Effects of clopidogrel with or without aspirin on the generation of extracellular vesicles in the microcirculation and in venous blood: A randomized placebo controlled trial

2018 ◽  
Vol 167 ◽  
pp. 149-155 ◽  
Author(s):  
L. Traby ◽  
A. Kaider ◽  
M. Kollars ◽  
S. Eichinger ◽  
M. Wolzt ◽  
...  
Author(s):  
Andreas Breenfeldt Andersen ◽  
Thomas Christian Bonne ◽  
Jacob Bejder ◽  
Grace Jung ◽  
Tomas Ganz ◽  
...  

Current markers of iron deficiency (ID) such as ferritin and hemoglobin have shortcomings, and hepcidin and erythroferrone (ERFE) could be of clinical relevance in relation to early assessment of ID. Here, we evaluate whether exposure to altitude-induced hypoxia (2,320 m) alone, or in combination with recombinant human erythropoietin (rHuEPO) treatment, affects hepcidin and ERFE levels before alterations in routine ID biomarkers and stress erythropoiesis manifest. Two interventions were completed, each comprising a four-week baseline, a four-week intervention at either sea level or altitude, and a four-week follow-up. Participants (n=39) were randomly assigned to 20 IU·kg bw-1 rHuEPO or placebo injections every second day for three weeks during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (P≤0.001) with no changes in hepcidin or routine iron biomarkers, making ERFE of clinical relevance as an early marker of moderate hypoxia. rHuEPO treatment at sea level induced a similar pattern of changes in ERFE (P<0.05) and hepcidin levels (P<0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared to altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (P<0.05) and ERFE (P≤0.001) parallel with increases in hematocrit (P<0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (R2=0.13, P<0.001). The findings demonstrate that hepcidin and ERFE are more rapid biomarkers of changes in iron demands than routine iron markers. Finally, ERFE and hepcidin may be sensitive markers in an anti-doping context.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Liam J. Ward ◽  
Sigrid Nilsson ◽  
Mats Hammar ◽  
Lotta Lindh-Åstrand ◽  
Emilia Berin ◽  
...  

AbstractPhysical inactivity and the onset of menopause increase the risk of cardiovascular disease amongst postmenopausal women. We aim to investigate the effect of resistance training (RT) on plasma levels of selected cytokines, adipokines, myokines, and sex hormones in postmenopausal women with vasomotor symptoms. This was a sub-study of a randomised controlled trial investigating the effects of RT on vasomotor symptoms in postmenopausal women. Women were randomised to join a 15-week RT program (n = 26) or remain sedentary as control (n = 29). Venous blood samples were taken at week-0 and week-15 for all participants. Enzyme-linked immunosorbent assays and multiple bead assays were used to measure cytokines, adipokines, myokines, and sex hormones in plasma. Plasma measurements of 16 of 33 analytes were within detectable limits. After adjusting for good compliance in the RT group (58% of RT participants), after 15 weeks, significantly lower plasma levels of adiponectin (p < 0.001), lipocalin-2 (p < 0.01) and resistin (p = 0.04) were found. Comparing control and RT women, using change-over-time values, significant increases in median testosterone and sex hormone binding globulin levels were seen in RT women. RT intervention lowers the levels of adipokines, particularly adiponectin, in postmenopausal women with vasomotor symptoms. These results were secondary outcomes of a clinical trial, and further investigations in a larger cohort are essential with the additional control of diet control and body composition analyses. Nevertheless, our study shows RT may be a beneficial intervention in reducing inflammation amongst postmenopausal women.


2013 ◽  
Vol 118 (6) ◽  
pp. 1322-1331 ◽  
Author(s):  
Yan Chen ◽  
Xiaodong Liu ◽  
Christopher H. K. Cheng ◽  
Tony Gin ◽  
Kate Leslie ◽  
...  

Abstract Background: Nitrous oxide inactivates methionine synthase and may lead to DNA damage and wound infection. By using single-cell gel electrophoresis (comet assay), the authors determined the effect of nitrous oxide on DNA damage in circulating leukocytes. Methods: In this double-blind, randomized controlled trial, 91 patients undergoing major colorectal surgery were randomized to receive 70% nitrous oxide (n = 31) or nitrous oxide-free anesthesia using 30 (n = 30) or 80% (n = 30) oxygen. Venous blood was collected before and 24 h after surgery. The primary outcome was extent of DNA damage, quantified as the percentage of DNA staining intensity in the comet tail using digital fluorescence microscopy. Incidence of postoperative wound infection was also recorded. Results: Nitrous oxide exposure was associated with a two-fold increase in the percentage of DNA intensity in tail (P = 0.0003), but not in the 30 (P = 0.181) or 80% oxygen groups (P = 0.419). There was a positive correlation between the duration of nitrous oxide exposure and extent of DNA damage, r = 0.33, P = 0.029. However, no correlation was observed in nitrous oxide-free patients. The proportions of postoperative wound infection, using the Centers for Disease Control and Prevention criteria, were 19.4% (6 of 31) in the 70% nitrous oxide group and 6.7% (2 of 30) in both the 30 and 80% oxygen groups, P = 0.21. An increase in DNA damage was associated with a higher risk of wound infection, adjusted odds ratio (95% CIs): 1.19 (1.07–1.34), P = 0.003. Conclusions: Nitrous oxide increased DNA damage compared with nitrous oxide-free anesthesia and was associated with postoperative wound infection.


2020 ◽  
Vol 10 (19) ◽  
pp. 6961
Author(s):  
Alessandra Maria Vitale ◽  
Radha Santonocito ◽  
Giuseppe Vergilio ◽  
Antonella Marino Gammazza ◽  
Claudia Campanella ◽  
...  

