Correlation between serum osteoprotegerin and atherosclerotic vascular disorders in rheumatoid arthritis patients

The aim of the present study was to investigate the association of serum osteoprotegerin [OPG] level with the presence of angiographically documented asymptomatic coronary artery disease [CAD] in patients with rheumatoid arthritis [RA] and to evaluate its relationship with plasma thrombomodulin [TM], as a marker of endothelial dysfunction and with carotid artery intima media thickness [IMT], as a marker of atherosclerosis. The study included 20 rheumatoid patients without CAD [negative results on exercise ECG stress test] and other 20 rheumatoid patients with CAD [positive results on exercise ECG stress test and confirmed by coronary angiography]. In addition, 20 age and sex matched normal control subjects were studied. Serum OPG and plasma TM levels were measured and carotid artery IMT was determined. The study revealed that serum OPG levels were significantly higher in rheumatoid patients with and without CAD than in controls [P < 0.001,P < 0.01; respectively] and were positively correlated with age, duration of disease, Disease active score 28[DAS28], Erythrocyte sedimentation rate [ESR], C-reactive protein [CRP] and carotid IMT in rheumatoid patients with and without CAD. Serum OPG level was correlated significantly with plasma TM only in rheumatoid patients with CAD [P < 0.001]. Osteoprotegerin is a clinically important molecule independently associated with the presence of coronary artery disease and may be a good indicator of atherosclerotic vascular damage and macroangiopathy in asymptomatic rheumatoid patients. Hence, measurement of serum OPG merits further investigation as a simple test for improving early diagnosis of asymptomatic CAD in rheumatoid patients

Proinflammatory cytokines and thrombomodulin in patients with peptic ulcer disease and gastric cancer, infected with Helicobacter pylori.

Backgrounds: Helicobacter pylori infect more than half of the global population. It is suggested to be related with gastritis, peptic ulcer disease (PUD), and gastric cancer. Aims: The aim of this present study was to evaluate proinflammatory cytokines including interleukin 1, 6, 8, 10, and thrombomodulin in H. pylori-infected patients with PUD and gastric cancer. Patients: This cross-sectional study was conducted in Taleghani Hospital on 111 patients with H. pylori infection. Materials and Methods: Patients were divided into three groups of PUD, cancer, and control (normal on endoscopy), according to the results of endoscopy. The serum levels of interleukins 1, 6, 8, and 10 and thrombomodulin was determined using enzyme-linked immunosorbent assay (ELISA) technique. H. pylori infection was diagnosed by histological examination of the endoscopic biopsy. Results: One hundred eleven patients were included in the study; 30 as PUD group, 30 as gastric cancer group, and 51 as controls. There was no significant difference between the means of IL-1 and IL-10 levels among the three groups (P = 0.744 and 0.383, respectively). IL-6, IL-8, and thrombomodulin levels were found to be statically different among the three groups (P < 0.05). The level of IL-6, IL-8, and thrombomodulin in cancer group was significantly higher than PUD and control groups (P < 0.05). Conclusion: There is a significant association between H. pylori infection and serum IL-6, IL-8, and thrombomodulin but such relation is not present between H. pylori and IL-1 and IL-10. Immunity response (IL-6, IL-8 and thrombomodulin) is more severe in cancer patient than PUD.

Correlation between blood levels of adhesion molecules ICAM-1 and VCAM-1 and thrombomodulin with coronary artery disease

The results of studies on coronary artery disease risk factors have demonstrated that some adhesion molecules could be risk factors for coronary artery disease. ICAM-1 and VACM-1 are the most important adhesion molecules. On the other hand, thrombomodulin is an anti-inflammatory factor and can reduce the risk for coronary artery disease. In this study, as well as evaluating these factors, we also studies the effect of the interaction between these factors on coronary artery disease. One hundred twenty-three patients between the ages of 45 and 70 years old who were admitted for coronary angiography in the cardiovascular center and met the inclusion criteria for the research, were selected in the first half of 2008. After recording their personal information and medical history in the questionnaires, blood samples were collected and after routine examination, the blood levels of these factors were measured. WE then entered the acquired results of the blood examination and the angiography in the patients' charts and analyzed the results using statistical methods. The angiography results in patient showed that 18 [14.7%] had normal coronary arteries, 5 [4%] had minimal coronary artery disease, 40 [32.5%] had single-vessel disease, 25 [20.3%] had two-vessel disease, and 35 [28.5%] had three-vessel disease. In laboratory tests, the mean soluble ICAM-1 level in patients with normal coronary arteries was 236 ngr/mL; however, in patients with coronary artery disease, the mean level was 274 ngr/mL. The average amount of VCAM-1 in patients with normal coronary arteries was 697 ngr/mL, whereas patients with coronary artery disase had an average of 108 ngr/mL. Thrombomodulin in the normal coronary artery group was 42 ngr/mL, but in patients with coronary artery disease the average level was 30 ngr/mL. The results in this research showed that increased levels of soluble ICAM-1 and also decreased levels of soluble thrombomodulin increased the risk and intensity of coronary artery disease, with statistical significance. The increase in soluble VCMA-1 also increased the risk of coronary artery disease; this was, however, not statistically significant. The important point is that increased levels of soluble ICAM-1 is a risk factor when the level of thrombomodulin is normal or below normal. When the levels of thrombomodulin and ICAM-1 have both increased, the increased risk and intensity of coronary disease is not statistically important

