肝癌患者粘附分子和细胞因子的变化及其意义

目的：观察肝癌患者外周血清可溶性P-选择素(soluble P-selectin，CD62P)，细胞间粘附分子-1(soluble intercellular adhesion molecule-1，sICAM-1，CD54)，血管细胞粘附分子(soluble vascular cell adhesion molecule-1，sVCAM-1，CD106)和白细胞粘附分子β2整合素(β2-integrin，CD18)的变化，并探讨其临床意义。方法：采用流式细胞仪技术检测了48例不同期肝癌患者外周血清sP-selectin，sICAM-1 sVCAM-1水平和白细胞CD18的表达。结果：与正常对照组相比，血清sP-selectin，sICAM-1 sVCAM-1水平和白细胞CD18的表达显著增加。结论：肝癌患者外周血清sP-selectin，sICAM-1 sVCAM11水平和白细胞CD18的表达对肝癌的早期临床分期具有一定的参考价值。     

Homocysteinemia is inversely correlated with platelet count and directly correlated with sE- and sP-selectin levels in females homozygous for C677T methylenetetrahydrofolate reductase

Plasma homocysteine levels depend in part on the molecular nature of the methylenetetrahydrofolate reductase (MTHFR) and on blood folate intake. Little has been reported on platelet counts in the presence of hyperhomocysteinemia and MTHFR polymorphisms, with the exception of delayed platelet recovery in homozygous MTHFR C677T subjects after treatment with methotrexate for ovarian cancer. The aim of this investigation was to evaluate the possibility of a link between the platelet count and plasma homocysteine levels in different MTHFR variants in 165 female patients. Determinations of plasma homocysteine levels were by ELISA and of MTHFR polymorphisms (A1298C and C677T) were by inverse hybridization. Serum P- and E-selectin concentrations were obtained by ELISA. An inverse correlation (R?=??0.88, P?<?0.001) was observed between blood platelet counts and plasma homocysteine levels in the women homozygous for MTHFR C677T. This correlation did not depend on pregnancy or other variables reported. Serum concentrations of sE- and sP-selectin, markers of endothelial and platelet activation, were significantly and positively correlated with homocysteine levels. These findings suggest that homocysteine affects platelet numbers in women with MTHFR C677T possibly consequent to endothelial and platelet activation.     

结直肠癌患者血清sP-selectin和IL-8 水平的变化及其临床意义

目的　探讨结直肠癌患者手术前后血清中可溶性P -selectin和IL - 8含量的变化及其临床意义。方法　用ELISA法和RIA法分别测定结直肠癌患者手术前 ,手术后及复发病人血清sP -selectin和IL - 8的含量 ,并与对照组进行比较。结果　结直肠癌患者血清sP -selectin和IL - 8的含量明显高于正常人 (P <0 .0 1) ,术后 3个月下降至接近正常人水平 ,而复发患者则再次升高 (P <0 .0 1)。结论　血清sP -selectin和IL - 8的含量与结直肠癌的发生 ,发展及预后密切相关。     

结直肠癌患者血清sP-selectin和IL-8水平的变化及其临床意义

目的 :探讨结直肠癌患者手术前后血清中可溶性sP -selectin和IL -8含量的变化及其临床意义。方法 :用ELISA法和RIA法分别测定结直肠癌患者手术前、手术后及复发病人血清sP -selectin和IL -8的含量 ,并与对照组进行比较。结果 :结直肠癌患者血清sP -selectin和IL -8的含量明显高于正常人 (P<0.01) ,术后3个月下降至接近正常人水平 ,而复发患者则再次升高 (P<0.01)。结论 :血清sP -selectin和IL -8的含量与结直肠癌的发展及预后密切相关     

Synthetic isoxazole as antiplatelet agent

Abstract

Nine synthetic isoxazoles were evaluated as antiplatelet agents and studied the possible mechanism of more active compound. The initial screening was evaluating all compounds against platelet aggregation assays. The most active compound was isoxazole 8 showing an inhibition of platelet aggregation around 70%. In subsequent experiments, ADP and collagen were used as agonists to explore the possible inhibitory mechanisms of isoxazole 8 in platelet aggregation and secretion. We reported the effect of isoxazole 8 for reducing the expression of inflammatory markers, such as soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin), on activated platelets. Of this form, an inhibition of sCD40L and sP-selectin can prevent the onset of an atherosclerotic lesion.     

