Móleculas protrombóticas en niños con Diabetes Mellitus Tipo 1 / Study of prothrombotic molecules in type 1 diabetes mellitus children

Introducción: la hiperglucemia contribuye a cambios moleculares que alteran la hemostasia. Objetivos: determinar moléculas circulantes que indiquen la presencia de un estado protrombótico en una población infanto juvenil con diabetes mellitus tipo 1 (DM1), sin manifestación clínica de enfermedad vascular, y compararla con una población control. Pacientes y métodos: se estudiaron 35 pacientes con DM1, de 11,0±2,5 años de edad y 3,7±2,0 años de evolución de la enfermedad, sin complicaciones vasculares y 20 controles sanos de edad, sexo e IMC semejantes. Se determinaron: fibrinógeno (Fg), inhibidor del activador del plasminógeno 1 (PAI-1), antígeno del factor von Willebrand (FvW:Ag), ligando CD40 soluble (sCD40L) y pruebas globales de coagulación como recuento de plaquetas, tiempo de protrombina (TP) y tiempo de tromboplastina parcial activado (APTT). El control glucémico se evaluó mediante glucemia en ayunas y A1c, y se descartó la presencia de retinopatía y nefropatía. Los datos se analizaron con el programa SPSS 20 para Windows y se expresaron como media±DE. El coeficiente de Pearson se usó para investigar las correlaciones entre las variables estudiadas. Resultados: los pacientes con DM1 presentaron valores significativamente mayores de Fg (308±66 vs 246±18 mg/dL, p=0,0001), PAI-1 (41,6±12 vs 11,7±1,0 ng/mL, p=0,0001), FvW:Ag (284±55 vs 121±19 %, p=0,0001) y sCD40L (1608±109 vs 149±17 pg/mL, p=0,0001). Sin embargo las pruebas globales de hemostasia no mostraron diferencias entre ambos grupos. El PAI-1 y sCD40L se correlacionaron con glucemia, A1c, Fg y FvW:Ag. Conclusiones: los niveles elevados de Fg, PAI-1, FvW:Ag y sCD40L sugieren la presencia de un estado protrombótico en la población infanto juvenil con DM1

Introduction: hyperglycemia contributes to molecular changes that alter hemostasis. Objectives: to determine molecules of a prothrombotic state in a child-juvenile population with type 1 diabetes (T1D), without clinical manifestation of vascular disease, and compare it with a control population. Patients and methods: thirty-five patients with T1D (11.0±2.5 years and 3.7±2.0 years of disease duration), without vascular complications and 20 healthy controls were studied. Plasma fibrinogen (Pf), plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor antigen vWF:Ag and soluble CD40 ligand (sCD40L) and coagulation global tests such as platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) were determined. The data obtained were analized by Statistics SPSS 20 software and were expressed as the mean±standard desviation. Pearson coefficient was used to investigate correlations between variables. Results: diabetic patients presented significantly higher values of glycaemia, A1c, Fg (308± 66 vs 246±18 mg/dL, p=0.0001), PAI-1 (41.6±12 vs 11.7±1, 0 ng/mL, p=0.0001), vWF:Ag (284±55 vs 121±19%, p= 0.0001) and sCD40L (1608±109 vs 149±17 pg/mL, p=0.0001). However, overall hemostasis tests showed no differences between both groups, PAI-1 and sCD40L correlated with glycemia, A1c, Fg and vWF:Ag. Conclusions: high levels of Fg, PAI-1, vWF:Ag and sCD40L suggest the presence of a prothrombotic state in the infant population juvenil with DT1

Investigation of expression and relationship between serum MMP -9 and sCD40L in patients with acute ;coronary syndrome / 中国基层医药

