459 research outputs found
Effect of Cathodic Current on Bond Strength Between Concrete and Beinforcing Steel
Chemical Engineerin
The Impact of Exercising During Haemodialysis on Blood Pressure, Markers of Cardiac Injury and Systemic Inflammation - Preliminary Results of a Pilot Study
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for commercial purposes as well as any distribution of modified material requires written permission.Background/Aims: Patients requiring haemodialysis have cardiovascular and immune
dysfunction. Little is known about the acute effects of exercise during haemodialysis. Exercise
has numerous health benefits but in other populations has a profound impact upon blood
pressure, inflammation and immune function; therefore having the potential to exacerbate
cardiovascular and immune dysfunction in this vulnerable population. Methods: Fifteen
patients took part in a randomised-crossover study investigating the effect of a 30-min
bout of exercise during haemodialysis compared to resting haemodialysis. We assessed
blood pressure, plasma markers of cardiac injury and systemic inflammation and neutrophil
degranulation. Results: Exercise increased blood pressure immediately post-exercise; however,
1 hour after exercise blood pressure was lower than resting levels (106±22 vs. 117±25 mm
Hg). No differences in h-FABP, cTnI, myoglobin or CKMB were observed between trial arms.
Exercise did not alter circulating concentrations of IL-6, TNF-α or IL-1ra nor clearly suppress
neutrophil function. Conclusions: This study demonstrates fluctuations in blood pressure
during haemodialysis in response to exercise. However, since the fall in blood pressure
occurred without evidence of cardiac injury, we regard it as a normal response to exercise
superimposed onto the haemodynamic response to haemodialysis. Importantly, exercise did
not exacerbate systemic inflammation or immune dysfunction; intradialytic exercise was well
tolerated
EURL ECVAM strategy to replace, reduce and refine the use of animals in the assessment of acute mammalian systemic toxicity
Information on acute systemic toxicity represents a standard requirement within several pieces of chemicals legislation in the EU. One of the main drivers of conducting the test is classification and labelling. Currently, only in vivo tests are accepted by regulatory bodies and most of the standard tests use lethality as endpoint. Based on an assessment of the regulatory needs and the scientific state-of-the art in the area, EURL ECVAM considers that efforts should be directed towards a) the reduction and replacement of animal tests for the identification and classification of acute systemic toxicity, and b) the refinement of in vivo studies. Consideration should be given to collecting, organising and applying mechanistic knowledge related to this endpoint, to provide a strong mechanistic basis for the design and validation of integrated prediction models. EURL ECVAM proposes to evaluate promising components of integrated approaches for testing and assessment (IATA), including the better use of existing alternative methods, such as mechanistically relevant in vitro assays. Information on repeated dose toxicity might also be useful in supporting classification and labelling for acute systemic toxicity. One clear target is minimising animal use for satisfying information requirements for acute systemic toxicity in relation to the 2018 REACH registration deadline. The aims and objectives underpinning the EURL ECVAM strategy can only be achieved through the coordinated and concerted efforts of all stakeholders.JRC.I.5-Systems Toxicolog
The impact of exercising during haemodialysis on blood pressure, markers of cardiac injury and systemic inflammation - preliminary results of a pilot study
Background/Aims: Patients requiring haemodialysis have cardiovascular and immune
dysfunction. Little is known about the acute effects of exercise during haemodialysis. Exercise
has numerous health benefits but in other populations has a profound impact upon blood
pressure, inflammation and immune function; therefore having the potential to exacerbate
cardiovascular and immune dysfunction in this vulnerable population. Methods: Fifteen
patients took part in a randomised-crossover study investigating the effect of a 30-min
bout of exercise during haemodialysis compared to resting haemodialysis. We assessed
blood pressure, plasma markers of cardiac injury and systemic inflammation and neutrophil
degranulation. Results: Exercise increased blood pressure immediately post-exercise; however,
1 hour after exercise blood pressure was lower than resting levels (106±22 vs. 117±25 mm
Hg). No differences in h-FABP, cTnI, myoglobin or CKMB were observed between trial arms.
Exercise did not alter circulating concentrations of IL-6, TNF-α or IL-1ra nor clearly suppress
neutrophil function. Conclusions: This study demonstrates fluctuations in blood pressure
during haemodialysis in response to exercise. However, since the fall in blood pressure
occurred without evidence of cardiac injury, we regard it as a normal response to exercise
superimposed onto the haemodynamic response to haemodialysis. Importantly, exercise did
not exacerbate systemic inflammation or immune dysfunction; intradialytic exercise was well
tolerated
An increase in circulating monocyte and platelet derived microparticles during haemodialysis
An increase in circulating monocyte and platelet derived microparticles during haemodialysi
Regular exercise during haemodialysis promotes an anti-inflammatory leucocyte profile
Background
Cardiovascular disease (CVD) is the most common cause of mortality in haemodialysis (HD) patients and is highly predicted by markers of chronic inflammation. Regular exercise may have beneficial anti-inflammatory effects, but this is unclear in HD patients. This study assessed the effect of regular intradialytic exercise on soluble inflammatory factors and inflammatory leukocyte phenotypes.