role of Thrombomodulin, IL-12, transforming growth factor-beta2 in early onset preeclamsia: a potential biomarker for disease severity

Early onset Preeclampsia is a pregnancy specific heterogeneous syndrome with genetic predisposition ranging from hypertension, proteinuria and edema to severe preeclampsia with complications. A defective implantation and placentation, circulating factors including proinflammatory molecules, cytokines and adhesion molecules have been implicated in the pathogenesis of preeclampsia. Was to assess the clinical value of assaying maternal serum concentration of thrombomodulin [TM] interleukin-12 [IL-12] and transforming growth factor beta-2 [TGF-beta 2], in normotensive, mild and severe preeclamptic pregnant women, and to evaluate the correlation between these factors and the blood pressure, uric acid and creatinine. The second objective was to look for differences between mild and severe early onset preeclampsia, compared with a healthy pregnant and non pregnant cross sectional investigated groups. Serum TM, IL-12 and TGF-beta 2 were measured using enzyme linked immunoassay [ELISA] and enzyme immunoassay respectively in 45 women with preeclampsia divided into 24 mild and 21 severe preeclamptic patients and compared with 21 pregnant normotensive and 20 non pregnant controls. Serum uric acid and creatinine were measured as well. Severe preeclamptic women had significantly increased levels of TM [p<0.01], IL-12 [p<0.01] and TGF-beta 2 p<0.01] compared with women with normal pregnancy and non pregnant women. Serum creatinine and uric acid co1Icentrations were significantly higher in severe preeclamptic patients [1.35 +/- 0.17mg/dL, 7.43 +/- 0.74mg/dL, respectively, mean +/- SD] and did not change significantly in mild preeclamptic women compared with those of healthy normotensive pregnant women. Significant positive correlations existed between serum TGF-beta 2 concentrations and mean arterial blood pressure, TM. serum creatinine and uric acid concentrations in severe pre peclamptic patients. Conclusion: Increase concentration of thrombomodulin, II-12 and TGF-beta 2, in severe preeclamptic patient might explain the shallow placentation, endothelial cell dysfunction and renal involvement described in severe preeclampsia. Measurement of maternal plasma of TM, IL-l2, TGF-beta 2 levels in preeclampsia can be useful biomarker for the assessment of the severity of the disease

Serum thrombomodulin level in children with beta thalassaemia major

In recent years, it is suspected that vascular endothelial cells may have some role in vascular complications noted in thalassemic patients. Activated or injured endothelial cells release their protein constituents mainly thrombomodulin into the circulation. Thrombomodulin is considered the most important indicator of vascular endothelial injury. To study serum thrombomodulin level in children with B-thalassaemia major and its relation to the duration of disease and extent of iron overload. The present study was carried out on 35 patients with fl-thalassaemia major. They were divided according to the age into two groups. Group I: included 15 young children aged less than 10 years. Their mean disease duration was 5.5 years. Group II: included 20 older children and adolescents aged from 10 to 20 years. Their mean disease duration was 15.6 years. Ten apparently healthy children of matching age and sex served as control group. Estimation of serum levels of Thrombomodulin [TM] by ELISA. Echocardiography, two-dimensional, M-mode, and Doppler studies. Cardiomegaly was found in 7 [35%] patients of group II. Pulmonary hypertension was encountered only in 4 [20%] patients of group II. Thromboembolic manifestations [femoral deep vein thrombosis] were found in only 1 [5%] thalassaemic patient in group II. The serum TM level was significantly higher in both groups, in comparison with controls [F=10.36, p<0.001]. No significant difference was found between both thalassaemic groups [t=0.421, p=0.673]. Moreover, no significant difference was found between TM levels in splenectomized and non-splenectomized cases [t=0.62, p=0.541]. TM levels of both thalassemic groups showed no significant correlation with serum ferritin level [r=-0.02, p=0.914]. A significantly higher mean value of right ventricular wall thickness was encountered in group II thalassaemic patient as compared to group I [t=2, 57, P=0.019]. In conclusion, increased serum TM level in our polytransfused thalassaemic patients reflects a state of endothelial cell activation and/or injury in these patients. The statistically significant negative correlation between serum TM level and pulmonary acceleration time [r=-0.45, p=0.047], may point to the possible role of pulmonary vascular endothelium injury as a contributory factor in the pathogenesis of pulmonary hypertension in our thalassaemic patients

