Intracoronary platelet and monocyte activation status within platelet-monocyte complexes are determinants of inflammation in ST elevation myocardial infarction1

INTRODUCTION: Platelet Monocyte Complexes (PMCs) are commonly expressed in coronary artery disease but their pathologic significance in ST elevation myocardial infarction (STEMI) is unclear. This study evaluates the relationship between locally activated PMCs and intracoronary inflammation in stable and unstable coronary disease. MATERIAL AND METHODS: Micro catheter aspirated blood samples of 15 STEMI and 7 stable angina patients are collected from the coronary artery (CA), aorta (AO) and right atrium (RA). Samples are labelled with monoclonal antibodies and prepared for flow cytometry. CD 14 and CD 61 double positive cells are identified as PMC. P-selectin expression is identified by additional CD62P positivity and TF expression by additional CD142 positivity. Plasma TNF-alpha and IL-6 are measured using ELISA and CRP is measured in plasma using a high sensitivity automated microparticle enhanced latex turbidimetric immunoassay. RESULTS: No site-specific difference is seen in overall PMC expression in STEMI or stable angina. Surface P-selectin expression in STEMI [median (IQR)] is significantly higher in CA [35.01 (23.15-56.99)] compared with AO [15.99 (10.3-18.85)] or RA [14.02 (10.42-26.08)] (p = 0.003). Intracoronary PMC correlates significantly with intracoronary TNF-alpha (r = 0.87, p = 0.001) and intracoronary IL-6 (r = 0.76, p = 0.03). Bound monocytes within P-selectin positive and tissue factor positive complexes correlate positively with intracoronary TNF-alpha (r = 0.81, p = 0.008 & r = 0.80, p = 0.009 respectively) and IL-6 (r = 0.54, p = 0.16 & r = 0.71, p = 0.05 respectively). No such correlation is observed in the peripheral circulation of STEMI and stable angina patients. CONCLUSION: Inflammation is not attributable to PMC formation per se. However, increased intracoronary P-selectin expression by activated platelets and tissue factor expression by activated monocytes within the complexes are determinants of local intracoronary inflammatory burden in STEMI

Microparticles in acute coronary syndrome

BACKGROUND: Emerging evidence supports the role of cell-derived microparticles (MPs) in the pathophysiology of acute coronary syndrome (ACS). OBJECTIVES: To explore the relationship between coronary and systemic MP levels, investigate the correlation between MPs, inflammatory markers and Troponin T in patients with ACS. METHODS: Thirty seven patients with ACS scheduled for percutaneous coronary interventions (PCI) were studied. Eleven patients with stable angina (SA) were included as a control group. AnnexinV+MPs (AnV+MPs) and activated platelet-monocyte aggregates (PMA) from right atrium (RA) and culprit coronary artery (CO) distal to culprit lesion were measured using flow cytometry. High sensitivity C-reactive protein (CRP), Interleukin - 6 (IL-6), tumour necrosis factor - α (TNF-α), serum amyloid A (SAA) and Troponin T were assayed. RESULTS: Total and cell specific AnV+MP expression were higher in the ACS group in both the CO and RA, with greater levels detected in the CO. Platelet activation showed positive correlation with Troponin-T and platelet MP in both CO and RA of the ACS group (r=0.4 for both; p=0.04 & p=0.03 respectively). Inflammatory markers levels did not differ between the ACS and SA patients. CONCLUSIONS: Elevated coronary and systemic MP levels and positive correlation of platelet activation with Troponin-T and platelet MPs suggest a pathogenic role for MPs in ACS

Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe

Sensitivity analysis of a FBR fuel reprocessing flowsheet

142-145Processing of the first core of FBTR for plutonium recycle to the reactor will be required in near future. PUREX based reprocessing flowsheets are being developed at the laboratory for closing the fuel cycle. Reprocessing of Plutonium rich FBTR fuel (70% Pu for the first core) is special in several respects e.g., aqueous solutions bearing large percentage of fissile Pu have to be processed in small batches unlike the reprocessing of PHWR/LWR fuels where Pu content remains with in a few percent. Process upsets like plutonium polymerization, disproportionation, second organic phase formation and criticality in reprocessing facility have to be avoided in all conditions. First extraction cycle of a proposed unique three cycle high plutonium flowsheet was analysed for parametric sensitivity using a 2N factorial design and safe operating limits were established for the process to remain stable even during operational deviations arising out of random variations and anticipated fault sequences. In this paper, results of the sensitivity analysis are presented.</span

