[The forgotten urinary catheter]. / 5 minutes pour apprendre - La sonde urinaire que l'on traîne à retirer.

Catheter-associated urinary tract infections (CAUTI) are the most common type of healthcare-associated infection. They have a major impact on morbi-mortality and costs. Approximately 25 % of inpatients receive urinary catheters during their hospital stay. The most important risk factor for CAUTI is prolonged use of the catheter, and its appropriate use is on the Top Five list of the Choosing wisely campaign for the inpatient sector in Switzerland. Through the report of this clinical case, we review the guidelines for the appropriate use of urinary catheters, with a particular focus on reducing the risk of recurrent acute urinary retention after catheter ablation in men with benign prostatic hyperplasia.

Regulation of the voltage-dependent sodium channel NaV1.1 by AKT1.

The voltage-sensitive sodium channel NaV1.1 plays a critical role in regulating excitability of GABAergic neurons and mutations in the corresponding gene are associated to Dravet syndrome and other forms of epilepsy. The activity of this channel is regulated by several protein kinases. To identify novel regulatory kinases we screened a library of activated kinases and we found that AKT1 was able to directly phosphorylate NaV1.1. In vitro kinase assays revealed that the phosphorylation site was located in the C-terminal part of the large intracellular loop connecting domains I and II of NaV1.1, a region that is known to be targeted by other kinases like PKA and PKC. Electrophysiological recordings revealed that activated AKT1 strongly reduced peak Na+ currents and displaced the inactivation curve to more negative potentials in HEK-293 cell stably expressing NaV1.1. These alterations in current amplitude and steady-state inactivation were mimicked by SC79, a specific activator of AKT1, and largely reverted by triciribine, a selective inhibitor. Neurons expressing endogenous NaV1.1 in primary cultures were identified by expressing a fluorescent protein under the NaV1.1 promoter. There, we also observed a strong decrease in the current amplitude after addition of SC79, but small effects on the inactivation parameters. Altogether, we propose a novel mechanism that might regulate the excitability of neural networks in response to AKT1, a kinase that plays a pivotal role under physiological and pathological conditions, including epileptogenesis.

Localization of the glycine transporter GLYT1 in glutamatergic synaptic vesicles.

We have previously shown the presence of the glycine transporter GLYT1 in glutamatergic terminals of the rat brain. In this study we present immunohistochemical and biochemical evidence indicating that GLYT1 is expressed not only at the plasma membrane of glutamatergic neurons, but also at synaptic vesicles. Confocal microscopy, immunoblots analysis of a highly purified synaptic vesicle fraction and immunoisolation of synaptic vesicles with anti-synaptophysin antibodies strongly suggested the presence of GLYT1 in synaptic vesicles. Moreover, direct observation with the electron microscope of purified vesicles immunoreacted with anti-GLYT1 and colloidal gold demonstrated that about 40% of the small vesicles of the purified vesicle fraction contained GLYT1. Double labeling for GLYT1 and synaptophysin of this vesicular fraction revealed that more of ninety percent of them were synaptic vesicles. Moreover, a significant part of the GLYT1 containing vesicles (86%) also contained the vesicular glutamate transporter vGLUT1, suggesting a functional role of GLYT1 in a subpopulation of glutamatergic vesicles.

Differentiation of human umbilical cord matrix mesenchymal stem cells into neural-like progenitor cells and maturation into an oligodendroglial-like lineage.

Mesenchymal stem cells (MSCs) are viewed as safe, readily available and promising adult stem cells, which are currently used in several clinical trials. Additionally, their soluble-factor secretion and multi-lineage differentiation capacities place MSCs in the forefront of stem cell types with expected near-future clinical applications. In the present work MSCs were isolated from the umbilical cord matrix (Wharton's jelly) of human umbilical cord samples. The cells were thoroughly characterized and confirmed as bona-fide MSCs, presenting in vitro low generation time, high proliferative and colony-forming unit-fibroblast (CFU-F) capacity, typical MSC immunophenotype and osteogenic, chondrogenic and adipogenic differentiation capacity. The cells were additionally subjected to an oligodendroglial-oriented step-wise differentiation protocol in order to test their neural- and oligodendroglial-like differentiation capacity. The results confirmed the neural-like plasticity of MSCs, and suggested that the cells presented an oligodendroglial-like phenotype throughout the differentiation protocol, in several aspects sharing characteristics common to those of bona-fide oligodendrocyte precursor cells and differentiated oligodendrocytes.

Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells.

INTRODUCTION: The ability to self-renew, be easily expanded in vitro and differentiate into different mesenchymal tissues, render mesenchymal stem cells (MSCs) an attractive therapeutic method for degenerative diseases. The subsequent discovery of their immunosuppressive ability encouraged clinical trials in graft-versus-host disease and auto-immune diseases. Despite sharing several immunophenotypic characteristics and functional capabilities, the differences between MSCs arising from different tissues are still unclear and the published data are conflicting. METHODS: Here, we evaluate the influence of human MSCs derived from umbilical cord matrix (UCM), bone marrow (BM) and adipose tissue (AT), co-cultured with phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (MNC), on T, B and natural killer (NK) cell activation; T and B cells' ability to acquire lymphoblast characteristics; mRNA expression of interleukin-2 (IL-2), forkhead box P3 (FoxP3), T-bet and GATA binding protein 3 (GATA3), on purified T cells, and tumor necrosis factor-alpha (TNF-α), perforin and granzyme B on purified NK cells. RESULTS: MSCs derived from all three tissues were able to prevent CD4+ and CD8+ T cell activation and acquisition of lymphoblast characteristics and CD56 dim NK cell activation, wherein AT-MSCs showed a stronger inhibitory effect. Moreover, AT-MSCs blocked the T cell activation process in an earlier phase than BM- or UCM-MSCs, yielding a greater proportion of T cells in the non-activated state. Concerning B cells and CD56 bright NK cells, UCM-MSCs did not influence either their activation kinetics or PHA-induced lymphoblast characteristics, conversely to BM- and AT-MSCs which displayed an inhibitory effect. Besides, when co-cultured with PHA-stimulated MNC, MSCs seem to promote Treg and Th1 polarization, estimated by the increased expression of FoxP3 and T-bet mRNA within purified activated T cells, and to reduce TNF-α and perforin production by activated NK cells. CONCLUSIONS: Overall, UCM-, BM- and AT-derived MSCs hamper T cell, B cell and NK cell-mediated immune response by preventing their acquisition of lymphoblast characteristics, activation and changing the expression profile of proteins with an important role in immune function, except UCM-MSCs showed no inhibitory effect on B cells under these experimental conditions. Despite the similarities between the three types of MSCs evaluated, we detect important differences that should be taken into account when choosing the MSC source for research or therapeutic purposes.

[Smoking and cardiovascular risk factors in Barão do Corvo Health Center]. / Tabagismo e factores de risco cardiovascular no Centro de Saúde de Barão do Corvo.

INTRODUCTION: Smoking is the leading cause of preventable death and is associated with an increased risk of various diseases. The 2005-2006 National Health Survey revealed a national prevalence of 19.6% of active smokers. As a cardiovascular risk factor (CVRF), it as an independent role, for sudden death as for myocardial infarction. GOALS: To assess the prevalence and characteristics of smoking behavior of users using the Barão do Corvo Health Center (BCHC), and its relationship with other CVRF. MATERIALS AND METHODS: Observational study, cross-sectional analysis. Collection of data through survey applied to 502 users users CSBC, aged = 18 years. Non-random sample of convenience. RESULTS: In the sample we found 17.9% active smokers and 17.3% ex-smokers. In active smokers, 80% smoked between 1 to 25 cigarettes per day. 48% of respondents started smoking between 15 and 19 years. The abandonment of consumption occurred mainly between 35 and 44 years (24.7%) and was earlier in women (41.7% stopped smoking between 25 and 34 years). As for CVRF, there was a prevalence of smoking in hypertensive patients of 12.9%, 9.4% in diabetic patients, 12.3% of users with hypercholesterolaemia, 13.9% of users who had BMI > or = 25 and 20.5 % in sedentary. DISCUSSION: Compared with data from the population, the prevalence of active smokers is lower in the BCHC and ex-smokers is higher, the daily consumption of tobacco is also lower. The age of initiation of consumption was similar to national data, and age of abandonment was delayed, which is mostly between 35 and 44 years. The women left the tobacco earlier, and the most prevalent age group here was of 25 to 34 years, leading to think about a possible relationship with motherhood or reproductive age. For other CVRF studied, there was a lower prevalence of smokers in the groups of hypertension, diabetes, users with hypercholesterolaemia and overweight and obese users - this relationship was statistically significant. Is the promotion of healthy lifestyle in these groups taking effect?