Microparticle-associated vascular adhesion molecule-1 and tissue factor follow a circadian rhythm in healthy human subjects

2008 ◽  
Vol 99 (11) ◽  
pp. 909-915 ◽  
Author(s):  
Rebecca Vince ◽  
Marie Sandström ◽  
Lee Taylor ◽  
Lars McNaughton ◽  
Gerard Laden ◽  
...  

SummaryAn increased risk of death or severe injury due to late-morning thrombotic events is well established. Tissue factor (TF) is the initiator of the coagulation cascade, and endothelial stresses, coupled with production of pro-coagulant microparticles (MP) are also important factors in loss of haemostasis. TF and vascular cell adhesion molecule-1 (VCAM-1) -positive cell microparticles were assessed periodically over a 24-hour (h) period in healthy human subjects to ascertain if they followed a circadian rhythm. Eleven healthy male subjects were assessed in a temperature-controlled environment with dietary intake consistent between subjects. Blood samples were taken every 4 h by venipuncture, and TF and VCAM-1 positive microparticles were quantified by flow cytometry. A significant circadian rhythm was observed in VCAM-1 MP (p=<0.0001), and a trend was shown, although not statistically significant (p=0.065) in TF microparticles. A peak was observed at 9 a.m. for VCAM-1 positive MP, followed by a decrease and subsequent peak at 9 p.m. and a minimum at 5 a.m. TF-positive MP followed a strikingly similar trend in both variation and absolute numbers with a delay. A circadian rhythm was observed in VCAM-1 and less so TF-positive MP. This has significant implications in terms of the well known increased risk of cardiovascular thrombotic events matching this data. To our knowledge this is the first such report of quantified measurements of these MP over a 24-h period and the only measurement of a 24-h variation of in-vivo blood-borne TF.

2012 ◽  
Vol 112 (6) ◽  
pp. 937-943 ◽  
Author(s):  
A. J. Hajari ◽  
D. A. Yablonskiy ◽  
A. L. Sukstanskii ◽  
J. D. Quirk ◽  
M. S. Conradi ◽  
...  

Despite decades of research into the mechanisms of lung inflation and deflation, there is little consensus about whether lung inflation occurs due to the recruitment of new alveoli or by changes in the size and/or shape of alveoli and alveolar ducts. In this study we use in vivo 3He lung morphometry via MRI to measure the average alveolar depth and alveolar duct radius at three levels of inspiration in five healthy human subjects and calculate the average alveolar volume, surface area, and the total number of alveoli at each level of inflation. Our results indicate that during a 143 ± 18% increase in lung gas volume, the average alveolar depth decreases 21 ±5%, the average alveolar duct radius increases 7 ± 3%, and the total number of alveoli increases by 96 ± 9% (results are means ± SD between subjects; P < 0.001, P < 0.01, and P < 0.00001, respectively, via paired t-tests). Thus our results indicate that in healthy human subjects the lung inflates primarily by alveolar recruitment and, to a lesser extent, by anisotropic expansion of alveolar ducts.


2003 ◽  
Vol 10 (3) ◽  
pp. 495-497 ◽  
Author(s):  
Evert de Jonge ◽  
Philip W. Friederich ◽  
George P. Vlasuk ◽  
William E. Rote ◽  
Margaretha B. Vroom ◽  
...  

ABSTRACT The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue factor-factor VIIa.


2019 ◽  
Author(s):  
Rabina Giri ◽  
Emily C. Hoedt ◽  
Khushi Shamsunnahar ◽  
Michael A. McGuckin ◽  
Mark Morrison ◽  
...  

AbstractEvidence is emerging that microbiome–immune system crosstalk regulates the tenor of host intestinal immunity and predisposition to inflammatory bowel disease (IBD). We identified five NF-κB suppressive strains affiliated with Clostridium clusters IV, XIVa and XV that independently suppressed secretion of the chemokine IL-8 by peripheral blood mononuclear cells and gut epithelial organoids from healthy human subjects, as well as patients with the predominant IBD subtypes, Crohn’s disease and ulcerative colitis. The NF-κB suppressive Clostridium bolteae AHG0001, but not C. bolteae BAA-613, suppressed cytokine-driven inflammatory responses and endoplasmic reticulum stress in gut epithelial organoids derived from Winnie mice that develop spontaneous colitis. This predicted in vivo responses thereby validating a precision medicine approach to treat Winnie colitis and suggesting the microbiome may function as an extrinsic regulator of host immunity. Finally, we identified a novel molecule associated with NF-κB suppression indicating gut bacteria could be harnessed to develop new therapeutics.


