Serum aspirin esterase is strongly associated with glucose and lipids in healthy subjects: different association patterns in subjects with type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Aspirin esterase (AE) activity can account for part of aspirin pharmacokinetics in the circulation, possibly being associated with the impairment of aspirin effectiveness as an inhibitor of platelet aggregation.</p> <p>Aims</p> <p>The study was aimed at investigating the correlations of serum AE activity with cholinesterase (ChE) and metabolic variables in healthy subjects in comparison to subjects with type 2 diabetes mellitus (T2DM).</p> <p>Methods</p> <p>In cardiovascular disease-free T2DM subjects and healthy controls, the AE activity levels and/or the correlation patterns between AE and the other variables were analyzed.</p> <p>Results</p> <p>Neither AE nor ChE activities were higher in the subjects with T2DM. Serum AE activity strongly correlated with ChE as well as glucose/lipids variables such as total cholesterol and triglyceride in healthy subjects, while the correlations between AE and glucose/lipids variables were not present in T2DM subjects.</p> <p>Conclusions</p> <p>These data may reflect the pathophysiological changes between healthy and T2DM subjects. Our data may thus provide the basis for future studies to unravel the mechanisms.</p

When pharmacotherapeutic recommendations may lead to the reverse effect on physician decision-making

For long the medical literature has shown that patients do not always receive appropriate care, including pharmacotherapeutic treatment. To achieve improved patient care, a number of physician-oriented interventions are being delivered internationally in an attempt to implement evidence based medicine in routine daily practice of medical practitioners. The pharmacy profession has taken an active role in the delivery of intervention strategies aimed at promoting evidence based prescribing and improved quality and safety of medicine use. However, the medical literature also supports the notion that valid clinical care recommendations do not always have the desired impact on physician behaviour. We argue that the well-established theory of psychological reactance might at least partially explain instances when physicians do not act upon such recommendations. Reactance theory suggests that when recommended to take a certain action, a motivational state compels us to react in a way that affirms our freedom to choose. Often we choose to do the opposite of what the recommendation is proposing that we do or we just become entrenched in our initial position. The basic concepts of psychological reactance are universal and likely to be applicable to the provision of recommendations to physicians. Making recommendations regarding clinical care, including pharmacotherapy, may carry with it implied threats, as it can be perceived as an attempt to restrict one’s freedom of choice potentially generating reactance and efforts to avoid them. By identifying and taking into account factors likely to promote reactance, physician-oriented interventions could become more effective

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Sleep patterns over 15-day period in rats with spinal cord injury

Study design: Experimental, controlled trial.Objectives: the purpose of this study was to evaluate over a 15-day period alterations in sleep pattern of rats after spinal cord injury (SCI).Setting: Federal University of São Paulo, Department of Psychobiology.Methods: in total, 20 male Wistar rats were used. the rats were divided in two groups: SHAM and SCI. the rats were submitted to the following procedures: electrode insertion surgery, 24 h duration baseline sleep recording, SCI (level T9) and subsequent sleep recording for 15 consecutive days.Results: the results showed a reduction in sleep efficiency in the light period for Days 1-3, 5, 10 and 12 after SCI in relation to the SHAM group, with alterations in total waking time and sleep stages. Limb movements were observed 4 days after SCI.Conclusion: the present findings suggest that SCI may be heavily involved in altering sleep pattern in SCI subjects and that the inactivity caused by SCI may be exacerbating this altered sleep pattern.Universidade Federal de São Paulo, Dept Psychobiol, BR-04020060 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Psychobiol & Exercise Res, BR-04020060 São Paulo, BrazilSanta Casa, Dept Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04020060 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Psychobiol & Exercise Res, BR-04020060 São Paulo, BrazilWeb of Scienc

Three dimensional three component whole heart cardiovascular magnetic resonance velocity mapping: comparison of flow measurements from 3D and 2D acquisitions

