Background: The goal of this study was to analyze the in vitro effect of plasma-isolated extracellular vesicles (EVs) from patients with impaired fasting glucose (IFG) on cell migration and ...angiogenic score on human endothelial cells (EA.hy926) cultures. Methods: Plasma samples from five patients with IFG, five with Type 2 diabetes mellitus (T2DM), and five normoglycemic subjects (controls) were used. Plasma-derived EVs were characterized by electron microscopy, dynamic light scattering and Western blotting, vascular endothelial growth factor receptor 2 (VEGFR-2), and endoglin detected in EVs by flow cytometry; wound closure assays and angiogenic score by matrigel assays in EA.hy926 cells were performed. Results: EA.hy926 cell migration induced by plasma-derived EVs from patients with IFG was greater than in control subjects (P = 0.023). EVs from patients with T2DM and IFG induced higher angiogenic scores than EVs from control subjects (P = 0.012 and P = 0.036, respectively). Conclusions: Endoglin and VEGFR-2 levels in EVs from IFG or T2DM patients were not different from those in control subjects. Plasma-derived EVs from patients with IFG and T2DM positively influenced human endothelial cell migration and angiogenic activity in vitro.
La fracción exhalada de óxido nítrico (FeNO) se relaciona con el nivel de inflamación eosinofílica en las vías aéreas y los niveles de interleucina-13, por lo que podría ser una herramienta ...diagnóstica y de seguimiento en el asma. Se convocó un grupo de trabajo integrado por neumólogos, expertos en fisiología de la respiración y alergólogos, con la finalidad de establecer criterios para el uso de la FeNO en asma en México. Mediante un método Delphi simplificado y discusión grupal, se consensaron varios puntos clave en relación con el uso de la FeNO. Sugerimos que la medición de la FeNO sirve para el diagnóstico de asma en clínicas especializadas, tanto en niños como adultos, así como para determinar el nivel de tratamiento con corticosteroides. En asma grave, recomendamos la FeNO para la endotipificación, detectar la mala adherencia terapéutica, el subtratamiento y el riesgo de crisis. Sugerimos su uso para determinar el nivel de tratamiento con corticosteroides e identificar pacientes con riesgo de tener una pérdida de la función pulmonar. También la recomendamos en el adulto para mejorar la elección de medicamentos biológicos y, en este contexto, solo la sugerimos en casos selectos en niños.
Abstract
BACKGROUND AND AIMS
Peritoneal dialysis (PD) is the current replacement therapy for end-stage renal disease (ESRD) patients until renal transplantation can be achieved. However, chronic ...exposure to non-physiological PD fluids (PDF) and occasional infection episodes may lead to peritoneal damage and membrane transport failure. Chronic inflammation, together with mesothelial-to-mesenchymal transition (MMT) and submesothelial fibrosis, is a hallmark of PDF-associated peritoneal damage whose intrinsic mechanisms are still expected to be disclosed 1–2. Activation of the innate immunity is the cornerstone for infectious agents’ elimination, also enrolled in response to damage-associated molecular patterns (DAMPs) released from stressed or injured host cells. Leakage of DNA from stressed mitochondria and damaged genomic DNA may act as DAMPs that are recognized by cytosolic double-strand DNA sensors, like the stimulator of interferon gene (STING), to mount an inflammatory response 3. Excessive activation of STING is involved in autoinflammatory, autoimmune, and increasingly related to several chronic inflammatory conditions 4. Thus, this study aimed to investigate the role of STING in experimental peritoneal damage.
METHOD
We induced peritoneal fibrosis in wild-type and STING-KO mice by intraperitoneal administration of 0.1% chlorhexidine gluconate (CHX) daily for 4 weeks. No treated WT and STING-KO mice were used as control. Then, mice were euthanized, and peritoneal tissue and peritoneal lavage fluids were recollected for the following experiments. STING mRNA (Tmem173) and protein levels in control and CHX-treated wild-type were measured by RT-qPCR, western blot and immunohistochemistry. Peritoneal levels of the STING downstream proteins TBK1 and IRF3 and their phosphorylated isoforms were assayed by western blot. Peritoneal membrane thickness was measured in formalin-fixed paraffin-embedded tissues stained with Masson's trichrome stain. Fibronectin protein levels were evaluated by western blot and MMT, fibrosis, and inflammation markers were determined by RT-qPCR. Inflammatory cells present in peritoneal effluents were assayed by flow cytometry.