Objective To observe serum sCD40L,MMP9 levels and their relevance with different types of coronary heart disease(CHD).Methods The present study was involved in 90 patients with CHD,including acute myocardial infarction(AMI)30 case,unstable angina pectoris(UAP)31 case,stable angina pectoris (SAP)29 case and another 25 normal controls.The serum MMP9 and sCD40L levels were detected with enzyme-linked immunosor-bent assay.Results The levels of MMP9,sCD40L in AMI and UAP group were significantly higher than those in SAP group[(69.48 ±4.76)ng/mL,(66.61 ±5.30)ng/mL,(30.44 ±7.66)ng/mL,t=1.425,0.075,all P0.05 ),and also there were no ststitically signiticant differeces in the serum MMP9,sCD40L levels between SAP group with control group (all P>0.05).MMP9 level in AMI and UAP group was positively related with sCD40L (r=0.96,P<0.01 and r=0.97,P<0.01 ).Conclusion The serum sCD40L and MMP9 levels of acute coronary syndrome(ACS)increase significantly,and can be used as an important index to assess the severity of CAD and predict the instability of plaque in CAD patients.

The correlation between YKL-40,sCD40L,AFP and coronary heart disease / 国际检验医学杂志

Objective To study the chitin enzyme protein(YKL-40),sCD40L,AFP and the correlation of hypertension with cor-onary heart disease(CHD).Methods 75 cases of elderly patients with CHD were selected as observation group,and then were di-vided into hypertension group and non hypertension group according to the blood pressure.103 cases of healthy elderly were select-ed as control group.ELISA method was used to detect YKL-40 and sCD40L,and AFP was detected by chemiluminescence immuno-assay.Results Clinical data comparison revealed that the relative risk of CHD with hypertension group and non hypertension of hy-perlipidemia,drinking,smoking,diabetes mellitus,were 1.56,1.33,1.23,1.15 times,data show that relative risk of CHD with hy-pertension were much greater than CHD without hyperlipidemia.The concentration of YKL-40 in CHD with hypertension(92.66± 12.04)ng/mL was significant higher than that in CHD without hypertension (57.08 ± 10.07 )ng/mL,and the concentration of sCD40L in CHD with hypertension (186.59 ± 69.63 )ng/mL was significant higher than that in CHD without hypertension (128.14±48.37)ng/mL(P 0.05).Conclusion The levels of YKL-40,CD40L and AFP in the peripheral blood of elderly patients with CHD were significantly increased.And the concentration of sCD40L and YKL-40 was positively correlated with hy-pertension,which can be used to assess the stability and prognosis of CHD.

The study of plasma levels of sCD40 and sCD40L in Alzheimer’s disease and mild cognitive impairment / 中国神经精神疾病杂志

Objective To explore the plasma levels of soluble CD40 (sCD40) and soluble CD40 ligand (sCD40L) in the patients with Alzheimer’s disease (AD) and those with amnestic mild cognitive impairment (aMCI). Methods The levels of plasma sCD40 and sCD40L were measured in 20 patients with AD, 35 patients with aMCI, and 32 cognitively normal controls (NC) using commercially available ELISAs. The cognitive function of AD and aMCI patients was mea?sured by mini-mental state examination (MMSE). Results There were significant differences in plasma sCD40 among AD, aMCI and NC groups (P<0.05) as the medians (the upper and lower quartiles) of plasma levels were 123.3 (97.4, 149.5) pg/mL, 102.9 (63.6, 124.0) pg/mL and 70.66 (51.0, 90.8) pg/mL, respectively. There were significant differences in plasma sCD40L among AD, aMCI and NC groups (P<0.05) as plasma levels were 537.0 (316.0, 1134.0) pg/mL, 316.0 (190.0,546.0) pg/mL and 167.0 (107.5,478.0) pg/mL. A negative correlation between the plasma concentrations of sCD40L and the MMSE scores was found in aMCI patients (r=-0.736, P<0.001). Conclusions There are relevant chang?es of plasma sCD40 and sCD40L levels in patients with AD and aMCI. The present results suggest that plasma levels of sCD40 and sCD40L may be appropriate biomarkers for AD patients and indicate that CD40-CD40L signaling may be in?volved in AD pathophysiology.

