La creencia epistemológica constructivista sobre el conocimiento científico varía en función del año de formación en los estudiantes de Medicina pero no en los estudiantes de otras carreras de la salud / The constructivist epistemological belief about scientific knowledge varies according to the year of training in medical students but not in students of other health careers

Background: To optimize the teaching-learning process it is fundamental to know the representations that students have regarding knowledge. Epistemological beliefs are implicit theories that guide the practical actions of people. Aim: To characterize and compare epistemological beliefs regarding the nature and acquisition of scientific knowledge of health career students. Material and Methods: Between 2012 and 2013, 726 students coursing first, third or fifth year from six health careers answered a validated questionnaire that includes closed and open questions aimed to characterize their epistemological beliefs about scientific knowledge. Results: Irrespective of the career, when students had to select predefined answers, most of them appeared as constructivists (61%). On the other hand, when they had to argue, the majority seemed objectivist (47%). First-year medical students have the highest frequency of constructivist epistemological beliefs (56%). Paradoxically, the lowest percentage is found (34%) in the fifth year. The students of the health careers, in particular those of Medicine, recognize that knowledge is not acquired immediately (83%) and that its distribution is shared (92%). Conclusions: Discordance between selections and arguments suggests that epistemological sophistication is achieved declaratively but not practically. The lower proportion of students who presented constructivist beliefs in the fifth year compared to first year of Medicine could be associated with the pedagogical approaches used in the different cycles of the career.

Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells has a neutral effect on obesity-induced diabetic cardiomyopathy

Obesity is a major global health issue. Obese patients develop metabolic syndrome, which is a cluster of clinical features characterized by insulin resistance and dyslipidemia. Its cardiac manifestation, diabetic cardiomyopathy, leads to heart failure. Bone marrow-derived multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSC) are envisioned as a therapeutic tool not only for cardiovascular diseases but also for other degenerative conditions. Our aim was to evaluate whether the intravenous administration of MSC modifies cardiac dysfunction in obese mice. To this end, C57BL/6 mice were fed a regular (normal) or high-fat diet (obese). Obese animals received the vehicle (obese), a single dose (obese + 1x MSC) or three doses (obese + 3x MSC) of 0.5x10(6) syngeneic MSC. Two to three months following MSC administration, cardiac function was assessed by cardiac catheterization, at basal condition and after a pharmacological stress. Compared to normal mice, obese mice presented hyperglycemia, hyperinsulinemia, hypercholesterolemia and cardiac dysfunction after stress condition. Exogenous MSC neither improved nor impaired this cardiac dysfunction. Thus, intravenous administration of MSC has neutral effect on obesity-induced diabetic cardiomyopathy.

MSC transplantation: a promising therapeutic strategy to manage the onset and progression of diabetic nephropathy

Currently, one of the main threats to public health is diabetes mellitus. Its most detrimental complication is diabetic nephropathy (DN), a clinical syndrome associated with kidney damage and an increased risk of cardiovascular disease. Irrespective of the type of diabetes, DN follows a well-known temporal course. The earliest detectable signs are microalbuminuria and histopathological changes including extracellular matrix deposition, glomerular basement membrane thickening, glomerular and mesangial expansion. Later on macroalbuminuria appears, followed by a progressive decline in glomerular filtration rate and the loss of glomerular podocytes, tubulointerstitial fibrosis, glomerulosclerosis and arteriolar hyalinosis. Tight glycemic and hypertension controls remain the key factors for preventing or arresting the progression of DN. Nevertheless, despite considerable educational effort to control the disease, a significant number of patients not only develop DN, but also progress to chronic kidney disease. Therefore, the availability of a strategy aimed to prevent, delay or revert DN would be highly desirable. In this article, we review the pathophysiological features of DN and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs). The perfect match between them, together with encouraging pre-clinical data available, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage DN onset and progression, not only because of the safety of this procedure, but mainly because of the renoprotective potential of MSCs.

Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin gene

Transgenic mice carrying the human insulin gene driven by the K-cell glucose-dependent insulinotropic peptide (GIP) promoter secrete insulin and display normal glucose tolerance tests after their pancreatic p-cells have been destroyed. Establishing the existence of other types of cells that can process and secrete transgenic insulin would help the development of new gene therapy strategies to treat patients with diabetes mellitus. It is noted that in addition to GIP secreting K-cells, the glucagon-like peptide 1 (GLP-1) generating L-cells share/ many similarities to pancreatic p-cells, including the peptidases required for proinsulin processing, hormone storage and a glucose-stimulated hormone secretion mechanism. In the present study, we demonstrate that not only K-cells, but also L-cells engineered with the human preproinsulin gene are able to synthesize, store and, upon glucose stimulation, release mature insulin. When the mouse enteroendocrine STC-1 cell line was transfected with the human preproinsulin gene, driven either by the K-cell specific GIP promoter or by the constitutive cytomegalovirus (CMV) promoter, human insulin co-localizes in vesicles that contain GIP (GIP or CMV promoter) or GLP-1 (CMV promoter). Exposure to glucose of engineered STC-1 cells led to a marked insulin secretion, which was 7-fold greater when the insulin gene was driven by the CMV promoter (expressed both in K-cells and L-cells) than when it was driven by the GIP promoter (expressed only in K-cells). Thus, besides pancreatic p-cells, both gastrointestinal enteroendocrine K-cells and L-cells can be selected as the target cell in a gene therapy strategy to treat patients with type 1 diabetes mellitus.