Study of soluble thrombomodulin as an early marker of endothelial cell injury in obese children

Obesity in children is associated with various cardiovascular risk factors as well as an increased cardiovascular disease morbidity and mortality in adulthood. Thrombomodulin, a glycoprotein with vasoprotective and anticoagulant properties, is located at the luminal endothelial cell surface. Its soluble form results from endothelial cell injury. The aim of this work was to study thrombomodulin as an early marker of endothelial cell injury in obese children. This study was done on 40 children: 20 obese and 20 non-obese control children. They were subjected to clinical examination and the following investigations, CBC, blood urea and serum creatinine, fasting blood glucose, serum cholesterol serum triglyceride, HDL-cholesterol, LDL- cholesterol and soluble thrombomodulin by ELISA. There was significant increase in blood pressure, fasting blood glucose, cholesterol, LDL-cholesterol, triglycerides and soluble thrombomodulin in obese children compared to control group [p < 0.05]. HDL-cholesterol was significantly lower in obese children compared to non-obese ones [p < 0.05]. There was significant positive correlation between blood pressure and plasma soluble thrombomodulin. From this study it could be concluded that obese children had more elevated blood pressure, fasting blood glucose and dyslipidemia. Soluble thrombomodulin was higher in obese children compared to controls. It was positively correlated with elevated blood pressure denoting endothelial cell injury in obese children

Recurrent myocardial infarction: new concepts in predisposing factors

At one end of the clinical spectrum of coronary artery disease [CAD] are subjects who have had repeated acute ischemic events [unstable angina, acute myocardial infarction or sudden death], and at the other end are those with longstanding stable angina who have never been unstable. The variability of serum level of thrombomodulin [TM] in various phases of ischemic heart disease [IHD] raised the question of variable pathphysiological role as vasoprotective, thromboresistant, and anti-inflammatory factor. To answer the question of TM variable levels in IHD, we studied 100 patients [90 males and 10 females, mean age 57 +/- 11.3 range 38 to 69 years,] with IHD including 5 groups [20 pts for each], Recurrent MI [RMI], Old stable MI [OSMI], Stable Angina [SAP], Acute MI [AMI], and a control group [normal coronary angiography]. Following clinical examination TM level was determined using ELIZA technique. Genetic studies using single strand conformation polymorphism [SSCP] method was done to determine mutation in TM gene G-33 A. Compared to control group, patients with IHD had significantly lower TM level [5.7 +/- 3.6 VS 3.06 +/- 2.8; p=0.002]. Serum TM in patients with SAP was significantly lower compared to control subjects [5.7 +/- 3.6 VS 3.92 +/- 2.8; p=0.004]. Compared to pts with OSMI., Pts with RMI had significantly higher levels of TM [4.52 +/- 4.3 VS 5.85 +/- 3.8; p=0.031]. Compared to pts with SAP, Pts with OSMI had significantly higher level of TM [3.06 +/- 2.8 VS 4.52 +/- 4.3; p=0.003]. In ischemic pts, there is a constant tendency of increased TM level from SAP to OSMI to RMI [3.06 +/- 2.8, 4.52 +/- 4.3 and 5.85 +/- 3.8, respectively]. There was no significant difference between pts with RMI and the control group [5.85 +/- 3.8 VS 5.7 +/- 3.6; p=0.93]. Compared to control group, pts with AMI had significantly lower level of TM [2.8 +/- 2.1 VS 5.7 +/- 3.6; p=0.0001] and significantly lower level of TM compared to pts with IHD not in the acute stage [p=0.026]. Regarding TM gene mutation, this study revealed that patients with a mutant TM gene have a significantly less TM level compared to patients with the mild type TM gene [2.85 +/- 2.1 vs 4.7 +/- 3.6, p=0.04] with the consequences of decreased surface expression of TM and decreased level of soluble TM in plasma. Our data point to the duality of the role of thrombomodulin in IHD as a thromboresistant and anti-inflammatory molecule. Reduced serum levels of TM could predispose to IHD and acute MI. Higher TM levels in normal population reflect activation of thrombin through protein C pathway activation [antithrombotic mechanism] whereas the lower levels of thrombomodulin in stable angina and acute MI might reflect a deficient anti thrombotic mechanism and may speak of the underestimated anti inflammatory role of thrombomodulin knocked down by inflammatory mediators released in the ischemic process. Recurrence of MI might explain the high levels of TM which serves as endothelial anti-inflammatory maker which is signaled by the continued inflammatory state caused by recurrent MI. The reduced TM expression on the coronary endothelium could facilitate thrombus formation at the site of plaque injury, highlighting the cardioprotective role played by TM at the coronary vasculature