Primary and metastatic brain tumors are usually serious conditions with poor prognosis, which reveal the urgent need of developing rapid diagnostic tools and efficacious treatments. To achieve these objectives, progress must be made in the understanding of brain tumor biology, for example, how they resist natural defenses and therapeutic intervention. One resistance mechanism involves extracellular vesicles that are released by tumors to meet target cells nearby or distant via circulation and reprogram them by introducing their cargo. This consists of different molecules among which are microRNAs (miRNAs) and molecular chaperones, the focus of this article. miRNAs modify target cells in the immune system to avoid antitumor reaction and chaperones are key survival molecules for the tumor cell. Extracellular vesicles cargo reflects the composition and metabolism of the original tumor cell; therefore, it is a source of markers, including the miRNAs and chaperones discussed in this article, with potential diagnostic and prognostic value. This and their relatively easy availability by minimally invasive procedures (e.g., drawing venous blood) illustrate the potential of extracellular vesicles as useful materials to manage brain tumor patients. Furthermore, understanding extracellular vesicles circulation and interaction with target cells will provide the basis for using this vesicle for delivering therapeutic compounds to selected tumor cells.


Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 218
Author(s):  
Paul M. Haller ◽  
Bernhard Jäger ◽  
Edita Piackova ◽  
Larissa Sztulman ◽  
Claudia Wegberger ◽  
...  

(1) Background: Extracellular vesicles (EVs) have been recognized as a cellular communication tool with cardioprotective properties; however, it is unknown whether cardioprotection by remote ischemic conditioning (RIC) involves EVs. (2) Methods: We randomized patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) to additionally receive a protocol of RIC or a sham-intervention. Blood was taken before and immediately, 24 h, four days and one month after PCI. Additionally, we investigated EVs from healthy volunteers undergoing RIC. EVs were characterized by a high-sensitive flow cytometer (Beckman Coulter Cytoflex S, Krefeld, Germany). (3) Results: We analyzed 32 patients (16 RIC, 16 control) and five healthy volunteers. We investigated platelet-, endothelial-, leukocyte-, monocyte- and granulocyte-derived EVs and their pro-thrombotic sub-populations expressing superficial phosphatidylserine (PS+). We did not observe a significant effect of RIC on the numbers of circulating EVs, although granulocyte-derived EVs were significantly higher in the RIC group. In line, RIC had not impact on EVs in healthy volunteers. Additionally, we observed changes of PS+/PEV, EEVs and PS+/CD15+ EVs irrespective of RIC with time following STEMI. 4) Conclusion: We provide further insights into the course of different circulating EVs during the acute and sub-acute phases of STEMI. With respect to the investigated EV populations, RIC seems to have no effect, with only minor differences found for granulocyte EVs.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ana Palacios ◽  
Kristen Hurley ◽  
Silvia De Ponce ◽  
Victor Alfonso ◽  
Nicholas Tilton ◽  
...  

Abstract Objectives Anemia is a major public health problem among young children. In addition to iron deficiency, other micronutrient deficiencies have been associated with anemia. The purpose of this study was to identify biomarkers associated with anemia in children <5 years from rural Guatemala. Methods A total of 182 infants (6–24 m) and 207 preschoolers (36–60 m) were recruited from community surveillance to participate in a randomized controlled trial of nutrition and child development. Methods included measured weight, length/height and venous blood draws. Inclusion criteria were length/height-for-age z-score <-1.0 and Hb >7.0 g/dL. Cross-sectional analyses using generalized linear mixed models of baseline data examined associations between anemia (Hb <11.0 g/dL) and micronutrient deficiencies, adjusting for maternal, child and sociodemographic variables. Iron deficiency was defined as low ferritin based on inflammation status, and/or high soluble transferrin receptor, ≥1.97 mg/L. Deficiencies for other parameters were designated as: zinc <65 µg/dL; vitamin B12 < 200 pg/mL; and plasma folate <3 ng/mL or erythrocyte folate <100 ng/mL. Results Prevalence of anemia was 56% in infants and 12% in preschoolers. Among anemic infants/preschoolers, rates of iron, zinc, folate and vitamin B12 deficiencies were 83/75%; 63/18%; 3/4%; and 9/0%, respectively. For infants, the odds of anemia were higher when children were zinc deficient [OR = 3.59;95%CI (1.64–7.85)], after adjusting for community cluster, sex, age, maternal education and household size. No biomarkers were associated with anemia in preschoolers. Conclusions Iron and zinc are common micronutrient deficiencies in children from low- and middle-income countries. These findings suggest that micronutrient deficiencies coexist among children in Guatemala, and that zinc should be considered as part of the prevention strategies to reduce anemia. In preschoolers, no biomarkers were associated with anemia, suggesting that other biological and psychosocial factors could be influencing anemia in this age group. Funding Sources The Mathile Institute for the Advancement of Human Nutrition, Sackler Institute for Nutrition Science of the New York Academy of Sciences.


PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159105 ◽  
Author(s):  
Kristina Svennerholm ◽  
Pouria Rodsand ◽  
Urban Hellman ◽  
Anders Waldenström ◽  
Marie Lundholm ◽  
...  

2014 ◽  
Vol 112 (12) ◽  
pp. 1137-1141 ◽  
Author(s):  
Stan Shapiro ◽  
Thierry Ducruet ◽  
Philip Wells ◽  
Marc Rodger ◽  
Michael Kovacs ◽  
...  

SummaryAcute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30–40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.


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