Soluble P-selectin and the postoperative course following cardiopulmonary bypass in children

BACKGROUND: Cytokine-inducible leucocyte-endothelial adhesion molecules were shown to affect the postoperative inflammatory response following cardiopulmonary bypass (CPB). Soluble P-selectin (sP-selectin) is one of these molecules. We investigated the correlation between plasma sP-selectin levels and the intra- and postoperative course in children undergoing CPB. METHODS: Serial blood samples of 13 patients were collected preoperatively upon initiation of CPB and seven times postoperatively. Plasma was recovered immediately and frozen at - 70 degrees C until use. Circulating soluble selectin molecules were measured with a sandwich enzyme-linked immunoabsorbent assay technique. RESULTS: The significant post-CPB changes in sP-selectins plasma levels were associated with patient characteristics, operative variables and postoperative course. sP-selectin levels correlated significantly with surgery time, aortic cross-clamping time and inotropic support, as well as with the postoperative Pediatric Risk of Mortality score, hypotension and tachycardia. CONCLUSIONS: A relation between CPB-induced mediators and both early and late clinical effects is suggested. The up-regulation and expression of sP-selectin indicate neutrophil activation as a possible mechanism for the increase, and inhibiting it may reduce the inflammatory response associated with CPB.     

Serial changes in neutrophil-endothelial activation markers during the course of sepsis associated with disseminated intravascular coagulation

INTRODUCTION: For systematic elucidation of serial changes in neutrophil-endothelial activation markers as well as to investigate the correlationship among the inflammation markers, disseminated intravascular coagulation (DIC), and multiple organ dysfunction syndrome (MODS) in patients with sepsis, we made this prospective study. MATERIALS AND METHODS: Forty-five patients with sepsis, severe sepsis, and septic shock were subdivided into two groups, 27 with DIC and 18 without DIC. Eight normal healthy volunteers served as control subjects. Serial levels of soluble L-, P-, and E-selectins, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), thrombomodulin (sTM), and neutrophil elastase were measured within 12 h after the diagnosis of sepsis (day 0) and on days 1-4 after the diagnosis. The numbers of systemic inflammatory response syndrome (SIRS) criteria that patients met and the DIC score were determined simultaneously. RESULTS: Acute Physiology and Chronic Health Evaluation (APACHE) II score was identical between the two groups. In the DIC patients, higher DIC scores, lower platelet counts, and more maximum numbers of SIRS criteria being met were observed compared with the non-DIC patients. The incidence of MODS and the number of the dysfunctioning organs were higher in the patients with DIC than those without DIC, and the DIC patients had poor outcome. Soluble L-selectin (sL-selectin) levels in both groups tended to be lower than those in the control subjects. All other parameters both in the two groups were continuously higher than those in the control subjects during study period. The levels of soluble E-selectin (sE-selectin), sICAM-1, sVCAM-1, neutrophil elastase, and sTM were more elevated in the DIC patients than those in the non-DIC patients. There were no differences in the sP-selectin levels between the two groups; however, more increased sP-selectin levels per platelet were found in the DIC patients compared with the non-DIC patients. Maximum DIC scores in the DIC group positively correlated with the peak levels of neutrophil elastase and sTM and the number of the dysfunctioning organs. CONCLUSIONS: We found close relations among the neutrophil-endothelial cell interactions, DIC, and MODS in patients with sepsis, severe sepsis, and septic shock. The results indirectly confirm the concept that DIC can produce organ dysfunction and that DIC reflects an inflammatory disorder of the microvasculature.     