Study of thrombomodulin level in infants with respiratory problems of diabetic mothers

In our study, we found statistical significant increase in the soluble form of thrombomodulin PTM was positively correlated to the duration of the disease, age of the mother, PCO2 [in BOA] and CRP. The longer the duration of symptoms, the older the age of the mother or the higher in the PCO2 or CRP +ve, the higher will be PTM. In the other hand, PTM was negatively correlated to gestational age, Apgar score, PH in [BOA], HCO3 in [BGA] and platelet count. The in the Apgar score, PH, HCO3 and platelet count, the lower will be PTM level

Plasma level of soluble thrombomodulin in acute myocardial infarction and acute ischemic stroke in type 2 diabetes mellitus

The present study was carried out on 40 patients with acute myocardial infarction [AMI] or acute ischemic stroke [AIS]. The patients were divided into four groups [each group comprised ten patients]: Group I included nondiabetic patients with AMI, group II included diabetic patients with AMI, group III included nondiabetic patients with AIS and group IV included diabetic patients with AIS. In addition, ten healthy subjects were taken as a control group. Mean plasma soluble thrombomodulin [sTM] level was significantly lower in patients with AMI [group I + group II] [3.88 ng/ml + 3.8] and in patients with AIS [group III + IV] [3.75 ng/ml + 2.8] compared with the control group [6.64 ng/ml + 2.33] with no significant difference between patients with AMI and AIS. Acute myocardial infarction [AMI] and acute ischemic stroke [AIS] were associated with decreased plasma sTM, reflecting the decreased expression of endothelial TM, thus disturbing the balance between procoagulant and anticoagulant factors towards a pro-coagulant state. In patients with AIS, diabetics have lower plasma sTM than non-diabetics

Changes in hematologic markers in patients with mitral stenosis after successful percutaneous balloon mitral valvuloplasty.

Systemic embolism is a major complication of mitral stenosis which is usually related to a presence of left atrial thrombus. Percutaneous balloon mitral valvuloplasty (PBMV) was previously reported to reduce the incidence of this complication. However, the mechanisms of this beneficial procedure was under investigated. The aim of this study was to investigate the changes in coagulation activity, platelet activity and endocardial function in 29 patients with mitral stenosis after successful PBMV. All subjects had good left ventricular systolic function and 48.3% had atrial fibrillation. There was a significant reduction in thrombin-antithrombin complex (TAT) after a successful procedure and the level of thrombomodulin was also significantly higher one month after successful procedure. However, the level of platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were increased after this procedure but not achieved the statistical significance. In conclusion, successful PBMV can reduce the prethrombotic state in patients with mitral stenosis. In addition, it may improve endocardial function of the left atrium in those without atrial fibrillation.

