Inhibitory Effect of Clopidogrel on Release of Soluble CD40 Ligand by ADP-activated Platelet in Patients With Non-ST-segment-elevation Acute Coronary Syndromes

Objectives To investigate the inhibitory effect of clopidogrel on release of soluble CD40 ligand （sCD40L） by ADP-activated platelet in patients with non-ST-segment elevation acute coronary syndromes（NSTEACS）. Methods Forty-two patients with NSTEACS were treated with clopidogrel for 6 - 8 days. In order to obtain platelet rich plasma （PRP） samples, the venous blood was drawn before and after treatment, respectively. The platelets were activated by adenosine diphosphate （ADP） , thus releasing sCD40L, sCD40L levels were determined by en- zyme-linked immunosorbent assay （ELISA） at different time of the reaction. Results Plasma sCD40L concentration before treatment was （0. 199 ± 0. 155 ） ng/mL, and （0. 190 ± 0. 176） ng/mL after treatment （ P 〉 0.05 ）. Before treatment the PRP sCD40L level at 20-minute of platelet activation was （4.34 ± 2.51 ） ng/mL, and decreased to （2.79 ±1.93 ） ng/mL after treatment （ P 〈 0. 001 ）. The corresponding level at 40 - minute of platelet activation was （5.29 ± 3. 13 ） ng/mL before treatment and （ 2.87 ± 1.59 ） ng/mL after treatment（ P 〈 0. 001 ）. Conclusions Short-term clopidogrel administration might inhibit the release of sCD40L by ADP-activated platelet in patients with NSTEACS, suggesting that, in addition to its antiplatelet potency, clopidogrel may still have an anti-inflammatory effect.

Soluble CD40 ligand is associated with angiographic severity of coronary artery disease in patients with acute coronary syndrome

Background Recently,studies have disclosed soluble CD40 ligand （sCD40L） during atherosclerosis development and plaque destabilization.The objective of the present study was to test the hypothesis that sCD40L levels are higher in acute coronary syndrome （ACS） patients with a greater extent of angiographic coronary involvement.Methods This cross-sectional study examined ACS patients who underwent coronary angiography by measuring their sCD40L levels.In order to estimate the serum levels of sCD40L,10 ml of peripheral venous blood was drawn within 24 hours of admission.sCD40L levels were measured using an enzyme-linked immunosorbent assay （ELISA,RapidBio,West Hills,CA,USA）.Demographic data,presence of concomitant diseases,ACS characteristics,and angiographic findings were evaluated.A review of medical records and patient interviews were conducted to assess coronary risk factors.And the severity of coronary artery disease was evaluated using the Gensini score index.Results Two hundred and eighty-nine patients were included in the study,of whom 186 were male,with an average age of 64.1±10.0 years.Median sCD40L levels were 1.7 ng/ml （0.3-7.3 ng/ml） and Gensini scores were 50 （0-228）.After adjusting for demographic variables and cardiovascular risk factors,the Gensini score was associated with the natural logarithm of the sCD40L level （Coefficient b=0.002,95％ CI 0.000-0.003,P=0.029）.Conclusion sCD40L levels were independently associated with angiographic severity of coronary artery disease in patients with ACS.

Soluble CD40 in plasma and malignant pleural effusion with non-small cell lung cancer:A potential marker of prognosis

Objective: Soluble CD40 (sCD40) is a potential modulator for both antitumor responses and CD40-based immunotherapy;however the levels and significance of sCD40 in non-small cell lung cancer (NSCLC) patients with malignant pleural effusion are unknown. Methods: Forty-eight patients with lung cancer were treated in our institutions from January 2008 to January 2010. Peripheral blood and pleural effusion samples were collected from each subject. sCD40 levels in plasma and malignant pleural effusions supernatant were measured. The CD40L expression on CD3t T-cells was confirmed by flow cytometric direct immunofluorescence analysis. All patients were followed up after the study ended on January 1, 2010. Results: Patients with malignant pleural effusion of NSCLC had elevated circulating and pleural effusion levels of sCD40, and these elevated sCD40 levels were associated with advanced diseases and a poor prognosis. Conclusions: These findings indicate that elevated sCD40 may have a role in modulating antitumor responses and may also be a useful prognostic marker. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Role of platelet TLR4 expression in pathogensis of septic thrombocytopenia

