ABSTRACT
The Snail1 transcriptional repressor plays a key role in triggering epithelial-to-mesenchymal transition. Although Snail1 is widely expressed in early development, in adult animals it is limited to a subset of mesenchymal cells where it has a largely unknown function. Using a mouse model with inducible depletion of Snail1, here we demonstrate that Snail1 is required to maintain mesenchymal stem cells (MSCs). This effect is associated to the responsiveness to transforming growth factor (TGF)-ß1 that shows a strong Snail1 dependence. Snail1 depletion in conditional knockout adult animals causes a significant decrease in the number of bone marrow-derived MSCs. In culture, Snail1-deficient MSCs prematurely differentiate to osteoblasts or adipocytes and, in contrast to controls, are resistant to the TGF-ß1-induced differentiation block. These results demonstrate a new role for Snail1 in TGF-ß response and MSC maintenance.
Subject(s)
Cell Differentiation/drug effects , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Transcription Factors/metabolism , Transforming Growth Factor beta/pharmacology , 3T3-L1 Cells , Animals , Biomarkers/metabolism , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Cell Count , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Expression Regulation/drug effects , Gene Knockout Techniques , Male , Mesenchymal Stem Cells/metabolism , Mice , Snail Family Transcription Factors , Transcription Factors/deficiency , Transcription Factors/geneticsABSTRACT
We report a previously healthy 43 years old male, that one year ago presented with a hyperthyroidism, treated with metimazole and radioiodine. Two months after receiving the latter, he was admitted to the hospital for dyspnea, tachycardia and chest pain. An atrial fibrillation with a frequency of 190 beats per minute was found. During hospital stay, the patient suffered a cardiogenic shock that recovered. The patient was discharged five days after admission. During follow up, there was a progressive reduction of cardiac symptoms.
Subject(s)
Humans , Male , Adult , Cardiomyopathies/etiology , Hyperthyroidism/complications , Cardiomyopathies/drug therapy , Atrial Fibrillation/etiology , Graves Disease , Hyperthyroidism/drug therapy , Thyrotoxicosis , Treatment OutcomeABSTRACT
Pierre Robin sequence is a pathology derived from alteration in the first and second branchial arch. Patients have breathing problems due to micrognathia and glossoptosis, causing severe upper airway obstruction. One surgical treatment is distraction osteogenesis. Three patients with Pierre Robin sequence (case 1, 3 months old; cases 2 and 3, 1 month old) with severe upper airway obstruction requiring mechanical ventilator assistance, underwent mandibular distraction osteogenesis prematurely with a new anchoring system, thus avoiding tracheostomy and its consequences. An intraoral approach was used to avoid scarring. A new anchoring device with transfixing Kirschner wire in the proximal (mandibular ramus) and distal segment (chin zone) was used. This diminishes the risk of distractor device displacement, guaranteeing optimal stability. A more anterior installation reduces the risk of damaging tooth buds in the mandibular body and the inferior alveolar nerve. The more anterior the fixation, the more horizontal the distraction vector becomes. The position and stability of the device are crucial. In these three patients the placement of two transfixing Kirschner wires using an intraoral approach showed good results and stability during the period of distraction and consolidation, with optimal results on the upper airway, avoiding tracheostomy.
