 mRNA and protein. We also report that specific antigens were able to promote NFAT2 protein translocation to the nucleus, an effect that was mimicked by the treatment of neutrophils with anti-immunoglobulin E (anti-IgE) or anti-Fc{epsilon}-receptor antibodies. Antigens, anti-IgE and anti-Fc{epsilon}Rs also increased Ca2+ release and the intracellular activity of calcineurin, which was able to interact physically with NFAT2, in parallel to eliciting an enhanced NFAT2 DNA-binding activity. In addition, specific chemical inhibitors of the NFAT pathway, such as cyclosporin A and VIVIT peptide, abolished antigen and anti-IgE-induced cyclooxygenase-2 (COX2) gene upregulation and prostaglandin (PGE2) release, suggesting that this process is through NFAT. Our results provide evidence that NFAT2 is constitutively expressed in human neutrophils, and after IgE-dependent activation operates as a transcription factor in the modulation of genes, such as COX2, during allergic inflammation.A.V. and P.C. were supported by fellowships from the Ministerio de Ciencia y Tecnología, and Fundación Alergol, Spain. R.E. is a recipient of a postdoctoral grant (Juan de la Cierva) (SAF2003-00200) from the Ministerio de Educación y Ciencia, Spain. This work was funded by grants from the Consejería de Salud, Junta de Andalucía (SAS-55/04 and SAS-74/04)

15-Deoxy-Δ12,14-prostaglandin J2 induces heme oxygenase-1 gene expression in a reactive oxygen species-dependent manner in human lymphocytes

15-Deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) has been recently proposed as a potent anti-inflammatory agent. However, the mechanisms by which 15dPGJ2 mediates its therapeutic effects in vivo are unclear. We demonstrate that 15dPGJ2 at micromolar (2.5–10 µM) concentrations induces the expression of heme oxygenase-1 (HO-1), an anti-inflammatory enzyme, at both mRNA and protein levels in human lymphocytes. In contrast, troglitazone and ciglitazone, two thiazolidinediones that mimic several effects of 15dPGJ2 through their binding to the peroxisome proliferator-activated receptor (PPAR)-γ, did not affect HO-1 expression, and the positive effect of 15dPGJ2 on this process was mimicked instead by other cyclopentenone prostaglandins (PG), such as PGD2 (the precursor of 15dPGJ2) and PGA1 and PGA2 which do not interact with PPAR-γ. Also, 15dPGJ2 enhanced the intracellular production of reactive oxygen species (ROS) and increased xanthine oxidase activity in vitro. Inhibition of intracellular ROS production by N-acetylcysteine, TEMPO, Me2SO, 1,10-phenanthroline, or allopurinol resulted in a decreased 15dPGJ2-dependent HO-1 expression in the cells. Furthermore, buthionine sulfoximine, an inhibitor of reduced glutathione synthesis, or Fe2+/Cu2+ ions enhanced the positive effect of 15dPGJ2 on HO-1 expression. On the other hand, the inhibition of phosphatidylinositol 3-kinase or p38 mitogen-activated protein kinase, or the blockade of transcription factor NF-κB activation, hindered 15dPGJ2-elicited HO-1 expression. Collectively, the present data suggest that 15dPGJ2 anti-inflammatory actions at pharmacological concentrations involve the induction of HO-1 gene expression through mechanisms independent of PPAR-γ activation and dependent on ROS produced via the xanthine/xanthine oxidase system and/or through Fenton reactions. Both phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase signaling pathways also appear implicated in modulation of HO-1 expression by 15dPGJ2.This work was supported in part by Ministerio de Ciencia y Tecnología Grants SAF/2000-117 (to F. S.) and SAF/2000-161 (to F. J. B.) and by a grant from the Fundación SEIAC, Spain (to J. M.)

Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-κB

Neutrophils are mobilized to the vascular wall during vessel inflammation. Published data are conflicting on phagocytic nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activation during the hypertensive state, and the capacity of angiotensin II (Ang II) to modulate the intracellular redox status has not been analyzed in neutrophils. We here describe that Ang II highly stimulates endogenous and extracellular O2- production in these cells, consistent with the translocation to the cell membrane of the cytosolic components of NADPH oxidase, p47phox, and p67phox. The Ang II–dependent O2- production was suppressed by specific inhibitors of AT1 receptors, of the p38MAPK and ERK1/2 pathways, and of flavin oxidases. Furthermore, Ang II induced a robust phosphorylation of p38MAPK, ERK1/2, and JNK1/2 (particularly JNK2), which was hindered by inhibitors of NADPH oxidase, tyrosine kinases, and ROS scavengers. Ang II increased cytosolic Ca2+ levels—released mainly from calcium stores—enhanced the synthesis de novo and activity of calcineurin, and stimulated the DNA-binding activity of the transcription factor NF-κB in cultured human neutrophils. Present data demonstrate for the first time a stimulatory role of Ang II in the activation of phagocytic cells, underscore the relevant role of ROS as mediators in this process, and uncover a variety of signaling pathways by which Ang II operates in human neutrophils.Supported by Ministerio de Ciencia y Tecnología grants SAF/2000-117 (F.S.) and SAF/2000-161 (F.J.B.) and by grants from the Fundacion SEIAC, Bial-Arıstegui, and Hycor Biomedical Inc (J.M.). A.V. was supported by a predoctoral fellowship from the Ministerio de Ciencia y Tecnología

Homocysteine enhances superoxide anion release and NADPH oxidase assembly by human neutrophils: effects on MAPK activation and neutrophil migration

Hyperhomocysteinaemia has recently been recognized as a risk factor of cardiovascular disease. However, the action mechanisms of homocysteine (Hcy) are not well understood. Given that Hcy may be involved in the recruitment of monocytes and neutrophils to the vascular wall, we have investigated the role of Hcy in essential functions of human neutrophils. We show that Hcy increased superoxide anion (O2√−) release by neutrophils to the extracellular medium, and that this effect was inhibited by superoxide dismutase and diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase activity. The enzyme from rat peritoneal macrophages displayed a similar response. These effects were accompanied by a time-dependent increased translocation of p47phox and p67phox subunits of NADPH oxidase to the plasma membrane. We also show that Hcy increased intracellular H2O2 production by neutrophils, that Hcy enhanced the activation and phosphorylation of mitogen-activated protein kinases (MAPKs), specifically p38-MAPK and ERK1/2, and that the migration of neutrophils was increased by Hcy. Present results are the first evidence that Hcy enhances the oxidative stress of neutrophils, and underscore the potential role of phagocytic cells in vascular wall injury through O2√− release in hyperhomocysteinaemia conditions.This work was financed by Grants from the Ministerio de Ciencia y Tecnología SAF/2000-117 (awarded to F.S.) and SAF/2000-161 (given to F.J.B.), and by a Grant from the Fundación SEIAC, Spain (awarded to J.M.)

Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination in Kidney Transplant Recipients.

The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses

Red “Universidad, género, docencia e igualdad”

La Red de investigación en docencia universitaria “Universidad, docencia, genero e igualdad” persigue avanzar en la calidad e innovación de las enseñanzas universitarias a partir de la inclusión de la perspectiva de género. Se busca dar cumplimiento a las directrices generales de los nuevos planes de estudio respecto del principio de igualdad de oportunidades entre hombres y mujeres en la formación universitaria (Real Decreto 1393/2007. BOE nº 260, 30 de octubre de 2007). En la séptima edición de la Red, y tomando como referentes la “Guía de recomendaciones para la inclusión de la perspectiva de género en la docencia universitaria: práctica (I)” y la “Guía de recomendaciones para la inclusión de la perspectiva de género en la docencia universitaria: claves conceptuales y teóricas (II)”, elaboradas por la propia Red en ediciones pasadas, el trabajo desarrollado se ha dirigido a introducir las recomendaciones recogidas en las referencias citadas (y disponibles en la colección en línea “apuntes para la igualdad”, de la Unidad de Igualdad de la Universidad de Alicante) en las guías docentes de las asignaturas recogidas en el proyecto de Redes presentado Asimismo, se ha continuado en el mantenimiento del “Portal web con recursos docentes con perspectiva de género”, proyecto financiado por el Instituto de la Mujer (PACUI, 2012)