Evaluation of plasma thrombomodulin in patients with type II diabetes mellitus

Thrombumodulin is an important endothelial anticoagulant protein that decreases thrombin activity and activates protein C. Increased plasma concentrations of various markers of endothelial damage especially thrombomodulin, have been observed in type I diabetic patients particularly in those with microangiopathy. So we aimed in this study to evaluate the significance of plasma thrombomodulin as a biochemical marker for early detection of microvascular complication such as diabetic nephropathy in patients with Type II diabetes mellitus Thirty diabetic patients fulfilled the WHO criteria for type II diabetes-were included in this study together with 10 normal volunteers as normal control.-The type II diabetic patients were classified into three groups according to the level of microalbuminuria in 24hours urine: Group I: included 10 diabetic patients [without nephropathy] microalbumin/24 hours urine<30 mg, Group II included 10 diabetic patients with [incipient diabetic nephropathy] microalbomin/24 hours urine ranged from 30 to 300 mg, and Group III included 10 diabetic patients with [overt diabetic nephropathy], microalbuminl24 hours urine>300mg. For all patients and control the following were done serum creatinine, glycated hemoglobin [HbAlc] Plasma thrombomodulin [TM] and 24 hours urinary micro-albuminuria-In this study we found that, TM were highly significantly elevated in diabetic patients with microalbominuria [group II] and with macroalbuminuria [group III] as compared to the control group [P<0.01] [Table 2]. Also group III showed highly significant elevation in TM than group II [P<0.0 1]. TM showed highly significant correlation with albumin concentration in 24 hours urine HbAlc, and duration of diabetes [P<0.01] [tables]. Because plasma TM level was strongly affected by kidney function. TM index [TM[FU/ml]/serum creatinine [mg%] was used as an endothelial marker. TM index showed a highly significant elevation in diabetic patients [p<0.01] especially in patients with macroalbuminurea [group III] as compared to normal control [p<0.01] [Table 2] also its level was significantly higher in group III than both group I and group II [p<0.01] while no significant difference was found between neither group I nor group II and control group [p>0.05]. TM index showed a highly significant positive correlation with duration of diabetes, but it showed no significant correlation with HbAlc [P>0.05] [Table 6]. These results suggested that a generalized vascular endothelial damage occurs in diabetic nephropathy including the microalbuminuric stage, and TM could be used as a marker for early detection of diabetic microvascular complications

Von Willebrand factor, thrombomodulin and nitric oxide in Behcet's disease

Twenty-six patients with Behcet's disease [BD] [15 patients with active disease and 11 with inactive disease] and 20 healthy subjects, as a control group, were included in this study. All patients and controls were subjected to measurement of plasma levels of von Willebrand factor [vWF] and thrombomodulin [TM] as well as serum NO, in addition to complete blood picture, erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]. The results showed that, means of vWF, TM and NO levels were significantly higher in BD patients than controls. Mean levels of vWF were high in patients with recurrent oral ulcer [ROU] and those with arthritis/arthralgia. Mean values of NO were significantly high in patients with ROU, RGU, patients with arthritis/arthralgia and thrombosis. Mean levels of vWF, TM and NO were significantly higher in active group than inactive group. Positive correlations were found between vWF with ESR2, CRP, TM and NO. Also, positive correlations were found between TM with ESR1 and ESR2. Also, positive correlations were found between NO with ESR1, ESR2 and CRP

Proteína C reactiva y trombomodulina soluble: predictores bioquímicos de mantención de ritmo sinusal a 1 año en pacientes con fibrilación auricular no valvular / C reactive protein and soluble trobomodulin: biochemical markers in the maintenance of sinusal rhythm at 1 year follow-up in patients with non valvular atrial fibrillation