TRALI, una amenaza enmascarada: biología y fisiopatología / TRALI, a masked menace: biology and pathophysiology

El daño pulmonar agudo ocasionado por la transfusión o TRALI (por sus siglas en inglés), definido como la aparición de un distrés respiratorio agudo en un paciente recién transfundido, pasó de ser considerado una complicación infrecuente de la terapia transfusional a ser actualmente la principal causa de mortalidad por transfusión, según sistemas de hemovigilancia de Europa y Norteamérica. Su desarrollo en forma clínicamente reconocible se atribuye a la interacción entre factores dependientes de la unidad transfundida (tipo de componente, presencia de sustancias biológicamente activas, etc.) y el estado de las respuestas celulares en el receptor. La heterogeneidad en cuanto al cuadro clínico de los pacientes afectados,la variación en el volumen infundido, el tipo de componente implicado y el tiempo desde el inicio de la transfusión hasta la aparición de los síntomas, ha hecho evolucionar la explicación a la génesis de este evento adverso, en el afán de incluir los casos sin explicación mediante las distintas hipótesis. Dos interesantes acercamientos patogénicos resultan la teoría de dos golpes y el modelo basado en el umbral que impone la relación entre los distintos factores de riesgo. La naturaleza multicausal del TRALI y el sinnúmero de variables que pueden influir en su aparición y reconocimiento, continúan haciendo de este un reto médico importante en el contexto de la medicina transfusional, donde su mejor enfoque terapéutico sigue siendo el preventivo(AU)

Transfusion-related acute lung injury (TRALI) defined as the onset of an acute respiratory distress in a recently transfused patient, has passed from been considered a rare complication of transfusion therapy to be the leading cause of transfusion-associated death, as reported by hemovigilance systems in Europe and America. In a previous paper definition, epidemiology and some clinical aspects of TRALI are reviewed. Now we focused our efforts in reviewing the incompletely understood world of its pathogenesis. Clinically recognizable TRALI´s development depends on the interaction between risk factors from both the transfused component unit (as the kind of component and substances within it) and receiver patient´s cellular response. Heterogeneity of clinical features, transfused volumes, component type and time elapsed from the beginning of transfusion to the onset of symptoms have pushed the explanations for its genesis to evolve in an effort to include as much cases as the different hypotheses allowed. Two interesting approaches to TRALI´s pathogenesis are the two hit; theory and the threshold; model imposed by risk factors interactions. The large diversity of variables and causes which can influence its onset and clinical recognition continue to make it a real challenge for clinicians, mainly within transfusion medicine, where the best therapeutic approach available is prevention(AU)

Impacts of tirofiban on plasma levels of sCD40L, HIF-1α, and iNOS / 实用医学杂志

Objective To observe the impacts of tirofiban on plasma levels of sCD40L and HIF-1α, and iNOS activity in patients undergoing emergency PCI. Methods A total of 80 patients with acute STEMI received primary PCI were randomly divided into a tirofiban group and a control group. The tirofiban group received tirofiban of 10 μg/kg, followed by an infusion of tirofiban of 0.15 μg/(kg·min) for 24 ~ 36 hours; while the control group directly received stent implantation after balloon angioplasty. Plasma levels of sCD40L , HIF-1α, and iNOS were detected in baselines and 12 hours after the procedrue. Results 12 hours after the procedure, serum levels of sCD40L, HIF-1α, and iNOS were higher than the baseline levels (P < 0.05). As compared with the control group, levels of sCD40L, HIF-1α, and iNOS were significantly lower (P < 0.05). Conclusions This study preliminarily sugguests tirofiban has a role in anti-inflammation and protection of vascular endothelium besides anti-platelet effects.