RESULTS
We found that in the peritoneum of CHX-treated wild-type mice both Tmem173 expression and STING protein levels were increased. Interestingly, STING-positive cells were located in areas of peritoneal thickness and immune infiltration. Moreover, the protein levels of IRF3, p-IRF3, TBK1 and p-TBK1 were increased, indicating that the STING pathway is activated in experimental peritoneal damage. In STING-KO mice, CHX-induced peritoneal damage was prevented. STING-KO mice under CHX treatment showed decreased peritoneal membrane thickness and attenuated CHX-induced expression of fibrosis and MMT markers, such as Tgb1, Snai1, Cdh2, Col1a1, Fn1 and fibronectin protein when compared with CHX-treated WT mice. The absence of STING also prevented the gene expression of cytokines (Il1b, Il6 and Ifng) and chemokines (Ccl5, Ccl2 and Ccl19) and macrophages infiltration into the peritoneum. Inflammatory cell recruitment into the peritoneal cavity was also decreased in STING-KO mice, including CD3+CD4+ lymphocytes and CD11b+F4/80+ macrophages.
CONCLUSION
In summary, STING absence prevents peritoneal membrane thickness, fibrosis, and inflammation induced by CHX in a mice model. These results suggest that STING plays a key role in peritoneal membrane injury. Therefore, STING may become a new potential therapeutic target in PD-associated peritoneal damage.
INTRODUCTIONClinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with ...asthma.METHODSIn this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants.RESULTSSurveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4-6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice.CONCLUSIONSIn line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.
Resumen: La granulomatosis eosinofílica con poliangitis (GEPA), anteriormente denominado síndrome de Churg-Strauss (SCS), es un trastorno poco frecuente, de etiología desconocida, caracterizada por ...una vasculitis necrosante que afecta a vasos de pequeño a mediano calibre. Los pacientes presentan como rasgo característico antecedentes de asma, rinitis alérgica y eosinofilia en sangre periférica. La GEPA, antes denominado SCS es poco común en la infancia. Aunque la GEPA es una vasculitis asociada a la presencia de anticuerpos anticitoplasma de neutrófilo (ANCA), en niños sólo se encuentran en menos del 40% de los casos. La detección temprana de la enfermedad es importante ya que un retraso en el diagnóstico puede llevar a la afectación orgánica de grado variable con resultados fatales. La GEPA de inicio en la infancia representa menos del 2% de los casos de vasculitis en edad pediátrica, y sólo 50 casos de GEPA en menores de 18 años se habían publicado hasta el año 2013. Presentamos el caso de un niño de 13 años de edad con asma de difícil control y deterioro de su estado general, que finalmente fue diagnosticado con GEPA-ANCA negativo.
Resumen: La eventración diafragmática es una patología infrecuente en la edad pediátrica, definida como una elevación anormal, ya sea parcial o total del diafragma, sin una solución de la continuidad ...asociada con el desplazamiento de los órganos abdominales hacia el tórax. Algunos reportes refieren una incidencia de 1-3/1,000 recién nacidos. Se presenta con mayor frecuencia en el sexo masculino y representa el 5% de todas las anomalías diafragmáticas. Según su origen se clasifican en congénita y adquirida teniendo cada una de ellas características particulares. Puede presentarse de manera aislada o asociada con otros defectos congénitos como: hipoplasia pulmonar, enfermedad cardíaca congénita, pectum excavatum, paladar hendido, hipospadias, criptorquidia y tortícolis congénita. El diagnóstico se realiza con una radiografía de tórax posteroanterior y una lateral en donde se muestre una elevación del hemidiafragma derecho al menos dos espacios intercostales por arriba del izquierdo, o el izquierdo elevado un espacio intercostal por arriba del derecho. El tratamiento de la ED difiere dependiendo de su origen y manifestaciones clínicas, siendo en algunos casos necesario el manejo quirúrgico por lo que se presenta un caso clínico así como la revisión de la literatura.
Resumen: La mucormicosis es una infección grave causada por hongos del género Mucor y Rizhopus (del orden Mucorales, clase: Zygomycetes) que se presenta en pacientes inmunocomprometidos, constituye ...una micosis oportunista. Ingresan al organismo por inhalación de las esporas a través de la vía aérea, contaminación de heridas o catéteres o por ingestión de las mismas. Las formas de presentación clínica son muy variadas; sin embargo, las más importantes son la rinocerebral y la pulmonar, siendo la última la más reportada en niños. El diagnóstico es difícil por lo que es necesario el hallazgo de las hifas en muestras de lavado broncoalveolar, secreciones corporales o biopsias. El tratamiento se basa en tres aspectos fundamentales: 1) tratamiento de la enfermedad de base, 2) tratamiento antimicótico y 3) debridación de tejido necrótico.
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