2004 ◽  
Vol 91 (1) ◽  
pp. 101-106 ◽  
Author(s):  
André Grandgirard ◽  
Lucy Martine ◽  
Luc Demaison ◽  
Catherine Cordelet ◽  
Corinne Joffre ◽  
...  

The oxidised derivatives of phytosterols (oxyphytosterols) were identified in plasma samples from thirteen healthy human volunteers, using MS. All the samples contained noticeable quantities of (24R)-5β,6β-epoxy-24-ethylcholestan-3β-ol (β-epoxysitostanol) and (24R)-ethylcholestan-3β,5α,6β-triol (sitostanetriol) and also trace levels of (24R)-5α,6α-epoxy-24-ethylcholestan-3β-ol (α-epoxysitostanol), (24R)-methylcholestan-3β,5α,6β-triol (campestanetriol) and (24R)-ethylch olest-5-en-3β-ol-7-one(7-ketositosterol). The amounts of these oxyphytosterols in plasma varied from 4·8 to 57·2 ng/ml. There are two possibilities concerning the origin of these compounds. First, they could come from the small amounts of oxyphytosterols in food. Second, they could originate from the in vivo oxidation of phytosterols in plasma. Very few data actually exist concerning these compounds. Their identification in human samples suggests that further research is necessary in this field.


1999 ◽  
Vol 6 (3) ◽  
pp. 273-278 ◽  
Author(s):  
Latchezar Traykov ◽  
Bertrand Tavitian ◽  
Antoinette Jobert ◽  
Francois Boller ◽  
Francoise Forette ◽  
...  

2016 ◽  
Vol 54 ◽  
pp. 149-157 ◽  
Author(s):  
Naoki Kanegawa ◽  
Karin Collste ◽  
Anton Forsberg ◽  
Martin Schain ◽  
Ryosuke Arakawa ◽  
...  

2014 ◽  
Vol 171 (5) ◽  
pp. 623-631 ◽  
Author(s):  
Poul F Vestergaard ◽  
Mikkel H Vendelbo ◽  
Steen B Pedersen ◽  
Anders Juul ◽  
Steffen Ringgard ◽  
...  

ObjectiveThe mechanisms underlying the impact of age and gender on the GH–IGF1 axis remain unclear. We tested the hypothesis that age and gender have impacts on GH signaling in human subjects in vivo.DesignA total of 20 healthy non-obese adults (‘young group’ <30 years (5F/5M) and ‘old group’ >60 years (5F/5M)) were studied after: i) an i.v. GH bolus (0.5 mg) and ii) saline.MethodsMuscle and fat biopsies were obtained after 30 and 120 min. Total and phosphorylated STAT5B proteins, gene expression of IGF1, SOCS1, SOCS2, SOCS3 and CISH, body composition, VO2max, and muscle strength were measured.ResultsIn the GH-unstimulated state, women displayed significantly elevated levels of CISH mRNA in muscle (P=0.002) and fat (P=0.05) and reduced levels of IGF1 mRNA in fat. Phosphorylated STAT5B (pSTAT5b) was maximally increased in all subjects 30 min after GH exposure and more pronounced in women when compared with men (P=0.01). IGF1, SOCS1, SOCS2, SOCS3, and CISH mRNA expression increased significantly in muscle after 120 min in all subjects with no impact of age and gender. GH-induced pSTAT5b correlated inversely with lean body mass (LBM; r=−0.56, P=0.01) and positively with the CISH mRNA response (r=0.533, P=0.05).Conclusioni) GH signaling in muscle and fat after a single GH bolus in healthy human subjects is age independent, ii) we hypothesize that constitutive overexpression of CISH may contribute to the relative GH resistance in women, and iii) experimental studies on the impact of sex steroid administration and physical training on GH signaling in human subjects in vivo are required.


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