Lipid-soluble smoke particles damage endothelial cells and reduce endothelium-dependent dilatation in rat and man

BACKGROUND: Cigarette smoking is a strong risk factor for vascular disease and known to cause dysfunction of the endothelium. However, the molecular mechanisms involved are still not fully understood. METHODS: In order to reveal the direct effects of lipid-soluble smoke particles on the endothelium, ring segments isolated from rat mesenteric arteries and human middle cerebral arteries (MCA) obtained at autopsy were incubated for 6 to 48 hrs in the presence of dimethylsulphoxide (DMSO)-soluble particles from cigarette smoke (DSP), i.e. lipid-soluble smoke particles. The endothelial microstructure was examined by transmission electron microscopy. The endothelial function was evaluated by acetylcholine (ACh)-induced endothelium-dependent vasodilatation, using a sensitive myograph. RESULTS: After DSP treatment, the arterial endothelium was swollen and loosing its attachment. In functional tests, the total ACh-induced dilatation, the nitric oxide (NO)-mediated and the endothelium-derived hyperpolarization factor (EDHF)-mediated dilatations were significantly decreased by DSP in a time- and concentration-dependent manner (p < 0.05). Nicotine, an important compound in cigarette smoke had, in an equivalent concentration as in DSP, no such effects (p > 0.05). Similar results were obtained in the human MCA. CONCLUSION: Thus, we demonstrate that the lipid-soluble smoke particles, but not nicotine, caused damage to arterial endothelium and reduced the endothelium-dependent dilatation in man and rat

Quantitative temporal in vivo proteomics (QTiPs) deciphers the transition of virus-driven myeloid cells into M2 macrophages

Myeloid cells play a central role in the context of viral eradication, yet precisely how these cells differentiate throughout the course of acute infections is poorly understood. In this study, we have developed a novel quantitative temporal in vivo proteomics (QTiPs) platform to capture proteomic signatures of temporally transitioning virus-driven myeloid cells directly in situ, thus taking into consideration host–virus interactions throughout the course of an infection. QTiPs, in combination with phenotypic, functional, and metabolic analyses, elucidated a pivotal role for inflammatory CD11b⁺, Ly6G‾, Ly6C^high-low cells in antiviral immune response and viral clearance. Most importantly, the time-resolved QTiPs data set showed the transition of CD11b⁺, Ly6G‾, Ly6C^high-low cells into M2-like macrophages, which displayed increased antigen-presentation capacities and bioenergetic demands late in infection. We elucidated the pivotal role of myeloid cells in virus clearance and show how these cells phenotypically, functionally, and metabolically undergo a timely transition from inflammatory to M2-like macrophages in vivo. With respect to the growing appreciation for in vivo examination of viral–host interactions and for the role of myeloid cells, this study elucidates the use of quantitative proteomics to reveal the role and response of distinct immune cell populations throughout the course of virus infection.This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and Terry Fox Research Institute (TFRI) to S.G. and P.W.L. Authors D.R.C., Y.K., and T.S. are supported by the CIHR. J.P.M. and B.E.K. are supported through the Cancer Research Training Program (CRTP) of BHCRI. D.R.C. was supported previously by CRTP from BHCRI and the Nova Scotia Health Research Foundation (NSHRF). Nova Scotia Graduate Scholarships fund both N.H. and P.K. Work by J.A.P. was funded in part by NIH/NIDDK grant K01 DK098285. M.P.W. was supported by a Wellcome Trust Senior Fellowship (108070/Z/15/Z). We acknowledge Devanand Pinto and Ken Chisholm (National Research Council) as well as Alejandro Cohen at the Dalhousie Proteomics Core Facility and Derek Rowter and Renee Raudonis at Dalhousie Flow cytometry suites

Endothelial Dysfunction: Associations with Exposure to Ambient Fine Particles in Diabetic Individuals