Methods
Twenty-two HD patients from a centre where intradialytic cycling was offered thrice-weekly and 16 HD patients receiving usual care volunteered. Exercising patients aimed to cycle for 30 min at RPE of “somewhat hard”. Baseline characteristic were compared with 16 healthy age-matched individuals. Physical function, soluble inflammatory markers and leukocyte phenotypes were assessed again after 6 months of regular exercise.
Results
Patients were less active than their healthy counterparts and had significant elevations in
measures of inflammation (IL-6, CRP, TNF-α, intermediate and non-classical monocytes; all
P<0.001). Six months of regular intradialytic exercise improved physical function (sit-to-stand 60). After 6 months the proportion of intermediate monocytes in the exercising patients reduced compared to non-exercisers (7.58±1.68 to 6.38±1.81% vs. 6.86±1.45 to 7.88±1.66%; P<0.01). Numbers (but not proportion) of regulatory T cells decreased in the non-exercising patients only (P<0.05). Training had no significant effect on circulating IL-6, CRP or TNF-α concentrations.
Conclusions
These findings suggest regular intradialytic exercise is associated with an anti-inflammatory effect at a circulating cellular level but not in circulating cytokines. This may be protective against the increased risk of CVD and mortality that is associated with chronic inflammation and elevated numbers of intermediate monocytes
Implementing a theory-based intradialytic exercise programme in practice: a quality improvement project
Background Research evidence outlines the benefits of intradialytic exercise (IDE), yet implementation into practice has been slow, ostensibly due to lack of patient and staff engagement. The aim of this quality improvement project was to improve patient outcomes via the introduction of an IDE programme; evaluate patient uptake, sustainability and enhance the engagement of routine haemodialysis (HD) staff with the delivery of the IDE programme. Methods We developed and refined an IDE programme, including interventions designed to increase
patient and staff engagement that were based upon the Theoretical Domains Framework, using a series of ‘Plan, Do, Study, Act’ cycles. The programme was introduced at two UK NHS HD units. Process measures included patient uptake, withdrawals, adherence and HD staff involvement. Outcomes measures were patient-reported functional capacity, anxiety, depression and symptomology. All measures were collected over 12 months. Results 95 patients enrolled in the IDE programme. 64 (75%) were still participating at three months, dropping to 41 (48%) at 12 months. Adherence was high (78%) at three months, dropping to 63% by 12 months. Provision of IDE by HD staff accounted for a mean of 2 (5%) sessions per three-month time point. Patients displayed significant improvements in functional ability (p=0.01), and reduction in depression (p=0.02) over 12 months, but effects seen were limited to those who completed the programme. Conclusions A theory-based IDE programme is feasible and leads to improvement in functional capacity and depression. Sustaining IDE over time is marred by high levels of patient withdrawal from the programme. Significant change at an organisational level is required to enhance
sustainability by increasing HD staff engagement or access to exercise professional support
Long Non-Coding RNA ZFAS1 Is a Major Regulator of Epithelial-Mesenchymal Transition through miR-200/ZEB1/E-Cadherin, Vimentin Signaling in Colon Adenocarcinoma
Colon adenocarcinoma is a common cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition is a major regulator of cancer metastasis, and increased understanding of this process is essential to improve patient outcomes. Long non-coding RNA (lncRNA) are important regulators of carcinogenesis. To identify lncRNAs associated with colon carcinogenesis, we performed an exploratory differential gene expression analysis comparing paired colon adenocarcinoma and normal colon epithelium using an RNA-sequencing data set. This analysis identified lncRNA ZFAS1 as significantly increased in colon cancer compared to normal colon epithelium. This finding was validated in an institutional cohort using laser capture microdissection. ZFAS1 was also found to be principally located in the cellular cytoplasm. ZFAS1 knockdown was associated with decreased cellular proliferation, migration, and invasion in two colon cancer cell lines (HT29 and SW480). MicroRNA-200b and microRNA-200c (miR-200b and miR-200c) are experimentally validated targets of ZFAS1, and this interaction was confirmed using reciprocal gene knockdown. ZFAS1 knockdown regulated ZEB1 gene expression and downstream targets E-cadherin and vimentin. Knockdown of miR-200b or miR-200c reversed the effect of ZFAS1 knockdown in the ZEB1/E-cadherin, vimentin signaling cascade, and the effects of cellular migration and invasion, but not cellular proliferation. ZFAS1 knockdown was also associated with decreased tumor growth in an in vivo mouse model. These results demonstrate the critical importance of ZFAS1 as a regulator of the miR-200/ZEB1/E-cadherin, vimentin signaling cascade
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