Introducción: Recientemente, hemos demostrado la existencia de un estado proinflamatorio sistémico (elevación de niveles de proteína C-reactiva [PCR]) en pacientes con fibrilación auricular (FA) no valvular. Este estado inflamatorio se asocia a la pérdida de ritmo sinusal a largo plazo en estos pacientes. Hipótesis: Determinar si los niveles de PCR, como marcadores de inflamación sistémica, trombomodulina soluble (sTM,) como marcador de función endotelial, y P-selectina, como índice de activación plaquetaria, se encontraban o no, asociados a la mantención de ritmo sinusal a 1 año en pacientes con FA no valvular. Métodos: Se estudiaron 130 pacientes en forma prospectiva con FA no valvular ingresados a un hospital universitario. Ningún paciente tenía antecedente de tratamiento anticoagulante previo al ingreso. En todos ellos se midieron niveles de PCR, sTM, y marcadores hemostáticos (complejos trombina-antitrombina [TAT] y P-selectina). En todos los pacientes se realizó un ecocardiograma transtorácico y transesofágico durante las primeras 24 hrs del ingreso. Resultados: La edad promedio del grupo fue de 67±13 años (70 hombres; 46 por ciento >70 años, 59 por ciento hipertensos, 15 por ciento diabéticos y 34 por ciento con cardiopatía previa). Los niveles de PCR basales del grupo con FA fueron significativamente más altos que los niveles del grupo control de 20 sujetos (pareados por edad y sexo) en ritmo sinusal (10,5±2,2 versus 3,25 mg/L, p=0,001). Los niveles de sTM en los pacientes con FA fueron también más elevados que los controles, sin embargo, no alcanzaron significación estadística (52,2±111 versus 44±13ng/mL respectivamente). Tanto los niveles de P-selectina (219±141 ng/mL) como TAT (54±237 ng/mL) fueron significativamente más elevados que los del grupo control (p<0,05 para ambos versus el grupo control). Sin embargo, en el análisis multivariado se demostró que sólo los niveles elevados de PCR (OR =4,8 p=0,02) y sTM (OR=1,05, p=0,04), fueron predictores de mantención de ritmo sinusal a 1 año en pacientes con FA no valvular (ajustados por edad, parámetros ecocardiográficos de mantención de ritmo sinusal a largo plazo y de los niveles de TAT y P-selectina). Ni los niveles de P-selectina ni los de TAT demostraron su asociación a la mantención de ritmo sinusal a largo plazo. Conclusiones: Este estudio demuestra que los niveles de PCR y sTM contribuyen a predecir el ritmo cardíaco a largo plazo en pacientes con FA no valvular.

Clinical significance of measurements of serum and urinary thrombomodulin and serum e-selectin in diabetic patients with and without complications

Serum and urinary levels of soluble thrombomodulin [TM] and the serum levels of the soluble leucocyte adhesion molecule E-selectin, were measured in 80 diabelic patients. Fourty patients with insulm-dependent diabetes mellitus [IDDM] were divided into 20 non-complicated patients [group I] and 20 complicated patients [group II]. Ten age-matched healthy subjects were used as a control [group III] for the IDDM patients. Another 40 patients with non-insulin-dependent diabetes mellitus [NIDDM] comprised 20 non-complicated patients [group IV] and 20 complicated patients [group V]. Ten more age-matched healthy subjects were selected as a control [group VI] for the NIDDM patients. Serum and urinary concentrations of TM were significantly higher in diabetic patients compared with controls. Moreover, serum and urinary TM levels were significantly increased in complicated IDDM and NIDDM patients compared with the non-complicaied patients and the control subjects. Similarly, serum concentrations of E-selectin were found to be significantly higher in complicated diabetic patients versus the non-complicated patients and the control groups. In all diabetic patients of the four studied groups and in each separale group, serum and urinary levels of TM and serum E-selectin concentrations correlated positively with the duration of diabetes, fasting and postprandial blood glucose, HbA[IC] and urinary albumin excretion. A significant positive correlation was also found between urinary and serum levels of TM in the four studied groups of patients. Furthermore, serum and urinary levels of TM together with serum E-selectin concentrations correlated positively with the frequency of complications in complicated IDDM and NIDDM patients. The results suggest that serum and urinary TM levels could be a sensitive and predictive marker for the generalized vascular endothelial mjury induced by hyperglycemia and/or premicroangiopathy in diabetic patients. The present data point to a functional role for the soluble leucocyte adhesion molecule E-selectin in the development and progressions! complications in diabetic patients. The results also indicate that the concentrations of TM and E-selectin may be retated to metabolic control

Plasma endothelin-1 and thrombomodulin: correlation with the extent of pulmonary hypertension in patients whith chronic hypoxic pulmonary disease

This study included 47 pulmonary hypertensive patients secondary to chronic hypoxia due to chronic obstructive pulmonary diseases [COPD] and interstitial pulmonary fibrosis [IPF]. They were sampled in the morning after an overnight fast, before medication and after termination of treatment. Endothelin-1 level was 1.45 +/- 0.32 pg/ml which was increased compared with the normal controls [0.5 +/- 0.02]; the difference was statistically significant. Endothelin-1 was significantly correlated with pulmonary pressure and its degree of severity, especially among chronic obstructive pulmonary disease patients. There was a significant reduction in the level of endothelin-1 after long-term oxygen therapy; whereas, it did not correlate with the level of PaO2 either before or after oxygen therapy. Plasma thrombomodulin level was measured to study its pathophysiological significance in pulmonary hypertension secondary to hypoxia. Patients with pulmonary hypertension had higher concentrations of thrombomodulin [15.25 +/- 1.5] than the age matched normal controls [4.8 +/- 0.5 ng/ml]. There was a significant reduction in thrombomodulin after oxygen therapy. Plasma concentrations of thrombomodulin were significantly correlated with time to peak velocity [TPV] as a strong echo parameter of pulmonary hypertension and its severity in mild PH thrombomodulin level was 10.46 +/- 0.56 ng/ml versus 15.82 +/- 3.08 ng/ml among patients with severe pulmonary hypertension. Moreover, thrombomodulin correlated with PaO2 after oxygen therapy especially with patients of IPF