Soluble platelet selectin (sP-selectin) and soluble vascular cell adhesion molecule-1 (sVCAM-1) decrease during therapy with benznidazole in children with indeterminate form of Chagas' disease

The immune response against Trypanosoma cruzi infection has been associated with both protection and pathogenesis. Central events in host defence system- and immune-mediated damage are tightly regulated by cell adhesion molecules (CAM). Levels of sP-selectin and sVCAM-1 were measured in sera from 41 children with the indeterminate phase of Chagas' disease. Simultaneously, levels of soluble adhesion molecule were also quantified in Chagas' disease children undergoing specific chemotherapy with benznidazole. Levels of sP-selectin and sVCAM-1 were found to be elevated in children with indeterminate Chagas' disease before aetiologic therapy was started. However, a small group of patients showed sP-selectin and sVCAM-1 levels comparable to those of non-infected children. A positive correlation between levels of sVCAM-1 and sP-selectin in sera from Chagas' disease patients was found. There was a significantly greater decrease in the titres of sP-selectin and sVCAM-1 in those children receiving benznidazole therapy compared with those children receiving placebo. Measurement of soluble adhesion molecules revealed differences in the activation of the immune system in children with the indeterminate form of Chagas' disease. The early decrease of sP-selectin and sVCAM-1 levels after anti-parasitic treatment suggests that these molecules might be valuable indicators of effective parasitologic clearance.     

病毒性脑炎患者血清sP-选择素和sICAM-1的水平及临床意义

目的观察病毒性脑炎患者血清中可溶性P -选择素 (sP -selectin)和可溶性细胞间粘附分子 - 1(sICAM - 1)水平变化 ,并探讨其临床意义。方法应用ELISA分别检测 15例病毒性脑炎患者急性期、恢复期及 18例健康人血清中sP 选择素和sICAM 1水平。结果病毒性脑炎患者急性期血清中的sP 选择素和sICAM 1显著高于健康人对照组 (P <0 .0 1) ,恢复期血清中sP 选择素、s I CAM与对照组比较无差异性 (P >0 .0 5 )。结论病毒性脑患者sP 选择素、sICAM 1与病程密切相关 ,检测血清sP 选择素和sICAM 1对病情的判断具有一定的参考价值。     

Umbilical sP-selectin levels are different in preeclamptic pregnancies with intrauterine normal growth and growth restricted fetus

Objective.?The aim of this study was the analysis of the umbilical cord serum sP-selectin levels in pregnancies complicated by severe preeclampsia with and without intrauterine growth restriction and in normotensive pregnancies.

Patients and methods. The study was carried out on 18 patients with singleton pregnancies complicated by severe preeclampsia with appropriate-for-gestational-age weight infants (group P) and 18 pregnant patients with severe preeclampsia complicated by intrauterine fetal growth restriction (IUGR) (group PI). The control group consisted of 34 patients with singleton uncomplicated pregnancies (group C). Umbilical serum sP-selectin concentrations were estimated using a sandwich ELISA assay according to the manufacturer's instruction (ELISA kit Bender MedSystems Vienna, Austria).

Results.?Our study revealed different concentrations of soluble P-selectin in the umbilical cord in our both studied groups of preeclamptic women with and without IUGR. The umbilical cord levels of sP-selectin were decreased in the group with preeclampsia complicated by IUGR and increased in the preeclamptic women with the normal intrauterine fetal growth. The mean values of umbilical sP-selectin were 839.008?±?625.703?ng/ml in group P, 275.873?±?174.339?ng/ml in group PI, and 288.719?±?199.039?ng/ml in the control group, respectively.

Conclusions.?Higher levels of the umbilical sP-selectin may confirm the presence of platelet and endothelial cell activation and confirm a hypercoagulant state in preeclamptic disorder, especially in preeclampsia without IUGR.