The effect of Tirofiban on the expression of sCD40L and matrix metalloproteinase-9 in patients with ACS after PCI / 中国综合临床

Objective To investigate the effects of Tirofiban on the expression of matrix metalloproteinase(MMP-9)and sCD40L in patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI)and to explore the potential mechanism of anti-artherosclerosis and stabilize plaque by Tirofiban.Methods Eighty-six patients with ACS were enrolled and were randomly divided into the control group and the Tirofiban group with different time periods after PCI.The expression of MMP-9 and sCD40L were tested by ELISA at 6 h,12 h,24 h,36 h after PCI.Results After application of Tirofiban 6 h,12 h,24 h,36 h,the expression of MMP-9 decreased from(228.25 ±0.015)ug/L to(53.56 ±0.02)μg/L and the expression of sCD40L decreased from(321.12 ±0.02)ng/L to(123.32 ±0.02)ng/L,compared with the control group,the difference was significant(P ＜ 0.05).Conclusions Tirofiban can inhibite the expression of sCD40L and MMP-9,the inhibition of the expression of MMP-9 may be related to the CD40/CD40L pathway.This effect may be one of the mechanism of reducing atherosclerotic plaque inflammation and preventing plaque rupture by Tirofiban.

Soluble CD40 Ligand and fibrinogen in acute myocardial infarction / 中国综合临床

Objective To observe the changes of serum soluble CD40 ligand (sCD40L) and fibrinogen in acute myocardial infarction (AMI) patients and to investigate the clinical predictive value of increased serum sCD40L and fibrinogen. Methods Serum sCD40L level of 60 AMI patients was determined by enzyme-linked im-munosorbent assay (ELISA). Plasma level of fibrinogen was measured. The patients were followed up for 2 years af-ter discharge from the hospital and were observed for cardiovascular event. Results AMI patients had higher sCD40L and fibrinogen levels than those of controls [(15.36±7.32) μg/L vs. (5.79±2.78) μg/L, (4.60±1.37)g/L vs. (3.03±0.82) g/L,P<0.001] ,which were significantly higher in the patients experiencing cardio-vascular event than those without cardiovascular event [(18.14±6.34) μg/L vs. (14.38±6.67) μg/L and (4.97±1.33)g/L vs. (4.20±1.24} g/L] (P<0.05). The patients with sCD40L≥14.5 μg/L or fibrinogen≥ 4.4 g/L experienced increased risk of adverse cardiovascular events (P<0.05). In AMI patients, sCD40L level was significantly higher in patients with diabetes than in nondiabetics [(18.38±6.71) μg/L vs. (14.46±6.48) μg/L, P<0.05)]. Fibrinogen level was related to sCD40L (r=0.27, P<0.05) and LVEF(r=-0.319, P<0.05). Conclusion Increased sCD40L and fibrinogen levels,which maybe related to the pathogenesis of AMI,can be found in AMI patients and can indicate an independent increased risk of major adverse cardiovascular events. Diabetes is independently associated with elevated sCD40L level in AMI patients.

Soluble sCD80-Linker-sCD40L fusion protein induces unspecific anti-tumor immunity in vitro / 中国肿瘤生物治疗杂志

Objective:To investigate the influence of sCD80-Linker-sCD40L fusion protein on the unspecific anti- tumor immunity in vitro.Methods:Ovarian cancer SKOV3 cells were separately transfected with recombinant adenoviral vectors containing sCD80-Linker-sCD40L fusion gene,sCD80 gene,sCD40L gene or with control adenovirus.The expres- sion of the sCD80-Linker-sCD40L fusion protein,sCD80 protein and sCD40L protein in the supernatants of SKOV3 cells was determined by ELISA.Dendritic cells(DCs)were cultured with peripheral blood mononuclear cells from a patient with ovarian carcinoma.DCs and autologous T cells were co-cuhured and were exposed to different supernatants for 48 h. The allostimulatory effects of DCs on T cells were determined by mixed lymphocyte reaction(MLR).The unspecific kill- ing activities of induced T cells against SKOV3/K562 cells were measured by LDH-releasing assay.Results:ELISA assay showed that levels of the sCD80-Linker-sCD40L fusion protein,sCD80 protein and sCD40L protein in the supernatants of transfeced SKOV3 cells were 2.791 ng/ml,1.956 ng/ml and 1.407 ng/ml,respectively.The fusion protein-exposed DCs ([0.382?0.053]vs[0.167?0.028],P

