3,753 research outputs found
The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence
Purpose: Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli. Methods: IL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA. Results: Baseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression. Conclusion: Sildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level
Testosterone insulin-like effects: an in vitro study on the short-term metabolic effects of testosterone in human skeletal muscle cells
Testosterone by promoting different metabolic pathways contributes to short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue and the primary site for insulin-stimulated glucose utilization. Despite evidences indicate a close relationship between testosterone and glucose metabolism, the molecular mechanisms responsible for a possible testosterone-mediated insulin-like effects on skeletal muscle are still unknown
Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis
The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies.
Phenobarbital use in benzodiazepine and z-drug detoxification: a single-centre 15-year observational retrospective study in clinical practice
Cardiomyopathy associated with diabetes. the central role of the cardiomyocyte
The term diabetic cardiomyopathy (DCM) labels an abnormal cardiac structure and performance due to intrinsic heart muscle malfunction, independently of other vascular co-morbidity. DCM, accounting for 50%-80% of deaths in diabetic patients, represents a worldwide problem for human health and related economics. Optimal glycemic control is not sufficient to prevent DCM, which derives from heart remodeling and geometrical changes, with both consequences of critical events initially occurring at the cardiomyocyte level. Cardiac cells, under hyperglycemia, very early undergo metabolic abnormalities and contribute to T helper (Th)-driven inflammatory perturbation, behaving as immunoactive units capable of releasing critical biomediators, such as cytokines and chemokines. This paper aims to focus onto the role of cardiomyocytes, no longer considered as "passive" targets but as "active" units participating in the inflammatory dialogue between local and systemic counterparts underlying DCM development and maintenance. Some of the main biomolecular/metabolic/inflammatory processes triggered within cardiac cells by high glucose are overviewed; particular attention is addressed to early inflammatory cytokines and chemokines, representing potential therapeutic targets for a prompt early intervention when no signs or symptoms of DCM are manifesting yet. DCM clinical management still represents a challenge and further translational investigations, including studies at female/male cell level, are warranted
Feasibility and safety of minimal-incision thyroidectomy for Graves' disease: A prospective, single-center study
Development of FTK architecture: a fast hardware track trigger for the ATLAS detector
The Fast Tracker (FTK) is a proposed upgrade to the ATLAS trigger system that
will operate at full Level-1 output rates and provide high quality tracks
reconstructed over the entire detector by the start of processing in Level-2.
FTK solves the combinatorial challenge inherent to tracking by exploiting the
massive parallelism of Associative Memories (AM) that can compare inner
detector hits to millions of pre-calculated patterns simultaneously. The
tracking problem within matched patterns is further simplified by using
pre-computed linearized fitting constants and leveraging fast DSP's in modern
commercial FPGA's. Overall, FTK is able to compute the helix parameters for all
tracks in an event and apply quality cuts in approximately one millisecond. By
employing a pipelined architecture, FTK is able to continuously operate at
Level-1 rates without deadtime. The system design is defined and studied using
ATLAS full simulation. Reconstruction quality is evaluated for single muon
events with zero pileup, as well as WH events at the LHC design luminosity. FTK
results are compared with the tracking capability of an offline algorithm.Comment: To be published in the proceedings of DPF-2009, Detroit, MI, July
2009, eConf C09072
The Evolution of FTK, a Real-Time Tracker for Hadron Collider Experiments
We describe the architecture evolution of the highly-parallel dedicated
processor FTK, which is driven by the simulation of LHC events at high
luminosity (1034 cm-2 s-1). FTK is able to provide precise on-line track
reconstruction for future hadronic collider experiments. The processor,
organized in a two-tiered pipelined architecture, execute very fast algorithms
based on the use of a large bank of pre-stored patterns of trajectory points
(first tier) in combination with full resolution track fitting to refine
pattern recognition and to determine off-line quality track parameters. We
describe here how the high luminosity simulation results have produced a new
organization of the hardware inside the FTK processor core.Comment: 11th ICATPP conferenc
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