An extended Setschenow model for aqueous solubility of TBP in 5-100% TBP/<i>n-</i>dodecane- nitric acid-water biphasic system at 298.2 K

90-92Reported experimental data on aqueous solubility of Tri-n-Butyl Phosphate (TBP) in 5-100% TBP/n-dodecane-nitric acid-water biphasic system at 298.2 K was analyzed by least-squares technique and an extended Setschenow model was proposed for correlating the same. Database could be correlated with a standard deviation of about 7%. A further extension was proposed for presence of multiple solutes (extracting/non-extracting)

Modelling of distribution coefficients of nitrous acid in 15-30 vol.% TBP/n-dodecane-nitric acid system

336-337During partitioning of uranium and plutonium, nitrous acid re-oxidises Pu(III) to Pu(IV). Therefore a large excess of U(IV) is required. Since the scavenger reagent ‘‘hydrazine’’ is not extracted into the organic phase, even a small amount of extracted nitrous acid will cause cyclic reactions in the organic phase. In this scenario, study of the distribution behaviour of nitrous acid is important. In this paper, a model, based on extraction mechanism, is reported and compared with the model reported in the literature. The model reported here is considered more reliable than the model available in the literature

A simple two-parameter equation for predicting the densities of pure liquids and a case study involving six esters

342-343A simple two-parameter empirical equation with one reference density value at reference temperature is proposed for predicting saturated liquid densities. The proposed equation is simpler than the other correlations from the literature. For the case study reported in involving six liquids, standard deviations for the proposed equation arc lower than those for the DIPPR equation

Computer simulation of technetium scrubbing in PUREX systems

176-178Technetium interferes in reductive partitioning of uranium and plutonium by catalysing destruction of hydrazine, a stabiliser added to prevent oxidation of U(IV) by nitrous acid. In this communication, computer simulation results of technetium removal step by using a high acid scrub have been compared with the results from a published flowsheet.</span

Modelling and simulation of extraction behaviour of <i>n</i>-butyraldehyde in 30<i>%</i>TBP/<i>n-dodecane </i>purex biphasic system

346-349Use of butyraldehyde for selective reduction of Neptunium has been reported earlier. As there is no model available to account for its extraction behaviour in the conventional purex system, the reported experimental results could be explained only on the qualitative basis. The reported data were analyzed to determine its solvation number and an empirical model was developed for estimation of its distribution coefficients under purex conditions. The reported counter-current extraction run in mixer-settlers was also computer simulated using an in-house developed purex code SIMPSEX. The simulated profiles were compared with the experimental stage profiles and a satisfactory agreement was observed. </span

Purex distribution modelling: Benchmarking of an empirical model for nitric acid extraction in biphasic system

368-370<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "times="" new="" roman";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:="" minor-latin;mso-bidi-font-family:"times="" roman";mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">In course of development of a code for high plutonium flowsheets, an improved model of Purex distribution equilibria based on the activity coefficients has been developed. Incidentally, it is observed that this model performed quite satisfactorily even in low aqueous acid concentration range, normally not considered in other popular models of Purex. For In(DH)<span style="font-size: 11.0pt;line-height:115%;font-family:" calibri","sans-serif";mso-ascii-theme-font:="" minor-latin;mso-fareast-font-family:"times="" new="" roman";mso-fareast-theme-font:="" minor-fareast;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:arial;="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">=f<span style="font-size:11.0pt; line-height:115%;font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;="" mso-fareast-font-family:"times="" new="" roman";mso-fareast-theme-font:minor-fareast;="" mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">[In(XH)] dependency, discussed by Kolarik in an earlier paper, good agreement among theoretical, predicted and experimental results has been observed. In this paper experimental results of nitric acid extraction for several case studies are compared with predictions from the model.</span