Inducement of specific anti-hepatoma immunity of DC activated by HSP70-H22 peptide complexes and sCD40L / 第三军医大学学报

Objective To study the specific anti-tumor immunity of dendritic cell(DC) modified by HSP70-tumor peptide complexes and sCD40L in vitro and in vivo.Methods The murine marrow cells were cultured for 7 d,and then randomized to 4 groups: control,only HSP70-H22 peptide complexes,sCD40L,and HSP70-H22 peptide complexes combined with sCD40L.After intervention for 24 h,IL-12 and IL-10 in the supernatant were detected by ELISA assay,CD40 and CD80 of DC by FACS,and the proliferation of spleen lymphocytes by MRL.The ability of spleen lymphocytes activated by DC to H22 cells in vitro was investigated by MTT.The models of murine hepatoma were established,and then randomized to 5 groups(Ⅰ,Ⅱ,Ⅲ,Ⅳ and Ⅴ),followed by interference with normal saline and DC respectively.At 21 d,mice were sacrificed and the weight of tumor was measured.The levels of IL-10 and IFN-? in blood serum were detected by ELISA assay.Results Compared with that in the groups of control,only sCD40L,and HSP70-H22 peptide complexes,the level of IL-10 in the group stimulated by HSP70-H22 peptide complexes combined with sCD40L decreased significantly,but other indexes in this group increased significantly(P

The inhibitory repressive effect of IL-10 on the monocyte-derived DC maturation,differation and biological function in vitro / 中国免疫学杂志

Objective:To investigate the negative effect of the IL-10 on monocyte-derived DC maturation and differation iv vitro,and the potentiation of the TNF-? or sCD40L to inhibit or reverse the IL-10′s inhibitory effect on monocyte-derived DC.Methods:The expression of the surface molecules on DC was detected by FACS analysis.The potentiation to stimulate T cell proliferation was assayed by 3H-TdR incorporation,and IL-12 secretion in the DC supernatant measured by ELISA.Results:In vitro DC-inducing system IL-10 had an obviously negative effect on the maturation as well as the potentiation to stimulate the T cell proliferation and IL-12 secretion of the immature monocyte-derived DC,and IL-10 could drive monocyte-derived DC differentiate into the macrophages.The negative effect was also correlative to the concentration of the added IL-10;The results also showed that IL-10 hadn′t any negative effect on mature DC induced by sCD40L,but to some extent could reduce the mature DC induced by TNF-? to produce IL-12;Furthermore the inhibitory effect of IL-10 can′t be reversed by adding TNF-? or sCD40L after IL-10 was added to the DC-inducing culture system for three days.Interesting by adding sCD40L not TNF-? to the DC-inducing culture system with IL-10 at the same time can inhibit the negative effect of IL-10 completely.Conclusion:IL-10 is an important biological factor produced in tumor microenvironment for escaping the attack of the immune system by repressing maturation,potentiation to costimulate the T cells and IL-12 secretion of the immature monocyte-derived DC.The reverse effect of TNF-? and sCD40L on IL-10 negative effect on monocyte-derived was different.All together suggested that CD40 signal has important values to obtain the therapeutic DC for the tumor immune intervention.

The role of serum soluble CD40 ligand in diagnosis of acute coronary syndrome / 西安交通大学学报(医学版)

0.05).② On diagnosing ACS,the area under ROC curve of sCD40L was 0.773,the sensitivity,specificity and validity are 82.8%,61.9% and 85.7%,respectively,which were all highest among so much indexes.Conclusion High serum sCD40L levels may suggest vulnerable plaque,and it's somewhat valuable in diagnosing ACS.