Efectos protectores de la hipotermia moderada en modelo de injuria pulmonar inducida por ventilación mecánica / Protector effects of moderated hypothermia in model of pulmonary injury caused by mechanical ventilation

Se ha establecido que el empleo inapropiado de la ventilación mecánica (VM) es capaz de generar daño pulmonar y de amplificar una noxa pulmonar pre-existente. Éste fenómeno mecánico, denominado injuria pulmonar inducida por VM (VILI), es capaz de gatillar consecuencias biológicas locales y a distancia. La hipotermia ha sido empleada en situaciones clínicas que generan un desequilibrio entre la entrega y el consumo tisular de oxígeno, debido a su capacidad de reducir este último. Nuestro objetivo fue determinar el efecto de la hipotermia moderada (HM) sobre marcadores biológicos de VILI e intercambio gaseoso.Se emplearon 12 ratas Sprague-Dawley machos adultas. Tras ser anestesiadas se intubaron y ventilaron mecánicamente en modalidad presión control, PIM 40 cmH2O, ZEEP, FR 60/min, TIM 25 por ciento, FIO2 100 por ciento. Los animales se aleatorizaron a grupos normotermia (N) (37 ± 1ºC) y HM (34 ± 1ºC), medido a nivel de esófago torácico. Se registró gasometría arterial, gravimetría, análisis histológico y medición de concentración de proteínas, interleukina (IL)-1[beta] (IL-1b) y factor de necrosis tumoral (TNF)-[alfa] (TNF-a) en el sobrenadante del lavado bronco alveolar (LBA) y plasma.Los animales con HM redujeron relación peso húmedo/seco y la PaCO2, respecto a los animales normotérmicos, no siendo significativa la mejoría de la PaO2. Hubo además una reducción de los niveles sistémicos de citoquinas inflamatorias en el grupo HM. No hubo diferencias respecto al score histológico de daño pulmonar ni de concentración de proteínas en LBA. En este modelo experimental la HM provocó una reducción del agua extravascular pulmonar y citoquinas inflamatorias plasmáticas, lo que refleja menor daño, asociado a una disminución significativa en la PaCO2. Estos hechos ameritan la realización de nuevos estudios que demuestre su rol como terapia adyuvante al manejo ventilatorio de pulmones agudamente dañados, ampliando el tradicional rol de la HM en cuidados críticos.

The inadequate use of Mechanical Ventilation (MV) has proved to generate lung damage and to increase a pre-existing pulmonary injury. This mechanical event, called ventilator induced lung injury (VILI), can generate local and distant biological effects. Hypothermia has been used in clinical situations, which result in an imbalance between oxygen consumption (VO2) and delivery (DO2) due to its ability to reduce VO2. Our objective was to determine the effect of Moderate Hypothermia (MH) on biological markers of VILI and in gas exchange.Twelve Sprague-Dawley adult male rats were used. After anesthesia, the rats were randomly assigned to normothermia (37ºC) and MH (34ºC), which was induced by surface cooling. They were cannulated and mechanically ventilated with controlled pressure ventilation, PIP 40 cmH2O, ZEEP, (PEEP=0) RR 60/min, Ti 25 percent, FIO2 100 percent. The esophageal temperature was maintained within ± 1°C. Arterial blood gases, lung gravimetry, histological analysis and measurement of protein content, IL-1b and TNF-a were registered in the bronchoalveolar lavage (BAL) supernatant, both cytokines were also measured in plasma.The animals with MH showed a significant reduction in the wet lung weight/dry lung weight ratio and the PaCO2, in relation to the normothermic animals. There was also a reduction of the inflammatory systemic cytokines in the MH group. There were no differences in PaO2, histological score and protein content in BAL. In this experimental model, MH reduced extra vascular lung water, which reflects lesser damage associated to a significative reduction in PaCO2 and inflammatory systemic cytokines. These facts justify new studies, which would prove its role as an aid in the ventilatory management of severely damaged lungs, increasing the traditional role of MH in critical care.