BACKGROUND: Exposure to fine airborne particulate matter [&lt;= 2.5 mu m in aerodynamic diameter (PM2.5)] has been associated with cardiovascular and hematologic effects, especially in older people with cardiovascular disease. Some epidemiologic studies suggest that adults with diabetes also may be a particularly susceptible population. OBJECTIVES: The purpose of this study was to analyze the short-term effects of ambient PM2.5 on markers of endothelial function in diabetic volunteers.METHODS: We conducted a prospective panel study in 22 people with type 2 diabetes mellitus in Chapel Hill, North Carolina (USA), from November 2004 to December 2005. We acquired daily measurements of PM2.5 and meteorologic data at central monitoring sites. On 4 consecutive days, we measured endothelial function by brachial artery ultrasound in all participants and by pulsewave measurements in a subgroup. Data were analyzed using additive mixed models with a random participant effect and adjusted for season, day of the week, and meteorology. RESULTS: Flow-mediated dilatation decreased in association with PM2.5 during the first 24 hr, whereas small-artery elasticity index decreased with a delay of 1 and 3 days. These PM2.5-associated decrements in endothelial function were greater among participants with a high body mass index, high glycosylated hemoglobin Ale, low adiponectin, or the null polymorphism of glutathione S-transferase M1. However, high levels of myeloperoxidase on the examination day led to strongest effects on endothelial dysfunction. CONCLUSIONS: These data demonstrate that PM2.5 exposure may cause immediate endothelial dysfunction. Clinical characteristics associated with insulin resistance were associated with enhanced effects of PM on endothelial function. In addition, participants with greater oxidative potential seem to be more susceptible

Study Of ICH Score At 24-Hour Of Hospitalisation as a Predictor Of Mortality In Intracerebral Hemorrhage

Introduction: Intracerebral hemorrhage (ICH) constitutes 10% to 15% of all strokes and remains without any treatment of proven benefit.No standard clinical grading scale for ICH analogous to those for traumatic brain injury, subarachnoid hemorrhage, or ischemic stroke.The intracerebral hemorrhage (ICH) score was developed as a predictive tool for mortality at 30 days after hemorrhagicstroke.The utility of using a predictive scoring system at 24-hours instead of on admission to predict outcomes increases the predictive value of the scoring system.Aims &amp; Objectives:To see if ICH score calculated 24-hours after admission is a better predictor of in-hospital and 30-day mortality than ICH-score calculated on admission.Materials &amp; Methods:In this prospective observational study carried out at tertiary care center from central India, total 161 cases of Haemorrhagic stroke proven on CT Brain fulfilling inclusion &amp; exclusion criteria were enrolled Initial ICH score was calculated based on CT-Head and GCS score on admission.Repeat ICH score was calculated using follow up imaging and GCS score at 24 hours (+) 6 hours.CT angiography was done, 24 hours after presentation, to see for the presence of spot sign and its presence or absence was correlated with the hematoma expansion and functional outcome.CT head on admission Follow up CT Head at 24 + 6 hours after admission. CT Angiography at 24 + 6 hours after admission.Results:Mean age of the cases was 53.29 +10.94in males &amp; 52.96 +9.45 in females with M:F 4.3:1. Maximum number of cases were falling in Moderate GCS score (9-12) 65(40.37%) 46(28.3%) cases were having severe GCS score (3-8) 82 (50.93%) patients had an ICH score of 2 at presentation. While the ICH score of maximum patients at the end of 24 hours was 0.56 (34.78%) patients had an ICH score of 0 at 24 hours after hospitalisation. The change in ICH score during the&nbsp;first 24 hours of hospitalisation was highly significant with a p-value of 0.0087.Based on the mRS score, 34 (21.12%) patients had a poor in-hospital functional outcome, while 37 (25.34%) patients had a poor 30-day functional outcome.The on-admission ICH score was significantly associated with both, the in-hospital and 30-day functional outcome as suggested by the p-value which was &lt;0.0001 for both. Higher the on-admission ICH score, the poorer was the functional outcome.On comparing the on-admission and 24-hour ICH score as a predictor of poor functional outcome, the 24-hour ICH score had an RR of 1.71 and 2.69 respectively for having a poor in-hospital and 30-day functional outcome. While the RR with on-admission ICH score was 1.54 and 1.42 respectively for having a poor in-hospital and 30-day functional outcome. This data was suggestive that the 24-hour ICH score was a better predictor of in-hospital and 30-day mortality when compared to the on-admission ICH score. The presence of spot sign on CT angiography was associated with a poor ICH score and functional outcome. Of the 12 patients with positive spot sign on CT angiography, all 12 (100%) had a poor ICH score (&gt;1), while 9 (75%) had a poor functional outcome.Multivariate analysis was suggestive that the GCS score was the single most significant factor affecting the ICH score as well as the outcome of patients with ICH.Conclusion: 1.The 24-hour ICH score is a valid predictor of in-hospital and 30-day mortality and functional outcome in patients with intracerebral hemorrhage.2.The 24-hour ICH score is a better predictor of mortality than on-admission ICH score in patients with intracerebral hemorrhage.3.The presence of ‘spot sign’ correlated well with a poor ICH score