<p>Abstract</p> <p>Background</p> <p>Two-dimensional, unidirectionally encoded, cardiovascular magnetic resonance (CMR) velocity mapping is an established technique for the quantification of blood flow in large vessels. However, it requires an operator to correctly align the planes of acquisition. If all three directional components of velocity are measured for each voxel of a 3D volume through the phases of the cardiac cycle, blood flow through any chosen plane can potentially be calculated retrospectively. The initial acquisition is then more time consuming but relatively operator independent.</p> <p>Aims</p> <p>To compare the curves and volumes of flow derived from conventional 2D and comprehensive 3D flow acquisitions in a steady state flow model, and in vivo through planes transecting the ascending aorta and pulmonary trunk in 10 healthy volunteers.</p> <p>Methods</p> <p>Using a 1.5 T Phillips Intera CMR system, 3D acquisitions used an anisotropic 3D segmented k-space phase contrast gradient echo sequence with a short EPI readout, with prospective ECG and diaphragm navigator gating. The 2D acquisitions used segmented k-space phase contrast with prospective ECG and diaphragm navigator gating. Quantitative flow analyses were performed retrospectively with dedicated software for both the in vivo and in vitro acquisitions.</p> <p>Results</p> <p>Analysis of in vitro data found the 3D technique to have overestimated the continuous flow rate by approximately 5% across the entire applied flow range. In vivo, the 2D and the 3D techniques yielded similar volumetric flow curves and measurements. Aortic flow: (mean ± SD), 2D = 89.5 ± 13.5 ml & 3D = 92.7 ± 17.5 ml. Pulmonary flow: 2D = 98.8 ± 18.4 ml & 3D = 94.9 ± 19.0 ml). Each in vivo 3D acquisition took about 8 minutes or more.</p> <p>Conclusion</p> <p>Flow measurements derived from the 3D and 2D acquisitions were comparable. Although time consuming, comprehensive 3D velocity acquisition could be relatively operator independent, and could potentially yield information on flow through several retrospectively chosen planes, for example in patients with congenital or valvular heart disease.</p

Time-Lapse Imaging of the Dynamics of CNS Glial-Axonal Interactions In Vitro and Ex Vivo

Myelination is an exquisite and dynamic example of heterologous cell-cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualize the various stages of myelination.We took two approaches to follow myelination over time: i) time-lapse imaging of mixed CNS myelinating cultures generated from mouse spinal cord to which exogenous GFP-labelled murine cells were added, and ii) ex vivo imaging of the spinal cord of shiverer (Mbp mutant) mice, transplanted with GFP-labelled murine neurospheres. We demonstrate that oligodendrocyte-axonal interactions are dynamic events with continuous retraction and extension of oligodendroglial processes. Using cytoplasmic and membrane-GFP labelled cells to examine different components of the myelin-like sheath, we provide evidence from time-lapse fluorescence microscopy and confocal microscopy that the oligodendrocytes' cytoplasm-filled processes initially spiral around the axon in a corkscrew-like manner. This is followed subsequently by focal expansion of the corkscrew process to form short cuffs, which then extend longitudinally along the axons. We predict from this model that these spiral cuffs must extend over each other first before extending to form internodes of myelin.These experiments show the feasibility of visualizing the dynamics of glial-axonal interaction during myelination over time. Moreover, these approaches complement each other with the in vitro approach allowing visualization of an entire internodal length of myelin and the ex vivo approach validating the in vitro data

Postgraduate education for Chinese medicine practitioners: a Hong Kong perspective

&lt;b&gt;Background&lt;/b&gt; Despite Hong Kong government's official commitment to the development of traditional Chinese medicine (TCM) over the last ten years, there appears to have been limited progress in public sector initiated career development and postgraduate training (PGT) for public university trained TCM practitioners. Instead, the private TCM sector is expected to play a major role in nurturing the next generation of TCM practitioners. In the present study we evaluated TCM graduates' perspectives on their career prospects and their views regarding PGT.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Method&lt;/b&gt; Three focus group discussions with 19 local TCM graduates who had worked full time in a clinical setting for fewer than 5 years. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; Graduates were generally uncertain about how to develop their career pathways in Hong Kong with few postgraduate development opportunities; because of this some were planning to leave the profession altogether. Despite their expressed needs, they were dissatisfied with the current quality of local PGT and suggested various ways for improvement including supervised practice-based learning, competency-based training, and accreditation of training with trainee involvement in design and evaluation. In addition they identified educational needs beyond TCM, in particular a better understanding of western medicine and team working so that primary care provision might be more integrated in the future. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; TCM graduates in Hong Kong feel let down by the lack of public PGT opportunities which is hindering career development. To develop a new generation of TCM practitioners with the capacity to provide quality and comprehensive care, a stronger role for the government, including sufficient public funding, in promoting TCM graduates' careers and training development is suggested. Recent British and Australian experiences in prevocational western medicine training reform may serve as a source of references when relevant program for TCM graduates is planned in the futur

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

<p>Abstract</p> <p>Background</p> <p>Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level.</p> <p>Methods</p> <p>Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done.</p> <p>Results</p> <p>Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as <it>CCL3</it>, <it>CCL4</it>, <it>CXCL2</it>, and <it>MMP12 </it>in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as <it>S100A8</it>, <it>S100A9 </it>and <it>MMP9</it>.</p> <p>Conclusions</p> <p>Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume.</p