EParasite density and morbidity in relation to serum levels of thrombomodulin and E-selectin in the acute phase of plasmodium vivax malaria

Standardized questionnaires, clinical examination and parasitological diagnosis were performed on 40 patients in the acute phase of vivax malaria from the out patient clinics, El Abbassia Fevers Hospital. Serum levels of Thrombomadulin [TM], E-selectin and creatinine were determined in inrolled patients and also in 20 healthy controls. The results, based on multivariable analysis, showed that the clinical diagnosis of malaria including history of fever, rigors, headache, myalgia and palpable spleen was strongly associated with the presence and density of P. vivax malaria even in patients with parasite densities less than l000/micro l of blood and significantly increased the odds of the clinical diagnosis. Results revealed also that the patient's mean +/- SD serum levels of TM and E-selectin were 12.8 +/- 3.67 and 125 +/- 61.4 [u/micro l] respectively, significantly greater than in the controls [TM, P<0.001, E-selectin, P<0.001]. However, no significant differences were identified between patients and controls for serum creatinine values. On the other hand, there was a high significant correlation between levels of parasitemia and serum levels of TM and E-selectin

Avaliaçäo dos vasos, da agregaçäo plaquetária e do mecanismo da anticoagulaçäo natural nas doenças coronarianas / Vessels, platelet aggregation and natural anticoagulation mechanism evaluations in coronarian diseases

Este trabalho teve como objetivo investigar a presença de lesäo e seu efeito sobre a competência funcional do mecanismo da anticoagulaçäo natural. Foram analizadas 45 amostras de sangue de pacientes com angina de peito (n=11), indivíduos com alto risco para desenvolverem essas doenças, porém, assintomáticos (n=16) e de indivíduos sadios empregados como controle (n=10). Foram realizadas a avaliaçäo de trombomodulina (marcador de lesäo endotelial), da agregaçäo plaquetária, do fibrinogênio, do fator VIII e da proteína C, essa envolvida no sistema da anticoagulaçäo natural. Os níveis de trombomodulina, fator VIII e fibrinogênio se mostraram elevados nos pacientes com infarto e angina, ao contrário da proteína C, que se mostrou diminuída nesses pacientes, quando comparados ao controle. Diferenças entre os grupos controle e de risco foram observadas apenas para o teste da agregaçäo plaquetária, cujos resultados foram similares para os grupos de risco, angina e infarto, sugerindo que este teste pode ser utilizado como um parâmetro preditivo de risco para doença coronariana. Uma interpretaçäo dos resultados permite estabelecer a ocorrência de lesäo endotelial e sua consequência sobre a competência funcional do sistema da anticoagulaçäo em pacientes com tais doenças, resultando em um desequilíbrio entre procoagulantes e anticoagulantes, o que favorece a formaçäo de trombo.

Elevated thrombomodulin plasma level in preeclampsia as a measure of disease severity

This study was carried out to assess the relationship between serum thrombomodulin and preeclampsia. Venous plasma samples were collected from 78 pregnant women; 18 women with severe preeclampsia, 21 women with mild preeclampsia and 39 normotensive healthy women with singleton pregnancies in the third trimester. The effect of preeclampsia on thrombomodulin release from endothelial cells was tested. Thrombomodulin levels were measured with specific immunoassays. Plasma thrombomodulin levels [mean +/- standard error of the mean] were elevated in pregnant women with severe preeclampsia [16.8 +/- 2.2 compared with 9.1 +/- 0.6 [matched control] n/ml]. Also, serum thrombomodulin levels correlated positively with serum creatinine and serum uric acid levels. In severe preeclamptic pregnancies, serum thrombomodulin levels were significantly high; therefore, elevated serum thrombomodulin levels can serve as a clinically important marker in the differentiation of the severity of preeclampsia