Subject(s)
External Fixators , Mandible/surgery , Osteogenesis, Distraction/instrumentation , Pierre Robin Syndrome/surgery , Airway Obstruction/surgery , Bone Wires , Chin/surgery , Equipment Design , Follow-Up Studies , Humans , Infant , Infant, Newborn , Mandible/abnormalities , Mandible/growth & development , Micrognathism/surgery , Osteogenesis, Distraction/methods , Osteotomy/instrumentation , Osteotomy/methods , Time FactorsABSTRACT
El presente estudio tuvo como objetivo caracterizar el efecto de un inhibidor de la enzima convertidora de angiotensina (ECA) sobre los cambios estructurales y funcionales miocárdicos post infarto al miocardio (IAM) experimental en ratas. Se evaluaron los cambios morfológicos y las propiedades mecánicas del miocardio en el corazón aislado perfundido. El estudio se efectuó en dos grupos experimentales, uno tratado con placebo (n = 22) y otro administrando el inhibidor de ECA ramipril (10 mg/l en agua a beber, n = 15) durante 45 días. Al comparar con el grupo placebo, en el grupo tratado con ramipril observamos menor relación peso ventricular derecho/peso corporal (0.83 ñ 0.38 vs 1.16 ñ 0.31, respectivamente, p < 0.05), mayor espesor de la pared ventricular izquierda en la zona de la cicatriz del infarto (0.89 ñ 0.58 vs 0.57 ñ 0.28 mm, respectivamente, p < 0.05) y una menor pendiente de la relación tensión-elongación diastólica (106.8 ñ 0.9 vs 13.7 ñ 1.2 g/cm², respectivamente, p < 0.05). El porcentaje del área ocupado por el infarto fue 39.4 ñ 12.1 en el grupo placebo y 34.8 ñ 13.4 en el grupo tratado con ramipril (ns). En conclusión, el inhibidor de la ECA ramipril, a las dosis utilizadas durante 6 semanas en ratas con infarto al miocardio experimental, demostró prevenir el desarrollo de hipertrofia ventricular derecha, con el desarrollo de una cicatriz de mayor grosor y un VI menos rígido con una tendencia a un menor tamaño del infarto que en las ratas no tratadas.Estos efectos morfofuncionales podrían explicar en parte el efecto benéfico de los inhibidores de la ECA en el curso clínico del IAM
Subject(s)
Animals , Rats , Angiotensin-Converting Enzyme Inhibitors/pharmacokinetics , Myocardial Infarction/physiopathology , Hypertrophy, Right Ventricular/physiopathology , Ramipril/pharmacokinetics , Rats, Sprague-DawleyABSTRACT
To study the capacity to predict successful early extubation of ventilatory and gas exchange parameters, 230 patients admitted to an intensive care unit after coronary or valvular surgery were studied. Measurements were made through a T piece 30 minutes after discontinuing mechanical ventilation. Six patients died in the postoperative period. Two hundred ten patients tolerated early extubation (14ñ5 h of mechanical ventilation) and 20 required prolonged mechanical ventilation (74ñ107 h). The latter had longer surgical procedures (291ñ65 and 240ñ67 min respectively) and extracorporeal circulation times (138ñ42 and 104ñ43 min respectively), required more vasoactive drugs, had more episodes of confusion and had a higher surgical risk. Tidal volume, respiratory frequency, maximal inspiratory pressure and blood gases at the moment of extubation were similar in both groups. Pulmonary function parameters and blood gases measured during a T piece trial are not good predictors of early extubation in cardiac surgery
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Thoracic Surgery , Respiration, Artificial/methods , Postoperative Care/standards , Lung Volume Measurements , Blood Gas Analysis/methods , Intubation, Intratracheal/methodsABSTRACT
El shock cardiogénico secundario al infarto del miocardio (IAM) ocurre en realción a infartos muy extensos y tiene alta mortalidad. Para evaluar el impacto del tratamiento actual del infarto, hemos comparado la incidencia y características del shock cardiogénico entre 252 pacientes admitidos por IAM entre 1983-1985 (Grupo 1), con 228 pacientes admitidos después de 1990 (Grupo 2). Mientras en el Grupo 1 sólo se trataron las complicaciones del infarto, en el Grupo 2 hubo 69 pacientes (31 por ciento ) que se sometieron a trombolisis o angioplastía en las primeras seis horas y todos recibieron heparina, antiagregantes plaquetarios y nitroglicerina i.v. La incidencia de shock cardiogénico fue la misma en Grupo 1 y Grupo 2 (13 por ciento y 12,8 por ciento ). Tampoco hubo diferencias en la incidencia de shock no relacionada a ruptura cardiaca (8,3 por ciento para el Grupo 1 y 7,9 por ciento para el grupo 2). Los grupos se diferenciaron, sin embargo, en el momento de aparición del shock. Mientras en el Grupo 1 el 53 por ciento de los casos lo desarrollaron después de 24 horas de iniciado el infarto, en el Grupo 2 la mayor parte lo presentó en las primeras 24 horas del infarto (88 por ciento ), período en el que se concentra la mayor mortalidad. En conclusión, el tratamiento actual del IAM ha disminuido la incidencia de shock cardiogénico por falla miocárdica tardía, pero no ha influido en la incidencia del shock que se presenta en las primeras horas del infarto