BACKGROUND： Infection-induced thrombocytopenia （TCP） is an independent risk factor for death of patients with sepsis, but its mechanism is unknown. This study aimed to explore the underlying mechanism of TCP based on the relationship between TLR4 expression and platelet activation in septic patients. METHODS： A total of 64 patients with sepsis were prospectively studied. Platelet count （PC）, mean platelet volume （MPV）, platelet distribution width （PDW）, platelet TLR4 expression, platelet PAC-1 expression, sCD40L and TNF-a concentrations were compared between the healthy control group （15 volunteers） and sepsis group （64 patients） at admission and on the 3, 5, and 9 days after admission. The changes of MPV and PDW in the TCP and non-TCP subgroups of sepsis before and after treatment were recorded. Prognostic index was analyzed. RESULTS：PC was lower in the sepsis group （P=0.006）, and MPV and PDW were higher in the sepsis group than those in the healthy control group （P=0.046, P=0.001）. Platelet TLR4 and PAC-1 expressions, and sCD40L and TNF-a levels increased more significantly in the sepsis group （P〈0.001）. PAC-1 expression and TNF-a level were higher in the TCP group than in the non-TCP group before and after treatment （P=0.023, P=0.011）. sCD40L concentration and platelet TLR4 expression were significantly higher in the treated TCP group than in the non-TCP group （P=0.047, P=0.001）. Compared to the non-TCP group, the rate of bleeding was higher （P=0.024） and the length of ICU stay was longer （P=0.013）. The APACHE II score and the 28-day mortality were higher in the TCP group （P〈0.01, P=0.048）. CONCLUSIONS：The elevation of platelet TLR4 expression in sepsis along with platelet activation is closely related to the incidence of thrombocytopenia. The occurrence of TCP is a sign of poor prognosis in sepsis patients.

Levels of circulating follicular helper T cells,T helper 1 cells,and the prognostic significance of soluble form of CD40 ligand on survival in patients with alcoholic cirrhosis

Background:Excessive drinkers(ED)and patients with alcoholic liver disease(ALD)are several times more susceptible to bacterial and viral infections and have a decrease in antibody responses to vaccinations.Follicular helper T(TFH)cells are essential to select B cells in the germinal center and to produce antibodies.TFH cells express both a membrane-associated and a soluble form of CD40 ligand(sCD40L),in which the latter form is released to circulation upon T cell activation.The effect of alcohol on TFH cells has not been studied.Objectives:The goals of this study are to determine the levels of TFH and T helper 1(Th1)cells in ED and those with alcoholic cirrhosis(AC)when compared to healthy controls and to determine the prognostic significance of sCD40L in a cohort of patients with AC.Methods:Controls,ED,and those with AC were enrolled.Baseline demographic,laboratory tests,and peripheral blood mononuclear cells(PBMCs)were isolated and assessed via flow cytometry for TFH cells.In vitro study was performed to determine the ability of PBMCs to secrete interferon(IFN)-ɣupon stimulation.Serum sCD40L was also determined and its prognostic significance was tested in a cohort of AC patients.Results:The levels of circulating TFH(cTFH)cells were significantly lower in peripheral blood of subjects with ED and AC compared to controls(P<0.05).IFN-ɣsecretion from PBMCs upon stimulation was also lower in ED and those with cirrhosis.Serum sCD40L was significantly lower in ED and AC when compared to that in controls(P<0.0005).Its level was an independent predictor of mortality.Conclusions:Patients with AC had significantly lower level of cTFH and sCD40L.The level of sCD40L was an independent predictor of mortality in these patients.

Impact of intensive statin therapy on hs-CRP and sCD40L in AMI patients during perioperative period of emergency PCI

Background It＇s an effective treatment to achieve percutaneous coronary intervention （PCI） in acute myocardial infarction （AMI） patients for reperfusion of coronary artery. The PCI treatment can improve the blood supply of coronary artery, make some adverse effects at the same time. Studies have shown that statins have other effects in addition to lipid-lowering, such as anti-inflammatory effects. It can significantly reduce the incidence of coronary heart disease, cardiovascular disease mortality and even all-cause mortality. The aim of this study was to investigate the clinical effects and significance of intensive atorvastatin in AMI patients during perioperative period of PCI. Methods One hundred twelve AMI patients were randomly divided into three groups. The control group （n = 32） was given the routine medicine, and the two therapy groups were administered atorvastatin 80 mg or 40 mg before PCI,and then were administered atorvastati 40 mg q.d or 20 mg q.d after PCI. Levels of high-sensitive C-reactive protein （hs-CRP）, compared after PCI. Results sCD40L, myocardial enzymes and lipid was determined and Compared with the control group, the levels of serum hs-CRP, CD40L in treatment group 1 （n = 40） and treatment 2 group （n = 40） was significant difference between two treatment groups （ atorvastatin in AMI patients during PCI perioperative period i anti-inflammatory, anti-platelets, and stability of plaque and were significantly decreased （P 〈 0.05）, and there P 〈 0.01 ）. Conclusion Intensive treatment of s beneficial, possibly through Mechanisms such as coronary vascular endothelial function.